RESUMEN
Leprosy is a stigmatizing, chronic infection which degenerates the nervous system and often leads to incapacitation. Multi-drug therapy which consists of dapsone, rifampicin and clofazimine has been effective to combat this disease. In Indonesia, especially in Papua Island, leprosy is still a problem. Furthermore, there had been higher reports of Dapsone Hypersensitivity Syndrome (DHS) which also challenges leprosy elimination in certain aspects. Globally, DHS has a prevalence rate of 1.4% and a fatality rate up to 13%. The aim of this study is to validate HLA-B*13:01, a previously discovered biomarker for DHS in the Chinese population, as a biomarker for DHS in the Papua population.This is a case-control study of 34 leprosy patients who presented themselves with DHS (case subjects) and 52 leprosy patients without DHS (control subjects). Patients were recruited from 2 provinces: Papua and West Papua. DNA was extracted from 3 ml blood specimens. HLA-B alleles were typed using the gold-standard sequence based typing method. Results were then analysed using logistic regression and risk assessment was carried out. The results of HLA-typing showed that HLA-B*13:01 was the most significant allele associated with DHS, with odds ratio = 233.64 and P-value = 7.11×10-9, confirming the strong association of HLA-B*13:01 to DHS in the Papua population. The sensitivity of this biomarker is 91.2% and specificity is 96.2%, with an area under the curve of 0.95. HLA-B*13:01 is validated as a biomarker for DHS in leprosy patients in Papua, Indonesia, and can potentially be a good predictor of DHS to help prevent this condition in the future.
Asunto(s)
Dapsona/efectos adversos , Hipersensibilidad a las Drogas/prevención & control , Antígeno HLA-B13/genética , Leprostáticos/efectos adversos , Lepra/tratamiento farmacológico , Adolescente , Adulto , Alelos , Biomarcadores , Estudios de Casos y Controles , Clofazimina/administración & dosificación , Dapsona/administración & dosificación , Hipersensibilidad a las Drogas/epidemiología , Quimioterapia Combinada , Femenino , Humanos , Indonesia , Leprostáticos/administración & dosificación , Modelos Logísticos , Masculino , Rifampin/administración & dosificación , Medición de Riesgo , Síndrome , Adulto JovenRESUMEN
Indonesia had the third highest number of new leprosy cases worldwide in 2017. This disease is still prevalent in Papua province, where the number of new cases in 2014 (3.0 cases per 10,000 people) is considered highly endemic and is well above the World Health Organization's (WHO) cutoff of <1 new case per 10,000 people. Since 1995, the WHO has supplied Papua province with a multi-drug therapy (MDT) in which multibacillary (MB) patients are treated with rifampicin, clofazimine, and dapsone and paucibacillary (PB) patients are treated with rifampicin and dapsone. Recent published data on global drug resistance reported cases of dapsone resistance in relapsed and newly diagnosed cases in Indonesia during this period. The detection of specific point mutations in folP1 that encode dihydropteroate synthases (DHPS) is used exclusively to identify dapsone resistant strains of Mycobacterium leprae. The purpose of this study was to test for the presence of folP1 mutations in M. leprae strains isolated from patients residing in Papua Island, Indonesia who responded less effectively to dapsone. This study identified a folP1 point mutation that changed a valine (V) residue at amino acid position 39 (from the N-terminus) to isoleucine (I) (V39I) of DHPS. The V39I variant is located within an α-helix motif that may not much affect its structure. Molecular docking analysis indicated that the binding affinity of the V39I variant was slightly reduced as compared to the wildtype of DHPS. The decreasing of affinity may have a consequence of increasing inhibition constants (Ki) of dapsone on the variant V39I of DHPS. The data suggest that the DHPS V39I variant might cause less sensitive to dapsone. However, in vivo studies (e.g., mouse footpad model) are needed to confirm the effect of this DHPS variant on dapsone therapy.
