Anaphylaxis: a ten years inpatient retrospective study.

Background: The actual incidence of anaphylaxis is unknown. Periodical study of the anaphylaxis in different countries will raise the awareness to improve further the prevention and care. Methods: To investigate anaphylaxis among inpatients in the previous decade, we conducted a retrospective study of adult patients between 1992 and2001 at a tertiary care center in Bangkok. Results: Of 448,211 admissions, 80 events of anaphylaxis in 79 patients (0.017%) were found. The incidence had increased from 2.6 to 46 per 100,000 inpatients. Mean age±SD was 36±16 years-old, with an equal male:female ratio. Drugs, mainly antibiotics and nonsteroidal anti-inflammatory agents, (48%) and food (31%) were the most common causes. Over-the-counter medication and multiple drug use were responsible for up to a half of the unspecified drug causes. There was no fatality. 84% received epinephrine, but in only 7 % it was given intramuscularly. Fifteen cases (20%) had a history of prior anaphylaxis, nonetheless only one had received prefilled epinephrine. Conclusions: the rise in the incidence of anaphylaxis over the two decades of the study period is alarming. Raising the awareness of anaphylaxis management among healthcare providers and the public is warranted.

Thai national guidelines for antiretroviral therapy in HIV-1 infected adults and adolescents 2010.

In Thailand, more than 150,000 patients are currently treated with antiretroviral drugs under the support of the National AIDS Program (NAP). The appointed Adults and Adolescents Committee consisted of 28 members who are experts in HIV research, patient care or health care policy. Relevant published literature, guidelines, and the most recent relevant clinical trials presented internationally were reviewed. Several peer review and clinical studies conducted in Thailand were included in the review process. Special considerations for patients with co-infection of tuberculosis or hepatitis B were incorporated. Appropriate cut-off of CD4+ T-cell counts when to commence ART among Thai patients have been considered. It is now recommended to start ART at CD4+ T-cell count <350 cells/mm3. For treatment-naive patients, the preferred initial therapy is a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen containing lamivudine plus zidovudine or tenofovir. Stavudine will be phased out in a two-year plan at the national program level. Viral load and CD4+ T-cell counts should be monitored at least once and twice a year. To achieve long-term treatment success, enhancing adherence together with the proper management of antiretroviral-related toxicity is critical. In summary, the major changes from the Thai 2008 guidelines include commencing ART earlier. ART is recommended regardless of CD4+ T cell count if patients have an indication to treat their HBV co-infection. Preferred first regimen uses AZT or TDF, not d4T as the NRTI-backbone. Furthermore, efavirenz is now considered a preferred NNRTI, along with nevirapine.

Guidelines for antiretroviral therapy in HIV-1 infected adults and adolescents: the recommendations of the Thai AIDS Society (TAS) 2008.

BACKGROUND: More than 100,000 patients have been treated, since the implementation of the National Universal Coverage for antiretroviral therapy (ART) in Thailand Although there are several comprehensive guidelines available internationally, there is a need to have guidelines that can be implemented in Thailand. MATERIAL AND METHOD: The guidelines were developed by a panel of 17 members who are the experts on HIV research and/or HIV patient care and appointed without incentive by the Thai AIDS Society (TAS). The recommendations were based on evidences from the published studies and availability of antiretroviral agents. Published studies that are relevant and applicable to Thailand in particular have been taken into consideration. RESULTS: The recommendations include: when to start ART; what to start; how to monitor the therapy; adverse effects and its management; diagnosis of treatment failure; and antiretroviral treatment options in patients with treatment failure. ART in special circumstances, i.e., patients with co-infection of tuberculosis or hepatitis B virus, is also included Appropriate level of CD4+ T-cell count to start ART among Thai patients has been considered carefully. The authors recommend to start ART at CD4+ T-cell count < 200 cells/mm3. CONCLUSION: ART should be initiated in adults and adolescents HIV-1 infected patients with a history of HIV-related illness or AIDS or with a CD4+ T-cell count <200 cells/mm3. For treatment-naive patients, the preferred initial therapy is a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen. CD4' T-cell count and viral load should be monitored for at least twice and once a year, respectively. Proper management of antiretroviral-related toxicity and enhancement of adherence are crucial for the long-term success of ART.

Cost savings by reagent reduction in flow cytometry-based CD4+ T cell counts: an approach to improve accessibility for HIV management.

