Multibacillary leprosy patients with high and persistent serum antibodies to leprosy IDRI diagnostic-1/LID-1: higher susceptibility to develop type 2 reactions

Leprosy inflammatory episodes [type 1 (T1R) and type 2 (T2R) reactions] represent the major cause of irreversible nerve damage. Leprosy serology is known to be influenced by the patient’s bacterial index (BI) with higher positivity in multibacillary patients (MB) and specific multidrug therapy (MDT) reduces antibody production. This study evaluated by ELISA antibody responses to leprosy Infectious Disease Research Institute diagnostic-1 (LID-1) fusion protein and phenolic glycolipid I (PGL-I) in 100 paired serum samples of 50 MB patients collected in the presence/absence of reactions and in nonreactional patients before/after MDT. Patients who presented T2R had a median BI of 3+, while MB patients with T1R and nonreactional patients had median BI of 2.5+ (p > 0.05). Anti-LID-1 and anti-PGL-I antibodies declined in patients diagnosed during T1R (p < 0.05). Anti-LID-1 levels waned in MB with T2R at diagnosis and nonreactional MB patients (p < 0.05). Higher anti-LID-1 levels were seen in patients with T2R at diagnosis (vs. patients with T1R at diagnosis, p = 0.008; vs. nonreactional patients, p = 0.020) and in patients with T2R during MDT (vs. nonreactional MB, p = 0.020). In MB patients, high and persistent anti-LID-1 antibody levels might be a useful tool for clinicians to predict which patients are more susceptible to develop leprosy T2R.

Unveiling healthy carriers and subclinical infections among household contacts of leprosy patients who play potential roles in the disease chain of transmission

Leprosy transmission still occurs despite the availability of highly effective treatment. The next step towards successfully eliminating leprosy is interrupting the chain of transmission of the aetiological agent, Mycobacterium leprae. In this investigation, we provide evidence that household contacts (HHCs) of leprosy patients might not only have subclinical infections, but may also be actively involved in bacilli transmission. We studied 444 patients and 1,352 contacts using anti-phenolic glycolipid-I (PGL-I) serology and quantitative polymerase chain reaction (qPCR) to test for M. leprae DNA in nasal swabs. We classified the patients according to the clinical form of their disease and the contacts according to the characteristics of their index case. Overall, 63.3% and 34.2% of patients tested positive by ELISA and PCR, respectively. For HHCs, 13.3% had a positive ELISA test result and 4.7% had a positive PCR test result. The presence of circulating anti-PGL-I among healthy contacts (with or without a positive PCR test result from nasal swabs) was considered to indicate a subclinical infection. DNA detected in nasal swabs also indicates the presence of bacilli at the site of transmission and bacterial entrance. We suggest that the concomitant use of both assays may allow us to detect subclinical infection in HHCs and to identify possible bacilli carriers who may transmit and disseminate disease in endemic regions. Chemoprophylaxis of these contacts is suggested.

High rates of undiagnosed leprosy and subclinical infection amongst school children in the Amazon Region

Leprosy in children is correlated with community-level factors, including the recent presence of disease and active foci of transmission in the community. We performed clinical and serological examinations of 1,592 randomly selected school children (SC) in a cross-sectional study of eight hyperendemic municipalities in the Brazilian Amazon Region. Sixty-three (4%) SC, with a mean age of 13.3 years (standard deviation = 2.6), were diagnosed with leprosy and 777 (48.8%) were seropositive for anti-phenolic glycolipid-I (PGL-I). Additionally, we evaluated 256 house-hold contacts (HHCs) of the students diagnosed with leprosy; 24 (9.4%) HHC were also diagnosed with leprosy and 107 (41.8%) were seropositive. The seroprevalence of anti-PGL-I was significantly higher amongst girls, students from urban areas and students from public schools (p < 0.0001). Forty-five (71.4%) new cases detected amongst SC were classified as paucibacillary and 59 (93.6%) patients did not demonstrate any degree of physical disability at diagnosis. The results of this study suggest that there is a high rate of undiagnosed leprosy and subclinical infection amongst children in the Amazon Region. The advantages of school surveys in hyperendemic areas include identifying leprosy patients at an early stage when they show no physical disabilities, preventing the spread of the infection in the community and breaking the chain of transmission.

