|
1
|
Flynn TG, Paredes Olortegui M, Garcia Bardales PF, Schiaffino F, Pinedo Vasquez TN, Shapiama López WV, Peñataro Yori P, Ramal Asayag CJ, Meza Sánchez GR, Colston JM, Kosek MN. Epstein-Barr Virus in the RIVERA Case-Control Study of Acute Febrile Illness: Acute Mononucleosis Nearly Absent as an Etiology in the Peruvian Amazon. Am J Trop Med Hyg 2025; 112:200-207. [PMID: 39531721 PMCID: PMC11720789 DOI: 10.4269/ajtmh.24-0051] [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: 01/23/2024] [Accepted: 08/26/2024] [Indexed: 11/16/2024] Open
Abstract
Large diagnostic panels allow for pathogens with high or low likelihood of causing attributable illness to be tested simultaneously. Infectious mononucleosis (IM) due to primary infection with Epstein-Barr virus (EBV) is a common cause of acute febrile illness (AFI) in case series from high-income countries, though its contribution to AFI in tropical low-income settings is unclear. As part of a case-control study using multiplex quantitative polymerase chain reaction (qPCR) diagnostics, we set out to determine if primary EBV infection was an underrecognized cause of AFI in the Peruvian Amazon. Presence of EBV DNA in whole-blood samples was equally prevalent among febrile cases and afebrile controls (34.6% [247/714] versus 35.7% [248/695]) and was not correlated with classic IM symptoms. Given the clear lack of clinical significance of the whole-blood PCR results, additional testing was pursued to ascertain the true prevalence of IM among cases of AFI in this population. The presence of EBV DNA in plasma, a marker of active EBV-related processes, was detected in 7% (5/68). Anti-EBNA-1 IgG, a late marker of prior infection, was tested via ELISA and detected in 4/5 of the plasma-positive patients, thereby excluding an acute primary EBV infection in all but one patient. Infectious mononucleosis due to primary infection with EBV was not an important etiology of AFI in the Peruvian Amazon, despite high rates of initial test positivity.
Collapse
Affiliation(s)
- Thomas G. Flynn
- Division of Infectious Diseases and International Health, School of Medicine, University of Virginia, Charlottesville, Virginia
| | | | | | - Francesca Schiaffino
- Division of Infectious Diseases and International Health, School of Medicine, University of Virginia, Charlottesville, Virginia
- Faculty of Veterinary Medicine, Universidad Peruana Cayetano Heredia, San Martín de Porres, Perú
| | | | | | - Pablo Peñataro Yori
- Division of Infectious Diseases and International Health, School of Medicine, University of Virginia, Charlottesville, Virginia
- Asociación Benéfica Prisma, Investigaciones Biomédicas, Iquitos, Perú
| | | | | | - Josh M. Colston
- Division of Infectious Diseases and International Health, School of Medicine, University of Virginia, Charlottesville, Virginia
| | - Margaret N. Kosek
- Division of Infectious Diseases and International Health, School of Medicine, University of Virginia, Charlottesville, Virginia
- Asociación Benéfica Prisma, Investigaciones Biomédicas, Iquitos, Perú
| |
Collapse
|
|
2
|
Silva-Caso W, Aguilar-Luis MA, Espinoza-Espíritu W, Vilcapoma-Balbin M, Del Valle LJ, Misaico-Revate E, Soto-Febres F, Pérez-Lazo G, Martins-Luna J, Perona-Fajardo F, Del Valle-Mendoza J. Leptospira spp. and Rickettsia spp. as pathogens with zoonotic potential causing acute undifferentiated febrile illness in a central-eastern region of Peru. BMC Res Notes 2024; 17:171. [PMID: 38902784 PMCID: PMC11188165 DOI: 10.1186/s13104-024-06837-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Accepted: 06/17/2024] [Indexed: 06/22/2024] Open
Abstract
OBJETIVE this study was to determine the relationship between acute febrile illness and bacterial pathogens with zoonotic potential that cause emerging and re-emerging diseases in a central-eastern region of Peru. RESULTS Out of the 279 samples analyzed, 23 (8.2%) tested positive for infection by Rickettsia spp., while a total of 15 (5.4%) tested positive for Leptospira spp. Women had a higher frequency of infection by Rickettsia spp., with 13 cases (53.3%), while men had a higher frequency of infection by Leptospira spp., with 10 cases (66.7%). The most frequently reported general symptom was headache, with 100.0% (n = 23) of patients with Rickettsia (+) and 86.7% (n = 13) of patients with Leptospira (+) experiencing it. Arthralgia was the second most frequent symptom, reported by 95.6% (n = 22) and 60% (n = 9) of patients with Rickettsia (+) and Leptospira (+), respectively. Myalgia was reported by 91.3% (n = 21) and 66.7% (n = 10) of patients with Rickettsia (+) and Leptospira (+), respectively. Retroocular pain, low back pain, and skin rash were also present, but less frequently. Among the positives, no manifestation of bleeding was recorded, although only one positive case for Leptospira spp. presented a decrease in the number of platelets.
Collapse
Affiliation(s)
- Wilmer Silva-Caso
- School of Medicine, Research Centre of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru.
- Facultad de Medicina Humana, Unidad de Post Grado, Universidad de San Martín de Porres, Lima, Peru.
| | - Miguel Angel Aguilar-Luis
- School of Medicine, Research Centre of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru
| | | | | | - Luis J Del Valle
- Centre d'Enginyeria Biotecnologica i Molecular (CEBIM), Departament d'Enginyeria Quıímica, ETSEIB, Universidad Politécnica de Catalunya (UPC), Barcelona Tech, Spain
| | | | - Fernando Soto-Febres
- Division of Infectious Diseases, Guillermo Almenara Irigoyen National Hospital-EsSalud, Lima, 15033, Peru
| | - Giancarlo Pérez-Lazo
- Division of Infectious Diseases, Guillermo Almenara Irigoyen National Hospital-EsSalud, Lima, 15033, Peru
| | - Johanna Martins-Luna
- School of Medicine, Research Centre of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru
| | - Francisco Perona-Fajardo
- School of Medicine, Research Centre of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru
| | - Juana Del Valle-Mendoza
- School of Medicine, Research Centre of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru.
