Leprosy in French Guiana, 2015 to 2021: Dynamics of a Persistent Public Health Problem.

A resurgence of leprosy as a public health problem in French Guiana was reported over the period 2007 to 2014, particularly among Brazilians gold miners. Prolonged multidrug therapy and reversal reactions represent a therapeutic challenge. The objective of this study was to assess the evolution of leprosy in this European overseas territory. All patients with leprosy confirmed in histopathology between 1 January 2015 and 31 December 2021 were included. A total of 86 patients were included, including 64 new cases and 22 previously diagnosed cases. Sixty patients (70%) were male, 6 cases were paediatric. Brazilian gold miners represented 44.1% of reported occupations (15/34). Maroons represented the second community (13 patients, 15%). Multibacillary and paucibacillary forms were found in 53 (71%) and 22 (29%) patients, respectively. The annual prevalence never exceeded the threshold of 1/10,000. The mean incidence and prevalence were significantly lower than during the period 2007 to 2014 (p < 0.0001). Reversal reactions were found in 29 patients and almost always required a long course of steroids. Infliximab allowed a reduction in the length of treatment with steroids in 2/2 cases. In conclusion, the prevalence of leprosy has decreased significantly in French Guiana, but remains driven by the population of illegal gold miners. Anti-tumour necrosis factor (anti-TNF) drugs represent a promising option in the management of reversal reactions.

Protocol, rationale and design of BE-PEOPLE (Bedaquiline enhanced exposure prophylaxis for LEprosy in the Comoros): a cluster randomized trial on effectiveness of rifampicin and bedaquiline as post-exposure prophylaxis of leprosy contacts.

BACKGROUND: Leprosy is an ancient infectious disease with an annual global incidence of around 200,000 over the past decade. Since 2018, the World Health Organization (WHO) recommends single-dose rifampicin as post-exposure prophylaxis (SDR-PEP) for contacts of leprosy patients. The Post ExpOsure Prophylaxis for Leprosy (PEOPLE) trial evaluated PEP with a double dose of rifampicin in Comoros and Madagascar. Preliminary results of this trial show some reduction in leprosy incidence in intervention villages but a stronger regimen may be beneficial. The objective of the current Bedaquiline Enhanced ExpOsure Prophylaxis for LEprosy trial (BE-PEOPLE) is to explore effectiveness of a combination of bedaquiline and rifampicin as PEP. METHODS: BE-PEOPLE is a cluster-randomized trial in which 44 clusters in Comoros will be randomized to two study arms. Door-to-door screening will be conducted annually during four years, leprosy patients identified will be offered standard of care treatment. Based on study arm, contacts aged five years and above and living within a 100-meter radius of an index case will either receive bedaquiline (400-800 mg) and rifampicin (150-600 mg) or only rifampicin (150-600 mg). Contacts aged two to four years will receive rifampicin only. Household contacts randomized to the bedaquiline plus rifampicin arm will receive a second dose four weeks later. Incidence rate ratios of leprosy comparing contacts who received either of the PEP regimens will be the primary outcome. We will monitor resistance to rifampicin and/or bedaquiline through molecular surveillance in all incident tuberculosis and leprosy patients nationwide. At the end of the study, we will assess anti-M. leprae PGL-I IgM seropositivity as a proxy for the population burden of M. leprae infection in 8 villages (17,000 individuals) that were surveyed earlier as part of the PEOPLE trial. DISCUSSION: The COLEP trial on PEP in Bangladesh documented a reduction of 57% in incidence of leprosy among contacts treated with SDR-PEP after two years, which led to the WHO recommendation of SDR-PEP. Preliminary results of the PEOPLE trial show a lesser reduction in incidence. The BE-PEOPLE trial will explore whether reinforcing SDR-PEP with bedaquiline increases effectiveness and more rapidly reduces the incidence of leprosy, compared to SDR-PEP alone. TRIAL REGISTRATION: NCT05597280. Protocol version 5.0 on 28 October 2022.

The development, implementation, and evaluation of an optimal model for the case detection, referral, and case management of Neglected Tropical Diseases.

