Diabetes mellitus is strongly associated with tuberculosis in Indonesia.

SETTING: Diabetes mellitus is a known risk factor for tuberculosis (TB), but no studies have been reported from South-East Asia, which has a high burden of TB and a rapidly growing prevalence of diabetes. OBJECTIVE: To examine if and to what extent diabetes is associated with an increased risk of TB in an urban setting in Indonesia. DESIGN: Case-control study comparing the prevalence of diabetes mellitus (fasting blood glucose level >126 mg/dl) among newly diagnosed pulmonary TB patients and matched neighbourhood controls. RESULTS: Patients and control subjects had a similar age (median 30 years) and sex distribution (52% male), but malnutrition was more common among TB patients (median body mass index 17.7 vs. 21.5 kg/m2). HIV infection was uncommon (1.5% of patients). Diabetes mellitus was present in 60 of 454 TB patients (13.2%) and 18 of 556 (3.2%) control subjects (OR 4.7; 95%CI 2.7-8.1). Adjustment for possible confounding factors did not reduce the risk estimates. Following anti-tuberculosis treatment, hyperglycaemia reverted in a minority (3.7%) of TB patients. CONCLUSION: Diabetes mellitus is strongly associated with TB in young and non-obese subjects in an urban setting in Indonesia. This may have implications for TB control and patient care in this region.     

Genetic variations and relationship among dengue virus type 3 strains isolated from patients with mild or severe form of dengue disease in Indonesia and Thailand

Sequence analysis was conducted on structural and non-structural genes of 7 strains of dengue virus type-3 (DENV-3 virus) isolated in Indonesia and Thailand in the year 1973, 1994, and 1998 from patients with different clinical manifestations. In general, sequence similarity among isolates was greater than 93%, indicating that the mutation rate of DENV-3 circulating in this region was not more than 7% in the last 3 decades and suggesting that sequences that may responsible for viral architectures and/or biological function were strictly conserved. Mutations unique to viral strains associated with specific clinical manifestations were not found. Alignment of PrM/M and E nucleic acid sequences followed by parsimony analysis of sequences obtained in this study and published elsewhere allowed generation of phylogenetic trees, demonstrating that DENV-3 strains isolated in Indonesia in 1998 belonged to a separate cluster (subtype 2) from those isolated between 1973-1985 (subtype 1).     

Enhancing knowledge and awareness of dengue during a prospective study of dengue fever

In 1992, the Indonesian CDC implemented strategies to control and prevent dengue fever (DF) by including community involvement to reduce larva breeding sites and a mass health education program. To contribute to this effort, we incorporated an educational component into a prospective study of DF conducted at two textile factories in Bandung. This education provided: a lecture on the signs and symptoms of dengue and ways to prevent the disease, posters in the health clinic at each factory and handouts given to each volunteer with an explanation of symptoms. Upon enrollment, each participant completed a questionnaire to gather demographic information. Additionally they were given a brief (non-standardized) test (PRE-test) of their dengue knowledge, which was verbally administered by the study physicians. Five questions (15 point system) were designed to assess the participant's ability to recognize and describe aspects of dengue in lay terms. The subject material included: the symptoms of acute DF, transmission of dengue virus, and basic steps for disease prevention. The same questionnaire was re-administered 18 months later (POST-test), and the results were compared. A total of 2,340 participants completed both the PRE- and POST-tests; there were 1,373 males and 967 females, median age 36 years (range 18-59). Only 0.3% of participants scored EXCELLENT (15-14 points) on the PRE-test whereas 8.4% scored EXCELLENT on the POST-test. Fewer participants scored VERY BAD (2-0 points) on the POST-test compared to the PRE-test (1.4% vs 4.0%). The average raw scores for the PRE- and POST-tests were 7.8 and 10.1, respectively. Improvement of individual scores correlated highly with educational level. No significant correlation was identified for gender, age, factory location or a diagnosis of dengue during the study. These findings demonstrate that our prospective study enhanced knowledge and awareness of dengue in the volunteers.     

Perinatal mortality and morbidity in rural West-Java, Indonesia. Part I: Vital statistics based on cross-sectional surveys

The first part of this article gives the summary result of 4 cross-sectional surveys conducted in 3 rural villages in West Java. It is expected that these surveys provide the researchers with more precise data on perinatal mortality and its associated causes in order to plan and implement the Tanjungsari Intervention Study (1986-1990). This comprises a mapping and numbering survey, and a census survey. Based on a sampling frame of 7964 houses, a systematic sample (one in eleven) was drawn for the Household and for the Married Women Surveys. The survey results yield some basic demographic indicators, occupational information and data on education. Also data on environmental health and vital statistics are presented. It is shown that the crude birth rate is 40 per thousand and that the estimated infant mortality rate reaches a figure of 120%. Furthermore, during individual interviews data was collected on characteristics, attitudes habits as well as on reproductive behaviour, of all married women under 50 years of age.     

