Serological evidence of virus infection in Eidolon helvum fruit bats: implications for bushmeat consumption in Nigeria.

Introduction: The Eidolon helvum fruit bat is one of the most widely distributed fruit bats in Africa and known to be a reservoir for several pathogenic viruses that can cause disease in animals and humans. To assess the risk of zoonotic spillover, we conducted a serological survey of 304 serum samples from E. helvum bats that were captured for human consumption in Makurdi, Nigeria. Methods: Using pseudotyped viruses, we screened 304 serum samples for neutralizing antibodies against viruses from the Coronaviridae, Filoviridae, Orthomyxoviridae and Paramyxoviridae families. Results: We report the presence of neutralizing antibodies against henipavirus lineage GH-M74a virus (odds ratio 6.23; p < 0.001), Nipah virus (odds ratio 4.04; p = 0.00031), bat influenza H17N10 virus (odds ratio 7.25; p < 0.001) and no significant association with Ebola virus (odds ratio 0.56; p = 0.375) in this bat cohort. Conclusion: The data suggest a potential risk of zoonotic spillover including the possible circulation of highly pathogenic viruses in E. helvum populations. These findings highlight the importance of maintaining sero-surveillance of E. helvum, and the necessity for further, more comprehensive investigations to monitor changes in virus prevalence, distribution over time, and across different geographic locations.

Alternative epidemic indicators for COVID-19 in three settings with incomplete death registration systems.

Not all COVID-19 deaths are officially reported, and particularly in low-income and humanitarian settings, the magnitude of reporting gaps remains sparsely characterized. Alternative data sources, including burial site worker reports, satellite imagery of cemeteries, and social media-conducted surveys of infection may offer solutions. By merging these data with independently conducted, representative serological studies within a mathematical modeling framework, we aim to better understand the range of underreporting using examples from three major cities: Addis Ababa (Ethiopia), Aden (Yemen), and Khartoum (Sudan) during 2020. We estimate that 69 to 100%, 0.8 to 8.0%, and 3.0 to 6.0% of COVID-19 deaths were reported in each setting, respectively. In future epidemics, and in settings where vital registration systems are limited, using multiple alternative data sources could provide critically needed, improved estimates of epidemic impact. However, ultimately, these systems are needed to ensure that, in contrast to COVID-19, the impact of future pandemics or other drivers of mortality is reported and understood worldwide.

Baylisascaris procyonis Roundworm Infection in Child with Autism Spectrum Disorder, Washington, USA, 2022.

We describe a case of Baylisascaris procyonis roundworm infection in a child in Washington, USA, with autism spectrum disorder. Environmental assessment confirmed nearby raccoon habitation and B. procyonis eggs. B. procyonis infections should be considered a potential cause of human eosinophilic meningitis, particularly among young children and persons with developmental delays.

Seasonal dynamics of Anopheles stephensi and its implications for mosquito detection and emergent malaria control in the Horn of Africa.

Invasion of the malaria vector Anopheles stephensi across the Horn of Africa threatens control efforts across the continent, particularly in urban settings where the vector is able to proliferate. Malaria transmission is primarily determined by the abundance of dominant vectors, which often varies seasonally with rainfall. However, it remains unclear how An. stephensi abundance changes throughout the year, despite this being a crucial input to surveillance and control activities. We collate longitudinal catch data from across its endemic range to better understand the vector's seasonal dynamics and explore the implications of this seasonality for malaria surveillance and control across the Horn of Africa. Our analyses reveal pronounced variation in seasonal dynamics, the timing and nature of which are poorly predicted by rainfall patterns. Instead, they are associated with temperature and patterns of land use; frequently differing between rural and urban settings. Our results show that timing entomological surveys to coincide with rainy periods is unlikely to improve the likelihood of detecting An. stephensi. Integrating these results into a malaria transmission model, we show that timing indoor residual spraying campaigns to coincide with peak rainfall offers little improvement in reducing disease burden compared to starting in a random month. Our results suggest that unlike other malaria vectors in Africa, rainfall may be a poor guide to predicting the timing of peaks in An. stephensi-driven malaria transmission. This highlights the urgent need for longitudinal entomological monitoring of the vector in its new environments given recent invasion and potential spread across the continent.

