Population survey to determine risk factors for Mycobacterium leprae transmission and infection

Background: Not every leprosy patient is equally effective in transmitting Mycobacterium leprae. We studied the spatial distribution of infection (using seropositivity as a marker) in the population to identifity which disease characteristics of leprosy patients are important in transmission. Methods: Clinical data and blood samples for anti-M.leprae ELISA were collected during a cross-sectional survey on five Indonesian islands highly endemic for leprosy. A geographic information system (GIS) was used to define contacts of patients. We investigated spatial clustering of patients and seropositive people and used logist regression to determine risk factors for seropositivity. Results: Of the 3986 people examined for leprosy, 3271 gave blood. Seroprevalence varied between islands (1.7-8.7%) and correlated significantly with leprosy prevalence. Five clusters of patients and two clusters of seropositives were detected. In multivariate analysis, seropositivity significantly differed to be the best discriminator of contact groups with higher seroprevalence: contacts of seropositive patients had an adjusted odds ratio (aOR) of 1.75 (95% CI: 0.92-3,31). This increased seroprevalence was strongest for contact groups living _< 75 metres of two seropositive patients (aOR:3.07;95%CI:1.74-5.42). Conclusions: In this highly endemic area for leprosy, not only household contacts of seropositive patients, but also persons living in the vicinity of seropositive patient were more likely to harbour antibodies against M.leprae. Through measuring the serological status of patients and using a broader definition of contacts, higher risk groups can be more specifically identified

Prevention of leprosy using rifampicin as chemoprophylaxis

An intervention study was implemented on five Indinesian island highly endemic for leprosy to determine whether rifampicin can be used as chemoprophylaxis to prevent leprosy. The population was actively screened before the intervention and subsequently once a year for three years. In the control group, no chemoprophylaxis was given. In the contact group, chemoprophylaxis was only given to contacts of leprosy patients and in the blanket group to all aligible persons. The cohort consited of 3,965 persons. The yearly incidence rate in the control group was 39/10,000; the cumulative incidence after three years was significantly lower in the blanket group (P=0.031). No difference was found between the contact and the control groups (P=0.93). Whether this apparent reduced leprosy incidence in the first three years in the blanket group is due to a delayed development of leprosy or a complete clearence of infections needs to be determined

Patient contact is the major determinant in incident leprosy: implications for future control.

Notwithstanding the elimination efforts, leprosy control programs face the problem of many leprosy patients remaining undetected. Leprosy control focuses on early diagnosis through screening of household contacts, although this high-risk group generates only a small proportion of all incident cases. For the remaining incident cases, leprosy control programs have to rely on self-reporting of patients. We explored the extent to which other contact groups contribute to incident leprosy. We examined retrospectively incident leprosy over 25 years in a high-endemic village of 2283 inhabitants in Sulawesi, Indonesia, by systematically reviewing data obtained from the local program and actively gathering data through interviews and a house-to-house survey. We investigated the contact status in the past of every incident case. In addition to household contact, we distinguished neighbor and social contacts. Of the 101 incident cases over a 25-year period, 79 (78%) could be associated to contact with another leprosy patient. Twenty-eight (28%) of these 101 cases were identified as household contacts, 36 (36%) as neighbors, and the remaining 15 (15%) as social contacts. Three patients had not had a traceable previous contact with another leprosy patient, and no information could be gathered from 19 patients. The median span of time from the registration of the primary case to that of the secondary case was 3 years; 95% of the secondary cases were detected within 6 years after the primary case. The estimated risk for leprosy was about nine times higher in households of patients and four times higher in direct neighboring houses of patients compared to households that had had no such contact with patients. The highest risk of leprosy was associated with households of multibacillary patients. The risk of leprosy for households of paucibacillary patients was similar to the risk of leprosy for direct neighboring houses of multibacillary patients, indicating that both the type of leprosy of the primary case and the distance to the primary case are important contributing factors for the risk of leprosy. Contact with a leprosy patient is the major determinant in incident leprosy; the type of contact is not limited to household relationships but also includes neighbor and social relationships. This finding can be translated into a valuable and sustainable tool for leprosy control programs and elimination campaigns by focusing case detection and health promotion activities not only on household contacts but also on at least the neighbors of leprosy cases.

The epidemiology of Mycobacterium leprae: recent insight.

Leprosy is still a health problem in many countries. Because the causative organism, Mycobacterium leprae cannot be cultured in vitro, it is virtually impossible to assess exposure, and the onset of infection and disease. As a consequence, the chain of infection, considered as the relationships between M. leprae, transmission and human host, is poorly understood. Here, we discuss a number of organism-, host- and environmental-related factors which may be incriminated in the dynamic process of the development of leprosy disease. The use of modern molecular and immunological tools has become a valuable addition to epidemiological research. Understanding of the epidemiology of leprosy is a prerequisite for effective control of the disease.

Distribution and persistence of Mycobacterium leprae nasal carriage among a population in which leprosy is endemic in Indonesia.

In order to understand better the relationship among Mycobacterium leprae, its transmission and the human host or the chain of infection which may lead to the development of leprosy, we performed a population survey in which nasal carriage of M. leprae was determined by a specific polymerase chain reaction (PCR), 2 years after an earlier survey in the same population. 1923 persons were registered, 1171 were clinically examined for signs of leprosy, and 418 were tested by PCR. The detection rate of leprosy in the study area had not changed significantly during the 2 years' observation period since the introduction of multi-drug therapy, i.e. 6/1000 compared to 7.7/1000 2 years before. Of 6 newly detected cases, 5 were diagnosed as having paucibacillary leprosy. The presence of M. leprae could be demonstrated by PCR in 2.9% (12/418) of the persons. PCR positivity was not persistent over the 2 years. All the PCR positive persons identified in the first survey were negative in the second, indicating that M. leprae nasal carriage is transient. As in the previous survey, we found evidence for widespread M. leprae nasal carriage as determined by PCR among the general population in an area in which leprosy is endemic. In addition, our data indicated that PCR positivity can occur in certain clusters in the community. This clustering seems to be time-dependent, not necessarily related to the presence of patients.

An epidemiological study of leprosy infection by serology and polymerase chain reaction.

A population-based study has been carried out in two adjacent villages in a highly leprosy-endemic area of South Sulawesi, Indonesia. The prevalence of clinical leprosy was 10.0 per 1000 inhabitants. A total of 1015 serum samples and 1228 nasal swab specimens were collected. IgM antibodies in blood to phenolic glycolipid-I (PGL-I) of Mycobacterium leprae were demonstrated by the gelatin particle agglutination test (MLPA) and by indirect ELISA (IgM-PGL). IgG antibodies to PGL-I (IgG-PGL) and lipoarabinomannan-B (IgG-LAM) were measured by indirect ELISA. The presence of M. leprae in nasal swab specimens was established by a polymerase chain reaction (PCR). The seropositivity rates in the population were 32% for MLPA, 30.8% for IgM-PGL, 6.7% for IgG-PGL, and 11.6% for IgG-LAM. Seropositivity rates for MLPA and IgM-PGL were highest in the younger age groups. There was no difference in seropositivity in any of the tests between household contacts of leprosy patients and noncontacts. The seropositivity rates in the MLPA and IgM-PGL were not randomly distributed among all households. The presence of M. leprae by PCR was demonstrated in 7.8% of the nasal swab specimens. No correlation was found between the results of the PCR and serology. This study indicates that M. leprae is widespread in the population, and that in endemic areas many individuals carry M. leprae in their nasal cavities without having obvious symptoms of leprosy.