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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 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

International audience; PURPOSE:The Ebola outbreak of 2013-2016 severely affected West Africa and resulted in 2544 deaths and 1270 survivors in Guinea, the country where it began. This Ebola virus was the Zaire strain of the virus family Filoviridae. In this outbreak the case fatality rate was about 67%. The survivors, declared cured after 2 negative blood polymerase chain reaction (PCR) results, face psychosocial disorders and rheumatic, ear-nose-throat, neurocognitive, and ophthalmologic complications. The goal of this study was to detect and describe ocular complications afflicting these survivors and to observe their occurrence and recurrences.DESIGN:Prospective observational cohort study.METHODS:This prospective observational multicenter cohort study was initiated in March 2015. The cohort study included 341 survivors followed up in the infectious disease ward of Conakry, Forecariah, and Nzérékoré as of May 2016. The patients received multidisciplinary medical follow-up expected to last at least 1 year that included an eye examination as part of complete, free treatment.RESULTS:Systematic examination of 341 patients revealed 46 cases of uveitis (13.5%), 6 cases of episcleritis (1.8%), and 3 cases of interstitial keratitis (0.9%). Uveitis was most frequently unilateral (78.3%) and anterior (47.8%) and occurred within the 2 months after discharge from the Ebola treatment center. Moreover, uveitis relapses were found up to 13 months after the negative PCR result for Ebola in the blood.CONCLUSION:Nearly 1 out of 6 survivors presented ocular disorders after discharge from the Ebola treatment center. An ophthalmologic follow-up for Ebola-infected patients should start, if possible, during the acute phase of the disease and last more than 1 year. Treatment guidelines need to be urgently developed and implemented.

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

Background:The tremendous size of the 2013-2016 West African outbreak of Ebola virus disease (EVD) resulted in a sizeable population of survivors, many reporting short-term sequelae such as arthralgia and myalgia.Objectives:We aimed to report a detailed and long-term description of patients’ musculoskeletal (MS) symptoms.Methods:We performed a cross-sectional study following systematic rheumatological screening of patients included in the Postebogui cohort (Conakry district). We used regression models to establish the magnitude of EVD as a risk factor for developing chronic MS pain by comparison with a control cohort and to establish risk factors for developing MS pain among survivors.Results:The study included 313 patients (55.6% female), with a median age of 28.2 years (IQR 21-37), and a median time from ETC discharge to rheumatological visit of 26.2 months (IQR 23-30). Chronic MS pain was reported in 216 (69%) patients, and was predominantly mechanical (48%). Enthesis and painful peripheral joints were largely involved (91%) with symmetrical distribution. Previous Ebola infection was a major risk factor for chronic MS pain (aOR, 6.662 [95% CI, 4.522–9.921]). Among survivors, increasing age (OR 1.14, 95% CI 1.08-1.22) and female gender (OR 3.58, 95% CI 1.22-11.80) were both associated with persistent MS pain, while myalgia experienced during the acute phase of EVD appeared protective (OR 0.14, 95% CI 0.04-0.42).Conclusion:Our study provides the most accurate long-term description of MS disorders among Ebola survivors. Joint and muscle pain sequelae are frequent and require specialized care.Disclosure of Interests:None declared

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.

