Feasibility, safety, efficacy and potential scaling-up of sofosbuvir-based HCV treatment in Central and West Africa: (TAC ANRS 12311 trial).

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.

Rodent control strategies and Lassa virus: some unexpected effects in Guinea, West Africa.

The Natal multimammate mouse (Mastomys natalensis) is the host of Lassa mammarenavirus, causing Lassa haemorrhagic fever in West Africa. As there is currently no operational vaccine and therapeutic drugs are limited, we explored rodent control as an alternative to prevent Lassa virus spillover in Upper Guinea, where the disease is highly endemic in rural areas. In a seven-year experiment, we distributed rodenticides for 10-30 days once a year and, in the last year, added intensive snap trapping for three months in all the houses of one village. We also captured rodents both before and after the intervention period to assess their effectiveness by examining alterations in trapping success and infection rates (Lassa virus RNA and IgG antibodies). We found that both interventions reduced the rodent population by 74-92% but swiftly rebounded to pre-treatment levels, even already six months after the last snap-trapping control. Furthermore, while we observed that chemical control modestly decreased Lassa virus infection rates annually (a reduction of 5% in seroprevalence per year), the intensive trapping unexpectedly led to a significantly higher infection rate (from a seroprevalence of 28% before to 67% after snap trapping control). After seven years, we conclude that annual chemical control, alone or with intensive trapping, is ineffective and sometimes counterproductive in preventing Lassa virus spillover in rural villages. These unexpected findings may result from density-dependent breeding compensation following culling and the survival of a small percentage of chronically infected rodents that may spread the virus to a new susceptible generation of mice.

The dawn of the tropical Atlantic invasion into the Mediterranean Sea.

The Mediterranean Sea is a marine biodiversity hotspot already affected by climate-driven biodiversity collapses. Its highly endemic fauna is at further risk if global warming triggers an invasion of tropical Atlantic species. Here, we combine modern species occurrences with a unique paleorecord from the Last Interglacial (135 to 116 ka), a conservative analog of future climate, to model the future distribution of an exemplary subset of tropical West African mollusks, currently separated from the Mediterranean by cold upwelling off north-west Africa. We show that, already under an intermediate climate scenario (RCP 4.5) by 2050, climatic connectivity along north-west Africa may allow tropical species to colonize a by then largely environmentally suitable Mediterranean. The worst-case scenario RCP 8.5 leads to a fully tropicalized Mediterranean by 2100. The tropical Atlantic invasion will add to the ongoing Indo-Pacific invasion through the Suez Canal, irreversibly transforming the entire Mediterranean into a novel ecosystem unprecedented in human history.

Evaluation of analytical performance of the STANDARDTM M10 MPX/OPX assay for the simultaneous DNA detection and clade attribution of Monkeypox virus.

Monkeypox virus (MPXV) infection confirmation needs reliable polymerase chain reaction (PCR) assays; in addition, viral clade attribution is a key factor in containment measures, considering a more severe syndrome in clade I and the possibility of simultaneous circulation. This study evaluates the performance of all-in-one STANDARD M10 MPX/OPX (SD BIOSENSOR, South Korea - M10). Frozen samples from 205 subjects were selected and stratified according to routine test results (RealStar® Orthopoxvirus PCR Kit 1.0, Altona DIAGNOTICS, Germany - RS; RS-1): in detail, 100 negative skin lesions (SL) and 200 positive samples at the variable stage of infection were analysed. Positive samples were retested with RS (RS-2). Positive and Negative Percent Agreements (PPA, NPA) were calculated. The median (IQR) Ct values of RS and M10 (OPXV target) assays were highly similar. The PPA of M10 compared to RS-1 was 89.5% considering system interpretation, and 96.0% when the operator classified results as positive if any target was detected; NPA was 100%. Comparing the RS-2 run and M10, an overall concordance of 95.3% between assays was found; however, considering operator interpretation, M10 returned more positive results than RS-2. The occurrence of False-Negative results was likely associated with the influence of thawing on low viral concentration; no False-Positive tests were observed. All samples collected at the time of Mpox diagnosis were positive and M10 correctly attributed the clade (West-Africa/II). The M10 MPX/OPX assay demonstrated high reliability in confirming MPXV infection and clade attribution.

