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Genetic variation in CYP2B6 and CYP2A6 is known to impact interindividual response to antiretrovirals, nicotine, and bupropion, among other drugs. However, the full catalogue of clinically relevant pharmacogenetic variants in these genes is yet to be established, especially across African populations. This study therefore aimed to characterize the star allele (haplotype) distribution in CYP2B6 and CYP2A6 across diverse and understudied sub‐Saharan African (SSA) populations. We called star alleles from 961 high‐depth full genomes using StellarPGx, Aldy, and PyPGx. In addition, we performed CYP2B6 and CYP2A6 star allele frequency comparisons between SSA and other global biogeographical groups represented in the new 1000 Genomes Project high‐coverage dataset (n = 2,000). This study presents frequency information for star alleles in CYP2B6 (e.g., *6 and *18; frequency of 21–47% and 2–19%, respectively) and CYP2A6 (e.g., *4, *9, and *17; frequency of 0–6%, 3–10%, and 6–20%, respectively), and predicted phenotypes (for CYP2B6), across various African populations. In addition, 50 potentially novel African‐ancestry star alleles were computationally predicted by StellarPGx in CYP2B6 and CYP2A6 combined. For each of these genes, over 4% of the study participants had predicted novel star alleles. Three novel star alleles in CYP2A6 (*54, *55, and *56) and CYP2B6 apiece, and several suballeles were further validated via targeted Single‐Molecule Real‐Time resequencing. Our findings are important for informing the design of comprehensive pharmacogenetic testing platforms, and are highly relevant for personalized medicine strategies, especially relating to antiretroviral medication and smoking cessation treatment in Africa and the African diaspora. More broadly, this study highlights the importance of sampling diverse African ethnolinguistic groups for accurate characterization of the pharmacogene variation landscape across the continent. [ABSTRACT FROM AUTHOR]

Background: Poor medication adherence is a major barrier to HIV control among youth living with HIV (Y-PLWH). The PEERNaija application (app) is an adapted smartphone app grounded in social cognitive and contigency management theories and designed to harness peer-based social incentives and conditional financial incentives to promote medication adherence. The app delivers a multifaceted medication adherence intervention including (1) peer-based social incentives, (2) financial incentives, (3) virtual peer social support, and (4) early clinic-based outreach for non-adherent Y-PLWH. A pilot trial of the app will be conducted in Nigeria, Africa's most populous country with the 4th largest HIV epidemic, and home to 10% of the world's four million Y-PLWH. Methods: In this randomized controlled trial, we will compare implementation outcomes (feasibility, acceptability, appropriateness measured via validated scales, enrollment and application installation rates, feedback surveys and focus group discussions with participants, and back-end application data), and preliminary efficacy (in improving medication adherence and viral suppression) of the PEERNaija app at 6 months. Participants in Arm 1 (PEERNaija) will receive daily medication reminders, peer-based social incentives, and virtual peer social support. Participants in Arm 2 (PEERNaija +) will additionally receive a conditional financial incentive based on their adherence performance. Eligibility for Y-PLWH includes (1) being aged 14–29 years, (2) being on ART, (3) owning a smartphone, (4) being willing to download an app, and (5) being able to read simple text in English. Discussion: This study will serve as the basis for a larger intervention trial evaluating the PEERNaija app (and the integration of mHealth, incentive, and peer-support-based strategies) to improve HIV outcomes in a critically important region of the world for Y-PLWH. Trial registration: ClinicalTrials.gov. NCT04930198. First submitted date: May 25, 2021. Study start: August 1, 2021, https://clinicaltrials.gov/. Protocol version: January 21, 2022. [ABSTRACT FROM AUTHOR]

Cytochrome P450 2D6 (CYP2D6) is a key enzyme in drug response owing to its involvement in the metabolism of ~ 25% of clinically prescribed medications. The encoding CYP2D6 gene is highly polymorphic, and many pharmacogenetics studies have been performed worldwide to investigate the distribution of CYP2D6 star alleles (haplotypes); however, African populations have been relatively understudied to date. In this study, the distributions of CYP2D6 star alleles and predicted drug metabolizer phenotypes—derived from activity scores—were examined across multiple sub‐Saharan African populations based on bioinformatics analysis of 961 high‐depth whole genome sequences. This was followed by characterization of novel star alleles and suballeles in a subset of the participants via targeted high‐fidelity Single‐Molecule Real‐Time resequencing (Pacific Biosciences). This study revealed varying frequencies of known CYP2D6 alleles and predicted phenotypes across different African ethnolinguistic groups. Twenty‐seven novel CYP2D6 star alleles were predicted computationally and two of them were further validated. This study highlights the importance of studying variation in key pharmacogenes such as CYP2D6 in the African context to better understand population‐specific allele frequencies. This will aid in the development of better genotyping panels and star allele detection approaches with a view toward supporting effective implementation of precision medicine strategies in Africa and across the African diaspora. [ABSTRACT FROM AUTHOR]

