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Excised lateral buds of taro [Colocasia esculentar var. esculenta (L.) A.F. Hill] developed into plantlets and formed callus if cultured on media containing taro extract. .alpha.-Naphthaleneacetic acid enhanced the process but only if taro extract was also present. The tissue requirements for this variety of taro are different from those of Colocasia esculenta var. antiquorum (L.) A.F. Hill.

Abstract DNA mutation data currently reside in many online databases, which differ markedly in the terminology used to describe or define the mutation and also in completeness of content, potentially making it difficult both to locate a mutation of interest and to find sought-after data (eg phenotypic effect). To highlight the current deficiencies in the accessibility of web-based genetic variation information, we examined the ease with which various resources could be interrogated for five model mutations, using a set of simple search terms relating to the change in amino acid or nucleotide. Fifteen databases were investigated for the time and/or number of mouse clicks; clicks required to find the mutations; availability of phenotype data; the procedure for finding information; and site layout. Google and PubMed were also examined. The three locus-specific databases (LSDBs) generally yielded positive outcomes, but the 12 genome-wide databases gave poorer results, with most proving not to be search-able and only three yielding successful outcomes. Google and PubMed searches found some mutations and provided patchy information on phenotype. The results show that many web-based resources are not currently configured for fast and easy access to comprehensive mutation data, with only the isolated LSDBs providing optimal outcomes. Centralising this information within a common repository, coupled with a simple, all-inclusive interrogation process, would improve searching for all gene variation data.

Despite a global drive to improve staff well-being in healthcare, distress and absenteeism continue to persist, posing consequences for patient care and organisational functioning. Current research and subsequent strategies implemented to remediate such problems have primarily focused on occupational experiences, disregarding the contribution of problems occurring outside of the workplace. The current study sought to establish the prevalence of work and non-work problems, and their respective impacts on several well-being outcomes, in this occupational group. Secondary analysis of data from a cross-sectional survey of 323 staff in a secure UK mental healthcare organisation was conducted. Exposure to non-work problems was pervasive across the sample (79.3%). Demographic discrepancies in exposure to types of problems were apparent, though number of problems reported was comparable across the sample. Number of non-work problems was a significant predictor of depression, anxiety, functional impairment, and complex post-traumatic stress disorder symptoms, when controlling for exposure to work problems. The findings implicate the need for a broader conceptualisation of distress in secure mental healthcare staff, who typically report exposure to several non-work problems, in the context of occupational challenges. Policy, practice and service implications are discussed, with consideration for the availability and modality of support offered to staff.

