Linkage analysis of susceptibility to leprosy type using an IBD regression method.

Leprosy is a chronic disease caused by infection with Mycobacterium leprae, which is manifested across a wide clinical spectrum. There is evidence that susceptibility both to leprosy per se and to the clinical type of leprosy is influenced by host genetic factors. This paper describes the application of an identity by descent regression search for genetic determinants of leprosy type among families from Karonga District, Northern Malawi. Suggestive evidence was found for linkage to leprosy type on chr 21q22 (P<0.001). The methodological implications of the approach and the findings are discussed.

[Anetoderma Schwenninger-Buzzi in a dark-skinned patient]. / Anetodermie Schwenninger-Buzzi auf dunkler Haut.

A 10-year-old boy in Uganda developed primary anetoderma (Schwenninger-Buzzi). It is important not to confuse anetoderma with BL leprosy in spite of some superficial resemblance of the two diseases. Primary anetoderma is probably extremely rare in patients with dark skin although this may partly be due to a lack of dermatologists in Africa who could diagnose the disease.

Environmental mycobacteria in northern Malawi: implications for the epidemiology of tuberculosis and leprosy.

More than 36000 individuals living in rural Malawi were skin tested with antigens derived from 12 different species of environmental mycobacteria. Most were simultaneously tested with RT23 tuberculin, and all were followed up for both tuberculosis and leprosy incidence. Skin test results indicated widespread sensitivity to the environmental antigens, in particular to Mycobacterium scrofulaceum, M. intracellulare and one strain of M. fortuitum. Individuals with evidence of exposure to 'fast growers' (i.e. with induration to antigens from fast growers which exceeded their sensitivity to tuberculin), but not those exposed to 'slow growers', were at reduced risk of contracting both tuberculosis and leprosy, compared to individuals whose indurations to the environmental antigen were less than that to tuberculin. This evidence for cross protection from natural exposure to certain environmental mycobacteria may explain geographic distributions of mycobacterial disease and has important implications for the mechanisms and measurement of protection by mycobacterial vaccines.

[Cutaneous manifestation of cysticercosis]. / Kutane Manifestation der Zystizerkose.

Cysticercosis, an infection with the larva of Taenia solium, is caused by the accidental ingestion of the parasite's eggs. In many countries of the Third World, cysticercosis, and especially neurocysticercosis, is a widespread problem. A patient from Northern Malawi presented not only with cysticercosis but also with BT leprosy and pityriasis versicolor. Dermatologists should be familiar with the clinical picture of cysticercosis in order to make an early diagnosis in patients from at-risk areas.

[Disabilities observed in new cases of leprosy diagnosed in the Bamako district (Mali) in 1994]. / Les infirmités observées chez les nouveaux cas de lèpre dépistés dans le district de Bamako (Mali) en 1994.

Our study concerns 244 new cases of leprosy diagnosed in the Bamako district in 1994. 154/244 patients could be contacted and were examined in the Leprosy Department of the Marchoux Institute in Bamako. Results showed that the presence of leprosy induced physical disabilities was associated with male gender (59%), advanced age (68%) and multibacillary disease (68%). Disabilities were also more frequent among patients having a rural or manual occupation at the time of screening or afterwards. There was a significant increase (p < 0.001) in the prevalence of disabilities when comparing patients at the time of diagnosis (29%) and thereafter (48%). This means that in 40% of disability cases, lesions developed during or after the treatment. Disabilities were predominantly observed in hands (33%) and feet (29%) with more frequent lesions in lateral popliteal, superior ulnar and posterior tibial nerves. Our results seem to demonstrate the inadequacy of preventive measures and management. This stresses the need for adequate prevention and therapy of leprosy induced disabilities in order to obtain proper eradication of leprosy induced health problems.

Delayed-type hypersensitivity to Mycobacterium leprae soluble antigens as a test for infection with the leprosy bacillus.

