Abstract Background Tungiasis is a cutaneous parasitic disease caused by the female flea Tunga penetrans. The World Health Organization recommends two-component dimeticone (NYDA®) as the sole treatment for tungiasis; however, this topical medication is not available in Kenya. In western Kenya, sodium carbonate has been adopted as a traditional village-based treatment. A pilot study found that the proportion of dead fleas on day 7 was higher with NYDA® treatment than that with 5% sodium carbonate treatment (87% vs. 64%, respectively). This study was aimed at assessing the 11-day cure rates of tungiasis by comparing the efficacy of sodium carbonate and NYDA® treatments in Vihiga County, Kenya. Methods A randomised, observer-blinded, non-inferiority trial was conducted, with the non-inferiority margin set at 10%. A total of 160 eligible children with 941 flea infections were matched and randomised. The number of lesions per child per foot ranged from 1 to 10, with a median of 5 lesions. Each participant received both treatments, with one treatment applied to each foot. Health conditions, including inflammation scores and adverse events, were recorded. Observations were recorded on days 3, 5, 7, 9, and 11 using a digital microscope to determine flea viability. Results Data from 157 children aged 4–15 years were analysed, comprising a total of 843 lesions. On day 11, the proportion of dead fleas was 88% for NYDA® and 77% for 5% sodium carbonate solution (p < 0.05). No significant differences were observed in inflammation scores or symptoms such as pain and itchiness between the two treatments. Conclusions This study demonstrated that 5% sodium carbonate did not meet the non-inferiority margin compared with NYDA® in treating tungiasis. Nevertheless, in settings where NYDA® is not accessible, it may still be considered an alternative. Trial registration This study was registered with UMIN-CTR (Trial ID: UMIN000044320; reception desk number: R000050621) on 28 May 2021.

IntroductionSyphilis is a leading cause of adverse pregnancy outcomes, excessively affecting sub-Saharan Africa. Early diagnosis and treatment are crucial to prevent mother-to-child transmission. The aims of the present study were to assess prevalence and epidemiological and clinical correlates of active syphilis diagnosed using serological [treponemal and non-treponemal (lipoidal)] assays and the research-use-only (RUO) Aptima Treponema pallidum assay [Hologic; transcription-mediated amplification (TMA) assay] among pregnant women attending four antenatal care facilities in Nchelenge, Zambia in 2023.MethodsSyphilis serology was performed using rapid diagnostic test [RDT; Core tests® ONE STEP Syphilis Test Kit (Core Technology, Atlanta, USA)]; positive samples were further evaluated by rapid plasma reagin [RPR; RPR Carbon Antigen Reagent (Eurocarb Products Ltd., Bristol, United Kingdom)] test. Active syphilis was defined as a positive RDT plus a positive RPR test, or a positive RUO Aptima T. pallidum assay. T. pallidum and other non-viral STIs (Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, and Trichomonas vaginalis) were detected in clinician-collected vaginal swab samples using Aptima assays on the Panther system (Hologic). HIV testing was performed with the Determine HIV Test Kit, and bacterial vaginosis (BV) was diagnosed using Nugent's score. Active syphilis correlates were identified using univariable and multivariable logistic regression.ResultsIn total, 996 pregnant women were included in the analysis, of whom 136 women (13.7%) had an active syphilis infection. Of these women with active syphilis, 117 (86.0%) were positive in serology only, 15 (11.0%) in serology plus RUO Aptima T. pallidum assay, and four (2.9%) in RUO Aptima T. pallidum assay only. Rates of other current STIs and reproductive tract infections included: BV (23.3%), T. vaginalis (22.7%), M. genitalium (12.7%), HIV (8.7%), N. gonorrhoeae (8.4%), and C. trachomatis (7.4%). Secundigravidity, history of stillbirth, current concomitant M. genitalium, N. gonorrhoeae, T. vaginalis, and HIV infections were significant risk factors of active syphilis. Advanced gestational age (from 28 to 39 weeks) at enrolment was associated with significantly lower risk of syphilis positivity.DiscussionA remarkably high burden of syphilis and high co-infection rates with HIV and other non-viral STIs in pregnant women in Zambia underscore the urgent need for integrating syphilis and HIV universal screening programs, as well as to consider concurrent testing for selected other non-viral STIs. Where feasible due to the increased cost, supplementing serological screening with a highly sensitive and specific molecular test such as the RUO Aptima T. pallidum assay for suspected early syphilis can ensure timely detection of both seroconverted and seronegative early syphilis cases, early treatment and effective prevention of mother-to-child transmission.