The possible predicting factor of the plantar ulcer in patients with leprosy / 나학회지

TOBJECTS: Leprosy is a chronic infection principally affecting the skin and peripheral nerves caused by the obligate intracellular organism Mycobacterium leprae. Complications secondary to the neuropathy can result in deformity and disability. The plantar ulcer is the commonest complication in leprosy. And the plantar pressure is important factors developing plantar ulcer. So the author is studied about the possible predicting factor of the plantar ulcer in patients with leprosy. SUBJECTS AND METHOD: Subjects included 100 leprosy patients, divided two groups according to the recent plantar ulcer history. The author analyzed the relations between that significant factors and various factors (PGL-I titer, sensory level). RESULTS: The correlations between the PGL-I antibody titer(Spearman's rho=0.215, p=0.048) and PGL-I antibody group(Spearman's rho=0.215, p=0.045) and the recent plantar ulcer history were found. CONCLUSION: The author ascertained that the PGL-I antibody titer and PGL-I antibody group PGL-I antibody titer would be the possible tool for predicting the plantar ulcer of the Hansen disease program.

Sorologia da hanseníase utilizando PGL-I: revisão sistemática / Leprosy serology using PGL-I: a systematic review

A sorologia utilizando o antígeno espécie-específico do Mycobacterium leprae, PGL-I, pode ser um marcador de carga bacteriana em pacientes com hanseníase. Estudos identificaram potencial de uso da sorologia na classificação de pacientes para fins de tratamento, monitoramento de terapia, risco de recidiva e na seleção dos contatos com maior risco de adoecer. Foi realizada uma revisão sistemática e 26 artigos foram incluídos na análise comparativa. Avaliamos os resultados do uso da sorologia PGL-I em diferentes situações, suas limitações e possíveis aplicações. Estudos mostraram eficácia da sorologia PGL-I na classificação de pacientes, monitoramento da terapia, e nas reações hansênicas como teste preditivo. Para diagnóstico precoce e seguimento de população de alto risco, as metodologias utilizadas ainda não demonstraram custo-benefício favorável, porém estudos indicam que a utilização do teste poderá influenciar positivamente nos programas de controle da hanseníase. Com técnicas simples e robustas, o uso da sorologia PGL-I é viável.

Serology using a species-specific antigen for Mycobacterium leprae, PGL-I, could be a marker for the bacterial load of patients with leprosy. Various studies have identified the potential use of serology in the classification of patients for treatment purposes, case monitoring, identification of the risk of relapse and selection of household contacts with a higher risk of contracting the disease. A systematic review of the literature was conducted and 26 articles were included in this comparative analysis. The results of the use of PGL-I serology in different situations, its limitations and possible applications were evaluated. Studies show the efficacy of PGL-I serology in the classification of patients, treatment monitoring and as a predictive test for leprosy reactions. To improve early diagnosis and follow-up of the population at greatest risk of developing leprosy, the methodologies used in the past have yet to show a favorable cost-benefit ratio, although studies indicate that the use of the test might positively influence leprosy control programs. With simple and robust techniques, the use of PGL-I serology is viable.

Comportamento dos testes sorológicos ML Flow e ELISA (PGL-I) em áreas endêmica e não endêmica de hanseníase / The result patterns of ML Flow and ELISA (PGL-I) serologic tests in leprosy-endemic and non-endemic areas

O ML Flow e o ELISA PGL-I são testes sorológicos que detectam anticorpos IgM contra o glicolipídio fenólico I específico do Mycobacterium leprae. Para avaliar o comportamento destes testes em áreas endêmica e não endêmica para hanseníase foram estudados 351 voluntários no Brasil e no Chile, incluindo pacientes com hanseníase, controles sadios, portadores de outras doenças infecciosas, não infecciosas e dermatoses que fazem diagnóstico diferencial com hanseníase. O ponto de corte do ELISA foi estabelecido pelo método da Curva ROC (> 0,157). Em área endêmica, o ML Flow apresentou resultados positivos em 70 por cento dos pacientes com hanseníase; o ELISA foi positivo em 53,3%. Em área não endêmica, o ML Flow foi negativo em todos os voluntários testados; o ELISA foi positivo em 4 voluntários. O ML Flow é um ensaio mais rápido, facilmente aplicável e, portanto, mais adequado para ser utilizado na Atenção Básica; o ELISA necessita, alem de uma infra-estrutura de laboratório adequada, pessoal treinado e especializado em sua execução.

ML Flow and anti-PGL-I ELISA are serological tests that detect IgM antibodies against the phenolic glycolipid I (PGL-I), specific to Mycobacterium leprae. To evaluate the outcomes of ML Flow and ELISA (PGL-I) serological tests in leprosy-endemic areas in comparison to non-endemic ones, a total of 351 volunteers from Brazil and Chile were examined, including leprosy patients, healthy controls and others affected by other infectious or non-infectious diseases that are common differential diagnoses for leprosy. The ELISA cut-off point was established using the ROC Curve method (> 0.157). In endemic areas, 70% of leprosy patients present positive ML Flow results and 53.3% were ELISA-positive. In non-endemic areas, ML Flow was negative in all the subjects tested and ELISA was positive in 4 volunteers. ML Flow is faster and more easily performed and, therefore, a more adequate test for use in basic, primary-level health care centers. ELISA requires trained personnel, in addition to a more complex laboratory infrastructure.