BACKGROUND: People affected by Neglected Tropical Diseases (NTDs), specifically leprosy, Buruli ulcer (BU), yaws, and lymphatic filariasis, experience significant delays in accessing health services, often leading to catastrophic physical, psychosocial, and economic consequences. Global health actors have recognized that Sustainable Development Goal 3:3 is only achievable through an integrated inter and intra-sectoral response. This study evaluated existing case detection and referral approaches in Liberia, utilizing the findings to develop and test an Optimal Model for integrated community-based case detection, referral, and confirmation. We evaluate the efficacy of implementing the Optimal Model in improving the early diagnosis of NTDs, thus minimizing access delays and reducing disease burden. METHODS: We used a participatory action research approach to develop, implement, and evaluate an Optimal Model for the case detection, referral, and management of case management NTDs in Liberia. We utilized qualitative and quantitative methods throughout the cycle and implemented the model for 12 months. RESULTS: During the implementation of our optimal model, the annual number of cases detected increased compared to the previous year. Cases were detected at an earlier stage of disease progression, however; gendered dynamics in communities shape the case identification process for some individuals. Qualitative data showed increased knowledge of the transmission, signs, symptoms, and management options among community health workers (CHW). CONCLUSION: The results provide evidence of the benefits of an integrated approach and the programmatic challenges to improve access to health services for persons affected by NTDs. The effectiveness of an integrated approach depends on a high level of collaboration, joint planning, and implementation embedded within existing health systems infrastructure.

Methotrexate as a corticosteroid-sparing agent in leprosy reactions: A French multicenter retrospective study.

INTRODUCTION: Leprosy reactions (LRs) are inflammatory responses observed in 30%-50% of people with leprosy. First-line treatment is glucocorticoids (GCs), often administered at high doses with prolonged courses, resulting in high morbi-mortality. Methotrexate (MTX) is an immunomodulating agent used to treat inflammatory diseases and has an excellent safety profile and worldwide availability. In this study, we describe the efficacy, GCs-sparing effect and safety of MTX in LRs. METHODS: We conducted a retrospective multicentric study in France consisting of leprosy patients receiving MTX for a reversal reaction (RR) and/or erythema nodosum leprosum (ENL) since 2016. The primary endpoint was the rate of good response (GR) defined as the complete disappearance of inflammatory cutaneous or neurological symptoms without recurrence during MTX treatment. The secondary endpoint was the GCs-sparing effect, safety and clinical relapse after MTX discontinuation. RESULTS: Our study included 13 patients with LRs (8 men, 5 women): 6 had ENL and 7 had RR. All patients had had at least one previous course of GCs and 2 previous treatment lines before starting MTX. Overall, 8/13 (61.5%) patients had GR, allowing for GCs-sparing and even GCs withdrawal in 6/11 (54.5%). No severe adverse effects were observed. Relapse after MTX discontinuation was substantial (42%): the median relapse time was 5.5 months (range 3-14) after stopping treatment. CONCLUSION: MTX seems to be an effective alternative treatment in LRs, allowing for GCs-sparing with a good safety profile. Furthermore, early introduction during LRs may lead to a better therapeutic response. However, its efficacy seems to suggest prolonged therapy to prevent recurrence.

The application of digital health as a nursing solution for leprosy patients during the COVID-19 pandemic: A systematic review.

Objectives: To analyse the effect of using digital health technology on leprosy control programmes. Method: The systematic review comprised search on PubMed, Scopus, ScienceDirect, SAGE and ProQuest databases for interventional studies published in English language from 2013 to 2021 which used digital health technology for leprosy contact tracing, active leprosy detection, monitoring of multi-drug therapy and treatment management during the corona virus disease-2019 pandemic A standard risk of bias tool was used to evaluate bias in the studies, and the Joanna Briggs Institute protocol was used to assess the quality of the studies analysed. RESULTS: Of the 205 studies initially identified, 15(7.3%) were analysed in detail. Quasi-experimental studies had a low risk of bias compared to the rest. The e-leprosy framework was being used along with applications based on smartphones and artificial intelligence Digital health technology was found to be practical, accessible and effective in leprosy control programmes. CONCLUSIONS: Studies reported favourable findings regarding the use of digital health technology in services related to leprosy patients.

