Representativeness of whole-genome sequencing approaches in England: the importance for understanding inequalities associated with SARS-CoV-2 infection.

Whole-genome sequencing (WGS) information has played a crucial role in the SARS-CoV-2 (COVID-19) pandemic by providing evidence about variants to inform public health policy. The purpose of this study was to assess the representativeness of sequenced cases compared with all COVID-19 cases in England, between March 2020 and August 2021, by demographic and socio-economic characteristics, to evaluate the representativeness and utility of these data in epidemiological analyses. To achieve this, polymerase chain reaction (PCR)-confirmed COVID-19 cases were extracted from the national laboratory system and linked with WGS data. During the study period, over 10% of COVID-19 cases in England had WGS data available for epidemiological analysis. With sequencing capacity increasing throughout the period, sequencing representativeness compared to all reported COVID-19 cases increased over time, allowing for valuable epidemiological analyses using demographic and socio-economic characteristics, particularly during periods with emerging novel SARS-CoV-2 variants. This study demonstrates the comprehensiveness of England's sequencing throughout the COVID-19 pandemic, rapidly detecting variants of concern, and enabling representative epidemiological analyses to inform policy.

Increased Residential Clustering of COVID-19 Cases Associated With SARS-CoV-2 Variant of Concern B.1.1.7.

BACKGROUND: The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.7 variant in England in 2020 and subsequent global spread emphasized the need to understand epidemiologic characteristics of SARS-CoV-2 variants. A diagnostic proxy for this variant, referred to as S-gene target failure, provided a rich dataset to assess transmissibility of the variant in an analysis of clustering in residential settings. METHODS: We used a pair-matched case-control study design to estimate odds of onward transmission within households with S-gene target failure index cases versus nontarget failure index cases. We defined cases as the index in a household cluster (clustered case) and controls as a case with no subsequent household cluster (sporadic). We matched clustered and sporadic cases one-to-one on specimen week, geography, and property type. We used conditional logistic regression, adjusting for age, sex, ethnicity, and symptom status, to assess odds of residential clustering. RESULTS: Our study population comprised 57,244 individuals with specimen dates from 23 November 2020 to 4 January 2021. Crude analysis yielded 54% increased odds (odds ratio [OR] = 1.5; 95% confidence interval [CI] = 1.5, 1.6) of residential clustering associated with S-gene target failure; the association remained in the fully adjusted model (OR = 1.6, 95% CI = 1.5, 1.6). Stratified analyses by region showed increased odds of residential clustering associated with target failure in all regions apart from the Southwest, where we observed lower precision. Similar adjusted odds ratios with precise confidence intervals remained in stratified analyses by property category. CONCLUSION: We observed increased odds in all property types, consistent with greater transmissibility of the B.1.1.7 variant in this high-risk setting.

Enhancing epidemiological surveillance of the emergence of the SARS-CoV-2 Omicron variant using spike gene target failure data, England, 15 November to 31 December 2021.

When SARS-CoV-2 Omicron emerged in 2021, S gene target failure enabled differentiation between Omicron and the dominant Delta variant. In England, where S gene target surveillance (SGTS) was already established, this led to rapid identification (within ca 3 days of sample collection) of possible Omicron cases, alongside real-time surveillance and modelling of Omicron growth. SGTS was key to public health action (including case identification and incident management), and we share applied insights on how and when to use SGTS.

On the Sensitivity and Specificity of Postmortem Upper Respiratory Tract Testing for SARS-CoV-2.

