Our findings strongly suggest that the aerosol route of infection and transmission is predominant and that HHCs contribute to the infection risk to themselves and probably to others.

Leprosy transmission still occurs despite the availability of highly effective treatment. The next step towards successfully eliminating leprosy is interrupting the chain of transmission of the aetiological agent, Mycobacterium leprae. In this investigation, we provide evidence that household contacts (HHCs) of leprosy patients might not only have subclinical infections, but may also be actively involved in bacilli transmission. We studied 444 patients and 1,352 contacts using anti-phenolic glycolipid-I (PGL-I) serology and quantitative polymerase chain reaction (qPCR) to test for M. leprae DNA in nasal swabs. We classified the patients according to the clinical form of their disease and the contacts according to the characteristics of their index case. Overall, 63.3% and 34.2% of patients tested positive by ELISA and PCR, respectively. For HHCs, 13.3% had a positive ELISA test result and 4.7% had a positive PCR test result. The presence of circulating anti-PGL-I among healthy contacts (with or without a positive PCR test result from nasal swabs) was considered to indicate a subclinical infection. DNA detected in nasal swabs also indicates the presence of bacilli at the site of transmission and bacterial entrance. We suggest that the concomitant use of both assays may allow us to detect subclinical infection in HHCs and to identify possible bacilli carriers who may transmit and disseminate disease in endemic regions. Chemoprophylaxis of these contacts is suggested

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.

This cross-sectional retrospective study evaluated 440 leprosy patients; 57% (251/440) had leprosy reactions during and/or after multidrug therapy, 80.5% (202/251) of whom presented with multibacillary leprosy. At diagnosis, positive bacterial index (BI) [odds ratio (OR) = 6.39; 95% confidence interval (CI): 4.1-10.1)] or polymerase chain reaction (PCR) (OR = 9.15; 95% CI: 5.4-15.5) in skin smears, anti-phenolic glycolipid-1 (anti-PGL-1) ELISA (OR = 4.77; 95% CI: 2.9-7.9), leucocytosis (OR = 9.97; 95% CI: 3.9-25.7), thrombocytopenia (OR = 5.72; 95% CI: 2.3-14.0) and elevated lactate dehydrogenase (OR = 2.38; 95% CI: 1.4-4.0) were potential markers for the development of reactions during treatment. After treatment, positive BI (OR = 8.47; 95% CI: 4.7-15.3) and PCR (OR = 6.46; 95% CI: 3.4-12.3) in skin smears, anti-PGL-1 ELISA (OR = 2.25; 95% CI: 1.3-3.9), anaemia (OR = 2.36; 95% CI: 1.2-4.5), leucocytosis (OR = 4.14; 95% CI: 1.5-11.6) and thrombocytopenia (OR = 3.70; 95% CI: 1.3-2.2) were risk factors for the occurrence of reactions during the study period. The identification of groups with an increased risk for developing reactions will allow for the timely development of a treatment plan to prevent nerve damage and, therefore, the appearance of the disabling sequelae associated with the stigma of leprosy.

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BackgroundSerological tests can be important tools to assist in the diagnosis of leprosy and can contribute to an earlier diagnosis. The aim of this study was to evaluate the antibody responses against phenolic glycolipid-1 (PGL-1), natural disaccharide linked to human serum albumin via an octyl (NDO-HSA), Leprosy IDRI Diagnostic-1 (LID-1) and natural disaccharide octyl - Leprosy IDRI Diagnostic-1 (NDO-LID) in leprosy patients, household contacts of patients and the general population.MethodsEnzyme-linked immunosorbent assays were used to analyze the antigen-specific antibody responsesof 94 leprosy cases, 104 household contacts of cases and 2.494 individuals from the general population.ResultsA positive correlation was observed for the antibody responses to all antigens studied. A higher proportion of seropositivity for all antigens, along with stronger magnitude of response, was observed in multibacillary (MB) leprosy patients and household contacts of MB leprosy patients compared with the levels observed in paucibacillary (PB) leprosy patients and household contacts of PB leprosy patients. A substantial and significant positive correlation was found between seropositivity and the bacterial index for the leprosy patients. Anti-PGL-1 tests were more frequently positive than anti-NDO-HSA tests among patients with all clinical forms of leprosy and among the group of household contacts. The LID-1 and NDO-LID antigens showed a greater capacity to identify household contacts and individuals from the general population infected with M. leprae.ConclusionsTests that measure the antibody responses against LID-1, NDO-LID, NDO-HSA and PGL-1 were effective tools for the detection of patients with MB leprosy. Our data indicate that the anti-LID-1 and anti-NDO-LID responses were more effective than an anti-NDO-HSA response for the identification of individuals with subclinical infection.

dBlood donor samples (1,007) were assessed for anti-phenolic glycolipid 1 (PGL-1) IgM antibodies and Mycobacterium leprae DNA presence, which had 3.8% and 0.3% positivity, respectively. After a 5-year follow-up period, six individuals with positive markers developed leprosy, raising the hypothesis that asymptomatic infection among blood donors may be an undisclosed mode of leprosy transmission via transfusion. Leprosy is one of the oldest infectious diseases known to affect humans and remains a public health issue, particularly in Brazil, which accounts for almost all new cases detected in the Americas (1).Untreated leprosy patients are considered the main source of transmission. However, the dichotomy between the highly effective treatment and the occurrence of new cases among people without previous contact with patients indicates that other infectious sources must be investigated (2).The majority of exposed individuals will not develop the disease, although cumulative evidence demonstrates widespread dissemination of bacilli in regions where leprosy is endemic, strengthening the hypothesis that asymptomatic individuals are involved in the Mycobacterium leprae chain of transmission (3).Serological reactivity to M. leprae antigens has been used as an immunological marker for exposure and infection (4). Seropositivity for antibodies against phenolic glycolipid 1 (PGL-1), M. leprae-specific cell surface antigenic molecule has been correlated to a greater chance for later onset of leprosy among household contacts of leprosy patients (5).Studies regarding the detection of M. leprae DNA in peripheral blood samples are scarce. It has recently been suggested that whole-blood nested-PCR amplification could be used for early diagnosis of leprosy (6) and that the presence of M. leprae DNA in peripheral blood may be associated with bacillary migration and a high risk for disease onset (7).There are no published data on the assessment of randomly selected healthy blood donors for any kind of M. leprae marker. Therefore, this is the first epidemiological study to assess donor blood samples for the presence of antibodies against M. leprae and bacillary DNA through enzyme-linked immunosorbent assay (ELISA) and real-time PCR, respectively.Subjects were screened from a population of 1,035 blood donors at the regional blood bank of Uberlandia, Minas Gerais, Brazil. All subjects had normal dermatoneurological clinical examinations, and 28 people who reported prior contact with leprosy patients were excluded from the study. The reported new-case detection rate in the Uberlandia region was 11 per 100,000 population.A total of 1,007 peripheral blood samples were assessed for the presence of anti-PGL-1 antibodies and M. leprae DNA. Indirect ELISA against M. leprae native PGL-1 molecule was applied to detect specific IgM antibodies in serum samples, according to previously described methodology (4). Detection of DNA was performed with a species-specific TaqMan primer/probe assay targeting the repetitive region RLEP element of disperse...