- Instituto de Investigación Nutricional, Lima, Peru.
| |
Collapse
|
|
3
|
Ximenes D, de Jesus G, de Sousa ASCFC, Soares C, Amaral LC, Oakley T, Alves L, Amaral S, Sarmento N, Guterres H, Cabral JADD, Boavida F, Yan J, Francis JR, Martins N, Arkell P. A pilot study investigating severe community-acquired febrile illness through implementation of an innovative microbiological and nucleic acid amplification testing strategy in Timor-Leste (ISIN-MANAS-TL). IJID REGIONS 2024; 11:100345. [PMID: 38596819 PMCID: PMC11002651 DOI: 10.1016/j.ijregi.2024.02.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Revised: 02/27/2024] [Accepted: 02/29/2024] [Indexed: 04/11/2024]
Abstract
Objectives Acute febrile illness (AFI) causes significant health-seeking, morbidity, and mortality in Southeast Asia. This pilot study aimed to describe presentation, etiology, treatment, and outcomes of patients with AFI at one hospital in Timor-Leste and assessing the feasibility of conducting larger studies in this setting. Methods Patients attending Hospital Nacional Guido Valadares with tympanic or axillary temperature ≥37.5°C in whom a blood culture was taken as part of routine clinical care were eligible. Participants were followed up daily for 10 days and again after 30 days. Whole blood was analyzed using a real-time quantitative polymerase chain reaction assay detecting dengue virus serotypes 1-4 and other arthropod-borne infections. Results A total of 82 participants were recruited. Polymerase chain reaction testing was positive for dengue in 14 of 82 (17.1%) participants and blood culture identified a bacterial pathogen in three of 82 (3.7%) participants. Follow-up was completed by 75 of 82 (91.5%) participants. High rates of hospital admission (58 of 82, 70.7%), broad-spectrum antimicrobial treatment (34 of 82, 41.5%), and mortality (9 of 82, 11.0%) were observed. Conclusions Patients with AFI experience poor clinical outcomes. Prospective observational and interventional studies assessing interventions, such as enhanced diagnostic testing, clinical decision support tools, or antimicrobial stewardship interventions, are required and would be feasible to conduct in this setting.
Collapse
Affiliation(s)
- Deolindo Ximenes
- Global and Tropical Health Division, Menzies School of Health Research Timor-Leste Office, Charles Darwin University, Dili, Timor-Leste
| | - Gustodio de Jesus
- Emergency Department, Hospital Nacional Guido Valadares, Dili, Timor-Leste
| | - Antonio SCFC de Sousa
- Global and Tropical Health Division, Menzies School of Health Research Timor-Leste Office, Charles Darwin University, Dili, Timor-Leste
- Molecular and Serology Department, Laboratorio Nacional da Saúde, Dili, Timor-Leste
| | - Caetano Soares
- Emergency Department, Hospital Nacional Guido Valadares, Dili, Timor-Leste
| | - Luciana C. Amaral
- Emergency Department, Hospital Nacional Guido Valadares, Dili, Timor-Leste
| | - Tessa Oakley
- Global and Tropical Health Division, Menzies School of Health Research Timor-Leste Office, Charles Darwin University, Dili, Timor-Leste
| | - Lucsendar Alves
- Global and Tropical Health Division, Menzies School of Health Research Timor-Leste Office, Charles Darwin University, Dili, Timor-Leste
| | - Salvador Amaral
- Global and Tropical Health Division, Menzies School of Health Research Timor-Leste Office, Charles Darwin University, Dili, Timor-Leste
| | - Nevio Sarmento
- Global and Tropical Health Division, Menzies School of Health Research Timor-Leste Office, Charles Darwin University, Dili, Timor-Leste
| | - Helio Guterres
- Internal Medicine Department, Hospital Nacional Guido Valadares, Dili, Timor-Leste
| | | | - Flavio Boavida
- Emergency Department, Hospital Nacional Guido Valadares, Dili, Timor-Leste
| | - Jennifer Yan
- Global and Tropical Health Division, Menzies School of Health Research Timor-Leste Office, Charles Darwin University, Dili, Timor-Leste
| | - Joshua R. Francis
- Global and Tropical Health Division, Menzies School of Health Research Timor-Leste Office, Charles Darwin University, Dili, Timor-Leste
| | - Nelson Martins
- Global and Tropical Health Division, Menzies School of Health Research Timor-Leste Office, Charles Darwin University, Dili, Timor-Leste
| | - Paul Arkell
- Global and Tropical Health Division, Menzies School of Health Research Timor-Leste Office, Charles Darwin University, Dili, Timor-Leste
| |
Collapse
|
|
4
|
Aguilar-Luis MA, Watson H, Tarazona-Castro Y, Troyes-Rivera L, Cabellos-Altamirano F, Silva-Caso W, Aquino-Ortega R, Carrillo-Ng H, Zavaleta-Gavidia V, del Valle-Mendoza J. The Chikungunya virus: A reemerging cause of acute febrile illness in the high jungle of northern Peru. PLoS Negl Trop Dis 2023; 17:e0011787. [PMID: 38079402 PMCID: PMC10712839 DOI: 10.1371/journal.pntd.0011787] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Accepted: 11/09/2023] [Indexed: 12/18/2023] Open
Abstract
BACKGROUND The Chikungunya virus (CHIKV) is an emerging arthropod-borne virus (arbovirus) that causes undifferentiated acute febrile illness. Cases of CHIKV may be under-reported in Peru, given the various difficulties in diagnosing it, such as lack of diagnostic tests in remote areas, the passive nature of epidemiological surveillance, and co-circulation of other arthropod-borne pathogens. Therefore, a study was conducted in the high jungle of northern Peru to determine the prevalence of CHIKV among febrile patients and describe their clinical characteristics. METHODS A cross-sectional study was conducted in the province of Jaen, Cajamarca, located in the high jungle of northern Peru. Patients attending primary healthcare centers within Cajamarca's Regional Health Directorate were enrolled. The study took place from June 2020 through June 2021. Patients were eligible if they sought outpatient healthcare for a clinical diagnosis of acute febrile illness (AFI). Serum samples were collected from all patients, and the diagnosis of CHIKV was determined using real-time RT-PCR, as well as the detection of IgM antibodies by ELISA. A logistic regression model was employed to identify the risk factors for CHIKV, and the odds ratios (ORs) were calculated, along with their corresponding 95% confidence intervals (95% CI). RESULTS A total of 1 047 patients with AFI were included during the study period. CHIKV was identified in 130 patients of 1 047 (12.4%). Among the CHIKV positive cases, 84 of 130 (64.6%) were diagnosed by RT-PCR, 42 of 130 (32.3%) by IgM ELISA detection, and 4 of 130 (3.1%) by both assays. The majority of patients with CHIKV infection fell within the 18-39 years age group (50.0%), followed by the 40-59 years age group (23.9%) and those with 60 years or older (10.8%). The most common clinical symptoms observed in patients with CHIKV infection were headache (85.4%), myalgias (72.3%), and arthralgias (64.6%). The highest number of positive CHIKV cases occurred in May (23.1%), followed by March (20.0%) and February (13.8%) of 2021. CONCLUSION The study reports a considerable frequency of CHIKV infections among patients with AFI from the high jungle of northern Peru. These findings highlight the importance of recognizing CHIKV as an ongoing pathogen with continuous transmission in various areas of Peru. It is crucial to enhance epidemiological surveillance by implementing reliable diagnostic techniques, as the clinical symptoms of CHIKV infection can be nonspecific.