BACKGROUND: Postmortem testing can improve our understanding of the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) if sufficiently sensitive and specific. METHODS: We investigated the postmortem sensitivity and specificity of reverse transcriptase polymerase chain reaction (PCR) testing on upper respiratory swabs using a dataset of everyone tested for SARS-CoV-2 before and after death in England, 1 March to 29 October 2020. We analyzed sensitivity in those with a positive test before death by time to postmortem test. We developed a multivariate model and conducted time-to-negativity survival analysis. For specificity, we analyzed those with a negative test in the week before death. RESULTS: Postmortem testing within a week after death had a sensitivity of 96.8% if the person had tested positive within a week before death. There was no effect of age, sex, or specimen type on sensitivity, but individuals with coronavirus disease 2019 (COVID-19)-related codes on their death certificate were 5.65 times more likely to test positive after death (95% confidence interval, 2.31-13.9). Specificity was 94.2%, increasing to 97.5% in individuals without COVID-19 on the death certificate. CONCLUSION: Postmortem testing has high sensitivity (96.8%) and specificity (94.2%) if performed within a week after death and could be a useful diagnostic tool.

Mapping the global endemicity and clinical burden of Plasmodium vivax, 2000-17: a spatial and temporal modelling study.

BACKGROUND: Plasmodium vivax exacts a significant toll on health worldwide, yet few efforts to date have quantified the extent and temporal trends of its global distribution. Given the challenges associated with the proper diagnosis and treatment of P vivax, national malaria programmes-particularly those pursuing malaria elimination strategies-require up to date assessments of P vivax endemicity and disease impact. This study presents the first global maps of P vivax clinical burden from 2000 to 2017. METHODS: In this spatial and temporal modelling study, we adjusted routine malariometric surveillance data for known biases and used socioeconomic indicators to generate time series of the clinical burden of P vivax. These data informed Bayesian geospatial models, which produced fine-scale predictions of P vivax clinical incidence and infection prevalence over time. Within sub-Saharan Africa, where routine surveillance for P vivax is not standard practice, we combined predicted surfaces of Plasmodium falciparum with country-specific ratios of P vivax to P falciparum. These results were combined with surveillance-based outputs outside of Africa to generate global maps. FINDINGS: We present the first high-resolution maps of P vivax burden. These results are combined with those for P falciparum (published separately) to form the malaria estimates for the Global Burden of Disease 2017 study. The burden of P vivax malaria decreased by 41·6%, from 24·5 million cases (95% uncertainty interval 22·5-27·0) in 2000 to 14·3 million cases (13·7-15·0) in 2017. The Americas had a reduction of 56·8% (47·6-67·0) in total cases since 2000, while South-East Asia recorded declines of 50·5% (50·3-50·6) and the Western Pacific regions recorded declines of 51·3% (48·0-55·4). Europe achieved zero P vivax cases during the study period. Nonetheless, rates of decline have stalled in the past five years for many countries, with particular increases noted in regions affected by political and economic instability. INTERPRETATION: Our study highlights important spatial and temporal patterns in the clinical burden and prevalence of P vivax. Amid substantial progress worldwide, plateauing gains and areas of increased burden signal the potential for challenges that are greater than expected on the road to malaria elimination. These results support global monitoring systems and can inform the optimisation of diagnosis and treatment where P vivax has most impact. FUNDING: Bill & Melinda Gates Foundation and the Wellcome Trust.

Mapping the global prevalence, incidence, and mortality of Plasmodium falciparum, 2000-17: a spatial and temporal modelling study.

