Use of Short Tandem Repeat Sequences to Study Mycobacterium leprae in Leprosy Patients in Malawi and India

Molecular typing has provided an important tool for studies of many pathogens. Such methods could be particularly useful in studies of leprosy, given the many outstanding questions about the pathogenesis and epidemiology of this disease. The approach is particularly difficult with leprosy, however, because of the genetic homogeneity of M. leprae and our inability to culture it. This paper describes molecular epidemiological studies carried out on leprosy patients in Malawi and in India, using short tandem repeat sequences (STRS) as markers of M. leprae strains. It reveals evidence for continuous changes in these markers within individual patients over time, and for selection of different STRS-defined strains between different tissues (skin and nerve) in the same patient. Comparisons between patients collected under different circumstances reveal the uses and limitations of the approach—STRS analysis may in some circumstances provide a means to trace short transmission chains, but it does not provide a robust tool for distinguishing between relapse and reinfection. This encourages further work to identify genetic markers with different stability characteristics for incorporation into epidemiological studies of leprosy

Leprosy among Patient Contacts: A Multilevel Study of Risk Factors

Leprosy is an infectious disease that can lead to physical disabilities, social stigma, and great hardship. Transmitted from person to person, it is still endemic in developing countries, like Brazil and India. Effective treatment has been available since 1960, but early diagnosis of the disease remains the most effective way to stop the transmission chain and avoid late diagnoses and subsequent disabilities. Knowledge of the risk factors for leprosy can facilitate early detection; therefore, our study aimed to investigate the factors presented by leprosy patients and their contacts, who are considered at highest risk of contracting the disease. We studied 6,158 contacts of 1,201 patients under surveillance from 1987 to 2007 in a Public Health Care Center in the City of Rio de Janeiro, Brazil. We evaluated the ways patient and contact demographics and epidemiological characteristics were associated with the detection of leprosy. Statistical analyses took into account both individual and group characteristics and their interrelationships. The main characteristics facilitating the contraction of leprosy among contacts were shown to be consanguinity and household association. Conversely, the bacillary load index of leprosy patients was the principle factor leading to disease among their contacts

BCG Revaccination Does Not Protect Against Leprosy in the Brazilian Amazon: A Cluster Randomised Trial

BCG is a vaccine developed and used to protect against tuberculosis, but it can also protect against leprosy. In Brazil, children receive BCG at birth, and since 1996 a trial has been conducted to find out if a second dose of BCG administered to schoolchildren gives additional protection against tuberculosis. We use this trial to find out if such vaccination protects against leprosy. The trial was conducted in the Brazilian Amazon, involving almost 100,000 children aged 7–14 years who had received neonatal BCG. Half of them received a second dose of BCG at school, and the other half did not. We followed the children for 6 years and observed that there were as many new cases of leprosy in the vaccinated children as in the unvaccinated children. Therefore, we concluded that a second dose of BCG given at school age in the Brazilian Amazon offers no additional protection against leprosy

Risk Factors for Buruli Ulcer: A Case Control Study in Cameroon

Buruli ulcer (BU) is a neglected tropical infectious disease caused by Mycobacterium ulcerans. While BU is associated with areas where the water is slow-flowing or stagnant, the exact mechanism of transmission of the bacillus is unknown, impairing efficient control programs. Two hypotheses are proposed in the literature: previous trauma at the lesion site, and transmission through aquatic insect bites. Using results from a face-to-face questionnaire, our study compared characteristics from Cameroonian patients with Buruli ulcer to people without Buruli ulcer. This latter group of people was chosen within the community or within the family of case patients. The statistical analysis confirmed some well-known factors associated with the presence of BU, such as wearing short lower-body clothing while farming, but it showed that the use of bed nets and the treatment of wounds with leaves is less frequent in case patients. These newly identified factors may provide new insight into the mode of transmission of M. ulcerans. The implication of domestic or peridomestic insects, suggested by the influence of the use of bed nets, should be confirmed in specific studies

Control of (multi)drug resistance and tuberculosis incidence over 23 years in the context of a well-supported tuberculosis programme in rural Malawi.

BACKGROUND: The rise in tuberculosis (TB) incidence following generalized HIV epidemics can overwhelm TB control programmes in resource-limited settings, sometimes accompanied by rising rates of drug resistance. This has led to claims that DOTS-based TB control has failed in such settings. However, few studies have described the effect of a sustained and well-supported DOTS programme on TB incidence and drug resistance over a long period. We present long-term trends in incidence and drug resistance in rural Malawi. METHODS: Karonga District in northern Malawi has an adult HIV prevalence of ≈ 10%. A research group, the Karonga Prevention Study, collaborates with the National Tuberculosis Programme to support core TB control activities. Bacteriological, demographic and clinical (including HIV status) information from all patients starting TB treatment in the District have been recorded since 1988. During that period isolates from each culture-positive TB patient were exported for drug sensitivity testing. Antiretroviral therapy (ART) has been widely available since 2005. RESULTS: Incidence of new smear-positive adult TB peaked at 124/100,000/year in the mid-90 s, but has since fallen to 87/100,000/year. Drug sensitivity information was available for 95% (3132/3307) of all culture-positive cases. Initial resistance to isoniazid was around 6% with no evidence of an increase. Fewer than 1% of episodes involved a multi-drug resistant strain. DISCUSSION: In this setting with a generalised HIV epidemic and medium TB burden, a well-supported DOTS programme enhanced by routine culture and drug sensitivity testing may well have reduced TB incidence and maintained drug resistance at low levels

Estimating the extent of household contact misclassification with index cases of disease in longitudinal studies using a stochastic simulation model

Background: Household contact with an index case of an infectious disease is a known risk factor for infection transmission. However, such contact may be underestimated due to the dynamic nature of households, particularly in longitudinal studies. Such studies generally begin with contact defined at a single point in time ('snap-shot'), leading to contact misclassification for some individuals who actually experienced contact before and after the snapshot. Objective: To quantify contact misclassification with index cases of disease in households. Methods: Historical data of 112,026 individuals from 17,889 households from an epidemiological study on leprosy in northern Malawi were used. Individuals were interviewed in the early 1980s and followed up over 5 years. It was possible to trace whether individuals died, changed household within the area, or moved out of the area between the two surveys. Using a 10% sample of households as the starting population and parameters for demographic and household changes over 5 years, the extent of contact misclassification was estimated through a simulation model of household dynamics, which traced contact with index cases in households over time. The model thereafter compared initial contact status and 'true' contact status generated from simulations. Results: The starting population had 11,401 individuals, 52% female, and 224 (2%) leprosy index cases. Eleven percent of the households had at least one index case resident and 10% (1, 177) of non-case individuals were initial contacts. Sensitivity of initial contact status ranged from 0.52 to 0.74 and varied by age and sex. Sensitivity was low in those aged 20-29 and under 5 years but high in 5- to 14-year-olds. By gender, there were no differences among those aged under 5; females had lower sensitivity among those aged under 20 and higher for those above 30, respectively. Sensitivity was also low in simulations of long incubation periods. Conclusion: This work demonstrates the implications of changes in households on household contact-associated disease spread, particularly for long durations of follow-up and infections with long incubation periods where earlier unobserved contact is critical