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Mosquitoes Reared in Nearby Insectaries at the Same Institution Have Significantly Divergent Microbiomes
Get PDFThe microbiome influences critical aspects of mosquito biology and variations in microbial composition can impact the outcomes of laboratory studies. To investigate how biotic and abiotic conditions in an insectary affect the composition of the mosquito microbiome, a single cohort of Aedes aegypti eggs was divided into three batches and transferred to three different climate-controlled insectaries within the Liverpool School of Tropical Medicine. The bacterial microbiome composition was compared as mosquitoes developed, the microbiome of the mosquitoes' food sources was characterised, environmental conditions over time in each insectary were measured, and mosquito development and survival were recorded. While developmental success was similar across all three insectaries, differences in microbiome composition were observed between mosquitoes from each insectary. Environmental conditions and bacterial input via food sources varied between insectaries, potentially contributing to the observed differences in microbiome composition. At both adult and larval stages, specific members of the mosquito microbiome were associated with particular insectaries; the insectary with less stable and cooler conditions resulted in a slower pupation rate and higher diversity of the larval microbiome. These findings underscore that even minor inconsistencies in rearing conditions can affect the composition of the mosquito microbiome, which may influence experimental outcomes
Progress and Challenges in the Field of Snakebite Envenoming Therapeutics
No full textSnakebite envenoming kills and maims hundreds of thousands of people every year, especially in the rural settings of tropical regions. Envenomings are still treated with animal-derived antivenoms, which have prevented many lives from being lost but which are also medicines in need of innovation. Strides are being made to improve envenoming therapies, with promising efforts made toward optimizing manufacturing and quality aspects of existing antivenoms, accelerating research and development of recombinant antivenoms based on monoclonal antibodies, and repurposing of small-molecule inhibitors that block key toxins. Here, we review the most recent advances in these fields and discuss therapeutic opportunities and limitations for different snakebite treatment modalities. Finally, we discuss challenges related to preclinical and clinical evaluation, regulatory pathways, large-scale manufacture, and distribution and access that need to be addressed to fulfill the goals of the World Health Organization's global strategy to prevent and control snakebite envenoming
Larviciding for malaria control and elimination in Africa
Get PDFBackground: Global progress toward malaria elimination and eradication goals has stagnated in recent years, with many African countries reporting increases in malaria morbidity and mortality. Insecticide-treated nets and indoor residual spraying are effective, but the emergence and increased intensity of insecticide resistance and the challenge of outdoor transmission are undermining their impact. New tools are needed to get back on track towards global targets. This Perspective explores the major challenges hindering wider-scale implementation of larviciding in Africa and identifies potential solutions and opportunities to overcome these barriers. Larviciding in Africa: overview, challenges, and solutions: Larviciding is a valuable vector control tool with strong potential for regional scale-up. There is considerable evidence of its effectiveness, and the World Health Organization (WHO) recommends it as a supplemental intervention. However, malaria programmes hoping to implement larviciding face significant barriers, including (1) poor global technical, policy, and funding support; (2) fragmented implementation and experience; (3) high complexity of delivery and impact evaluation; and (4) limited access to the full range of WHO prequalified larvicide products. Strategic barriers related to global policy and donor hesitancy can be overcome through a coordinated demonstration of cost-effectiveness. Technological advancements and strengthened operational capacity have already overcome technical barriers related to larvicide delivery, targeting, coverage, and evaluation. Developing a Community of Practice platform for larviciding has strong potential to consolidate efforts, addressing the challenge of fragmented implementation and experience. Such a platform can serve as a resource center for African malaria programmes, collating and disseminating technical guidance, facilitating the exchange of best practices, and aiding malaria programmes and partners in designing and evaluating larviciding projects. Conclusion: The global shift toward targeted and adaptive interventions enables the incorporation of larviciding into an expanded vector control toolbox. As more African countries implement larvicide programmes, establishing a regional Community of Practice platform for exchanging experiences and best practices is necessary to strengthen the evidence base for cost-effective implementation, advocate for support, and inform policy recommendations, thus supporting Africa’s progress toward malaria elimination
