Viruses and Gram-negative bacilli dominate the etiology of community-acquired pneumonia in Indonesia, a cohort study.

OBJECTIVE: Knowledge about the etiology of community-acquired pneumonia (CAP) is essential for adequate management. Presently, few studies about CAP are available from Southeast Asia. This study aimed to investigate the etiology, severity, and outcome of CAP in the most populous Southeast Asia country, Indonesia. METHODS: From October 2007 to April 2009, adult patients admitted with CAP to two hospitals in Semarang, Indonesia, were included to detect the etiology of CAP using a full range of diagnostic methods. The severity of disease was classified according to the Pneumonia Severity Index (PSI). The outcome was assessed as 30-day mortality. RESULTS: In total, 148 consecutive patients with CAP were included. Influenza virus (18%), Klebsiella pneumoniae (14%), and Streptococcus pneumoniae (13%) were the most common agents identified. Other Gram-negative bacilli, Mycobacterium tuberculosis, Chlamydia pneumoniae each accounted for 5%. The bacteria presented wild type antibiotic susceptibility profiles. Forty-four percent of subjects were high-risk patients (PSI class IV-V). The mortality rate (30%) was significantly associated with disease severity score (P<0.001), and with failure to establish an etiological diagnosis (P=0.027). No associations were found between etiology and underlying diseases, PSI class, nor mortality. CONCLUSIONS: Viruses and Gram-negative bacilli are dominant causes of CAP in this region, more so than S. pneumoniae. Most of the bacteria have wild type susceptibility to antimicrobial agents. Patients with severe disease and those with unknown etiology have a higher mortality risk.

Combination of Aspartate Aminotranferase and Tumor Necrosis Factor-α as Non Invasive Diagnostic Tools for Non Alcoholic Steatohepatitis (NASH).

AIM: to develop a non-invasive diagnostic test for non-alcoholic steatohepatitis NASH. METHODS: this is a cross-sectional study on non-alcoholic fatty liver disease (NAFLD) subjects. Sample was taken by consecutive sampling method. Diagnostic criteria of NAFLD were confirmed by liver biopsy. Clinical variables include metabolic syndrome, aspartate aminotransferase (AST), alanine aminotransferase (ALT), adiponectine, TNF-, insulin, homeostatic model assessment insulin resistance (HOMA-IR) index and liver biopsy. Patients were divided into two groups based on their liver biopsy, group 1: Non-NASH (NAFLD activity score <3) and group 2: NASH (NAFLD activity score of >4). Statistical analyses were performed using Student's t-test, Mann Whitney U, chi-square, the ROC curve, sensitivity and specificity test. RESULTS: fifty NAFLD patients were recruited, 30 males and 20 females. Among these patients, 12 (24%) had type 2 diabetes, 36 (72%) had metabolic syndrome, the remaining 2 (4%) did not fulfilled metabolic syndrome. Liver biopsy confirmed 21 (42%) non- NASH and 29 (58%) NASH respectively. Level of AST and ALT, plasma level of adiponectine and TNF- were statistically different between two groups. The AST level (>25 U/L) in combination with TNF- (>3.28 pg/cc) demonstrated a good diagnostic accuracy for NASH (Accuracy 82%, Sensitivity 76%, Specificity 90%, PPV 92%, and NPV 73%). CONCLUSION: the combined diagnostic tests of AST and TNF- plasma levels demonstrated a good accuracy for the detection of NASH among NAFLD patients. This combination test can be used as a noninvasive method to diagnose NASH.

The effects of oral plain kefir supplementation on proinflammatory cytokine properties of the hyperglycemia Wistar rats induced by streptozotocin.

