Quantifying the risk of spillover reduction programs for human health.

Reducing spillover of zoonotic pathogens is an appealing approach to preventing human disease and minimizing the risk of future epidemics and pandemics. Although the immediate human health benefit of reducing spillover is clear, over time, spillover reduction could lead to counterintuitive negative consequences for human health. Here, we use mathematical models and computer simulations to explore the conditions under which unanticipated consequences of spillover reduction can occur in systems where the severity of disease increases with age at infection. Our results demonstrate that, because the average age at infection increases as spillover is reduced, programs that reduce spillover can actually increase population-level disease burden if the clinical severity of infection increases sufficiently rapidly with age. If, however, immunity wanes over time and reinfection is possible, our results reveal that negative health impacts of spillover reduction become substantially less likely. When our model is parameterized using published data on Lassa virus in West Africa, it predicts that negative health outcomes are possible, but likely to be restricted to a small subset of populations where spillover is unusually intense. Together, our results suggest that adverse consequences of spillover reduction programs are unlikely but that the public health gains observed immediately after spillover reduction may fade over time as the age structure of immunity gradually re-equilibrates to a reduced force of infection.

Re-Emergence of Rift Valley Fever Virus Lineage H in Senegal in 2022: In Vitro Characterization and Impact on Its Global Emergence in West Africa.

Rift Valley fever (RVF) is a re-emerging vector-borne zoonosis with a high public health and veterinary impact. In West Africa, many lineages were previously detected, but since 2020, lineage H from South Africa has been the main cause of the outbreaks. In this study, clinical samples collected through national surveillance were screened for RVF virus (RVFV) acute infection by RT-PCR and IgM ELISA tests. Sequencing, genome mapping and in vitro phenotypic characterization in mammal cells were performed on RT-PCR positive samples in comparison with other epidemic lineages (G and C). Four RVFV human cases were detected in Senegal and the sequence analyses revealed that the strains belonged to lineage H. The in vitro kinetics and genome mapping showed different replication efficiency profiles for the tested RVFV lineages and non-conservative mutations, which were more common to lineage G or specific to lineage H. Our findings showed the re-emergence of lineage H in Senegal in 2022, its high viral replication efficiency in vitro and support the findings that genetic diversity affects viral replication. This study gives new insights into the biological properties of lineage H and calls for deeper studies to better assess its potential to cause a future threat in Senegal.

Replication properties of a contemporary Zika virus from West Africa.

Zika virus (ZIKV) has become a global health problem over the past decade due to the extension of the geographic distribution of the Asian/American genotype. Recent epidemics of Asian/American ZIKV have been associated with developmental disorders in humans. There is mounting evidence that African ZIKV may be associated with increased fetal pathogenicity necessitating to pay a greater attention towards currently circulating viral strains in sub-Saharan Africa. Here, we generated an infectious molecular clone GUINEA-18 of a recently transmitted human ZIKV isolate from West Africa, ZIKV-15555. The available infectious molecular clone MR766MC of historical African ZIKV strain MR766-NIID was used for a molecular clone-based comparative study. Viral clones GUINEA-18 and MR766MC were compared for their ability to replicate in VeroE6, A549 and HCM3 cell lines. There was a lower replication rate for GUINEA-18 associated with weaker cytotoxicity and reduced innate immune system activation compared with MR766MC. Analysis of chimeric viruses between viral clones stressed the importance of NS1 to NS4B proteins, with a particular focus of NS4B on GUINEA-18 replicative properties. ZIKV has developed strategies to prevent cytoplasmic stress granule formation which occurs in response to virus infection. GUINEA-18 was greatly efficient in inhibiting stress granule assembly in A549 cells subjected to a physiological stressor, with NS1 to NS4B proteins also being critical in this process. The impact of these GUINEA-18 proteins on viral replicative abilities and host-cell responses to viral infection raises the question of the role of nonstructural proteins in the pathogenicity of currently circulating ZIKV in sub-Saharan Africa.

Modelling Lassa virus dynamics in West African Mastomys natalensis and the impact of human activities.