Background: Vaccine responses differ between populations and are often impaired in rural and low-income settings. The reasons for this are not fully understood, but observational data suggest that the immunomodulating effects of parasitic helminths might contribute. We hypothesised that Schistosoma mansoni infection suppresses responses to unrelated vaccines, and that suppression could be reversed-at least in part-by intensive praziquantel administration., Methods: We conducted an open-label, randomised controlled trial of intensive versus standard intervention against S mansoni among schoolchildren aged 9-17 years from eight primary schools in Koome islands, Uganda. Children were randomly allocated to either an intensive group or a standard group with a computer-generated 1:1 randomisation using permuted blocks sizes 4, 6, 8, and 10. Participants in the intensive group received three praziquantel doses (approximately 40 mg/kg) 2 weeks apart before first vaccination at week 0, and every 3 months thereafter. Participants in the standard group were given one dose of approximately 40 mg/kg praziquantel after the week 8 primary endpoint. Participants in both groups received the BCG vaccine (Serum Institute of India, Pune, India) at week 0; the yellow fever (Sanofi Pasteur, Lyon, France), oral typhoid (PaxVax, London, UK), and first human papillomavirus (HPV) vaccination (Merck, Rahway, NJ, USA) at week 4; and the HPV booster and tetanus-diphtheria vaccine (Serum Institute of India) at week 28. The primary outcome was vaccine response at week 8 (except for tetanus and diphtheria, which was assessed at week 52). The primary analysis population was participants who were infected with S mansoni at baseline, determined retrospectively using either plasma circulating anodic antigen (CAA) or stool PCR. The safety population comprised all randomly allocated participants. The trial was registered at the ISRCTN Registry (ISRCTN60517191) and is complete., Findings: Between July 9 and Aug 14, 2019, we enrolled 478 participants, with 239 children per group. 276 (58%) participants were male and 202 (42%) participants were female. Among participants who were positive for S mansoni at baseline (171 [72%] in the intensive group and 164 [69%] in the standard group) intensive praziquantel administration significantly reduced pre-vaccination infection intensity (to median 30 CAA pg/mL [IQR 7-223] vs 1317 [243-8562], p<0·001) compared with standard treatment. Intensive praziquantel administration also reduced week 8 HPV-16-specific IgG response (geometric mean ratio 0·71 [95% CI 0·54-0·94], p=0·017), but had no effect on other primary outcomes. Among all participants (regardless of S mansoni status at baseline) intensive praziquantel administration significantly improved week 8 BCG-specific IFNγ ELISpot response (1·20 [1·01-1·43], p=0·038). Recognised adverse effects of praziquantel were reported more frequently in the intensive group. There were no recorded serious adverse events in either group., Interpretation: We show evidence suggesting that praziquantel administration improves the BCG-specific cellular response, but not humoral responses to other vaccines. Despite observational evidence that helminths impair vaccine response, these results show minimal immediate benefits of reducing helminth burden. The effect of longer-term helminth control should be investigated., Funding: UK Medical Research Council., Translation: For the Luganda translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests GN and AME report grants from the Wellcome Trust. GN reports funding from the EDCTP2 programme supported by the EU. AME and SC report funding from UK Medical Research Council (MRC) for conduct of the study. AME reports funding from the US National Institutes for Health, Science for Africa Foundation, the Royal Society, and DELTAS Africa, outside the submitted work. AME and AN report support from UK National Institute of Health and care Research (NIHR). AME further reports support from the Serum Institute of India, Uganda National Expanded Program on Immunization, and Emergent BioSolutions for conduct of the study. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Several important vaccines differ in immunogenicity and efficacy between populations. We hypothesised that malaria suppresses responses to unrelated vaccines and that this effect can be reversed-at least partially-by monthly malaria intermittent preventive treatment (IPT) in high-transmission settings., Methods: We conducted an individually randomised, double-blind, placebo-controlled trial of the effect of malaria IPT with dihydroartemisinin-piperaquine on vaccine responses among schoolchildren aged 9-17 years in Jinja district, Uganda. Participants were recruited from two schools and did not have exposure to vaccines of interest after the age of 5 years, with the exception of human papillomavirus (HPV). Computer-generated 1:1 randomisation was implemented in REDCap. 3-day courses of dihydroartemisinin-piperaquine (dosage by weight) or placebo were administered monthly, including twice before the first vaccination. Trial participants were vaccinated with the live parenteral BCG vaccine (Serum Institute of India, Pune, India) at week 0; yellow fever vaccine (YF-17D; Sanofi Pasteur, Lyon, France); live oral typhoid vaccine (Ty21a; PaxVax, London, UK), and quadrivalent virus-like particle HPV vaccine (Merck, Rahway, NJ, USA) at week 4; and toxoid vaccines (tetanus-diphtheria; Serum Institute of India) and an HPV booster at week 28. An additional HPV vaccination at week 8 was provided to female participants older than 14 years who had not previously been vaccinated, and a tetanus-diphtheria booster was given after completion of the trial at week 52. Primary outcomes were vaccine responses at week 8 and, for tetanus-diphtheria, at week 52, and analysis was done in the intention-to-treat population. Malaria parasite prevalence at enrolment and during follow-up was determined retrospectively by PCR. The safety population comprised all randomly allocated participants. The trial was registered at the ISRCTN Registry (ISRCTN62041885) and is complete., Findings: Between May 25 and July 14, 2021, we assessed 388 potential participants for eligibility. We enrolled and randomly allocated 341 participants to the two groups (170 [50%] to dihydroartemisinin-piperaquine and 171 [50%] to placebo); 192 (56%) were female and 149 (44%) participants were male. 145 (85%) participants in the dihydroartemisinin-piperaquine group and 140 participants (82%) in the placebo group were followed up until the week 52 endpoint. At enrolment, 109 (64%) of all participants in the dihydroartemisinin-piperaquine group and 99 (58%) of 170 participants in the placebo group had malaria; this reduced to 6% or lower at all follow-up visits in the dihydroartemisinin-piperaquine group. There was no effect of dihydroartemisinin-piperaquine versus placebo on primary outcomes: BCG-specific IFNγ ELISpot response had a geometric mean ratio (GMR) of 1·09 (95% CI 0·93-1·29), p=0·28; yellow fever neutralising antibody was 1·19 (0·91-1·54), p=0·20 for plaque reduction neutralising reference tests (PRNT 50 ) titres (the reciprocal of the last plasma dilution that reduced by 50%) and 1·24 (0·97-1·58), p=0·09 for PRNT 90 titres (reciprocal of the last plasma dilution that reduced by 90%); and IgG to Salmonella enterica serovar Typhi O-lipopolysaccharide was 1·09 (0·81-1·46), p=0·58, HPV-16 was 0·72 (0·44-1·77), p=0·19, HPV-18 was 0·71 (0·47-1·09), p=0·11; tetanus toxoid was 1·22 (0·91-1·62), p=0·18, and diphtheria toxoid was 0·97 (0·83-1·13), p=0·72. There was some evidence that dihydroartemisinin-piperaquine reduced waning of the yellow fever response., Interpretation: IPT for malaria with dihydroartemisinin-piperaquine did not improve peak vaccine responses, despite reducing malaria prevalence. Possible longer-term effects on response waning should be further explored., Funding: UK Medical Research Council., Translation: For the Luganda translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests GN reports funding from the EDCTP2 programme supported by the EU, and from the Wellcome Trust. AME, PK and SC report funding from the UK Medical Research Council (MRC) for conduct of the study; AME reports funding from UK National Institute of Health and care Research (NIHR), Science for Africa Foundation, and DELTAS Africa, outside the submitted work. AME and SC further report support from the Serum Institute of India and Emergent BioSolutions; AME reports support from Uganda National Expanded Program on Immunization; SC reports support from Bliss GVS Pharma, India, for conduct of the study. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Vaccine immunogenicity and effectiveness vary geographically. Chronic immunomodulating parasitic infections including schistosomes and malaria have been hypothesised to be mediators of geographical variations., Methods: We compared vaccine-specific immune responses between three Ugandan settings (schistosome-endemic rural, malaria-endemic rural, and urban) and did causal mediation analysis to assess the role of Schistosoma mansoni and malaria exposure in observed differences. We used data from the control groups of three linked randomised trials investigating the effects of intensive parasite treatment among schoolchildren. All participants received the BCG vaccine (week 0); yellow fever (YF-17D), oral typhoid (Ty21a), human papillomavirus (HPV; week 4); and HPV booster and tetanus-diphtheria (week 28). Primary outcomes were vaccine responses at week 8 and, for tetanus-diphtheria, week 52. We estimated the total effect (TE) of setting on vaccine responses and natural indirect effect (NIE) mediated through current or previous infection with S mansoni or malaria, and baseline vaccine-specific responses., Findings: We included 239 (43%) participants from the schistosomiasis-endemic setting, 171 (30%) from the malaria-endemic setting, and 151 (27%) from the urban setting. At week 8, vaccine responses were lower in rural settings: schistosomiasis-endemic versus urban settings (TE geometric mean ratio for YF-17D plaque reduction neutralisation at 50% (PRNT 50 ) titres 0·58 [95% CI 0·37 to 0·91], for S Typhi O-lipopolysaccharide-specific IgG 0·61 [0·40 to 0·93], and for tetanus-specific IgG 0·33 [0·22 to 0·51]); malaria-endemic versus urban settings (YF-17D 0·70 [0·49 to 0·99], S Typhi O-lipopolysaccharide-specific IgG 0·29 [0·20 to 0·43], and tetanus-specific IgG 0·53 [-0·35 to 0·80]). However, we found higher BCG-specific IFNγ responses in the malaria-endemic versus urban setting (1·54 [1·20 to 1·98]). The estimated NIEs of setting on vaccine responses mediated through previous and current S mansoni and malaria were not statistically significant. For malaria-endemic versus urban settings, baseline vaccine-specific responses contributed to some but not all differences: S Typhi O-lipopolysaccharide-specific IgG at week 8 (57.9% mediated [38·6 to 77·2]) and week 52 (70·0% mediated [49·4 to 90·6]) and BCG at week 52 (46.4% mediated [-4·8 to 97·7])., Interpretation: We found significant variation in vaccine response between urban and rural settings but could not confirm a causal role for schistosome or malaria exposure. Other exposures require consideration., Funding: UK Medical Research Council., Competing Interests: Declaration of interests GN and AME report grants from Wellcome Trust. GN reports funding from the EDCTP2 programme supported by the EU. AME and SC report funding from the UK Medical Research Council (MRC) for conduct of the study. AME reports funding from the US National Institutes of Health, Science for Africa Foundation, the Royal Society, and DELTAS Africa, outside the submitted work. AME and AN report support from the UK National Institute of Health and Care Research (NIHR). AME further reports support from the Serum Institute of India, Uganda National Expanded Programme on Immunisation, and Emergent BioSolutions for conduct of the study. BN is currently affiliated with the Jenner Institute, University of Oxford, Oxford, UK. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Immune responses induced by several important vaccines differ between populations, with reduced responses in low-income and rural settings compared with high-income and urban settings. BCG immunisation boosts immune responses to some unrelated vaccines in high-income populations. We aimed to test the hypothesis that BCG revaccination can enhance responses to unrelated vaccines in Ugandan schoolchildren., Methods: We conducted an open-label, randomised controlled trial to compare the effects of BCG revaccination versus no BCG revaccination on the immunogenicity of subsequent unrelated vaccines among adolescents aged 13-17 years who are participants in an urban Ugandan birth cohort study, in which BCG vaccination was documented at birth. Participants were excluded if they had received any of the trial vaccines or related agents when aged 5 years or older. Computer-generated 1:1 randomisation was implemented in REDCap. Participants were excluded if they were concurrently enrolled in other trials; had a clinically significant history of immunodeficiency, or serious psychiatric conditions or moderate to severe acute illnesses; were taking immunosuppressive medications; had allergies to vaccine components, a predisposition towards developing keloid scarring; positive HIV tests or pregnancy tests; were female participants who were lactating; or if they planned to use investigational drugs, vaccines, blood products, or any combination thereof. Trial participants assigned to the BCG revaccination group received the live parenteral BCG-Russia vaccine (Serum Institute of India, Pune, India; 0·1 mL intradermally, right upper arm) at week 0. All participants received yellow fever vaccine (YF-17D; Sanofi Pasteur, Lyon, France; 0·5 mL intramuscularly, left upper arm), live oral typhoid vaccine (Ty21a; PaxVax, London, UK; one capsule per day taken for three alternate days), and quadrivalent virus-like particle human papillomavirus (HPV) vaccine (Merck, Rahway, NJ, USA; 0·5 mL intramuscularly, left upper arm) at week 4; and toxoid vaccines (tetanus-diphtheria; Serum Institute of India; 0·5 mL intramuscularly, left upper arm) and an HPV booster at week 28. An additional HPV vaccination at week 8 was provided to female participants older than 14 years who had not previously been vaccinated. The primary outcomes were yellow fever neutralising antibody titres at 4 weeks post-YF-17D vaccination, Salmonella enterica serovar Typhi (henceforth S Typhi) O-lipopolysaccharide (O:LPS)-specific IgG concentration at 4 weeks post-Ty21a vaccination, and HPV-16 and HPV-18 L1 protein-specific IgG concentration at 4 weeks post-HPV vaccination. Primary outcome assays were conducted at week 8, and at week 52 for tetanus-diphtheria. We conducted an intention-to-treat analysis comparing log-transformed outcomes between trial groups, with results back-transformed to geometric mean ratios (GMRs). The safety population comprised all randomly allocated participants. The trial was registered at the ISRCTN Registry (ISRCTN10482904) and is complete., Findings: Between Aug 31 and Oct 12, 2020, we screened 376 potential participants for eligibility. We enrolled and randomly allocated 300 participants to the two groups (151 [50%] to the BCG group and 149 [50%] to the no BCG group). 178 (59%) of 300 participants were male and 122 (41%) were female. 142 (91%) of 151 participants in the BCG group and 139 (93%) of 149 in the no BCG group completed follow-up. There was no effect of BCG revaccination, compared with no BCG revaccination, on the response observed for any vaccine. Yellow fever plaque reduction neutralising reference tests (PRNT 50 ) titres (the reciprocal of the last plasma dilution that reduced by 50%) had a GMR of 0·95 (95% CI 0·75-1·19; p=0·62) and PRNT 90 (reciprocal of the last plasma dilution that reduced by 90%) had a GMR of 0·94 (0·74-1·19; p=0·60); IgG to S Typhi O:LPS was 0·99 (0·80-1·23; p=0·94); IgG to HPV-16 was 0·97 (0·69-1·35; p=0·85) and to HPV-18 was 1·03 (0·76-1·40; p=0·83); and toxoid-specific IgG for tetanus was 1·13 (0·87-1·47; p=0·36) and was 1·00 (0·87-1·16; p=0·97) for diphtheria. There were no serious adverse events in either group., Interpretation: We found no evidence that BCG revaccination is an effective strategy to improve immunogenicity of other vaccines in this low-income, urban setting., Funding: UK Medical Research Council., Translation: For the Luganda translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests GN reports funding from the Wellcome Trust and from the EDCTP2 programme supported by the EU. AME, SC, and PK report funding from the UK Medical Research Council (MRC) for conduct of the study; AME and SC report funding from DELTAS Africa, outside the submitted work, and support from the UK National Institute for Health and Care Research (NIHR). AME reports funding from the Science for Africa Foundation, outside the submitted work. AME and SC further report support from the Serum Institute of India, Uganda National Expanded Program on Immunization, and Emergent BioSolutions for conduct of the study. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Vaccine efficacy varies globally, often showing reduced immune responses in low- and middle-income countries, possibly due to the immunomodulatory effects of parasitic infections like malaria. This systematic review evaluates the impact of malaria on immune responses to unrelated vaccines in humans and animals. We systematically searched five databases-MEDLINE, Web of Science, Global Health, Scopus and Embase-up to 5th December 2023. Eligible studies compared immune responses to WHO-approved vaccines between malaria-infected and uninfected groups, or between antimalarial-treated and untreated groups. Meta-analysis was performed using random-effects models with standardised mean differences (SMDs) as summary statistics. The study is registered with PROSPERO (CRD42022298053). Twenty-four articles (17 human, 7 animal) met the inclusion criteria, with 13 human articles contributing data for the meta-analysis. Significant heterogeneity was observed. Vaccine responses were higher in malaria uninfected individuals (SMD 0.34, 95% CI 0.07 to 0.60, I 2  = 87.15%) with weaker differences between antimalarial-treated and untreated groups (SMD 0.07, 95% CI -0.01 to 0.16, I 2  = 85.01%). The overall SMD for malaria uninfected/treated vs. infected/untreated was 0.15, 95% CI 0.05-0.26, I 2  = 90.91. Narrative analysis suggested malaria's adverse impact on vaccine responses in animals. Malaria infection may impair vaccines responses; with preventive treatment of malaria partially reversing these effects, highlighting the need for targeted public health interventions., (© 2024 The Author(s). Parasite Immunology published by John Wiley & Sons Ltd.)

