Liverpool School of Tropical Medicine

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    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.</p

    Epidemiology of Group B Streptococcus: Maternal Colonization and Infant Disease in Kampala, Uganda: Maternal Colonization and Infant Disease in Kampala, Uganda

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    Background: Child survival rates have improved globally, but neonatal mortality due to infections, such as group B Streptococcus (GBS), remains a significant concern. The global burden of GBS-related morbidity and mortality is substantial. However, data from low and middle-income countries are lacking. Vaccination during pregnancy could be a feasible strategy to address GBS-related disease burden. Methods: We assessed maternal rectovaginal GBS colonization and neonatal disease rates in a prospective cohort of 6062 women-infant pairs. Surveillance for invasive infant disease occurred in parallel at 2 Kampala hospital sites. In a nested case-control study, we identified infants &lt;90 days of age with invasive GBS disease (iGBS) (n = 24) and healthy infants born to mothers colonized with GBS (n = 72). We measured serotype-specific anticapsular immunoglobulin G (IgG) in cord blood/infant sera using a validated multiplex Luminex assay. Results: We found a high incidence of iGBS (1.0 per 1000 live births) within the first 90 days of life across the surveillance sites, associated with a high case fatality rate (18.2%). Maternal GBS colonization prevalence was consistent with other studies in the region (14.7% [95% confidence interval, 13.7%-15.6%]). IgG geometric mean concentrations were lower in cases than controls for serotypes Ia (0.005 vs 0.12 μg/mL; P =. 05) and III (0.011 vs 0.036 μg/mL; P =. 07) and in an aggregate analysis of all serotypes (0.014 vs 0.05 μg/mL; P =. 02). Conclusions: We found that GBS is an important cause of neonatal and young infant disease in Uganda and confirmed that maternally derived antibodies were lower in early-onset GBS cases than in healthy exposed controls

    A pilot study to explore utility of electronic informed consent in a low- income setting; the case of a Controlled human infection study in Blantyre, Malawi

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    BackgroundElectronic informed consent can improve accuracy, workflow, and overall patient experience in clinical research but has not been used in Malawi, owing to uncertainty about availability, utility, patient data security and technical support.ObjectivesWe aimed to explore the utility of electronic consent (e-consent) in an ongoing human infection study in Blantyre, Malawi.MethodsThe approved paper consent forms were digitized using Open Data Kit (ODK). Following participant information giving by the research staff, healthy literate adult participants with no audio-visual impairments completed a self-administered e-consent and provided an electronic signature. We dual-consented participants by both paper-based and electronic-consenting. Signed e-consent forms were uploaded to a secure study server. Utility of e-consenting was observed by participation rate, user-friendliness, documentation error rate, and staff perception of the overall consenting process.ResultsAll 109 participants offered e-consenting accepted participation. E-consenting was user-friendly, had no identifiable documentation errors as compared to 43.1% (n 47/109) error rate with paper-based consenting, and ensured data safety, and unravelled areas for consideration. Challenges with e-consenting included difficult digitization of ethics stamped documents, as well as present but infrequent delays of retrieval of e-consent forms.ConclusionE-consenting is feasible, has a utility benefit in a controlled human infection study in Malawi; a low-income country, and can supplement paper-based consenting. Its usefulness can improve the consenting process in research conducted in such settings. Additionally, success of e-consenting requires a careful consideration.</p

    Recruitment strategies used to enrol healthy volunteers in the first pneumococcal human infection study in Africa: Lessons from Blantyre, Malawi.

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    BackgroundHuman Infection Studies (HIS) also known as Controlled Human Infection Models (CHIM) are a relatively new concept in African countries to clinicians, scientists, and communities alike. We have introduced HIS/CHIM studies to Malawi during the last four years by developing an experimental human pneumococcal carriage model. This CHIM was used to test the efficacy of a licensed 13-valent Pneumococcal Conjugate Vaccine (PCV13) against experimental nasal pneumococcal carriage. Traditional and digital recruitment strategies into this novel trial were explored.ObjectivesTo describe various methods of recruitment in this first CHIM study in Malawi.MethodsThe clinical trial within the context of which these data were recorded was registered with the Pan African Clinical Trials Registry (REF: PACTR202008503507113) on 03 August 2020. The project was conducted at the Malawi Liverpool Wellcome Programme (MLW) in Blantyre, Malawi between April 2021, and September 2022. Source populations were college students and community members within Blantyre. Recruitment strategies included sharing study information in written or visual form, community sensitization meetings, snowball contacts (word of mouth from previous volunteers), branded clothing and participating in radio and television programs.Results299 volunteers attended screening clinic, of whom 278 were recruited. Sixty-six recruited volunteers (23.7%) were college students and 212 (76.3%) were from the community. Snowball word-of-mouth contacting was the most successful recruitment strategy, with 201 (72.3%) participants recruited using this method. 195 (70.1%) were men of whom 149 (76.4%) joined the study through snowballing.</p

