Feasibility of post-exposure-prophylaxis with single-dose rifampicin and identification of high prevalent clusters in villages' hyperendemic for leprosy in Senegal.

INTRODUCTION: Senegal is a leprosy low-endemic country with nine villages known to be hyperendemic with a leprosy incidence rate above 1,000 per million inhabitants. We aim to implement a door-to-door screening strategy associated with the administration of a single-dose-rifampicin (SDR) as post-exposure prophylaxis (PEP) to household and social contacts in these villages and to identify spatial clustering and assess the risk of leprosy in population according to the physical distance to the nearest index-case. METHODS: From October/2020 to February/2022 active door-to-door screening for leprosy was conducted in nine villages. Using an open-source application, we recorded screening results, demographic and geographic coordinate's data. Using Poisson model we analysed clustering and estimated risk of contracting leprosy in contacts according to the distance to the nearest new leprosy patient. RESULTS: In nine villages, among 9086 contacts listed, we examined 7115. Among 6554 eligible contacts, 97.8% took SDR. We found 39(0.64%) new leprosy cases among 6,124 examined in six villages. Among new cases, 21(53.8%) were children, 10(25.6%) were multibacillary and 05(12.8%) had grade 2 disability. The prevalent risk ratio and 95% confidence intervale(95%CI) adjusted by village were 4.2(95%CI 1.7-10.1), 0.97(95%CI 0.2-4.4), 0.87(95%CI 0.2-25), 0.89(95%CI 0.3-2.6) and 0.70(95%CI 0.2-2.5) for the contacts living in the same household of an index case, 1-25m, 26-50m, 51-75m and 76-100m compared to those living at more than 100m respectively. We identified nine high prevalent clusters including 27/39(69%) of new cases in 490/7,850(6%) inhabitants, with relative risks of 46.6(p-value = 0.01), and 7.3, 42.8, 8.2, 12.5, 11.4, 23.5, 22.3, and 14.6 (non-significant p-values). CONCLUSIONS: Our strategy has proved the feasibility of active screening for leprosy in contacts and the introduction of PEP for leprosy under programmatic conditions. Only individuals living in the same household as the leprosy patient had a significant risk of contracting leprosy. We documented nine clusters of leprosy that could benefit from tailored control activities while optimizing resources.

Bioarchaeological investigation of individuals with suspected multibacillary leprosy from the mediaeval leprosarium of St Mary Magdalen, Winchester, Hampshire, UK.

Introduction. We have examined four burials from the St Mary Magdalen mediaeval leprosarium cemetery in Winchester, Hampshire, UK. One (Sk.8) was a male child, two (Sk.45 and Sk.52) were adolescent females and the fourth (Sk.512) was an adult male. The cemetery was in use between the 10th and 12th centuries. All showed skeletal lesions of leprosy. Additionally, one of the two females (Sk.45) had lesions suggestive of multi-cystic tuberculosis and the second (Sk.52) of leprogenic odontodysplasia (LO), a rare malformation of the roots of the permanent maxillary incisors.Gap statement. Relatively little is known of the manifestations of lepromatous leprosy (LL) in younger individuals from the archaeological record.Aims and Methodology. To address this, we have used ancient DNA testing and osteological examination of the individuals, supplemented with X-ray and microcomputed tomography (micro-CT) scan as necessary to assess the disease status.Results and Conclusions. The presence of Mycobacterium leprae DNA was confirmed in both females, and genotyping showed SNP type 3I-1 strains but with a clear genotypic variation. We could not confirm Mycobacterium tuberculosis complex DNA in the female individual SK.45. High levels of M. leprae DNA were found within the pulp cavities of four maxillary teeth from the male child (Sk.8) with LO, consistent with the theory that the replication of M. leprae in alveolar bone may interfere with root formation at key stages of development. We report our biomolecular findings in these individuals and review the evidence this site has contributed to our knowledge of mediaeval leprosy.

Characterization of cases and epidemiological and operational indicators of leprosy: analysis of time series and spatial distribution, Piauí state, Brazil, 2007-2021.