BACKGROUND: Since 2000, the scale-up of malaria control interventions has substantially reduced morbidity and mortality caused by the disease globally, fuelling bold aims for disease elimination. In tandem with increased availability of geospatially resolved data, malaria control programmes increasingly use high-resolution maps to characterise spatially heterogeneous patterns of disease risk and thus efficiently target areas of high burden. METHODS: We updated and refined the Plasmodium falciparum parasite rate and clinical incidence models for sub-Saharan Africa, which rely on cross-sectional survey data for parasite rate and intervention coverage. For malaria endemic countries outside of sub-Saharan Africa, we produced estimates of parasite rate and incidence by applying an ecological downscaling approach to malaria incidence data acquired via routine surveillance. Mortality estimates were derived by linking incidence to systematically derived vital registration and verbal autopsy data. Informed by high-resolution covariate surfaces, we estimated P falciparum parasite rate, clinical incidence, and mortality at national, subnational, and 5 × 5 km pixel scales with corresponding uncertainty metrics. FINDINGS: We present the first global, high-resolution map of P falciparum malaria mortality and the first global prevalence and incidence maps since 2010. These results are combined with those for Plasmodium vivax (published separately) to form the malaria estimates for the Global Burden of Disease 2017 study. The P falciparum estimates span the period 2000-17, and illustrate the rapid decline in burden between 2005 and 2017, with incidence declining by 27·9% and mortality declining by 42·5%. Despite a growing population in endemic regions, P falciparum cases declined between 2005 and 2017, from 232·3 million (95% uncertainty interval 198·8-277·7) to 193·9 million (156·6-240·2) and deaths declined from 925 800 (596 900-1 341 100) to 618 700 (368 600-952 200). Despite the declines in burden, 90·1% of people within sub-Saharan Africa continue to reside in endemic areas, and this region accounted for 79·4% of cases and 87·6% of deaths in 2017. INTERPRETATION: High-resolution maps of P falciparum provide a contemporary resource for informing global policy and malaria control planning, programme implementation, and monitoring initiatives. Amid progress in reducing global malaria burden, areas where incidence trends have plateaued or increased in the past 5 years underscore the fragility of hard-won gains against malaria. Efforts towards elimination should be strengthened in such areas, and those where burden remained high throughout the study period. FUNDING: Bill & Melinda Gates Foundation.

Global estimation of anti-malarial drug effectiveness for the treatment of uncomplicated Plasmodium falciparum malaria 1991-2019.

BACKGROUND: Anti-malarial drugs play a critical role in reducing malaria morbidity and mortality, but their role is mediated by their effectiveness. Effectiveness is defined as the probability that an anti-malarial drug will successfully treat an individual infected with malaria parasites under routine health care delivery system. Anti-malarial drug effectiveness (AmE) is influenced by drug resistance, drug quality, health system quality, and patient adherence to drug use; its influence on malaria burden varies through space and time. METHODS: This study uses data from 232 efficacy trials comprised of 86,776 infected individuals to estimate the artemisinin-based and non-artemisinin-based AmE for treating falciparum malaria between 1991 and 2019. Bayesian spatiotemporal models were fitted and used to predict effectiveness at the pixel-level (5 km × 5 km). The median and interquartile ranges (IQR) of AmE are presented for all malaria-endemic countries. RESULTS: The global effectiveness of artemisinin-based drugs was 67.4% (IQR: 33.3-75.8), 70.1% (43.6-76.0) and 71.8% (46.9-76.4) for the 1991-2000, 2006-2010, and 2016-2019 periods, respectively. Countries in central Africa, a few in South America, and in the Asian region faced the challenge of lower effectiveness of artemisinin-based anti-malarials. However, improvements were seen after 2016, leaving only a few hotspots in Southeast Asia where resistance to artemisinin and partner drugs is currently problematic and in the central Africa where socio-demographic challenges limit effectiveness. The use of artemisinin-based combination therapy (ACT) with a competent partner drug and having multiple ACT as first-line treatment choice sustained high levels of effectiveness. High levels of access to healthcare, human resource capacity, education, and proximity to cities were associated with increased effectiveness. Effectiveness of non-artemisinin-based drugs was much lower than that of artemisinin-based with no improvement over time: 52.3% (17.9-74.9) for 1991-2000 and 55.5% (27.1-73.4) for 2011-2015. Overall, AmE for artemisinin-based and non-artemisinin-based drugs were, respectively, 29.6 and 36% below clinical efficacy as measured in anti-malarial drug trials. CONCLUSIONS: This study provides evidence that health system performance, drug quality and patient adherence influence the effectiveness of anti-malarials used in treating uncomplicated falciparum malaria. These results provide guidance to countries' treatment practises and are critical inputs for malaria prevalence and incidence models used to estimate national level malaria burden.

The contribution of non-malarial febrile illness co-infections to Plasmodium falciparum case counts in health facilities in sub-Saharan Africa.

