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Objective: The outbreak of coronavirus disease 2019 (COVID-19) in South Kivu, Democratic Republic of Congo raised concerns regarding additional morbidity and mortality. Updating these indicators before a second wave is essential in order to prepare for additional help. Methods: From mid-May to mid-December 2020, weekly surveys were undertaken in sampled streets from 10 health areas to quantify the use of barrier measures, and interview pedestrians about sickness and deaths in their households. Crude death rates (CDRs) were estimated. Results: Minimal use or no use of face masks was observed in at least half of the streets. From May to December 2020, the number of suspected cases of COVID-19 increased six-fold (P < 0.05). Of deaths within 30 days preceding the interviews, 20% were considered to be related to COVID-19. The monthly CDRs at the beginning and end of the study were approximately 5 and 25 per 1000 population, respectively (P < 0.05); that is, annual CDRs of 60 and 260 per 1000 population, respectively. Thus, during the first wave, the estimated mortality rate increased by 50% compared with previous years, and increased at least four-fold by the end of 2020. Conclusion: Despite possible overestimations, the excess mortality in South Kivu is extremely concerning. This crisis calls for a rapid response and increased humanitarian assistance.

Background Persistence of Ebola virus (EBOV) in semen remains of deep concern, as sexual transmission of EBOV seems plausible up to 6 months after acute phase of Ebola virus disease (EVD). Favipiravir, a broad spectrum antiviral product, has been evaluated in reducing EVD mortality in Guinea in 2014–2015 in the JIKI trial, the pharmacokinetic results of which suggest that an increase of dose might be necessary to achieve a therapeutically relevant exposure. In FORCE trial, we aimed at evaluating the tolerance and activity of high doses of favipiravir in male EVD survivors with EBOV RNA detection in semen in Guinea. Case In 2016, we launched a phase IIa open-labeled multicenter dose escalation study. Male survivors of EVD with EBOV RT-PCR positive on semen received a loading dose of 2400 mg BID of favipiravir on day 1 then a maintenance dose of 1800 mg BID from day 2–14. The primary outcome was the tolerance, assessed daily during period treatment and up to day 90. Unfortunately only two participants were included and the trial was stopped for lack of recruitment. No clinical adverse event of grade 3/4 was reported for both patients. One patient experienced a grade 3 hypocalcemia at day 10 and 14. Conclusions High doses of favipiravir were well tolerated in these two participants. Better characterized tolerance and pharmacokinetics of high doses of favipiravir are of utmost importance considering that favipiravir is a candidate treatment for a variety of emerging severe viral diseases with poor prognosis., Highlights • Ebola virus (EBOV) RNA in semen of survivors of EBOV disease up to 17 months after disease onset. • High doses of Favipiravir were well tolerated in EBOV disease survivors. • No QTc interval prolongation of grade 2, 3 or 4 with high doses of Favipiravir.

Background Worldwide, COVID-19 outbreaks in nursing homes have often been sudden and massive. The study investigated the role SARS-CoV-2 virus spread in nearby population plays in introducing the disease in nursing homes. Material and methods This was carried out through modelling the occurrences of first cases in each of 943 nursing homes of Auvergne-Rhône-Alpes French Region over the first epidemic wave (March-July, 2020). The cumulative probabilities of COVID-19 outbreak in the nursing homes and those of hospitalization for the disease in the population were modelled in each of the twelve Départements of the Region over period March-July 2020. This allowed estimating the duration of the active outbreak period, the dates and heights of the peaks of outbreak probabilities in nursing homes, and the dates and heights of the peaks of hospitalization probabilities in the population. Spearman coefficient estimated the correlation between the two peak series. Results The cumulative proportion of nursing homes with COVID-19 outbreaks was 52% (490/943; range: 22–70% acc. Département). The active outbreak period in the nursing homes lasted 11 to 21 days (acc. Département) and ended before lockdown end. Spearman correlation between outbreak probability peaks in nursing homes and hospitalization probability peaks in the population (surrogate of the incidence peaks) was estimated at 0.71 (95% CI: [0.66; 0.78]). Conclusion The modelling highlighted a strong correlation between the outbreak in nursing homes and the external pressure of the disease. It indicated that avoiding disease outbreaks in nursing homes requires a tight control of virus spread in the surrounding populations.

Background Combined prevention interventions, including early antiretroviral therapy initiation, may substantially reduce HIV incidence in hyperendemic settings. Our aim was to assess the potential short-term impact of combined interventions on HIV spreading in the adult population of Mbongolwane and Eshowe (KwaZulu-Natal, South Africa) using sex- and age-specific scenarios, and age-targeted interventions. Methods A mathematical model was used with data on adults (15–59 years) from the Mbongolwane and Eshowe HIV Impact in Population Survey to compare the effects of various interventions on the HIV incidence rate. These interventions included increase in antiretroviral therapy (ART) coverage with extended eligibility criteria, increase in voluntary medical male circumcision (VMMC), and implementation of pre-exposure prophylaxis (PrEP) among women. Results With no additional interventions to the ones in place at the time of the survey (ART at CD4

Objective HIV diagnosis and linkage to care are the main barriers in Africa to achieving the UNAIDS 90-90-90 targets. We assessed HIV-positive status awareness and linkage to care among survey participants in Chiradzulu District, Malawi. Method Nested cohort study within a population-based survey of persons aged 15–59 years between February and May 2013. Participants were interviewed and tested for HIV (and CD4 if found HIV-positive) in their homes. Multivariable regression was used to determine factors associated with HIV-positive status awareness prior to the survey and subsequent linkage to care. Results Of 8277 individuals eligible for the survey, 7270 (87.8%) participated and were tested for HIV. The overall HIV prevalence was 17.0%. Among HIV-positive participants, 77.0% knew their status and 72.8% were in care. Women (adjusted odds ratio [aOR] 6.5, 95% CI 3.2–13.1) and older participants (40–59 vs. 15–29 years, aOR 10.1, 95% CI 4.0–25.9) were more likely to be aware of their positive status. Of those newly diagnosed, 47.5% were linked to care within 3 months. Linkage to care was higher among older participants (40–59 vs. 15–29, adjusted hazard ratio [aHR] 3.39, 95% CI 1.83–6.26), women (aHR 1.73, 95% CI 1.12–2.67) and those eligible for ART (aHR 1.61, 95% CI 1.03–2.52). Conclusions In settings with high levels of HIV awareness, home-based testing remains an efficient strategy to diagnose and link to care. Men were less likely to be diagnosed, and when diagnosed to link to care, underscoring the need for a gender focus in order to achieve the 90-90-90 targets.

Supplemental Digital Content is Available in the Text., Introduction: Identifying gaps in HIV testing and treatment is essential to design specific strategies targeting those not accessing HIV services. We assessed the prevalence and factors associated with being HIV untested, unaware, untreated, and virally unsuppressed in KwaZulu-Natal, South Africa. Methods: Cross-sectional population-based survey. People aged 15–59 years were eligible. Interviews, HIV testing, and blood collection for antiretroviral drug presence test, CD4, and viral load were done at the participants' home. Results: Of the 5649 individuals included, 81.4% (95% CI: 79.8 to 82.9) had previously been tested. HIV prevalence was 25.2%. HIV-positivity awareness rate was 75.2% (95% CI: 72.9 to 77.4). Of all unaware, 73.3% of people were aged

Funding Institut National de la Santé et de la Recherche Médicale, Reacting, the French Ebola Task Force, Institut de Recherche pour le Développement, and Montpellier University Of Excellence-University of Montpellier.; International audience; BACKGROUND : The prevalence of Ebola virus infection among people who have been in contact with patients with Ebola virus disease remains unclear, but is essential to understand the dynamics of transmission. This study aimed to identify risk factors for seropositivity and to estimate the prevalence of Ebola virus infection in unvaccinated contact persons.METHODS : In this retrospective, cross-sectional observational study, we recruited individuals between May 12, 2016, and Sept 8, 2017, who had been in physical contact with a patient with Ebola virus disease, from four medical centres in Guinea (Conakry, Macenta, N'zérékoré, and Forécariah). Contact persons had to be 7 years or older and not diagnosed with Ebola virus disease. Participants were selected through the Postebogui survivors' cohort. We collected self-reported information on exposure and occurrence of symptoms after exposure using a questionnaire, and tested antibody response against glycoprotein, nucleoprotein, and 40-kDa viral protein of Zaire Ebola virus by taking a blood sample. The prevalence of Ebola virus infection was estimated with a latent class model.FINDINGS : 1721 contact persons were interviewed and given blood tests, 331 of whom reported a history of vaccination so were excluded, resulting in a study population of 1390. Symptoms were reported by 216 (16%) contact persons. The median age of participants was 26 years (range 7-88) and 682 (49%) were male. Seropositivity was identified in 18 (8·33%, 95% CI 5·01-12·80) of 216 paucisymptomatic contact persons and 39 (3·32%, 5·01-12·80) of 1174 (2-4) asymptomatic individuals (p=0·0021). Seropositivity increased with participation in burial rituals (adjusted odds ratio [aOR] 2·30, 95% CI 1·21-4·17; p=0·0079) and exposure to blood or vomit (aOR 2·15, 1·23-3·91; p=0·0090). Frequency of Ebola virus infection varied from 3·06% (95% CI 1·84-5·05) in asymptomatic contact persons who did not participate in burial rituals to 5·98% (2·81-8·18) in those who did, and from 7·17% (3·94-9·09) in paucisymptomatic contact persons who did not participate in burial rituals to 17·16% (12·42-22·31) among those who did.INTERPRETATION : This study provides a new assessment of the prevalence of Ebola virus infection among contact persons according to exposure, provides evidence for the occurrence of paucisymptomatic cases, and reinforces the importance of closely monitoring at-risk contact persons.