Threat of mining to African great apes.

The rapid growth of clean energy technologies is driving a rising demand for critical minerals. In 2022 at the 15th Conference of the Parties to the Convention on Biological Diversity (COP15), seven major economies formed an alliance to enhance the sustainability of mining these essential decarbonization minerals. However, there is a scarcity of studies assessing the threat of mining to global biodiversity. By integrating a global mining dataset with great ape density distribution, we estimated the number of African great apes that spatially coincided with industrial mining projects. We show that up to one-third of Africa's great ape population faces mining-related risks. In West Africa in particular, numerous mining areas overlap with fragmented ape habitats, often in high-density ape regions. For 97% of mining areas, no ape survey data are available, underscoring the importance of increased accessibility to environmental data within the mining sector to facilitate research into the complex interactions between mining, climate, biodiversity, and sustainability.

Sequencing and Analysis of Lumpy Skin Disease Virus Whole Genomes Reveals a New Viral Subgroup in West and Central Africa.

Lumpy skin disease virus (LSDV) is a member of the capripoxvirus (CPPV) genus of the Poxviridae family. LSDV is a rapidly emerging, high-consequence pathogen of cattle, recently spreading from Africa and the Middle East into Europe and Asia. We have sequenced the whole genome of historical LSDV isolates from the Pirbright Institute virus archive, and field isolates from recent disease outbreaks in Sri Lanka, Mongolia, Nigeria and Ethiopia. These genome sequences were compared to published genomes and classified into different subgroups. Two subgroups contained vaccine or vaccine-like samples ("Neethling-like" clade 1.1 and "Kenya-like" subgroup, clade 1.2.2). One subgroup was associated with outbreaks of LSD in the Middle East/Europe (clade 1.2.1) and a previously unreported subgroup originated from cases of LSD in west and central Africa (clade 1.2.3). Isolates were also identified that contained a mix of genes from both wildtype and vaccine samples (vaccine-like recombinants, grouped in clade 2). Whole genome sequencing and analysis of LSDV strains isolated from different regions of Africa, Europe and Asia have provided new knowledge of the drivers of LSDV emergence, and will inform future disease control strategies.

The Anopheles coluzzii range extends into Kenya: detection, insecticide resistance profiles and population genetic structure in relation to conspecific populations in West and Central Africa.

BACKGROUND: Anopheles coluzzii is a primary vector of malaria found in West and Central Africa, but its presence has hitherto never been documented in Kenya. A thorough understanding of vector bionomics is important as it enables the implementation of targeted and effective vector control interventions. Malaria vector surveillance efforts in the country have tended to focus on historically known primary vectors. The current study sought to determine the taxonomic status of samples collected from five different malaria epidemiological zones in Kenya as well as describe the population genetic structure and insecticide resistance profiles in relation to other An. coluzzii populations. METHODS: Mosquitoes were sampled as larvae from Busia, Kwale, Turkana, Kirinyaga and Kiambu counties, representing the range of malaria endemicities in Kenya, in 2019 and 2021 and emergent adults analysed using Whole Genome Sequencing (WGS) data processed in accordance with the Anopheles gambiae 1000 Genomes Project phase 3. Where available, historical samples from the same sites were included for WGS. Comparisons were made with An. coluzzii cohorts from West and Central Africa. RESULTS: This study reports the detection of An. coluzzii for the first time in Kenya. The species was detected in Turkana County across all three time points from which samples were analyzed and its presence confirmed through taxonomic analysis. Additionally, there was a lack of strong population genetic differentiation between An. coluzzii from Kenya and those from the more northerly regions of West and Central Africa, suggesting they represent a connected extension to the known species range. Mutations associated with target-site resistance to DDT and pyrethroids and metabolic resistance to DDT were found at high frequencies up to 64%. The profile and frequencies of the variants observed were similar to An. coluzzii from West and Central Africa but the ace-1 mutation linked to organophosphate and carbamate resistance present in An. coluzzii from coastal West Africa was absent in Kenya. CONCLUSIONS: These findings emphasize the need for the incorporation of genomics in comprehensive and routine vector surveillance to inform on the range of malaria vector species, and their insecticide resistance status to inform the choice of effective vector control approaches.

