• Correction: host genetic factors and vaccine-induced immunity to hepatitis B virus infection.

    17 July 2018

    [This corrects the article on p. e1898 in vol. 3.].

  • Changing patterns of gastrointestinal parasite infections in Cambodian children: 2006-2011.

    17 July 2018

    We studied gastrointestinal parasites in symptomatic Cambodian children attending a provincial hospital in Siem Reap, Cambodia between 2006 and 2011. A total of 16 372 faecal samples were examined by direct microscopy. Parasites were detected in 3121 (19.1%) samples and most common were Giardia lamblia (8.0% of samples; 47.6% disease episodes), hookworm (5.1%; 30.3%) and Strongyloides stercoralis (2.6%; 15.6%). The proportion of infected children increased, and the number of disease episodes effectively treated with a single dose of mebendazole decreased, over the 5-year period.

  • Enteric fever in Cambodian children is dominated by multidrug-resistant H58 Salmonella enterica serovar Typhi with intermediate susceptibility to ciprofloxacin.

    17 July 2018

    Infections with Salmonella enterica serovar Typhi isolates that are multidrug resistant (MDR: resistant to chloramphenicol, ampicillin, trimethoprim-sulphamethoxazole) with intermediate ciprofloxacin susceptibility are widespread in Asia but there is little information from Cambodia. We studied invasive salmonellosis in children at a paediatric hospital in Siem Reap, Cambodia. Between 2007 and 2011 Salmonella was isolated from a blood culture in 162 children. There were 151 children with enteric fever, including 148 serovar Typhi and three serovar Paratyphi A infections, and 11 children with a non-typhoidal Salmonella infection. Of the 148 serovar Typhi isolates 126 (85%) were MDR and 133 (90%) had intermediate ciprofloxacin susceptibility. Inpatient antimicrobial treatment was ceftriaxone alone or initial ceftriaxone followed by a step-down to oral ciprofloxacin or azithromycin. Complications developed in 37/128 (29%) children admitted with enteric fever and two (1.6%) died. There was one confirmed relapse. In a sample of 102 serovar Typhi strains genotyped by investigation of a subset of single nucleotide polymorphisms, 98 (96%) were the H58 haplotype, the majority of which had the common serine to phenylalanine substitution at codon 83 in the DNA gyrase. We conclude that antimicrobial-resistant enteric fever is common in Cambodian children and therapeutic options are limited.

  • Lack of association between Toll-like receptor 2 polymorphisms and susceptibility to severe disease caused by Staphylococcus aureus.

    17 July 2018

    To investigate a putative link between genetically determined variations in Toll-like receptor 2 (TLR2) and the occurrence of severe Staphylococcus aureus infection, the functional Arg753Gln single-nucleotide polymorphism and the GT repeat microsatellite in the TLR2 gene were examined in a large case-control study. No associations with disease or mortality attributable to these features were found.

  • Reduction of invasive pneumococcal disease 3 years after the introduction of the 13-valent conjugate vaccine in the Oxfordshire region of England.

    17 July 2018

    The 7-valent pneumococcal conjugate (PCV7) vaccine's impact on invasive pneumococcal disease (IPD) is well described, but few reports exist on the additional impact of the 13-valent vaccine (PCV13).We calculated the IPD incidence across all ages in a surveillance project following implementation of PCV7 (in September 2006) and PCV13 (in April 2010) in children aged <2 years (11 hospitals; 4935 cases).The overall incidence decreased from 10 cases/100 000 persons per year in 1996-1997 to 8 cases/100 000 persons per year in 2007-2008 and 7 cases/100 000 in 2012-2013. Declines were greater in children aged <2 years (from 37 cases/100 000 in 1996-1997 to 29 and 14 cases/100 000 in 2007-2008 and 2012-2013, respectively). The incidence of IPD due to PCV7 serotypes decreased in all ages after PCV7 introduction (P < .001), whereas the incidence of IPD due to the additional 6 serotypes in PCV13 and to nonvaccine types (NVTs) increased in children aged ≥2 years (P < .001 for both comparisons). The incidence of IPD due to the 6 additional serotypes in PCV13 declined significantly after PCV13 introduction in all ages (P ≤ .01), and the incidence of IPD due to NVTs declined significantly in children aged ≥2 years (P = .003). In 2011-2013, the overall incidences of IPD due to PCV7 serotypes, the 6 additional serotypes in PCV13, and NVTs were 0.3, 2.8, and 4.4 cases/100 000; the incidences among children aged <2 years were 0.9, 2.4, and 10.8 cases/100 000, respectively.The annual incidence of IPD due to vaccine serotypes (1-3 cases/100 000) among children aged <2 years and nontarget groups demonstrates the success of PCV7 and PCV13. A substantially higher incidence of IPD due to NVTs indicates the importance of ongoing surveillance and extension of vaccine polyvalency.

