Prevalence of antiretroviral drug resistance in treated HIV-1 infected patients: under the initiative of access to the NNRTI-based regimen in Thailand.

To determine the prevalence of antiretroviral resistance in treatment-failure HIV-1 infected individuals, under the initiative of the non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen in Thailand, plasma samples were collected from 1,376 HIV-1 infected patients, who were failing in their current HAART therapy during 2000-2004. They were stratified into 2 intervals: group one (1), 558 HIV-1 infected patients (2000-2002; before the initiative of access to HAART), and group two (2), 818 HIV-1 infected patients (2003-2004; after the initiative of access to HAART). Genotypic resistance testing was performed. The frequency of antiretroviral drug resistance in treatment-failure HIV-1 infected patients has significantly increased over time from 68.5% (382/558) during 2000-2002 to 74.9% (613/818) during 2003-2004 (P<0.01). Resistance to NNRTI during 2003-2004 (59.2%) was much higher than that during 2000-2002 (36.9%; P<0.001). However, the frequency of nucleoside reverse transcriptase inhibitor (NRTI) drug resistance was not significantly higher (P=0.153). We showed that this correlated with an increase in the NNRTI-based regimen prescribed during 2003-2004, especially the Thai-produced combination pill, GPO-VIR. Our finding also showed that a high level of genotypic drug resistance is associated with GPO-VIR (40.8% lamivudine, 40.6% stavudine, 43.8% nevirapine). In order to avoid the rapid emergence of resistant viruses in a resource-poor setting, a close surveillance of antiretroviral drug resistance is feasible and should be considered.

Surveillance of genotypic resistance mutations in chronic HIV-1 treated individuals after completion of the National Access to Antiretroviral Program in Thailand.

BACKGROUND: Due to the establishment of the National Access to Antiretroviral Program for People who have AIDS (NAPHA), approximately 80,000 Thai HIV-1 infected patients received antiretroviral drugs through the NAPHA program, which was completed at the end of 2005. The development of drug resistance is required for access to ARV drugs. The objective of this study was to determine the prevalence of antiretroviral drug resistance in Thai HIV-1 treated individuals after completing the NAPHA program. PATIENTS AND METHODS: Viral genotypic resistance testing was carried out for 1,880 HIV-infected patients experiencing treatment failure, who enrolled during 2000-2005. All patients were in a follow-up treatment with ARV drugs available in clinical practice. The genotype was performed with the TRUGENE HIV-1 kit to assess resistant mutations to reverse transcriptase inhibitors and to protease inhibitors. RESULTS: The frequency of ARV drug resistance has significantly increased after the National Access To Antiretroviral Program was implemented. The reverse transcriptase genes M184V/I (919/1,880; 48.9%) and K103S/H (416/1,880; 22.1%) were the most frequent in nucleoside reverse transcriptase and non-nucleoside reverse transcriptase, respectively. In the protease genes, minor mutations or polymorphisms were found in the majority. Thymidine analogue mutations were presented and increased over time. This study showed a sharp increase in the prevalence of mutations associated with the GPO-VIR combination; nevirapine (948/1,880; 50.4%), lamivudine (889/1,880; 47.3%), and stavudine (703/1,880; 37.4%) after the program was completed. CONCLUSION: With the increased availability of antiretroviral therapy in a resource-constrained country, antiretroviral drug resistance should be closely monitored. HIV-1 drug resistance testing to enable the salvage therapy will remain a priority in Thailand. Furthermore, resistance testing should also become routine before prescribing treatment, and the consequences of continuing to provide a failing regimen must be considered.

The efficacy and safety of 30 mg fexofenadine HCl bid in pediatric patients with allergic rhinitis.