Interventions to Reduce Self-Stigma Among People Living With HIV: A Systematic Review
Get PDFOver 4 decades into the global HIV pandemic, HIV-related self-stigma—a mindset of negative beliefs, thoughts, and behaviors a person holds about themselves—remains a major barrier to HIV treatment, management, and care. HIV-related self-stigma is a persistent public health threat and leads to depression and other mental health problems, lowers adherence to antiretroviral medication, and acts as a barrier to health services. Not enough is known about what interventions work and how they work to reduce self-stigma. We conducted a systematic review of existing interventions that address self-stigma among people living with HIV to address this gap. We searched PubMed, Embase, and Web of Science; used Covidence review software; dual-screened the results; extracted data from each included study; analyzed the data using Cochrane guidelines and the Template for Intervention Description and Replication Framework; and categorized the content based on emerging themes around the intervention/program. We included 35 studies in the review, with the majority (32/35, 91%) showing promise to reduce HIV self-stigma or components of self-stigma. Intervention approaches included working on thoughts, feelings, and beliefs through a range of cognitive-based, inquiry-based, and mindful-based techniques, often with a forward-looking goal-setting focus. However, comparison of studies was difficult with different definitions and understandings of self-stigma and different measurement scales. Many studies were small-scale and lacked sufficient in-depth descriptions. This study makes an important contribution to the field of HIV more broadly and HIV-related stigma, specifically, in proposing a common definition of self-stigma and providing in-depth descriptions of interventions in terms of content, type, level, and effectiveness
Clinical and psychosocial context of HIV perinatally infected young mothers in Harare, Zimbabwe: A longitudinal mixed-methods study
Get PDFBackground
The lives of adolescents and young people living with HIV (LHIV) are dominated by complex psychological and social stressors. These may be more pronounced among those perinatally infected. This longitudinal mixed-methods study describes the clinical and psychosocial challenges faced by HIV perinatally infected young mothers in Harare, Zimbabwe to inform tailored support.
Methods
HIV perinatally infected young mothers were recruited in 2013 and followed up in 2019. In 2013, they completed a structured interview, clinical examination, psychological screening and had viral load and drug resistance testing. A subset completed in-depth interviews (n = 10). In 2019, they were re-interviewed and had viral load testing. Data were analyzed using STATA 15.0. and thematic analysis.
Results
Nineteen mothers aged 17–24 years were recruited in 2013. Eleven (57.9%) were successfully recontacted in 2019; 3 had died, 2 had relocated and 3 were untraceable. In 2013, all 19 mothers were taking antiretroviral therapy (median duration 8 years, range 2–11 years) and median CD4 count was 524 (IQR 272). In 2013, eight mothers (42.1%) had virological failure (≥1000 copies/ml) (3 of whom subsequently died) and 7 (36.8%) had evidence of drug resistance. In 2019, the proportion with virological failure was 2/11 (18.1%). Six of 11 (54.5%) had switched to second line therapy. In 2013, 64.3% were at risk of common mental disorder and this risk was higher at follow-up (72.7%). Qualitative data highlighted three pertinent themes: HIV status disclosure, adherence experiences and, social and emotional support.
Conclusions
Findings from this study underscore the significant clinical, social and psychological challenges faced by perinatally infected young mothers. The high rates of virological failure, drug resistant mutations, mental health issues and mortality observed in this population indicate the need for tailored and comprehensive health and support services to assist these young mothers
A blended learning approach for capacity strengthening to improve the quality of integrated HIV, TB, and malaria services during antenatal and postnatal care in LMICs: a feasibility study
Get PDFBackground: The blended learning (BL) approach to training health care professionals is increasingly adopted in many countries because of high costs and disruption to service delivery in the light of severe human resource shortage in low resource settings. The Covid-19 pandemic increased the urgency to identify alternatives to traditional face-to-face (f2f) education approach. A four-day f2f antenatal care (ANC) and postnatal care (PNC) continuous professional development course (CPD) was repackaged into a 3-part BL course; (1) self-directed learning (16 h) (2) facilitated virtual sessions (2.5 h over 3 days) and (3) 2-day f2f sessions. This study assessed the feasibility, change in healthcare providers’ knowledge and costs of the BL package in Nigeria, Tanzania, and Kenya.
