London School of Hygiene & Tropical Medicine

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    Phylogenetic Study of Local Patterns Influenza A(H3N2) Virus Transmission in a Semi-Isolated Population in a Remote Island in Japan Between 2011 and 2013.

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    BACKGROUND: Influenza A outbreak risk is impacted by the potential for importation and local transmission. Reconstructing transmission history with phylogenetic analysis of genetic sequences can help assess outbreak risk but relies on regular collection of genetic sequences. Few influenza genetic sequences are collected in Japan, which makes phylogenetic analysis challenging, especially in rural, remote settings. We generated influenza A genetic sequences from nasopharyngeal swabs (NPS) samples collected using rapid influenza diagnostic tests and used them to analyze the transmission dynamics of influenza in a remote island in Japan. METHODS: We generated 229 whole genome sequences of influenza A/H3N2 collected during 2011/12 and 2012/13 influenza seasons in Kamigoto Island, Japan, of which 178 sequences passed the quality check. We built time-resolved phylogenetic trees from hemagglutinin sequences to classify the circulating clades by comparing the Kamigoto sequences to global sequences. Spatiotemporal transmission patterns were then analyzed for the largest local clusters. RESULTS: Using a time-resolved phylogenetic tree, we showed that the sequences clustered in six independent transmission groups (1 in 2011/12, 5 in 2012/13). Sequences were closely related to strains from mainland Japan. All 2011/12 strains were identified as clade 3C.2 (n = 29), while 2012/13 strains fell into two clades: clade 3C.2 (n = 129) and 3C.3a (n = 20). Clusters reported in 2012/13 circulated simultaneously in the same regions. The spatiotemporal analysis of the largest cluster revealed that while the first sequences were reported in the busiest district of Kamigoto, the later sequences were scattered across the island. CONCLUSION: Kamigoto Island was exposed to repeated importations of Influenza A(H3N2), mostly from mainland Japan, sometimes leading to local transmission and ultimately outbreaks. As independent groups of sequences overlapped in time and space, cases may be wrongly allocated to the same transmission group in the absence of genomic surveillance, thereby underestimating the risk of importations. Our analysis highlights how NPS could be used to better understand influenza transmission patterns in little-studied settings and improve influenza surveillance in Japan

    Are cash transfers enough to reduce poverty and inequalities for people with disabilities?: a qualitative study on factors affecting the impact of the disability allowance in the Maldives

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    Cash transfers are frequently used as a policy instrument to reduce poverty and address disability-related costs amongst people with disabilities. Recent evaluations, however, have found that these programmes often only have modest impacts. This study presents qualitative research linked to an impact evaluation in the Maldives, involving interviews with 43 people with disabilities. It highlighted factors that could affect the effectiveness of the Disability Allowance: the value of the cash transfer was insufficient to cover both basic needs and disability-related goods and services; many adult recipients lacked control over the allowance and how it was spent; many recipients were not referred to complementary programmes that could cover some extra costs; poor availability and quality of needed goods and services; and the broader lack of adequate disability-inclusive planning. These findings carry implications for the 170+ countries implementing disability-targeted programmes, indicating areas for improvement in the design and delivery of social protection

    “We need workable micronutrient data!”: a qualitative study assessing the need for integrated micronutrient data to support evidence-based decisions by Indian food system stakeholders

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    Stakeholders in decision-making roles require that data are available, accessible and useable to ensure evidence-informed design, implementation and evaluation of programs and policies to alleviate micronutrient deficiencies in India. This study determined the typical uses, data sources, priority and unmet needs, common challenges, and aspirations of key Indian food system stakeholders in relation to usage and interpretation of publicly available micronutrient data from health, nutrition, agriculture, and program domains. A qualitative, descriptive study was conducted, with purposive sampling of stakeholders from state and national-level government, development agencies, non-governmental organisations, research institutes, private organisations, and academia. Data were generated through focus group discussions and semi-structured key informant interviews. Themes and sub-themes were identified using framework analysis with a deductive approach. Stakeholders emphasized the pressing need for consolidated, harmonized district-level data from health, nutrition, and agriculture sources to better understand the causes and sources of variation in micronutrient deficiencies, and to inform decision-making on supplementation and fortification program planning, and policy evaluation. Biomarker data, nutrition dashboards and food consumption data were most used; data on food composition, program cost, and soil/crop micronutrient composition were not typically used, despite their relevance. A need for district-level data with further geographical and temporal (including seasonal) disaggregation, with improved accessibility was also identified. Current challenges include limited district-level data, outdated surveys, and data accessibility, while there is demand for customisable tools that integrate varied datasets, reflecting a shared vision for evidence-based decision-making and policy formulation

    Blood Transfusions for Chronic Malaria Anemia in Prisoners of War on the Thai-Burma Railway 1943-1945.

