Publications by authors named "Reiko Miyahara"

15 Publications

  • Page 1 of 1

Stillbirths, Neonatal Morbidity, and Mortality in Health-Facility Deliveries in Urban Gambia.

Front Pediatr 2021 15;9:579922. Epub 2021 Feb 15.

Medical Research Council Unit the Gambia at London School of Hygiene and Tropical Medicine, Banjul, Gambia.

The Gambia Demographic and Health Survey 2013 data showed that up to 63% of deliveries in the country occur in health facilities. Despite such a high rate, there are few facility-based studies on delivery outcomes in the country. This analysis ancillary to a randomized control trial describes occurrence of poor pregnancy outcomes in a cohort of women and their infants delivering in a government health facility in urban Gambia. Using clinical information obtained during the trial, we calculated rates of poor pregnancy outcomes including stillbirths, hospitalization and neonatal deaths. Logistic regression was used to calculate odds ratio (OR) and 95% confidence interval (CI) in the risk factors analysis. Between April 2013 and 2014, 829 mothers delivered 843 babies, including 13 stillbirths [15.4 (7.1-23.8)] per 1,000 births. Among 830 live born infants, 7.6% ( = 63) required hospitalization during the 8-week follow-up period. Most of these hospitalizations (74.6%) occurred during the early neonatal period (<7 days of life). Severe clinical infections (i.e., sepsis, meningitis and pneumonia) ( = 27) were the most common diagnoses, followed by birth asphyxia ( = 13), major congenital malformations ( = 10), jaundice ( = 6) and low birth weight ( = 5). There were sixteen neonatal deaths, most of which also occurred during the early neonatal period. Overall, neonatal mortality rate (NMR) and perinatal mortality rate (PMR) were 19.3 (CI: 9.9-28.7) per 1,000 live births and 26.1 (CI: 15.3-36.9) per 1,000 total births, respectively. Severe clinical infections and birth asphyxia accounted for 37 and 31% of neonatal deaths, respectively. The risk of hospitalization was higher among neonates with severe congenital malformations, low birth weight, twin deliveries, and those born by cesarean section. Risk of mortality was higher among neonates with severe congenital malformations and twin deliveries. Neonatal hospitalization and deaths in our cohort were high. Although vertical interventions may reduce specific causes of morbidity and mortality, data indicate the need for a holistic approach to significantly improve the rates of poor pregnancy outcomes. Critically, a focus on decreasing the high rate of stillbirths is warranted. ClinicalTrials.gov Identifier: NCT01800942.
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http://dx.doi.org/10.3389/fped.2021.579922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917219PMC
February 2021

Familial Clusters of Coronavirus Disease in 10 Prefectures, Japan, February-May 2020.

Emerg Infect Dis 2021 03;27(3):915-918

The overall coronavirus disease secondary attack rate (SAR) in family members was 19.0% in 10 prefectures of Japan during February 22-May 31, 2020. The SAR was lower for primary cases diagnosed early, within 2 days after symptom onset. The SAR of asymptomatic primary cases was 11.8%.
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http://dx.doi.org/10.3201/eid2703.203882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920650PMC
March 2021

Risk factors associated with large clusters of tuberculosis patients determined by whole-genome sequencing in a high-tuberculosis-burden country.

Tuberculosis (Edinb) 2020 12 11;125:101991. Epub 2020 Sep 11.

National Centre for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani, Thailand; Pornchai Matangkasombut Centre of Microbial Genomics, Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand. Electronic address:

