High burden of cryptococcal antigenemia and meningitis among patients presenting at an emergency department in Maputo, Mozambique

Deiss, Robert; Loreti, Carolina V; Gutiérrez, Ana García; Filipe, Eudoxia; Tatia, Milton; Issufo, Sheila; Ciglenečki, Iza; Loarec, Anne; Vivaldo, Henriques; Barra, Carmen; Siufi, Carolina; Molfino, Lucas; Antabak, Natalia Tamayo

doi:10.1371/journal.pone.0250195

Cited by 10 publications

(16 citation statements)

References 30 publications

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“…Results of this study show that Cryptococcus neoformans is responsible for 38.6% of all laboratory-confirmed cases, thus making it the leading cause of meningitis among adults. These are similar to previously reported findings from other Sub-Saharan African countries, having found frequencies ranging from 60.5% to 71.6% [ 1 , 11 , 16 , 33 – 38 ].…”

Section: Discussionsupporting

confidence: 92%

“…We also investigated predictors for meningitis in adults in Mozambique and found that CD4 cell count < 100 cells/μL had strong association (aOR = 59, p = 0.001) with meningitis, as also reported in other countries [ 1 , 11 , 13 , 49 – 51 , 54 – 61 ].…”

Section: Discussionsupporting

confidence: 55%

“…In sub-Saharan Africa, the region which is most affected by HIV worldwide, co-occurrence with meningitis is common [ 1 , 5 , 10 ]. The HIV infection has contributed to modifications in the aetiological profile of adulthood meningitis in African countries, including Mozambique [ 1 , 10 , 11 ], where Cryptococcus neoformans and Mycobacterium tuberculosis have become common causes of meningitis in adults living with HIV [ 11 – 19 ]. However, despite the improvement in the access to combined antiretroviral therapy (ART), mortality due to meningitis remains high [ 11 – 19 ].…”

Section: Introductionmentioning

confidence: 99%

“…The HIV infection has contributed to modifications in the aetiological profile of adulthood meningitis in African countries, including Mozambique [ 1 , 10 , 11 ], where Cryptococcus neoformans and Mycobacterium tuberculosis have become common causes of meningitis in adults living with HIV [ 11 – 19 ]. However, despite the improvement in the access to combined antiretroviral therapy (ART), mortality due to meningitis remains high [ 11 – 19 ]. The sub-optimal ART coverage and retention on ART in the African continent [ 20 ] are major causes of the high burden of meningitis in adults.…”

Section: Introductionmentioning

confidence: 99%

“…In case of cephalosporin-resistant strains, treatment regimens consist of the use of the aforementioned cephalosporins combined with vancomycin 15–20 mg/Kg IV and 600 mg of rifampicin IV/orally 12 hourly, both for 7 to 14 days, twice a day. Current protocols for treatment of cryptococcal meningitis among patients living with HIV include the use of Amphotericin B and oral Flucytosine for seven days, followed by another week of administration of either orally or intravenous infusion Fluconazole [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Etiology of meningitis among adults in three quaternary hospitals in Mozambique, 2016–2017: The role of HIV

et al. 2022

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Background Meningitis remains an important cause of morbi-mortality in adults in sub-Saharan Africa. Data on the etiological investigation of meningitis in adults in Mozambique is limited and most studies were conducted in southern Mozambique. Identification of the etiology of meningitis in adults are crucial to guide prevention and treatments strategies. In this study, we determine the burden of fungal and bacterial meningitis among adults at the three largest hospitals in Mozambique. Method We performed analysis of data from the routine sentinel surveillance system for meningitis in Mozambique from January 2016 to December 2017. Cerebrospinal fluid (CSF) samples were collected from eligible adults (≥18 years old) who met World Health Organization (WHO) case definition criteria for Meningitis. All samples were tested by cryptococcal antigen (CrAg) lateral flow assay (LFA), culture and triplex real-time polymerase chain reaction (qPCR) assay and all patients were tested for human immunodeficiency virus (HIV) using the national algorithm for HIV testing. Results Retrospective analysis of 1501 CSF samples from adults clinically suspected of meningitis revealed that 10.5% (158/1501) were positive for bacterial and fungal meningitis. Of these 158 confirmed cases, the proportion of Cryptococcal meningitis and pneumococcal meningitis was38.6% (95% CI: 31.0% to 46.7%) and 36.7% (95% CI: 29.2% to 44.7%), respectively. The other bacterial agents of meningitis identified include Neisseria meningitidis (8.9%; 14/158), Escherichia coli (6.3%; 10/158), Haemophilus influenzae (5.1%; 8/158) and S. aureus (4.4%; 7/158), which represent (24.7%; 39/158) of the total confirmed cases. Conclusion Altogether, our findings show a high burden of Cryptococcal meningitis among adults in Mozambique, especially in people living with HIV, followed by pneumococcal meningitis. Our findings suggest that rollout of CrAg Lateral Flow Assay in the health system in Mozambique for early detection of cryptococcus neoformans is necessary to improve overall patient care.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Etiology of meningitis among adults in three quaternary hospitals in Mozambique, 2016–2017: The role of HIV

et al. 2022

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Divergent Neuroimmune Signatures in the Cerebrospinal Fluid Predict Differential Gender-Specific Survival Among Patients With HIV-Associated Cryptococcal Meningitis