Bacterial vaginosis (BV) is associated with adverse pregnancy outcomes. OSOM® BVBlue® is a chromogenic point-of-care (POC) test that detects sialidase, an enzyme produced by Gardnerella vaginalis and some other anaerobic bacteria associated with BV. This study, part of the World Health Organization’s global ProSPeRo study, aimed to evaluate the performance of this POC test compared with the Nugent score reference standard among pregnant women in Zambia. Additionally, the operational characteristics and patient acceptability of the POC test were evaluated. Pregnant women attending four health centres in Nchelenge, Zambia, for antenatal care between 15 February and 26 May 2023 participated. Clinician-collected vaginal swabs for OSOM® BVBlue® and Nugent scoring were obtained from each participant. POC test results were read independently by two staff members. Study staff completed a questionnaire on the operational characteristics of the POC test, whereas participants were asked about the length of time that they would be willing to wait for POC test results. Paired POC and reference test vaginal swabs from 999 participants were analysed. Overall, 23.1

Background:Streptococcus pneumoniae is a leading cause of child mortality in Nepal despite the introduction of the 10-valent pneumococcal conjugate vaccine (PCV10). Vaccine effectiveness is threatened by the emergence of non-vaccine serotypes (NVTs) and the multiple serotypes carriage which often fail to be detected by traditional methods. We aimed to study changes in serotype distribution before and after PCV10 immunization among infants, including serotype dominance in Nepalese infants in the post-vaccine era. Methods: We enrolled infants in a longitudinal cohort study (2020-2022) conducted in Bhaktapur, Nepal. Nasopharyngeal swabs were collected before PCV10 dose 1 (6 weeks) and at 9 and 12 months post-immunization. We used a sensitive nanofluidic qPCR platform to detect multiple serotypes and establish their hierarchy by quantifying the bacterial load of each strain. Inverse Probability Weighting (IPW) adjusted risk factor analysis was used to account for loss to follow-up. Results: PCV10 successfully reduced vaccine-type (VT) carriage, declining sharply from 32.8% at 6 weeks to 4.8% at 12 months. VTs were pushed from being the dominant strain to occupying subdominant roles in co-colonization. Conversely, NVTs rapidly filled the vacated niche, showing a significant increase in their dominant status (p < 0.001). The most common replacing NVTs that rose to dominance were 35B, 19A, 6C/6D, and 15B/15C. Significant risk factors for carriage included older infancy (aOR 3.4, 95%CI: 2.6-4.5 at 9 months), a household kitchen in the living area (aOR 1.4, 95%CI: 1.0-1.9), and winter (aOR 1.7, 95%CI: 1.5-2.7) and pre-monsoon seasons (aOR 2.0, 95%CI: 1.5-2.8). Conclusions: While PCV10 reduced overall VT circulation, the persistence of VTs in subdominant niches creates a continuous reservoir for potential re-emergence and antibiotic resistance. This clear hierarchical shift in dominance towards NVTs underscores the urgent need for a public health strategy that includes the adoption of a higher-valent PCV to provide broader protection, and interventions targeting environmental risk factors are essential to sustain long-term reductions in pneumococcal colonization.

