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Kuraeiad S, Kotepui KU, Mahittikorn A, Anabire NG, Masangkay FR, Wilairatana P, Wangdi K, Kotepui M. A Systematic Review and Meta-Analysis of MIP-1α and MIP-1β Chemokines in Malaria in Relation to Disease Severity. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:676. [PMID: 40282967 PMCID: PMC12028554 DOI: 10.3390/medicina61040676] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/26/2025] [Revised: 04/01/2025] [Accepted: 04/02/2025] [Indexed: 04/29/2025]
Abstract
Background and Objectives: Macrophage inflammatory protein-1α (MIP-1α) and MIP-1β act as signaling molecules that recruit immune cells to sites of infection and inflammation. This study aimed to synthesize evidence on blood levels of MIP-1α and MIP-1β in Plasmodium-infected individuals and to determine whether these levels differ between severe and uncomplicated malaria cases. Materials and Methods: The study protocol was registered in PROSPERO (CRD42024595818). Comprehensive literature searches were conducted in six databases (EMBASE, MEDLINE, Ovid, Scopus, ProQuest, and PubMed) to identify studies reporting blood levels of MIP-1α and MIP-1β in Plasmodium infections and clinical malaria. A narrative synthesis was used to describe variations in MIP-1α and MIP-1β levels between malaria patients and controls and between severe and non-severe malaria cases. Meta-analysis was used to aggregate quantitative data utilizing a random-effects model. Results: A total of 1638 records were identified, with 20 studies meeting the inclusion criteria. Most studies reported significantly higher MIP-1α and MIP-1β levels in malaria patients compared to non-malarial controls. The meta-analysis showed a significant elevation in MIP-1α levels in malaria patients (n = 352) compared to uninfected individuals (n = 274) (p = 0.0112, random effects model, standardized mean difference [SMD]: 1.69, 95% confidence interval [CI]: 0.38 to 3.00, I2: 96.0%, five studies, 626 individuals). The meta-analysis showed no difference in MIP-1α levels between severe malaria cases (n = 203) and uncomplicated cases (n = 106) (p = 0.51, SMD: -0.48, 95% CI: -1.93 to 0.96, I2: 97.3%, three studies, 309 individuals). Conclusions: This study suggests that while MIP-1α and MIP-1β levels are elevated in malaria patients compared to uninfected individuals, these chemokines show a limited ability to differentiate between severe and uncomplicated malaria or predict severe outcomes. Further research is needed to clarify their role in malaria pathogenesis and explore potential clinical applications.
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Affiliation(s)
- Saruda Kuraeiad
- Medical Technology, School of Allied Health Sciences, Walailak University, Tha Sala, Nakhon Si Thammarat 80160, Thailand;
- Center of Excellence in Tropical Pathobiology, Walailak University, Nakhon Si Thammarat 80160, Thailand
| | | | - Aongart Mahittikorn
- Department of Protozoology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
| | - Nsoh Godwin Anabire
- Department of Biochemistry & Molecular Medicine, School of Medicine, University for Development Studies, Tamale P.O. Box TL 1882, Ghana
- West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell & Molecular Biology, University of Ghana, Accra P.O. Box LG 226, Ghana
| | | | - Polrat Wilairatana
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
| | - Kinley Wangdi
- HEAL Global Research Centre, Health Research Centre, Faculty of Health, University of Canberra, Canberra, ACT 2617, Australia
- National Centre for Epidemiology and Population Health, Australian National University, Canberra, ACT 2601, Australia
| | - Manas Kotepui
- Medical Technology, Faculty of Science, Nakhon Phanom University, Nakhon Phanom 48000, Thailand
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Tesine P, Woon SA, Laman M, Yadi G, Yambo P, Kasian B, Lorry L, Robinson LJ, Salman S, Batty KT, Pomat W, Manning L, Davis WA, Davis TME, Moore BR. Artemisinin combination therapy at delivery to prevent postpartum malaria: A randomised open-label controlled trial. Int J Infect Dis 2024; 149:107258. [PMID: 39396742 DOI: 10.1016/j.ijid.2024.107258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 09/30/2024] [Accepted: 10/01/2024] [Indexed: 10/15/2024] Open
Abstract
OBJECTIVES Although the incidence of malaria is increased in women in endemic areas after delivery compared to non-pregnant women, no studies have assessed the benefit of presumptive antimalarial treatment given postpartum. METHODS A randomised controlled trial investigating the efficacy of antimalarial treatment in preventing postpartum malaria was performed in healthy Papua New Guinea mothers immediately following delivery. Participants were randomised 1:1 to no treatment (n = 90) or artemisinin combination therapy (ACT), with further 1:1 ACT randomisation to artemether-lumefantrine (AL; n = 45) or dihydroartemisinin-piperaquine (DP; n = 45). Standardised reviews were conducted monthly for 6 months, including clinical assessment, malaria screening and haemoglobin measurement. The primary endpoint was incidence of slide-positive malaria within 6 months of delivery. RESULTS Of 183 recruited participants, 151 completed study procedures and were included in per-protocol analyses (no treatment n = 71, AL n = 40, DP, n = 40). Those allocated to ACT were significantly less likely to develop slide-positive malaria during the 6-month follow-up period compared to those who were untreated (n = 17 (21%) vs n = 27 (38%); P = 0.016; hazard ratio 0.49 (95% confidence intervals 0.27-0.90). There was no significant difference in malaria incidence between the two ACT groups. CONCLUSION A treatment course of ACT at time of delivery halved the incidence of malaria infection during the first 6-month postpartum.
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Affiliation(s)
- Paula Tesine
- Vector Borne Disease Unit, Papua New Guinea Institute of Medical Research, Madang, Madang Province, Papua New Guinea
| | - Sze-Ann Woon
- Medical School, The University of Western Australia, Perth, Western Australia, Australia
| | - Moses Laman
- Vector Borne Disease Unit, Papua New Guinea Institute of Medical Research, Madang, Madang Province, Papua New Guinea
| | - Gumul Yadi
- Vector Borne Disease Unit, Papua New Guinea Institute of Medical Research, Madang, Madang Province, Papua New Guinea
| | - Phantica Yambo
- Vector Borne Disease Unit, Papua New Guinea Institute of Medical Research, Madang, Madang Province, Papua New Guinea
| | - Bernadine Kasian
- Vector Borne Disease Unit, Papua New Guinea Institute of Medical Research, Madang, Madang Province, Papua New Guinea
| | - Lina Lorry
- Vector Borne Disease Unit, Papua New Guinea Institute of Medical Research, Madang, Madang Province, Papua New Guinea
| | - Leanne J Robinson
- Vector Borne Disease Unit, Papua New Guinea Institute of Medical Research, Madang, Madang Province, Papua New Guinea; Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia; Burnet Institute, Melbourne, Victoria, Australia
| | - Sam Salman
- Medical School, The University of Western Australia, Perth, Western Australia, Australia; Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Western Australia, Australia; Clinical Pharmacology and Toxicology Unit, PathWest, Perth, Western Australia, Australia
| | - Kevin T Batty
- Curtin Medical School, Curtin University, Perth, Western Australia, Australia; Curtin Heath Innovation Research Institute, Curtin University, Perth, Western Australia, Australia
| | - William Pomat
- Vector Borne Disease Unit, Papua New Guinea Institute of Medical Research, Madang, Madang Province, Papua New Guinea
| | - Laurens Manning
- Medical School, The University of Western Australia, Perth, Western Australia, Australia; Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Western Australia, Australia
| | - Wendy A Davis
- Medical School, The University of Western Australia, Perth, Western Australia, Australia
| | - Timothy M E Davis
- Medical School, The University of Western Australia, Perth, Western Australia, Australia
| | - Brioni R Moore
- Medical School, The University of Western Australia, Perth, Western Australia, Australia; Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Western Australia, Australia; Curtin Medical School, Curtin University, Perth, Western Australia, Australia; Curtin Heath Innovation Research Institute, Curtin University, Perth, Western Australia, Australia.
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Ding J, Hoglund RM, Tagbor H, Tinto H, Valéa I, Mwapasa V, Kalilani‐Phiri L, Van Geertruyden J, Nambozi M, Mulenga M, Hachizovu S, Ravinetto R, D'Alessandro U, Tarning J. Population pharmacokinetics of amodiaquine and piperaquine in African pregnant women with uncomplicated Plasmodium falciparum infections. CPT Pharmacometrics Syst Pharmacol 2024; 13:1893-1903. [PMID: 39228131 PMCID: PMC11578137 DOI: 10.1002/psp4.13211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 06/28/2024] [Accepted: 07/02/2024] [Indexed: 09/05/2024] Open
Abstract
Artemisinin-based combination therapy (ACT) is the first-line recommended treatment for uncomplicated malaria. Pharmacokinetic (PK) properties in pregnant women are often based on small studies and need to be confirmed and validated in larger pregnant patient populations. This study aimed to evaluate the PK properties of amodiaquine and its active metabolite, desethylamodiaquine, and piperaquine in women in their second and third trimester of pregnancy with uncomplicated P. falciparum infections. Eligible pregnant women received either artesunate-amodiaquine (200/540 mg daily, n = 771) or dihydroartemisinin-piperaquine (40/960 mg daily, n = 755) for 3 days (NCT00852423). Population PK properties were evaluated using nonlinear mixed-effects modeling, and effect of gestational age and trimester was evaluated as covariates. 1071 amodiaquine and 1087 desethylamodiaquine plasma concentrations, and 976 piperaquine plasma concentrations, were included in the population PK analysis. Amodiaquine concentrations were described accurately with a one-compartment disposition model followed by a two-compartment disposition model of desethylamodiaquine. The relative bioavailability of amodiaquine increased with gestational age (1.25% per week). The predicted exposure to desethylamodiaquine was 2.8%-32.2% higher in pregnant women than that reported in non-pregnant women, while day 7 concentrations were comparable. Piperaquine concentrations were adequately described by a three-compartment disposition model. Neither gestational age nor trimester had significant impact on the PK of piperaquine. The predicted exposure and day 7 concentrations of piperaquine were similar to that reported in non-pregnant women. In conclusion, the exposure to desethylamodiaquine and piperaquine was similar to that in non-pregnant women. Dose adjustment is not warranted for women in their second and their trimester of pregnancy.
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Affiliation(s)
- Junjie Ding
- Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical MedicineMahidol UniversityBangkokThailand
- Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical MedicineUniversity of OxfordOxfordUK
| | - Richard M. Hoglund
- Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical MedicineMahidol UniversityBangkokThailand
- Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical MedicineUniversity of OxfordOxfordUK
| | | | | | | | - Victor Mwapasa
- Department of Community and Environmental Health, Kamuzu University of Health SciencesBlantyreMalawi
| | - Linda Kalilani‐Phiri
- Department of Community and Environmental Health, Kamuzu University of Health SciencesBlantyreMalawi
| | | | | | | | | | - Raffaella Ravinetto
- Public Health DepartmentInstitute of Tropical MedicineAntwerpBelgium
- School of Public HealthUniversity of the Western CapeCape TownSouth Africa
| | - Umberto D'Alessandro
- MRC Unit The Gambia at the London School of Hygiene and Tropical MedicineFajaraGambia
| | - Joel Tarning
- Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical MedicineMahidol UniversityBangkokThailand
- Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical MedicineUniversity of OxfordOxfordUK
- The WorldWide Antimalarial Resistance NetworkOxfordUK
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Pillay Y, Ngonzi J, Nguyen V, Payne BA, Komugisha C, Twinomujuni AH, Vidler M, Lavoie PM, Bebell LM, Christoffersen-Deb A, Kenya-Mugisha N, Kissoon N, Ansermino JM, Wiens MO. The epidemiology and risk factors for postnatal complications among postpartum women and newborns in southwestern Uganda: A prospective cohort study. PLOS GLOBAL PUBLIC HEALTH 2024; 4:e0003458. [PMID: 39110697 PMCID: PMC11305527 DOI: 10.1371/journal.pgph.0003458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Accepted: 06/13/2024] [Indexed: 08/10/2024]
Abstract
Sub-Saharan Africa accounts for two-thirds of the global burden of maternal and newborn deaths. Adverse outcomes among postpartum women and newborns occurring in the first six weeks of life are often related, though data co-examining patients are limited. This study is an exploratory analysis describing the epidemiology of postnatal complications among postpartum women and newborns following facility birth and discharge in Mbarara, Uganda. This single-site prospective cohort observational study enrolled postpartum women following facility-based delivery. To capture health information about both the postpartum women and newborns, data was collected and categorized according to domains within the continuum of care including (1) social and demographic, (2) pregnancy history and antenatal care, (3) delivery, (4) maternal discharge, and (5) newborn discharge. The primary outcomes were readmission and mortality within the six-week postnatal period as defined by the WHO. Multivariable logistic regression was used to identify risk factors. Among 2930 discharged dyads, 2.8% and 9.0% of women and newborns received three or more postnatal visits respectively. Readmission and deaths occurred among 108(3.6%) and 25(0.8%) newborns and in 80(2.7%) and 0(0%) women, respectively. Readmissions were related to sepsis/infection in 70(88%) women and 68(63%) newborns. Adjusted analysis found that caesarean delivery (OR:2.91; 95%CI:1.5-6.04), longer travel time to the facility (OR:1.54; 95%CI:1.24-1.91) and higher maternal heart rate at discharge (OR:1.02; 95%CI:1.00-1.01) were significantly associated with maternal readmission. Discharge taken on all patients including maternal haemoglobin (per g/dL) (OR:0.90; 95%CI:0.82-0.99), maternal symptoms (OR:1.76; 95%CI:1.02-2.91), newborn temperature (OR:1.66; 95%CI:1.28-2.13) and newborn heart rate at (OR:1.94; 95%CI:1.19-3.09) were risk factors among newborns. Readmission and death following delivery and discharge from healthcare facilities is still a problem in settings with low rates of postnatal care visits for both women and newborns. Strategies to identify vulnerable dyads and provide better access to follow-up care, are urgently required.