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    Allied prisoners of war (POWs) working on the Imperial Japanese Army's railroad from Thailand to Burma during 1943-1945 devised a blood transfusion service to rescue severely ill fellow prisoners who were otherwise unlikely to survive the war. Extant transfusion records (1,251 recipients, 1,189 donors) in ledger books held by the United Kingdom National Archives at Kew were accessed and analyzed. Survival to the end of the war in 1945 was determined from Commonwealth War Graves Commission records. The records examined indicate that freshly donated whole blood was manually defibrinated and transfused after crossmatches based on POW medic sera. Overall survival to the end of the war was 74% in recipients and 88% in donors. Postwar survival rates were significantly higher for transfusion recipients with malaria (89.3%) than for other diagnoses: 52.6% for malnutrition, 59.3% for dysentery, 67.2% for skin ulcers, and 75.4% for other causes (odds ratio: 3.97; 95% CI: 2.79-5.28; P <0.0001). By 1945, the vast majority of blood transfusions were given for severe anemia caused by chronic relapsing vivax malaria. Although the POW situation was admittedly extreme, our data provide evidence that blood transfusions to treat severe anemia were associated with higher survival among patients with Plasmodium vivax infection than among those with other morbidities

    Immunogenicity of yellow fever vaccine co-administered with 13-valent pneumococcal conjugate vaccine in rural Gambia: A cluster-randomised trial.

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    INTRODUCTION: Because booster doses of pneumococcal conjugate vaccine (PCV) may be given at a similar time to yellow fever vaccine (YF), it is important to assess the immune response to YF when co-administered with PCV. This has been investigated during a reduced-dose PCV trial in The Gambia. METHODS: In this phase 4, parallel-group, cluster-randomized trial, healthy infants aged 0-10 weeks were randomly allocated to receive either a two-dose schedule of PCV13 with a booster dose co-administered with YF vaccine at age 9 months (1 + 1 co-administration) or YF vaccine administered separately at age 10 months (1 + 1 separate) or the standard three early doses of PCV13 with YF vaccine at age 9 months (3 + 0 separate). Blood samples were collected 28-35 days post-vaccination and YF neutralizing antibody (NA) titres were measured. Proportions with seroprotective YF NA titres ≥ 1:8 were calculated with 95 % confidence intervals (CI). Non-inferiority was demonstrated if the lower limit of the CI for the difference in proportions between the co-administration and separate groups was greater than - 10 %. RESULTS: Forty-eight, 66, and 98 participants enrolled in 3 + 0 separate, 1 + 1 co-administration, and 1 + 1 separate groups respectively had NA results. Per protocol analysis of the 3 + 0 separate, 1 + 1 co-administration, 1 + 1 separate, and the combined 1 + 1 separate and 3 + 0 separate groups found that 81 %, 85 %, 92 %, and 88 % of participants respectively had YF NA titres ≥1:8. Results were similar with analysis by intention-to-treat. The difference in proportions comparing 1 + 1 co-administration and 1 + 1 separate groups was -7 % (95 % CI, -18 % to 3 %). The difference between 1 + 1 co-administration and 3 + 0 separate groups was 4 % (95 % CI, -10 % to 15 %). There was no statistical difference in the YF seroresponse when the YF vaccine was co-administered with PCV or administered separately. CONCLUSIONS: No evidence was found of the non-inferiority of the seroresponse to YF vaccine when co-administered with PCV13. The levels of YF NA attaining seroprotection (NT ≥1:8) were high in all groups. PCV13 co-administered with YF vaccine at 9 months does not affect seroresponse to YF vaccine. http://www.isrctn.org/ - ISRCTN72821613