O uso da sorologia como ferramenta adicional no apoio ao diagnóstico de casos difíceis de hanseníase multibacilar: lições de uma unidade de referência / The use of serology as an additional tool to support diagnosis of difficult multibacillary leprosy cases: lessons from clinical care

Sete casos de hanseníase multibacilar (MB) e dois casos com suspeição de hanseníase atendidos em situações distintas do atendimento clínico-dermatológico na Universidade Federal do Rio de Janeiro são descritos. Todos apresentaram dificuldades no diagnóstico visto que não tinham sinais e sintomas cardinais da hanseníase. Um teste sorológico utilizado como ferramenta auxiliar foi útil no processo de diagnóstico ou exclusão de cada caso e facilitou as discussões acadêmicas na hora do exame clínico. A sorologia e baciloscopia de linfa são consideradas como os únicos instrumentos rápidos e de baixo custo para a confirmação de casos MB atípicos, e as vantagens e desvantagens de cada exame são discutidas. Ambos os testes complementam o processo diagnóstico e classificação dos casos para fins terapêuticos. A vantagem da baciloscopia está na sua capacidade de confirmação do diagnóstico. As vantagens da sorologia são: (a) sua aplicabilidade para uso direto por profissionais de saúde no momento da consulta, visto que os resultados são imediatos, (b) a possibilidade da participação dos pacientes no processo, e (c) oferece uma oportunidade para melhor ensino da patogênese da hanseníase.

Seven multibacillary leprosy and two suspected cases assisted in different situations during clinical care activities at the university in Rio de Janeiro city are described. All cases presented some difficulties for diagnosis, since they evolved with few or no cardinal signs or symptoms of leprosy. A serological test used as an auxiliary tool was helpful in the diagnosis or exclusion procedure of each case, facilitating academic discussions at the time of case examination. Considering serology and bacilloscopy (skin smear) as the only rapid and relatively cheap available tests for confirmation of atypical MB leprosy, the advantages and disadvantages of their use were discussed. Both tests support the diagnostic procedure and the classification of cases for treatment purposes. The advantage of bacilloscopy is its capacity for diagnosis confirmation. The advantages of serology are: (a) its applicability for direct use by health workers, providing immediate results; (b) the potential for patient participation in the process; and (c) it provides a learning opportunity, allowing for improved teaching of leprosy pathogenesis.

Pesquisa de anticorpos anti PGL-I através de ELISA em tatus selvagens do Brasil / Research regarding anti-PGL-I antibodies by ELISA in wild armadillos from Brazil

Tatus têm sido envolvidos na transmissão da hanseníase e considerados como fonte de Mycobacterium leprae em muitas publicações. Médicos de partes dos EUA consideram o contato com tatus um fator de risco para hanseníase. Entretanto, há um desafio associado ao papel do tatu na perpetuação da hanseníase no Continente Americano. Foi pesquisada a presença de anticorpos anti-PGL-I em tatus selvagens de áreas endêmicas em hanseníase do Estado do Espírito Santo, Brasil, através de ELISA realizado em amostras de soro de 47 animais. Elisa positivo foi encontrado em 5 (10.6%) tatus. Tatus infectados podem ter algum papel na transmissão da hanseníase disseminando bacilos no meio ambiente, talvez tornando mais difícil a interrupção da cadeia de transmissão e redução do número de casos novos de hanseníase. A técnica de ELISA é um eficiente método para investigação soroepidemiológica da presença do Mycobacterium leprae em tatus.

Armadillos have been involved in leprosy transmission and are considered a source of Mycobacterium leprae in numerous reports. Clinicians from certain areas of the USA consider contact with armadillos a risk factor for leprosy. However, there is a challenge associated with the role of wild armadillos perpetuating human leprosy in the American Continent. The presence of anti-PGL-I antibodies was investigated in wild nine-banded armadillos from leprosy-endemic areas in State of Espirito Santo, Brazil, by ELISA performed on serum samples from 47 armadillos. Positive ELISA was obtained from 5 (10.6%) armadillos. Infected armadillos may play some role in leprosy transmission, disseminating bacilli in the environment, perhaps making it more difficult to interrupt transmission and reduce the number of new leprosy cases. ELISA is an efficient tool for seroepidemiological investigations of Mycobacterium leprae in armadillos.

