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Characteristics of healthcare workers and health facilities associated with inaccurate recording of malaria rapid diagnostic test results: a multi-country study
No full textBackground: Malaria rapid diagnostic tests (RDTs) have improved case management and surveillance across sub-Saharan Africa by reducing presumptive treatment and enhancing diagnostic specificity. However, healthcare workers’ (HCWs) concerns about limitations of RDTs, the lack of other diagnostic tools and patient expectations may result in non-adherence to RDT outcomes in treatment decisions. This study aimed to determine associations between HCW characteristics and the accuracy of recording malaria RDT results. Methods: A multi-country, mixed-methods observational study was conducted in 64 public health facilities across Benin, Côte d’Ivoire, Nigeria, and Uganda between June and December 2023. HCW demographic characteristics, attitudes and perceptions of RDTs, and proficiency performing RDTs were collected via surveys and structured observations. Completed RDTs were photographed, interpreted by a trained panel, and compared with health facility registers. Multivariable logistic regression models were used to identify factors associated with misrecording. Results: Among more than 100,000 RDTs performed by 499 HCWs, 5.1–7.3% of results were misrecorded as positive, and 0.7–3.7% were misrecorded as negative. The test positivity rate (TPR) was highest in Côte d’Ivoire (59.7%) and lowest in Nigeria (45.3%). Overall agreement on RDT results between the external panel and the result recorded by HCWs in the health facility register ranged from 90.2% in Nigeria to 94.3% in Benin. Misrecording of negative or invalid results as positive varied by country. In Benin, older HCWs and those with stronger malaria knowledge were less likely to misrecord, but HCWs who believed patients should still be treated after a negative test were more likely to do so. In Côte d’Ivoire, community health workers had higher odds of misrecording, while higher education reduced the risk. In Nigeria, medical auxiliary staff were less likely to misrecord than other cadres. In Uganda, misrecording was more common in high-volume, high-positivity facilities and among HCWs recently observed by a supervisor. Conclusion: Misrecording of RDT results is influenced by a combination of individual, contextual, and systemic factors, with differing patterns for results misrecorded as positive and negative. Improving malaria surveillance will require interventions that address both HCW behaviour and broader facility- and system-level influences.</p
Molecular pathogenesis—Part B
No full textIn 1967, an outbreak of an unknown causative agent triggering hemorrhagic fever in laboratory workers in Europe resulted in the first discovery of filoviruses. Laboratory workers in Marburg, Frankfurt, Germany and Belgrade, Serbia, were infected with a virus that was traced back to African green monkeys (Chlorocebus sabaeus), imported from Uganda. This led to the discovery of the deadly Marburg virus (MARV). The more notorious Ebola viruses were discovered in 1976, in northern Zaire, currently known as the Democratic Republic of Congo, and in South Sudan. Shortly thereafter, the classification of the filoviridae family was established. To date, multiple filoviruses have been discovered throughout the world. The Filovirus family belong to the order Mononegavirales. Within the Marburg virus genus, there is only one virus species, MARV, though the presence of different lineages resulted in the classification of a second virus, Ravn virus (RAVN), both of which are highly pathogenic in humans. Within the Ebola virus genus, there are four members known to cause severe hemorrhagic fever in humans: Ebola virus (EBOV), Sudan virus (SUDV), Bundibugyo virus (BDBV), and Tai forest virus (TAFV). While the human pathogenic filoviruses are considered extremely dangerous with case fatality ratios of up to 90%, there are also several nonhuman pathogenic Ebola viruses, Bombali virus and Reston virus, though the reason for their lack of pathogenicity in humans is still unknown. The Arenaviridae are single-stranded ambisense RNA viruses endemic in rodent species across various geographical areas. Some are capable of zoonotic spillover to humans, frequently causing fatal viral hemorrhagic fever. There are two genera, Mammarenavirus and Reptarenavirus. The Mammarenaviruses are divided into Old World and New World viruses based on their phylogenetic, serological, and geographical distribution. The New World Arenaviruses are further divided into four lineages: clades A, B, C, and D based on their host, geographical location, antigenic cross-reactivity, and amino acid sequence differences (i.e., greater than 12% divergence in the nucleoprotein (NP) amino acid sequence). Of all the members of the Old World Arenaviridae, the Lassa fever virus (LASV) is the most economically important pathogen. It is listed as a priority pathogen and disease by the WHO and Coalition for Epidemic Preparedness Innovation (CEPI) and ranks among the top 50 pathogens with pandemic potential. Similarly, the Junin virus, which causes the Argentinian hemorrhagic disease with over five million people at risk of disease and a case fatality between 15% and 30% is the most economically important member of the New World arenavirus. It is also unique because it is the only arenavirus with an effective treatment and vaccine. This section will focus on both Lassa fever virus and Junin virus as representatives of both Old World and New World arenaviruses, respectively, with economic importance.</p
