Erni J. Nelwan

The Effect of Type 2 Diabetes Mellitus on the Presentation and Treatment Response of Pulmonary Tuberculosis

BACKGROUND Diabetes mellitus (DM) is a known risk factor for tuberculosis (TB), and with the increasing prevalence of type 2 DM in less developed regions, many patients with TB will have concomitant DM. Presently, little is known about the effect of DM on the clinical presentation and treatment outcome of TB. METHODS In an urban setting in Indonesia, 737 patients with pulmonary TB were screened for DM and were followed up prospectively during TB treatment. Clinical characteristics and outcome were compared between patients with TB who had DM and patients with TB who did not have DM. RESULTS DM was diagnosed in 14.8% of patients with TB and was associated with older age and a greater body weight. On presentation, diabetic patients with TB had more symptoms but had no evidence of more-severe TB. After 2 months, results of sputum microscopic examination was more often positive in diabetic patients (18.1% vs. 10.0%). After 6 months, 22.2% of cultured sputum specimens from diabetic patients were positive for Mycobacterium tuberculosis (adjusted odds ratio, 7.65; P=.004). CONCLUSION DM seems to have a negative effect on the outcome of TB treatment. The underlying mechanisms for the different response to treatment in diabetic patients with TB must be explored. Screening for DM and subsequent glycemic control may improve the outcome of TB treatment.

Exposure to Rifampicin Is Strongly Reduced in Patients with Tuberculosis and Type 2 Diabetes

BACKGROUND Type 2 diabetes (DM) is a strong risk factor for tuberculosis (TB) and is associated with a slower response to TB treatment and a higher mortality rate. Because lower concentrations of anti-TB drugs may be a contributing factor, we compared the pharmacokinetics of rifampicin in patients with TB, with and without DM. METHODS Seventeen adult Indonesian patients with TB and DM and 17 age- and sex-matched patients with TB and without DM were included in the study during the continuation phase of TB treatment. All patients received 450 mg of rifampicin (10 mg/kg) and 600 mg of isoniazid 3 times weekly. Steady-state plasma concentrations of rifampicin and its metabolite desacetylrifampicin were assessed at 0, 2, 4, and 6 h after drug intake. RESULTS Geometric means of rifampicin exposure (AUC(0-6 h)) were 12.3 mg x h/L (95% confidence interval [CI], 8.0-24.2) in patients with TB and DM, and 25.9 mg x h/L (95% CI, 21.4-40.2) in patients with TB only (P=.003). Similar differences were found for the maximum concentration of rifampicin. No significant differences in time to maximum concentration of rifampicin were observed. The AUC(0-6 h) of desacetylrifampicin was also much lower in patients with TB and DM versus patients with TB only (geometric mean, 0.60 vs. 3.2 mg x h/L; P=.001). Linear regression analysis revealed that higher body weight (P<.001), the presence of DM (P=.06), and plasma glucose concentration (P=.016) were correlated with exposure to rifampicin. CONCLUSION Exposure (AUC(0-6 h)) to rifampicin was 53% lower in Indonesian patients with TB and DM, compared with patients with TB only. Patients with TB and DM who have a higher body weight may need a higher dose of rifampicin.

The role of interferon-gamma in the increased tuberculosis risk in type 2 diabetes mellitus

As patients with diabetes mellitus are at increased risk of developing tuberculosis, we hypothesized that this susceptibility to mycobacterial infection is due to a defective Th1-cytokine response. To explore this hypothesis, we examined four groups of subjects in Indonesia: 23 patients with tuberculosis, 34 patients with tuberculosis and diabetes, 32 patients with diabetes only and 36 healthy controls. Ex-vivo production of interferon (IFN)γ, tumour necrosis factor-α and interleukin (IL)-1β, 6, 10, -12 and -4 was measured following stimulation with Mycobacterium tuberculosis, Escherichia coli lipopolysaccharide and phytohaemagglutinin. Patients with active tuberculosis were found to have lower IFNγ levels and a higher production of other pro-inflammatory cytokines and IL-4, both in the presence and absence of diabetes. Diabetes patients without tuberculosis, however, showed strongly reduced non-specific IFNγ production, which is essential for inhibition of the initial growth of M. tuberculosis. Our data suggest that a defective non-specific immune response in diabetes may contribute to an increased susceptibility to develop tuberculosis.

Human immunodeficiency virus, hepatitis B and hepatitis C in an Indonesian prison: prevalence, risk factors and implications of HIV screening.

Objective  To determine the prevalence and behavioural correlates of HIV, HBV and HCV infections among Indonesian prisoners and to examine the impact of voluntary counselling and testing for all incoming prisoners on access to antiretroviral treatment (ART).

Association of Impaired Cytochrome P450 2D6 Activity Genotype and Phenotype With Therapeutic Efficacy of Primaquine Treatment for Latent Plasmodium vivax Malaria

Key Points Question How is natural variation in cytochrome P450 2D6 activity associated with therapeutic efficacy of primaquine phosphate against latent Plasmodium vivax malaria? Findings In this nested case-control study of 57 patients who had participated in a clinical trial of primaquine for radical cure of acute P vivax malaria, exposure to low levels of cytochrome P450 2D6 activity determined by genotype or measured by dextromethorphan metabolism phenotype was associated with a significantly increased likelihood of relapse of malaria in the year after directly observed high-dose primaquine therapy. Meaning Impaired cytochrome P450 2D6 activity was significantly associated with high risk of therapeutic failure of primaquine, and this finding suggests cytochrome P450 2D6 involvement in producing a therapeutically active metabolite.

Spontaneous rectus sheath hematomas in dengue hemorrhagic fever: A case report

Muscle hematomas are rare complications in dengue hemorrhagic fever (DHF). We report a case of 58-year-old-female admitted with dengue fever who developed spontaneous rectus sheath hematoma complicating DHF. She presented with progressive thrombocytopenia with platelet count reaching 13000/μL at its lowest point. There was evidence of plasma leakage and persistent cough during the course of illness. During the recovery phase, she reported severe abdominal pain and developed hematoma in the right rectus sheath, which was confirmed by abdominal computed-tomography scan and serial magnetic resonance imaging. This complication during convalescent period of DHF needs to be recognized so it can be managed appropriately.

Severe coagulopathy and transient hypertension following a Rhabdophis subminiatus bite: a case report

Because the majority of colubrid species are considered harmless to human beings, colubrid snakebites are rarely reported. However, the venom of Rhabdophis, which is part of the Colubridae family, is procoagulant and leads to severe coagulopathy. Here, we present a case of disseminated intravascular coagulation with enhanced fibrinolysis following a Rhabdophis bite. Although coagulopathy can be treated effectively with the specific Rhabdophis antivenom, this antivenom is not widely available in Indonesia. We also found transient hypertension secondary to the colubrid venom, an unusual finding.