Lassa fever is a West African rodent-borne viral haemorrhagic fever that kills thousands of people a year, with 100 000 to 300 000 people a year probably infected by Lassa virus (LASV). The main reservoir of LASV is the Natal multimammate mouse, Mastomys natalensis. There is reported asynchrony between peak infection in the rodent population and peak Lassa fever risk among people, probably owing to differing seasonal contact rates. Here, we developed a susceptible-infected-recovered ([Formula: see text])-based model of LASV dynamics in its rodent host, M. natalensis, with a persistently infected class and seasonal birthing to test the impact of changes to seasonal birthing in the future owing to climate and land use change. Our simulations suggest shifting rodent birthing timing and synchrony will alter the peak of viral prevalence, changing risk to people, with viral dynamics mainly stable in adults and varying in the young, but with more infected individuals. We calculate the time-average basic reproductive number, [Formula: see text], for this infectious disease system with periodic changes to population sizes owing to birthing using a time-average method and with a sensitivity analysis show four key parameters: carrying capacity, adult mortality, the transmission parameter among adults and additional disease-induced mortality impact the maintenance of LASV in M. natalensis most, with carrying capacity and adult mortality potentially changeable owing to human activities and interventions.

Prevalence of somatic symptoms among Ebola Virus Disease (EVD) survivors in Africa: a systematic review and meta-analysis.

BACKGROUND: Many Ebola virus disease (EVD) survivors have reported somatic and neuropsychological symptoms after discharge from the Ebola Treatment Unit (ETU). Since the 2014-2016 Ebola epidemic in West Africa, various studies have investigated and identified these symptoms. Evidence on somatic symptoms is widely available in the literature, however, there is no concise overview of the prevalence across different time intervals. METHODS: This meta-analysis was conducted following the (PRISMA) guidelines. A database search was conducted to identify original studies that reported the prevalence of symptoms. The primary outcome measure was the prevalence rate of several somatic symptoms. Results were pooled, and prevalence rates were assessed over time, to elucidate any particular trends. RESULTS: We included 23 studies (5,714 participants). The pooled prevalence was: arthralgia 50% (95% CI: 41%-59%); headache 44% (95% CI: 36%-52%); myalgia 32% (95% CI: 26%-38%); abdominal pain 27% (95% CI: 15%-39%); fatigue 25% (95% CI: 19%-31%); numbness of feet 16% (95% CI: 14%-18%); numbness of hands 12% (95% CI: 10%-14%) and hearing loss 9% (95% CI: 5%-12%). Prevalence across different time intervals revealed significant patterns. All the symptoms persisted for more than 2 years after discharge except for abdominal pain. CONCLUSION: The pooled prevalence rates of somatic symptoms are notably high. Arthralgia and headache are the most prevalent of the symptoms, with hearing loss and numbness in hands and feet being the least. We found that arthralgia, myalgia, and abdominal pain decreased over time. However, headache, fatigue, numbness of hands and feet, and hearing loss increased over time.

Opinion review of drug resistant tuberculosis in West Africa: tackling the challenges for effective control.

Drug-resistant (DR) tuberculosis (TB) is a major public health concern globally, complicating TB control and management efforts. West Africa has historically faced difficulty in combating DR-TB due to limited diagnostic skills, insufficient access to excellent healthcare, and ineffective healthcare systems. This has aided in the emergence and dissemination of DR Mycobacterium tuberculosis complex (MTBC) strains in the region. In the past, DR-TB patients faced insufficient resources, fragmented efforts, and suboptimal treatment outcomes. However, current efforts to combat DR-TB in the region are promising. These efforts include strengthening diagnostic capacities, improving access to quality healthcare services, and implementing evidence-based treatment regimens for DR-TB. Additionally, many West African National TB control programs are collaborating with international partners to scale up laboratory infrastructure, enhance surveillance systems, and promote infection control measures. Moreso, novel TB drugs and regimens, such as bedaquiline and delamanid, are being introduced to improve treatment outcomes for DR-TB cases. Despite these obstacles, there is optimism for the future of DR-TB control in West Africa. Investments are being made to improve healthcare systems, expand laboratory capacity, and support TB research and innovation. West African institutions are now supporting knowledge sharing, capacity building, and resource mobilization through collaborative initiatives such as the West African Network for TB, AIDS, and Malaria (WANETAM), the West African Health Organization (WAHO), and other regional or global partners. These efforts hold promise for improved diagnostics, optimized treatment regimens, and provide better patient outcomes in the future where drug-resistant TB in WA can be effectively controlled, reducing the burden of the disease, and improving the health outcomes of affected individuals.