    Efficacy of antipsychotics in delusional infestation

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    Background Data remain scarce for the first‐line antipsychotic choice in treating delusional infestation (DI).Objectives We evaluated the treatment responses associated with different antipsychotics in DI patients.Methods We undertook a multicentre, retrospective observational study using anonymised electronic patient records from two hospitals in the United Kingdom from 1 January 2011 to 1 January 2023. Eligible participants were adults (≥18 years) diagnosed with DI treated with an antipsychotic, and had both an assigned baseline and follow‐up Clinical Global Impression Scale (CGI‐S) score. The CGI‐S is a validated psychiatric research tool. Participants were excluded if they had known limited or non‐adherence to an antipsychotic, or if no CGI‐S scores were present at follow‐up. First clinic visits before the initiation of an antipsychotic were assigned as the baseline CGI‐S score. The last available CGI‐S score before the patient either changed antipsychotic or left the clinic for any reason was used to assign follow‐up CGI‐S scores. The primary outcome was the response to each individual antipsychotic treatment, measured by the difference in the baseline and last available follow‐up CGI‐S scores. Differences in CGI‐S changes between antipsychotic episodes were tested by analysis of variance (ANOVA).ResultsIn total, 414 patient records were analysed, and data were extracted. The mean age was 61.8 years (SD 14.1). One hundred seventy (41%) of 414 patients were men and 244 (59%) were women. In total, 156 (38%) of 414 patients were eligible, yielding a total of 315 antipsychotic prescribing episodes. The ANOVA, ranking in order of treatment response, showed that the highest mean score (expressing highest treatment response) was observed in amisulpride (31 [67%] of 46) and risperidone (95 [57%] of 167), followed by some distance by quetiapine (9 [36%] of 25), aripiprazole (13 [28%] of 46) and olanzapine (7 [25%] of 28).ConclusionsAmisulpride and risperidone were associated with a higher treatment response than quetiapine, aripiprazole and olanzapine. Amisulpride and risperidone should therefore be considered the first‐line treatment options in DI patients.</p

    A Comparison of Clinical and Laboratory Features of Crimean-Congo Hemorrhagic Fever in Children and Adults: A Retrospective Single-Center Cohort Study and Literature Review

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    Background: Crimean-Congo hemorrhagic fever (CCHF) is a major emerging infectious disease threat, and children are reported to have a milder disease course compared with adults, in contrast to other viral hemorrhagic fevers. The aim of this study was to compare adult and pediatric patients with CCHF to improve understanding of pathogenesis and the natural history of the disease.Materials and Methods: A retrospective analysis of all children and adults admitted with confirmed CCHF between 2011 and 2020. Epidemiological, clinical, and laboratory features were collated on proformas, together with clinical management details. The Severity Grading Score (SGS) system was used to stratify mortality risk. Data from children were compared with adults in the same center and with other published pediatric cohort studies.Results: A total of 47 children with a median (ranges) age of 14 (2–17) years and 176 adults with a median (ranges) age of 52 (18–83) years with confirmed CCHF were included. The most frequent symptoms in adults were fever, muscle-joint pain, headache, nausea, and vomiting; the most frequent in children were fever, anorexia, nausea, vomiting, and abdominal pain. Adults had lower lymphocyte and platelet counts and higher liver transaminase and creatinine levels than children. SGS values were lower in children, but 97.9% children received ribavirin compared with 8.5% of adults (p &lt; 0.001), and they had associated longer median lengths of hospital admission (10 vs. 7 days, p &lt; 0.001). Mortality of 1 out of 47 (2.1%) children was similar to 11 other cohorts reported in Türkiye and lower than 13.1% in adults (23/176) in the same center (p = 0.059).Conclusions: Children have lower CCHF-related mortality, less severe disease, and different clinical syndromes at presentation. The majority of published case definitions for screening for CCHF in the main endemic countries do not differentiate between adults and children and omit four of the five most common presenting features in children.</p