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Affiliation(s)
- Yashodani Pillay
- Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada
- Institute for Global Health, BC Children’s Hospital Research Institute, Vancouver, British Columbia, Canada
| | - Joseph Ngonzi
- Department of Obstetrics and Gynaecology, Mbarara University of Science and Technology and Mbarara Regional Referral Hospital, Mbarara, Uganda
| | - Vuong Nguyen
- Institute for Global Health, BC Children’s Hospital Research Institute, Vancouver, British Columbia, Canada
| | - Beth A. Payne
- Digital Health, BC Children’s Hospital Research Institute, Vancouver, British Columbia, Canada
| | | | | | - Marianne Vidler
- Department of Obstetrics and Gynaecology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Pascal M. Lavoie
- Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada
| | - Lisa M. Bebell
- Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
| | - Astrid Christoffersen-Deb
- Department of Obstetrics and Gynaecology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | | | - Niranjan Kissoon
- Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada
| | - J. Mark Ansermino
- Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada
- Institute for Global Health, BC Children’s Hospital Research Institute, Vancouver, British Columbia, Canada
| | - Matthew O. Wiens
- Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada
- Institute for Global Health, BC Children’s Hospital Research Institute, Vancouver, British Columbia, Canada
- WALIMU, Kololo, Kampala, Uganda
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5
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Vatankhah M, Panahizadeh R, Safari A, Ziyabakhsh A, Mohammadi-Ghalehbin B, Soozangar N, Jeddi F. The role of Nrf2 signaling in parasitic diseases and its therapeutic potential. Heliyon 2024; 10:e32459. [PMID: 38988513 PMCID: PMC11233909 DOI: 10.1016/j.heliyon.2024.e32459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 05/24/2024] [Accepted: 06/04/2024] [Indexed: 07/12/2024] Open
Abstract
In response to invading parasites, one of the principal arms of innate immunity is oxidative stress, caused by reactive oxygen species (ROS). However, oxidative stresses play dual functions in the disease, whereby free radicals promote pathogen removal, but they can also trigger inflammation, resulting in tissue injuries. A growing body of evidence has strongly supported the notion that nuclear factor erythroid 2-related factor 2 (NRF) signaling is one of the main antioxidant pathways to combat this oxidative burst against parasites. Given the important role of NRF2 in oxidative stress, in this review, we investigate the activation mechanism of the NRF2 antioxidant pathway in different parasitic diseases, such as malaria, leishmaniasis, trypanosomiasis, toxoplasmosis, schistosomiasis, entamoebiasis, and trichinosis.
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Affiliation(s)
- Mohammadamin Vatankhah
- Zoonoses Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
- Students Research Committee, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Reza Panahizadeh
- Zoonoses Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
- Students Research Committee, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Ali Safari
- Zoonoses Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Alireza Ziyabakhsh
- Zoonoses Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | | | - Narges Soozangar
- Zoonoses Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Farhad Jeddi
- Department of Genetics and Pathology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
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Olowe RA, Ojo JA, Funwei RI, Oyedeji SI, Olowe OA, Thomas BN, Ojurongbe O. Genetic diversity of Plasmodium falciparum among asymptomatic pregnant women on intermittent preventive treatment with sulfadoxine-pyrimethamine in Nigeria. Afr Health Sci 2023; 23:765-773. [PMID: 37545953 PMCID: PMC10398500 DOI: 10.4314/ahs.v23i1.80] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/08/2023] Open
Abstract
This study investigated the genetic diversity of Plasmodium falciparum among asymptomatic pregnant women on intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-Sp) in Osogbo, southwest Nigeria. Blood sample was obtained from consenting pregnant women attending antenatal clinics. Microscopy and Polymerase chain reaction (PCR) were employed to diagnose and analyse genetic diversity. Of the 301 samples, 53 (18%) and 83 (28%) were positive for P. falciparum by microscopy and PCR, respectively. Using the merozoite surface protein (msp)-1, msp-2, and glutamate-rich protein (glurp) genes of P. falciparum as polymorphic markers, the msp-1 gene showed nine alleles with R033 (66.7%) being predominant, followed by K1 (45.5%) and MAD20 (33.3%). The msp-2 gene had 16 alleles (eight each for FC27 and 3D7). The 3D7 alleles (82.1%) was significantly more than FC27 alleles (48.2%) (p = 0.0093). Nine alleles were detected with glurp gene, presenting with the highest monoclonal and the lowest polyclonal infection. The multiplicity of infection (MOI) of 1.5, 1.8, and 1.2 were obtained for msp-1, msp-2 and glurp genes. In light of the high P. falciparum genetic diversity among pregnant women on IPT-Sp in this study, additional strategies for preventing and controlling malaria in pregnancy might be required.
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Affiliation(s)
- Rita A Olowe
- Ladoke Akintola University of Technology, Department of Medical Microbiology and Parasitology
| | - Johnson A Ojo
- Ladoke Akintola University of Technology, Department of Medical Microbiology and Parasitology
| | | | - Segun I Oyedeji
- Federal University Oye-Ekiti, Department of Animal & Environmental Biology
| | - Olugbenga A Olowe
- Ladoke Akintola University of Technology, Department of Medical Microbiology and Parasitology
| | - Bolaji N Thomas
- Rochester Institute of Technology, Department of Biomedical Sciences
| | - Olusola Ojurongbe
- Ladoke Akintola University of Technology, Department of Medical Microbiology and Parasitology
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Wang X, Chen J, Zheng J. The roles of COX-2 in protozoan infection. Front Immunol 2023; 14:955616. [PMID: 36875123 PMCID: PMC9978824 DOI: 10.3389/fimmu.2023.955616] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Accepted: 02/06/2023] [Indexed: 02/18/2023] Open
Abstract
Protozoan diseases cause great harm in animal husbandry and require human-provided medical treatment. Protozoan infection can induce changes in cyclooxygenase-2 (COX-2) expression. The role played by COX-2 in the response to protozoan infection is complex. COX-2 induces and regulates inflammation by promoting the synthesis of different prostaglandins (PGs), which exhibit a variety of biological activities and participate in pathophysiological processes in the body in a variety of ways. This review explains the roles played by COX-2 in protozoan infection and analyzes the effects of COX-2-related drugs in protozoan diseases.
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Affiliation(s)
- Xinlei Wang
- Department of Clinical Laboratory, The Second Hospital of Jilin University, Jilin University, Changchun, China
| | - Jie Chen
- Institute of Theoretical Chemistry, Jilin University, Changchun, China
| | - Jingtong Zheng
- Department of Pathogenobiology, College of Basic Medical Sciences, Jilin University, Changchun, China
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Nachega JB, Sam-Agudu NA, Machekano RN, Rosenthal PJ, Schell S, de Waard L, Bekker A, Gachuno OW, Kinuthia J, Mwongeli N, Budhram S, Vannevel V, Somapillay P, Prozesky HW, Taljaard J, Parker A, Agyare E, Opoku AB, Makarfi AU, Abdullahi AM, Adirieje C, Ishoso DK, Pipo MT, Tshilanda MB, Bongo-Pasi Nswe C, Ditekemena J, Sigwadhi LN, Nyasulu PS, Hermans MP, Sekikubo M, Musoke P, Nsereko C, Agbeno EK, Yeboah MY, Umar LW, Ntakwinja M, Mukwege DM, Birindwa EK, Mushamuka SZ, Smith ER, Mills EJ, Otshudiema JO, Mbala-Kingebeni P, Tamfum JJM, Zumla A, Tsegaye A, Mteta A, Sewankambo NK, Suleman F, Adejumo P, Anderson JR, Noormahomed EV, Deckelbaum RJ, Stringer JSA, Mukalay A, Taha TE, Fowler MG, Wasserheit JN, Masekela R, Mellors JW, Siedner MJ, Myer L, Kengne AP, Yotebieng M, Mofenson LM, Langenegger E, for the AFREhealth Research Collaboration on COVID-19 and Pregnancy. Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Pregnancy in Sub-Saharan Africa: A 6-Country Retrospective Cohort Analysis. Clin Infect Dis 2022; 75:1950-1961. [PMID: 36130257 PMCID: PMC9214158 DOI: 10.1093/cid/ciac294] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND Few data are available on COVID-19 outcomes among pregnant women in sub-Saharan Africa (SSA), where high-risk comorbidities are prevalent. We investigated the impact of pregnancy on SARS-CoV-2 infection and of SARS-CoV-2 infection on pregnancy to generate evidence for health policy and clinical practice. METHODS We conducted a 6-country retrospective cohort study among hospitalized women of childbearing age between 1 March 2020 and 31 March 2021. Exposures were (1) pregnancy and (2) a positive SARS-CoV-2 RT-PCR test. The primary outcome for both analyses was intensive care unit (ICU) admission. Secondary outcomes included supplemental oxygen requirement, mechanical ventilation, adverse birth outcomes, and in-hospital mortality. We used log-binomial regression to estimate the effect between pregnancy and SARS-CoV-2 infection. Factors associated with mortality were evaluated using competing-risk proportional subdistribution hazards models. RESULTS Our analyses included 1315 hospitalized women: 510 pregnant women with SARS-CoV-2, 403 nonpregnant women with SARS-CoV-2, and 402 pregnant women without SARS-CoV-2 infection. Among women with SARS-CoV-2 infection, pregnancy was associated with increased risk for ICU admission (adjusted risk ratio [aRR]: 2.38; 95% CI: 1.42-4.01), oxygen supplementation (aRR: 1.86; 95% CI: 1.44-2.42), and hazard of in-hospital death (adjusted sub-hazard ratio [aSHR]: 2.00; 95% CI: 1.08-3.70). Among pregnant women, SARS-CoV-2 infection increased the risk of ICU admission (aRR: 2.0; 95% CI: 1.20-3.35), oxygen supplementation (aRR: 1.57; 95% CI: 1.17-2.11), and hazard of in-hospital death (aSHR: 5.03; 95% CI: 1.79-14.13). CONCLUSIONS Among hospitalized women in SSA, both SARS-CoV-2 infection and pregnancy independently increased risks of ICU admission, oxygen supplementation, and death. These data support international recommendations to prioritize COVID-19 vaccination among pregnant women.