BACKGROUND: Mycobacterium leprae (M. leprae) soluble antigen (MLSA) reagents have been developed with the aim of finding a reagent, comparable to tuberculin, which could identify individuals infected with the leprosy bacillus. They have yet to be evaluated fully in human populations. METHODS: More than 15000 individuals living in a leprosy endemic area of northern Malawi were skin tested with one of five batches of MLSA prepared using two different protocols. The main difference in preparation was the introduction of a high G centrifugation step in the preparation of the last three ('second-generation') batches. RESULTS: The prevalence of skin-test positivity (delayed-type hypersensitivity (DTH)) and association with the presence of a BCG scar were greater for first (batches A6, A22) than second (batches AB53, CD5, CD19) generation reagents. The association of positivity with M. leprae infection was investigated by comparing results among known (household) contacts of leprosy cases, and among newly diagnosed leprosy patients with those in the general population. While positivity to 'first-generation' antigens appeared to be associated with M. leprae infection, positivity to later antigens was unrelated either to exposure to leprosy cases or presence of leprosy disease. There were geographical differences in the prevalence of DTH to the various batches, probably reflecting exposure to various mycobacteria in the environment. CONCLUSIONS: Our results suggest that the 'second-generation' batches have lost antigens that can detect M. leprae infections, but that they retain one or more antigens which are shared between M. leprae and environmental mycobacteria. Natural exposure to these both sensitizes individuals and provides natural protection against M. leprae infection or disease. Identification of antigens present in these groups of skin test reagents may assist in production of improved skin test reagents.

Epidemiologic aspects of scabies in Mali, Malawi, and Cambodia.

BACKGROUND: The prevalence rates of scabies are compared in Bamako, Mali, Karonga District, Malawi, and Battambang Province, Cambodia. METHODS: In Mali, children attending three different urban schools catering for different socio-economic levels were examined specifically for scabies. In Malawi, data were collected during a total population survey for leprosy. In Cambodia, a sample survey was carried out in a rural area to determine the prevalence of leprosy and other skin diseases. RESULTS: In Mali, the prevalence rate of scabies among all the children examined was 4% (44/1103), but only 1.8% (7/388) in the higher socio-economic group. In Malawi, the overall prevalence rate of scabies was 0.7% (408/61,735). The highest rate (1.1%) was found among children 0-9 years of age. In Cambodia, the overall prevalence in the 13 villages screened was 4.3% (645/14,843). The highest rate (6.5%) was found among children 0-9 years of age. CONCLUSIONS: Scabies was most prevalent among children in Cambodia and Malawi, but there were considerable differences in the overall rates between the two areas studied. The data from all three countries indicate that poor socio-economic conditions, in particular crowding and public water supplies, are risk factors for scabies.

Household and dwelling contact as risk factors for leprosy in northern Malawi.

Data on household and dwelling contact with known leprosy cases were available on more than 80,000 initially disease-free individuals followed up during the 1980s in a rural district of northern Malawi. A total of 331 new cases of leprosy were diagnosed among them. Individuals recorded as living in household or dwelling contact with multibacillary patients at the start of follow-up were at approximately five- to eightfold increased risk of leprosy, respectively, compared with individuals not living in such households or dwellings. Individuals living in household or dwelling contact with paucibacillary cases were both at approximately twofold increased risk. The higher risk associated with multibacillary contact and the fact that dwelling contact entailed a greater risk than household contact if the association was with multibacillary, but not with paucibacillary, disease suggest that paucibacillary cases may not themselves be sources of transmission, but rather just markers that a household has had contact with some (outside) source of infection. When household contact was considered alone, the risks of disease were appreciably higher for younger than for older contacts and for male compared with female contacts. Despite the elevated risk of leprosy associated with household or dwelling contact, only 15% of all incidence cases arose among recognized household contacts. Given the dynamic nature of household membership and consequent misclassification of contact status, the true contribution to overall incidence of contact within household or dwelling settings is likely to be much higher than this, perhaps 30% or higher. Considering the predilection of males for infectious multibacillary forms of the disease, the transmission of Mycobacterium leprae at an early age, in particular to males, may be of particular importance for the persistence of leprosy in endemic communities. Although residential contact with a multibacillary case is the strongest known determinant of leprosy risk, the vast majority of such contacts never manifest disease, which indicates a crucial role for genetic and/or environmental factors in the transmission of M. leprae infection and/or the pathogenesis of clinical leprosy.

