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.

Trends in antituberculosis drug resistance in Karonga District, Malawi, 1986-1998.

SETTING: Karonga District, Malawi. OBJECTIVES: To examine long term trends in initial and acquired resistance to antituberculosis drugs in a rural area of Africa. DESIGN: Monitoring of all patients with culture-confirmed tuberculosis 1986-1998. RESULTS: Initial drug resistance results were available for 1121 patients. The proportion resistant to any of the first line drugs (streptomycin, isoniazid, rifampicin or ethambutol) was 9.6%, and to isoniazid 7.2%. Initial resistance to at least isoniazid and rifampicin (multidrug resistance) was seen in only six patients. No initial resistance to ethambutol was found. There was no significant change in initial drug resistance over time. Overall, 22/120 (18%) patients with previous treatment were resistant to at least one drug; only one had multidrug resistance. Acquired resistance decreased over the period of the study. There were no associations between age, sex or human immunodeficiency virus (HIV) status and initial or acquired drug resistance. CONCLUSIONS: Changes in acquired resistance may reflect the recent performance of a control programme more quickly than those in initial resistance. It is encouraging that acquired resistance decreased and levels of multidrug resistance were low despite more than a decade of use of rifampicin. The lack of association between HIV and drug resistance confirms findings elsewhere in Africa.

BCG scars in northern Malawi: sensitivity and repeatability of scar reading, and factors affecting scar size.

SETTING: Karonga district, northern Malawi. OBJECTIVE: To assess the sensitivity and repeatability of BCG scar reading, and factors affecting scar size. DESIGN: Follow-up of individuals aged > 3 months who were recruited into a BCG vaccine trial (1986-1989), and of infants vaccinated in health centres (1989-1991), who were examined for presence and size of BCG scars in subsequent years. All examinations were carried out blind of information on true vaccination status or the results of previous examinations. RESULTS: For trial individuals who were considered scar negative at recruitment and received BCG, the sensitivity of scar reading was > or = 93%, repeatability was > or = 94% for those < 60 years old at vaccination, and only around 1% were assessed as having > 1 BCG scar post-vaccination. For infants vaccinated when < 1 month old in health centres, the proportion who still had recognisable scars 4 years later was < 80%. Scars were larger in individuals with a prior BCG vaccination, and for those aged 15-59 at vaccination the scars were approximately 1 mm larger for males than for females. CONCLUSIONS: A BCG scar is a highly sensitive and repeatable indicator of vaccination status when the vaccine is properly handled, delivered appropriately, and given at over 3 months of age, but not for vaccinations given within 1 month of birth. Given that most vaccinations in the world are given soon after birth, this low sensitivity will lead to both vaccine coverage and vaccine efficacy being underestimated in studies in which vaccination status is inferred from the presence/absence of a distinctive BCG scar. Age-sex patterns identified for scar size show important similarities to those found with skin test responses to tuberculin.

[Therapy of lymphomatoid papulosis with balneo-PUVA-photochemotherapy]]. / Therapie der lymphomatoiden Papulose mit Bade-PUVA-(Balneo-) Photochemotherapie.

Lymphomatoid papulosis is a rare lymphoproliferative disorder of the skin. The standard therapeutic regimen is systemic (oral) photochemotherapy (PUVA). We examined the efficacy of PUVA-bath photochemotherapy in a patient requiring heart transplantation because of idiopathic dilatated cardiomyopathy and a relative contraindication against systemic 8-methoxypsoralen. The 42-years old male patient had suffered for 15 years with itching papules and plaques which clinically, immunohistochemically and molecular biologically were diagnosed as lymphomatoid papulosis. PUVA-bath photochemotherapy with 8-MOP was initiated. After 29 treatments the plaques disappeared completely. After 44 sessions (cumulative UV-A dose 206 J/cm2) the patient's skin almost was clear. PUVA-bath photochemotherapy proved to be a therapeutic alternative to systemic PUVA-treatment in this case of lymphomatoid papulosis.

Tuberculosis: associations with HIV and socioeconomic status in rural Malawi.

Tuberculosis (TB) is associated with human immunodeficiency virus (HIV) infection, increasing age and male sex, but less is known about other risk factors in developing countries. As part of the Karonga Prevention Study in northern Malawi, we conducted a retrospective cohort study in the general population to assess risk factors for the development of TB. Individuals were identified in 1986-89 and TB cases diagnosed up to 1996 were included. TB was confirmed in 62/11,059 (0.56%) HIV negative individuals and 7/182 (3.9%) HIV positive individuals (relative risk 7.1, 95% confidence interval 3.2-15.7). This association was little altered by adjustment for age, sex or socioeconomic factors. The risk of TB was higher in those aged over 30 years than in younger individuals, in men than in women, in those engaged in occupations other than farming than in subsistence farmers, in those living in households with burnt brick dwellings than in those with less well built dwellings, and in those with some schooling than in those with none. These associations persisted after adjusting for age, sex, HIV status and population density. The absolute risks of TB were low in this study due to the passive follow-up and strict diagnostic criteria. The relative risk with HIV was of a similar magnitude to that measured elsewhere. Increased risks of TB with age and in men are expected. Associations with measures of higher socioeconomic status were unexpected. They may reflect a greater likelihood of diagnosis in this group.

[Pruritus of dark skin in hookworm infection]. / Pruritus auf dunkler Haut bei Hakenwurminfektion.

Using the example of a young man from Senegal we would like to point out that in cases of pruritus without an underlying skin disease an intestinal parasitosis might be the cause of the pruritus should the patient come from the tropics. However, it is important to use concentration methods when examining stool specimens so as to be able to diagnose the parasitosis. The causal connection between a pruritus and an intestinal parasitosis needs to be confirmed by a successful treatment.