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Affiliation(s)
- Jean B Nachega
- Division of Infectious Diseases, Department of Medicine, Stellenbosch University Faculty of Medicine and Health Sciences, Cape Town, South Africa
- Department of Epidemiology, Infectious Diseases, and Microbiology, and Center for Global Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
- Department of International Health, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Nadia A Sam-Agudu
- International Research Center of Excellence, Institute of Human Virology Nigeria, Abuja, Nigeria
- Department of Paediatrics and Child Health, University of Cape Coast School of Medical Sciences, Cape Coast, Ghana
- Institute of Human Virology and Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, USA
| | - Rhoderick N Machekano
- Division of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Philip J Rosenthal
- Department of Medicine, Division of Infectious Diseases, University of California, San Francisco, California, USA
| | - Sonja Schell
- Department of Obstetrics and Gynecology, Tygerberg Teaching Hospital and Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Liesl de Waard
- Department of Obstetrics and Gynecology, Tygerberg Teaching Hospital and Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Adrie Bekker
- Department of Paediatrics and Child Health; Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Onesmus W Gachuno
- Department of Obstetrics and Gynaecology, University of Nairobi, Nairobi, Kenya
| | - John Kinuthia
- Department of Obstetrics and Gynaecology, University of Nairobi, Nairobi, Kenya
- Department of Research, Department of Reproductive Health, Kenyatta National Hospital, Nairobi, Kenya
| | - Nancy Mwongeli
- Department of Research, Department of Reproductive Health, Kenyatta National Hospital, Nairobi, Kenya
| | - Samantha Budhram
- Department of Obstetrics and Gynecology, University of KwaZulu Natal, Durban, South Africa
| | - Valerie Vannevel
- Department of Obstetrics and Gynecology, Kalafong Hospital, University of Pretoria, Pretoria, South Africa
| | - Priya Somapillay
- Maternal Foetal Medicine; Steve Biko Hospital, University of Pretoria, Pretoria, South Africa
| | - Hans W Prozesky
- Division of Infectious Diseases, Department of Medicine, Stellenbosch University Faculty of Medicine and Health Sciences, Cape Town, South Africa
| | - Jantjie Taljaard
- Division of Infectious Diseases, Department of Medicine, Stellenbosch University Faculty of Medicine and Health Sciences, Cape Town, South Africa
| | - Arifa Parker
- Division of Infectious Diseases, Department of Medicine, Stellenbosch University Faculty of Medicine and Health Sciences, Cape Town, South Africa
| | - Elizabeth Agyare
- Department of Microbiology, School of Medical Sciences, University of Cape Coast and Cape Coast Teaching Hospital, Cape Coast, Ghana
| | - Akwasi Baafuor Opoku
- Department of Obstetrics and Gynaecology, Komfo Anokye Teaching Hospital, Kumasi, Ghana
| | - Aminatu Umar Makarfi
- Department of Obstetrics and Gynaecology, College of Health Sciences, Ahmadu Bello University and Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
| | - Asara M Abdullahi
- Department of Medicine, College of Health Sciences, Ahmadu Bello University and Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
| | - Chibueze Adirieje
- International Research Center of Excellence, Institute of Human Virology Nigeria, Abuja, Nigeria
| | | | | | - Marc B Tshilanda
- Monkole Hospital Center, Kinshasa, Democratic Republic of the Congo
| | - Christian Bongo-Pasi Nswe
- Department of Public Health, Centre Interdisciplinaire de Recherche en Ethnopharmacologie, Faculty of Medicine, Université Notre-Dame du Kasayi, Kananga, Democratic Republic of the Congo
- Faculty of Public Health, Université Moderne de Kinkole, Kinshasa, Democratic Republic of the Congo
| | - John Ditekemena
- University of Kinshasa School of Medicine, Kinshasa, Democratic Republic of the Congo
| | - Lovemore Nyasha Sigwadhi
- Division of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Peter S Nyasulu
- Division of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Michel P Hermans
- Department of Endocrinology and Nutrition, Cliniques Universitaires St-Luc, Brussels, Belgium
| | - Musa Sekikubo
- Department of Obstetrics and Gynaecology, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda
| | - Philippa Musoke
- Department of Paediatrics and Child Health, School of Medicine, Makerere University, Kampala, Uganda
| | - Christopher Nsereko
- Department of Medicine, Entebbe Regional Reference Hospital, Entebbe, Uganda
| | - Evans K Agbeno
- Department of Obstetrics and Gynecology, School of Medical Sciences, University of Cape Coast and Cape Coast Teaching Hospital, Cape Coast, Ghana
| | - Michael Yaw Yeboah
- Department of Obstetrics and Gynaecology, College of Health Sciences, Ahmadu Bello University and Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
| | - Lawal W Umar
- Department of Pediatrics, College of Health Sciences, Ahmadu Bello University and Ahmadu Bello Teaching Hospital, Zaria, Nigeria
| | - Mukanire Ntakwinja
- Gynaecology and General Surgery, Panzi General Referral Hospital, Bukavu, and Université Evangelique en Afrique (UEA), Bukavu, Democratic Republic of the Congo
| | - Denis M Mukwege
- Gynaecology and General Surgery, Panzi General Referral Hospital, Bukavu, and Université Evangelique en Afrique (UEA), Bukavu, Democratic Republic of the Congo
| | - Etienne Kajibwami Birindwa
- Hôpital Provincial Général de Référence de Bukavu and Faculty of Medicine, Université Catholique de Bukavu (UCB), Bukavu, Democratic Republic of the Congo
| | - Serge Zigabe Mushamuka
- Hôpital Provincial Général de Référence de Bukavu and Faculty of Medicine, Université Catholique de Bukavu (UCB), Bukavu, Democratic Republic of the Congo
| | - Emily R Smith
- Department of Global Health, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA
| | - Edward J Mills
- Department of Health Research Evidence and Impact, Faculty of Health Sciences, McMaster University, Hamilton, Canada
| | - John Otokoye Otshudiema
- Epidemiological Surveillance Team, COVID-19 Response, Health Emergencies Program, World Health Organization, Kinshasa, Democratic Republic of the Congo
| | - Placide Mbala-Kingebeni
- Department of Medical Microbiology and Virology, Faculty of Medicine, University of Kinshasa, National Institute of Biomedical Research, Kinshasa, Democratic Republic of the Congo
| | - Jean-Jacques Muyembe Tamfum
- Department of Medical Microbiology and Virology, Faculty of Medicine, University of Kinshasa, National Institute of Biomedical Research, Kinshasa, Democratic Republic of the Congo
| | - Alimuddin Zumla
- Division of Infection and Immunity, Department of Infection, Centre for Clinical Microbiology, University College London, London, United Kingdom
- National Institute for Health Research Biomedical Research Centre, University College London Hospitals, London, United Kingdom
| | - Aster Tsegaye
- Department of Medical Laboratory Sciences, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Alfred Mteta
- Kilimanjaro Christian Medical University College, Moshi, United Republic of Tanzania
| | - Nelson K Sewankambo
- School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda
| | - Fatima Suleman
- Discipline of Pharmaceutical Sciences, University of KwaZulu-Natal, Durban, South Africa
| | - Prisca Adejumo
- Department of Nursing, University of Ibadan, Ibadan, Nigeria
| | - Jean R Anderson
- Department of Obstetrics and Gynecology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
| | | | - Richard J Deckelbaum
- Department of Pediatrics, Columbia University Irving Medical Center, New York, New York, USA
| | - Jeffrey S A Stringer
- Department of Obstetrics and Gynecology, University of North Carolina, School of Medicine, Chapel Hill, North Carolina, USA
| | - Abdon Mukalay
- Faculty of Medicine, University of Lubumbashi, Lubumbashi, Democratic Republic of the Congo
| | - Taha E Taha
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Mary Glenn Fowler
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Judith N Wasserheit
- Departments of Global Health and Medicine, Schools of Medicine and Public Health, University of Washington, Seattle, Washington, USA
| | - Refiloe Masekela
- Department of Pediatrics and Child Health, School of Clinical Medicine, College of Health Sciences, University of KwaZulu Natal, Durban, South Africa
| | - John W Mellors
- Department of Medicine, Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Mark J Siedner
- Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, USA
- Mbarara University of Science and Technology, Mbarara, Uganda
| | - Landon Myer
- Division of Epidemiology and Biostatistics, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa
| | - Andre-Pascal Kengne
- Non-Communicable Diseases Research Unit, South African Medical Research Council, Cape Town, South Africa
| | - Marcel Yotebieng
- Department of Medicine, Albert Einstein College of Medicine, New York, New York, USA
| | | | - Eduard Langenegger
- Department of Obstetrics and Gynecology, Tygerberg Teaching Hospital and Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
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9
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Ikegbunam MN, Uba C, Flügge J, Abone H, Ezeagwuna D, Ushie S, Esimone C. Malaria surveillance amongst pregnant women attending antenatal care in private hospitals in Onitsha metropolis, South Eastern Nigeria. MALARIAWORLD JOURNAL 2022; 13:2. [PMID: 35813272 PMCID: PMC9242532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Background Recent reports suggest that pregnant women living in holoendemic regions of sub-Sahara Africa die in great numbers annually due to malaria disease resulting from their higher susceptibility, reduced immunity and demographic associated factors. This work investigated the prevalence of Plasmodium falciparum in pregnant women attending antenatal care (ANC) in selected private hospitals in Onitsha metropolis South East Nigeria. Methods Venous blood samples were collected from 270 pregnant women during ANC visits between October 2016 and December 2017. A questionnaire was used to collect demographic data, gestational age, knowledge of malaria and preventive measures while clinical presentations and symptoms were extracted from the physician's clerking form. Laboratory diagnosis was done using microscopy. The effect of the demographic variables and other associated factors on prevalence and parasite densities was studied using Chi-square and ANOVA tests. Results The overall P. falciparum prevalence was 42.6%. Prevalence varied with the maternal age, gestational age, preventive measures adopted by the pregnant women and clinical presentations. 27.8 % of the infected women were highly parasitized (>5000 parasites/μl); 67% had a moderate parasite density (1,000-4,999 parasites/μl) and 5.2% showed a low parasite density (1-999 parasites/μl). We observed that 35.2%, 30%, 18.9% and 5.2% of the study cohorts preferred and used treated bed nets, insecticides, windows and door screening and non-treated bed nets respectively as malaria preventive measures. 5.9% did not use any protection. Conclusions The findings of this study revealed high prevalence of malaria among pregnant women living in Onitsha metropolis with high mean parasite densities despite strong adherence to use of sulphadoxine-pyrimethamine (SP) for intermittent preventive treatment in pregnancy (IPTp) and other malaria preventive measures.
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Affiliation(s)
- Moses N. Ikegbunam
- Department of Pharmaceutical Microbiology and Biotechnology, Nnamdi Azikiwe University, Awka, Nigeria,Molecular Research Foundation for Students and Scientists, Nnamdi Azikiwe University, Awka, Nigeria,Institute for Tropical Medicine, Tübingen, Germany,,
| | - Chibuzo Uba
- Department of Pharmaceutical Microbiology and Biotechnology, Nnamdi Azikiwe University, Awka, Nigeria
| | | | - Harrison Abone
- Department of Pharmaceutical Microbiology and Biotechnology, Nnamdi Azikiwe University, Awka, Nigeria
| | - Dorothy Ezeagwuna
- Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka, Nigeria
| | - Simeon Ushie
- Department of Medical Microbiology and Parasitology, Nnamdi Azikiwe University, Awka, Nigeria
| | - Charles Esimone
- Department of Pharmaceutical Microbiology and Biotechnology, Nnamdi Azikiwe University, Awka, Nigeria,Molecular Research Foundation for Students and Scientists, Nnamdi Azikiwe University, Awka, Nigeria
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10
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Okiring J, Epstein A, Namuganga JF, Kamya EV, Nabende I, Nassali M, Sserwanga A, Gonahasa S, Muwema M, Kiwuwa SM, Staedke SG, Kamya MR, Nankabirwa JI, Briggs J, Jagannathan P, Dorsey G. Gender difference in the incidence of malaria diagnosed at public health facilities in Uganda. Malar J 2022; 21:22. [PMID: 35062952 PMCID: PMC8778495 DOI: 10.1186/s12936-022-04046-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Accepted: 01/11/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Routine malaria surveillance data in Africa primarily come from public health facilities reporting to national health management information systems. Although information on gender is routinely collected from patients presenting to these health facilities, stratification of malaria surveillance data by gender is rarely done. This study evaluated gender difference among patients diagnosed with parasitological confirmed malaria at public health facilities in Uganda. METHODS This study utilized individual level patient data collected from January 2020 through April 2021 at 12 public health facilities in Uganda and cross-sectional surveys conducted in target areas around these facilities in April 2021. Associations between gender and the incidence of malaria and non-malarial visits captured at the health facilities from patients residing within the target areas were estimated using poisson regression models controlling for seasonality. Associations between gender and data on health-seeking behaviour from the cross-sectional surveys were estimated using poisson regression models controlling for seasonality. RESULTS Overall, incidence of malaria diagnosed per 1000 person years was 735 among females and 449 among males (IRR = 1.72, 95% CI 1.68-1.77, p < 0.001), with larger differences among those 15-39 years (IRR = 2.46, 95% CI 2.34-2.58, p < 0.001) and over 39 years (IRR = 2.26, 95% CI 2.05-2.50, p < 0.001) compared to those under 15 years (IRR = 1.46, 95% CI 1.41-1.50, p < 0.001). Female gender was also associated with a higher incidence of visits where malaria was not suspected (IRR = 1.77, 95% CI 1.71-1.83, p < 0.001), with a similar pattern across age strata. These associations were consistent across the 12 individual health centres. From the cross-sectional surveys, females were more likely than males to report fever in the past 2 weeks and seek care at the local health centre (7.5% vs. 4.7%, p = 0.001) with these associations significant for those 15-39 years (RR = 2.49, 95% CI 1.17-5.31, p = 0.018) and over 39 years (RR = 2.56, 95% CI 1.00-6.54, p = 0.049). CONCLUSIONS Females disproportionately contribute to the burden of malaria diagnosed at public health facilities in Uganda, especially once they reach childbearing age. Contributing factors included more frequent visits to these facilities independent of malaria and a higher reported risk of seeking care at these facilities for febrile illnesses.