Rapid detection of monkeypox virus and differentiation of West African and Congo Basin strains using endonuclease restriction-mediated real-time PCR-based testing.

The ongoing multi-country outbreak of monkeypox virus (MPXV) has continuously attracted global attention, highlighting the critical need for timely and accurate methods to detect MPXV and differentiate its clades. Herein, we devised a novel multiplex ET-PCR (endonuclease restriction-mediated real-time PCR) assay that integrates PCR amplification, restriction endonuclease cleavage and real-time fluorescence detection to diagnose MPXV infection and distinguish the Congo Basin and West African MPXV strains. In the MPXV ET-PCR system, three sets of specific primers were designed for MPXV, Congo Basin and West African strains. A short sequence, which could be recognized by restriction endonuclease enzyme BstUI, was added to the 5'end of amplification primers. Then, the modified primers were assigned different reporter dyes and corresponding quenching dyes to each of the three targets, enabling real-time fluorescence reporting of the results and multiplex detection. The designed assay enabled the detection of single or three targets in a single tube, with excellent specificity and analytical sensitivity in terms of plasmid and pseudotyped virus. Moreover, the clinical feasibility of our assay was validated using artificially simulated plasma, nasopharyngeal swab and skin swab samples. In conclusion, the multiplex ET-PCR assay devised here had the advantages of simple primer design, cost-effectiveness, low contamination risk, excellent sensitivity, high specificity and multiplex detection, making it a valuable and dependable tool for curbing the extensive spread of MPXV.

FSC-certified forest management benefits large mammals compared to non-FSC.

More than a quarter of the world's tropical forests are exploited for timber1. Logging impacts biodiversity in these ecosystems, primarily through the creation of forest roads that facilitate hunting for wildlife over extensive areas. Forest management certification schemes such as the Forest Stewardship Council (FSC) are expected to mitigate impacts on biodiversity, but so far very little is known about the effectiveness of FSC certification because of research design challenges, predominantly limited sample sizes2,3. Here we provide this evidence by using 1.3 million camera-trap photos of 55 mammal species in 14 logging concessions in western equatorial Africa. We observed higher mammal encounter rates in FSC-certified than in non-FSC logging concessions. The effect was most pronounced for species weighing more than 10 kg and for species of high conservation priority such as the critically endangered forest elephant and western lowland gorilla. Across the whole mammal community, non-FSC concessions contained proportionally more rodents and other small species than did FSC-certified concessions. The first priority for species protection should be to maintain unlogged forests with effective law enforcement, but for logged forests our findings provide convincing data that FSC-certified forest management is less damaging to the mammal community than is non-FSC forest management. This study provides strong evidence that FSC-certified forest management or equivalently stringent requirements and controlling mechanisms should become the norm for timber extraction to avoid half-empty forests dominated by rodents and other small species.

Application of advanced very high-resolution radiometer (AVHRR)-based vegetation health indices for modelling and predicting malaria in Northern Benin, West Africa.

BACKGROUND: Vegetation health (VH) is a powerful characteristic for forecasting malaria incidence in regions where the disease is prevalent. This study aims to determine how vegetation health affects the prevalence of malaria and create seasonal weather forecasts using NOAA/AVHRR environmental satellite data that can be substituted for malaria epidemic forecasts. METHODS: Weekly advanced very high-resolution radiometer (AVHRR) data were retrieved from the NOAA satellite website from 2009 to 2021. The monthly number of malaria cases was collected from the Ministry of Health of Benin from 2009 to 2021 and matched with AVHRR data. Pearson correlation was calculated to investigate the impact of vegetation health on malaria transmission. Ordinary least squares (OLS), support vector machine (SVM) and principal component regression (PCR) were applied to forecast the monthly number of cases of malaria in Northern Benin. A random sample of proposed models was used to assess accuracy and bias. RESULTS: Estimates place the annual percentage rise in malaria cases at 9.07% over 2009-2021 period. Moisture (VCI) for weeks 19-21 predicts 75% of the number of malaria cases in the month of the start of high mosquito activities. Soil temperature (TCI) and vegetation health index (VHI) predicted one month earlier than the start of mosquito activities through transmission, 78% of monthly malaria incidence. CONCLUSIONS: SVM model D is more effective than OLS model A in the prediction of malaria incidence in Northern Benin. These models are a very useful tool for stakeholders looking to lessen the impact of malaria in Benin.

