A comparative study of the serological response to Japanese encephalitis vaccine in HIV-infected and uninfected Thai children.

We report a prospective study of mouse brain derived inactivated Japanese encephalitis (JE) vaccine, given in 3-dose EPI program to human immune deficiency virus (HIV)-exposed Thai infants. 18 HIV-infected receiving antiretroviral therapy with median baseline CD4 of 33.1%, and 92 HIV-uninfected children were studied. All but one HIV-infected child seroconverted after the second dose. The geometric mean titers (GMTs) 3 months after the second and third doses in HIV-infected vs HIV-uninfected children were 247 vs 938 (p=0.022), and 2273 vs 24069 (p=0.009), respectively. Urticaria or angioedema found in 4% and 6% in HIV-infected and -uninfected children, respectively (p=1.0). The vaccine was safe and immunogenic but antibody response in HIV-infected children was not as high as in uninfected children.

Efficacy and tolerability of nevirapine- versus efavirenz-containing regimens in HIV-infected Thai children.

BACKGROUND: Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral therapy (HAART) has been the most affordable regimen for the HIV-infected in developing countries. There are limited data comparing nevirapine (NVP) to efavirenz (EFV) in HIV-infected children. This study aimed to assess the efficacy and tolerability of NVP-based regimens compared to EFV-based regimens in HIV-infected children in Thailand. METHODS: The medical records of HIV-infected children who had received NNRTI-based regimens for more than 6 months at the Department of Pediatrics, Siriraj Hospital, Mahidol University, Thailand, were reviewed. RESULTS: Of the 139 HIV-infected children studied, 70 were male, and the median age at treatment initiation was 6.08 years (range 0.32-14.56 years); the median duration of follow-up was 36 months (range 6-66 months). The median baseline CD4 cell count was 185cells/mm(3) (range 2-3482cells/mm(3)) and the median baseline CD4 percentage was 7.20% (range 0.11-36.57%). An NVP-based regimen was initiated in 61 (44%): 38 antiretroviral (ARV)-naïve and 23 ARV-experienced. An EFV-based regimen was initiated in 78 (56%): 34 ARV-naïve and 44 ARV-experienced. The CD4 cell count and percentage gains were not different between the NVP and EFV groups in both the ARV-naïve and the ARV-experienced. However, ARV-naïve children who received an EFV regimen had significantly lower baseline CD4 levels than those who received an NVP regimen. ARV-naïve children had a better CD4 response than the ARV-experienced. The survival rates of children in the NVP groups were not different from those in the EFV groups for both the ARV-naïve and the ARV-experienced. Treatment failure occurred in one ARV-naïve NVP case (2.6%), two ARV-naïve EFV cases (5.8%), and nine ARV-experienced NVP cases (39%) at 24 months of treatment, and 11 ARV-experienced EFV cases (25%) at 18 months of treatment. Seven (10%) children had adverse effects from treatment with NVP. The main side effects were rash and hepatitis; six had to switch to EFV. Four (5%) children had adverse effects from treatment with EFV; two had to switch to NVP. CONCLUSIONS: Both NVP- and EFV-based HAART regimens were effective in children in Thailand for at least 3 years. HIV-infected Thai children generally tolerated NNRTI well.

Infection with hepatitis C virus among HIV-infected pregnant women in Thailand.

OBJECTIVE: The purpose of this study was to describe the epidemiology of coinfection with hepatitis C virus (HCV) and HIV among a cohort of pregnant Thai women. METHODS: Samples from 1771 pregnant women enrolled in three vertical transmission of HIV studies in Bangkok, Thailand, were tested for HCV. RESULTS: Among HIV-infected pregnant women, HCV seroprevelance was 3.8% and the active HCV infection rate was 3.0%. Among HIV-uninfected pregnant women, 0.3% were HCV-infected. Intravenous drug use by the woman was the factor most strongly associated with HCV seropositivity. Among 48 infants tested for HCV who were born to HIV/HCV coinfected women, two infants were HCV infected for an HCV transmission rate of 4.2% (95% 0.51-14.25%). CONCLUSIONS: HCV seroprevalence and perinatal transmission rates were low among this Thai cohort of HIV-infected pregnant women.

