Thai national guidelines for the prevention of mother-to-child transmission of HIV: March 2010.

Thailand has been one of the leading developing countries to implement a national program to prevent mother-to-child transmission (MTCT) of HIV. Although the recent transmission rate has been low, the goal is to eliminate MTCT altogether. The Thai National HIV Guidelines Working Group issued treatment guidelines to prevent MTCT in Thailand in March 2010. These guidelines will be implemented nationwide within a year. The most important aspects of these new guidelines are as follows: Treatment in HIV-infected pregnant women who have not been on antiretroviral treatment prior to pregnancy. Antepartum treatment is recommended for all pregnant women regardless of CD4 count with highly active antiretroviral therapy (HAART) containing zidovudine (AZT) + lamivudine (3TC) + lopinavir/ritonavir (LPV/r). Treatment should be started immediately irrespective of gestational age in women with CD4 count <350 cells/ mm3, and as early as 14 weeks of gestation in those with CD4 count >350 cells/mm3. After delivery, women with baseline CD4 count <350 cells/mm3 are referred for long-term care and HAART according to the National Adult HIV Treatment and Care Guidelines 2010. Women with CD4 count >350 cells/mm3 do not need HAART and can stop all drugs after delivery. The treatment in infants includes AZT syrup for four weeks and exclusive formula feeding. Treatment in HIV-infected pregnant women who conceive while on HAART. Women who are stable on HAART should continue the treatment during the whole period of pregnancy. Those who are taking efavirenz (EFV) and present during the first trimester should have EFV switched to another drug. Whenever possible, AZT should be used during pregnancy. Treatment in infants is similar to the above scenario. Treatment in women who present in labor without antenatal care. Single-dose nevirapine (SD-NVP) 200 mg must be given immediately along with oral AZT 300 mg every three hours until delivery, or oral AZT 600 mg given as a single dose. The tail therapy of AZT + 3TC + LPV/r for four weeks should be given unless these women have a CD4 count of <350 cells/mm3 and therefore require life-long HAART. SD-NVP should not be given if the women are to deliver within two hours. The infants in this situation should receive AZT + 3TC + NVP for four weeks. Treatment during delivery and mode of delivery. During labor, oral AZT 300 mg every three hours or oral AZT 600 mg given as a single dose is recommended regardless of antepartum antiretroviral (ARV) regimen or the woman’s history of AZT resistance. Elective caesarean section is suggested in women who did not receive HAART (including those without antenatal care), received HAART for less than four weeks prior to delivery, had poor adherence, or had incomplete viral suppression at 36 weeks of gestation.

Thai national guidelines for the use of antiretroviral therapy in pediatric HIV infection in 2010.

With better knowledge and availability of antiretroviral treatments, the Thai National HIV Guidelines Working Group has issued treatment guidelines for children in Thailand in March 2010. The most important aspects of these new guidelines are detailed below. ART should be initiated in infants less than 12 months of age at any CD4 level regardless of symptoms and in all children at CDC clinical stage B and C or WHO clinical stages 3 and 4. For children with no or mild symptoms consider CD4-guided thresholds of CD4 <25% (children aged one to five years) or CD4 <350 cells/mm3 (children 5 years or older). The preferred first-line regimen in children aged < 3 years is AZT+3TC+NVP. For children >3 years of age the preferred regimen is AZT+3TC+EFV. If an infant has previously been exposed to NVP perinatally, use AZT+3TC+LPV/r as empirical first regimen. In adolescents, consider TDF+3TC+EFV. The preferred ARV treatment in children who failed first line regimens of 2NRTI+NNRTI (Salvage treatment) comprises 2NRTI (guided by genotype) +LPV/r, and an alternative regimen is 2NRTI (guided by genotype) +ATV/ r (use in cases with dyslipidemia who are six years or older). In cases with extensive NRTI resistance with no effective NRTI option available, double boosted PI with LPV/r+SQV or LPV/r+IDV can be considered. Consultation with an expert is recommended. Laboratory monitoring is recommended for CD4 and every six months. Viral load at least at 6 and 12 months after initiation or change of regimen, then yearly thereafter. More frequent viral load monitoring is advised for cases with unsuccessful virologic response, infants, children with imperfect adherence, or those using of third line regimens. Toxicity monitoring depends on the drug received, at least every six months, and more often as clinically indicated. These include, but are not limited to, complete blood count, renal function tests, liver function tests, urinanalysis, and lipid profiles. Therapeutic drug monitoring is recommended in cases that have ARV-related toxicity, receiving non-standard dosing or regimens, using double boosted PI, and in those with renal or hepatic impairment.