Equatorial East Africa (EEA) suffers from significant flood risks. These can be mitigated with preemptive action; however, currently available early warnings are limited to a few days' lead time. Extending warnings using subseasonal climate forecasts could open a window for more extensive preparedness activity. However, before these forecasts can be used, the basis of their skill and relevance for flood risk must be established. Here we demonstrate that subseasonal forecasts are particularly skillful over EEA. Forecasts can skillfully anticipate weekly upper-quintile rainfall within a season, at lead times of 2 weeks and beyond. We demonstrate the link between the Madden–Julian oscillation (MJO) and extreme rainfall events in the region, and confirm that leading forecast models accurately represent the EEA teleconnection to the MJO. The relevance of weekly rainfall totals for fluvial flood risk in the region is investigated using a long record of streamflow from the Nzoia River in western Kenya. Both heavy rainfall and high antecedent rainfall conditions are identified as key drivers of flood risk, with upper-quintile weekly rainfall shown to skillfully discriminate flood events. We additionally evaluate GloFAS global flood forecasts for the Nzoia basin. Though these are able to anticipate some flooding events with several weeks lead time, analysis suggests action based on these would result in a false alarm more than 50% of the time. Overall, these results build on the scientific evidence base that supports the use of subseasonal forecasts in EEA, and activities to advance their use are discussed. [ABSTRACT FROM AUTHOR]

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Copyright of Tropical Medicine & International Health is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Future projections of precipitation at regional scales are vital to inform climate change adaptation activities. Therefore, is it important to quantify projected changes and associated uncertainty, and understand model processes responsible. This paper addresses these challenges for southern Africa and the adjacent Indian Ocean focusing on the local wet season. Precipitation projections for the end of the twenty-first century indicate a pronounced dipole pattern in the CMIP5 multimodel mean. The dipole indicates future wetting (drying) to the north (south) of the climatological axis of maximum rainfall, implying a northward shift of the ITCZ and south Indian Ocean convergence zone that is not consistent with a simple "wet get wetter" pattern. This pattern is most pronounced in early austral summer, suggesting a later and shorter wet season over much of southern Africa. Using a decomposition method we determine physical mechanisms underlying this dipole pattern of projected change, and the associated intermodel uncertainty. The projected dipole pattern is largely associated with the dynamical component of change indicative of shifts in the location of convection. Over the Indian Ocean, this apparent northward shift in the ITCZ may reflect the response to changes in the north-south SST gradient over the Indian Ocean, consistent with a "warmest get wetter" mechanism. Over land subtropical drying is relatively robust, particularly in the early wet season. This has contributions from dynamical shifts in the location of convection, which may be related to regional SST structures in the southern Indian Ocean, and the thermodynamic decline in relative humidity. Implications for understanding and potentially constraining uncertainty in projections are discussed. [ABSTRACT FROM AUTHOR]

Background: Malaria control is heavily reliant on insecticides, especially pyrethroids. Resistance of mosquitoes to insecticides may threaten the effectiveness of insecticide-based vector control and lead to a resurgence of malaria in Africa. Methods: In 21 villages in Southern Benin with high levels of insecticide resistance, the resistance status of local vectors was measured at the same time as the prevalence of malaria infection in resident children. Results: Children who used LLINs had lower levels of malaria infection [odds ratio = 0.76 (95% CI 0.59, 0.98, p = 0.033)]. There was no evidence that the effectiveness of nets was different in high and low resistance locations (p = 0.513). There was no association between village level resistance and village level malaria prevalence (p = 0.999). Conclusions: LLINs continue to offer individual protection against malaria infection in an area of high resistance. Insecticide resistance is not a reason to stop efforts to increase coverage of LLINs in Africa. [ABSTRACT FROM AUTHOR]