OBJECTIVE: To analyze epidemiological characteristics, temporal trends and spatial distribution of leprosy cases and indicators in the state of Piauí, 2007-2021. METHODS: This was an ecological time-series study using data from the Notifiable Health Conditions Information System, describing the spatial distribution and the temporal trend of leprosy using Prais-Winsten regression. RESULTS: A total of 17,075 new cases of leprosy were reported. There was a falling trend in the overall detection rate [annual percentage change (APC) = -6.3; 95%CI -8.1;-4.5)], detection in children under 15 years of age (APC = -8,6; 95%CI -12,7;-4,3) and detection of cases with grade 2 physical disability (APC = -4,4; 95%CI -7,0;-1,8). There was a rising trend in the proportion of multibacillary cases. Spatial distribution of the average detection rate identified hyperendemic areas in the Carnaubais, Entre Rios, Vale dos Rios Piauí e Itaueiras regions. CONCLUSION: High leprosy detection rates were found, despite the falling trend of indicators, except the proportion of multibacillary cases. MAIN RESULTS: Between 2007 and 2021, Piauí showed an improving trend in all indicators analyzed, except the proportion of new multibacillary cases. Spatial distribution identified hyperendemic areas in different regions of the state. IMPLICATIONS FOR SERVICES: This study provides health services with a broad overview of the epidemiological situation of leprosy in Piauí, with evidence of the populations and locations most affected by the disease, whereby public authorities need to reinforce the promotion of health actions. PERSPECTIVES: It is expected that actions to prevent and control the disease will be adopted, such as offering early diagnosis, ensuring correct treatment and implementing measures to prevent physical disabilities.

Challenges and advances in serological and molecular tests to aid leprosy diagnosis.

Leprosy is a neglected chronic infectious disease caused by obligate intracellular bacilli, Mycobacterium leprae and Mycobacterium lepromatosis. Despite multidrug therapy (MDT) success, leprosy accounts for more than 200,000 new cases yearly. Leprosy diagnosis remains based on the dermato-neurologic examination, but histopathology of skin biopsy and bacilloscopy of intradermal scraping are subsidiary diagnostic tests that require expertise and laboratory infrastructure. This minireview summarizes the state of the art of serologic tests to aid leprosy diagnosis, highlighting enzyme-linked immunosorbent assay (ELISA) and point-of-care tests (POCT) biotechnologies. Also, the impact of the postgenomic era on the description of new recombinantly expressed M. leprae-specific protein antigens, such as leprosy Infectious Disease Research Institute (IDRI) diagnostic (LID)-1 is summarized. Highly specific and sensitive molecular techniques to detect M. leprae DNA as the quantitative polymerase chain reaction (qPCR) and the loop-mediated isothermal amplification (LAMP) are briefly reviewed. Serology studies using phenolic glycolipid-I (PGL-I) semi-synthetic antigens, LID-1 fusion antigen, and the single fusion complex natural disaccharide-octyl (NDO)-LID show high sensitivity in multibacillary (MB) patients. However, serology is not applicable to paucibacillary patients, as they have weak humoral response and robust cell-mediated response, requiring tests for cellular biomarkers. Unlike ELISA-based tests, leprosy-specific POCT based on semi-synthetic PGL-I antigens and NDO-LID 1 antigen is easy to perform, cheaper, equipment-free, and can contribute to early diagnosis avoiding permanent incapacities and helping to interrupt M. leprae transmission. Besides its use to help diagnosis of household contacts or at-risk populations in endemic areas, potential applications of leprosy serology include monitoring MDT efficacy, identification of recent infection, especially in young children, as surrogate markers of disease progression to orient adult chemoprophylaxis and as a predictor of type 2 leprosy reactions. Advances in molecular biology techniques have reduced the complexity and execution time of qPCR confirming its utility to help diagnosis while leprosy-specific LAMP holds promise as an adjunct test to detect M. leprae DNA.

Evaluating active leprosy case identification methods in six districts of Nepal.

