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.

Schistosome infection among pregnant women in the rural highlands of Madagascar: A cross-sectional study calling for public health interventions in vulnerable populations.

INTRODUCTION: Schistosomiasis is a parasitic infection highly prevalent in sub-Saharan Africa (SSA) with Madagascar being among the countries with highest burden of the disease worldwide. Despite WHO recommendations, suggesting treatment of pregnant women after the first trimester, this group is still excluded from Mass Drug Administration programs. Our study, had the objective to measure the prevalence of schistosome infection among pregnant women in Madagascar in order to inform public health policies for treatment in this vulnerable population. METHODS: Women were recruited for this cross-sectional study between April 2019 and February 2020 when attending Antenatal Care Services (ANCs) at one of 42 included Primary Health Care Centers. The urine-based upconverting reporter particle, lateral flow (UCP-LF) test detecting circulating anodic antigen was used for the detection of schistosome infections. To identify factors associated with the prevalence of schistosome infection crude and adjusted prevalence ratios and 95% CIs were estimated using mixed-effect Poisson regression. RESULTS: Among 4,448 participating women aged between 16 and 47 years, the majority (70.4%, 38 n = 3,133) resided in rural settings. Overall, the prevalence of schistosome infection was 55.9% (n = 2486, CI 95%: 53.3-58.5). A statistically significant association was found with age group (increased prevalence in 31-47 years old, compared to 16-20 years old (aPR = 1.15, CI 95%: 1.02-1.29) and with uptake of antimalaria preventive treatment (decreased prevalence, aPR = 0.85, CI 95%: 0.77-0.95). No other associations of any personal characteristics or contextual factors with schistosome infection were found in our multivariate regression analysis. DISCUSSION AND CONCLUSION: The high prevalence of schistosome infection in pregnant women supports the consideration of preventive schistosomiasis treatment in ANCs of the Malagasy highlands. We strongly advocate for adapting schistosomiasis programs in highly endemic contexts. This, would contribute to both the WHO and SDGs agendas overall to improving the well-being of women and consequently breaking the vicious cycle of poverty perpetuated by schistosomiasis.

Awareness and knowledge of female genital schistosomiasis in a population with high endemicity: a cross-sectional study in Madagascar.

Introduction: Female genital schistosomiasis (FGS) is a neglected disease with long-term physical and psychosocial consequences, affecting approximately 50 million women worldwide and generally representing an unmet medical need on a global scale. FGS is the chronic manifestation of a persistent infection with Schistosoma haematobium. FGS services are not routinely offered in endemic settings with a small percentage of women at risk receiving adequate care. Madagascar has over 60% prevalence of FGS and no guidelines for the management of the disease. This study aimed to determine FGS knowledge among women and health care workers (HCWs) in a highly endemic area of Madagascar. Methods: A convenience sampling strategy was used for this cross-sectional study. Descriptive statistics including proportions and 95% confidence intervals (CI) were calculated, reporting socio-demographic characteristics of the population. Knowledge sources were evaluated descriptively. Binary Poisson regression with robust standard errors was performed; crude (CPR) and adjusted prevalence ratio (APR) with 95% CIs were calculated. Results: A total of 783 participants were included in the study. Among women, 11.3% (n = 78) were aware of FGS while among the HCWs 53.8% (n = 50) were aware of FGS. The highest level of knowledge was observed among women in an urban setting [24%, (n = 31)] and among those with a university education/vocational training [23% (n = 13)]. A lower APR of FGS knowledge was observed in peri-urban [APR 0.25 (95% CI: 0.15; 0.45)] and rural [APR 0.37 (95% CI 0.22; 0.63)] settings in comparison to the urban setting. Most HCWs reported other HCWs [40% (n = 20)] while women mainly reported their family [32% (n = 25)] as being their main source of information in the 6 months prior to the survey. Discussion and conclusions: Our study shows limited awareness and knowledge of FGS among population groups in the highly endemic Boeny region of Madagascar. With this study we contribute to identifying an important health gap in Madagascar, which relates to a disease that can silently affect millions of women worldwide. In alignment with the targets of the NTD roadmap, addressing schistosomiasis requires a paradigm shift for its control and management including a greater focus on chronic forms of the disease.

Female genital schistosomiasis, human papilloma virus infection, and cervical cancer in rural Madagascar: a cross sectional study.

