Standardization of Clinical Assessment and Sample Collection Across All PERCH Study Sites.

BACKGROUND.: Variable adherence to standardized case definitions, clinical procedures, specimen collection techniques, and laboratory methods has complicated the interpretation of previous multicenter pneumonia etiology studies. To circumvent these problems, a program of clinical standardization was embedded in the Pneumonia Etiology Research for Child Health (PERCH) study. METHODS.: Between March 2011 and August 2013, standardized training on the PERCH case definition, clinical procedures, and collection of laboratory specimens was delivered to 331 clinical staff at 9 study sites in 7 countries (The Gambia, Kenya, Mali, South Africa, Zambia, Thailand, and Bangladesh), through 32 on-site courses and a training website. Staff competency was assessed throughout 24 months of enrollment with multiple-choice question (MCQ) examinations, a video quiz, and checklist evaluations of practical skills. RESULTS.: MCQ evaluation was confined to 158 clinical staff members who enrolled PERCH cases and controls, with scores obtained for >86% of eligible staff at each time-point. Median scores after baseline training were ≥80%, and improved by 10 percentage points with refresher training, with no significant intersite differences. Percentage agreement with the clinical trainer on the presence or absence of clinical signs on video clips was high (≥89%), with interobserver concordance being substantial to high (AC1 statistic, 0.62-0.82) for 5 of 6 signs assessed. Staff attained median scores of >90% in checklist evaluations of practical skills. CONCLUSIONS.: Satisfactory clinical standardization was achieved within and across all PERCH sites, providing reassurance that any etiological or clinical differences observed across the study sites are true differences, and not attributable to differences in application of the clinical case definition, interpretation of clinical signs, or in techniques used for clinical measurements or specimen collection

Pneumococcal colonization prevalence and density among Thai children with severe pneumonia and community controls.

BACKGROUND:Pneumococcal colonization prevalence and colonization density, which has been associated with invasive disease, can offer insight into local pneumococcal ecology and help inform vaccine policy discussions. METHODS:The Pneumonia Etiology Research for Child Health Project (PERCH), a multi-country case-control study, evaluated the etiology of hospitalized cases of severe and very severe pneumonia among children aged 1-59 months. The PERCH Thailand site enrolled children during January 2012-February 2014. We determined pneumococcal colonization prevalence and density, and serotype distribution of colonizing isolates. RESULTS:We enrolled 224 severe/very severe pneumonia cases and 659 community controls in Thailand. Compared to controls, cases had lower colonization prevalence (54.5% vs. 62.5%, p = 0.12) and lower median colonization density (42.1 vs. 210.2 x 103 copies/mL, p <0.0001); 42% of cases had documented antibiotic pretreatment vs. 0.8% of controls. In no sub-group of assessed cases did pneumococcal colonization density exceed the median for controls, including cases with no prior antibiotics (63.9x103 copies/mL), with consolidation on chest x-ray (76.5x103 copies/mL) or with pneumococcus detected in whole blood by PCR (9.3x103 copies/mL). Serotype distribution was similar among cases and controls, and a high percentage of colonizing isolates from cases and controls were serotypes included in PCV10 (70.0% and 61.8%, respectively) and PCV13 (76.7% and 67.9%, respectively). CONCLUSIONS:Pneumococcal colonization is common among children aged <5 years in Thailand. However, colonization density was not higher among children with severe pneumonia compared to controls. These results can inform discussions about PCV introduction and provide baseline data to monitor PCV impact after introduction in Thailand

Epidemiology and antimicrobial resistance of invasive non-typhoidal Salmonellosis in rural Thailand from 2006-2014

