Bamrasnaradura Infectious Diseases Institute Research Articles

Prevalence, Risk Factors, and Prognosis of Liver Involvement in Adult Patients with Chikungunya in Thailand.

Chikungunya is a mosquito-borne disease mainly characterized by fever with polyarthralgia. Currently, liver complications of chikungunya remain rarely described. This study assesses the prevalence, severity, and risk factors of liver involvement, and the association between liver involvement severity and prognosis. We conducted a retrospective cohort study at two referral centers for tropical infectious diseases-the Hospital for Tropical Diseases and Bamrasnaradura Infectious Diseases Institute in Thailand-from January 2016 to April 2021. The study included 400 patients diagnosed with chikungunya. Of them, 254 (63.5%) were female with a mean age of 41.5 ± 14.1 years, and 98.5% of them presented with fever with arthralgia. Gastrointestinal presentations included nausea or vomiting (n = 62, 15.5%), diarrhea (n = 33, 8.3%), and abdominal pain (n = 4, 1%). Of 88 patients with available liver function tests, 39.8% had hepatitis (abnormal alanine aminotransferase levels), of whom 5.7% had moderate hepatitis. Nausea or vomiting is a clinical risk factor associated with liver involvement (adjusted odds ratio, 5.17; 95% CI, 1.20-22.34). Liver involvement was usually observed during the first 2 weeks of illness and resolved eventually. None of the patients experienced severe hepatitis, liver failure, or death caused by a liver problem. In conclusion, most of the patients with chikungunya did not have significant liver involvement. In those patients with severe liver injury, coexisting causes should be considered.

Effects of nutrition counselling on iron deficiency anemia in pregnancy

Anemia is a significant public health concern in pregnant women and women of reproductive age globally. The prevalence of anemia in Thailand was approximately 36.7%. Common causes of anemia were iron deficiency anemia (IDA) and beta-thalassemia trait (BTT). World Health Organization (WHO) recommends that dietary adjustments focusing on iron-rich foods foster the improvement of IDA and IDA with BTT. This study aimed to evaluate the effect of nutrition counselling in pregnant women with IDA on anemia parameters and dietary intake records. Retrospective data were obtained from the Division of Nutrition and Antenatal Care (ANC) Clinic at Bamrasnaradura Infectious Diseases Institute (BIDI) in Nonthaburi, Thailand. Nutrition Care Process Model was used in nutrition service at BIDI. During the second trimester, nutrition counselling was provided at the ANC Clinic by a dietitian routinely based on WHO guidelines for nutritional anemia. The anemia parameters and dietary intake records were recorded during ANC visits at the second and third trimesters. A paired t-test was used to evaluate differences within each group. Collected data from 61 pregnant women with anemia were analyzed (IDA: 55; BTT: 6). In the third trimester, the changes in hematocrit levels were significantly high in both IDA (p ≤ 0.001) and BTT groups (p = 0.016). In addition, the improvement in daily energy consumption and iron-rich foods was significantly observed in both groups (p ≤ 0.001). In conclusion, the delivery of nutrition counselling focusing on iron-rich foods significantly enhanced IDA parameters and eating behaviours, including increased hematocrit levels, and improved daily energy intake and iron-rich foods intake among pregnant women with anemia.

Serological Differences after Acute Zika Virus Infections between Children and Adults: Implication for Use of a Serological Test.

