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Dynamics of asymptomatic Plasmodium falciparum and Plasmodium vivax infections and their infectiousness to mosquitoes in a low transmission setting of Ethiopia: a longitudinal observational study.
Get PDFObjective: A 15-month longitudinal study was conducted to determine the duration and infectivity of asymptomatic qPCR-detected Plasmodium falciparum and Plasmodium vivax infections in Ethiopia.
Method: Total parasite and gametocyte kinetics were determined by molecular methods; infectivity to Anopheles arabiensis mosquitoes by repeated membrane feeding assays. Infectivity results were contrasted with passively recruited symptomatic malaria cases.
Results: For P. falciparum and P. vivax infections detected at enrolment, median durations of infection were 37 days (95% confidence interval [CI], 15-93) and 60 days (95% CI, 18-213), respectively. P. falciparum and P. vivax parasite densities declined over the course of infections. From 47 feeding assays on 22 asymptomatic P. falciparum infections, 6.4% (3/47) were infectious and these infected 1.8% (29/1579) of mosquitoes. No transmission was observed in feeding assays on asymptomatic P. vivax mono-infections (0/56); one mixed-species infection was highly infectious. Among the symptomatic cases, 4.3% (2/47) of P. falciparum and 73.3% (53/86) of P. vivax patients were infectious to mosquitoes.
Conclusion: The majority of asymptomatic infections were of short duration and low parasite density. Only a minority of asymptomatic individuals were infectious to mosquitoes. This contrasts with earlier findings and is plausibly due to the low parasite densities in this population
The Use of Evidence to Design an Essential Package of Health Services in Pakistan: A Review and Analysis of Prioritisation Decisions at Different Stages of the Appraisal Process.
Get PDFBACKGROUND: Pakistan embarked on a process of designing an essential package of health services (EPHS) as a pathway towards universal health coverage (UHC). The EPHS design followed an evidence-informed deliberative process; evidence on 170 interventions was introduced along multiple stages of appraisal engaging different stakeholders tasked with prioritising interventions for inclusion. We report on the composition of the package at different stages, analyse trends of prioritised and deprioritised interventions and reflect on the trade-offs made.
METHODS: Quantitative evidence on cost-effectiveness, budget impact, and avoidable burden of disease was presented to stakeholders in stages. We recorded which interventions were prioritised and deprioritised at each stage and carried out three analyses: (1) a review of total number of interventions prioritised at each stage, along with associated costs per capita and disability-adjusted life years (DALYs) averted, to understand changes in affordability and efficiency in the package, (2) an analysis of interventions broken down by decision criteria and intervention characteristics to analyse prioritisation trends across different stages, and (3) a description of the trajectory of interventions broken down by current coverage and cost-effectiveness.
RESULTS: Value for money generally increased throughout the process, although not uniformly. Stakeholders largely prioritised interventions with low budget impact and those preventing a high burden of disease. Highly cost-effective interventions were also prioritised, but less consistently throughout the stages of the process. Interventions with high current coverage were overwhelmingly prioritised for inclusion.
CONCLUSION: Evidence-informed deliberative processes can produce actionable and affordable health benefit packages. While cost-effective interventions are generally preferred, other factors play a role and limit efficiency
Detecting changes in generation and serial intervals under varying pathogen biology, contact patterns and outbreak response.
Get PDFThe epidemiological characteristics of SARS-CoV-2 transmission have changed over the pandemic due to emergence of new variants. A decrease in the generation or serial intervals would imply a shortened transmission timescale and, hence, outbreak response measures would need to expand at a faster rate. However, there are challenges in measuring these intervals. Alongside epidemiological changes, factors like varying delays in outbreak response, social contact patterns, dependence on the growth phase of an outbreak, and effects of exposure to multiple infectors can also influence measured generation or serial intervals. To guide real-time interpretation of variant data, we simulated concurrent changes in the aforementioned factors and estimated the statistical power to detect a change in the generation and serial interval. We compared our findings to the reported decrease or lack thereof in the generation and serial intervals of different SARS-CoV-2 variants. Our study helps to clarify contradictory outbreak observations and informs the required sample sizes under certain outbreak conditions to ensure that future studies of generation and serial intervals are adequately powered
The absence of mandatory pregnancy warning labels in online alcohol purchasing contexts.
