BACKGROUND:Cutaneous leishmaniasis (CL) is a major public health challenge in Ethiopia, with 20-30,000 new cases annually. Limited awareness and misconceptions contribute to delayed care seeking, stigma, prolonged healing, and reduced uptake of preventive measures in CL-endemic communities. To address these challenges, a participatory community dialogue (CD) intervention was implemented to evaluate a structured CD intervention in improving knowledge, attitudes, and preventive practices related to CL in Kalu District, Ethiopia. METHODS:A convergent parallel mixed-methods study was conducted in three CL-endemic clusters. Structured CD sessions were held between May and September 2024. Post-intervention qualitative data were collected through in-depth interviews with facilitators and mobilisers (n = 6) and 10 focus group discussions with participants (n = 81), analysed thematically. Quantitative data were obtained from questionnaires before (n = 128) and after the intervention (n = 109), compared using paired t-tests and odds ratios. RESULTS:Participants in group discussions explained that CD sessions helped them to abandon misconceptions, such as beliefs that CL is transmitted through bat urine and that CL-affected people need to self-isolate during treatment to avoid contacts with those who had sexual intercourse and might cast a 'shadow' that could harm their healing. The intervention reframed contagion fears and encouraged biomedical explanations. Questionnaire data indicated attribution of CL to 'germs/parasites' increased from 21% (27/128) before the CD to 88% (96/109) after the CD and belief in self-isolation declined from 61% (78/128) to 8% (9/109). Perceptions of CL as preventable and treatable at health facilities increased, with modest improvements in preventive practices. CONCLUSIONS:The CD intervention addressed behavioural determinants of CL by improving knowledge, reducing misconceptions, and encouraging timely care seeking. It reduced shadow-related isolation beliefs and increased correct causal attribution, underscoring its potential to strengthen CL control in endemic settings. Integrating participatory approaches into public health strategies offers a pathway to sustain behavioural change.

BACKGROUND:Sexually transmitted infections (STIs) including Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis during pregnancy are associated with adverse birth outcomes. However, there are limited published data available on cost estimates for implementing such screening. The aim of this study was to estimate the cost of integrating point-of-care STI screening into antenatal care in Harare, Zimbabwe, compared with a modelled standard of care (syndromic management). METHODS:We implemented screening for C. trachomatis, N. gonorrhoeae and T. vaginalis in antenatal care at two primary healthcare clinics in Harare, Zimbabwe, between 12 January 2023 and 23 October 2023. Economic costs required to deliver the testing strategy from a health system perspective were collected using a bespoke cost extraction tool based on study records, staff interviews, time-and-motion studies, local authority salary scales and other secondary sources. During the study, implementation within high-volume settings was found to not be operationally feasible, so implementation within a low-volume setting in routine care, without time required for research processes, was modelled for a 12-month period. The incremental cost per person screened and treated was calculated comparing point-of-care testing to a modelled standard of care using syndromic management. RESULTS:The composite prevalence of C. trachomatis, N. gonorrhoeae and/or T. vaginalis as measured in the intervention was 28.3% (283/1000). As a proportion of the total cost of the intervention, the largest components were test kits (55.4%), personnel (31.0%), and equipment costs (7.5%). The costs per person screened and treated were $41 and $146, respectively. The incremental costs per person screened and treated compared with syndromic management were $41 and $169, respectively. CONCLUSION:The incremental cost per person screened and treated for an STI using a point-of-care antenatal screening strategy was driven by test kit and personnel costs, underlining the need for lower cost point-of-care STI diagnostics. TRIAL REGISTRATION NUMBER:NCT05541081.

