Tuberculosis preventive treatment in children and adolescents: an observational study of secondary data

Abstract Objective To analyze the effectiveness, safety, outcomes, and associated factors of tuberculosis preventive treatment (TPT) in children and adolescents in Paraná, southern Brazil. Method This was an observational cohort study with a retrospective collection of secondary data from the TPT information systems of the state of Paraná from 2009 to 2016, and tuberculosis in Brazil from 2009 to 2018. Results In total, 1,397 people were included. In 95.4% of the individuals, the indication for TPT was a history of patient-index contact with pulmonary tuberculosis. Isoniazid was used in 99.9% of the cases with TPT, and 87.7% completed the treatment. The TPT protection was 98.7%. Among the 18 people who had TB, 14 (77.8%) became ill after the second year of treatment, and four (22.2%) in the first two years (p < 0.001). Adverse events were reported in 3.3% of cases, most of them were gastrointestinal and medication was discontinued in only 2 (0.1%) patients. No risk factors associated with the illness were observed. Conclusions The authors observed a low rate of illness in pragmatics routine conditions in TPT for children and adolescents, especially within the first two years after the end of treatment, with good tolerability and a good percentage of adherence to the treatment. TPT should be encouraged to achieve the goals of the End TB Strategy of the World Health Organization as an essential strategy to reduce the incidence rate of the disease, but studies with new schemes must continue to be carried out in real-life scenarios.

Meta-analysis of infection and disease among household contacts of patients with drug-resistant tuberculosis / 中国热带医学

@#Abstract: Objective　To analyze the association between drug resistance and the risk of latent tuberculosis infection and disease among household contacts of patients with pulmonary tuberculosis, and to explore whether the compensatory mutation of drug-resistant Mycobacterium tuberculosis will enhance its pathogenicity or transmission ability. Methods　The English and Chinese databases, including PubMed, web of science, EMBASE, Cochrane library database, CNKI and Wanfang database, were searched by computer from the time of establishment of the database to January 2022. Cohort studies on the risk of infection and disease among household contacts of patients with drug-resistant and sensitive pulmonary tuberculosis were searched and screened according to the inclusion and exclusion criteria. The data were extracted and evaluated by NOS scale, using stata16.0 software meta-analysis to calculate the combined effect of tuberculosis infection and disease risk of family contacts, and carry out heterogeneity test, subgroup analysis and sensitivity analysis. Results　A total of 7 cohort studies involving 9653 TB index cases and 29, 734 house contacts were included. The results of meta-analysis showed that compared with drug-sensitive pulmonary tuberculosis patients, the risk of tuberculosis infection in house contacts of drug-resistant pulmonary tuberculosis patients was increased (OR=1.56, 95%CI=1.25-1.96, P<0.001), but there was no difference in the risk of incidence (RR=1.06, 95%CI=0.80-1.41, P=0.67>0.05). Subgroup analysis showed that the risk of latent tuberculosis infection in house contacts was affected by the study area, and the size of family contacts had an impact on the risk of TB . Sensitivity analysis showed that the results of meta-analysis were robust. Conclusion　Compared with drug sensitive TB patients, household contacts with drug-resistant TB patients had a higher risk of tuberculosis, but there was no difference in the risk of TB among the two groups.

Factors associated with seropositivity for APGL-Iamong household contacts of leprosy patients