Rapid detection of Ebolavirus using isothermal recombinase-aided amplification.

Ebolavirus disease (EVD) is an often-lethal disease caused by the genus Ebolavirus (EBOV). Although vaccines are being developed and recently used, outbreak control still relies on a combination of various factors, including rapid identification of EVD cases. This allows rapid patient isolation and control measure implementation. Ebolavirus diagnosis is performed in treatment centers or reference laboratories, which usually takes a few hours to days to confirm the outbreak or deliver a clear result. A fast and field-deployable molecular detection method, such as the isothermal amplification recombinase-aided amplification (RAA), could significantly reduce sample-to-result time. In this study, a RT-RAA assay was evaluated for EBOV detection. Various primer and probe combinations were screened; analytical sensitivity and cross-specificity were tested. A total of 40 archived samples from the 2014 to 2016 Ebola outbreak in West Africa were tested with both the reference method real-time RT-PCR and the established RT-RAA assay. The assay could detect down to 22.6 molecular copies per microliter. No other pathogens were detected with the Ebolavirus RT-RAA assay. Testing 40 samples yield clinical sensitivity and specificity of 100% each. This rapid isothermal RT-RAA assay can replace the previous RT-RPA and continue to offer rapid EBOV diagnostics.

Exploring the path to optimal diabetes care by unravelling the contextual factors affecting access, utilisation, and quality of primary health care in West Africa: A scoping review protocol.

BACKGROUND: The prevalence of diabetes in West Africa is increasing, posing a major public health threat. An estimated 24 million Africans have diabetes, with rates in West Africa around 2-6% and projected to rise 129% by 2045 according to the WHO. Over 90% of cases are Type 2 diabetes (IDF, World Bank). As diabetes is ambulatory care sensitive, good primary care is crucial to reduce complications and mortality. However, research on factors influencing diabetes primary care access, utilisation and quality in West Africa remains limited despite growing disease burden. While research has emphasised diabetes prevalence and risk factors in West Africa, there remains limited evidence on contextual influences on primary care. This scoping review aims to address these evidence gaps. METHODS AND ANALYSIS: Using the established methodology by Arksey and O'Malley, this scoping review will undergo six stages. The review will adopt the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Review (PRISMA-ScR) guidelines to ensure methodological rigour. We will search four electronic databases and search through grey literature sources to thoroughly explore the topic. The identified articles will undergo thorough screening. We will collect data using a standardised data extraction form that covers study characteristics, population demographics, and study methods. The study will identify key themes and sub-themes related to primary healthcare access, utilisation, and quality. We will then analyse and summarise the data using a narrative synthesis approach. RESULTS: The findings and conclusive report will be finished and sent to a peer-reviewed publication within six months. CONCLUSION: This review protocol aims to systematically examine and assess the factors that impact the access, utilisation, and standard of primary healthcare services for diabetes in West Africa.

Determinants of early initiation of breastfeeding following birth in West Africa: A multilevel analysis using data from multi-country national health surveys.

BACKGROUND: Early initiation of breastfeeding (EIBF), within the first hour of birth, is crucial for promoting exclusive breastfeeding and establishing optimal nursing practices. However, global EIBF rates remain low, with even lower rates observed in Africa. Despite existing research gaps, this study aims to determine the prevalence of EIBF and identify maternal and child-related factors associated with its practice in West Africa. METHODS: This study utilized West African Demographic and Health Survey (DHS) data from 13 countries, including 146,964 children's records. To assess model fit, likelihood test and deviance were used. Similarly, intraclass correlation coefficient, median odds ratio, and proportional change in variance were employed for random effect. A multilevel logistic regression model was used to identify individual- and community-level factors influencing EIBF due to the hierarchical nature of the data. Variables with p-values ≤0.2 in the binary model and <0.05 in the final analysis were considered significantly associated with EIBF. RESULTS: The pooled prevalence of EIBF in West African nations was 50.60% (95% CI; 50.34-50.85%). The highest prevalence rate was observed in Serra Leone (75.33%) and the lowest prevalence was found in Senegal (33.94%). In the multilevel multiple logistic regression model, maternal education (AOR = 1.10, 95% CI, 1.03,1.16), marital status AOR = 1.07, 95% CI, 1.01,1.13), birth weight (AOR = 0.91, CI 0.86,0.96), birth orders (AOR = 1.09, CI 1.03,1.16), and (AOR = 1.11, CI 1.03,1.19), place of residence (AOR = 1.14, CI 1.07,1.21), and mode of delivery type (AOR = 0.26, CI 0.24,0.29) were significantly correlated with EIBF in West Africa. CONCLUSIONS: The incidence of EIBF in West Africa was found to be low. The study emphasizes the need for targeted behavioral change communication programs to address timely breastfeeding initiation, specifically targeting mothers and child characteristics. Factors such as education, delivery mode, marital status, birth weight, birth order, and place of residence were significantly associated with EIBF. Special attention should be given to improving EIBF rates among women undergoing caesarean sections, infants with low birth weight, and primiparous mothers, along with structural improvements in the healthcare sector in West Africa.