International audience; Background: Despite substantial progress in antiretroviral therapy (ART) scale up, some people living with HIV (PLHIV) continue to present with advanced HIV disease, contributing to ongoing HIV-related morbidity and mortality.Objective: We aimed to quantify population-level estimates of advanced HIV from three high HIV prevalence settings in Sub-Saharan Africa.Methods: Three cross-sectional surveys were conducted in (Ndhiwa (Kenya): September-November 2012), (Chiradzulu (Malawi): February-May 2013) and (Eshowe (South Africa): July-October 2013). Eligible individuals 15-59 years old who consented were interviewed at home followed by rapid HIV test and CD4 count test if tested HIV-positive. Advanced HIV was defined as CD4 < 200 cells/µl. We used logistic regression to identify patient characteristics associated with advanced HIV.Results: Among 18,991 (39.2% male) individuals, 4113 (21.7%) tested HIV-positive; 385/3957 (9.7% (95% Confidence Interval [CI]: 8.8-10.7)) had advanced HIV, ranging from 7.8% (95%CI 6.4-9.5) Chiradzulu (Malawi) to 11.8% (95%CI 9.8-14.2) Ndhiwa (Kenya). The proportion of PLHIV with advanced disease was higher among men 15.3% (95% CI 13.2-17.5) than women 7.5% (95%CI 6.6-8.6) p < 0.001. Overall, 62.7% of all individuals with advanced HIV were aware of their HIV status and 40.3% were currently on ART. Overall, 65.6% of individuals not on ART had not previously been diagnosed with HIV, while only 29.6% of those on ART had been on ART for ≥6 months. Individuals with advanced HIV disease were more likely to be men (adjusted Odds Ratio [aOR]; 2.1 (95%CI 1.7-2.6), and more likely not to be on ART (aOR; 1.7 (95%CI 1.3-2.1).Conclusion: In our study, about 1 in 10 PLHIV had advanced HIV with nearly 40% of them unaware of their HIV status. However, a substantial proportion of patients with advanced HIV were established on ART. Our findings suggest the need for a dual focus on alternative testing strategies to identify PLHIV earlier as well as improving ART retention.

International audience; Background: Buruli ulcer (BU) is a cutaneous infectious disease caused by Mycobacterium ulcerans. In this prospective study, we aim to clarify the main histopathological features of cutaneous BU based on 4-mm skin punch biopsies and to evaluate the diagnostic value of this method.Methods: Between 2011 and 2013, a prospective study was conducted in Cameroon. Dry swabs from ulcerative lesions and fine-needle aspirates of nonulcerative lesions were examined for Ziehl-Neelsen (ZN) staining, followed by PCR targeting IS2404 and culture. Two 4-mm punch biopsies were performed in the center and in the periphery of each lesion.Results: The 364 patients included in the study had 422 lesions (381 were ulcerative and 357 lesions were biopsied). Among the 99 ulcerated lesions with a final diagnosis of BU, histological features for BU were fulfilled in 32 lesions. 32/32 showed subcutaneous necrosis with a neutrophilic inflammatory infiltrate. 26/32 presented alcohol-resistant bacilli confirmed by ZN stain on histology.Conclusion: Punch biopsies help in establishing the correct diagnosis of BU and also in the differential diagnosis of chronic ulcers. The main histological feature for BU is diffuse coagulative necrosis of subcutaneous tissue, with acid-fast bacilli detected by ZN stain.

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

Background The Joint United Nations Programme on HIV/AIDS (UNAIDS) has developed an ambitious strategy to end the AIDS epidemic. After eight years of antiretroviral therapy (ART) program we assessed progress towards the UNAIDS 90–90-90 targets in Mbongolwane and Eshowe, KwaZulu-Natal, South Africa. Methods We conducted a cross-sectional household-based community survey using a two-stage stratified cluster probability sampling strategy. Persons aged 15–59 years were eligible. We used face-to-face interviewer-administered questionnaires to collect information on history of HIV testing and care. Rapid HIV testing was performed on site and venous blood specimens collected from HIV-positive participants for antiretroviral drug presence test, CD4 count and viral load. At the time of the survey the CD4 threshold for ART initiation was 350 cells/μL. We calculated progression towards the 90–90-90 UNAIDS targets by estimating three proportions: HIV positive individuals who knew their status (first 90), those diagnosed who were on ART (second 90), and those on ART who were virally suppressed (third 90). Results We included 5649/6688 (84.5%) individuals. Median age was 26 years (IQR: 19–40), 62.3% were women. HIV prevalence was 25.2% (95% CI: 23.6–26.9): 30.9% (95% CI: 29.0–32.9) in women; 15.9% (95% CI: 14.0–18.0) in men. Overall progress towards the 90–90-90 targets was as follows: 76.4% (95% CI: 74.1–78.6) knew their status, 69.9% (95% CI: 67.0–72.7) of those who knew their status were on ART and 93.1% (95% CI: 91.0–94.8) of those on ART were virally suppressed. By sex, progress towards the 90–90-90 targets was: 79%–71%–93% among women; and 68%–68%–92% among men (p-values of women and men comparisons were