BACKGROUND: Women's health in resource-limited settings can benefit from the integrated management of high-burden diseases, such as female genital schistosomiasis (FGS) and human papilloma virus (HPV)-related cervical cancer. In schistosomiasis-endemic countries such as Madagascar, data on FGS and HPV prevalence are lacking as well as preventive measures for both conditions. This study aims to estimate the prevalence of FGS and HPV in rural Madagascar, and to examine associated risk factors to identify opportunities for improving women's health. METHODS: After initial community outreach activities, interested women aged 18-49 years were recruited consecutively in 2021 at three primary health care centers in the district of Marovoay. FGS was detected by colposcopy. Colposcopy images were double-blind reviewed by two independent specialists. A Luminex bead-based assay was performed on cervical vaginal lavage specimens for HPV typing. Crude (CPR) and adjusted prevalence ratios (APR) of associations between selected factors and FGS and HPV positivity were estimated using univariable and multivariable binary Poisson regression with 95% confidence intervals (CIs). RESULTS: Among 500 women enrolled, 302 had complete information on FGS and HPV diagnosis, and were thus eligible for analysis. Within the sample, 189 (62.6%, 95% CI: 56.9-68.1) cases of FGS were detected. A total of 129 women (42.7%, 95% CI: 37.1-48.5) tested positive for HPV. In total, 80 women (26.5%, 95% CI: 21.6-31.8]) tested positive for both conditions. No association was observed between FGS and HPV positivity, while previous pregnancy (APR = 0.65, 95% CI: 0.43-0.78) and older age (APR = 0.59, 95% CI: 0.42-0.81) are showing a negative association with HPV infection compared to no previous pregnancy and younger age groups. CONCLUSIONS: The results of the study show that FGS and HPV are highly prevalent in rural Madagascar. The concurrent prevalence of these two conditions requires urgent adaptations of public health strategies to improve women's health, such as integrated services at primary level of care.

Schistosomiasis elimination in Madagascar: challenges and opportunities for implementing the new WHO guidelines.

Madagascar is one of the countries with the highest burden of schistosomiasis worldwide. The release from the WHO of the new 2021-2030 neglected tropical disease (NTD) roadmap alongside with the schistosomiasis guidelines sets the ambitious goal of eliminating schistosomiasis as a public health problem worldwide. In Madagascar, implementation barriers exist. This paper has the objective of identifying strengths, weaknesses, opportunities and threats in order to build on their basis practices and policies that can help the country to align with the international global health agenda and reach the ambitious goal set by the WHO.

Prevalence and risk distribution of schistosomiasis among adults in Madagascar: a cross-sectional study.

BACKGROUND: The goal to eliminate the parasitic disease of poverty schistosomiasis as a public health problem is aligned with the 2030 United Nations agenda for sustainable development goals, including universal health coverage (UHC). Current control strategies focus on school-aged children, systematically neglecting adults. We aimed at providing evidence for the need of shifting the paradigm of schistosomiasis control programs from targeted to generalized approaches as key element for both the elimination of schistosomiasis as a public health problem and the promotion of UHC. METHODS: In a cross-sectional study performed between March 2020 and January 2021 at three primary health care centers in Andina, Tsiroanomandidy and Ankazomborona in Madagascar, we determined prevalence and risk factors for schistosomiasis by a semi-quantitative PCR assay from specimens collected from 1482 adult participants. Univariable and multivariable logistic regression were performed to evaluate odd ratios. RESULTS: The highest prevalence of S. mansoni, S. haematobium and co-infection of both species was 59.5%, 61.3% and 3.3%, in Andina and Ankazomborona respectively. Higher prevalence was observed among males (52.4%) and main contributors to the family income (68.1%). Not working as a farmer and higher age were found to be protective factors for infection. CONCLUSIONS: Our findings provide evidence that adults are a high-risk group for schistosomiasis. Our data suggests that, for ensuring basic health as a human right, current public health strategies for schistosomiasis prevention and control need to be re-addressed towards more context specific, holistic and integrated approaches.

High seroprevalence of SARS-CoV-2 in Burkina-Faso, Ghana and Madagascar in 2021: a population-based study.