Okurut

Boulware

Okafor

et al. 2023

Preprint

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Survival among people with HIV-associated cryptococcal meningitis (CM) remains low, exceptionally among women with the increased threat of death on the current optimal use of antifungal drugs. Cryptococcus dissemination into the central nervous system (CNS) prompts a neuroimmune reaction to activate pathogen-concomitant factors. However, no consistent diagnostic or prognostic immune-mediated signature is reported to underpin the risk of death or mechanism to improve treatment or survival. We theorized that the distinct neuroimmune cytokine or chemokine signatures in the cerebrospinal fluid (CSF), distinguish survivors from people who died on antifungal treatment, who may benefit from tailored therapy. We considered the baseline clinical disease features, cryptococcal microbiologic factors, and CSF neuroimmune modulated signatures among 419 consenting adults by gender (biological sex assigned at birth) (168 females and 251 males) by 18 weeks of survival on antifungal management. Survival at 18 weeks was inferior among females than males (47% vs. 59%; hazard ratio HR=1.4, 95% CI: 1.0 to 1.9, and p=0.023). Unsupervised principal component analysis (PCA) demonstrated the divergent neuroimmune signatures by gender, survival, and intragender-specific survival. Overall, females displayed lower levels of PD-L1, IL-1RA, and IL-15 than males (all p<=0.028). Female survivors compared with those who died, expressed significant fold elevations in levels of CSF (CCL11 - myeloid and CXCL10 - lymphoid chemokine (in both p=0.001), and CSF Th1, Th2, and Th17 cytokines. In contrast, male survivors expressed distinctly lower levels of CSF IL-15 and IL-8 compared with those who died. Survivors of either gender demonstrated a significant increase in the levels of immune regulatory element, IL-10. In the finale, we classified divergent neuroimmune key signatures in CSF by gender, survival, and intragender-specific survival among people with HIV-associated cryptococcal meningitis. These intragender-specific survival-associated neuroimmune signatures suggest the discrete role of gender immune regulating mechanisms as the possible targets for interventions to advance therapy to improve survival among people with HIV-associated cryptococcal meningitis.

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Management and outcome of intracranial fungal infections in children and adults in Africa: a scoping review

Takoutsing,

Ooi,

Egu

et al. 2024

BMC Infect Dis

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Introduction Intracranial fungal infections’ (IcFIs) varying clinical manifestations lead to difficulties in diagnosis and treatment. African populations are disproportionately affected by the high burden of the disease. There is a lack of clarity as to the diagnostic and treatment modalities employed across the continent. In this review, we aim to detail the management, and outcome of IcFIs across Africa. Methods This scoping review was conducted using the Arksey and O'Malley framework. MEDLINE, EMBASE, Cochrane Library, African Index Medicus, and African Journals Online were searched for relevant articles from database inception to August 10th, 2021. The Preferred Reporting Items for Systematic Review and Meta-Analysis extension for Scoping Reviews guidelines were used to report the findings of the review. Results Of the 5,779 records identified, 131 articles were included. The mean age was 35.6 years, and the majority (56.4%) were males. The majority ( n = 8,433/8,693, 97.0%) of IcFIs presented as a meningitis, the most common communicable predisposing factor of IcFIs was HIV/AIDS ( n = 7,815/8,693, 89.9%), and the most common non-communicable risk factor was diabetes mellitus ( n = 32/8,693, 0.4%). Cryptococcus species was the most common ( n = 8,428/8,693, 97.0%) causative organism. The most commonly used diagnostic modality was cerebrospinal (CSF) cultures ( n = 4,390/6,830, 64.3%) for diffuse IcFIs, and MRI imaging (n = 12/30, 40%) for focal IcFIs. The most common treatment modality was medical management with antifungals only ( n = 4,481/8,693, 51.6%). The most commonly used antifungal agent in paediatric, and adult patients was amphotericin B and fluconazole dual therapy (51.5% vs 44.9%). The overall mortality rate was high ( n = 3,475/7,493, 46.3%), and similar for both adult and paediatric patients (47.8% vs 42.1%). Conclusion Most IcFIs occurred in immunosuppressed individuals, and despite the new diagnostic techniques, CSF culture was mostly used in Africa. Antifungals regimens used was similar between children and adults. The outcome of IcFIs in Africa was poor for both paediatric and adult patients. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-024-09694-2.

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High burden of cryptococcal antigenemia and meningitis among patients presenting at an emergency department in Maputo, Mozambique

Cited by 10 publications

References 30 publications

Etiology of meningitis among adults in three quaternary hospitals in Mozambique, 2016–2017: The role of HIV

Etiology of meningitis among adults in three quaternary hospitals in Mozambique, 2016–2017: The role of HIV

Divergent Neuroimmune Signatures in the Cerebrospinal Fluid Predict Differential Gender-Specific Survival Among Patients With HIV-Associated Cryptococcal Meningitis

Management and outcome of intracranial fungal infections in children and adults in Africa: a scoping review

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