Implications of the global increase of diabetes for tuberculosis control and patient care

Objectives To review the current knowledge about tuberculosis (TB) and diabetes, assessing the implication of the global increase of diabetes for TB control and patient care. Methods Systematic literature review. Results Using public databases, it can be estimated that 12.6% (95% CI 9.2–17.3%) of new TB cases in the 10 countries with the highest TB burden will be attributable to TB in 2030, a relative increase of 25.5% compared to 2010. Diabetes is associated with a higher age and body weight among patients with TB, but probably not with a specific clinical presentation of TB. Rifampicin hampers glycemic control by increasing the metabolism of most oral antidiabetic drugs, while diabetes patients may have lower concentrations of anti‐TB drugs. This might be one factor contributing to higher TB treatment failure rates. Conclusions The global epidemic of diabetes has implications for control and treatment of TB. Prospective studies are needed to improve prevention, early detection and treatment of concomitant diabetes and TB, especially in developing countries.     

Association of polymorphisms in IL-12/IFN-gamma pathway genes with susceptibility to pulmonary tuberculosis in Indonesia

Upon infection with mycobacteria the IL-12/IFN-gamma axis plays an essential role in the activation of cell-mediated immunity required for the elimination of pathogens. Mutations in genes of the IL-12/IFN-gamma axis are known to cause extreme susceptibility to infection with environmental mycobacteria, and subtle variations in these genes may influence susceptibility to more virulent mycobacteria. We analyzed the distribution of polymorphisms in four essential genes from the IL-12/IFN-gamma axis, IL12B, IL12RB1, IFNG and IFNGR1, in 382 pulmonary tuberculosis patients and 437 healthy controls from an endemic region in Jakarta, Indonesia. The IL12RB1 gene was sequenced in a subset of individuals. Nine known single nucleotide polymorphisms (SNPs) and two new silent variations, 135G>A and 1056C>T, were detected in IL12RB1. Six functional SNPs (-2C>T, 467G>A, 641A>G, 1312C>T, 1573G>A, 1781G>A) in IL12RB1, an IL12B promoter insertion/deletion polymorphism and CA repeats in IFNG and IFNGR1 were analyzed in the cohort. The IFNGR1 allele CA(12) (p=0.004) and genotype CA(12)/CA(12) (p=0.01; OR 0.5) were associated with protection from pulmonary tuberculosis. Interestingly, IL12B promoter heterozygosity was associated with protection from tuberculosis in BCG-vaccinated individuals (p=0.03; OR=0.6). This new finding supports the role that IL-23-of which IL12B encodes a subunit--plays in generation of memory T cells.     

Iron deficiency and NRAMP1 polymorphisms (INT4, D543N and 3'UTR) do not contribute to severity of anaemia in tuberculosis in the Indonesian population

Fe-deficiency anaemia is the most common cause of anaemia in developing countries. In these settings, many chronic infections, including tuberculosis (TB), are highly prevalent. Fe is an essential nutrient for both host and mycobacteria that play a pivotal role in host immunity and mycobacterial growth. A case-control study was performed in a TB-endemic region in Jakarta, Indonesia, among 378 pulmonary TB patients and 436 healthy controls from the same neighbourhood with the same socio-economic status. In a number of these subjects the Fe status could be explored. The distribution of three polymorphisms in the natural resistance-associated macrophage protein gene (NRAMP1) including INT4, D543N and 3'UTR was examined for a possible association with susceptibility to TB. Anaemia (corrected for sex) was present in 63.2 % of active TB compared with 6.8 % of controls, with female patients more often affected. Anaemia was more pronounced in advanced TB as diagnosed by chest radiography. Lower Hb concentrations in TB patients were accompanied by lower plasma Fe concentrations, lower Fe-binding capacity and higher plasma ferritin. After successful TB therapy, Fe parameters improved towards control values and Hb levels normalised, even without Fe supplementation. NRAMP1 gene polymorphisms were not associated with TB susceptibility, TB severity or anaemia. In conclusion, most active TB patients had anaemia, which was probably due to inflammation and not to Fe deficiency since TB treatment without Fe supplementation was sufficient to restore Hb concentration.     

Epidemiology of dengue and dengue hemorrhagic fever in a cohort of adults living in Bandung, West Java, Indonesia

A prospective study of dengue fever (DF) and dengue hemorrhagic fever (DHF) was conducted in a cohort of adult volunteers from two textile factories located in West Java, Indonesia. Volunteers in the cohort were bled every three months and were actively followed for the occurrence of dengue (DEN) disease. The first two years of the study showed an incidence of symptomatic DEN disease of 18 cases per 1,000 person-years and an estimated asymptomatic/ mild infection rate of 56 cases per 1,000 person-years in areas of high disease transmission. In areas where no symptomatic cases were detected, the incidence of asymptomatic or mild infection was 8 cases per 1,000 person-years. Dengue-2 virus was the predominant serotype identified, but all four serotypes were detected among the cohort. Four cases of DHF and one case of dengue shock syndrome (DSS) were identified. Three of the four DHF cases were due to DEN-3 virus. The one DSS case occurred in the setting of a prior DEN-2 virus infection, followed by a secondary infection with DEN-1 virus. To our knowledge, this is the first report of a longitudinal cohort study of naturally acquired DF and DHF in adults.