AIM: to validate the effect of plain kefir on immune responses of hyperglycemia wistar rats induced by Streptozotocin. METHODS: the randomized pretest - posttest control group study design was conducted in male hyperglycemia Wistar rats induced by streptozotocin (STZ). Rats were randomized into four groups: (1) STZ-induced group were given insulin treatment 0.76 UI/200 g bw, (2) STZ-induced group and treated with plain kefir 3.6 cc/200 g bw/day for 30 days, (3) STZ-induced group as control, (4) normal animal group as a negative control. Blood glucose was measured from whole blood that was taken 0.1 ml from retroorbitalis vein by microhematocrit on day 1 (pretest) and day 30 (post test) by enzymatic methods. Immune responses (cytokines IL1, IL6, IL10, TNF) were measured by ELISA. Data were analyzed by one way Anova, Mann Whitney test and Duncan with significant level of p<0.05. RESULTS: plain kefir supplementation 3.6 cc/day affect blood glucose, proinflamatory cytokines (IL1, IL6, TNF) and antiinflamatory cytokine (IL10). Statistical analysis showed decrease of glucose -111.00±44.23 ml (p<0.001) and proinflamatory cytokines IL1 about -18.62±23.59 and IL6 -3.21±7.57 mU/mL (p<0.001), respectively compared to the control groups. TNF decreased 1.65±4.62 mU/mL, but not significant (p>0.05), except for controls group. In addition, antiinflammatory (IL10) showed also increase about 15.11±2.16 (p<0.05), except for the control. CONCLUSION: plain kefir supplementation significantly decreased blood glucose, level of cytokines (IL1, IL6) and lowered TNF level. On the contrary, the level of IL10 is increased compare to control groups.

Poor food hygiene and housing as risk factors for typhoid fever in Semarang, Indonesia.

To identify risk factors for typhoid fever in Semarang city and its surroundings, 75 culture-proven typhoid fever patients discharged 2 weeks earlier from hospital and 75 controls were studied. Control subjects were neighbours of cases with no history of typhoid fever, not family members, randomly selected and matched for gender and age. Both cases and controls were interviewed at home by the same trained interviewer using a standardized questionnaire. A structured observation of their living environment inside and outside the house was performed during the visit and home drinking water samples were tested bacteriologically. Univariate analysis showed the following risk factors for typhoid fever: never or rarely washing hands before eating (OR = 3.28; 95% CI = 1.41-7.65); eating outdoors at least once a week (OR = 3.00; 95% CI = 1.09-8.25); eating outdoors at a street food stall or mobile food vendor (OR = 3.86; 95% CI = 1.30-11.48); consuming ice cubes in beverage in the 2-week period before getting ill (OR = 3.00, 95% CI = 1.09-8.25) and buying ice cubes from a street vendor (OR = 5.82; 95% CI = 1.69-20.12). Water quality and living environment of cases were worse than that of controls, e.g. cases less often used clean water for taking a bath (OR = 6.50; 95% CI = 1.47-28.80), for brushing teeth (OR = 4.33; 95% CI = 1.25-15.20) and for drinking (OR = 3.67; 95% CI = 1.02-13.14). Cases tended to live in houses without water supply from the municipal network (OR=11.00; 95% CI = 1.42-85.2), with open sewers (OR = 2.80; 95% CI = 1.0-7.77) and without tiles in the kitchen (OR = 2.67; 95% CI = 1.04-6.81). Multivariate analysis showed that living in a house without water supply from the municipal network (OR = 29.18; 95% CI = 2.12-400.8) and with open sewers (OR = 7.19; 95% CI = 1.33-38.82) was associated with typhoid fever. Never or rarely washing hands before eating (OR = 3.97; 95% CI = 1.22-12.93) and being unemployed or having a part-time job (OR = 31.3; 95% CI = 3.08-317.4) also were risk factors. In this population typhoid fever was associated with poor housing and inadequate food and personal hygiene.

The ThyroMobil model for standardized evaluation of iodine deficiency disorder control in Indonesia.