In Thailand, the cost of antiretrovirals has recently been reduced more than 10 fold. Likewise strategies for a cost reduction in laboratory monitoring are warranted. This study was designed to explore if the most expensive reagent in flow cytometry based CD4+ cell monitoring, the CD4+/CD8+ monoclonal antibodies, can be reduced without a loss of accuracy. Blood samples from 55 HIV seronegative (HIV-) and 76 HIV+ subjects were analyzed for %CD4+ and %CD8+ T cells using a two color monoclonal antibody panel (BD Biosciences, CA, USA) with 3 different amounts of the recommended reagents for staining: 1) standard, 2) half, and 3) one-fourth. A significant Spearman correlation of 0.987 was shown for the % CD4+ T cell test results for one half as well as one-fourth of the recommended amount compared to the standard staining according to the manufacturer's instruction (p < 0.0001). For the % CD8+ T cell test results, the correlation between the standard and the half or one-fourth reduced staining was 0.972 (p < 0.0001). Bland-Altman analysis showed no significant bias between the results from one half or one-fourth of the recommended amount versus the standard. The sensitivity and specificity of the two methods at the CD4+ T cell count cut-off of 200 cells/microl were 93% and 100%; and 96% and 99%, respectively. Our study indicates that a reduction of the reagents to half or one-fourth of the amount recommended by the manufacturer was still able to generate reliable results for CD4+ and CD8+ T cell counts. Such an approach will significantly reduce the cost of CD4+ monitoring for resource limited settings where a flow cytometer is available.

Three suitable antigens for delayed-type hypersensitivity skin testing in a tropical country like Thailand.

Delayed type hypersensitivity (DTH) skin test is a standard tool to assess in vivo cell-mediated immunity. Mantoux method using 4-5 common recalled antigens is recommended. However, not all antigens are widely available and appropriate antigens for tropical countries are not known. The objective of this study is to investigate what and how many antigens should be included in the DTH testing panel that suitable for Thailand and may be for this region. The DTH skin tests were done by Mantoux method in a double blinded fashion. Average induration size of > or = 5 mm defined as a positive test. Antigens included purified protein derivative (PPD), Candida albicans, tetanus toxoid (TT), Trichophyton mentagrophytes and hepatitis B vaccine (HBV). The negative control was normal saline. Of 95 healthy subjects, all showed DTH positive to > or = 1 antigen. The positivity to C. albicans, tetanus toxoid, PPD, T. mentagrophytes, and HBV was 92.6%, 83.2%, 82.1%, 50.5%, and 5.3%, respectively. When three antigens: PPD, TT and C. albicans were analyzed, 100% of subjects showed a positive response to > or = 1 antigen and 96.8% showed a positive response to > or = 2 antigens. When only PPD and TT were analyzed, 100% of subjects showed > or = 1 antigen positive and 68.4% showed both antigens positive. C. albicans antigen at 1:100 was associated with a high incidence of fever (2/20) and large local reaction (7/20), 1:500 was found to be the optimal concentration. PPD, TT and C. albicans are suitable to be included in a DTH skin testing in a tropical country like Thailand. However, in a setting where C. albicans extract is not available, testing with only two antigens of PPD and tetanus toxoid may be an alternative, but with a lower sensitivity.

High prevalence of indinavir-associated renal complications in Thai HIV-infected patients.

BACKGROUND: Indinavir (IDV) is the protease inhibitor (PI) used most often in resource-limited countries. The present study aimed to determine the prevalence of IDV-associated renal complications as well as their clinical characteristics. MATERIAL AND METHOD: The authors reviewed all patients participating in cohorts of indinavir-containing regimens at the HIV-NAT research center during the period of indinavir treatment. Patients who had pre-existing renal diseases were excluded. Renal toxicities included presence of urologic symptoms, nephrolithiasis, abnormal urine sediments, crystalluria and loss of renal function. Radiological studies of KUB system were reviewed as well. RESULTS: Two-hundred and four patients treated with IDV were included. Median (IQR) follow up period was 216 (150-312) weeks. One hundred and eighty patients were treated with ritonavir-boosted regimens at some point, and 24 patients were treated only with unboosted regimens. Leukocyturia (51.9%) was the most common finding of IDV-associated renal complications. Thirty-five percent of patients had urologic symptoms such as flank pain or dysuria. Almost half of the patients had significant loss of renal function that was associated with prolonged use of IDV The most common radiological finding was nephrolithiasis. Less common, but of greater clinical importance, are nephrocalcinosis or renal atrophy. CONCLUSION: A high prevalence of IRC was found in Thai HIV-infected patients. As long as no other cost-effective boosted PI regimens are available, strategies to prevent irreversible loss of renal function are warranted.