Information is limited regarding differential serological responses after acute Zika virus (ZIKV) infections and prevalence of cross-reactivity with anti-dengue virus (DENV) assays comparing children and adults. Early convalescent sera from a cohort of suspected mild DENV cases between December 2016 and September 2018 at Bamrasnaradura Infectious Diseases Institute in Thailand were tested for nonstructural protein 1 (NS1)-based anti-ZIKV IgM and IgG ELISAs (Euroimmun), and in-house anti-DENV IgM- and IgG-capture ELISAs. ZIKV cases were identified by positive real-time reverse transcriptase-polymerase chain reaction on urine. Sera from 26 (10 children and 16 adults) ZIKV and 227 (153 children and 74 adults) non-ZIKA cases collected at the median duration of 18 days (interquartile range [IQR] 18,19) post-onset of symptoms were tested. Comparing pediatric ZIKV to adult ZIKV cases, the mean anti-ZIKV IgM ratio was higher (2.12 versus 1.27 units, respectively; P = 0.07), whereas mean anti-ZIKV IgG ratio was lower (3.13 versus 4.24 units, respectively; P = 0.03). Sensitivity of anti-ZIKV IgM and specificity of anti-ZIKV IgG in pediatric ZIKV were higher than in adult ZIKV cases (80.0% versus 43.7% and 79.1% versus 43.2%, respectively). No cross-reactivity with anti-DENV IgM- and IgG-capture ELISA were reported in pediatric ZIKV cases in our study, whereas 25% and 12.5% were found in adult ZIKV cases, respectively. Age-related ZIKV serological differences have been observed. Positive NS1-based anti-ZIKV IgM and IgG ELISA at the early convalescent phase could be useful for ZIKV diagnosis in children, even in a dengue endemic setting.

Lung Ultrasound Findings of Patients with Dengue Infection: A Prospective Observational Study.

Lung ultrasound (LUS) is a more sensitive method of detecting pathological pulmonary changes than chest X-ray. Therefore, LUS for patients with dengue could be an important tool for the early detection of pleural effusions and pulmonary edema signifying capillary plasma leakage, which is the hallmark of severe dengue pathophysiology. We conducted a prospective observational study of pulmonary changes identifiable with LUS in dengue patients admitted to the Hospital for Tropical Diseases in Mahidol University, Bangkok, and the Bamrasnaradura Infectious Diseases Institute, Nonthaburi, Thailand. The LUS findings were described according to standard criteria, including the presence of A, B1, B2, and C patterns in eight chest regions and the presence of pleural effusions. From November 2017 to April 2018, 50 patients with dengue were included in the study. LUS was performed during the febrile phase for nine patients (18%) and during the critical-convalescence phase for 41 patients (82%). A total of 33 patients (66%) had at least one abnormality discovered using LUS. Abnormal LUS findings were observed more frequently during the critical-convalescence phase (N = 30/41; 73%) than during the febrile phase (N = 3/9; 33%) (P = 0.047). Abnormal aeration patterns were observed in 31 patients (62%). Only B patterns with only multiple B lines were observed in 21 patients (42%); of these patients, three had already exhibited B patterns during the febrile phase (N = 3). C patterns (N = 10; 24%), pleural effusion (N = 10; 24%), and subpleural abnormalities (N = 11; 27%) were observed only during the critical-convalescence phase. LUS can detect signs of capillary leakage, including interstitial edema and pleural effusions, early during the course of dengue.

SARS-Cov-2 Viral Kinetics in Mild COVID-19 Patients Treated with Chloroquine Regimens or Standard of Care

This study measures the impact of chloroquine (CQ) therapy in reducing SARS-CoV-2 viral load in infected individuals and hence its transmissibility by describing changes in nasopharyngeal SARS-CoV-2 RNA kinetics in patients receiving standard of care (SOC) or CQ +/- ritonavir-boosted lopinavir (LPV/r). The nasopharyngeal (NP) samples were collected from mild COVID-19 patients admitted at Bamrasnaradura Infectious Diseases Institute between March and April of 2020. These patients either received SOC, or a high dose of CQ with loading dose, or high dose of CQ plus LPV/r. The samples were tested at AFRIMS using a quantitative RT-PCR assay. Levels of CQ in the plasma were measured 6 days post initiation of their treatment. In some instances, viral isolation was attempted to determine SARS-CoV-2 viability. Analyses of the clinical outcomes showed that CQ +/- lopinavir did not contribute significantly to decreasing the number of days with detected SARS-CoV-2 RNA. Viral NP GEs declined faster in the CQ group, but benefits diminished rapidly with delays in treatment initiation. Funding Global Emerging Infections Surveillance, Armed Forces Health Surveillance Branch (GEIS-AFHSB) for all research-related activities at the AFRIMS