BackgroundGiardiasis is one of the most common enteric protozoal infections worldwide. It is frequently reported as an enteric parasitic infection in the United States of America (USA) and Europe, whereas reported incidence in Japan is substantially lower. This study characterized age-specific, geographic, and temporal patterns of reported giardiasis incidence in Japan, the USA, and Europe using publicly available surveillance data.Methodology/principal findingsThis retrospective study analyzed surveillance data from the National Institute of Infectious Diseases (NIID) in Japan, the Centers for Disease Control and Prevention (CDC), and the European Centre for Disease Prevention and Control (ECDC) to describe epidemiological patterns, possible explanatory factors, and temporal trends before and during the COVID-19 pandemic. Annual trends were examined using all available surveillance years: 2007-2023 for Japan and Europe and 2007-2022 for the USA. Age-specific patterns were compared between the pre-pandemic (2017-2019) and pandemic (2020-2022) periods, and geographic patterns were examined using available regional data. Incidence rates in the USA and Europe were approximately 5 per 100,000 population, whereas reported incidence in Japan remained below 0.1 per 100,000. Age-specific patterns differed: incidence peaked in children aged 0-14 years in Europe, and in children aged 0-4 years and adults aged 25-39 years in the USA, whereas in Japan, incidence was highest among adults aged 25-44 years and relatively high among those aged ≥65 years. Geographic patterns also differed, with higher incidence in Tokyo, Nordic and Baltic countries and selected European countries, and New England and Midwestern states. Annual incidence was significantly lower in the COVID-19-onset period than in the pre-COVID-19 period across all regions.Conclusions/significanceThese findings suggest that exposure patterns and possible explanatory factors differ by region and age group, highlighting the importance of region- and age-specific prevention strategies.

Pathogen genomic surveillance is essential for monitoring high-risk lineages and antimicrobial resistance in Salmonella enterica serovar Typhi (S. Typhi), yet implementing whole-genome sequencing in sentinel hospital laboratories remains challenging. We evaluated whether mechanically sheared DNA, paired with high accuracy or super accuracy (SUP) basecalling, enables reliable Oxford Nanopore Technologies (ONT)-only sequencing for multiplexed S. Typhi genomic surveillance. Genomic DNA from three benchmark strains (Ty2, Ty42 and Ty43) was either mechanically sheared to ~15 kb or left unsheared and sequenced in a controlled 6-plex run. The optimized workflow was subsequently evaluated in a 24-plex field run that included 3 benchmark strains and 21 clinical isolates from a sentinel hospital in Manila, Philippines. Both runs were performed using the ONT Ligation Sequencing Kit with Native Barcoding 24 V14 (SQK-NBD114.24) and R10.4.1 flow cells (FLO-MIN114). Assembly metrics, single-nucleotide variation (SNV) concordance, core-genome MLST and downstream functional outputs were compared across DNA preparations and basecalling modes. In the 6-plex run, sheared libraries consistently achieved >1,000× pre-filtered coverage across all strains, whereas unsheared libraries showed highly variable depths and reduced stability after downsampling. When paired with SUP basecalling, sheared datasets produced assemblies comparable to Illumina and hybrid references across both structural accuracy and functional outputs. In the 24-plex run, all samples achieved >100× coverage, and 18 of the 22 retained S. Typhi genomes (81.8%) yielded fully circularized assemblies after exclusion of 2 non-S. Typhi isolates. Serotype prediction, genotyping and in silico antimicrobial resistance predictions remained concordant with the corresponding 6-plex benchmark results. These findings demonstrate that mechanical DNA shearing improves coverage uniformity under multiplexed conditions and, together with SUP basecalling, supports ONT-only S. Typhi genome reconstruction for routine genomic surveillance and broad phylogenetic contextualization. However, for fine-scale transmission analysis and high-resolution SNV interpretation, short-read or hybrid sequencing remains important. Overall, this approach provides a scalable framework for high-multiplex S. Typhi genomic surveillance in sentinel laboratory settings.

Background: Little is known about snakebites by Naja samarensis, a species unique to the Philippines. The aim here is to describe the clinical and epidemiological characteristics of patients bitten by this medically important cobra in the Eastern Visayas. Methods: A hospital-based prospective study analysed the features of snakebite patients attending Eastern Visayas Medical Center between June 2022 and May 2023. Logistic regression analysis identified the factors associated with severity. Results: A total of 175 snakebite patients with five fatalities were included. Naja samarensis was most commonly implicated (n=49, 28.0%), although it could be definitively identified, by examining photographs of the snake responsible, in only four cases. The N. samarensis bites occurred in grass or rice fields, in daytime, and during farming activities, but the people bitten were most frequently students (34.7%) who were bitten at home (36.7%). Patients bitten by N. samarensis often presented with cytotoxic (63.3%) and neurotoxic signs (46.9%). Traditional remedies were common, resulting in delayed presentation to the hospital. Bites by N. samarensis, and older age (>44 y) were independently associated with severity (adjusted OR of 10.33 and 7.89, respectively). Conclusion: Naja samarensis is a major cause of severe snakebites in this region. Pre-hospital treatment frequently involves wasted time and unproven traditional methods. Enhancement of public awareness is urgently needed. Development of a diagnostic test for species identification is warranted to improve future surveys and management.