RESUMEN
BACKGROUND: Despite the implementation of Directly Observed Treatment Short-course (DOTS) strategy in all public health centers in Papua Province, Indonesia, since 1998, the rate of loss to follow-up (LTFU) during tuberculosis (TB) treatment remains high (above 16%). OBJECTIVES: We aimed to identify factors associated with non-adherence during TB treatment among patients treated at public health centers (PHCs) in Jayapura, Papua. METHOD: We conducted a case-control study including new TB patients registered at eight PHCs from 2007 to 2009. Non-adherent cases were TB patients with a history of not taking anti-TB drugs for >2 consecutive weeks or >30 days cumulatively. Controls were randomly selected from patients who completed all doses of TB drugs in time. Data were collected by face-to-face interview using a pre-structured questionnaire and analyzed with logistic regression models. RESULTS: Data were available for 81 of 103 eligible cases and 183 of 206 eligible controls. Difficult access to healthcare (i.e. reported to have a problem with distance/travel cost and history of moving residence in the past year), lack of TB knowledge (i.e. lack of knowledge about TB transmission and the cause of TB and unawareness of the consequences of stopping TB treatment), and treatment experience (i.e. lack of TB education provided by TB nurse and the use of loose vs. fixed-dose combinations) were associated with non-adherence during TB treatment in the adjusted model, as were being aged under 35 years and having a history of TB in the family. CONCLUSION: Our results suggest the need to improve TB treatment delivery especially to those who have difficult access to healthcare, and to routinely provide education to increase patients' knowledge about TB and TB treatment. In addition, more attention to younger patients and those with a history of TB in their family is also needed.
Asunto(s)
Antituberculosos/uso terapéutico , Terapia por Observación Directa/estadística & datos numéricos , Cumplimiento de la Medicación/psicología , Tuberculosis/tratamiento farmacológico , Adulto , Factores de Edad , Antituberculosos/administración & dosificación , Translocador Nuclear del Receptor de Aril Hidrocarburo , Estudios de Casos y Controles , Proteínas de Drosophila , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Indonesia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Salud Pública , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
Mycobacterium tuberculosis genotype distribution is different between West and Central Indonesia, but there are no data on the most Eastern part, Papua. We aimed to identify the predominant genotypes of M. tuberculosis responsible for tuberculosis in coastal Papua, their transmission, and the association with patient characteristics. A total of 199 M. tuberculosis isolates were collected. Spoligotyping was applied to describe the population structure of M. tuberculosis, lineage identification was performed using a combination of lineage-specific markers, and genotypic clusters were identified using a combination of 24-locus-MIRU-VNTR and spoligotyping. A high degree of genetic diversity was observed among isolates based on their spoligopatterns. Strains from modern lineage 4 made up almost half of strains (46.9%), being more abundant than the ancient lineage 1 (33.7%), and modern lineage 2 (19.4%). Thirty-five percent of strains belonged to genotypic clusters, especially strains in the Beijing genotype. Previous TB treatment and mutations associated with drug resistance were more common in patients infected with strains of the Beijing genotype. Papua shows a different distribution of M. tuberculosis genotypes compared to other parts of Indonesia. Clustering and drug resistance of modern strains recently introduced to Papua may contribute to the high tuberculosis burden in this region.
Asunto(s)
Mycobacterium tuberculosis/clasificación , Mycobacterium tuberculosis/genética , Tuberculosis/microbiología , Tuberculosis/transmisión , Adulto , Evolución Molecular , Femenino , Variación Genética , Genotipo , Humanos , Indonesia/epidemiología , Masculino , Repeticiones de Minisatélite , Tipificación Molecular , Filogenia , Tuberculosis/epidemiología , Adulto JovenRESUMEN
When it comes to sexuality and norms, young Indonesians are becoming more open. Concern about this is related to the rapid increase in HIV prevalence in Indonesia, especially in Papua and West Papua Provinces. While much research has been conducted among youth who have left school, little is known about senior high school students' sexuality and sexual practices in these provinces. Using qualitative and quantitative data, we explore perspectives on and experiences of sexuality, contraceptive use, unintended pregnancy and unsafe abortion among 1082 Year 11 students from 16 senior high schools in both provinces. Findings suggest that around 38.3% of students reported having had sexual intercourse and 36.5% of these having had their first sexual encounter before they were 15 years old. Furthermore, contraceptive use among sexually active students was very low. Around 32% of female students who reported having had sexual intercourse also reported having an unintended pregnancy and the majority of them had had unsafe abortions. The paper points to the implications of students' high-risk sexual behaviours for HIV prevention.