Introduction: Investigating variation in genes involved in the absorption, distribution, metabolism, and excretion (ADME) of drugs are key to characterizing pharmacogenomic (PGx) relationships. ADME gene variation is relatively well characterized in European and Asian populations, but data from African populations are under-studied—which has implications for drug safety and effective use in Africa. Results: We identified significant ADME gene variation in African populations using data from 458 high-coverage whole genome sequences, 412 of which are novel, and from previously available African sequences from the 1,000 Genomes Project. ADME variation was not uniform across African populations, particularly within high impact coding variation. Copy number variation was detected in 116 ADME genes, with equal ratios of duplications/deletions. We identified 930 potential high impact coding variants, of which most are discrete to a single African population cluster. Large frequency differences (i.e., >10%) were seen in common high impact variants between clusters. Several novel variants are predicted to have a significant impact on protein structure, but additional functional work is needed to confirm the outcome of these for PGx use. Most variants of known clinical outcome are rare in Africa compared to European populations, potentially reflecting a clinical PGx research bias to European populations. Discussion: The genetic diversity of ADME genes across sub-Saharan African populations is large. The Southern African population cluster is most distinct from that of far West Africa. PGx strategies based on European variants will be of limited use in African populations. Although established variants are important, PGx must take into account the full range of African variation. This work urges further characterization of variants in African populations including in vitro and in silico studies, and to consider the unique African ADME landscape when developing precision medicine guidelines and tools for African populations. [ABSTRACT FROM AUTHOR]

Background: Insecticide-based interventions have averted more than 500 million malaria cases since 2000, but insecticide resistance in mosquitoes could bring about a rebound in disease and mortality. This study investigated whether insecticide resistance was associated with increased incidence of clinical malaria. Methods: In an area of southern Benin with insecticide resistance and high use of insecticide-treated nets (ITNs), malaria morbidity and insecticide resistance were measured simultaneously in 30 clusters (villages or collections of villages) multiple times over the course of 2 years. Insecticide resistance frequencies were measured using the standard World Health Organization bioassay test. Malaria morbidity was measured by cases recorded at health facilities both in the whole population using routinely collected data and in a passively followed cohort of children under 5 years old. Results: There was no evidence that incidence of malaria from routinely collected data was higher in clusters with resistance frequencies above the median, either in children aged under 5 (RR = 1.27 (95% CI 0.81–2.00) p = 0.276) or in individuals aged 5 or over (RR = 1.74 (95% CI 0.91–3.34) p = 0.093). There was also no evidence that incidence was higher in clusters with resistance frequencies above the median in the passively followed cohort (RR = 1.11 (0.52–2.35) p = 0.777). Conclusions: This study found no association between frequency of resistance and incidence of clinical malaria in an area where ITNs are the principal form of vector control. This may be because, as other studies have shown, ITNs continue to offer some protection from malaria even in the presence of insecticide resistance. Irrespective of resistance, nets provide only partial protection so the development of improved or supplementary vector control tools is required to reduce Africa's unacceptably high malaria burden. [ABSTRACT FROM AUTHOR]

Objectives: To explore communities' perceptions about COVID-19 in the context of the ANRS COV33 Coverage-Africa clinical trial evaluating the efficacy of treatments in preventing clinical worsening of COVID-19., Design: Descriptive qualitative study using semistructured in-depth individual interviews conducted by telephone in French and Soussou between May and September 2021. Data were transcribed, translated in French when applicable and analysed with the thematic analysis method., Setting: The eight neighbourhoods most affected by COVID-19 in Conakry's urban context, capital of Guinea., Participants: 4 community leaders acting as key informants-providing insights regarding population's opinions-and six community members, who were exposed to an information session conducted as part of Coverage-Africa., Results: According to participants, community members have heterogeneous viewpoints about COVID-19: it exists and is dangerous; it is benign ('bad cold'); or it is fictitious (eg, government conspiracy). The fear of stigmatisation and social isolation of those sick or cured of COVID-19 was largely reported by participants, with illustrations of distressing situations for the victims. To avoid stigma, many patients seem to adopt strategies of discretion (eg, lying/hiding about the disease). Although community attitudes were reported to have evolved since the beginning of the epidemic, stigma remained a pervasive concern for many people., Conclusions: Community perceptions about COVID-19 in Conakry may be partly explained by the Guinean context of Ebola history and of sociopolitical tensions. Stigmatisation of COVID+ people seems to be aimed at protecting others against contamination. However, social avoidance can greatly affect the morale of stigmatised people, especially in collectivist cultures like Guinea. Further investigating stigma, including its role on seeking COVID-19 screening and treatment services, and its consequences on mental health among affected/exposed people, would contribute to identifying improved prevention and care interventions in preparation for future health threats, and to promoting participation in health research., Trial Registration Number: NCT04920838 (Pre-results stage)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