BACKGROUND: The disease burden of Plasmodium falciparum malaria illness is generally estimated using one of two distinct approaches: either by transforming P. falciparum infection prevalence estimates into incidence estimates using conversion formulae; or through adjustment of counts of recorded P. falciparum-positive fever cases from clinics. Whilst both ostensibly seek to evaluate P. falciparum disease burden, there is an implicit and problematic difference in the metric being estimated. The first enumerates only symptomatic malaria cases, while the second enumerates all febrile episodes coincident with a P. falciparum infection, regardless of the fever's underlying cause. METHODS: Here, a novel approach was used to triangulate community-based data sources capturing P. falciparum infection, fever, and care-seeking to estimate the fraction of P. falciparum-positive fevers amongst children under 5 years of age presenting at health facilities that are attributable to P. falciparum infection versus other non-malarial causes. A Bayesian hierarchical model was used to assign probabilities of malaria-attributable fever (MAF) and non-malarial febrile illness (NMFI) to children under five from a dataset of 41 surveys from 21 countries in sub-Saharan Africa conducted between 2006 and 2016. Using subsequent treatment-seeking outcomes, the proportion of MAF and NMFI amongst P. falciparum-positive febrile children presenting at public clinics was estimated. RESULTS: Across all surveyed malaria-positive febrile children who sought care at public clinics across 41 country-years in sub-Saharan Africa, P. falciparum infection was estimated to be the underlying cause of only 37.7% (31.1-45.4, 95% CrI) of P. falciparum-positive fevers, with significant geographical and temporal heterogeneity between surveys. CONCLUSIONS: These findings highlight the complex nature of the P. falciparum burden amongst children under 5 years of age and indicate that for many children presenting at health clinics, a positive P. falciparum diagnosis and a fever does not necessarily mean P. falciparum is the underlying cause of the child's symptoms, and thus other causes of illness should always be investigated, in addition to prescribing an effective anti-malarial medication. In addition to providing new large-scale estimates of malaria-attributable fever prevalence, the results presented here improve comparability between different methods for calculating P. falciparum disease burden, with significant implications for national and global estimation of malaria burden.

malariaAtlas: an R interface to global malariometric data hosted by the Malaria Atlas Project.

BACKGROUND: The Malaria Atlas Project (MAP) has worked to assemble and maintain a global open-access database of spatial malariometric data for over a decade. This data spans various formats and topics, including: geo-located surveys of malaria parasite rate; global administrative boundary shapefiles; and global and regional rasters representing the distribution of malaria and associated illnesses, blood disorders, and intervention coverage. MAP has recently released malariaAtlas, an R package providing a direct interface to MAP's routinely-updated malariometric databases and research outputs. METHODS AND RESULTS: The current paper reviews the functionality available in malariaAtlas and highlights its utility for spatial epidemiological analysis of malaria. malariaAtlas enables users to freely download, visualise and analyse global malariometric data within R. Currently available data types include: malaria parasite rate and vector occurrence point data; subnational administrative boundary shapefiles; and a large suite of rasters covering a diverse range of metrics related to malaria research. malariaAtlas is here used in two mock analyses to illustrate how this data may be incorporated into a standard R workflow for spatial analysis. CONCLUSIONS: malariaAtlas is the first open-access R-interface to malariometric data, providing a new and reproducible means of accessing such data within a freely available and commonly used statistical software environment. In this way, the malariaAtlas package aims to contribute to the environment of data-sharing within the malaria research community.

Descriptive epidemiology of SARS-CoV-2 Beta (B.1.351) variant cases in England, December 2020 to June 2022.