Whole-genome sequencing (WGS) analysis has great discriminative power for detecting similar molecular fingerprints of suspected tuberculosis (TB) clusters. The proportion of TB cases within clusters and the associated risk factors are important epidemiological parameters guiding appropriate outbreak control strategies in endemic settings. We conducted a hospital-based TB case-cohort study between 2003 and 2011 in the northernmost province of Thailand. We identified TB clusters by Mycobacterium tuberculosis WGS and analysed the risks of TB clustering and the characteristics of large clusters compared with small clusters. Among 1146 TB isolates, we identified 77 clusters with 251 isolates defined by a 5-single-nucleotide variant (SNV) cutoff and 112 clusters with 431 isolates defined by a 12-SNV cutoff. Twelve large clusters with 6 isolates or more in each cluster were identified by a 12-SNV cutoff. Sublineage 2.2.1 (both Ancestral and Modern) strains and imprisonment were independently associated with large clusters. Furthermore, although large clusters of Lineage 2.2.1/Ancestral strains included a high number of prisoners, Lineage 2.2.1/Modern strain clusters were only associated with treatment failures and drug resistance. Heterogeneity among lineage strains was observed with respect to large-cluster characteristics. Patients with an increased TB-transmission tendency should be priority targets for contact investigations and outbreak interventions to prevent ongoing transmission.
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http://dx.doi.org/10.1016/j.tube.2020.101991DOI Listing
December 2020

Clusters of Coronavirus Disease in Communities, Japan, January-April 2020.

Emerg Infect Dis 2020 09 10;26(9). Epub 2020 Jun 10.

We analyzed 3,184 cases of coronavirus disease in Japan and identified 61 case-clusters in healthcare and other care facilities, restaurants and bars, workplaces, and music events. We also identified 22 probable primary case-patients for the clusters; most were 20-39 years of age and presymptomatic or asymptomatic at virus transmission.
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http://dx.doi.org/10.3201/eid2609.202272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454082PMC
September 2020

Author Correction: Exposure to paternal tobacco smoking increased child hospitalization for lower respiratory infections but not for other diseases in Vietnam.

Sci Rep 2020 Apr 6;10(1):6162. Epub 2020 Apr 6.

Department of Clinical Tropical Medicine, Institute of Tropical Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-62383-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136198PMC
April 2020

High tuberculosis burden among HIV-infected populations in Thailand due to a low-sensitivity tuberculin skin test.

J Infect Public Health 2020 Apr 26;13(4):657-660. Epub 2019 Sep 26.

Ministry of Public Health, Thailand.

The current Thai guideline recommends that among people living with HIV, isoniazid preventive therapy (IPT) should be given to those with a positive tuberculin skin test (TST). We conducted a case-control study, nested within a cohort study, in Chiang Rai Province in Thailand to determine the role of TST in predicting the development of active tuberculosis (TB) within the following 2 years. Comparison between participants with CD4+ counts <50cells/mm to those with CD4+ ≥200cells/mm revealed that TST results were less sensitive (7.7% vs 50.0%) and had a lower negative predictive value (73.1% vs 97.3%) in those with a CD4+ count <50cells/mm. In people with HIV, using a positive TST result as a criterion for initiating IPT inadvertently decreases the benefits of IPT, especially among those with low CD4+ counts.
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http://dx.doi.org/10.1016/j.jiph.2019.08.010DOI Listing
April 2020

A novel Ancestral Beijing sublineage of Mycobacterium tuberculosis suggests the transition site to Modern Beijing sublineages.

Sci Rep 2019 09 23;9(1):13718. Epub 2019 Sep 23.

Department of Microbiology, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok, Thailand.

Global Mycobacterium tuberculosis population comprises 7 major lineages. The Beijing strains, particularly the ones classified as Modern groups, have been found worldwide, frequently associated with drug resistance, younger ages, outbreaks and appear to be expanding. Here, we report analysis of whole genome sequences of 1170 M. tuberculosis isolates together with their patient profiles. Our samples belonged to Lineage 1-4 (L1-L4) with those of L1 and L2 being equally dominant. Phylogenetic analysis revealed several new or rare sublineages. Differential associations between sublineages of M. tuberculosis and patient profiles, including ages, ethnicity, HIV (human immunodeficiency virus) infection and drug resistance were demonstrated. The Ancestral Beijing strains and some sublineages of L4 were associated with ethnic minorities while L1 was more common in Thais. L2.2.1.Ancestral 4 surprisingly had a mutation that is typical of the Modern Beijing sublineages and was common in Akha and Lahu tribes who have migrated from Southern China in the last century. This may indicate that the evolutionary transition from the Ancestral to Modern Beijing sublineages might be gradual and occur in Southern China, where the presence of multiple ethnic groups might have allowed for the circulations of various co-evolving sublineages which ultimately lead to the emergence of the Modern Beijing strains.
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http://dx.doi.org/10.1038/s41598-019-50078-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6757101PMC
September 2019

Predicting the risk of pulmonary tuberculosis based on the neutrophil-to-lymphocyte ratio at TB screening in HIV-infected individuals.

