Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-30 (of 40 Records) |
Query Trace: Hammitt LL[original query] |
---|
Streptococcus pneumoniae serotype 3 population structure in the era of conjugate vaccines, 2001-2018
Cella E , Sutcliffe CG , Grant LR , Tso C , Weatherholtz RC , Littlepage S , Becenti L , Jubair M , Simons BC , Harker-Jones M , Reid R , Yazzie D , Santosham M , O'Brien KL , Hammitt LL , Azarian T . Microb Genom 2024 10 (3) Background. Despite use of highly effective conjugate vaccines, invasive pneumococcal disease (IPD) remains a leading cause of morbidity and mortality and disproportionately affects Indigenous populations. Although included in the 13-valent pneumococcal conjugate vaccine (PCV13), which was introduced in 2010, serotype 3 continues to cause disease among Indigenous communities in the Southwest USA. In the Navajo Nation, serotype 3 IPD incidence increased among adults (3.8/100 000 in 2001-2009 and 6.2/100 000 in 2011-2019); in children the disease persisted although the rates dropped from 5.8/100 000 to 2.3/100 000.Methods. We analysed the genomic epidemiology of serotype 3 isolates collected from 129 adults and 63 children with pneumococcal carriage (n=61) or IPD (n=131) from 2001 to 2018 of the Navajo Nation. Using whole-genome sequencing data, we determined clade membership and assessed changes in serotype 3 population structure over time.Results. The serotype 3 population structure was characterized by three dominant subpopulations: clade II (n=90, 46.9 %) and clade Iα (n=59, 30.7 %), which fall into Clonal Complex (CC) 180, and a non-CC180 clade (n=43, 22.4 %). The proportion of clade II-associated IPD cases increased significantly from 2001 to 2010 to 2011-2018 among adults (23.1-71.8 %; P<0.001) but not in children (27.3-33.3 %; P=0.84). Over the same period, the proportion of clade II-associated carriage increased; this was statistically significant among children (23.3-52.6 %; P=0.04) but not adults (0-50.0 %, P=0.08).Conclusions. In this setting with persistent serotype 3 IPD and carriage, clade II has increased since 2010. Genomic changes may be contributing to the observed trends in serotype 3 carriage and disease over time. |
Factors predicting mortality in hospitalised HIV-negative children with lower-chest-wall indrawing pneumonia and implications for management
Gallagher KE , Awori JO , Knoll MD , Rhodes J , Higdon MM , Hammitt LL , Prosperi C , Baggett HC , Brooks WA , Fancourt N , Feikin DR , Howie SRC , Kotloff KL , Tapia MD , Levine OS , Madhi SA , Murdoch DR , O'Brien KL , Thea DM , Baillie VL , Ebruke BE , Kamau A , Moore DP , Mwananyanda L , Olutunde EO , Seidenberg P , Sow SO , Thamthitiwat S , Scott JAG . PLoS One 2024 19 (3) e0297159 INTRODUCTION: In 2012, the World Health Organization revised treatment guidelines for childhood pneumonia with lower chest wall indrawing (LCWI) but no 'danger signs', to recommend home-based treatment. We analysed data from children hospitalized with LCWI pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) study to identify sub-groups with high odds of mortality, who might continue to benefit from hospital management but may not be admitted by staff implementing the 2012 guidelines. We compare the proportion of deaths identified using the criteria in the 2012 guidelines, and the proportion of deaths identified using an alternative set of criteria from our model. METHODS: PERCH enrolled a cohort of 2189 HIV-negative children aged 2-59 months who were admitted to hospital with LCWI pneumonia (without obvious cyanosis, inability to feed, vomiting, convulsions, lethargy or head nodding) between 2011-2014 in Kenya, Zambia, South Africa, Mali, The Gambia, Bangladesh, and Thailand. We analysed risk factors for mortality among these cases using predictive logistic regression. Malnutrition was defined as mid-upper-arm circumference <125mm or weight-for-age z-score <-2. RESULTS: Among 