Hansen Disease (Leprosy) and Armadillo Exposure in Arkansas: A Case Series.

BACKGROUND: Although most cases of Hansen disease (HD) in the United States are imported from endemic areas, a subset of cases are relate to exposure to nine-banded armadillos. Several recent cases of HD in Arkansas occurred in patients who had not traveled to endemic areas and who reported variable degrees of armadillo exposure. OBJECTIVE: The purpose of this study was to report 6 cases of HD diagnosed in Arkansas between 2004 and 2016. The secondary purpose was to explore the correlation between exposure to the nine-banded armadillo as it pertains to transmission of the disease. METHODS: The referring clinician of each patient was contacted to gather information regarding the patient's clinical presentation, armadillo exposure, and travel history. In addition, the Arkansas Department of Health was consulted to review the demographics of individuals diagnosed with HD in the past 15 years and to review the distribution of HD throughout the state of Arkansas. RESULTS: Six domestic cases of HD were associated with both direct and indirect exposure to armadillos. LIMITATIONS: Armadillo exposure may be underreported in patients with HD because of fear of stigmatization and/or lack of access to care. CONCLUSIONS: Direct exposure to armadillos does not appear to be required for transmission of HD making a soil-mediated mechanism of indirect exposure plausible.

Incidence of and Factors Associated With Leprosy Among Household Contacts of Patients With Leprosy in Brazil.

Importance: Despite progress toward reducing global incidence, leprosy control remains a challenge in low- and middle-income countries. Objective: To estimate new case detection rates of leprosy among household contacts of patients with previously diagnosed leprosy and to investigate its associated risk factors. Design, Setting, and Participants: This population-based cohort study included families registered in the 100 Million Brazilian Cohort linked with nationwide registries of leprosy; data were collected from January 1, 2007, through December 31, 2014. Household contacts of patients with a previous diagnosis of leprosy from each household unit were followed up from the time of detection of the primary case to the time of detection of a subsequent case or until December 31, 2014. Data analysis was performed from May to December 2018. Exposures: Clinical characteristics of the primary case and sociodemographic factors of the household contact. Main Outcomes and Measures: Incidence of leprosy, estimated as the new case detection rate of leprosy per 100 000 household contacts at risk (person-years at risk). The association between occurrence of a subsequent leprosy case and the exposure risk factors was assessed using multilevel mixed-effects logistic regressions allowing for state- and household-specific random effects. Results: Among 42 725 household contacts (22 449 [52.5%] female; mean [SD] age, 22.4 [18.5] years) of 17 876 patients detected with leprosy, the new case detection rate of leprosy was 636.3 (95% CI, 594.4-681.1) per 100 000 person-years at risk overall and 521.9 (95% CI, 466.3-584.1) per 100 000 person-years at risk among children younger than 15 years. Household contacts of patients with multibacillary leprosy had higher odds of developing leprosy (adjusted odds ratio [OR], 1.48; 95% CI, 1.17-1.88), and the odds increased among contacts aged 50 years or older (adjusted OR, 3.11; 95% CI, 2.03-4.76). Leprosy detection was negatively associated with illiterate or preschool educational level (adjusted OR, 0.59; 95% CI, 0.38-0.92). For children, the odds were increased among boys (adjusted OR, 1.70; 95% CI, 1.20-2.42). Conclusions and Relevance: The findings in this Brazilian population-based cohort study suggest that the household contacts of patients with leprosy may have increased risk of leprosy, especially in households with existing multibacillary cases and older contacts. Public health interventions, such as contact screening, that specifically target this population appear to be needed.

Chemoprophylaxis of leprosy with rifampicin in contacts of multibacillary patients: study protocol for a randomized controlled trial.

BACKGROUND: The annual new-case detection rate for leprosy, while generally stable over the last decade, shows that transmission rates have remained stagnant despite the successful worldwide administration of multidrug therapy since the 1980s. As such, novel control strategies are urgently needed. Focusing on managing leprosy patient contacts, the most susceptible to contracting the disease, has been seen as a potential strategy in limiting the spread of leprosy as shown by a number of recent epidemiological studies. Immunoprophylaxis with Bacillus Calmette-Guérin (BCG) has been seen as an effective preventive measure due to its ability to stimulate the development of cellular immunity which is essential in controlling the disease, especially in its multibacillary (MB) forms. The association of immunoprophylaxis with chemoprophylaxis in a single dose of rifampicin has been shown to be a promising preventive strategy, although a variety of studies have found instances of early case detection just a few months after BCG vaccination. METHODS/DESIGN: The present study is a phase IV chemoprophylactic clinical trial consisting of administration of a single dose of rifampicin in MB leprosy patient contacts under care at the Souza Araújo Outpatient Clinic/FIOCRUZ as part of a randomized (2:1), double-blind, placebo-controlled study. It is comprised of two groups: 1) rifampicin + BCG; and 2) placebo + BCG. DISCUSSION: The aim is to evaluate whether the use of chemoprophylaxis with a single dose of rifampicin in MB leprosy patient contacts prior to the BCG vaccine would be able to prevent the onset of leprosy in those cases that may occur just a few months after vaccination. Contact subclinical infections (polymerase chain reaction) and the immunological parameters (anti-PGL-1, anti-LID-1, and IFN-γ) will be evaluated and the results will be compared after 12 months of follow-up. TRIAL REGISTRATION: The Brazilian Registry of Clinical Trials (ReBEC), RBR-69QK5P . Retrospectively registered on 1 June 2017.