Birth weight mediates the association of maternal undernutrition with child undernutrition prevalence in West Africa.

BACKGROUND: Maternal nutritional status before and during pregnancy is an important determinant of foetal health. In West Africa, maternal and child undernutrition remains a major public health problem and it is important to establish the mechanistic pathway linking the two disorders to help address the problem. We therefore assessed the mediating role of low birth weight (LBW) in the relationship of maternal undernutrition with child undernutrition in West Africa. METHODS: We included recent (2010-2019) DHS data from thirteen West African countries. Poisson regression model with robust standard errors was used to assess the relationship between maternal undernutrition (body mass index and anaemia) and child undernutrition (stunting, wasting, underweight, and anaemia). Structural equation modelling was used to conduct the mediation analysis. RESULTS: Prevalence of stunting, wasting, underweight, and anaemia among under-five children in West Africa was found to be 32.4%, 8.1%, 20.1%, and 71.5%, respectively. We found children of underweight mothers to be more likely to be undernourished (stunted, wasted, and underweight) and anaemic compared to children of normal-weight mothers. Also, children of anaemic mothers were more likely to be stunted and anaemic but not wasted compared with children of non-anaemic mothers. LBW mediated the observed relationships between maternal BMI and childhood stunting (22.6%), and maternal anaemia and childhood stunting (24.9%), wasting (11.7), and anaemia (6.6%). CONCLUSION: We found maternal undernutrition to be associated with child undernutrition in West Africa with LBW noted to be a mediator of the observed relationship. We recommend that, to address the child undernutrition problem in West Africa, governments and policymakers must integrate measures to address the burden of LBW.

A novel indicator in epidemic monitoring through a case study of Ebola in West Africa (2014-2016).

The E/S (exposed/susceptible) ratio is analyzed in the SEIR model. The ratio plays a key role in understanding epidemic dynamics during the 2014-2016 Ebola outbreak in Sierra Leone and Guinea. The maximum value of the ratio occurs immediately before or after the time-dependent reproduction number (Rt) equals 1, depending on the initial susceptible population (S(0)). It is demonstrated that transmission rate curves corresponding to various incubation periods intersect at a single point referred to as the Cross Point (CP). At this point, the E/S ratio reaches an extremum, signifying a critical shift in transmission dynamics and aligning with the time when Rt approaches 1. By plotting transmission rate curves, ß(t), for any two arbitrary incubation periods and tracking their intersections, we can trace CP over time. CP serves as an indicator of epidemic status, especially when Rt is close to 1. It provides a practical means of monitoring epidemics without prior knowledge of the incubation period. Through a case study, we estimate the transmission rate and reproduction number, identifying CP and Rt = 1 while examining the E/S ratio across various values of S(0).

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.

Frequent chlamydia and gonorrhoea but very infrequent syphilis among men who have sex with men using HIV pre-exposure prophylaxis in West Africa.