Protected area downgrading, downsizing, and degazettement (PADDD) is a common occurrence. Although PADDD is expected to weaken biodiversity protection, PADDD offsets and new unrelated protected areas (PAs) could help restore representation of biodiversity features to the reserve network affected by PADDD. Globally, we analyzed 16 territories with terrestrial PADDD and 4 territories with marine PADDD from 2011 to 2020. Our objective was to evaluate whether PADDD offsets and new PAs could restore the PAs, key biodiversity areas (KBAs), ecoregions, and threatened amphibian, mammal, bird, and reptile species ranges where PADDD had occurred. In our studied territories, offsets of PADDD were rare (enacted in 3 [19%] terrestrial territories and one [25%] marine territory). One territory had PADDD losses that were compensated fully by PADDD offsets in terms of area coverage and ecoregions represented. All other territories failed to achieve compensation goals. In territories affected by PADDD, PADDD offsets and new PAs partially restored area representation (63%) and KBA coverage (57%). However, only 38% of ecoregion representation and 20%, 33%, 31%, and 21% of threatened amphibian, mammal, bird, and reptile representation, respectively, were restored. Overall, we found a large shortfall in PADDD offsets, even when unrelated PAs were included in the calculus. There is an urgent need to expand PADDD offsets and PAs to advance biodiversity conservation and achieve the Global Biodiversity Framework's 30×30 target. Future planning of newly enacted conservation areas needs to prioritize biodiversity conservation and consider the purpose of restoring reserve networks affected by PADDD, rather than solely focusing on areal targets., (© 2024 The Author(s). Conservation Biology published by Wiley Periodicals LLC on behalf of Society for Conservation Biology.)

Objective: To investigate the prevalence of non-communicable diseases among household contacts of people with tuberculosis., Methods: We conducted a systematic review and individual participant data meta-analysis. We searched Medline, Embase and the Global Index Medicus from inception to 16 May 2023. We included studies that assessed for at least one non-communicable disease among household contacts of people with clinical tuberculosis. We estimated the non-communicable disease prevalence through mixed effects logistic regression for studies providing individual participant data, and compared it with estimates from aggregated data meta-analyses. Furthermore, we compared age and sex-standardised non-communicable disease prevalence with national-level estimates standardised for age and sex., Results: We identified 39 eligible studies, of which 14 provided individual participant data (29,194 contacts). Of the remaining 25 studies, 18 studies reported aggregated data suitable for aggregated data meta-analysis. In individual participant data analysis, the pooled prevalence of diabetes in studies that undertook biochemical testing was 8.8% (95% confidence interval [CI], 5.1%-14.9%, four studies). Age-and sex-standardised prevalence was higher in two studies (10.4% vs. 6.9% and 11.5% vs. 8.4%) than the corresponding national estimates and similar in two studies. Prevalence of diabetes mellitus based on self-report or medical records was 3.4% (95% CI 2.6%-4.6%, 14 studies). Prevalence did not significantly differ compared to estimates from aggregated data meta-analysis. There were limited data for other non-communicable diseases., Conclusion: The prevalence of diabetes mellitus among household contacts was high while that of known diabetes was substantially lower, suggesting the underdiagnosis. tuberculosis household contact investigation offers opportunities to deliver multifaceted interventions to identify tuberculosis infection and disease, screen for non-communicable diseases and address shared risk factors., (© 2024 The Author(s). Tropical Medicine & International Health published by John Wiley & Sons Ltd.)