2189 cases, 76 (3·6%) died. Mortality was associated with oxygen saturation <92% (aOR 3·33, 1·99-5·99), HIV negative but exposed status (4·59, 1·81-11·7), moderate or severe malnutrition (6·85, 3·22-14·6) and younger age (infants compared to children 12-59 months old, OR 2·03, 95%CI 1·05-3·93). At least one of three risk factors: hypoxaemia, HIV exposure, or malnutrition identified 807 children in this population, 40% of LCWI pneumonia cases and identified 86% of the children who died in hospital (65/76). Risk factors identified using the 2012 WHO treatment guidelines identified 66% of the children who died in hospital (n = 50/76). CONCLUSIONS: Although it focuses on treatment failure in hospital, this study supports the proposal for better risk stratification of children with LCWI pneumonia. Those who have hypoxaemia, any malnutrition or those who were born to HIV positive mothers, experience poorer outcomes than other children with LCWI pneumonia. Consistent identification of these risk factors should be prioritised and children with at least one of these risk factors should not be managed in the community. |
Trends in otitis media ambulatory visits in American Indian and Alaska native children during the pneumococcal conjugate vaccine period and the COVID-19 Pandemic
Bressler SS , Bruden D , Hammitt LL , Chukwuma U , Fischer M , Singleton R . Pediatr Infect Dis J 2024 Otitis media-associated outpatient visits among American Indians/Alaska Natives children aged <5 years decreased by 52% (100 to 48 per 100 children per year) from 2003 to 2019. Otitis media visits decreased by another 50% from 2019 to 2020, but rebounded between 2020 and 2021 back to a rate similar to 2019. |
RSV among American Indian and Alaska Native children: 2019 to 2020
Atwell JE , Hartman RM , Parker D , Taylor K , Brown LB , Sandoval M , Ritchie N , Desnoyers C , Wilson AS , Hammes M , Tiesinga J , Halasa N , Langley G , Prill MM , Bruden D , Close R , Moses J , Karron RA , Santosham M , Singleton RJ , Hammitt LL . Pediatrics 2023 152 (2) Respiratory syncytial virus (RSV) is the leading viral cause of acute lower respiratory tract infections, including bronchiolitis and pneumonia, in children under 5 years of age globally.1 Historically, RSV-associated hospitalization rates among American Indian and Alaska Native (AI/AN) children have been among the highest in the world.2,–7 Contemporary estimates of RSV-acute respiratory infection (ARI) are needed to inform RSV prevention strategies for AI/AN children. |
Effectiveness of COVID-19 mRNA vaccines in preventing COVID-19-associated outpatient visits and hospitalizations among American indian and Alaska native persons, January-November 2021: A test-negative case-control analysis using surveillance data
Lutz CS , Hartman RM , Vigil DE , Britton A , Burrage AB , Campbell AP , Close RM , Desnoyers C , Dobson J , Garcia S , Halasa N , Honie E , Kobayashi M , McMorrow M , Mostafa HH , Parker D , Pohl K , Prill MM , Richards J , Roessler KC , Sutcliffe CG , Taylor K , Swango-Wilson A , Va P , Verani JR , Singleton RJ , Hammitt LL . Open Forum Infect Dis 2023 10 (4) ofad172 BACKGROUND: Despite the disproportionate morbidity and mortality expeHealth Equity and Health Disparitiesrienced by American Indian and Alaska Native (AI/AN) persons during the coronavirus disease 2019 (COVID-19) pandemic, few studies have reported vaccine effectiveness (VE) estimates among these communities. METHODS: We conducted a test-negative case-control analysis among AI/AN persons aged ≥12 years presenting for care from January 1, 2021, through November 30, 2021, to evaluate the effectiveness of mRNA COVID-19 vaccines against COVID-19-associated outpatient visits and hospitalizations. Cases and controls were patients with ≥1 symptom consistent with COVID-19-like illness; cases were defined as those test-positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and controls were defined