Is Madagascar at the edge of a generalised HIV epidemic? Situational analysis.

OBJECTIVES: To describe the epidemiological situation of the HIV/AIDS epidemic and to identify the main drivers for vulnerability in Madagascar. DESIGN: Literature review, qualitative research and situational analysis. DATA SOURCES: Search of electronic bibliographic databases, national repositories of documentation from 1998 to 2018. Search keywords included Madagascar, HIV, sexually transmitted infections, men who have sex with men (MSM), sex workers (SWs), transactional sex (TS), injecting drug users (IDUs), vulnerability and sexual behaviour. Qualitative sources were interviews and focus group discussions. REVIEW METHODS: Studies focused on HIV and/or vulnerability of HIV in Madagascar in general, and key populations (KPs) and HIV/AIDS response were taken into account. National reports from key HIV response actors were included. RESULTS: Madagascar is characterised by a low HIV/AIDS epidemic profile in the general population (GP) (0.3%) combined with a high prevalence of HIV among KPs (SWs, MSM and IDUs).An increase in HIV prevalence among KP has been observed during recent years. Hospital-based data suggest an increase in HIV prevalence among the GP. The vulnerability traits are inconsistent use of condoms, multipartner relationships and other contextual factors like widespread TS and gender inequality. A high prevalence/incidence of sexually transmitted infections could indicate a high vulnerability to HIV/AIDS. However, there are no reports of HIV prevalence of >1% in antenatal consultation. CONCLUSION: There is not enough evidence to make a conclusion about the HIV epidemiological situation in Madagascar due to the scarcity of the epidemiological data. However, Madagascar may be closer to a turning point towards a high-prevalence epidemic with severe consequences, particularly when taking into account its socioeconomical fragility and underlying vulnerabilities. More precise epidemiological data and improved HIV/AIDS diagnosis and case management should be a public health priority.

Knowledge, attitudes, perception and practices regarding antiretroviral therapy among HIV-infected adults in Antananarivo, Madagascar: a cross-sectional survey.

BACKGROUND: Adherence to antiretroviral therapy (ART) may be influenced by knowledge, perception and perception regarding ART. The purpose of this study was to assess knowledge, attitude/perception and practice regarding ART among people living with HIV/AIDS (PLHIV). METHODS: We conducted a cross-sectional survey to assess knowledge, attitudes, perception and practices ART in PLHIV. The survey was suggested to all PLHIV of at least 18 years old and who were on ART for at least 1 month. PLHIV who were unable to answer questions correctly and those who did not complete the survey for any reason were excluded. RESULTS: During the study period, 234 PLHIV were included. Participants were mostly men (75.2%). The median age was 33 years (IQR: 27-41). The median time since HIV diagnosis was 25 months (IQR: 9-56) and the median duration of ART was 18 months (IQR: 8-48). 87.6% had an overall good knowledge of ART. However, only 3.2% knew the name of their ART, 31.2% were aware that ART should be taken at a fixed time and 17.1% knew how to take ART in relation to food intake. 75.6% of participants had an overall positive attitude/perception of ART. However, 10.7% were convinced that other methods were more effective than ART for treating HIV and 42.7% thought that taking ART was shameful. The assessment of practices showed that in case of missed dose, 48.3% of participants routinely skipped this dose instead of trying to take it as soon as possible. In multivariate analysis, good knowledge of ART was independently associated with high level of education (aOR: 4.7, IC95%: 1.6-13.7, p = 0.004) and disclosure of HIV status (aOR: 2.7, IC95%: 1.1-6.6, p = 0.029). CONCLUSIONS: This study showed an overall good knowledge and a predominantly positive attitude/perception of ART. However, accurate knowledge of ART intake was insufficient and the stigma associated with taking ART remained very present. Furthermore, very heterogeneous practices may reflect lack of instruction given by the physician regarding ART intake.

Novel Streptococcus suis Sequence Type 834 among Humans, Madagascar.