BACKGROUND: Nepal has achieved and sustained the elimination of leprosy as a public health problem since 2009, but 17 districts and 3 provinces with 41% (10,907,128) of Nepal's population have yet to eliminate the disease. Pediatric cases and grade-2 disabilities (G2D) indicate recent transmission and late diagnosis, respectively, which necessitate active and early case detection. This operational research was performed to identify approaches best suited for early case detection, determine community-based leprosy epidemiology, and identify hidden leprosy cases early and respond with prompt treatment. METHODS: Active case detection was undertaken in two Nepali provinces with the greatest burden of leprosy, Madhesh Province (40% national cases) and Lumbini Province (18%) and at-risk prison populations in Madhesh, Lumbini and Bagmati provinces. Case detection was performed by (1) house-to-house visits among vulnerable populations (n = 26,469); (2) contact examination and tracing (n = 7608); in Madhesh and Lumbini Provinces and, (3) screening prison populations (n = 4428) in Madhesh, Lumbini and Bagmati Provinces of Nepal. Per case direct medical and non-medical costs for each approach were calculated. RESULTS: New case detection rates were highest for contact tracing (250), followed by house-to-house visits (102) and prison screening (45) per 100,000 population screened. However, the cost per case identified was cheapest for house-to-house visits [Nepalese rupee (NPR) 76,500/case], followed by contact tracing (NPR 90,286/case) and prison screening (NPR 298,300/case). House-to-house and contact tracing case paucibacillary/multibacillary (PB:MB) ratios were 59:41 and 68:32; female/male ratios 63:37 and 57:43; pediatric cases 11% in both approaches; and grade-2 disabilities (G2D) 11% and 5%, respectively. Developing leprosy was not significantly different among household and neighbor contacts [odds ratios (OR) = 1.4, 95% confidence interval (CI): 0.24-5.85] and for contacts of MB versus PB cases (OR = 0.7, 95% CI 0.26-2.0). Attack rates were not significantly different among household contacts of MB cases (0.32%, 95% CI 0.07-0.94%) and PB cases (0.13%, 95% CI 0.03-0.73) (χ2 = 0.07, df = 1, P = 0.9) and neighbor contacts of MB cases (0.23%, 0.1-0.46) and PB cases (0.48%, 0.19-0.98) (χ2 = 0.8, df = 1, P = 0.7). BCG vaccination with scar presence had a significant protective effect against leprosy (OR = 0.42, 0.22-0.81). CONCLUSIONS: The most effective case identification approach here is contact tracing, followed by house-to-house visits in vulnerable populations and screening in prisons, although house-to-house visits are cheaper. The findings suggest that hidden cases, recent transmission, and late diagnosis in the community exist and highlight the importance of early case detection.

A qualitative study of groin hernia management in adolescents.

INTRODUCTION: Groin hernias in adolescents are rare and their management is associated with challenges for surgeons as some adolescents are fully grown, whereas others are not. Current groin hernia guidelines only differentiate between young children and adults; hence, no guidelines exist that may aid surgeons in handling adolescents. The aim of this study was to explore surgeons' considerations on the management of groin hernias in adolescents. METHODS: We conducted a qualitative study using pilot-tested individual semi-structured interviews. The participants were surgical specialists with experience in groin hernia repair in adolescents aged 10-17 years. Data were analysed using content analysis where essential quotes were extracted from transcripts and coded, categorised and interpreted into themes. RESULTS: Sixteen surgeons were included. Their considerations were reflected in four themes: 1) mesh-related concerns, 2) watchful waiting, 3) growth and 4) lack of evidence and guidelines. Surgeons performed sutured repairs on adolescents who are still growing due to concerns about mesh-related complications. A watchful waiting strategy was used by some to postpone surgery until adolescents were fully grown, thereby enabling mesh repair. Methods for evaluating growth varied and were not standardised. Finally, surgeons highlighted the need for evidence and guidelines to support their decision-making. CONCLUSIONS: This study found a lack of consensus and uniformity on the management of groin hernias in adolescents. Increased research efforts producing clinical guidelines are needed. FUNDING: This study was funded by the Michaelsen Foundation, the Aage and Johanne Louis-Hansens Foundation, Direktør Emil C. Hertz and Hustru Inger Hertz' Foundation, and the Torben and Alice Frimodts Foundation. The funders had no role in the design, conduct or reporting of the study. TRIAL REGISTRATION: not relevant.

Childhood borderline lepromatous leprosy: a case report.