Introduction: Direct measurement of antiretroviral treatment (ART) program indicators essential for evidence-based planning and evaluation – especially HIV incidence, population viral load, and ART eligibility – is rare in sub-Saharan Africa. Design/methods: To measure key indicators in rural western Kenya, an area with high HIV burden, we conducted a population survey in September to November 2012 via multistage cluster sampling, recruiting everyone aged 15–59 years living in 3330 randomly selected households. Consenting individuals were interviewed and tested for HIV at home. Participants testing positive were assessed for CD4+ cell count and viral load, and their infections classified as either recent or long term based on Limiting Antigen Avidity assays. HIV-negative participants were tested by nucleic acid amplification to detect acute infections. Results: Of 6833 household members eligible for the study, 6076 (94.7% of all women and 81.0% of men) agreed to participate. HIV prevalence and incidence were 24.1% [95% confidence interval [CI] 23.0–25.2] and 1.9 new cases/100 person-years (95% CI 1.1–2.7), respectively. Among HIV-positive participants, 59.4% (95% CI 56.8–61.9) were previously diagnosed, 53.1% (95% CI 50.5–55.7) were receiving care, and 39.7% (95% CI 37.1–42.4) had viral load less than 1000 copies/ml. Applying 2013 WHO recommendations for ART initiation increased the proportion of ART-eligible people from 60.0% (based on national guidelines in place during the survey; 95% CI 57.3–62.7) to 82.0% (95% CI 79.5–84.5). Among HIV-positive people not receiving ART, viral load increased with decreasing CD4+ cell count (500–749 vs. ≥750 cells/μl, adjusted mean difference, 0.40 log10 copies/ml, 95% CI 0.20–0.60, P

International audience; OBJECTIVE: To examine how patient characteristics combined with ART eligibility expansions affect the initiation of antiretroviral therapy (ART) among eligible patients attending a referral center in Senegal from 1998 to 2015. METHODS: This is a retrospective observational study carried out at the outpatient treatment Centre (Centre de Traitement Ambulatoire) in Dakar, Senegal, based on computerized medical records, gathered from 1998 to 2015, of ART-naïve patients over 15 years of age. ART eligibility was defined as (CD4 count below 200) or as (WHO stage 4) or as (WHO stage 3 with (CD4 count below 350 or with unavailable CD4 count)) in 1998-2010; as (CD4 count below 350) or as (WHO stage 3 or 4) in 2011-2013; as (CD4 count below 500) or as (WHO stage 3 or 4) in 2014-2015. Four periods were defined according to ART eligibility expansions and Senegal's HIV care history: 1998-2003 (P 1), 2004-2010 (P 2), 2011-2013 (P3), and 2014-2015 (P4). Patients were expected to participate financially in their treatment during the first period (P1). RESULTS: A total of 3651 patient records were included. The median patient age was 40 years (IQR: 32-48). Women represented 56% of the population. The median CD4 count was 183 cells/mm3. Overall, 53% of patients had CD4 \textless 200 cells/mm3 at entry. This proportion reached 45% in 2014-2015. 2535 patients (69%) were eligible for therapy, including 1503 (41%) who started ART. The proportion of treated patients among those who were eligible at entry or later increased steadily from 25%, 47%, 75% to 82% in the four periods, respectively. The median time to treatment decreased from 5.6 months (IQR: 3-11) in P1 to 0.8 months (IQR: 0-2) in P4. Eligible patients with more advanced disease (CD4\textless200 cells/mm3 and/or clinical stage 3 or 4) were more likely to be ART initiated than those with CD4>=200 cells/mm3 and/or clinical stage 1 or 2 at each stage of ART eligibility expansion. CONCLUSION: ART eligibility expansions were marked by a sharp increase in the proportion of eligible patients initiating treatment. These results show that in terms of management, the target of "Test and Treat" can be easily reached but that HIV testing will remain a key element to improve treatment success, as illustrated by the high proportion of people with advanced stage of infection at the time of ART initiation.

Background Malaria endemic countries need to assess efficacy of anti-malarial treatments on a regular basis. Moreover, resistance to artemisinin that is established across mainland South-East Asia represents today a major threat to global health. Monitoring the efficacy of artemisinin-based combination therapies is of paramount importance to detect as early as possible the emergence of resistance in African countries that toll the highest burden of malaria morbidity and mortality. Methods A WHO standard protocol was used to assess efficacy of the combinations artesunate–amodiaquine (AS–AQ Winthrop®), dihydroartemisinin–piperaquine (DHA–PPQ, Eurartesim®) and artemether–lumefantrine (AM–LM, Coartem®) taken under supervision and respecting pharmaceutical recommendations. The study enrolled for each treatment arm 212 children aged 6–59 months living in Maradi (Niger) and suffering with uncomplicated falciparum malaria. The Kaplan–Meier 42-day PCR-adjusted cure rate was the primary outcome. A standardized parasite clearance estimator was used to assess delayed parasite clearance as surrogate maker of suspected artemisinin resistance. Results No early treatment failures were found in any of the study treatment arms. The day-42 PCR-adjusted cure rate estimates were 99.5, 98.4 and 99.0% in the AS–AQ, DHA–PPQ and AM–LM arms, respectively. The reinfection rate (expressed also as Kaplan–Meier estimates) was higher in the AM–LM arm (32.4%) than in the AS–AQ (13.8%) and the DHA–PPQ arm (24.9%). The parasite clearance rate constant was 0.27, 0.26 and 0.25 per hour for AS–AQ, DHA–PPQ and AM–LM, respectively. Conclusions All the three treatments evaluated largely meet WHO criteria (at least 95% efficacy). AS–AQ and AL–LM may continue to be used and DHA–PPQ may be also recommended as first-line treatment for uncomplicated falciparum malaria in Maradi. The parasite clearance rate were consistent with reference values indicating no suspected artemisinin resistance. Nevertheless, the monitoring of anti-malarial drug efficacy should continue. Trial registration details Registry number at ClinicalTrial.gov: NCT01755559

Background: In resource-limited countries, estimating CD4-specific incidence rates of mortality and morbidity among patients receiving antiretroviral therapy (ART) may help assess the effectiveness of care and treatment programmes, identify program weaknesses, and inform decisions. Methods: We pooled data from 13 research cohorts in 5 sub-Saharan African (Benin, Burkina Faso, Cameroon, Cote d'Ivoire, and Senegal) and 2 Asian (Cambodia and Laos) countries. HIV-infected adults (18 years and older) who received ART in 1998-2008 and had at least one CD4 count available were eligible. Changes in CD4 counts over time were estimated by a linear mixed regression. CD4-specific incidence rates were estimated as the number of first events occurring in a given CD4 stratum divided by the time spent within the stratum. Results: Overall 3917 adults (62% women) on ART were followed up during 10,154 person-years. In the

Background The performance of different malaria rapid diagnostic tests (RDT) may be influenced by transmission intensity and by the length of time each test requires to become negative after treatment and patient’s recovery. Methods Results of three RDTs (two HRP2 and one pLDH antigen-based tests) were compared to blood smear microscopy (the gold standard method) in children under 5 years of age living in a high versus low malaria intensity setting in southwestern Uganda. In each setting, 212 children, who tested positive by at least one RDT and by microscopy, were treated with artemether-lumefantrine. RDTs and microscopy were then repeated at fixed intervals to estimate each test’s time to negativity after treatment and patient recovery. Results In the two settings, sensitivities ranged from 98.4 to 99.2 % for the HRP2 tests and 94.7 to 96.1 % for the pLDH test. Specificities were 98.9 and 98.8 % for the HRP2 tests and 99.7 % for the pLDH test in the low-transmission setting and 79.7, 80.7 and 93.9 %, respectively, in the high-transmission setting. Median time to become negative was 35–42 or more days for the HRP2 tests and 2 days for the pLDH test. Conclusions High transmission contexts and a long time to become negative resulted in considerably reduced specificities for the HRP2 tests. Choice of RDT for low- versus high-transmission settings should balance risks and benefits of over-treatment versus missing malaria cases. Trial registration: Registry number at ClinicalTrial.gov: NCT01325974 Electronic supplementary material The online version of this article (doi:10.1186/s12936-016-1529-6) contains supplementary material, which is available to authorized users.

Background Multiple prevention interventions, including early antiretroviral therapy initiation, may reduce HIV incidence in hyperendemic settings. Our aim was to predict the short-term impact of various single and combined interventions on HIV spreading in the adult population of Ndhiwa subcounty (Nyanza Province, Kenya). Methods A mathematical model was used with data on adults (15–59 years) from the Ndhiwa HIV Impact in Population Survey to compare the impacts on HIV prevalence, HIV incidence rate, and population viral load suppression of various interventions. These interventions included: improving the cascade of care (use of three guidelines), increasing voluntary medical male circumcision (VMMC), and implementing pre-exposure prophylaxis (PrEP) use among HIV-uninfected women. Results After four years, improving separately the cascade of care under the WHO 2013 guidelines and under the treat-all strategy would reduce the overall HIV incidence rate by 46 and 58 %, respectively, vs. the baseline rate, and by 35 and 49 %, respectively, vs. the implementation of the current Kenyan guidelines. With conservative and optimistic scenarios, VMMC and PrEP would reduce the HIV incidence rate by 15–25 % and 22–28 % vs. the baseline, respectively. Combining the WHO 2013 guidelines with VMMC would reduce the HIV incidence rate by 35–56 % and combining the treat-all strategy with VMMC would reduce it by 49–65 %. Combining the WHO 2013 guidelines, VMMC, and PrEP would reduce the HIV incidence rate by 46–67 %. Conclusions The impacts of the WHO 2013 guidelines and the treat-all strategy were relatively close; their implementation is desirable to reduce HIV spread. Combining several strategies is promising in adult populations of hyperendemic areas but requires regular, reliable, and costly monitoring. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-1520-4) contains supplementary material, which is available to authorized users.