Two cases of meningitis caused by Streptococcus suis occurred in Madagascar, 1 in 2015 and 1 in 2016. We report the characterization of the novel sequence type, 834, which carried the mrp+/sly+/epf+ virulence marker and a mutation G→T at position 174, leading to a substitution mutS1 to mutS284.

Dynamics of Epstein-Barr viral load after hematopoietic stem cell transplantation and effect of preemptive rituximab therapy.

BACKGROUND: Epstein-Barr virus (EBV) displays oncogenic properties, particularly in the immunocompromised host. Notably, hematopoietic stem cell transplantation (HSCT) recipients with a detectable blood EBV viral load (BEBVL) are considered at higher risk of post-transplant lymphoproliferative diseases (PTLD). Therefore, BEBVL is monitored after HSCT, and preemptive rituximab may be used in patients with high values. However, little is known about post-HSCT BEBVL dynamics, and the threshold that should lead to anti-CD20 therapy is poorly defined. METHODS: We retrospectively analyzed the post-HSCT BEBVL of 332 adult HSCT recipients in our center from 2005 to 2013, including the effect of rituximab. RESULTS: Detection of BEBVL >100, 1000, 5000, 10 000, and 50 000 copies/mL occurred in, respectively, 77.7%, 69.6%, 37.0%, 27.1%, and 7.5% of the patients after a respective median time of 9, 14, 15, 16, and 14 weeks. No BEBVL threshold was associated with an overall survival difference. Seventy-eight patients received rituximab, with a BEBVL decrease in most. Among patients with detectable BEBVL, long-term survival did not differ in rituximab treated and non-treated, except for patients with BEBVL ≥50 000. Only one case of PTLD was observed. CONCLUSIONS: BEBVL is frequently detectable after HSCT, but suggests no strong association with survival. Preemptive rituximab therapy threshold remains to be defined.

Implementation of an antibiotic resistance surveillance tool in Madagascar, the TSARA project: a prospective, observational, multicentre, hospital-based study protocol.

INTRODUCTION: Antimicrobial resistance (AMR) has become a significant public health threat. Without any interventions, it has been modelled that AMR will account for an estimated 10 million deaths annually by 2050, this mainly affects low/middle-income countries. AMR has a systemic negative perspective affecting the overall healthcare system down to the patient's personal outcome. In response to this issue, the WHO urged countries to provide antimicrobial stewardship programmes (ASPs). ASPs in hospitals are a vital component of national action plans for AMR, and have been shown to significantly reduce AMR, in particular in low-income countries such as Madagascar.As part of an ASP, AMR surveillance provides essential information needed to guide medical practice. We developed an AMR surveillance tool-Technique de Surveillance Actualisée de la Résistance aux Antimicrobiens (TSARA)-with the support of the Mérieux Foundation. TSARA combines bacteriological and clinical information to provide a better understanding of the scope and the effects of AMR in Madagascar, where no such surveillance tool exists. METHODS AND ANALYSIS: A prospective, observational, hospital-based study was carried out for data collection using a standardised data collection tool, called TSARA deployed in 2023 in 10 hospitals in Madagascar participating in the national Malagasy laboratory network (Réseau des Laboratoires à Madagascar (RESAMAD)). Any hospitalised patient where the clinician decided to take a bacterial sample is included. As a prospective study, individual isolate-level data and antimicrobial susceptibility information on pathogens were collected routinely from the bacteriology laboratory and compiled with clinical information retrieved from face-to-face interviews with the patient and completed using medical records where necessary. Analysis of the local ecology, resistance rates and antibiotic prescription patterns were collected. ETHICS AND DISSEMINATION: This protocol obtained ethical approval from the Malagasy Ethical Committee n°07-MSANP/SG/AGMED/CNPV/CERBM on 24 January 2023. Findings generated were shared with national health stakeholders, microbiologists, members of the RESAMAD network and the Malagasy academic society of infectious diseases.

