SUMMARYRational: Female genital mutilation (FGM) is prevalent in northern Ghana, as the practice is seen as a passage rite to women adulthood and thus undertaken just before marriage. Objectives: We determined the changes in trend of FGM in deliveries at the Navrongo War Memorial hospital, and compared the outcomes and FGM status. Design: Retrospective extraction and analysis of delivery data at the hospital from 1 st January 1996 to 31 st December 2003. Results: Of the 5071 deliveries, about 29% (1466/5071) were associated with FGM. The highest prevalence (95% CI) of 61.5% (50.9, 71.2) was in women aged 40 years and above, and the lowest of 14.4% (11.7, 17.0) was in women below 20 years. The all-age prevalence of FGM showed a significant decline (p-value for linear trend < 0.01) from 35.2% in 1996 to 21.1% in 2003. About 6% (89/1466) of mothers with FGM had stillbirths compared with about 3% (123/3605) of mothers without FGM. Again FGM was associated with 8.2% (120/1466) caesarean section rate compared with 6.7% (241/3605) in mothers without FGM. Mean birth weight and frequency of low birth weights were not significantly associated with FGM status. Conclusion: Although there is a high rate of FGM among mothers in the district and is associated with a higher proportion of stillbirths and caesarean sections, practice has shown a significant decline in the district in recent years due to the prevailing campaigns and intervention studies. There is therefore the need to sustain the ongoing intervention efforts.

IntroductionClimate and weather variability can have significant health consequences of increased morbidity and mortality. However, today the impact of climate and weather variability, and consequentially, of climate change on population health in sub-Saharan Africa is not well understood. In this study, we assessed the association of daily temperature and precipitation with daily mortality by age and sex groups in Northern Ghana.MethodsWe analysed daily mortality and weather data from 1995 to 2010. We adopted a time-series Poisson regression approach to examine the short-term association of daily mean temperature and daily mean precipitation with daily mortality. We included time factors and daily lagged weather predictors. The correlation between lagged weather predictors was also considered.ResultsFor all populations, a statistically significant association of mean daily temperature with mortality at lag days 0–1 was observed below and above the 25th (27.48°C) and 75th (30.68°C) percentiles (0.19%; 95% confidence interval CI: 0.05%, 0.21%) and (1.14%; 95% CI: 0.12%, 1.54%), respectively. We also observed a statistically significant association of mean daily temperature above 75th percentile at lag days 2–6 and lag days 7–13 (0.32%; 95% CI: 0.16%, 0.25%) and (0.31% 95% CI: 0.14%, 0.26%), respectively. A 10 mm increase in precipitation was significantly associated with a 1.71% (95% CI: 0.10%, 3.34.9%) increase in mortality for all ages and sex groups at lag days 2–6. Similar results were also observed at lag days 2–6 and 14–27 for males, 2.92% (95% CI: 0.80%, 5.09%) and 2.35% (95% CI: 0.28%, 4.45%).ConclusionShort-term weather variability is strongly associated with mortality in Northern Ghana. The associations appear to differ among different age and sex groups. The elderly and young children were found to be more susceptible to short-term temperature-related mortality. The association of precipitation with mortality is more pronounced at the short-term for all age and sex groups and in the medium short-term among males. Reducing exposure to extreme temperature, particularly among the elderly and young children, should reduce the number of daily deaths attributable to weather-related mortality.

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We measured the type-specific incidence of paediatric rotavirus diarrhoea in an area of northern Ghana. Over 1 year, diarrhoea 1717 episodes were identified, of which 677 (39%) were positive for rotavirus. Risk factors for rotavirus infection included old age, wasting, high Vesikari score and the episode occurring in the dry season. Rotavirus-positive episodes tended to be more acute, causing vomiting and greater dehydration, and were more likely to require hospitalization. The incidence was 0.089 episodes per person-year for all diarrhoea, and 0.035 for rotavirus diarrhoea. The observed incidence decreased markedly with distance from the nearest health centre, suggesting a large unobserved burden. G2P[6], G3P[4] and G9P[8] made up more than half the genotypes detected, but the remainder were diverse. There is a large burden of rotavirus diarrhoea, but the effectiveness of future vaccines could be diluted by the high polymorphism of the virus, and the difficulty of reaching remote populations.

