Gates Open Research最新文献

Typhoid intestinal perforation (TIP) is a life-threatening, late complication of typhoid fever that disproportionately impacts children in low resource settings and continues to have devastating consequences worldwide. Despite elimination of typhoid fever in most high income countries, typhoid fever and TIP remain endemic in many countries around the world as a result of inadequate investments in water, sanitation, and hygiene (WASH) and lack of access to vaccines. A first National Typhoid Conference was held in Niamey, Niger on July 22, 2023, where surgeons and other medical and health professionals from Niger convened with local and international health professionals to discuss their experiences with TIP and advocate for better prevention and treatment of the disease. The high number of intestinal perforations diagnosed during surgery, and the lack of capacity for performing blood cultures motivated surgeons in Niger to convene and share data on complications of typhoid, epidemiology, and diagnosis. TIP, a leading cause of peritonitis in Africa, often results in emergency surgery and has reported mortality rates up to 30% in pediatric patients. The availability of four safe and effective typhoid conjugate vaccines, two with committed financial support from Gavi, the Vaccine Alliance, makes prevention through vaccination a realistic near-option for typhoid fever to complement improvements in WASH.

Background: Expanding contraceptive options could better meet users' diverse needs and preferences. Annovera ^® is a contraceptive vaginal ring that provides a year of pregnancy prevention while remaining under user control and allowing for regular menstrual cycles. This method may also help to reduce burdens on some health care and supply chain systems. However, knowledge gaps exist regarding initial and ongoing acceptability of contraceptive vaginal rings in African settings.

Methods: We will undertake an open-label, non-randomized, two-arm, parallel clinical acceptability study with an embedded qualitative component, based in clinics providing contraceptive services in Kenya and Zimbabwe. Women aged 18-45 interested in newly initiating or switching contraception will choose from among all available contraceptive options, including Annovera. We aim to enroll 200 participants selecting Annovera and 200 participants selecting either contraceptive injectables or pills. We will compare method uptake, continuation, and satisfaction over one year. Participants will complete questionnaires administered by study staff during two in-person visits (a screening/enrollment visit, and an end of study visit after 52 weeks of method use or at discontinuation) and four phone appointments (at 4, 12, 24, and 36 weeks of use). We will evaluate used rings for discoloration and residual drug levels. The qualitative component involve in-depth interviews with women in the clinical study, their sexual partners, and their service providers, to further examine drivers of and barriers to interest in and use of contraceptive vaginal rings.

Discussion: This study will explore acceptability of contraceptive vaginal rings in 'real-world' contraceptive service settings in two African countries. Findings will be based on actual ring use and contextualized via comparison to two other commonly available methods. As vaginal rings are being considered for multiple reproductive health indications, this work can fill key knowledge gaps and empower decision-makers with information needed to inform future investments in reproductive health.

Background: The emergence of insecticide resistance in insects has led researchers to develop new control tools so that historic gains made in reducing disease transmission are not lost. Attractive targeted sugar baits (ATSBs) are a vector control tool being widely trialled to target insects that feed on plant sugars and blood. We designed a field-friendly, economical and more environmentally responsible sugar feeder for maintaining mosquito colonies and screening potential ATSB candidates.

Methods: We simultaneously tested, in both male and female Anopheles gambiae mosquitoes, the effect of adding three water-soluble medical and food dyes (Allura Red, fluorescein and tartrazine) to the sugar solution to identify those insects that had ingested sugar from the feeder. To test feeder efficacy to deliver a toxic substance, we assessed the killing using boric acid, which kills both male and female mosquitoes when ingested. Using microscopy techniques compatible with fieldwork, including the use of a mobile phone camera, we documented the efficacy and tissue specificity of the dyes on mosquitoes after they were continuously fed dyed sugar solutions.

Results: The easy-to-construct sugar feeder is an economical option for testing the efficacy of ATSB components on Anopheles gambiae mosquitoes . Allura Red AC was the preferred dye as it has low toxicity to mosquitoes and allows the researcher to quickly visualise the imbibed sugar meal within the abdomen. Feeding 1% fluorescein dye, but not 0.1%, for longer than five days induced systemic dye distribution, where the mosquito's wing veins, antennae and legs brightly fluoresced when examined by a handheld black light torch (395-400nm emission).

Discussion: Developing an affordable sugar feeder to maintain insectary-reared insects and test the efficacy of ATSB candidates involves designing a dye-labelled sugar bait station that is of low-toxicity, reusable and easy to construct using components available in low resource settings such as field stations.

Background: Understanding people's interest in using modern contraception is critical to ensuring programs align with people's preferences and needs. Current measures of demand for contraception are misinterpreted. More direct measures of intention to use (ITU) contraception do exist but remain underexplored. This systematic review examines the relationship between intention to use and actual use of contraception.