IntroductionMycoplasma genitalium (MG) is a sexually transmitted bacterium of public health importance, associated with genitourinary disorders, and adverse reproductive and perinatal outcomes. Global data on MG prevalence and antimicrobial resistance (AMR) are primarily available from high-income countries, whereas there is a dearth of information from resource-constrained settings including sub-Saharan Africa. Furthermore, international data on MG rates and AMR in the antenatal population are scarce. Understanding MG prevalence and AMR patterns is crucial for developing effective public health strategies and treatment guidelines. The aim of this study was to investigate the prevalence and epidemiology of MG and the presence of macrolide resistance-associated mutations (MRAMs) among pregnant women attending antenatal care facilities in Zambia.MethodsA cross-sectional study was conducted at four antenatal care facilities in Nchelenge, Zambia, among 1,021 pregnant women. Vaginal swabs were collected and tested using the Aptima Mycoplasma genitalium assay, Aptima Combo 2 assay and Aptima Trichomonas vaginalis assay on the Panther System (Hologic). MG-positive samples were further analyzed for MRAMs using the ResistancePlus™ MG assay (SpeeDx).ResultsThe prevalence of MG was 12.6% (127 of 1,005 valid samples) among the pregnant women. Only 12 MG-positive women (9.4%) had symptoms of a genitourinary infection, which was similar to the frequency of genitourinary symptoms among MG-negative women (6.1%). The rates of Chlamydia trachomatis, Neisseria gonorrhoeae, T. vaginalis, and HIV seropositivity were 7.4, 8.3, 23.0, and 8.6%, respectively. MG infection was significantly associated with the presence of all other tested sexually transmitted infections and HIV seropositivity: the detection rates of C. trachomatis, N. gonorrhoeae, T. vaginalis, and HIV seropositivity were significantly higher in MG-positive than in MG-negative women (15.1% vs. 6.2, 15.0% vs. 7.5, 32.3% vs. 22.0, and 14.3% vs. 7.5%, respectively). The ResistancePlus™ MG assay detected MG in 66.1% (84/127) of samples positive by the Aptima M. genitalium assay, however, no MRAMs were detected in the 23S rRNA gene for any of these 84 samples.DiscussionThis study emphasizes the high prevalence of MG among pregnant women in Zambia, but also lack of MRAMs in MG. These findings suggest that azithromycin remains an efficacious treatment option for MG in this population. Nevertheless, continuous surveillance and judicious macrolide use to maintain treatment efficacy are imperative. Further research and sustained monitoring of MG are essential to inform public health strategies and clinical guidelines in Zambia and similar settings worldwide.

Background A wide inequality exists between high- and low-income countries in the outcome of paediatric acute lymphoblastic leukaemia (ALL). At a tertiary-level hospital in Tanzania, multidimensional approaches have been taken to improve cancer care for children. This study aimed to update the outcomes of paediatric ALL at Muhimbili National Hospital (MNH), Tanzania from 2016 to 2020. Methods We performed a retrospective chart review of children who were treated with modified UKALL2003 protocol at MNH from January 1, 2016 to December 31, 2020. We used the Cox proportional hazards model to estimate the effect of each prognostic factor on event-free survival (EFS). Results We identified 202 patients who had confirmatory diagnoses of ALL and initiated treatment at MNH. Fifty-two patients (26%, 52/202) died ( n = 47) or abandoned treatment ( n = 5) before the end of remission induction. The main causes of death during this period were infections and bleeding complications. The median EFS was 9 months and 2-year EFS was 36%. Oedema, non-early rapid responder, and non-remission were associated with short EFS in the multivariable analysis. Conclusions The number of new paediatric ALL admissions at MNH has doubled in the past decade. The prevention of early deaths is critical to improve the long-term survival of paediatric ALL in Tanzania.