Get PDFINTRODUCTION: As people increasingly migrate to online shopping platforms, hard-won improvements in requirements for consumer information provision at the point of sale are being eroded. An example is the alcohol pregnancy warning label for packaged alcoholic beverages that has been recently introduced in Australia and New Zealand. The aim of the present study was to assess the extent to which the pregnancy warning was visible at the online point of sale when the requirement became mandatory in August 2023.
METHODS: Data for alcohol products sold on the websites of the two largest alcohol retailers in Australia were web-scraped from 1 to 3 August 2023. The captured data for 8343 alcoholic beverages were inspected to determine whether the pregnancy warning was visible.
RESULTS: Virtually no products (0.1%) had the mandatory warning visible on the main sales page, and only 7% enabled visibility of the warning via optional product image rotation functionality.
DISCUSSION AND CONCLUSIONS: The almost complete absence of the mandatory pregnancy warnings on the main product pages of major alcohol retailers' websites highlights the regulatory problems posed by the emerging shift to online shopping. The very low prevalence of visible pregnancy warnings is likely to be an overestimate of the extent to which consumers would be exposed to warnings due to images being counted as being present regardless of their quality or readability. New regulation is needed to ensure that mandatory information requirements for harmful products are applied to online shopping contexts
The Rapid Assessment of Avoidable Blindness survey: Review of the methodology and protocol for the seventh version (RAAB7).
Get PDFThe Rapid Assessment of Avoidable Blindness (RAAB) is a population-based cross-sectional survey methodology used to collect data on the prevalence of vision impairment and its causes and eye care service indicators among the population 50 years and older. RAAB has been used for over 20 years with modifications to the protocol over time reflected in changing version numbers; this paper describes the latest version of the methodology-RAAB7. RAAB7 is a collaborative project between the International Centre for Eye Health and Peek Vision with guidance from a steering group of global eye health stakeholders. We have fully digitised RAAB, allowing for fast, accurate and secure data collection. A bespoke Android mobile application automatically synchronises data to a secure Amazon Web Services virtual private cloud when devices are online so users can monitor data collection in real-time. Vision is screened using Peek Vision's digital visual acuity test for mobile devices and uncorrected, corrected and pinhole visual acuity are collected. An optional module on Disability is available. We have rebuilt the RAAB data repository as the end point of RAAB7's digital data workflow, including a front-end website to access the past 20 years of RAAB surveys worldwide. This website ( https://www.raab.world) hosts open access RAAB data to support the advocacy and research efforts of the global eye health community. Active research sub-projects are finalising three new components in 2024-2025: 1) Near vision screening to address data gaps on near vision impairment and effective refractive error coverage; 2) an optional Health Economics module to assess the affordability of eye care services and productivity losses associated with vision impairment; 3) an optional Health Systems data collection module to support RAAB's primary aim to inform eye health service planning by supporting users to integrate eye care facility data with population data
Lessons learned from implementation of four HIV self-testing (HIVST) distribution models in Zambia: applying the Consolidated Framework for Implementation Research to understand impact of contextual factors on implementation.
Get PDFBACKGROUND: Although Zambia has integrated HIV-self-testing (HIVST) into its Human Immunodeficiency Virus (HIV) regulatory frameworks, few best practices to optimize the use of HIV self-testing to increase testing coverage have been documented. We conducted a prospective case study to understand contextual factors guiding implementation of four HIVST distribution models to inform scale-up in Zambia.