    A qualitative exploration of midwives' and ambulance clinicians' experiences working together

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    Background/Aims Effective teamwork represents a significant component of high-quality maternity care. Midwives and ambulance clinicians are sometimes required to work together in the pre-hospital setting, but these interactions are not well documented or understood. This study aimed to explore the views and experiences of clinicians, to describe the barriers to and facilitators of effective teamwork in this context. Methods Focus group discussions and in-depth interviews were conducted with 30 London-based clinicians who had experience of providing emergency maternity care in the pre-hospital setting as part of a multidisciplinary team. Data were analysed thematically, informed by principles of grounded theory. Results Three overarching themes emerged: significance of the patient environment, reaching a shared mental model and interpersonal dynamics. Challenges included conflicting priorities and lack of understanding each other's roles and skillsets. Civility and multidisciplinary training were perceived as conducive to effective teamwork. Conclusions The findings provide insight to the factors that were perceived to impact teamwork in a pre-hospital maternity context. Actions to improve patient safety include increased partnership working between acute and ambulance trusts, including the provision of multidisciplinary training. Implications for practice Midwives and ambulance clinicians report a shared goal of a safe and positive experience for the families in their care. When working towards these outcomes, teams require leadership that acknowledges the various professional remits present

    Understanding experiences of neglected tropical diseases of the skin: a mixed-methods study to inform intervention development in Ethiopia.

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    BACKGROUND: The WHO and Ethiopia's Ministry of Health have developed strategies to expand and integrate services for co-endemic neglected tropical diseases (NTDs) which manifest in the skin. To inform these strategies, we aimed to understand the social, economic and health system context of skin NTD care in Kalu woreda, Amhara region, Ethiopia, where cutaneous leishmaniasis (CL) and leprosy are endemic. METHODS: Between October 2020 and May 2022, we surveyed and reviewed records of 41 primary healthcare facilities and explored common disease experiences in focus group discussions (n=40) and interviews with people affected by leprosy (n=37) and CL (n=33), health workers (n=23), kebele authorities and opinion leaders (n=33) and traditional healers (n=7). Opportunities for integrated skin NTD service provision were explored through policy document review, interviews with health officials (n=25), and stakeholder meetings. RESULTS: Availability of diagnostic supplies and health worker competence to provide skin care was very limited across primary healthcare facilities, particularly for CL. People with leprosy commonly sought care from healthcare facilities, while people with CL administered self-care or sought help from traditional healers. Travel and costs of care at specialised facilities outside the district inhibited timely care-seeking for both diseases. Transmission discourses shaped different understandings of who was affected by leprosy and CL and expectations of behaviour during and after treatment. Many policy actors felt that existing supply chain interventions, decentralised treatment approaches and community engagement initiatives for leprosy could also benefit CL, but others also warned against increasing care-seeking unless CL treatment could be provided on a scale commensurate with the large burden they perceived. CONCLUSION: Our findings demonstrate significant gaps in the provision of care for skin NTDs within primary healthcare, very different health-seeking patterns for leprosy and CL, and a need to develop new models of care, especially for CL

    Do community-level factors play a role in HIV self-testing uptake, linkage to services and HIV-related outcomes? A mixed methods study of community-led HIV self-testing in rural Zimbabwe.

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    Community-led interventions, where communities plan and lead implementation, are increasingly being adopted within public health programmes. We explore factors associated with successful community-led distribution of HIV self-test (HIVST) kits to guide future service delivery. Twenty rural communities were supported to distribute HIVST kits for 1-month between January and September 2019. Social science researchers observed communities during planning and HIVST distribution, documenting findings in a standard observation template. Three months post-intervention, a population-based survey measured self-reported new HIV diagnosis, HIVST uptake, linkage to post-test services; and collected blood samples for viral load testing. The survey also included questions related to community cohesion; respondents' communities were grouped into low/medium/high based on community cohesion scores. We used mixed effect logistic regression to assess how outcomes differed based on community cohesion scores. In total, 27,812 kits were distributed by 348 distributors. Two HIVST distribution models were implemented: door-to-door only or at community venues/events. Of 5,683 participants surveyed, 1,831 (32.2%) received kits and 1,229 (67.1%) reported self-testing; overall HIVST uptake was 1,229/5,683 (21.6%). New HIV diagnosis increased with community cohesion, from 32/1,770 (1.8%) in the low-cohesion group to 40/1,871 (2.1%) in the medium-cohesion group, adjusted odds ratio (aOR) 2.94 (1.41-6.12, p = 0.004) and 66/2,042 (3.2%) in the high-cohesion group, aOR 7.20 (2.31-22.50, p = 0.001). Other outcomes did not differ by extent of cohesion. Our findings demonstrate the more cohesive communities are, the more effective they may be at distributing HIVST kits and identifying people with undiagnosed HIV. Efforts to increase community cohesion should be considered as part of public health programmes and for planning and scaling-up HIVST implementation in communities