BMC Infect Dis 2019 Jul 29;19(1):667. Epub 2019 Jul 29.

Research Institute of Tuberculosis (RIT), Anti-Tuberculosis Association (JATA), Tokyo, Japan.

Background: The neutrophil to lymphocyte ratio (NL ratio) has been reported to be a predictive biomarker of tuberculosis (TB). We assessed the association between the NL ratio and the incidence of active TB cases within 1 year after TB screening among HIV-infected individuals in Thailand.

Methods: A day care center that supports HIV-infected individuals in northernmost Thailand performed TB screening and follow-up visits. We compared the baseline characteristics between the TB screening positive group and the TB screening negative group. The threshold value of NL ratio was determined by cubic-spline curves and NL ratios were categorized as high or low NL ratio. We assessed the association between NL ratio and progression to active TB within 1-year using the Cox-proportional hazard model.

Results: Of the 1064 HIV-infected individuals who screened negative for TB at baseline, 5.6% (N = 60) eventually developed TB and 26 died after TB diagnosis. A high NL ratio was associated with a higher risk of TB (adjusted hazard ratio (aHR) 2.19, 95% CI: 1.23-3.90), after adjusting for age, sex, ethnicity, CD4 counts, and other risk factors. A high NL ratio in HIV-infected individuals with normal chest X-ray predicted TB development risk. In particular, a high NL ratio with TB symptoms could predict the highest risk of TB development (aHR 2.58, 95%CI: 1.07-6.23).

Conclusions: Our results showed that high NL ratio increased the risk of TB. NL ratio combined with TB symptoms could increase the accuracy of TB screening among HIV-infected individuals.
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http://dx.doi.org/10.1186/s12879-019-4292-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6664723PMC
July 2019

Nosocomial Outbreak of Upper Respiratory Tract Infection With β-Lactamase-Negative Ampicillin-Resistant Nontypeable Haemophilus influenzae.

Infect Control Hosp Epidemiol 2018 06 3;39(6):652-659. Epub 2018 Apr 3.

4Chikamori Hospital,Kochi,Japan.

OBJECTIVETo describe the epidemiologic features of an outbreak of an acute respiratory tract infection (ARI) caused by β-lactamase-negative ampicillin-resistant (BLNAR) nontypeable Haemophilus influenzae (NTHi) in an acute-care ward.DESIGNCross-sectional case-control study.SETTINGAn acute-care ward (ward A) in a general hospital of Kochi in western Japan.METHODSPatients who shared a room with an index patient and all staff in ward A were screened and followed from July 1 to August 31, 2015. Sputum or throat swab samples were collected from participants and tested by culture and polymerase chain reaction (PCR). The association between detected pathogens and ARI development among all participants was examined. A case-control study was conducted to identify risk factors for disease.RESULTSIn total, 78 participants, including the index patient, were enrolled. Of all participants, 27 (34.6%) developed mild respiratory symptoms during a 3-week period: 24 were diagnosed as upper respiratory tract infections, and 3 were diagnosed as lower respiratory tract infections. The presence of BLNAR NTHi was confirmed in 13 participants, and multilocus sequence typing demonstrated that these isolates belonged to sequence type 159. All isolates showed identical pulsed-field gel electrophoresis patterns. The presence of BLNAR NTHi was strongly associated with ARI development, whereas viruses were not associated with the disease. Multivariate analyses demonstrated that a history of contact with the index patient was independently associated with ARI caused by BLNAR NTHi.CONCLUSIONSBLNAR NTHi has the potential to cause upper respiratory tract infections among adults and to spread rapidly in hospital settings.Infect Control Hosp Epidemiol 2018;39:652-659.
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http://dx.doi.org/10.1017/ice.2018.56DOI Listing
June 2018

Impact of HLA Allele-KIR Pairs on Disease Outcome in HIV-Infected Thai Population.