The emergence of the SARS-CoV-2 Beta (B.1.351) variant in November 2020 raised concerns of increased transmissibility and severity. We describe the epidemiology of 949 confirmed SARS-CoV-2 Beta variant cases in England, identified between December 2020 and June 2022. Most cases were detected in the first 3 months. A total of 10 deaths (1.1%; 10/949) were identified among all cases and of those with travel information, 38 (4.9%; 38/781) cases with hospital admissions within 14 days of a positive test being detected. 52.9% (413/781) cases were imported. This study reinforces the importance of monitoring of travel-associated cases to inform public health response and reduce transmissibility of new variants.

Trends in treatment-seeking for fever in children under five years old in 151 countries from 1990 to 2020.

Access to medical treatment for fever is essential to prevent morbidity and mortality in individuals and to prevent transmission of communicable febrile illness in communities. Quantification of the rates at which treatment is accessed is critical for health system planning and a prerequisite for disease burden estimates. In this study, national data on the proportion of children under five years old with fever who were taken for medical treatment were collected from all available countries in Africa, Latin America, and Asia (n = 91). We used generalised additive mixed models to estimate 30-year trends in the treatment-seeking rates across the majority of countries in these regions (n = 151). Our results show that the proportions of febrile children brought for medical treatment increased steadily over the last 30 years, with the greatest increases occurring in areas where rates had originally been lowest, which includes Latin America and Caribbean, North Africa and the Middle East (51 and 50% increase, respectively), and Sub-Saharan Africa (23% increase). Overall, the aggregated and population-weighted estimate of children with fever taken for treatment at any type of facility rose from 61% (59-64 95% CI) in 1990 to 71% (69-72 95% CI) in 2020. The overall population-weighted average for fraction of treatment in the public sector was largely unchanged during the study period: 49% (42-58 95% CI) sought care at public facilities in 1990 and 47% (44-52 95% CI) in 2020. Overall, the findings indicate that improvements in access to care have been made where they were most needed, but that despite rapid initial gains, progress can plateau without substantial investment. In 2020 there remained significant gaps in care utilisation that must be factored in when developing control strategies and deriving disease burden estimates.

Household transmission of COVID-19 cases associated with SARS-CoV-2 delta variant (B.1.617.2): national case-control study.

BACKGROUND: The SARS-CoV-2 Delta variant (B.1.617.2), first detected in India, has rapidly become the dominant variant in England. Early reports suggest this variant has an increased growth rate suggesting increased transmissibility. This study indirectly assessed differences in transmissibility between the emergent Delta variant compared to the previously dominant Alpha variant (B.1.1.7). METHODS: A matched case-control study was conducted to estimate the odds of household transmission (≥ 2 cases within 14 days) for Delta variant index cases compared with Alpha cases. Cases were derived from national surveillance data (March to June 2021). One-to-two matching was undertaken on geographical location of residence, time period of testing and property type, and a multivariable conditional logistic regression model was used for analysis. FINDINGS: In total 5,976 genomically sequenced index cases in household clusters were matched to 11,952 sporadic index cases (single case within a household). 43.3% (n=2,586) of cases in household clusters were confirmed Delta variant compared to 40.4% (n= 4,824) of sporadic cases. The odds ratio of household transmission was 1.70 among Delta variant cases (95% CI 1.48-1.95, p <0.001) compared to Alpha cases after adjusting for age, sex, ethnicity, index of multiple deprivation (IMD), number of household contacts and vaccination status of index case. INTERPRETATION: We found evidence of increased household transmission of SARS-CoV-2 Delta variant, potentially explaining its success at displacing Alpha variant as the dominant strain in England. With the Delta variant now having been detected in many countries worldwide, the understanding of the transmissibility of this variant is important for informing infection prevention and control policies internationally.

Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study.

BACKGROUND: The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes. METHODS: This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status. FINDINGS: Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17-43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32-3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08-1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47-8·05] and for hospital admission or emergency care attendance 1·58 [0·69-3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29-4·16] and 1·43 [1·04-1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low. INTERPRETATION: This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant. FUNDING: Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research.

Risk of hospital admission for patients with SARS-CoV-2 variant B.1.1.7: cohort analysis.

