Long-term Mortality and Disability in Cryptococcal Meningitis: A Systematic Literature Review.

Cryptococcal meningitis (CM) is the primary cause of meningitis in adults with human immunodeficiency virus (HIV) infection and an emerging disease in HIV-seronegative individuals. No literature review has studied the long-term outcome of CM. We performed a systematic review on the long-term (≥3-month) impact of CM (Cryptococcus neoformans and Cryptococcus gattii) on mortality and disability in HIV-infected and non-HIV-infected adults. Although the quality of current evidence is limited, the long-term impact of CM on survival and disability seems to be high. One-year mortality ranged from 13% in an Australian non-HIV-infected C. gattii-infected cohort to 78% in a Malawian HIV-infected cohort treated with fluconazole monotherapy. One-year impairment proportions among survivors ranged from 19% in an Australian C. gattii cohort to >70% in a Taiwanese non-HIV- and HIV-infected cohorts. Ongoing early therapeutic interventions, early detection of impairments and access to rehabilitation services may significantly improve patients' survival and quality of life.

Timing of malaria in pregnancy and impact on infant growth and morbidity: a cohort study in Uganda.

BACKGROUND: Malaria in pregnancy (MiP) is a major cause of fetal growth restriction and low birth weight in endemic areas of sub-Saharan Africa. Understanding of the impact of MiP on infant growth and infant risk of malaria or morbidity is poorly characterized. The objective of this study was to describe the impact of MIP on subsequent infant growth, malaria and morbidity. METHODS: Between 2006 and 2009, 82 % (832/1018) of pregnant women with live-born singletons and ultrasound determined gestational age were enrolled in a prospective cohort with active weekly screening and treatment for malaria. Infants were followed monthly for growth and morbidity and received active monthly screening and treatment for malaria during their first year of life. Multivariate analyses were performed to analyse the association between malaria exposure during pregnancy and infants' growth, malaria infections, diarrhoea episodes and acute respiratory infections. RESULTS: Median time of infant follow-up was 12 months and infants born to a mother who had MiP were at increased risk of impaired height and weight gain (-2.71 cm, 95 % CI -4.17 to -1.25 and -0.42 kg, 95 % CI -0.76 to -0.08 at 12 months for >1 MiP compared to no MiP) and of malaria infection (relative risk 10.42, 95 % CI 2.64-41.10 for infants born to mothers with placental malaria). The risks of infant growth restriction and infant malaria infection were maximal when maternal malaria occurred in the 12 weeks prior to delivery. Recurrent MiP was also associated with acute respiratory infection (RR 1.96, 95 % CI 1.25-3.06) and diarrhoea during infancy (RR 1.93, 95 % CI 1.02-3.66). CONCLUSION: This study shows that despite frequent active screening and prompt treatment of MiP, impaired growth and an increased risk of malaria and non-malaria infections can be observed in the infants. Effective preventive measures in pregnancy remain a research priority. This study was registered with ClinicalTrials.gov, number NCT00495508.

Early biting and insecticide resistance in the malaria vector Anopheles might compromise the effectiveness of vector control intervention in Southwestern Uganda.

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.

Disability and HIV: a systematic review and a meta-analysis of the risk of HIV infection among adults with disabilities in Sub-Saharan Africa.

More than one billion people worldwide are estimated to be living with a disability. A significant proportion of them lives in Sub-Saharan Africa where they are reported to be at increased risk of HIV. However, quantitative evidence on this remains scarce. A systematic review and a meta-analysis of the risk of HIV infection among people with disabilities living in Sub-Saharan Africa were undertaken. We searched all published or unpublished studies and national surveys reporting HIV prevalence among adults with disabilities living in Sub-Saharan Africa between 2000 and 2013. The risk ratio (RR) of HIV infection in people with disabilities versus people without disabilities was estimated through a random-effects meta-analysis. Of the 12,252 references screened, 13 studies were selected. HIV prevalence varied widely across studies from 1.1% to 29%. Pooled RRs of HIV infection in people with disabilities compared to the general population were 1.31 (1.02-1.69) overall; 1.16 (0.71-1.87) among people with mental illness or intellectual disabilities and 1.07 (0.58-1.95) among people with hearing disabilities. This meta-analysis provides evidence that people with disabilities do not have a lower risk of HIV when compared to the general population, and that women with disabilities are especially affected. A clear increasing gradient in the risk of HIV according to gender and disability status was also observed. The important heterogeneity across studies and their varying quality warrant a closer look at the intersection between disability and HIV. Additional studies with more systematic approaches and with higher-quality methodologies are required to further address this knowledge gap.