as those test-negative for SARS-CoV-2. We used unconditional multivariable logistic regression to estimate VE, defined as 1 minus the adjusted odds ratio for vaccination among cases vs controls. RESULTS: The analysis included 207 cases and 267 test-negative controls. Forty-four percent of cases and 78% of controls received 2 doses of either BNT162b2 or mRNA-1273 vaccine. VE point estimates for 2 doses of mRNA vaccine were higher for hospitalized participants (94.6%; 95% CI, 88.0-97.6) than outpatient participants (86.5%; 95% CI, 63.0-95.0), but confidence intervals overlapped. CONCLUSIONS: Among AI/AN persons, mRNA COVID-19 vaccines were highly effective in preventing COVID-associated outpatient visits and hospitalizations. Maintaining high vaccine coverage, including booster doses, will reduce the burden of disease in this population. |
Etiology and clinical characteristics of severe pneumonia among young children in Thailand: Pneumonia Etiology Research for Child Health (PERCH) case-control study findings, 2012-2013
Bunthi C , Rhodes J , Thamthitiwat S , Higdon MM , Chuananon S , Amorninthapichet T , Paveenkittiporn W , Chittaganpitch M , Sawatwong P , Hammitt LL , Feikin DR , Murdoch DR , Deloria-Knoll M , O'Brien KL , Prosperi C , Maloney SA , Baggett HC , Akarasewi P . Pediatr Infect Dis J 2021 40 S91-s100 BACKGROUND: Pneumonia remains the leading cause of death among children <5 years of age beyond the neonatal period in Thailand. Using data from the Pneumonia Etiology Research for Child Health (PERCH) Study, we provide a detailed description of pneumonia cases and etiology in Thailand to inform local treatment and prevention strategies in this age group. METHODS: PERCH, a multi-country case-control study, evaluated the etiology of hospitalized cases of severe and very severe pneumonia among children 1-59 months of age. The Thailand site enrolled children for 24 consecutive months during January 2012-February 2014 with staggered start dates in 2 provinces. Cases were children hospitalized with pre-2013 WHO-defined severe or very severe pneumonia. Community controls were randomly selected from health services registries in each province. Analyses were restricted to HIV-negative cases and controls. We calculated adjusted odds ratios (ORs) and 95% CIs comparing organism prevalence detected by nasopharyngeal/oropharyngeal (NP/OP) polymerase chain reaction between cases and controls. The PERCH Integrated Analysis (PIA) used Bayesian latent variable analysis to estimate pathogen-specific etiologic fractions and 95% credible intervals. RESULTS: Over 96% of both cases (n = 223) and controls (n = 659) had at least 1 organism detected; multiple organisms were detected in 86% of cases and 88% of controls. Among 98 chest Radiograph positive (CXR+) cases, respiratory syncytial virus (RSV) had the highest NP/OP prevalence (22.9%) and the strongest association with case status (OR 20.5; 95% CI: 10.2, 41.3) and accounted for 34.6% of the total etiologic fraction. Tuberculosis (TB) accounted for 10% (95% CrI: 1.6-26%) of the etiologic fraction among CXR+ cases. DISCUSSION: More than one-third of hospitalized cases of severe and very severe CXR+ pneumonia among children 1-59 months of age in Thailand were attributable to RSV. TB accounted for 10% of cases, supporting evaluation for TB among children hospitalized with pneumonia in high-burden settings. Similarities in pneumonia etiology in Thailand and other PERCH sites suggest that global control strategies based on PERCH study findings are relevant to Thailand and similar settings. |
Introduction to the site-specific etiologic results from the Pneumonia Etiology Research for Child Health (PERCH) Study