High prevalence of olfactory impairment among leprosy patients: A cross-sectional study.

BACKGROUND: The effect of leprosy on the sense of smell is not yet fully established. Studies that have relied only on patients' perceptions may have under- or over-estimated the change in smell perception. A validated and psychophysical method is necessary to avoid these errors in assessment. OBJECTIVES: This study aimed to validate the existence of olfactory involvement in leprosy patients. METHODS: A cross-sectional, controlled study was conducted, in which individuals with leprosy (exposed individuals) and individuals without leprosy (control patients) were recruited. For each exposed individual, we selected two control patients. A total of 108 patients (72 control patients and 36 exposed individuals) with no history of infection with the new coronavirus (COVID-19) took the University of Pennsylvania Smell Identification Test (UPSIT). RESULTS: Most exposed individuals had olfactory dysfunction [n = 33, 91.7% (CI 95%: 77.5%-98.3%)] when compared with the control patients [n = 28, 38.9% (CI 95%: 27.6%-51.1%)], but only two (5.6%) had olfactory complaints. The olfactory function was significantly worse among exposed individuals [UPSIT leprosy = 25.2 (CI 95%: 23.1-27.3) when compared with the UPSIT control patients = 34.1 (CI 95%: 33.0-35.3); p<0.001]. The risk of olfactory loss was higher among the exposed individuals [OR: 19.5 (CI 95%: 5.18-105.70; p < 0.001)]. CONCLUSIONS: Olfactory dysfunction was highly prevalent among exposed individuals, although they had little or no self-knowledge of the disorder. The results show that it is important to assess the sense of smell in exposed individuals.

Little Doctors: Agents of change in Indian rural communities.

The child-to-child approach to health advocacy is one that draws on the strengths and agency of children to make a positive impact within their communities. The approach has been popularly used for health education in low- and middle-income countries. This article describes the 'Little Doctors' program that implemented the child-to-child approach in the towns of KC Patty and Oddanchatram, located in remote hilly regions of Tamil Nadu, India starting in 1986 to train middle- and high school children to respond to diseases prevalent in their communities along with practices for preventative measures. The program involved sessions that used a combination of creative instructional methods to engage students and provided take-home messages for them to act on with their families and community. The program was successful in creating a creative learning environment for children, offering a shift from the traditional methods of classroom instruction. Students who successfully completed the program were awarded certificates as 'Little Doctors' in their communities. Although the program did not conduct formal evaluations of the program effectiveness, students reported successfully recalling complex topics such as early signs of diseases like tuberculosis and leprosy that were prevalent in the community during the time . The program experienced several challenges and had to be discontinued despite its continued benefits to the communities.

Clinico-Epidemiological profile of new leprosy cases detected in leprosy case detection campaign in North Maharashtra during 2018-2020.

Leprosy is a leading cause of disability in India. The percentage of disability and deformity can be reduced by diagnosing leprosy at an early stage. In order to detect the hidden leprosy cases, leprosy case detection campaigns, on line with Pulse Polio Campaign have been introduced specifically for high endemic districts, by the Central Leprosy Division. Records of cases from 2018 to 2020 were evaluated retrospectively to study the trend of new cases. The present study denotes the presence of hidden undiagnosed cases in the community and will require an intensification of leprosy control activities through contact tracing and active case detection. Continued quality surveillance is required for early detection, timely management, and prevention of the spread of the disease.

Mycobacterium leprae and host immune transcriptomic signatures for reactional states in leprosy.

