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The 2022 global mpox outbreak raises questions about how this zoonotic disease established effective human-to-human transmission and its potential for further adaptation. The 2022 outbreak virus is related to an ongoing outbreak in Nigeria originally reported in 2017, but the evolutionary path linking the two remains unclear due to a lack of genomic data between 2018, when virus exportations from Nigeria were first recorded, and 2022, when the global mpox outbreak began. Here, 18 viral genomes obtained from patients across southern Nigeria in 2019-2020 reveal multiple lineages of monkeypox virus (MPXV) co-circulated in humans for several years before 2022, with progressive accumulation of mutations consistent with APOBEC3 activity over time. We identify Nigerian A.2 lineage isolates, confirming the lineage that has been multiply exported to North America independently of the 2022 outbreak originated in Nigeria, and that it has persisted by human-to-human transmission in Nigeria for more than 2 years before its latest exportation. Finally, we identify a lineage-defining APOBEC3-style mutation in all A.2 isolates that disrupts gene A46R, encoding a viral innate immune modulator. Collectively, our data demonstrate MPXV capacity for sustained diversification within humans, including mutations that may be consistent with established mechanisms of poxvirus adaptation.
BackgroundWidespread artemisinin resistance in Africa could be catastrophic when drawing parallels with the failure of chloroquine in the 1970s and 1980s. This article explores the role of anti-malarial market characteristics in the emergence and spread of arteminisin resistance in African countries, drawing on perspectives from Burkina Faso.MethodsData were collected through in-depth interviews and focus group discussions. A representative sample of national policy makers, regulators, public and private sector wholesalers, retailers, clinicians, nurses, and community members were purposively sampled. Additional information was also sought via review of policy publications and grey literature on anti-malarial policies and deployment practices in Burkina Faso.ResultsThirty seven in-depth interviews and 6 focus group discussions were conducted. The study reveals that the current operational mode of anti-malarial drug markets in Burkina Faso promotes arteminisin resistance emergence and spread. The factors are mainly related to the artemisinin-based combination therapy (ACT) supply chain, to ACT quality, ACT prescription monitoring and to ACT access and misuse by patients.ConclusionStudy findings highlight the urgent requirement to reform current characteristics of the anti-malarial drug market in order to delay the emergence and spread of artemisinin resistance in Burkina Faso. Four recommendations for public policy emerged during data analysis: (1) Address the suboptimal prescription of anti-malarial drugs, (2) Apply laws that prohibit the sale of anti-malarials without prescription, (3) Restrict the availability of street drugs, (4) Sensitize the population on the value of compliance regarding correct acquisition and intake of anti-malarials. Funding systems for anti-malarial drugs in terms of availability and accessibility must also be stabilized.
Prevalence and Risk Factors of Neonatal Hyperbilirubinemia in a Semi-Rural Area of the Democratic Republic of Congo: A Cohort Study
Neonatal hyperbilirubinemia (NH) is a frequent condition that, if left untreated, can lead to neurological disability and death. We assessed the prevalence of NH and associated neonatal and maternal risk factors in 362 mothers and 365 newborns in a semi-rural area of the Democratic Republic of Congo. In addition, we explored the knowledge and practices of mothers regarding this condition. We collected demographic data, anthropometric data, and obstetric and medical anamneses. We examined newborns at birth and at 24, 48, and 72 hours and measured bilirubin at birth in umbilical cord and capillary blood and thereafter in capillary blood. Hemoglobin, hematocrit, ABO group, Rhesus factor, glucose-6-phosphate dehydrogenase (G6PD) deficiency, Hemoglobin S (HbS), and malaria were assessed in mothers and newborns. Among 296 newborns (all time points available), 5.7% developed NH (95% CI: 3.4–9.0) between 24 and 72 hours according to National Institute for Health and Care Excellence (NICE) UK guidelines. There was a significantly higher risk in newborns with G6PD deficiency (homo- and hemizygous adjusted Odd Ratio [aOR]: 21.0, 95% CI: 4.1–105.9), preterm births (aOR: 6.1, 95% CI: 1.4–26.9), newborns with excessive birth weight loss (aOR: 5.8, 95% CI: 1.4–23.2), and hyperbilirubinemia at birth (aOR: 14.8, 95% CI: 2.7–79.6). Newborns with feto-maternal ABO incompatibility and G6PD deficiency had significantly higher bilirubin at birth than others. More than 60% of mothers had adequate knowledge of NH, but compliance with phototherapy in the absence of symptoms was low. Although risk factors for NH are common in this area, prevalence was not high, suggesting a need for better case definition. Implementation of point-of-care devices for diagnosis and awareness programs on risk prevention could help reduce neonatal morbidity and mortality associated with hyperbilirubinemia in these areas.