Use of colorimetric culture methods for detection of Mycobacterium tuberculosis complex isolates from sputum samples in resource-limited settings.

Despite recent advances, tuberculosis (TB) diagnosis remains imperfect in resource-limited settings due to its complexity and costs, poor sensitivity of available tests, or long times to reporting. We present a report on the use of colorimetric methods, based on the detection of mycobacterial growth using colorimetric indicators, for the detection of Mycobacterium tuberculosis in sputum specimens. We evaluated the nitrate reductase assay (NRA), a modified NRA using para-nitrobenzoic acid (PNB) (NRAp), and the resazurin tube assay using PNB (RETAp) to differentiate tuberculous and nontuberculous mycobacteria. The performances were assessed at days 18 and 28 using mycobacterium growth indicator tube (MGIT) and Löwenstein-Jensen (LJ) medium culture methods as the reference standards. We enrolled 690 adults with suspected pulmonary tuberculosis from a regional referral hospital in Uganda between March 2010 and June 2011. At day 18, the sensitivities and specificities were 84.6% and 90.0% for the NRA, 84.1% and 92.6% for the NRAp, and 71.2% and 99.3% for the RETAp, respectively. At day 28, the sensitivity of the RETAp increased to 82.6%. Among smear-negative patients with suspected TB, sensitivities at day 28 were 64.7% for the NRA, 61.3% for the NRAp, and 50% for the RETAp. Contamination rates were found to be 5.4% for the NRA and 6.7% for the RETAp, compared with 22.1% for LJ medium culture and 20.4% for MGIT culture. The median times to positivity were 10, 7, and 25 days for colorimetric methods, MGIT culture, and LJ medium culture,respectively. Whereas the low specificity of the NRA/NRAp precludes it from being used for TB diagnosis, the RETAp might provide an alternative to LJ medium culture to decrease the time to culture results in resource-poor settings.

Impact of malaria during pregnancy on pregnancy outcomes in a Ugandan prospective cohort with intensive malaria screening and prompt treatment.

BACKGROUND: Malaria in pregnancy (MiP) is a major public health problem in endemic areas of sub-Saharan Africa and has important consequences on birth outcome. Because MiP is a complex phenomenon and malaria epidemiology is rapidly changing, additional evidence is still required to understand how best to control malaria. This study followed a prospective cohort of pregnant women who had access to intensive malaria screening and prompt treatment to identify factors associated with increased risk of MiP and to analyse how various characteristics of MiP affect delivery outcomes. METHODS: Between October 2006 and May 2009, 1,218 pregnant women were enrolled in a prospective cohort. After an initial assessment, they were screened weekly for malaria. At delivery, blood smears were obtained from the mother, placenta, cord and newborn. Multivariate analyses were performed to analyse the association between mothers' characteristics and malaria risk, as well as between MiP and birth outcome, length and weight at birth. This study is a secondary analysis of a trial registered with ClinicalTrials.gov, number NCT00495508. RESULTS: Overall, 288/1,069 (27%) mothers had 345 peripheral malaria infections. The risk of peripheral malaria was higher in mothers who were younger, infected with HIV, had less education, lived in rural areas or reported no bed net use, whereas the risk of placental infection was associated with more frequent malaria infections and with infection during late pregnancy. The risk of pre-term delivery and of miscarriage was increased in mothers infected with HIV, living in rural areas and with MiP occurring within two weeks of delivery.In adjusted analysis, birth weight but not length was reduced in babies of mothers exposed to MiP (-60 g, 95%CI: -120 to 0 for at least one infection and -150 g, 95%CI: -280 to -20 for >1 infections). CONCLUSIONS: In this study, the timing, parasitaemia level and number of peripherally-detected malaria infections, but not the presence of fever, were associated with adverse birth outcomes. Hence, prompt malaria detection and treatment should be offered to pregnant women regardless of symptoms or other preventive measures used during pregnancy, and with increased focus on mothers living in remote areas.