Collapse
Affiliation(s)
- Miguel Angel Aguilar-Luis
- School of Medicine, Research Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru
| | - Hugh Watson
- Antiviral Research Unit, Evotec ID, Lyon, France
| | - Yordi Tarazona-Castro
- School of Medicine, Research Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru
| | | | | | - Wilmer Silva-Caso
- School of Medicine, Research Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru
| | - Ronald Aquino-Ortega
- School of Medicine, Research Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru
| | - Hugo Carrillo-Ng
- School of Medicine, Research Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru
| | - Victor Zavaleta-Gavidia
- Regional Laboratory of Cajamarca, Regional Health Directorate (Dirección Regional de Salud, DIRESA) of Cajamarca, Cajamarca, Peru
| | - Juana del Valle-Mendoza
- School of Medicine, Research Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru
| |
Collapse
|
|
5
|
Nooh F, Chernet A, Reither K, Okuma J, Brattig NW, Utzinger J, Probst-Hensch N, Paris DH, Dreyfus A. Prevalence of fever of unidentified aetiology in East African adolescents and adults: a systematic review and meta-analysis. Infect Dis Poverty 2023; 12:55. [PMID: 37231500 DOI: 10.1186/s40249-023-01105-z] [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: 01/17/2023] [Accepted: 05/16/2023] [Indexed: 05/27/2023] Open
Abstract
BACKGROUND Primary health care settings and hospitals of low- and middle-income countries have few accessible diagnostic tools and limited laboratory and human resources capacity to identify multiple pathogens with high accuracy. In addition, there is a paucity of information on fever and its underlying aetiology in the adolescent and adult population in East Africa. The purpose of this study was to estimate the pooled prevalence of fever of unidentified aetiology among adolescent and adult febrile patients seeking health care in East Africa. METHODS We pursued a systematic review using readily available electronic databases (i.e. PubMed, Cumulative Index to Nursing & Allied Health Literature, Scopus, Cochrane Library and Web of Science) without language restriction from inception date of the respective databases to October 31, 2022. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Identified studies were screened for relevance. Further analyses based on pre-set eligibility criteria were carried out for final inclusion. Two reviewers independently screened and extracted data. Risk of study bias was assessed. Meta-analysis of the prevalence of fever of unidentified aetiology was performed. RESULTS We identified 14,029 articles of which 25 were eligible for inclusion, reporting data from 8538 participants. The pooled prevalence of febrile cases with unidentified aetiology was 64% [95% confidence interval (CI): 51-77%, I2 = 99.6%] among febrile adolescents and adults in East Africa. For the proportion of patients with identified aetiology, the studies documented bacterial pathogens (human bloodstream infections), bacterial zoonotic pathogens and arboviruses as the main non-malarial causative agents in East Africa. CONCLUSIONS Our study provides evidence that almost two-thirds of adolescent and adult febrile patients attending health care facilities in East Africa might receive inappropriate treatments due to unidentified potential life-threatening fever aetiology. Hence, we call for a comprehensive fever syndromic surveillance to broaden a consequential differential diagnosis of syndromic fever and to considerably improve the course of patients' disease and treatment outcomes.
Collapse
Affiliation(s)
- Faisal Nooh
- Swiss Tropical and Public Health Institute, Kreuzstrasse 2, 4123, Allschwil, Switzerland.
- University of Basel, Basel, Switzerland.
- College of Medicine and Health Sciences, Jigjiga University, Jigjiga, Ethiopia.
- College of Medicine and Health Sciences, University of Hargeisa, Hargeisa, Somaliland.
| | - Afona Chernet
- Swiss Tropical and Public Health Institute, Kreuzstrasse 2, 4123, Allschwil, Switzerland
- University of Basel, Basel, Switzerland
| | - Klaus Reither
- Swiss Tropical and Public Health Institute, Kreuzstrasse 2, 4123, Allschwil, Switzerland
- University of Basel, Basel, Switzerland
| | - James Okuma
- Swiss Tropical and Public Health Institute, Kreuzstrasse 2, 4123, Allschwil, Switzerland
- University of Basel, Basel, Switzerland
| | - Norbert W Brattig
- Department Infectious Disease Epidemiology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany
| | - Jürg Utzinger
- Swiss Tropical and Public Health Institute, Kreuzstrasse 2, 4123, Allschwil, Switzerland
- University of Basel, Basel, Switzerland
| | - Nicole Probst-Hensch
- Swiss Tropical and Public Health Institute, Kreuzstrasse 2, 4123, Allschwil, Switzerland
- University of Basel, Basel, Switzerland
| | - Daniel H Paris
- Swiss Tropical and Public Health Institute, Kreuzstrasse 2, 4123, Allschwil, Switzerland
- University of Basel, Basel, Switzerland
| | - Anou Dreyfus
- Swiss Tropical and Public Health Institute, Kreuzstrasse 2, 4123, Allschwil, Switzerland
- University of Basel, Basel, Switzerland
- Section of Epidemiology, University of Zürich, Zurich, Switzerland
| |
Collapse
|
|
6
|
Circular Whole-Transcriptome Amplification (cWTA) and mNGS Screening Enhanced by a Group Testing Algorithm (mEGA) Enable High-Throughput and Comprehensive Virus Identification. mSphere 2022; 7:e0033222. [PMID: 36005385 PMCID: PMC9599668 DOI: 10.1128/msphere.00332-22] [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] [Indexed: 12/03/2022] Open
Abstract
Metagenomic next-generation sequencing (mNGS) offers a hypothesis-free approach for pathogen detection, but its applicability in clinical diagnosis, in addition to other factors, remains limited due to complicated library construction. The present study describes a PCR-free isothermal workflow for mNGS targeting RNA, based on a multiple displacement amplification, termed circular whole-transcriptome amplification (cWTA), as the template is circularized before amplification. The cWTA approach was validated with clinical samples and nanopore sequencing. Reads homologous to dengue virus 2 and chikungunya virus were detected in clinical samples from Bangladesh and Brazil, respectively. In addition, the practicality of a high-throughput detection system that combines mNGS and a group testing algorithm termed mNGS screening enhanced by a group testing algorithm (mEGA) was established. This approach enabled significant library size reduction while permitting trackability between samples and diagnostic results. Serum samples of patients with undifferentiated febrile illnesses from Vietnam (n = 43) were also amplified with cWTA, divided into 11 pools, processed for library construction, and sequenced. Dengue virus 2, hepatitis B virus, and parvovirus B19 were successfully detected without prior knowledge of their existence. Collectively, cWTA with the nanopore platform opens the possibility of hypothesis-free on-site comprehensive pathogen diagnosis, while mEGA contributes to the scaling up of sample throughput. IMPORTANCE Given the breadth of pathogens that cause infections, a single approach that can detect a wide range of pathogens is ideal but is impractical due to the available tests being highly specific to a certain pathogen. Recent developments in sequencing technology have introduced mNGS as an alternative that provides detection of a wide-range of pathogens by detecting the presence of their nucleic acids in the sample. However, sequencing library preparation is still a bottleneck, as it is complicated, costly, and time-consuming. In our studies, alternative approaches to optimize library construction for mNGS were developed. This included isothermal nucleic acid amplification and expansion of sample throughput with a group testing algorithm. These methods can improve the utilization of mNGS as a diagnostic tool and can serve as a high-throughput screening system aiding infectious disease surveillance.