An open-label, randomized, non-inferiority trial of the efficacy and safety of ciprofloxacin versus an aminoglycoside + ciprofloxacin in the treatment of bubonic plague (IMASOY): study protocol for a randomized control trial-an update to the published protocol.

This article reports an update to the protocol of the IMASOY trial, which was prospectively registered on clinicaltrials.gov (NCT04110340) in October 2019.

Prevalence of pulmonary tuberculosis and HIV infections and risk factors associated to tuberculosis in detained persons in Antananarivo, Madagascar.

The incidence rate of tuberculosis in prisons is estimated to be 8 times greater than that in the general population in Madagascar. Our objectives were to estimate the prevalence of pulmonary tuberculosis and HIV infection among prisoners and to identify risk factors associated with tuberculosis. We conducted a cross-sectional study at the central prison of Antananarivo from March to July 2021. Individual male and female inmates aged ≥ 13 years who had lived in the prison for at least three months prior to the study period were included as participants. Acid-fast bacilli detection by microscopy and/or culture, an intradermal tuberculin test, a chest X-ray, and a rapid diagnostic orientation test for HIV were performed. Among 748 participants, 4 (0.5%) were confirmed to have pulmonary tuberculosis. Overall, 14 (1.9%) patients had "confirmed" or "probable" tuberculosis [0.90-2.84, 95% CI]. The proportion of participants with latent tuberculosis infection was 69.6% (517/743) based on a positive tuberculin test without clinical symptoms or radiography images indicating tuberculosis. Out of 745 HIV screening tests, three showed reactive results (0.4%). Age (OR = 4.4, 95% CI [1.4-14.0]) and prior tuberculosis treatment (or episodes) were found to be associated with confirmed and probable tuberculosis.

Solicited Cough Sound Analysis for Tuberculosis Triage Testing: The CODA TB DREAM Challenge Dataset.

Cough is a common and commonly ignored symptom of lung disease. Cough is often perceived as difficult to quantify, frequently self-limiting, and non-specific. However, cough has a central role in the clinical detection of many lung diseases including tuberculosis (TB), which remains the leading infectious disease killer worldwide. TB screening currently relies on self-reported cough which fails to meet the World Health Organization (WHO) accuracy targets for a TB triage test. Artificial intelligence (AI) models based on cough sound have been developed for several respiratory conditions, with limited work being done in TB. To support the development of an accurate, point-of-care cough-based triage tool for TB, we have compiled a large multi-country database of cough sounds from individuals being evaluated for TB. The dataset includes more than 700,000 cough sounds from 2,143 individuals with detailed demographic, clinical and microbiologic diagnostic information. We aim to empower researchers in the development of cough sound analysis models to improve TB diagnosis, where innovative approaches are critically needed to end this long-standing pandemic.

An independent, multi-country head-to-head accuracy comparison of automated chest x-ray algorithms for the triage of pulmonary tuberculosis.