Cardiac Amyloidosis Due to Transthyretin Protein: A Review.

Importance: Systemic amyloidosis from transthyretin (ATTR) protein is the most common type of amyloidosis that causes cardiomyopathy. Observations: Transthyretin (TTR) protein transports thyroxine (thyroid hormone) and retinol (vitamin A) and is synthesized predominantly by the liver. When the TTR protein misfolds, it can form amyloid fibrils that deposit in the heart causing heart failure, heart conduction block, or arrhythmia such as atrial fibrillation. The biological processes by which amyloid fibrils form are incompletely understood but are associated with aging and, in some patients, affected by inherited variants in the TTR genetic sequence. ATTR amyloidosis results from misfolded TTR protein deposition. ATTR can occur in association with normal TTR genetic sequence (wild-type ATTR) or with abnormal TTR genetic sequence (variant ATTR). Wild-type ATTR primarily manifests as cardiomyopathy while ATTR due to a genetic variant manifests as cardiomyopathy and/or polyneuropathy. Approximately 50 000 to 150 000 people in the US have heart failure due to ATTR amyloidosis. Without treatment, heart failure due to ATTR amyloidosis is associated with a median survival of approximately 5 years. More than 130 different inherited genetic variants in TTR exist. The most common genetic variant is Val122Ile (pV142I), an allele with an origin in West African countries, that is present in 3.4% of African American individuals in the US or approximately 1.5 million persons. The diagnosis can be made using serum free light chain assay and immunofixation electrophoresis to exclude light chain amyloidosis combined with cardiac nuclear scintigraphy to detect radiotracer uptake in a pattern consistent with amyloidosis. Loop diuretics, such as furosemide, torsemide, and bumetanide, are the primary treatment for fluid overload and symptomatic relief of patients with ATTR heart failure. An ATTR-directed therapy that inhibited misfolding of the TTR protein (tafamidis, a protein stabilizer), compared with placebo, reduced mortality from 42.9% to 29.5%, reduced hospitalizations from 0.7/year to 0.48/year, and was most effective when administered early in disease course. Conclusions and Relevance: ATTR amyloidosis causes cardiomyopathy in up to approximately 150 000 people in the US and tafamidis is the only currently approved therapy. Tafamidis slowed progression of ATTR amyloidosis and improved survival and prevented hospitalization, compared with placebo, in people with ATTR-associated cardiomyopathy.

'It's about time': policymakers' and health practitioners' perspectives on implementing fertility care in the Gambian health system.

BACKGROUND: Infertility is a major health issue worldwide, yet very few examples of interventions addressing infertility in the Global South have been documented to date. In The Gambia, West Africa, infertility is recognised as a burden and the health authorities have included it in several health policies and the new National Reproductive Health Strategy however, a detailed operationalisation plan for fertility care has not yet been established. Here, we aim to understand and document the factors that influence the implementation of fertility care in The Gambia. METHODS: We conducted 46 semi-structured interviews with policymakers, implementers, and health practitioners in both the public and private sectors from July to November 2021. The interviews were transcribed, anonymised and analysed with NVivo Pro version 1.6.1. The analysis was initially inductive, with themes arising from the coding categorised according to the WHO health systems building blocks framework. RESULTS: This study identified several barriers to a successful implementation of fertility care in The Gambia, including (i) a lack of routinely collected infertility data; (ii) an absence of financial protection mechanisms for patients, and/or a specific budget for infertility; (iii) limited cooperation between the public and private sectors in the provision of fertility care; and (iv) gaps in fertility care training among health practitioners. Conversely, enablers included: (i) strong national infertility leadership; and (ii) the integration of infertility care within public reproductive health services. CONCLUSION: The Gambian health system is not yet in the position to support a comprehensive fertility care package in its public health facilities. Several aspects of the implementation of fertility care must be considered in operationalising the health strategy including the systematic collection of infertility data, fertility awareness, and the provision of specialised fertility care training. Furthermore, a stronger partnership between the public and private sectors must be developed. Given the increasing availability of assisted reproductive technologies in the sub-Saharan Africa region, and the tendency to locate these technologies in the private sector, further research is needed to understand and identify the processes underlying the implementation of fertility care and to foster better integration with the existing health system.