Zika Virus Disease Comparing Children and Adults in a Dengue-Endemic Setting

.Acute Zika virus (ZIKV) infection may mimic dengue virus (DENV) infection. We aimed to study the clinical difference of ZIKV disease among suspected non-severe DENV patients comparing children and adults. Patients with acute illness suspected of DENV disease plus no evidence of plasma leakage at the Bamrasnaradura Infectious Diseases Institute, Nonthaburi, Thailand, were enrolled from December 2016 to September 2018. Clinical data including DENV rapid diagnostic test (RDT) results were collected. Zika virus diagnosis was confirmed by real-time reverse transcription PCR on urine. Of 291 (180 pediatric and 111 adult) cases enrolled, 27 (10 pediatric and 17 adult) confirmed ZIKV cases were found. Rash was more frequent among pediatric ZIKV than pediatric non-ZIKV cases (100% versus 60%, P = 0.01). Rash, arthralgia, and conjunctivitis were more frequent among adult ZIKV than adult non-ZIKV cases (100% versus 29.8%, 64.7% versus 26.6%, 52.9% versus 9.7%, all P < 0.01, respectively). The median (interquartile range [IQR]) duration of rash was 4.5 (3.0, 7.25) days and 6.0 (4.5, 7.0) days in pediatric and adults ZIKV cases, respectively. Pediatric ZIKV cases had more fever (100% versus 58.5%, P = 0.03) but less arthralgia (20% versus 64.7%, P = 0.04) and less conjunctivitis (10% versus 52.9%, P = 0.04) than adult ZIKV cases. No ZIKV cases with DENV RDTs performed around day 3 of illness were positive for dengue nonstructural protein 1 (NS1) antigen. In dengue-endemic settings, rash and fever in children, and rash, arthralgia, and conjunctivitis in adults, particularly if rash persists for ≥ 3 days, plus negative dengue NS1 Ag during early febrile phase should prompt ZIKV diagnostic testing.

Clinical course and potential predictive factors for pneumonia of adult patients with Coronavirus Disease 2019 (COVID-19): A retrospective observational analysis of 193 confirmed cases in Thailand.

Clinical spectrum of Coronavirus Disease 2019 (COVID-19) remains unclear, especially with regard to the presence of pneumonia. We aimed to describe the clinical course and final outcomes of adult patients with laboratory-confirmed COVID-19 in the full spectrum of disease severity. We also aimed to identify potential predictive factors for COVID-19 pneumonia. We conducted a retrospective study among adult patients with laboratory-confirmed COVID-19 who were hospitalized at Bamrasnaradura Infectious Diseases Institute, Thailand, between January 8 and April 16, 2020. One-hundred-and-ninety-three patients were included. The median (IQR) age was 37.0 (29.0-53.0) years, and 58.5% were male. The median (IQR) incubation period was 5.5 (3.0-8.0) days. More than half (56%) of the patients were mild disease severity, 22% were moderate, 14% were severe, and 3% were critical. Asymptomatic infection was found in 5%. The final clinical outcomes in 189 (97.9%) were recovered and 4 (2.1%) were deceased. The incidence of pneumonia was 39%. The median (IQR) time from onset of illness to pneumonia detection was 7.0 (5.0-9.0) days. Bilateral pneumonia was more prevalent than unilateral pneumonia. In multivariable logistic regression, increasing age (OR 2.55 per 10-year increase from 30 years old; 95% CI, 1.67-3.90; p<0.001), obesity (OR 8.74; 95%CI, 2.06-37.18; p = 0.003), and higher temperature at presentation (OR 4.59 per 1°C increase from 37.2°C; 95% CI, 2.30-9.17; p<0.001) were potential predictive factors for COVID-19 pneumonia. Across the spectrum of disease severities, most patients with COVID-19 in our cohort had good final clinical outcomes. COVID-19 pneumonia was found in one-third of them. Older age, obesity, and higher fever at presentation were independent predictors of COVID-19 pneumonia.