No effect of interleukin-2 on IgE levels given in addition to antiretroviral therapy in HIV-infected adults with CD4 >300 cells/mm3.

HIV-infected patients may have frequent atopy caused by an imbalance of Th1 and Th2 cytokines. The objective of the present study was to investigate whether IL-2 given in addition to antiretrovirals (ARV) would result in lower IgE levels and less allergic symptoms. Patients naive to IL-2 (n=28) began IL-2 plus ARV and were followed for 12 months. IgE, eosinophil and CD4 counts, HIV RNA, symptom scoring, PFT and skin prick test (SPT) were performed. It was found that the baseline median CD4 and IgE were 386.5 cells/mm3 and 63.5 IU/ml, respectively. Four patients had allergic rhinitis (AR) and 61% had a positive SPT to at least 1 antigen. At month 12, patients had higher CD4 counts (p < 0.001) compared to the baseline; however, there were no differences in IgE levels, allergic symptom scores or HIV RNA. The eosinophil count was higher after IL-2 administration. It was concluded that IL-2 plus ARV resulted in higher CD4 counts but had no effect on atopy.

Undetectable plasma HIV-1 RNA with strong gag-pol specific interferon-gamma ELISPOT response in an HIV-1 clade A/E-infected child untreated with antiretroviral therapy.

We report a 7-year HIV-1 clade A/E-infected child untreated with antiretroviral therapy who had positive HIV antibody testing but undetectable plasma HIV-1 RNA by Roche Amplicor version 1.5 and bDNA version 3.0. DNA PCR was positive by methods using gag/pol primers but not env/pol primers. The patient had strong HIV-1-specific cytotoxic T lymphocyte responses, which likely contributed to her low viral burden and undetectable plasma HIV-1 RNA.

Continuous ambulatory peritoneal dialysis improves both the number and memory function of CD4 T cells in uremic patients.

Cell-mediated immune response (CMIR) was studied in 16 ESRD (end-stage renal disease) patients prior to and after 6 months of treatment with CAPD (continuous ambulatory peritoneal dialysis). Quantitative assessment of the CMI system showed that the mean values of number and percentage of total lymphocyte count, CD4, CD8, and CD4/CD8 in ESRD patients were lower than in the normal population. Such values, however, were significantly increased after 6 months of CAPD treatment. To determine qualitative function of the CMI system, both in vitro (PHA stimulation test) and in vivo (multi CMI skin test) tests were examined. There were no significant changes in the results of PHA stimulation test after 6 months of CAPD treatment. In multi CMI skin test, the number of patients converting from negative to positive result was obviously noted following CAPD therapy for 6 months. In conclusion, both quantitative and qualitative CMI impairment existing in ESRD patients could be corrected, although not completely, by 6-month CAPD treatment.

Construction and immunogenicity study of a 297-bp humanized HIV V3 DNA of an approximated last common ancestor in mice.

DNA immunization represents one of the promising HIV-1 vaccine approaches. To overcome the obstacle of genetic variation, we used the last common ancestor (LCA) or "center-of-the-tree" approach to study a DNA fragment of the HIV-1 envelope surrounding the V3 region. A humanized codon of the 297-bp consensus ancestral sequence of the HIV-1 envelope (codons 291-391) was derived from the 80 most recent HIV-1 isolates from the 8 circulating HIV-1 subtypes worldwide. This 297-bp humanized "multi-clade" V3 DNA was amplified by a PCR-based technique. The PCR product was well expressed in vitro whereas the corresponding non-humanized V3 DNA (subtype A/E) could not be expressed. However, both V3 DNA constructs as well as the full-length HIV-1 envelope construct (A/E) were found to be immunogenic in mice by the footpad-swelling assay. Moreover, intracellular and extracellular interferon-gamma could be detected upon in vitro stimulation of spleen cells although the response was relatively weak. Further improvement of our humanized V3 DNA is needed.

Significant differences between plasma HIV-1 RNA assays in HIV-1 subtype E infected patients treated with antiretroviral therapy.

