Evaluación de Técnicas Serodiagnósticas para la Lepra. Estudio en una población endémica del sur de la India / tab

Para evaluar la utilidad de los antígenos disacárido natural (PGL1) y 35 kDa en determinaciones serológicas de lepra sobre todo para la detección de grupos de alto riesgo para contraer la enfermedad, se llevó a cabo este estudio en una población endémica del sur de la India. De 3.346 casos y sus convivientes y vecinos, se obtuvieron muestras de suero de 2.994 y 2.875 individuos y se cribaron para detectar antígenos frente al PGL1 y 35 kDa respectivamente. Mientras que la positividad total para contactos y casos de lepra era del 3,3% para anticuerpos PGL1, la positividad para el anticuerpo 35 kDa era del 6,3%. La seropositividad para la población contacto era del 2,7% y 5,4% para anticuerpos PGL1 Y 35 kDa, respectivamente. Los pacientes lepromatosos y bordeline lepromatosos presentaron positividades del 35,1% para anticuerpos PGL1 y 45,7% para el 35 kDa. El seguimiento de los contactos reveló que la mayoría de los analizados permanece (>90%9 seronegativos para ambos anticuerpos y la mayoría de nuevos casos se presentaron precisamente en el grupo seronegativo. El ensayo demuestra claramente que las técnicas serológicas específicas no son lo suficientemente sensibles para su aplicación, tanto para el diagnóstico como para identificar individuos en riesgo de contraer lepra en esta población endémica del sur de la India (AU)

In order to evaluate the usefulness of natural disaccharide (PGL1) and 35 kDa antigens based serology in diagnosis of leprosy and in detecting high risk groups for leprosy, this study was conducted in an endemic population in South India. 90%) remained seronegative for both the antibodies and most of the new cases emerged form the seronegative group. The study clearly indicates that specific serological assays are not sensitive enough for application, both for diagnosis and for identifying any individuals at risk for leprosy in the south Indian endemic population (AU)

Utility of serodiagnostic tests for leprosy: a study in an endemic population in South India.

In order to evaluate the usefulness of natural disaccharide (PGL1) and 35 kDa antigens based serology in diagnosis of leprosy and in detecting high risk groups for leprosy, this study was conducted in an endemic population in South India. Out of 3346 cases and their households and neighbouring household contacts, serum samples from 2994 and 2875 individuals were screened for antibodies against PGL1 and 35kDa antigens respectively. While the overall positivity for contacts and leprosy cases was 3.3% for PGL1 antibody, the positivity for 35 kDa antibody was 6.3%. The positivity for contact population was 2.7% and 5.4% for PGL1 and 35 kDa antibodies, respectively. Lepromatous and borderline lepromatous patients showed positivity of 35.1% for PGL1 antibody and 45.7% for 35 kDa antibody. Follow-up of contacts showed that the majority (>90%) remained seronegative for both the antibodies and most of the new cases emerged from the seronegative group. The study clearly indicates that specific serological assays are not sensitive enough for application, both for diagnosis and for identifying any individual at risk for leprosy in the south Indian endemic population.

Unexplained acute severe methaemoglobinaemia in a young adult.

This report describes the case of an otherwise healthy young adult female, who presented with a 12-h history of progressive bluish discolouration of lips and limbs. She denied ingesting or inhaling any drug or substance. A high PaO2 in the presence of 'cyanosis' and 'dark blood' led to suspicion of methaemoglobinaemia. Co-oximetry revealed the methaemoglobin level to be 47%. A urinary screen for drugs of abuse was negative and blood methaemoglobin reductase activity was within the normal range. The aetiology was traced to dapsone detected in the urine by gas chromatography/mass spectrometry. The therapeutic and diagnostic approach in such patients is discussed.

Comparative leprosy vaccine trial in south India.

This report provides results from a controlled, double blind, randomized, prophylactic leprosy vaccine trial conducted in South India. Four vaccines, viz BCG, BCG+ killed M. leprae, M.w and ICRC were studied in this trial in comparison with normal saline placebo. From about 3,00,000 people, 2,16,000 were found eligible for vaccination and among them, 1,71,400 volunteered to participate in the study. Intake for the study was completed in two and a half years from January 1991. There was no instance of serious toxicity or side effects subsequent to vaccination for which premature decoding was required. All the vaccine candidates were safe for human use. Decoding was done after the completion of the second resurvey in December 1998. Results for vaccine efficacy are based on examination of more than 70% of the original "vaccinated" cohort population, in both the first and the second resurveys. It was possible to assess the overall protective efficacy of the candidate vaccines against leprosy as such. Observed incidence rates were not sufficiently high to ascertain the protective efficacy of the candidate vaccines against progressive and serious forms of leprosy. BCG+ killed M. leprae provided 64% protection (CI 50.4-73.9), ICRC provided 65.5% protection (CI 48.0-77.0), M.w gave 25.7% protection (CI 1.9-43.8) and BCG gave 34.1% protection (CI 13.5-49.8). Protection observed with the ICRC vaccine and the combination vaccine (BCG+ killed M. leprae) meets the requirement of public health utility and these vaccines deserve further consideration for their ultimate applicability in leprosy prevention.

Sensitization potential and reactogenicity of BCG with and without various doses of killed Mycobacterium leprae.