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Affiliation(s)
- Jaffer Okiring
- Clinical Epidemiology Unit, School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda. .,Infectious Diseases Research Collaboration, 2C Nakasero Hill Road, Kampala, Uganda.
| | - Adrienne Epstein
- Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, USA
| | - Jane F Namuganga
- Infectious Diseases Research Collaboration, 2C Nakasero Hill Road, Kampala, Uganda
| | - Emmanuel V Kamya
- Infectious Diseases Research Collaboration, 2C Nakasero Hill Road, Kampala, Uganda
| | - Isaiah Nabende
- Infectious Diseases Research Collaboration, 2C Nakasero Hill Road, Kampala, Uganda
| | - Martha Nassali
- Infectious Diseases Research Collaboration, 2C Nakasero Hill Road, Kampala, Uganda
| | - Asadu Sserwanga
- Infectious Diseases Research Collaboration, 2C Nakasero Hill Road, Kampala, Uganda
| | - Samuel Gonahasa
- Infectious Diseases Research Collaboration, 2C Nakasero Hill Road, Kampala, Uganda
| | - Mercy Muwema
- Clinical Epidemiology Unit, School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
| | - Steven M Kiwuwa
- Department of Child Health and Development Centre, School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
| | - Sarah G Staedke
- London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK
| | - Moses R Kamya
- Infectious Diseases Research Collaboration, 2C Nakasero Hill Road, Kampala, Uganda.,School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
| | - Joaniter I Nankabirwa
- Clinical Epidemiology Unit, School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.,Infectious Diseases Research Collaboration, 2C Nakasero Hill Road, Kampala, Uganda
| | - Jessica Briggs
- Department of Medicine, University of California San Francisco, San Francisco, USA
| | - Prasanna Jagannathan
- Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, USA
| | - Grant Dorsey
- Department of Medicine, University of California San Francisco, San Francisco, USA
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11
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Rojas-Pirela M, Medina L, Rojas MV, Liempi AI, Castillo C, Pérez-Pérez E, Guerrero-Muñoz J, Araneda S, Kemmerling U. Congenital Transmission of Apicomplexan Parasites: A Review. Front Microbiol 2021; 12:751648. [PMID: 34659187 PMCID: PMC8519608 DOI: 10.3389/fmicb.2021.751648] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Accepted: 09/01/2021] [Indexed: 12/17/2022] Open
Abstract
Apicomplexans are a group of pathogenic protists that cause various diseases in humans and animals that cause economic losses worldwide. These unicellular eukaryotes are characterized by having a complex life cycle and the ability to evade the immune system of their host organism. Infections caused by some of these parasites affect millions of pregnant women worldwide, leading to various adverse maternal and fetal/placental effects. Unfortunately, the exact pathogenesis of congenital apicomplexan diseases is far from being understood, including the mechanisms of how they cross the placental barrier. In this review, we highlight important aspects of the diseases caused by species of Plasmodium, Babesia, Toxoplasma, and Neospora, their infection during pregnancy, emphasizing the possible role played by the placenta in the host-pathogen interaction.
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Affiliation(s)
- Maura Rojas-Pirela
- Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.,Instituto de Biología, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile.,Facultad de Farmacia y Bioanálisis, Universidad de Los Andes, Mérida, Venezuela
| | - Lisvaneth Medina
- Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Maria Verónica Rojas
- Instituto de Biología, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile
| | - Ana Isabel Liempi
- Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Christian Castillo
- Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.,Núcleo de Investigación Aplicada en Ciencias Veterinarias y Agronómicas, Facultad de Medicina Veterinaria y Agronomía, Universidad de Las Américas, Santiago, Chile
| | | | - Jesús Guerrero-Muñoz
- Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Sebastian Araneda
- Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.,Facultad de Salud y Odontología, Universidad Diego Portales, Santiago, Chile
| | - Ulrike Kemmerling
- Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
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12
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De-Gaulle VF, Magnussen P, Kamgno J, Mbacham W, Orish VN, Tagbor H. Assessing health system factors affecting access and delivery of IPTp-SP and ITN to pregnant women attending ANC clinics in Ghana. BMC Health Serv Res 2021; 21:1056. [PMID: 34610842 PMCID: PMC8493749 DOI: 10.1186/s12913-021-07055-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 09/08/2021] [Indexed: 01/28/2023] Open
Abstract
Introduction Malaria interventions including use of Sulfadoxine-Pyrimethamine as Intermittent Preventive Treatment (IPTp-SP) and distribution of Insecticide Treated Nets (ITNs) have been implemented through ante-natal clinic (ANC) services in Ghana. Yet, the high ANC attendance is not commensurate with the uptake of these interventions, with missed opportunities to deliver the interventions. This study sought to assess the health system factors affecting access and delivery of IPTp-SP and ITN as defined by the Ghana Malaria Policy Guideline to eligible pregnant women attending ANC clinic sessions. Methods A quantitative cross-sectional study was conducted in the Volta Region of Ghana, with data collected across three levels of health care delivery facilities, including hospitals, health centres and Community-Based Health Planning Service (CHPS) compounds. Data collection included structured observation checklists to document the communication and interaction between the ANC health staff and pregnant women. Additionally, structured questionnaires were used to elicit information on cadre, trainings attended, knowledge and delivery practices of health workers on IPTp-SP and ITN. Stata 16 was used for data analysis, and a defined delivery algorithm was used to compute appropriate and inappropriate delivery practices, using the Ghana policy directive as a guide. Predictors of appropriate delivery were determined using logistic regression analysis. Results Approximately 97% of the 680 ANC observations had complete information for analysis. Of these, 78% (511/657) were eligible for IPTp-SP after excluding women who have less than 16 weeks of gestation, G6PD deficient, malaria positive and have taken 5 doses of IPTp-SP prior to day of observation. Appropriate delivery of IPTp-SP was 76% (390/511). Despite the availability of SP, 15% (75/511) of all eligible women were not offered the medication and 37% (44/119) of inappropriate delivery was recorded during periods of stock out. ITNs were appropriately delivered to 59% (139) out of 237 eligible women. Thirty-two percent (77/237) of eligible women, mostly continuing ANC clients, were not given ITN despite stock availability. Conclusions IPTp-SP was appropriately delivered to most of the eligible pregnant women compared to ITN. While stock out of both intervention could account for inappropriate delivery, despite stock availability, IPTp-SP and ITN were not delivered to some eligible women.
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Affiliation(s)
| | - Pascal Magnussen
- Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Joseph Kamgno
- Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon
| | - Wilfred Mbacham
- Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon
| | - Verner N Orish
- School of Medicine, University of Health and Allied Science, Ho, Ghana
| | - Harry Tagbor
- School of Medicine, University of Health and Allied Science, Ho, Ghana
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13
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McLean ARD, Opi DH, Stanisic DI, Cutts JC, Feng G, Ura A, Mueller I, Rogerson SJ, Beeson JG, Fowkes FJI. High Antibodies to VAR2CSA in Response to Malaria Infection Are Associated With Improved Birthweight in a Longitudinal Study of Pregnant Women. Front Immunol 2021; 12:644563. [PMID: 34220804 PMCID: PMC8242957 DOI: 10.3389/fimmu.2021.644563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Accepted: 05/17/2021] [Indexed: 11/23/2022] Open
Abstract
Introduction Pregnant women have an increased risk of P. falciparum infection, which is associated with low birth weight and preterm delivery. VAR2CSA, a variant surface antigen expressed on the parasitized erythrocyte surface, enables sequestration in the placenta. Few studies have prospectively examined relationships between antibody responses during pregnancy and subsequent adverse birth outcomes, and there are limited data outside Africa. Methods Levels of IgG against VAR2CSA domains (DBL3; DBL5) and a VAR2CSA-expressing placental-binding P. falciparum isolate (PfCS2-IE) were measured in 301 women enrolled at their first visit to antenatal care which occurred mid-pregnancy (median = 26 weeks, lower and upper quartiles = 22, 28). Associations between antibody levels at enrolment and placental infection, birthweight and estimated gestational age at delivery were assessed by linear and logistic regression with adjustment for confounders. For all outcomes, effect modification by gravidity and peripheral blood P. falciparum infection at enrolment was assessed. Results Among women who had acquired P. falciparum infection at enrolment, those with higher levels of VAR2CSA antibodies (75th percentile) had infants with higher mean birthweight (estimates varied from +35g to +149g depending on antibody response) and reduced adjusted odds of placental infection (aOR estimates varied from 0.17 to 0.80), relative to women with lower levels (25th percentile) of VAR2CSA antibodies. However, among women who had not acquired an infection at enrolment, higher VAR2CSA antibodies were associated with increased odds of placental infection (aOR estimates varied from 1.10 to 2.24). Conclusions When infected by mid-pregnancy, a better immune response to VAR2CSA-expressing parasites may contribute to protecting against adverse pregnancy outcomes.
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Affiliation(s)
- Alistair R D McLean
- Burnet Institute, Melbourne, VIC, Australia.,Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - D Herbert Opi
- Burnet Institute, Melbourne, VIC, Australia.,Department of Immunology and Pathology, Monash University, Melbourne, VIC, Australia.,Department of Medicine at the Doherty Institute, University of Melbourne, Melbourne, VIC, Australia
| | - Danielle I Stanisic
- Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.,Institute for Glycomics, Griffith University, Southport, QLD, Australia
| | - Julia C Cutts
- Burnet Institute, Melbourne, VIC, Australia.,Department of Medicine at the Doherty Institute, University of Melbourne, Melbourne, VIC, Australia
| | - Gaoqian Feng
- Burnet Institute, Melbourne, VIC, Australia.,Department of Medicine at the Doherty Institute, University of Melbourne, Melbourne, VIC, Australia
| | - Alice Ura
- Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea
| | - Ivo Mueller
- Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.,Population, Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.,Département Parasites et Insectes Vecteurs, Institute Pasteur, Paris, France
| | - Stephen J Rogerson
- Department of Medicine at the Doherty Institute, University of Melbourne, Melbourne, VIC, Australia
| | - James G Beeson
- Burnet Institute, Melbourne, VIC, Australia.,Department of Medicine at the Doherty Institute, University of Melbourne, Melbourne, VIC, Australia.,Department of Microbiology, Monash University, Clayton, VIC, Australia
| | - Freya J I Fowkes
- Burnet Institute, Melbourne, VIC, Australia.,Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, VIC, Australia.,Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, VIC, Australia.,Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia
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14
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Gómez A, Pernía B, Zamora L, Spencer LM. Effect of Plasmodium berghei infection on fetuses in pregnant BALB/c mice at two periods of pregnancy. BIONATURA 2021. [DOI: 10.21931/rb/2021.06.02.25] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Malaria is a disease caused by a protozoan of the genus Plasmodium in humans and vertebrates. It has a high morbidity and mortality rate, especially in pregnant women living in countries with high transmission rates. Murine models have been an excellent tool to evaluate the effects of malarial infection in the mother-fetus relationship. For this reason, we evaluated the effect of malarial infection on fetal development at the beginning and middle of the gestational period in BALB/c mice infected with Plasmodium berghei ANKA. Our results show that malarial infection at the beginning of pregnancy markedly affects the development of the fetus in size, weight, and development of its limbs so that the control of the pregnant mother is relevant at the beginning of gestation
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Affiliation(s)
- Andreina Gómez
- Cell Biology Department, Simón Bolívar University, Valle de Sartenejas, Caracas
| | - Beatriz Pernía
- University of Guayaquil, Faculty of Natural Sciences, Av. Raúl Gómez Lince s/n y Av. Juan Tanca Marengo, Guayaquil, Ecuador
| | - Lizbeth Zamora
- School of Biological Sciences and Engineering, Yachay Tech University, San Miguel de Urcuquí, Ecuador
| | - Lilian M. Spencer
- School of Biological Sciences and Engineering, Yachay Tech University, San Miguel de Urcuquí, Ecuador Cell Biology Department, Simón Bolívar University, Valle de Sartenejas, Caracas
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15
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Omer S, Franco-Jarava C, Noureldien A, Omer M, Abdelrahim M, Molina I, Adam I. Impact of placental malaria on maternal, placental and fetal cord responses and its role in pregnancy outcomes in women from Blue Nile State, Sudan. Malar J 2021; 20:35. [PMID: 33422078 PMCID: PMC7797158 DOI: 10.1186/s12936-021-03580-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Accepted: 01/02/2021] [Indexed: 01/05/2023] Open
Abstract
Background The sequestration of Plasmodium falciparum infected cells in the placenta results in placental malaria (PM). It activates the mother's immune cells and induces secretion of inflammatory cytokines, which might influence pregnancy outcomes. This study aims to investigate the cytokines (levels IL-4, IL-6, IL-10, IL-17A, and INF γ) in maternal peripheral, placental, and umbilical cord blood in response to PM and the extent to which this may influence maternal haemoglobin levels and birth weight. Methods A total of 185 consenting Sudanese women from Blue Nile State were enrolled at delivery time in a cross-sectional study conducted between Jan 2012-Dec 2015. Malaria infection in the collected maternal peripheral, placental, umbilical cord samples was determined microscopically, and ELISA was used to measure the plasma levels IL-4, IL-6, IL-10, IL-17A, and INF γ in the collected positive and negative malaria samples. Results Elevated levels of IL-4 and IL-10 and reduced levels of IL-6 were detected in the malaria positive samples in comparison to the negative ones in the three types of the samples investigated. Maternal, IL-4 and IL-10 were significantly higher in the samples collected from the PM infected group compared to the non-infected control (P < 0.001). While the absence of PM was significantly associated with the IL-6 and maternal IFN-γ levels, maternal IL-17A, placental and umbilical cord IFN-γ levels showed no significant difference (P = 0.214, P = 0.065, P = 0.536, respectively) due to infection. Haemoglobin level and birth weight were increased in the group with high levels of IL-6 and IL-17A, but not in the group with IL-4 and IL-10 levels. While significantly negative correlation was found between IFN-γ levels and birth weight for all three types of samples, only maternal peripheral IFN-γ level was significantly positively correlated with maternal haemoglobin (r = 0.171, P = 0.020). Conclusion These results suggest that PM induces mother’s immune response and impairs her cytokine profile, which might alter maternal haemoglobin levels and the baby's birth weight.