BACKGROUND:Leptospirosis is a zoonotic bacterial infection occurring worldwide. It is of particular public health concern due to its global distribution, epidemic potential and high mortality without appropriate treatment. The method for the management of leptospirosis, particularly in severe disease, is clouded by methodological inconsistency and a lack of standardized outcome measures. The study this protocol details aims to develop a core outcome set (COS) for leptospirosis research. A COS is a set of outcomes with international consensus as a minimum for reporting in future studies focusing on leptospirosis. Establishing a COS will contribute to harmonizing Leptospirosis treatment research and will be instrumental in constructing a high-quality evidence base to feed into a planned future rigorous international clinical trial on leptospirosis. METHODS:The COS-LEP study will employ a COS development methodology standardized by the COMET initiative framework. This includes (1) a systematic review of available quantitative and qualitative literature reporting therapeutic response and safety outcomes and measures; (2) focused interviews with healthcare professional and people treated for leptospirosis exploring outcomes of interests using qualitative methodology; (3) narrowing the choice of outcomes by international consensus using a Delphi survey process; and (4) undertaking a hybrid consensus meeting with key stakeholders to build the final COS. DISCUSSION:This protocol describes the method to develop the first core outcome set for use in human leptospirosis studies. This will not only be a key feature in the design of a future definitive randomized controlled trial, but also provide a structure for clinicians and researchers collecting treatment cohort data in the various settings where leptospirosis is a public health issue.

Tetanus remains a rare but potentially fatal disease, typically associated with traumatic wounds. However, necrotic malignancies such as fungating breast tumors may also serve as an entry point for Clostridium tetani infection. We report the case of a 58-year-old female with a 3-year history of a fungating left breast mass who presented with trismus. A diagnosis of tetanus was made clinically. The patient received treatment with anti-tetanus globulin, metronidazole, and she was placed in a dark room with sound insulation and shielding. The surgical team was consulted for wound management. However, in accordance with the patient’s refusal, surgical debridement was not performed. Instead, local wound cleansing and supportive management were initiated. Tetanus should be considered in patients with necrotic tumors presenting with trismus, especially in low-resource settings where immunization histories are uncertain. Early intervention is crucial to reduce morbidity and prevent complications.

SARS-CoV-2 seroepidemiological studies, which have been used to describe population-level immunity, are limited in the Philippines, despite the protracted course of the epidemic in the country. We follow-up on our previous work and aimed to estimate SARS-CoV-2 seroprevalence and infection rate among outpatient clinic attendees in Metro Manila, a year after the implementation of the national COVID-19 vaccination program. We conducted four repeated cross-sectional surveys at the outpatient department of San Lazaro Hospital between March 2022 and January 2023. We performed χ2 test and analysis of variance to assess the differences in characteristics across different data collection periods. A total of 765 participants were enrolled, ranging from 170 to 200 per period. Participant demographic, socioeconomic, and medical history were comparable across all data collection periods. Between March and October 2022, the proportion of participants who received a vaccine or booster dose significantly increased, from 77.9

Problem:Once COVID-19 vaccines were rolled out, there was a need to monitor real-world vaccine effectiveness to accumulate evidence to inform policy and risk communication. This was especially true in Japan and the Philippines, given historical issues that affected vaccine confidence. Context:Neither country had public health surveillance that could be enhanced to evaluate vaccine effectiveness or readily available national vaccination databases. Action:Study groups were established in multiple health-care facilities in each country to assess vaccine effectiveness against both symptomatic infection and severe disease. Outcome:In Japan, multiple study reports were published in Japanese on the web site of the National Institute of Infectious Diseases and presented at the national government's advisory board. Nationwide media coverage facilitated transparency and increased the confidence of the government and the public in the vaccination programme. In the Philippines, the launch of the study was delayed so as to align the research plan with the interests of various stakeholders and to obtain institutional review board approval. Ultimately, the studies were successfully initiated and completed. Discussion:There were four main challenges in conducting our studies: finding health-care facilities for data collection; obtaining exposure (vaccination) data; identifying epidemiological biases and confounders; and informing policy and risk communication in a timely manner. Preparedness during inter-emergency/epidemic/pandemic periods to rapidly evaluate relevant interventions such as vaccination is critical and should include the following considerations: (1) the establishment and maintenance of prospective data collection platforms, ideally under public health surveillance (if not, clinical research networks or linked databases); (2) uniform and practical protocols considering biases and confounders; and (3) communication with stakeholders including institutional review boards.