Background: Variations in vaccine responses have been observed between populations. A role for helminth infections has been proposed due to their immunomodulatory properties. In a secondary analysis of data from a randomised trial assessing effects of anthelminthic treatment on vaccine responses, we examined associations between helminth infections at baseline prior to vaccine administration, and vaccine responses among adolescents (9-17 years) in Koome Islands, Lake Victoria, Uganda., Methods: Participants received BCG [week 0], yellow fever (YF-17D), oral typhoid (Ty21a), HPV-prime [week 4], and HPV-boost, tetanus/diphtheria [week 28]. Outcomes were BCG-specific interferon-γ ELISpot responses and antibody responses to yellow-fever-, typhoid-, HPV-, tetanus- and diphtheria-specific antigens measured at two time points post vaccination. S. mansoni infection was determined as positive if either the plasma Circulating Anodic Antigen (CAA) assay or stool PCR were positive. Hookworm and Strongyloides were determined by stool PCR. Linear mixed effects regression was used to assess associations., Results: Among 478 adolescents, 70% were Schistosoma mansoni (Sm) infected and 23% hookworm infected at baseline. Sm was associated with lower Salmonella Typhi O:LPS-specific IgG responses (adjusted geometric mean ratio (aGMR) 0.69 (0.57-0.83)), and hookworm with higher diphtheria-specific IgG (aGMR 1.16 (1.02, 1.31)) and lower HPV-16-specific IgG (aGMR 0.70 (0.55, 0.90)) post-vaccination. High Sm intensity was associated with lower BCG-specific interferon-γ and S. Typhi O:LPS-specific IgG., Conclusions: We found inverse associations between Sm and responses to two live vaccines, whereas hookworm was positively associated with diphtheria-specific IgG. These findings support the hypothesis that helminth infections can modulate vaccine responses, while also highlighting potential heterogeneity in the direction of these effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Natukunda, Zirimenya, Nkurunungi, Nassuuna, Nkangi, Mutebe, Corstjens, van Dam, Elliott and Webb.)

Background: Hookworm infection and schistosomiasis are two of sub-Saharan Africa's most common neglected tropical diseases. An annual mass drug administration (MDA) program against schistosomiasis and soil-transmitted helminths (STHs), including hookworm, has been implemented in Mayuge district, Uganda, since 2003 to date. However, hookworm and schistosomiasis remain prevalent in Mayuge district. Understanding the factors that predispose children to these infections in the context of MDA could inform interventions to reduce prevalence in Uganda and similar settings., Method: This cross-sectional study took place in 33 randomly selected primary schools in the Mayuge district from January to February 2022. Children in primary classes 4 or 5, in the selected schools provided single stool samples and completed questionnaires. Stool specimens were examined using the Kato-Katz method to determine the prevalence of hookworm and schistosomiasis. We performed univariable and multivariable logistic regression to assess the associations of each infection with potential risk factors., Result: A total of 1,617 students (mean age 12.1 years, 50.1% male) were enrolled. The prevalence of hookworm infection and schistosomiasis was 21.8% (95% confidence interval (CI): 19.8-23.9%) and 18.7% (95% CI: 16.8-20.7%), respectively. In multivariable analysis, longer water fetching time (over 30 min versus less than 30 min) and working daily in the soil were associated with increased odds of hookworm infection (adjusted odds ratio (AOR): 1.49, 95% CI: 1.13-1.96 and 1.37, 95% CI: 1.03-1.82, respectively). Higher odds of schistosomiasis were linked to proximity to water bodies within a one-hour walking distance (AOR: 1.84, 95% CI: 1.35-2.50), and not always washing hands before eating (AOR: 2.00, 95% CI: 1.50-2.67). Swimming, bathing, or washing in water bodies twice a week, compared to never, also increased schistosomiasis odds (AOR: 2.91, 95% CI: 1.66-5.13)., Conclusion: Consistent with the mechanisms of acquisition, hookworm infection increased with exposure to soil, and schistosomiasis increased with exposure to unclean water. Our findings highlight the importance of Water, Sanitation, and Hygiene programs and strategies aimed at reducing exposure within the framework of Neglected Tropical Disease elimination programs., (© 2024. The Author(s).)

Each year, an average of 45 tropical cyclones affect coastal areas and potentially impact forests. The proportion of the most intense cyclones has increased over the past four decades and is predicted to continue to do so. Yet, it remains uncertain how topographical exposure and tree characteristics can mediate the damage caused by increasing wind speed. Here, we compiled empirical data on the damage caused by 11 cyclones occurring over the past 40 years, from 74 forest plots representing tropical regions worldwide, encompassing field data for 22,176 trees and 815 species. We reconstructed the wind structure of those tropical cyclones to estimate the maximum sustained wind speed (MSW) and wind direction at the studied plots. Then, we used a causal inference framework combined with Bayesian generalised linear mixed models to understand and quantify the causal effects of MSW, topographical exposure to wind (EXP), tree size (DBH) and species wood density (ρ) on the proportion of damaged trees at the community level, and on the probability of snapping or uprooting at the tree level. The probability of snapping or uprooting at the tree level and, hence, the proportion of damaged trees at the community level, increased with increasing MSW, and with increasing EXP accentuating the damaging effects of cyclones, in particular at higher wind speeds. Higher ρ decreased the probability of snapping and to a lesser extent of uprooting. Larger trees tended to have lower probabilities of snapping but increased probabilities of uprooting. Importantly, the effect of ρ decreasing the probabilities of snapping was more marked for smaller than larger trees and was further accentuated at higher MSW. Our work emphasises how local topography, tree size and species wood density together mediate cyclone damage to tropical forests, facilitating better predictions of the impacts of such disturbances in an increasingly windier world., (© 2024 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Objectives: Schistosomiasis is persistent in Lake Albert, Uganda, but local data are limited. This study aims to describe the local burden of moderate-to-heavy infection and associated morbidity in all ages and identify factors associated with these outcomes to guide further research., Methods: This cross-sectional pilot study was conducted in July-August, 2022 in four village sites (Walukuba, Rwentale, Kyabarangwa and Runga) of the Praziquantel in Preschoolers (PIP) trial. Residents (approximately four per household) of any age of households of PIP participants were eligible, but individuals <10 years were only enrolled if no older individuals were available. Socio-demographic information, household location, single stool Kato-Katz and hepatic ultrasound results were obtained for a convenience sampled subset of trial households. The primary outcome, moderate-to-heavy infection (≥100 eggs per gram of faeces), was analysed using mixed-effects logistic regression, with a household random effect. Univariate analyses were used for the secondary outcome, periportal fibrosis (Niamey protocol ultrasound image pattern C-F)., Results: Of 243 participants with a median age of 22 (interquartile range 12-33) years from 66 households, 49.8% (103/207 with a Kato-Katz result) had moderate-to-heavy infection and 11.2% (25/224 with ultrasound data) had periportal fibrosis. Moderate-to-heavy infection clustered by household (intraclass correlation coefficient = 0.11) and, in multivariable analysis, varied by village (Walukuba vs. Kyabarangwa adjusted odds ratio [aOR] 0.11, 95% CI 0.02-0.71), was highest in participants aged 10-15 years (vs. 5-9 years aOR 6.14, 95% CI 1.61-23.38) and lower in those reporting praziquantel treatment in the past year (aOR 0.39, 95% CI 0.18-0.88)., Conclusions: In this setting, schistosome infection and morbidity are pervasive in all age groups. More intensive interventions are needed, for example more frequent praziquantel treatment, under investigation in the PIP trial and improved water and sanitation. More research is needed to understand local treatment barriers and optimal control strategies., (© 2024 The Authors Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