To meet the 1.5 °C target, methane (CH4) from ruminants must be reduced by 11 to 30% by 2030 and 24 to 47% by 2050 compared to 2010 levels. A meta-analysis identified strategies to decrease product-based (PB; CH4 per unit meat or milk) and absolute (ABS) enteric CH4 emissions while maintaining or increasing animal productivity (AP; weight gain or milk yield). Next, the potential of different adoption rates of one PB or one ABS strategy to contribute to the 1.5 °C target was estimated. The database included findings from 430 peer-reviewed studies, which reported 98 mitigation strategies that can be classified into three categories: animal and feed management, diet formulation, and rumen manipulation. A random-effects meta-analysis weighted by inverse variance was carried out. Three PB strategies—namely, increasing feeding level, decreasing grass maturity, and decreasing dietary forage-to-concentrate ratio—decreased CH4 per unit meat or milk by on average 12% and increased AP by a median of 17%. Five ABS strategies—namely CH4 inhibitors, tanniferous forages, electron sinks, oils and fats, and oilseeds—decreased daily methane by on average 21%. Globally, only 100% adoption of the most effective PB and ABS strategies can meet the 1.5 °C target by 2030 but not 2050, because mitigation effects are offset by projected increases in CH4 due to increasing milk and meat demand. Notably, by 2030 and 2050, low- and middle-income countries may not meet their contribution to the 1.5 °C target for this same reason, whereas high-income countries could meet their contributions due to only a minor projected increase in enteric CH4 emissions.

Introduction: Low/middle-income countries (LMICs) have a growing need for trauma and orthopaedic (T&O) surgical interventions but lack surgical resources. Part of this is due to the high amount of road traffic accidents in LMICs. We aimed to develop recommendations for an essential list of equipment for three different levels of care providers., Methods: The Delphi method was used to achieve consensus on essential and desirable T&O equipment for LMICs. Twenty experts with T&O experience from LMICs underwent two rounds of questionnaires. Feedback was given after each round of questionnaires. The first round of questionnaire consisted of 45 items graded on a Likert scale with the second round consisting of 50 items. We used an electronic questionnaire to collect our data for three different levels of care: non-operative-based provider, specialist provider with operative fracture care and tertiary provider with operative fracture care and orthopaedics., Results: After two rounds of questionnaires, recommendations for each level of care in LMICs included 4 essential equipment items for non-operative-based providers; 27 essential equipment items for specialist providers with operative fracture care and 46 essential equipment items for tertiary providers with operative fracture care and orthopaedic care., Conclusion: These recommendations can facilitate in planning of appropriate equipment required in an institution which in turn has the potential to improve the capacity and quality of T&O care in LMICs. The essential equipment lists provided here can help direct where funding for equipment should be targeted. Our recommendations can help with planning and organising national T&O care in LMICs to achieve appropriate capacity at all relevant levels of care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Neisseria meningitidis, together with the non-pathogenic Neisseria species (NPNs), are members of the complex microbiota of the human pharynx. This paper investigates the influence of NPNs on the epidemiology of meningococcal infection., Methods: Neisseria isolates were collected during 18 surveys conducted in six countries in the African meningitis belt between 2010 and 2012 and characterized at the rplF locus to determine species and at the variable region of the fetA antigen gene. Prevalence and risk factors for carriage were analyzed., Results: A total of 4694 isolates of Neisseria were obtained from 46,034 pharyngeal swabs, a carriage prevalence of 10.2% (95% CI, 9.8-10.5). Five Neisseria species were identified, the most prevalent NPN being Neisseria lactamica. Six hundred and thirty-six combinations of rplF/fetA_VR alleles were identified, each defined as a Neisseria strain type. There was an inverse relationship between carriage of N. meningitidis and of NPNs by age group, gender and season, whereas carriage of both N. meningitidis and NPNs was negatively associated with a recent history of meningococcal vaccination., Conclusion: Variations in the prevalence of NPNs by time, place and genetic type may contribute to the particular epidemiology of meningococcal disease in the African meningitis belt., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)