Background: Mycobacterium leprae transcriptomic and human host immune gene expression signatures that demonstrate a plausible association with type I (T1R) and type II reactions (T2R) aid in early diagnosis, prevention of nerve damage and consequent demyelinating neuropathy in leprosy. The aim of the study is to identify M. leprae and host-associated gene-expression signatures that are associated with reactional states in leprosy. Methods: The differentially expressed genes from the whole transcriptome of M. leprae were determined using genome-wide hybridization arrays with RNA extracted from skin biopsies of 20 T1R, 20 T2R and 20 non reactional controls (NR). Additionally, human immune gene-expressions were profiled using RT2-PCR profiler arrays and real-time qPCRs. Results: The RNA quality was optimal in 16 NR, 18 T1R and 19 T2R samples. Whole transcriptome expression array of these samples revealed significant upregulation of the genes that encode integral and intrinsic membrane proteins, hydrolases and oxidoreductases. In T1R lesional skin biopsy specimens, the top 10 significantly upregulated genes are ML2064, ML1271, ML1960, ML1220, ML2498, ML1996, ML2388, ML0429, ML2030 and ML0224 in comparison to NR. In T2R, genes ML2498, ML1526, ML0394, ML1960, ML2388, ML0429, ML0281, ML1847, ML1618 and ML1271 were significantly upregulated. We noted ML2664 was significantly upregulated in T1R and repressed in T2R. Conversely, we have not noted any genes upregulated in T2R and repressed in T1R. In both T1R and T2R, ML2388 was significantly upregulated. This gene encodes a probable membrane protein and epitope prediction using Bepipred-2.0 revealed a distinct B-cell epitope. Overexpression of ML2388 was noted consistently across the reaction samples. From the host immune gene expression profiles, genes for CXCL9, CXCL10, CXCL2, CD40LG, IL17A and CXCL11 were upregulated in T1R when compared to the NR. In T2R, CXCL10, CXCL11, CXCL9, CXCL2 and CD40LG were upregulated when compared to the NR group. Conclusion: A gene set signature involving bacterial genes ML2388, ML2664, and host immune genes CXCL10 and IL-17A can be transcriptomic markers for reactional states in leprosy.

Association between asthma, rhinitis and atopic dermatitis with leprosy: A case-control study.

Background Considering the cross-regulation of Th1 and Th2 responses, we hypothesised that atopic diseases (Th2) inhibit the protective Th1 immune response to Mycobacterium leprae and exacerbates leprosy. Objective In this study, we aimed to evaluate the association between leprosy and atopic diseases. Methods To evaluate the association of atopic diseases with leprosy, we conducted a case-control study that included leprosy patients (n = 333) and their household contacts (n = 93). The questionnaire from the International Study of Asthma and Allergies in Childhood, which is validated in several countries for epidemiological diagnosis of atopic diseases, was applied to determine the occurrence of atopic diseases, allergic rhinitis, asthma, and atopic dermatitis among leprosy patients and the household contacts. Results Considering clinical and epidemiological data, among the leprosy group 51.6% (n = 172) were determined to have at least one atopic disease, while atopy was observed less frequently at 40.86% among household contacts (n = 38). When two or more atopic diseases were assessed, the frequency was significantly higher among the leprosy patients than in the household contacts (21.9% vs. 11.8%; P-value = 0.03). Likewise, the frequency of asthma was significantly higher among leprosy patients (21%) than in the household contacts (10.8%; P-value = 0.02). Thus, our analyses revealed an association of atopic diseases with leprosy, with a significant linear increase in the occurrence of leprosy with an increase in the number of atopic diseases (P-value = 0.01). Limitation Due to the difficulties in recruiting household contacts that have prolonged contact with patients, but are not genetically related to the patient, the household contacts group is smaller than the leprosy patient group. Conclusion The data reveal an association between atopic diseases and leprosy outcomes. This knowledge could improve the treatment of leprosy patients with co-incident atopic diseases.

The association of psoriasis and psoriatic arthritis with periodontitis: A hospital-based case-control study.

Background Periodontitis can trigger and perpetuate inflammation in several chronic inflammatory diseases. The association of periodontitis with psoriasis has been investigated earlier, but data are incomplete and the influence of confounders has not been fully evaluated. We examined the relationship of dental and periodontal health parameters in patients with psoriasis and/or psoriatic arthritis. Methods This hospital-based cross-sectional analytical study was conducted in patients with chronic plaque psoriasis, psoriatic arthritis or both, and compared with controls. Dental and periodontal health parameters were assessed based on the WHO oral health assessment method. Multivariate logistic regression was done on variables with significant or near-significant values to find the association between periodontitis and psoriasis and/or psoriatic arthritis after adjusting for confounders. Results Psoriasis and/or psoriatic arthritis were independently and significantly associated with periodontal pockets ≥4 mm in depth. Limitations Causality and temporal relationship cannot be established as this was a cross-sectional study. As in all observational studies, the possibility of unmeasured or unknown confounders exists. Psoriatic arthritis was present only in a small subset of patients. Conclusion Patients with psoriasis and/or psoriatic arthritis have significant periodontal inflammation. This needs to be addressed by dental examination and intervention.