Tuberculin sensitivity: conversions and reversions in a rural African population.

SETTING: Karonga District, northern Malawi, 1980-1989. OBJECTIVE: To measure and interpret incidence and prevalence of tuberculin sensitivity. DESIGN: Tuberculin testing carried out within two total population surveys. Tuberculin 'positivity' and 'conversion' were defined using criteria recommended by the Tuberculosis Surveillance Research Unit and the American Thoracic Society, respectively. RESULTS: Data on 64,225 tests were available for analysis, including paired results on 6991 individuals tested in both surveys. Frequency distributions of induration varied by age, sex, BCG scar status and zone within the district. The prevalence of 'positivity' was similar in males and females until age 15, then higher among males, and was consistently higher among individuals with than among those without a BCG scar. Tuberculin 'conversion' rates estimated from cross-sectional data ranged from 0.34 to 1.15 per cent per annum. Conversion rates derived from longitudinal data were found to increase linearly with age, and the reversion rates declined rapidly with age among younger individuals. Such trends, which have been reported in other populations, are shown here to arise as an artefact of test instability. Prospective follow-up of observed converters showed greatly increased risks of tuberculosis, in particular during the two years following the second ('converted') test (relative risk > 10). CONCLUSION: Estimation of a convincing 'true' annual risk of infection from tuberculin survey data is not possible from either cross-sectional or longitudinal data, due to misclassifications and the instability of delayed type hypersensitivity over time. An apparent increase in infection risk with age can arise as an artefact of test instability. BCG-induced tuberculin sensitivity declines rapidly in this population in most individuals. It is necessary to consider tuberculin reversions, whether real or apparent, when interpreting tuberculin data on individuals or populations.

[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.

Measurement and determinants of tuberculosis outcome in Karonga District, Malawi.

Evaluation of disease outcome is central to the assessment of tuberculosis (TB) control programmes. In the study reported in this article we examined the factors influencing the measurement of outcome, survival rates during and after treatment, smear conversion rates, and relapse rates for patients diagnosed with TB in a rural area of Malawi between 1986 and mid-1994. Patients with less certain diagnoses of TB were more likely to die than those with confirmed TB, both among those who were seropositive and those who were seronegative to human immunodeficiency virus (HIV). The mortality rate among smear-positive patients with a separate culture-positive specimen was half that of patients with no such diagnostic confirmation. Patients not registered by the Ministry of Health had much higher mortality and default rates than did registered patients. Among smear-positive patients, HIV serostatus was the most important influence on mortality both during and after treatment (crude hazard ratios (95% confidence intervals) = 5.6 (3.0-10) and 7.7 (3.4-17), resp.), but HIV serostatus did not influence smear conversion rates. The initial degree of smear positivity influenced smear conversion rates, but not mortality rates. No significant predictors of relapse were identified. Unless considerable care is taken to include all TB patients, and to exclude nontuberculous patients, recorded TB outcome statistics are difficult to interpret and may be misleading. In populations with high rates of HIV infection, TB target cure rates of 85% are unrealistic. When new interventions are assessed it cannot be assumed that factors which influence the smear conversion rate will also influence the mortality rate.

PIP: Measurement of treatment outcome is central to tuberculosis control programs. A study conducted in Malawi's rural Karonga District in 1986-94 examined factors influencing the measurement of outcome: survival rates during and after treatment, smear conversion rates, and relapse rates for patients diagnosed with tuberculosis. Information was available on 1655 certain, probable, or possible tuberculosis patients. Overall, 22.5% of patients died before the end of treatment, 57.9% completed treatment and were discharged, 4.3% moved out of the district, and 15.3% defaulted or were lost to follow-up. 35% of HIV-positive patients, compared with 11% of HIV-negative patients, died before the end of treatment. Patients with uncertain tuberculosis diagnoses were more likely to die than those with certain diagnoses, regardless of their HIV serostatus. The mortality rate among smear-positive patients with a separate culture-positive specimen was half that of patients with no such diagnostic confirmation. Patients not registered by the Ministry of Health had substantially higher mortality and default rates than registered patients. HIV serostatus was the most important determinant of mortality both during and after treatment in smear-positive patients (crude hazards ratios, 5.6 and 7.7, respectively; 95% confidence intervals, 3.0-10 and 3.4-17, respectively), but HIV status did not influence smear conversion rates. The initial degree of smear positivity influenced smear conversion rates but not mortality rates. No significant predictors of relapse were identified. These findings indicate that tuberculosis outcome statistics may be misleading unless care is taken to include all tuberculosis patients and exclude nontubercular patients.

Detection of HHV-8 DNA in a German patient with classical Kaposi's sarcoma may allow an estimation of the incubation period.

DNA of HHV-8 (Kaposi's sarcoma-associated Herpes virus [KSHV]) was detected in a biopsy of a Kaposi's sarcoma in an elderly male patient from Saxony (East Germany). The diagnosis of classical Kaposi's sarcoma was first made in 1986. During World War II, the patient had been on active service on the Greek Islands of Crete and Rhodes only, he did not travel outside East Germany after the war. It is assumed that the patient was infected during his stay on the islands of Crete or Rhodes, where classical Kaposi's sarcoma is endemic. If so, the incubation period of classical Kaposi's sarcoma could be as long as 40 years.

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.

[Herpes gestationis--oral corticosteroids cannot be avoided]. / Herpes gestationis--an internen Kortikosteroiden führt kein Weg vorbei.

An immunpathologically proven gestational herpes case is presented. Herpes gestationis may begin at any stage of pregnancy but it is usually seen during the second trimester. As a rule oral prednisolone therapy is required. We report on a patient who initially insisted on local therapy only. However this local treatment with steroids proved to be insufficient.