BACKGROUND: The current COVID-19 pandemic affects the entire world population and has serious health, economic and social consequences. Assessing the prevalence of COVID-19 through population-based serological surveys is essential to monitor the progression of the epidemic, especially in African countries where the extent of SARS-CoV-2 spread remains unclear. METHODS: A two-stage cluster population-based SARS-CoV-2 seroprevalence survey was conducted in Bobo-Dioulasso and in Ouagadougou, Burkina Faso, Fianarantsoa, Madagascar and Kumasi, Ghana between February and June 2021. IgG seropositivity was determined in 2,163 households with a specificity improved SARS-CoV-2 Enzyme-linked Immunosorbent Assay. Population seroprevalence was evaluated using a Bayesian logistic regression model that accounted for test performance and age, sex and neighbourhood of the participants. RESULTS: Seroprevalence adjusted for test performance and population characteristics were 55.7% [95% Credible Interval (CrI) 49·0; 62·8] in Bobo-Dioulasso, 37·4% [95% CrI 31·3; 43·5] in Ouagadougou, 41·5% [95% CrI 36·5; 47·2] in Fianarantsoa, and 41·2% [95% CrI 34·5; 49·0] in Kumasi. Within the study population, less than 6% of participants performed a test for acute SARS-CoV-2 infection since the onset of the pandemic. CONCLUSIONS: High exposure to SARS-CoV-2 was found in the surveyed regions albeit below the herd immunity threshold and with a low rate of previous testing for acute infections. Despite the high seroprevalence in our study population, the duration of protection from naturally acquired immunity remains unclear and new virus variants continue to emerge. This highlights the importance of vaccine deployment and continued preventive measures to protect the population at risk.

Giant compressive emphysema: a rare complication of COVID-19.

BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a new ribonucleic acid (RNA) beta-coronavirus, responsible for a worldwide pandemic. Very few cases of SARS-COV-2-related emphysema have been described, except among patients with chronic obstructive pulmonary disease. The thoracic CT scan is the key examination for the diagnosis and allows to evaluate the severity of the pulmonary involvement. The prognosis of the patient with giant emphysema (GE) on coronavirus disease 2019 (COVID-19) in critical or severe form remains poor. We report an original case of COVID-19 pneumonia, critical form, complicated by a giant compressive left emphysema of 22.4 cm in a young subject without respiratory comorbidities. CASE PRESENTATION: A 34-year-old man was hospitalized for left laterothoracic pain. He had no prior medical history. The physical examination revealed tympany on percussion of the left lung. The CT scan confirmed COVID-19 pneumonia with 95% lung involvement. Also, the presence of a voluminous left sub pleural emphysema of 22.4 cm with compression of the ipsilateral pulmonary parenchyma as well as the mediastinal structures towards the right side. The diagnosis COVID-19 pneumonia, critical form, complicated by a compressive left giant emphysema was made. He was put on oxygen, a dual antibiotic therapy, a corticotherapy, and curative doses of enoxaparin. A thoracic drainage surgery was performed at 24th day of hospitalization, which confirmed the giant emphysema. The patient remains on long-term oxygen therapy. CONCLUSION: The COVID-19 has polymorphic manifestations, pneumonia is the most important one. There are relatively few reports associating COVID-19 and emphysema; furthermore, reports associating COVID-19 and giant emphysema are extremely scarce. CT scans can confirm the diagnosis and differentiate it from a pneumothorax. The pulmonary prognosis of the association of COVID-19 in its severe or critical form with giant emphysema remains poor.

Seroprevalence of SARS-CoV-2 in urban settings in three sub-Saharan African countries (SeroCoV): a study protocol for a household-based cross-sectional prevalence study using two-stage cluster sampling.

INTRODUCTION: The current COVID-19 pandemic has impacted the entire world with increasing morbidity and mortality and has resulted in serious economic and social consequences. Assessing the burden of COVID-19 is essential for developing efficient pandemic preparedness and response strategies and for determining the impact of implemented control measures. Population-based seroprevalence surveys are critical to estimate infection rates, monitor the progression of the epidemic and to allow for the identification of persons exposed to the infection who may either have been asymptomatic or were never tested. This is especially important for countries where effective testing and tracking systems could not be established and where non-severe cases or under-reported deaths might have blurred the true burden of COVID-19. Most seroprevalence surveys performed in sub-Saharan Africa have targeted specific high risk or more easily accessible populations such as healthcare workers or blood donors, and household-based estimates are rarely available. Here, we present the study protocol for a SARS-CoV-2 seroprevalence estimation in the general population of Burkina Faso, Ghana and Madagascar in 2021. METHODS AND ANALYSIS: The SeroCoV study is a household-based cross-sectional prevalence investigation in persons aged 10 years and older living in urban areas in six cities using a two-stage geographical cluster sampling method stratified by age and sex. The presence of anti-SARS-CoV-2 IgG antibodies will be determined using a sensitive and specific SARS-CoV-2 IgG ELISA. In addition, questionnaires will cover sociodemographic information, episodes of diseases and history of testing and treatment for COVID-like symptoms, travel history and safety measures. We will estimate the seroprevalence of SARS-CoV-2, taking into account test performance and adjusting for the age and sex of the respective populations. ETHICS AND DISSEMINATION: Ethical approval was received for all participating countries. Results will be disseminated through reports and presentations at the country level as well as peer-reviewed publications and international scientific conferences presentations.

