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.

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.

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.

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.

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.

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.

Plasma sex hormones, prolactin, cortisol, lipids and lipoproteins in elderly Thai men and women.

Measurements of plasma testosterone or estradiol, prolactin, cortisol, total cholesterol, HDLC, LDLC and triglycerides were carried out for healthy elderly Thai men and women. Estradiol and testosterone levels were higher while the estradiol to testosterone ratio was lower in elderly men compared with elderly women. No significant difference in plasma prolactin and cortisol was found between men and women of advanced age. A significant decrease in the estradiol level in older women was detected, but testosterone in older men did not alter. Elderly women had higher plasma total cholesterol and HDLC than elderely men, but there were no differences in LDLC, LDLC/HDLC ratio and triglycerides between the sexes. No significant age-related alteration of lipids and lipoproteins was observed in older men and women. The relationship between studied hormones levels and lipids or lipoproteins was not shown. Gender was found to be only factor affecting plasma , testosterone and E/T ratio in healthy aging Thais.

Efficacy and safety of azithromycin in the treatment of pediatric upper respiratory tract infections, an open non-comparative multicentre study.

The clinical efficacy and safety of a three-day course of azithromycin was evaluated in 39 children (aged 1-15 years) with clinical diagnosis of acute upper respiratory tract infections (acute pharyngitis and/or acute tonsillitis, acute otitis media and acute sinusitis). Patients received azithromycin in a single daily dose of 10 mg/kg (maximum 500 mg) orally for three days. Clinical assessment and throat culture were carried out before and after therapy. Overall clinical efficacy was fund to be satisfactory (cured or improved) in 37/39 (94.8 percent) of patients. Bacteriological efficacy, which was evaluated by eradication of the pathogens, was found in 16/18 (88.8 percent). In the remaining two patients, one was clinically cured despite persistent Staphylococcus aureus, while the other case of clinical failure was associated with a resistant strain of Psuedomonas seruginosa. The drug was well tolerated and treatment-related side-effects, which were reported in only 3*39 (7.69 percent) of the patients, were gastrointestinal in nature and of mild severity. The results of the study indicated that a single daily dose, in a three-day regimen, of azithromycin is effective and well-tolerated in the treatment of children with acute upper respiratory tract infections.

The mortality of infants and children born to HIV-infected mothers.

A retrospective study was made on seventy-one infants and children born to HIV-1 infected mothers, who admitted and expired at Department of Pediatrics, Siriraj Hospital from September 1991 to August 1995. Sixty-three were diagnosed to be HIV infected and 8 were undetermined. In the group of undetermined HIV-infection, the causes of death included sepsis, prematurity, pneumonia and congenital heart disease. Among the 63 of HIV-infected group, 25 (40%) died before age 6 months, 36 (57%) and diarrhea 29 (46%). Other causes of death included gastrointestinal heamorrhage, congestive heart failure, candida esophagitis, wasting syndrome and liver failure. P.carinii was identified in 5 cases (12.2%) among the group of children who died with pneumonia. Of 36 children who died with sepsis, the etiologic agent were confirmed by blood culture 29 (80.5%). A single pathogen was isolated in 18 cases (62%) whereas multiple pathogens were isolated in 10 cases (38%) and only 1 yielded Candida albican. Gram-positive bacteria was identified in 11 cases (38%) which 8 cases (73%) of S.aureus were the most common isolated bacteria. Gram negative bacteria were confirmed in 22 cases (62%) of which 7 cases (32%) of salmonella species were the most frequent isolated bacteria. In the group of children who died of diarrhea, the causative agents wee identified in 12 cases (43%) by which 8 cases (66%) of cryptosporidium and 6 cases (50%) of salmonella species were the most common isolated pathogens. Among the 63 of HIV-infected children, 20 (32%) were the first admitted group and pneumonia 17 (85%) was found to be the most common cause of death.