Gates Open Research最新文献

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: 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: 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.

Effective contraceptive education is essential to reducing unwanted pregnancy, increasing uptake of modern contraceptive methods, and thoughtfully planning desired births. New World Health Organization (WHO) and family planning organization guidelines recommend situating contraceptive education and counseling within a broader context of self-care that emphasizes individual agency and reproductive empowerment. Digital health interventions, and games for health specifically, have been validated as effective and scalable tools for self-guided and interactive health education, especially among younger tech-savvy individuals. Barbados currently supplements provider-based contraceptive counseling with analog materials (pamphlets and posters) and informational videos that play on a screen in the waiting room. As part of an implementation framework, this study seeks to conduct a formative evaluation of the What's My Method? (WMM) game intervention as a tool to support contraceptive counseling and increase reproductive empowerment among childbearing persons in Barbados. We test-deployed the WMM game in Bridgetown, Barbados, conducting playtests and unstructured discussions with prototypes of the WMM game among three groups of stakeholders (youth contraception ambassadors: n=8; healthcare providers: n=7; and nursing students: n=27) to determine acceptability of the intervention, efficacy of the game as a learning tool, and willingness to adopt the tool in their healthcare context. Feedback on acceptability of the game was largely positive. Detailed constructive comments informed modifications and improvements to the game. The questionnaire used to assess contraceptive knowledge gain did not prove effective. Results indicate that the WMM game is well-received and accepted by the healthcare professionals who would be deploying it. This pilot testing has informed the design of the modified WMM for a randomized controlled trial (RCT) to test the deployment of the game in a healthcare setting.

Faced with declining donor funding for HIV, low- and middle-income countries must identify efficient and cost-effective ways to integrate HIV prevention programs into public health systems for long-term sustainability. In Zambia, donor support to the voluntary medical male circumcision (VMMC) program, which previously funded non-governmental organizations as implementing partners, is increasingly being directed through government structures instead. We developed a framework to understand how the behaviors of individual decision-makers within the government could be barriers to this transition. We interviewed key stakeholders from the national, provincial, and district levels of the Ministry of Health, and from donors and partners funding and implementing Zambia's VMMC program, exploring the decisions required to attain a sustainable VMMC program and the behavioral dynamics involved at personal and institutional levels. Using pattern identification and theme matching to analyze the content of the responses, we derived three core decision-making phases in the transition to a sustainable VMMC program: 1) developing an alternative funding strategy, 2) developing a policy for early-infant (0-2 months) and early-adolescent (15-17 years) male circumcision, which is crucial to sustainable HIV prevention; and 3) identifying integrated and efficient implementation models. We formulated a framework showing how, in each phase, a range of behavioral dynamics can form barriers that hinder effective decision-making among stakeholders at the same level (e.g., national ministries and donors) or across levels (e.g., national, provincial and district). Our research methodology and the resulting framework offer a systematic approach for in-depth investigations into organizational decision-making in public health programs, as well as development programs beyond VMMC and HIV prevention. It provides the insights necessary to map organizational development and policy-making transition plans to sustainability, by explaining tangible factors such as organizational processes and systems, as well as intangibles such as the behaviors of policymakers and institutional actors.

Background: South African adolescents experience barriers to sexual and reproductive health (SRH) knowledge and uptake. This study provides insight into contraceptive and other SRH service knowledge, perceptions, and uptake among adolescents in high HIV prevalence settings.

Methods: A baseline cross sectional survey was conducted among 3432 grade 8s enrolled into the Girls Achieve Power (GAP Year) trial from 26 public high schools across three South African townships (Soweto, Thembisa and Khayelitsha) (2017 - 2018). An interviewer-led survey collected information on SRH knowledge and perceptions; an audio computer-assisted self-interviewing technique gathered SRH service uptake. Descriptive analysis indicates frequency distribution of socio-demographics and knowledge, uptake and perceptions of SRH services. Chi-square test tested for associations between age and sex and selected variables that measure SRH knowledge and uptake.

Results: In total, 2383 participants completed both survey components. Of these, 63.1% (n=1504) were female and 81.4% (n=1938) aged 12-14. Almost a fifth (18.3%, n=436) had ever had sex and less than 1% had accessed SRH services in the last year. Of the 157 females who had ever had sex, 50.9% had ever used contraception. Of those who had sex in the last three months, 59.0% reported using a contraceptive method. Condom use was inconsistent: almost all females said they had not used or could not remember if a condom was used at last sex.

Conclusion: This paper contributes to the evidence strengthening learner SRH education, including the national Integrated School Health Programme. Key themes include the need for age-appropriate, differentiated comprehensive sexuality education (CSE) for the range of ages found in the same grade in South African schools. Education on different contraceptive methods, informed decision-making, and emergency contraception is key. School-based interventions should embrace integrated HIV, STI, and pregnancy prevention messages. Closer links with health services need to be constantly fostered and reinforced.

Background: The global prevalence of diseases transmitted by Aedes aegypti mosquitoes, such as dengue, Zika and Yellow Fever, is increasing, but development of promising new mosquito control technologies could reverse this trend. Target Product Profiles (TPPs) and Preferred Product Characteristics (PPCs) documents issued by the World Health Organization can guide the research and development pathways of new products and product combinations transitioning from proof of concept to operational use.

Methods: We used high resolution global maps of the case and economic burden of dengue to derive programmatic cost targets to support a TPP for Wolbachia replacement. A compartmental entomological model was used to explore how release size, spacing and timing affect replacement speed and acceptability. To support a PPC for a hybrid suppress-then-replace approach we tested whether Wolbachia replacement could be achieved faster, more acceptably or at a lower cost if preceded by a mosquito suppression programme.

Results: We show how models can reveal trade-offs, identify quantitative thresholds and prioritise areas and intervention strategies for further development. We estimate that for Wolbachia replacement to be deployable in enough areas to make major contributions to reducing global dengue burden by 25% (in line with 2030 WHO targets), it must have the potential for cost to be reduced to between $7.63 and $0.24 (USD) per person protected or less. Suppression can reduce the number of Wolbachia mosquitoes necessary to achieve replacement fixation by up to 80%. A hybrid approach can also achieve fixation faster and potentially improve acceptability, but may not justify their cost if they require major new investments in suppression technologies.

Conclusions: Here we demonstrate the value dedicated modelling can provide for interdisciplinary groups of experts when developing TPPs and PPCs. These models could be used by product developers to prioritise and shape development decisions for new Wolbachia replacement products.