Correction: The epidemiology of Mayaro virus in the Americas: A systematic review and key parameter estimates for outbreak modelling.

[This corrects the article DOI: 10.1371/journal.pntd.0009418.].

The potential impact of Anopheles stephensi establishment on the transmission of Plasmodium falciparum in Ethiopia and prospective control measures.

BACKGROUND: Sub-Saharan Africa has seen substantial reductions in cases and deaths due to malaria over the past two decades. While this reduction is primarily due to an increasing expansion of interventions, urbanisation has played its part as urban areas typically experience substantially less malaria transmission than rural areas. However, this may be partially lost with the invasion and establishment of Anopheles stephensi. A. stephensi, the primary urban malaria vector in Asia, was first detected in Africa in 2012 in Djibouti and was subsequently identified in Ethiopia in 2016, and later in Sudan and Somalia. In Djibouti, malaria cases have increased 30-fold from 2012 to 2019 though the impact in the wider region remains unclear. METHODS: Here, we have adapted an existing model of mechanistic malaria transmission to estimate the increase in vector density required to explain the trends in malaria cases seen in Djibouti. To account for the observed plasticity in An. stephensi behaviour, and the unknowns of how it will establish in a novel environment, we sample behavioural parameters in order to account for a wide range of uncertainty. This quantification is then applied to Ethiopia, considering temperature-dependent extrinsic incubation periods, pre-existing vector-control interventions and Plasmodium falciparum prevalence in order to assess the potential impact of An. stephensi establishment on P. falciparum transmission. Following this, we estimate the potential impact of scaling up ITN (insecticide-treated nets)/IRS (indoor residual spraying) and implementing piperonyl butoxide (PBO) ITNs and larval source management, as well as their economic costs. RESULTS: We estimate that annual P. falciparum malaria cases could increase by 50% (95% CI 14-90) if no additional interventions are implemented. The implementation of sufficient control measures to reduce malaria transmission to pre-stephensi levels will cost hundreds of millions of USD. CONCLUSIONS: Substantial heterogeneity across the country is predicted and large increases in vector control interventions could be needed to prevent a major public health emergency.

Exploring agricultural land-use and childhood malaria associations in sub-Saharan Africa.

Agriculture in Africa is rapidly expanding but with this comes potential disbenefits for the environment and human health. Here, we retrospectively assess whether childhood malaria in sub-Saharan Africa varies across differing agricultural land uses after controlling for socio-economic and environmental confounders. Using a multi-model inference hierarchical modelling framework, we found that rainfed cropland was associated with increased malaria in rural (OR 1.10, CI 1.03-1.18) but not urban areas, while irrigated or post flooding cropland was associated with malaria in urban (OR 1.09, CI 1.00-1.18) but not rural areas. In contrast, although malaria was associated with complete forest cover (OR 1.35, CI 1.24-1.47), the presence of natural vegetation in agricultural lands potentially reduces the odds of malaria depending on rural-urban context. In contrast, no associations with malaria were observed for natural vegetation interspersed with cropland (veg-dominant mosaic). Agricultural expansion through rainfed or irrigated cropland may increase childhood malaria in rural or urban contexts in sub-Saharan Africa but retaining some natural vegetation within croplands could help mitigate this risk and provide environmental co-benefits.

Mapping environmental suitability of Haemagogus and Sabethes spp. mosquitoes to understand sylvatic transmission risk of yellow fever virus in Brazil.

