Spatial-temporal trends in leprosy burden and its associations with socioeconomic and physical geographic factors: results from the Global Burden of Disease Study 2019.

OBJECTIVES: The purpose of our study was to assess the multiscalar changes in leprosy burden and its associated risk factors over the last three decades. STUDY DESIGN: We conducted an in-depth examination of leprosy's spatial-temporal trends at multiple geographical scale (global, regional, and national), utilizing information from Global Burden of Disease, Injuries, and Risk Factors Study (GBD 2019). METHODS: Incidence and the estimated annual percentage change (EAPC) in age-standardized incidence rate (ASIR) of leprosy were determined, with countries categorized based on leprosy incidence changes. We examined socioeconomic and physical geography influences on leprosy incidence via Spearman correlation analysis, using ternary phase diagrams to reveal the synergetic effects on leprosy occurrence. RESULTS: Globally, incident cases of leprosy decreased by 27.86% from 1990 to 2019, with a reduction in ASIR (EAPC = -2.53), yet trends were not homogeneous across regions. ASIR and EAPC correlated positively with sociodemographic index (SDI), and an ASIR growth appeared in high SDI region (EAPC = 3.07). Leprosy burden was chiefly distributed in Tropical Latin America, Oceania, Central Sub-Saharan Africa, and South Asia. Negative correlations were detected between the incidence of leprosy and factors of SDI, GDP per capita, urban population to total population, and precipitation, whereas the number of refugee population, temperature, and elevation showed opposite positive results. CONCLUSIONS: Despite a global decline in leprosy over the past three decades, the disparities of disease occurrence at regional and national scales still persisted. Socioeconomic and physical geographic factors posed an obvious influence on the transmission risk of leprosy. The persistence and regional fluctuations of leprosy incidence necessitate the ongoing dynamic and multilayered control strategies worldwide in combating this ancient disease.

Temporary Cast Application in Dislocated Ankle Fractures Leads to High Rates of Secondary Loss of Reduction: Does the Lauge-Hansen Injury Type Matter?

BACKGROUND: For the temporary treatment of ankle fracture dislocations (AFDs), previous studies indicate higher rates of secondary loss of reduction (LOR) with splint immobilization, prompting consideration for expanding indications for external fixation (ExFix). However, these studies did not investigate the influence of fracture morphology to further improve patient selection. The aim of this study was to investigate the influence of Lauge-Hansen injury type on the LOR rate in bimalleolar or trimalleolar AFDs for temporary cast vs ExFix immobilization. METHODS: In this retrospective cohort study, patients with isolated AFD cases treated at our institution from 2011 to 2020 were reviewed. Inclusion criteria required radiographs depicting initial dislocation and appropriate reduction after Cast or ExFix immobilization. Exclusion criteria encompassed concomitant injuries, open fractures, conservative management as well as surgery performed within 48 hours or at a different facility. Patients were grouped by temporary treatment (Cast or ExFix). The primary endpoint was LOR prior to definitive surgery across various Lauge-Hansen types. RESULTS: The LOR rate was significantly higher in the cast group (40/152, 26.3%) compared to the ExFix group (5/191, 2.6%; P < .0001). In the cast group, LOR was associated with an increase in time to definitive surgery by a mean of 3 days (P < .002). During cast treatment, LOR was significantly more likely for pronation abduction (P = .001) and supination external rotation injuries (P < .0001), whereas no significant differences were observed for pronation external rotation (P = .006), supination adduction (P > .99), and fractures not classifiable (P > .99). CONCLUSION: In cases of AFDs resulting from supination external rotation or pronation abduction trauma according to the Lauge-Hansen classification, especially in the setting of an additional posterior malleolar fracture, primary application of external fixation should be considered to reduce the risk for secondary loss of reduction. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Microbiological, physicochemical and sensory changes throughout ripening of an experimental soft smear-ripened cheese in relation to salt concentrations.

