Efficacy of BCG vaccine against leprosy and tuberculosis in northern Malawi

Protection afforded BCG vaccines against tuberculosis and leprosy varies widely between different populations. In the only controlled trial which assessed protective efficacy of BCG (Danish and Pasteur strains) against both diseases; there was slightly more protection against leprosy than against tuberculosis. Protection was estimated at 50 percent or greater against leprosy; and there was no evidence for lower protection against multibacillary than against paucibacillary disease. There was no statistically significant protection by BCG against tuberculosis in this population

Four-year follow-up results of a WHO-recommended multiple-drug regimen in paucibacillary leprosy patients in Malawi

An evaluation of a World Health Organization-recommended multidrug therapy (WHO/MDT) in 499 paucibacillary leprosy patients is described. Patients were followed for 48 months after completion of treatment. Overall relapse rates after treatment were found to be 6.5 per 1000 person years (95 percent confidence interval 3.4-11.4). There were 12 relapses. A relative lack of cell-mediated immunity; as suggested by number of lesions; clinical classification and lepromin test results; and poor compliance with the dapsone component of WHO/MDT; appeared to be associated with a marginally increased risk of relapse. Severe type 1 reactions after completion of treatment occurred in 17 (3.5 percent ) patients; 15/17 during the first 12 months of follow-up. Overall; 12 (2.5 percent ) patients developed new disabilities during or after WHO/MDT

The anatomical distribution of single leprosy lesions in an African population; and its implications for the pathogenesis of leprosy

Data on the anatomical sites of single leprosy lesions found in 635 newly diagnosed and biopsy-confirmed leprosy patients are presented. These patients were found during total population surveys carried out by the Lepra Evaluation Project; a prospective longitudinal study of the epidemiology of leprosy in Karonga District; Northern Malawi. There was a striking excess of single lesions on the face and the back of the arms; compared to the distribution of skin surface area; and a deficit on the legs; regardless of age. There is some evidence for a sex difference in lesion distribution among adults; with facial and arm lesions being relatively more common in females and back lesions being more common in males. The excess of lesions on the face compared to the lower limbs is similar to data from Uganda; but very unlike data from Burma and elsewhere in Asia. Overall; the distribution of lesions does not suggest a pattern reflecting entry of Mycobacterium leprae; nor does it suggest an association with anatomical distribution of the nervous or vascular system. It is argued that the distribution reflects the influence of some 'local' environmental or behavioural factors. Author.90.Z1-542-363-300901121

Disabilities in leprosy patients ascertained in a total population survey in Karonga District; northern Malawi

This paper describes the pattern of disability among 1654 leprosy patients ascertained between 1973 and 1987 in Karonga District; Northern Malawi. Approximately 20 percent of patients identified prior to 1980 had some disability at registration; but this percentage fell to approximately 10 percent with the introduction of total population surveys in the Lepra Evaluation Project. The proportion of patients with disabilities at registration increased with age; was higher among males than females; was higher among borderline and lepromatous than tuberculoid patients; and was higher for passively than for actively detected patients. The risk of developing disabilities among patients without any disabilities at registration was approximately 5 per 1000 person years; and appeared to be slightly higher after the completion of treatment than during treatment

The distribution and implications of BCG scars in northern Malawi

"Reported are data on the BCG scar status of more than 112;000 individuals who were surveyed in Karonga District; northern Malawi; between 1979 and 1984. The age and sex patterns of apparent BCG scars reflect the history of BCG vaccination activities in the district. Repeated independent examinations of large numbers of people revealed that the proportions remaining with the same observed scar status among those initially classified as being scar ""positive"" or scar ""negative"" were each approximately 90 percent . The repeatability of positive scar reading was lower among children and older adults than among young adults aged 15-24 years; and blind follow-up of children known to have been vaccinated as infants in child health clinics indicated that less than 60 percent had a detectable scar 3 years after receiving the vaccine. ""Negative"" repeatability increased consistently with age. The implications of these findings for estimating BCG vaccine uptake and for assessing its efficacy in case-control and cohort studies are discussed. The finding that BCG scars may be difficult to read suggests there is a danger of observer bias that could lead to distortion--in particular; to overestimates of vaccine efficacy."

