Access to Hepatis C treatment in Sub-Saharan Africa is a clinical, public health and ethical concern. The multi-country open-label trial TAC ANRS 12311 allowed assessing the feasibility, safety, efficacy of a specific care model of HCV treatment and retreatment in patients with hepatitis C in Sub Saharan Africa. Between November 2015 and March 2017, with follow-up until mid 2019, treatment-naïve patients with HCV without decompensated cirrhosis or liver cancer were recruited to receive 12 week-treatment with either sofosbuvir + ribavirin (HCV genotype 2) or sofosbuvir + ledipasvir (genotype 1 or 4) and retreatment with sofosbuvir + velpatasvir + voxilaprevir in case of virological failure. The primary outcome was sustained virological response at 12 weeks after end of treatment (SVR12). Secondary outcomes included treatment adherence, safety and SVR12 in patients who were retreated due to non-response to first-line treatment. The model of care relied on both viral load assessment and educational sessions to increase patient awareness, adherence and health literacy. The study recruited 120 participants, 36 HIV-co-infected, and 14 cirrhotic. Only one patient discontinued treatment because of return to home country. Neither death nor severe adverse event occurred. SVR12 was reached in 107 patients (89%): (90%) in genotype 1 or 2, and 88% in GT-4. All retreated patients (n = 13) reached SVR12. HCV treatment is highly acceptable, safe and effective under this model of care. Implementation research is now needed to scale up point-of-care HCV testing and SVR assessment, along with community involvement in patient education, to achieve HCV elimination in Sub-Saharan Africa.

Efficacy of sulfadoxine-pyrimethamine, the malaria chemoprophylaxis used in pregnant women, and in children when combined with amodiaquine, is threatened by the accumulation of mutations in the Plasmodium falciparum dihydropteroate synthase (pfdhps) and dihydrofolate reductase (pfdhfr) genes. Data on the prevalence of resistant alleles in central Africa and the new pfdhps I431V mutation, particularly associated with other mutations to form the pfdhps vagKgs allele, are scarce. We explored the frequency and geographical distribution of pfdhps and pfdhfr mutations in central Africa in 2014-18, and assessed the evolutionary origin of the vagKgs allele.
Samples were collected at 18 health-care centres in seven countries (Angola, Cameroon, Central African Republic, Democratic Republic of the Congo, Gabon, Nigeria, and Republic of the Congo) from patients who showed possible symptoms of malaria between March 1, 2014, and Oct 31, 2018. Samples that were positive for P falciparum were transported to a laboratory in Toulouse, France, and genotyped. The frequency of pfdhfr and pfdhps mutations was studied in 1749 samples. Microsatellites in pfdhps flanking regions and whole-genome analysis compared with parasite genomes from the data-sharing network MalariaGEN were performed on samples carrying the vagKgs allele.
Mapping of the prevalence of single nucleotide polymorphisms and corresponding alleles of pfdhfr and pfdhps showed a substantial spread of alleles associated with sulfadoxine-pyrimethamine resistance in central Africa during the 2014-18 period, especially an increase going west to east in pfdhps alleles carrying the K540E and A581G mutations. A high prevalence of the pfdhps I431V mutation was observed in Cameroon (exceeding 50% in the northern region) and Nigeria. Genomic analysis showed a recent African emergence and a clonal expansion of the most frequent pfdhps vagKgs allele.
Reduced sulfadoxine-pyrimethamine efficacy due to increased resistance is a worrying situation, especially because the malaria transmission level is high in central Africa. Although the resistance phenotype remains to be confirmed, the emergence and spread of the vagKgs allele in west and central Africa could challenge the use of sulfadoxine-pyrimethamine.
Toulouse Institute for Infectious and Inflammatory Diseases.

OBJECTIVE: To investigate contextual factors and their influence on implementing a 90-credit midwifery education programme for nurses at a university in the eastern DRC.
BACKGROUND: To improve maternal and neonatal health, there is a government policy in the Democratic Republic of Congo (DRC) to educate midwives at a higher education level according to international norms. This study investigates contextual factors and their influence on the implementation of a midwifery education programme which is based on national curriculum and has a profile of person-centred care, simulation-based learning pedagogy and information and communication technology.
METHODS: A qualitative study was conducted with data collected through semi-structured interviews with 22 participants who were directly or indirectly involved in establishing the midwifery education programme. Transcribed interviews were analysed using content analysis.
RESULTS: The factors influencing the implementation of the new midwifery education programme comprise facilitating and hindering factors. Facilitating factors were: (i) awareness that midwives educated at a higher education level can deliver higher-quality health care, (ii) women are motivated to seek care from well-educated midwives, (iii) the planned programme is attractive and (iv) the university has a stable academic administration and established collaborations. Hindering factors were: (i) Students\' lack of prerequisites for study; (ii) objections to educating midwives at a higher education level; (iii) inadequate teaching resources; and (iv) inadequate working conditions for midwives.
CONCLUSIONS: The facilitating factors strengthen the belief that it is possible to implement this midwifery education programme, while the hindering factors need to be addressed to run the programme successfully. The findings can guide higher education institutions starting similar midwifery education programmes in the DRC and elsewhere, although it is crucial to conduct a context study in those specific contexts.