Lessons From the Wrong Isolation Policy Violating Human Rights for Leprosy in Japan.

Leprosy, caused by Mycobacterium leprae , is one of the so-called "neglected tropical diseases" and is found today mainly in Africa, Asia and South America. Although oral antibiotics capable of curing leprosy are now available, the disease is still misunderstood and feared by the public because of the unsightly deformities that it may cause. In Japan, leprosy has been present since the 8th century and was regarded as a hereditary disease; people avoided marrying into a family with a member affected by leprosy. At the beginning of the 20th century, the Japanese government instituted a policy of lifetime quarantine of individuals with leprosy to eradicate the disease, thereby purposely disseminating negative and inaccurate perceptions of the disease as deadly and highly contagious and fostering a long-lasting prejudice among the general public towards those affected. Even after effective treatments became available, the government continued quarantining patients until 1996. The government has since then apologized to the patients for violating their constitutionally guaranteed human rights. Children with leprosy and children born to parents with leprosy were also victims of the policy and prejudice created. We describe herein the history of leprosy-related policies in Japan to emphasize the importance of balancing public health policy with human rights.

The pipeline for drugs for control and elimination of neglected tropical diseases: 1. Anti-infective drugs for regulatory registration.

The World Health Organization 'Ending the neglect to attain the Sustainable Development Goals: A road map for neglected tropical diseases 2021-2030' outlines the targets for control and elimination of neglected tropical diseases (NTDs). New drugs are needed to achieve some of them. We are providing an overview of the pipeline for new anti-infective drugs for regulatory registration and steps to effective use for NTD control and elimination. Considering drugs approved for an NTD by at least one stringent regulatory authority: fexinidazole, included in WHO guidelines for Trypanosoma brucei gambiense African trypanosomiasis, is in development for Chagas disease. Moxidectin, registered in 2018 for treatment of individuals ≥ 12 years old with onchocerciasis, is undergoing studies to extend the indication to 4-11-year-old children and obtain additional data to inform WHO and endemic countries' decisions on moxidectin inclusion in guidelines and policies. Moxidectin is also being evaluated for other NTDs. Considering drugs in at least Phase 2 clinical development, a submission is being prepared for registration of acoziborole as an oral treatment for first and second stage T.b. gambiense African trypanosomiasis. Bedaquiline, registered for tuberculosis, is being evaluated for multibacillary leprosy. Phase 2 studies of emodepside and flubentylosin in O. volvulus-infected individuals are ongoing; studies for Trichuris trichuria and hookworm are planned. A trial of fosravuconazole in Madurella mycetomatis-infected patients is ongoing. JNJ-64281802 is undergoing Phase 2 trials for reducing dengue viral load. Studies are ongoing or planned to evaluate oxantel pamoate for onchocerciasis and soil-transmitted helminths, including Trichuris, and oxfendazole for onchocerciasis, Fasciola hepatica, Taenia solium cysticercosis, Echinococcus granulosus and soil-transmitted helminths, including Trichuris. Additional steps from first registration to effective use for NTD control and elimination include country registrations, possibly additional studies to inform WHO guidelines and country policies, and implementation research to address barriers to effective use of new drugs. Relative to the number of people suffering from NTDs, the pipeline is small. Close collaboration and exchange of experience among all stakeholders developing drugs for NTDs may increase the probability that the current pipeline will translate into new drugs effectively implemented in affected countries.

Shorter regimens improved treatment outcomes of multidrug-resistant tuberculosis patients in Tanzania in 2018 cohort.

