Genomic insights into the 2016-2017 cholera epidemic in Yemen.

Yemen is currently experiencing, to our knowledge, the largest cholera epidemic in recent history. The first cases were declared in September 2016, and over 1.1 million cases and 2,300 deaths have since been reported1. Here we investigate the phylogenetic relationships, pathogenesis and determinants of antimicrobial resistance by sequencing the genomes of Vibrio cholerae isolates from the epidemic in Yemen and recent isolates from neighbouring regions. These 116 genomic sequences were placed within the phylogenetic context of a global collection of 1,087 isolates of the seventh pandemic V. cholerae serogroups O1 and O139 biotype El Tor2-4. We show that the isolates from Yemen that were collected during the two epidemiological waves of the epidemic1-the first between 28 September 2016 and 23 April 2017 (25,839 suspected cases) and the second beginning on 24 April 2017 (more than 1 million suspected cases)-are V. cholerae serotype Ogawa isolates from a single sublineage of the seventh pandemic V. cholerae O1 El Tor (7PET) lineage. Using genomic approaches, we link the epidemic in Yemen to global radiations of pandemic V. cholerae and show that this sublineage originated from South Asia and that it caused outbreaks in East Africa before appearing in Yemen. Furthermore, we show that the isolates from Yemen are susceptible to several antibiotics that are commonly used to treat cholera and to polymyxin B, resistance to which is used as a marker of the El Tor biotype.

Publisher Correction: Genomic insights into the 2016-2017 cholera epidemic in Yemen.

In the HTML version of this Letter, the affiliations for authors Andrew S. Azman, Dhirendra Kumar and Thandavarayan Ramamurthy were inverted (the PDF and print versions of the Letter were correct); the affiliations have been corrected online.

A case-control study on risk factors for visceral leishmaniasis in West Pokot County, Kenya.

BACKGROUND: Visceral leishmaniasis (VL) is a severe parasitic disease transmitted by phlebotomine sandflies. VL is endemic in West Pokot County, Kenya, where effective strategies to interrupt transmission are impeded by the limited understanding of VL risk factors. Therefore, this case-control study aimed to explore environmental, behavioural and household determinants of VL in West Pokot. METHODS: From November 2022 to January 2023, a structured questionnaire was administered to 36 symptomatic primary VL cases attending Kacheliba Sub-County Hospital in West Pokot and to 50 healthy controls from local villages. The VL status of all participants was confirmed using an rK39 rapid diagnostic test. Associations between questioned determinants and VL were investigated by means of age-corrected univariate logistic regression analysis. RESULTS: Significant associations were found between VL and housing characteristics, such as window presence and floor type. VL cases more frequently reported the presence of cattle, dogs and sheep in their house yards. VL was also associated with cutting down trees in the house yard and house proximity to several Acacia tree species. Furthermore, outdoor activities, including travelling outside the residence for more than 2 weeks, activities near termite mounds, and forest activities during the rainy season, increased the risk of VL. CONCLUSIONS: This work reports a number of previously undescribed risk factors for VL in the understudied West Pokot focus. The results suggest VL transmission occurs both peri-domestically at night and outdoors during the day, particularly when sandfly resting sites are disturbed. Our findings warrant further research into sandfly ecology and potential zoonotic parasite reservoirs in West Pokot.

Cytokine profiles, blood parasite load and clinical features of visceral leishmaniasis in West Pokot County, Kenya.

Visceral leishmaniasis (VL) is a severe infectious disease caused by protozoan parasites of the Leishmania donovani complex. Blood cytokine concentrations in VL patients can inform us about underlying immunopathogenesis and may serve as a biomarker for treatment effectiveness. However, cytokine levels have not yet been studied in VL patients from Kenya, where case load is high. This study measured the serum cytokine profile, blood parasite load and clinical and haematological features of VL patients from West Pokot County, Kenya, over the course of treatment with sodium stibogluconate and paromomycin (SSG-PM). VL patients recruited at the hospital presented with splenomegaly and weight loss, and frequently had pancytopenia and anaemia. Median Leishmania parasite load in blood, determined with real-time polymerase chain reaction, was 2.6 × 104 parasite equivalents mL−1. Compared to endemic healthy controls, serum interferon gamma (IFN-γ), interleukin 5 (IL-5), IL-6, IL-10, IL-12p70, IL-17A and IL-27 were significantly elevated in untreated VL patients. Severe VL was associated with higher IL-10 and lower IFN-γ levels. After 17 daily injections with SSG-PM, disease symptoms disappeared, leukocyte and thrombocyte counts significantly increased, and blood parasite load decreased to undetectable levels in all VL patients. There was a significant decrease in IL-10 and IL-6, whereas IL-17A levels increased; the remaining cytokines showed no significant concentration change during treatment. In conclusion, the results suggest that SSG-PM treatment of VL patients from West Pokot was effective. Moreover, both inflammatory and regulatory immune responses appeared to decrease during treatment, although the increase in IL-17A could reflect a partial continuation of immune activation.