Evaluation of a practical method to assess antiretroviral adherence in HIV-infected Thai children.

The objective of this study was to evaluate a practical method to assess adherence to antiretroviral therapy by observing virological and immunological responses. We conducted a 12-month longitudinal cohort study of 162 HIV-infected Thai children. Adherence was assessed using 5 methods (self reporting calendar, records of missed doses, pill counts, physician assessment, and an interview questionnaire). CD4 count, percentage and viral load were performed at baseline and at 12 months. Mean adherence rates at 2, 6, and 12 months were 98, 100, and 99% by the calendar method; 98, 100, and 100% by recording missed doses; 96, 96, and 92% by pill count; and 90, 94, and 97% by physician assessment. Poor agreement (kappa < or = 0.1) was found among the methods. There was a statistically significant difference (p = 0.05) in virological response between participants with > or = 95% adherence (0.8 log10) and those with < 95% adherence (0.2 log10) when pill counts were used to assess adherence. In conclusion, despite poor agreement among these tools, a pill count appeared to be the only practical, validated method to differentiate the virological outcome between those who were fully and partially adhere to the treatment regimen.

Factors associated with the development of tuberculosis in BCG immunized children.

In this hospital-based case-control study, children attending Siriraj Hospital and Queen Sirikit National Institute of Child Health from 1 December 2002 to 30 June 2003 were studied to define factors associated with TB in BCG immunized children (n = 260). Subjects of the same age and sex were divided into case and control groups by tuberculosis status. Caregivers were interviewed with a structured questionnaire. Data were analyzed by univariate analysis and multivariate analysis for biological factors (birth weight, health status, nutritional status), socioeconomic factors (parental education, education of caregiver, parental occupation, household incomes, and stability of household incomes), and environmental factors (history of contact with a tuberculosis patient, housing ventilation, child's bedroom ventilation, biomass smoke, passive smoking, crowded family and crowded in child's bedroom). Our findings show that children who had contact with TB patients had a very high risk of tuberculosis, even though they were vaccinated at birth. The risks vary according to the closeness level: very close (OR 85.67, 95%CI = 11.33-647.79), close (OR 31.11, 95%CI = 3.93-246.22) and not close (OR 32.70, 95%CI = 4.18-255.94). In order to identify the effect of others variables, the data was reanalyzed only in the group with no history of TB patient contacts (n = 192). Living in a crowded family, which was reflected by an average of 5 or more persons per room, also increased the risk (OR 11.18, 95%CI = 2.35-53.20). The other factor that increased the risk for tuberculosis was passive smoking. Children who were exposed to passive smoking had a 9.31 times increased risk of getting tuberculosis (95%CI = 3.14-27.58). These findings suggest that the public health department must develop a TB surveillance system in high TB prevalence areas, and in high density communities, and encourage smokers in every family to avoid smoking near children. Latent tuberculosis treatment recommendations for TB control cluster, as set by the Bureau of AIDS/TB and STIs, must be implemented in all health centers and an effective TB control program must be reinforced.

Effect of antiretroviral therapy in human immunodeficiency virus-infected children.

