Molecular characterization and complete genome analysis of human enterovirus 71 and coxsackievirus A16 from children with hand, foot and mouth disease in Thailand during 2008-2011

Hand, foot and mouth disease (HFMD) has mostly been caused by enterovirus 71 (EV71) and coxsackievirus A16 (CA16). CA 16 was the most common cause of HFMD in 2010. EV71 had a high prevalence in 2008-2009 and has been identified with a higher frequency since 2011. Nearly complete genome sequences of three EV71 strains (2008-2009 strains) and two CA16 strains (2010 strains) obtained from outbreaks in Thailand in 2008 to 2010 were characterized. Based on a phylogenetic tree of the complete VP1 region, three EV71 strains grouped into the B5, C1 and C4 genotypes, and two CA16 strains grouped into the C genotype. Based on sequence analysis, nucleotide changes were found to cluster in the internal ribosome entry site (IRES) element of the 5′-untranslated region (5′-UTR). Amino acid differences identified in all strains were located in the non-structural protein. These data also provide the molecular epidemiology of EV71 and CA16 outbreaks in Thailand.     

Incidence of active tuberculosis among people living with HIV receiving long‐term antiretroviral therapy in high TB/HIV burden settings in Thailand: implication for tuberculosis preventive therapy

IntroductionAmong high tuberculosis (TB) and HIV burden countries in Asia, tuberculosis preventive therapy (TPT) in people living with HIV (PLWH) has been underutilized despite its proven benefits independent of antiretroviral therapy (ART). Therefore, we determined the incidence of active TB and mortality among 9179 adult PLWH who attended and received ART from 15 tertiary care hospitals across Thailand.MethodsA retrospective study was conducted in 2018 using follow‐up data from 1999 to 2018. The primary endpoint was incident TB disease after ART initiation. Factors associated with TB incidence were analysed using competing risk regression. The Kaplan–Meier method was used to estimate mortality after ART initiation.ResultsDuring a median of 5.1 years of ART (IQR 2.2–9.5 years), 442 (4.8%) PLWH developed TB (TB/HIV), giving an overall incidence of 750 (95% CI 683–823) per 100,000 persons‐year of follow up (PYFU). In multivariate analysis, lower CD4 at ART initiation (≤100 cells/mm³, adjusted sub‐distribution hazard ratio [aSHR]: 2.08, 95% CI, 1.47–2.92; 101–200 cells/mm³, aSHR: 2.21, 95% CI, 1.54–3.16; 201–350 cells/mm³, aSHR: 1.59, 95% CI, 1.11–2.28 vs. >350 cells/mm³), male sex (aSHR: 1.40, 95% CI, 1.11–1.78), lower body weight (<50 kg, aSHR: 1.52, 95% CI, 1.17–1.95) and prior TB event (aSHR: 3.50, 95% CI, 2.72–4.52) were associated with TB incidence. PLWH with HIV RNA ≥50 copies/ml had 5–9 times higher risk of active TB disease higher than those with HIV RNA <50 copies/ml at the same CD4 level. The risk for developing TB was remarkably high during the initial period of ART (175,511 per 100,000 PYFU at<3 months) and was comparable to the general population after 10 years of ART (151 per 100,000 PYFU). TB/HIV had higher mortality (10% vs. 5%) and poorer HIV treatment outcomes: HIV RNA <50 copies/ml (63.8% vs. 82.8%), CD4 cells count (317 vs. 508 cells/mm³) at the most recent visit.ConclusionsIn this high TB burden country, TB incidence was remarkably high during the first few years after ART initiation and thereafter decreased significantly. Rapid ART initiation and appropriate TPT can be potential key interventions to tackle the TB epidemic and reduce mortality among PLWH in TB/HIV high burden settings.     

Complete genome sequence analysis of enterovirus 71 isolated from children with hand,foot, and mouth disease in Thailand, 2012–2014

The complete genomic sequences of 14 enterovirus 71 (EV71) strains isolated from children with hand, foot, and mouth disease in Thailand from 2012 to 2014 were determined and compared to enterovirus group A prototypes. Phylogenetic analysis revealed that 13 strains resembled the B5 subgroup, while one strain from a fatal case designated THA_1219 belonged to the C4 subgroup. Similarity plot and bootscan analyses suggested that THA_1219 underwent recombination in the P2 and P3 regions. Full-genome data from this work will contribute to the study of evolution dynamics of EV71.     

Neither branded nor generic lopinavir/ritonavir produces adequate lopinavir concentrations at a reduced dose of 200/50 mg twice daily

We assessed pharmacokinetic (PK) parameters of reduced dose lopinavir/ritonavir (LPV/r) and compared generic and branded tablets. Twenty HIV-infected patients using protease inhibitors with HIV RNA <50 copies per milliliter were randomized to generic or branded LPV/r 200/50mg twice daily (BID). At week 2, PK-sampling was performed. Patients crossed over to the other arm until week 12, with another PK-sampling at week 4. Subtherapeutic lopinavir concentrations were observed in 10/40 samples. PK parameters were comparable between branded and generic tablets. All patients remained virologically suppressed at week 12. In conclusion, LPV/r 200/50mg BID does not lead to adequate lopinavir plasma concentrations. Generic and branded LPV/r have comparable PK-parameters.