Abstract: INTRODUCTION: Leprosy is mainly transmitted among family members who share genetic and ambient factors. The clinical form of leprosy in the index case and kinship could be risk factors for leprosy transmission. High antibody levels in household contacts (HC) in the absence of neural or skin lesions may characterize latent infection. This study aimed to evaluate the association between seropositivity for anti-phenolic glycolipid-I immunoglobulin M antibodies (APGL-I) in HC and the clinical classification of the index case and to analyze the association between APGL-I positivity with other factors such as age, kinship, and gender. METHODS: We performed a survey among 320 HC of 120 leprosy patients who were evaluated and followed-up in a leprosy outpatient clinic of a university hospital. All HC underwent complete skin examination, peripheral nerve palpation, skin sensory tests, and serologic tests for the detection and quantification of APGL-I. RESULTS: The overall seropositivity rate was 20%, and was greatly affected by kinship. APGL-I seropositivity was higher in siblings (41%), followed by parents (28%), spouses (26%), other (19%), and offspring (14%). Independent risk factors for seropositivity were being siblings (OR 3.3) and being a HC of an index case with indeterminate leprosy (OR 5.3). APGL-I seropositivity was associated with index cases with a bacillary index of 4 (88%; p<.001). Seropositivity among HC was not significantly associated with their gender and age. There was no statistical difference in the seropositivity rates of HC of index patients with paucibacillary and multibacillary leprosy. CONCLUSIONS: Strict evaluation and follow-up of HC with positive results for APGL-I is recommended. Special attention should be paid during the screening of siblings of the index cases, HC of patients with a high bacillary index, and HC of patients with indeterminate leprosy.

Screening outcomes of household contacts of multidrug-resistant tuberculosis patients in Peshawar, Pakistan

OBJECTIVE@#To assess the profile of TB/multidrug-resistant TB (MDR-TB) among household contacts of MDR-TB patients.@*METHODS@#Close contacts of MDR-TB patients were traced in the cross-sectional study. Different clinical, radiological and bacteriological were performed to rule out the evidence of TB/MDR-TB.@*RESULTS@#Between January 2012 and December 2012, a total of 200 index MDR-TB patients were initiated on MDR-TB treatment, out of which home visit and contacts screening were conducted for 154 index cases. Of 610 contacts who could be studied, 41 (17.4%) were diagnosed with MDR-TB and 10 (4.2%) had TB. The most common symptoms observed were cough, chest pain and fever.@*CONCLUSIONS@#The high incidence of MDR-TB among close contacts emphasize the need for effective contact screening programme of index MDR-TB cases in order to cut the chain of transmission of this disease.

Screening outcomes of household contacts of multidrug-resistant tuberculosis patients in Peshawar, Pakistan

Objective To assess the profile of TB/multidrug-resistant TB (MDR-TB) among household contacts of MDR-TB patients. Methods Close contacts of MDR-TB patients were traced in the cross-sectional study. Different clinical, radiological and bacteriological were performed to rule out the evidence of TB/MDR-TB. Results Between January 2012 and December 2012, a total of 200 index MDR-TB patients were initiated on MDR-TB treatment, out of which home visit and contacts screening were conducted for 154 index cases. Of 610 contacts who could be studied, 41 (17.4%) were diagnosed with MDR-TB and 10 (4.2%) had TB. The most common symptoms observed were cough, chest pain and fever. Conclusions The high incidence of MDR-TB among close contacts emphasize the need for effective contact screening programme of index MDR-TB cases in order to cut the chain of transmission of this disease.

Identification of serological biomarkers of infection, disease progression and treatment efficacy for leprosy

Although leprosy is curable with drug treatment, the identification of biomarkers of infection, disease progression and treatment efficacy would greatly help to reduce the overall prevalence of the disease. Reliable biomarkers would also reduce the incidence of grade-2 disability by ensuring that those who are most at risk are diagnosed and treated early or offered repeated treatments in the case of relapse. In this study, we examined the reactivity of sera from lepromatous and tuberculoid leprosy patients (LPs) against a panel of 12 recombinant Mycobacterium leprae proteins and found that six proteins were strongly recognised by multibacillary (MB) patients, while only three were consistently recognised by paucibacillary patients. To better understand the dynamics of patient antibody responses during and after drug therapy, we measured antibody titres to four recombinant proteins, phenolic glycolipid-I and lipoarabinomannan at baseline and up to two years after diagnosis to investigate the temporal changes in the antibody titres. Reactivity patterns to individual antigens and decreases in antibody titres were patient-specific. Antibody titres to proteins declined more rapidly vs. those to carbohydrate and glycolipid antigens. Compared to baseline values, increases in antibody titres were observed during reactional episodes in one individual. Additionally, antibody responses against a subset of antigens that provided a good prognostic indicator of disease progression were analysed in 51 household contacts of MB index cases for up to two years. Although the majority of these contacts showed no change or exhibited decreases in antibody titres, seven individuals developed higher titres towards one or more of these antigens and one individual with progressively higher titres was diagnosed with borderline lepromatous leprosy 19 months after enrolment. The results of this study indicate that antibody titres to specific M. leprae antigens can be used to monitor treatment efficacy in LPs and assess disease progression in those most at risk for developing this disease.