A cluster randomized controlled trial for assessing POC-CCA test based praziquantel treatment for schistosomiasis control in pregnant women and their young children: study protocol of the freeBILy clinical trial in Madagascar.

BACKGROUND: Mass drug administration (MDA) of praziquantel is one of the main control measures against human schistosomiasis. Although there are claims for including pregnant women, infants and children under the age of 5 years in high-endemic regions in MDA campaigns, they are usually not treated without a diagnosis. Diagnostic tools identifying infections at the primary health care centre (PHCC) level could therefore help to integrate these vulnerable groups into control programmes. freeBILy (fast and reliable easy-to-use-diagnostics for eliminating bilharzia in young children and mothers) is an international consortium focused on implementing and evaluating new schistosomiasis diagnostic strategies. In Madagascar, the study aims to determine the effectiveness of a test-based schistosomiasis treatment (TBST) strategy for pregnant women and their infants and children up until the age of 2 years. METHODS: A two-armed, cluster-randomized, controlled phase III trial including 5200 women and their offspring assesses the impact of TBST on child growth and maternal haemoglobin in areas of medium to high endemicity of Schistosoma mansoni. The participants are being tested with the point of care-circulating cathodic antigen (POC-CCA) test, a commercially available urine-based non-invasive rapid diagnostic test for schistosomiasis. In the intervention arm, a POC-CCA-TBST strategy is offered to women during pregnancy and 9 months after delivery, for their infants at 9 months of age. In the control arm, study visit procedures are the same, but without the POC-CCA-TBST procedure. All participants are being offered the POC-CCA-TBST 24 months after delivery. This trial is being integrated into the routine maternal and child primary health care programmes at 40 different PHCC in Madagascar's highlands. The purpose of the trial is to assess the effectiveness of the POC-CCA-TBST for controlling schistosomiasis in young children and mothers. DISCUSSION: This trial assesses a strategy to integrate pregnant women and their children under the age of 2 years into schistosomiasis control programmes using rapid diagnostic tests. It includes local capacity building for clinical trials and large-scale intervention research. TRIAL REGISTRATION: Pan-African Clinical Trial Register PACTR201905784271304. Retrospectively registered on 15 May 2019.

Prospective, observational study to assess the performance of CAA measurement as a diagnostic tool for the detection of Schistosoma haematobium infections in pregnant women and their child in Lambaréné, Gabon: study protocol of the freeBILy clinical trial in Gabon.

BACKGROUND: Schistosoma antigen detection in urine is a valuable diagnostic approach for schistosomiasis control programmes because of the higher sensitivity compared to parasitological methods and preferred sampling of urine over stool. Highly accurate diagnostics are important in low Schistosoma transmission areas. Pregnant women and young children could particularly benefit from antigen testing as praziquantel (PZQ) can be given to only confirmed Schistosoma cases. This prevents the unborn baby from unnecessary exposure to PZQ. We present here the protocol of a diagnostic study that forms part of the freeBILy project. The aim is to evaluate the accuracy of circulating anodic antigen (CAA) detection for diagnosis of Schistosoma haematobium infections in pregnant women and to validate CAA as an endpoint measure for anti-Schistosoma drug efficacy. The study will also investigate Schistosoma infections in infants. METHODS: A set of three interlinked prospective, observational studies is conducted in Gabon. The upconverting phosphor lateral flow (UCP-LF) CAA test is the index diagnostic test that will be evaluated. The core trial, sub-study A, comprehensively evaluates the accuracy of the UCP-LF CAA urine test against a set of other Schistosoma diagnostics in a cross-sectional trial design. Women positive for S. haematobium will proceed with sub-study B and will be randomised to receive PZQ treatment immediately or after delivery followed by weekly sample collection. This approach includes comparative monitoring of CAA levels following PZQ intake and will also contribute further data for safety of PZQ administration during pregnancy. Sub-study C is a longitudinal study to determine the incidence of S. haematobium infection as well as the age for first infection in life-time. DISCUSSION: The freeBILy trial in Gabon will generate a comprehensive set of data on the accuracy of the UCP-LF CAA test for the detection of S. haematobium infection in pregnant women and newborn babies and for the use of CAA as a marker to determine PZQ efficacy. Furthermore, incidence of Schistosoma infection in infants will be reported. Using the ultrasensitive diagnostics, this information will be highly relevant for Schistosoma prevalence monitoring by national control programs as well as for the development of medicaments and vaccines. TRIAL REGISTRATION: The registration number of this study is NCT03779347 ( clinicaltrials.gov , date of registration: 19 December 2018).