BACKGROUND: The appropriate timing of antiretroviral (ARV) therapy initiation in children with human immunodeficiency virus (HIV) infection has been uncertain. There was evidence of poorer outcome in adults who initiated treatment at lower baseline CD4 cell count. However, early initiation may not be possible in resource-limited setting and would increased risk of long term side effects and non-adherence. OBJECTIVE: To elucidate the outcome of HIV-infected children who ARV treatment was initiated at different disease stages. MATERIAL AND METHOD: Data from medical records of HIV-infected children who had been followed at Infectious Disease Division, Department of Pediatric Siriraj Hospital were retrospectively reviewed. Clinical response and outcome data were analyzed. RESULTS: From September 1996 to March 2004, there were 200 patients with a median age at treatment initiation of 38 (2-175) months. The median duration of follow up period was 26 (1-91) months. The median baseline CD4 cell count was 545 (2-5016) cells/mm3. The median baseline CD4 percentage was 14.25 (0.11-60). Monotherapy or dual nucleoside reverse transcriptase inhibitor (NRTI) regimens were initiated in 134 (67%), and HAARTwas initiated in 66 (33%) patients. The survival rate in patients who initiated with HAART tended to be better than those initiated with dual NRTI regimens but salvaged appropriately (p=0.2377). The survival rate in those initiated treatment at baseline CD4 > or = 15% was better than those initiated at baseline CD4 < 15% (p=0.0471). CONCLUSION: Initiation of ARV treatment at CD4 more than 15% resulted in a better survival rate than at CD4 below 15%. Initiation with HAART regimen tended to improve survival and resulted in higher CD4 gain especially in cases with baseline CD4< 15%.

The first pediatric case of Staphylococcus aureus with heterogenous resistant to vancomycin endocarditis in Thailand.

Staphylococcus aureus with reduced susceptibility to vancomycin has been reports worldwide. Here we report the first pediatric case of heterogeneous vancomycin intermediate resistance Staphylacoccus aureus (hVISA) causing endocarditis in Thailand. A 4 months old girl with truncus arteriosus type IV and ventricular septal defect developed methicillin-resistant S. aureus (MRSA) bacteremia and endocarditis after total repair operation. The patient did not respond to combination antimicrobial treatment including vancomycin. The strain was susceptible to trimethoprim-sulfamethoxazole and vancomycin by conventional antimicrobial susceptibily test. The vancomycin minimal inhibitory concentration by E-test was 2 microg/ml. The strain was judged to be possible heteroresistant when screening was done by one-point population analysis. The subsequent population analysis and testing for the emergence of mutants with reduced susceptible to vancomycin confirmed that this strain was hVISA. Despite the treatment with vancomycin, amikacin, rifampicin and cotrimoxazole, the patient died. hVISA should be suspected in MRSA infections that were refractory to vancomycin therapy could be due to. The emergence hVISA underscored the importance of the prudent use of antibiotics, the laboratory capacity to identify MRSA and hVISA and proper communication with treating clinicians, and the meticulous infection-control measures to prevent transmission.

Initiation of antiretroviral treatment with dual nucleoside reverse transcriptase inhibitors in human immunodeficiency virus-infected infants with less advanced disease in a resource-limited setting: a multi-center study in Thailand 1998-2000.

OBJECTIVES: To evaluate the feasibility, duration of efficacy, and outcome of therapy with dual nucleoside reverse transcriptase inhibitors (NTRI) initiated in HIV-infected infants with mild to moderate disease. MATERIAL AND METHOD: During 1998-2000, a multi-center prospective open-labeled operational study was conducted. Antiretroviral naôve HIV-infected infants were enrolled in seven hospitals to receive either zidovudine (AZT) plus lamivudine (3TC) or AZT plus didanosine (ddI). Infants who were in CDC stage "C3" were excluded from the study. RESULTS: Of the 88 infants, the mean age of treatment initiation was 6.8 months, and the mean initial CD4 was 1538 cells/mm3 (21.4%). The z-scores for weight and height increased after 4-8 months of treatment, and by the 24th month, were +0.89 and +0.69 higher than at enrollment. The CD4% peak increased at 8 months of treatment, by a mean increment of 4.19%, but decreased to the level of 1.08% above baseline by the 24th month of treatment. Three (3.4%) infants died, 11 (12%) had disease progression, 7 (8%) was prematurely discontinued from the study protocol due to poor compliance, and 37 (42%) were lost to follow-up. At the end of 24 months, all remaining 30 children were in stable condition with a chance of clinical and immunological stability of 34% and 68% by intention-to-treat and on-treatment analysis, respectively. CONCLUSION: Clinical and immunological benefit from dual NRTI was limited. Treatment of HIV-infected infant with mild to moderate disease in a resource-limited setting may have limited feasibility due to the high drop-out rate.