Objective To assess the effectiveness of blood transfusions in a hospital of north-eastern Democratic Republic of the Congo. Methods Prospective study of children admitted for severe anaemia. During admission, data were collected on clinical condition and haemoglobin levels, before and after blood transfusion. A linear regression model was built to explore factors associated with haemoglobin level after transfusion. Risk factors for mortality were explored through multivariate logistic regression. Results Haemoglobin level (Hb) was below 4 g/dl in 35% (230/657), between 4 and 6 g/dl in 58% (348/657) and at least 6 g/dl in another 6% (43/657) of the transfused children. A transfusion of 15 ml/kg of whole blood increased the Hb from 4.4 to 7.8 g/dl. Haemoglobin level after transfusion was associated with baseline Hb, quantity of delivered blood and history of previous transfusions. Overall case-fatality rate was 5.6% (37/657). Risk factors for deaths were co-morbidities such as chest infection, meningitis or malnutrition, Hb ≥ 6 g/dl, impaired consciousness or jugular venous distention on admission, and provenance. Conclusion Transfusion was a frequent practice, the use of which could clearly have been rationalised. While indications should be restricted, quantities of transfused blood should be adapted to needs. Objectif: Evaluer l’efficacite des transfusions sanguines dans un hopital du nord-est de la Republique Democratique du Congo. Methodes: Etude prospective sur des enfants admis pour une anemie severe. Lors de l’admission, les donnees ont ete recueillies sur l’etat clinique et le taux d’hemoglobine, avant et apres la transfusion sanguine. Un modele de regression lineaire a ete construit pour etudier les facteurs associes au taux d’hemoglobine apres la transfusion. Les facteurs de risque de mortalite ont ete explores par la regression logistique multivariee. Resultats: Le taux d’hemoglobine (Hb) etait inferieur a 4 g/dl chez 35% (230/657), entre 4 et 6 g/dl chez 58% (348/657) et au moins 6 g/dl chez 6% (43/657) des enfants transfuses. Une transfusion de 15 ml/kg de sang total augmentait le taux d’Hb de 4.4 a 7.8 g/dl. Le taux d’hemoglobine apres la transfusion etait associea l’Hb de base, la quantite de sang delivree et l’histoire de transfusions anterieures. Le taux global de letaliteetait de 5.6% (37/657). Les facteurs de risque pour les deces etaient les co-morbidites telles que l’infection des voies respiratoires, la meningite ou la malnutrition, l’Hb ≥ 6 g/dl, les troubles de la conscience ou la distension veineuse jugulaire lors de l’admission et l’origine. Conclusion: La transfusion etait une pratique frequente dont l’utilisation aurait bien pu etre rationalisee. Alors que les indications devraient etre limitees, les quantites de sang transfuse devraient etre adaptee aux besoins. Objetivo: Evaluar la efectividad de las transfusiones de sangre en un hospital en el noreste de la Republica Democratica del Congo. Metodos: Estudio prospectivo de ninos admitidos con anemia severa. Durante la admision, se recolectaron datos sobre la condicion clinica y los niveles de hemoglobina, antes y despues de recibir la transfusion de sangre. Se construyo un modelo de regresion linear para explorar factores asociados con los niveles de hemoglobina despues de la transfusion. Los factores de riesgo asociados a mortalidad se exploraron mediante una regresion logistica multivariable. Resultados: Los niveles de hemoglobina (Hb) estaban por debajo de 4 g/dl en un 35% (230/657), entre 4 y 6 g/dl en un 58% (348/657) y al menos en 6 g/dl en otro 6% (43/657) de los ninos transfundidos. Una transfusion de 15 ml/kg de sangre completa aumento la Hb de 4.4 a 7.8g/dl. Los niveles de hemoglobina despues de la transfusion estaban asociados con la Hb basal, la cantidad de sangre transfundida y el historial de transfusiones previas. La tasa de letalidad era del 5.6% (37/657). Los factores de riesgo asociados a muertes eran co-morbilidades tales como la infeccion de vias respiratorias, la meningitis o la desnutricion, Hb ≥ 6 g/dl, alteracion de la conciencia o distension de la vena yugular en el momento de la admision, y la procedencia. Conclusion: La transfusion es una practica frecuente, cuyo uso podria haber estado claramente racionalizado. Mientras que las indicaciones deberian de restringirse, las cantidades de sangre transfundida deberian adaptarse a las necesidades.

OBJECTIVE The use of didanosine (ddI) in first-line antiretroviral therapy has been recently promoted for resource-limited settings. We therefore compared the long-term effectiveness and safety of the regimen combining ddI, lamivudine, and efavirenz or nevirapine with that of the WHO-recommended regimen of zidovudine (ZDV), lamivudine, and efavirenz or nevirapine in antiretroviral-naive patients in Senegal. METHODS Observational cohort study of patients enrolled between January 2000 and April 2002 in the Senegalese antiretroviral drug access initiative. Multivariate analyses were performed to compare, between the ddI and ZDV groups, the proportion of patients with a viral load 0.3). The rate of death tended to be higher in the ddI group (P = 0.06). ddI was less commonly discontinued than ZDV (P = 0.03). CONCLUSION The combination of ddI, lamivudine, and efavirenz or nevirapine resulted in sustained viral suppression and immunological recovery.

Background Clinical diagnosis of Buruli ulcer (BU) due to Mycobacterium ulcerans can be challenging. We aimed to specify the differential diagnosis of skin lesions in a BU endemic area. Method We conducted a prospective diagnostic study in Akonolinga, Cameroon. Patients presenting with a skin ulcer suspect of BU were included. M. ulcerans was detected using swabs for Ziehl-Neelsen staining, PCR and culture. Skin punch biopsies were taken and reviewed by two histopathologists. Photographs of the lesions were taken and independently reviewed by two dermatologists. Final diagnosis was based on consensus, combining the results of laboratory tests and expert opinion. Results/ Discussion Between October 2011 and December 2013, 327 patients with ulcerative lesions were included. Median age was 37 years (0 to 87), 65% were males, and 19% HIV-positive. BU was considered the final diagnosis for 27% of the lesions, 85% of which had at least one positive laboratory test. Differential diagnoses were vascular lesions (22%), bacterial infections (21%), post-traumatic (8%), fistulated osteomyelitis (6%), neoplasia (5%), inflammatory lesions (3%), hemopathies and other systemic diseases (2%) and others (2%). The proportion of BU was similar between HIV-positive and HIV-negative patients (27.0% vs. 26.5%; p = 0.940). Half of children below 15 years of age were diagnosed with BU, compared to 26.8% and 13.9% among individuals 15 to 44 years of age and above, respectively (chi2 p, Author Summary In some areas of Africa, Australia or Japan, a specific skin infection presents as a wound which progressively increases in size in children and people of any age. The agent which causes this infection is named Mycobacterium ulcerans, close to the tuberculosis agent. This wound, also named Buruli ulcer (BU), may be confused with other common cutaneous diseases. During two years in Akonolinga, Cameroon, we evaluated the wounds of all patients who presented with suspected BU. This wound presentation was most frequently recorded in young children and males. Buruli ulcer was indeed the most frequent diagnosis in this area. However, with the help of laboratory and radiological techniques, we found that many of those patients not diagnosed with BU were suffering from: vascular insufficiency (older persons), benign superficial infections and bone infections (children). This observation is important and should help improve the diagnosis and treatment of patients with skin ulcers in Africa.

Background Access to laboratory diagnosis can be a challenge for individuals suspected of Buruli Ulcer (BU). Our objective was to develop a clinical score to assist clinicians working in resource-limited settings for BU diagnosis. Methododology/Principal Findings Between 2011 and 2013, individuals presenting at Akonolinga District Hospital, Cameroon, were enrolled consecutively. Clinical data were collected prospectively. Based on a latent class model using laboratory test results (ZN, PCR, culture), patients were categorized into high, or low BU likelihood. Variables associated with a high BU likelihood in a multivariate logistic model were included in the Buruli score. Score cut-offs were chosen based on calculated predictive values. Of 325 patients with an ulcerative lesion, 51 (15.7%) had a high BU likelihood. The variables identified for the Buruli score were: characteristic smell (+3 points), yellow color (+2), female gender (+2), undermining (+1), green color (+1), lesion hyposensitivity (+1), pain at rest (-1), size >5cm (-1), locoregional adenopathy (-2), age above 20 up to 40 years (-3), or above 40 (-5). This score had AUC of 0.86 (95%CI 0.82–0.89), indicating good discrimination between infected and non-infected individuals. The cut-off to reasonably exclude BU was set at scores, Author Summary In most Buruli ulcer (BU) endemic areas, laboratory diagnosis is hard to access and comes at a high cost. Clinicians are in need of new tools to assist them in identifying which patients truly require additional work-up and which can be treated directly. We analyzed the clinical data of all patients with ulcerative skin lesions that presented to Akonolinga District Hospital in Cameroon and identified which parameters were associated with BU diagnosis. We attributed a certain number of points to each parameter to build a “Buruli score”. Based on score results, clinicians can be advised either to directly treat BU (score ≥4), to look for another diagnosis (score