BACKGROUND: Yellow fever (YF) is an arboviral disease which is endemic to Brazil due to a sylvatic transmission cycle maintained by infected mosquito vectors, non-human primate (NHP) hosts, and humans. Despite the existence of an effective vaccine, recent sporadic YF epidemics have underscored concerns about sylvatic vector surveillance, as very little is known about their spatial distribution. Here, we model and map the environmental suitability of YF's main vectors in Brazil, Haemagogus spp. and Sabethes spp., and use human population and NHP data to identify locations prone to transmission and spillover risk. METHODOLOGY/PRINCIPAL FINDINGS: We compiled a comprehensive set of occurrence records on Hg. janthinomys, Hg. leucocelaenus, and Sabethes spp. from 1991-2019 using primary and secondary data sources. Linking these data with selected environmental and land-cover variables, we adopted a stacked regression ensemble modelling approach (elastic-net regularized GLM, extreme gradient boosted regression trees, and random forest) to predict the environmental suitability of these species across Brazil at a 1 km x 1 km resolution. We show that while suitability for each species varies spatially, high suitability for all species was predicted in the Southeastern region where recent outbreaks have occurred. By integrating data on NHP host reservoirs and human populations, our risk maps further highlight municipalities within the region that are prone to transmission and spillover. CONCLUSIONS/SIGNIFICANCE: Our maps of sylvatic vector suitability can help elucidate potential locations of sylvatic reservoirs and be used as a tool to help mitigate risk of future YF outbreaks and assist in vector surveillance. Furthermore, at-risk regions identified from our work could help disease control and elucidate gaps in vaccination coverage and NHP host surveillance.

Feasibility, acceptability, and effectiveness of non-pharmaceutical interventions against infectious diseases among crisis-affected populations: a scoping review.

BACKGROUND: Non-pharmaceutical interventions (NPIs) are a crucial suite of measures to prevent and control infectious disease outbreaks. Despite being particularly important for crisis-affected populations and those living in informal settlements, who typically reside in overcrowded and resource limited settings with inadequate access to healthcare, guidance on NPI implementation rarely takes the specific needs of such populations into account. We therefore conducted a systematic scoping review of the published evidence to describe the landscape of research and identify evidence gaps concerning the acceptability, feasibility, and effectiveness of NPIs among crisis-affected populations and informal settlements. METHODS: We systematically reviewed peer-reviewed articles published between 1970 and 2020 to collate available evidence on the feasibility, acceptability, and effectiveness of NPIs in crisis-affected populations and informal settlements. We performed quality assessments of each study using a standardised questionnaire. We analysed the data to produce descriptive summaries according to a number of categories: date of publication; geographical region of intervention; typology of crisis, shelter, modes of transmission, NPI, research design; study design; and study quality. RESULTS: Our review included 158 studies published in 85 peer-reviewed articles. Most research used low quality study designs. The acceptability, feasibility, and effectiveness of NPIs was highly context dependent. In general, simple and cost-effective interventions such as community-level environmental cleaning and provision of water, sanitation and hygiene services, and distribution of items for personal protection such as insecticide-treated nets, were both highly feasible and acceptable. Logistical, financial, and human resource constraints affected both the implementation and sustainability of measures. Community engagement emerged as a strong factor contributing to the effectiveness of NPIs. Conversely, measures that involve potential restriction on personal liberty such as case isolation and patient care and burial restrictions were found to be less acceptable, despite apparent effectiveness. CONCLUSIONS: Overall, the evidence base was variable, with substantial knowledge gaps which varied between settings and pathogens. Based on the current landscape, robust evidence-based guidance is not possible, and a research agenda is urgently required that focusses on these specific vulnerable populations. Although implementation of NPIs presents unique practical challenges in these settings, it is critical that such an agenda is put in place, and that the lessons learned from historical and present experiences are documented to build a firm evidence base.

Optimising the deployment of vector control tools against malaria: a data-informed modelling study.