Genetic surveillance in the Greater Mekong Subregion and South Asia to support malaria control and elimination
ABSTRACTNational Malaria Control Programmes (NMCPs) currently make limited use of parasite genetic data. We have developed GenRe-Mekong, a platform for genetic surveillance of malaria in the Greater Mekong Subregion (GMS) that enables NMCPs to implement large-scale surveillance projects by integrating simple sample collection procedures in routine public health procedures. Samples are processed by high-throughput technologies to genotype several drug resistance markers, species markers and a genomic barcode, delivering reports of genotypes and phenotype predictions, used to map prevalence of resistance to multiple drugs. GenRe-Mekong has worked with NMCPs and research projects in eight countries, processing 9,623 samples from clinical cases. Monitoring resistance markers has been valuable for tracking the rapid spread of parasites resistant to the dihydroartemisinin-piperaquine combination therapy. In Vietnam and Laos, GenRe-Mekong data have provided novel knowledge about the spread of these resistant strains into previously unaffected provinces. GenRe-Mekong facilitates data sharing by aggregating results from different countries, enabling cross-border resistance monitoring.Impact StatementLarge-scale genetic surveillance of malaria implemented by National Malaria Control Programmes informs public health decision makers about the spread of strains resistant to antimalarials.FundingBill & Melinda Gates Foundation, Wellcome Trust, UK Medical Research Council, UK Department for International Development, NIAID
ABSTRACT Enteric fever, caused by oral infection with typhoidal Salmonella serovars, presents as a non-specific febrile illness preceded by an incubation period of 5 days or more. The enteric fever human challenge model provides a unique opportunity to investigate the innate immune response during this incubation period, and how this response is altered by vaccination with the Vi polysaccharide or conjugate vaccine. We find that on the same day as ingestion of typhoidal Salmonella , there is already evidence of an immune response, with 199 genes upregulated in the peripheral blood transcriptome 12 hours post-challenge (false discovery rate <0.05). Gene sets relating to neutrophils, monocytes, and innate immunity were over-represented (false discovery rate <0.05). Estimating cell proportions from gene expression data suggested a possible increase in activated monocytes 12 hours post-challenge ( P = 0.036, paired Wilcoxon signed-rank test). Furthermore, plasma TNF-α rose following exposure ( P = 0.011, paired Wilcoxon signed-rank test). There were no significant differences in gene expression (false discovery rate <0.05) in the 12 hours response between those who did and did not subsequently develop clinical or blood culture confirmed enteric fever or between vaccination groups. Together, these results demonstrate early perturbation of the peripheral blood transcriptome after enteric fever challenge and provide initial insight into early mechanisms of protection.
This study summarizes progress made in rolling out COVID-19 vaccinations in the African region in 2022, and analyzes factors associated with vaccination coverage. Data on vaccine uptake reported to the World Health Organization (WHO) Regional Office for Africa by Member States between January 2021 and December 2022, as well as publicly available health and socio-economic data, were used. A negative binomial regression was performed to analyze factors associated with vaccination coverage in 2022. As of the end of 2022, 308.1 million people had completed the primary vaccination series, representing 26.4% of the region's population, compared to 6.3% at the end of 2021. The percentage of health workers with complete primary series was 40.9%. Having carried out at least one high volume mass vaccination campaign in 2022 was associated with high vaccination coverage (β = 0.91, p < 0.0001), while higher WHO funding spent per person vaccinated in 2022 was correlated with lower vaccination coverage (β = -0.26, p < 0.03). All countries should expand efforts to integrate COVID-19 vaccinations into routine immunization and primary health care, and increase investment in vaccine demand generation during the transition period that follows the acute phase of the pandemic.
Quality of maternal healthcare and travel time influence birthing service utilisation in Ghanaian health facilities: a geographical analysis of routine health data.