Collapse
|
|
7
|
Durango-Chavez HV, Toro-Huamanchumo CJ, Silva-Caso W, Martins-Luna J, Aguilar-Luis MA, del Valle-Mendoza J, Puyen ZM. Oropouche virus infection in patients with acute febrile syndrome: Is a predictive model based solely on signs and symptoms useful? PLoS One 2022; 17:e0270294. [PMID: 35881626 PMCID: PMC9321406 DOI: 10.1371/journal.pone.0270294] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 06/08/2022] [Indexed: 11/18/2022] Open
Abstract
Background
Oropouche fever is an infectious disease caused by the Oropouche virus (OROV). The diagnosis and prediction of the clinical picture continue to be a great challenge for clinicians who manage patients with acute febrile syndrome. Several symptoms have been associated with OROV virus infection in patients with febrile syndrome; however, to date, there is no clinical prediction rule, which is a fundamental tool to help the approach of this infectious disease.
Objective
To assess the performance of a prediction model based solely on signs and symptoms to diagnose Oropouche virus infection in patients with acute febrile syndrome.
Materials and methods
Validation study, which included 923 patients with acute febrile syndrome registered in the Epidemiological Surveillance database of three arbovirus endemic areas in Peru.
Results
A total of 97 patients (19%) were positive for OROV infection in the development group and 23.6% in the validation group. The area under the curve was 0.65 and the sensitivity, specificity, PPV, NPV, LR + and LR- were 78.2%, 35.1%, 27.6%, 83.6%, 1.20 and 0.62, respectively.
Conclusions
The development of a clinical prediction model for the diagnosis of Oropouche based solely on signs and symptoms does not work well. This may be due to the fact that the symptoms are nonspecific and related to other arbovirus infections, which confuse and make it difficult to predict the diagnosis, especially in endemic areas of co-infection of these diseases. For this reason, epidemiological surveillance of OROV in various settings using laboratory tests such as PCR is important.
Collapse
Affiliation(s)
| | - Carlos J. Toro-Huamanchumo
- Universidad San Ignacio de Loyola, Unidad para la Generación y Síntesis de Evidencias en Salud, Lima, Peru
- Clínica Avendaño, Unidad de Investigación Multidisciplinaria, Lima, Peru
| | - Wilmer Silva-Caso
- School of Medicine, Research and Innovation Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru
- Laboratorio de Biologia Molecular, Instituto de Investigación Nutricional, Lima, Peru
| | - Johanna Martins-Luna
- School of Medicine, Research and Innovation Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru
| | - Miguel Angel Aguilar-Luis
- School of Medicine, Research and Innovation Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru
- Laboratorio de Biologia Molecular, Instituto de Investigación Nutricional, Lima, Peru
| | - Juana del Valle-Mendoza
- School of Medicine, Research and Innovation Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru
- Laboratorio de Biologia Molecular, Instituto de Investigación Nutricional, Lima, Peru
- * E-mail: (ZMP); (JVM)
| | - Zully M. Puyen
- School of Medicine, Universidad Peruana de Ciencias Aplicadas, Lima, Peru
- Instituto Nacional de Salud, Lima, Peru
- * E-mail: (ZMP); (JVM)
| |
Collapse
|
|
8
|
Tarazona-Castro Y, Troyes-Rivera L, Martins-Luna J, Cabellos-Altamirano F, Aguilar-Luis MA, Carrillo-Ng H, del Valle LJ, Kym S, Miranda-Maravi S, Silva-Caso W, Levy-Blitchtein S, del Valle-Mendoza J. Detection of SARS-CoV-2 antibodies in febrile patients from an endemic region of dengue and chikungunya in Peru. PLoS One 2022; 17:e0265820. [PMID: 35395015 PMCID: PMC8993000 DOI: 10.1371/journal.pone.0265820] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 03/08/2022] [Indexed: 01/08/2023] Open
Abstract
INTRODUCTION The rapid expansion of the novel SARS-CoV-2 virus has raised serious public health concerns due to the possibility of misdiagnosis in regions where arboviral diseases are endemic. We performed the first study in northern Peru to describe the detection of SARS-CoV-2 IgM antibodies in febrile patients with a suspected diagnosis of dengue and chikungunya fever. MATERIALS AND METHODS A consecutive cross-sectional study was performed in febrile patients attending primary healthcare centers from April 2020 through March 2021. Patients enrolled underwent serum sample collection for the molecular and serological detection of DENV and CHIKV. Also, serological detection of IgM antibodies against SARS-CoV-2 was performed. RESULTS 464 patients were included during the study period, of which (40.51%) were positive for one pathogen, meanwhile (6.90%) presented co-infections between 2 or more pathogens. The majority of patients with monoinfections were positive for SARS-CoV-2 IgM with (73.40%), followed by DENV 18.09% and CHIKV (8.51%). The most frequent co-infection was DENV + SARS-CoV-2 with (65.63%), followed by DENV + CHIKV and DENV + CHIKV + SARS-CoV-2, both with (12.50%). The presence of polyarthralgias in hands (43.75%, p<0.01) and feet (31.25%, p = 0.05) were more frequently reported in patients with CHIKV monoinfection. Also, conjunctivitis was more common in patients positive for SARS-CoV-2 IgM (11.45%, p<0.01). The rest of the symptoms were similar among all the study groups. CONCLUSION SARS-CoV-2 IgM antibodies were frequently detected in acute sera from febrile patients with a clinical suspicion of arboviral disease. The presence of polyarthralgias in hands and feet may be suggestive of CHIKV infection. These results reaffirm the need to consider SARS-CoV-2 infection as a main differential diagnosis of acute febrile illness in arboviruses endemic areas, as well as to consider co-infections between these pathogens.