Agreement between skin testing and QuantiFERON®d-TB Gold In-Tube assay (QFT-TB) in detecting latent tuberculosis infection among household contacts in India.

Aims: The present study was designed to find the agreement between Tuberculin Skin Test and interferon gamma assay test in detecting latent tuberculosis infection in household contacts of sputum culture positive tuberculosis cases. Setting: Department of Community Medicine, Christian Medical College, Vellore. Methods: One hundred and fifty household contacts of sputum culture positive tuberculosis cases were tested with both the methods simultaneously and actual as well as kappa agreement was determined. Results: The overall actual agreement between both the tests was found to be 82% with a kappa agreement of 0.57. Conclusion: The agreement was very high (both percentage agreement and Kappa) in pediatric contacts but it was poor in adult contacts.

Caracterización sero-epidemiológicade convivientes de pacientes conlepra en Colombia entre 2003 y 2007 / Sero-epidemiological characterization of household contactsof leprosy patients from Colombia 2003-2007

Introducción: los convivientes de los pacientes con lepra son una población con alto riesgo dedesarrollar la enfermedad. En este estudio se hizo una caracterización de los convivientes depacientes con lepra en la región Caribe y el departamento de Antioquia.Materiales y métodos: se realizó un estudio descriptivo transversal con 383 convivientes de 95pacientes multibacilares y paucibalares registrados dentro del programa de lepra de los estudiosrealizados por el Instituto Colombiano de Medicina Tropical (ICMT) en el periodo 2003-2007en Bolívar, Córdoba, Sucre y Antioquia. Se aplicó un formulario de preguntas en busca de obtener las variables de interés en cuanto al conviviente yal paciente y se definió el valor de inmunoglobulina M (IgM) anti PGL-1 para cada conviviente por medio delmétodo ELISA (Enzyme-Linked Immuno Sorbent Assay, por su nombre en inglés). Para el procesamiento dela información se utilizó el programa estadístico SPSS versión 8.0®.Resultados: el porcentaje de convivientes de 0 a 19 años de sexo masculino fue superior a los de sexo femenino, siendo contraria esta frecuencia en mayores de 20años. La mayoría de los convivientes son amas de casa (27 %) y agricultores (4,4 %). El 53% residía en Córdoba,29,4 % en Bolívar, 11,5 % en Sucre y la menor proporción correspondió al departamento de Antioquia. Losconvivientes cursaron primaria y secundaria incompletas en una proporción de 32 % y 20 %, respectivamente. Fue poco el grado de educación superior encontrado enlos convivientes (2,3 %). El riesgo de presentar anticuerposIgM antiPGL-1 positivos es mayor para las mujeres que para los hombres con un OR de 2,01. Conclusión: esta caracterización permite identificar lapoblación de convivientes en tres regiones de Colombia, para orientar posibles acciones que impacten en la transmisión de la enfermedad.