Background: Computer-aided detection (CAD) algorithms for automated chest X-ray (CXR) reading have been endorsed by the World Health Organization for tuberculosis (TB) triage, but independent, multi-country assessment and comparison of current products are needed to guide implementation. Methods: We conducted a head-to-head evaluation of five CAD algorithms for TB triage across seven countries. We included CXRs from adults who presented to outpatient facilities with at least two weeks of cough in India, Madagascar, the Philippines, South Africa, Tanzania, Uganda, and Vietnam. The participants completed a standard evaluation for pulmonary TB, including sputum collection for Xpert MTB/RIF Ultra and culture. Against a microbiological reference standard, we calculated and compared the accuracy overall, by country and key groups for five CAD algorithms: CAD4TB (Delft Imaging), INSIGHT CXR (Lunit), DrAid (Vinbrain), Genki (Deeptek), and qXR (qure.AI). We determined the area under the ROC curve (AUC) and if any CAD product could achieve the minimum target accuracy for a TB triage test (≥90% sensitivity and ≥70% specificity). We then applied country- and population-specific thresholds and recalculated accuracy to assess any improvement in performance. Results: Of 3,927 individuals included, the median age was 41 years (IQR 29-54), 12.9% were people living with HIV (PLWH), 8.2% living with diabetes, and 21.2% had a prior history of TB. The overall AUC ranged from 0.774-0.819, and specificity ranged from 64.8-73.8% at 90% sensitivity. CAD4TB had the highest overall accuracy (73.8% specific, 95% CI 72.2-75.4, at 90% sensitivity), although qXR and INSIGHT CXR also achieved the target 70% specificity. There was heterogeneity in accuracy by country, and females and PLWH had lower sensitivity while males and people with a history of TB had lower specificity. The performance remained stable regardless of diabetes status. When country- and population-specific thresholds were applied, at least one CAD product could achieve or approach the target accuracy for each country and sub-group, except for PLWH and those with a history of TB. Conclusions: Multiple CAD algorithms can achieve or exceed the minimum target accuracy for a TB triage test, with improvement when using setting- or population-specific thresholds. Further efforts are needed to integrate CAD into routine TB case detection programs in high-burden communities.

An extensive arterial thrombosis with lower limb ischemia in a COVID-19 patient: A case report.

The coronavirus disease 2019 (COVID-19) pandemic is responsible for huge morbidity and mortality throughout the world. Several serious complications of this disease have been reported. It can cause hypercoagulability, which may lead to venous and arterial thromboembolic diseases. This hypercoagulability state is also associated with high morbidity and mortality. Arterial thrombosis in COVID-19 is poorly described compared to venous thrombosis and pulmonary embolism. We report a case of an extensive arterial thrombosis leading to a limb ischemia with extremely high D-dimer in a COVID-19 patient. A 69-year-old man was hospitalized for febrile dyspnea. He is a hypertensive and diabetic patient. On admission, pulse oxygen saturation was 72% on room air. He had cyanosis of the left foot up to the mid-thigh. The left pedal, posterior tibial, popliteal and femoral pulses were abolished. Chest CT scan was in favor of COVID-19. He has a high D-dimer level of 257,344 ng/mL. Arterial Echo-Doppler found an extensive intraluminal thrombus along the arterial axes of the left lower limb, completely obstructing them, starting from the primitive iliac artery just after its bifurcation with the aorta, and extending distally (external iliac; common femoral; superficial femoral; popliteal; anterior tibial; posterior tibial; fibular and pedal). The patient was diagnosed with COVID-19 critical form, associated with ischemia of the left lower limb secondary to an extensive arterial thrombosis. He was receiving anticoagulation, and underwent surgical amputation of the ischemic limb. The patient survived the event; however, he was on long-term oxygen therapy at home. Arterial thrombosis may occur during COVID-19 and may be responsible for peripheral or central ischemia aggravating morbidity and mortality. The occurrence of these events is related to the D-dimer value. Anticoagulation is an important part of the management of COVID-19, especially in severe forms in order to limit the occurrence of these thromboembolic diseases.

A retrospective cohort analysis of people living with HIV/AIDS enrolled in HIV care at a reference center in Antananarivo, Madagascar.