Background: Congenital syphilis remains a major global health challenge, driven partly by maternal reinfection during pregnancy. Partner notification (PN) is critical to prevent reinfection and reduce mother-to-child transmission, yet evidence on its uptake and effectiveness is limited. We aimed to assess PN coverage, outcomes, and barriers among pregnant women with syphilis in Blantyre, Malawi. Methods: We conducted a mixed-methods study at 4 primary health centers (Mpemba, Zingwangwa, South Lunzu, and Bangwe). A cross-sectional survey at delivery enrolled women with documented syphilis in the current pregnancy (positive treponemal rapid diagnostic test). PN was defined as informing partners of potential exposure and the need for testing; appropriate partner management was defined as partner testing and treatment according to results. Semistructured interviews with women and healthcare workers were analyzed using reflexive thematic analysis. Results: Among 131 women, 117/131 (89.3%) reported notifying partners; however, only 76/131 (58.0%) partners were tested, and a similar but nonidentical 76/131 (58.0%) received treatment. Appropriate partner management was completed in 40/131 (30.5%). Partner treatment was associated with being married or cohabiting (74/76, 97.4% vs 43/55, 78.2%; P = 0.0005), but not with age, HIV status, education, or adverse birth outcomes. Qualitative findings identified predominantly patient-led PN, with barriers, including fear of partner reaction, stigma, misinformation, and partner reluctance to access care; facilitators included community sensitization and healthcare worker involvement. Conclusions: Substantial attrition occurs between notification and partner management, highlighting critical gaps in the cascade. These findings support the need for standardized PN metrics and context-specific, multicomponent interventions addressing health system barriers.

BACKGROUND:We aimed to establish an external quality assessment (EQA) programme for the yaws eradication campaign that would meet the needs of reference and district-level laboratories in low- and middle-income countries. METHODOLOGY/PRINCIPAL FINDINGS:We designed proficiency testing items (PTIs) using a plasmid containing gene target sequences for Treponema pallidum (TP) and Haemophilus ducreyi (HD). The storage stability of the plasmids under different environmental conditions was then tested. A proficiency testing panel of seven swabs loaded with different concentrations of plasmids in different combinations, as well as human HEK293 cells to simulate the sample background, was prepared and sent to participating reference (RL) and district (DL) laboratories in Ghana, Côte d'Ivoire and Cameroon followed by three rounds of blinded proficiency testing. We tested quantitative real-time PCR (qPCR) performance of reference laboratories and loop-mediated isothermal amplification (LAMP) performance of district laboratories and retested 20% of human field samples at the London School of Hygiene & Tropical Medicine laboratories to further assess qPCR quality. FINDINGS:PTIs proved to be stable in dry conditions with no significant loss of copy number. Participating laboratories achieved qPCR results with a concordance of 95.0-100.0% (97.7% ± 5.2% (mean±standard deviation ((SD)) with the provider and a concordance of 76.0-100.0% (TP: 90.3 ± 13.7% and HD: 78.5 ± 7.5% (mean±SD)) for LAMP results, with inconsistencies, particularly in the detection of low HD plasmid DNA levels combined with high TP plasmid copies. Retesting of field samples resulted in 100% correct TP and HD sample identification by the African reference laboratories. CONCLUSIONS/SIGNIFICANCE:We have developed a functional plasmid-based EQA programme specifically designed to meet the needs of resource-poor settings in the tropics. The programme is suitable as a blueprint for other disease programmes.

Abstract Introduction Cutaneous leishmaniasis (CL) is a neglected tropical disease associated with reduced health-related quality of life (HRQoL) that leads to permanent scars, anatomical damage and functional impairment. We aimed to translate, culturally adapt and validate the disease specific HRQoL measure the Cutaneous Leishmaniasis Impact Questionnaire (CLIQ) into Afan Oromo. Methods The English version of the CLIQ was translated into Afan Oromo, and culturally adapted by experts with feedback from individuals affected by CL. The finalized Afan Oromo version was then administered to adults with CL. Its psychometric properties were examined using internal reliability, inter rater reliability, construct validity, and responsiveness to change. In addition, the clinical importance difference (CID) and cut-off points for the total CLIQ score were determined. Results The Afan Oromo CLIQ demonstrated acceptable content validity, with I-CVI values ranging 0.83 to1.00. One hundred and forty-four individuals with confirmed CL with a mean age of 35.5 (±16.5) years were interviewed using the Afan-Oromo version of the CLIQ. The overall median CLIQ score was 40 (IQR=24). The median score for general impacts of CL (Cluster-1), and perceptions about health services and treatment (Cluster-2) were 32 and 9 respectively. The internal consistency (Cronbach alpha= 0.87) and inter-rater reliability (ICC=0.98) were excellent. The differences in median CLIQ scores between physicians determined CL severity classifications and between small and larger lesions were significant. The Afan Oromo CLIQ was responsive to change following treatment (P = 0.037). The CID was 9 and 7 units, using distribution and anchor methods, respectively. Conclusion The Afan Oromo CLIQ is a valid and reliable disease-specific instrument to assess HRQoL of CL affected individuals.