Introduction: Leprosy is a disease with catastrophicconsequences for health. In this articlethe household contacts of leprosy patients in the Caribbean region and the department of Antioquiawere characterized.Materials and methods: A retrospective study was conducted with 383 contacts of 95 patients with multibacillary or paucibacillary leprosy recordedin the Leprosy program studies carriedout by the Colombian Institute of Tropical Medicine (ICMT) at the period 2003 - 2007 in the departments of Bolivar, Cordoba and Sucre. Asurvey was taken seeking to obtain the variables of interest in terms of the household contactand the patient, and it was defined the presence or absence of anti PGL-1 antibodies using theEnzyme-Linked ImmunoSorbent Assay (ELISA) technique. The software SPSS version 8.0 wasused to process the information; and the data analysis included absolute and relative frequenciesof qualitative variables, summary measures for quantitative variables, and proportion differences by sex were determined by using a levelof significance of 5 %. Results: The percentage of women was higherthan men after age 20, while men predominated in the five-year periods from 0 to 19 years. Mostof were households contacts were housewives (27 %) and 4.4 % farmers. 53 % lived in Cordoba,29.4 % in Bolivar, 11.5 % in Sucre and the lowest corresponded to the department of Antioquia.The households contacts studied elementary school and incomplete high school at a rate of 32 % and 20 % respectively, and had a low degreeof higher education (2.1 % -2.3 %). Women have a higher risk of presenting anti PGL-1 antibodiesthan men (OR 2.01). Conclusion: the household contacts of leprosypatients are mainly female, with a mean cohabitation time of 12 years. This characterization allowsthe recognition of the population in three Colombian regions, in order to direct possible actions which could impact the illnesses transmission.

Early detection of leprosy by examination of household contacts, determination of serum anti-PGL-1 antibodies and consanguinity

A cross-sectional clinical trial in which the serum anti-phenolic glycolipid (anti-PGL-1) antibodies were analysed in household contacts (HHC) of patients with leprosy as an adjunct early leprosy diagnostic marker was conducted. The families of 83 patients underwent clinical examination and serum anti-PGL1 measurement using enzyme-linked immunosorbent assay. Of 320 HHC, 98 were contacts of lepromatous leprosy (LL), 80 were contacts of borderline lepromatous (BL), 28 were contacts of borderline (BB) leprosy, 54 were contacts of borderline tuberculoid (BT), 40 were contacts of tuberculoid (TT) and 20 were contacts of indeterminate (I) leprosy. Consanguinity with the patients was determined for 232 (72.5 percent) HHC. Of those 232 contacts, 183 had linear consanguinity. Forty-nine HHC had collateral consanguinity. Fifty-eight contacts (18.1 percent) tested positive for anti-PGL1 antibodies. The number of seropositive contacts based on the clinical forms of the index case was 17 (29.3 percent) for LL, 15 (25.9 percent) for BL, one (1.7 percent) for BB, 14 (24.1 percent) for BT, three (5.2 percent) for TT and eight (13.7 percent) for I. At the one year follow-up, two (3.4 percent) of these seropositive contacts had developed BT leprosy. The results of the present study indicate that the serum anti-PGL-1 IgM antibody may be useful for evaluating antigen exposure and as a tool for an early leprosy diagnosis in HHC.

Resposta imune humoral ao antígeno rGroES do mycobacterium tuberculosis em pacientes com tuberculose e seus contatos domiciliares / Humoral immune response to mycobacterium tuberculosis rGroES antigen in patients with tuberculosis and their household contacts

A tuberculose (TB) continua sendo um dos mais urgentes problemas de saúde pública do mundo, com 8 a 10 milhões de novos casos e 2 a 3 milhões de mortes a cada ano. Cerca de 50 milhõesde pessoas estão infectadas com o Mycobacterium tuberculosis. A fim de desenvolver testes para imunodiagnóstico da TB, vários antígenos têm sido testados na resposta imune humoral de pacientes com TB ativa. O teste imunoenzimático de ELISA realizado com amostras de plasma de 45 pacientes com tuberculose pulmonar e 172 contatos (96 prova tuberculínica negativa e 76, positiva) foi conduzido para avaliação da resposta imune humoral, com pesquisa de anticorpos das classesIgM e IgG contra o antígeno recombinante GroEs do Mycobacterium tuberculosis (MtGroEs). Pacientes com tuberculose pulmonar ativa apresentaram maiores níveis de IgG anti-rGroEs do que indivíduos saudáveis, o que permitiu a discriminação entre os dois grupos e sugeriu resposta imune humoral específica a este antígeno.