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

Objective:We examined sociobehavioural factors associated with SARS-CoV-2 infection and estimated COVID-19 vaccine effectiveness against symptomatic SARS-CoV-2 infection in the Philippines. Such studies are limited in low- and middle-income countries, especially in Asia and the Pacific. Methods:A case-control study was conducted in two hospitals in Manila, Philippines, from March 2022 to June 2023. Sociobehavioural factors and vaccination history were collected. PCR-positive individuals were cases, while PCR-negative individuals were controls. Adjusted odds ratios (aORs) were calculated to examine associations between sociobehavioural factors/vaccination and medically attended SARS-CoV-2 infection. Results:The analysis included 2489 individuals (574 positive cases, 23.1%; 1915 controls, 76.9%; median age [interquartile range]: 35 [27-51] years). Although education and household income were not associated with infection, being a health-care worker was (aOR: 1.45; 95% confidence interval [CI]: 1.03-2.06). The odds of infection were higher among individuals who attended gatherings of five or more people compared to those who attended smaller gatherings (aOR: 2.58; 95% CI: 1.14-5.83). Absolute vaccine effectiveness for vaccination status was not estimated due to a high risk of bias, for example, unascertained prior infection. Moderate relative vaccine effectiveness for the first booster (32%; 95% CI: -120-79) and the second booster (48%; 95% CI: -23-78) were observed (both with wide CI), albeit with a waning trend after half a year. Discussion:The higher odds of infection among health-care workers emphasize the importance of infection prevention and control measures. Moderate relative vaccine effectiveness with a waning trend reiterates the need for more efficacious vaccines against symptomatic infection caused by circulating variants and with longer duration of protection.

BACKGROUND:Infection with Trichomonas vaginalis (TV) is the most prevalent curable sexually transmitted infection (STI) globally and is associated with prelabour rupture of membranes, preterm delivery, and low birthweight. Point-of-care (POC) testing for TV during pregnancy may facilitate rapid antenatal case detection and treatment. This study, part of the World Health Organization's global ProSPeRo study, aimed to evaluate the performance of OSOM® Trichomonas Rapid Test, an antigen-based POC test, against a reference nucleic acid amplification test (NAAT) among pregnant women in Zambia. We also assessed the operational characteristics and patient acceptability of the POC test, within the context of WHO's target product profiles for STI POC tests. METHODS:We enrolled pregnant women attending four health centres in Nchelenge, Zambia, for antenatal care between 15 February and 26 May 2023. Vaginal swabs for the TV POC test and a reference NAAT (Aptima® Trichomonas vaginalis assay) were obtained. POC test results were read independently by two study staff members. Study staff filled a questionnaire on the operational characteristics of the POC test, and participants were asked about their willingness to wait for results. RESULTS:Paired POC and reference test samples were collected from 1,015 participants. Overall, 23.0% (233/1015) tested positive for TV by NAAT, and 15.3% (155/1015) tested positive by the POC test, with three inconclusive results. The overall sensitivity and specificity of the POC test were 66.4% (95% confidence intervals [CI] 57.7-74.1%) and 99.6% (95% CI: 98.8-99.9%), respectively. Sensitivity was higher among those with TV-associated symptoms compared to those without (83.6% versus 60.4%, relative ratio 1.39, 95% CI 1.14-1.68). Inter-rater agreement was 99.7% (Cohen's Kappa 0.989). The study staff (n = 14) found the test easy to use and interpret, with most staff (12/14) reporting results were available within 25 min. CONCLUSION:Overall, the TV POC test showed lower sensitivity than WHO's 85% target, but exceeded the 99% specificity target. Among symptomatic pregnant women, sensitivity nearly reached the WHO target. The assay was user-friendly, required minimal training, and delivered results quickly. Further studies are needed to determine the optimal antenatal settings for this technology. TRIAL REGISTRATION:PACTR202302766902029.