Background: Syphilis diagnosis in resource-limited settings relies on syndromic management and treponemal-based antibody screening tests that cannot distinguish active infection from past-treated infection, both of which can lead to overtreatment. Point-of-care (POC) tests that detect active infection could reduce unnecessary treatment. Methods: We developed an agent-based model of co-transmitting syphilis and human immunodeficiency virus, calibrated to Zimbabwe using population-based survey data (ZIMPHIA) and UNAIDS estimates. We modeled five scenarios involving two hypothetical new POC diagnostic products introduced from 2027: (1) a test detecting Treponema pallidum DNA in genital ulcer specimens, and (2) a non-treponemal test identifying active infection following a treponemal-positive result, applied across antenatal care, key population, and human immunodeficiency virus care settings. We also conducted a threshold-based cost analysis to assess whether reductions in unnecessary treatment alone could be cost-saving. Results: Under the current standard of care, approximately 112,000 adult syphilis treatments are administered annually across all modeled detection and screening use cases, of which approximately 80% are unnecessary (i.e., administered to individuals who do not have an active syphilis infection). Combining both diagnostics reduces overtreatment to 24% (a 3.4-fold reduction). Across use cases, each test avoids approximately 0.4 to 0.8 unnecessary treatments, implying cost savings whenever the test price is less than 40% to 80% of the treatment cost. Conclusions: Even under the conservative assumption that current syndromic management and screening practices achieve high syphilis treatment rates among care-seeking individuals, introducing POC diagnostics for active syphilis could substantially reduce overtreatment while maintaining treatment of individuals with active infection. Reductions in unnecessary treatment alone may be cost-saving at low test prices, even without accounting for downstream health outcomes. This analysis does not model the impact of improved diagnostics on transmission dynamics, congenital syphilis burden, or other health outcomes; studies that quantify these additional benefits are needed to inform a full economic evaluation.

BACKGROUND:Preexisting multiple (two or more) long-term conditions (MLTCs) may negatively affect recovery after COVID-19. We investigated how preexisting MLTCs, including different categorization and patterns of MLTCs, affect 1-year health outcomes after severe COVID-19. METHODS:Adults post-hospitalization after COVID-19 were recruited during 2020-2021. We compared recovery at 1 year after discharge using adjusted multivariable logistic regression in 1:1 propensity-matched adults (for age, sex, ethnicity, social deprivation, obesity, and smoking history) with and without preexisting MLTCs. In adults with MLTCs, different categorization such as number of conditions, number and types of body systems involved (e.g. respiratory, cardiovascular), and latent class analysis-derived patterns of condition co-occurrence were assessed for their association with recovery at 1 year. RESULTS:A total of 647 adults with MLTCs were matched with 647 adults without MLTCs (n = 1294; 61.9% male, 79.6% of White ethnicity, median age 59 [interquartile range 52-67] years). The presence of MLTCs was associated with lower odds of feeling fully recovered (odds ratio 0.66 [95% confidence interval 0.51-0.85], P = 0.001). In those with MLTCs, recovery was negatively affected by number and type of body systems involved (e.g. respiratory [odds ratio 0.49 (95% confidence interval 0.34-0.69), P <0.001]) but not by the number of conditions (P >0.1). Four latent classes of MLTC co-occurrence were estimated with different risks of recovery (P <0.01). CONCLUSION:Adults with preexisting MLTCs were 34% less likely to feel fully recovered at 1 year after COVID-19 hospitalization than adults without MLTCs. We describe prognostic classifications of MLTCs, with future work needed to understand whether they have prognostication in broader post-acute infection sequalae.