To evaluate the sodium chloride content effect on microbiological, biochemical, physicochemical and sensorial characteristics, Munster cheeses were prepared from pasteurized milk seeded with 3 yeasts (Kluyveromyces marxianus, Debaryomyces hansenii, Geotrichum candidum) and 5 ripening bacteria (Arthrobacter arilaitensis, Brevibacterium aurantiacum, Corynebacterium casei, Hafnia alvei, and Staphylococcus equorum). Experiments were performed under 1.0%, 1.7% and 2.4% NaCl levels in cheese in triplicate. Ripening (d2 - d27) was carried under 12°C and 96% RH. These kinetics were both reproducible and repeatable at 99% confidence level. For each microbial, biochemical and physicochemical parameter, 2 kinetic descriptors (maximal or minimal rate and its occurrence time) were defined. On d2 the physicochemical variables (water activity, dry matter, water content) were strongly dependent on the salting level. From d2 to d27 K. lactis was insensitive to salt while D. hansenii was stimulated. G. candidum growth appeared very sensitive to salt in cheese: at 1.0% NaCl G. candidum exhibited overgrowth, negatively impacting rind appearance, underrind consistency and thickness and off-flavor flaws. Salt concentration of 2.4% induced death of G. candidum. Four bacteria (A. arilaitensis, B. aurantiacum, C. casei, and H. alvei) were moderately sensitive to salt while S. equorum was insensitive to it. Salt level in cheese had a significant effect on carbon substrate consumption rates. Lactate consumption rate in 1.0% salted cheeses was approximately twice higher than under 2.4% NaCl. Data analysis of microorganism, biochemical, and physicochemical kinetics and sensory analysis showed that the best salt level in Munster-type cheeses to achieve an optimum balance between cheese characteristics, sensory qualities and marketability was 1.7% NaCl.

Raw, Unadulterated African Honey for Ulcer Healing in Leprosy: Protocol for the Honey Experiment on Leprosy Ulcer (HELP) Randomized Controlled Trial.

Background: Leprosy leads to nerve damage and slow-healing ulcers, which are treatable with routine therapy. There has been a recent resurgence of interest in the use of honey for the treatment of different kinds of wounds. Objective: The aim of this study, Honey Experiment on Leprosy Ulcer (HELP), is to evaluate the healing properties of raw, unadulterated African honey in comparison with normal saline dressing for the treatment leprosy ulcers. Methods: This is a multicenter, comparative, prospective, single-blinded, parallel-group, and 1:1 individually randomized controlled trial to be conducted at The Leprosy Referral Hospital, Chanchaga in Minna, Niger State, North Central Nigeria, and St. Benedict Tuberculosis and Leprosy Rehabilitation Hospital in Ogoja, Cross River State, South-South Nigeria. Raw, unadulterated honey will be used in the ulcer dressing of eligible, consenting participants in the intervention group, whereas those in the control group will be treated by dressing with normal saline. The main outcomes will be the proportion of complete healing and the rate of healing up to 84 days after randomization. Follow-up will be conducted 6 months after randomization. We aim to enroll 90-130 participants into the study. Blinded observers will examine photographs of ulcers to determine the outcomes. Results: The recruitment of trial participants began on March 14, 2022, and has been continuing for approximately 24 months. Conclusions: Our study will provide an unbiased estimate of the effect of honey on the healing of neuropathic ulcers.

Competition for Nitrogen Resources: An Explanation of the Effects of a Bioprotective Strain Metschnikowia pulcherrima on the Growth of Hanseniaspora Genus in Oenology.

As a biological alternative to the antimicrobial action of SO2, bioprotection has been proposed to winemakers as a means to limit or prevent grape musts microbial alteration. Competition for nitrogenous nutrients and for oxygen are often cited as potential explanations for the effectiveness of bioprotection. This study analyses the effect of a bioprotective M. pulcherrima strain on the growth of one H. valbyensis strain and one H. uvarum strain. Bioprotection efficiency was observed only against H. valbyensis inoculated at the two lowest concentrations. These results indicate a potential species-dependent efficiency of the bioprotective strain and a strong impact of the initial ratio between bioprotective and apiculate yeasts. The analysis of the consumption of nitrogen compounds revealed that leucine, isoleucine, lysine and tryptophan were consumed preferentially by all three strains. The weaker assimilation percentages of these amino acids observed in H. valbyensis at 24 h growth suggest competition with M. pulcherrima that could negatively affects the growth of the apiculate yeast in co-cultures. The slowest rate of O2 consumption of H. valbyensis strain, in comparison with M. pulcherrima, was probably not involved in the bioprotective effect. Non-targeted metabolomic analyses of M. pulcherrima and H. valbyensis co-culture indicate that the interaction between both strains particularly impact lysin and tryptophan metabolisms.

Leprosy in Colombia: A look from life experience.

Leprosy continues to be stigmatized, causing harm to fundamental rights, pain and hopelessness in those who have suffered from it and their families. From its relationship with public and mental health, effective strategies must be implemented to reduce stigma and unlearn myths and wrong perceptions, support families, and improve quality of life through early care and detection. This article shows that those affected by leprosy are capable, functional people with much to contribute to society anywhere in the world.

An evaluation of mental health integration in the neglected tropical diseases program in Zamfara, North-west Nigeria.