BACKGROUND: Concern that insecticide resistant mosquitoes are threatening malaria control has driven the development of new types of insecticide treated nets (ITNs) and indoor residual spraying (IRS) of insecticide. Malaria control programmes have a choice of vector control interventions although it is unclear which controls should be used to combat the disease. The study aimed at producing a framework to easily compare the public health impact and cost-effectiveness of different malaria prevention measures currently in widespread use. METHODS: We used published data from experimental hut trials conducted across Africa to characterise the entomological effect of pyrethroid-only ITNs versus ITNs combining a pyrethroid insecticide with the synergist piperonyl butoxide (PBO). We use these estimates to parameterise a dynamic mathematical model of Plasmodium falciparum malaria which is validated for two sites by comparing simulated results to empirical data from randomised control trials (RCTs) in Tanzania and Uganda. We extrapolated model simulations for a series of potential scenarios likely across the sub-Saharan African region and include results in an online tool (Malaria INtervention Tool [MINT]) that aims to identify optimum vector control intervention packages for scenarios with varying budget, price, entomological and epidemiological factors. FINDINGS: Our model indicates that switching from pyrethroid-only to pyrethroid-PBO ITNs could averted up to twice as many cases, although the additional benefit is highly variable and depends on the setting conditions. We project that annual delivery of long-lasting, non-pyrethroid IRS would prevent substantially more cases over 3-years, while pyrethroid-PBO ITNs tend to be the most cost-effective intervention per case averted. The model was able to predict prevalence and efficacy against prevalence in both RCTs for the intervention types tested. MINT is applicable to regions of sub-Saharan Africa with endemic malaria and provides users with a method of designing intervention packages given their setting and budget. INTERPRETATION: The most cost-effective vector control package will vary locally. Models able to recreate results of RCTs can be used to extrapolate outcomes elsewhere to support evidence-based decision making for investment in vector control. FUNDING: Medical Research Council, IVCC, Wellcome Trust. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Understanding the Potential Impact of Different Drug Properties on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission and Disease Burden: A Modelling Analysis.

BACKGROUND: The public health impact of the coronavirus disease 2019 (COVID-19) pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. METHODS: Using a mathematical model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care. RESULTS: The impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R = 1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalization) could have much greater benefits, particularly in resource-poor settings facing large epidemics. CONCLUSIONS: Advances in the treatment of COVID-19 to date have been focused on hospitalized-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.

The epidemiology of Mayaro virus in the Americas: A systematic review and key parameter estimates for outbreak modelling.

Mayaro virus (MAYV) is an arbovirus that is endemic to tropical forests in Central and South America, particularly within the Amazon basin. In recent years, concern has increased regarding MAYV's ability to invade urban areas and cause epidemics across the region. We conducted a systematic literature review to characterise the evolutionary history of MAYV, its transmission potential, and exposure patterns to the virus. We analysed data from the literature on MAYV infection to produce estimates of key epidemiological parameters, including the generation time and the basic reproduction number, R0. We also estimated the force-of-infection (FOI) in epidemic and endemic settings. Seventy-six publications met our inclusion criteria. Evidence of MAYV infection in humans, animals, or vectors was reported in 14 Latin American countries. Nine countries reported evidence of acute infection in humans confirmed by viral isolation or reverse transcription-PCR (RT-PCR). We identified at least five MAYV outbreaks. Seroprevalence from population based cross-sectional studies ranged from 21% to 72%. The estimated mean generation time of MAYV was 15.2 days (95% CrI: 11.7-19.8) with a standard deviation of 6.3 days (95% CrI: 4.2-9.5). The per-capita risk of MAYV infection (FOI) ranged between 0.01 and 0.05 per year. The mean R0 estimates ranged between 2.1 and 2.9 in the Amazon basin areas and between 1.1 and 1.3 in the regions outside of the Amazon basin. Although MAYV has been identified in urban vectors, there is not yet evidence of sustained urban transmission. MAYV's enzootic cycle could become established in forested areas within cities similar to yellow fever virus.

Seasonality of agricultural exposure as an important predictor of seasonal yellow fever spillover in Brazil.

Yellow fever virus (YFV) is a zoonotic arbovirus affecting both humans and non-human primates (NHP's) in Africa and South America. Previous descriptions of YF's seasonality have relied purely on climatic explanations, despite the high proportion of cases occurring in people involved in agriculture. We use a series of random forest classification models to predict the monthly occurrence of YF in humans and NHP's across Brazil, by fitting four classes of covariates related to the seasonality of climate and agriculture (planting and harvesting), crop output and host demography. We find that models captured seasonal YF reporting in humans and NHPs when they considered seasonality of agriculture rather than climate, particularly for monthly aggregated reports. These findings illustrate the seasonality of exposure, through agriculture, as a component of zoonotic spillover. Additionally, by highlighting crop types and anthropogenic seasonality, these results could directly identify areas at highest risk of zoonotic spillover.

