Drug-resistant tuberculosis in children in Thailand.

SETTING: Few data on drug-resistant (DR) tuberculosis (TB) in children are available in Thailand. OBJECTIVES: To evaluate the rate, clinical features and risk of DR-TB in children. DESIGN: Observational prospective study conducted in children diagnosed with TB at a tertiary care centre in Bangkok. RESULTS: Of 230 children diagnosed with TB, the median age was 6.5 years; 63% had identified adult source cases, and only 7% had received prior isoniazid treatment for latent tuberculous infection. Of the 195 (85%) specimens submitted, 57 (25%) were positive using culture or polymerase chain reaction. Of the 53 positive specimens available for drug susceptibility testing (DST), 18 (34%) had any resistance, 13 (24.5%) were mono-resistant, 2 (3.8%) polyresistant and 3 (5.7%) were multidrug-resistant. In multivariate analysis, prior TB treatment (P < 0.001), presence of atelectasis (P = 0.039) or lobar consolidation (P = 0.012) on chest X-ray were associated with DR-TB. DR-TB required longer treatment but there were no differences in rate of cure, treatment completion or death. CONCLUSIONS: The high rate of DR-TB underscores the importance of routine DST. History of treatment and drug susceptibility in source cases was useful in guiding initial treatment in children.

Mother-to-child transmission of GB virus C in a cohort of women coinfected with GB virus C and HIV in Bangkok, Thailand.

BACKGROUND: GB virus C (GBV-C) is an apathogenic virus that inhibits human immunodeficiency virus (HIV) replication in vitro. Mother-to-child transmission (MTCT) of GBV-C has been observed in multiple small studies. Our study examined the rate and correlates of MTCT of GBV-C in a large cohort of GBV-C-HIV-coinfected pregnant women in Thailand. METHODS: Maternal delivery plasma specimens from 245 GBV-C-HIV-infected women and specimens from their infants at 4 or 6 months of age were tested for GBV-C RNA. Associations with MTCT of GBV-C were examined using logistic regression. RESULTS: One hundred one (41%) of 245 infants acquired GBV-C infection. MTCT of GBV-C was independently associated with maternal antiretroviral therapy (adjusted odds ratio [AOR], 5.21 [95% confidence interval {CI}, 2.12-12.81]), infant HIV infection (AOR, 0.05 [95% CI, 0.01-0.26]), maternal GBV-C load (8.0 log(10) copies/mL: AOR, 86.77 [95% CI, 15.27-481.70]; 7.0-7.9 log(10) copies/mL: AOR, 45.62 [95% CI, 8.41-247.51]; 5.0-6.9 log(10) copies/mL: AOR, 9.07 [95% CI, 1.85-44.33]: reference, <5 log(10) viral copies/mL), and caesarean delivery (AOR, 0.26 [95% CI, 0.12-0.59]). CONCLUSIONS: Associations with maternal GBV-C load and mode of delivery suggest transmission during pregnancy and delivery. Despite mode of delivery being a common risk factor for virus transmission, GBV-C and HIV were rarely cotransmitted. The mechanisms by which maternal receipt of antiretroviral therapy might increase MTCT of GBV-C are unknown.

Penicilliosis-associated hemophagocytic syndrome in a human immunodeficiency virus-infected child: the first case report in children.

Infection-associated hemophagocytic syndrome (IAHS) has been found in many systemic infectious conditions with a high mortality rate. Disseminated Penicillium marneffei infection is a common opportunistic condition among HIV-infected patients in many regions in Southeast Asia. We report the first case of IAHS caused by penicilliosis in an HIV-infected child who presented with cytopenias and recovered promptly after antifungal and intravenous immunoglobulin therapy.

Nosocomial bloodstream infection in pediatric patients: Siriraj Hospital, Bangkok; 1996-1999.

