Clinical Features and Outcome in Adult Cases of Tuberculous Meningitis in Tertiary Care Hospital in Antananarivo, Madagascar

Purpose. We aimed to describe and to assess prognosis factors in tuberculous meningitis in adult patients. Methods. We performed a retrospective study of case records of adult patients. Patients classified as definite, probable, or possible tuberculous meningitis according to standardized definition criteria were included and assessed in the study. Results. Seventy-five patients were included in the study. Tuberculous meningitis was classified as definite in 8 (10.7%), probable in 44 (58.7%), and possible in 23 patients (30.6%). HIV was found in 3% of patients. Patients were in advanced stages at admission in 82.7%. Median duration of symptoms prior to admission was 3 weeks (IQR: 2–5). Median time to diagnosis following admission was 5 days (IQR: 3–8). Median CSF WCC was 75 per mm3 with lymphocytic predominance in 38 cases (52.8%). Median CSF glucose level was 1.48 mmol/L and median CSF protein level was 1 g/L. Mortality rate was 28%. Age ≥ 35 years (aOR: 4.06; 95% CI: 1.16–14.26) and coma (aOR: 12.98; 95% CI: 1.13–149.16) predicted inpatient mortality. Conclusion. Most of the patients experienced more than 3 weeks of diagnostic delay prior to admission. Mortality was high and occurred early after admission. Age and coma were identified as independent prognosis factors

Hospitalization of HIV positive patients in a referral tertiary care hospital in Antananarivo Madagascar, 2010-2016: Trends, causes and outcome.

BACKGROUND:During the last few years, significant efforts have been made to improve access to antiretroviral therapy which led to dramatic reduction in AIDS-related events and mortality in HIV positive patients at the global level. However, current data in Africa suggested modest impact of widespread antiretroviral therapy scale-up especially regarding HIV-related hospitalization. In this study, we aimed to describe causes of hospitalization and factors associated with AIDS-defining events and inpatient mortality. MATERIALS AND METHODS:A retrospective study was performed on medical records of HIV positive patients admitted for at least 24 hours in the Infectious Diseases Unit of the University Hospital Joseph Raseta Befelatanana Antananarivo. Cause of hospitalization was considered as the main diagnosis related to the symptoms at admission. Diagnostic criteria were based on criteria described in WHO guidelines. AIDS-defining events were defined as diseases corresponding to WHO stage 4 or category C of CDC classification. RESULTS:From 2010 to 2016, 236 hospital admissions were included. AIDS-defining events were the most frequent cause of hospitalization (61.9%) with an increasing trend during the study period. Tuberculosis (28.4%), pneumocystis pneumonia (11.4%), cerebral toxoplasmosis (7.2%) and cryptococcosis (5.5%) were the most frequent AIDS-defining events. Tuberculosis was also the most frequent cause of overall hospitalization. In multivariate analysis, recent HIV diagnosis (aOR = 2.0, 95% CI: 1.0-3.9), CD4<200 cells/μl (aOR = 4.0, 95%CI: 1.9-8.1), persistent fever (aOR = 4.4, 95%CI: 2.1-9.0), duration of symptoms≥ 6 weeks (aOR = 2.6, 95%CI: 1.2-5.4) were associated with AIDS-defining events. Overall inpatient mortality was 19.5%. Age≥55 years (aOR = 4.9, 95%CI: 1.5-16.6), neurological signs (aOR = 3.2, 95%CI: 1.5-6.9) and AIDS-defining events (aOR = 2.9, 95%CI: 1.2--7.2) were associated with inpatient mortality. CONCLUSIONS:AIDS-defining events were the most frequent cause of hospitalization during the study period. Factors associated with AIDS-defining events mostly reflected delay in HIV diagnosis. Factors associated with mortality were advanced age, neurological signs and AIDS-defining events

Epidemiological characteristics of cryptococcal meningoencephalitis associated with Cryptococcus neoformans var. grubii from HIV-infected patients in Madagascar: A cross-sectional study

International audienceCryptococcal meningoencephalitis (CM) remains the most prevalent invasive fungal infection worldwide. The main objective of this study was to describe the prevalence of CM and cryptococcal infection in HIV-infected patients in Madagascar. The secondary objectives were to assess the adjusted prevalence of CM according to clinical presentation and patient characteristics, to determine crude 90-day survival according to cryptococcal antigen (CrAg) status and CM, and to identify the genotypes of Cryptococcus clinical isolates. This cross-sectional study was carried out at two urban hospitals in Antananarivo (central highlands) and Toamasina (east coast) between November 2014 and December 2016. Consecutive HIV-infected adults presenting with CD4 cell counts ≤200/μl were enrolled. Lateral flow immunoassays of CrAg were performed on serum for all patients, and on cerebrospinal fluid for patients with CM symptoms. MALDI-ToF MS, ITS sequencing, and determinations of the molecular and mating types of the isolates were performed. Fluconazole is the only drug for CM treatment available in Madagascar. Patients were treated orally, with high doses (1200 mg/day) for 10-12 weeks and then with 200 mg/day. Minimum inhibitory concentrations were determined for amphotericin B, flucytosine, voriconazole and fluconazole in E-tests. Overall prevalence was 13.2% (95% CI 7.9-20.3) for cryptococcal infection and 10.9% (95% CI 6.1-17.5) for CM, among the 129 HIV-infected patients studied. The 90-day mortality rate was 58.8% (10/17) in CrAg-positive patients and 17.9% (20/112) in CrAg-negative patients (p<0.001). The 13 Cryptococcus strains obtained at baseline were all Cryptococcus neoformans var. grubii, genotypes VNI-αA (3 isolates), VNII-αA (4 isolates) or hybrid VNI/VNII-αAAα (6 isolates), suggesting high diversity. Two strains acquired fluconazole resistance after four and five months of exposure, respectively. The prevalence of cryptococcosis is high in Madagascar and this serious condition is life-threatening in HIV-infected patients. These findings will be used to raise the awareness of national authorities to strengthen the national HIV/AIDS control program

Factors Influencing Atypical Clinical Presentations during the 2017 Madagascar Pneumonic Plague Outbreak: A Prospective Cohort Study

International audienceIn late 2017, Madagascar experienced a large urban outbreak of pneumonic plague, the largest outbreak to date this century. During the outbreak, there were widespread reports of plague patients presenting with atypical symptoms, such as prolonged duration of illness and upper respiratory tract symptoms. Reported mortality among plague cases was also substantially lower than that reported in the literature (25% versus 50% in treated patients). A prospective multicenter observational study was carried out to investigate potential reasons for these atypical presentations. Few subjects among our cohort had confirmed or probable plague, suggesting that, in part, there was overdiagnosis of plague cases by clinicians. However, 35% subjects reported using an antibiotic with anti-plague activity before hospital admission, whereas 55% had antibiotics with anti-plague activity detected in their serum at admission. Although there may have been overdiagnosis of plague by clinicians during the outbreak, the high frequency of community antibiotic may partly explain the relatively few culture-positive sputum samples during the outbreak. Community antibiotic use may have also altered the clinical presentation of plague patients. These issues make accurate detection of patients and the development of clinical case definitions and triage algorithms in urban pneumonic plague outbreaks difficult