Burden of and risk factors for sexual violence among women with and without disabilities in two sub-Saharan African countries.

BACKGROUND: Available data suggest that women with disabilities have an increased risk of sexual violence, but little is known about the situation of those women living in resource-limited settings. OBJECTIVES: To assess the burden and examine the drivers of sexual violence among women with disabilities. METHODS: This is a pooled analysis of two population-based surveys conducted in Cameroon and Burundi. Adults with and without disabilities were randomly recruited from the general population. Structured interviews were conducted at both sites to collect data on participants' functional limitations, life-course history of sexual violence, education, employment, and resources. Only women with disabilities whose impairments started before the age of 10 years (n = 359) and women without disabilities (n = 720) are included in this analysis. The age-adjusted prevalence of violence was computed, and risk factors were assessed using a discrete survival regression and mediation analysis. RESULTS: At both sites, the participants with disabilities had a lower education level and had an increased risk of food insecurity. The pooled age-adjusted prevalence of lifetime sexual violence was 19.8% (95%CI:15.3-24.3) among women with disabilities and 11.7% (95%CI:9.3-14.1) among those without disabilities (ORap: 2.0, 95%CI:1.4-2.8). Women with cognitive limitations and those with visual impairments had the highest risk of sexual violence (ORap: 3.5 (95%CI:2.0-6.3) and 2.7 (95%CI:1.4-5.0), respectively). Over the life course, the risk of sexual violence was especially high among women with disabilities who had lived with an intimate partner before the age of 25 years (p < 0.001). Education level mediated approximately one-third of the total association between disability and sexual violence (p = 0.001). There was no evidence of an indirect effect through food insecurity. CONCLUSION: This study provides evidence of the high burden of sexual violence among women with disabilities who live in urban African contexts. The social environment and access to education may be key contributors to this vulnerability.

Heterogeneous decrease in malaria prevalence in children over a six-year period in south-western Uganda.

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.

Incidence and determinants of new AIDS-defining illnesses after HAART initiation in a Senegalese cohort.

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.

Pro-equity legislation, health policy and utilisation of sexual and reproductive health services by vulnerable populations in sub-Saharan Africa: a systematic review.

Twenty-five years ago, the International Conference on Population and Development highlighted the need to address sexual and reproductive health (SRH) rights on a global scale. The sub-Saharan Africa region continues to have the highest levels of maternal mortality and HIV, primarily affecting the most vulnerable populations. Recognising the critical role of policy in understanding population health, we conducted a systematic review of original primary research which examined the relationships between equity-focused legislation and policy and the utilisation of SRH services by vulnerable populations in sub-Saharan Africa. We searched nine bibliographic databases for relevant articles published between 1994 and 2019. Thirty-two studies, conducted in 14 sub-Saharan African countries, met the inclusion criteria. They focused on maternal health service utilisation, either through specific fee reduction/removal policies, or through healthcare reforms and insurance schemes to increase SRH service utilisation. Findings across most of the studies showed that health-related legislation and policy promoted an increase in service utilisation, over time, especially for antenatal care, skilled birth attendance and facility-based delivery. However, social health inequalities persisted among subgroups of women. Neither the reviewed studies nor the policies specifically addressed youth, people living with HIV and people with disabilities. In the era of the sustainable development goals, addressing health inequities in the context of social determinants of health becomes unavoidable. Systematic and rigorous quantitative and qualitative research, including longitudinal policy evaluation, is required to understand the complex relationships between policy addressing upstream social determinants of health and health service utilisation.