Implementation of community case management of malaria in malaria endemic counties of western Kenya: are community health volunteers up to the task in diagnosing malaria?

BACKGROUND: Community case management of malaria (CCMm) is an equity-focused strategy that complements and extends the reach of health services by providing timely and effective management of malaria to populations with limited access to facility-based healthcare. In Kenya, CCMm involves the use of malaria rapid diagnostic tests (RDT) and treatment of confirmed uncomplicated malaria cases with artemether lumefantrine (AL) by community health volunteers (CHVs). The test positivity rate (TPR) from CCMm reports collected by the Ministry of Health in 2018 was two-fold compared to facility-based reports for the same period. This necessitated the need to evaluate the performance of CHVs in conducting malaria RDTs. METHODS: The study was conducted in four counties within the malaria-endemic lake zone in Kenya with a malaria prevalence in 2018 of 27%; the national prevalence of malaria was 8%. Multi-stage cluster sampling and random selection were used. Results from 200 malaria RDTs performed by CHVs were compared with test results obtained by experienced medical laboratory technicians (MLT) performing the same test under the same conditions. Blood slides prepared by the MLTs were examined microscopically as a back-up check of the results. A Kappa score was calculated to assess level of agreement. Sensitivity, specificity, and positive and negative predictive values were calculated to determine diagnostic accuracy. RESULTS: The median age of CHVs was 46 (IQR: 38, 52) with a range (26-73) years. Females were 72% of the CHVs. Test positivity rates were 42% and 41% for MLTs and CHVs respectively. The kappa score was 0.89, indicating an almost perfect agreement in RDT results between CHVs and MLTs. The overall sensitivity and specificity between the CHVs and MLTs were 95.0% (95% CI 87.7, 98.6) and 94.0% (95% CI 88.0, 97.5), respectively. CONCLUSION: Engaging CHVs to diagnose malaria cases under the CCMm strategy yielded results which compared well with the results of qualified experienced laboratory personnel. CHVs can reliably continue to offer malaria diagnosis using RDTs in the community setting.

Community perception of epilepsy and its treatment in onchocerciasis-endemic villages of Maridi county, western equatoria state, South Sudan.

OBJECTIVE: To assess the community's perception of epilepsy and its treatment in onchocerciasis-endemic villages of Maridi County, Western Equatoria State, South Sudan. The study was conducted prior to the setting up of a community-based intervention to manage the important disease burden caused by onchocerciasis-associated epilepsy in these villages. METHOD: Five focus group discussions (FGD) were conducted with community leaders and with persons with epilepsy (PWE) and their families between November and December 2019. RESULTS: Villages close to the Maridi dam were considered to be most affected by epilepsy. Misconceptions about the cause and treatment of epilepsy were identified. Most people believed that epilepsy is caused by bad spirits and is contagious, transmitted through saliva, air, and contact with PWE. Very few participants were aware of the link between onchocerciasis and epilepsy. Persons with epilepsy are restricted in their day-to-day activities and children with epilepsy are often denied going to school. Persons with epilepsy are stigmatized and seen as unfit for marriage. Most participants considered both traditional and medical treatment as ineffective. Uninterrupted anti-seizure treatment continuously was unaffordable for most families with one or more PWE. CONCLUSION: There is a need to establish a comprehensive epilepsy treatment program which addresses misconceptions about epilepsy and reduces epilepsy-related stigma. Explaining the link between onchocerciasis and epilepsy could lead to a reduction in epilepsy-related stigma.

Performance of a fully-automated system on a WHO malaria microscopy evaluation slide set.