Within-country age-based prioritisation, global allocation, and public health impact of a vaccine against SARS-CoV-2: A mathematical modelling analysis.

The worldwide endeavour to develop safe and effective COVID-19 vaccines has been extraordinary, and vaccination is now underway in many countries. However, the doses available in 2021 are likely to be limited. We extend a mathematical model of SARS-CoV-2 transmission across different country settings to evaluate the public health impact of potential vaccines using WHO-developed target product profiles. We identify optimal vaccine allocation strategies within- and between-countries to maximise averted deaths under constraints on dose supply. We find that the health impact of SARS-CoV-2 vaccination depends on the cumulative population-level infection incidence when vaccination begins, the duration of natural immunity, the trajectory of the epidemic prior to vaccination, and the level of healthcare available to effectively treat those with disease. Within a country we find that for a limited supply (doses for < 20% of the population) the optimal strategy is to target the elderly. However, with a larger supply, if vaccination can occur while other interventions are maintained, the optimal strategy switches to targeting key transmitters to indirectly protect the vulnerable. As supply increases, vaccines that reduce or block infection have a greater impact than those that prevent disease alone due to the indirect protection provided to high-risk groups. Given a 2 billion global dose supply in 2021, we find that a strategy in which doses are allocated to countries proportional to population size is close to optimal in averting deaths and aligns with the ethical principles agreed in pandemic preparedness planning.

Mental health and psychosocial support in conflict: children's protection concerns and intervention outcomes in Syria.

Child protection and mental health during conflict intersects with a variety of adverse conflict-related factors, and intervention outcomes in the field are often difficult to predict. Using the casefiles of 376 school children registered in a Mental Health and Psychosocial Support (MHPSS) project in the Northwest governorate of Idleb in Syria, this study aimed to determine (i) the rates of various protection concerns (potential mental health conditions, psychosocial deprivation issues, and social, behavioural and emotional issues) for students enrolled in this project, (ii) whether the rates of any of the protection concerns varied between children and adolescents, or between boys and girls, and (iii) which of the identified demographic and protection sector factors predicted the presence of potential mental health conditions and MHPSS intervention outcomes. MHPSS interventions (including individual MHPSS sessions tailored for children in conflict, resilience building activities, tutoring, peer building activities, community awareness, and other tailored services) were implemented at schools operated by the UK-based organization, Syria Relief. The variables tested included demographic variables of age group (208 children, aged 4-9 years; 168 adolescents, aged 10-14 years) and gender (211 males, 165 females), and 23 protection sector variables including 11 potential mental health problems (anxiety, attention deficit hyperactivity disorder, conduct disorder, autism, epilepsy, motor tics, depression, post-traumatic-stress disorder, social phobia, specific phobia, learning disability), 7 psychosocial deprivation (PSD) variables (war injury, child labour, loss of caregiver, neglect, domestic abuse, displacement, poverty), and 5 social, behavioural and emotional (SBE) variables (low/abnormal socialization, emotional issue, peer issues/being bullied, peer issues/being aggressive, educational decline). Within the sample, 73.7% were found with a probable mental health problem, with 30.6% showing signs of anxiety, 36.2% of depression and 26.6% showing signs of post-traumatic-stress disorder. Additionally, 74.5% of the sample had at least one form of PSD present (42.6% were displaced, 39.6% suffered from abject poverty), and 64.9% had a reported SBE concern. Children were more likely to have a potential mental health concern, especially autism and PTSD, and poor socialization; while adolescents were more likely to engage in child labour, experience abject poverty, exhibit aggressive behaviour, and educational decline. Male gender was associated with child labour and aggressive behaviour while female gender was associated with the presence of potential mental health problems, especially depression, and loss of caregiver, and poor socialisation. Odds ratios (ORs) indicated significant negative impact of the presence of SBE concerns (any), 4.45 (95% CI: 1.68-12.7), emotional issue, 11.02 (95% CI: 2.76-74.49), low/abnormal socialization, 8.37 (95% CI, 2-57.71), and displacement, 2.91 (95% CI, 1.21-7.48) on the child's mental health. MHPSS intervention outcomes were categorized as case improvement, decline, or incomplete/limited information available; with case improvement noted for 63.6% of the sample, decline noted for 14.4%, and incomplete treatment/limited follow-up noted for 22.1% of the sample. Additional analysis of predictors of treatment success found that child labour was significantly associated with a lack of treatment success, OR 0.24 (95% CI, 0.07-0.92). These findings provide important insights into the complex tailoring needs that protection and MHPSS field projects require.