A novel mutation of the IL12RB1 gene in a child with nocardiosis, recurrent salmonellosis and neurofibromatosis type I: First case report from Thailand.

Genetic defects of interleukin (IL)-12/23-and interferon (IFN)-γ-mediated immunity can cause in-creased susceptibility to intracellular microbes. Among these defects, a mutation of the gene encoding the IL-12 receptor β1 (IL-12Rβ1) is the most common worldwide. A 12-year old Thai boy with pre-existing neurofibromatosis type 1 (NF1) was evaluated for primary immunodeficiency after a history of tuberculous lymphadenitis, recurrent Salmonella infections and nocardiosis. Flow cytometry of phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) revealed a defect in the IL-12Rβ1 surface expression. A genetic study showed a novel nonsense homozygous mutation of the IL12RB1 gene in exon 4 (402C>A), confirming the diagnosis of IL-12Rβ1 deficiency. This is the first case report of a primary IL-12Rβ1 deficiency in Thailand with the interesting finding of a coexisting NF1.

Detection of dengue virus in platelets isolated from dengue patients.

Though thrombocytopenia or dysfunction of platelets is common in dengue virus infection, the role of platelets has not been established. We enrolled 33 hospitalized children with serologically confirmed dengue virus infection. Blood specimens were collected during hospitalization. Platelets and plasma were isolated from the whole blood. Detection of dengue virus in plasma and platelets was carried out by RT-PCR with primers that can differentiate different dengue serotypes simultaneously, and by electron transmission microscopy (EM). Dengue viral RNA was detected in the platelets and plasma by conventional RT-PCR. A significantly higher percentage of dengue viral RNA was detected in platelets than in plasma (p = 0.03). Platelets isolated 5 days after onset of fever were most likely positive for viral RNA. Concurrent infection or co-circulation with multiple dengue serotypes was observed in 12% of patients. Infrequently, negative-stranded dengue viral RNA was detected in platelets and in plasma. Importantly, EM confirmed the presence of dengue viral-like particles inside platelets prepared from dengue patients. Our findings suggest the presence of dengue virus in platelets may be associated with the dysfunction of platelets observed in dengue patients.

Cryptococcus neoformans septicemia in an immunocompetent neonate: first case report in Thailand.

Neonatal infection due to Cryptococcus neoformans is extremely rare. We report a case of a 21-day-old neonate diagnosed with cryptococcal septicemia who was successfully treated with amphotericin B. He was born to a human immunodeficiency virus (HIV) seronegative mother. This report alerts general pediatricians and neonatologists to consider Cryptococcus neoformans infection as a possible cause of sepsis in newborn infants.

Antimicrobial susceptibility of Streptococcus pneumoniae isolated from patients with respiratory tract infections in Thailand.

A total of 400 clinical Streptococcus pneumoniae strains from patients with respiratory diseases were collected from January 2002 to December 2005. In this study, an increased prevalence of penicillin-nonsusceptible S. pneumoniae (PNSP) from 63% in 2002-2003 to 69% in 2004-2005 was found. During 2004-2005, 56% were erythromycin-nonsusceptible S. pneumoniae (ENSP) and 54% were both PNSP and ENSP. The PNSP, ENSP and PNSP+ENSP groups showed similar trends, ie, sensitive to amoxicillin/clavulanate (range 97.2-98.5%), levofloxacin (range 90.7-92.4%), ceftriaxone (range 87.1-89.4%), and ofloxacin (range 64.8-66.1%). Lower levels of susceptibility were detected for azithromycin, clarithromycin, cefdinir, cefprozil, clindamycin, co-trimoxazole, chloramphenicol and tetracycline in penicillin and erythromycin-nonsusceptible strains. Of the macrolide-resistant S. pneumoniae, 55% of strains exhibited the M phenotype and 45% the constitutive MLS(B) phenotype. No pneumococci with the inducible MLS(B) phenotype were detected in Thailand.

Treatment of cytomegalovirus (CMV) retinitis with intravitreous ganciclovir in HIV-infected children.