BACKGROUND: Manual microscopy remains a widely-used tool for malaria diagnosis and clinical studies, but it has inconsistent quality in the field due to variability in training and field practices. Automated diagnostic systems based on machine learning hold promise to improve quality and reproducibility of field microscopy. The World Health Organization (WHO) has designed a 55-slide set (WHO 55) for their External Competence Assessment of Malaria Microscopists (ECAMM) programme, which can also serve as a valuable benchmark for automated systems. The performance of a fully-automated malaria diagnostic system, EasyScan GO, on a WHO 55 slide set was evaluated. METHODS: The WHO 55 slide set is designed to evaluate microscopist competence in three areas of malaria diagnosis using Giemsa-stained blood films, focused on crucial field needs: malaria parasite detection, malaria parasite species identification (ID), and malaria parasite quantitation. The EasyScan GO is a fully-automated system that combines scanning of Giemsa-stained blood films with assessment algorithms to deliver malaria diagnoses. This system was tested on a WHO 55 slide set. RESULTS: The EasyScan GO achieved 94.3 % detection accuracy, 82.9 % species ID accuracy, and 50 % quantitation accuracy, corresponding to WHO microscopy competence Levels 1, 2, and 1, respectively. This is, to our knowledge, the best performance of a fully-automated system on a WHO 55 set. CONCLUSIONS: EasyScan GO's expert ratings in detection and quantitation on the WHO 55 slide set point towards its potential value in drug efficacy use-cases, as well as in some case management situations with less stringent species ID needs. Improved runtime may enable use in general case management settings.

Towards harmonization of microscopy methods for malaria clinical research studies.

Microscopy performed on stained films of peripheral blood for detection, identification and quantification of malaria parasites is an essential reference standard for clinical trials of drugs, vaccines and diagnostic tests for malaria. The value of data from such research is greatly enhanced if this reference standard is consistent across time and geography. Adherence to common standards and practices is a prerequisite to achieve this. The rationale for proposed research standards and procedures for the preparation, staining and microscopic examination of blood films for malaria parasites is presented here with the aim of improving the consistency and reliability of malaria microscopy performed in such studies. These standards constitute the core of a quality management system for clinical research studies employing microscopy as a reference standard. They can be used as the basis for the design of training and proficiency testing programmes as well as for procedures and quality assurance of malaria microscopy in clinical research.

How we do it: shifting MR arthrogram compounding from the fluoroscopy suite to the sterile pharmacy.

OBJECTIVE: To assess the impact of shifting arthrogram injectate compounding from the fluoroscopy suite to the main hospital sterile pharmacy on cost, examination delays, and infection rates. MATERIALS AND METHODS: All arthrograms from the 12 months before (629 in total) and the 12 months after (699 in total) the change in arthrogram preparation procedure were compared to identify differences in examination delays and infection rate. The arthrogram formulation was sent to the Compounder's International Analytical Laboratory for stability testing. Finally, cost per injection analysis was performed to compare fluoroscopy suite with sterile pharmacy compounding. RESULTS: In the 699 arthrograms performed in the 12 months following transfer of arthrogram preparation to the main hospital pharmacy, there were 0 reported examination delays, 0 reported infections, and a 53% decrease in the material cost per arthrogram. There were three recorded instances of fluoroscopy suite preparation of arthrogram injectate due to unexpected add-on patients. Outside stability testing determined that the arthrogram injectate retained at least 90% potency 30 h post-preparation. CONCLUSION: Shifting the compounding of the arthrogram injectate from the fluoroscopy room to the main hospital sterile pharmacy provides a modest cost saving and can be accomplished without examination delays or any increase in infection rate. It brought our practice into compliance with USP797, which is the current guideline for compounding practitioners, by transferring the compounding preparation of the arthrogram injectate from a procedure room to the sterile pharmacy.

The role of the miR-200 family in epithelial-mesenchymal transition in colorectal cancer: a systematic review.