Methods: We searched PubMed, PsycInfo, Web of Science, and the Cochrane Collaboration to identify studies published from 1975-2020 that: (1) examined contraceptive behaviour, (2) included measures of ITU and future contraceptive use, and (3) included at least one quantitative measure of association between ITU and actual use. The inclusion criteria were: 1) examined contraceptive behaviour (excluding condom use only), (2) included disaggregated integral measures of ITU contraceptives and later contraceptive use, (3) included at least one quantitative measure of the association between ITU contraceptives and actual contraceptive use, (4) study population was women of reproductive age, (5) were peer-reviewed, and (6) written in English.

Results: 10 prospective cohort studies met the inclusion criteria; these provided 28,749 person-years of data (N=10,925). Although we could pool the data for unadjusted odds ratios, a metanalysis was not possible. We calculated that 6 of the 10 studies indicated significant, increased, unadjusted odds of subsequent contraceptive use after reporting ITU. Of those, 3 study analyses reported significant, positive adjusted odds ratios for the relationship between intention to use and later contraceptive use across varying covariates. The range of confounding factors, particularly around sub-populations, points to the need for more research so that a meta-analysis can be done in the future.

Conclusions: People's self-reported ITU contraception has the potential to be a strong predictor of subsequent contraceptive use. Few studies directly examined the relationship between ITU and contraceptive uptake and recruitment was primarily pregnant or postpartum samples.

The Kenya Multi Site Serosurveillance (KEMIS) collaboration set out to implement an integrated, nationally representative, population-based program of serological surveillance for past infection for a number of important infectious diseases in Kenya. The project started in December 2021 and built on a portfolio of SARS-CoV-2 research conducted in 2020 and 2021. In this profile paper, we describe the background of the KEMIS collaboration, its aim and objectives, the Health and Demographic Surveillance System sites that were involved in data collection, and the key activities undertaken. We also explain how we established governance and management of the KEMIS collaboration, and reflect on opportunities, challenges, lessons learned, and future directions.

Background: Disproportionate uptake of and access to maternal and child health services remain significant challenges across and within countries. Differing geographic, economic, environmental, and social factors contribute to varying degrees of vulnerabilities among individuals, which manifest as disparities in maternal and newborn health outcomes. Designing solutions according to need is vital to improve maternal and child health outcomes. In this paper, we describe our study protocol on developing and evaluating the effectiveness of human-centered design (HCD) solutions to improve maternal health service uptake among vulnerable pregnant women in rural areas of Ethiopia.

Methods: The study has two distinct phases. In Phase 1, HCD solutions were developed through co-design workshops with vulnerable pregnant women and key stakeholders. Final solutions included home visit education, audio programs promoting couple discussion, and print materials, implemented in collaboration with community health workers and health officers. A community-based, quasi-experimental, mixed-method study design was used to assess differences between intervention and control arms. A panel sample was enrolled after screening for pregnancy and vulnerability level and surveyed at baseline and midline in Phase 1. Phase 2 adopts an identical design approach with a focus on refining Phase 1 solutions. Newly recruited pregnant women will receive refined solutions for six months, which will be evaluated using post-only end-line surveys and in-depth interviews.

Conclusions and implications: Our sequential approach to evaluating initial solutions, which in turn will inform the enhancement of solutions, will provide practical insights into how solutions are accepted among vulnerable women and how they can be better integrated into women's lives and health systems. This will inform equity-focused practice and policies targeting populations experiencing greater barriers to accessing care and provide insights into system strengthening in rural areas. Our findings will be disseminated to the Ethiopian Ministry of Health and its partners to inform large-scale implementation at the national level.

Background: Adequate antenatal care (ANC) and facility-based delivery are linked to improved maternal and neonatal outcomes. Adequate ANC attendance and facility birth rates are increasing in Ethiopia but remain well below national goals and global recommendations. Group ANC (G-ANC), when implemented at higher-level facilities, is associated with improved quality and experience of ANC and increased ANC retention and facility-based delivery. The objectives of this study are to evaluate the acceptability, feasibility, and effectiveness of G-ANC delivered by health extension workers at the health-post level compared to conventional ANC on ANC attendance and facility-based delivery.

Methods: Group ANC will be piloted in five purposively selected health posts. The study design is a stepped-wedge trial to be conducted in 36 health posts within the catchment of six health centers, with randomization of the order of the intervention introduction done at the health-center level (clusters). The design includes three time periods: a six-month control period with no G-ANC implementation, followed by another six-month period when G-ANC will be introduced in half (n=18) of the study health posts, then a final six-month period when G-ANC will be implemented in the remaining 18 health posts. Each health post will form one cohort and conduct six monthly G-ANC meetings on a fixed day/time. The study will use quantitative and qualitative data collection approaches. The study has "pause and reflect" points designed for intervention iteration before rolling out to the next set of sites. The primary outcomes are the proportion of women with at least four ANC visits and the proportion who delivered in a health facility. Qualitative research will be conducted using in-depth interviews with pregnant women, health workers, facility managers, and regional health managers. The study will enroll 770 women across all phases.