Background: The impact of the "Treat all" policy on the individual and in terms of public health is closely related to early diagnosis and retention in care. Patient-level data are scarce in Madagascar. In this study, we aimed to describe the profile of a cohort of newly diagnosed people living with HIV/AIDS (PLHIV), identify their outcomes, and assess factors associated with attrition from care and advanced HIV disease (AHD) at presentation. Methods: We conducted a retrospective cohort study of PLHIV aged ≥15 years newly diagnosed at the University Hospital Joseph Raseta Befelatanana Antananarivo from 1 January 2010 to 31 December 2016. Results: A total of 490 PLHIV were included in the cohort analysis. In total, 67.1% were male. The median age (interquartile range) at enrollment in care was 29 years (24-38). Overall, 36.1% of PLHIV were diagnosed with AHD at baseline. The proportion of patients with WHO stage IV at baseline increased significantly from 3.3% in 2010 to 31% in 2016 (p = 0.001 for trend). The probability of retention in care after the diagnosis at 12 months, 24 months, and 36 months was 71.8%, 65.5%, and 61.3%, respectively. Age ≥ 40 years (aHR: 1.55; 95% CI: 1.05-2.29; p = 0.026), low level of education (aHR:1.62; 95% CI: 1.11-2.36; p = 0,013), unspecified level of education (aHR:2.18; 95% CI: 1.37-3.47; p = 0.001) and unemployment (aHR:1.52; 95% CI: 1.07-2.16; p = 0.019) were independently associated with attrition from care. Factors associated with AHD at baseline were age ≥ 40 (aOR: 2.77; 95% CI: 1.38-5.57, p = 0.004), unspecified level of education (aOR: 3.80; 95% CI: 1.58-9.16, p = 0.003) and presence of clinical symptoms at baseline (aOR: 23.81; 95% CI: 10.7-52.98; p < 0.001). Sex workers were independently less likely to have an AHD at presentation (aOR: 0.23; 95% CI: 0.05-0.96, p = 0.044). Conclusion: Sociodemographic determinants influenced retention in care more than clinical factors. The presence of clinical symptoms and sociodemographic determinants were the main factors associated with AHD at baseline.

High Seroprevalence of IgG Antibodies to Multiple Arboviruses in People Living with HIV (PLWHIV) in Madagascar.

To estimate the prevalence of IgG antibodies against six arboviruses in people living with HIV-1 (PLWHIV) in Madagascar, we tested samples collected between January 2018 and June 2021. We used a Luminex-based serological assay to detect IgG antibodies against antigens from Dengue virus serotypes 1-4 (DENV1-4), Zika virus (ZIKV), West Nile virus (WNV), Usutu virus (USUV), Chikungunya virus (CHIKV), and O'nyong nyong virus (ONNV). Of the 1036 samples tested, IgG antibody prevalence was highest for ONNV (28.4%), CHIKV (26.7%), WNV-NS1 (27.1%), DENV1 (12.4%), USUV (9.9%), and DENV3 (8.9%). ZIKV (4.9%), DENV2 (4.6%), WNV-D3 (5.1%), and DENV4 (1.4%) were lower. These rates varied by province of origin, with the highest rates observed in Toamasina, on the eastern coast (50.5% and 56.8%, for CHIKV and ONNV, respectively). The seroprevalence increased with age for DENV1 and 3 (p = 0.006 and 0.038, respectively) and WNV DIII (p = 0.041). The prevalence of IgG antibodies against any given arborvirus varied over the year and significantly correlated with rainfalls in the different areas (r = 0.61, p = 0.036). Finally, we found a significant correlation between the seroprevalence of antibodies against CHIKV and ONNV and the HIV-1 RNA plasma viral load. Thus, PLWHIV in Madagascar are highly exposed to various arboviruses. Further studies are needed to explain some of our findings.

SARS-CoV-2 infection rate in Antananarivo frontline health care workers, Madagascar.

BACKGROUND: Health care workers (HCWs) represent a vulnerable population during epidemic periods. Our cohort study aimed to estimate the risk of infection and associated factors among HCWs during the first wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Madagascar. METHODS: A prospective cohort study was carried out in three hospitals that oversaw the first cases of COVID-19. Monthly ELISA-based serological tests were conducted, and nasopharyngeal swabs were collected in the case of symptoms linked to COVID-19 for RT-PCR analysis. Survival analyses were used to determine factors associated with SARS-CoV-2 infection. RESULTS: The study lasted 7 months from May 2020. We included 122 HCWs, 61.5% of whom were women. The median age was 31.9 years (IQR: 26.4-42.3). In total, 42 (34.4%) had SARS-CoV-2 infections, of which 20 were asymptomatic (47.6%). The incidence of SARS-CoV-2 infection was 9.3% (95% CI [6.5-13.2]) person-months. Sixty-five HCWs presented symptoms, of which 19 were positive by RT-PCR. When adjusted for exposure to deceased cases, infection was more frequent in HCWs younger than 30 years of age (RR = 4.9, 95% CI [1.4-17.2]). CONCLUSION: Our results indicate a high incidence of infection with SARS-CoV-2 among HCWs, with a high proportion of asymptomatic cases. Young HCWs are more likely to be at risk than others. Greater awareness among young people is necessary to reduce the threat of infection among HCWs.