The Central African Region is an agricultural and fishing-based economy, with 40% of the population living in rural communities. The negative impacts of climate change have caused economic/health-related adverse impacts and food insecurity. This original article aims to research four key themes: (i) acute food insecurity (AFI); (ii) childhood malnutrition and mortality; (iii) infectious disease burden; and (iv) drought and mean temperature projections throughout the twenty-first century. Food insecurity was mapped in Central Africa based on the Integrated Food Security Phase Classification (IPC) for AFI. The global hunger index (GHI) was presented along with the proportion of children with undernourishment, stunting, wasting, and mortality. Data for infectious disease burden was computed by assessing the adjusted rate of change (AROC) of mortality due to diarrhea among children and the burden of death rates due to pneumonia across all age groups. Finally, the mean drought index was computed through the year 2100. This population-based study identifies high levels of hunger across a majority of the countries, with the mean drought index suggesting extreme ends of wet and dry days and an overall rise of 1-3 °C. This study is a source of evidence for stakeholders, policymakers, and the population residing in Central Africa.

Population-based cancer survival is a key measurement of cancer control performance linked to diagnosis and treatment, but benchmarking studies that include lower-income settings and that link results to health systems and human development are scarce. SURVCAN-3 is an international collaboration of population-based cancer registries that aims to benchmark timely and comparable cancer survival estimates in Africa, central and south America, and Asia.
In SURVCAN-3, population-based cancer registries from Africa, central and south America, and Asia were invited to contribute data. Quality control and data checks were carried out in collaboration with population-based cancer registries and, where applicable, active follow-up was performed at the registry. Patient-level data (sex, age at diagnosis, date of diagnosis, morphology and topography, stage, vital status, and date of death or last contact) were included, comprising patients diagnosed between Jan 1, 2008, and Dec 31, 2012, and followed up for at least 2 years (until Dec 31, 2014). Age-standardised net survival (survival where cancer was the only possible cause of death), with 95% CIs, at 1 year, 3 years, and 5 years after diagnosis were calculated using Pohar-Perme estimators for 15 major cancers. 1-year, 3-year, and 5-year net survival estimates were stratified by countries within continents (Africa, central and south America, and Asia), and countries according to the four-tier Human Development Index (HDI; low, medium, high, and very high).
1 400 435 cancer cases from 68 population-based cancer registries in 32 countries were included. Net survival varied substantially between countries and world regions, with estimates steadily rising with increasing levels of the HDI. Across the included cancer types, countries within the lowest HDI category (eg, CÔte d\'Ivoire) had a maximum 3-year net survival of 54·6% (95% CI 33·3-71·6; prostate cancer), whereas those within the highest HDI categories (eg, Israel) had a maximum survival of 96·8% (96·1-97·3; prostate cancer). Three distinct groups with varying outcomes by country and HDI dependant on cancer type were identified: cancers with low median 3-year net survival (<30%) and small differences by HDI category (eg, lung and stomach), cancers with intermediate median 3-year net survival (30-79%) and moderate difference by HDI (eg, cervix and colorectum), and cancers with high median 3-year net survival (≥80%) and large difference by HDI (eg, breast and prostate).
Disparities in cancer survival across countries were linked to a country\'s developmental position, and the availability and efficiency of health services. These data can inform policy makers on priorities in cancer control to reduce apparent inequality in cancer outcome.
Tata Memorial Hospital, the Martin-Luther-University Halle-Wittenberg, and the International Agency for Research on Cancer.