Conclusions: The study will inform decision-makers locally and globally on whether G-ANC is a feasible service delivery model at the health-post level. Effectiveness of G-ANC at increasing ANC retention and facility-based delivery and its acceptability to pregnant women and health extension workers will be reported. Registration NCT05054491, ClinicalTrials.gov (September 23, 2021).

Background: The TaqMan Array Card (TAC) is an arrayed, high-throughput qPCR platform that can simultaneously detect multiple targets in a single reaction. However, the manual post-run analysis of TAC data is time consuming and subject to interpretation. We sought to automate the post-run analysis of TAC data using machine learning models.

Methods: We used 165,214 qPCR amplification curves from two studies to train and test two eXtreme Gradient Boosting (XGBoost) models. Previous manual analyses of the amplification curves by experts in qPCR analysis were used as the gold standard. First, a classification model predicted whether amplification occurred or not, and if so, a second model predicted the cycle threshold (Ct) value. We used 5-fold cross-validation to tune the models and assessed performance using accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and mean absolute error (MAE). For external validation, we used 1,472 reactions previously analyzed by 17 laboratory scientists as part of an external quality assessment for a multisite study.

Results: In internal validation, the classification model achieved an accuracy of 0.996, sensitivity of 0.997, specificity of 0.993, PPV of 0.998, and NPV of 0.991. The Ct prediction model achieved a MAE of 0.590. In external validation, the automated analysis achieved an accuracy of 0.997 and a MAE of 0.611, and the automated analysis was more accurate than manual analyses by 14 of the 17 laboratory scientists.

Conclusions: We automated the post-run analysis of highly-arrayed qPCR data using machine learning models with high accuracy in comparison to a manual gold standard. This approach has the potential to save time and improve reproducibility in laboratories using the TAC platform and other high-throughput qPCR approaches.

In the last two decades, HIV programs have been able to avert millions of AIDS-related deaths and reduce HIV incidence. However, the 1.3 million new HIV infections in 2022 remain significantly above the UNAIDS target of fewer than 370,000 new infections by 2025. HIV programs worldwide also did not achieve the UN's 90-90-90 target for testing and treatment set for 2020. Within this broader picture, HIV continues to disproportionately affect key and at-risk populations, including gay men and other men who have sex with men, female sex workers, and adolescent girls and young women. As HIV incidence declines and biomedical advances continue, it will become critical for public-health practitioners to reach key and at-risk populations with prevention services and limit primary transmission. In this Open Letter, we focus on factors that influence uptake of HIV prevention products and thereby demand for HIV prevention products and services. These factors exist at three levels of the decision-making ecosystem - the individual level, interaction level and systemic level. We argue that approaching HIV prevention solely through the lens of these levels creates a static view of prevention decision-making. There is a need instead for a dynamic viewpoint that can mirror the changing contexts in which users find themselves and make prevention decisions. We demonstrate that the current ecosystem viewpoint is useful to understand the gaps that exist in program implementation, but does not provide adequate insights into the underlying behaviors that contribute to these gaps. To address this, we suggest an approach to include dynamic aspects of decision-making with factors that influence the individual's assessment of risk, their evaluation of the opportunities to use HIV prevention, and their effective use of prevention products.

Typhoid fever is a significant public health problem endemic in Southeast Asia and Sub-Saharan Africa. Antimicrobial treatment of typhoid is however threatened by the increasing prevalence of antimicrobial resistant (AMR) S. Typhi, especially in the globally successful lineage (4.3.1) which has rapidly spread in East and Southern Africa. AMR elements can be found either on plasmids or in one of the three chromosomal integration sites, and there is variability of this across the lineage. Several previous studies with Malawian isolates indicated a clonal, locally spreading lineage with chromosomally integrated resistance genes. In a recent study however we noted three isolates with predicted resistance genes unusual for the region, and we here present the resolved genomes of these isolates using long- and short-read sequencing. Our work shows that these isolates are potentially imported cases, most closely related to the recently described sub-lineage 4.3.1.EA1, although they encode IncHI1 plasmids with reduced resistance gene repertoire compared to the main IncHI1 plasmids spreading in East Africa. Similar reduced plasmids were reported in a recent large-scale study in five isolates from Tanzania, highlighting the urgency for better coverage of the African continent in genome studies to better understand the dynamics of these potentially co-circulating plasmids.