High-malaria burden countries in sub-Saharan Africa are shifting from malaria control towards elimination. Hence, there is need to gain a contemporary understanding of how indoor residual spraying (IRS) with non-pyrethroid insecticides when combined with long-lasting insecticidal nets (LLINs) impregnated with pyrethroid insecticides, contribute to the efforts of National Malaria Control Programmes to interrupt transmission and reduce the reservoir of Plasmodium falciparum infections across all ages. Using an interrupted time-series study design, four age-stratified malariometric surveys, each of ~2,000 participants, were undertaken pre- and post-IRS in Bongo District, Ghana. Following the application of three-rounds of IRS, P. falciparum transmission intensity declined, as measured by a >90% reduction in the monthly entomological inoculation rate. This decline was accompanied by reductions in parasitological parameters, with participants of all ages being significantly less likely to harbor P. falciparum infections at the end of the wet season post-IRS (aOR = 0.22 [95% CI: 0.19–0.26], p-value < 0.001). In addition, multiplicity of infection (MOIvar) was measured using a parasite fingerprinting tool, designed to capture within-host genome diversity. At the end of the wet season post-IRS, the prevalence of multi-genome infections declined from 75.6% to 54.1%. This study demonstrates that in areas characterized by high seasonal malaria transmission, IRS in combination with LLINs can significantly reduce the reservoir of P. falciparum infection. Nonetheless despite this success, 41.6% of the population, especially older children and adolescents, still harboured multi-genome infections. Given the persistence of this diverse reservoir across all ages, these data highlight the importance of sustaining vector control in combination with targeted chemotherapy to move high-transmission settings towards pre-elimination. This study also points to the benefits of molecular surveillance to ensure that incremental achievements are not lost and that the goals advocated for in the WHO’s High Burden to High Impact strategy are realized.

Background Cipargamin (KAE609) is a potent antimalarial in a phase II trial. Here we report efficacy, pharmacokinetics, and resistance marker analysis across a range of cipargamin doses. These were secondary endpoints from a study primarily conducted to assess the hepatic safety of cipargamin (hepatic safety data are reported elsewhere). Methods This phase II, multicenter, randomized, open-label, dose-escalation trial was conducted in sub-Saharan Africa in adults with uncomplicated Plasmodium falciparum malaria. Cipargamin monotherapy was given as single doses up to 150 mg or up to 50 mg once daily for 3 days, with artemether-lumefantrine as control. Key efficacy endpoints were parasite clearance time (PCT), and polymerase chain reaction (PCR)–corrected and uncorrected adequate clinical and parasitological response (ACPR) at 14 and 28 days. Pharmacokinetics and molecular markers of drug resistance were also assessed. Results All single or multiple cipargamin doses ≥50 mg were associated with rapid parasite clearance, with median PCT of 8 hours versus 24 hours for artemether-lumefantrine. PCR-corrected ACPR at 14 and 28 days was &gt;75% and 65%, respectively, for each cipargamin dose. A treatment-emerging mutation in the Pfatp4 gene, G358S, was detected in 65% of treatment failures. Pharmacokinetic parameters were consistent with previous data, and approximately dose proportional. Conclusions Cipargamin, at single doses of 50 to 150 mg, was associated with very rapid parasite clearance, PCR-corrected ACPR at 28 days of &gt;65% in adults with uncomplicated P. falciparum malaria, and recrudescent parasites frequently harbored a treatment-emerging mutation. Cipargamin will be further developed with a suitable combination partner. Clinical Trials Registration ClinicalTrials.gov (NCT03334747).