Collapse
Affiliation(s)
- Yordi Tarazona-Castro
- School of Medicine, Research Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru
- Laboratorio de Biologia Molecular, Instituto de Investigación Nutricional, Lima, Peru
| | | | - Johanna Martins-Luna
- School of Medicine, Research Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru
- Laboratorio de Biologia Molecular, Instituto de Investigación Nutricional, Lima, Peru
| | | | - Miguel Angel Aguilar-Luis
- School of Medicine, Research Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru
- Laboratorio de Biologia Molecular, Instituto de Investigación Nutricional, Lima, Peru
| | - Hugo Carrillo-Ng
- School of Medicine, Research Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru
- Laboratorio de Biologia Molecular, Instituto de Investigación Nutricional, Lima, Peru
| | - Luis J. del Valle
- Barcelona Research Center for Multiscale Science and Engineering, Departament d’Enginyeria Química, EEBE, Universitat Politècnica de Catalunya (UPC), Barcelona, Spain
| | - Sungmin Kym
- Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea
| | | | - Wilmer Silva-Caso
- School of Medicine, Research Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru
- Laboratorio de Biologia Molecular, Instituto de Investigación Nutricional, Lima, Peru
| | - Saul Levy-Blitchtein
- School of Medicine, Research Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru
| | - Juana del Valle-Mendoza
- School of Medicine, Research Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru
- Laboratorio de Biologia Molecular, Instituto de Investigación Nutricional, Lima, Peru
| |
Collapse
|
|
9
|
Del Valle-Mendoza J, Palomares-Reyes C, Carrillo-Ng H, Tarazona-Castro Y, Kym S, Aguilar-Luis MA, Del Valle LJ, Aquino-Ortega R, Martins-Luna J, Peña-Tuesta I, Verne E, Silva-Caso W. Leptospirosis in febrile patients with suspected diagnosis of dengue fever. BMC Res Notes 2021; 14:209. [PMID: 34051849 PMCID: PMC8164282 DOI: 10.1186/s13104-021-05627-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Accepted: 05/20/2021] [Indexed: 12/23/2022] Open
Abstract
Objective This study was carried out to determine the prevalence of leptospirosis among febrile patients with a suspicious clinical diagnosis of dengue fever in northern Peru. Results A total of 276 serum samples from patients with acute febrile illness (AFI) and suspected diagnosis for dengue virus (DENV) were analyzed. We identified an etiological agent in 121 (47.5%) patients, DENV was detected in 30.4% of the cases, leptospirosis in 11.2% and co-infection by both pathogens was observed in 5.9% of the patients. In this study the most common clinical symptoms reported by the patients were: headache 89.1%, myalgias 86.9% and arthralgias 82.9%. No differences in symptomatology was observed among the different study groups.
Collapse
Affiliation(s)
- Juana Del Valle-Mendoza
- School of Medicine, Research and Innovation Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru. .,Laboratorio de Biologia Molecular, Instituto de Investigación Nutricional, Lima, Peru.
| | - Carlos Palomares-Reyes
- School of Medicine, Research and Innovation Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru
| | - Hugo Carrillo-Ng
- Laboratorio de Biologia Molecular, Instituto de Investigación Nutricional, Lima, Peru.,Facultad de Medicina Alberto Hurtado, Universidad Peruana Cayetano Heredia, Lima, Perú
| | - Yordi Tarazona-Castro
- School of Medicine, Research and Innovation Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru.,Laboratorio de Biologia Molecular, Instituto de Investigación Nutricional, Lima, Peru
| | - Sungmin Kym
- Division of Infectious Disease, Department of Internal Medicine, Chungnam National University School of Medicine , Daejeon, Korea
| | - Miguel Angel Aguilar-Luis
- School of Medicine, Research and Innovation Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru.,Laboratorio de Biologia Molecular, Instituto de Investigación Nutricional, Lima, Peru
| | - Luis J Del Valle
- Barcelona Research Center for Multiscale Science and Engineering, Departament D'Enginyeria Química, EEBE, Universitat Politècnica de Catalunya (UPC), Barcelona, Spain
| | - Ronald Aquino-Ortega
- School of Medicine, Research and Innovation Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru.,Laboratorio de Biologia Molecular, Instituto de Investigación Nutricional, Lima, Peru
| | - Johanna Martins-Luna
- School of Medicine, Research and Innovation Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru.,Laboratorio de Biologia Molecular, Instituto de Investigación Nutricional, Lima, Peru
| | - Isaac Peña-Tuesta
- School of Medicine, Research and Innovation Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru.,Laboratorio de Biologia Molecular, Instituto de Investigación Nutricional, Lima, Peru
| | | | - Wilmer Silva-Caso
- School of Medicine, Research and Innovation Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru. .,Laboratorio de Biologia Molecular, Instituto de Investigación Nutricional, Lima, Peru.
| |
Collapse
|
|
10
|
Del Valle-Mendoza J, Vasquez-Achaya F, Aguilar-Luis MA, Martins-Luna J, Bazán-Mayra J, Zavaleta-Gavidia V, Silva-Caso W, Carrillo-Ng H, Tarazona-Castro Y, Aquino-Ortega R, Del Valle LJ. Unidentified dengue serotypes in DENV positive samples and detection of other pathogens responsible for an acute febrile illness outbreak 2016 in Cajamarca, Peru. BMC Res Notes 2020; 13:467. [PMID: 33023645 PMCID: PMC7541171 DOI: 10.1186/s13104-020-05318-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 09/28/2020] [Indexed: 02/07/2023] Open
Abstract
Objective To describe the prevalence of dengue virus serotypes, as well as other viral and bacterial pathogens that cause acute febrile illness during an outbreak in Cajamarca in 2016. Results Dengue virus (DENV) was the most frequent etiologic agent detected in 25.8% of samples (32/124), followed by Rickettsia spp. in 8.1% (10/124), Zika virus in 4.8% (6/124), Chikungunya virus 2.4% (3/124) and Bartonella bacilliformis 1.6% (2/124) cases. No positive cases were detected of Oropouche virus and Leptospira spp. DENV serotypes identification was only achieved in 23% of the total positive for DENV, two samples for DENV-2 and four samples for DENV-4. During the 2016 outbreak in Cajamarca—Peru, it was observed that in a large percentage of positive samples for DENV, the infecting serotype could not be determined by conventional detection assays. This represents a problem for the national surveillance system and for public health due to its epidemiological and clinical implications. Other viral and bacterial pathogens responsible for acute febrile syndrome were less frequently identified.
Collapse
Affiliation(s)
- Juana Del Valle-Mendoza
- School of Medicine, Research and Innovation Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Av. San Marcos cuadra 2, Chorrillos, Lima, Peru. .,Laboratorio de Biologia Molecular, Instituto de Investigación Nutricional, Lima, Peru.