The objectives were to assess long-term adherence of the first HIV-1 patients receiving highly active antiretroviral therapy (HAART) in Senegal and to identify the main determinants of adherence. The first 180 patients enrolled in the Senegalese HAART initiative between August 1998 and April 2001 followed up for at least 30 days were eligible. Adherence was assessed monthly at each drug dispensation between November 1999 and November 2006 by a pharmacist using a pill count completed by a questionnaire. Adherence was expressed as the proportion of tablets taken to prescribed tablets. An adherence of 95% was considered to be good. A random-intercept logit model was fitted to identify the main determinants of adherence. Adherence data were available for 158 of 167 eligible patients. Twenty-nine patients died during the study period and 10 were lost to follow-up. Median treatment duration was 78 months accruing to 6657 person-months of observation. Overall mean adherence reached 91% [median: 100% interquartile range (IQR) 96-100%] and adherence exceeded 95% in 78% [95% CI 77-79%] of observations. After 4 years of treatment mean adherence stabilized around 90% and adherence >/= 95% stabilized around 70%. Treatment duration and protease inhibitor (PI)-based regimen (indinavir) had a negative effect on adherence but adherence tended to improve with time for patients receiving a PI. Patient-level variance was highly significant and accounted for a third of total variance. This work demonstrates that good long-term adherence can be achieved in the sub-Saharan context given close monitoring and adherence support measures confirms the worse adherence for indinavir and underlines the importance of patient heterogeneity. (authors)

Background Improving knowledge on local determinants of visceral leishmaniasis (VL) is crucial to guide the development of relevant control strategies. This study aimed to identify individual and household level determinants of primary VL in 24 highly endemic villages of Tabarak Allah hospital’s catchment area, Gedaref State, Sudan. Methods From September 2012 to July 2013, in an unmatched case-control design, 198 patients with primary VL were compared to 801 controls free of VL symptoms and with a negative VL rapid test. Using random spatial sampling, controls were selected with a distribution of age, sex and village of residence proportionate to the distribution of the target population. Data were collected using a structured questionnaire. Results Children and men were at higher risk of VL. Reporting VL patient(s) in the household in the previous year was the strongest VL risk factor. In a multivariate analysis, VL risk increased with household size, sleep location (outside the yard, not in the farm), evening outdoor activities in the rainy season (playing, watching TV, radio listening), use of ground nut oil as animal repellent and of smoke of Acacia seyal as indoor repellent, presence of dogs in the yard at night, Acacia nilotica in the yard’s immediate surroundings and of a forest at eye range. VL risk appeared to decrease with the use of drinking water sources other than the village water tank, a buffer distance from the adjacent house yard, and with the presence of animals other than dogs in the yard at night. In contrast with previous studies, housing factors, mosquito-net use, black cotton soil, ethnicity, socioeconomic index, presence of Balanites aegyptica and Azadirachta indica in the yard were not independent VL determinants. Discussion and conclusion Although these results do not provide evidence of causality, they provide useful suggestions for guiding further intervention studies on VL preventive measures., Author Summary Visceral leishmaniasis (VL), a fatal disease without treatment, is caused by a parasite (Leishmania) transmitted to humans through sandflies. Its epidemiology and the vectors involved in its transmission differ importantly between endemic zones. Preventive measures aim at reducing the parasite reservoirs and at limiting human exposure to sandflies. In Sudan, there is a lack of knowledge on VL risk and protective factors, limiting the possibility of development of control strategies. We conducted a study in a VL endemic area, Gedaref State (Sudan), to identify individual and household level determinants of clinical VL. We compared several characteristics of VL patients and inhabitants free of VL. We found that having a household member sick with VL in the previous year was the strongest VL risk factor. VL risk also seemed to be influenced by the household size, sleep location, evening outdoor activities, use of some repellents, and proximity to dogs at night. VL risk also appeared to decrease with a buffer distance between adjacent house yard and with the proximity to animals other than dogs at night. Our findings provide useful suggestions for guiding further intervention studies on VL preventive measures.

Treatment with inhaled nitric oxide as an adjuvant therapy for pediatric patients with cerebral malaria for 48 hours did not result in a significant difference in plasma Angiopoietin-1 levels when compared with placebo in a phase II open-label clinical trial., Background. Children with cerebral malaria (CM) have high rates of mortality and neurologic sequelae. Nitric oxide (NO) metabolite levels in plasma and urine are reduced in CM. Methods. This randomized trial assessed the efficacy of inhaled NO versus nitrogen (N2) as an adjunctive treatment for CM patients receiving intravenous artesunate. We hypothesized that patients treated with NO would have a greater increase of the malaria biomarker, plasma angiopoietin-1 (Ang-1) after 48 hours of treatment. Results. Ninety-two children with CM were randomized to receive either inhaled 80 part per million NO or N2 for 48 or more hours. Plasma Ang-1 levels increased in both treatment groups, but there was no difference between the groups at 48 hours (P = not significant [NS]). Plasma Ang-2 and cytokine levels (tumor necrosis factor-α, interferon-γ, interleukin [IL]-1β, IL-6, IL-10, and monocyte chemoattractant protein-1) decreased between inclusion and 48 hours in both treatment groups, but there was no difference between the groups (P = NS). Nitric oxide metabolite levels—blood methemoglobin and plasma nitrate—increased in patients treated with NO (both P < .05). Seven patients in the N2 group and 4 patients in the NO group died. Five patients in the N2 group and 6 in the NO group had neurological sequelae at hospital discharge. Conclusions. Breathing NO as an adjunctive treatment for CM for a minimum of 48 hours was safe, increased blood methemoglobin and plasma nitrate levels, but did not result in a greater increase of plasma Ang-1 levels at 48 hours.

OBJECTIVES: Process evaluation has become the mainstay of safe motherhood evaluation in developing countries, yet the extent to which indicators measuring access to obstetric services at the population level reflect levels of maternal mortality is uncertain. In this study we examine the association between population indicators of access to obstetric care and levels of maternal mortality in urban and rural West Africa. METHODS: In this ecological study we used data on maternal mortality and access to obstetric services from two population-based studies conducted in 16 sites in eight West African countries: the Maternal Mortality and Obstetric Care in West Africa (MAMOCWA) study in rural Senegal, Guinea-Bissau and The Gambia and the Morbidite Maternelle en Afrique de l'Ouest (MOMA) study in urban Burkina Faso, Cote d'Ivoire, Mali, Mauritanie, Niger and Senegal. RESULTS: In rural areas, maternal mortality, excluding early pregnancy deaths, was 601 per 100,000 live births, compared with 241 per 100,000 for urban areas [RR = 2.49 (CI 1.77-3.59)]. In urban areas, the vast majority of births took place in a health facility (83%) or with a skilled provider (69%), while 80% of the rural women gave birth at home without any skilled care. There was a relatively close link between levels of maternal mortality and the percentage of births with a skilled attendant (r = -0.65), in hospital (r = -0.54) or with a Caesarean section (r = -0.59), with marked clustering in urban and rural areas. Within urban or rural areas, none of the process indicators were associated with maternal mortality. CONCLUSION: Despite the limitations of this ecological study, there can be little doubt that the huge rural-urban differences in maternal mortality are due, at least in part, to differential access to high quality maternity care. Whether any of the indicators examined here will by themselves be good enough as a proxy for maternal mortality is doubtful however, as more than half of the variation in mortality remained unexplained by any one of them.

Background: Southwestern Uganda has high malaria heterogeneity despite moderate vector control and other interventions. Moreover, the early biting transmission and increased resistance to insecticides might compromise strategies relying on vector control. Consequently, monitoring of vector behaviour and insecticide efficacy is needed to assess the effectiveness of strategies aiming at malaria control. This eventually led to an entomological survey in two villages with high malaria prevalence in this region. Methods: During rainy, 2011 and dry season 2012, mosquitoes were collected in Engari and Kigorogoro, Kazo subcounty, using human landing collection, morning indoor resting collection, pyrethrum spray collection and larval collection. Circumsporozoite protein of Plasmodium falciparum sporozoites in female Anopheles mosquitoes was detected using ELISA assay. Bioassays to monitor Anopheles resistance to insecticides were performed. Results: Of the 1,021 female Anopheles species captured, 62% (632) were Anopheles funestus and 36% (371) were Anopheles gambiae s.l. The most common species were Anopheles gambiae s.l. in Engari (75%) and A. funestus in Kigorogoro (83%). Overall, P. falciparum prevalence was 2.9% by ELISA. The daily entomological inoculation rates were estimated at 0.17 and 0.58 infected bites/person/night during rainy and dry season respectively in Engari, and 0.81 infected bites/person/night in Kigorogoro during dry season. In both areas and seasons, an unusually early evening biting peak was observed between 6 - 8 p.m. In Engari, insecticide bioassays showed 85%, 34% and 12% resistance to DDT during the rainy season, dry season and to deltamethrin during the dry season, respectively. In Kigorogoro, 13% resistance to DDT and to deltamethrin was recorded. There was no resistance observed to bendiocarb and pirimiphos methyl. Conclusions: The heterogeneity of mosquito distribution, entomological indicators and resistance to insecticides in villages with high malaria prevalence highlight the need for a long-term vector control programme and monitoring of insecticide resistance in Uganda. The early evening biting habits of Anopheles combined with resistance to DDT and deltamethrin observed in this study suggest that use of impregnated bed nets alone is insufficient as a malaria control strategy, urging the need for additional interventions in this area of high transmission.