Background Physical inactivity is a risk factor for severe COVID-19 and often worsens after hospitalisation. Clinicians need quick, accurate assessments to target interventions. We aimed to assess the validity of the General Practice Physical Activity Questionnaire (GPPAQ) in adults recovering one year after COVID-19 hospitalisation . Methods Post-hospitalisation for COVID-19, adults attended a one-year-visit and completed the GPPAQ Physical Activity Index (PAI-4 active), 14-day wrist-worn accelerometry (Moderate-Vigorous PA [MVPA]- active), and other health outcomes. Validity was examined via : (i) internal consistency (factor analysis); (ii) measurement invariance across sex, age, and ethnicity using differential item functioning (DIF); (iii) convergent validity (GPPAQ sensitivity/specificity versus accelerometry); and (iv) construct validity (correlations with health outcomes). Results 752 participants had GPPAQ and accelerometry (265 female, mean± sd age 60.9±11.6 years, MVPA 18.75 min·day −1 (IQR 7.55, 36.11), PAI-1 46.8%, PAI-2 15.6%, PAI-3 19.4%, PAI-4 18.2%. Factor analyses supported good internal consistency with two factors (daily activities, physical exercise). Confirmatory factor Index (CFI) showed excellent fit (CFI 0.965). DIF indicated moderate variability by sex and age. GPPAQ-PAI showed limited sensitivity (26.3%) for correctly classifying physically active individuals, but higher specificity (88.4%) for classifying physical inactivity, and weak-to-moderate correlations with health outcomes. Conclusions GPPAQ demonstrates internal consistency, with construct and convergent validity in adults 1-year post-COVID-19 hospitalisation. GPPAQ effectively identifies inactive individuals to support clinical care; however, its sensitivity suggests underestimation of activity relative to accelerometry. Future pathways should combine GPPAQ with device-based assessment to optimise evaluation of physical activity to guide pulmonary rehabilitation and targeted interventions.

BACKGROUND:Yaws, a neglected tropical disease caused by Treponema pallidum subspecies pertenue (T p pertenue), has evaded eradication, in part due to a high proportion of asymptomatic cases. Repeated mass drug administration (MDA), whereby an entire population is repeatedly treated irrespective of disease, could provide a solution. Here, we aimed to investigate the effect of MDA on the genomic epidemiology of T p pertenue. METHODS:We conducted a retrospective genomic epidemiology study on samples collected during a cluster-randomised trial of mass administration of azithromycin for yaws eradication in the Namatanai District of Papua New Guinea. Participants were in 38 wards (administrative units encompassing several villages) in three local-level government areas (LLGs). The experimental group received an initial round of MDA followed by two further rounds 6 months and 12 months after the first round. The control group received one round of MDA followed by two rounds of treatment targeting clinical cases and contacts only, on the same schedule as the MDA in the experimental group. A follow-up survey on both groups was done 18 months after the first MDA round. Swab samples were collected at each round from ulcerative and nodular skin lesions, and blood was collected by finger-prick for serological testing at 18 months. Metadata on ulcer size (cm) and duration (days) were recorded at each round, and treponemal and non-treponemal antibodies were recorded at 18 months. Samples from swabs positive for T p pertenue underwent library preparation and whole-genome sequencing. We examined the phylogenetic relationships between genomes, linking them with geospatial and patient metadata to understand the impact of MDA on T p pertenue diversity and transmission. FINDINGS:Swabs collected from 297 individuals with active yaws from April 30, 2018, to Nov 2, 2019, yielded 222 good-quality Tp pertenue genomes. We identified 20 sublineages of T p pertenue in the control group and 21 in the experimental group at the beginning of the study. At the end of the study, there were 13 sublineages in the control group and three in the experimental group, of which two persisted in both groups. Three sublineages not detected at baseline were observed in the control group after commencing MDA. The two sublineages that persisted in both groups had non-synonymous mutations in penicillin-binding proteins. One of these sublineages evolved macrolide resistance in three individuals and was associated with lowered treponemal antibody (p=0·0036) and longer ulcer duration (p=0·015). Despite the study taking place within a small island, sublineages were geographically clustered, with pairs of samples from the same ward (odds ratio 7·1, 95% CI 5·7-8·8; p<0·0001) or neighbouring wards (4·3, 3·3-5·4; p<0·0001) more likely to share the same sublineages compared with pairs from different LLGs. Additionally, older individuals were more likely to share sublineages than were younger individuals (1·5, 1·2-1·9; p<0·0001). INTERPRETATION:Repeated MDA was successful in reducing and maintaining the genetic diversity of T p pertenue at a low level but was associated with the development of macrolide resistance. Yaws re-emergence after MDA was attributed to multiple sublineages, of which the majority were detected in the population before MDA. Participants within the same ward were more likely to share sublineages than those that were more widely geographically separated, suggesting that re-emergence was driven by local transmission. These findings could inform future yaws elimination strategies. FUNDING:European Research Council, EU, Provincial Deputation of Barcelona, Barberà Solidària Foundation, Wellcome, and Fundació "la Caixa".