The socioecological benefits and consequences of oil palm cultivation in its native range: The Sustainable Oil Palm in West Africa (SOPWA) Project.

Agriculture is expanding rapidly across the tropics. While cultivation can boost socioeconomic conditions and food security, it also threatens native ecosystems. Oil palm (Elaeis guineensis), which is grown pantropically, is the most productive vegetable oil crop worldwide. The impacts of oil palm cultivation have been studied extensively in Southeast Asia and - to a lesser extent - in Latin America but, in comparison, very little is known about its impacts in Africa: oil palm's native range, and where cultivation is expanding rapidly. In this paper, we introduce a large-scale research programme - the Sustainable Oil Palm in West Africa (SOPWA) Project - that is evaluating the relative ecological impacts of oil palm cultivation under traditional (i.e., by local people) and industrial (i.e., by a large-scale corporation) management in Liberia. Our paper is twofold in focus. First, we use systematic mapping to appraise the literature on oil palm research in an African context, assessing the geographic and disciplinary focus of existing research. We found 757 publications occurring in 36 African countries. Studies tended to focus on the impacts of palm oil consumption on human health and wellbeing. We found no research that has evaluated the whole-ecosystem (i.e., multiple taxa and ecosystem functions) impacts of oil palm cultivation in Africa, a knowledge gap which the SOPWA Project directly addresses. Second, we describe the SOPWA Project's study design and-using canopy cover, ground vegetation cover, and soil temperature data as a case study-demonstrate its utility for assessing differences between areas of rainforest and oil palm agriculture. We outline the socioecological data collected by the SOPWA Project to date and describe the potential for future research, to encourage new collaborations and additional similar projects of its kind in West Africa. Increased research in Africa is needed urgently to understand the combined ecological and sociocultural impacts of oil palm and other agriculture in this unique region. This will help to ensure long-term sustainability of the oil palm industry-and, indeed, all tropical agricultural activity-in Africa.

Stop, in the Name of COVID! Using Social Media Data to Estimate the Effects of COVID-19-Related Travel Restrictions on Migration.

In the wake of the COVID-19 pandemic, the International Organization for Migration has postulated that international migrant stocks fell short of their pre-pandemic projections by nearly 2 million as a result of travel restrictions. However, this decline is not testable with migration data from traditional sources. Key migration stakeholders have called for using data from alternative sources, including social media, to fill these gaps. Building on previous work using social media data to analyze migration responses to external shocks, we test the hypothesis that COVID-related travel restrictions reduced migrant stock relative to expected migration without such restrictions using estimates of migrants drawn from Facebook's advertising platform and dynamic panel models. We focus on four key origin countries in North and West Africa (Côte d'Ivoire, Algeria, Morocco, and Senegal) and on their 23 key destination countries. Between February and June 2020, we estimate that a destination country implementing a month-long total entry ban on arrivals from Côte d'Ivoire, Algeria, Morocco, or Senegal might have expected a 3.39% reduction in migrant stock from the restricted country compared with the counterfactual in which no travel restrictions were implemented. However, when broader societal disruptions of the pandemic are accounted for, we estimate that countries implementing travel restrictions might paradoxically have expected an increase in migrant stock. In this context, travel restrictions do not appear to have effectively curbed migration and could have resulted in outcomes opposite their intended effects.

Differentiation of Bulinus senegalensis and Bulinus forskalii Snails in West Africa Using Morphometric Analysis.