We review the theoretical framework for exploring the impact of individual and spatial heterogeneities in patterns of exposure and contamination and on the basic reproduction number, R0, for human schistosomes. Analysis of water contact data for 5 communities in Zimbabwe and Mali suggests that the impact is substantial, increasing R0 by factors of up to 6·5, mostly due to highly overdispersed distributions of contact rates among individuals. Several practical conclusions emerge: concentration of contacts at a single site should be avoided; the impact of control targeted at certain sites cannot be predicted without knowledge of how individuals' contacts are distributed among sites; control programmes targeted at individuals or sites contributing most to transmission can be very efficient but, conversely, will be ineffective if any of these individuals or sites are missed.

BACKGROUND Efficient malaria vector control requires knowledge of spatio-temporal vector dynamics. We have classified village groups according to the biting rate profiles of both Anopheles coluzzii and An. gambiae, the major malaria vectors in these villages. METHODS Mosquitoes were captured by human bait in 28 South Benin villages during 2009. Both An. coluzzii and An. gambiae counts in each village were standardized to focus on changes in the vector biting rate over time. Latent class trajectory modeling, allowing for random intercept at the 'village' level, was adjusted to standardized values. RESULTS The villages could be classified into two groups with distinct vector biting rate profiles (continuous/transient). This classification helped creating a map of vector biting rates in the area. The biting rate profiles were found to be significantly correlated with mean rainfall, altitude, average number of larval sites, and average normalized difference vegetation index. CONCLUSIONS In highly malaria-prone regions, knowledge of vector biting rate profiles is important to improve vector control interventions. A similar methodology may be applied to study the biting rate profiles of other vector-borne infections.

The authors describe the results of a program for the management of Buruli ulcers in Akonolinga (Cameroon). Its principal objective is to improve the diagnosis of dermatologic lesions and thereby to improve the indications for specific antibiotic therapy. This study, conducted in February, 2013, included 271 patients. Differential diagnosis of suspicious lesions was best with diagnostic examinations completed by histologic examination of a punch biopsy sample and advice from expert dermatologists.

Background Since December 2009, Médecins Sans Frontières has diagnosed and treated patients with visceral leishmaniasis (VL) in Tabarak Allah Hospital, eastern Gedaref State, one of the main endemic foci of VL in Sudan. A survey was conducted to estimate the VL incidence in villages around Tabarak Allah. Methods Between the 5th of May and the 17th of June 2011, we conducted an exhaustive door-to-door survey in 45 villages of Al-Gureisha locality. Deaths were investigated by verbal autopsies. All individuals with (i) fever of at least two weeks, (ii) VL diagnosed and treated in the previous year, and (iii) clinical suspicion of post-kala-azar dermal leishmaniasis (PKDL) were referred to medical teams for case ascertainment. A new case of VL was a clinical suspect with a positive rk39 rapid test or direct agglutination test (DAT). Results In the 45 villages screened, 17,702 households were interviewed, for a population of 94,369 inhabitants. The crude mortality rate over the mean recall period of 409 days was 0.13/10'000 people per day. VL was a possible or probable cause for 19% of all deaths. The VL-specific mortality rate was estimated at 0.9/1000 per year. The medical teams examined 551 individuals referred for a history of fever of at least two weeks. Out of these, 16 were diagnosed with primary VL. The overall incidence of VL over the past year was 7.0/1000 persons per year, or 7.9/1000 per year when deaths possibly or probably due to VL were included. Overall, 12.5% (11,943/95,609) of the population reported a past VL treatment episode. Discussion and Conclusion VL represents a significant health burden in eastern Gedaref State. Active VL case detection had a very low yield in this specific setting with adequate access to care and may not be the priority intervention to enhance control in similar contexts., Author Summary Visceral leishmaniasis (VL) is a life-threatening parasitic disease, transmitted by a sandfly. A survey was conducted to estimate the VL incidence in 45 villages located in the eastern part of Gedaref State, the main endemic focus of VL in Sudan. Between the 5th of May and the 17th of June 2011, we interviewed 17,702 households for a population of 94,369. Sixteen individuals were diagnosed with primary VL through active case-detection, and 725 reported VL treatment over the past year. The overall incidence rate of VL over the past year was 7.0/1000 persons per year. The crude mortality rate over the mean recall period of 409 days was 0.13/10'000 persons per day. VL was a possible or probable cause for 19% of all deaths. Taking also into account the VL-specific mortality of 0.9/1000 per year, the incidence was estimated at 7.9/1000 per year. Overall, 12.5% of the population reported having been treated for VL in the past. VL is a major public health issue in Gedaref. Active VL case detection had a very low yield in a context of adequate access to care. Such strategy seems redundant if patients already have access to care.

Background In April 2003, Médecins Sans Frontières launched an HIV/AIDS programme to provide free HAART to HIV-infected patients in Laos. Although HIV prevalence is estimated as low in this country, it has been increasing in the last years. This work reports the first results of an observational cohort study and it aims to identify the principal determinants of the CD4 cells evolution and to assess mortality among patients on HAART. Methods We performed a retrospective database analysis on patients initiated on HAART between 2003 and 2009 (CD4 Results A total of 1365 patients entered the programme and 913 (66.9%) received an HAART with a median CD4 of 49 cells/μL [IQR 15–148]. High baseline CD4 cell count and female gender were associated with a higher CD4 level over time. In addition, this gender difference increased over time. Two typical latent CD4 trajectories were revealed showing that 31% of women against 22% of men followed a high CD4 trajectory. In the long-term, women were more likely to attend appointments without delay. Mortality reached 6.2% (95% CI 4.8-8.0%) at 4 months and 9.1% (95% CI 7.3-11.3%) at 1 year. Female gender (HR=0.17, 95% CI 0.07-0.44) and high CD4 trajectory (HR=0.19, 95% CI 0.08-0.47) were independently associated with a lower death rate. Conclusions Patients who initiated HAART were severely immunocompromised yielding to a high early mortality. In the long-term on HAART, women achieved a better CD4 cells reconstitution than men and were less likely to die. This study highlights important differences between men and women regarding response to HAART and medical care, and questions men’s compliance to treatment.

Objective: We investigated the association between immune response and mortality in four HIV African programs supported by Medecins Sans Frontieres. Design: Multicentric retrospective cohort study. Methods: All antiretroviral therapy (ART) naive adults (>15 years) who initiated therapy between March 2001 and November 2010 and receiving therapy for 9 months or more were included. We described the evolution of mortality over time. Mixed Poisson models were used to assess the effect of updated CD4 cell counts and other potential risk factors on mortality. Findings: A total of 24 037 patients, of which 68% were women, contributed 69 516.2 person-years of follow-up. At ART initiation, 5718 patients (23.7%) were classified as WHO clinical stage 4, 1587 (6.6%) had a BMI below 16 kg/m2 and 2568 (10.7%) had CD4 cell count below 50 cells/μl. A total of 568 (2.4%) deaths were recorded during the study period. In the CD4 response categories 500 cells/μl or more, 350–499, 200–349, 50–199 cells/μl and less than 50 cells/μl, unadjusted mortality rates were 0.36; 0.58; 0.88; 1.91 and 7.43 per 100 person-years, respectively. In multivariate analysis, higher mortality was observed in patients with CD4 response levels 350–499 cells/μl [adjusted hazard ratio (aHR) 1.70, 95% confidence interval (CI) 1.26–2.30] and for those between 200–349 (aHR 2.56; 95% CI 1.93–3.38), compared to those with 500 cells/μl or more. Interpretation: The observed higher survival of patients with a CD4 response to ART higher than 500 cells/μl supports the need of further research to evaluate the individual benefit of initiating ART at higher CD4 levels in sub-Saharan Africa.

Background Human African trypanosomiasis is fatal without treatment. The long post-treatment follow-up (24 months) required to assess cure complicates patient management and is a major obstacle in the development of new therapies. We analyzed individual patient data from 12 programs conducted by Médecins Sans Frontières in Uganda, Sudan, Angola, Central African Republic, Republic of Congo and Democratic Republic of Congo searching for early efficacy indicators. Methodology/Principal Findings Patients analyzed had confirmed second-stage disease with complete follow-up and confirmed outcome (cure or relapse), and had CSF leucocytes counts (CSFLC) performed at 6 months post-treatment. We excluded patients with uncertain efficacy outcome: incomplete follow-up, death, relapse diagnosed with CSFLC below 50/µL and no trypanosomes. We analyzed the 6-month CSFLC via receiver-operator-characteristic curves. For each cut-off value we calculated sensitivity, specificity and likelihood ratios (LR+ and LR−). We assessed the association of the optimal cut-off with the probability of relapsing via random-intercept logistic regression. We also explored two-step (6 and 12 months) composite algorithms using the CSFLC. The most accurate cut-off to predict outcome was 10 leucocytes/µL (n = 1822, 76.2% sensitivity, 80.4% specificity, 3.89 LR+, 0.29 LR−). Multivariate analysis confirmed its association with outcome (odds ratio = 17.2). The best algorithm established cure at 6 months with = 50 leucocytes/µL; patients between these values were discriminated at 12 months by a 20 leucocytes/µL cut-off (n = 2190, 87.4% sensitivity, 97.7% specificity, 37.84 LR+, 0.13 LR−). Conclusions/Significance The 6-month CSFLC can predict outcome with some limitations. Two-step algorithms enhance the accuracy but impose 12-month follow-up for some patients. For early estimation of efficacy in clinical trials and for individual patients in the field, several options exist that can be used according to priorities., Author Summary Because Human African trypanosomiasis is fatal, it is crucial for the patient to determine if curative treatment has been effective. Unfortunately this is not possible without a 24-month laboratory follow-up, which is problematic and largely unaccomplished in the field reality. Studies that assessed early indicators have used small cohorts, yielding limited statistical power plus potential bias because of including patients with equivocal outcome. We tackled this problem by pooling a large dataset which allowed for selecting cases providing strictly unequivocal information, still numerous enough to produce sound statistical evidence. We studied predictors based on the CSF leucocytes count, a laboratory technique already available in the field, evaluating their predictive power at 6 and 12 months post-treatment. We found a predictor at 6 months (10 leucocytes/µL of CSF) that has sub-optimal accuracy but may be valuable in some particular situations, plus two-step algorithms at 6 and 12 months that offer sufficient confidence to shorten the patients' follow-up. Until better biomarkers are identified, these findings represent a significant advance for this neglected disease. Benefits are foreseen both for patients and for overburdened treatment facilities. In addition, research for new treatments can be accelerated by using early predictors.