Colorectal cancer (CRC) is associated with significant morbidity and mortality as many patients are diagnosed with advanced stage disease. MicroRNAs are small, noncoding RNA molecules that have a major role in gene expression regulation and are dysregulated in CRC. The miR-200 family is involved in epithelial-mesenchymal transition (EMT). This systematic review describes the roles of the miR-200 family in EMT in CRC. A search of electronic databases (PubMed and Embase) was conducted between January 2000 and July 2017. Both in vitro and human studies reporting on the miR-200 family and CRC were included. Studies describing molecular pathways and the role of the miR-200 family in the diagnostic and therapeutic management of CRC were analyzed. Thirty-four studies (22 in vitro and 18 human studies) were included. miR-200 family expression is regulated epigenetically and via transcriptional factor regulation. In vitro studies show that transfection of miR-200 family members into chemo-resistant colon cancer cell lines results in improved chemo-sensitivity and epithelial phenotype restoration. There is intra-tumoral variability in the tissue expression of miR-200 family members with decreased expression at the invasive front. Clinical studies in CRC patients have shown decreased primary tumor tissue expression of miR-429, miR-200a and miR-200c may be associated with worse survival. Conversely, increased blood levels of miR-141, miR-200a and miR-200c may be associated with worse outcomes. The miR-200 family has a central role in EMT. The miR200 family has potential for both prognostic and therapeutic management of CRC.

Blood-based microRNAs as biomarkers for the diagnosis of colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: Colorectal cancer (CRC) is common and associated with significant mortality. Current screening methods for CRC lack patient compliance. microRNAs (miRNAs), identified in body fluids, are negative regulators of gene expression and are dysregulated in many cancers, including CRC. This paper summarises studies identifying blood-based miRNAs dysregulated in CRC compared with healthy controls in an attempt to evaluate their use as a screening tool for the diagnosis of CRC. METHODS: A search of electronic databases (PubMed and EMBASE) and grey literature was performed between January 2002 and April 2016. Studies reporting plasma or serum miRNAs in the diagnosis of CRC compared with healthy controls were selected. Patient demographics, type of patient sample (serum or plasma), method of miRNA detection, type of normalisation, and the number of significantly dysregulated miRNAs identified were recorded. Statistical evaluation of dysregulated miRNAs using sensitivity, specificity, and area under the curve (AUC) was performed. RESULTS: Thirty-four studies investigating plasma or serum miRNAs in the diagnosis of CRC were included. A total of 31 miRNAs were found to be either upregulated (n=17) or downregulated (n=14) in CRC cases as compared with controls. Fourteen studies identified panels of ⩾2 dysregulated miRNAs. The highest AUC, 0.943, was identified using a panel of 4 miRNAs with 83.3% sensitivity and 93.1% specificity. Meta-analysis of studies identifying a single dysregulated miRNA in CRC cases compared with controls was performed. Overall sensitivity and specificity of 28 individual miRNAs in the diagnosis of CRC were 76% (95% CI 72%-80%) and 76% (95% CI 72%-80%), respectively, indicating good discriminative ability of miRNAs as biomarkers for CRC. These data did not change with sensitivity analyses. CONCLUSIONS: Blood-based miRNAs distinguish patients with CRC from healthy controls with high sensitivity and specificity comparable to other common and invasive currently used screening methods for CRC. In future, miRNAs may be used as a relatively non-invasive blood-based marker for detection of CRC.

Effectiveness of three commonly used transition phase diets in the inpatient management of children with severe acute malnutrition: a pilot randomized controlled trial in Malawi.

BACKGROUND: The case fatality rate of severely malnourished children during inpatient treatment is high and mortality is often associated with diarrhea. As intestinal carbohydrate absorption is impaired in severe acute malnutrition (SAM), differences in dietary formulations during nutritional rehabilitation could lead to the development of osmotic diarrhea and subsequently hypovolemia and death. We compared three dietary strategies commonly used during the transition of severely malnourished children to higher caloric feeds, i.e., F100 milk (F100), Ready-to-Use Therapeutic Food (RUTF) and RUTF supplemented with F75 milk (RUTF + F75). METHODS: In this open-label pilot randomized controlled trial, 74 Malawian children with SAM aged 6-60 months, were assigned to either F100, RUTF or RUTF + F75. Our primary endpoint was the presence of low fecal pH (pH ≤ 5.5) measured in stool collected 3 days after the transition phase diets were introduced. Secondary outcomes were duration of hospital stay, diarrhea and other clinical outcomes. Chi-square test, two-way analysis of variance and logistic regression were conducted and, when appropriate, age, sex and initial weight for height Z-scores were included as covariates. RESULTS: The proportion of children with acidic stool (pH ≤5.5) did not significantly differ between groups before discharge with 30, 33 and 23% for F100, RUTF and RUTF + F75, respectively. Mean duration of stay after transitioning was 7.0 days (SD 3.4) with no differences between the three feeding strategies. Diarrhea was present upon admission in 33% of patients and was significantly higher (48%) during the transition phase (p < 0.05). There was no significant difference in mortality (n = 6) between diets during the transition phase nor were there any differences in other secondary outcomes. CONCLUSIONS: This pilot trial does not demonstrate that a particular transition phase diet is significantly better or worse since biochemical and clinical outcomes in children with SAM did not differ. However, larger and more tightly controlled efficacy studies are needed to confirm these findings. TRIAL REGISTRATION: ISRCTN13916953 Registered: 14 January 2013.