OBJECTIVES: Although oral pre-exposure prophylaxis (PrEP) for HIV is being rolled out in West Africa, data on sexually transmitted infections (STIs) in PrEP users are scarce. We assessed the prevalence, incidence and determinants of bacterial STIs in men who have sex with men (MSM) taking PrEP in Burkina Faso, Côte d'Ivoire, Mali and Togo. METHODS: A prospective cohort study among MSM initiating PrEP as part of a comprehensive HIV prevention package was conducted between 2017 and 2021 in community-based clinics in the four study countries. Molecular screening for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) was performed at months 0, 6 and 12. Serological testing for syphilis was performed every 3 months over the first year of follow-up. Determinants of CT and/or NG incidence were identified using Poisson generalised linear mixed models. RESULTS: A total of 598 participants with a median age of 24.7 years were included. Prevalence of CT and/or NG was 24.4% (95% CI 21.0 to 28.1), 22.4% (95% CI 18.4 to 26.8) and 29.0% (95% CI 24.2 to 34.1) at months 0, 6 and 12, respectively. The prevalence of syphilis ranged from 0.2% (95% CI 0.0 to 0.9) at month 0 to 0.8% (95% CI 0.2 to 2.4) at month 12. Ninety incident CT and/or NG infections occurred during a total follow-up time of 280.6 person-years (incidence rate 32.1 per 100 person-years, 95% CI 25.8 to 39.4). Three incident syphilis infections were detected during a total follow-up time of 459.7 person-years (incidence rate 0.7 per 100 person-years, 95% CI 0.1 to 1.9). CT and/or NG incidence was associated with condomless insertive anal sex (adjusted incidence rate ratio 1.96, 95% CI 1.04 to 3.71, p=0.038). CONCLUSIONS: CT and NG were frequent but syphilis was very infrequent in MSM using HIV PrEP in West Africa. HIV programme managers should integrate STI services into PrEP programmes.

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.

Ebola-specific therapeutic antibodies from lab to clinic: The example of ZMapp.

In the 1990s, monoclonal antibodies (mAbs) progressed from scientific tools to advanced therapeutics, particularly for the treatment of cancers and autoimmune and inflammatory disorders. In the arena of infectious disease, the inauguration of mAbs as a post-exposure treatment in humans against Ebola virus (EBOV) occurred in response to the 2013-2016 West Africa outbreak. This review recounts the history of a candidate mAb treatment, ZMapp, beginning with its emergency use in the 2013-2016 outbreak and advancing to randomized controlled trials into the 2018-2020 African outbreak. We end with a brief discussion of the hurdles and promise toward mAb therapeutic use against infectious disease.

Effects of the COVID-19 Pandemic on ART Initiation and Access to HIV Viral Load Monitoring in Adults Living With HIV in West Africa: A Regression Discontinuity Analysis.

OBJECTIVES: Efforts to control the COVID-19 pandemic have potentially compromised the availability and/or quality of HIV services. We aimed to assess the pandemic's impact on antiretroviral therapy (ART) initiation and HIV viral load (VL) monitoring in 3 West African countries. METHODS: We used routinely collected data from 5 clinics contributing to the International epidemiologic Database to Evaluate AIDS collaboration in Burkina Faso, Côte d'Ivoire, and Nigeria. We included ART-naïve adults living with HIV initiating ART from January 1, 2018. We conducted regression discontinuity analysis to estimate changes in the number of ART initiations and VL measures per week, before and during the pandemic period in each country. RESULTS: In clinics in Burkina Faso and Côte d'Ivoire, ART initiations per week remained constant throughout the studied periods (-0.24 points (p) of ART initiations/week 95% CI: -5.5 to 5.9, -0.9 p, 95% CI: -8.5 to 8.6, respectively), whereas in Nigeria's clinic, they decreased significantly (-6.3 p, 95% CI: -10.8 to -1.7) after the beginning of the pandemic. The volume of VL tests performed decreased significantly in all 3 countries (-17.0 p, 95% CI: -25.3 to -8.6 in Burkina Faso, -118.4 p, 95% CI: -171.1 to -65.8 in Côte d'Ivoire and -169.1 p, 95% CI: -282.6 to -55.6 in Nigeria). CONCLUSIONS: HIV clinics in two out of three countries in West Africa demonstrated resilience as they successfully maintained access to ART for ALWH despite the challenges imposed by the pandemic. However, VL monitoring was severely disrupted and did not return to prepandemic levels approximately 1 year after the beginning of the pandemic. Continued monitoring of the HIV care continuum in the postpandemic period is essential to mitigate potential enduring effects on ALWH's virological and clinical outcomes.