ObjectivesTo investigate how the quality of maternal health services and travel times to health facilities affect birthing service utilisation in Eastern Region, Ghana.DesignThe study is a cross-sectional spatial interaction analysis of birth service utilisation patterns. Routine birth data were spatially linked to quality care, service demand and travel time data.Setting131 Health facilities (public, private and faith-based) in 33 districts in Eastern Region, Ghana.ParticipantsWomen who gave birth in health facilities in the Eastern Region, Ghana in 2017.Outcome measuresThe count of women giving birth, the quality of birthing care services and the geographic coverage of birthing care services.ResultsAs travel time from women's place of residence to the health facility increased up to two2 hours, the utilisation rate markedly decreased. Higher quality of maternal health services haves a larger, positive effect on utilisation rates than service proximity. The quality of maternal health services was higher in hospitals than in primary care facilities. Most women (88.6%) travelling via mechanised transport were within two2 hours of any birthing service. The majority (56.2%) of women were beyond the two2 -hour threshold of critical comprehensive emergency obstetric and newborn care (CEmONC) services. Few CEmONC services were in urban centres, disadvantaging rural populations.ConclusionsTo increase birthing service utilisation in Ghana, higher quality health facilities should be located closer to women, particularly in rural areas. Beyond Ghana, routinely collected birth records could be used to understand the interaction of service proximity and quality.
Spatio-temporal modelling of routine health facility data for malaria risk micro-stratification in mainland Tanzania.
As malaria transmission declines, the need to monitor the heterogeneity of malaria risk at finer scales becomes critical to guide community-based targeted interventions. Although routine health facility (HF) data can provide epidemiological evidence at high spatial and temporal resolution, its incomplete nature of information can result in lower administrative units without empirical data. To overcome geographic sparsity of data and its representativeness, geo-spatial models can leverage routine information to predict risk in un-represented areas as well as estimate uncertainty of predictions. Here, a Bayesian spatio-temporal model was applied on malaria test positivity rate (TPR) data for the period 2017-2019 to predict risks at the ward level, the lowest decision-making unit in mainland Tanzania. To quantify the associated uncertainty, the probability of malaria TPR exceeding programmatic threshold was estimated. Results showed a marked spatial heterogeneity in malaria TPR across wards. 17.7 million people resided in areas where malaria TPR was high (≥ 30; 90% certainty) in the North-West and South-East parts of Tanzania. Approximately 11.7 million people lived in areas where malaria TPR was very low (
Geographic accessibility and hospital competition for emergency blood transfusion services in Bungoma, Western Kenya.
BackgroundEstimating accessibility gaps to essential health interventions helps to allocate and prioritize health resources. Access to blood transfusion represents an important emergency health requirement. Here, we develop geo-spatial models of accessibility and competition to blood transfusion services in Bungoma County, Western Kenya.MethodsHospitals providing blood transfusion services in Bungoma were identified from an up-dated geo-coded facility database. AccessMod was used to define care-seeker's travel times to the nearest blood transfusion service. A spatial accessibility index for each enumeration area (EA) was defined using modelled travel time, population demand, and supply available at the hospital, assuming a uniform risk of emergency occurrence in the county. To identify populations marginalized from transfusion services, the number of people outside 1-h travel time and those residing in EAs with low accessibility indexes were computed at the sub-county level. Competition between the transfusing hospitals was estimated using a spatial competition index which provided a measure of the level of attractiveness of each hospital. To understand whether highly competitive facilities had better capacity for blood transfusion services, a correlation test between the computed competition metric and the blood units received and transfused at the hospital was done.Results15 hospitals in Bungoma county provide transfusion services, however these are unevenly distributed across the sub-counties. Average travel time to a blood transfusion centre in the county was 33 min and 5% of the population resided outside 1-h travel time. Based on the accessibility index, 38% of the EAs were classified to have low accessibility, representing 34% of the population, with one sub-county having the highest marginalized population. The computed competition index showed that hospitals in the urban areas had a spatial competitive advantage over those in rural areas.ConclusionThe modelled spatial accessibility has provided an improved understanding of health care gaps essential for health planning. Hospital competition has been illustrated to have some degree of influence in provision of health services hence should be considered as a significant external factor impacting the delivery, and re-design of available services.