OBJECTIVE: In 2018, shorter treatment regimens (STR) for people with drug-resistant tuberculosis (DR-TB) were introduced in Tanzania and included kanamycin, high-dose moxifloxacin, prothionamide, high-dose isoniazid, clofazimine, ethambutol and pyrazinamide. We describe treatment outcomes of people diagnosed with DR-TB in a cohort initiating treatment in 2018 in Tanzania. METHODS: This was a retrospective cohort study conducted at the National Centre of Excellence and decentralised DR-TB treatment sites for the 2018 cohort followed from January 2018 to August 2020. We reviewed data from the National Tuberculosis and Leprosy Program DR-TB database to assess clinical and demographic information. The association between different DR-TB regimens and treatment outcome was assessed using logistic regression analysis. Treatment outcomes were described as treatment complete, cure, death, failure or lost to follow-up. A successful treatment outcome was assigned when the patient achieved treatment completion or cure. RESULTS: A total of 449 people were diagnosed with DR-TB of whom 382 had final treatment outcomes: 268 (70%) cured; 36 (9%) treatment completed; 16 (4%) lost to follow-up; 62 (16%) died. There was no treatment failure. The treatment success rate was 79% (304 patients). The 2018 DR-TB treatment cohort was initiated on the following regimens: 140 (46%) received STR, 90 (30%) received the standard longer regimen (SLR), 74 (24%) received a new drug regimen. Normal nutritional status at baseline [adjusted odds ratio (aOR) = 6.57, 95% CI (3.33-12.94), p < 0.001] and the STR [aOR = 2.67, 95% CI (1.38-5.18), p = 0.004] were independently associated with successful DR-TB treatment outcome. CONCLUSION: The majority of DR-TB patients on STR in Tanzania achieved a better treatment outcome than on SLR. The acceptance and implementation of STR at decentralised sites promises greater treatment success. Assessing and improving nutritional status at baseline and introducing new shorter DR-TB treatment regimens may strengthen favourable treatment outcomes.

Early diagnosis of neural impairment in seropositive leprosy household contacts: The experience of a reference center in Brazil.

Introduction: Leprosy is an infectious disease that remains with a high number of new cases in developing countries. Household contacts have a higher risk for the development of the disease, but the neural impairment in this group is not well elucidated yet. Here, we measured the chance of occurrence of peripheral neural impairment in asymptomatic leprosy household. Methods: Contacts who present anti-PGL-I IgM seropositivity, through electroneuromyography (ENMG) evaluation. We recruited 361 seropositive contacts (SPC) from 2017 to 2021, who were subjected to an extensive protocol that included clinical, molecular, and electroneuromyographic evaluations. Results: Our data revealed a positivity of slit skin smear and skin biopsy qPCR of 35.5% (128/361) and 25.8% (93/361) respectively. The electroneuromyographic evaluation of the SPC showed neural impairment in 23.5% (85/361), with the predominance of a mononeuropathy pattern in 62.3% (53/85). Clinical neural thickening was observed in 17.5% (63/361) of seropositive contacts, but among the individuals with abnormal ENMG, only 25.9% (22/85) presented neural thickening in the clinical exam. Discussion: Ours results corroborates the need to make the approach to asymptomatic contacts in endemic countries more timely. Since leprosy in its early stages can present an indolent and subclinical evolution, serological, molecular, and neurophysiological tools are essential to break the disease transmission chain.

Evolution of anti-malaria policies and measures in P.R. China for achieving and sustaining malaria-free.

Malaria is a major public health threat worldwide, and it was also widely prevalent in the history in China, seriously endangering people's health and affecting socioeconomic development. China was certified malaria elimination in 2021 with unremitting efforts since the founding of the People's Republic of China in 1949. This great achievement has been another milestone in the fight against major infectious diseases following the elimination of smallpox, poliomyelitis, leprosy, filariasis, neonatal tetanus and blinding trachoma in China. This paper briefly introduces the malaria burden dynamics and the corresponding malaria transmission risk stratificantions, as well as systematically reviews the evolution of anti-malaria policies and measures from severe epidemic to elimination in China. Meanwhile, five key lessons in malaria control and elimination in China are also briefly summarized. All of the above provide evidences for promoting global malaria eradication and preventing reestablishment of malaria transmission, finally benefit all individuals still suffering from the scourge of malaria.