J Acquir Immune Defic Syndr 2018 07;78(3):356-361

National Institute of Health, Ministry of Public Health, Nonthaburi, Thailand.

Background: Class I human leukocyte antigen (HLA) molecules contribute to HIV control through antigen presentation to both cytotoxic T lymphocytes and natural killer cells. Contribution of cytotoxic T lymphocytes to HIV clinical outcome by HLA alleles has been well studied. However, reports about the role of natural killer cells in HIV clinical outcome, particularly, about the effect of HLA-killer immunoglobulin-like receptor (KIR) pairs, remain incomplete.

Methods: The effects of HLA allele-KIR pairs on HIV clinical outcome were statistically analyzed in a Thai cohort of treatment-naive chronically infected population (n = 209).

Results: Five HLA allele-KIR pairs scored significantly in viral load (VL) differences. Among them, opposing effects on VL were identified among subjects expressing KIR2DL2 ligands within the HLA-C1 group: higher VL in individuals expressing HLA-B*46:01+KIR2DL2+ compared with individuals without KIR (HLA-B*46:01+KIR2DL2-) (5.0 vs 4.6 log10 copies/mL, P = 0.02), in HLA-C*01:02+KIR2DL2+ (5.0 vs 4.6 log10 copies/mL; P = 0.02), and lower VL in HLA-C*12:03+KIR2DL2+ (4.3 vs 5.6 log10 copies/mL; P = 0.01). In the longitudinal analysis of a ten-year follow-up, HLA-B*46:01+KIR2DL2+ve subjects also had a higher mortality rate compared with the subjects without that pair, independent of variables including antiretroviral treatment, as well as CD4 T-cell count, sex, and age (adjusted hazard ratio 5.9, P = 0.02).

Conclusion: We identified several HLA allele-KIR pairs associated with clinical outcome differences including opposing effects on VL within 1 HLA group with the same KIR. Among them, HLA-B*46:01 emerged in Southeast Asia about 50,000 years ago and is now the most prevalent HLA-B allele in that area. These findings highlight that each endemic area has unique features of anti-HIV innate immunity that impact clinical outcome.
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http://dx.doi.org/10.1097/QAI.0000000000001676DOI Listing
July 2018

Exposure to paternal tobacco smoking increased child hospitalization for lower respiratory infections but not for other diseases in Vietnam.

Sci Rep 2017 03 31;7:45481. Epub 2017 Mar 31.

Department of Clinical Tropical Medicine, Institute of Tropical Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.

Exposure to environmental tobacco smoke (ETS) is an important modifiable risk factor for child hospitalization, although its contribution is not well documented in countries where ETS due to maternal tobacco smoking is negligible. We conducted a birth cohort study of 1999 neonates between May 2009 and May 2010 in Nha Trang, Vietnam, to evaluate paternal tobacco smoking as a risk factor for infectious and non-infectious diseases. Hospitalizations during a 24-month observation period were identified using hospital records. The effect of paternal exposure during pregnancy and infancy on infectious disease incidence was evaluated using Poisson regression models. In total, 35.6% of 1624 children who attended follow-up visits required at least one hospitalization by 2 years of age, and the most common reason for hospitalization was lower respiratory tract infection (LRTI). Paternal tobacco smoking independently increased the risk of LRTI 1.76-fold (95% CI: 1.24-2.51) after adjusting for possible confounders but was not associated with any other cause of hospitalization. The population attributable fraction indicated that effective interventions to prevent paternal smoking in the presence of children would reduce LRTI-related hospitalizations by 14.8% in this epidemiological setting.
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http://dx.doi.org/10.1038/srep45481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374438PMC
March 2017

Barriers to timely administration of birth dose vaccines in The Gambia, West Africa.