Protocol for a phase IV, Experimental Human Pneumococcal Challenge (EHPC) model to investigate Streptococcus pneumoniae serotype 3 (SPN3) colonisation following PCV15, a double-blind randomised controlled trial in healthy participants aged 18–50 years in the UK (RATIONALE-15)
Get PDFIntroduction Streptococcus pneumoniae serotype 3 (SPN3) remains a significant contributor to invasive pneumococcal disease globally, despite its inclusion in widely administered vaccines. The next generation of pneumococcal vaccines may confer better protection against this serotype, reducing disease burden. We describe an ethically approved protocol for a double-blind randomised controlled trial assessing the impact of VAXNEUVANCE (15-valent pneumococcal conjugated vaccine (PCV15)) and 0.9% saline (placebo) on the acquisition, density and duration of SPN3 carriage using a controlled human infection model. Methods and analysis Healthy adults aged 18–50 years will be randomised 1:1 to receive PCV15 or placebo. Participants will be considered enrolled on the trial at vaccination. One month following vaccination, all participants will be intranasally inoculated with SPN3. Following inoculation, participants will be followed up on days 2, 7, 14 and 28 to monitor safety, SPN3 colonisation status, density and duration, as well as immune responses. The primary endpoint of the study is to assess the rate of SPN3 acquisition between vaccinated and unvaccinated participants defined by classical microbiological methods. Secondary endpoints will determine the density and duration of SPN3 colonisation and compare the immune responses between study groups. An exploratory cohort of 5 participants will be asked to consent to a nasal biopsy procedure during a screening visit and a second nasal biopsy 28 days after PCV15 vaccination. This cohort will only receive PCV15 and will not be challenged. Through this exploratory cohort, we will explore gene expression changes induced by PCV15 vaccination and their visualisation (spatial location) within the nasal tissue. Ethics and dissemination This protocol has been reviewed by the sponsor, funder and external peer reviewers. The study is approved by the NHS Research and Ethics Committee (Reference: 24/SC/0388) and by the Medicines and Healthcare Products Regulatory Agency (Reference: CTA 21584/0485/001-0001).</p
Spatial and temporal distribution of Culex and Aedes mosquitoes in Ghana
Get PDFIn Africa, Culex is an important vector that transmits West Nile virus, whilst Aedes mosquitoes transmit dengue, yellow fever, chikungunya, and Zika. However, very limited data is available on their bionomics and ecology. Here, we provide data on the abundance and distribution of Culex and Aedes mosquitoes in Ghana between 2017 and 2025. We collected 39,761 Culex and 6,047 Aedes mosquitoes using various mosquito-trapping tools. Both vectors were predominantly observed outdoors. Aedes aegypti was the most dominant Aedes vector observed in Ghana. The invasive Aedes albopictus was sampled in 2023, whereas Aedes vittatus was observed in Accra. Our data provides important information to support vector surveillance, ecological risk assessments, and integrated vector-management strategies.</p
Peter J Diggle’s contribution to the Discussion of ‘Some statistical aspects of the COVID-19 response’ by Wood et al.
No full textIntegrative One Health strategies for the surveillance, control, and prevention of vector-borne and zoonotic diseases bridging human, animal, and environmental health in a changing world
Get PDFVector-borne and zoonotic diseases (VBZDs) represent over 75% of emerging infections globally and continue to impose severe health and economic burdens, especially in lowand middle-income countries. This review examines integrative One Health strategies for the surveillance, control, and prevention of VBZDs, emphasizing the interconnectedness of human, animal, and environmental health. Using thematic synthesis, evidence from multidisciplinary studies were analyzed to identify effective interventions and persistent challenges. The findings reveal that the environmental, socioeconomic, behavioral, climate change, and cultural factors have contributed to the emergence and global spread of these diseases, rendering public health efforts ineffective with fragmented surveillance systems, weak governance, and inequitable access impeding early outbreak detection and coordinated responses. However, hybrid and digital surveillance models, including artificial intelligencedriven and genomic tools, have demonstrated improved predictive capacity and real-time data sharing. Integrated vector management approaches combining biological, chemical, environmental measures and effective governance mechanisms show enhanced sustainability when coupled with community participation. To protect communities and reduce the burden, we recommend strengthened policy and financing frameworks such as multisectoral coordination committees, pooled One Health budgets, and legally mandated governance, promoting equitable community-driven approaches, incorporating gender-sensitive, participatory, and indigenous knowledge-based approaches. The review highlights that climate change, deforestation, and urbanization remain major drivers of VBZDs' emergence, necessitating eco-biosocial strategies that integrate environmental sustainability with health security. Achieving effective VBZDs prevention and response, therefore, requires embedding One Health principles into national health policies, leveraging technological innovation, and fostering community-centered resilience. One Health is not only a scientific paradigm but a social contract for global health equity in an era of environmental and epidemiological change.</p
Trends and patterns of insecticide susceptibility of Anopheles gambiae between 2015 and 2020: implications for malaria vector control interventions in Ghana