Leveraging community mortality indicators to infer COVID-19 mortality and transmission dynamics in Damascus, Syria.

The COVID-19 pandemic has resulted in substantial mortality worldwide. However, to date, countries in the Middle East and Africa have reported considerably lower mortality rates than in Europe and the Americas. Motivated by reports of an overwhelmed health system, we estimate the likely under-ascertainment of COVID-19 mortality in Damascus, Syria. Using all-cause mortality data, we fit a mathematical model of COVID-19 transmission to reported mortality, estimating that 1.25% of COVID-19 deaths (sensitivity range 1.00% - 3.00%) have been reported as of 2 September 2020. By 2 September, we estimate that 4,380 (95% CI: 3,250 - 5,550) COVID-19 deaths in Damascus may have been missed, with 39.0% (95% CI: 32.5% - 45.0%) of the population in Damascus estimated to have been infected. Accounting for under-ascertainment corroborates reports of exceeded hospital bed capacity and is validated by community-uploaded obituary notifications, which confirm extensive unreported mortality in Damascus.

The global burden of yellow fever.

Yellow fever (YF) is a viral, vector-borne, haemorrhagic fever endemic in tropical regions of Africa and South America. The vaccine for YF is considered safe and effective, but intervention strategies need to be optimised; one of the tools for this is mathematical modelling. We refine and expand an existing modelling framework for Africa to account for transmission in South America. We fit to YF occurrence and serology data. We then estimate the subnational forces of infection for the entire endemic region. Finally, using demographic and vaccination data, we examine the impact of vaccination activities. We estimate that there were 109,000 (95% credible interval [CrI] [67,000-173,000]) severe infections and 51,000 (95% CrI [31,000-82,000]) deaths due to YF in Africa and South America in 2018. We find that mass vaccination activities in Africa reduced deaths by 47% (95% CrI [10%-77%]). This methodology allows us to evaluate the effectiveness of vaccination and illustrates the need for continued vigilance and surveillance of YF.

Reduction in mobility and COVID-19 transmission.

In response to the COVID-19 pandemic, countries have sought to control SARS-CoV-2 transmission by restricting population movement through social distancing interventions, thus reducing the number of contacts. Mobility data represent an important proxy measure of social distancing, and here, we characterise the relationship between transmission and mobility for 52 countries around the world. Transmission significantly decreased with the initial reduction in mobility in 73% of the countries analysed, but we found evidence of decoupling of transmission and mobility following the relaxation of strict control measures for 80% of countries. For the majority of countries, mobility explained a substantial proportion of the variation in transmissibility (median adjusted R-squared: 48%, interquartile range - IQR - across countries [27-77%]). Where a change in the relationship occurred, predictive ability decreased after the relaxation; from a median adjusted R-squared of 74% (IQR across countries [49-91%]) pre-relaxation, to a median adjusted R-squared of 30% (IQR across countries [12-48%]) post-relaxation. In countries with a clear relationship between mobility and transmission both before and after strict control measures were relaxed, mobility was associated with lower transmission rates after control measures were relaxed indicating that the beneficial effects of ongoing social distancing behaviours were substantial.