A Highly Predictive Model for Diagnosis of Colorectal Neoplasms Using Plasma MicroRNA: Improving Specificity and Sensitivity.

OBJECTIVE: To develop a plasma-based microRNA (miRNA) diagnostic assay specific for colorectal neoplasms, building upon our prior work. BACKGROUND: Colorectal neoplasms [colorectal cancer (CRC) and colorectal advanced adenoma (CAA)] frequently develop in individuals at ages when other common cancers also occur. Current screening methods lack sensitivity, specificity, and have poor patient compliance. METHODS: Plasma was screened for 380 miRNAs using microfluidic array technology from a "Training" cohort of 60 patients, (10 each) control, CRC, CAA, breast cancer, pancreatic cancer, and lung cancer. We identified uniquely dysregulated miRNAs specific for colorectal neoplasia (P < 0.05, false discovery rate: 5%, adjusted α = 0.0038). These miRNAs were evaluated using single assays in a "Test" cohort of 120 patients. A mathematical model was developed to predict blinded sample identity in a 150 patient "Validation" cohort using repeat-sub-sampling validation of the testing dataset with 1000 iterations each to assess model detection accuracy. RESULTS: Seven miRNAs (miR-21, miR-29c, miR-122, miR-192, miR-346, miR-372, and miR-374a) were selected based upon P value, area under the curve (AUC), fold change, and biological plausibility. Area under the curve (±95% confidence interval) for "Test" cohort comparisons were 0.91 (0.85-0.96) between all neoplasia and controls, 0.79 (0.70-0.88) between colorectal neoplasia and other cancers, and 0.98 (0.96-1.0) between CRC and colorectal adenomas. In our "Validation" cohort, our mathematical model predicted blinded sample identity with 69% to 77% accuracy, 67% to 76% accuracy, and 86% to 90% accuracy for each comparison, respectively. CONCLUSIONS: Our plasma miRNA assay and prediction model differentiate colorectal neoplasia from patients with other neoplasms and from controls with higher sensitivity and specificity compared with current clinical standards.

The 'Necksafe' head articulation control system: a novel cervical immobilisation device.

INTRODUCTION: The early application of a semirigid disposable cervical collar following trauma is considered a routine practice. The aim of these devices is to immobilise the cervical spine and minimise the risk of additional neurological damage. However, these collars provide only partial immobilisation, are uncomfortable and are associated with a number of complications. Our team designed and tested a novel cervical immobilisation device that aims to improve immobilisation with reduced complications: the 'Necksafe'. METHODS: Human volunteers were recruited and consented to test the novel Necksafe device in comparison with a conventional collar (the AMBU Perfit ACE) in a range of evaluations. These included assessments of the cervical range of movement (CROM) that occurred during scripted movements of the head and neck, and the effect of the new and conventional devices on jugular vein dimensions, assessed using ultrasound scanning. RESULTS: CROM analysis showed that, under standardised testing conditions, the Necksafe device offers cervical immobilisation that is at least equivalent to a conventional collar, and is superior in the planes of extension, lateral flexion and rotation. Ultrasound examination of the jugular veins was inconclusive and did not reveal any differences in jugular venous diameter or flow. Qualitative feedback from ambulance paramedics was highly supportive of the new design, suggesting that it is more comfortable, easier to fit, less confining and better tolerated than a conventional collar, with improved immobilisation effectiveness. CONCLUSIONS: The results of quantitative and qualitative testing are highly supportive of the new Necksafe design, with improved cervical immobilisation, comfort and access to the airway.