A retrospective study on nosocomial bloodstream infection (NBSI) in pediatric patients hospitalized at Siriraj Hospital from January 1996 to December 1999 was performed. Of the 18,087 blood specimens sent for culture, 533 (3%) were positive for organisms after 72 hours of hospitalization and were defined as NBSI. The rate of NBSI detected in blood culture specimens was highest among neonates (5.2%). Gram-positive cocci and gram-negative rods caused NBSI in an equal proportion (46% and 44% respectively) and Candida caused 10 per cent of NBSI. Coagulase-negative staphylococci was the most common pathogen followed by K. pneumoniae and Enterobacter. Antibiogram showed that 15 of the 35 (43%) S. aureus identified were methicillin-resistant. Only 35-38 per cent of Enterobacteriaceae were sensitive to cefotaxime or ceftazidime. Cefoxitin was still effective against 95 per cent of K. pneumoniae. Compared with other third generation cephalosporins, combination of cefoperazone and betalactamase-inhibitor (sulbactam) possessed an increased in vitro efficacy against K. pneumoniae, Enterobacter, E. coli, Acinetobacter and non-fermentative gram-negative rods. Resistant rate of amikacin among all gram negative rods was 25-69 per cent. Ciprofloxacin sensitivity varied from 62-100 per cent among all gram-negative rods. Imipenem was excellent against all gram-negative rods with the sensitivity of 80-100 per cent. Epidemiological data of this study is important for the decision of the appropriate empirical antimicrobial treatment in our hospital.

HIV seroconversion during pregnancy and risk for mother-to-infant transmission.

Pregnant women infected with HIV-1 were enrolled in a prospective mother-to-infant transmission study from 1992 through 1994 in Bangkok. In participating hospitals, voluntary HIV testing was routinely offered at the beginning of antenatal care and again in the middle of the third trimester of pregnancy. Women who seroconverted to HIV during pregnancy were compared with women who had tested positive on their first antenatal test. Maternal HIV RNA levels were determined during pregnancy, at delivery, and postpartum using RNA polymerase chain reaction (PCR), and infection status in infants was determined by DNA PCR. No infants were breast-fed, but prophylactic antiretroviral therapy was not yet used in Thailand to prevent transmission from mother to infant. Among enrolled women, 16 who seroconverted during pregnancy and 279 who were HIV-1-seropositive at their first antenatal test gave birth. Median plasma RNA levels at delivery were similar for the two groups (17,505 and 20,845 copies/ml, respectively; p =.8). Two (13.3%) of 15 infants born to women who seroconverted and 66 (24.8%) of 266 infants born to previously HIV-seropositive women were infected with HIV (p =.5). There was no increased risk for mother-to-infant HIV transmission and no significant difference in viral load at delivery between HIV-infected women who seroconverted to HIV during pregnancy and those who were HIV-seropositive when first tested.

Safety of late in utero exposure to zidovudine in infants born to human immunodeficiency virus-infected mothers: Bangkok. Bangkok Collaborative Perinatal HIV Transmission Study Group.

BACKGROUND: Short-course zidovudine (ZDV) given in the late antenatal period can reduce mother-infant human immunodeficiency virus (HIV) transmission by one half. Because this intervention is being implemented in developing countries, evidence of its safety is needed. METHODS: In a randomized, double-blinded, placebo-controlled trial in Bangkok, HIV-infected pregnant women received either ZDV (300 mg twice daily from 36 weeks' gestation until labor, then every 3 hours until delivery) or an identical placebo regimen. Infants were evaluated at birth and at 1, 2, 4, 6, 9, 12, 15, and 18 months of age. Growth, clinical events, and hematologic and immunologic measurements were compared between treatment groups. RESULTS: Of the 395 children born (196 in ZDV group and 199 in placebo group), 330 were uninfected, 55 were infected, and 10 had indeterminate infection status. Overall, 319 children (81%) completed 18 months of follow-up, and 14 (4%) died before 18 months of age. Among uninfected children, the mean hematocrit was lower in the ZDV group at birth (49.1% vs 51.5%) but not at later ages; mean weight, height, head circumference, and CD4(+) and CD8(+) T lymphocyte counts were similar in both groups at all ages. Five uninfected children in the ZDV group but only one in the placebo group had a febrile convulsion. No other signs suggestive of mitochondrial dysfunction and no tumors were observed. Among infected children, an estimated 62% in the ZDV group and 77% in the placebo group survived free of Centers for Disease Control and Prevention class C disease during the 18-month follow-up. CONCLUSIONS: No significant adverse events were associated with short-course ZDV during 18 months of follow-up in this population.

Intestinal parasitic infections among human immunodeficiency virus-infected and -uninfected children hospitalized with diarrhea in Bangkok, Thailand.