Seroepidemiological studies of leprosy in northern Malawi based on an enzyme-linked immunosorbent assay using synthetic glycoconjugate antigen

"A total of 6002 blood samples from total population samples in four separate areas within Karonga District; Northern Malawi; were tested for anti-Mycobacterium leprae antibody using an ELISA based on synthetic glycoconjugate antigen. Results are presented using different criteria for seropositivity. Regardless of the criterion used; the proportion of individuals classified as ""positive"" rose to a peak at 20-30 years of age and then fell; and it was higher at all ages in females than in males. There was no difference in seropositivity levels between individuals with or without BCG scars. Although leprosy cases; in particular those with positive smears; had higher antibody levels than nonleprosy cases; analysis of age- standardized data revealed only weak evidence for a correlation between the prevalence rates of clinical leprosy and of seropositivity within the four areas. There was no evidence for higher seropositivity levels in household contacts of leprosy cases compared to noncontacts. The implications of these results for the epidemiology of leprosy in this population are discussed."

Preliminary appraisal of a WHO-recommended multiple drug regimen in paucibacillary leprosy patients in Malawi

A study was undertaken within the framework of the LEPRA Evaluation Project and the LEPRA Control Project in Malawi (Central Africa) to study the incidence rates of type 1 reactions and of relapses in paucibacillary leprosy patients treated with the current World Health Organization-recommended multiple drug regimen (WHO/MDT). Of 503 patients recruited into the study; 488 were reviewed at the end of treatment and 480 have now been followed for 1 year after completion of treatment. At the end of treatment the skin lesions had completely disappeared in 27.4 percent ; but were judged to be still active in 4.3 percent . During the follow-up period two patients were found with new active skin lesions; giving a relapse rate of 4.17 (2 of 480) per 1000 person years during the first year after completion of WHO/MDT (95 percent confidence interval 1.14 to 15.06 per 1000 person years). The incidence rate of marked type 1 reaction (renewed inflammation in previously inactive lesions) during the first year after completion of WHO/MDT was 47.8 per 1000 person years in self-reporting patients but zero in patients identified by active case finding. Data are presented which suggest that the incidence rate of late type 1 reactions is closely related to the classification and stage of the disease at detection

Leprosy in Malawi. 2. Background; design and prospects of the Karonga Prevention Trial; a leprosy vaccine trial in northern Malawi

The Karonga Prevention Trial is the largest vaccine trial ever mounted in Africa. It is designed to test two hypotheses: (i) whether the addition of killed Mycobacterium leprae can increase the protection against leprosy (and tuberculosis) imparted by BCG alone; and (ii) whether repeating a BCG vaccination can increase upon the protection provided by an initial dose. The rationale and design of the trial are discussed in relation to the history of vaccination against leprosy and to several contending arguments which determined the ultimate protocol. The potential of the trial to reveal statistically significant differences between the vaccines being compared is discussed; as are the implications of possible results for future research and control of leprosy

Leprosy in Malawi. 1. Sensitivity and specificity of the diagnosis and the search for risk factors for leprosy

The sensitivity and specificity of the diagnosis of leprosy in the context of a total population survey are examined. It is apparent that diagnostic tools are unsatisfactory with regard to reaching a highly sensitive and specific case definition of paucibacillary leprosy; particularly in actively found suspects. Histopathological examination of 4 mm punch biopsy specimens contributed appreciably to both the sensitivity and specificity of the diagnosis of leprosy; though there was evidence for false positive and false negative histopathology results. The needs for high sensitivity during the intake phase of a vaccine trial and for high specificity during follow-up surveys for risk factors are discussed

Histopathological examination of skin biopsies from an epidemiological study of leprosy in northern Malawi

