Uptake of lumbar puncture and mortality among patients with advanced human immunodeficiency virus disease who screened for serum cryptococcal-antigen in Africa

Table 1 Context descriptions of included studies

Ref.	Study setting and population	Number of sites	Country guidelines at the time of screening	Reasons for not performing LP	Design and data sources	Quality assessment
Boyd et al[39], 2022	Adults ≥ 18 years with AHD based on CD4 < 200 cells/mm3 in Zimbabwe	Multiple sites	ART-naïve people with HIV were required to have CD4 count measurement and CrAg screening if CD4 count is ≤ 200 cells/mm3	Undocumented	Cross-sectional study evaluated diagnostic accuracy of point of care finger prick whole blood compared with laboratory-based serum antigen testing	7
Blasich et al[40], 2021	Adults ≥ 18 years with AHD based on CD4 < 100 cells/mm3 in South Africa. Identified during routine laboratory reflex screening	Multiple sites involving Helen Joseph and Tambo Memorial hospitals in South Africa	ART-naïve people with HIV were required to have CD4 count measurement and CrAg screening if CD4 count is ≤ 100 cells/mm3	Undocumented	Prospective cohort study evaluated laboratory tests to quantify the amount of CrAg in plasma of patients with AHD and to gauge the risk of CM	8
Longley et al[15], 2016	ART-naive patients with no prior history of cryptococcal disease, aged > 18 years, and with a CD4 cell count ≤ 100 cells/μL in South Africa	Two ART clinics in Cape Town, South Africa	ART-naïve people with HIV were required to have CD4 count measurement and CrAg screening if CD4 count is ≤ 100 cells/mm3	Refusals	Prospective cohort with patients being followed for a period of one year to determine mortality among CrAg positive and negative individuals	9
Enock et al[41], 2022	All people living with HIV who receive routine HIV care from facilities of different administrative level in five districts (2-Urban and 3-Rural) in Uganda	Fourteen facilities. The fourteen health facilities (six health center level three, three health center level four, three general referral hospitals, and two regional referral hospitals)	ART-naïve people with HIV were required to have CD4 count measurement and CrAg screening if CD4 count is ≤ 100 cells/mm3. Routine assessment with provider initiated	Attending rural facilities translating to training gaps and resources	Retrospective review of medical records from CD4 and CrAg registers standard Uganda Ministry of Health (MoH) tools that are used for documentation and generation of routine performance reports	9
Tiam et al[42], 2023	Enrolled 15 years or older people with AHD (CD4 < 200 cells/mm3 or WHO stage III/IV)	Two largest hospitals ART clinics at the Motebang and Berea District. The hospital serves one-third of Lesotho’s population	Same-day serum CrAg screening test for all patients enrolling in care with CD4 count < 200 cells/mm3. Routine assessment with provider initiated	Undocumented	Prospective evaluation of routinely collected data from ART clinics. Follow up 6 months	8
Blankley et al[29], 2019	Enrolled 19 years or older ART naïve people with AHD (CD4 < 200 cells/mm3 or WHO stage III/IV) at a semi-urban polyclinic in Epworth, Zimbabwe	Single site study at Epworth polyclinic (a nurse led with support from Me´decins Sans Frontières and Ministry of Health doctors	From 2015, recommended CrAg screening for those with CD4 < 100 cells/mm3. Routine assessment with provider initiated	Undocumented	Retrospective assessment of outcomes and management of patients with AHD	9
Heller et al[30], 2022	In patient evaluation of AHD management practices at a tertiary hospital in Malawi	Single site at Kamuzu Central Hospital. A tertiary hospital located in Lilongwe	2017: Recommended CrAg screening for those with CD4 < 100 cells/mm3. 2020: Recommended CrAg screening for those with CD4 < 200 cells/mm3. Routine assessment with provider initiated	Undocumented	Evaluation of outcome for patients with AHD using routinely collected data	9