A Study on Bacterial Index and Anti-PGL-I Antibody under Multidrug Therapy in Leprosy Patients / 나학회지

A study on the status of Mycobacterium leprae in the skin smear and the anti-PGL-I IgM antibody titers, examined by ELISA using ND-O-BSA against sera, the according to multidrug therapy (MDT) for 504 patients with leprosy including 224 new cases and 280 relapse cases in the institute was carried out and the following results were obtained. And the anti-PGL-I IgM antibody titers were examined by ELISA 752 contacts and 606 normal persons as control group. The results obtained were summerized as follows: 1. In 504 patients with leprosy, the mean bacterial index(BI) before starting MDT was 4.82 and the mean BI at 2, 5 and 10 years after starting MDT were 4.3, 2.8, and 1.5 respectively. So average BI declining rate per year was 1.1 2. In 504 patients with leprosy, the mean absorbance of anti-PGL-1 IgM antibody before starting MDT was 0.79287 and the mean absorbance at 2, 5 and 10 years after starting MDT were 0.58268, 0.38551 and 0.31003 respectively. So average absorbance declining rate per year was 0.48284. Between multibacillary (mean absorbance: 0.85762) and paucibacillary(mean absorbance: 0.35555) leprosy patients, the 3. In 504 patients with leprosy, the mean absorbance of anti-PGL-1 IgM antibody of the each bacterial index(BI)-0, 1+, 2+, 3+, 4+, 5+ and 6+ were 0.35555, 0.620, 0.72169, 0.74537, 0.81038, 0.89762, and 1.09664 respectively. The positive linear correlation between the bacterial index (BI) and anti-PGL-I IgM antibody was confirmed(F ratio: 10.49701, F critical point: 2.1168131 p=0.05, prediction trend line: y=107.42x + 389). 4. The mean absorbance of anti-PGL-1 IgM antibody was 0.79287 in patients with leprosy, 0.06027117 in contacts and 0.05021 in normal control persons. Between contacts and normal controls, the

Prevalence of IgM antibodies to phenolic glycolipid I of Mycobacterium leprae among controls, workers and foreigners in Korea / 나학회지

Phenolic glycolipid I (PGL-I) is a Mycobacterium leprae-specific antigen, and the antibodies to the antigen may suggest an M. leprae infection. To compare the M. leprae infection among the populations, we compared the seropositivity and average O.D. of anti-PGL-I IgM antibodies among controls, workers in the leprosy control program offices and foreigners in Korea, the seropositivity of anti- PGL-I antibodies were 3.7% among controls, 7.8% among workers with occupational exposure and 13.6% among foreigners and the average O.D. of anti-PGL-I antibodies were 0.055 among controls, 0.065 among workers and 0.102 among foreigners. And a slightly difference was noted in the seropositivity rate and average O.D. of anti-PGL-I antibodies between children under 9 years old (0%, 0.029) and persons over 10 years old (1.97-6.38%, 0.046-0.065).

Evaluation of a Simple Immunochromatographic Assay as Qualitative Screening Test for Anti-PGL-I Antibodies in Serodiagnosis of Leprosy (I) / 나학회지

Among many reported applications of detection of antibodies to phenolic glycolipid-I (PGL-I) of Mycobacterium leprae, seroprevalence may turn out to be very useful as an indicator of the magnitude of leprosy problem in its control program. Recently, simple tests for the detection of antibodies to PGL-I have been developed. As an effort to assess meaning of qualitative test for anti-PGL-I antibodies, we compared enzyme-linked immunosorbent assay (ELISA) and an immunochromatographic assay (ICA) using PGL-I neoglycoconjugate antigens for detection of antibodies in sera from 165 leprosy patients and 746 healthy controls. The upper limit of normal control O.D. in ELISA was 0.236, and the sensitivity of ICA was 56.4%, and its specificity was 93.9%.

The Study of the Applicablility of the results of PGL-I Antibody IgM ELISA test for the Leprosy Control Program / 나학회지

Though the early detection of leprosy is very important, it has been difficult to determine the M. leprae transmission in the community partly due to a lack of easy specific tools to measure it. A development of a seroepidemiological tool based on the phenolic glycolipid I(PGL-I), an M. leprae-specific antigen, made it possible to detect the M. leprae infection or exposure to the organism. In Korea, 11 studies, used it, were reported in the Korean Leprosy Bulletin. For the reduction of bias, we performed the integrated study of past 11 studies. In our study, we tried to find the useful values of the results of PGL-I Antibody IgM ELISA test for the control of leprosy and to know the further study for more valuable results.