    Plasmodium falciparum isolates: ex vivo drug response.

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    OBJECTIVES: While artemisinin-based combination therapies (ACTs) are effective in sub-Saharan Africa, clinical isolates that are refractory to artemisinin derivatives are emerging in East Africa and ACT partner drugs are becoming less effective in West Africa. We investigated the ex vivo responses of Plasmodium falciparum clinical isolates to frontline antimalarials and the contribution of validated molecular markers of antimalarial drug resistance. METHODS: Ex vivo susceptibility was measured for 66 clinical isolates collected from uncomplicated malaria patients. IC50 was measured for dihydroartemisinin, artesunate, lumefantrine, amodiaquine and chloroquine using a SYBR Green I growth inhibition assay. We also assessed known drug resistance-mediating polymorphisms in pfcrt, pfmdr1 and pfkelch13 using Oxford Nanopore amplicon sequencing. RESULTS: P. falciparum clinical isolates were susceptible to dihydroartemisinin and artesunate. Clinical isolates showed a wide distribution of susceptibility to lumefantrine and amodiaquine, with some parasites having IC50 values above reference cut-offs for resistance to lumefantrine (150 nM) and amodiaquine (60 nM), suggesting decreased drug susceptibility. Ninety-seven percent of the isolates carried WT pfcrt K76 and pfmdr1 N86 alleles, reported to mediate reduced response to lumefantrine and artemether/lumefantrine. pfmdr1 N86 and 184F haplotype was carried by 62.1% of parasites. None of the clinical isolates carried validated pfkelch13 mutations known to mediate artemisinin partial resistance. CONCLUSIONS: Clinical isolates from coastal Ghana remain susceptible to artemisinin derivatives in commonly used ACTs in Ghana. However, we observed lower susceptibility to the ACT partner drugs lumefantrine and amodiaquine, suggesting the emergence of drug-tolerance phenotypes. Consistent surveillance of drug phenotype-genotype is needed to support ACT efficacy in Ghana

    Barriers and enablers for group-based manual emptying services for onsite sanitation facilities in Nairobi, Kenya: a qualitative study.

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    Onsite sanitation, such as pit latrines, is essential to achieving universal access to safe sanitation, as outlined in Sustainable Development Goal target 6.2. However, manual emptying for pit latrines in low-income areas is often unhygienic, posing health and environmental risks. Enhancing the safety of these services increases costs, yet affordability for customers is essential. Thus, reducing service costs is a key priority. Group-based approach, where emptiers visit multiple toilets consecutively, has potential to improve both service efficiency and affordability. However, few studies have investigated its applicability to manual emptying. This paper aims to identify barriers and enablers for group-based manual emptying services in low-income neighbourhoods of Nairobi. We conducted 12 focus group discussions with landlords, tenants, and manual emptiers in the Korogocho informal settlement in Nairobi and interviewed 20 key informants from relevant sectors in Kenya. We identified five categories of barriers and enablers that affected general and group-based manual emptying: 1) funding, 2) expertise and equipment, 3) social and commercial habits, 4) physical conditions, and 5) regulatory systems. Of these, a norm that pits are not emptied until they get full, operating time constraints, fair and transparent pricing, and an organiser who can arrange group-based emptying from Category 3, and transport capacity from Category 4 specifically affected group-based manual emptying. Given that the barriers have a cascade structure, addressing some primary barriers such as capacity building and recognising manual emptiers' role in the sanitation policies could be effective ways to ensure safe and affordable emptying services

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