Methods: A mixed methods design was used. A total of 89 healthcare professionals, were purposively selected. Quantitative data was collected through an online questionnaire and skills assessments, analyzed using STATA 12 software. Qualitative data was collected through key informant interviews and focus group discussions, analysed using thematic analysis.
Results: Majority of participants (86%) accessed the online sessions using a mobile phone from home and health facilities. The median (IQR) time of completing the self-directed component was 16 h, IQR (8, 30). A multi-disciplinary team comprising of 42% nurse-midwives, 28% doctors, 20% clinical officers and 10% other healthcare professionals completed the BL course. Participants liked the BL approach due to its flexibility in learning, highly educative/relevant content, mixing of health worker cadres and CPD points. Aspects that were noted as challenging were related to personal log-in details and network connectivity issues during the self-directed learning and facilitated virtual sessions respectively.
Conclusion: The blended learning approach to ANC-PNC in-service training was found to be acceptable, feasible and cost less to implement compared to face-to-face training approach in the study settings. The BL training approach was effective in improving the knowledge and skills of healthcare providers who participated in the training
De novo designed proteins neutralize lethal snake venom toxins
Get PDFSnakebite envenoming remains a devastating and neglected tropical disease, claiming over 100,000 lives annually and causing severe complications and long-lasting disabilities for many more1,2. Three-finger toxins (3FTx) are highly toxic components of elapid snake venoms that can cause diverse pathologies, including severe tissue damage3 and inhibition of nicotinic acetylcholine receptors, resulting in life-threatening neurotoxicity4. At present, the only available treatments for snakebites consist of polyclonal antibodies derived from the plasma of immunized animals, which have high cost and limited efficacy against 3FTxs5,6,7. Here we used deep learning methods to de novo design proteins to bind short-chain and long-chain α-neurotoxins and cytotoxins from the 3FTx family. With limited experimental screening, we obtained protein designs with remarkable thermal stability, high binding affinity and near-atomic-level agreement with the computational models. The designed proteins effectively neutralized all three 3FTx subfamilies in vitro and protected mice from a lethal neurotoxin challenge. Such potent, stable and readily manufacturable toxin-neutralizing proteins could provide the basis for safer, cost-effective and widely accessible next-generation antivenom therapeutics. Beyond snakebite, our results highlight how computational design could help democratize therapeutic discovery, particularly in resource-limited settings, by substantially reducing costs and resource requirements for the development of therapies for neglected tropical diseases
“Boys and Men”: The Making of Senegambian and Congolese Masculinity and Identities in Tropical Africa: A Reflection
Get PDFOur paper focuses on two white pioneering scientists, Dr Dutton, who was English, and Dr Todd, a Canadian, employed by the Liverpool School of Tropical Medicine (LSTM) to study sleeping sickness in colonial Senegambia, West Africa. We analysed photographs and some published personal letters to help us reflect on some of their constructions of Senegambian and Congolese male identities in tropical colonial Africa. In this paper, we connect with the history of tropical medicine, a precursor to public health. Public health was a research area that was central to Peter Aspinall’s work as he argued for shifts from simplistic hegemonic terminologies to refer to an incredibly diverse Black African population, as failure to do so impacts on service provisions. Within the context of tropical medicine, we reflect on the paternalistic terminology and use of the word ‘boy’ to refer to their unnamed male helpers who they photographed during these expeditions. We hope that by interpreting the photographs and reflecting on the literature and letters, exercises that are influenced by our positionality, we can obtain a glimpse into the past and obtain some insights that contribute to our understanding of the production of colonial masculinities, terminology, and race. As female authors employed by LSTM, we are aware that our positionalities influence the lenses through which we view and interpret the literature and the photos. Our paper contributes towards the ongoing debates on terminology, race, and whiteness in colonial tropical medicine
Acceptability of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine plus dihydroartemisinin-piperaquine in Papua New Guinea: a qualitative study
Get PDFBackground
In moderate-to-high malaria transmission regions, the World Health Organization recommends intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) alongside insecticide-treated bed nets to reduce the adverse consequences of pregnancy-associated malaria. Due to high-grade Plasmodium falciparum resistance to SP, novel treatment regimens need to be evaluated for IPTp, but these increase pill burden and treatment days. The present qualitative study assessed the acceptability of IPTp-SP plus dihydroartemisinin-piperaquine (DP) in Papua New Guinea, where IPTp-SP was implemented in 2009.