OBJECTIVES: To evaluate the efficacy, visual outcomes, and complications of intravitreous ganciclovir treatment in cytomegalovirus (CMV) retinitis in HIV-infected children. MATERIAL AND METHOD: The medical records of HIV-infected children who were screened for CMV retinitis from February 2002 to February 2005 were reviewed. The children with CD4+ < 15%, or with clinical category C would have complete ophthalmic examination every 3 months. Ganciclovir (4 mg/0.04 ml) was administered intravitreously to the eye with CMV retinitis every 2 weeks under general anaesthesia. After injection, fundi were examined immediately, 1 day, 14 days and every 2 weeks until the lesions were stable. RESULTS: Six (9 eyes) out of 45 children (13%) aged 2-12 years were found to have CMV retinitis. All CMV retinitis lesions were "cheese and ketchup like" (retinal hemorrhage and exudate) lesions and presented in the posterior pole. Bilateral CMV retinitis were found in 3 children. Intravitreous ganciclovir was injected in 4 children (5 eyes). The average number of intravitreous injections for each patient was 5.6 (3-7) times. All of the children received antiretroviral therapy and 3 children also received intravenous ganciclovir CMV retinitis lesions were improved in every eye. The visual acuity (VA) remained stable in 4 eyes, but endophthalmitis developed in one eye a few days after injection. The average duration of follow-up was 13.5 months (3-23 months). CONCLUSION: CMV retinitis was not uncommon. The authors found that intravitreous ganciclovir was effective but may cause complications. This treatment should be considered in a resource-limited setting.

Successful treatment of disseminated BCG infection in a SCID patient with granulocyte colony stimulating factor.

Severe combined immunodeficiencies (SCID) are disorders with impairment of humoral and cellular immune functions. The prognosis of disseminated bacillus Calmette-Guérin (BCG) infection in immunocompromised host is unfavorable since response to standard therapy is poor. We report a successful treatment of disseminated BCG infection with granulocyte colony stimulating factor (G-CSF) in a patient with severe combined immunodeficiency. The patient failed to response to intensive anti-tuberculous (anti-TB) therapy. After 2 months of G-CSF, in addition to anti-TB treatment, the clinical signs of disseminated BCG infection were improved. Since serious BCG infections in SCID are not uncommon in developing countries, where BCG vaccination is mandatory to all newborns, the combination of G-CSF and anti-TB drugs should be considered in immunocompromised patients with protracted mycobacterial infection.

A novel mutation of the CYBB gene resulting in severe form of X-linked chronic granulomatous disease.

We evaluated a boy who had multiple Salmonella septicemia, Aspergillus pneumonia and brain abscesses. His nitroblue tetrazolium (NBT) test was reportedly abnormal. The dihydrorhodamine (DHR) flow cytometry assay was compatible with typical X-linked chronic granulomatous disease (X-CGD). CYBB analysis revealed a novel complex mutation atggacg --> ttca in exon 12 (base pairs 1532-1538). As a result, 3 amino acids Tyr 511, Gly 512 and Arg 513 were deleted and replaced by 2 amino acids, Phe and Gln. The DHR and mutation analysis of his mother showed normal DHR pattern and no mutations in exon 12 of CYBB gene. In conclusion, any children with multiple Salmonella and Aspergillus infection should be suspected of CGD. NBT test, DHR assay and gene analysis are helpful toolsto confirm the diagnosis e v en i n the case of de novo mutation.

Sensitive detection of Pneumocystis jirovecii DNA in gastric wash using nested polymerase chain reaction.

One hundred and five samples of gastric washes were obtained from 52 pediatric patients. Eleven of the 105 samples (10%) gave positive results using immunofluorescence antibody test (IFA) for Pneumocystis jirovecii. Single-step polymerase chain reaction (PCR) produced 13% (14 samples), whereas detection by nested PCR was increased to 65 samples (62%). Moderate agreement (kappa = 0.5) was found between test results of IFA and single-step PCR, but no agreement was found between the results of IFA and nested PCR (kappa = 0.1).

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.

Five-year study of antimicrobial susceptibility and beta-lactamase production in Haemophilus influenzae.

We evaluated 582 Haemophilus influenzae isolates from patients between January 2000 and December 2004. Overall, 433 isolates were obtained from sputum and bronchial washings, 124 isolates were from pus, 19 isolates were from blood and 6 isolates form cerebrospinal fluid. H. influenzae was sensitive to amoxicillin/clavulanate, ampicillin/sulbactam, gentamicin, cefuroxime, ceftriaxone, cefotaxime, ciprofloxacin, ofloxacin, imipenem, meropenem (range 97-100%), chloramphenicol (75%), ampicillin/amoxicillin (52%), but resistant to trimethoprim-sulphamethoxazole. As for beta-lactamase production, 48.4% of the isolates tested were positive.

Serotypes and antimicrobial susceptibilities of Streptococcus pneumoniae isolated from hospitalized patients in Thailand.