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Affiliation(s)
- Samia Omer
- Department of Immunology and Biotechnology, Tropical Medicine Research Institute, Khartoum, Sudan.
| | | | - Ali Noureldien
- Department of Microbiology and Parasitology, Faculty of Medicine, University of Khartoum, Khartoum, Sudan
| | - Mona Omer
- Bioscience Research Institute, Ibn Sina University, Khartoum, Sudan
| | - Mutasim Abdelrahim
- Ed-Damazin Hospital, Blue Nile State Ministry of Health, Ed-Damazin, Sudan
| | - Israel Molina
- Infectious Diseases Department, Vall d Hebron University Hospital, Barcelona, Spain
| | - Ishag Adam
- Department of Obstetrics and Gynecology, Unaizah College of Medicine and Medical Sciences, Qassim University, Unaizah, Kingdom of Saudi Arabia
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Oumarou ZM, Lamine MM, Issaka T, Moumouni K, Alkassoum I, Maman D, Doutchi M, Alido S, Laminou IM. [Malaria infection during pregnancy in Niamey, Niger]. Pan Afr Med J 2020; 37:365. [PMID: 33796178 PMCID: PMC7992404 DOI: 10.11604/pamj.2020.37.365.20034] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Accepted: 02/14/2020] [Indexed: 11/17/2022] Open
Abstract
Introduction le paludisme chez la femme enceinte est un problème majeur de santé publique en Afrique. Il a des conséquences graves aussi bien sur la mère, le fœtus que le nouveau-né. Il est responsable d´un fort taux de morbi-mortalité maternelle et infantile. L´objectif de l´étude est de déterminer la prévalence de l´infection plasmodiale chez la femme enceinte, décrire ses signes cliniques et ses complications éventuelles, analyser les facteurs associés et proposer des mesures de prévention. Méthodes il s´agit d´une étude transversale, conduite du 1er juin au 30 novembre 2017 à la Maternité Issaka Gazobi (MIG) de Niamey. Le diagnostic a été fait par microscopie. Résultats deux cents quarante-neuf (249) femmes ont été incluses dans cette étude. La prévalence de l´infection plasmodiale était de 36,5% (IC95%; [30,6; 42,9]). La densité parasitaire moyenne était de 177 P/μl (DS: 121; [40; 800]). Toutes les infections étaient à P. falciparum. Un peu plus de soixante-treize pourcent (73,6%). Seules 26,4% (24/91) ont fait un paludisme non compliqué ; 9,6% (6/91) ont avorté ; 38,4% des nouveau-nés avaient un faible poids à la naissance et 26,51% (66/249) ont développé un paludisme congénital. Le taux de létalité était de 1,1% (1/91). Le traitement préventif intermittent (TPI) protège significativement contre le paludisme gestationnel (p=0,01). Conclusion l´infection des femmes enceintes par le P. falciparum est très fréquente au Niger. Ce portage est le plus souvent asymptomatique mais peut évoluer vers un paludisme non compliqué ou même sévère. Les principales conséquences sont l´avortement, le faible poids à la naissance, le retard de croissance intra utero, le paludisme congénital et le décès maternel. Le TPI et l´utilisation de la moustiquaire imprégnée d´insecticide à longue durée d´action (MILDA) permettent de prévenir l´infection.
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Affiliation(s)
- Zara Maman Oumarou
- Service de Gynécologie-Obstétrique, Maternité Issaka Gazobi, Niamey, République du Niger
| | - Mahaman Moustapha Lamine
- Département de Parasitologie, Université Cheick Anta Diop, Dakar, République du Sénégal.,Unité de Paludologie-Entomologie Médicale, Centre de Recherche Médicale et Sanitaire, Niamey, République du Niger
| | - Tahirou Issaka
- Département de Médecine, Faculté de Science de la Santé de l´Université Abdou Moumouni, Niamey, République du Niger
| | - Kamayé Moumouni
- Département de Médecine, Faculté de Science de la Santé de l´Université Abdou Moumouni, Niamey, République du Niger
| | - Ibrahim Alkassoum
- Département de Santé Publique, Faculté de Science de la Santé de l´Université Abdou Moumouni, Niamey, République du Niger
| | - Daou Maman
- Département de Médecine, Faculté de Science de la Santé de l´Université Abdou Moumouni, Niamey, République du Niger
| | - Mahamadou Doutchi
- Département de Médecine, Université de Zinder, Zinder, République du Niger
| | - Soumana Alido
- Département de Médecine, Faculté de Science de la Santé de l´Université Abdou Moumouni, Niamey, République du Niger
| | - Ibrahim Maman Laminou
- Unité de Paludologie-Entomologie Médicale, Centre de Recherche Médicale et Sanitaire, Niamey, République du Niger
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Kiyonga Aimeé K, Lengu TB, Nsibu CN, Umesumbu SE, Ngoyi DM, Chen T. Molecular detection and species identification of Plasmodium spp. infection in adults in the Democratic Republic of Congo: A population-based study. PLoS One 2020; 15:e0242713. [PMID: 33227017 PMCID: PMC7682816 DOI: 10.1371/journal.pone.0242713] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Accepted: 11/07/2020] [Indexed: 11/19/2022] Open
Abstract
Background In efforts to control malaria infection, the Democratic Republic of Congo has implemented several strategies. Studies assessing their efficiency mainly involved at-risk groups, especially children under five years of age. This study aimed to determine the prevalence and identify the risk factors associated with Plasmodium spp. infection. Methods From October 2014 to March 2015, individuals aged at least 15 years were selected randomly and enrolled in a cross-sectional study conducted throughout the country. Microscopy and polymerase chain reaction (PCR) analysis were used for the detection of Plasmodium ssp. Results From 2286 individuals recruited, 1870 with valid laboratory results were included in the study for further analysis. The prevalence of Plasmodium spp. infection assessed by microscopy (355/ 1870 (19%) was lower than that estimated by PCR (580/1870 (31%). In addition, the difference between the two results was statistically significant (P < 0.0001). The most prevalent Plasmodium species was P. falciparum, either as mono-infection (96.3%; 95% C.I. 93.9–98.1) or combined with P. malariae (3.7%; 95% C.I. 2.8–5.9). The mean parasite density was 3272739 trophozoites/μL of blood. Women had higher risks of being infected than men (OR 2.03, 95% C.I.: 1.96. 2.62, P = 0.041)]. Conclusion In this study, the molecular detection and species identification of Plasmodium spp. showed that, despite all efforts for malaria control, malaria remains a public health problem in the Democratic Republic of Congo. The high prevalence and parasite density of Plasmodium spp. in adults make this age group a potential parasitic infectious reservoir for the at-risk groups and supports the need to include this age group in further programs for malaria control.
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Affiliation(s)
- Kahindo Kiyonga Aimeé
- Department of Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, People’s Republic of China
- Department of Tropical Medicine Infectious and Parasitic Diseases, University of Kinshasa, Kinshasa, Democratic Republic of Congo
- Institut National de Recherche Biomédicale (INRB), Kinshasa, Democratic Republic of Congo
- * E-mail:
| | - Thierry Bobanga Lengu
- Department of Tropical Medicine Infectious and Parasitic Diseases, University of Kinshasa, Kinshasa, Democratic Republic of Congo
| | - Célestin Ndosimao Nsibu
- Department of Pediatrics, University Hospital of Kinshasa, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of Congo
- Programme National de Lutte Contre le Paludisme (PNLP), Kinshasa, République Démocratique du Congo
| | - Solange Efundu Umesumbu
- Programme National de Lutte Contre le Paludisme (PNLP), Kinshasa, République Démocratique du Congo
| | - Dieudonné Mumba Ngoyi
- Department of Tropical Medicine Infectious and Parasitic Diseases, University of Kinshasa, Kinshasa, Democratic Republic of Congo
- Institut National de Recherche Biomédicale (INRB), Kinshasa, Democratic Republic of Congo
| | - Tie Chen
- Department of Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, People’s Republic of China
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Saito M, Briand V, Min AM, McGready R. Deleterious effects of malaria in pregnancy on the developing fetus: a review on prevention and treatment with antimalarial drugs. THE LANCET CHILD & ADOLESCENT HEALTH 2020; 4:761-774. [PMID: 32946830 DOI: 10.1016/s2352-4642(20)30099-7] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/05/2020] [Revised: 03/09/2020] [Accepted: 03/25/2020] [Indexed: 12/29/2022]
Abstract
All malaria infections are harmful to both the pregnant mother and the developing fetus. One in ten maternal deaths in malaria endemic countries are estimated to result from Plasmodium falciparum infection. Malaria is associated with a 3-4 times increased risk of miscarriage and a substantially increased risk of stillbirth. Current treatment and prevention strategies reduce, but do not eliminate, malaria's damaging effects on pregnancy outcomes. Reviewing evidence generated from meta-analyses, systematic reviews, and observational data, the first paper in this Series aims to summarise the adverse effects of malaria in pregnancy on the fetus and how the current drug treatment and prevention strategies can alleviate these effects. Although evidence supports the safety and treatment efficacy of artemisinin-based combination therapies in the first trimester, these therapies have not been recommended by WHO for the treatment of malaria at this stage of pregnancy. Intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine is contraindicated in the first trimester and provides imperfect chemoprevention because of inadequate dosing, poor (few and late) antenatal clinic attendance, increasing antimalarial drug resistance, and decreasing naturally acquired maternal immunity due to the decreased incidence of malaria. Alternative strategies to prevent malaria in pregnancy are needed. The prevention of all malaria infections by providing sustained exposure to effective concentrations of antimalarial drugs is key to reducing the adverse effects of malaria in pregnancy.
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Affiliation(s)
- Makoto Saito
- Division of Infectious Diseases, Advanced Clinical Research Center, The Institute of Medical Science, University of Tokyo, Tokyo, Japan
| | - Valérie Briand
- Infectious Diseases in Lower Income Countries, Research Institute for Sustainable Development, French National Institute of Health and Medical Research, University of Bordeaux, Bordeaux, France
| | - Aung Myat Min
- Shoklo Malaria Research Unit, Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand
| | - Rose McGready
- Shoklo Malaria Research Unit, Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
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Penman BS, Gandon S. Adaptive immunity selects against malaria infection blocking mutations. PLoS Comput Biol 2020; 16:e1008181. [PMID: 33031369 PMCID: PMC7544067 DOI: 10.1371/journal.pcbi.1008181] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Accepted: 07/22/2020] [Indexed: 11/18/2022] Open
Abstract
The mutation responsible for Duffy negativity, which impedes Plasmodium vivax infection, has reached high frequencies in certain human populations. Conversely, mutations capable of blocking the more lethal P. falciparum have not succeeded in malarious zones. Here we present an evolutionary-epidemiological model of malaria which demonstrates that if adaptive immunity against the most virulent effects of malaria is gained rapidly by the host, mutations which prevent infection per se are unlikely to succeed. Our results (i) explain the rarity of strain-transcending P. falciparum infection blocking adaptations in humans; (ii) make the surprising prediction that mutations which block P. falciparum infection are most likely to be found in populations experiencing low or infrequent malaria transmission, and (iii) predict that immunity against some of the virulent effects of P. vivax malaria may be built up over the course of many infections.
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Affiliation(s)
- Bridget S. Penman
- Zeeman Institute and School of Life Sciences, University of Warwick, Coventry, United Kingdom
| | - Sylvain Gandon
- CEFE, CNRS, University of Montpellier, Paul Valéry University of Montpellier, EPHE, IRD, Montpellier, France
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Corder RM, de Lima ACP, Khoury DS, Docken SS, Davenport MP, Ferreira MU. Quantifying and preventing Plasmodium vivax recurrences in primaquine-untreated pregnant women: An observational and modeling study in Brazil. PLoS Negl Trop Dis 2020; 14:e0008526. [PMID: 32735631 PMCID: PMC7423143 DOI: 10.1371/journal.pntd.0008526] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Revised: 08/12/2020] [Accepted: 06/26/2020] [Indexed: 12/27/2022] Open
Abstract
Each year, 4.3 million pregnant women are exposed to malaria risk in Latin America and the Caribbean. Plasmodium vivax causes 76% of the regional malaria burden and appears to be less affected than P. falciparum by current elimination efforts. This is in part due to the parasite's ability to stay dormant in the liver and originate relapses within months after a single mosquito inoculation. Primaquine (PQ) is routinely combined with chloroquine (CQ) or other schizontocidal drugs to supress P. vivax relapses and reduce the risk of late blood-stage recrudescences of parasites with low-grade CQ resistance. However, PQ is contraindicated for pregnant women, who remain at increased risk of repeated infections following CQ-only treatment. Here we apply a mathematical model to time-to-recurrence data from Juruá Valley, Brazil's main malaria transmission hotspot, to quantify the extra burden of parasite recurrences attributable to PQ ineligibility in pregnant women. The model accounts for competing risks, since relapses and late recrudescences (that may be at least partially prevented by PQ) and new infections (that are not affected by PQ use) all contribute to recurrences. We compare recurrence rates observed after primary P. vivax infections in 158 pregnant women treated with CQ only and 316 P. vivax infections in non-pregnant control women, matched for age, date of infection, and place of residence, who were administered a standard CQ-PQ combination. We estimate that, once infected with P. vivax, 23% of the pregnant women have one or more vivax malaria recurrences over the next 12 weeks; 86% of these early P. vivax recurrences are attributable to relapses or late recrudescences, rather than new infections that could be prevented by reducing malaria exposure during pregnancy. Model simulations indicate that weekly CQ chemoprophylaxis extending over 4 to 12 weeks, starting after the first vivax malaria episode diagnosed in pregnancy, might reduce the risk of P. vivax recurrences over the next 12 months by 20% to 65%. We conclude that post-treatment CQ prophylaxis could be further explored as a measure to prevent vivax malaria recurrences in pregnancy and avert their adverse effects on maternal and neonatal health.