Background Latest WHO guidelines recommend starting HIV-positive individuals on antiretroviral therapy treatment (ART) regardless of CD4 count. We assessed additional impact of adopting new WHO guidelines. Methods We used data of individuals aged 15–59 years from three HIV population surveys conducted in 2012 (Kenya) and 2013 (Malawi and South Africa). Individuals were interviewed at home followed by rapid HIV and CD4 testing if tested HIV-positive. HIV-positive individuals were classified as “eligible for ART” if (i) had ever been initiated on ART or (ii) were not yet on ART but met the criteria for starting ART based on country’s guidelines at the time of the survey (Kenya–CD4< = 350 cells/μl and WHO Stage 3 or 4 disease, Malawi as for Kenya plus lifelong ART for all pregnant and breastfeeding women, South Africa as for Kenya plus ART for pregnant and breastfeeding women until cessation of breastfeeding). Findings Of 18,991 individuals who tested, 4,113 (21.7%) were HIV-positive. Using country’s ART eligibility guidelines at the time of the survey, the proportion of HIV-infected individuals eligible for ART was 60.0% (95% CI: 57.2–62.7) (Kenya), 73.4% (70.8–75.8) (South Africa) and 80.1% (77.3–82.6) (Malawi). Applying WHO 2013 guidelines (eligibility at CD4< = 500 and Option B+ for pregnant and breastfeeding women), the proportions eligible were 82.0% (79.8–84.1) (Kenya), 83.7% (81.5–85.6) (South Africa) and 87.6% (85.0–89.8) (Malawi). Adopting “test and treat” would mean a further 18.0% HIV-positive individuals (Kenya), 16.3% (South Africa) and 12.4% (Malawi) would become eligible. In all countries, about 20% of adolescents (aged 15–19 years), became eligible for ART moving from WHO 2013 to “test and treat” while no differences by sex were observed. Conclusion Countries that have already implemented 2013 WHO recommendations, the burden of implementing “test and treat” would be small. Youth friendly programmes to help adolescents access and adhere to treatment will be needed.

IntroductionThere is a notable absence of consensus on how to generate estimates ofpopulation-level incidence. Incidence is a considerably more sensitive and harder to estimate indicator of epidemiological trends than prevalence. We used a novel hybrid method to estimate HIV incidence by age and sex in a rural district of KwaZulu-Natal, South Africa.MethodsOur novel method uses an ‘optimal weighting’ of estimates based on an implementation of a particular ‘synthetic cohort’ approach (interpreting the age/time structure of prevalence, in conjunction with estimates of excess mortality) and biomarkers of ‘recent infection’ (combining Lag-Avidity, Bio-Rad Avidity and viral load results to define recent infection, and adapting the method for age-specific incidence estimation). Data were obtained from a population-based cross-sectional HIV survey conducted in Mbongolwane and Eshowe health service areas in 2013.ResultsUsing the combined method, we find that age-specific HIV incidence in females rose rapidly during adolescence, from 1.33 cases/100 person-years (95% CI:0.98,1.67) at age 15 to a peak of 5.01/100PY (4.14,5.87) at age 23. In males, incidence was lower, 0.34/100PY (0.00-0.74) at age 15, and rose later, peaking at 3.86/100PY(2.52-5.20) at age 30. Susceptible population-weighted average incidence in females aged 15-29 was estimated at 3.84/100PY (3.36-4.40), in males aged 15-29 at 1.28/100PY(0.68-1.50) and in all individuals aged 15-29 at 2.55/100PY (2.09-2.76). Using the conventional recency biomarker approach, we estimated HIV incidence among females aged 15-29 at 2.99/100PY (1.79-4.36), among males aged 15-29 at 0.87/100PY(0.22-1.60) and among all individuals aged 15-59 at 1.66/100PY (1.13-2.27).DiscussionHIV incidence was very high in women aged 15-30, peaking in the early 20s. Men had lower incidence, which peaked at age 30. The estimates obtained from the hybrid method are more informative than those produced by conventional analysis of biomarker data, and represents a more optimal use of available data than either the age-continuous biomarker or synthetic cohort methods alone. The method is mainly useful at younger ages, where excess mortality is low and uncertainty in the synthetic cohort estimates is reasonably small.ConclusionApplication of this method to large-scale population-based HIV prevalence surveys is likely to result in improved incidence surveillance over methods currently in wide use. Reasonably accurate and precise age-specific estimates of incidence are important to target better prevention, diagnosis and care strategies.