| | - Fernando Vasquez-Achaya
- School of Medicine, Research and Innovation Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Av. San Marcos cuadra 2, Chorrillos, Lima, Peru
| | - Miguel Angel Aguilar-Luis
- School of Medicine, Research and Innovation Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Av. San Marcos cuadra 2, Chorrillos, Lima, Peru.,Laboratorio de Biologia Molecular, Instituto de Investigación Nutricional, Lima, Peru
| | - Johanna Martins-Luna
- School of Medicine, Research and Innovation Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Av. San Marcos cuadra 2, Chorrillos, Lima, Peru.,Laboratorio de Biologia Molecular, Instituto de Investigación Nutricional, Lima, Peru
| | - Jorge Bazán-Mayra
- Laboratorio Regional de Cajamarca, Dirección Regional de Salud de Cajamarca (DIRESA), Cajamarca, Peru
| | - Victor Zavaleta-Gavidia
- Laboratorio Regional de Cajamarca, Dirección Regional de Salud de Cajamarca (DIRESA), Cajamarca, Peru
| | - Wilmer Silva-Caso
- School of Medicine, Research and Innovation Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Av. San Marcos cuadra 2, Chorrillos, Lima, Peru.,Laboratorio de Biologia Molecular, Instituto de Investigación Nutricional, Lima, Peru
| | - Hugo Carrillo-Ng
- School of Medicine, Research and Innovation Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Av. San Marcos cuadra 2, Chorrillos, Lima, Peru.,Laboratorio de Biologia Molecular, Instituto de Investigación Nutricional, Lima, Peru
| | - Yordi Tarazona-Castro
- Laboratorio de Biologia Molecular, Instituto de Investigación Nutricional, Lima, Peru.,Escuela Profesional de Genética y Biotecnología. Facultad de Ciencias Biológicas, Universidad Nacional Mayor de San Marcos, Lima, Peru
| | - Ronald Aquino-Ortega
- School of Medicine, Research and Innovation Center of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Av. San Marcos cuadra 2, Chorrillos, Lima, Peru.,Laboratorio de Biologia Molecular, Instituto de Investigación Nutricional, Lima, Peru
| | - Luis J Del Valle
- Barcelona Research Center for Multiscale Science and Engineering, Departament D'Enginyeria Química, EEBE, Universitat Politècnica de Catalunya (UPC), Barcelona, Spain.
| |
Collapse
|
|
11
|
Masika MM, Korhonen EM, Smura T, Uusitalo R, Vapalahti K, Mwaengo D, Jääskeläinen AJ, Anzala O, Vapalahti O, Huhtamo E. Detection of dengue virus type 2 of Indian origin in acute febrile patients in rural Kenya. PLoS Negl Trop Dis 2020; 14:e0008099. [PMID: 32126086 PMCID: PMC7069648 DOI: 10.1371/journal.pntd.0008099] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Revised: 03/13/2020] [Accepted: 01/29/2020] [Indexed: 01/25/2023] Open
Abstract
Dengue virus (DENV) has caused recent outbreaks in coastal cities of Kenya, but the epidemiological situation in other areas of Kenya is largely unknown. We investigated the role of DENV infection as a cause of acute febrile disease in non-epidemic settings in rural and urban study areas in Kenya. Altogether, 560 patients were sampled in 2016–2017 in rural Taita–Taveta County (n = 327) and urban slums of Kibera, Nairobi (n = 233). The samples were studied for DENV IgM, IgG, NS1 antigen and flaviviral RNA. IgG seroprevalence was found to be higher in Taita–Taveta (14%) than in Nairobi (3%). Five Taita–Taveta patients were positive for flaviviral RNA, all identified as DENV-2, cosmopolitan genotype. Local transmission in Taita–Taveta was suspected in a patient without travel history. The sequence analysis suggested that DENV-2 strains circulating in coastal and southern Kenya likely arose from a single introduction from India. The molecular clock analyses dated the most recent ancestor to the Kenyan strains a year before the large 2013 outbreak in Mombasa. After this, the virus has been detected in Kilifi in 2014, from our patients in Taita–Taveta in 2016, and in an outbreak in Malindi in 2017. The results highlight that silent transmission occurs between epidemics and also affects rural areas. More information is needed to understand the local epidemiological characteristics and future risks of dengue in Kenya. Dengue virus (DENV) is an emerging mosquito-borne global health threat in the tropics and subtropics. The majority of the world’s population live in areas at risk of dengue that can cause a wide variety of symptoms from febrile illness to haemorrhagic fever. Information of DENV in Africa is limited and fragmented. In Kenya, dengue is a recognized disease in coastal cities that have experienced recent outbreaks. We investigated the role of DENV infection as a cause of acute febrile disease in non-epidemic settings in rural and urban study areas in Kenya. We found DENV-2 in five febrile patients from rural Taita–Taveta, where no dengue has been reported before. Genetic analysis of the virus suggests it to be most likely of Indian origin. This Indian origin DENV-2 was detected in the Mombasa outbreak in 2013, in Kilifi in 2014, in Taita–Taveta in 2016 (our study samples) and again in the Malindi outbreak in 2017. The results suggest that dengue is unrecognized in rural Kenya and more studies are needed for local risk assessment. Our findings of virus transmission between epidemics contribute to better understanding of the epidemiological situation and origins of DENV in Kenya.
Collapse
Affiliation(s)
- Moses Muia Masika
- Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya
- KAVI Institute of Clinical Research, University of Nairobi, Nairobi, Kenya
| | - Essi M. Korhonen
- Department of Virology, Medicum, University of Helsinki, Helsinki, Finland
- Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland
- * E-mail:
| | - Teemu Smura
- Department of Virology, Medicum, University of Helsinki, Helsinki, Finland
| | - Ruut Uusitalo
- Department of Virology, Medicum, University of Helsinki, Helsinki, Finland
- Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland
- Department of Geosciences and Geography, University of Helsinki, Helsinki, Finland
| | - Katariina Vapalahti
- Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland
| | - Dufton Mwaengo
- Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya
- Institute of Tropical and Infectious Diseases, University of Nairobi, Nairobi, Kenya
| | - Anne J. Jääskeläinen
- Department of Virology, Medicum, University of Helsinki, Helsinki, Finland
- Department of Virology and Immunology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Omu Anzala
- Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya
- KAVI Institute of Clinical Research, University of Nairobi, Nairobi, Kenya
| | - Olli Vapalahti
- Department of Virology, Medicum, University of Helsinki, Helsinki, Finland
- Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland
- Department of Virology and Immunology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Eili Huhtamo
- Department of Virology, Medicum, University of Helsinki, Helsinki, Finland
- Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland
| |
Collapse
|
|
12
|
Martins-Luna J, Del Valle-Mendoza J, Silva-Caso W, Sandoval I, Del Valle LJ, Palomares-Reyes C, Carrillo-Ng H, Peña-Tuesta I, Aguilar-Luis MA. Oropouche infection a neglected arbovirus in patients with acute febrile illness from the Peruvian coast. BMC Res Notes 2020; 13:67. [PMID: 32041646 PMCID: PMC7011230 DOI: 10.1186/s13104-020-4937-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Accepted: 02/03/2020] [Indexed: 02/04/2023] Open
Abstract
Objective To evaluate the frequency of infection caused by the Oropouche virus (OROV) in 496 patients with acute febrile disease (AFI), whose samples were obtained for the analysis of endemic arboviruses in a previous investigation carried out in 2016. Results OROV was detected in 26.4% (131/496) of serum samples from patients with AFI. Co-infections with Dengue virus (7.3%), Zika virus (1.8%) and Chikungunya (0.2%) were observed. The most common clinical symptoms reported among the patients with OROV infections were headache 85.5% (112/131), myalgia 80.9% (106/131), arthralgia 72.5% (95/131) and loss of appetite 67.9% (89/131). Headache and myalgia were predominant in all age groups. Both OROV infections and co-infections were more frequent in May, June and July corresponding to the dry season of the region.