BACKGROUND: Mental health and neglected tropical diseases (NTDs) are critical in healthcare systems, especially in low- and middle-income countries. Several policies are planned or designed by health stakeholders to address the mental health needs of people affected by NTDs. Still, the impact of such policies seems to be of no consequence. METHODS: The GAD-7 and PHQ-9 tools were used to determine the rate of depression and anxiety, respectively, among people affected by skin NTDs (leprosy and lymphatic filariasis [LF]) in Zamfara State, North-west Nigeria. The study also evaluated the barriers to the uptake of mental health services for people affected by skin NTDs in the state. We assessed 48 people affected by NTDs (leprosy, 32; lymphatic filariasis, 16) along with a corresponding 48 people who served as controls in the study. Qualitative interviews were carried out with the participants to elicit the barriers to mental health services for people affected by NTDs. Additionally, 48 selected healthcare workers from the state were assessed for their skills and capacity to offer mental health services. RESULTS: We found anxiety disorder present in 100% of the people living with LF and in 62% of the people living with leprosy. Depression was also found in 56% and 75% of the people living with leprosy and LF, respectively. An assessment of the barriers to the uptake of mental health services reveals that most people with NTDs are constrained by a lack of money to visit hospitals, the fear of stigmatisation and discrimination and long distances to health centres. Regarding the healthcare workers, the skills and capacity to offer mental health services were very low. CONCLUSIONS: We conclude that for mental health services to be integrated into the community health system for people with NTDs, there should be a concerted effort by all stakeholders and the intervention should be context specific instead of generalised. CONTEXTE: La santé mentale et les maladies tropicales négligées (MTN) sont des problématiques centrales dans la santé, en particulier dans les pays à revenu faible ou intermédiaire. Plusieurs politiques sont conçues par les acteurs de la santé publique pour répondre aux besoins de soins en santé mentale pour les personnes touchées par les MTN. Pourtant, le bilan reste mitigé quant à l'efficacité de ces soins. MÉTHODES: Les outils GAD-7 et PHQ-9 ont été utilisés pour déterminer le taux de dépression et d'anxiété chez les personnes atteintes de MTN cutanées (lèpre et filariose lymphatique) dans l'État de Zamfara, au nord-ouest du Nigeria. L'étude a également évalué les obstacles à l'utilisation des services de santé mentale pour les personnes atteintes de MTN cutanées dans l'État. Nous avons évalué 48 personnes atteintes de MTN (lèpre : 32, filariose lymphatique : 16) ainsi que 48 personnes correspondantes qui ont servi de témoins dans l'étude. Des entretiens qualitatifs ont été menés avec les participants afin d'identifier les obstacles aux services de santé mentale pour les personnes atteintes de MTN. En outre, 48 professionnels de la santé sélectionnés dans l'État ont été évalués pour déterminer leurs compétences et leur capacité à offrir des services de santé mentale. RÉSULTATS: Nous avons trouvé des troubles anxieux chez 100% des personnes atteintes de filariose lymphatique et chez 62% des personnes atteintes de lèpre. La dépression touche 56% et 75% des personnes vivant avec la lèpre et la filariose lymphatique respectivement. Une évaluation des obstacles à l'utilisation des services de santé mentale révèle que la plupart des personnes atteintes de MTN sont limitées par le manque d'argent pour se rendre à l'hôpital, la peur de la stigmatisation et de la discrimination, et les longues distances à parcourir pour se rendre dans les centres de santé. Les compétences et les capacités des professionnels de la santé à offrir des services de santé mentale sont très faibles. CONCLUSION: L'efficacité d'un protocole de soins pour les patients atteints de MTN (traitant la pathologie physique et d'éventuelles pathologies psychiatriques associées) nécessite une intégration des services de santé mentale dans le système de santé communautaire. ANTECEDENTES: La salud mental y las enfermedades tropicales desatendidas (ETDs), son fundamentales en los sistemas sanitarios, especialmente en los países de renta baja y media. Las partes interesadas en la sanidad planean o diseñan varias políticas para abordar las necesidades de salud mental de las personas afectadas por ETDs. Sin embargo, el impacto de dichas políticas parece ser nulo. MÉTODOS: Se utilizaron las herramientas GAD-7 y PHQ-9 para determinar la tasa de depresión y ansiedad, respectivamente, entre las personas afectadas por ETDs cutáneas (lepra y filariasis linfática) en el Estado de Zamfara, al noroeste de Nigeria. El estudio también evaluó las barreras para la aceptación de los servicios de salud mental por parte de las personas afectadas por ETDs cutáneas en el Estado. Se evaluó a 48 personas afectadas por ETDs (lepra: 32; filariasis linfática: 16) y a otras 48 que sirvieron de control en el estudio. Se llevaron a cabo entrevistas cualitativas con los participantes para determinar las barreras a los servicios de salud mental para las personas afectadas por ETDs. Además, se evaluaron las habilidades y la capacidad para ofrecer servicios de salud mental de 48 profesionales sanitarios del Estado. RESULTADOS: Encontramos trastorno de ansiedad presente en el 100% de las personas que vivían con filariasis linfática y en el 62% de las personas que vivían con lepra. También se encontró depresión en el 56% y el 75% de las personas que vivían con lepra y filariasis linfática respectivamente. Una evaluación de los obstáculos para la utilización de los servicios de salud mental revela que la mayoría de las personas con ETDs se ven limitadas por la falta de dinero para acudir a los hospitales, el miedo a la estigmatización, la discriminación y las largas distancias hasta los centros sanitarios. Por parte del personal sanitario, los conocimientos y la capacidad para ofrecer servicios de salud mental eran muy escasos. CONCLUSIONES: Para que los servicios de salud mental para personas con ETD se integren en el sistema sanitario comunitario, debe haber una concertación entre todas las partes interesadas y la intervención debe ser específica para cada contexto en lugar de generalizada.