Fast and reliable easy-to-use diagnostics for eliminating bilharzia in young children and mothers: An introduction to the freeBILy project.

Schistosoma antigen detection tests have a large potential for schistosomiasis control programs due to their ability to detect active and ongoing Schistosoma infections, their much higher sensitivity compared to microscopical methods, and the possibility to use non-invasive urine samples. Pregnant women and young children could especially benefit from affordable and easy-to-use antigen tests as inclusion of these vulnerable groups in mass drug administration campaigns will always require higher justification hurdles, especially in low to middle endemic regions with a higher proportion of individuals who are not infected and thus unnecessarily exposed to praziquantel. The overall objective of the 'fast and reliable easy-to-use diagnostics for eliminating bilharzia in young children and mothers' (freeBILy, www.freeBILy.eu) project is to thoroughly evaluate the point-of-care circulating cathodic antigen (POC-CCA) and the up-converting phosphor reporter particle, lateral flow circulating anodic antigen (UCP-LF CAA) urine strip tests to diagnose Schistosoma infections in pregnant women and young children and to assess their potential as a schistosomiasis control tool in test-and-treat strategies. The freeBILy project will generate valuable, evidence-based findings on improved tools and test-and-treat strategies to reduce the burden of schistosomiasis in pregnant women and young children.

Needs assessment for a formal emergency medicine residency program in southern Madagascar.

INTRODUCTION: World Health Organization data for Madagascar reveal that the nation's under age five mortality rate is 56/1000, and that its maternal mortality rate is 440/100,000. Malaria, leprosy, plague, and tuberculosis remain significant communicable disease threats. Malnutrition rates are improving but continue to impact negatively on the general health of the Malagasy population, especially in the southern region with its 1.9 million inhabitants. There are no emergency medicine (EM) training programs to serve the southern half of Madagascar, which has a large urban population in Fianarantsoa. This study aimed to assess the need for and potential feasibility of an emergency medicine training program in southern Madagascar. METHODS: We met with the institutional leadership on site at the university hospital in Fianarantsoa. A needs assessment was performed on multiple domains. Domain 1: existing hospital infrastructure and its physical plant and emergency centre (EC) space allotment. Domain 2: existing clinical and technological resources. Domain 3: educational resources and the existing curriculum for EM. Domain 4: medical student educational program and availability of prospective residency candidates. Domain 5: pre-hospital care and emergency medical services. RESULTS: The size of the EC is adequate for the current census. Clinical resources are typical of many developing countries, with significant need for technological advancement and support, which we delineate in the body of our paper. There is an existing curriculum in Antananarivo and in Majanga, as well as one available through the African Federation for Emergency Medicine. The medical school in the area is relatively new, with graduating classes numbering approximately 30. There is no organised pre-hospital care system, no 9-1-1 equivalent, and no pre-hospital treatment from within metropolitan Fianarantsoa. CONCLUSIONS: While the needs assessment indicates substantial need for emergency medicine development in southern Madagascar, the yield (particularly for the metropolitan Fianarantsoa area) would serve the population well.