TH17 cells, interleukin-17 and interferon-γ in patients and households contacts of leprosy with multibacillary and paucibacillary forms before and after the start of chemotherapy treatment.

BACKGROUND: Studies on the immunology of leprosy are fundamental to the understanding of the various forms of clinical manifestation of the disease. In some diseases, lymphocytes TH17 and one of its key cytokines, interleukin-17 has been shown to be essential in developing an effective immune response. In leprosy, involvement of lymphocyte TH17 and interleukin-17 remains understudied. OBJECTIVES: This study is the first investigation to examine the association between TH17 cells, interleukin-17 and interferon- γ in patients and households contacts of leprosy. METHODS: To document the participation of TH17 cells and interleukin-17 in the immunology of leprosy, to observe the behavior of interferon-γ in relation to interleukin-17 and to verify the differences found between individuals paucibacillary, multibacillary and household contacts, we analyzed samples peripheral blood to identify TH-17 cells, interleukin-17 and IFN-γ; establishing relationships between all the groups. RESULTS: There was a significant difference in the results found in the comparison between the paucibacillary and multibacillary groups of patients (P < 0.001), as well with the household contacts (P < 0.005). The polychemotherapeutic treatment modified the profile of immune response in multibacillary patients compared to what was observed before the start of treatment. CONCLUSION: The principal finding was that TH17 lymphocytes and interleukin-17 actively participating in the immune response of Hansen's disease as well these cells can stimulate the cellular immunity.

Mycobacterium leprae is identified in the oral mucosa from paucibacillary and multibacillary leprosy patients.

In leprosy, the nasal mucosa is considered as the principal route of transmission for the bacillus Mycobacterium leprae. The objective of this study was to identify M. leprae in the oral mucosa of 50 untreated leprosy patients, including 21 paucibacillary (PB) and 29 multibacillary (MB) patients, using immunohistochemistry (IHC), with antibodies against bacillus Calmette-Guérin (BCG) and phenolic glycolipid antigen-1 (PGL-1), and polymerase chain reaction (PCR), with MntH-specific primers for M. leprae, and to compare the results. The material was represented by 163 paraffin blocks containing biopsy samples obtained from clinically normal sites (including the tongue, buccal mucosa and soft palate) and visible lesions anywhere in the oral mucosa. All patients and 158 available samples were included for IHC study. Among the 161 available samples for PCR, 110 had viable DNA. There was viable DNA in at least one area of the oral mucosa for 47 patients. M. leprae was detected in 70% and 78% of patients using IHC and PCR, respectively, and in 94% of the patients by at least one of the two diagnostic methods. There were no differences in detection of M. leprae between MB and PB patients. Similar results were obtained using anti-BCG and anti-PGL-1 antibodies, and immunoreactivity occurred predominantly on free-living bacteria on the epithelial surface, with a predilection for the tongue. Conversely, there was no area of predilection according to the PCR results. M. leprae is present in the oral mucosa at a high frequency, implicating this site as a potential means of leprosy transmission.

Current trends in leprosy transmission in eastern India in the era of 12-month multi-drug treatment: a hospital-based retrospective study.

OBJECTIVES: Our objective was to study current trends in the occurrence of new cases of leprosy (Hansen's disease [HD]) a decade after significant operational changes in the National Leprosy Elimination Program (NLEP) were enacted by shortening the duration of multi-drug treatment for multibacillary cases of HD to 12 months and stopping post-treatment follow-up. METHODS: The percentages represented by newly diagnosed cases of HD among all new patients attending the dermatology outpatient department (OPD) from April 2008 to March 2011 were calculated from hospital records. Patient age and sex, and type of disease were noted in each case, and annual data were compared. The OPD data were also matched with population data for the catchment area of the hospital (i.e. the South 24-Parganas district). RESULTS: There was a slight annual decline in the percentage of new cases represented by HD, but this was not statistically significant. This trend broadly corroborated changes in the annual new case detection rate in the catchment area of the hospital. In addition, the percentage of HD cases represented by paucibacillary disease was significantly higher than that represented by multibacillary HD (P=0.0072). CONCLUSIONS: To the best of our knowledge, this is the first study of this type to be conducted in eastern India. The present data indicate that significant transmission of HD is ongoing in the community.

Mycobacterium leprae DNA in peripheral blood may indicate a bacilli migration route and high-risk for leprosy onset.