Background Following a 30-year development process, RTS,S/AS01E (GSK, Belgium) is the first malaria vaccine to reach Phase IV assessments. The World Health Organization-commissioned Malaria Vaccine Implementation Programme (MVIP) is coordinating the delivery of RTS,S/AS01E through routine national immunization programmes in areas of 3 countries in sub-Saharan Africa. The first doses were given in the participating MVIP areas in Malawi on 23 April, Ghana on 30 April, and Kenya on 13 September 2019. The countries participating in the MVIP have little or no baseline incidence data on rare diseases, some of which may be associated with immunization, a deficit that could compromise the interpretation of possible adverse events reported following the introduction of a new vaccine in the paediatric population. Further, effects of vaccination on malaria transmission, existing malaria control strategies, and possible vaccine-mediated selective pressure on Plasmodium falciparum variants, could also impact long-term malaria control. To address this data gap and as part of its post-approval commitments, GSK has developed a post-approval plan comprising of 4 complementary Phase IV studies that will evaluate safety, effectiveness and impact of RTS,S/AS01E through active participant follow-up in the context of its real-life implementation. Methods EPI-MAL-002 (NCT02374450) is a pre-implementation safety surveillance study that is establishing the background incidence rates of protocol-defined adverse events of special interest. EPI-MAL-003 (NCT03855995) is an identically designed post-implementation safety and vaccine impact study. EPI-MAL-005 (NCT02251704) is a cross-sectional pre- and post-implementation study to measure malaria transmission intensity and monitor the use of other malaria control interventions in the study areas, and EPI-MAL-010 (EUPAS42948) will evaluate the P. falciparum genetic diversity in the periods before and after vaccine implementation. Conclusion GSK’s post-approval plan has been designed to address important knowledge gaps in RTS,S/AS01E vaccine safety, effectiveness and impact. The studies are currently being conducted in the MVIP areas. Their implementation has provided opportunities and posed challenges linked to conducting large studies in regions where healthcare infrastructure is limited. The results from these studies will support ongoing evaluation of RTS,S/AS01E’s benefit-risk and inform decision-making for its potential wider implementation across sub-Saharan Africa. Graphic abstract

Artemisinin resistant Plasmodium falciparum is advancing across Southeast Asia in a soft selective sweep involving at least 20 independent kelch13 mutations. In a large global survey, we find that kelch13 mutations which cause resistance in Southeast Asia are present at low frequency in Africa.We show that African kelch13 mutations have originated locally, and that kelch13 shows a normal variation pattern relative to other genes in Africa, whereas in Southeast Asia there is a great excess of non-synonymous mutations, many of which cause radical amino-acid changes. Thus, kelch13 is not currently undergoing strong selection in Africa, despite a deep reservoir of standing variation that could potentially allow resistance to emerge rapidly. The practical implications are that public health surveillance for artemisinin resistance should not rely on kelch13 data alone, and interventions to prevent resistance must account for local evolutionary conditions, shown by genomic epidemiology to differ greatly between geographical regions. IntroductionArtemisinin combination therapy (ACT), the frontline treatment for P. falciparum infection, has played a major part in reducing the number of deaths due to malaria over the past decade (World Health Organization 2014). However artemisinin resistant P. falciparum, which has recently spread across large parts of Southeast Asia, now threatens to destabilise malaria control worldwide (Dondorp et al. 2009;Hien et al. 2012;Phyo et al. 2012;Kyaw et al. 2013;Ashley et al. 2014; World Health Organization 2014). One of the main contemporary challenges in global health is to prevent artemisinin resistance from becoming established in Africa, where the consequences for childhood mortality could be disastrous (Dondorp and Ringwald 2013).. CC-BY-NC-ND 4.0 International license not peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was . http://dx.doi.org/10.1101/019737 doi: bioRxiv preprint first posted online May. 22, 2015; Genomic epidemiology of the current wave of artemisinin resistant malaria Page 2Understanding the epidemiological and evolutionary processes that are driving the current wave of artemisinin resistance is essential to develop effective strategies to stop it spreading. At the molecular level, artemisinin resistance is caused by mutations in a kelch protein encoded by PF3D7_1343700 on P. falciparum chromosome 13, referred to here as kelch13. More specifically, non-synonymous mutations in the kelch13 propeller and BTB-POZ domains (KPBD) result in reduced sensitivity of P. falciparum to artemisinin, as demonstrated by multiple lines of evidence including laboratory studies of artificially acquired resistance, genetic association studies of natural resistance and allelic replacement experiments (Ariey et al. 2014;Ghorbal et al. 2014;Miotto et al. 2015; Straimer et al. 2015; Takala-Harrison et al. 2015). The precise biological function of kelch13 is still not fully understood, but parasites with KBPD mut...