Virat Sirisanthana

Disseminated Penicillium marneffei infection in human immunodeficiency virus-infected children

Disseminated infection with the fungus Penicillium marneffei is one of the most common opportunistic infections in human immunodeficiency virus (HIV) disease in northern Thailand. We report the clinical, laboratory and therapeutic features of 21 human immunodeficiency virus-infected children with disseminated P. marneffei who were prospectively followed. Significant clinical and laboratory features included generalized lymphadenopathy (90%), hepatomegaly (90%), body temperature >38.5°C (81%), papular skin lesions with central umbilication (67%), splenomegaly (67%), failure to thrive (52%), severe anemia (hemoglobin <60 g/liter) (43%) and thrombocytopenia (platelet count <0.5 × 1011/liter) (21%). The response rate in patients who were treated with appropriate antifungal therapy (amphotericin B, fluconazole or ketoconazole) was 82%. No relapse was observed in patients given ketoconazole prophylactically. Skin lesions, usually papules with central necrotic umbilication, provide the most significant clue to the diagnosis. Early diagnosis based on finding P. marneffei in the skin smear or lymph node provides the basis for prompt administration of antifungal therapy and improved outcome.

Efficacy of Highly Active Antiretroviral Therapy in HIV-Infected Children Participating in Thailand's National Access to Antiretroviral Program

BACKGROUND Programs for access to antiretroviral treatment were only recently implemented in developing countries. This study aimed to describe the effect of highly active antiretroviral therapy (HAART) in treating human immunodeficiency virus (HIV)-infected children in Thailands National Access to Antiretroviral Program for People Living with HIV/AIDS. METHODS From August 2002 to July 2003, a total of 107 children were enrolled in the study. They received HAART consisting of either nevirapine or efavirenz, together with lamivudine and stavudine. Generic drugs and/or adult formulations were used. CD4 lymphocyte count, plasma HIV RNA level, and weight-for-age and height-for-age z scores were measured before, 2 months after, and every 6 months after initiation of HAART. A genotypic resistance assay was performed for patients with poor virological response. RESULTS The mean age of the patients was 7.7 years (range, 2.1-13.8 years). At baseline, the median CD4 cell percentage was 3%, and the plasma HIV RNA level was 5.4 log10 copies/mL. Four patients died from HIV-related illness. After 72 weeks of HAART, the median CD4 cell percentage was 21%, and 76% of patients had HIV RNA levels of < 50 copies/mL. The mean weight-for-age and height-for-age z scores increased from -1.9 to -1.3 (P < .0001) and from -2.3 to -2.0 (P < .0001), respectively. The percentage of patients who took > or = 95% of prescribed medications during the interval between every follow-up visit was 86% For patients with suboptimal virological response, the most common resistance mutations among HIV isolates were associated with lamivudine and with nonnucleoside reverse-transcriptase inhibitors. CONCLUSION In this resource-limited setting, HAART is safe and effective for HIV-infected children despite initiation of treatment during the advanced stage of disease. The use of generic and nonpediatric drug formulations is feasible.

Immune Reconstitution Syndrome After Highly Active Antiretroviral Therapy in Human Immunodeficiency Virus-Infected Thai Children

Background: There is little information about the immune reconstitution syndrome (IRS) in children, especially from resource-poor countries. Objective: To determine the incidence and spectrum of IRS in advanced stage human immunodeficiency virus (HIV)-infected children after initiation of highly active antiretroviral therapy (HAART). Methods: Between May 2002 and April 2004, 153 symptomatic HIV-infected children who had CD4 lymphocyte percentage ≤15% initiated HAART in a national antiretroviral drug access program. All patients were followed for 48 weeks. In this study, IRS was defined as a disease event caused by microorganisms or conditions previously reported to be associated with IRS in patients having immunologic and/or virologic response to HAART. Results: The incidence of IRS was 19% (95% confidence interval, 13.1–26.1). The median time of onset was 4 weeks after start of HAART (range, 2–31). There were 32 episodes of IRS, including 14 caused by mycobacterial organisms, 7 by varicella-zoster virus, 7 by herpes simplex virus, 3 by Cryptococcus neoformans and 1 episode of Guillain-Barré syndrome. Patients who had IRS develop had lower baseline CD4 lymphocyte percentages compared with those who did not (P = 0.02). Conclusions: IRS is common among HIV-infected children who received HAART in their advanced stage of disease. Educational programs for patients and health care workers on recognizing and treating these conditions should be integrated into antiretroviral treatment access programs.