Catch-up vaccination against Haemophilus influenzae type b in human immunodeficiency virus-infected Thai children older than 2 years old.

Although most of Thai children older than 2 years are immune against Haemophilus influenzae type b (Hib) without prior vaccination, it may not be the case in HIV-infected children. Of 44 HIV-infected children tested before vaccination at the mean age of 36 months (range 24-84 months), 32 (73%) were susceptible (anti-PRP <0.15 microg/ml). At 6 months after a single dose of tetanus-conjugated Hib vaccination, 67% developed anti-PRP >/=0.15 microg/ml, however, only 33% developed titer of >/=1 microg/ml. Four of seven (57%) with anti-PRP 0.15-0.99 microg/ml at baseline were boosted to the titer of >/=1 microg/ml after vaccination. Seroconversion rate and geometric mean titer (GMT) level in response to the vaccination did not correlate with HIV stage, but did correlate with viral load level of 100,000 copies/ml. HIV-infected children older than 2 years would benefit from Hib vaccination, although, one dose catch-up schedule is not sufficient in a third of these children. A second dose is needed in these children especially those with viral load of level of >100,000 copies/ml.

Diagnosis of dengue infection using various diagnostic tests in the early stage of illness.

In order to elucidate the usefulness of various tests in the early course of dengue infection, in terms of diagnosis and correlation with clinical severity, blood specimens were collected every 48 hours on 3 occasions from patients with clinical suspicion of dengue infection with fever for less than 4 days. Viral isolation was attempted by mosquito inoculation (MI), tissue culture inoculation (TC), and reverse transcriptase polymerase chain reaction (RT-PCR). Antibodies were detected by hemagglutination inhibition test (HI), an in-house-ELISA (IH-ELISA), and an ELISA by MRL diagnostics Clinical data were collected from the time of enrollment to complete recovery. Of the 40 patients enrolled, 31 were diagnosed as dengue infection and confirmed by either serology or viral isolation. Of these, 12 had primary infection and 19 had secondary infection. Dengue fever occurred in 9 cases. Dengue viruses were isolated from 28 out of 31 patients, and dengue hemorrhagic fever was diagnosed in 22 patients. Viral serotypes identified by viral isolation, and RT-PCR were concordant: DEN1 was isolated in 8, DEN2 in 13, DEN3 in 5, and DEN4 in 2 patients. Viral isolation yielded positive results on blood collected before the 5th day of fever. MI was more sensitive than TC. RT-PCR was less sensitive than viral isolation during the early days of fever, but became more sensitive after the 5th day of fever. RT-PCR was able to detect virus up to day 7-8 of fever, even after defervescence, and in the presence of antibody. During the febrile stage, serological diagnosis on blood samples taken 48 hours apart was carried out by HI, IH-ELISA, and MRL-ELISA, facilitating diagnosis in 3 (10%), 21 (67%), and 27 (87%) of patients, respectively. All of the patients with secondary infection were diagnosed by MRL-ELISA before defervescence. By the 8th day of fever, a serological diagnosis aided to diagnose in 9 (29%), 29 (93%), and 31 (100%) of patients by HI, IH-ELISA, and MRL-ELISA, respectively.

Breakthrough neurological manifestation during appropriate antituberculous therapy of miliary tuberculosis.

We report a 20-month-old girl with miliary pulmonary tuberculosis and normal neurological findings. While on treatment with isoniazid, rifampicin, pyrazinamide, and ethambutol for 1 month, she developed weakness of the lower extremities without meningism or altered consciousness. A computerized tomogram revealed tuberculomas and basal arachnoiditis. The cerebrospinal fluid findings were compatible with tuberculous meningitis. She responded well to systemic corticosteroids.

Short-course therapy with zidovudine plus lamivudine for prevention of mother-to-child transmission of human immunodeficiency virus type 1 in Thailand.