The current research examines potentially morally injurious events (PMIEs) faced by healthcare professionals working in forensic and psychiatric environments. A systematic literature review was conducted to identify peer-reviewed articles reporting on sources of moral injury or similar concepts (e.g., moral distress) for healthcare workers in such settings. Thirty articles were included and analyzed using a meta-ethnographic approach. Synthesis yielded three third-order factors, each reflecting a moral dichotomy: (a) "between profession and system," (b) "between relations with patients and relations with others," and (c) "between principles and practices." Findings illustrated the hierarchical relationships between dichotomies, with discordance between values of the healthcare profession and features of the healthcare system providing the conditions for PMIEs to occur. The review advances conceptual understandings of PMIEs in forensic and psychiatric settings, illustrating the multilayered dimensions within which morally injurious events are experienced. Theoretical and practical implications are offered that may support the early detection and prevention of moral injury in healthcare professionals., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: BCG confers reduced, variable protection against pulmonary tuberculosis. A more effective vaccine is needed. We evaluated the safety and immunogenicity of candidate regimen ChAdOx1 85A-MVA85A compared with BCG revaccination among Ugandan adolescents., Methods: After ChAdOx1 85A dose escalation and age de-escalation, we did a randomised open-label phase 2a trial among healthy adolescents aged 12-17 years, who were BCG vaccinated at birth, without evident tuberculosis exposure, in Entebbe, Uganda. Participants were randomly assigned (1:1) using a block size of 6, to ChAdOx1 85A followed by MVA85A (on day 56) or BCG (Moscow strain). Laboratory staff were masked to group assignment. Primary outcomes were solicited and unsolicited adverse events (AEs) up to day 28 and serious adverse events (SAEs) throughout the trial; and IFN-γ ELISpot response to antigen 85A (day 63 [geometric mean] and days 0-224 [area under the curve; AUC)., Findings: Six adults (group 1, n=3; group 2, n=3) and six adolescents (group 3, n=3; group 4, n=3) were enrolled in the ChAdOx1 85A-only dose-escalation and age de-escalation studies (July to August, 2019). In the phase 2a trial, 60 adolescents were randomly assigned to ChAdOx1 85A-MVA85A (group 5, n=30) or BCG (group 6, n=30; December, 2019, to October, 2020). All 60 participants from groups 5 and 6 were included in the safety analysis, with 28 of 30 from group 5 (ChAdOx1 85A-MVA85A) and 29 of 30 from group 6 (BCG revaccination) analysed for immunogenicity outcomes. In the randomised trial, 60 AEs were reported among 23 (77%) of 30 participants following ChAdOx1 85A-MVA85A, 31 were systemic, with one severe event that occurred after the MVA85A boost that was rapidly self-limiting. All 30 participants in the BCG revaccination group reported at least one mild to moderate solicited AE; most were local reactions. There were no SAEs in either group. Ag85A-specific IFN-γ ELISpot responses peaked on day 63 in the ChAdOx1 85A-MVA85A group and were higher in the ChAdOx1 85A-MVA85A group compared with the BCG revaccination group (geometric mean ratio 30·59 [95% CI 17·46-53·59], p<0·0001, day 63; AUC mean difference 57 091 [95% CI 40 524-73 658], p<0·0001, days 0-224)., Interpretation: The ChAdOx1 85A-MVA85A regimen was safe and induced stronger Ag85A-specific responses than BCG revaccination. Our findings support further development of booster tuberculosis vaccines., Funding: UK Research and Innovations and Medical Research Council., Translations: For the Swahili and Luganda translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

In a cross-sectional analysis of 354 Ugandan children (age 12-48 months) infected with Schistosoma mansoni, we assessed relationships between infection intensity and nutritional morbidities. Higher intensity was associated with an increased risk for anemia (RR = 1.05, 95% confidence interval [CI] 1.01-1.10) yet not associated with risk for underweight, stunting, or wasting., Competing Interests: Potential conflicts of interest. A. L. B. reports grants from UKRI Future Leaders Fellowship in Global Health (grant number MR/T041900/1) and Wellcome Trust Biomedical Facilities Grant (Schistosomiasis Snail Resource Facilities—SSR). S. C. reports receipt of the Thrasher Early Career Award. J. F. F. reports a Midcareer Investigator Award in Patient Oriented Research from US National Institutes of Health/NIAID (award number K24 AI112964-06). E. L. W. reports grants from UK Medical Research Council (MRC), UK National Institute for Health and Care Research (NIHR), and European and Developing Countries Clinical Trial Partnership—European Union (EDCTP). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Trees structure the Earth's most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge. Here we investigate abundance patterns of common tree species using inventory data on 1,003,805 trees with trunk diameters of at least 10 cm across 1,568 locations 1-6 in closed-canopy, structurally intact old-growth tropical forests in Africa, Amazonia and Southeast Asia. We estimate that 2.2%, 2.2% and 2.3% of species comprise 50% of the tropical trees in these regions, respectively. Extrapolating across all closed-canopy tropical forests, we estimate that just 1,053 species comprise half of Earth's 800 billion tropical trees with trunk diameters of at least 10 cm. Despite differing biogeographic, climatic and anthropogenic histories 7 , we find notably consistent patterns of common species and species abundance distributions across the continents. This suggests that fundamental mechanisms of tree community assembly may apply to all tropical forests. Resampling analyses show that the most common species are likely to belong to a manageable list of known species, enabling targeted efforts to understand their ecology. Although they do not detract from the importance of rare species, our results open new opportunities to understand the world's most diverse forests, including modelling their response to environmental change, by focusing on the common species that constitute the majority of their trees., (© 2024. The Author(s).)