Deloria Knoll M , Prosperi C , Baggett HC , Brooks WA , Feikin DR , Hammitt LL , Howie SRC , Kotloff KL , Madhi SA , Murdoch DR , Scott JAG , Thea DM , O'Brien KL . Pediatr Infect Dis J 2021 40 S1-s6 The Pneumonia Etiology Research for Child Health (PERCH) study evaluated the etiology of severe and very severe pneumonia in children hospitalized in 7 African and Asian countries. Here, we summarize the highlights of in-depth site-specific etiology analyses published separately in this issue, including how etiology varies by age, mortality status, malnutrition, severity, HIV status, and more. These site-specific results impart important lessons that can inform disease control policy implications. |
Epidemiology of the Rhinovirus (RV) in African and Southeast Asian Children: A Case-Control Pneumonia Etiology Study
Baillie VL , Moore DP , Mathunjwa A , Baggett HC , Brooks A , Feikin DR , Hammitt LL , Howie SRC , Knoll MD , Kotloff KL , Levine OS , O'Brien KL , Scott AG , Thea DM , Antonio M , Awori JO , Driscoll AJ , Fancourt NSS , Higdon MM , Karron RA , Morpeth SC , Mulindwa JM , Murdoch DR , Park DE , Prosperi C , Rahman MZ , Rahman M , Salaudeen RA , Sawatwong P , Somwe SW , Sow SO , Tapia MD , Simões EAF , Madhi SA . Viruses 2021 13 (7) Rhinovirus (RV) is commonly detected in asymptomatic children; hence, its pathogenicity during childhood pneumonia remains controversial. We evaluated RV epidemiology in HIV-uninfected children hospitalized with clinical pneumonia and among community controls. PERCH was a case-control study that enrolled children (1-59 months) hospitalized with severe and very severe pneumonia per World Health Organization clinical criteria and age-frequency-matched community controls in seven countries. Nasopharyngeal/oropharyngeal swabs were collected for all participants, combined, and tested for RV and 18 other respiratory viruses using the Fast Track multiplex real-time PCR assay. RV detection was more common among cases (24%) than controls (21%) (aOR = 1.5, 95%CI:1.3-1.6). This association was driven by the children aged 12-59 months, where 28% of cases vs. 18% of controls were RV-positive (aOR = 2.1, 95%CI:1.8-2.5). Wheezing was 1.8-fold (aOR 95%CI:1.4-2.2) more prevalent among pneumonia cases who were RV-positive vs. RV-negative. Of the RV-positive cases, 13% had a higher probability (>75%) that RV was the cause of their pneumonia based on the PERCH integrated etiology analysis; 99% of these cases occurred in children over 12 months in Bangladesh. RV was commonly identified in both cases and controls and was significantly associated with severe pneumonia status among children over 12 months of age, particularly those in Bangladesh. RV-positive pneumonia was associated with wheezing. |
Global Landscape Review of Serotype-Specific Invasive Pneumococcal Disease Surveillance among Countries Using PCV10/13: The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) Project
Deloria Knoll M , Bennett JC , Garcia Quesada M , Kagucia EW , Peterson ME , Feikin DR , Cohen AL , Hetrich MK , Yang Y , Sinkevitch JN , Ampofo K , Aukes L , Bacci S , Bigogo G , Brandileone MC , Bruce MG , Camilli R , Castilla J , Chan G , Chanto Chacón G , Ciruela P , Cook H , Corcoran M , Dagan R , Danis K , de Miguel S , De Wals P , Desmet S , Galloway Y , Georgakopoulou T , Hammitt LL , Hilty M , Ho PL , Jayasinghe S , Kellner JD , Kleynhans J , Knol MJ , Kozakova J , Kristinsson KG , Ladhani SN , Lara CS , León ME , Lepp T , Mackenzie GA , Mad'arová L , McGeer A , Mungun T , Mwenda JM , Nuorti JP , Nzoyikorera N , Oishi K , De Oliveira LH , Paragi M , Pilishvili T , Puentes R , Rafai E , Saha SK , Savrasova L , Savulescu C , Scott JA , Scott KJ , Serhan F , Setchanova LP , Sinkovec Zorko N , Skoczyńska A , Swarthout TD , Valentiner-Branth P , van der Linden M , Vestrheim DF , von Gottberg A , Yildirim I , Hayford K , Pserenade Team . Microorganisms 2021 9 (4) Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon. |
Upper Respiratory Tract Co-detection of Human Endemic Coronaviruses and High-density Pneumococcus Associated With Increased Severity Among HIV-Uninfected Children Under 5 Years Old in the PERCH Study.