To access this article, please click on "Additional Links"., Adherence is one of the main predictors of antiretroviral treatment success. A governmental initiative was launched in 1998 for HIV-infected patients in Senegal to provide access to highly active antiretroviral therapy.

BackgroundTo compare the incidence and timing of toxicity associated with the use of a reduced dose of stavudine from 40 to 30 mg in first-line antiretroviral therapy (ART) for HIV treatment and to investigate associated risk factors.MethodsMulticohort study including 23 HIV programs in resource-limited countries. Adults enrolled between January 2005 and December 2009. Four-year rates of all-cause and stavudine-specific toxicity were estimated. Multilevel mixed-effect Poisson and accelerated failure models were used to investigate factors associated with toxicity and timing of diagnosis.FindingsA total of 48,785 patients contributed 62,505 person-years of follow-up. Rate of all-cause toxicity was 7.80 (95%CI 7.59-8.03) per 100 person-years, but varied greatly across sites (range 0.41-21.76). Patients treated with stavudine 40 mg had higher rates of toxicity (adjusted rate ratio [aRR] 1.18, 95%CI 1.06-1.30 during the first year of ART; and 1.51, 95%CI 1.32-1.71 during the second year). Women, older age, initial advanced clinical stage, and low CD4 count were associated with increased toxicity rate ratios. Timing of lipodystrophy and peripheral neuropathy diagnosis were 12% and 13% shorter, respectively, in patients treated with stavudine 40 mg than in those receiving 30 mg stavudine dose (P = 0.03 and 0.07, respectively). INSTERPRETATION: Higher rates of drug-related toxicity were reported in patients receiving stavudine 40 mg compared with 30 mg, and the time to toxicity diagnosis was shorter in patients treated with the higher dose. Higher rates of toxicity were observed during the first two years of ART.

Background Although a dramatic decrease in AIDS progression has been observed after Highly Active Anti Retroviral Therapy (HAART) in both low- and high-resource settings, few data support that fact in low-resource settings. This study describes the incidence of AIDS-defining illnesses (ADI) after HAART initiation and analyzes their risk factors in a low-resource setting. A focus was put on CD4 cell counts and viral load measurements. Methods 404 HIV-1-infected Senegalese adult patients were enrolled in a prospective observational cohort and data censored as of April 2008. A Poisson regression was used to model the incidence of ADIs over two periods and to assess its association with baseline variables, current CD4, current viral load, CD4 response, and virological response. Results ADI incidence declined from 20.5 ADIs per 100 person-years, 95% CI = [16.3;25.8] during the first year to 4.3, 95% CI = [2.3;8.1] during the fourth year but increased afterwards. Before 42 months, the decrease was greater in patients with clinical stage CDC-C at baseline and with a viral load remaining below 1000 cp/mL but was uniform across CD4 strata (p = 0.1). After 42 months, 293 patients were still at risk. The current CD4 and viral load were associated with ADI incidence (decrease of 21% per 50 CD4/mm3 and of 61% for patients with a viral load < 1000 cp/mL). Conclusions During the first four years, a uniform decline of ADI incidence was observed even in patients with low CD4-cell counts at HAART initiation as long as the viral load remained undetectable. An increase was noted later in patients with immunologic and virological failures but also in patients with only virological failure.

Background It is important to establish whether or not the presence of malaria parasites in peripheral blood of asymptomatic individuals is a predictor of future clinical mild malaria attacks (MMA). The aim of this study was to determine how an asymptomatic positive thick blood smear could be related to the occurrence of a MMA during the nine following days. Methods The study was conducted in a cohort of 569 Senegalese children, who were investigated for Plasmodium falciparum asymptomatic carriage at two different times of the transmission season, the beginning (September) and the end (November). The occurrence of MMA was investigated in asymptomatic carriers and non-carriers, every three days for nine consecutive days. Survival analysis was performed and risk estimates were calculated by Cox proportional hazards model. Results At the beginning of the transmission season, 27.8% (147/529) of the children were asymptomatic carriers (ACs) and 5.4% (8/147) of MMA occurred among these, versus 1% (4/382) among non-carriers (RR = 5.32; IC = [1.56–18.15], p = 0.008). At the end of the transmission season, the frequency of asymptomatic carriers was similar to that observed at the beginning of the season (31.9%, p = 0.15), but no MMA was detected during this period. Conclusion A significant association between P. falciparum asymptomatic carriage and the occurrence of MMA at the beginning of the transmission season was demonstrated, with a five-fold increase in the risk of developing a MMA in ACs. In the context of a possible distribution of IPTc in the future, drug strategies may have dramatic consequences due to the existence of ACs (both long term and short term), as they seem to play an important role in the individual protection to malaria, in the most exposed age groups.

The aim of this study was to determine hepatitis co-infection in a cohort of HIV infected patients at their inclusion in the Senegalese Initiative of ART Access. B, C, and D Hepatitis viruses serological markers were checked retrospectively on 363 stored plasma. For HBV, the Abbott laboratories equipment IMx was used to detect HBs Ag and anti Core Ab on negative HBs Ag samples. For HDV, anti Delta Ab was performed using the Abbott Murex Kit on all HBs Ag positive samples. For HCV, anti HCV Ab was detected by IMx as double screening test and confirmed by INNO-LIA(TM) HCV Core of Innogenetics laboratories. The statistical analysis was done with STATA V8. The study population was composed of 164 men and 199 women aged between 16 and 66 years. The immune and virological markers averages at their enrollment were 154 cell/mm(3) for TLCD4+ (n = 355 patients) and 4.9 log for viral load (n = 277 patients). HBs Ag was found in 61 patients or 16.8% and the prevalence of anti-HBc Ab was 83.2% (252/295). 2 patients or 3% on HBs Ag positive sample presents HBV/HDV co-infection Ab anti HCV was detects in 6 patients or 1.6% after confirmation and 2 patients had triple infection with HBV. These results showed that the prevalence of HBV and HCV in the population of persons living with HIV/AIDS in Senegal is similar to that found in the general population. Our data indicated that hepatitis pathology in the PLwHIV was essentially due to HBV. Further studies are needed to diagnose occult hepatitis in order to set up therapeutic strategies taking into account co-infections by hepatitis viruses in the ART programmes.

Owing to their low toxicity, low price, and ease of use, efavirenz (EFV) and nevirapine (NVP) are frequently used as part of antiretroviral regimens for AIDS treatment. Several clinical trials have already studied their efficacy and tolerance. However, long-term observations of the effects of these drugs in patients are limited. We used data from a prospective Senegalese cohort to analyze long-term tolerance and efficacy of these two drugs in a low-resources setting. Patients were included if they started their therapy with EFV or NVP. They were censored after treatment discontinuation. The primary endpoint was the time to treatment discontinuation. Secondary endpoints included time to death, time to disease progression, occurrence of severe adverse effects, CD4 cell recovery, and virological response. Confounding factors were controlled using marginal structural models. The median follow-up time in both EFV and NVP arms was 48 months. The hazard ratio (HR) of drug discontinuation in the EFV arm vs. the NVP arm was 0.84 (0.34; 1.87). There was a borderline difference in virological response [HR = 1.38 (0.999; 1.89)] but no differences in time to death [HR = 1.15 (0.41; 3.24)], time to AIDS progression [HR = 1.25 (0.61; 2.58)], or time to increase in CD4 cell count above 500 cells/mm(3). Adverse effects were different between NVP and EFV, but long-term tolerance was good for both. This analysis provided further information on long-term tolerance and efficacy of EFV and NVP in a resource-limited setting.