PURPOSE: Accurate identification of medically important intermediate host and vector species is crucial for understanding disease transmission and control. Identifying Bulinus snails which act as intermediate host species for the transmission of schistosomiasis is typically undertaken using conchological and genital morphology as well as molecular methods. METHODS: Here, a landmark-based morphometric analysis of shell morphology was undertaken to determine its utility to distinguish the closely related and morphologically similar sister species Bulinus senegalensis and Bulinus forskalii. The method was developed to increase the accuracy of conchological morphology methods to identify Bulinus species in the field. Both species are found in West Africa, but only B. senegalensis is implicated in the transmission of urogenital schistosomiasis. RESULTS: We found when scaled down to the same length, 3-whorl and 4-whorl (juvenile) B. senegalensis shells had a longer spire, narrower body whorl and shorter aperture than B. forskalii. In contrast, 5-whorl (adult) B. senegalensis had a shorter spire, but still had a shorter aperture and narrower body whorl than B. forskalii. Canonical Variate Analysis (CVA) showed minimal overlap between B. senegalensis and B. forskalii for 3-whorl and 4-whorl shells, with a clear separation for 5-whorl shells. Overall, B. senegalensis had a consistently shorter aperture size and narrower body whorl than B. forskalii for all development stages. Spire length was variable depending on the stage of development, with 3-whorl and 4-whorl shells having the opposite trends of adult shells. CONCLUSIONS: Our study demonstrates the applicability of landmark-based morphometrics in distinguishing the medically important, Bulinus senegalensis from its morphologically similar sister species, Bulinus forskalii. We recommend using measurements based on spire length, penultimate whorl length, body whorl width and aperture size to differentiate B. senegalensis and B. forskalii, when used with the appropriate information for each shell's development stage.

Two new Later Stone Age sites from the Final Pleistocene in the Falémé Valley, eastern Senegal.

The understanding of cultural dynamics at work at the end of the Final Pleistocene in West Africa suffers from a significant lack of excavated and dated sites, particularly in the Sahelian and Sudanian ecozones. While the Later Stone Age shows varied behavioral developments in different parts of the continent, the chrono-cultural framework of this period remains largely unknown in West Africa. We report on archaeological, geomorphological, and chronological research on two Final Pleistocene Later Stone Age sites in the Falémé Valley, eastern Senegal. Optically stimulated luminescence ages place the site of Toumboura I-2017 between 17 ± 1 and 16 ± 1 ka and the Ravin de Sansandé site between 13 ± 1 ka and 12 ± 1.1 ka. The excavated lithics show typical Later Stone Age industries, characterized by chaînes opératoires of core reduction mainly producing flakes and bladelets as well as blades and laminar flakes. Segments dominate the toolkits but a few backed bladelets and end-scrapers on flake blanks were recognized. Local raw materials were used, with a preference for chert and quartz, as well as greywacke. These Later Stone Age lithic assemblages are the oldest known in Senegal so far and add to the small number of sites known in West Africa for this period, which are mainly located farther south, in sub-tropical ecozones. The Later Stone Age sites of the Falémé Valley are contemporaneous with typical Middle Stone Age technologies in Senegal dated to at least the Pleistocene/Holocene transition. Our results thus provide new archaeological evidence highlighting the complex cultural processes at work during the Final Pleistocene in West Africa.

Genomic characterization of SARS-CoV-2 in Guinea, West Africa.

SARS-CoV-2 has claimed several million lives since its emergence in late 2019. The ongoing evolution of the virus has resulted in the periodic emergence of new viral variants with distinct fitness advantages, including enhanced transmission and immune escape. While several SARS-CoV-2 variants of concern trace their origins back to the African continent-including Beta, Eta, and Omicron-most countries in Africa remain under-sampled in global genomic surveillance efforts. In an effort to begin filling these knowledge gaps, we conducted retrospective viral genomic surveillance in Guinea from October 2020 to August 2021. We found that SARS-CoV-2 clades 20A, 20B, and 20C dominated throughout 2020 until the coincident emergence of the Alpha and Eta variants of concern in January 2021. The Alpha variant remained dominant throughout early 2021 until the arrival of the Delta variant in July. Surprisingly, despite the small sample size of our study, we also found the persistence of the early SARS-CoV-2 clade 19B as late as April 2021. Together, these data help fill in our understanding of the SARS-CoV-2 population dynamics in West Africa early in the COVID-19 pandemic.