Comparison of bacillary indexes in slit-skin smears, skin and nerve biopsies; a study from Malawi.

Data analyzed in this paper were collected within the framework of the Lepra Evaluation Project, an epidemiological study of leprosy in Karonga District, northern Malawi. For 212 patients information on the number of skin lesions, slit-skin smear and skin biopsy results were available. Among 61 patients with a single lesion none were slit-skin-smear positive and two had bacilli detected in skin biopsies. In contrast, among 119 patients with four or more lesions 34 (28.6%) versus 59 (49.6%) had bacilli detectable in slit-skin smears or skin biopsies, respectively. In a further 47 patients skin biopsy results could be compared with split-nerve biopsy results. In 20 of 47 patients the bacterial indexes (BIs) were identical in skin and nerve biopsies, while in 26 of 47 patients the BIs were higher in nerve than in skin biopsies. This difference, which is consistent with several other studies in the literature, provides an insight into the pathogenesis of leprosy.

Does bacille Calmette-Guérin scar size have implications for protection against tuberculosis or leprosy?

SETTING: Total population study in Karonga District, northern Malawi, in which the overall vaccine efficacy of bacille Calmette-Guérin (BCG) has been found to be -7% against tuberculosis and 54% against leprosy. OBJECTIVE: To examine the relationship between BCG scar size and protection against tuberculosis and leprosy. DESIGN: Cohort study in which 85,134 individuals were screened for tuberculosis and 82,265 for leprosy between 1979 and 1984, and followed up between 1986 and 1989. RESULTS: Of the BCG scar positive individuals whose scars were measured, 31/3 2471 were later identified with tuberculosis and 81/31 879 with leprosy. In 19,114 individuals, of whom 17 developed tuberculosis, tuberculin induration was measured at first examination. Mean scar sizes increased with increasing tuberculin induration in all except the oldest individuals. Mean scar sizes were lowest in individuals aged < 10 years, highest in individuals aged 10-29 years and intermediate in older individuals. There was some evidence (P = 0.08) for an increase in tuberculosis risk with increasing scar size, which probably reflects the known correlation between scar size and tuberculin status at the time of vaccination. There was no clear association between BCG scar size and leprosy incidence. CONCLUSIONS: We find no evidence that increased BCG scar size is a correlate of vaccine-induced protective immunity against either tuberculosis or leprosy.

Geographic determinants of leprosy in Karonga District, Northern Malawi.

BACKGROUND: Geographical differences in leprosy risk are not understood, but may provide clues about the natural history of the disease. We report an analysis of the geographical distribution of leprosy in Karonga District, a rural area of Northern Malawi, between 1979 and 1989. METHODS: Cohort study of the incidence of leprosy based on two total population surveys. Area of residence was determined using aerial photographs, which allowed identification of households, as well as location of roads, rivers and the lake shore. RESULTS: Incidence rates were between two and three times higher in the north compared to the south of the district, and lowest in the semi-urban district capital. The most obvious environmental difference between these regions is the north's higher rainfall and more fertile soil. There was no overall association between leprosy incidence and population density, although highest rates were observed in the least densely populated areas. Looking at the entire district, incidence rates increased with increasing distance from a main road, but declined with increasing distance from a river or from the shore of Lake Malawi. The negative association with proximity to rivers may reflect the larger number of rivers in the north of the district. Apparent differences in incidence rates between groups speaking different languages reflected confounding by area of residence. CONCLUSIONS: There is a marked variation, not explained by socioeconomic or cultural factors, in the incidence of leprosy within Karonga District. Our results are consistent with a theme in the literature associating the environment, particularly proximity to water, with leprosy.