暂无摘要。

Seasonal malaria chemoprevention (SMC) aims to prevent malaria in children during the high malaria transmission season. The Achieving Catalytic Expansion of SMC in the Sahel (ACCESS-SMC) project sought to remove barriers to the scale-up of SMC in seven countries in 2015 and 2016. We evaluated the project, including coverage, effectiveness of the intervention, safety, feasibility, drug resistance, and cost-effectiveness.
For this observational study, we collected data on the delivery, effectiveness, safety, influence on drug resistance, costs of delivery, impact on malaria incidence and mortality, and cost-effectiveness of SMC, during its administration for 4 months each year (2015 and 2016) to children younger than 5 years, in Burkina Faso, Chad, The Gambia, Guinea, Mali, Niger, and Nigeria. SMC was administered monthly by community health workers who visited door-to-door. Drug administration was monitored via tally sheets and via household cluster-sample coverage surveys. Pharmacovigilance was based on targeted spontaneous reporting and monitoring systems were strengthened. Molecular markers of resistance to sulfadoxine-pyrimethamine and amodiaquine in the general population before and 2 years after SMC introduction was assessed from community surveys. Effectiveness of monthly SMC treatments was measured in case-control studies that compared receipt of SMC between patients with confirmed malaria and neighbourhood-matched community controls eligible to receive SMC. Impact on incidence and mortality was assessed from confirmed outpatient cases, hospital admissions, and deaths associated with malaria, as reported in national health management information systems in Burkina Faso and The Gambia, and from data from selected outpatient facilities (all countries). Provider costs of SMC were estimated from financial costs, costs of health-care staff time, and volunteer opportunity costs, and cost-effectiveness ratios were calculated as the total cost of SMC in each country divided by the predicted number of cases averted.
12 467 933 monthly SMC treatments were administered in 2015 to a target population of 3 650 455 children, and 25 117 480 were administered in 2016 to a target population of 7 551 491. In 2015, among eligible children, mean coverage per month was 76·4% (95% CI 74·0-78·8), and 54·5% children (95% CI 50·4-58·7) received all four treatments. Similar coverage was achieved in 2016 (74·8% [72·2-77·3] treated per month and 53·0% [48·5-57·4] treated four times). In 779 individual case safety reports over 2015-16, 36 serious adverse drug reactions were reported (one child with rash, two with fever, 31 with gastrointestinal disorders, one with extrapyramidal syndrome, and one with Quincke\'s oedema). No cases of severe skin reactions (Stevens-Johnson or Lyell syndrome) were reported. SMC treatment was associated with a protective effectiveness of 88·2% (95% CI 78·7-93·4) over 28 days in case-control studies (2185 cases of confirmed malaria and 4370 controls). In Burkina Faso and The Gambia, implementation of SMC was associated with reductions in the number of malaria deaths in hospital during the high transmission period, of 42·4% (95% CI 5·9 to 64·7) in Burkina Faso and 56·6% (28·9 to 73·5) in The Gambia. Over 2015-16, the estimated reduction in confirmed malaria cases at outpatient clinics during the high transmission period in the seven countries ranged from 25·5% (95% CI 6·1 to 40·9) in Nigeria to 55·2% (42·0 to 65·3) in The Gambia. Molecular markers of resistance occurred at low frequencies. In individuals aged 10-30 years without SMC, the combined mutations associated with resistance to amodiaquine (pfcrt CVIET haplotype and pfmdr1 mutations [86Tyr and 184Tyr]) had a prevalence of 0·7% (95% CI 0·4-1·2) in 2016 and 0·4% (0·1-0·8) in 2018 (prevalence ratio 0·5 [95% CI 0·2-1·2]), and the quintuple mutation associated with resistance to sulfadoxine-pyrimethamine (triple mutation in pfdhfr and pfdhps mutations [437Gly and 540Glu]) had a prevalence of 0·2% (0·1-0·5) in 2016 and 1·0% (0·6-1·6) in 2018 (prevalence ratio 4·8 [1·7-13·7]). The weighted average economic cost of administering four monthly SMC treatments was US$3·63 per child.
SMC at scale was effective in preventing morbidity and mortality from malaria. Serious adverse reactions were rarely reported. Coverage varied, with some areas consistently achieving high levels via door-to-door campaigns. Markers of resistance to sulfadoxine-pyrimethamine and amodiaquine remained uncommon, but with some selection for resistance to sulfadoxine-pyrimethamine, and the situation needs to be carefully monitored. These findings should support efforts to ensure high levels of SMC coverage in west and central Africa.
Unitaid.