METHODS: We used the qualitative case study method to explore user and provider experiences with four HIVST distribution models (two secondary distribution models in Antenatal Care (ANC) and Antiretroviral Therapy (ART) clinics, community-led, and workplace) to understand factors influencing HIVST distribution. Participants were purposefully selected based on their participation in HIVST and on their ability to provide rich contextual experience of the distribution models. Data were collected using observations (n = 31), group discussions (n = 10), and in-depth interviews (n = 77). Data were analyzed using the thematic approach and aligned to the four Consolidated Framework for Implementation Research (CFIR) domains.
RESULTS: Implementation of the four distribution models was influenced by an interplay of outer and inner setting factors. Inadequate compensation and incentives for distributors may have contributed to distributor attrition in the community-led and workplace HIVST models. Stockouts, experienced at the start of implementation in the secondary-distribution and community-led distribution models often disrupted distribution. The existence of policy and practices aided integration of HIVST in the workplace. External factors complimented internal factors for successful implementation. For instance, despite distributor attrition leading to excessive workload, distributors often multi-tasked to keep up with demand for kits, even though distribution points were geographically widespread in the workplace, and to a less extent in the community-led models. Use of existing communication platforms such as lunchtime and safety meetings to promote and distribute kits, peers to support distributors, reduction in trips by distributors to replenish stocks, increase in monetary incentives and reorganisation of stakeholder roles proved to be good adaptations.
CONCLUSION: HIVST distribution was influenced by a combination of contextual factors in variable ways. Understanding how the factors interacted in real world settings informed adaptations to implementation devised to minimize disruptions to distribution
New reference genomes to distinguish the sympatric malaria parasites, Plasmodium ovale curtisi and Plasmodium ovale wallikeri.
Get PDFDespite Plasmodium ovale curtisi (Poc) and wallikeri (Pow) being important human-infecting malaria parasites that are widespread across Africa and Asia, little is known about their genome diversity. Morphologically identical, Poc and Pow are indistinguishable and commonly misidentified. Recent rises in the incidence of Poc/Pow infections have renewed efforts to address fundamental knowledge gaps in their biology, and to develop diagnostic tools to understand their epidemiological dynamics and malaria burden. A major roadblock has been the incompleteness of available reference assemblies (PocGH01, PowCR01; ~ 33.5 Mbp). Here, we applied multiple sequencing platforms and advanced bioinformatics tools to generate new reference genomes, Poc221 (South Sudan; 36.0 Mbp) and Pow222 (Nigeria; 34.3 Mbp), with improved nuclear genome contiguity (> 4.2 Mbp), annotation and completeness (> 99% Plasmodium spp., single copy orthologs). Subsequent sequencing of 6 Poc and 15 Pow isolates from Africa revealed a total of 22,517 and 43,855 high-quality core genome SNPs, respectively. Genome-wide levels of nucleotide diversity were determined to be 2.98 × 10-4 (Poc) and 3.43 × 10-4 (Pow), comparable to estimates for other Plasmodium species. Overall, the new reference genomes provide a robust foundation for dissecting the biology of Poc/Pow, their population structure and evolution, and will contribute to uncovering the recombination barrier separating these species
Time of exposure and assessment influence the mortality induced by insecticides against metabolic resistant mosquitoes.
Get PDFBACKGROUND: Increasing metabolic resistance in malaria vector mosquitoes resulted in the development of insecticide-treated nets (ITNs) with active ingredients (AI) that target them. Bioassays that accurately measure the mortality induced by these AIs on ITNs are needed. Mosquito metabolic enzyme expression follows a circadian rhythm. Thus, this study assessed (i) influence of the time of day of mosquito exposure and (ii) timing of assessment of mortality post exposure (24 and 72 h) to ITNs against vectors that are susceptible to pyrethroids and those with metabolic and knockdown resistance mechanisms.