Trauma-informed behavioral supports (TIBS) for inpatient treatment of individuals who experience BPD.

Trauma-Informed Behavioral Supports (TIBS) is a novel treatment approach targeting aggression against self or against others in individuals who experience borderline personality disorder (BPD). It is based on applied behavior analysis and uses a person-centered and trauma-informed framework. People with BPD hospitalized because of concerning behaviors, [aggression to others, verbal aggression (e.g., defined as aggression in the forms of verbal threats, etc.), physical aggression, and self-injury, etc.] may experience exacerbations of such behavior in the hospital. Individuals diagnosed with BPD were treated with TIBS to diminish the frequency of concerning behaviors in the context of a pilot study. Functioning during a three-month pre-treatment phase was compared with a six-month treatment phase. The TIBS intervention resulted in statistically significant and clinically meaningful decreases in physical and verbal aggression. The results of this pilot investigation approach suggests that TIBS can promote behavior change in the inpatient setting.

Does gender still matter in the pursuit of a career in anaesthesia?

A survey sent to fellows of the Australian and New Zealand College of Anaesthetists (ANZCA) aimed to document issues affecting gender equity in the anaesthesia workplace. A response rate of 38% was achieved, with women representing a greater proportion of respondents (64.2%). On average women worked fewer hours than men and spent a larger percentage of time in public practice; however, satisfaction rates were similar between genders. There was a gender pay gap which could not be explained by the number of hours worked or years since achieving fellowship. The rates of bullying and harassment were high among all genders and have not changed in 20 years since the first gender equity survey by Strange Khursandi in 1998. Women perceived that they were more likely to be discriminated against particularly in the presence of other sources of discrimination, and highlighted the importance of the need for diversity and inclusion in anaesthetic workplaces. Furthermore, women reported higher rates of caregiving and unpaid domestic responsibilities, confirming that anaesthetists are not immune to the factors affecting broader society despite our professional status. The overall effect was summarised by half of female respondents reporting that they felt their gender was a barrier to a career in anaesthesia. While unable to be included in statistics due to low numbers, non-binary gendered anaesthetists responded and must be included in all future work. The inequities documented here are evidence that ANZCA's gender equity subcommittee must continue promoting and implementing policies in workplaces across Australia and New Zealand.

Epidemiology of epilepsy in Wulu County, an onchocerciasis-endemic area in South Sudan.

Background: We sought to investigate the epidemiology of epilepsy in Wulu County (Lakes State, South Sudan), and document the onchocerciasis transmission status in the study villages. Methods: In February 2024, a community-based epilepsy study was conducted Wulu County and participants were surveyed via a door-to-door approach in five villages, namely: Kombi, Makundi Center, Tonjo, War-Pac, and Woko. All village residents were asked about ivermectin intake during the 2023 round of community-directed treatment with ivermectin (CDTI). In addition, children aged 3-9 years were tested for Ov16 antibodies using a rapid diagnostic test. Epilepsy diagnosis in screened individuals was confirmed by a physician. Results: We surveyed 1355 persons in the five study sites. The overall CDTI coverage in 2023 was 67.4 %. Fifty-five persons with epilepsy (PWE) were identified (prevalence 4.1 %) and a history of nodding seizures was noted in 11/55 (20 %) PWE. The mean age of PWE was 21.5 ± 9.6 years, with 32 (58.2 %) being males. Epilepsy onset frequently occurred under 5 years of age (38.6 % of cases). In two PWE, seizure onset occurred during the past 12 months (annual incidence: 147.6 per 100,000 persons). Twenty-nine PWE (52.7 %) were taking anti-seizure medicines, but only five were taking them daily. Overall, Ov16 seroprevalence in children aged 3-9 years (n = 119) was 15.1 % and differed across villages, peaking at 30.9 % in Woko village where epilepsy prevalence was also highest (7.1 %). Of the 35 recorded deaths during the past two years, 9 (25.7 %) occurred in PWE. Annual estimates for epilepsy mortality and fatality rates were 323.7 per 100,000 persons and 7031.3 per 100,000 PWE, respectively. Conclusion: High epilepsy prevalence was found in Wulu, particularly in villages with persistent onchocerciasis transmission. Frequent epilepsy onset among under-fives suggests that perinatal/early childhood etiologies are common. Appropriate measures should be instituted to prevent and treat epilepsy in Wulu villages.