Training and Active Case Detection to Prevent Leprosy: Effect on Knowledge, Attitude and Skills of Health Workers on Early Diagnosis of Leprosy in a Leprosy Hotspot District in Ethiopia.

BACKGROUND: Despite all of the efforts, leprosy continues to affect hundreds of thousands of people every year, including children, showing the ongoing transmission of the disease within the population. The transmission of leprosy can be interrupted through an integrated approach that includes active case-finding, contact tracing and capacity building of health workers. METHODS: A cross-sectional study design was used to assess the knowledge, attitudes and skills of health workers in the screening and diagnosis of leprosy. One hundred and eighty-one and eighty-eight health care workers participated in the pre-and post-assessment surveys, respectively. Data were collected through interviews and an observational checklist. Frequency tables and graphs were used to describe the study variables, and statistical significance between pre- and post-assessment surveys was declared at p-value < 0.5. RESULT: The percentages of healthcare workers with good knowledge, positive attitudes and skills were 61.2%, 55.6% and 51.7% in the pre-assessment survey and 77.3%, 56.3% and 75.0%, respectively, in the post-assessment survey. There was a significant improvement in the knowledge and skill scores of participants in the post-assessment survey (p < 0.01). During the campaign, 3780 index contacts were screened; 570 (15.1%) were diagnosed with skin diseases, and 17 new leprosy cases were diagnosed (case detection rate of 45 per 10,000 contacts). CONCLUSION: Training improved the knowledge and skills of healthcare workers, and a large number of skin diseases were detected through mass screening and active case findings. Providing training for frontline healthcare workers contributed to the detection of more cases and facilitated early detection of leprosy cases.

Single-Dose Rifampicin Leprosy Chemoprophylaxis for Household Contacts in Kiribati: An Audit of a Combined Retrospective and Prospective Approach.

Kiribati is a Pacific Island nation with a widely dispersed population and one of the highest rates of leprosy worldwide. Single-dose rifampicin post-exposure prophylaxis (SDR-PEP) of leprosy contacts has reduced new case detection rates in controlled trials. In 2018, an SDR-PEP programme was introduced in Kiribati that included screening and chemoprophylaxis of household contacts of leprosy cases retrospectively (2010-2017) and prospectively (2018-2022). We conducted a retrospective audit to determine the comprehensiveness, timeliness and feasibility of the SDR-PEP programme. Overall, 13,641 household contacts were identified (9791 in the retrospective and 3850 in the prospective cohort). In the retrospective cohort, 1044 (11%) contacts were absent, 403 (4%) were ineligible for SDR, and 42 new cases were detected (0.4%) Overall, SDR coverage was 84.7%. In the prospective cohort, 164 (4%) contacts were absent, 251 (7%) were ineligible for SDR, and 23 new cases were diagnosed (0.6%). Overall, SDR coverage was 88.1%. Across both cohorts, there were 23 SDR refusals. The median time to SDR administration was 220 days (IQR 162-468) and 120 days (IQR 36-283) for the retrospective and prospective cohorts, respectively. SDR was readily accepted in both cohorts. The new case detection rate (0.5%) is consistent with that in other studies. Overall SDR coverage in both the retrospective and prospective phases met programmatic expectations.

Percent predicted peak oxygen uptake is superior to weight-indexed peak oxygen uptake in risk stratification before lung cancer lobectomy.