BACKGROUND: Leprosy in children is a strong indicator of the recent failure of leprosy control and disease transmission programs. For twenty-two years, leprosy has been declared `eliminated as a public health hazard,` yet new cases continue to emerge in endemic areas. The new case detection rate among the child population was recorded at 4.4 per million children. Because of their underdeveloped or neonatal immunity and exposure to intrafamilial contacts, children tend to be the most vulnerable population. CASE: We present a case of the borderline lepromatous type of leprosy in a 9-year-old Indonesian male patient with the chief complaint of three stiff fingers on his left hand that began four years ago and hypopigmented patches on the back and buttocks that began five years ago. In this case, there was a history of leprosy in his mother`s sister, who had died. Leprosy in the patient was suspected of possibly being transmitted from his mother`s sister who had intense contact with the patient. The results of bacteriological examination with Ziehl- Neelsen staining of tissue scrapings found acid-fast bacilli. He was treated with a multibacillary multidrug regimen for 12 months. Periodical observations after the patient received the treatment revealed no new spots on the patient`s skin, some of the previous hypopigmented patches seemed to fade, especially those on the back. CONCLUSIONS: In the absence of an effective vaccine, early diagnosis and treatment are critical in preventing disability and deformity and reducing the physical, psychosocial, and economic burden of the disease.

Leprosy - neglected tropical disease in Pygmies inhabiting Central African Republic.

Leprosy is a neglected tropical disease that is still present worldwide despite efforts aimed at elimination of the disease. The BaAka Pygmy community inhabiting rural areas in the Central African Republic is one of the most leprosy-vulnerable populations. The aim of the study was to assess the prevalence of leprosy in the BaAka Pygmy population. People living in the Dzanga Sangha protected area were regularly visited by a mobile clinic in 2019/2020. The diagnosis was based on the clinical manifestation of the disease. Deformations of skin and extremities were assessed. In a 12-month period 26 cases of leprosy were diagnosed and 25 patients received treatment. 24 of those patients were BaAka Pygmies, 10 were women, 7 were children under 15 years old and 8 were diagnosed with grade 2 disability. Presented data shows that leprosy in Dzanga Sangha region is not well controlled due to the high transmission rate. Efforts to diagnose and report new leprosy cases should be intensified.

Efficiency and equity of bed utilization in China's health institutions: based on the rank-sum ratio method.

OBJECTIVE: The study aimed to analyze the efficiency and equity of bed utilization in Please check if the section headings are assigned to appropriate levels.China's healthcare institutions and to compare and analyze the overall health resource utilization efficiency in recent years and some specific utilization conditions in 2021, to provide empirical experience for the allocation of health care resources in epidemic China. METHODS: To compare and analyze the overall health resource utilization efficiency of the whole country with that of the East, middle, and West in 2021, and to analyze the bed utilization efficiency of different types of healthcare institutions in China and the bed utilization efficiency of various types of specialist hospitals in the country in 2021 by using the rank-sum ratio method. RESULTS: In 2021, the bed utilization rate of China's health institutions was 69.82%, and the number of bed turnover times was 27.65 times; the bed utilization rate of hospitals was 74.6%, and the number of bed turnover times was 26.08 times. The number of hospital bed turnovers was highest in the western region, lowest in the central region, and close to the national average in the eastern region. The average length of stay for discharged patients was the highest in the central region, the lowest in the eastern region, and the same as the national average in the western region. The analysis of rank-sum ratio method shows that among different types of health institutions' bed utilization efficiency (r = 0.935, P = 0.000), general hospitals and traditional Chinese medicine hospitals have the best bed utilization rate, and the bed utilization rate of community health service centers (stations) needs to be improved; while among various types of specialized hospitals' bed utilization efficiency (r = 0.959, P = 0.000), oncology hospitals, thoracic hospitals, and hematology hospitals, children's hospitals have high bed utilization efficiency; leprosy hospitals, cosmetic hospitals, and stomatology hospitals have low bed utilization efficiency. Health technicians per 1,000 population are highest in the western region, lowest in the central region, and lower in the eastern region than in the western region but slightly higher than the national average. The number of beds in health institutions per 1,000 population is the highest in the central region, the lowest in the eastern region, and slightly lower in the northwest than in the central region but higher than the national average. CONCLUSION: China's investment in health funding in the field of health care has been on the rise in recent years. However, there still exists the situation of uneven investment in health expenses and inconsistent medical efficiency among regions. And change such a status quo can be further improved in terms of government, capital, human resources, technology, information system, and so on.