Needs assessment for a formal emergency medicine residency program in southern Madagascar

Introduction:World Health Organization data for Madagascar reveal that the nation's under age five mortality rate is 56/1000, and that its maternal mortality rate is 440/100,000. Malaria, leprosy, plague, and tuberculosis remain significant communicable disease threats. Malnutrition rates are improving but continue to impact negatively on the general health of the Malagasy population, especially in the southern region with its 1.9 million inhabitants. There are no emergency medicine (EM) training programs to serve the southern half of Madagascar, which has a large urban population in Fianarantsoa. This study aimed to assess the need for and potential feasibility of an emergency medicine training program in southern Madagascar. Methods:We met with the institutional leadership on site at the university hospital in Fianarantsoa. A needs assessment was performed on multiple domains. Domain 1: existing hospital infrastructure and its physical plant and emergency centre (EC) space allotment. Domain 2: existing clinical and technological resources. Domain 3: educational resources and the existing curriculum for EM. Domain 4: medical student educational program and availability of prospective residency candidates. Domain 5: pre-hospital care and emergency medical services.Results: The size of the EC is adequate for the current census. Clinical resources are typical of many developing countries, with significant need for technological advancement and support, which we delineate in the body of our paper. There is an existing curriculum in Antananarivo and in Majanga, as well as one available through the African Federation for Emergency Medicine. The medical school in the area is relatively new, with graduating classes numbering approximately 30. There is no organised pre-hospital care system, no 9-1-1 equivalent, and no pre-hospital treatment from within metropolitan Fianarantsoa. Conclusions:While the needs assessment indicates substantial need for emergency medicine development in southern Madagascar, the yield (particularly for the metropolitan Fianarantsoa area) would serve the population well

Hydrophobia of human rabies.

Hydrophobia is a clinical sign characteristic of human rabies. This sign occurs following paroxysmal contractions of pharynx responsible for hydrophobic spasms.

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.

[Antibiotic consumption at Antananarivo University Hospital: prevalence and strategic challenges]. / Consommation d’'antibiotiques au Centre Hospitalier Universitaire d’Antananarivo : prévalence et défis stratégiques.

INTRODUCTION: Very few studies have been conducted on antibiotic consumption in Madagascar. The objective of this study was to describe antibiotic consumption in a tertiary university hospital in Antananarivo, Madagascar to more clearly define good antibiotic use strategies. MATERIALS AND METHOD: A one-day prevalence survey was conducted on 5 April 2011 in the 339-bed Befelatanana Hospital with a bed occupation rate of 65.5%. RESULTS: The prevalence of antibiotic therapy among the 222 patients hospitalised on the day of the survey was 57.2%. Almost one half (49.6%) of patients received a combination of at least two antibiotics. The classes of antibiotics most commonly prescribed were beta-lactam antibiotics (55.3%), imidazoles (14.9%), aminoglycosides (14.9%), quinolones (7.9%) and macrolides with 7% of prescriptions. Penicillins accounted for 55.5% of all beta-lactam antibiotic prescriptions, followed by third-generation cephalosporins. Children under the age of 14 years (p<0.019) and patients with invasive devices (p<10(-6)) received more antibiotics. Antibiotic prescription in the Emergency Room­Intensive Care Unit was significantly higher than in the other wards (p<0.01). CONCLUSION: A high rate of antibiotic use was observed in Befelatanana University Hospital. Beta-lactam antibiotics were the agents most commonly prescribed and the Emergency Room­Intensive Care Unit was the leading antibiotic prescriber. It is essential to set up a good antibiotic use policy.

Identification of nasal colonization with ß-lactamase-producing Enterobacteriaceae in patients, health care workers and students in Madagascar.

This study assesses the nasal occurrence of ß-lactamase-producing Enterobacteriaceae both in patients in a hospital department of infectious diseases at admission and in healthy Madagascan students and health care workers. Nasal swabs from 681 students, 824 health care workers, and 169 patients were obtained in Antananarivo, Madagascar, and transferred to Germany. Screening for ß-lactamase (ESBL, ampC) producing Enterobacteriaceae was performed by cultural and molecular approaches, comprising Brilliance ESBL agar, E-testing, ABCD-testing, and commercial hyplex ESBL and SuperBug ID PCR. Regarding ESBL-positive strains and strains with resistance against at least three out of the four tested bactericidal antibiotic drugs, 0.3% (five out of 1541) of the students and health care workers group showed nasal colonization, whereas colonization was observed in 7.1% (12 out of 169) of the hospitalized patients at admission. No appreciably reduced detection rates after sample storage and intercontinental transport were observed. A considerable proportion of nasal colonization with cephalosporin-resistant Enterobacteriaceae was demonstrated in Madagascan hospital patients at admission, posing a risk of developing future endogenous infections. The nasal colonization of healthy individuals was negligible. Good storage and transport stability of Enterobacteriaceae will allow for future studies even in areas difficult to access.