To evaluate the efficacy and safety of short-course therapy with zidovudine plus lamivudine for reduction of perinatal transmission of human immunodeficiency virus type 1 (HIV-1), a single-arm, open-label, prospective, nonrandomized study was conducted. One hundred six treatment-naive pregnant women received zidovudine (300 mg) plus lamivudine (150 mg) twice daily from week 34 of gestation until the onset of labor. During labor, zidovudine and lamivudine were given every 3 h. Neonates received zidovudine syrup for 4 weeks and were bottle fed. The median maternal virus load and CD4+ cell count at weeks 32-34 of gestation were 4.33 log10 copies/mL and 274 cells/mm3, respectively. At delivery, the mothers' mean decrease in virus load was 1.55 log10 copies/mL and the mean increase in CD4+ cell count was 93 cells/mm3, compared with enrollment levels. Three neonates were HIV-1 infected, for a transmission rate of 2.83% (95% confidence interval, 1%-8%). There were no serious adverse events in the mothers. Adverse events noted in neonates were anemia (in 6 neonates), elevated transaminase levels (in 1), and thrombocytopenia (in 3). Short-course therapy with zidovudine plus lamivudine appeared to be safe and effective for prevention of perinatal transmission of HIV-1.

Mycobacterium avium complex in HIV-infected Thai children.

Of the 169 human immunodeficiency virus (HIV)-infected children being cared for at Siriraj Hospital from January 1998 to September 2000, 10 had Mycobacterium avium complex (MAC) infection; seven had disseminated disease and three had MAC pneumonia. Nine children were in the advanced stage of HIV disease at the time of diagnosis with the median CD4 count of 7 cells/mm3 and 127 cells/mm3 and the median age of 65 months and 63 months in disseminated MAC and MAC pneumonia respectively. None of these children had received prior chemoprophylaxis. Common clinical findings included prolonged fever, weight loss, lymphadenopathy, hepatosplenomegaly, diarrhea, anemia and leukopenia. The outcome of MAC infection was poor, with a mortality rate of 60 per cent. In in vitro susceptibility testing, clarithromycin was the least resistant drug. With the incidence rate of 2.15 per 100 person-years, the high rate of antimicrobial resistance, and the poor outcome, primary chemoprophylaxis for MAC infection in conjunction with effective antiretroviral therapy should be considered for Thai children in the advanced stage of HIV infection.

Survival, disease manifestations, and early predictors of disease progression among children with perinatal human immunodeficiency virus infection in Thailand.

OBJECTIVE: To describe survival and signs of human immunodeficiency virus (HIV) infection in perinatally infected children in Thailand. METHODS: At 2 large Bangkok hospitals, 295 infants born to HIV-infected mothers were enrolled at birth from November 1992 through September 1994 and followed up with clinical and laboratory evaluations every 1 to 3 months for 18 months. Infected children remained in follow-up thereafter. For the infected children, we used data collected through October 2000 to estimate survival times and compare characteristics among those whose disease progressed at rapid (died within 1 year), intermediate (died at 1-5 years), and slow (survived at least 5 years) rates. RESULTS: None of the 213 uninfected children died during the follow-up period. Of the 68 infected children, 31 (46%) died; median survival was 60 months (95% confidence interval: 31-89 months). The most common cause of death was pneumonia (52% of deaths). Thirty-two children (47%) started antiretroviral therapy. Six children died in their first year before developing specific signs of HIV infection; all others developed signs of HIV infection between 1 and 42 months old (median: 4 months). Severe clinical (Centers for Disease Control and Prevention Class C) conditions were diagnosed in 23 children at a median age of 12 months, 15 (65%) of whom died a median of 3 months later. Compared with children whose disease progressed slowly, those whose disease progressed rapidly gained less weight by 4 months old (median 1.7 vs 2.6 kg), and their mothers had higher viral loads (median 5.1 vs 4.5 log(10) copies/mL) and lower CD4(+) counts (median 350 vs 470 cells/ micro L) at delivery. CONCLUSIONS: Among HIV-infected Thai children, survival times are longer than among children in many African countries, but shorter than among children in the United States and Europe. Signs of HIV develop early in most children. Growth failure and advanced maternal disease can predict rapid HIV disease progression and may be useful markers for treatment decisions.