Knowledge, attitudes and practices among Brazzaville midwives on cervical cancer screening.

INTRODUCTION: cervical cancer is an illness that causes 250,000 deaths worldwide. Data on Health professional's skills is highly important for the elaboration of prevention strategies. Objective: assess the knowledge, attitudes and practices (KAP) among Brazzaville midwives on cervical cancer screening. METHODS: analytical KAP Study, from May 2nd to August 10th 2018. Participants are midwives working in the Gynaecology-Obstetrics departments of six hospitals in Brazzaville (Republic of Congo). Variables were related to their socio-demographic and occupational characteristics, as well as to their knowledge, attitudes and practices. Analyses were done using the Epi Info 7.2.2.6 software. Frequencies, central trend parameters, as well as rib ratios were calculated. Pearson, Fisher and Wald statistical tests with a significance level of 5% where used. RESULTS: the study included 114 midwives aged 43.07 (± 7.40) years. They had an unsatisfactory level of knowledge (59.64%), favourable attitudes (92.98%) and poor practices (71.05%). The factors linked with best (satisfactory) knowledge were, seniority at workplace (10-27 years) [29.31%] vs. 51, 79%; OR; 2.59 (1.19-5.60)] and age (42-60 years) [31.81% vs. 52.08%; OR 2.32 (1.08-5.01)]. The best knowledge were related to the best practices (good) [16.18% vs. 47.83%; OR a = 2.95 (1.87-4.67)]; Midwives attitudes seem to not impact on their practices (p = 0.53). CONCLUSION: Brazzaville midwives have little knowledge and practices on cervical cancer screening. Therefore, the need of training them and equipping cervical cancer screening.

Outcome of Children With Presumptive Tuberculosis in Mbarara, Rural Uganda.

BACKGROUND: Mortality among children with presumptive tuberculosis (TB) empiric TB treatment can be high. We describe the predictors of death among children with presumptive TB, and the relation between treatment and mortality. METHODS: A prospective cohort of children with presumptive TB who underwent clinical assessment, chest radiograph, tuberculin skin test and sputum bacterial tests for TB was followed up for 3 months. TB diagnosis was based on mycobacterial, clinical and radiologic findings. Predictors of deaths were determined using cox regression model. RESULTS: Of 360 children included in the analysis, 31.4% were younger than 2 years; 31.6% were HIV infected and 11.3% were severely malnourished. One hundred forty (38.9%) were diagnosed with TB, 18 (13%) of whom were bacteriologically confirmed. At 3 months of follow up, 25 of 360 (6.9%) children had died: 15 of 140 (10.7%) were receiving TB treatment versus 10 of 220 (4.5%) were not receiving treatment (P = 0.025). Severely malnourished children [adjusted hazard ratio (aHR), 9.86; 95% confidence interval (CI): 3.11-31.23] and those with chest radiographs suggestive of TB (aHR, 4.20; 95% CI: 0.93-19.01) were more likely to die. Children receiving empiric TB treatment had an increased risk of death (aHR, 2.37; 95% CI: 1.01-5.55) compared with children without treatment after adjustment for age, sex, HIV status and Bacillus Calmette-Guérin (BCG) vaccination. CONCLUSIONS: The high mortality in children receiving empirically TB treatment highlights the difficulty in diagnosing childhood TB, the increased likelihood of starting treatment in critically ill children and in children with chronic disease, and the possibility of misdiagnosis. It strengthens the need to invest further in early TB detection and diagnosing nonsevere illness.

Prevalence of HIV infection among people with disabilities: a population-based observational study in Yaoundé, Cameroon (HandiVIH).