Household transmission of COVID-19 among the earliest cases in Antananarivo, Madagascar.

BACKGROUND: Households are among the highest risk for the transmission of SARS-CoV-2. In sub-Saharan Africa, very few studies have described household transmission during the COVID-19 pandemic. Our work aimed to describe the epidemiologic parameters and analyze the secondary attack rate (SAR) in Antananarivo, Madagascar, following the introduction of SARS-CoV-2 in the country in March 2020. METHODS: A prospective case-ascertained study of all identified close contacts of laboratory-confirmed COVID-19 infections was conducted in Antananarivo from March to June 2020. Cases and household contacts were followed for 21 days. We estimated epidemic parameters of disease transmission by fitting parametric distributions based on infector-infected paired data. We assessed factors influencing transmission risk by analyzing the SAR. FINDINGS: Overall, we included 96 index cases and 179 household contacts. Adjusted with the best-fit normal distribution, the incubation period was 4.1 days (95% CI 0.7-7.5]). The serial interval was 6.0 days (95% CI [2.4-9.6]) after adjusting with the best-fit Weibull distribution. On average, each index case infected 1.6 family members (95%CI [0.9-2.3]). The mean SAR among close contacts was 38.8% (95% CI [19.5-58.2]) with the best-fit gamma distribution. Contacts older than 35 years old were more likely to be infected, and the highest SAR was found among them. CONCLUSION: The results of our study provide key insights into the epidemiology of the first wave of SARS-CoV-2 in Madagascar. High rates of household transmission were found in Antananarivo, emphasizing the need for preventive measures to reduce community transmission.

Intensified tuberculosis treatment to reduce the mortality of HIV-infected and uninfected patients with tuberculosis meningitis (INTENSE-TBM): study protocol for a phase III randomized controlled trial.

BACKGROUND: Tuberculous meningitis (TBM) is the most lethal and disabling form of tuberculosis (TB), particularly in sub-Saharan Africa. Current anti-TB treatment is poorly effective since TBM mortality reaches 40% in HIV-negative patients and up to 70% in HIV-co-infected patients. To reduce TBM-induced morbidity and mortality, the INTENSE-TBM trial evaluates two interventions in both HIV-infected and uninfected patients: an anti-TB treatment intensification using oral high-dose rifampicin (35 mg/kg daily) and linezolid (1200 mg daily and then 600 mg daily) during the first 8 weeks of the anti-TB treatment and the use of adjunctive aspirin (200 mg daily). METHODS: This is a randomized controlled, phase III, multicenter, 2 × 2 factorial plan superiority trial. The trial has four arms, combining the two experimental treatments (intensified TBM regimen and aspirin) with the two reference treatments (WHO standard TB treatment and placebo), and is open-label for anti-TB treatment and double-blind placebo-controlled for aspirin treatment. This trial is conducted in adults or adolescents of age ≥15 years with TBM defined as "definite," "probable," or "possible" using Tuberculosis Meningitis International Research Consortium criteria, in four African countries: Ivory Coast, Madagascar, Uganda, and South Africa. The primary outcome is all-cause death between inclusion and week 40. DISCUSSION: The INTENSE-TBM trial represents a key opportunity to enhance TBM treatment with widely available existing drugs notably in high-incidence settings of both TB and HIV. The trial design is pragmatic and the results will permit early and effective applications in TBM patient care, in both HIV and TB high-incidence countries. TRIAL REGISTRATION: ClinicalTrials.gov NCT04145258. Registered on October 30, 2019.