Adjunctive favipiravir for severe COVID-19: a retrospective observational study of the first 41 patients in Thailand

Abstract Background Favipiravir is a promising drug for COVID-19, but evidence from a robust clinical trial is limited. Objective To describe the demographics, clinical characteristics, and various antiviral treatment regimens (with and without favipiravir) of patients with severe and nonsevere COVID-19. Method We conducted a retrospective observational study in all COVID-19 patients admitted at Bamrasnaradura Infectious Diseases Institute (BIDI) from January 8 to March 30, 2020. We compared the demographics, clinical characteristics, and various antiviral treatment regimens of 12 severe and 29 nonsevere COVID-19 patients in Thailand. Results Adjunctive favipiravir was given to only severe cases. The median length of hospitalization of patients either receiving favipiravir or not receiving favipiravir was not significantly different (P = 0.8549), but those who received adjunctive favipiravir became reverse transcriptase–polymerase chain reaction negative 2 days sooner than the other group (median: 6 days vs. 8 days; P = 0.1125). Conclusion The findings suggested that adjunctive favipiravir might not be effective for patients with severe COVID-19, but further studies with larger sample sizes are needed.

Molecular Characteristics of Dengue Viruses in Patients Hospitalized at the Bamrasnaradura Infectious Diseases Institute, Thailand.

Dengue virus (DENV), one of the rapidly spreading mosquito-borne pathogens, causes acute febrile illness with various clinical symptoms. Four DENV serotypes are known, designated DENV-1 to 4. We previously determined whole-genome sequences of 21 DENV isolates during 2016-2017 and reported the emergence of the Cosmopolitan genotype of DENV-2 and genotype III of DENV-3 in Thailand. The objective of this study, conducted in 2018 at the Bamrasnaradura Infectious Diseases Institute, was to study the prevalence of DENV genotype. A total of 100 patients, hospitalized with severe dengue infection, were enrolled with written informed consent. Serum specimens were tested by multiplex real-time reverse transcription-polymerase chain reaction. Among them, 94 were DENV-positive, with 46 DENV-1, 38 DENV-2, 10 DENV-4, and no DENV-3 cases. Nucleotide sequence of DENV gene for envelope-protein was determined in 73 cases. Genotyping of the sequences revealed 40 cases with DENV-1 genotype I, 26 with DENV-2, that included 18 of Cosmopolitan and 8 Asian I genotypes, and 7 with DENV-4 genotype I. DENV-1 was the most prevalent in this study, and the frequency of DENV-2 Cosmopolitan genotype appears to have increased since our previous study, indicating that genotypic diversity of DENV is increasing in Thailand.

Emergence of genotype Cosmopolitan of dengue virus type 2 and genotype III of dengue virus type 3 in Thailand.

Dengue is a mosquito-borne disease that has spread to over 100 countries. Dengue fever is caused by dengue virus (DENV), which belongs to the Flavivirus genus of the family Flaviviridae. DENV comprises 4 serotypes (DENV-1 to DENV-4), and each serotype is divided into distinct genotypes. Thailand is an endemic area where all 4 serotypes of DENV co-circulate. To understand the current genotype distribution of DENVs in Thailand, we enrolled 100 cases of fever with dengue-like symptoms at the Bamrasnaradura Infectious Diseases Institute during 2016–2017. Among them, 37 cases were shown to be dengue-positive by real-time PCR. We were able to isolate DENVs from 21 cases, including 1 DENV-1, 8 DENV-2, 4 DENV-3, and 8 DENV-4. To investigate the divergence of the viruses, RNA was extracted from isolated DENVs and viral near-whole genome sequences were determined. Phylogenetic analysis of the obtained viral sequences revealed that DENV-2 genotype Cosmopolitan was co-circulating with DENV-2 genotype Asian-I, the previously predominating genotype in Thailand. Furthermore, DENV-3 genotype III was found instead of DENV-3 genotype II. The DENV-2 Cosmopolitan and DENV-3 genotype III found in Thailand were closely related to the respective strains found in nearby countries. These results indicated that DENVs in Thailand have increased in genotypic diversity, and suggested that the DENV genotypic shift observed in other Asian countries also might be taking place in Thailand.