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Affiliation(s)
- Rodrigo M. Corder
- Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
- * E-mail: (RMC); (MUF)
| | - Antonio C. P. de Lima
- Department of Statistics, Institute of Mathematics and Statistics, University of São Paulo, São Paulo, Brazil
| | - David S. Khoury
- Kirby Institute for Infection and Immunity, University of New South Wales, Sidney, Australia
| | - Steffen S. Docken
- Kirby Institute for Infection and Immunity, University of New South Wales, Sidney, Australia
| | - Miles P. Davenport
- Kirby Institute for Infection and Immunity, University of New South Wales, Sidney, Australia
| | - Marcelo U. Ferreira
- Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
- * E-mail: (RMC); (MUF)
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Imported Malaria in Countries where Malaria Is Not Endemic: a Comparison of Semi-immune and Nonimmune Travelers. Clin Microbiol Rev 2020; 33:33/2/e00104-19. [PMID: 32161068 DOI: 10.1128/cmr.00104-19] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
The continuous increase in long-distance travel and recent large migratory movements have changed the epidemiological characteristics of imported malaria in countries where malaria is not endemic (here termed non-malaria-endemic countries). While malaria was primarily imported to nonendemic countries by returning travelers, the proportion of immigrants from malaria-endemic regions and travelers visiting friends and relatives (VFRs) in malaria-endemic countries has continued to increase. VFRs and immigrants from malaria-endemic countries now make up the majority of malaria patients in many nonendemic countries. Importantly, this group is characterized by various degrees of semi-immunity to malaria, resulting from repeated exposure to infection and a gradual decline of protection as a result of prolonged residence in non-malaria-endemic regions. Most studies indicate an effect of naturally acquired immunity in VFRs, leading to differences in the parasitological features, clinical manifestation, and odds for severe malaria and clinical complications between immune VFRs and nonimmune returning travelers. There are no valid data indicating evidence for differing algorithms for chemoprophylaxis or antimalarial treatment in semi-immune versus nonimmune malaria patients. So far, no robust biomarkers exist that properly reflect anti-parasite or clinical immunity. Until they are found, researchers should rigorously stratify their study results using surrogate markers, such as duration of time spent outside a malaria-endemic country.
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Kofie P, Tarkang EE, Manu E, Amu H, Ayanore MA, Aku FY, Komesuor J, Adjuik M, Binka F, Kweku M. Prevalence and associated risk factors of anaemia among women attending antenatal and post-natal clinics at a public health facility in Ghana. BMC Nutr 2019; 5:40. [PMID: 32153953 PMCID: PMC7050900 DOI: 10.1186/s40795-019-0303-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Accepted: 07/11/2019] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND Anaemia among pregnant women and post-partum mothers is a public health challenge in Ghana, especially in the Volta Region. While literature abounds on anaemia among pregnant women, the same cannot be said for anaemia among post-partum mothers in the region. This study, therefore, examined the prevalence and associated risk factors of anaemia among women attending antenatal care and post-natal care. METHODS This descriptive cross-sectional survey recruited 409 pregnant women and 194 post-natal mothers attending antenatal and post-natal care, at the Hohoe Municipal Hospital. Background characteristics were collected using a semi-structured questionnaire, blood samples were analysed for the presence of anaemia and malaria parasitaemia and folders were reviewed for estimated blood loss. RESULTS We found the prevalence of anaemia among pregnant women and post-partum mothers to be 33 and 16% respectively. Higher malaria parasitaemia (2%) was found in pregnant women compared with postpartum mothers (1%). We found that 4% of post-partum mothers had abnormal blood loss (301mls-500mls) whereas 5% of them had postpartum haemorrhage (>500mls) during child birth. A univariate logistics regression of anaemia status on some risk factors in pregnant women showed no significant association between anaemia and any of the risk factors. Among post-partum mothers, only mothers' age was statistically significant in the univariate analysis [COR = 0.27 (95% CI:0.103, 0.72);0.008]. Mothers aged 20-29 were 73% less likely to be anaemic. CONCLUSION The prevalence of anaemia among pregnant women found in this study points to a situation of moderate public health problem according to WHO cut-off values for the public health significance of anaemia. Strategies should therefore be put in place to encourage thorough health education and promotion programmes among both pregnant and post-partum women.
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Affiliation(s)
- Philip Kofie
- Department of Epidemiology and Biostatistics, School of Public Health, University of Health and Allied Sciences, PMB 31, Ho, Volta Region Ghana
| | - Elvis E. Tarkang
- Department of Population and Behavioural Sciences, School of Public Health, University of Health and Allied Sciences, PMB 31, Ho, Volta Region Ghana
| | - Emmanuel Manu
- Department of Population and Behavioural Sciences, School of Public Health, University of Health and Allied Sciences, PMB 31, Ho, Volta Region Ghana
| | - Hubert Amu
- Department of Population and Behavioural Sciences, School of Public Health, University of Health and Allied Sciences, PMB 31, Ho, Volta Region Ghana
| | - Martin Amogre Ayanore
- Department of Family and Community Health, University of Health and Allied Sciences, PMB 31, Ho, Volta Region Ghana
| | - Fortress Yayra Aku
- Department of Epidemiology and Biostatistics, School of Public Health, University of Health and Allied Sciences, PMB 31, Ho, Volta Region Ghana
| | - Joyce Komesuor
- Department of Population and Behavioural Sciences, School of Public Health, University of Health and Allied Sciences, PMB 31, Ho, Volta Region Ghana
| | - Martin Adjuik
- Department of Epidemiology and Biostatistics, School of Public Health, University of Health and Allied Sciences, PMB 31, Ho, Volta Region Ghana
| | - Fred Binka
- Department of Epidemiology and Biostatistics, School of Public Health, University of Health and Allied Sciences, PMB 31, Ho, Volta Region Ghana
| | - Margaret Kweku
- Department of Epidemiology and Biostatistics, School of Public Health, University of Health and Allied Sciences, PMB 31, Ho, Volta Region Ghana
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Clark RL. Genesis of placental sequestration in malaria and possible targets for drugs for placental malaria. Birth Defects Res 2019; 111:569-583. [PMID: 30919596 PMCID: PMC7432169 DOI: 10.1002/bdr2.1496] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Revised: 03/05/2019] [Accepted: 03/06/2019] [Indexed: 01/11/2023]
Abstract
Malaria during pregnancy results in intrauterine growth restriction, fetal anemia, and infant mortality. Women are more susceptible to malaria during pregnancy due to malaria‐induced inflammation and the sequestration of infected red blood cells in the placenta, which bind to the chondroitin sulfate portion of syndecan‐1 on the syncytiotrophoblast and in the intervillous space. Syndecan‐1 is a dimeric proteoglycan with an extracellular ectodomain that is cleaved from the transmembrane domain (referred to as “shedding”) by matrix metalloproteinases (MMPs), likely the secreted MMP‐9. The ectodomain includes four binding sites for chondroitin sulfate, which are proximal to the transmembrane domain, and six distal binding sites primarily for heparan sulfate. This “shedding” of syndecan‐1 is inhibited by the presence of the heparan sulfate chains, which can be removed by heparanase. The intervillous space contains fibrin strands and syndecan‐1 ectodomains free of heparan sulfate. The following is proposed as the sequence of events that leads to and is primarily responsible for sequestration in the intervillous space of the placenta. Inflammation associated with malaria triggers increased heparanase activity that degrades the heparan sulfate on the membrane‐bound syndecan‐1. Inflammation also upregulates MMP‐9 and the removal of heparan sulfate gives MMP‐9 access to cleave syndecan‐1, thereby releasing dimeric syndecan‐1 ectodomains with at least four chondroitin sulfate chains attached. These multivalent ectodomains bind infected RBCs together leading to their aggregation and entrapment in intervillous fibrin. This mechanism suggests possible new targets for anti‐placental malaria drugs such as the inhibition of MMP‐9. Doxycycline is an antimalarial drug which inhibits MMP‐9.
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Seitz J, Morales-Prieto DM, Favaro RR, Schneider H, Markert UR. Molecular Principles of Intrauterine Growth Restriction in Plasmodium Falciparum Infection. Front Endocrinol (Lausanne) 2019; 10:98. [PMID: 30930847 PMCID: PMC6405475 DOI: 10.3389/fendo.2019.00098] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2018] [Accepted: 02/01/2019] [Indexed: 12/21/2022] Open
Abstract
Malaria in pregnancy still constitutes a particular medical challenge in tropical and subtropical regions. Of the five Plasmodium species that are pathogenic to humans, infection with Plasmodium falciparum leads to fulminant progression of the disease with massive impact on pregnancy. Severe anemia of the mother, miscarriage, stillbirth, preterm delivery and intrauterine growth restriction (IUGR) with reduced birth weight are frequent complications that lead to more than 10,000 maternal and 200,000 perinatal deaths annually in sub-Saharan Africa alone. P. falciparum can adhere to the placenta via the expression of the surface antigen VAR2CSA, which leads to sequestration of infected erythrocytes in the intervillous space. This process induces a placental inflammation with involvement of immune cells and humoral factors. Especially, monocytes get activated and change the release of soluble mediators, including a variety of cytokines. This proinflammatory environment contributes to disorders of angiogenesis, blood flow, autophagy, and nutrient transport in the placenta and erythropoiesis. Collectively, they impair placental functions and, consequently, fetal growth. The discovery that women in endemic regions develop a certain immunity against VAR2CSA-expressing parasites with increasing number of pregnancies has redefined the understanding of malaria in pregnancy and offers strategies for the development of vaccines. The following review gives an overview of molecular processes in P. falciparum infection in pregnancy which may be involved in the development of IUGR.
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Affiliation(s)
- Johanna Seitz
- Placenta Lab, Department of Obstetrics, Jena University Hospital, Jena, Germany
| | | | - Rodolfo R. Favaro
- Placenta Lab, Department of Obstetrics, Jena University Hospital, Jena, Germany
| | - Henning Schneider
- Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland
- Department of Obstetrics and Gynecology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Udo Rudolf Markert
- Placenta Lab, Department of Obstetrics, Jena University Hospital, Jena, Germany
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Seroprevalence of Malaria and Hepatitis B Coinfection among Pregnant Women in Tamale Metropolis of Ghana: A Cross-Sectional Study. CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY 2018; 2018:5610981. [PMID: 30344800 PMCID: PMC6174787 DOI: 10.1155/2018/5610981] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Revised: 06/29/2018] [Accepted: 07/22/2018] [Indexed: 01/21/2023]
Abstract
Background Coinfections are becoming common risk factors that may contribute to the increased burden of morbidity in pregnancy. The aim of this study was to assess the seroprevalence of coinfections of malaria, hepatitis B (HBV), human immunodeficiency virus (HIV), and syphilis among pregnant women attending antenatal clinics (ANC) in the Tamale Metropolis. Methods By means of rapid diagnostic tests (RDTs), pregnant women attending the Tamale Teaching Hospital (TTH) were screened for malaria, HBV infection, HIV infection, and syphilis from March 2013 to February 2015. Haemoglobin (Hb) values, sickling, and glucose-6-phosphate dehydrogenase deficiency (G6PDd) statuses were also assessed using full blood count (FBC), sodium metabisulphite, and methaemoglobin reduction tests, respectively. Logistic regression analysis was performed to estimate the risks/odds ratios (ORs) for the coinfections and other variables (age, gravidity, and time of the first ANC visit) with 95% confidence intervals (CIs) and set p values for accepting any differences at <0.05. Results Within the two-year study period, data were collected from 3,127 pregnant women. The mean age (SD) of the pregnant women was 28.5 (±5.0) years. Of the total number, seroprevalence was high for malaria (11.6%) and HBV infection (4.2%) and low for HIV infection (1.0%) and syphilis (0.4%) monoinfections. Mal/HBV coinfection was higher (0.7%) when compared with Mal/HIV (0.1%), Mal/syphilis (0.0%), HBV/HIV (0.0%), HBV/syphilis (0.1%), and HIV/syphilis (0.0%) coinfections. The mean Hb (g/dl) for the women with the four monoinfections was significantly different from one another (p=0.009). Pregnant women with malaria infection were about 2 times more likely to be coinfected with HBV even after adjusting for potential confounders (adjusted odds ratio (AOR) = 1.66, 95% CI = 1.04-2.65, p=0.031). Those in their third trimester and visiting the ANC for the first time were significantly less likely to be infected with HBV (AOR = 0.45, 95% CI = 0.28-0.73, p=0.001), with malaria/HBV coinfection (AOR = 0.09, 95% CI = 0.01-0.68, p=0.020), and with any coinfection (AOR = 0.19, 95% CI = 0.06-0.63, p=0.007). Conclusion A comparatively high seroprevalence of malaria and its coinfection with HBV in pregnant women was observed in this study. Considering the effects that both malaria and HBV have on the liver, it would be expedient to conduct further studies to assess liver function among malaria/HBV-infected individuals, while interventions to prevent coinfections among pregnant women are intensified.