<div><p>Introduction</p><p>Invasive salmonellosis is a common cause of bloodstream infection in Southeast Asia. Limited epidemiologic and antimicrobial resistance data are available from the region.</p><p>Methods</p><p>Blood cultures performed in all 20 hospitals in the northeastern province of Nakhon Phanom (NP) and eastern province of Sa Kaeo (SK), Thailand were captured in a bloodstream infection surveillance system. Cultures were performed as clinically indicated in hospitalized patients; patients with multiple positive cultures had only the first included. Bottles were incubated using the BacT/Alert system (bioMérieux, Thailand) and isolates were identified using standard microbiological techniques; all <i>Salmonella</i> isolates were classified to at least the serogroup level. Antimicrobial resistance was assessed using disk diffusion.</p><p>Results</p><p><i>Salmonella</i> was the fifth most common pathogen identified in 147,535 cultures with 525 cases (211 in Nakhon Phanom (NP) and 314 in Sa Kaeo (SK)). The overall adjusted iNTS incidence rate in NP was 4.0 cases/100,000 person-years (95% CI 3.5–4.5) and in SK 6.4 cases/100,000 person-years (95% CI 5.7–7.1; p = 0.001). The most common serogroups were C (39.4%), D (35.0%) and B (9.9%). Serogroup D predominated in NP (103/211) with 59.2% of this serogroup being <i>Salmonella</i> serovar Enteritidis. Serogroup C predominated in SK (166/314) with 84.3% of this serogroup being <i>Salmonella</i> serovar Choleraesuis. Antibiotic resistance was 68.2% (343/503) for ampicillin, 1.2% (6/482) for ciprofloxacin (or 58.1% (280/482) if both intermediate and resistant phenotypes are considered), 17.0% (87/512) for trimethoprim-sulfamethoxazole, and 12.2% (59/484) for third-generation cephalosporins (cefotaxime or ceftazidime). Multidrug resistance was seen in 99/516 isolates (19.2%).</p><p>Conclusions</p><p>The NTS isolates causing bloodstream infections in rural Thailand are commonly resistant to ampicillin, cefotaxime, and TMP-SMX. Observed differences between NP and SK indicate that serogroup distribution and antibiotic resistance may substantially differ throughout Thailand and the region.</p></div

Epidemiology and antimicrobial resistance of invasive non-typhoidal Salmonellosis in rural Thailand from 2006-2014 - Fig 3

<p><b>Incidence of invasive non-typhoidal Salmonellosis by age group and year in Sa Kaeo (SK, left) and Nakhon Phanom (NP, right) provinces, 2006–2014.</b> RR = relative risk, measured differences between SK and NP. Relative risk is given with upper and lower 95% confidence intervals. * designates age group differences between NP and SK within the specified year (p-value < 0.05) and likely to be driving the differences.</p

Distribution of invasive non-typhoidal Salmonella serovars isolated in two rural Thai provinces between 2006 and 2014.

<p>Distribution of invasive non-typhoidal Salmonella serovars isolated in two rural Thai provinces between 2006 and 2014.</p

Antibiotic resistance among invasive non-typhoidal <i>Salmonella</i> isolates by province and year.

<p>Solid line graph shows number of positive blood cultures and the dashed line indicates the total number of bottles incubated by year (z-axis). TMP-SMX = trimethoprim-sulfamethoxazole.</p

Demographic and clinical characteristics of patients with invasive non-typhoidal Salmonellosis in Nakhon Phanom and Sa Kaeo provinces, 2006–2014.

<p>Demographic and clinical characteristics of patients with invasive non-typhoidal Salmonellosis in Nakhon Phanom and Sa Kaeo provinces, 2006–2014.</p

Map of Thailand showing the two rural provinces, Nakhon Phanom (NP) and Sa Kaeo (SK), participating in population-based bloodstream surveillance.

<p>The enlarged map of each province details the number of invasive non-typhoidal Salmonella (iNTS) cases for each hospital as indicated by the size of circle in each district. The color of the marker represents the number of beds for each hospital (the darker the color the higher the number of beds: range from 10–306). Map generated using ArcGIS version 10.5.1, (Environmental Systems Research Institute, Redlands, CA, USA); the base-layer country map was from the ArcGIS software and provincial level overlay file was obtained from the Ministry of Land, Thailand. Donut diagrams show the distribution of iNTS serogroups isolated in each province from 2006 to 2014.</p

Age distributions for the major serogroups of invasive non-typhoidal <i>Salmonella</i> in Nakhon Phanom and Sa Kaeo provinces.

<p>Age distributions for the major serogroups of invasive non-typhoidal <i>Salmonella</i> in Nakhon Phanom and Sa Kaeo provinces.</p

Flow diagram of blood culture data identifying non-typhoidal Salmonella cases, Nakhon Phanom and Sa Kaeo provinces, 2006-2014.

<p>Blood culture bottles were incubated at 35°C for up to 5 and 42 days (F and MB bottles respectively), or until the instrument signaled positive for growth (i.e., positive signal). Culture bottles that did not signal positive after the specified incubation periods (no signal) were considered to be negative without terminal subculture. A. The following organisms were considered likely contaminants and not included in the analysis: S<i>treptococcus viridans</i> group, <i>Corynebacterium</i> spp., <i>Bacillus</i> spp. (other than <i>B</i>. <i>anthracis</i>), <i>Staphylococcus</i> spp. (other than <i>S</i>. <i>aureus</i>), and <i>Aerococcus</i> spp. B. The unknown category were non-identifiable isolates using our standard biochemical testing including Gram-positive and negative cocci (n = 197 and 11 respectively), and Gram-positive bacilli (n = 343); these are likely contaminants. Gram-negative bacilli (n = 12) and unknown other (n = 708). C. The automated blood culture instrument signaled positive, but subculture yielded no organism.</p