Introduction : The antiretroviral therapy (ART) programme supported by Medecins Sans Frontieres in the rural Malawian district of Chiradzulu was one of the first in sub-Saharan Africa to scale up ART delivery in 2002. After more than a decade of continuous involvement, we conducted a population survey to evaluate the cascade of care, including population viral load, in the district. Methods : A cross-sectional household-based survey was conducted between February and May 2013. Using a multistage cluster sampling method, we recruited all individuals aged 15 to 59 years living in 4125 randomly selected households. Each consenting individual was interviewed and tested for HIV at home. All participants who tested positive had their CD4 count and viral load measured. The LAg-Avidity assay was used to distinguish recent from long-term infections. Viral suppression was defined as a viral load below 1000 copies/mL. Results : Of 8271 individuals eligible for the study, 7269 agreed to participate and were tested for HIV (94.1% inclusion for women and 80.3% for men). Overall HIV prevalence and incidence were 17.0% (95% CI 16.1 to 17.9) and 0.39 new cases per 100 person-years (95% CI 0.0 to 0.77), respectively. Coverage at the other steps along the HIV care cascade was as follows: 76.7% (95% CI 74.4 to 79.1) had been previously diagnosed, 71.2% (95% CI 68.6 to 73.6) were under care and 65.8% (95% CI 62.8 to 68.2) were receiving ART. Finally, the proportion of participants who were HIV positive with a viral load ≤1000 copies/mL reached 61.8% (95% CI 59.0 to 64.5). Conclusions : This study demonstrates that a high level of population viral suppression and low incidence can be achieved in high HIV prevalence and resource-limited settings. Keywords: HIV; incidence; prevalence; viral load. (Published: 15 February 2016) Citation: Maman D et al. Journal of the International AIDS Society 2016, 19 :20673 http://www.jiasociety.org/index.php/jias/article/view/20673 | http://dx.doi.org/10.7448/IAS.19.1.20673

The occurrence of an outbreak of meningitis during three consecutive years in a study area under demographic and epidemiologic longitudinal surveillance allowed evaluating the impact of mass immunisation campaigns on the incidence of meningitis. During an outbreak of meningitis in the neighbouring region occurred 2 years before the first epidemic wave in the study area, 8 out of the 30 villages of the zone were immunised. The incidences of meningitis in these villages were compared with those of the villages that did not benefited from mass campaign. It appeared a very significant difference between the two groups of villages. More than a half of the cases of meningitis seemed to be avoided in the vaccinated villages compared to the others, suggesting that a previous immunisation limits the diffusion of the epidemic. After the second outbreak hit the study zone, a mass immunisation campaign concerned all the 30 villages. The incidences of meningitis were significantly different between villages according to the observed vaccine coverage. These results indicate that preventive immunisation could have a significant impact on meningitis outbreak diffusion.

Objectives: To evaluate survival and investigate causes of death among HIV-1 infected adults receiving HAART in Senegal. Design: An observational prospective cohort. Methods: Mortality was assessed in the first patients enrolled between August 1998 and April 2002 in the Senegalese antiretroviral drug access initiative. First-line regimen combined two nucleoside reverse transcriptase inhibitors and either a non-nucleoside reverse transcriptase inhibitor or a protease inhibitor. The most likely causes of death were ascertained through medical records or post-mortem interviews (verbal autopsy). Results: Four hundred and four patients (54.7% women) were enrolled in the study and were followed for a median of 46 months (interquartile range: 32-57 months) after HAART initiation. At baseline, 5% were antiretroviral therapy (ART) non-naive, 39 and 55% were respectively at CDC stage B and C, median age, CD4 cell count and viral load were 37 years, 128 cells/mu l and 5.2 log cp/ml, respectively. Ninety-three patients died during follow-up and the overall incidence rate of death was 6.3/100 person-years [95% confidence interval (CI), 5.2-7.7]. During the first year after HAART initiation, 47 patients died and seven were lost to follow-up, yielding to a probability of dying of 11.7% (95% CI, 8.9-15.3%). The death rate, which was highest during the first year after HAART initiation, decreased with time yielding a cumulative probability of dying of 17.4% (95% Cl, 13.9-21.5%) and 24.6% (95% CI, 20.4-29.4%) at 2 and 5 years. Causes of death were ascertained in 76 deaths. Mycobacterial infections, neurotropic infections and septicaemia were the most frequent likely causes of death. Conclusions: This study underlines the early mortality pattern after HAART initiation and highlights the leading role of mycobacterial infections in the causes of death.

We explore a possible link between malaria and maternal death in a rural area of Senegal by assessing the seasonal pattern of maternal mortality by cause and examining whether this pattern coincides with the malaria season. Overall mortality in women 15-49 years of age did not differ by season, while maternal and direct obstetric deaths were significantly more frequent during the rainy/malaria season than during the rest of the year, even after adjusting for place of delivery.

OBJECTIVES To report the findings of a direct, community-based, assessment of maternal mortality and medical causes of death using verbal autopsy in three unique cohorts in rural Senegal. METHODS Methods from ongoing demographic surveillance systems. We obtained records of all deaths and births in women of age 15-49 over a period of 14 years in Niakhar, 10 years in Bandafassi and 13 years in Mlomp. Relatives of all women who died were interviewed using a standard questionnaire. Causes of death were assigned by three physicians independently. Maternal deaths were defined according to the ninth and tenth revisions of the International Classification of Diseases. RESULTS The maternal mortality ratio was similar in Mlomp [436 per 100 000 live births (95% confidence interval 209-802)] and Niakhar [516 per 100 000 (413-636)] but significantly higher in the more remote area of Bandafassi [852 (587-1196)] [relative risk compared with Niakhar 1.6 (1.0-2.4)]. Two-thirds of the maternal deaths were from direct obstetric causes, haemorrhage being the most common. Abortion was rare. CONCLUSIONS Demographic surveillance systems are useful tools for the measurement of maternal mortality provided special studies are carried out to arrive at the levels and causes of maternal death. The estimates of maternal mortality reported here are lower than those published by the WHO and UNICEF but remain extremely high, particularly in the very remote areas with very limited health infrastructure, where as many as one in 19 women may be expected to die as a consequence of childbirth.

The effect of age, previous intensity of infection, and exposure on reinfection with Schistosoma haematobium after treatment was studied in a cohort of 468 subjects six years of age and over living in an irrigation scheme area in Mali. Prevalence and intensity of S. haematobium infection were measured each year between 1989 and 1991, but the reinfection study period was restricted to the last year of the follow-up. Observations were made at the principal water contact sites where the number of Bulinus truncatus shedding furcocercous cercariae was recorded. A cumulative index of exposure taking into account time, duration and type of contact, and malacologic data was calculated for each subject. Univariate analysis showed that the reinfection risk decreased with age and increased with exposure and pretreatment intensity. These results were confirmed by fitting a logistic model that showed that this risk was seven times lower among those 15 years of age and older than among the 6–14-year-old children, while linear trends with exposure to infection and pretreatment intensity were significant. This study supports the concept of an age-acquired resistance to reinfection and is in favor of a predisposition to infection that raises the question of a genetic factor controlling susceptibility/resistance to S. haematobium infection.

To the Editor: Prevalence of chronic hepatitis C virus (HCV) among blood donors has been assessed in a few West African countries; most recent estimates range from 1.1% to 6.7% (1–4). A recent meta-analysis of studies, including a confirmation test, yielded an average prevalence of HCV infection of 3.0% (5). Until 2001, no systematic screening of HCV infection occurred among blood donors in Senegal, and blood donation legislation is still pending. We report an assessment of the proportion of blood donors from the Hopital Principal de Dakar who had HCV antibodies in 2001. Blood donors were all volunteers, recruited independently from the hospitalized patients and registered in a local donors association. We screened for risk factors for bloodborne infections in potential donors through a clinical examination and a confidential questionnaire. Persons with a history of jaundice or a risk behavior were excluded. Serum samples collected from blood donors from June to December 2001 were screened for HCV antibodies by a third-generation enzyme immunoassay (EIA) (HCV Murex 4.0; Abbott Laboratories, Abbott, IL). Confirmation was performed by a recombinant-immunoblot assay (INNO-LIA HCV Ab III update; [Innogenetics, Gent, Belgium]). HCV RNA was detected by a qualitative reverse transcription–polymerase chain reaction (Roche Amplicor HCV test [Hoffman-LaRoche, Basel, Switzerland]). Genotype was determined by the INNO-LiPA HCV II assay (Innogenetics). Presence of hepatitis B surface antigen (HbsAg) and alanine-aminotransferase (ALAT) level are routinely assessed, as well as HIV and human T-lymphotropic virus type l infection. The age of the 1,081 donors ranged from 18 years to 61 years (mean 35.6 years), and 81% were men. First-time donors accounted for 31% and were younger than repeat donors (mean 30.5 years vs. 37.8 years; p 50 years 1.8%; chi-square trend = 4.39; p = 0.03). ALAT levels of infected study participants were in the normal range (17–55 IU). One participant had an ALAT level above normal. Genotype 2ac has been identified on line immunoassay–positive samples (three samples not tested). HBsAg was detected in 13% of the new donors. No co-infection with HCV and hepatitis B virus was found. The prevalence of HCV antibodies in blood donors in Dakar in 2001 appears to be one of the lowest in West Africa, close to published estimates for Mauritania and Benin (1.1% and 1.4%, respectively) and lower than in other West African countries such as Ghana or Guinea, where prevalence ranges from 2.8% to 6.7% (1–4). This finding is in keeping with results of a hospital case-control study on HCV infection and liver cirrhosis or cancer, conducted in 1995 in Dakar. While that study did not identify HCV infection in 73 controls, 2 of 73 case-patients (2.7%) had HCV antibodies (6). Conversely, high HCV prevalence was found in groups at risk: antibodies were present in 12 of 15 hemodialysis patients, and HCV RNA was found in 6 of the 12 HVC antibody-positive patients (genotype 2ac, the same as in our study); 7% of a cohort of 58 HIV-1 patients receiving highly active antiretroviral therapy had a positive HCV serologic result (7,8). In the urban setting of Dakar, HCV infection seems still to be confined to groups at risk. The contribution of HCV to chronic liver diseases has not been yet demonstrated. Approximately 15,000 blood donations are annually made in Dakar. A systematic screening of HCV antibodies in blood donors could prevent, on average, 120 bloodborne HCV infections each year. Given these data and the price of EIA and LIA, the screening cost per HCV-positive sample identified, and infection subsequently averted, is approximately 200,300 CFA (U.S.$305). This estimate is low since it includes only the marginal cost of the reagent kits. This screening cost could be reduced by discarding blood units that test positive after only one enzyme-linked immunosorbent assay (156,000 CFA or U.S.$237), at the price of nearly 3% of blood units wrongly discarded. France has demonstrated that this strategy has the best cost-effectiveness ratio, as long as the prevalence remains below 8% (9). This cost compares favorably with the cost per HIV infection averted through improvement of blood safety (range U.S.$20–U.S.$1,000), assessed in some highly HIV-prevalent southern African countries (Tanzania, Zambia, Zimbabwe) (10). The HCV-positive discarded blood units will be added to the blood units testing positive for hepatitis B surface (13%), HIV, and HTLV, which accounted for nearly one third of all donations in 2001. These findings argue in favor of maintaining a roster of regular, seronegative donors to save numbers of blood units.