    Acceptability of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine plus dihydroartemisinin-piperaquine in Papua New Guinea: a qualitative study

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    BackgroundIn 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.MethodsIndividual 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.ResultsWomen 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.ConclusionsIn 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.</p

    Evaluating the potential of Kalanchoe pinnata, Piper amalago amalago, and other botanicals as economical insecticidal synergists against Anopheles gambiae

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    Synergists reduce insecticide metabolism in mosquitoes by competing with insecticides for the active sites of metabolic enzymes, such as cytochrome P450s (CYPs). This increases the availability of the insecticide at its specific target site. The combination of both insecticides and synergists increases the toxicity of the mixture. Given the demonstrated resistance to the classical insecticides in numerous Anopheles spp., the use of synergists is becoming increasingly pertinent. Tropical plants synthesize diverse phytochemicals, presenting a repository of potential synergists.MethodsExtracts prepared from medicinal plants found in Jamaica were screened against recombinant Anopheles gambiae CYP6M2 and CYP6P3, and Anopheles funestus CYP6P9a, CYPs associated with anopheline resistance to pyrethroids and several other insecticide classes. The toxicity of these extracts alone or as synergists, was evaluated using bottle bioassays with the insecticide permethrin. RNA sequencing and in silico modelling were used to determine the mode of action of the extracts.ResultsAqueous extracts of Piper amalago var. amalago inhibited CYP6P9a, CYP6M2, and CYP6P3 with IC50s of 2.61 ± 0.17, 4.3 ± 0.42, and 5.84 ± 0.42 μg/ml, respectively, while extracts of Kalanchoe pinnata, inhibited CYP6M2 with an IC50 of 3.52 ± 0.68 μg/ml. Ethanol extracts of P. amalago var. amalago and K. pinnata displayed dose-dependent insecticidal activity against An. gambiae, with LD50s of 368.42 and 282.37 ng/mosquito, respectively. Additionally, An. gambiae pretreated with K. pinnata (dose: 1.43 μg/mosquito) demonstrated increased susceptibility (83.19 ± 6.14%) to permethrin in a bottle bioassay at 30 min compared to the permethrin only treatment (0% mortality). RNA sequencing demonstrated gene modulation for CYP genes in anopheline mosquitoes exposed to 715 ng of ethanolic plant extract at 24 h. In silico modelling showed good binding affinity between CYPs and the plants’ secondary metabolites.ConclusionThis study demonstrates that extracts from P. amalago var. amalago and K. pinnata, with inhibitory properties, IC50 &lt; 6.95 μg/ml, against recombinant anopheline CYPs may be developed as natural synergists against anopheline mosquitoes. Novel synergists can help to overcome metabolic resistance to insecticides, which is increasingly reported in malaria vectors.</p

    Insights into the transmission cycle of cutaneous leishmaniasis from an endemic community in rural Guatemala

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    Cutaneous leishmaniasis (CL) is a parasitic vector-borne disease prevalent in 90 countries. Despite its endemicity in Guatemala, key transmission factors are still unknown. To address this, we characterized sand fly populations and Leishmania parasites in a Guatemalan community in 2022. We visited the households of 23 patients with lesions compatible with CL, sampled for sand flies and analysed Leishmania spp. presence in patients’ skin scrapings and in collected sand flies. We collected 93 sand flies, predominantly females including the vector species Nyssomyia ylephiletor, Bichromomyia olmeca and Lutzomyia cruciata. Nyssomyia ylephiletor was the most abundant species indoors. Four Leishmania spp. were identified including L. panamensis, L. guyanensis, L. braziliensis and L. infantum in CL lesions, L. guyanensis complex species (L. guyanensis or L. panamensis) and Leishmania sp. in sand flies. Sand fly species positive for Leishmania spp. were Ny. ylephiletor, Dampfomyia deleoni, Dampfomyia sp. and Brumptomyia sp. Blood-meal analysis revealed human and pig blood in engorged Ny. ylephiletor collected inside and in the proximity of the households. This is the first report of L. guyanensis in Guatemalan patients and provides insights into CL transmission dynamics, suggesting potential indoor transmission, pending more studies.</p

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