A prospective observational study was conducted to determine the prevalence and the clinical impact of intestinal parasitic infections in diarrheal illness among HIV-infected and HIV-uninfected children hospitalized with diarrhea in Bangkok, Thailand. Stool samples were examined for intestinal parasites using a simple smear method, a formalin-ether concentration method, a modified acid-fast stain and a modified trichrome stain. Intestinal parasites (IP) were identified in the stool specimens of 27 of 82 (33%) HIV-infected and 12 of 80 (15%) HIV-uninfected children (p=0.01). Microsporidia and Cryptosporidium were the most common IP found. Eighty-two percent of HIV-infected and 97% of HIV-uninfected groups presented with acute diarrhea and 76% of each group had watery diarrhea. Pneumonia was the most common concurrent illness, found in 22%. Clinical findings were unable to differentiate children infected with IP. Sixty-three percent of HIV-infected and 83% of HIV-uninfected children who had IP made a satisfactory recovery without specific anti-parasitic therapy. However, 9 children (7 HIV-infected and 2 HIV-uninfected) with persistent diarrhea who also had cryptosporidiosis and/or microsporidiosis did not respond to azithromycin and/or albendazole respectively. HIV-infected children with cryptosporidiosis were older and had more advanced HIV infection than those with microsporidiosis. Routine stool examination for IP should be considered due to the absence of clinical markers. The lack of effective therapy for the major IP found underscores the importance of preventive measures.

Perinatal asphyxia: multivariate analysis of risk factors.

UNLABELLED: Perinatal asphyxia contributes greatly to neonatal mortality and morbidity. In developing countries, the need for risk assessment in perinatal asphyxia is obvious because of the high birth rate and limited perinatal resources. OBJECTIVE: To determine the incidence and risk factors of perinatal asphyxia in infants who were delivered from mothers with high-risk conditions. STUDY DESIGN: A prospective study over a 5-year period from 1993 to 1997 was performed at a tertiary level, referral hospital. PATIENTS AND METHOD: Nine hundred and sixty-one infants who were delivered from 878 high-risk mothers were recruited. All of the risk factors that might have contributed to asphyxia were identified and recorded. Univariate and stepwise multiple logistic regression analysis was performed to identify significant factors that might have contributed to asphyxia, the odds ratios and 95 per cent confidence interval were computed. RESULTS: Abnormal fetal heart rate pattern, thick meconium stained amniotic fluid, and premature delivery, were three common risk factors for asphyxia. The mean gestational age was 37.6 +/- 3.5 weeks, 10.5 per cent (101/961) were infants less than 33 weeks. The incidence of asphyxia was 9.7 per cent and was highest (26.7%) in infants less than 1000 g. By univariate analysis, significant relationships between perinatal factors and asphyxia were found among birth weight, gestational age, premature and breech delivery but stepwise multiple logistic regression analysis revealed that only birth weight was significantly associated with perinatal asphyxia. CONCLUSION: In countries where resources are limited, a neonatal resuscitation team should be available for very low birth weight infants, premature and breech delivery.

Evaluating a new strategy for prophylaxis to prevent Pneumocystis carinii pneumonia in HIV-exposed infants in Thailand. Bangkok Collaborative Perinatal HIV Transmission Study Group.

OBJECTIVE: To evaluate a strategy for prophylaxis against Pneumocystis carinii pneumonia (PCP) for infants in Thailand. METHODS: HIV-infected women were offered trimethoprim-sulfamethoxazole for PCP prophylaxis for their children at 1-2 months of age. When the children reached 6 months of age, investigators simulated a decision to continue or stop prophylaxis on the basis of clinical criteria, and compared their decisions with results of polymerase chain reaction (PCR) testing for HIV. We calculated the proportions of children who received and completed prophylaxis, and compared the rates of pneumonia and death from pneumonia with rates from an earlier prospective cohort. RESULTS: Of 395 eligible infants, 383 (97%) started prophylaxis. By 6 months of age, 10 (2.6%) were lost to follow-up, three (0.8%) were non-adherent, seven (2%) had stopped because of adverse events, four (1%) had died, and 359 (94%) still received prophylaxis. At 6 months of age, 30 (70%) of 43 HIV-infected children and 16 (5%) of 316 uninfected children met the clinical criteria to continue prophylaxis. The incidence of pneumonia at 1 to 6 months of age was 22% (15/68) in the earlier cohort, and 13% (6/46) in the recent cohort [relative risk (RR) 0.6, 95% confidence interval (CI) 0.3-1.4; P= 0.22]; mortality rates were 9% and 4%, respectively (RR 0.5; 95% CI 0.1-2.3; P = 0.47). CONCLUSION: This PCP prophylaxis strategy appeared to be acceptable and safe, may have reduced morbidity and mortality from pneumonia, and should be considered in developing countries where early laboratory diagnosis of perinatal HIV infection is unavailable.