Leprosy epidemiological studies have been restricted to Mycobacterium leprae DNA detection in nasal and oral mucosa samples with scarce literature on peripheral blood. We present the largest study applying quantitative real-time PCR (qPCR) for the detection of M. leprae DNA in peripheral blood samples of 200 untreated leprosy patients and 826 household contacts, with results associated with clinical and laboratory parameters. To detect M. leprae DNA a TaqMan qPCR assay targeting the M. leprae ML0024 genomic region was performed. The ML0024 qPCR in blood samples detected the presence of bacillus DNA in 22.0% (44/200) of the leprosy patients: 23.2% (16/69) in paucibacillary (PB), and 21.4% (28/131) in multibacillary (MB) patients. Overall positivity among contacts was 1.2% (10/826), with similar percentages regardless of whether the index case was PB or MB. After a follow-up period of 7 years, 26 contacts have developed leprosy. Comparing the results of healthy contacts with those that become ill, ML0024 qPCR positivity at the time of diagnosis of their index case represented an impressive 14.78-fold greater risk for leprosy onset (95% CI 3.6-60.8; p <0.0001). In brief, contacts with positive PCR in blood at diagnosis of index cases are at higher risk of later leprosy onset and this marker might be combined with other prognostic markers for management of contacts, which requires further studies.

Dynamics of Mycobacterium leprae transmission in environmental context: deciphering the role of environment as a potential reservoir.

Leprosy is a disease caused by Mycobacterium leprae. Various modes of transmission have been suggested for this disease. Transmission and risk of the infection is perhaps related to presence of the infectious cases and is controlled by environmental factors. Evidence suggests that humidity may favor survival of M. leprae in the environment. Several reports show that non-human sources like 'naturally' infected armadillos or monkeys could act as reservoir for M. leprae. Inanimate objects or fomites like articles used by infectious patients may theoretically spread infection. However, it is only through detailed knowledge of the biodiversity and ecology that the importance of this mode of transmission can be fully assessed. Our study focuses here to decipher the role of environment in the transmission of the disease. Two hundred and seven soil samples were collected from a village in endemic area where active cases also resided at the time of sample collection. Slit skin smears were collected from 13 multibacillary (MB) leprosy patients and 12 household contacts of the patients suspected to be hidden cases. DNA and RNA of M. leprae were extracted and amplified using M. leprae specific primers. Seventy-one soil samples showed presence of M. leprae DNA whereas 16S rRNA could be detected in twenty-eight of these samples. Samples, both from the environment and the patients, exhibited the same genotype when tested by single nucleotide polymorphism (SNP) typing. Genotype of M. leprae found in the soil and the patients residing in the same area could help in understanding the transmission link in leprosy.

Trends in new leprosy case detection over 57 years (1952-2008) in Yuxi, Yunnan Province of Southwest China.

BACKGROUND: Leprosy control and management in China was maintained via a vertical system. Despite substantial achievements in leprosy control in the past decades, leprosy has not been completely eliminated in several endemic areas of Yunnan Province, China. OBJECTIVES: To report the epidemiological trends and management of leprosy in Yuxi, Yunnan Province from 1952 to 2008. DESIGN: Diagnosis, control, and treatment data for 2223 leprosy cases detected from 1952 to 2008 were analysed. RESULTS: Two large-scale house-to-house surveys were launched in 1957-1958 and 1964-1965, and a remarkable number of new cases were identified during these two surveys. The overall prevalence rate of leprosy in the Yuxi region presented a roughly unimodal distribution between 1952 and 2008, with a peak (9.27 per 10000 population) in 1965. This reflects a combination of case detection and duration of treatment. Overall, the age distribution of the patients changed dramatically over the years, and there were only two childhood cases between 1995 and 2008 (both occurring in 1998). Nearly half of the total cases (49.1%) were classified as multibacillary leprosy type. With the introduction and ubiquitous coverage of the WHO multi-drug therapy (MDT) in this area, leprosy elimination was achieved in 1992. In recent years, the majority of cases (> 80%) were detected by passive approaches, and there is an increasing tendency to find multibacillary leprosy patients. CONCLUSIONS: Our results provide an overall profile of our 57-year effort regarding the leprosy control in the Yuxi region. The trend in detection of new cases in recent years suggested that the transmission of leprosy has stopped in the area or, at least, dramatically declined.

Nonpruritic erythematous plaques.

A 43-year-old man visiting Texas from Hawaii sought care at our dermatology clinic for nonpruritic erythematous plaques on his chest, back, and extremities. The patient reported occasional numbness in his fingers and feet, but denied constitutional symptoms. The patient, who'd had these symptoms for a year, had been previously diagnosed with chronic urticaria and treated with oral antihistamines. He reported that the lesions were never particularly pruritic and he had not responded to previous treatments. An avid outdoorsman, our patient was born and raised in Texas and had been living in Hawaii. His past medical history was significant for severe hand eczema and when asked about medications he was taking, he listed cetirizine, doxepin, and hydroxyzine. On physical examination the patient had multiple pink to red, nonscaly to minimally scaly flat plaques on his forehead, chest, proximal upper extremities, lower back, and distal lower extremities. A 4-mm punch biopsy was taken from a lesion on his lower back and sent for histologic evaluation. The patient's erythrocyte sedimentation rate, rapid plasma reagin, and complete blood count were all within normal limits. What is your diagnosis? How would you treat this patient?