This letter discusses the possibility of Takotsubo cardiomyopathy (TTC) as an alternative diagnosis in a recently reported case of acute myocardial infarction following a hump-nosed viper bite. The patient's presentation, including delayed chest tightness, elevated troponin, ECG changes, and normal coronary arteries, coupled with complete recovery within 3 months, strongly suggests TTC. Multiple case reports have documented the association between snakebites and TTC, with proposed pathophysiological mechanisms including sympathetic surge from pain and stress, direct cardiotoxic effects of venom, and inflammatory mediators during envenomation. The excessive catecholamine response may trigger transient cardiac dysfunction characteristic of TTC. Recognizing TTC as a potential complication of snakebites has important clinical implications, as its management and prognosis differ from acute coronary syndrome. Understanding this association may enhance diagnostic approaches and treatment strategies in similar cases, particularly when normal coronary arteries and complete cardiac recovery are observed.

BACKGROUND:Leptospirosis is a bacterial disease caused by Leptospira spp, a zoonotic pathogen spread via contaminated soil and water. Corticosteroids have been used for the treatment or prevention of severe manifestations of disease, but the indications for their use and treatment efficacy remain uncertain. This review evaluates the existing evidence for the use of corticosteroids in leptospirosis from randomised trials. OBJECTIVES:To assess the benefits and harms of corticosteroids versus no intervention, no intervention beyond standard of care, or placebo for the treatment of people with leptospirosis. SEARCH METHODS:Electronic searches in the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials in the Cochrane Library, MEDLINE, Embase, LILACS, Science Citation Index Expanded, Conference Proceedings Citation Index - Science, and other resources were conducted. We searched online clinical trial registries to identify unpublished or ongoing trials, and reviewed reference lists from the identified publications for potential trials. We contacted authors of identified trials, relevant individuals, and organisations for additional information. The last search date was 10 April 2025. SELECTION CRITERIA:We considered the inclusion of randomised clinical trials of any trial design which assessed corticosteroids for the treatment of leptospirosis. We imposed no restrictions on age, sex, occupation, comorbidity of trial participants, or outcomes reported. We looked for trials assessing corticosteroids irrespective of type, route of administration, dosage, and schedule versus no intervention, placebo, or no intervention beyond standard care. We included trials meeting any of these criteria, irrespective of the manuscript's primary language. DATA COLLECTION AND ANALYSIS:We adhered to Cochrane methodology. Data entry and analysis were facilitated by the use of the Review Manager. The primary outcomes were all-cause mortality and the proportion of individuals experiencing serious adverse events. The secondary outcomes were quality of life, the proportion of individuals experiencing non-serious adverse events, days of hospitalisation, and the proportion of individuals experiencing Jarisch-Herxheimer reactions. We employed the risk of bias 2 tool (RoB 2) to assess the bias risk of included trials. We used the GRADEPro software to evaluate the certainty of evidence. We presented dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean differences (MD), both accompanied by their corresponding 95% confidence intervals (CI). We applied a random-effects meta-analysis for the primary analysis and a fixed-effect model for the sensitivity analyses. Our primary outcome analyses included trial data at the longest follow-up. We analysed the outcome data regardless of the risk of bias. MAIN RESULTS:Four randomised trials were included in this review, with a pooled total of 253 participants. Each of the trials compared a corticosteroid (prednisolone, hydrocortisone, a combined treatment regimen of dexamethasone and prednisolone, or methylprednisolone) versus no intervention, no intervention beyond standard of care, or placebo. Participants in three trials received similarly administered co-interventions as standard of care, and had no further intervention in the fourth trial. All participants were recruited from populations presenting to general hospitals in leptospirosis endemic settings. The ages of the participants ranged from six years to 65 years. Depending on the trial, the treatment duration ranged from over four hours to seven days. All included trials were judged to have either some concerns or to be at high risk of bias. The certainty of evidence for all evaluated outcomes was judged to be very low. Quality of evidence was downgraded for risk of bias arising from the randomisation process, measurement of outcome, and selection of reporting of results; indirectness of evidence due to choice of intervention; inconsistency due to different point estimates and unexplained heterogeneity; and imprecision attributable to confidence intervals (CI) crossing clinically important thresholds, failure to meet optimal information size, or an upper/lower CI boundary more than three risk ratios. Corticosteroids compared with no intervention beyond standard of care or placebo may have little to no effect on all-cause mortality (RR 1.04, 95% CI 0.38 to 2.80, I2 = 0%, 3 trials, 123 participants, very low-certainty evidence) and on the proportion of individuals experiencing serious adverse events (RR 1.15, 95% CI 0.32 to 4.11, I2 = 62%, 3 trials, 123 participants, very low-certainty evidence), but the evidence is very uncertain. Corticosteroids compared to no intervention beyond standard of care or placebo may increase the proportion of individuals experiencing non-serious adverse events (RR 2.00, 95% CI 0.21 to 18.98, 1 trial, 22 participants, very low-certainty evidence), but the evidence is very uncertain. Corticosteroids compared to no intervention beyond standard of care or placebo may decrease the number of days of hospitalisation (MD 0.46, 95% CI -1.81 to 2.73, I2 = 83%, 3 trials, 123 participants, very low-certainty of evidence), but the evidence is very uncertain. Corticosteroids compared to no intervention may reduce the risk of Jarisch-Herxheimer reaction events (RR 0.13, 95% CI 0.04 to 0.41, 1 trial, 130 participants, very low-certainty evidence), but the evidence is very uncertain. None of the four trials assessed health-related quality of life. We have listed one trial registered as 'randomised' in studies awaiting classification because we could not identify further information. We have listed one trial in the ongoing section because trial recruitment has not yet started. AUTHORS' CONCLUSIONS:Based on the very low certainty of evidence attributable to our analyses, we do not know whether corticosteroids compared with no intervention, no intervention beyond standard of care, or placebo, reduce all-cause mortality, increase the risk of serious or non-serious adverse events, decrease days of hospitalisation, or decrease the proportion of people experiencing Jarisch-Herxheimer reaction events. None of the four trials assessed health-related quality of life. There is a lack of harmonised treatment strategies, clinically relevant outcome definitions, and definitive and rigorously designed randomised trials to support the use of corticosteroids for leptospirosis. Future research should focus on these evidence gaps.