  • Limited polymorphism in the dihydropteroate synthetase gene (dhps) of Plasmodium vivax isolates from Thailand.

    17 July 2018

    The dhps sequences of 55 Plasmodium vivax isolates (39 from Thailand and 16 from elsewhere) revealed mutant Pvdhps at codons 383 and/or 553 (A --> G) in 33 isolates, all from Thailand. Mutations of Pvdhps and Pvdhfr were correlated. Multiple mutations were associated with high-grade sulfadoxine-pyrimethamine resistance.

  • Comparison of multilocus sequence typing and pulsed-field gel electrophoresis as tools for typing Staphylococcus aureus isolates in a microepidemiological setting.

    17 July 2018

    Multilocus sequence typing (MLST) of Staphylococcus aureus is well suited to the study of global or long-term epidemiology, but its role in local epidemiology has not been defined. The present study has compared MLST with pulsed-field gel electrophoresis (PFGE) by using S. aureus isolates associated with carriage and disease in a busy regional renal unit. One hundred forty-four patients were prospectively recruited, of whom 103 were receiving hemodialysis and 41 were on continuous ambulatory peritoneal dialysis. Three nasal swab specimens were obtained 1 month apart on entering the study. A nasal swab was positive for S. aureus on at least one occasion in 50 patients (35%). Typing of the 104 carriage isolates demonstrated 21 PFGE types and 21 sequence types (STs). Thirty-one carriers had two or more positive nasal swabs; of these, the isolates in all swabs from a given carrier had identical PFGE types for 29 carriers; the isolates in all of the same 29 swabs had identical STs. The carriage strain in two patients changed both PFGE type and STs during the period of swabbing. Eight patients (6%) had an episode of S. aureus bacteremia during the 12-month study period, and two of these were nasal carriers. One of these invasive isolates had the same PFGE type and ST as the carriage isolate. There were no differences between Simpson's index of diversity for PFGE and Simpson's index of diversity for MLST for both invasive and carriage isolates, suggesting that the two methods have very similar discriminatory abilities. We conclude that PFGE and MLST performed equally in this study.

  • Enhanced determination of Streptococcus pneumoniae serotypes associated with invasive disease in Laos by using a real-time polymerase chain reaction serotyping assay with cerebrospinal fluid.

    17 July 2018

    A prospective hospital-based study was undertaken to define the incidence of invasive pneumococcal disease (IPD) and circulating serotypes in Laos. Of 10,799 patients with hemocultures and 353 patients with cerebrospinal fluid samples, 0.21% and 5.4%, respectively, were positive for Streptococcus pneumoniae, giving a total of 35 IPD patients. We developed a real-time polymerase chain reaction to detect serotypes represented in the 13-valent pneumococcal vaccine. A blinded evaluation comparing serotype as defined by the Quellung reaction versus the polymerase chain reaction demonstrated 100% concordance. The most frequent serotype (n = 33 patients) was 1 (n = 6), followed by serotypes 5, 6A/B/C, 14, and 23F. Serotypes represented in the 7-valent polysaccharide-protein conjugate vaccine (PCV-7) infected 39% of patients, with 73% coverage for the PCV-10 and PCV-13 vaccines. Although the sample size is small, these data suggest that the PCV-7 vaccine may have relatively low efficacy in Laos. Further studies are urgently needed to guide pneumococcal vaccine policy in Laos.

  • Virulent combinations of adhesin and toxin genes in natural populations of Staphylococcus aureus.

    17 July 2018

    Most cases of severe Staphylococcus aureus disease cannot be explained by the action of a single virulence determinant, and it is likely that a number of factors act in combination during the infective process. This study examined the relationship between disease in humans and a large number of putative virulence determinants, both individually and in combination. S. aureus isolates (n = 334) from healthy blood donors and from patients with invasive disease were compared for variation in the presence of 33 putative virulence determinants. After adjusting for the effect of clonality, seven determinants (fnbA, cna, sdrE, sej, eta, hlg, and ica) were significantly more common in invasive isolates. All seven factors contributed independently to virulence. No single factor predominated as the major predictor of virulence, their effects appearing to be cumulative. No combinations of the seven genes were either more or less likely to cause disease than others with the same number of virulence-associated genes. There was evidence of considerable horizontal transfer of genes on a background of clonality. Our findings also suggested that allelic variants of a polymorphic locus can make different contributions to the disease process, further study of which is likely to expand our understanding of staphylococcal disease pathogenesis.