PIP: Researchers do not understand how geographical differences relate to the risk of contracting leprosy. The study of such differences, however, may provide clues about the natural history of the disease. The authors report findings from an analysis of the geographical distribution of leprosy in Karonga District, a rural area in Northern Malawi, between 1979 and 1989. Findings are based data from two total population surveys. The areas of residence were determined using aerial photographs, which allowed the identification of households, roads, rivers, and the lake shore. Analysis revealed that incidence rates were 2-3 times higher in the north compared to the south of the district, and lowest in the semi-urban district capital. The north has higher rainfall and more fertile soil. There was no overall association between the incidence of leprosy and population density, although the highest rates were observed in the least densely populated areas. Considering the entire district, incidence rates increased with increasing distance from a main road, but declined with increasing distance from a river or from the shore of Lake Malawi. This negative association with proximity to rivers may reflect the larger number of rivers in the north of the district. Apparent differences in incidence rates between groups speaking different languages reflected confounding by area of residence. The authors conclude that there is a marked variation, not explained by socioeconomic or cultural factors, in the incidence of leprosy within Karonga District. These results are consistent with literature which associates the environment, especially proximity to water, with leprosy.

Prevalence rates of leprosy in Cambodia; results of a sample survey.

A total population survey was carried out in early 1994 in 13 villages around Battambang (northwest Cambodia). Coverage was 87.5% (12,992 out of 14,842). Among the 12,922 household members examined 21 known patients and 20 new patients were found. Five of the 21 known and none of the newly found patients had disabilities. Among males total prevalence rates (known and newly found patients combined) appear to rise up to the age of 25 to 34, after which rates remain roughly stable until they start to decline in the 65 to 74-year age group. Among females prevalence rates reach a plateau in the 35 to 44-year age group.

Testing for antibody to human immunodeficiency virus type 1 in a population in which mycobacterial diseases are endemic.

During a large epidemiologic study in the Karonga District of northern Malawi, serum samples from 139 patients with incident leprosy, 124 with newly diagnosed leprosy, 277 patients with incident tuberculosis, and 2296 controls were tested for antibodies to human immunodeficiency virus. Sera were tested according to a four-test protocol using two ELISAs and two particle agglutination assays. Overall, 188 samples were considered positive, 2634 were considered negative, and 14 were indeterminate. All 18 available positive specimens from leprosy patients, a random sample of 14 positive specimens from tuberculosis patients, and 15 positive specimens from controls were tested by Western blot. There was no evidence of substantial numbers of ELISA false-positives in any patient group or among controls.

Leprosy. The beginning of an end to a public health problem?

Incidence rates of leprosy seem to be falling in most countries around the world, despite the HIV epidemic. Among the reasons for the declining rates are changing socioeconomic conditions and high BCG vaccination coverage. The numbers of people disabled by leprosy, however, are more important than incidence rates of leprosy per se. The issue of the disabled will remain a public health problem for many decades to come.

Patterns of initial and acquired antituberculosis drug resistance in Karonga District, Malawi.

There is concern that drug-resistant tuberculosis is increasing and may be concentrated among HIV-positive patients. Little information is available from developing countries, where surveillance studies are often unable to distinguish resistance in previously untreated patients (initial resistance) from resistance acquired following drug therapy, and where information on the HIV status of the patients is rare. Initial resistance patterns reflect the strains being transmitted in the community. We have studied patterns of resistance in northern Malawi, where the Lepra Evaluation Project has been collecting data on drug resistance since 1986. Initial drug sensitivity results were available for 373 new cases of tuberculosis. Initial resistance to at least one drug was found in 44 of these patients (11.8%, 95% CI 8.5-15.1): 13 were resistant to streptomycin alone, 13 to isoniazid alone, and 17 to more than one drug. Only 3 patients showed initial rifampicin resistance-1 in isolation, 1 in combination with streptomycin, and 1 with triple resistance. Drug resistance was not related to age, sex, or HIV status of the patient and there was no evidence of any increase over the period studied. There was no evidence of geographic clustering of the resistant strains, or of any increased risk of resistant strains in households with previous tuberculosis cases. Acquired resistance during follow-up was found in 5 of 329 patients with documented initially fully sensitive strains. 5 patients with initial resistance seemed to show reversion to sensitivity. The absence of an increase in drug resistance, despite an increase in tuberculosis cases over the period, is encouraging for the control programme. It emphasises the need to collect information from many areas before assuming that increases in antituberculosis drug resistance are occurring worldwide.