Lack of association between human immunodeficiency virus type 1 antibody in cervicovaginal lavage fluid and plasma and perinatal transmission, in Thailand.

To determine the association between human immunodeficiency virus type 1 (HIV)-specific antibody and RNA levels in cervicovaginal lavage (CVL) samples and plasma, zidovudine treatment, and perinatal transmission, HIV subtype E gp160-specific IgG and IgA were serially measured in a subset of 74 HIV-infected women in a placebo-controlled trial of zidovudine, beginning at 36 weeks of gestation. HIV IgG was detected in 100% of plasma and 97% of CVL samples; HIV IgA was consistently detected in 62% of plasma and 31% of CVL samples. Antibody titers in CVL samples correlated better with the RNA level in CVL samples than with plasma antibody titers. Zidovudine did not affect antibody titers. Perinatal HIV transmission was not associated with antibody in CVL samples or plasma. HIV-specific antibody is present in the cervicovaginal canal of HIV-infected pregnant women; its correlation with the RNA level in CVL fluid suggests local antibody production. However, there was no evidence that these antibodies protected against perinatal HIV transmission.

Oral zidovudine during labor to prevent perinatal HIV transmission, Bangkok: tolerance and zidovudine concentration in cord blood. Bangkok Collaborative Perinatal HIV Transmission Study Group.

OBJECTIVES: To evaluate tolerance for the oral administration of zidovudine (ZDV) during labor and measure the resulting ZDV concentrations in umbilical cord blood. DESIGN: A cross-sectional study of women in a placebo-controlled trial of short-course ZDV (twice a day from 36 weeks' gestation until labor and every 3 h during labor) to prevent perinatal HIV transmission in Bangkok. METHODS: Umbilical cord blood was collected. Sixty control specimens and specimens from 372 women (182 in the ZDV group, 190 in the placebo group) were tested for ZDV by radioimmunoassay (lower detection limit < 1 ng/ml). RESULTS: All women in the ZDV group took one or more labor dose, 170 (93%) took their last dose within 3 h of delivery, and only five (3%) experienced nausea or vomiting, a proportion similar to the placebo group. The median concentration of ZDV in the cord blood in the ZDV group was 252 ng/ml (range, < 1-1133 ng/ml); 31 (17%) specimens were less than 130 ng/ml (0.5 microM), the concentration thought to be active against HIV in vitro. Median concentrations were 189 ng/ml in specimens from women taking one or two labor doses, 290 ng/ml in those taking three or four doses, and 293 ng/ml in those taking more than four doses (P < 0.01). The ZDV concentration was not associated with time since the last dose, body weight, or perinatal transmission. CONCLUSION: Oral intrapartum ZDV was feasible and well tolerated. Most ZDV concentrations in the cord blood after oral dosing during labor were at therapeutic concentrations but were lower than those reported after continuous intravenous administration. Although concentrations were not associated with perinatal transmission, these data do not exclude the possibility that intrapartum and neonatal chemoprophylaxis is effective.

Evaluation of susceptibility status of invasive pneumococcal isolates to various antibiotics and risk factors associated with invasive penicillin-nonsusceptible pneumococcal infection: Bangkok 1997-1998.

The antibiotic susceptibility pattern of Streptococcus pneumoniae isolated from specimens of invasive infections was examined at Siriraj Hospital, a tertiary care center in Bangkok, during December 1996 April 1998. The percentage of S. pneumoniae isolates intermediate and resistant to various antibiotics were: penicillin, 25% and 21%; amoxicillin-clavulanate, 24% and 0%; cefuroxime, 6% and 36%; cefotaxime, 6% and 1.4%; ceftibuten, 5% and 42%; imipenem 22% and 0%; co-trimoxazole, 6% and 41%; chloramphenicol, 2% and 26%; erythromycin, 12% and 16%; azithromycin, 0% and 30%; and roxithromycin 0% and 33%. Most of the penicillin-nonsusceptible S. pneumoniae (PNSP) were also nonsusceptible to other antibiotics except cefotaxime, and imipenem. The isolates from respiratory specimens have a higher rate of resistance to all antimicrobial agents with a significant rise in MIC50 of beta-lactam antibiotics. There was no difference in the outcome of infections caused by penicillin-susceptible and -nonsuscetible S. pneumoniae. The only identifiable risk factor associated with PNSP infection was prior use of antibiotic within 3 weeks.

A randomized clinical trial comparing the efficacy of ranitidine and famotidine on intragastric acidity in critically ill pediatric patients.