Background: Periportal fibrosis is a late-stage manifestation of chronic infection with Schistosoma mansoni . Praziquantel (PZQ), the only drug available for the treatment of schistosomiasis, has limited effect in treating established morbidity. Preschool-age children (PSAC) are not considered to be an at-risk population for severe morbidity. However, the prevalence of periportal fibrosis in PSAC in S. mansoni endemic settings is unknown., Methods: As part of a phase II clinical trial comparing different dosing regimens of PZQ in children age 12-47 months infected with S. mansoni in Uganda ("praziquantel in preschoolers" trial), we present baseline results assessing liver ultrasound (US) findings as per the WHO Niamey Protocol., Results: A total of 7/347 (2%) PSAC had Image Pattern C with pipe stems and echogenic rings suggestive of periportal fibrosis, 29/347 (8%) had Image Pattern B and 58 (17%) had evidence of periportal thickening There were higher adjusted odds of periportal thickening with older age [odds ratio (OR): 1.04; 95% confidence interval (CI): 1.00-1.07], primary maternal education (OR: 1.04; 95% CI: 1.00-1.07) and being taken to the lake weekly (OR: 3.02; 95% CI: 1.19-7.63). A further 44/347 children (13%) had a rounded caudal liver edge which was associated with high S. mansoni infection intensity (adjusted OR: 3.31; 95% CI: 1.46-7.51)., Conclusions: Incipient schistosomiasis-related liver morbidity was detected in young children enrolled in the praziquantel in preschoolers trial. Adequate age-adjusted reference measurements for liver ultrasound findings in very small children are lacking but urgently needed. Schistosomiasis-related fibrosis may be delayed or averted with early and repeated PZQ treatment., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The penile epithelial microbiome remains underexplored. We sequenced human RNA and a segment of the bacterial 16S rRNA gene from the foreskin tissue of 144 adolescents from South Africa and Uganda collected during penile circumcision after receipt of 1-2 doses of placebo, emtricitabine + tenofovir disoproxil fumarate, or emtricitabine + tenofovir alafenamide to investigate the microbiome of foreskin tissue and its potential changes with antiretroviral use. We identified a large number of anaerobic species, including Corynebacterium acnes, which was detected more frequently in participants from South Africa than Uganda. Bacterial populations did not differ by treatment received, and no differentially abundant taxa were identified between placebo versus active drug recipients. The relative abundance of specific bacterial taxa was negatively correlated with expression of genes downstream of the innate immune response to bacteria and regulation of inflammation. Our results show no difference in the tissue microbiome of the foreskin with short-course antiretroviral use but that bacterial taxa were largely inversely correlated with inflammatory gene expression, consistent with commensal colonization., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Impaired linear growth and slower pubertal growth can be associated with perinatal HIV infection. We characterised growth relative to population norms, among the full adolescent period in southern Africa to better understand processes leading to morbidity in adulthood. We conducted a secondary analysis of 945 adolescents aged 8-20 years from urban Malawi and Zimbabwe; we included children with HIV (CWH), an uninfected comparison group from a cohort study, and CWH with co-morbid chronic lung disease (CLD) from a randomised controlled trial. We used latent class analysis of anthropometric Z-scores generated from British 1990 reference equations at two annual time-points, to identify growth trajectory profiles and used multinomial logistic regression to identify factors associated with growth profiles. Growth faltering (one or more of weight-for-age, height-for-age, or BMI-for-age Z-scores < -2) occurred in 38% (116/303) of CWH from the cohort study, 62% (209/336) of CWH with CLD, and 14% (44/306) of HIV-uninfected participants. We identified seven different growth profiles, defined, relatively, as (1) average growth, (2) tall not thin, (3) short not thin, (4) stunted not thin, (5) thin not stunted, (6) thin and stunted and (7) very thin and stunted. Females in profile 3 exhibited the highest body fat percentage, which increased over 1 year. Males at older age and CWH especially those with CLD were more likely to fall into growth profiles 4-7. Improvements in height-for-age Z-scores were observed in profiles 6-7 over 1 year. Interventions to target those with the worst growth faltering and longer-term follow-up to assess the impact on adult health are warranted.

Objectives: As topical pre-exposure prophylaxis (PrEP) has been shown to cause immune modulation in rectal or cervical tissue, our aim was to examine the impact of oral PrEP on lymphoid and myeloid changes in the foreskin in response to dosing and timing of drug administration., Design: HIV-negative male individuals ( n  = 144) were recruited in South Africa and Uganda into an open-label randomized controlled trial in a 1 : 1 : 1 : 1 : 1 : 1 : 1 : 1 : 1 ratio to control arm (with no PrEP) or one of eight arms receiving emtricitabine-tenofovir disoproxil fumarate (F/TDF) or emtricitabine-tenofovir alafenamide (F/TAF) at one of two different doses, 5 or 21 h before undergoing voluntary medical male circumcision (VMMC)., Methods: After dorsal-slit circumcision, foreskin tissue sections were embedded into Optimal Cutting Temperature media and analysed, blinded to trial allocation, to determine numbers of CD4 + CCR5 + , CD1a + cells and claudin-1 expression. Cell densities were correlated with tissue-bound drug metabolites and p24 production after ex-vivo foreskin challenge with HIV-1 bal ., Results: There was no significant difference in CD4 + CCR5 + or CD1a + cell numbers in foreskins between treatment arms compared with the control arm. Claudin-1 expression was 34% higher ( P  = 0.003) in foreskin tissue from participants receiving PrEP relative to controls, but was no longer statistically significant after controlling for multiple comparisons. There was neither correlation of CD4 + CCR5 + , CD1a + cell numbers, or claudin-1 expression with tissue-bound drug metabolites, nor with p24 production after ex-vivo viral challenge., Conclusion: Oral doses and timing of on-demand PrEP and in-situ drug metabolite levels in tissue have no effect on numbers or anatomical location of lymphoid or myeloid HIV target cells in foreskin tissue., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Control of schistosomiasis depends on a single drug, praziquantel, with variable cure rates, high reinfection rates, and risk of drug resistance. A vaccine could transform schistosomiasis control. Preclinical data show that vaccine development is possible, but conventional vaccine efficacy trials require high incidence, long-term follow-up, and large sample size. Controlled human infection studies (CHI) can provide early efficacy data, allowing the selection of optimal candidates for further trials. A Schistosoma CHI has been established in the Netherlands but responses to infection and vaccines differ in target populations in endemic countries. We aim to develop a CHI for Schistosoma mansoni in Uganda to test candidate vaccines in an endemic setting. This is an open-label, dose-escalation trial in two populations: minimal, or intense, prior Schistosoma exposure. In each population, participants will be enrolled in sequential dose-escalating groups. Initially, three volunteers will be exposed to 10 cercariae. If all show infection, seven more will be exposed to the same dose. If not, three volunteers in subsequent groups will be exposed to higher doses (20 or 30 cercariae) following the same algorithm, until all 10 volunteers receiving a particular dose become infected, at which point the study will be stopped for that population. Volunteers will be followed weekly after infection until CAA positivity or to 12 weeks. Once positive, they will be treated with praziquantel and followed for one year. The trial registry number is ISRCTN14033813 and all approvals have been obtained. The trial will be subjected to monitoring, inspection, and/or audits., Competing Interests: The authors declare that the research was conceptualized and protocol written in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology.)

The benefits of exclusive breastfeeding (EBF) for infant health and survival are well documented. However, its impact on educational outcomes has been contested and poorly researched in Africa. It has been hypothesised that positive associations reported in high-income countries can be attributed to residual confounding by socioeconomic status (SES). Our study investigated whether EBF duration in infancy is associated with educational attainment and age-for-grade attainment trajectories at school-age in rural Malawi. Longitudinal data on 1021 children at the Karonga demographic surveillance site in Malawi were analysed. Breastfeeding data were collected 3 months after birth and again at age one. The school grade of each child was recorded each year from age 6 until age 13. We calculated age-for-grade based on whether a child was at, over, or under the official expected age for a grade. Generalised estimating equations estimated the average effect of breastfeeding on age-for-grade. Latent class growth analysis identified age-for-grade trajectories, and multinomial logistic regression examined their associations with EBF. Maternal-child characteristics, SES, and HIV status were controlled. Overall, 35.9% of the children were exclusively breastfed for 6 months. Over-age for grade steadily increased from 9.6% at age 8 to 41.9% at age 13. There was some evidence that EBF for 6 months was associated with lower odds of being over-age for grade than EBF for less than 3 months (aOR = 0.82, 95%CI = 0.64-1.06). In subgroup analyses, children exclusively breastfed for 6 months in infancy were less likely to be over-age for grades between ages 6-9 (aOR = 0.64, 95%CI = 0.43-0.94). Latent class growth analysis also provided some evidence that EBF reduced the odds of falling behind in the early school grades (aOR = 0.66, 95%CI = 0.41-1.08) but not later. Our study adds to the growing evidence that EBF for 6 months has benefits beyond infant health and survival, supporting the WHO's recommendation on EBF., (© 2023. The Author(s).)