Background Early treatment for cutaneous leishmaniasis (CL) is effective but remains restricted to specialised hospitals in Ethiopia. We explored the experiences of CL-affected people receiving treatment at Boru Meda and ALERT hospitals to understand their perspectives on issues that may require specific interventions. Methods We interviewed 22 adults receiving care for complicated CL and observed the culture of service delivery in both settings. Results Care-seeking was driven by failure of traditional remedies, recommendations from former patients, or referrals from other health facilities. However, treatment initiation was delayed by drug stockouts, insufficient bed capacity and the financial costs of treatment monitoring tests. CL-affected people’s lack of prior knowledge about the requirement for prolonged hospital admission and unclear communication about treatment by hospital staff contributed to initial confusion and anxiety. The daily intramuscular injections of sodium stibogluconate were experienced as extremely painful. Despite this, participants expressed optimism in hospital-based CL treatment. Healthcare staff compassion and support from other CL in-patients were positive experiences associated with hospital-based treatment. 13/18 people rated their lesions as ‘better’ after treatment. Individuals with poor outcomes attributed lack of healing to taboo behaviors said to exacerbate CL (sexual intercourse, agricultural work and social mixing) and delayed care-seeking. Conclusion Strengthening community engagement may reduce treatment delays and suffering by improving access to culturally appropriate information through trusted channels, enhance provider–patient communication by incorporating community feedback into services, and reduce out-of-pocket expenses by increasing awareness of free or subsidized care. However, better tolerated, non-hospital-based CL treatments remain essential.

Genomic pathogen surveillance is a powerful tool for public health and research, but is costly and unachievable in low-resource settings. Most sub-genomic typing methods sacrifice resolution whilst remaining costly. We developed "Phylo-Plex", a novel approach that identifies information-rich genomic regions to maximise phylogenetic information whilst minimising the number of regions. Applied to Treponema pallidum and Neisseria gonorrhoeae, we designed a high-resolution multiplex PCR sequencing scheme for lineage tracking pathogens with different extremes of genome variation. For Treponema pallidum, we also designed and evaluated the Phylo-Plex scheme in the laboratory and field settings by sequencing 72 clinical samples using MinION Flongle cells. Our T. pallidum scheme comprising 59 multiplex amplicons achieved high discrimination of fine-scale sublineages comparable to those defined using whole genomes, and demonstrating a qPCR detection limit ≤Ct 32. Variant calls from MinION amplicon sequencing were highly correlated with Illumina whole genome sequencing. We successfully deployed the method in a low-resource laboratory in Zimbabwe, costed at <£300/24 samples (£12.47/sample). Phylo-Plex enables low-cost tracking of priority pathogenic lineages in low resource settings and at scale.