Collapse
Affiliation(s)
- Johanna Martins-Luna
- Research and Innovation Centre of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Av. San Marcos Cuadra 2, Chorrillos, Lima, Peru
| | - Juana Del Valle-Mendoza
- Research and Innovation Centre of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Av. San Marcos Cuadra 2, Chorrillos, Lima, Peru. .,School of Medicine, Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru. .,Laboratorio de Biología Molecular, Instituto de Investigación Nutricional, Lima, Peru.
| | - Wilmer Silva-Caso
- Research and Innovation Centre of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Av. San Marcos Cuadra 2, Chorrillos, Lima, Peru.,School of Medicine, Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru.,Laboratorio de Biología Molecular, Instituto de Investigación Nutricional, Lima, Peru.,Comité del Médico Joven-Consejo Nacional, Colegio Médico del Perú, Lima, Peru
| | - Isabel Sandoval
- Red de Salud de Morropón Chulucanas, Dirección Regional de Salud de Piura (DIRESA-Piura), Piura, Peru
| | - Luis J Del Valle
- Barcelona Research Center for Multiscale Science and Engineering, Departament d'Enginyeria Química, EEBE, Barcelona Universitat Politècnica de Catalunya (UPC), Barcelona, Spain
| | - Carlos Palomares-Reyes
- Research and Innovation Centre of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Av. San Marcos Cuadra 2, Chorrillos, Lima, Peru.,School of Medicine, Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru
| | - Hugo Carrillo-Ng
- Research and Innovation Centre of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Av. San Marcos Cuadra 2, Chorrillos, Lima, Peru.,Laboratorio de Biología Molecular, Instituto de Investigación Nutricional, Lima, Peru
| | - Isaac Peña-Tuesta
- Research and Innovation Centre of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Av. San Marcos Cuadra 2, Chorrillos, Lima, Peru
| | - Miguel Angel Aguilar-Luis
- Research and Innovation Centre of the Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Av. San Marcos Cuadra 2, Chorrillos, Lima, Peru. .,School of Medicine, Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru. .,Laboratorio de Biología Molecular, Instituto de Investigación Nutricional, Lima, Peru.
| |
Collapse
|
|
13
|
Zhang AZ, Negoescu D, Munoz-Zanzi C. When and what to test for: A cost-effectiveness analysis of febrile illness test-and-treat strategies in the era of responsible antibiotic use. PLoS One 2020; 15:e0227409. [PMID: 31914143 PMCID: PMC6948826 DOI: 10.1371/journal.pone.0227409] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Accepted: 12/18/2019] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Febrile illness caused by viral and bacterial diseases (e.g., dengue and leptospirosis) often have similar symptoms and are difficult to differentiate without diagnostic tests. If not treated appropriately, patients may experience serious complications. The question of what diagnostic tests to make available to providers in order to inform antibiotic therapy remains an open problem for health services facing limited resources. METHODS AND FINDINGS We formulated the problem of minimizing the weighted average of antibiotic underuse and overuse to inform the optimal diagnostic test and antibiotic treatment options for given occurrence probabilities of several bacterial and viral infections. We modeled the weight of antibiotic overuse as a monetary penalty per unnecessarily administered course, which we varied in both the base case and sensitivity analysis. Detailed Markov cohort models of febrile illness progression were used to estimate the weight of antibiotic underuse. The model accounted for multiple infections simultaneously and incorporated test, treatment, and other direct and indirect costs, as well as the effect of delays in seeking care and test turnaround times. We used the Markov models to numerically estimate disability-adjusted life years (DALYs), pre-penalty costs, and likelihood of antibiotics overuse per patient for fifteen different strategies in two example settings in Thailand, one with a higher probability of bacterial infections (Northern Thailand, Scenario A) and one with a higher probability of viral infections (Bangkok, Scenario B). We found that empirical antibiotic treatment to all patients always incurs the lowest pre-penalty cost (Scenario A: $47.5/patient, $100.6/patient, $149.5/patient for patients seeking care on day one, day four, and day ten respectively; Scenario B: $94.1/patient, $108.7/patient, $122.1/patient on day one, day four, and day ten respectively), and the lowest DALYs, (Scenario A: 0.2 DALYs/patient, 0.9 DALYs/patient, 1.7 DALYs/patient on day one, day four, and day ten, respectively; Scenario B: 0.5 DALYs/patient, 0.7 DALYs/patient, 0.9 DALYs/patient on day one, day four, and day ten, respectively). However, such strategy resulted in the highest proportion of antibiotic overuse per patient (Scenario A: 38.1%, 19.3%, 7.5% on day one, day four, and day ten, respectively; Scenario B: 82.9%, 42.1%, 16.3% on day one, day four, and day ten, respectively). Consequently, empirical antibiotic treatment became suboptimal with antibiotic overuse penalties above $12,800/course, $18,400/course, $23,900/course for patients presenting on day one, day four, and day ten in Scenario A and above $1,100/course, $1,500/course, $1,600/course for patients presenting on day one, day four, and day ten in Scenario B. CONCLUSIONS Empirical antibiotic treatment to all patients provided the best outcomes if antibiotic overuse was not the primary concern or if presenting with viral disease (such as dengue) was unlikely. Empirical antibiotic treatment to severe patients only was in most cases not beneficial. Otherwise, strategies involving diagnostic tests became optimal. In particular, our results indicated that single test strategies (bacterial RDT or viral PCR) were optimal in regions with a greater probability of presenting with viral infection. PCR-led strategies (e.g., parallel bacterial PCR, or multiplex PCR) are robust under parameter uncertainty (e.g., with uncertain disease occurrence probabilities).