The Effect of Detectable HIV Viral Load among HIV-Infected Children during Antiretroviral Treatment: A Cross-Sectional Study.

The RNA viral load of human immunodeficiency virus (HIV) is initially used to determine the status of the HIV infection. The goal of therapy following treatment failure is to achieve and maintain virologic suppression. A detectable viral load may relate to the progression of HIV infection. A cross-sectional survey was conducted from January 2013 to December 2014 at the Bamrasnaradura Infectious Diseases Institute, Thailand. The aim was to determine the prevalence of detectable HIV viral load (dVL) and analyze the factors associated with post-dVL conditions that occur independently of a switch to a new antiretroviral agent. The prevalence of dVL was 27% (27 of 101). The mean ages of dVL and non-dVL children were 12.0 and 12.3 years, respectively. Age, sex, body mass index for age z-scores, previous tuberculosis disease history and parental tuberculosis history of both groups were not significantly different (p > 0.05). The prevalence of poor adherence (<95%), influenza-like illness (ILI) and opportunistic infections were higher in dVL than non-dVL children (p < 0.05). The mean nadir CD4 cell count during the study was lower in dVL than non-dVL children (646 compared to 867, respectively; p < 0.05). Other factors were not significant (all p > 0.05). In multivariable analysis, dVL was significantly associated with ILI (odds ratio (OR) = 9.6, 95% confidence interval (CI) = 1.3–69.4), adherence (OR = 0.195, 95% CI = 0.047–0.811) and nadir CD4 during the study (OR = 1.102, 95% CI = 1.100–1.305). The prevalence of dVL was 27% with this dVL among HIV-infected children found to be associated with ILI, poor adherence and lower nadir CD4 during the study.

Prevalence and Risk Factors of Malnutrition among HIV-Infected Children Aged 2-18 Years: A Cross Sectional Study

Background: Malnutrition and underweightness are common problems among HIV-infected children in low and middle income countries. Methods and findings: A single-centered, retrospective, cross-sectional cohort survey was conducted between January 1, 2014 and June 30, 2014 to assess the prevalence and risk factors of malnutrition among HIV-infected children aged 2-18 years at the Bamrasnaradura Infectious Diseases Institute (BIDI), Thailand. Clinical and laboratory data were compared between a malnutrition group, (Group A): body mass index (BMI) for age 5th percentile and <95th percentile. One hundred and ninety-five HIVinfected children were retained for analyses. The prevalence of malnutrition was 43% (83 of 195). The following proportions were higher in Group A than B, respectively: advanced clinical staging (83% vs. 12%), PI-based HAART (73% vs. 38 %) and anaemia (48% vs. 8%) (all p<0.05). The median of Log10 plasma HIV RNA was higher in Group A than B (1.7 vs. 1.6, respectively; p<0.05). The proportions of RNA ≤ 40 copies/mL and parent caregivers in Group A were lower than B (48% vs. 86% and 35% vs. 54%, respectively; all p<0.05). Other factors did not differ significantly. In multivariate analysis, malnutrition was significantly associated severity (WHO stages 3 and 4) (OR=184.50, 95% CI=[35.72-952.73]), PI (OR= 5.38, 95% CI=[1.97-14.67]) and parent as caregivers (OR= 0.56, 95% CI=[0.34-0.92]). No significant differences between Group A and B were found in Log10 plasma HIV RNA, RNA ≤ 40 copies/mL, hemoglobin and anemia. Conclusion: The prevalence of malnutrition was 43%. Malnutrition among HIV-infected children was associated with the severity of disease, PI-based HAART and nonparent caregiver.