Prevalence of pretreatment HIV resistance to integrase inhibitors in West African and Southeast Asian countries.

OBJECTIVES: Integrase strand transfer inhibitors (INSTIs) have been recently recommended as the preferred first-line option for antiretroviral treatment initiators in low- and middle-income countries (LMICs) in response to the growing circulation of resistant HIV to non-nucleoside reverse transcriptase inhibitors (NNRTIs). In this study, we estimated the frequency of pretreatment drug resistance (PDR) to INSTIs in West Africa and Southeast Asia. MATERIALS AND METHODS: Using samples collected from 2015 to 2016, and previously used to assessed PI, NRTI and NNRTI resistance, we generated HIV integrase sequences and identified relevant INSTI PDR mutations using the Stanford and ANRS algorithms. RESULTS: We generated 353 integrase sequences. INSTI PDR frequency was low, 1.1% (4/353) overall, ranging from 0% to 6.3% according to country. However, frequency of PDR to any drug class was very high, 17.9% (95% CI: 13.9%-22.3%), and mostly associated with a high level of NNRTI PDR, 9.7%, and a moderate level of NRTI PDR, 5.3%. CONCLUSIONS: Our results support the recent introduction of INSTIs in LMICs to improve treatment outcome in these settings, but also stress the need for effective actions to prevent uncontrolled emergence of drug resistance to this drug class.

Evaluation of fendiline treatment in VP40 system with nucleation-elongation process: a computational model of Ebola virus matrix protein assembly.

Ebola virus (EBOV) infection is threatening human health, especially in Central and West Africa. Limited clinical trials and the requirement of biosafety level-4 laboratories hinder experimental work to advance our understanding of EBOV and the evaluation of treatment. In this work, we use a computational model to study the assembly and budding process of EBOV and evaluate the effect of fendiline on these processes in the context of fluctuating host membrane lipid levels. Our results demonstrate for the first time that the assembly of VP40 filaments may follow the nucleation-elongation theory, as this mechanism is critical to maintaining a pool of VP40 dimers for the maturation and production of virus-like particles (VLPs). We further find that this nucleation-elongation process is likely influenced by fluctuating phosphatidylserine (PS), which can complicate the efficacy of lipid-targeted therapies like fendiline, a drug that lowers cellular PS levels. Our results indicate that fendiline-induced PS reduction may actually increase VLP production at earlier time points (24 h) and under low fendiline concentrations (≤2 µM). However, this effect is transient and does not change the conclusion that fendiline generally decreases VLP production. In the context of fluctuating PS levels, we also conclude that fendiline can be more efficient at the late stage of VLP budding relative to earlier phases. Combination therapy with a VLP budding step-targeted drug may therefore further increase the treatment efficiency of fendiline. Finally, we also show that fendiline-induced PS reduction more effectively lowers VLP production when VP40 expression is high. Taken together, our results provide critical quantitative information on how fluctuating lipid levels (PS) affect EBOV assembly and egress and how this mechanism can be disrupted by lipid-targeting molecules like fendiline. IMPORTANCE: Ebola virus (EBOV) infection can cause deadly hemorrhagic fever, which has a mortality rate of ~50%-90% without treatment. The recent outbreaks in Uganda and the Democratic Republic of the Congo illustrate its threat to human health. Though two antibody-based treatments were approved, mortality rates in the last outbreak were still higher than 30%. This can partly be due to the requirement of advanced medical facilities for current treatments. As a result, it is very important to develop and evaluate new therapies for EBOV infection, especially those that can be easily applied in the developing world. The significance of our research is that we evaluate the potential of lipid-targeted treatments in reducing EBOV assembly and egress. We achieved this goal using the VP40 system combined with a computational approach, which both saves time and lowers cost compared to traditional experimental studies and provides innovative new tools to study viral protein dynamics.