The duration of febrile episodes in enteric fever patients infected with <i>S.</i> Typhi organisms with a range of MICs to ofloxacin.

<p>Kaplan Meir curve showing the proportion of patients remaining febrile (>38°C) after the start of treatment with ofloxacin. Data is composed from fever clearance times of 540 children and adults with uncomplicated enteric fever recruited to seven randomised clinical trial and treated with oral ofloxacin. The curves are divided according to the ofloxacin MIC of the infecting isolates and are highlighted on the diagram.</p

The relationship between increasing <i>S.</i> Typhi MIC to ofloxacin and clinical failure.

<p>Histogram showing the proportion of enteric fever patients who failed treatment (white columns) or had persistent fever (black columns) (>38°C) for more than seven days after the commencement of treatment. Data was combined from seven randomised clinical trials and is comprised from 540 children and adults recruited with uncomplicated enteric fever. The patients are divided according to the MIC to ofloxacin of the infecting isolate.</p

Admission features of 540 ofloxacin treated enteric fever patients recruited to clinical trials.

a<p>) continuous variables given as median (interquartile range), and proportions as number (%).</p>b<p>) Analysis of variance for proportions, Kruskall Wallis test for continuous variables.</p>c<p>) MDR – resistant to ampicillin, chloramphenicol and trimethoprim-sulfamethoxazole.</p>d<p>) NaR – resistant to nalidixic acid.</p

The distribution of <i>S.</i> Typhi MIC to ofloxacin in seven RCTs.

<p>Histogram showing the distribution of <i>S.</i> Typhi MICs (<0.06, 0.06, 0.125, 0.25, 0.5 and 1 µg/mL) to ofloxacin over seven individual randomised. The proportion of <i>S.</i> Typhi strains with the corresponding MIC are shaded accordingly, white; study TY1 (1992–1993) n = 19 <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0001163#pntd.0001163-Smith2" target="_blank">[25]</a>, very light grey; study CT1 (1993–1994) n = 102 <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0001163#pntd.0001163-Vinh1" target="_blank">[26]</a>, light grey; study TY2 (1993–1996) n = 103 <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0001163#pntd.0001163-Nguyen1" target="_blank">[24]</a>, mid grey; study DTC (1994–1995) n = 154 <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0001163#pntd.0001163-Vinh2" target="_blank">[28]</a>, dark grey; study DN (1995–1996) n = 55 <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0001163#pntd.0001163-Cao1" target="_blank">[29]</a>, very dark grey; study TY3 (1997–1998) n = 45 <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0001163#pntd.0001163-Chinh1" target="_blank">[23]</a> and black; study DTY2 (1998–2001) n = 62 <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0001163#pntd.0001163-Parry3" target="_blank">[27]</a>.</p

Extracellular levels of granzyme A and B on admission and during discharge in patients.

<p>Typhoid fever patients (n = 15) who were discharged from hospital had lower levels of granzymes at follow-up when patients were clinically improved (granzyme A; A), although this did only reach statistical significance for granzyme B (B). Medians are shown. Significance determined via Mann-Whitney <i>U</i> tests. *P<0.05. Gzm: granzyme.</p

Serotype results by age and vaccine coverage.

<p>Serotype results by age and vaccine coverage.</p

Expression of granzymes A, B and K by each lymphocyte subtype in patients with typhoid fever and controls.

<p>Percentage of lymphocyte population expressing each granzyme (A–D) and MFI of the intracellular expression of each granzyme in the lymphocyte populations (E–H). n = 36 controls and 8 patients. MFI values are expressed with Log10 scale. Significance determined via Mann-Whitney <i>U</i> tests. Medians are shown. Analysis was done by flow cytometry. MFI: median fluorescence intensity; NK cells: CD3⁻CD56⁺. *P<0.05, **P<0.01, ***P<0.001.</p

Characterisation of Invasive <i>Streptococcus pneumoniae</i> Isolated from Cambodian Children between 2007 – 2012

<div><p>Background</p><p>The 13-valent pneumococcal vaccine (PCV13) was introduced in Cambodia in January 2015. There are limited data concerning the common serotypes causing invasive pneumococcal disease (IPD). Knowledge of the circulating pneumococcal serotypes is important to monitor epidemiological changes before and after vaccine implementation.</p><p>Methods</p><p>All episodes of IPD defined by the isolation of <i>Streptococcus pneumoniae</i> from blood, cerebrospinal fluid or other sterile site in Cambodian children admitted to the Angkor Hospital for Children in Siem Reap, Northwestern Cambodia, between 1^st January 2007 and 1^st July 2012 were retrospectively studied. <i>Streptococcus pneumoniae</i> isolates that could be retrieved underwent phenotypic typing and whole genome sequencing.</p><p>Results</p><p>There were 90 Cambodian children hospitalized with IPD with a median (IQR) age of 2.3 years (0.9–6.2). The case fatality was 15.6% (95% CI 8–23). Of 50 <i>Streptococcus pneumoniae</i> isolates available for further testing, 46% were penicillin non-susceptible and 8% were ceftriaxone non-susceptible, 78% were cotrimoxazole resistant, 30% were erythromycin resistant and 30% chloramphenicol resistant. There were no significant changes in resistance levels over the five-year period. The most common serotypes were 1 (11/50; 22%), 23F (8/50; 16%), 14 (6/50; 12%), 5 (5/50; 10%) and 19A (3/50; 6%). Coverage by PCV7, PCV10 and PCV13 was 44%, 76% and 92% respectively. We identified novel multilocus sequence types and resistotypes using whole genome sequencing.</p><p>Conclusions</p><p>This study suggests IPD is an important disease in Cambodian children and can have a significant mortality. PCV13 coverage of the serotypes determined in studied strains was high and consistent with another recent study. The phenotypic resistance patterns observed were similar to other regional studies. The use of whole genome sequencing in the present study provides additional typing and resistance information together with the description of novel sequence types and resistotypes.</p></div

Extracellular levels of granzyme A and B in patients with typhoid fever and healthy controls, and correlation with IFN- γ levels.

<p>Plasma levels of granzyme A (A) and B (B) measured in healthy controls (n = 38) compared to admission samples of hospitalized typhoid fever patients (n = 28). Medians are shown. Significance determined via Mann-Whitney <i>U</i> tests. ***P<0.001. Granzyme A is correlated to granzyme B (C). Levels of granzyme A (D) and granzyme B (E) are correlated to interferon (IFN)-γ in patients. Correlation coefficient reported is for Spearman's Rho. Gzm: granzyme.</p

MLST, serotyping and resistotyping data for invasive <i>S</i>. <i>pneumoniae</i> isolates.

<p>MLST, serotyping and resistotyping data for invasive <i>S</i>. <i>pneumoniae</i> isolates.</p