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.

Objective.: Previous studies show that arthralgia is the most common symptom experienced by Ebola virus disease (EVD) survivors. Nevertheless, specific analyses of rheumatological sequelea are still lacking. Methods.: The Postebogui study is a prospective, multicentre cohort aiming to evaluate the long-term outcomes of EVD survivors infected during the 2014-15 outbreak in Guinea. Of the 216 participants enrolled in the study in October 2015, 44 patients with arthralgia/myalgia underwent a physical examination by a rheumatologist (the Eborheum cohort). Data were collected using a standardized questionnaire. Results.: In the Eborheum cohort, 61% of patients were female, the median age was 31.1 years, and the median time from Ebola Treatment Centre discharge was 8.8 months. Pain manifestation started after Ebola infection in all but one patient. Patients had mainly both mechanical and inflammatory pain (45%) and low back pain (77%). All patients reported pain in at least one peripheral joint. Pain in large joints was more frequently reported than in small joints (73 vs 41%). Oligo- and polyarticular presentations were similar, with symmetrical pain distribution. Furthermore, 36 patients had at least one painful 18-tender point count, most of whom reported extensive pain (n = 19) and symmetrical distribution (91%). Diagnoses were mainly non-specific musculoskeletal disorders (59%) and mechanical back pain (52%). No polyarthritis was observed. We found a higher percentage of depressed patients compared with the remaining Postebogui group (42 vs 11%; P < 0.001). Conclusion.: Results from the study come from the first complete rheumatological examination of a cohort of EVD survivors, nearly 9 months after Ebola Treatment Centre discharge. Importantly, we found that patients with arthralgia/myalgia included in the Eborheum cohort were more likely to experience depression than survivors not reporting these symptoms, highlighting the impact of pain symptoms among survivors.

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 2013–2016 West African Ebola outbreak infected 28,616 people and caused 11,310 deaths by 11 May 2016, across six countries. The outbreak has also resulted in the largest number of EVD survivors in history—over 17,000. Guinea was declared Ebola-free on 1 June 2016. Reports from the outbreak documented 3814 cases resulting in 2544 deaths and 1270 survivors. EVD survivors face various neuropsychological and psycho-affective alterations that have not been fully identified yet. This study aims to document the depressive symptoms among adult survivors in Guinea. Methods Depressive symptoms were investigated using the French version of the Center for Epidemiologic Studies-Depression Scale (CES-D) administered to all adult survivors (≥ 20 years) participating in the PostEboGui study and receiving care in Conakry. The study was combined with a clinical consultation by a psychiatrist at the Donka National Hospital in Conakry that ensured adapted care was provided when needed. Results Overall, 256 adult participants receiving care in Conakry participated in this study: 55% were women, median age 31 years [IQR: 26–40]. The median time since the Ebola Treatment Center (ETC) discharge was 8.1 months [IQR: 4.1–11.7]. 15% had a score above the threshold values indicating psychological suffering (15% for men and 14% for women). 33 people (16 women and 17 men) met with the psychiatrist, which resulted in the diagnosis of 3 cases of post-traumatic stress disorder (PTSD), 3 cases of mild depression, 13 cases of moderate depression, and 11 cases of severe depression, including 1 with kinesthetic hallucinations and another with visual hallucinations, and 1 with suicidal ideation and 3 with attempted suicide. Severe depression was diagnosed between 1 and 19 months after ETC discharge. The various identified forms of depression responded favorably to conventional drug therapies and cognitive behavioral therapy. Conclusion Long-term follow-up for EVD survivors will be necessary to understand the evolution of these pathologies. In the current post-epidemic context, these cases underscore the need to strengthen mental health diagnostic systems and treatment on a national scale. Electronic supplementary material The online version of this article (doi:10.1186/s12888-017-1280-8) contains supplementary material, which is available to authorized users.