The validity of clinical practice guidelines for empirical use of oseltamivir for influenza in Thai children

Background: Clinical practice guidelines for influenza have been implemented to maximise the appropriate use of empirical oseltamivir; however, good predictive values are required.Methods: Between October 2011 and September 2013, children aged < 15 years who presented at the Bamrasnaradura Infectious Diseases Institute with an influenza-like illness plus either (i) pneumonia or (ii) being in a higher risk group for influenza complications were prospectively enrolled. Respiratory specimens were taken for real-time polymerase chain reaction testing (RT-PCR). Clinical characteristics, laboratory data and oseltamivir therapy were recorded.Results: 85 cases were enrolled. Of these, the proportions of those with pneumonia, who were aged < 2 years and who had underlying diseases were 74.1%, 56.5% and 38.8%, respectively. RT-PCR detected respiratory syncytial virusamong (35.3%), influenza (22.3by%), adenovirus (14.1%), human metapneumovirus (5.9%), para-influenza (3.5%) and no viruses (25.9 %). Pneumonia (OR 0.16, 95% CI 0.05–0.50) and having two clinical criteria (OR 0.24, 95% CI 0.08–0.76) were significantly negative predictors of influenza. Having cluster transmissions (OR 5.18, 95% CI 1.38–19.37) and a monocyte proportion >7% (OR 3.58, 95% CI 1.15–11.17) were significantly positive predictors of influenza. The mean (SD) percentage of influenza-like illness during the study period was 7.04 (2.02).Conclusions: Clinical criteria guidelines yielded a low predictive value (22.3%) for influenza in children. Seasonality, cluster transmission, white blood cell and differential counts may be helpful in diagnosing influenza. Nonetheless, empirical oseltamivir should not be delayed for those in need.

Lack of transmission among healthcare workers in contact with a case of Middle East respiratory syndrome coronavirus infection in Thailand.

IntroductionA hospital-associated outbreak of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was reported. We aimed to assess the effectiveness of infection control measures among healthcare workers (HCWs) who were exposed to a MERS patient and/or his body fluids in our institute.MethodsA descriptive study was conducted among HCWs who worked with a MERS patient in Bamrasnaradura Infectious Diseases Institute, Thailand, between 18 June and 3 July 2015. Contacts were defined as HCWs who worked in the patient’s room or with the patient’s body fluids. Serum samples from all contacts were collected within 14 days of last contact and one month later. Paired sera were tested for detection of MERS‐CoV antibodies by using an indirect ELISA.ResultsThirty-eight (88.4 %) of 43 identified contacts consented to enroll. The mean (SD) age was 38.1 (11.1) years, and 79 % were females. The median (IQR) cumulative duration of work of HCWs in the patient’s room was 35 (20–165) minutes. The median (IQR) cumulative duration of work of HCWs with the patient’s blood or body fluids in laboratory was 67.5 (43.7–117.5) minutes. All contacts reported 100 % compliance with hand hygiene, using N95 respirator, performing respirator fit test, wearing gown, gloves, eye protection, and cap during their entire working period. All serum specimens of contacts tested for MERS-CoV antibodies were negative.ConclusionsWe provide evidence of effective infection control practices against MERS-CoV transmission in a healthcare facility. Strict infection control precautions can protect HCWs. The optimal infection control measures for MERS-CoV should be further evaluated.

Significant intolerability of efavirenz in HIV occupational postexposure prophylaxis