OBJECTIVE: To improve preoperative risk stratification in lung cancer lobectomy by identifying and comparing optimal thresholds for peak oxygen uptake (VO2peak) presented as weight-indexed and percent of predicted values, respectively. METHODS: This was a longitudinal cohort study including national registry data on patients scheduled for cancer lobectomy that used available data from preoperative cardiopulmonary exercise testing. The measured VO2peak was indexed by body mass (mL/kg/min) and also compared with 2 established reference equations (Wasserman-Hansen and Study of Health in Pomerania, respectively). By receiver operating characteristic analysis, a lower 90% specificity and an upper 90% sensitivity threshold were determined for each measure, in relation to the outcome of any major complication or death. For each measure and based on these thresholds, patients were categorized as low risk, intermediate risk, or high risk. The frequency of complications was compared between groups using χ2. RESULTS: The frequency of complications differed significantly between the proposed low-, intermediate-, and high-risk groups when using % predicted Study of Health in Pomerania (5%, 21%, 35%, P = .007) or % predicted Wasserman-Hansen (5%, 25%, 35%, P = .002) but not when using the weight-indexed VO2peak groups (7%, 23%, 15%, P = .08). Nonsignificant differences were found using the threshold <15 mL/kg/min (P = .34). CONCLUSIONS: This study showed that weight-indexed VO2peak was of less use as a marker of risk at the lower range of exercise capacity, whereas % predicted VO2peak was associated with a continuously increasing risk of major complications, also at the lower end of exercise capacity. As identifying subjects at high risk of complications is important, % predicted VO2peak is therefore preferable.

A morphological review of medial malleolar fractures - A large single centre series.

BACKGROUND: Many approaches to management of medial malleolar fractures are described in the literature however, their morphology is under investigated. The aim of this study was to analyse the morphology of medial malleolar fractures to identify any association with medial malleolar fracture non-union or malunion. METHODS: Patients who had undergone surgical fixation of their MMF were identified from 2012 to 2022, using electronic patient records. Retrospective analysis of their preoperative, intraoperative, and postoperative radiographs was performed to determine their morphology and prevalence of non-union and malunion. Lauge-Hansen classification was used to characterise ankle fracture morphology and Herscovici classification to characterise MMF morphology. RESULTS: A total of 650 patients were identified across a 10-year period which could be included in the study. The overall non-union rate for our cohort was 18.77% (122/650). The overall malunion rate was 6.92% (45/650). Herscovici type A fractures were significantly more frequently mal-reduced at time of surgery as compared to other fracture types (p = .003). Medial wall blowout combined with Hercovici type B fractures showed a significant increase in malunion rate. There is a higher rate of bone union in patients who had been anatomically reduced. CONCLUSION: The morphology of medial malleolar fractures does have an impact of the radiological outcome following surgical management. Medial wall blowout fractures were most prevalent in adduction-type injuries; however, it should not be ruled out in rotational injuries with medial wall blowouts combined with and Herscovici type B fractures showing a significant increase in malunions. Herscovici type A fractures had significantly higher malreductions. LEVEL OF EVIDENCE: Level 3 - Retrospective Cohort Study.

Epidemiological, clinical, and geographical characterization of Leprosy in the County of Santarém-Pará: Insights for effective control and targeted intervention.

Leprosy is an infectious disease characterized by slow and chronic evolution, caused by Mycobacterium leprae and or Mycobacterium lepromatosis, an intracellular alcohol-acid-resistant (BAAR) bacillus. The objective of this study was to provide an epidemiological, clinical, and geographic characterization of leprosy in the city of Santarém-Pará during the period 2011-2020. A cross-sectional, descriptive, and quantitative approach was used, employing maps and tables to illustrate clinical and epidemiological variables, including: sex, age, race, area of residence, operational classification, clinical form, number of skin lesions, number of affected nerves, and health units. During the analyzed period, 581 cases of leprosy were diagnosed, resulting in the following cumulative incidence rates: male (60%); age over 15 years (94%); urban area (73%); multibacillary (74%); borderline form (46%); skin lesions greater than 5 (34%); and no nerves affected (68%). In the urban perimeter, a higher cumulative incidence of cases was observed in the central area with 133 cases. However, the health unit reporting the largest number of cases belonged to the southern area, specifically the Basic Health Unit of Nova República, with 48 cases. This study highlights the need to characterize the nuances of leprosy and its variability within the urban environment, according to different areas. Further research is essential to inform the implementation of public policies aimed at addressing the population with the highest vulnerability index, thereby reducing leprosy rates in Santarém.

