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Competing Interests: Competing interests: None declared.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Raberahona, Rakotomalala, Andriananja, Andriamamonjisoa, Rakotomijoro, Andrianasolo, Rakotoarivelo and Randria.)

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., (© 2022 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

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., (© 2021 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

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., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Bubonic plague is the primary manifestation of infection with Yersinia pestis, accounting for 90% of all plague cases and with 75% of global cases reported in Madagascar. All drugs in use for treating plague are registered based on experimental data and anecdotal evidence, and no regimen currently recommended is supported by a randomized clinical trial. The IMASOY trial intends to fill this knowledge gap by comparing two 10-day regimens included in the national guidelines in Madagascar. The primary objective of the trial is to test the hypothesis that ciprofloxacin monotherapy is non-inferior to streptomycin followed by ciprofloxacin for the treatment of bubonic plague, thus avoiding the need for injectable, potentially toxic, aminoglycosides., Methods: A two-arm parallel-group randomized control trial will be conducted across peripheral health centres in Madagascar in five districts. Males and non-pregnant females of all ages with suspected bubonic or pneumonic plague will be recruited over the course of three plague 'seasons'. The primary endpoint of the trial is to assess the proportion of patients with bubonic plague who have a therapeutic response to treatment (defined as alive, resolution of fever, 25% reduction in the size of measurable buboes, has not received an alternative treatment and no clinical decision to continue antibiotics) as assessed on day 11., Discussion: If successful, the trial has the potential to inform the standard of care guidelines not just in Madagascar but in other countries afflicted by plague. The trial is currently ongoing and expected to complete recruitment in 2022., Trial Registration: ClinicalTrials.gov NCT04110340 . Registered on 1 October 2019.

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., Competing Interests: The authors have declared that no competing interests exist.

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.

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., Competing Interests: The authors have declared that no competing interests exist.

Background: The primary site of infection for Mycobacterium tuberculosis ( Mtb ) is the alveolar macrophages. However, Mtb can disseminate into other organs and causes extrapulmonary tuberculosis (EPTB). The diagnosis of EPTB is challenging due to relatively inaccessible infectious sites that may be paucibacillary and with clinical symptoms varying by site that are similar to those seen in other diseases. Hence, we sought to identify the expression patterns of a variety of cytokines that may be specific to EPTB from in vitro infections and in the plasma of TB patients. Methods: To define those cytokine secretions associated with EPTB, human THP-1 derived macrophages were first infected with Mtb clinical isolates from pulmonary and EPTB. Infected macrophages supernatants were harvested at different time points and cytokines known to play key roles in TB immune responses including TNF-α, IL-6, IL-10, IFN-γ, and VEGF-A were measured by ELISA. Those cytokines that were in vitro associated to EPTB were also measured in the plasma from patients with PTB, EPTB, non-EPTB-confirmed-like symptoms and healthy controls. Results: While all of the studied cytokine secretions varied after in vitro infection, higher levels of TNF-α and VEGF secretions were observed in vitro in the infected macrophages respectively in the PTB and EPTB infecting clinical isolates. Similar trends were observed from the plasma of patients where patients with PTB showed significantly higher level of TNF-α compared to EPTB and healthy control groups. The patients with EPTB showed higher plasma level of VEGF compared to those patients with the non-EPTB ( p < 0.01) and to healthy controls group ( p < 0.0001). Using Receiver Operating Curves (ROC), we showed that TNF-α and VEGF concentrations could distinguish EPTB from non-confirmed EPTB with high sensitivity and specificity. Conclusion: Pulmonary and extrapulmonary Mtb clinical isolates showed different cytokine induction pattern in human macrophages that is also found in the plasma level of the EPTB patients. Further investigations are needed to define cytokine secretions that can lead to the definition of bio-signatures to differentiate EPTB from other pathologies with confusing symptoms that hampered the diagnosis of TB.

The resurgence of invasive meningococcal disease caused by Neisseria meningitidis serogroup W with sequence type ST-11 (cc11) was observed in Madagascar in 2015-2016. Three cases were investigated in this study. Molecular characterization of the strains suggests the local transmission of a single genotype that may have been circulating for years., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)