Background Good adherence to treatment is crucial to control tuberculosis (TB). Efficiency and feasibility of directly observed therapy (DOT) under routine program conditions have been questioned. As an alternative, Medecins sans Frontieres introduced self-administered therapy (SAT) in several TB programs. We aimed to measure adherence to TB treatment among patients receiving TB chemotherapy with fixed dose combination (FDC) under SAT at the Homa Bay district hospital (Kenya). A second objective was to compare the adherence agreement between different assessment tools. Methods We conducted a cross-sectional survey amongst a series of new TB patients receiving 6 months of standard TB chemotherapy with FDC under SAT. Adherence was assessed at home with urine testing for Isoniazid (INH), pill count, interviewer-administered questionnaire and visual analogue scale (VAS). Results In November 2008 and in June 2009, 212 of 279 eligible patients were assessed for adherence. Overall, 95.2% [95%CI: 91.3–97.7] of the patients reported not having missed a tablet in the last 4 days. On the VAS, complete adherence was estimated at 92.5% [95%CI: 88.0–95.6]. INH urine test was positive for 97.6% [95%CI: 94.6–99.2] of the patients. Pill count could be assessed among only 70% of the interviewed patients. Among them, it was complete for 82.3% [95%CI: 75.1–88.1]. Among the 212 surveyed patients, 193 (91.0%) were successfully treated (cured or treatment completed). The data suggest a fair agreement between the questionnaire and the INH urine test (k = 0.43) and between the questionnaire and the VAS (k = 0.40). Agreement was poor between the other adherence tools. Conclusion These results suggest that SAT, together with the FDC, allows achieving appropriate adherence to antituberculosis treatment in a high TB and HIV burden area. The use of a combination of a VAS and a questionnaire can be an adequate approach to monitor adherence to TB treatment in routine program conditions.

Objective The evaluation of HIV treatment programs is generally based on an estimation of survival among patients receiving antiretroviral treatment (ART). In large HIV programs, loss to follow-up (LFU) rates remain high despite active patient tracing, which is likely to bias survival estimates and survival regression analyses. Methods We compared uncorrected survival estimates derived from routine program data with estimates obtained by applying six correction methods that use updated outcome data by a field survey targeting LFU patients in a rural HIV program in Malawi. These methods were based on double-sampling and differed according to the weights given to survival estimates in LFU and non-LFU subpopulations. We then proposed a correction of the survival regression analysis. Results Among 6,727 HIV-infected adults receiving ART, 9% were LFU after one year. The uncorrected survival estimates from routine data were 91% in women and 84% in men. According to increasing sophistication of the correction methods, the corrected survival estimates ranged from 89% to 85% in women and 82% to 77% in men. The estimates derived from uncorrected regression analyses were highly biased for initial tuberculosis mortality ratios (RR; 95% CI: 1.07; 0.76–1.50 vs. 2.06 to 2.28 with different correction weights), Kaposi sarcoma diagnosis (2.11; 1.61–2.76 vs. 2.64 to 3.9), and year of ART initiation (1.40; 1.17–1.66 vs. 1.29 to 1.34). Conclusions In HIV programs with high LFU rates, the use of correction methods based on non-exhaustive double-sampling data are necessary to minimise the bias in survival estimates and survival regressions.

Background: In sub-Saharan Africa, men living with HIV often start ART at more advanced stages of disease and have higher early mortality than women. We investigated gender difference in long-term immune reconstitution. Methods/Principal Findings: Antiretroviral-naive adults who received ART for at least 9 months in four HIV programs in sub-Saharan Africa were included. Multivariate mixed linear models were used to examine gender differences in immune reconstitution on first line ART. A total of 21,708 patients (68% women) contributed to 61,912 person-years of follow-up. At ART start,. Median CD4 at ART were 149 [IQR 85-206] for women and 125 cells/mu L [IQR 63-187] for men. After the first year on ART, immune recovery was higher in women than in men, and gender-based differences increased by 20 CD4 cells/mu L per year on average (95% CI 16-23; P250cells/mu L (difference between patients with 250 was 284 cells/mu L; 95% CI 272-296; LR test for interaction with time p = 0.63). Among patients with initial CD4 count of 150-200 cells/mu L, women reached 500 CD4 cells after 2.4 years on ART (95% CI 2.4-2.5) and men after 4.5 years (95% CI 4.1-4.8) of ART use. Conclusion: Women achieved better long-term immune response to ART, reaching CD4 level associated with lower risks of AIDS related morbidity and mortality quicker than men.

Background Malnutrition and malaria frequently coexist in sub-Saharan African countries. Studies on efficacy of antimalarial treatments usually follow the WHO standardized protocol in which severely malnourished children are systematically excluded. Few studies have assessed the efficacy of chloroquine, sulfadoxine-pyrimethamine and quinine in severe acute malnourished children. Overall, efficacy of these treatments appeared to be reduced, attributed to lower immunity and for some antimalarials altered pharmacokinetic profiles and lower drug concentrations. However, similar research on the efficacy and pharmacokinetic profiles of artemisinin-combination therapies (ACTs) and especially artemether-lumefantrine in malnourished children is currently lacking. The main objective of this study is to assess whether artemether-lumefantrine is less efficacious in children suffering from severe acute malnutrition (SAM) compared to non-SAM children, and if so, to what extent this can be attributed to a sub-optimal pharmacokinetic profile. Methods/design In two sites, Ouelessebougou, Mali and Maradi, Niger, children with uncomplicated microscopically-confirmed P. falciparum malaria aged between 6 and 59 months will be enrolled. Two non-SAM children will be enrolled after the enrolment of each SAM case. Children with severe manifestations of malaria or complications of acute malnutrition needing intensive treatment will be excluded. Treatment intakes will be supervised and children will be followed-up for 42 days, according to WHO guidance for surveillance of antimalarial drug efficacy. Polymerase Chain Reaction genotyping will be used to distinguish recrudescence from re-infection. SAM children will also benefit from the national nutritional rehabilitation program. Outcomes will be compared between the SAM and non-SAM populations. The primary outcome will be adequate clinical and parasitological response at day 28 after PCR correction, estimated by Kaplan-Meier analysis. To assess the pharmacokinetic profile of lumefantrine, a sparse sampling approach will be used with randomized allocation of sampling times (5 per child). A total of 180 SAM children and 360 non-SAM children will be recruited during the 2013 and 2014 malaria seasons. Discussion This study will provide important information that is currently lacking on the effect of SAM on therapeutic efficacy and pharmacokinetic profile of artemether-lumefantrine. If it shows lower therapeutic efficacy and decreased lumefantrine concentrations, it would inform dose optimization studies in SAM children. Trial registration ClinicalTrials.gov: NCT01958905

Background Malaria is a major public health problem, especially for children. However, recent reports suggest a decline in the malaria burden. The aim of this study was to assess the change in the prevalence of malaria infection among children below five years of age between 2004 and 2010 in a mesoendemic area of Uganda and to analyse the risk factors of malaria infection. Methods Two cross-sectional surveys were conducted in 2004 and in 2010 at the end of the rainy and dry seasons to measure the prevalence of P. falciparum infection among children less than five years of age. Rapid diagnostic tests and blood smears were used to diagnose malaria infection. In 2010, sampling was stratified by urban and rural areas. In each selected household, knowledge of malaria and bed nets, and bed net ownership and use, were assessed. Results In 2004 and 2010, respectively, a total of 527 and 2,320 (999 in the urban area and 1,321 in rural areas) children less than five years old were enrolled. Prevalence of malaria infection declined from 43% (95% CI: 34-52) in 2004, to 23% (95% CI: 17-30) in rural areas in 2010 and 3% (95% CI: 2-5) in the urban area in 2010. From the rainy to dry season in 2010, prevalence decreased from 23% to 10% (95% CI: 6-14) in rural areas (P = 0.001) and remained stable from 3% to 4% (95% CI: 1-7) in the urban area (P = 0.9). The proportion of households reporting ownership and use of at least one bed net increased from 22.9% in 2004 to 64.7% in the urban area and 44.5% in rural areas in 2010 (P < 0.001). In 2010, the risk of malaria infection was consistently associated with child age and household wealth. In rural areas, malaria infection was also associated with geographic factors. Conclusions This study reports a significant drop in the prevalence of malaria infection among children below five years of age, paralleled by an uptake in bed-net use. However, prevalence remains unacceptably high in rural areas and is strongly associated with poverty.