BACKGROUND: In resource-limited settings, people with disabilities have been left behind in the response to HIV. In the HandiVIH study, we estimate and compare HIV prevalence and associated risk factors between people with and without disabilities. METHODS: In this cross-sectional, population-based, observational study, we used two-phase random sampling to recruit adults with disabilities and a control group matched for age, sex, and residential location from households of the general population. We used the Washington Group Short Set of Questions on Disability to identify people with disabilities. We administered an HIV test and a life-course history interview to participants. The primary outcome was the prevalence of HIV among participants with and without disabilities. FINDINGS: Between Oct 2, 2014, and Nov 30, 2015, we recruited 807 people with disabilities and 807 participants without disabilities from Yaoundé, Cameroon. 28 of 716 people in the control population had a positive HIV test result (crude prevalence 3·9%, 95% CI 2·9-5·3) compared with 50 of 739 people with disabilities (6·8%, 5·0-8·6; conditional odds ratio [OR] 1·7; p=0·04). Women with disabilities were more often involved in paid sexual relationships than were women without disabilities (2·5% vs 0·5%, p=0·05). People with disabilities were also at increased risk of sexual violence than were women without disabilities (11·0% vs 7·5%, OR 1·5; p=0·01). Sexual violence and sex work were strongly associated with increased risk of HIV infection among participants with disabilities but not among controls (OR 3·0, 95% CI 1·6-5·6 for sexual violence and 12·3, 4·4-34·6 for sex work). Analyses were done in men and women. INTERPRETATION: The higher prevalence of HIV infection in people with disabilities than people without disabilities reflects a higher exposure to HIV infection as well as the presence of disability-associated HIV infection. The susceptibility of people with disabilities to HIV infection seems to be shaped by social and environmental factors. Research is needed to inform firm recommendations on how to protect this vulnerable population. FUNDING: Agence nationale de recherches sur le sida et les hépatites virales (ANRS-Inserm) and the 5% Initiative.

HandiVIH--A population-based survey to understand the vulnerability of people with disabilities to HIV and other sexual and reproductive health problems in Cameroon: protocol and methodological considerations.

INTRODUCTION: In resource-limited countries, people with disabilities seem to be particularly vulnerable to HIV infection due to barriers to accessing information and services, frequent exposure to sexual violence and social exclusion. However, they have often been left behind in the HIV response, probably because of the lack of reliable epidemiological data measuring this vulnerability. Multiple challenges in conducting good quality epidemiological surveys on people with disabilities require innovative methods to better understand the link between disability and HIV. This paper describes how the design and methods of the HandiVIH study were adapted to document the vulnerability of people with disabilities to HIV, and to compare their situation with that of people without disabilities. METHODS AND ANALYSIS: The HandiVIH project aims to combine quantitative and qualitative data. The quantitative component is a cross-sectional survey with a control group conducted in Yaoundé (Cameroon). A two-phase random sampling is used (1) to screen people with disabilities from the general population using the Washington Group questionnaire and, (2) to create a matched control group. An HIV test is proposed to each study participant. Additionally, a questionnaire including a life-event interview is used to collect data on respondents' life-course history of social isolation, employment, sexual partnership, HIV risk factors and fertility. Before the cross-sectional survey, a qualitative exploratory study was implemented to identify challenges in conducting the survey and possible solutions. Information on people with disabilities begging in the streets and members of disabled people's organisations is collected separately. ETHICS AND DISSEMINATION: This study has been approved by the two ethical committees. Special attention has been paid on how to adapt the consenting process to persons with intellectual disabilities. The methodological considerations discussed in this paper may contribute to the development of good practices for conducting quantitative health surveys on people with disabilities. TRIAL REGISTRATION NUMBER: NCT02192658.

Getting pregnant in HIV clinical trials: women's choice and safety needs. The experience from the ANRS12169-2LADY and ANRS12286-MOBIDIP trials.