Background: Tuberculosis case-finding interventions are critical to meeting World Health Organization End TB strategy goals. We investigated the impact of community-wide tuberculosis active case finding (ACF) alongside scale-up of human immunodeficiency virus (HIV) testing and care on trends in adult tuberculosis case notification rates (CNRs) in Blantyre, Malawi., Methods: Five rounds of ACF for tuberculosis (1-2 weeks of leafleting, door-to-door enquiry for cough and sputum microscopy) were delivered to neighborhoods ("ACF areas") in North-West Blantyre between April 2011 and August 2014. Many of these neighborhoods also had concurrent HIV testing interventions. The remaining neighborhoods in Blantyre City ("non-ACF areas") provided a non-randomized comparator. We analyzed TB CNRs from January 2009 until December 2018. We used interrupted time series analysis to compare tuberculosis CNRs before ACF and after ACF, and between ACF and non-ACF areas., Results: Tuberculosis CNRs increased in Blantyre concurrently with start of ACF for tuberculosis in both ACF and non-ACF areas, with a larger magnitude in ACF areas. Compared to a counterfactual where pre-ACF CNR trends continued during ACF period, we estimated there were an additional 101 (95% confidence interval [CI] 42 to 160) microbiologically confirmed (Bac+) tuberculosis diagnoses per 100 000 person-years in the ACF areas in 3 and a half years of ACF. Compared to a counterfactual where trends in ACF area were the same as trends in non-ACF areas, we estimated an additional 63 (95% CI 38 to 90) Bac + diagnoses per 100 000 person-years in the same period., Conclusions: Tuberculosis ACF was associated with a rapid increase in people diagnosed with tuberculosis in Blantyre., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Mass Drug Administration (MDA) is the main strategy for control of soil-transmitted helminth (STH) infections, with single-dose benzimidazole (albendazole or mebendazole) the principal MDA option. In Mayuge district, Uganda, an MDA programme has been in place for over fifteen years but hookworm infection remains common and there is concern that the effectiveness of single-dose albendazole as currently used for MDA may be sub-optimal. This study aims to assess the efficacy of dual- versus single-dose albendazole, with and without fatty food co-administration against hookworm, the dominant form of STHs in Mayuge district, Uganda., Methodology: This was a 2x2 factorial randomised controlled trial to investigate two interventions simultaneously; 1) dual-dose versus single-dose albendazole, 2) taking albendazole with or without fatty food (200 grams of avocado eaten directly after medication). School children with hookworm infection were randomised in a 1:1:1:1 ratio to the four possible treatment groups. Three weeks after the treatment, stool samples were collected from trial participants to evaluate trial outcomes: cure rate and egg reduction rate (ERR)., Principal Findings: A total of 225 participants were enrolled, and 222 (98.7%) seen at 3 weeks. The cure rate in the dual-dose group was 96.4% (95% CI: 90.9-99%), higher than 83.9% (95% CI: 75.7-90.2%) in the single-dose group (OR: 5.07, 95% CI:1.61-15.96, p = 0.002). The ERR was 97.6% and 94.5% in the dual-dose group and single-dose drug group, respectively (ERR difference 3.1%, 95% CI: -3.89-16.39%, p = 0.553). The cure rates among participants taking albendazole with and without avocado were 90.1% and 89.1%, respectively, with no statistical difference between the two groups (OR: 1.24, 95% CI: 0.51-3.03, p = 0.622). The ERR was 97.0% and 94.2% in the group receiving albendazole with and without avocado, respectively, and the difference in ERR between the two groups was 2.8% (95% CI -8.63-14.3%, p = 0.629)., Conclusions/significance: In Ugandan school children, dual-dose albendazole improves the cure rate of hookworm compared to single-dose albendazole. However, there was no significant improvement in cure rate or egg reduction rate of hookworm with fatty-food co-administration. Dual-dose albendazole is a feasible alternative for improving drug effectiveness against hookworm infection and minimising drug resistance., Trial Registration: PACTR202202738940158., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The efficacy of on-demand HIV pre-exposure prophylaxis (PrEP) for men in sub-Saharan Africa has not been evaluated, and the on-demand PrEP dosing requirement for insertive sex remains unknown., Methods: HIV-negative males 13-24 years, requesting voluntary medical male circumcision (VMMC), were enrolled into an open-label randomised controlled trial (NCT03986970), and randomised 1:1:1:1:1:1:1:1:1 to control arm or one of eight arms receiving emtricitabine-tenofovir disoproxil fumarate (F/TDF) or emtricitabine-tenofovir alafenamide (F/TAF) over one or two days, and circumcised 5 or 21 h thereafter. The primary outcome was foreskin p24 concentrations following ex vivo HIV-1 BaL challenge. Secondary outcomes included peripheral blood mononuclear cell (PBMC) p24 concentration, and drug concentrations in foreskin tissue, PBMCs, plasma and foreskin CD4+/CD4-cells. In the control arm, post-exposure prophylaxis (PEP) activity of non-formulated tenofovir-emtricitabine (TFV-FTC) or TAF-FTC was assessed with ex vivo dosing 1, 24, 48 or 72 h post-HIV-1 challenge., Findings: 144 participants were analysed. PrEP with F/TDF or F/TAF prevented ex vivo infection of foreskins and PBMCs both 5 and 21 h after PrEP dosing. There was no difference between F/TDF and F/TAF (p24 day15 geometric mean ratio 1.06, 95% confidence interval: 0.65-1.74). Additional ex vivo dosing did not further increase inhibition. In the control arm, PEP ex vivo dosing was effective up to 48 post-exposure diminishing thereafter, with TAF-FTC showing prolonged protection compared to TFV-FTC. Participants receiving F/TAF had higher TFV-DP concentrations in foreskin tissue and PBMCs compared with F/TDF, irrespective of dose and sampling interval; but F/TAF did not confer preferential TFV-DP distribution into foreskin HIV target cells. FTC-TP concentrations with both drug regimens were equivalent and ∼1 log higher than TFV-DP in foreskin., Interpretation: A double dose of either F/TDF or F/TAF given once either 5 or 21 h before ex vivo HIV-challenge provided protection across foreskin tissue. Further clinical evaluation of pre-coital PrEP for insertive sex is warranted., Funding: EDCTP2, Gilead Sciences, Vetenskapsrådet., Competing Interests: Declaration of interests CH has received research grants from EDCTP, Vetenskapsrådet and Gilead Sciences. LE has received research grants from EDCTP, and Gilead Sciences. LL has received research grants from EDCTP, Gilead Sciences, Roche Diagnostic, DO has received research grants from EDCTP, AS has received research grants from EDCTP, AP has received research grants from EDCTP, PN has received research grants from EDCTP, PS has received research grants from EDCTP, DS has received research grants from EDCTP, RM has received research grants from EDCTP, BA has received research grants from EDCTP, SP has received research grants from EDCTP, CC is an employee of Gilead Sciences, JS has received research grants from EDCTP, HW has received research grants from EDCTP, SK has received research funding, speaker honoraria and consulting fees from EDCTP, Gilead Sciences, ViiV, Merck, GSK, and Ridgeback. FC has received research grants from EDCTP and Vetenskapsrådet. ELW has received grants from EDCTP, MRC, and NIH. CG has received research grants from EDCTP. PK has received research grants from EDCTP. EW has received research grants from EDCTP, NIH and MRC. NM has received research grants from EDCTP, and Gilead Sciences and provided unpaid advice and leadership in the DSMB and Setshaba boards. CC is a full-time employee of Gilead Sciences. All other authors declare no competing interests aside from the research grant received for this study by EDCTP., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Each year, nearly 30 million children globally are at risk of developmental difficulties and disability as a result of newborn health conditions, with the majority living in resource-constrained countries. This study estimates the annual cost to families related to caring for a young child with developmental disability in Uganda. Nested within a feasibility trial of early care and support for young children with developmental disabilities, this sub-study estimated the cost of illness, the cost of paternal abandonment of the caregiver and the affordability of care by household. Seventy-three caregivers took part in this sub-study. The average annual cost of illness to families was USD 949. The main cost drivers were the cost of seeking care and income lost due to loss of employment. Households caring for a child with a disability spent more than the national average household expenditure, and the annual cost of illness for all households was more than 100% of the national GDP per capita. In addition, 84% of caregivers faced economic consequences and resorted to wealth-reducing coping strategies. Families caring for a child with severe impairment incurred USD 358 more on average than those with mild or moderate impairment. Paternal abandonment was common (31%) with affected mothers losing an average of USD 430 in financial support. Caring for a young child with developmental disability was unaffordable to all the study households. Programmes of early care and support have the potential to reduce these financial impacts. National efforts to curb this catastrophic health expenditure are necessary., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Katumba et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Mobility is linked to negative HIV care continuum outcomes. We sought to understand factors associated with short and long term mobility among women in fishing communities in Kenya, Tanzania, and Uganda. From 2018 through 2019 we conducted a cross-sectional survey of women aged 15 years and above, randomly selected from a census of six fishing villages, around Lake Victoria. Data collected included: demographics, risky sexual behaviour on the most recent trip, and travel behaviour in the previous 4 months. Mobility was recorded as any overnight trip outside the participant's village. A two-level multinomial logistic regression model was used to determine the associated factors. A total of 901 participants were enrolled, of whom 645 (71.6%) reported travelling (53.4%; short and 18.2% long term trips). Five factors were associated with long term travel: age, travel purpose, frequency of travel, sexual behaviour while travelling, and destination. Trips made by women aged 46-75 years were less likely to be long term. Long term trips were more common if the trip was to visit, rather than to trade, and more common for women who reported one or two trips rather than three or more trips. Women who made long term trips were more likely to engage in unprotected sex while on a trip. Women who travelled to a regional town/district or another town/district were more likely to take long term trips. The factors associated with travel duration among women living in fishing communities could inform planning of future health care interventions in these communities., (© 2022. The Author(s).)