Clinical-epidemiological characteristics and temporal trend of new cases of grade 2 disability leprosy in the state of Maranhão, Brazil, 2011- 2020.

MAIN RESULTS: Out of 2,147 grade 2 disability leprosy cases, the majority were male, of mixed race/skin color, multibacillary and borderline. The São Luís regional health unit showed a falling trend. IMPLICATIONS FOR SERVICES: The results can guide strategies for the leprosy control program in the state, aiming at new approaches towards early diagnosis, treatment and prevention of disabilities. PERSPECTIVES: Further studies are needed, such as spatial distribution of cases and detection rates of leprosy in children under 15 years of age, in order to gain a better understanding of the epidemiological profile of leprosy in Maranhão. OBJECTIVE: to describe the clinical and epidemiological characteristics of new cases of grade 2 disability leprosy and to analyze its trend in the state of Maranhão, from 2011 to 2020. METHODS: this was a descriptive cross-sectional and ecological time-series study, using data from the Notifiable Health Conditions Information System. A descriptive analysis of the event was carried out according to the sociodemographic and clinical-laboratory characteristics of the cases. The temporal trend of event incidence was analyzed using Prais-Winsten regression. RESULTS: of the 2,147 cases, 71.5% were male, 48.9% had up to 8 years of schooling, 66.5% were of mixed race/color, 95.5% had the multibacillary form, 58.8% were borderline, 32.3% had negative bacilloscopy at diagnosis. There was a stationary trend in the state and a falling trend in the São Luís Health Region (annual percentage change = -64.4%; 95% confidence interval: -73.7;-51.9). CONCLUSION: incidence trend was stable in the state of Maranhão and falling in São Luís.

The Voice of the Lost Toe: Pseudo-Ainhum Beyond Skin.

An 11-year-old boy presented with serial autoamputations of the right 4th and 5th toes during the past 6 years. This was associated with sensory loss on the right leg and development of constriction bands around the right 2nd and 3rd digits for the past 5 months. For a year, the patient had been treated with paucibacillary, multi-drug therapy (PB-MDT) with a presumptive diagnosis of leprosy. He was born from a nonconsanguinous marriage and the birth was uneventful. The developmental milestones were normal, and no family history of any congenital anomalies was reported.

A modelling analysis of a new multi-stage pathway for classifying achievement of public health milestones for leprosy.

Several countries have come close to eliminating leprosy, but leprosy cases continue to be detected at low levels. Due to the long, highly variable delay from infection to detection, the relationship between observed cases and transmission is uncertain. The World Health Organization's new technical guidance provides a path for countries to reach elimination. We use a simple probabilistic model to simulate the stochastic dynamics of detected cases as transmission declines, and evaluate progress through the new public health milestones. In simulations where transmission is halted, 5 years of zero incidence in autochthonous children, combined with 3 years of zero incidence in all ages is a flawed indicator that transmission has halted (54% correctly classified). A further 10 years of only occasional sporadic cases is associated with a high probability of having interrupted transmission (99%). If, however, transmission continues at extremely low levels, it is possible that cases could be misidentified as historic cases from the tail of the incubation period distribution, although misleadingly achieving all three milestones is unlikely (less than 1% probability across a 15-year period of ongoing low-level transmission). These results demonstrate the feasibility and challenges of a phased progression of milestones towards interruption of transmission, allowing assessment of programme status. This article is part of the theme issue 'Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.

Contact hypersensitivity to Indian standard patch test series correlates with disease severity among children with atopic dermatitis.