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.

Ebola virus disease (EVD) epidemic that spread in West Africa from the end of 2013 to early 2016 has reached more people than all past epidemics. Beyond care management of acute phase ill patients and measures for the control of the epidemic, the outcome of Ebola survivors became an important question as their number increased and raised new issues. A multidisciplinary prospective cohort of survivors in Guinea has been launched by IRD UMI 233 and Donka National Hospital, Conakry, Guinea, to assess the long-term clinical, psychological, sociological, immunological, and viral outcomes potentially related to EVD. This paper describes PostEboGui Programme, constraints and changes to the initial proposal, participants, first results, and new issues, 1 year after its start, in a descriptive and critical view. We started also to work on ethical aspects in the context of epidemics and of mass interventions with a risk of overinvestigation of patients.

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.

In 1998, with the launch of the Senegalese Initiative for Antiretroviral Access (ISAARV), Senegal became one of the first African countries to propose an antiretroviral access program. Our objective in this paper is to study the time to any first drug resistance, as well as predictors of the time to resistance. We propose a joint model to study the effect of adherence to the HAART therapy, and virological response on the time to resistance mutations. A logistic mixed model is used to model the time-dependent adherence process; and a Markov model is used to study the virological response. Given the presence of missing data in the adherence process and in the virological response, the latent adherence and virological states are then included in the linear predictor of the time to resistance model. The proposed time to resistance model takes into account interval-censored data as well as null hazard periods, during which the viral replication is very low. A Bayesian approach is used for accommodating with missing data and for prediction. We also propose model checking tools to study model adequacy.

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

BACKGROUND: Susceptible, exposed, infected, and recovered (SEIR) models are increasingly developed and used, but their simplicity contrasts with the wide variety of scenarios before launching vaccination campaigns. METHODS: We investigated the effects of some model-building choices (targets, pace, coverage rate) on the results of SEIR models in the case of vaccination against varicella and herpes zoster. RESULTS: The analysis demonstrated the need for a progressive unvaccinated to vaccinated transition and a dynamic system-equilibrium before vaccination onset. When several doses are considered, new compartments are needed to account for vaccination histories. For varicella, the delay to reach the expected coverage rate and the pace until reaching this rate have significant impacts, especially on the short-term incidence. The impact of vaccination through herd immunity should be systematically investigated. CONCLUSIONS: Graphs help understanding the progress of instantaneous incidence; however, tables of cumulative average incidence over decades should be preferred because of higher stability.

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.

BACKGROUND: In African rural settings, medically certified information on causes of death is largely lacking. The authors applied the verbal autopsy to identify causes of death before 15 years old in a rural area of Senegal where a demographic surveillance system is operating. METHODS: Between 1989 and 2000, a postmortem interview was conducted using a standardized questionnaire which was independently reviewed by two physicians who assigned the probable underlying cause of death. Discordant diagnoses were discussed by a panel of physicians. Causes of death were grouped into a few categories; cause-specific mortality rates and fractions were generated. RESULTS: Between 1989 and 1997, all-cause mortality fluctuated. Diarrhoeal diseases, malaria and acute respiratory infections explained between 30% and 70% of the mortality before 10 years of age. In children 1-9 years old, malaria death rate increased between 1989 and 1994 and thereafter did not change. The 1998-2000 years were marked by a peak in mortality, attributed to a meningitis outbreak in children more than one year old paralleled by an increase in death rate from fever of unknown origin, diarrhoeal diseases, and acute respiratory infections in children under 5 years. CONCLUSIONS: Verbal autopsy provided useful information on the mortality structure responsible for the 1998-2000 peak in mortality. It underlined that, outside outbreak situations, malaria was a leading cause of death for 1-9 year old children and that diarrhoea, acute respiratory infections, or fever from unknown origin accounted for up to 50% of the deaths among the children under 5 years.