Kanyama et al[31], 2022	Enrolled 14 years or older in patients from a tertiary hospital. AHD diagnosis based on CD4 < 200 cells/mm3	Single site at Kamuzu Central Hospital. A tertiary hospital located in Lilongwe	Between 1 August 2016 and 31 January 2017, CD4 cell count, urine lipoarabinomannan, urine X-pert and CrAg screening services for management of AHD were introduced. Routine assessment with provider initiated	Undocumented	Prospective evaluation of routinely collected data from medical wards among patients with AHD	8
Hurt et al[17], 2021	Tested laboratory samples for patients with AHD based on CD4 count < 100 cells/mm3	Data from 27 ART clinics and one central referral hospital in Botswana	Recommended CrAg screening for those with CD4 ≤ 100 cells/mm3. An evaluation of laboratory reflex CrAg screening	Undocumented	Evaluation of data from the Botswana. Harvard HIV reference laboratory	8
Deiss et al[32], 2021	People with AHD CD4 < 200 cells/mm3	Enrolled from Jose Macamo General Hospital, a tertiary hospital in Mozambique	Recommended CrAg screening for those with CD4 ≤ 200 cells/mm3	Undocumented	Retrospective review of routinely collected clinical data	9
Braide et al[43], 2023	People with AHD (CD4 < 200 cells/mm3 or WHO stage III/IV)	28 healthcare facilities across 4 high-burden states in Nigeria	Recommended CrAg screening for those with AHD	Limited/lack of LP packs	Newly identified PLHIV were screened for AHD. Those with AHD were screened for Tuberculosis and CM	8
Bornstein et al[33], 2014	HIV patients with CD4 < 100 cells/mm3	Single site Tertiary Tikur Anbessa Hospital in Addis Ababa	CrAg screening for those with CD4 ≤ 100 cells/mm3	Undocumented	Diagnostic evaluation between point of care finger stick and serum lateral flow assay	8
Faini et al[18], 2019	Newly diagnosed PLHIV, ART-naïve adults ≥ 18 years-old, with CD4 < 150 cells/mm3	Kilombero and Ulanga Antiretroviral Cohort involves patients attending Saint Francis Referral Hospital in Tanzania	CrAg screening for those with CD4 ≤ 100 cells/mm3. Routine laboratory-reflex CrAg screening	Undocumented	Prospective cohort to determine mortality among CrAg positive and negative individuals	9
Ndayishimiye et al[44], 2018	PLHIV with CD4 < 100 cells/mm3	17 clinics and one hospital (Prince Mshiyeni Memorial Hospital) in South Africa	CrAg screening for those with CD4 ≤ 100 cells/mm3. Routine laboratory-reflex CrAg screening	Undocumented	Retrospective review of National Laboratory data and medical record charts	7
Temfack et al[34], 2018	HIV-infected, ART naïve ambulatory adults (> 18 years) CD4 < 100 cells/mm3, no history of CM	Day Hospital of the Yaoundé Central Hospital in Cameroon. A tertiary hospital	CrAg screening for those with CD4 ≤ 100 cells/mm3	Undocumented	Prospective cohort with 1 year of follow up to demine incidence of cryptococcal meningitis and mortality	7
Mamuye et al[20], 2016	People living with HIV admitted at Tikur Anbessa	Tikur Anbessa (Black Lion) Hospital in Addis Ababa, a tertiary hospital	CrAg screening for those with CD4 ≤ 100 cells/mm3	All CrAg positive patients underwent LP	Cross-sectional study to determine prevalve of CrAg	8
Pac et al[35], 2015	Adults PLHIV with CD4 < 250 cells/mm3, but we reported those with CD < 200 cells/mm3	Kiboga District Hospital HIV clinic, a rural government hospital	CrAg screening for those with CD4 ≤ 200 cells/mm3. Routine provider-initiated screening	Refusals	Prospective cohort to ascertain new cases of meningitis and mortality	8
Nalintya et al[45], 2018	Adults living with HIV with CD4 < 9 cells/mm3	11 HIV clinics in Kampala	CrAg screening for those with CD4 ≤ 200 cells/mm3	Refusals	Prospective cohort study of HIV-infected patients to determine mortality	9
Oyella et al[36], 2012	Adults living with HIV with CD4 < 9 cells/mm3, no prior history of cryptococcal disease, not receiving fluconazole, both inpatients and outpatients	Mulago Hospital, a tertiary hospital in Uganda	CrAg screening for those with CD4 ≤ 9 cells/mm3	Refusal, comatose	Cross-sectional study to determine prevalence of CrAg antigenemia	9
Ssebambulidde et al[46], 2019	HIV-infected adults who presented with suspected meningitis and consented for LP	Mulago National Referral Hospital and Mbarara Regional Referral Hospital in Uganda	CrAg screening for those with CD4 ≤ 200 cells/mm3	All CrAg positive patients underwent LP	Prospectively consented HIV-infected adults who presented with suspected meningitis to evaluate for the etiology of meningitis	9