Indonesia used to be affected by varying degrees of iodine deficiency. Salt iodization has been the adopted strategy on a national basis since 1979. The prevalence of goiter in school-age children (SAC) determined by palpation subsequently markedly decreased within the next 15 years. The objective of the present work was to perform an updated evaluation of the status of iodine nutrition in Indonesia by using standardized methods for the measurement of thyroid volume by ultrasounds and the concentration of urinary iodine in SAC. The survey included 7,447 SAC ages 6 to 12 years from 129 sites selected by multistage and stratified sampling in five provinces (4 in Java plus Sumatra and the Province of Bali). A mobile unit (ThyroMobil van) equipped with a sonographic device and facilities for the collection of urine samples visited all sites. In Java plus Sumatra, the median urinary iodine was 195 microg/L. Thirty-four percent of the values were within normal limits (between 100 and 200 microg/L); 17.2% were below 100 microg/L and 48.8% were above 200 microg/L, including 18.2% above 300 microg/L and 0.7% above 1000 microg/L. In Bali, the median was 81 microg/L with 58.3% of the values below 100 microg/L and only 14.7% of the values above 200 microg/L. The prevalence of goiter determined by ultrasounds and using the World Health Organization/International Council for Control of Iodine Deficiency Disorders (WHO/ICCIDD) normative values for gender and age was 3.0% in Java plus Sumatra and 1.9% in Bali. The values were 8.0% and 12.5%, respectively, when using reference values for Indonesia established during the present survey in an iodine replete area in central Java. In conclusion, (1) iodine deficiency has been eliminated in large parts of Indonesia; (2) Bali is still affected by mild iodine deficiency; (3) in many places, iodine deficiency has been replaced by iodine excess, occasionally potentially toxic; (4) the WHO/ICCIDD normative values for thyroid volume measured by ultrasound in SAC are not valid for Indonesia; (5) in Indonesia, the level of salt iodization could be decreased and the biological monitoring of urinary iodine at the population level should be reinforced and maintained; (6) the ThyroMobil model has, as in other parts of the world, demonstrated its efficiency in the organization of partnership evaluation and monitoring of iodine nutrition, as well as in social mobilization.

Phospholipase A2 is a circulating mediator in typhoid fever.

Circulating proinflammatory mediators have not been found in studies on typhoid fever, although the patients suffer from a systemic disease with characteristic protracted fever. The 14-kDa group II extracellular phospholipase A2 (PLA2) is induced by interleukin-1 and tumor necrosis factor and may mediate some of the effects of these cytokines. Circulating PLA2 concentrations were measured in 12 typhoid fever patients on various days after admission and after recovery. On admission, mean concentrations of PLA2 were elevated (1444 +/- 1560 ng/mL) and decreased gradually and significantly to day 14 (55 +/- 48 ng/mL). patients with complicated disease had significantly higher PLA2 levels on admission. PLA2 was not produced in a lipopolysaccharide-stimulated whole blood culture, indicating that PLA2 originates from other types of cells. These data indicate that PLA2 may be a mediator of disease in protracted inflammatory diseases such as thyroid fever.

Culture of Salmonella typhi and Salmonella paratyphi from blood and bone marrow in suspected typhoid fever.

We studied the yield of blood and bone marrow (BM) cultures in 145 patients clinically suspected of typhoid fever (TF) in Indonesia. The objectives were to compare the positivity of blood culture using 3 ml versus 10 ml of blood and to examine in how far specific antibiotic treatment for TF interfered with the positivity of BM culture. Blood for culture was collected before antibiotic treatment was initiated in hospital and BM 1 to 10 days after the start of treatment. Cultures were performed with Oxgall subcultured on SS agar. Seventy-nine per cent of patients was treated for 14 days or more with oral chloramphenicol, 18% with chloramphenicol followed by ampicillin or cotrimoxazol and 3% with other antibiotics. Cultures were positive for Salmonella typhi or S-paratyphi A in 57 of the 145 patients (39.3%) when 3 ml of blood was cultured and in 58 (40%) when 10 ml of blood was cultured. BM culture was positive despite antibiotic treatment in 70 patients (48.2%); this positivity was significantly greater than that of blood cultures (p < 0.05). When we considered the positivity of BM culture in relation to the number of days on antibiotics in hospital, the yield of BM culture remained apparently unchanged during the first 5 days of treatment. This may be the consequence of slow elimination of S.typhi or S.paratyphi by the antibiotics used and could be responsible for relapses.

Patterns of proinflammatory cytokines and inhibitors during typhoid fever.