Molecular epidemiological characteristics of Mycobacterium leprae in highly endemic areas of China during the COVID-19 epidemic.

Objectives: The present study analyzed the impact of the COVID-19 pandemic on the prevalence and incidence of new leprosy cases, as well as the diversity, distribution, and temporal transmission of Mycobacterium leprae strains at the county level in leprae-endemic provinces in Southwest China. Methods: A total of 219 new leprosy cases during two periods, 2018-2019 and 2020-2021, were compared. We genetically characterized 83 clinical isolates of M. leprae in Guizhou using variable number tandem repeats (VNTRs) and single nucleotide polymorphisms (SNPs). The obtained genetic profiles and cluster consequences of M. leprae were compared between the two periods. Results: There was an 18.97% decrease in the number of counties and districts reporting cases. Considering the initial months (January-March) of virus emergence, the number of new cases in 2021 increased by 167% compared to 2020. The number of patients with a delay of >12 months before COVID-19 (63.56%) was significantly higher than that during COVID-19 (48.51%). Eighty-one clinical isolates (97.60%) were positive for all 17 VNTR types, whereas two (2.40%) clinical isolates were positive for 16 VNTR types. The (GTA)9, (TA)18, (TTC)21 and (TA)10 loci showed higher polymorphism than the other loci. The VNTR profile of these clinical isolates generated five clusters, among which the counties where the patients were located were adjacent or relatively close to each other. SNP typing revealed that all clinical isolates possessed the single SNP3K. Conclusion: COVID-19 may have a negative/imbalanced impact on the prevention and control measures of leprosy, which could be a considerable fact for official health departments. Isolates formed clusters among counties in Guizhou, indicating that the transmission chain remained during the epidemic and was less influenced by COVID-19 preventative policies.

The PEP++ study protocol: a cluster-randomised controlled trial on the effectiveness of an enhanced regimen of post-exposure prophylaxis for close contacts of persons affected by leprosy to prevent disease transmission.

BACKGROUND: Leprosy is an infectious disease with a slow decline in global annual caseload in the past two decades. Active case finding and post-exposure prophylaxis (PEP) with a single dose of rifampicin (SDR) are recommended by the World Health Organization as measures for leprosy elimination. However, more potent PEP regimens are needed to increase the effect in groups highest at risk (i.e., household members and blood relatives, especially of multibacillary patients). The PEP++ trial will assess the effectiveness of an enhanced preventive regimen against leprosy in high-endemic districts in India, Brazil, Bangladesh, and Nepal compared with SDR-PEP. METHODS: The PEP++ study is a cluster-randomised controlled trial in selected districts of India, Brazil, Bangladesh, and Nepal. Sub-districts will be allocated randomly to the intervention and control arms. Leprosy patients detected from 2015 - 22 living in the districts will be approached to list their close contacts for enrolment in the study. All consenting participants will be screened for signs and symptoms of leprosy and tuberculosis (TB). In the intervention arm, eligible contacts receive the enhanced PEP++ regimen with three doses of rifampicin (150 - 600 mg) and clarithromycin (150 - 500 mg) administered at four-weekly intervals, whereas those in the control arm receive SDR-PEP. Follow-up screening for leprosy will be done for each individual two years after the final dose is administered. Cox' proportion hazards analysis and Poisson regression will be used to compare the incidence rate ratios between the intervention and control areas as the primary study outcome. DISCUSSION: Past studies have shown that the level of SDR-PEP effectiveness is not uniform across contexts or in relation to leprosy patients. To address this, a number of recent trials are seeking to strengthen PEP regimens either through the use of new medications or by increasing the dosage of the existing ones. However, few studies focus on the impact of multiple doses of chemoprophylaxis using a combination of antibiotics. The PEP++ trial will investigate effectiveness of both an enhanced regimen and use geospatial analysis for PEP administration in the study communities. TRIAL REGISTRATION: NL7022 on the Dutch Trial Register on April 12, 2018. Protocol version 9.0 updated on 18 August 2022 https://www.onderzoekmetmensen.nl/en/trial/23060.

Performance Evaluation of No-Code Artificial Intelligence Models for the Detection of Acid-Fast Bacilli: A Comparative Analysis of Three Models.