Tuberculosis (TB) remains one of the most important public health problems ofthe world, with 8-10 million new cases and 2-3 million deaths each year. About 50 million people are infected with Mycobacterium tuberculosis. In order to develop immunodiagnostic tests for TB, several antigens have been tested for the humoral immune response of patients with active TB. ELISA was performed with plasma samples from 45 patients with pulmonary TB and 172 contacts (96 negative and 76 positive for the tuberculin skin test). The humoral immune response was evaluated through assessment of IgM and IgG antibodies against recombinant Mycobacterium tuberculosis GroES (MtGroEs). Patients with active pulmonary tuberculosis had higher levels of IgG anti-rGroEs than healthy individuals, allowing discriminationbetween the two groups.

Leprosy reactions: the effect of gender and household contacts

Various host-related factors have been reported as relevant risk factors for leprosy reactions. To support a new hypothesis that an antigenic load in local tissues that is sufficient to trigger the immune response may come from an external supply of Mycobacterium leprae organisms, the prevalence of reactional leprosy was assessed against the number of household contacts. The number of contacts was ascertained at diagnosis in leprosy patients coming from an endemic area of Brazil. The prevalence of reactions (patients with reactions/total patients) was fitted by binomial regression and the risk difference (RD) was estimated with a semi-robust estimation of variance as a measure of effect. Five regression models were fitted. Model 1 included only the main exposure variable "number of household contacts"; model 2 included all four explanatory variables ("contacts", "fertile age", "number of skin lesions" and "bacillary index") that were found to be associated with the outcome upon univariate analysis; models 3-5 contained various combinations of three predictors. Male and female patients were analyzed separately. In females, household contacts were a significant predictor for leprosy reactions in model 1 [crude RD = 0.06; 95 percent confidence interval (CI) = 0.01; 0.12] and model 5 (RD = 0.05; CI = 0.02; 0.09), which included contacts, bacillary index and skin lesions as predictors. Other models were unsatisfactory because the joint presence of fertile age and bacillary index was a likely source of multicollinearity. No significant results were obtained for males. The likely interpretation of our findings might suggest that in female patients, leprosy reactions may be triggered by an external spreading of M. leprae by healthy carrier family members. The small number of observations is an obvious limitation of our study which requires larger confirmatory studies.

Clinical, bacteriological and immunological follow-up of household contacts of leprosy patients from a post-elimination area - Antioquia, Colombia

Follow-up of the household contacts (HHC) of leprosy patients is still the best strategy for early detection of leprosy. HHC from a post-elimination region of Colombia studied in 2001-2002 were re-contacted in 2007. They were tested at both times by clinical examination, bacillary index (BI), PCR from a slit skin smear (SSS) and anti PGL-1 IgM titres. Thirty-two of 61 HHC (52 percent) were re-contacted. Nine HHC (28 percent) showed sero-conversion and one had a skin lesion (BI negative, nested PCR positive). Periodic evaluation of HHC can contribute to the detection of infected HHC as well as new and early leprosy cases.