INTRODUCTION: Pregnancy is an exclusion criteria in most clinical trials involving antiretroviral therapy (ART) and modern contraception methods are systematically proposed to women of childbearing age. Nevertheless pregnancies are often observed. Reproductive choices during clinical trials should be understood to adapt interventions to the level of risk for mother and baby safety. Our goal was to describe the reproductive behavior and pregnancy outcomes among HIV-infected women on second-line antiretroviral treatment enrolled in two clinical trials and to compare them with those of HIV-positive women in non-research settings. METHODS: The number and outcomes of pregnancies were recorded among 281 non menopausal women enrolled in the ANRS 12169-2LADY and ANRS 12286-MOBIDIP clinical trials in Cameroon, Senegal and Burkina Faso. All participants had agreed to use a least one contraceptive method (barrier or non-barrier) which was provided for free during the study. Data were collected through revision of pregnancy notification forms and by data extraction from the study database, regularly updated and checked during the study. RESULTS: Sixty-six women had 84 pregnancies between January 2010 and July 2015 resulting in a pregnancy rate of 8.0 per 100 women-years (WY) (95% CI 6.5-9.9) which is similar to the ones observed in cohort studies in Sub-Saharan Africa (varying from 2.5 to 9.4 pregnancies per 100 WY). Among 60 live births, 10 (16.6%) were born prematurely and 9 (15%) had a low birth weight. Sixteen miscarriages/stillbirths occurred (19.5%). This percentage is comparable to the one expected in the seronegative population which is reassuring for HIV-positive women considering pregnancy on ART. Only one minor birth defect was diagnosed. In univariate and multivariate analysis, miscarriages/stillbirths were not associated either with age, nadir of CD4 count, duration of ART, CD4 count, or viral load at the beginning of pregnancy. CONCLUSION: HIV-positive women participating in clinical trials conducted in Sub-Saharan Africa tend to get pregnant as often as seropositive women who received medical care in non-research settings. It is therefore essential to adopt a pragmatic approach by re-evaluating the relevance of the criteria for exclusion of pregnant women according to the risk associated with exposure and to seek more effective and innovating contraceptive strategies when using potentially teratogenic molecules.

Inhaled Nitric Oxide as an Adjunctive Treatment for Cerebral Malaria in Children: A Phase II Randomized 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]-1ß, 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.

Morbidity after antiretroviral therapy initiation in HIV-1-infected children in West Africa: temporal trends and relation to CD4 count.

BACKGROUND: Although 90% of HIV-1-infected children live in sub-Saharan Africa, morbidity data after highly active antiretroviral therapy (HAART) initiation in these settings are limited. The objective of this study was to document the incidence of AIDS-defining events and non-AIDS-defining diseases in African children receiving HAART. METHODS: Incidences rates (IRs) of AIDS-defining events and 10 other common diseases were estimated overall and by current CD4-strata (<15%, 15 - <25% and ≥25%) from 2 prospective cohorts of African children. RESULTS: One hundred eighty-eight children contributing to 355 children-years were included. The documented morbidity IRs per 100 children-years were upper respiratory infections, 100 (87-114); infectious diarrhea, 37 (31-44); World Health Organization (WHO) stage 2 events, 22.9 (18.2-28.1); and WHO stage 3/4 events, 12.3 (9.1-16.7). IRs of WHO stage 2 events, severe bacterial infections, infectious diarrhea and pneumonia decreased linearly across all CD4%-strata, whereas WHO stage 3/4 events and viral infections occurred mostly when CD4% <15%. Overall, IRs decreased during the first 2 years on HAART except for upper respiratory infection, mycosis and oral candidiasis. CONCLUSION: This incidence of AIDS- and non-AIDS-defining diseases declined substantially after HAART in 2 African cohorts, although estimates remained high compared with high-resource settings. Without renewed efforts to increase antiretroviral scale-up, children in developing countries will continue to have a high burden of infections.

Risk of virological failure and drug resistance during first and second-line antiretroviral therapy in a 10-year cohort in Senegal: results from the ANRS 1215 cohort.