Background There is emerging evidence of a relationship between atopic dermatitis (AD) and allergic contact dermatitis (ACD), though the data available are scarce with conflicting viewpoints. We explored the occurrence of contact hypersensitivity among children with atopic dermatitis by patch testing them with the Indian standard series and tried to correlate the presence of contact hypersensitivity with the clinical severity of AD in these children. Methods In this single-centre, cross-sectional study, children between 6 months and 12 years diagnosed with atopic dermatitis were included and patch tested with the Indian standard series. Outcome parameters were the proportion of patients having positive patch-test reactions, the proportion of positive patch-test reactions for each allergen and factors associated with patch test positivity in atopic dermatitis. Results Of the 136 patients, 80 were boys. The mean age of the study population was 5.6 ± 3.2 years. Twenty-eight (20.6%) patients had patch test positivity at 96 h. Fragrance mix was the commonest allergen, followed by potassium dichromate, cobalt chloride hexahydrate and nickel. SCORing atopic dermatitis (SCORAD) was significantly higher in patients with positive patch tests as compared to patients with negative patch tests (P = 0.009). Conclusion Greater disease severity in atopic dermatitis was found to be associated with patch test positivity. Limitations Inability to establish relevance in about 50% of the patients was a limitation of our study. Follow-up data regarding the impact of allergen avoidance is not available.

[Analysis of national leprosy surveillance data in Mauritania from 2009 to 2019]. / Analyse des données nationales de surveillance de la lèpre en Mauritanie de 2009 à 2019.

Introduction: Leprosy is a chronic infectious disease that mainly affects the skin, mucous membranes and the peripheral nervous system. Its elimination as a public health problem seems to lead to its ignorance and therefore to a risk of late diagnosis. An analysis of leprosy surveillance data in Mauritania was conducted to determine epidemiological trends and clinical forms of reported cases. Material and method: The retrospective study was based on the epidemiological records of leprosy in Mauritania from 2009 to 2019. The diagnosis of leprosy was made on the basis of the diagnostic criteria of the World Health Organization (WHO). Data were analyzed using Epi Info version 7.2.5.0. The frequencies, proportions, and rates were calculated. Results: Over the past 11 years, 164 cases have been notified. Among the notified cases, 96/164 (58.5%) were males and 68/164 (41.5%) females, with a sex ratio of 1.4. The mean age (± standard deviation) was 44.0 ± 17.1 years [range, 9 - 86 years], and the median was 45 years [interquartile range, 32.5; 57.5]. Children under the age of 16 accounted for 9/164 (5.5%). The wilayas (i.e. "regions") of Nouakchott were the most endemic regions in the country. The multibacillary form (MB) represented 109/164 (66.5%) cases among the observed clinical forms. The average annual incidence was 0.3 case/100,000 population for MB and 0.1 case/100,000 for PB (paucibacillary). All reported cases were treated with multidrug therapy. Conclusion: The results of leprosy surveillance showed a persistence of this disease in Mauritania. It is necessary to relaunch leprosy services at all levels in order to continue to reduce the morbidity associated with this disease, and eventually eliminate it from the country.

Dermatology journals from India: A critical appraisal of the journal metrics.

Background Bibliometrics refer to documents and citation-based measures that measure different aspects of performance of a journal, including impact, output and prestige. Objective The aim of this study was to collect bibliometric data of various Indian dermatology journals as well as Indian journals from other disciplines, in order to compare relative performances. Methods Journal metrics pertaining to various Indian journals, both from dermatology [Indian Journal of Dermatology, Venereology and Leprology (IJDVL), Indian Journal of Dermatology (IJD), Indian Dermatology Online Journal, Indian Journal of Pediatric Dermatology and International Journal of Trichology] and other disciplines [Indian Journal of Medical Research (IJMR), Indian Journal of Pediatrics (IJP), Indian Journal of Ophthalmology and Indian Journal of Pharmacology] were sought. Data pertaining to the following 8 metrics during the year 2021 was collected: Journal Impact factor, SCImago Journal Rank, h5-index, Eigenfactor score and normalized Eigenfactor Score, Journal Citation Indicator, Scimago Journal and Country Rank H-index, CiteScore and Source Normalized Impact per Paper. Results Among Indian dermatology journals, for the year 2021, IJDVL had the highest impact factor (2.217) and h-index (48). IJD led in terms of prestige metrics such as SCImago Journal Rank (0.403), Eigenfactor score (0.00231) and Source Normalized Impact per Paper (1.132). IJDVL underperformed with respect to an average dermatology journal on all three prestige metrics. Among selected journals from other disciplines, two (IJMR and IJP) had impact factor exceeding five, despite lagging behind IJDVL two years ago. Most had normalized scores exceeding 1, indicating better performance than an average journal from their respective fields. Limitations Non-inclusion of altmetrics related data Conclusion IJDVL is one of the leading Indian journals in the field of dermatology, followed closely by IJD. A rise in IJDVL influence is evident over the past decade, as evident by various metrics. However, the progress still trails behind the average of global dermatology journals as evident by the field-normalized journal metrics, indicating potential for further growth of journal influence.