Methods
Individual in-depth interviews (IDIs) and focus group discussions were conducted at health facilities where a clinical trial evaluated IPTp-SP plus DP (three-day regimen) versus IPTp-SP plus DP-placebo. IDIs were conducted with: (1) trial participants at different stages of engagement with ANC and IPTp, e.g. first antenatal clinic visit, subsequent antenatal clinic visits and postpartum; (2) local health workers (nurses, community health workers, midwives, health extension officers, doctors); and (3) representatives of district, provincial and national health authorities involved in programming ANC and IPTp. Focus group discussions comprised pregnant women only, including those engaged in the clinical trial and those receiving routine ANC outside of the trial. All interviews were audio recorded and transcribed. Transcripts were analysed using inductive and deductive thematic analysis applying a framework assessing: affective attitude, burden, ethicality, intervention coherence, opportunity costs, perceived effectiveness, and self-efficacy.
Results
Women expressed positive feelings and attitudes towards SP plus DP/DP-placebo; reported limited side effects; and found the size, number, colour, and taste of study medicines acceptable. Health workers and policymakers were concerned that, compared to SP alone, additional tablets, frequency (three-day regimen), and tablet size might be barriers to acceptability for users outside a non-trial setting. There was a high perceived effectiveness of SP plus DP; most women reported that they did not get malaria or felt sick during pregnancy. Broader healthcare benefits received through trial participation and the involvement of health workers, relatives and community members in the clinical trial enabled antenatal clinic attendance and perceived acceptability of this IPTp regimen.
Conclusions
In the trial context, IPTp-SP plus DP was acceptable to both users and providers. Healthcare providers were concerned about the realities of acceptability and adherence to SP plus DP outside a clinical trial setting
Optimized methods for the targeted surveillance of extended-spectrum beta-lactamase-producing Escherichia coli in human stool
Get PDFUnderstanding transmission pathways of important opportunistic, drug-resistant pathogens, such as extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, is essential to implementing targeted prevention strategies to interrupt transmission and reduce the number of infections. To link transmission of ESBL-producing E. coli (ESBL-EC) between two sources, single-nucleotide resolution of E. coli strains, as well as E. coli diversity within and between samples, is required. However, the microbiological methods to best track these pathogens are unclear. Here, we compared different steps in the microbiological workflow to determine the impact different pre-enrichment broths, pre-enrichment incubation times, selection in pre-enrichment, selective plating, and DNA extraction methods had on recovering ESBL-EC from human stool samples, with the aim to acquire high-quality DNA for sequencing and genomic epidemiology. We demonstrate that using a 4-h pre-enrichment in Buffered Peptone Water, plating on cefotaxime-supplemented MacConkey agar and extracting DNA using Lucigen MasterPure DNA Purification kit improves the recovery of ESBL-EC from human stool and produced high-quality DNA for whole-genome sequencing. We conclude that our optimized workflow can be applied for single-nucleotide variant analysis of an ESBL-EC from stool