BACKGROUND: In 1998, Senegal launched one of Africa's first antiretroviral therapy (ART) programs. Since then, the number of treated patients in Africa has substantially increased thanks to simplification in treatment management. Although good outcomes over the first years of ART have been observed in sub-Saharan Africa, little is known about the long-term (>5 years) risks of virological failure and drug resistance and about second-line treatment response. METHODS: Patients from the ANRS-1215 cohort in Senegal, started with either one nonnucleoside reverse transcriptase inhibitor or indinavir, a first-generation nonboosted protease inhibitor, followed for >6 months and having >1 viral load (VL) measurement were included. Virological failure was defined as 2 consecutive VL measurements >1000 copies/mL. RESULTS: Of the 366 patients included, 89% achieved a VL <500 copies/mL. The risk of virological failure at 12, 24, and 60 months was 5%, 16%, and 25%, being higher in younger patients (P = 0.05), those receiving a protease inhibitor-containing regimen (P = 0.05), and those with lower adherence (P = 0.03). The risk of resistance to any drug at 12, 24, and 60 months was 3%, 11%, and 18%. After virological failure, 60% of the patients were switched to second-line treatments. Although 81% of the patients achieved virological success, the risk of virological failure was 27% at 24 months, mostly in patients with multiple resistances. CONCLUSIONS: In this cohort, virological outcomes for first-line treatments were good compared with those from high-resource settings. However, the rate of virological failure for second-line treatment was high, probably because of accumulation of resistances.

Changes in the renal function after tenofovir-containing antiretroviral therapy initiation in a Senegalese cohort (ANRS 1215).

To describe and compare the changes in renal function between HIV-1 infected adult patients receiving antiretroviral therapy (ART) with and without tenofovir (TDF). The population consisted of 40 patients starting a TDF-containing regimen and 388 patients starting regimen not containing TDF, and followed during 42 months. The estimated glomerular filtration rate (eGFR) was calculated using the Cockroft-Gault and MDRD equations and modeled separately for the first 12 months and the subsequent period. Between baseline and 12 months, the eGFR decreased significantly in patients receiving TDF (-10.40 ml/min), whereas it increased in the other +4.33 ml/min). A significant variability in the eGFR trajectories of patients receiving TDF was observed; 12 (30%) of them experienced a persistent decrease, 5 (12%) had an initial transient increase, and 23 (58%) a steady slow increase in eGFR. The characteristics at baseline of the patients with persistent decrease were not different from the other patients but their immune reconstitution was impaired. After 12 months, patients receiving TDF experienced a higher rate of transition from mild renal impairment (60-90 ml/min/1.73 m(2)) to moderate renal impairment (30-60 ml/min/1.73 m(2)) when compared with patients not receiving TDF. A significant though moderate decline in the renal function was observed in one-third of the patients receiving TDF compared to patients not receiving TDF. Moreover, this impairment was persistent after the first year of treatment.

Short and Long-Term Incidence of Tuberculosis and CD4-Cell Count Dynamic on HAART in Senegal.

OBJECTIVES: Estimate tuberculosis (TB) incidence among patients receiving HAART. Compare the dynamic of the CD4-cell count and viral load before notification of the TB with the dynamic among patients remaining free of TB. DESIGN: Prospective cohort with ascertainment of TB cases from medical records. METHODS: The first 404 adults HIV-1 infected patients enrolled in the Senegalese antiretroviral drug access initiative were eligible. CD4-cell and viral load were assessed at baseline and every 6 months. Patients receiving an antituberculosis treatment at HAART initiation were excluded from analysis. Any TB case notified after the first month of HAART was considered as an incident case. Follow-up was censored at death or at the last visit before March 31, 2008. CD4-cell trajectories until TB notification were compared to non-TB developers within two distinct periods: from HAART initiation to 24 months and after. RESULTS: Over 404 eligible patients, 352 were included in this analysis. Median follow-up reached 73 months and 1821 person-years were accrued. Half of the 42 incident cases were notified before month 19 of HAART yielding to an overall incident rate of 2.3/100 PY [1.7-3.1]. Annual incidence decreased with duration of HAART (trend in incidence: RR=0.26, p<10(-4)). During the first period, CD4-cell count dynamic of most TB patients was identical to the dynamic among patients remaining free of TB. Most cases of the second period occurred in a context of an immunological failure. CONCLUSIONS: This study provides an estimate of TB incidence among patients on HAART in Senegal and supports two underlying mechanisms.