Background: Authors from low and middle-income country (LMIC) institutions are under-represented in publications of research based in LMICs. This case study of publications from authors within the Medical Research Council International Statistics and Epidemiology Group (MRC-ISEG), a global health research group affiliated to the London School of Hygiene & Tropical Medicine in the UK, aims to describe patterns in authorship and factors associated with under-representation., Methods: Papers were included if they were published between January 2016 and December 2020 inclusive, included an author from the MRC-ISEG and described work conducted in a LMIC. Authors' affiliations were classified using World Bank country income classifications into LMIC affiliations only, high-income country (HIC) affiliations only and mixed LMIC/HIC affiliations. Multinomial logistic regression analysis was used to assess associations of author affiliation category with authorship position, and whether patterns varied by journal impact factor quartile and multiple versus single-country studies., Results: A total of 882 papers, including 10 570 authors describing research conducted in 61 LMICs, were included. Compared with authors of HIC-only affiliation, those with LMIC-only affiliation were less likely to be in first authorship position (relative risk ratio (RRR)=0.51, 95% CI 0.44 to 0.60) and mixed HIC/LMIC affiliation authors were more likely (RRR=2.80, 95% CI 2.35 to 3.34). Compared with authors of HIC-only affiliation, those with LMIC-only affiliation were less likely to be in last authorship position (RRR=0.20, 95% CI 0.16 to 0.24) and those with mixed HIC/LMIC affiliations were more likely (RRR=1.95, 95% CI 1.65 to 2.30). The proportion of senior authors with LMIC-only affiliation was lowest for the highest impact journals, and in multicountry versus single-country studies., Conclusion: Alongside increasing research capacity within LMICs, HIC institutions should ensure that LMIC-affiliated researchers are properly represented in global research. Academics working in global health should be judged on their involvement in representative collaborative research rather than individual achievements in authorship position., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: People with subclinical tuberculosis (TB) have microbiological evidence of disease caused by Mycobacterium tuberculosis , but either do not have or do not report TB symptoms. The relationship between human immunodeficiency virus (HIV) and subclinical TB is not yet well understood. We estimated the prevalence of subclinical pulmonary TB in household contacts of index TB patients in two South African provinces, and how this differed by HIV status., Methods: This was a cross-sectional, secondary analysis of baseline data from the intervention arm of a household cluster randomised trial. Prevalence of subclinical TB was measured as the number of household contacts aged ≥ 5 years who had positive sputum TB microscopy, culture or nucleic acid amplification test (Xpert MTB/Rif or Xpert Ultra) results on a single sputum specimen and who did not report current cough, fever, weight loss or night sweats on direct questioning. Regression analysis was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for the association between HIV status and subclinical TB; adjusting for province, sex and age in household contacts; and HIV status in index patients., Results: Amongst household contacts, microbiologically confirmed prevalent subclinical TB was over twice as common as symptomatic TB disease (48/2077, 2.3%, 95% CI 1.7-3.1% compared to 20/2077, 1.0%, 95% CI 0.6-1.5%). Subclinical TB prevalence was higher in people living with HIV (15/377, 4.0%, 95% CI 2.2-6.5%) compared to those who were HIV-negative (33/1696, 1.9%, 95% CI 1.3-2.7%; p  = 0.018). In regression analysis, living with HIV (377/2077, 18.2%) was associated with a two-fold increase in prevalent subclinical TB with 95% confidence intervals consistent with no association through to a four-fold increase (adjusted OR 2.00, 95% CI 0.99-4.01, p  = 0.052). Living with HIV was associated with a five-fold increase in prevalent symptomatic TB (adjusted OR 5.05, 95% CI 2.22-11.59, p  < 0.001)., Conclusions: Most (70.6%) pulmonary TB diagnosed in household contacts in this setting was subclinical. Living with HIV was likely associated with prevalent subclinical TB and was associated with prevalent symptomatic TB. Universal sputum testing with sensitive assays improves early TB diagnosis in subclinical household contacts., Supplementary Information: The online version contains supplementary material available at 10.1186/s44263-023-00022-5., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2023.)

Background: Female genital schistosomiasis (FGS) occurs when Schistosoma haematobium eggs are deposited in reproductive tissue. Female genital schistosomiasis in the cervical mucosa is associated with increased vascularity. If FGS is associated with the presence of hemoglobin in cervicovaginal lavage (CVL), the use of urinary reagent strips to detect hemoglobin in CVL could supplement FGS diagnosis., Methods: Nonmenstruating, nonpregnant, sexually active women aged 18-31 participating in the HPTN 071 (PopART) Population-Cohort were invited in 2 Zambian communities. Genital self-swabs and a urine specimen were collected at a home visit, and CVL and hand-held colposcopy were performed at a midwife led clinic visit. Urinary reagent strips were used to identify hemoglobin in CVL. Eggs and circulating anodic antigen (CAA) were detected from urine. Visual-FGS was defined as the presence of sandy patches, rubbery papules, or abnormal blood vessels. Polymerase chain reaction (PCR)-FGS was defined as Schistosoma deoxyribonucleic acid detected by real-time PCR on CVL or cervical or vaginal swab., Results: Of 209 women with home genital swabs and companion CVL specimens, 66% (138 of 209) had detectable CVL hemoglobin, 13.4% (28 of 209) had PCR-defined FGS, and 17.2% (36 of 209) had visual-FGS. Active Schistosoma infection, diagnosed by CAA or urine microscopy, was present in 21.0% (44 of 209) participants. Active Schistosoma infection ( P = .4), PCR-FGS ( P = 0.7), and visual-FGS ( P = 0.3) were not associated with CVL hemoglobin presence. Results did not differ in subgroups with high infection burden (cycle threshold < 35 or 2-3 positive genital PCR)., Conclusions: Polymerase chain reaction-FGS, visual-FGS, and active Schistosoma infection were not associated with the presence of CVL hemoglobin. Further research is needed to establish accessible community-based FGS diagnostics., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)