Disclosure of HIV/AIDS diagnosis to HIV-infected children in Thailand

Background:  With the availability of highly active antiretroviral therapy, more HIV‐infected children have lived longer. Many children are at the age that they should know the diagnosis.

Hospitalization and Mortality among HIV-Infected Children after Receiving Highly Active Antiretroviral Therapy

BACKGROUND Pediatric antiretroviral therapy programs have recently been implemented in resource-limited settings. Their impact in a prospective cohort is not well documented. The aim of this study was to evaluate the rates and causes of hospitalization and mortality among human immunodeficiency virus (HIV)-infected Thai children after receiving highly active antiretroviral therapy (HAART). METHODS Children who started receiving HAART from August 2002 to March 2005 were prospectively observed. The patients included in the study were antiretroviral-naive HIV-infected children who had CD4 cell percentages < or =15% before treatment. All patients were observed for at least 48 weeks. RESULTS One hundred ninety-two children were included. The mean age at HAART initiation was 7.6 years (range, 0.4-14.8 years). At baseline, the mean CD4 cell percentage (+/-SD) was 5.2%+/-4.9%, and the mean plasma HIV RNA level (+/-SD) was 5.4+/-0.5 log(10) copies/mL. Sixty-seven children (35%) were hospitalized a total of 108 times. The hospitalization rate decreased from 30.7% during the first 24-week period to 2.0% during weeks 120-144 after initiation of HAART. Fifty-nine hospital admissions (54.6%) occurred during the first 24 weeks of HAART. Causes of hospitalization were pneumonia and other bacterial infections (61.7%), immune reconstitution syndrome (23.4%), noninfectious illness (6.5%), opportunistic infection (5.6%), and drug-related events (2.8%). The mortality rate decreased from 5.7% in the first 24 weeks to 0%-0.6% in the subsequent 24-week intervals. CONCLUSION Hospitalization and mortality rates significantly decreased among HIV-infected children receiving HAART. Most hospitalizations and deaths occurred during the first 24 weeks of HAART.

Studies on Serological Cross-Reaction in Sequential Flavivirus Infections

Acute‐ and convalescent‐phase sera from patients with dengue (DEN) hemorrhagic fever (DHF) and Japanese encephalitis (JE) that contained pre‐existing flavivirus antibodies were tested for cross‐reacting antibodies to DEN, JE and yellow fever (YF) viruses by a neutralization (N) test. A fourfold or greater rise in N antibody titer in the convalescent‐phase was considered significant. Of 39 DHF cases, obtained at Chiang Mai University Hospital, Thailand, 15 (38.5%) showed a rise in DEN antibody titer, while another 15 (38.5%) showed a significant rise in both DEN and JE N antibody titers. On the other hand, eight (61.5%) of 13 JE cases obtained at the same Hospital, showed a significant rise in JE antibody titer, while two (15.4%) showed a significant rise in both DEN and JE antibody titers. Sucrose gradient centrifugation and fractionation of these two cross‐reactive JE sera revealed that IgM class antibody was specific for JE, while IgG class antibody was cross‐reactive. Of three JE cases with pre‐existing YF antibody obtained in Okinawa, Japan, two showed a significant rise in YF and JE antibodies. Both IgM and IgG class antibodies to YF virus were elevated. These results indicate that the cross‐reactivity among flaviviruses in different subgroups (complexes), was observed quite often, even by the N test, in sequential flavivirus infection.