Zono et al[47], 2024	Asymptomatic outpatients with AHD (CD4 < 200 cells/mm3	Multiple sites in Kinshasa, Democratic republic of Congo	CrAg screening for those with CD4 ≤ 200 cells/mm3	Undocumented	Cross-sectional study to ascertain prevalence of CrAg and subtypes of Cryptococcal neoformans	9
Eigege et al[48], 2024	PLHIV aged ≥ 10 years newly diagnosed and presenting with a CD4+ cell count < 200 cells/mm3	28 health care facilities in Nigeria	CrAg screening for those with CD4 < 200 cells/mm3	Refusals (30%), lack of LP kits (27%), inability of patients to pay for LP (23%), pre-LP mortality (10%), lack of care worker competence (7%), and loss to follow-up	Programmatic evaluation of the implementation of AHD package of care	8
Smitson et al[21], 2024	ART experienced, CD4 < 200 cells/mm3	Two ART clinics in Addis Ababa	CrAg screening for those with CD4 ≤ 200 cells/mm3	Undocumented	A retrospective study with 12-month of follow up to assess CrAg, mortality, loss to follow up	9
Eric et al[49], 2023	People with AHD (CD4 < 200 cells/mm3 or WHO stage III/IV)	Mbale regional referral hospital and its associated clinics in Uganda	CrAg screening for those with CD4 ≤ 200 cells/mm3 or WHO stage III/IV)	All CrAg positive patients underwent LP	Cross-sectional study to determine prevalence of CrAg	9
Beyene Tufa et al[50], 2017	Adults living with HIV, CD4 < 150 cells/mm3	Adama and Asella hospitals in Ethiopia	CrAg screening for those with CD4 ≤ 200 cells/mm3	All CrAg positive patients underwent LP	Case-control study comparing the 6-month survival outcomes among CrAg positive and negative patients	8
Wajanga et al[37], 2011	Inpatients adults living with HIV, no history of CM, CD4 < 200 cells/mm3	Bugando Medical Center, a tertiary hospital	CrAg screening for those with CD4 ≤ 200 cells/mm3	All CrAg positive patients underwent LP	Prospective cohort to determine prevalence of CrAg	9
Magambo et al[51], 2018	Outpatients adults living with HIV, no history of CM, CD4 < 200 cells/mm3	Bugando Medical Center, a tertiary hospital and Sekoture Regional Hospital	CrAg screening for those with CD4 ≤ 200 cells/mm3	All CrAg positive patients underwent LP	Cross-sectional study to determine prevalence of CrAg	8
Wake et al[52], 2018	16 years or older, PLHIV with CD4 ≤ 9 cells/mm3	17 primary care clinics and 5 hospitals in South Africa	CrAg screening for those with CD4 ≤ 200 cells/mm3. Laboratory reflex screening	Undocumented	Cross-sectional study to establish the prevalence of concurrent CM, and the relationship with blood CrAg titer	8
Wake et al[53], 2020	Adults (18 years or older) PLHIV with CD4 ≤ 9 cells/mm3	Helen Joseph and Tambo Memorial Hospitals in South Africa	CrAg screening for those with CD4 ≤ 200 cells/mm3. Laboratory reflex screening	Not applicable	Prospective cohort study to investigate causes of morbidity and mortality during 6 months of follow-up among CrAg-positive and CrAg-negative	8
Makadzange et al[19], 2021	Adults (18 years or older) PLHIV with CD4 ≤ 9 cells/mm3, both ART naïve and ART experienced	20 outpatient facilities in Harare, Zimbabwe	CrAg screening for those with CD4 ≤ 9 cells/mm3	Refusals	Prospective cohort study to investigate mortality among CrAg-positive and CrAg-negative	9
Blanco-Arévalo et al[54], 2019	ART-naïve or poorly ART-adherent PLHIV (CD4 counts < 200 cells/mm3 or WHO stage III/IV)	Manhiça district, Mozambique	No country policy but the study adopted WHO guideline to screen for CrAg among those with CD4 ≤ 9 cells/mm3	Undocumented	Prospective cohort study to investigate CrAg and mortality	8
Lakoh et al[38], 2020	Patients aged 18 years or older with a CD4. Less than 9 cells/mm3 both inpatients and outpatients	Connaught tertiary adult referral hospital in Freetown, Siera Leone	No country policy but the study adopted WHO guideline to screen for CrAg among those with CD4 ≤ 9 cells/mm3	All CrAg positive patients underwent LP	Prospective cohort study to investigate CrAg and mortality	8

AHD: Advanced human immunodeficiency virus disease; ART: Antiretroviral therapy; CM: Cryptococcal meningitis; CrAg: Cryptococcal antigen; HIV: Human immunodeficiency virus; LP: Lumbar puncture; PLHIV: People living with the human immunodeficiency virus; WHO: World Health Organization.