OBJECTIVE: To evaluate the relation between diagnosis of covid-19 with SARS-CoV-2 variant B.1.1.7 (also known as variant of concern 202012/01) and the risk of hospital admission compared with diagnosis with wild-type SARS-CoV-2 variants. DESIGN: Retrospective cohort analysis. SETTING: Community based SARS-CoV-2 testing in England, individually linked with hospital admission data. PARTICIPANTS: 839 278 patients with laboratory confirmed covid-19, of whom 36 233 had been admitted to hospital within 14 days, tested between 23 November 2020 and 31 January 2021 and analysed at a laboratory with an available TaqPath assay that enables assessment of S-gene target failure (SGTF), a proxy test for the B.1.1.7 variant. Patient data were stratified by age, sex, ethnicity, deprivation, region of residence, and date of positive test. MAIN OUTCOME MEASURES: Hospital admission between one and 14 days after the first positive SARS-CoV-2 test. RESULTS: 27 710 (4.7%) of 592 409 patients with SGTF variants and 8523 (3.5%) of 246 869 patients without SGTF variants had been admitted to hospital within one to 14 days. The stratum adjusted hazard ratio of hospital admission was 1.52 (95% confidence interval 1.47 to 1.57) for patients with covid-19 infected with SGTF variants, compared with those infected with non-SGTF variants. The effect was modified by age (P<0.001), with hazard ratios of 0.93-1.21 in patients younger than 20 years with versus without SGTF variants, 1.29 in those aged 20-29, and 1.45-1.65 in those aged ≥30 years. The adjusted absolute risk of hospital admission within 14 days was 4.7% (95% confidence interval 4.6% to 4.7%) for patients with SGTF variants and 3.5% (3.4% to 3.5%) for those with non-SGTF variants. CONCLUSIONS: The results suggest that the risk of hospital admission is higher for people infected with the B.1.1.7 variant compared with wild-type SARS-CoV-2, likely reflecting a more severe disease. The higher severity may be specific to adults older than 30 years.

Maps and metrics of insecticide-treated net access, use, and nets-per-capita in Africa from 2000-2020.

Insecticide-treated nets (ITNs) are one of the most widespread and impactful malaria interventions in Africa, yet a spatially-resolved time series of ITN coverage has never been published. Using data from multiple sources, we generate high-resolution maps of ITN access, use, and nets-per-capita annually from 2000 to 2020 across the 40 highest-burden African countries. Our findings support several existing hypotheses: that use is high among those with access, that nets are discarded more quickly than official policy presumes, and that effectively distributing nets grows more difficult as coverage increases. The primary driving factors behind these findings are most likely strong cultural and social messaging around the importance of net use, low physical net durability, and a mixture of inherent commodity distribution challenges and less-than-optimal net allocation policies, respectively. These results can inform both policy decisions and downstream malaria analyses.

Mapping the endemicity and seasonality of clinical malaria for intervention targeting in Haiti using routine case data.

Towards the goal of malaria elimination on Hispaniola, the National Malaria Control Program of Haiti and its international partner organisations are conducting a campaign of interventions targeted to high-risk communities prioritised through evidence-based planning. Here we present a key piece of this planning: an up-to-date, fine-scale endemicity map and seasonality profile for Haiti informed by monthly case counts from 771 health facilities reporting from across the country throughout the 6-year period from January 2014 to December 2019. To this end, a novel hierarchical Bayesian modelling framework was developed in which a latent, pixel-level incidence surface with spatio-temporal innovations is linked to the observed case data via a flexible catchment sub-model designed to account for the absence of data on case household locations. These maps have focussed the delivery of indoor residual spraying and focal mass drug administration in the Grand'Anse Department in South-Western Haiti.

Spatiotemporal mapping of malaria prevalence in Madagascar using routine surveillance and health survey data.