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McCall MBB, Kremsner PG, Mordmüller B. Correlating efficacy and immunogenicity in malaria vaccine trials. Semin Immunol 2018; 39:52-64. [PMID: 30219621 DOI: 10.1016/j.smim.2018.08.002] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Accepted: 08/06/2018] [Indexed: 12/19/2022]
Abstract
The availability of an effective and appropriately implemented malaria vaccine would form a crucial cornerstone of public health efforts to fight this disease. Despite many decades of research, however, no malaria vaccine has yet shown satisfactory protective efficacy or been rolled-out. Validated immunological substitute endpoints have the potential to accelerate clinical vaccine development by reducing the required complexity, size, duration and cost of clinical trials. Besides facilitating clinical development of existing vaccine candidates, understanding immunological mechanisms of protection may drive the development of fundamentally new vaccination approaches. In this review we focus on correlates of protection in malaria vaccine development: Does immunogenicity predict malaria vaccine efficacy and why is this question particularly difficult? Have immunological correlates accelerated malaria vaccine development in the past and will they facilitate it in the future? Does Controlled Human Malaria Infection represent a valid model for identifying such immunological correlates, or a correlate of protection against naturally-acquired malaria in itself?
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Affiliation(s)
- Matthew B B McCall
- Institut für Tropenmedizin, Universität Tübingen and Deutsches Zentrum für Infektionsforschung, Germany; Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon.
| | - Peter G Kremsner
- Institut für Tropenmedizin, Universität Tübingen and Deutsches Zentrum für Infektionsforschung, Germany; Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon
| | - Benjamin Mordmüller
- Institut für Tropenmedizin, Universität Tübingen and Deutsches Zentrum für Infektionsforschung, Germany; Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon
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Zhao L, Kaiser M, Bode HB. Rhabdopeptide/Xenortide-like Peptides from Xenorhabdus innexi with Terminal Amines Showing Potent Antiprotozoal Activity. Org Lett 2018; 20:5116-5120. [PMID: 30095261 DOI: 10.1021/acs.orglett.8b01975] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Seven new rhabdopeptide/xenortide-like peptides (RXPs) (1-7) with putrescine or ammonia as the C-terminal amines were isolated from Xenorhabdus innexi DSM 16336. Their chemical structures were elucidated by high-resoultion mass spectroscopy (HR-MS) and one-dimensional (1D) and two-dimensional (2D) NMR. They were evaluated for their activities against protozoan parasites and cytotoxicity against rat skeletal myoblasts (L6 cells). All tested compounds exhibited strong effects against Trypanosoma brucei rhodesiense and Plasmodium falciparum, with IC50 values of 0.07-6.25 and 0.091-3.16 μM, respectively, making them the most active RXP derivatives known to date.
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Affiliation(s)
- Lei Zhao
- Molekulare Biotechnologie, Fachbereich Biowissenschaften , Goethe Universität Frankfurt , 60438 Frankfurt am Main , Germany.,Institute of Botany, Jiangsu Province and Chinese Academy of Sciences , 210014 Nanjing , China
| | - Marcel Kaiser
- Parasite Chemotherapy , Swiss Tropical and Public Health Institute , 4051 Basel , Switzerland.,University of Basel , 4003 Basel , Switzerland
| | - Helge B Bode
- Molekulare Biotechnologie, Fachbereich Biowissenschaften , Goethe Universität Frankfurt , 60438 Frankfurt am Main , Germany.,Buchmann Institute for Molecular Life Sciences (BMLS) , Goethe Universität Frankfurt , 60438 Frankfurt am Main , Germany
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de Lima Corvino DF, Chandorkar AA, Mora Carpio AL, Climaco A. When Epidemiology Is the Clue to a Positive Outcome: A Case of Malaria During Pregnancy. AMERICAN JOURNAL OF CASE REPORTS 2018; 19:128-132. [PMID: 29398694 PMCID: PMC5810195 DOI: 10.12659/ajcr.905543] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND Malaria infection during pregnancy is associated with increased perinatal and maternal morbidity and mortality. CASE REPORT A 29-year-old primigravida at 37 weeks of gestation, with no significant medical history, presented complaining of fever, chills, and generalized body aches. She had been living in Malawi for 1 year and was on atovaquone/proguanil prophylaxis until she was found to be pregnant. Prophylaxis was changed to mefloquine and discontinued upon her return to the US. Six weeks prior to presentation, she traveled to Malawi for 1 month when she was off prophylaxis. On admission, vital signs and physical exam results were normal. Given epidemiologic findings, a malaria smear was performed and showed 4% parasitemia. She was treated with mefloquine and discharged. Two days after discharge, she again presented with fever, chills, and body aches. A malaria smear showed <0.01% parasitemia, with 2 ring forms. Serologies for dengue, chikungunya, leptospira, and blood cultures were negative. These symptoms were deemed secondary to early recrudescence. The species was later identified as P. falciparum. The patient was treated with quinine sulfate and clindamycin. She delivered at full term without complication. CONCLUSIONS Pregnant women are more susceptible to severe forms of malaria, such as P. falciparum. A high index of suspicion and early identification of malaria are vital to prevent deleterious outcomes.
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Affiliation(s)
| | | | | | - Antonette Climaco
- Department of Infectious Diseases, Einstein Medical Center, Philadelphia, PA, USA
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29
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Kong LY, Libman MD, Yansouni CP. Travel-Related Infections Among Pregnant Travellers to the Tropics: An Overview. JOURNAL OF OBSTETRICS AND GYNAECOLOGY CANADA 2018; 40:460-472. [PMID: 29307707 DOI: 10.1016/j.jogc.2017.08.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2017] [Accepted: 08/10/2017] [Indexed: 10/18/2022]
Abstract
Infectious diseases acquired during travel pose a significant health risk to pregnant travellers, who are more susceptible to both acquiring certain infections and developing severe complications. A review of the literature focusing on recent evidence-based guidelines was conducted with attention to tropical infections in the pregnant patient. A summary meant to serve as a succinct reference for health care professionals caring for pregnant women is presented. Magnitude of risk, clinical features, management, and preventive strategies of major travel-acquired infections of pertinence to the pregnant traveller are summarized, including malaria, arboviral infections, foodborne infections, helminthic infections, and influenza. Tables with details on specific infections within each group and guidance for reducing travel-related health risks in the pregnant patient are presented.
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Affiliation(s)
- Ling Yuan Kong
- J.D. MacLean Centre for Tropical Diseases, McGill University Health Centre, Montréal, QC.
| | - Michael D Libman
- J.D. MacLean Centre for Tropical Diseases, McGill University Health Centre, Montréal, QC
| | - Cedric P Yansouni
- J.D. MacLean Centre for Tropical Diseases, McGill University Health Centre, Montréal, QC
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30
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McLean ARD, Boel M, McGready R, Ataide R, Drew D, Tsuboi T, Beeson JG, Nosten F, Simpson JA, Fowkes FJI. Antibody Responses to Plasmodium falciparum and Plasmodium vivax and Prospective Risk of Plasmodium spp. Infection Postpartum. Am J Trop Med Hyg 2017; 96:1197-1204. [PMID: 28500806 PMCID: PMC5417217 DOI: 10.4269/ajtmh.16-0690] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
Postpartum women may have an altered susceptibility to Plasmodium falciparum and Plasmodium vivax. The relationship between naturally acquired malarial immunity and susceptibility to malaria postpartum is yet to be determined. IgG levels were measured against P. falciparum and P. vivax antigens from delivery in 201 postpartum and 201 nonpregnant controls over 12 weeks. Associations between time-varying antibody levels and time to first microscopically confirmed species-specific infection were determined by Cox regression. Associations between antibody levels and prospective risk of Plasmodium infection were similar in postpartum and control women. A 2-fold increase in P. falciparum antibody levels was associated with increased prospective risk of P. falciparum infection (hazard ratio [HR] range = 1.37–1.94). Antibody levels against most P. vivax antigens displayed no association with prospective risk of P. vivax infection (HR range = 1.02–1.05) with the exception of PvMSP119 antibodies that were weakly associated with prospective risk of P. vivax infection (HR = 1.14 (95% confidence interval = 1.02, 1.28) per 2-fold increase in levels). Associations between antibody levels and prospective risk of infection attenuated when adjusted for documented retrospective exposure. Serology may be a useful tool to predict and monitor women at increased risk of P. falciparum infection postpartum, particularly in the absence of a detailed history of retrospective infections.
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Affiliation(s)
- Alistair R D McLean
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.,Macfarlane Burnet Institute of Medical Research, Melbourne, Australia
| | - Machteld Boel
- Shoklo Malaria Research Unit (SMRU), Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand
| | - Rose McGready
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.,Shoklo Malaria Research Unit (SMRU), Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand
| | - Ricardo Ataide
- Macfarlane Burnet Institute of Medical Research, Melbourne, Australia
| | - Damien Drew
- Macfarlane Burnet Institute of Medical Research, Melbourne, Australia
| | - Takafumi Tsuboi
- Division of Malaria Research, Proteo-Science Center, Ehime University, Ehime, Japan
| | - James G Beeson
- Department of Microbiology, Monash University, Victoria, Australia.,Macfarlane Burnet Institute of Medical Research, Melbourne, Australia
| | - François Nosten
- Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.,Shoklo Malaria Research Unit (SMRU), Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand
| | - Julie A Simpson
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia
| | - Freya J I Fowkes
- Department of Epidemiology and Preventative Medicine, Monash University, Victoria, Australia.,Macfarlane Burnet Institute of Medical Research, Melbourne, Australia.,Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia
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Bebell LM, Oduyebo T, Riley LE. Ebola virus disease and pregnancy: A review of the current knowledge of Ebola virus pathogenesis, maternal, and neonatal outcomes. Birth Defects Res 2017; 109:353-362. [PMID: 28398679 PMCID: PMC5407292 DOI: 10.1002/bdra.23558] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2016] [Revised: 06/30/2016] [Accepted: 07/28/2016] [Indexed: 11/09/2022]
Abstract
The 2014 to 2016 Ebola virus disease (EVD) outbreak in West Africa devastated local health systems and caused thousands of deaths. Historical reports from Zaire ebolavirus outbreaks suggested pregnancy was associated with an increased risk of severe illness and death, with mortality rates from 74 to 100%. In total, 111 cases of pregnant patients with EVD are reported in the literature, with an aggregate maternal mortality of 86%. Pregnancy-specific data published from the recent outbreak include four small descriptive cohort studies and five case reports. Despite limitations including reporting bias and small sample size, these studies suggest mortality in pregnant women may be lower than previously reported, with five of 13 (39%) infected women dying. Optimal treatments for pregnant women, and differences in EVD course between pregnant women and nonpregnant individuals, are major scientific gaps that have not yet been systematically addressed. Ebola virus may be transmitted from mother to baby in utero, during delivery, or through contact with maternal body fluids after birth including breast milk. EVD is almost universally fatal to the developing fetus, and limited fetal autopsy data prevent inferences on risk of birth defects. Decisions about delivery mode and other obstetric interventions should be individualized. WHO recommends close monitoring of survivors who later become pregnant, but does not recommend enhanced precautions at subsequent delivery. Although sexual transmission of Ebola virus has been documented, birth outcomes among survivors have not been published and will be important to appropriately counsel women on pregnancy outcomes and inform delivery precautions for healthcare providers. Birth Defects Research 109:353-362, 2017. © 2017 Wiley Periodicals, Inc.
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Affiliation(s)
- Lisa M. Bebell
- Department of Infectious Diseases, Massachusetts General Hospital, Boston, MA
- Massachusetts General Hospital Global Health Collaborative, Boston, MA
| | - Titilope Oduyebo
- Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention Atlanta, GA
- Epidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, GA
| | - Laura E. Riley
- Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA
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32
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Montague BT, Salas CM, Montague TL, Mileno MD. The immunosuppressed patient. Infect Dis (Lond) 2017. [DOI: 10.1002/9781119085751.ch28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Affiliation(s)
- Brian T. Montague
- Division of Infectious Diseases; University of Colorado; Aurora Colorado USA
| | | | | | - Maria D. Mileno
- Warren Alpert Medical School; Brown University; Providence Rhode Island USA
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Rogerson SJ, Unger HW. Prevention and control of malaria in pregnancy - new threats, new opportunities? Expert Rev Anti Infect Ther 2016; 15:361-375. [PMID: 27973923 DOI: 10.1080/14787210.2017.1272411] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
INTRODUCTION Over 100 million women and their babies are at risk of malaria in pregnancy each year. Malaria prevention in pregnancy relies on long-lasting insecticidal nets (LLINs), and, in Africa, intermittent preventive treatment in pregnancy (IPTp). Increasing resistance of malaria parasites to sulfadoxine-pyrimethamine, the only drug endorsed for IPTp, and increasing mosquito resistance to pyrethroids used in LLINs, threaten the efficacy of these proven strategies, while operational challenges restrict their implementation in areas of great need. Areas Covered: This review summarizes strategies for malaria prevention in pregnancy (both currently used and those undergoing preclinical and clinical evaluation), primarily drawing on publications and study protocols from the last decade. Challenges associated with each strategy are discussed, including the particular problem of HIV and malaria in pregnancy, and areas of further research are highlighted. Expert Commentary: Alternative drugs for IPTp are needed. Dihydroartemisinin-piperaquine is particularly promising, but requires further evaluation, and might contribute to artemisinin resistance. Intermittent screening and treatment in pregnancy (ISTp) is an alternative to IPTp that could reduce unnecessary antenatal drug exposure and resistance risk, but it is not recommended with current, insensitive screening tests. Optimal strategies for areas of low or declining malaria transmission remain to be determined.