The impact of COVID-19 on clinical research for Neglected Tropical Diseases (NTDs): A case study of bubonic plague.

BACKGROUND: Among the many collaterals of the COVID-19 pandemic is the disruption of health services and vital clinical research. COVID-19 has magnified the challenges faced in research and threatens to slow research for urgently needed therapeutics for Neglected Tropical Diseases (NTDs) and diseases affecting the most vulnerable populations. Here we explore the impact of the pandemic on a clinical trial for plague therapeutics and strategies that have been considered to ensure research efforts continue. METHODS: To understand the impact of the COVID-19 pandemic on the trial accrual rate, we documented changes in patterns of all-cause consultations that took place before and during the pandemic at health centres in two districts of the Amoron'I Mania region of Madagascar where the trial is underway. We also considered trends in plague reporting and other external factors that may have contributed to slow recruitment. RESULTS: During the pandemic, we found a 27% decrease in consultations at the referral hospital, compared to an 11% increase at peripheral health centres, as well as an overall drop during the months of lockdown. We also found a nation-wide trend towards reduced number of reported plague cases. DISCUSSION: COVID-19 outbreaks are unlikely to dissipate in the near future. Declining NTD case numbers recorded during the pandemic period should not be viewed in isolation or taken as a marker of things to come. It is vitally important that researchers are prepared for a rebound in cases and, most importantly, that research continues to avoid NTDs becoming even more neglected.

Light chain Amyloidosis (AL) associated with multiple myeloma revealed by peripheral bilateral polyarthritis: a case report.

In chronic polyarthritis, the presence of macroglossia with absence of rheumatoid factor and anti-CCP antibodies may be suggestive of amyloid arthopathy. Clinical evaluation takes precedence over classification criteria.

Clinical and epidemiological features discriminating confirmed COVID-19 patients from SARS-CoV-2 negative patients at screening centres in Madagascar.

Early and fast detection of COVID-19 patients help limit the transmission and wide spread of the virus in the community and will have impact on mortality by reducing the incidence of infection among vulnerable people. Therefore, community-based screening is critical. We aimed to identify clinical signs and symptoms and epidemiological features that could help discriminate confirmed cases of COVID-19 from SARS-CoV-2 negative patients. We found that age (aOR:1.02, 95%CI:1.02-1.03, p < 0.001), symptoms onset between 3 and 14 days (aOR:1.35, 95%CI:1.09)1.68, p = 0.006), fever or history of fever (aOR:1.75, 95%CI:1.42-2.14, p < 0.001), cough (aOR:1.68, 95%CI:1.31-2.04), sore throat (aOR:0.65, 95%CI:0.49-0.85, p = 0.002), ageusia (aOR:2.24, 95%CI:1.42-3.54, p = 0.001), anosmia (aOR:6.04, 95%CI:4.19-8.69, p < 0.001), chest pain (aOR:0.63, 95%CI:0.47-0.85, p = 0.003), myalgia and/or arthralgia (aOR:1.64, 95%CI:1.31-2.04, p < 0.001), household cluster (aOR:1.49, 95%CI:1.17-1.91, p = 0.001) and evidence of confirmed cases in the neighbourhood (aOR:1.92, 95%CI:1.56-2.37, p < 0.001) could help discriminate COVID-19 patients from SARS-CoV-2 negative. A screening score derived from multivariate logistic regression was developed to assess the probability of COVID-19 in patients. We suggest that a patient with a score ≥14 should undergo SARS-CoV-2 PCR testing. A patient with a score ≥30 should be considered at high risk of COVID-19 and should undergo testing but also needs prompt isolation and contact tracing.

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

Cryptococcal 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.