Collapse
Affiliation(s)
- Anthony Zhenhuan Zhang
- College of Science and Engineering, Industrial and System Engineering, University of Minnesota, Minneapolis, Minnesota, United States of America
- * E-mail: (AZZ); (CMZ)
| | - Diana Negoescu
- College of Science and Engineering, Industrial and System Engineering, University of Minnesota, Minneapolis, Minnesota, United States of America
| | - Claudia Munoz-Zanzi
- School of Public Health, Division of Environmental Health Sciences, University of Minnesota, Minneapolis, Minnesota, United States of America
- * E-mail: (AZZ); (CMZ)
| |
Collapse
|
|
14
|
Rhee C, Kharod GA, Schaad N, Furukawa NW, Vora NM, Blaney DD, Crump JA, Clarke KR. Global knowledge gaps in acute febrile illness etiologic investigations: A scoping review. PLoS Negl Trop Dis 2019; 13:e0007792. [PMID: 31730635 PMCID: PMC6881070 DOI: 10.1371/journal.pntd.0007792] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Revised: 11/27/2019] [Accepted: 09/18/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Acute febrile illness (AFI), a common reason for people seeking medical care globally, represents a spectrum of infectious disease etiologies with important variations geographically and by population. There is no standardized approach to conducting AFI etiologic investigations, limiting interpretation of data in a global context. We conducted a scoping review to characterize current AFI research methodologies, identify global research gaps, and provide methodological research standardization recommendations. METHODOLOGY/FINDINGS Using pre-defined terms, we searched Medline, Embase, and Global Health, for publications from January 1, 2005-December 31, 2017. Publications cited in previously published systematic reviews and an online study repository of non-malarial febrile illness etiologies were also included. We screened abstracts for publications reporting on human infectious disease, aimed at determining AFI etiology using laboratory diagnostics. One-hundred ninety publications underwent full-text review, using a standardized tool to collect data on study characteristics, methodology, and laboratory diagnostics. AFI case definitions between publications varied: use of self-reported fever as part of case definitions (28%, 53/190), fever cut-off value (38·0°C most commonly used: 45%, 85/190), and fever measurement site (axillary most commonly used: 19%, 36/190). Eighty-nine publications (47%) did not include exclusion criteria, and inclusion criteria in 13% (24/190) of publications did not include age group. No publications included study settings in Southern Africa, Micronesia & Polynesia, or Central Asia. We summarized standardized reporting practices, specific to AFI etiologic investigations that would increase inter-study comparability. CONCLUSIONS Wider implementation of standardized AFI reporting methods, with multi-pathogen disease detection, could improve comparability of study findings, knowledge of the range of AFI etiologies, and their contributions to the global AFI burden. These steps can guide resource allocation, strengthen outbreak detection and response, target prevention efforts, and improve clinical care, especially in resource-limited settings where disease control often relies on empiric treatment. PROSPERO: CRD42016035666.
Collapse
Affiliation(s)
- Chulwoo Rhee
- Division of Global Health Protection, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Grishma A. Kharod
- Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Disease, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Nicolas Schaad
- Division of Global Health Protection, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Nathan W. Furukawa
- Department of Medicine, University of Washington, Seattle, Washington, United States of America
| | - Neil M. Vora
- Division of Global Health Protection, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - David D. Blaney
- Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Disease, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - John A. Crump
- Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, North Carolina, United States of America
- Centre for International Health, University of Otago, New Zealand
| | - Kevin R. Clarke
- Division of Global Health Protection, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| |
Collapse
|
|
15
|
Rao PN, van Eijk AM, Choubey S, Ali SZ, Dash A, Barla P, Oraon RR, Patel G, Nandini P, Acharya S, Mohanty S, Carlton JM, Satpathi S. Dengue, chikungunya, and scrub typhus are important etiologies of non-malarial febrile illness in Rourkela, Odisha, India. BMC Infect Dis 2019; 19:572. [PMID: 31269906 PMCID: PMC6607595 DOI: 10.1186/s12879-019-4161-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Accepted: 06/04/2019] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND We conducted a diagnostic surveillance study to identify Plasmodium, dengue virus, chikungunya virus, and Orientia tsutsugamushi infections among febrile patients who underwent triage for malaria in the outpatient department at Ispat General Hospital, Rourkela, Odisha, India. METHODS Febrile patients were enrolled from January 2016-January 2017. Blood smears and small volumes or vacutainers of blood were collected from study participants to carry out diagnostic assays. Malaria was diagnosed using rapid diagnostic tests (RDT), microscopy, and PCR. Dengue, chikungunya, and scrub typhus infections were identified using rapid diagnostic test kits and ELISA. RESULTS Nine hundred and fifty-four patients were prospectively enrolled in our study. The majority of patients were male (58.4%) and more than 15 years of age (66.4%). All 954 enrollees underwent additional testing for malaria; a subset of enrollees (293/954) that had larger volumes of plasma available was also tested for dengue, chikungunya and scrub typhus by either RDT or ELISA or both tests. Fifty-four of 954 patients (5.7%) were positive for malaria by RDT, or microscopy, or PCR. Seventy-four of 293 patients (25.3%) tested positive for dengue by either RDT or ELISA, and 17 of 293 patients (5.8%) tested positive for chikungunya-specific IgM by either ELISA or RDT. Ten of 287 patients tested (3.5%) were positive for scrub typhus by ELISA specific for scrub typhus IgM. Seventeen patients among 290 (5.9%) with results for ≥3 infections tested positive for more than one infection. Patients with scrub typhus and chikungunya had high rates of co-infection: of the 10 patients positive for scrub typhus, six were positive for dengue (p = 0.009), and five of 17 patients positive for chikungunya (by RDT or ELISA) were also diagnosed with malaria (p < 0.001). CONCLUSIONS Dengue, chikungunya and scrub typhus are important etiologies of non-malarial febrile illness in Rourkela, Odisha, and comorbidity should be considered. Routine febrile illness surveillance is required to accurately establish the prevalence of these infections in this region, to offer timely treatment, and to implement appropriate methods of control.
Collapse
Affiliation(s)
- Pavitra N Rao
- Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY, USA.,, Present Address: Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA
| | - Anna Maria van Eijk
- Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY, USA
| | - Sandhya Choubey
- Center for the Study of Complex Malaria in India, Ispat General Hospital, Rourkela, Odisha, India
| | - Syed Zeeshan Ali
- Center for the Study of Complex Malaria in India, Ispat General Hospital, Rourkela, Odisha, India
| | - Aditee Dash
- Center for the Study of Complex Malaria in India, Ispat General Hospital, Rourkela, Odisha, India
| | - Punam Barla
- Center for the Study of Complex Malaria in India, Ispat General Hospital, Rourkela, Odisha, India
| | - Rajshri Rani Oraon
- Center for the Study of Complex Malaria in India, Ispat General Hospital, Rourkela, Odisha, India
| | - Gautam Patel
- Center for the Study of Complex Malaria in India, Ispat General Hospital, Rourkela, Odisha, India
| | - P Nandini
- Center for the Study of Complex Malaria in India, Ispat General Hospital, Rourkela, Odisha, India
| | - Subrata Acharya
- Center for the Study of Complex Malaria in India, Ispat General Hospital, Rourkela, Odisha, India
| | - Sanjib Mohanty
- Center for the Study of Complex Malaria in India, Ispat General Hospital, Rourkela, Odisha, India
| | - Jane M Carlton
- Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY, USA.
| | | |
Collapse
|
|
16
|
Wise EL, Pullan ST, Márquez S, Paz V, Mosquera JD, Zapata S, Jackson SK, Fejer G, Trueba G, Logue CH. Isolation of Oropouche Virus from Febrile Patient, Ecuador. Emerg Infect Dis 2019; 24:935-937. [PMID: 29664378 PMCID: PMC5938787 DOI: 10.3201/eid2405.171569] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
We report identification of an Oropouche virus strain in a febrile patient from Ecuador by using metagenomic sequencing and real-time reverse transcription PCR. Virus was isolated from patient serum by using Vero cells. Phylogenetic analysis of the whole-genome sequence showed the virus to be similar to a strain from Peru.
Collapse
|