METHODS: Two cone bioassay experiments were conducted following World Health Organization (WHO) guidelines. Firstly, on ITNs incorporated with 2 g AI/kg of deltamethrin (DM) alone, or combined with 8 g AI/kg piperonyl butoxide (PBO) synergist, during the day (9:00-14:00 h) and repeated in the evening (18:00-20:00 h). This was followed by a confirmatory experiment during the afternoon (12:00-14:00 h) and repeated in the night (22:00-24:00 h) using mosquitoes unexposed or pre-exposed to PBO for 1 h before exposure to DM ITNs. Each net piece was tested with a minimum of eight cones per time (N = 24). The outcome was mortality after 24 h (M24) or 72 h (M72) of holding.
RESULTS: The cone bioassays performed using metabolic resistant mosquitoes during the evening showed significantly lower M24 than those performed in the day for DM: odds ratio (OR) 0.14 [95% confidence interval (CI) 0.06-0.30, p < 0.0001] and DM PBO [OR 0.29 (95% CI 0.18-0.49, p < 0.0001). M72 was higher than M24 for metabolic resistant mosquitoes exposed to DM [OR 1.44 (95% CI 1.09-1.88), p = 0.009] and DM PBO [OR 1.82 (95% CI 1.42-2.34), p < 0.0001]. An influence of hour of experiment and time of assessment was not observed for mosquitoes that had knockdown resistance or that were pyrethroid-susceptible.
CONCLUSIONS: Time of day of experiment and hour of assessment of delayed mortality after exposure of mosquitoes are important considerations in evaluating insecticides that interact with mosquito metabolism to counter metabolic resistant mosquitoes. This is important when evaluating field-aged ITNs that may have lower concentrations of AI
Making the most of malaria chemoprevention.
Get PDFAgainst a backdrop of stalled progress in malaria control, it is surprising that the various forms of malaria chemoprevention are not more widely used. The World Health Organization (WHO) has recommended several malaria chemoprevention strategies, some of them for over a decade, and each with documented efficacy and cost effectiveness. In 2022, the WHO updated and augmented its malaria chemoprevention guidelines to facilitate their wider use. This paper considers new insights into the empirical evidence that supports the broader application of chemoprevention and encourages its application as a default strategy for young children living in moderate to high transmission settings given their high risk of severe disease and death. Chemoprevention is an effective medium-term strategy with potential benefits far outweighing costs. There is a strong argument for urgently increasing malaria chemoprevention in endemic countries
Sanitation in urban areas may limit the spread of antimicrobial resistance via flies.
Get PDFSynanthropic filth flies are common where sanitation is poor and fecal wastes are accessible to them. These flies have been proposed as mechanical vectors for the localized transport of fecal microbes including antimicrobial resistant (AMR) organisms and associated antimicrobial resistance genes (ARGs), increasing exposure risks. We evaluated whether an onsite sanitation intervention in Maputo, Mozambique reduced the concentration of enteric bacteria and the frequency of detection of ARGs carried by flies collected in household compounds of low-income neighborhoods. Additionally, we assessed the phenotypic resistance profile of Enterobacteriaceae isolates recovered from flies during the pre-intervention phase. After fly enumeration at study compounds, quantitative polymerase chain reaction was used to quantify an enteric 16S rRNA gene (i.e., specific to a cluster of phylotypes corresponding to 5% of the human fecal microflora), 28 ARGs, and Kirby Bauer Disk Diffusion of Enterobacteriaceae isolates was utilized to assess resistance to eleven clinically relevant antibiotics. The intervention was associated with a 1.5 log10 reduction (95% confidence interval: -0.73, -2.3) in the concentration of the enteric 16S gene and a 31% reduction (adjusted prevalence ratio = 0.69, [0.52, 0.92]) in the mean number of ARGs per fly compared to a control group with poor sanitation. This protective effect was consistent across the six ARG classes that we detected. Enterobacteriaceae isolates-only from the pre-intervention phase-were resistant to a mean of 3.4 antibiotics out of the eleven assessed. Improving onsite sanitation infrastructure in low-income informal settlements may help reduce fly-mediated transmission of enteric bacteria and the ARGs carried by them