A total of 72 HIV-1 infected Thai patients treated with didanosine (ddI) or stavudine (d4T) plus ddI at the time of interim analysis were analyzed. Sixty patients (83%) carried subtype E documented by HIV-1 V3 serotyping. HIV-1 RNA levels were measured using three commercial viral load assays. At baseline (n = 57), Quantiplex 2.0 and NucliSens 2.0 showed mean log10 HIV-1 RNA of 0.7 log10 or 5 fold lower than Amplicor 1.5 (mean 4.29 versus 5.0 log10, respectively, p < 0.001). At week 20 of treatment (n = 29), HIV-1 RNA levels were detected in 55.2%, 31%, and 33.5% of subjects tested by Amplicor 1.5, Quantiplex 2.0, and NucliSens 2.0, respectively. In conclusion: plasma HIV-1 RNA analyses showed comparable values with Quantiplex 2.0 and NucliSens 2.0 assays. In contrast, Amplicor 1.5 resulted in approximately 5 folds higher HIV-1 RNA levels and a 25% higher rate of detection of plasma HIV-1 RNA as compared to the other two assays. As the current goal of therapy is to suppress plasma viral load below the detection limit of the assays, the significant differences between the assays may influence antiretroviral efficacy evaluation and management.

Impact of particulate air pollutants on allergic diseases, allergic skin reactivity and lung function.

Elevated levels of particulate matter can exacerbate existing asthma and atopy, while evidence that it can promote the induction of atopy and asthma is limited. A cross sectional study was taken to compare the prevalence of eye, nose, ear and airway allergic symptoms, allergic skin sensitivity and lung function in 290 high school students with a history of high 24 hour average exposure to particulate matter less than 10 microm in diameter (PM10) = 170 microg/m3 versus low PM10 of 36 microg/m3 in central Bangkok. Multivariate analysis revealed an increased risk of eye and airway symptoms in groups exposed to higher PM10 levels (p = 0.003, and 0.05, respectively). Positive skin prick tests and a history of having a lawn at home were associated with nasal symptoms (p = 0.008 and 0.04, respectively). Mean FEF(25-75%) (forced expiratory flow that occurs during the middle 50% of the forced expiratory effort) was significantly lower in those who were exposed to higher PM10 levels (3.89 +/- 1 vs 4.42 +/- 0.9 l/sec, p < 0.001). A significant increase in days of school absence and medical expenses was associated with high PM10 exposure. It is concluded that chronic exposure to high PM 10 levels was significantly associated with increased prevalence of eye and airway symptoms and a decrement of FEF(25-75%) resulting in increase of school absence and medical expense.

Antibody response to hepatitis B immunization in infants born to HIV-infected mothers.

OBJECTIVES: To determine the antibody response of hepatitis B immunization begun at birth in HIV-1 exposed infants. DESIGN: Prospective, clinical trial. SITE: King Chulalongkorn Memorial Hospital, Bangkok, Thailand. MATERIAL AND METHOD: Seventy six infants born to HIV-1 seropositive mothers, who were not hepatitis B carriers, received three 10 microgram doses of recombinant DNA hepatitis B vaccine (Engerix B, Smith Kline, Belgium) in a 0, 1 and 6 month schedule. The first dose was given at birth. Serum hepatitis B surface antibody (Anti -HBs) was measured at age 3, 9 and 12 months. Anti-HBs levels were determined by enzyme-linked immunoassay using the commercial kits (AUSAB EIA diagnostic kits, Abbott Laboratories, Chicago, USA) Antibody titer > or = 10 mIU/ml was defined as seroconversion. HIV infection was diagnosed by a positive test of HIV antibody at age > or = 18 months and/or by positive test of HIV polymerase chain reaction at age > or = 3 months. RESULTS: There were 14 HIV-1 infected (group 1) and 62 HIV-1 non infected (group 2) infants enrolled in this study. Anti-HBs titers of group 1 infants were significantly lower than those of groups 2 infants at both 3 and 6 months after the 3rd dose of vaccine, (Mann Whitney U test, p=0.019 and 0.001 respectively). Ten infants in group 1 and 57 infants in group 2 had anti-HBs titer > or = 10 mIU/ml. Their peak antibody titers were also noted at both 3 and 6 months after the 3rd dose of vaccine. Seroconversion rates were 71.4 per cent and 91.9 per cent in group 1 and 2 infants respectively, (p<0.05). Among the infants who had blood tests performed at age 12 months or 6 months after the 3rd dose of vaccine, anti-HBs titers declined in approximately 50 per cent of both groups of infants. There was a significantly higher percentage of seroconverters in group 1 who lost their protective titers than those in group 2, (p<0.001). CONCLUSION: The results in this study suggested that HIV-1 infected infants have poor antibody response to hepatitis B immunization and the protection was less durable. A fourth dose of vaccine at 6 months after the 3rd dose may be necessary.