Completion of human immunodeficiency virus (HIV) occupational postexposure prophylaxis (PEP) is important for successful prophylaxis. To determine factors associated with failure to complete the four-week HIV PEP. A retrospective study was conducted among healthcare workers (HCWs) accidentally exposed to blood or body fluids of patients at the Bamrasnaradura Infectious Diseases Institute, Thailand, between March 1996 and June 2014. Logistic regression analysis was used to determine factors associated with failure to complete the four-week HIV PEP. In total, 225 exposure episodes were reported. The mean age of HCWs was 33.1 (standard deviation 9.9) years, and 189 (84%) were female. Nurses (43%) were exposed most frequently. The HIV status of the source was defined in 149 (66%) episodes, and 101 (68%) of these were positive. Of 225 exposures, PEP was prescribed in 155 (69%) cases, with intentional discontinuation in 26 cases. Ninety-one of 129 (71%) HCWs completed the four-week regimen. Multi-variate analysis showed that a regimen of two nucleotide reverse transcriptase inhibitors (NRTI) + efavirenz (EFV) was the only significant factor associated with non-completion of the four-week course (odds ratio 37.8, 95% confidence interval 4.2-342.3; P < 0.01). Other factors including age, sex, staff position, status of the source and other PEP regimens were not associated with non-completion of the four-week course (P > 0.05). None of the HCWs were documented to have HIV seroconversion. A regimen of two NRTIs + EFV was significantly associated with premature discontinuation of occupational PEP. This regimen should not be used for HIV prophylaxis following occupational exposure.

Genome-Wide Association Study of HIV-Related Lipoatrophy in Thai Patients: Association of a DLGAP1 Polymorphism with Fat Loss.

HIV-related lipoatrophy (LA) is a major adverse drug effect among HIV patients receiving the antiretroviral drug stavudine (d4T) in Southeast Asia. Although the development of LA could be observed in almost all HIV patients administered d4T for extended periods, there is considerable variation in the duration required to develop LA within this patient population. This study aimed to identify host genetic polymorphisms affecting the rate of LA onset in Thai HIV patients. We performed a genome-wide association study of HIV-related LA among patients at the Bamrasnaradura Infectious Diseases Institute, Thailand. Genotypes of HIV patients who developed LA within 2 years of treatment were compared with those of patients who did not develop LA after at least 4 years of treatment (non-LA patients). Genotypes of 49 LA and 92 non-LA patients at 578,525 single nucleotide polymorphisms (SNPs) were determined by Illumina bead arrays. The TaqMan real-time PCR method was used in a replication study. Five SNPs in the bead arrays, which showed the lowest p values in a comparison of LA with non-LA patients, were further tested in independent and sex-matched subpopulations consisting of 95 LA and 95 non-LA patients. This replication study revealed a significant association of LA with an SNP (rs12964965) in the gene encoding the Disks Large Homolog-Associated Protein 1 (DLGAP1), even after the correction for five multiple comparisons. These results strongly suggested involvement of the DLGAP1 gene product in the development of LA in Thai HIV patients.

CYP2B6 G516T and ABCB‐1 C3435T polymorphisms: implications for efavirenz‐associated liver toxicity in HIV/tuberculosis co‐infected Thai adults

Cytochrome P450 2B6 (CYP2B6) and ATP‐binding cassette, sub‐family B (ABCB‐1) play an important role in metabolism and transport of anti‐retroviral therapy (ART) agents. CYP2B6 516TT and ABCB‐1 3435CT polymorphisms affected plasma efavirenz levels. Efavirenz‐based ART was proofed to be beneficial in HIV/tuberculosis co‐infection management; however, the drug‐drug interactions and toxicity are major concerns. Factors affecting adverse drug events and liver toxicity were investigated in this study. Seventy‐one HIV patients with tuberculosis receiving efavirenz (600 mg/day)‐based ART were enrolled in the randomized trial: the N2R study in Bamrasnaradura Infectious Diseases Institute, Thailand. After 12 weeks of ART, 65 rifampicin recipients continued in the analysis of the factors influenced drug toxicity. Plasma efavirenz, serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total and direct bilirubins were determined. CYP2B6 and ABCB‐1 polymorphisms were genotyped. Mann‐Whitney U test was used to compare genotypes and laboratory parameters. CYP2B6 516TT and ABCB‐1 3435CT genotypes were found in 9 (13.85%) and 33 (50.77%) patients, respectively, while six (9.23%) carry both ‐516TT and ‐3435CT genotypes. Patients with 516TT genotype had significantly higher mean rank plasma efavirenz than GT and GG genotypes (54.78 vs. 29.50, p=1.97x10−4) while those carrying 3435CT had slightly higher than CC and TT genotypes. Patients carrying both ‐516TT and ‐3435CT had higher mean rank efavirenz levels than those without these two genotypes (60.17 vs. 30.24, p=2.21x10−4), and had significantly different ALT, total and direct bilirubin levels (p=0.044, 0.009, 0.021, respectively). CYP2B6 516TT and ABCB‐1 3435CT influenced plasma efavirenz levels and related to higher levels of ALT, total and direct bilirubin in patients implication for drug toxicity. The results might be useful for personalized therapy due to their impact on ART adherence related to drug resistance and treatment failure.