A study was conducted in 997 individuals in two villages in south India to find the acceptability and sensitizing effect of the antileprosy combination vaccine of BCG plus killed Mycobacterium leprae (KML). Three preparations of the combination, BCG 0.1 mg + 6 x 10(8) KML (I), BCG 0.1 mg + 5 x 10(7) KML (II), and BCG 0.1 mg + 5 x 10(6) KML (III), along with BCG 0.1 mg (IV), and normal saline (V), were used in the study. Each individual received one of the above five preparations by random allocation. They were also tested with Rees' M. leprae soluble skin-test antigen (MLSA) and lepromin-A, both at intake and 12 weeks after vaccination. Reactions to Rees' MLSA were measured after 48 hr; those to lepromin-A after 48 hr and 3 weeks. The character and size of the local response at the vaccination site were recorded at 3, 8, 12, 15, and 27 weeks after vaccination. The mean sizes of postvaccination sensitization to both Rees' MLSA and lepromin-A in the vaccine groups were significantly larger than those in the normal saline group, clearly demonstrating the ability of the vaccines to induce sensitization as measured by responses to the two skin tests. The sensitizing effect was the highest following vaccination with vaccine I. It was not significantly different for vaccines II, III, and IV, although, generally, a dose-response effect was observed. The sensitizing effect attributable to the vaccine was more clearly seen in children than in adults. The above conclusions were the same irrespective of which results were considered, reactions to Rees' MLSA or Fernandez or Mitsuda reactions to lepromin-A. A significant finding of the study was that at intake the Mitsuda reactions provided a measure of sensitizing effect due to vaccine. The healing of vaccination lesions was uneventful. In more than 90% of vaccinated individuals, the lesions had healed by the 12th week in vaccine groups II, III, and IV, and by the 15th week in vaccine group I. The results showed that vaccination with BCG or combination vaccines was equally safe in individuals with or without previous BCG scars. Thirteen persons, aged 10 years or older, developed suppurative lymphadenitis around the 8th week (7 in vaccine group I, 3 each in vaccine groups II and III). However, healing was prompt after drainage in these individuals.

Effect of skin test with M. leprae soluble antigen on reaction to a subsequent test with the same antigen.

Soluble skin-test antigens (STA), produced from armadillo-derived Mycobacterium leprae by Drs. Rees and Convit, were expected to meet the long-felt need of a test for leprosy infection and also to serve as tests for measuring postvaccination sensitization induced by vaccine preparations against leprosy. The present paper reports results from two studies examining the influence, if any, of skin testing with Rees' STA on reaction to a subsequent test with the same antigen. In the first study, 2168 persons from households of leprosy patients and from neighboring households were skin tested with Rees' STA twice at an interval of 6 months. In the second study, 1700 persons, free from leprosy, received either Rees' STA or normal saline by random allocation. A random subset of 850 persons was tested with Rees' STA after 3 months. The remaining 850 persons were tested with Rees' STA after 6 months. In addition, 242 leprosy patients were given Rees' STA or normal saline by random allocation, and all of these patients were tested with Rees' STA after 6 months. The results of the two studies showed that among persons reacting with a small size of reaction to Rees' STA, the size of the reaction to the repeat test was significantly larger. However, from the results of the second study, which included a control group, it was clearly seen that the quantum of boosting or sensitizing effect of the first test as well as that of new sensitization was small over a period of 3-6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Inter-observer agreement and clinical diagnosis of leprosy for prophylaxis studies.

Clinical diagnosis is still the most useful tool for detecting early cases of leprosy in field research. In prophylaxis studies accuracy of clinical diagnosis of leprosy is important during intake as well as for measuring efficacy of the intervention. This paper reports our observations regarding the extent of inter-observer variations in clinical diagnosis of leprosy and its implications for a prophylaxis study. Information on 225 suspects and cases of leprosy, each examined independently by three senior workers after initial standardization, was used for this purpose. Agreement among the examiners regarding the presence of skin patch, thickened nerve trunk and sensory deficit was fairly high (Kappa = 0.7). Agreement on the presence of infiltration in a skin patch was not satisfactory (Kappa = 0.4-0.5). It was observed that in clinical diagnosis of leprosy, presence of skin patch and sensory deficit, as well as thickened nerve trunk and related anaesthesia were correlated observations. The influence of inter-observer variations on defining leprosy problem in the community can be quite large. The paper suggests some ways of overcoming the problem.

Experiences with Mycobacterium leprae soluble antigens in a leprosy endemic population.

Rees and Convit antigens prepared from armadillo-derived Mycobacterium leprae were used for skin testing in two leprosy endemic villages to understand their use in the epidemiology of leprosy. In all, 2602 individuals comprising 202 patients with leprosy detected in a prevalence survey, 476 household contacts and 1924 persons residing in non-case households were tested with two antigens. There was a strong and positive correlation (r = 0.85) between reactions to the Rees and Convit antigens. The distribution of reactions was bimodal and considering reactions of 12 mm or more as 'positive', the positivity rate steeply increased with the increase in age. However, the distributions of reactions to these antigens in patients with leprosy, their household contacts and persons living in non-case households were very similar. These results indicate that Rees and Convit antigens are not useful in the identification of M. leprae infection or in the confirmation of leprosy diagnosis in a leprosy endemic population with a high prevalence of nonspecific sensitivity.

Reliability of direct skin smear microscopy in leprosy.

Skin smear direct microscopy is an important tool for diagnosis of leprosy. The study was planned to understand the reproducibility of skin smear reading by a trained technician. Skin smears were collected from known patients of leprosy from the field area. They were stained for acid fast bacilli following the standard cold staining procedure and were read following the Ridley scale. A sample of smears was re-examined on two occasions by the same technician, following blind procedure. There was a systematic under reading on the second occasion, which was attributed to the defective storage of the slides. However, the agreement between second and third examinations was very good (Concordance 81.34%, Kappa 0.74). The finding was confirmed on a repeat examination. It can be concluded that the Direct Skin Smear Microscopy is a reliable and reproducible technique under experimental conditions.