BACKGROUND:Cutaneous leishmaniasis (CL) is a major public health concern, particularly in Ethiopia, where about 40 000 new cases occur annually, predominantly caused by Leishmania aethiopica. Clinical phenotypes include localized CL (LCL), mucocutaneous leishmaniasis (MCL) and diffuse CL (DCL). Despite the high disease burden, treatment options and high-quality data on treatment outcomes are limited. OBJECTIVES:To evaluate the effectiveness of standard treatments in Ethiopia to inform future clinical trials. METHODS:We conducted an observational cohort study of patients with parasitologically confirmed cutaneous leishmaniasis at two specialized dermatology referral hospitals. Clinical- and patient-reported outcomes were assessed at baseline and at standardized times during follow-up. The primary clinical outcome measure ('cure') was complete re-epithelialization or flattening of the index lesion at day 90. Patient-reported outcomes were assessed using skin-specific and general quality-of-life scores. RESULTS:We enrolled 666 participants from April 2022 to October 2023. Median patient age was 20 years (interquartile range 14-35) and 405 patients were male (60.8%). More than half (n = 372; 55.9%) had previously received traditional treatment for CL. Most participants had LCL (n = 390; 58.6%) or MCL (n = 261; 39.1%). Intramuscular sodium stibogluconate 20 mg kg-1 daily was the most frequently used systemic therapy, either alone or in combination with lesion-directed therapy (cryotherapy or intralesional sodium stibogluconate). At day 90, 28.3% (n = 83/293) of participants with LCL, 23.5% (v = 47/200) with MCL and 8% (n = 1/12) with DCL were deemed cured. By day 90, all patient-reported outcomes of skin health improved for those with LCL or MCL, but skin and CL-related quality-of-life scores did not improve for those with DCL. Most participants (n = 522/641; 81.4%) experienced at least one clinical adverse event and 7.2% (n = 46/641) had abnormal laboratory findings during treatment. CONCLUSIONS:Current treatment strategies have low cure rates in Ethiopia. Well-designed randomized controlled trials are urgently needed to improve management of CL caused by L. aethiopica.

BACKGROUND:Zimbabwe's national guidelines for sexually transmitted infection (STI) management recommend that high-risk women presenting with vaginal discharge syndrome (VDS) are prescribed antibiotics for gonorrhoea (Neisseria gonorrhoeae (NG)), chlamydia (Chlamydia trachomatis (CT)), trichomoniasis (Trichomonas vaginalis (TV)) and bacterial vaginosis (BV). The performance of this approach depends on its clinical interpretation and implementation. Here, we investigate the potential relative impact of an NG/CT/TV point-of-care (POC) test on undertreatment, overtreatment and disease burden in the context of different implementations of syndromic management of women with VDS. METHODS:We created an agent-based model with an age- and risk-stratified sexual network and modelled co-circulation of NG, CT and TV along with HIV and BV. We estimated symptomatic proportions and care-seeking rates under three different scenarios around the implementation of treatment guidelines, corresponding to all, most or half of women being treated for NG+CT upon presentation with VDS. For each implementation scenario, we estimated disease burden and over/undertreatment rates assuming continuation of the standard of care with/without a POC NG/CT/TV test available over 2027-2040. RESULTS:Under a treat-all interpretation of the syndromic management guidelines, we estimate that 70%-80% of antibiotics for NG/CT would currently be given to women without these infections. Overtreatment would fall to less than 5% if a sensitive POC test for NG/CT/TV were available. However, if the implementation of the guidelines implies that only half of women seeking care for VDS are treated, then a POC test would also reduce undertreatment and disease burden, with >500 000 additional women correctly treated for NG and ~1.5 million correctly treated for CT and TV, and 24%/15% reductions in the number of women with NG/CT by 2040. CONCLUSION:Improved data on the functioning of syndromic management in practice would help refine the estimates of the health impact and the overall value proposition of a highly sensitive POC diagnostic for NG/CT/TV. However, even without such data, our analysis demonstrates the potential for such a diagnostic to reduce overtreatment by >90% relative to plausible assumptions regarding the standard of care.