"This report describes the histopathological findings in 686 biopsies obtained from 664 individuals during the course of a total population survey for leprosy in Northern Malawi. The criteria for the selection of cases for biopsy; the biopsy technique using a 4-mm punch; fixation method; transport of biopsies from Africa to the United Kingdom; and the method of coding histopathological results are described. Fifty-two percent (354) of the biopsies showed definite evidence of leprosy on histopathological examination. Using the Ridley-Jopling system; these biopsies were classified as follows: TT = 60 (17 percent ); TT/BT = 68 (19 percent ); BT = 194 (55 percent ); BT/BB = 4 (1 percent ); BB = 4 (1 percent ); BB/BL = 4 (1 percent ); BL = 7 (2 percent ); BL/LL = 3 (1 percent ); LL = 6 (2 percent ). In addition; four (1 percent ) biopsies were classified as ""indeterminate"" on histology; meaning that although there was evidence of leprosy it was not possible to provide a precise classification. A further 117 biopsies (17 percent of the total) had abnormal changes; often including epithelioid cell granulomas; possibly caused by leprosy but lacking specific criteria for that diagnosis. Finally; 203 (30 percent ) of the biopsies had nonspecific (often minimal) changes; and 11 (2 percent ) of the total showed evidence of some dermatological condition other than leprosy. Histopathological examination of biopsies in this study confirmed the clinical classification in 98 percent of the cases in which the histopathologist found evidence of leprosy; and supplied further evidence for the very high proportion of paucibacillary cases in this part of the world."

Sensitization studies with potential leprosy vaccine preparations in northern Malawi

"This paper describes a comparison between BCG alone and two different doses of killed Mycobacterium leprae; with or without BCG; in stimulating skin-test sensitivity to two different soluble antigens prepared from M. leprae. Skin test conversion was assessed three months after vaccination. Significant rates of skin test conversion were stimulated by each of the vaccines to both skin test antigens; but the observed conversion rates differed markedly as measured by the two antigens. All of the vaccines caused ulcers at the site of injection in most subjects; and these local reactions are described. A combined vaccine containing 0.03 mg BCG plus 5 X 10(7) killed M. leprae induced high rates of ""conversion"" to both skin tests but caused local reactions slightly larger than those caused by BCG alone. The implications of these findings for selection of an optimal vaccine formulation for use in large-scale preventive trials are discussed"

Comparability among histopathologists in the diagnosis and classification of lesions suspected of leprosy in Malawi

Identical slides from 200 biopsies obtained from individuals suspected of having leprosy during the course of an epidemiological survey in Northern Malawi were examined sequentially and independently by three histopathologists; using a standard protocol to report their findings. Their results are compared among themselves and with a standardized clinical assessment of each subject. There was more agreement among the histopathologists as to classification of leprosy cases than there was on the diagnosis of leprosy. The proportion of biopsies considered to show definite evidence of leprosy varied from 39 percent to 58 percent among the histopathologists. An appreciable additional proportion of biopsies (11.5 percent to 38.5 percent for the three histopathologists) was considered to show evidence suggestive but not pathognomonic of leprosy. Although there was; in general; good agreement on classification; the proportion of biopsies considered to show evidence of indeterminate leprosy varied from 1.5 percent to 21.5 percent among the three histopathologists. This suggests that some of the reported differences in the prevalence and proportion of indeterminate leprosy in different populations is due to terminology alone. A follow-up meeting of the study participants revealed that many of the differences in diagnosis certainty were due to difficulties in interpreting evidence of nerve involvement. It is recommended that greater attention be paid to the difficulties of diagnosing leprosy on histopathological as well as clinical grounds. A revised standard protocol for reporting histopathological evidence of leprosy is presented

Protective efficacy of BCG against leprosy in Northern Malawi

The effectiveness of a BCG vaccination programme in protecting against leprosy was assessed by case-control and cohort analyses of data from the Lepra Evaluation Project in Karonga District; Northern Malawi. Results indicate that BCG provides at least 50 percent protection against leprosy in this population and that protection is independent of age; sex; schooling status; or location within the project area. Agreement between these findings and those from a controlled trial in Uganda indicates that BCG is sufficiently effective against leprosy in East and Central Africa to be considered an important element of leprosy control in that region