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Affiliation(s)
- Stephen J Rogerson
- a Department of Medicine at the Doherty Institute , University of Melbourne , Melbourne , Australia
| | - Holger W Unger
- a Department of Medicine at the Doherty Institute , University of Melbourne , Melbourne , Australia.,b Department of Obstetrics and Gynaecology , Royal Infirmary of Edinburgh , Edinburgh , UK
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34
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Malaria: Biology and Disease. Cell 2016; 167:610-624. [PMID: 27768886 DOI: 10.1016/j.cell.2016.07.055] [Citation(s) in RCA: 503] [Impact Index Per Article: 55.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2016] [Revised: 07/17/2016] [Accepted: 07/29/2016] [Indexed: 11/22/2022]
Abstract
Malaria has been a major global health problem of humans through history and is a leading cause of death and disease across many tropical and subtropical countries. Over the last fifteen years renewed efforts at control have reduced the prevalence of malaria by over half, raising the prospect that elimination and perhaps eradication may be a long-term possibility. Achievement of this goal requires the development of new tools including novel antimalarial drugs and more efficacious vaccines as well as an increased understanding of the disease and biology of the parasite. This has catalyzed a major effort resulting in development and regulatory approval of the first vaccine against malaria (RTS,S/AS01) as well as identification of novel drug targets and antimalarial compounds, some of which are in human clinical trials.
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McLean ARD, Boel ME, McGready R, Ataide R, Drew D, Tsuboi T, Beeson JG, Nosten F, Simpson JA, Fowkes FJI. Antibody responses to Plasmodium falciparum and Plasmodium vivax blood-stage and sporozoite antigens in the postpartum period. Sci Rep 2016; 6:32159. [PMID: 27558000 PMCID: PMC4997260 DOI: 10.1038/srep32159] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2016] [Accepted: 08/03/2016] [Indexed: 11/17/2022] Open
Abstract
During pregnancy a variety of immunological changes occur to accommodate the fetus. It is unknown whether these changes continue to affect humoral immunity postpartum or how quickly they resolve. IgG levels were measured to P. falciparum and P. vivax antigens in 201 postpartum and 201 controls over 12 weeks. Linear mixed-effects models assessed antibody maintenance over time and the effect of microscopically confirmed Plasmodium spp. infection on antibody levels, and whether this was different in postpartum women compared with control women. Postpartum women had reduced Plasmodium spp. antibody levels compared to controls at baseline. Over 12 weeks, mean antibody levels in postpartum women increased to levels observed in control women. Microscopically confirmed P. falciparum and P. vivax infections during follow-up were associated with an increase in species-specific antibodies with similar magnitudes of boosting observed in postpartum and control women. Antibodies specific for pregnancy-associated, VAR2CSA-expressing parasites did not rapidly decline postpartum and did not boost in response to infection in either postpartum or control women. After pregnancy, levels of malaria-specific antibodies were reduced, but recovered to levels seen in control women. There was no evidence of an impaired ability to mount a boosting response in postpartum women.
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Affiliation(s)
- Alistair R D McLean
- Macfarlane Burnet Institute of Medical Research, Melbourne 3004, Australia.,Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne 3004, Australia
| | - Machteld E Boel
- Shoklo Malaria Research Unit (SMRU), Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot 63110, Thailand
| | - Rose McGready
- Shoklo Malaria Research Unit (SMRU), Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot 63110, Thailand.,Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford OX1 2JD, UK
| | - Ricardo Ataide
- Macfarlane Burnet Institute of Medical Research, Melbourne 3004, Australia
| | - Damien Drew
- Macfarlane Burnet Institute of Medical Research, Melbourne 3004, Australia
| | - Takafumi Tsuboi
- Division of Malaria Research, Proteo-Science Center, Ehime University, Matsuyuma 790-8577, Japan
| | - James G Beeson
- Macfarlane Burnet Institute of Medical Research, Melbourne 3004, Australia.,Department of Microbiology, Monash University 3800, Australia
| | - François Nosten
- Shoklo Malaria Research Unit (SMRU), Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot 63110, Thailand.,Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford OX1 2JD, UK
| | - Julie A Simpson
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne 3004, Australia
| | - Freya J I Fowkes
- Macfarlane Burnet Institute of Medical Research, Melbourne 3004, Australia.,Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne 3004, Australia.,Department of Epidemiology and Preventative Medicine, Monash University 3800, Victoria, Australia
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Plasmodium vivax malaria among pregnant women in Eastern Sudan. ASIAN PACIFIC JOURNAL OF TROPICAL DISEASE 2016. [DOI: 10.1016/s2222-1808(15)61058-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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Burger RJ, Visser BJ, Grobusch MP, van Vugt M. The influence of pregnancy on the pharmacokinetic properties of artemisinin combination therapy (ACT): a systematic review. Malar J 2016; 15:99. [PMID: 26891915 PMCID: PMC4757991 DOI: 10.1186/s12936-016-1160-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2015] [Accepted: 02/10/2016] [Indexed: 11/10/2022] Open
Abstract
Background Pregnancy has been reported to alter the pharmacokinetic properties of anti-malarial drugs, including the different components of artemisinin-based combination therapy (ACT). However, small sample sizes make it difficult to draw strong conclusions based on individual pharmacokinetic studies. The aim of this review is to summarize the evidence of the influence of pregnancy on the pharmacokinetic properties of different artemisinin-based combinations. Methods A PROSPERO-registered systematic review to identify clinical trials that investigated the influence of pregnancy on the pharmacokinetic properties of different forms of ACT was conducted, following PRISMA guidelines. Without language restrictions, Medline/PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, LILACS, Biosis Previews and the African Index Medicus were searched for studies published up to November 2015. The following components of ACT that are currently recommend by the World Health Organization as first-line treatment of malaria in pregnancy were reviewed: artemisinin, artesunate, dihydroartemisinin, lumefantrine, amodiaquine, mefloquine, sulfadoxine, pyrimethamine, piperaquine, atovaquone and proguanil. Results The literature search identified 121 reports, 27 original studies were included. 829 pregnant women were included in the analysis. Comparison of the available studies showed lower maximum concentrations (Cmax) and exposure (AUC) of dihydroartemisinin, the active metabolite of all artemisinin derivatives, after oral administration of artemether, artesunate and dihydroartemisinin in pregnant women. Low day 7 concentrations were commonly seen in lumefantrine studies, indicating a low exposure and possibly reduced efficacy. The influence of pregnancy on amodiaquine and piperaquine seemed not to be clinically relevant. Sulfadoxine plasma concentration was significantly reduced and clearance rates were higher in pregnancy, while pyrimethamine and mefloquine need more research as no general conclusion can be drawn based on the available evidence. For atovaquone, the available data showed a lower maximum concentration and exposure. Finally, the maximum concentration of cycloguanil, the active metabolite of proguanil, was significantly lower, possibly compromising the efficacy. Conclusion These findings suggest that reassessment of the dose of the artemisinin derivate and some components of ACT are necessary to ensure the highest possible efficacy of malaria treatment in pregnant women. However, for most components of ACT, data were insufficient and extensive research with larger sample sizes will be necessary to identify the exact influences of pregnancy on the pharmacokinetic properties of different artemisinin-based combinations. In addition, different clinical studies used diverse study designs with various reported relevant outcomes. Future pharmacokinetic studies could benefit from more uniform designs, in order to increase quality, robustness and effectiveness. Study registration: CRD42015023756 (PROSPERO) Electronic supplementary material The online version of this article (doi:10.1186/s12936-016-1160-6) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Renée J Burger
- Division of Internal Medicine, Department of Infectious Diseases, Academic Medical Center, Center of Tropical Medicine and Travel Medicine, University of Amsterdam, Meibergdreef 9, PO Box 22700, 1100 DE, Amsterdam, The Netherlands.
| | - Benjamin J Visser
- Division of Internal Medicine, Department of Infectious Diseases, Academic Medical Center, Center of Tropical Medicine and Travel Medicine, University of Amsterdam, Meibergdreef 9, PO Box 22700, 1100 DE, Amsterdam, The Netherlands. .,Centre de Recherches de Médicales de Lambaréné (CERMEL), Albert Schweitzer Hospital, Lambaréné, Gabon.
| | - Martin P Grobusch
- Division of Internal Medicine, Department of Infectious Diseases, Academic Medical Center, Center of Tropical Medicine and Travel Medicine, University of Amsterdam, Meibergdreef 9, PO Box 22700, 1100 DE, Amsterdam, The Netherlands. .,Centre de Recherches de Médicales de Lambaréné (CERMEL), Albert Schweitzer Hospital, Lambaréné, Gabon.
| | - Michèle van Vugt
- Division of Internal Medicine, Department of Infectious Diseases, Academic Medical Center, Center of Tropical Medicine and Travel Medicine, University of Amsterdam, Meibergdreef 9, PO Box 22700, 1100 DE, Amsterdam, The Netherlands.
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Charnaud SC, McGready R, Herten-Crabb A, Powell R, Guy A, Langer C, Richards JS, Gilson PR, Chotivanich K, Tsuboi T, Narum DL, Pimanpanarak M, Simpson JA, Beeson JG, Nosten F, Fowkes FJI. Maternal-foetal transfer of Plasmodium falciparum and Plasmodium vivax antibodies in a low transmission setting. Sci Rep 2016; 6:20859. [PMID: 26861682 PMCID: PMC4748262 DOI: 10.1038/srep20859] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2015] [Accepted: 01/04/2016] [Indexed: 11/10/2022] Open
Abstract
During pregnancy immunoglobulin G (IgG) antibodies are transferred from mother to neonate across the placenta. Studies in high transmission areas have shown transfer of P. falciparum-specific IgG, but the extent and factors influencing maternal-foetal transfer in low transmission areas co-endemic for both P. falciparum and P. vivax are unknown. Pregnant women were screened weekly for Plasmodium infection. Mother-neonate paired serum samples at delivery were tested for IgG to antigens from P. falciparum, P. vivax and other infectious diseases. Antibodies to malarial and non-malarial antigens were highly correlated between maternal and neonatal samples (median [range] spearman ρ = 0.78 [0.57-0.93]), although Plasmodium spp. antibodies tended to be lower in neonates than mothers. Estimated gestational age at last P. falciparum infection, but not P. vivax infection, was positively associated with antibody levels in the neonate (P. falciparum merozoite, spearman ρ median [range] 0.42 [0.33-0.66], PfVAR2CSA 0.69; P. vivax ρ = 0.19 [0.09-0.3]). Maternal-foetal transfer of anti-malarial IgG to Plasmodium spp. antigens occurs in low transmission settings. P. vivax IgG acquisition is not associated with recent exposure unlike P. falciparum IgG, suggesting a difference in acquisition of antibodies. IgG transfer is greatest in the final weeks of pregnancy which has implications for the timing of future malaria vaccination strategies in pregnant women.
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Affiliation(s)
- Sarah C Charnaud
- Macfarlane Burnet Institute of Medical Research, Melbourne, Australia
| | - Rose McGready
- Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.,Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.,Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Asha Herten-Crabb
- Macfarlane Burnet Institute of Medical Research, Melbourne, Australia.,Department of Medicine, University of Melbourne, Australia
| | - Rosanna Powell
- Macfarlane Burnet Institute of Medical Research, Melbourne, Australia
| | - Andrew Guy
- Macfarlane Burnet Institute of Medical Research, Melbourne, Australia.,Department of Immunology, Monash University, Alfred Medical Research and Education Precinct, Melbourne, Australia
| | - Christine Langer
- Macfarlane Burnet Institute of Medical Research, Melbourne, Australia
| | - Jack S Richards
- Macfarlane Burnet Institute of Medical Research, Melbourne, Australia.,Department of Medicine, University of Melbourne, Australia
| | - Paul R Gilson
- Macfarlane Burnet Institute of Medical Research, Melbourne, Australia
| | - Kesinee Chotivanich
- Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Thailand
| | - Takafumi Tsuboi
- Division of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, Japan
| | - David L Narum
- Laboratory of Malaria Immunology and Vaccinology, NIAID/NIH, Rockville, MD, USA
| | - Mupawjay Pimanpanarak
- Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand
| | - Julie A Simpson
- Centre for Epidemiology and Biostatistics, University of Melbourne, Australia
| | - James G Beeson
- Macfarlane Burnet Institute of Medical Research, Melbourne, Australia.,Department of Medicine, University of Melbourne, Australia
| | - François Nosten
- Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.,Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.,Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Freya J I Fowkes
- Macfarlane Burnet Institute of Medical Research, Melbourne, Australia.,Centre for Epidemiology and Biostatistics, University of Melbourne, Australia.,Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.,Department of Infectious Diseases, Monash University, Melbourne, Australia
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