HLA-Cw*04 allele associated with nevirapine-induced rash in HIV-infected Thai patients

BackgroundA high incidence of rash has been reported in HIV-1 patients who received the anti-retroviral drug nevirapine. In addition, several studies have suggested that polymorphisms of human leukocyte antigen (HLA) genes may play important roles in nevirapine-induced rash. The aim of the present study was to evaluate the effects of different HLA-C alleles on rash associated with nevirapine in patients who started highly active anti-retroviral therapy (HAART) containing nevirapine in Thailand.ResultsA case-control study was carried out involving HIV-1 patients under treatment at Bamrasnaradura Infectious Diseases Institute, Nonthaburi, Thailand between March 2007 and March 2008. The study included all HIV/AIDS patients being treated with nevirapine-containing regimens. The study population comprised 287 HIV/AIDS patients of whom 248 were nevirapine-tolerant and 39 developed rash after nevirapine treatment. From the nevirapine-tolerant patients, 60 were selected as the control group on the basis of age, sex, and therapy history matched for nevirapine-induced rash cases. We observed significantly more HLA-Cw*04 alleles in nevirapine-induced rash cases than in nevirapine-tolerant group, with frequencies of 20.51% and 7.50%, respectively (P = 0.009). There were no significant differences between the rash and tolerant groups for other HLA-C alleles except for HLA-Cw*03 (P = 0.015).ConclusionThis study suggests that HLA-Cw*04 is associated with rash in nevirapine treated Thais. Future screening of patients' HLA may reduce the number of nevirapine-induced rash cases, and patients with alleles associated with nevirapine-induced rash should be started on anti-retroviral therapy without nevirapine.

Immune reconstitution inflammatory syndrome of tuberculosis among HIV-infected patients receiving antituberculous and antiretroviral therapy

To determine the frequency, risk factors and mortality rate of immune reconstitution inflammatory syndrome (IRIS) of tuberculosis (TB) in patients co-infected with HIV/TB and receiving antiretroviral therapy (ART). A retrospective study was conducted in Bamrasnaradura Infectious Diseases Institute and Ramathibodi Hospital, Thailand. There were 167 patients with a mean age of 34.5 years. Median (IQR) CD4 cell counts was 36 (15-69) cells/mm(3) and median (IQR) HIV RNA was 427,000 (189,000-750,000) copies/ml. ART was initiated at a median (IQR) duration of 2.2 (1.4-3.7) months after TB treatment. IRIS was identified in 21 (12.6%) patients. Patients with IRIS had a higher proportion of extrapulmonary TB than patients without IRIS (P<0.001). By multivariate analysis, extrapulmonary TB was a risk factor for IRIS (odds ratio=8.225, 95% confidence interval=1.785-37.911, P=0.007). Of 21 patients with IRIS, 15 patients developed IRIS within the first two months of ART. The mortality rate in patients with and without IRIS was not different (9.5% versus 2.1%, P=0.119). The rate of TB IRIS is 13% in patients co-infected with HIV and TB. Extrapulmonary TB is a risk factor for IRIS. Closely monitored clinical care in the first few months of ART initiation and further interventional studies to minimize mortality of TB IRIS are needed.