Cytokines and inhibitors in plasma were measured in 44 patients with typhoid fever. Ex vivo production of the cytokines was analyzed in a whole blood culture system with and without lipopolysaccharide (LPS). Acute phase circulating concentrations of cytokines (+/- SD) were as follows: interleukin (IL)-1 beta, < 140 pg/mL; tumor necrosis factor-alpha (TNF alpha), 130 +/- 50 pg/mL; IL-6, 96 +/- 131 pg/mL; and IL-8, 278 +/- 293 pg/mL. Circulating inhibitors were elevated in the acute phase: IL-1 receptor antagonist (IL-1RA) was 2304 +/- 1427 pg/mL and soluble TNF receptors 55 and 75 were 4973 +/- 2644 pg/mL and 22,865 +/- 15,143 pg/mL, respectively. LPS-stimulated production of cytokines was lower during the acute phase than during convalescence (mean values: IL-1 beta, 2547 vs. 6576 pg/mL; TNF alpha, 2609 vs. 6338 pg/mL; IL-6, 2416 vs. 7713 pg/mL). LPS-stimulated production of IL-1RA was higher in the acute than during the convalescent phase (5608 vs. 3977 pg/mL). Inhibited production of cytokines during the acute phase may be due to a switch from a proinflammatory to an antiinflammatory mode.

Hypothyroidism in an area of endemic goiter and cretinism in Central Java, Indonesia.

In an area of severe endemic goiter in Central Java, Indonesia, clinical overt or mild hypothyroidism appeared to be present in 7 out of 20 cretins and also in 12 out of 94 non-cretinous subjects, all 5-20 years of age, living in the village of Sengi. Hypothyroidism was not found in a control group of 70 subjects of the same age living in Londjong just outside the edemia. In hypothyroid subjects the plasma PBI-concentration was 0.98+/-0.32 mug/100 ml (mean+/-SD) vs. 2.72+/-1.24 mug/100 ml in euthyroid subjects from Sengi and 4.86+/-0.80 mug/100 ml in controls from Londjong. Values for T3 were 56.3+/-3.17 ng/100 ml in hypothyroids, 140.5+/-38.5 ng/100 ml in euthyroids from Sengi and 121.6+/-27.4 ng/100 ml in controls. The TSH levels (geometric mean and range) in these 3 groups were, respectively, 210.1 (108.0-342), 15.6 (3.0-372) and 4.1 (0.8-7.0) muU/ml. The differences between the mean concentration of PBI, T3 and TSH in the hypothyroid and euthyroid groups were highly significant (P less than 0.001). These data strengthen the clinical diagnosis of hypothyroidism in cretins as well as in non-cretinous subjects. All hypothyroid subjects had a PBI less than 1.8 mug/100 ml and T3 less than 120 ng/100 ml and TSH greater than 100 muU/ml. In 8 hypothyroid subjects, restudied 18 months after iodized oil injection, hypothyroidism was either corrected or markedly improved. It therefore appears that iodine deficiency per se in postnatal life may lead to (juvenile) hypothyroidism, which can be corrected by iodine therapy. Our findings have implications for the definition and diagnosis of endemic cretinism. Not all hypothyroid subjects in an area of endemic iodine deficiency should be classified as cretins.

Studies on hearing loss in a community with endemic cretinism in Central Java, Indonesia.

An audiometric study was carried out in a community of 642 subjects severly affected by endemic goitre and cretinism. Hearing loss was measured in 34 out of 41 subjects diagnosed as cretins, 92 normal subjects aged 5-20 years from the same community and 54 subjects (also of 5-20 years) living in a nearby control area without endemic goitre. The excess number of hearing defects in the endemic area seems to be entirely due to the process that leads to cretinism. There is no reason to describe deafness and deafmutism in an area with severe endemic goitre as a separate entity. The hearing defect showed a definite greater loss in the higher frequencies than in the lower frequencies and was found in 92% of the cretins. Deafmutism was present in 5, a loss of more than 60 db in 8, a loss of 40-60 db in 10 cretins. A loss of 20-30 db was found in 2.2% of normal subjects in the endemic area and 1.8% of those living in the control area. It is concluded that audiometry is a simple and significant test to establish the presence of the neurological form of endemic cretinism, which is the most prevalent form in most endemias. The differential diagnosis and pathogenesis of the described hearing defect are discussed.