Malaria transmission in Madagascar is highly heterogeneous, exhibiting spatial, seasonal and long-term trends. Previous efforts to map malaria risk in Madagascar used prevalence data from Malaria Indicator Surveys. These cross-sectional surveys, conducted during the high transmission season most recently in 2013 and 2016, provide nationally representative prevalence data but cover relatively short time frames. Conversely, monthly case data are collected at health facilities but suffer from biases, including incomplete reporting and low rates of treatment seeking. We combined survey and case data to make monthly maps of prevalence between 2013 and 2016. Health facility catchment populations were estimated to produce incidence rates from the case data. Smoothed incidence surfaces, environmental and socioeconomic covariates, and survey data informed a Bayesian prevalence model, in which a flexible incidence-to-prevalence relationship was learned. Modelled spatial trends were consistent over time, with highest prevalence in the coastal regions and low prevalence in the highlands and desert south. Prevalence was lowest in 2014 and peaked in 2015 and seasonality was widely observed, including in some lower transmission regions. These trends highlight the utility of monthly prevalence estimates over the four year period. By combining survey and case data using this two-step modelling approach, we were able to take advantage of the relative strengths of each metric while accounting for potential bias in the case data. Similar modelling approaches combining large datasets of different malaria metrics may be applicable across sub-Saharan Africa.

Growing evidence of Plasmodium vivax across malaria-endemic Africa.

Effective malaria control strategies require an accurate understanding of the epidemiology of locally transmitted Plasmodium species. Compared to Plasmodium falciparum infection, Plasmodium vivax has a lower asexual parasitaemia, forms dormant liver-stages (hypnozoites), and is more transmissible. Hence, treatment and diagnostic policies aimed exclusively at P. falciparum are far less efficient against endemic P. vivax. Within sub-Saharan Africa, malaria control programmes justly focus on reducing the morbidity and mortality associated with P. falciparum. However, the recent emphasis on malaria elimination and increased accessibility of more sensitive diagnostic tools have revealed greater intricacies in malaria epidemiology across the continent. Since 2010, the number of studies identifying P. vivax endemic to Africa has expanded considerably, with 88 new scientific reports published since a review of evidence in 2015, approximately doubling the available data. There is evidence of P. vivax in all regions of Africa, apparent from infected vectors, clinical cases, serological indicators, parasite prevalence, exported infections, and P. vivax-infected Duffy-negative individuals. Where the prevalence of microscopic parasitaemia is low, a greater proportion of P. vivax infections were observed relative to P. falciparum. This evidence highlights an underlying widespread presence of P. vivax across all malaria-endemic regions of Africa, further complicating the current practical understanding of malaria epidemiology in this region. Thus, ultimate elimination of malaria in Africa will require national malaria control programmes to adopt policy and practice aimed at all human species of malaria.

Quantifying the incidence of severe-febrile-illness hospital admissions in sub-Saharan Africa.

Severe-febrile-illness (SFI) is a common cause of morbidity and mortality across sub-Saharan Africa (SSA). The burden of SFI in SSA is currently unknown and its estimation is fraught with challenges. This is due to a lack of diagnostic capacity for SFI in SSA, and thus a dearth of baseline data on the underlying etiology of SFI cases and scant SFI-specific causative-agent prevalence data. To highlight the public health significance of SFI in SSA, we developed a Bayesian model to quantify the incidence of SFI hospital admissions in SSA. Our estimates indicate a mean population-weighted SFI-inpatient-admission incidence rate of 18.4 (6.8-31.1, 68% CrI) per 1000 people for the year 2014, across all ages within areas of SSA with stable Plasmodium falciparum transmission. We further estimated a total of 16,200,337 (5,993,249-27,321,779, 68% CrI) SFI hospital admissions. This analysis reveals the significant burden of SFI in hospitals in SSA, but also highlights the paucity of pathogen-specific prevalence and incidence data for SFI in SSA. Future improvements in pathogen-specific diagnostics for causative agents of SFI will increase the abundance of SFI-specific prevalence and incidence data, aid future estimations of SFI burden, and enable clinicians to identify SFI-specific pathogens, administer appropriate treatment and management, and facilitate appropriate antibiotic use.