Survey to identify Mycobacterium leprae-infected household contacts of patients from prevalent regions of leprosy in Colombia

Leprosy in Colombia is in the post-elimination phase; nevertheless, there are regions of this country where the incidence is still around 3-4/100,000. Early detection of leprosy patients is a priority for achieving control and elimination of leprosy; however, the clinical exam is not very sensitive and thus, the majority of patients are diagnosed only when they demonstrate lesions, and damage to the nerves and skin has already occurred. The goal of the present study was to identify Mycobacterium leprae infection and immune responses in household contacts (HHC) of leprosy patients from three prevalent regions of Colombia. Clinical examination, the Mitsuda test, evaluation of IgM anti-PGL-I in the serum, the bacillar index (BI), and polymerase chain reaction (PCR) from nasal swabs (NS) were performed for 402 HHC of 104 leprosy patients during a cross-sectional survey. Positive titers for IgM anti-PGL1 were found for 54 HHC, and PCR-positive NS for 22. The Mitsuda reaction was negative for 38 HHC, although three were positive for IgM anti-PGL-1 titers. The data document that leprosy transmission among HHC is still occurring in a non-endemic country.

Estudo de 20 focos familiares de hanseníase no município de Duque de Caxias, Rio de Janeiro / Study of 20 families with leprosy cases from Duque de Caxias - Rio de janeiro - Brazil

FUNDAMENTOS: O conhecimento da transmissão da hanseníase ainda apresenta lacunas devido ao longo período de incubação e ao fato de poucas pessoas expostas adoecerem. Além da exposição ao M. leprae, a susceptibilidade genética é um importante fator de risco para o adoecimento. OBJETIVO: Caracterizar a transmissão da hanseníase em focos familiares de área endêmica urbana no segundo distrito de Duque de Caxias, Rio de Janeiro, RJ. MÉTODOS: Estudo de 20 famílias, a partir de 20 casos índices (CI), diagnosticados no segundo distrito de Duque de Caxias que apresentaram mais de um caso de hanseníase (co-prevalência), com intervalo de até 10 anos entre os diagnósticos. Foi realizado inquérito domiciliar com preenchimento de questionário estruturado e exame dermatoneurológico. RESULTADOS: Houve predominância da consangüinidade entre os que adoeceram (69/75). A possibilidade de adoecer entre os consangüíneos foi 2,8 vezes maior do que a verificada entre os não consangüíneos. Apenas três cônjuges foram acometidos entre os seis doentes não consangüíneos contra 14 filhos. Em duas famílias os casos foram restritos a uma única geração, em cinco houve acometimento de três gerações, e em 13, de duas gerações. CONCLUSÃO: Embora existam outros fatores de risco envolvidos na transmissão da doença (ambientais, sociais, epidemiológicos), não abordados neste estudo, a consangüinidade mostra associação estatística positiva e reforça a importância da vigilância do núcleo familiar, intra e extradomiciliar, considerando as diferentes situações de convivência. São apresentados aqui dados preliminares do estudo de 70 famílias. A inclusão de um maior número de famílias e o estudo do polimorfismo genético deverá aproximar os estudiosos da complexidade desse tema.

BACKGROUND: The transmission of leprosy has issues not understood due to the long incubation period and the fact that only a few of the exposed subjects get sick. Besides the exposure to the M. leprae, genetic susceptibility is an important risk fact for the disease. OBJECTIVE: To study the transmission of leprosy in family clusters in an endemic urban area in the second district of Duque de Caxias, Rio de Janeiro, Brazil. METHODS: Twenty families, who presented more than one case of the disease in a period of ten years, were studied, starting from 20 index cases. The patients were visited in their houses, for dermatologic and peripheric nerves examination. RESULTS: There was a predominance of the disease among consanguineous contacts (69/75). The risk of getting leprosy among those who were consanguineous was 2.8 times higher than among those who were not consanguineous. Only 3 partners were sick among the 6 non-consanguineous, although only 14 offsprings were affected. In two families the disease was restricted to one generation, in five the disease was present in three generations and in thirteen there were two generations of persons with leprosy. CONCLUSIONS: Although other risk factors, not focused in this paper, are involved in the transmission of leprosy, consanguinity shows a positive association and confirms the need of the epidemilogic surveillence of the relatives that are close to the leprosy patients. These are preliminary outcomes of a 70 families study. The inclusion of more families and the study of the genetic polymorphism will provide a better approach in this complex issue.