Unwanted side-effects are the leading cause of dissatisfaction and discontinuation of hormonal contraceptives worldwide. Yet contraceptive side-effects are commonly dismissed as minor and/or misconceptions within global health, in part due to the paucity of quantitative data on side-effects symptoms. This research aimed to (1) compare changes in symptom number and severity among hormonal contraceptive users and a control group over a 3-months period, (2) identify risk factors for such changes, and (3) evaluate their impact on women's daily lives. We conducted an observational baseline-controlled prospective cohort study among injectable and implant users and a control group of non-users in Central Oromia, Ethiopia. Sociodemographic, diet, activity data and monthly side-effect symptoms were collected from pre-initiation to three months. Multilevel models adjusted for temporal autocorrelation were used to evaluate change in the number and severity of symptoms. Minimally adjusted models were used to identify risk factors for increased negative symptoms among contraceptive users and evaluate the impact of experiencing symptoms on women's daily activities. A total of 278 participants (106 injectable, 72 implant, 100 non-users) were included for analysis. Compared to pre-initiation, injectable users experienced 28% more symptoms at month 3 (adjusted incident rate ratio (IRR): 1.28, 95% CI: 1.05 - 1.57 p = 0.015), implant users experienced a peak of 41% more symptoms at month 2 (adjusted IRR 1.41, 95% CI: 1.15 - 1.73, p = 0.002), and non-users experienced no changes over a similar time period. Contraceptive users with physically demanding occupations, food insecurity, and a history of recent infection experienced the greatest symptom severity, also associated with negative impacts on women's activities, including work, chores, and relationships. These findings indicate that reducing the burden of contraceptive side effects requires addressing underlying health stressors and considering the significant impact of side-effects on women's daily lives, rather than relying solely on dispelling misconceptions. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by a Wellcome Trust Seed Grant (210211/Z/18/Z) awarded to AA and an Economic and Social Research Council (ESRC) studentship awarded to RS (ES/P000649/1). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval was obtained from three bodies: the Oxford Tropical Research Ethics Committee (OxTREC) at the University of Oxford (562-18); the College of Health Sciences at Addis Ababa University (069/19/DMIP), and the Oromia Health Bureau (BEFO/HBTF/1-16/239). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Anonymised data underlying these analyses will be made available upon reasonable request.