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 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.

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.

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.

[Acute kidney injury and severe malaria in adults: A monocentric descriptive study in Madagascar using KDIGO criteria]. / Insuffisance rénale aiguë et paludisme grave chez l'adulte : étude descriptive monocentrique à Madagascar en utilisant les critères KDIGO.

INTRODUCTION: Acute Kidney Injury (AKI) is one of the criteria for severe malaria with a varied incidence. Our objectives are to determine the prevalence of malaria-associated AKI and to report the characteristics of patients with the evolution of cases. PATIENTS AND METHOD: This is a 5-year retrospective descriptive study from January 1, 2015 to December 31, 2019 in the Infectious Diseases department of the University Hospital Center of Befelatanana Antananarivo. Among 379 patients diagnosed, 103 patients (27,18%) with associated AKI were included. We used the criteria of Kidney Disease Improving Global Outcomes group to define AKI. RESULTS: The prevalence of AKI was 27.18%. The mean age of patients was 34.92 years and the sex-ratio was 3.68. Plasmodium falciparum was the causative agent in 98.06% of cases followed by Plasmodium vivax. Diuresis was preserved in 69.86% of cases. Jaundice was the main sign of severity associated (49.51%). The mean creatinine level was 466.93µmol/L. The evolution was favorable under antimalarial drug and rehydration. Dialysis was required in 25.24% of cases. Thirteen patients had died, a rate of 12.62%, of which 8 patients (61.54%) had dialysis criteria but had not been purged for economic reasons. CONCLUSION: AKI is a frequent complication of malaria. It is responsible for significant mortality despite improved care in the fight against malaria.

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.

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.

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

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.

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

In 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.

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.

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.

Epidemiological characteristics of an urban plague epidemic in Madagascar, August-November, 2017: an outbreak report.

BACKGROUND: Madagascar accounts for 75% of global plague cases reported to WHO, with an annual incidence of 200-700 suspected cases (mainly bubonic plague). In 2017, a pneumonic plague epidemic of unusual size occurred. The extent of this epidemic provides a unique opportunity to better understand the epidemiology of pneumonic plagues, particularly in urban settings. METHODS: Clinically suspected plague cases were notified to the Central Laboratory for Plague at Institut Pasteur de Madagascar (Antananarivo, Madagascar), where biological samples were tested. Based on cases recorded between Aug 1, and Nov 26, 2017, we assessed the epidemiological characteristics of this epidemic. Cases were classified as suspected, probable, or confirmed based on the results of three types of diagnostic tests (rapid diagnostic test, molecular methods, and culture) according to 2006 WHO recommendations. FINDINGS: 2414 clinically suspected plague cases were reported, including 1878 (78%) pneumonic plague cases, 395 (16%) bubonic plague cases, one (<1%) septicaemic case, and 140 (6%) cases with unspecified clinical form. 386 (21%) of 1878 notified pneumonic plague cases were probable and 32 (2%) were confirmed. 73 (18%) of 395 notified bubonic plague cases were probable and 66 (17%) were confirmed. The case fatality ratio was higher among confirmed cases (eight [25%] of 32 cases) than probable (27 [8%] of 360 cases) or suspected pneumonic plague cases (74 [5%] of 1358 cases) and a similar trend was seen for bubonic plague cases (16 [24%] of 66 confirmed cases, four [6%] of 68 probable cases, and six [2%] of 243 suspected cases). 351 (84%) of 418 confirmed or probable pneumonic plague cases were concentrated in Antananarivo, the capital city, and Toamasina, the main seaport. All 50 isolated Yersinia pestis strains were susceptible to the tested antibiotics. INTERPRETATION: This predominantly urban plague epidemic was characterised by a large number of notifications in two major urban areas and an unusually high proportion of pneumonic forms, with only 23% having one or more positive laboratory tests. Lessons about clinical and biological diagnosis, case definition, surveillance, and the logistical management of the response identified in this epidemic are crucial to improve the response to future plague outbreaks. FUNDING: US Agency for International Development, WHO, Institut Pasteur, US Department of Health and Human Services, Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases, Models of Infectious Disease Agent Study of the National Institute of General Medical Sciences, AXA Research Fund, and the INCEPTION programme.

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.

Cytokine Biomarkers Associated with Human Extra-Pulmonary Tuberculosis Clinical Strains and Symptoms.

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.

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.

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.