Background Acid-fast bacilli Mycobacterium tuberculosis and Mycobacterium leprae are the causative organisms behind two major diseases of developing nations, tuberculosis and leprosy, respectively. To efficiently tackle these diseases in developing nations, drugs must be augmented with improved detection modalities. This necessitates the development of enhanced tools that can aid the current detection modalities being used in high-incidence areas. A no-code artificial intelligence model based on image classification is one such tool that can be used in the identification of acid-fast bacilli. This study utilizes three such no-code artificial intelligence models that originate from three different platforms but share identical training, testing, and subsequent evaluation. Thereafter, the study is directed at comparing the three models created and identifying the one that can function as a promising support system for the detection of acid-fast bacilli. Methods To begin with, a total of 1000 images per class, i.e., positive and negative for each disease, were captured from the diagnosed slides of tuberculosis and leprosy, taken from the Department of Pathology. Subsequently, these slides were reviewed again by a pathologist to demarcate them as positive or negative for acid-fast bacilli. Once the required number of images was captured, 600 images of each class were selected as the training set, 300 images as the testing set, and the remaining 100 images as the evaluation set. Data augmentation was then performed using techniques such as rotating, mirroring, cropping, and position shifting. These designated data sets were then used to train the image classification software available on the following three platforms: Lobe (Microsoft Corporation, Redmond, Washington, United States), Create ML (Apple Inc., Cupertino, California, United States), Python-based open-source software (PerceptiLabs, Stockholm, Sweden). The final evaluation was based on different parameters such as sensitivity, specificity, ease of use, learning curve, technological resources required, and feasibility of implementation. All parameters put together served the purpose of comparison to identify the most promising model. Results Out of the three models tested, the one built using Lobe is the most promising in terms of the evaluation parameters considered. For tuberculosis, the sensitivity and specificity values obtained were 96% each, while for leprosy, they were 100% and 96%, respectively. Also, the model built using Lobe had a near-negligible learning curve, in addition to being the most cost-effective and feasible model to implement. Furthermore, it had a unique real-time training feature, which constantly improved the model throughout the testing period, till the final sensitivity and specificity values were achieved. Conclusions In clinical situations where a high number of cases are encountered each day, a no-code artificial intelligence model built using Lobe would get exposed to a huge database, getting trained in real time. Subsequently, such a model would reach considerable levels of sensitivity and specificity and in turn, act as a promising support system for the detection of acid-fast bacilli.

Spatiotemporal pattern of leprosy in southwest China from 2010 to 2020: an ecological study.

BACKGROUND: Despite many efforts to control leprosy worldwide, it is still a significant public health problem in low- and middle-income regions. It has been endemic in China for thousands of years, and southwest China has the highest leprosy burden in the country. METHODS: This observational study was conducted with all newly detected leprosy cases in southwest China from 2010 to 2020. Data were extracted from the Leprosy Management Information System (LEPMIS) database in China. The Joinpoint model was used to determine the time trends in the study area. Spatial autocorrelation statistics was performed to understand spatial distribution of leprosy cases. Spatial scan statistics was applied to identify significant clusters with high rate. RESULTS: A total of 4801 newly detected leprosy cases were reported in southwest China over 11 years. The temporal trends declined stably. The new case detection rate (NCDR) dropped from 4.38/1,000,000 population in 2010 to 1.25/1,000,000 population in 2020, with an average decrease of 12.24% (95% CI: -14.0 to - 10.5; P < 0.001). Results of global spatial autocorrelation showed that leprosy cases presented clustering distribution in the study area. Most likely clusters were identified during the study period and were frequently located at Yunnan or the border areas between Yunnan and Guizhou Provinces. Secondary clusters were always located in the western counties, the border areas between Yunnan and Sichuan Provinces. CONCLUSIONS: Geographic regions characterized by clusters with high rates were considered as leprosy high-risk areas. The findings of this study could be used to design leprosy control measures and provide indications to strengthen the surveillance of high-risk areas. These areas should be prioritized in the allocation of resources.

TB-free Ebeye: Results from integrated TB and noncommunicable disease case finding in Ebeye, Marshall Islands.

Background: Tuberculosis (TB) incidence rates in the Republic of the Marshall Islands are among the highest in the world, 480/100,000 in 2017. In response, the Health Ministry completed islandwide screening in Ebeye Island in 2017. Methods: Participants were interviewed to obtain TB history, exposures, and symptoms. TB assessment included chest radiography with sputum collection for GeneXpert® MTB-RIF if indicated. TB diagnosis was made by consensus of visiting TB experts. Participants were also screened for Hansen's disease (HD) and diabetes mellitus (DM). For persons aged ≥21 years, blood pressure, cholesterol, and blood glucose were assessed. Results: A total of 5,166 persons (90.0 % of target population) completed screening leading to the identification of 39 new cases of TB (755/100,000) and 14 persons with HD (270/100,000). DM was detected in 1,096 persons (27 %), including in 351 persons not previously diagnosed. The rate of hypertension was 61 % and of hypercholesterolemia was 15 %. New or prevalent TB diagnosis was associated with newly diagnosed or history of DM (aOR 4.68, 2.15-10.20). Conclusions: In Ebeye, an integrated TB screening campaign found TB, HD, DM, and hypertension. TB and DM were strongly associated.