Two hundred seven Streptococcus pneumoniae isolates were obtained from patients admitted to Siriraj Hospital. One hundred two, and 105 isolates were from sterile sites and non-sterile sites, respectively. They were serotyped by Quellung reaction with specific antisera from Statens Serum Institut; 81.6% of these pneumococci were typeable. These serotypes were included in the 23-valent pneumococcal polysaccharide vaccine. The five most common serotypes were serotype 6 (22.5%), followed by serotype 23 (18.9%), serotype 19 (16.6%), serotype 3 (7.7%) and serotype 11 (5.3%). Among typeable pneumococci (169 isolates), 52.7% were from sterile sites and 47.3% were from non-sterile sites. Serotypes 6, 23 and 19 were the predominant serotypes isolated from sterile sites. Of the 9 drugs tested, pneumococcal isolates were sensitive to ofloxacin (99%), ciprofloxacin (81.5%), meropenem (80%), imipenem (66.5%), ceftriaxone (65%), cefotaxime (63%), erythromycin (58%), penicillin (48%), and trimethoprim-sulfamethoxazole (34.5%).

Recurrent Campylobacter lari bacteremia in X-linked agammaglobulinemia: a case report and review.

X-linked agammaglobulinemia (XLA) is a primary immune deficiency disease with a B-cell defect. We present the first XLA patient who had recurrent Campylobacter lari bacteremia. High dose intravenous immunoglobulin combined with azithromycin once per week, and a complete avoidance of bacterial reservoirs may be helpful for the prevention of C. lari bacteremia.

Evaluation of guideline for treatment of febrile neutropenia in pediatric cancer at Siriraj Hospital.

BACKGROUND: Febrile neutropenia (FN) is a common and important clinical problem in pediatric cancer. Our Institution has developed a clinical practice guideline (CPG) for treatment of FN to assist the clinicians taking care of these patients.OBJECTIVE: To evaluate characteristics of FN, sources and causative agents of infection, applicability and effectiveness of the CPG, and factors that associated with response to treatment. MATERIALS AND METHODS: The medical records of patients with FN that had completed data from September, 2003 to May, 2005 were reviewed and analysed. RESULTS: A total of 148 FN episodes in 90 patients were analysed. The predominant underlying malignancy was acute leukemia. About 50% had absolute neutrophil count (ANC) less than 100 cells/mm3 at the beginning and at reassesment on day 3 of treatment. The causes of infection with microbiological confirmation was 25%. Urinary tract infection was the predominant source of infection and gram negative bacteria was the predominant causative agent. Sixty-two percents responded to initial treatment without changing of antibiotics. Of all episodes, 91.2% were able to complete treatment according to the CPG. The mortality rate was 1.4%. ANC of less than 100 cell/mm3 on day 3 of treatment was the significant risk factor for prolonged duration of fever and unresponsiveness to low risk regimen of antibiotics. ANC of less than 100 cell/mm3 on day 3, having hematologic malignancies, and recurrent fever were associated risks for the need for antifungal agent or referral to infectious diseases specialist or death. The pretreatment ANC more than 100 cells/mm3 was a significant predictor for the responsiveness to low risk regimen without recurrent fever. CONCLUSION: Our CPG could practically be applied in FN patients and resulted in low mortality 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%.

Diagnosis disclosure in HIV-infected Thai children.

BACKGROUND: Increasing number of children with perinatally acquired HIV-infection are now surviving into school age and adolescence. Disclosure of diagnosis to these children has become an important clinical issue. Clinical reports and studies from other countries suggest that a significant number of these children have not been told of their HIV status. The objective of this study was to assess diagnosis disclosure status of perinatally acquired HIV-infected Thai children. MATERIAL AND METHOD: Primary caregivers of 96 HIV-infected children aged 5 years and older were interviewed to assess the child disclosure status and the caregivers reasons to disclose or not to disclose the diagnosis to the child. The disclosed children were also interviewed to assess perception of their illness. RESULTS: Nineteen of 96 children (19.8%) had been told of their HIV diagnosis by their caregivers. The mean age of the disclosed children was 9.6 years. Eighty-four percent of the disclosed children reported perception of their illness as having HIV infection or AIDS. Common reasons for non-disclosing were concerns that the child was too young, that the child might be psychologically harmed, and that the child could not keep the secret. Of 77 non-disclosing caregivers, 54 reported that they plan to disclose HIV status to the children in the future. CONCLUSION: This study demonstrates that diagnosis disclosure was made in only 1/5 of HIV-infected children, and that most of the caregivers were reluctant in disclosing serostatus to the child. Development of an appropriate guideline for assisting the caregivers and the children to deal with the difficult disclosure process is needed.