Epidemiologic, clinical and laboratory features of scrub typhus in thirty Thai children

Background. Scrub typhus, a potentially fatal rickettsial infection, is common in Asia. Although serologic surveys suggested that as many as one-fourth of cases of scrub typhus might be in children, very few reports of childhood scrub typhus are available in the medical literature. Objectives. To document the clinical, laboratory and epidemiologic characteristics of pediatric patients with scrub typhus. Methods. From January 1, 2000 to December 31, 2001, all pediatric patients at Chiang Mai University Hospital who had obscure fever for >5 days were tested for indirect immunofluorescent antibody (IFA) against Orientia tsutsugamushi, the causative organism of scrub typhus. Scrub typhus was diagnosed on the basis of either a single IFA titer against O. tsutsugamushi ≥1/400 or a 4-fold or greater rise in IFA titer to at least 1/200. Results. Thirty children with scrub typhus were enrolled. Most were diagnosed during the rainy months of June to November. Common physical signs included lymphadenopathy (93%), hepatomegaly (73%), eschar (68%), conjunctival hyperemia (33%), maculopapular rash (30%) and splenomegaly (23%). Eleven patients had interstitial pneumonitis and 1 patient had meningitis. All patients responded well to doxycycline or chloramphenicol. The average interval to defervescence after treatment was 29 h (range, 6 to 72). Conclusions. Clinical and epidemiologic features of 30 pediatric patients with scrub typhus are reported in a prospective study. The presence of eschar was helpful in making the diagnosis. Complications included pneumonitis and meningitis. All cases responded well to treatment with antibiotic.

Immune Reconstitution Syndrome Due to Bacillus Calmette-Guérin after Initiation of Antiretroviral Therapy in Children with HIV Infection

The immune reconstitution syndrome caused by bacillus Calmette-Guerin (BCG) was found in 4 HIV-infected children who were immunized with BCG at birth. The localized, suppurative, BCG-related complications developed within 10 weeks after initiation of antiretroviral therapy. The incidence rate was 2.7 cases per 100 persons (95% confidence interval, 0.7-6.7). Patients responded well to treatment with isoniazid and rifampicin.

Response to Measles, Mumps, and Rubella Revaccination in HIV-Infected Children with Immune Recovery after Highly Active Antiretroviral Therapy

BACKGROUND The low prevalence of measles antibody in human immunodeficiency virus (HIV)-infected children after immune recovery as a result of highly active antiretroviral therapy increases the risk of morbidity and mortality from disease. The objective of our study was to evaluate the efficacy and safety of revaccination with measles, mumps, and rubella (MMR) vaccine in HIV-infected children with immune recovery. METHODS Inclusion criteria were (1) HIV-infected children aged >5 years, (2) a nadir CD4 lymphocyte percentage <or=15%, (3) immune recovery (defined as a CD4 lymphocyte percentage >15% for >or=3 months after highly active antiretroviral therapy), and (4) no protective antibody against measles. Each child received 1 dose of MMR vaccine, and antibodies were measured at 4 and 24 weeks after vaccination. Protective antibodies were defined as an antimeasles immunoglobulin G (IgG) level >or=320 mIU/mL, an antimumps IgG titer >1:500, and an antirubella IgG level >10 IU/mL. RESULTS There were 51 participants. The mean age (+/- standard deviation) was 10.2 +/- 2.5 years. Prior to revaccination, 28 participants (55%) had baseline protective antibody to mumps, and 11 (20%) had baseline protective antibody to rubella. The prevalence of protective antibody at 4 weeks was 90%, 100%, and 78% for measles, rubella, and mumps, respectively, and then slightly decreased to 80%, 94%, and 61%, respectively, at 24 weeks after revaccination. No serious adverse reactions were attributed to revaccination. CONCLUSIONS The majority of HIV-infected children with immune recovery can develop protective antibodies after MMR revaccination. Revaccination with MMR vaccine in HIV-infected children with immune recovery should be considered to ensure individual immunity and limit the spread of disease.

Sustained immunologic and virologic efficacy after four years of highly active antiretroviral therapy in human immunodeficiency virus infected children in Thailand.

We report the long-term efficacy of highly active antiretroviral therapy (HAART) in 107 antiretroviral-naive human immunodeficiency virus (HIV)-infected Thai children. In an intention-to-treat analysis, 70% of the children had undetectable HIV RNA titers after 192 weeks of HAART. The mean CD4 cell percentage increased from 5.3% to 26.6%. HAART is effective for HIV-infected children in this resource-poor setting despite initiation of treatment in the advanced stage of disease.