Get PDFBackground: The distribution and use of insecticide treated nets (ITNs) and indoor residual spraying (IRS) are the two main insecticide-based tools that have been scaled up in Ghana. Although insecticide resistance to different insecticides have been reported in parts of Ghana, there is little information on the status and extent of resistance in malaria vectors across different areas in the country. There was, therefore, a need to generate annual geographically specific insecticide resistance data to assist in the development of insecticide resistance management strategies in Ghana. This study presents five years data on monitoring of four classes of insecticides. Methods: Standard World Health Organization (WHO) insecticide susceptibility tube assays were carried out annually on adult female Anopheles gambiae reared from immature stages in 30 sentinel sites across Ghana each year from 2015 to 2020. Insecticide papers impregnated with seven insecticides in four classes were used for assays in the selected sites. PCR was performed to identify mosquito species and detect knock down resistance, kdr-west (L1014F) and acetylcholinesterase, ace-1 G119S gene mutations in forty randomly selected mosquitoes per site. Results: High resistance to pyrethroids and DDT was detected in all the sites with a decrease in susceptibility over the years. The susceptibility of carbamates and organophosphates reduced in all the sites over the 5 years. Anopheles gambiae sensu stricto (s.s.) and Anopheles coluzzii represented the two-main species of the complex living in sympatry mostly in the southern sentinel sites, with Anopheles arabiensis in smaller numbers in the northern Sahelian sites. The target site resistance frequency was significantly higher for the L1014F compared to the G119S with variations across the sites. Conclusion: Findings showed that resistance to deltamethrin, permethrin (pyrethroids), DDT (organochlorine) malathion and pirimiphos-methyl (organophosphates) and bendiocarb and propoxur (carbamates) was widespread in Ghana. There is high frequency of L1014F alleles (kdr-west) in all the sites with marginal increase for G119S ace-1 mutations. This highlights the need for continuous monitoring of the insecticide resistance of An. gambiae sensu lato in the country to ensure informed decision-making on resistance management strategies and choice of insecticides for malaria vector control in Ghana.</p
Gender disparities in complex association of metabolic syndrome with dietary habits and lifestyle risk factors in Chinese population
Get PDFThe purpose of this study is to explore individual and joint effect of comprehensive dietary habits and lifestyle on Metabolic syndrome(MetS), and its gender disparities. Data were derived from the baseline survey in the Regional Ethnic Cohort Study in northwest China. Unhealthy lifestyle index(ULI) and unhealthy dietary habits score(UDHS) were established. The association of MetS and its components with ULI or UDHS was analyzed by logistic model. The joint impact of UDHS and ULI on MetS was investigated. Potential masking effect of lifestyle was evaluated on the association between dietary habits and MetS. All analyses were conducted separately by gender. ULI was associated with a higher risk of MetS and its components, irrespective of gender. In males, higher UDHS was linked to a higher risk of MetS while in females it appeared to be associated with a lower risk of MetS. Participants with unhealthy dietary habits and an unhealthy lifestyle were found to have a higher risk of developing MetS compared to those maintaining healthy dietary habits and lifestyle, with 3.18 times(95% CI: 2.48 ~ 4.08) higher risk in males and 3.36 times(95%CI: 2.27 ~ 4.97) higher risk in females. However, females with healthy dietary habits but unhealthy lifestyle showed a higher OR of 5.52. ULI masked a 41.7% effect between UDHS and MetS in females. Unhealthy lifestyle was significantly associated with increased risk of MetS regardless of gender. Unhealthy dietary habits appear to increase the risk of MetS in males but not females. The unhealthy lifestyle may interfere with effect of unhealthy dietary habits on MetS in females. Adherence to healthy lifestyle and dietary habits would benefit prevention and control of MetS.</p
Autoantibodies against type I interferons correlate with low CD169/SIGLEC1 and severe non-viral infections in ER patients
Get PDFNeutralizing autoantibodies against type I interferons are a risk factor for multiple severe viral diseases. The timely detection of these autoantibodies remains an unmet need. We hypothesized that paradoxically low expression of type I IFN-induced CD169/SIGLEC1 expression analyzed by flow cytometry may allow rapid screening for the presence of these autoantibodies. In a prospective cohort study, we quantified monocytic CD169/SIGLEC1 expression and neutralizing autoantibodies against type I interferons in 808 patients who presented to the emergency room with signs of acute infections during the second wave of the SARS-CoV-2 pandemic in Germany in 2021. In patients, elevated CD169/SIGLEC1 (>2400 mAb/cell) demonstrated a negative predictive value of 100% for the detection of neutralizing autoantibodies against type I interferons. Low CD169/SIGLEC1 (<2400 mAb/cell) and a CRP >50 mg/L exhibited a positive predictive value of 70% for neutralizing autoantibodies against type I interferons. We further compared the adjusted odds ratio for mortality in patients with these autoantibodies to that in patients without autoantibodies against type I interferons. Neutralizing autoantibodies against type I interferons were associated with a worse clinical outcome, independent of SARS-CoV-2 infection, implying their presence is a risk factor for a worse general outcome.</p