Effectiveness of population-wide screening and mass drug administration for leprosy control in Kiribati: the COMBINE protocol.

INTRODUCTION: Progress towards leprosy elimination is threatened by increasing incidence in 'hot-spot' areas where more effective control strategies are urgently required. In these areas, active case finding and leprosy prevention limited to known contacts is insufficient for control. Population-wide active case-finding together with universal prevention through mass drug administration (MDA) has been shown to be effective in 'hot-spot' areas, but is logistically challenging and expensive. Combining leprosy screening and MDA with other population-wide screening activities such as for tuberculosis may increase programme efficiency. There has been limited evaluation of the feasibility and effectiveness of combined screening and MDA interventions. The COMBINE study aims to bridge this knowledge gap. METHODS AND ANALYSIS: This implementation study will assess the feasibility and effectiveness of active leprosy case-finding and treatment, combined with MDA using either single-dose rifampicin or rifamycin-containing tuberculosis preventive or curative treatment, for reducing leprosy incidence in Kiribati. The leprosy programme will run over 2022-2025 in concert with population-wide tuberculosis screening-and-treatment in South Tarawa. The primary research question is to what extent the intervention reduces the annual leprosy new case detection rate (NCDR) in adults and children compared with routine screening and postexposure prophylaxis (PEP) among close contacts (baseline leprosy control activities). Comparisons will be made with (1) the preintervention NCDR separably among adults and children in South Tarawa (before-after study) and (2) the corresponding NCDRs in the rest of the country. Additionally, the postintervention prevalence of leprosy obtained from a survey of a 'hot-spot' sub-population will be compared with prevalence documented during the intervention. The intervention will be implemented in collaboration with the Kiribati National Leprosy Programme. ETHICS AND DISSEMINATION: Approval has been obtained from the Kiribati Ministry of Health and Medical Services (MHMS), the University of Otago (H22/111) and the University of Sydney (2021/127) Human Research Ethics Committees. Findings will be shared with the MHMS, local communities and internationally through publication.

Changes in the gut mycobiome in pediatric patients in relation to the clinical activity of Crohn's disease.

BACKGROUND: Numerous studies have shown that in Crohn's disease (CD), the gut microbiota is of great importance in the induction and maintenance of inflammation in the gastrointestinal tract. Until recently, studies have focused almost exclusively on bacteria in the gut. Lately, more attention has been paid to the role of intestinal fungi. AIM: To study the gut mycobiome analysis of pediatric patients with CD (in different stages of disease activity) compared to healthy children. METHODS: Fecal samples were collected from patients: With active, newly diagnosed CD (n = 50); active but previously diagnosed and treated CD (n = 16); non-active CD and who were in clinical remission (n = 39) and from healthy volunteers (n = 40). Fungal DNA was isolated from the samples. Next, next generation sequencing (MiSeq, Illumina) was performed. The composition of mycobiota was correlated with clinical and blood parameters. RESULTS: Candida spp. were overrepresented in CD patients, while in the control group, the most abundant genus was Saccharomyces. In CD patients, the percentage of Malassezia was almost twice that of the control (P < 0.05). In active CD patients, we documented a higher abundance of Debaryomyces hansenii (D. hansenii) compared to the non-active CD and control (P < 0.05) groups. Moreover, statistically significant changes in the abundance of Mycosphaerella, Rhodotorula, and Microidium were observed. The analyses at the species level and linear discriminant analysis showed that in each group it was possible to distinguish a specific species characteristic of a given patient population. Moreover, we have documented statistically significant correlations between: D. hansenii and patient age (negative); C. zeylanoides and patient age (positive); C. dubliniensis and calprotectin (positive); C. sake and calprotectin (positive); and C. tropicalis and pediatric CD activity index (PCDAI) (positive). CONCLUSION: Mycobiome changes in CD patients, and the positive correlation of some species with calprotectin or PCDAI, give strong evidence that fungi may be of key importance in the development of CD.