HIV infection is a global health epidemic with current FDA-approved HIV-1 Protease inhibitors (PIs) designed against subtype B protease, yet they are used in HIV treatment world-wide regardless of patient HIV classification. In this study, double electron-electron resonance (DEER) electron paramagnetic resonance (EPR) spectroscopy was utilized to gain insights in how natural polymorphisms in several African and Brazilian protease (PR) variants affect the conformational landscape both in the absence and presence of inhibitors. Findings show that Subtypes F and H HIV-1 PR adopt a primarily closed conformation in the unbound state with two secondary mutations, D60E and I62V, postulated to be responsible for the increased probability for closed conformation. In contrast, subtype D, CRF_AG, and CRF_BF HIV-1 PR adopt a primarily semi-open conformation, as observed for PI-naïve-subtype B when unbound by substrate or inhibitor. The impact that inhibitor binding has on shifting the conformational land scape of these variants is also characterized, where analysis provides classification of inhibitor induced shifts away from the semi-open state into weak, moderate and strong effects. The findings are compared to those for prior studies of inhibitor induced conformational shifts in PI-naïve Subtype B, C and CRF_AE.

To explore the role of individual-level and household-level characteristics for practice of nutrition-specific and nutrition-sensitive interventions.
Secondary data analysis (cross-sectional).
West and Central Africa.
Data are from the Demographic and Health Surveys in the time period between 1986 and 2016. The final sample included between 116 325 and 272 238 observations depending on the outcome.
Nutrition-specific and nutrition-sensitive interventions were identified based on the UNICEF Conceptual Framework for child undernutrition. These were early breastfeeding initiation, minimum dietary diversity, full age-appropriate immunisation, iodised salt usage, vitamin A supplementation, iron supplementation, deworming in children aged 1 to 5, clean cooking fuel, safe drinking water and improved sanitation. Explanatory variables include household, mother and child characteristics. Linear probability models were fitted for each outcome, both unadjusted as well as fully adjusted including primary sampling unit fixed effects.
Prevalence of early breastfeeding initiation was 54.31% (95% CI: 53.22% to 55.41%), minimum dietary diversity 13.89% (95% CI: 13.19% to 14.59%), full age-appropriate immunisation 13.04% (95% CI: 12.49% to 13.59%), iodised salt usage 49.66% (95% CI: 46.79% to 52.53%), vitamin A supplementation 52.87% (95% CI: 51.41% to 54.33%), iron supplementation 10.73% (95% CI: 10.07% to 11.39%), deworming 31.33% (95% CI: 30.06% to 32.60%), clean cooking fuel usage 3.02% (95% CI: 2.66% to 3.38%), safe drinking water 57.85% (95% CI: 56.10% to 59.59%) and improved sanitation 42.49% (95% CI: 40.77% to 44.21%). There was a positive education and wealth gradient for the practices of all interventions except deworming. Higher birth order was positively associated with the practice of early breastfeeding initiation, minimum dietary diversity, vitamin A supplementation and negatively associated with full immunisation and improved sanitation.
Household, maternal, and child-level characteristics explain practices of nutrition-specific and nutrition-sensitive interventions beyond intervention delivery at the regional level.

Neuropsychiatric symptoms are common in dementia. Limited data are available concerning their association with dementia in developing countries. Our aim was to describe the severity of neuropsychiatric symptoms among older people, evaluate the distress experienced by caregivers, and assess which neuropsychiatric symptoms were specifically associated with dementia among older adults in Central Africa.
This study is part of the EPIDEMCA program, a cross-sectional multicenter population-based study.
The EPIDEMCA program was conducted from November 2011 to December 2012 in urban and rural areas of the Central African Republic and the Republic of the Congo.
Participants were older people (≥65 y) included in the EPIDEMCA program who underwent a neuropsychiatric evaluation. The sample included overall 532 participants, of whom 130 participants had dementia.
Neuropsychiatric symptoms were assessed with the brief version of the Neuropsychiatric Inventory including the evaluation of severity and associated distress. Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision, criteria were followed to diagnose dementia. A logistic regression model was used to identify associated neuropsychiatric symptoms.
The prevalence of neuropsychiatric symptoms was 89.9% (95% confidence interval = 84.6-95.1) among people living with dementia. The overall median severity score for neuropsychiatric symptoms was 9 [interquartile range [IQR] = 6-12], and the overall median distress score was 7 [IQR = 4-10]. Overall median scores of both severity and distress were significantly increased with the number of neuropsychiatric symptoms, the presence of dementia, and dementia severity. Depression, delusions, apathy, disinhibition, and aberrant motor behavior were associated with dementia after multivariate analysis.
This report is one of the few population-based studies on neuropsychiatric symptoms among older people with dementia in Sub-Saharan Africa and the first one evaluating the severity of those symptoms and distress experienced by caregivers. Individual neuropsychiatric symptoms were strongly associated with dementia in older people and require great attention considering their burden on populations. J Am Geriatr Soc 68:180-185, 2019.