Allergic rhinitis is one of the most common chronic disorders in children. It is also one of the most common causes of absence from school. This study reports on the efficacy and safety of a twice-daily oral dose of fexofenadine HCl 30 mg in Asian children aged 6-11 years diagnosed with seasonal or perennial allergic rhinitis. A total of 100 children with a history of allergic rhinitis for more than one year and a positive prick skin test response to at least one of the common aeroallergens in Thailand were enrolled in this multi-center, open-label, non comparative study. The severity of individual symptoms such as sneezing, rhinitis, etc. and adverse events were recorded in diary cards by the patients in form of scores as well as by the investigator at each visit. The total symptom score (TSS) with or without blocked nose at baseline, week 1 and week 2 was recorded. The TSS was defined as the sum of the individual symptom scores except for the nasal blockage score, as nasal blockage was not expected to respond to antihistamine treatment. Only patients with a total symptom score > or = 6 were included in the study. There was a statistically significant improvement at p < 0.01 for the TSS with or without blocked nose and for each symptom score such as blocked nose, sneezing, rhinorrhea, itchy nose/palate and/or throat, and itchy/watery/red eyes from baseline to week 1 and week 2. Additionally, there was a statistically significant improvement between week 1 and week 2 for itchy nose/palate and/or throat and itchy/watery/red eyes (p < 0.05). The Kappa measure of agreement was statistically significant at p < 0.001 between investigator's and patient's/parent's assessment, indicating the same degree of satisfaction with the overall effectiveness of the treatment. Fexofenadine 30 mg bid is effective in reducing the total symptom score of allergic rhinitis including blocked nose and is generally well tolerated. It is not cardiotoxic and is safe for pediatric patients as young as 6 years of age.

Plasmodium vivax malaria in Southeast Iran in 1999-2001: establishing the response to chloroquine in vitro and in vivo.

Chloroquine-resistant Plasmodium vivax is emerging in Oceania, Asia and Latin America. The drug sensitivity of P. vivax to chloroquine both in vivo and in vitro in the southern part of Iran was assessed; chloroquine-resistant Plasmodium falciparum has already been documented in this area. The in vitro sensitivity of 39 P. vivax isolates was assessed: the mean IC50 and IC90 were 189 ng/ml and 698 ng/ml blood respectively; for in vivo testing, all 39 vivax malaria patients were treated with a standard regimen of chloroquine and followed-up at 28 days: the mean parasite clearance time was 67.2 +/- 22.5 hours. The in vitro development of young parasites to mature schizonts in standard test medium was compared with that obtained in McCoy's 5A medium: no significant difference was observed. Synchronization of the blood-stage parasites was performed according to Lambros' method: the method was not suitable because it was detrimental to the parasites. A number of in vitro tests were performed using both our own laboratory-predosed microplates and WHO microplates: there was no significant difference between the results.

Normal plasma free amino acid levels in Thai children.

Analysis of plasma free amino acid levels is important for diagnosis of inborn errors of metabolism. Traditionally, this is performed using commercially available dedicated amino acid analyzers, but few such instruments are available in Thailand, and many are not used in routine operations. Here, the authors describe the analysis of plasma free amino acid levels in 57 normal children by reverse-phase HPLC and pre-column derivatization with phenylisothiocyanate. Plasma free amino levels are reported as mean +/- SD and 95 per cent confidence interval of mean for each of 5 age groups: 0-6 months; 6-12 months; 1-3 years; 3-6 years; 6-12 years. Mean amino acid levels were generally similar in all age groups (p > or = 0.01), except that hydroxyproline tended to be higher in the 0-6 months age group compared to other age groups (p<0.01). Comparisons were made between the present data with the normal free plasma amino acid levels in children of similar age groups reported both in Thailand and overseas in terms of both mean +/- SD and maximum and minimum values. Overall, our methodology involving HPLC can identify 35 amino acid derivatives, including all the major amino acids except for cysteine, which is substantially more than the number reported in earlier work on plasma free amino acid levels in normal Thai children. Moreover, the present methodology gives mean +/- SD values similar to an overseas report. For these reasons, HPLC should be considered as an alternative approach in laboratories, where demand does not justify the need for dedicated amino acid analyzers. However, there can be substantial variations between the results from different laboratories, and each laboratory should establish its own normal values.

Modelling recurrent malaria in Thailand.