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.

International audience; BackgroundMathematical models have played important roles in the understanding of epidemics and in the study of the impacts of various behavioral or medical measures. However, modeling accurately the future spread of an epidemic requires context-specific parameters that are difficult to estimate because of lack of data. Our objective is to propose a methodology to estimate context-specific parameters using Demographic and Health Survey (DHS)-like data that can be used in mathematical modeling of short-term HIV spreading.Methods and FindingsThe model splits the population according to sex, age, HIV status, and antiretroviral treatment status. To estimate context-specific parameters, we used individuals' histories included in DHS-like data and a statistical analysis that used decomposition of the Poisson likelihood. To predict the course of the HIV epidemic, sex-and age-specific differential equations were used. This approach was applied to recent data from Kenya. The approach allowed the estimation of several key epidemiological parameters. Women had a higher infection rate than men and the highest infection rate in the youngest age groups (15-24 and 25-34 years) whereas men had the highest infection rate in age group 25-34 years. The immunosuppression rates were similar between age groups. The treatment rate was the highest in age group 35-59 years in both sexes. The results showed that, within the 1524 year age group, increasing male circumcision coverage and antiretroviral therapy coverage at CD4

Background Several previous studies have shown relationships between adherence to HIV antiretroviral therapy (ART) and the viral load, the CD4 cell count, or mortality. However, the impact of variability in adherence to ART on the immunovirological response does not seem to have been investigated yet. Methods Monthly adherence data (November 1999 to April 2009) from 317 HIV-1 infected patients enrolled in the Senegalese ART initiative were analyzed. Latent-class trajectory models were used to build typical trajectories for the average adherence and the standardized variance of adherence. The relationship between the standardized variance of adherence and each of the change in CD4 cell count, the change in viral load, and mortality were investigated using, respectively, a mixed linear regression, a mixed logistic regression, and a Cox model with time-dependent covariates. All the models were adjusted on the average adherence. Results Three latent trajectories for the average adherence and three for the standardized variance of adherence were identified. The increase in CD4 cell count and the increase in the percentage of undetectable viral loads were negatively associated with the standardized variance of adherence but positively associated with the average adherence. The risk of death decreased significantly with the increase in the average adherence but increased significantly with the increase of the standardized variance of adherence. Conclusions The impacts of the level and the variability of adherence on the immunovirological response and survival justify the inclusion of these aspects into the process of patient education: adherence should be both high and constant. Electronic supplementary material The online version of this article (doi:10.1186/1471-2288-15-10) contains supplementary material, which is available to authorized users.

BACKGROUND: Although it is generally believed that pregnancy exposes women to a wide variety of excess health risks that go beyond the direct obstetric complications of pregnancy, the epidemiological evidence in support of such excess indirect risks is inconclusive. In this article we attempt to document the contribution of indirect causes of death to maternal mortality in rural Senegal by using an epidemiological approach whereby the time spent during pregnancy and postpartum is considered a transient period of exposure to the health hazards of childbearing. METHODS: We use data from an ongoing demographic surveillance system in Niakhar, Senegal and calculate rate ratios comparing death rates in pregnant or recently pregnant women (exposed) with death rates in other women (unexposed), including and excluding direct obstetric deaths. RESULTS: Between ages 20 and 44, pregnancy does not confer additional risks to women. After excluding direct obstetric deaths, exposed women aged 20--39 have surprisingly lower risks of death than unexposed women of the same age. For the very young (15-19) and the very old (45-49), on the other hand, the excess risks associated with pregnancy are considerable and, among women age 45 or older, persist even after excluding direct obstetric deaths. CONCLUSION: The apparent protective effect of pregnancy on women's health that is observed in this study illustrates the paradoxical nature of the concept of indirect causes of maternal mortality, and the difficulties in measuring the risks of death attributable to the pregnancy. Further studies aimed at separating risks attributable to the pregnancy from those that are incidental to the pregnancy are required.