Preparation and Characterization of a Rifampicin Coamorphous Material with Tromethamine Coformer: An Experimental-Theoretical Study.

Rifampicin (RIF) is an antibiotic used to treat tuberculosis and leprosy. Even though RIF is a market-available drug, it has a low aqueous solubility, hindering its bioavailability. Among the strategies for bioavailability improvement of poorly soluble drugs, coamorphous systems have been revealed as an alternative in the increase of the aqueous solubility of drug systems and at the same time also increasing the amorphous state stability and dissolution rate when compared with the neat drug. In this work, a new coamorphous form from RIF and tromethamine (TRIS) was synthesized by slow evaporation. Structural, electronic, and thermodynamic properties and solvation effects, as well as drug-coformer intermolecular interactions, were studied through density functional theory (DFT) calculations. Powder X-ray diffraction (PXRD) data allowed us to verify the formation of a new coamorphous. In addition, the DFT study indicates a possible intermolecular interaction by hydrogen bonds between the available amino and carbonyl groups of RIF and the hydroxyl and amino groups of TRIS. The theoretical spectra obtained are in good agreement with the experimental data, suggesting the main interactions occurring in the formation of the coamorphous system. PXRD was used to study the physical stability of the coamorphous system under accelerated ICH conditions (40 °C and 75% RH), indicating that the material remained in an amorphous state up to 180 days. The thermogravimetry result of this material showed a good thermal stability up to 153 °C, and differential scanning calorimetry showed that the glass temperature (Tg) was at 70.0 °C. Solubility studies demonstrated an increase in the solubility of RIF by 5.5-fold when compared with its crystalline counterpart. Therefore, this new material presents critical parameters that can be considered in the development of new coamorphous formulations.

Clofazimine-induced cutaneous hyperpigmentation as a source of stigma in the treatment of leprosy: A cross-sectional study.

OBJECTIVES: Cutaneous hyperpigmentation is one of the main adverse effects encountered in patients undergoing leprosy treatment with multidrug therapy (WHO-MDT). This adverse effect has been described as intolerable and capable of contributing to social stigma. The objectives of this study were to quantify the variation in skin colour induced by clofazimine during and after treatment and to assess the related stigma. METHODS: This observational cross-sectional study objectively measured skin colour in 51 patients by reading the individual typology angle (ITA°) with a spectrophotometer, followed by the application of the Stigma Scale of the Explanatory Model Interview Catalogue (EMIC). RESULTS: Skin hyperpigmentation was observed in 100% of the individuals. They showed more negative ITA° values in lesion areas than non-lesion areas, particularly in sun-exposed regions. Clofazimine-induced cutaneous hyperpigmentation was not homogeneous and seemed to follow the lesion locations. The mean EMIC score was 18.8 points. CONCLUSION: All patients presented skin hyperpigmentation caused by clofazimine, detectable through spectrophotometry. Hyperpigmentation strongly impacted the social domain, indicating the intersectionality of disease and skin colour stigma, contributing to the social isolation of these patients. Health authorities should consider the negative impact of clofazimine on treatment adherence.

A natural butter glyceride as a plasticizer for improving thermal, mechanical, and biodegradable properties of poly(lactide acid).

Polylactic acid (PLA) is a biobased and biodegradable thermoplastic polyester with great potential to replace petroleum-based plastics. However, its poor toughness and slow biodegradation rate affect broad applications of PLA in many areas. In this study, a glycerol triester existing in natural butter, glycerol tributyrate, was creatively explored and compared with previously investigated triacetin and tributyl citrate, as potential plasticizers of PLA for achieving improved mechanical and biodegradation performances. The compatibilities of these agents with PLA were assessed quantitively via the Hansen solubility parameter (HSP) and measured by using different testing methods. The incorporation of these compounds with varied contents ranging from 1 to 30 % in PLA altered thermal, mechanical, and biodegradation properties consistently, and the relationship and impacts of chemical structures and properties of these agents were systematically investigated. The results demonstrated that glycerol tributyrate is a novel excellent plasticizer for PLA and the addition of this triester not only effectively reduced the glass transition, cold crystallization, and melting temperatures and Young's modulus, but also led to a significant improvement in the enzymatic degradation rate of the plasticized PLA. This study paves a way for the development of sustainable and eco-friendly food grade plasticized PLA products.