BACKGROUND:Despite emerging evidence indicating an increasing burden of invasive Streptococcus anginosus group (SAG) intracranial infections in children, their wider epidemiology remains inadequately explored. We aimed to describe the epidemiology of SAG infections in adults and children in the UK. METHODS:We conducted a retrospective population-based surveillance study of microbiological laboratory samples, including all samples from which Streptococcus spp were identified, at Great Ormond Street Hospital (GOSH; London, UK), which processes local paediatric and national specimens from all ages, from Jan 1, 2000, to Dec 31, 2023, and at University College London Hospitals (UCLH; London, UK; all ages), from Jan 1, 2012, to Dec 31, 2023. Samples with missing data were excluded. We also analysed the nationally reported streptococcal bacteraemia data from Jan 1, 2015, to Dec 31, 2023, and calculated the annual rates of SAG sterile body site (SBS) infections per 1000 emergency admissions at each hospital. Temporal trends were analysed using negative-binomial regression with admission numbers as an offset. Descriptive statistics summarised infection characteristics by organism, species, body site, age, and sex. National bacteraemia trends were analysed relative to population denominators. Analyses included only records with complete routine laboratory data, and samples without sufficient information were excluded from relevant subgroup analyses. FINDINGS:As we only included routinely collected laboratory data, comprehensive demographic and ethnicity data were not available. The median age of patients from whom Streptococcus spp of interest (SOI) were isolated was 44·41 years (IQR 12·327-64·32). 2215 (59·8%) of 3702 patients with SOI SBS infection (defined as an infection of an anatomical area expected to be devoid of microorganisms) were male. At both GOSH and UCLH, incidence of SAG sterile body site infections increased year-on-year from 2·12 per 1000 emergency hospital admissions in 2012 to 11·51 per 1000 emergency hospital admissions in 2023 at GOSH (p<0·0001) and from 0·97 per 1000 emergency hospital admissions in 2012 to 6·04 per 1000 emergency hospital admissions in 2023 at UCLH (p<0·0001). SAG diagnoses in external samples, which were referred to GOSH for molecular diagnostics, also increased markedly over time compared with other Streptococcus spp diagnoses. In all groups, SAG is the current dominant cause of streptococcal sterile body site infection. SAG sterile body site infections most frequently involved the CNS (222 [19·6%] of 1133), especially in children (87 [39·2%] of 222), intrathoracic sites (283 [24·9%] of 1133), and abdominal sites (202 [17·8%] of 1133). At the species level, all three SAG species contributed to the increase in infections. S intermedius was the dominant cause of CNS and intrathoracic infections, whereas S anginosus and S constellatus were the dominant causes of abdominal infections. INTERPRETATION:SAG infections, predominantly deep pyogenic collections in SBSs, are increasing in both children and adults in the UK and represent a major cause of streptococcal SBS infections. This increase is unlikely to be explained solely by improved diagnostics or increased sampling and suggests a real change in epidemiology. Further work is urgently needed to understand whether this change is because of increasing virulence of SAG organisms, changes in carriage rates or dynamics, or the presence of alternative drivers. FUNDING:The European Society of Clinical Microbiology and Infectious Diseases (Europäische Gesellschaft für klinische Mikrobiologie und Infektionskrankheiten; ESCMID).

In Ethiopia, the incidence of cutaneous leishmaniasis (CL) is estimated to range from 20, 000–30, 000 new cases due to Leishmania aethiopica . Children and young adults, in rural communities with limited access to health care are most affected. The current standard of care, pentavalent sodium stibogluconate is only administered in specialist centres, has limited effectiveness and is associated with severe adverse effects. Cryotherapy is recommended in national guidelines at the primary care level to treat uncomplicated CL, but is rarely available due to limited numbers of trained clinicians and lack of resources. We co-developed and evaluated a decentralised intervention, administered at a rural health centre, using carbon dioxide (CO 2 ) cryotherapy, which is available for the treatment of cervical dysplasia. A pragmatic clinical trial design was used, providing training at the health centre that combined theoretical instruction with direct patient assessment. Study clinicians recruited patients with suspected CL who had a slit-skin smear performed with confirmation by expert microscopists. The diagnostic accuracy of trained clinical and laboratory staff at a rural health centre were compared to experts. Individuals aged ≥12 years with parasitologically confirmed uncomplicated CL received CO 2 cryotherapy. Participants were followed until Day 90. Cure was defined as complete re-epithelialization of the index lesion. The study was registered in the Pan African Clinical Trials Registry with trial number PACTR202605616785682. https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=41111 . We trained seven clinicians and laboratory professionals at Keteteya Health Centre. Of 331 individuals who attended the clinic with skin disease, 158 (47.7%) were clinically diagnosed by trained clinical staff with CL. Overall 123 (78%) had laboratory confirmed CL and of these 85 (53.8%) received CO 2 cryotherapy. By Day 90, 68 of 77 (88.3% (95% CI: 78.5–94.1%)) were cured. Adverse events were mild and transient, with no individual discontinuing treatment. Trained health centre clinical and laboratory staff were able to accurately diagnose CL. CO 2 cryotherapy was safe and efficacious when administered by trained staff. A training programme to facilitate CO 2 cryotherapy appears to be a feasible approach to decentralizing CL diagnosis and treatment to primary healthcare facilities in endemic areas of Ethiopia.