We examined the efficacy of intravenous ranitidine and famotidine on raising intragastric pH in each of 10 critically ill pediatric patients. The severity of illness was assessed by using the modified zinner index score. The study had 3 phases and each phase took 24 hours. Intragastric pH was measured by continuous pH monitoring digitrapper for 72 hours. In phase 1 and 3, the patients did not receive any H2 blockers. In phase 2, they were randomized to receive intravenous ranitidine or famotidine. The majority of cases had intragastric pH < 4 in day 1 (base line). Ranitidine and famotidine increased total time of intragastric pH > or = 4 from the base line during day 2, 38.2 +/- 16.9 per cent and 60.3 +/- 24.8 per cent respectively (P0.004), but there was no statistical difference between the 2 medications in both Zinner index score 1 and score greater than 1 group (P 0.08, 0.45). Three cases in the famotidine group had successful prophylaxis with total time pH > or = 4 more than 80 per cent. Famotidine appeared to have a trend toward increasing intragastric pH in critically ill pediatric patients.

Safety and immunogenicity of Salmonella typhi Ty21a vaccine in young Thai children.

Salmonella typhi Ty21a vaccine in a liquid formulation was evaluated in 634 Thai children 2 to 6 years of age. The seroconversion rate was 69% for those who received vaccine versus 14% for those who received placebo (P < 0.005). The immune responses among vaccine recipients ranged from 60% in 3-year-olds to 81% for 6-year-olds.

Use of serum gamma glutamyl transpeptidase to differentiate between extrahepatic biliary atresia and neonatal hepatitis.

The differentiation between extrahepatic biliary atresia (EHBA) and neonatal hepatitis (NH) was studied in 53 Thai infants (39 males, 14 females) with obstructive cholangiopathy at the Department of Pediatrics, Siriraj hospital. Prevalence of EHBA was 25 per cent (13 of 15) overall. A higher prevalence of EHBA was found in females (8 of 13) while a higher prevalence of NH occurred in males (34 of 40). No difference was demonstrated in serum conjugated and total bilirubin, SGOT or alkaline phosphatase between EHBA and NH groups. The EHBA group had a significantly higher mean serum GGTP (184 +/- 77 IU/L) than the NH group (58 +/- 40 IU/L). The diagnostic usefulness of GGTP was confirmed, but variation in laboratory measurements could limit its generalizability.

Height and weight of Thai children: high socioeconomic group of the some selected urban population.

A total of 4,371 high socioeconomic children, 2,220 boys and 2,151 girls, from Bangkok Metropolis, from 1985 to 1986 was studied. The height and weight were computed according to sex and age, height and weight for age, and weight for height were calculated in different percentiles (P5, P25, P50, P75 and P95). It was found that height and weight for age of a selected population of children are generally higher, they are taller and heavier than the children of previous studies. At 18 years of age, the average boy is 171 cm and 58 kg, while the average girls is 157.5 cm and 47 kg. The growth rate of Thai adults should be better with socioeconomic improvement in the standards of living in the future. Weight for height is not different from the previous studies, this is a more reliable and better parameter to evaluate the growth of children.

Disappearance of measles antibody in Thai infants after birth.

A seroepidemiology of measles hemagglutination inhibition antibody was studied in infants at birth to 8 months of age. It was found that at birth the antibody was greater than 1:8 in 56 of 64 newborns. At 2 and 4 months of age, 9 of 21 and 12 of 21 respectively had measles antibody titer less than 1:8, while at 8 months of age, only 1 of 6 had the antibody titer greater than 1:8. It shows that the maternal measles antibody can protect the infant at young age and the decrease in antibodies occur as the child grows. The measles vaccine should be given when the maternal passive immunity of measles disappears. This study indicates that the optimal age to recommend measles vaccination should be at the age of 9 months.

Cerebrospinal fluid lactate level in childhood purulent meningitis.

Cerebrospinal fluid lactate was determined in 54 pediatric patients by means of enzymatic method of Marbach and Weil. The mean value of cerebrospinal fluid lactate in 13 purulent meningitis patients was 80.4 mg/dl, in 9 clinical purulent meningitis patients was 72.7 mg/dl, in 18 non-purulent meningitis patients and 14 controls were 17.0 and 11.8 mg/dl respectively. The present study demonstrated that a cerebrospinal fluid lactate level of 35 mg/dl may be used as a cut off point to differentiate bacterial from non-bacterial infection of the central nervous system. It should served as a supplementary aid to clinical examinations and conventional methods to diagnose bacterial meningitis.