Vaccine 2016 06 17;34(29):3335-41. Epub 2016 May 17.

Medical Research Council, Banjul, The Gambia; Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK. Electronic address:

Objective: Although vaccine coverage in infants in sub-Saharan Africa is high, this is estimated at the age of 6-12 months. There is little information on the timely administration of birth dose vaccines. The objective of this study was to assess the timing of birth dose vaccines (hepatitis B, BCG and oral polio) and reasons for delayed administration in The Gambia.

Methods: We used vaccination data from the Farafenni Health and Demographic Surveillance System (FHDSS) between 2004 and 2014. Coverage was calculated at birth (0-1 day), day 7, day 28, 6 months and 1 year of age. Logistic regression models were used to identify demographic and socio-economic variables associated with vaccination by day 7 in children born between 2011 and 2014.

Results: Most of the 10,851 children had received the first dose of hepatitis B virus (HBV) vaccine by the age of 6 months (93.1%). Nevertheless, only 1.1% of them were vaccinated at birth, 5.4% by day 7, and 58.4% by day 28. Vaccination by day 7 was associated with living in urban areas (West rural: adjusted OR (AOR)=6.13, 95%CI: 3.20-11.75, east rural: AOR=6.72, 95%CI: 3.66-12.33) and maternal education (senior-educations: AOR=2.43, 95%CI: 1.17-5.06); and inversely associated with distance to vaccination delivery points (≧2km: AOR=0.41, 95%CI: 0.24-0.70), and Fula ethnicity (AOR=0.60, 95%CI: 0.40-0.91).

Conclusion: Vaccine coverage in The Gambia is high but infants are usually vaccinated after the neonatal period. Interventions to ensure the implementation of national vaccination policies are urgently needed.
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http://dx.doi.org/10.1016/j.vaccine.2016.05.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915601PMC
June 2016

The large contribution of twins to neonatal and post-neonatal mortality in The Gambia, a 5-year prospective study.

BMC Pediatr 2016 Mar 15;16:39. Epub 2016 Mar 15.

Medical Research Council, Banjul, The Gambia.

Background: A high twinning rate and an increased risk of mortality among twins contribute to the high burden of infant mortality in Africa. This study examined the contribution of twins to neonatal and post-neonatal mortality in The Gambia, and evaluated factors that contribute to the excess mortality among twins.

Methods: We analysed data from the Basse Health and Demographic Surveillance System (BHDSS) collected from January 2009 to December 2013. Demographic and epidemiological variables were assessed for their association with mortality in different age groups.

Results: We included 32,436 singletons and 1083 twins in the analysis (twining rate 16.7/1000 deliveries). Twins represented 11.8 % of all neonatal deaths and 7.8 % of post-neonatal deaths. Mortality among twins was higher than in singletons [adjusted odds ratio (AOR) 4.33 (95 % CI: 3.09, 6.06) in the neonatal period and 2.61 (95 % CI: 1.85, 3.68) in the post-neonatal period]. Post-neonatal mortality among twins increased in girls (P for interaction = 0.064), being born during the dry season (P for interaction = 0.030) and lacking access to clean water (P for interaction = 0.042).

Conclusion: Mortality among twins makes a significant contribution to the high burden of neonatal and post-neonatal mortality in The Gambia and preventive interventions targeting twins should be prioritized.
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http://dx.doi.org/10.1186/s12887-016-0573-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791939PMC
March 2016

The effect of KIR2D-HLA-C receptor-ligand interactions on clinical outcome in a HIV-1 CRF01_AE-infected Thai population.

AIDS 2015 Aug;29(13):1607-15

aDepartment of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan bDepartment of Paediatrics, University of Oxford, Oxford, UK cThai National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi dDay Care Centre, Lampang Hospital, Lampang, Thailand eNagasaki University Global COE Program, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.