BACKGROUND:Congenital syphilis (CS) remains a major cause of stillbirth and neonatal morbidity, with an estimated 700,000 cases and 390,000 adverse birth outcomes annually. We evaluated the diagnostic utility of combined treponemal (TT) and nontreponemal (NTT) rapid point-of-care test and Treponema pallidum polymerase chain reaction (PCR) for detecting active maternal syphilis, CS, and treatment response in a high-prevalence, low-resource setting. METHODS:Secondary analyses were conducted from a prospective case-control study at Queen Elizabeth Central Hospital, Malawi. Women were recruited ≤48 h postpartum. Maternal and infant sera underwent testing with the DPP® Syphilis Screen and Confirm (Dual rapid diagnostic test [RDT]) and T. pallidum PCR (maternal vaginal swabs and infant nasopharyngeal swabs), with predefined clinical-serological reference standards based on qualitative rapid plasma reagin (RPR). RESULTS:Among 504 of 510 women with complete data, Dual RDT identified 110 seropositive cases at delivery, including 86 new maternal syphilis diagnoses. The NTT band showed good performance in mothers versus RPR (sensitivity: 84.8% [95% confidence interval: 77.4%-92.1%]; specificity 92.7% [95% confidence interval: 90.3%-95.1%]) but reduced sensitivity in infants, increasing from 51.9% to 80.0% with RPR titer. Laboratory visual and microreader interpretation showed high concordance (99.5%), while bedside visual accuracy was lower (77.4%). Any Dual RDT positivity identified 19 high-risk infants, of whom 7 of 19 (36.8%) were NTT positive. PCR detected maternal infection in 11 of 504 (2.2%), including 3 serology-negative cases. CONCLUSIONS:Dual RDT improves detection over TT alone. The NTT band without quantitation is insufficient for treatment monitoring or infant diagnosis. Combining Dual RDT with PCR may enhance detection of active maternal infection and CS in high-burden settings.

BACKGROUND:Cutaneous leishmaniasis (CL) is a vector-borne, neglected tropical disease of the skin. It is a public health problem in Ethiopia, associated with reduced health-related quality of life (HRQoL). The Cutaneous Leishmaniasis Impact Questionnaire (CLIQ), a CL-specific measurement, was developed and validated in Brazil. This study aimed to translate, culturally adapt, and validate the CLIQ in Amharic. METHODS:Translation, cultural adaptation, and pilot-testing of an Amharic version of the CLIQ were performed, involving a group of experts and affected individuals. The translated Amharic version of the CLIQ was administered to adults with confirmed active CL between February and September 2023. The Amharic version of the CLIQ was evaluated using Cronbach's α, inter-rater reliability, and assessments of face, content, construct, and criterion validity. RESULTS:The translated and culturally modified Amharic version of the CLIQ was administered to 250 adults with CL. Of these, 158 (63.2%) participants had localized CL, and 114 (45.6%) were categorized as having moderately severe CL at enrolment. The Amharic version of the CLIQ had acceptable internal consistency (α = 0.913) and very good stability (ICC: 0.935 (95% C.I.: 0.908, 0.957)). It exhibited acceptable content validity with a modified kappa coefficient of 0.33 to 1.0. Confirmatory Factor Analysis revealed a two-cluster tool with factor loading of 0.33-0.83 for cluster 1 and 0.19 to 0.7 for cluster 2. A statistically significant difference was observed in median scores of severities (P < 0.001) and clinical phenotypes (P = 0.009). There was a significant reduction in CLIQ scores at Day 90 compared to Day 1 (P < 0.05). The clinically important difference of the CLIQ was calculated to be 12. CONCLUSION:The Amharic version of the CLIQ is a reliable and valid instrument to measure the HRQoL associated with CL in adults in Ethiopia and can be used as a patient-reported outcome measure in the assessment of CL and its treatment.