Impact of annual community-directed treatment with ivermectin on the incidence of epilepsy in Mvolo, a two-year prospective study.

OBJECTIVES: The potential impact of cumulative community-directed treatment with ivermectin (CDTI) on epilepsy epidemiology in Mvolo County, South Sudan, an onchocerciasis-endemic area with high epilepsy prevalence, was investigated. Annual CDTI was introduced in 2002 in Mvolo, with interruptions in 2016 and 2020. METHODS: Comprehensive house-to-house surveys in Mvolo (June 2020 and 2022) identified cases of epilepsy, including probable nodding syndrome (pNS). Community workers screened households in selected sites for suspected epilepsy, and medical doctors confirmed the diagnosis and determined the year of seizure onset. The incidence of epilepsy, including pNS, was analysed using 95% confidence intervals (CIs). Data on ivermectin intake and onchocerciasis-associated manifestations (itching and blindness) were collected. RESULTS: The surveys covered 15,755 (2020) and 15,092 (2022) individuals, identifying 809 (5.2%, 95% CI: 4.8-5.5%) and 672 (4.5%, 95% CI: 4.1-4.8%) epilepsy cases, respectively. Each survey reported that a third of the surveyed population experienced skin itching, and 3% were blind. Epilepsy incidence per 100,000 person-years gradually declined, from 326.5 (95% CI: 266.8-399.1) in 2013-2015 to 96.6 (95% CI: 65.5-141.7) in 2019-2021. Similarly, pNS incidence per 100,000 person-years decreased from 151.7 (95% CI: 112.7-203.4) to 27.0 (95% CI: 12.5-55.5). Coverage of CDTI was suboptimal, reaching only 64.0% of participants in 2019 and falling to 24.1% in 2021 following an interruption in 2020 due to COVID-19 restrictions. Additionally, while 99.4% of cases had active epilepsy in 2022, less than a quarter of these had access to antiseizure medication. CONCLUSIONS: The observed decrease in epilepsy incidence despite suboptimal CDTI coverage highlights the potential impact of onchocerciasis control efforts and underscores the need to strengthen these efforts in Mvolo County and across South Sudan. As a proactive measure, Mvolo and neighbouring counties are transitioning to biannual CDTI. Furthermore, the substantial epilepsy treatment gap in Mvolo should be addressed.

Defining a malaria diagnostic pathway from innovation to adoption: Stakeholder perspectives on data and evidence gaps.

Malaria, a major global health concern, requires effective diagnostic tools for patient care, disease control, and elimination. The pathway from concept to the adoption of diagnostic products is complex, involving multiple steps and stakeholders. To map this process, our study introduces a malaria-specific diagnostic pathway, synthesising existing frameworks with expert insights. Comprising six major stages and 31 related activities, the pathway retains the core stages from existing frameworks and integrates essential malaria diagnostic activities, such as WHO prequalification processes, global stakeholder involvement, and broader health systems considerations. To understand the scope and availability of evidence guiding the activities along this pathway, we conducted an online survey with 113 participants from various stages of the malaria diagnostic pathway. The survey assessed perceptions on four critical attributes of evidence: clear requirements, alignment with user needs, accuracy and reliability, and public and free availability. It also explored the types of evidence used and the challenges and potential solutions related to evidence generation and use. Respondents reported using a broad range of formal and informal data sources. Findings indicated differing levels of agreement on the attributes across pathway stages, with notable challenges in the Approvals and Manufacturing stage and consistent concerns regarding the public availability of data/evidence. The study offers valuable insights for optimising evidence generation and utilisation across the malaria diagnostic pathway. It highlights the need for enhanced stakeholder collaboration, improved data availability, and increased funding to support effective evidence generation, sharing, and use. We propose actionable solutions, including the use of public data repositories, progressive data sharing policies, open-access publishing, capacity-building initiatives, stakeholder engagement forums, and innovative funding solutions. The developed framework and study insights have broader applications, offering a model adaptable for other diseases, particularly for neglected tropical diseases, which face similar diagnostic challenges.