Objective: Class I human leukocyte antigen (HLA) alleles interact with both cytotoxic T lymphocytes through their T-cell receptors, and natural killer cells through their killer immunoglobulin-like receptors (KIRs). Compared with the reported protective effect of KIR3DL1/S1-HLA-Bw4 interactions in HIV-infected patients, the effect of KIR2D-HLA-C combinations on HIV control remains unclear. Here, we investigate the effect of KIR2D-HLA-C combinations on HIV disease progression.

Design: We performed a cross-sectional and longitudinal analysis of a Thai HIV cohort.

Methods: Two hundred and nine HIV-1 CRF01_AE-infected, treatment-naive Thai patients (CD4 T-cell counts of >200/μl) and 104 exposed seronegatives were studied. The effect of KIR-HLA receptor-ligand combinations on viral transmission and survival rate was statistically analyzed.

Results: We found the following results: higher frequency of patients expressing both KIR2DL3 and HLA-C1 among infected patients compared with exposed seronegative (odds ratio 4.8, P = 0.004), higher viral load in patients expressing HLA-C1 with KIR2DL3 compared with those without this receptor-ligand combination (median 4.8 vs. 4.2 log copies/ml, P = 0.033), higher numbers of KIR2DL3-HLA-C1 interactions was associated with a higher viral load (β = 0.13, P = 0.039 by linear regression model), and higher mortality rate in carriers of the KIR2DL3-HLA-C1 combination (adjusted hazard ratio 1.9, P = 0.012 by Cox hazard model).

Conclusion: We have identified a deleterious effect of the KIR2DL3-HLA-C1 receptor-ligand combination on HIV clinical outcomes in a Thai cohort. Further investigation into mechanisms underlying this susceptibility may aid the understanding of the role of natural killer cells in HIV disease control and pathogenesis.
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http://dx.doi.org/10.1097/QAD.0000000000000747DOI Listing
August 2015

HLA-B*35: 05 is a protective allele with a unique structure among HIV-1 CRF01_AE-infected Thais, in whom the B*57 frequency is low.

AIDS 2014 Apr;28(7):959-67

Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Sakamoto, Nagasaki City, Nagasaki, Japan.

Objective: To identify protective human leukocyte antigen (HLA) alleles in an HIV-infected south-east Asian population, in whom HLA-B*57 prevalence is lower than other ethnic groups, and HIV-1 CRF01_AE is the dominant circulating subtype.

Design: Cross-sectional study of Thai patients with chronic HIV infection.

Methods: Five hundred and fifty-seven HIV-1 CRF01_AE-infected Thais were recruited. Their HLA type and viral load were determined to statistically analyze the association of each allele in viral control. In-silico molecular dynamics was also used to evaluate the effect of HLA structure variants on epitope binding.

Results: HLA-B*35:05 was identified as the most protective allele (P=0.003, q=0.17), along with HLA-B*57:01 (P=0.044, q=0.31). Structurally, HLA-B*35:05 belonged to the HLA-B*35-PY group of HLA-B*35 alleles; however, unlike the other HLA-B*35 alleles that carry Arg (R) at residue 97, it has unique sequences at T94, L95, and S97, located within the peptide-binding groove. Analysis of the three-dimensional HLA structure and molecular dynamics indicates that S97 in HLA-B*35:05 leads to less flexibility in the groove, and shorter distances between the α-helixes compared with the disease-susceptible HLA-B*35-PY allele, HLA-B*35:01.

Conclusion: These data indicate the existence of a protective effect of HLA-B*57 across ethnic groups and highlight HLA-B*35:05 as an allele uniquely protective in subtype CRF01_AE-infected Thais. The divergence of HLA-B*35:05 from conventional HLA-B*35-PY structural sequences at the peptide-binding groove is consistent with previous studies that have identified HLA residue 97 as strongly influential in shaping HLA impact on immune control of HIV, and that a more restricted peptide-binding motif may be associated with improved control.
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http://dx.doi.org/10.1097/QAD.0000000000000206DOI Listing
April 2014