Malaria is a common infectious disease in many tropical countries. Thailand is located geographically in the tropical zone and the transmission of malaria is found widely, for instance, in the Tak province. The objective of this study is to find risk factors for the number of experiences with malaria of malaria patients, i.e. repeated recurrences of the disease within an infected individual in the Tak province in the rainy season by using Poisson regression models. Among the models fitted, the best are chosen based on the analysis of deviance. The results of this study show that the risk factors are race, spraying insecticides in houses in an infectious area, number of days staying overnight without protection against mosquitoes of malaria patients, and whether or not any members of the family of the malaria patient have had malaria.

Application of log-linear models to malaria patients in Thailand.

Malaria is a common infectious disease in many tropical countries, including Thailand. The country is located geographically in a tropical zone and the transmission of malaria is particularly common in some regions, for instance in Tak province. The objective of this study is to identify risk factors causing malaria in Tak province in the rainy season by using log-linear models. Tests of independence are used (chi-square and Cramer's V-value tests) to find out the relationships between any two variables. In addition two- and three-dimensional log-linear models are used to obtain estimated parameters and expected frequencies for these models. Amongst the models fitted, the best are chosen based on the analysis of deviance. The results of this study show that most observed variables are significantly related with p-values<0.05. Causes of migration and reasons for staying overnight are highly related to personal variables. Thus, it can be concluded that two of the risk factors for malaria are causes of migration and reasons for staying overnight. Knowledge of prevention is also related to personal variables. Therefore, knowledge of prevention was concluded to be a risk factor affecting prevalence of malaria. For each set of three variables, the best model shows interaction terms of variables that have a relationship but there are no interactions of three effects in these best models.

The changing pattern of head injury in Thailand.

OBJECTIVE: To determine whether patterns of head injury are changing with time. MATERIALS AND METHODS: A total of 3194 and 4217 consecutive trauma patients who attended the emergency room in 1985-86 and 1996 respectively were studied with respect to age, sex, cause of injury, injury severity, pathology, and outcome. RESULTS: The number of patients with head injury in 1996 nearly doubled (1224/4,217:29.03%) when compared to the 1985-86 study (504/3, 194; 15.78%). This was due to an increase in the outpatient subgroup (1009/1224). The admitted patients with head injury showed a pattern of less severe injury. Severe head injury decreased from 12.4 to 7. 9%. However, acute subdural haematoma and diffuse brain injury increased from 12.2% and 9% to 32% and 16.8% respectively. The mortality rate of admitted patients increased statistically significantly from 14.4% to 21.8% between the 1985-86 and 1996 studies. CONCLUSIONS: This comparative study showed attend toward less severe injury. This may be due to multiple factors. The predominant factor may be the compulsory use of motorcycle helmets. The limitation of this study was that it utilised tertiary hospital based data only. Tertiary hospital receive more and serious head injured patients from surrounding provincial hospitals this may be the major cause of the increased the mortality rate.

Antiparasite adherence activity in Thai individuals living in a P. falciparum endemic area.

Two types of antimalaria antibodies in the serum of 54 villagers living in a malaria endemic area of Thailand were determined by indirect immunofluorescence assay in order to define the status of malaria immunity within the group. Antibodies to parasite-derived antigens in the membrane of ring stage-infected erythrocytes were very high (> or = 1:1,250) in 44%, moderate to low (< or = 1:250) in 37% of the sera, and the rest did not have the antibody. However, all the sera had antibodies to antigens of the intraerythrocytic mature parasites, showing a very high level in 65% and moderate to low levels in 37% of the sera. Sera with high antibody titers to either type of antigen significantly inhibited cytoadherence of P. falciparum-infected erythrocytes. All the sera variably inhibited rosette formation of the parasites but showed no association with the antibody titers. These results suggest that the antibodies to cytoadherence and rosette formation can be elicited and sustained in the malaria experienced host while living in the endemic area. This may be a natural preventive mechanism against the severity of P. falciparum infection in the infected host. How long the antiparasite adherence activity will last remains to be investigated.