Park DE , Higdon MM , Prosperi C , Baggett HC , Brooks WA , Feikin DR , Hammitt LL , Howie SRC , Kotloff KL , Levine OS , Madhi SA , Murdoch DR , O'Brien KL , Scott JAG , Thea DM , Antonio M , Awori JO , Baillie VL , Bunthi C , Kwenda G , Mackenzie GA , Moore DP , Morpeth SC , Mwananyanda L , Paveenkittiporn W , Ziaur Rahman M , Rahman M , Rhodes J , Sow SO , Tapia MD , Deloria Knoll M . Pediatr Infect Dis J 2021 40 (6) 503-512 BACKGROUND: Severity of viral respiratory illnesses can be increased with bacterial coinfection and can vary by sex, but influence of coinfection and sex on human endemic coronavirus (CoV) species, which generally cause mild to moderate respiratory illness, is unknown. We evaluated CoV and pneumococcal co-detection by sex in childhood pneumonia. METHODS: In the 2011-2014 Pneumonia Etiology Research for Child Health study, nasopharyngeal and oropharyngeal (NP/OP) swabs and other samples were collected from 3981 children <5 years hospitalized with severe or very severe pneumonia in 7 countries. Severity by NP/OP detection status of CoV (NL63, 229E, OC43 or HKU1) and high-density (≥6.9 log10 copies/mL) pneumococcus (HDSpn) by real-time polymerase chain reaction was assessed by sex using logistic regression adjusted for age and site. RESULTS: There were 43 (1.1%) CoV+/HDSpn+, 247 CoV+/HDSpn-, 449 CoV-/HDSpn+ and 3149 CoV-/HDSpn- cases with no significant difference in co-detection frequency by sex (range 51.2%-64.0% male, P = 0.06). More CoV+/HDSpn+ pneumonia was very severe compared with other groups for both males (13/22, 59.1% versus range 29.1%-34.7%, P = 0.04) and females (10/21, 47.6% versus 32.5%-43.5%, P = 0.009), but only male CoV+/HDSpn+ required supplemental oxygen more frequently (45.0% versus 20.6%-28.6%, P < 0.001) and had higher mortality (35.0% versus 5.3%-7.1%, P = 0.004) than other groups. For females with CoV+/HDSpn+, supplemental oxygen was 25.0% versus 24.8%-33.3% (P = 0.58) and mortality was 10.0% versus 9.2%-12.9% (P = 0.69). CONCLUSIONS: Co-detection of endemic CoV and HDSpn was rare in children hospitalized with pneumonia, but associated with higher severity and mortality in males. Findings may warrant investigation of differences in severity by sex with co-detection of HDSpn and SARS-CoV-2. |
Serotype distribution of remaining pneumococcal meningitis in the mature PCV10/13 period: Findings from the PSERENADE Project
Garcia Quesada M , Yang Y , Bennett JC , Hayford K , Zeger SL , Feikin DR , Peterson ME , Cohen AL , Almeida SCG , Ampofo K , Ang M , Bar-Zeev N , Bruce MG , Camilli R , Chacón GC , Ciruela P , Cohen C , Corcoran M , Dagan R , De Wals P , Desmet S , Diawara I , Gierke R , Guevara M , Hammitt LL , Hilty M , Ho PL , Jayasinghe S , Kleynhans J , Kristinsson KG , Ladhani SN , McGeer A , Mwenda JM , Pekka Nuorti J , Oishi K , Ricketson LJ , Sanz JC , Savrasova L , Setchanova LP , Smith A , Valentiner-Branth P , Valenzuela MT , van der Linden M , van Sorge NM , Varon E , Winje BA , Yildirim I , Zintgraff J , Knoll MD . Microorganisms 2021 9 (4) Pneumococcal conjugate vaccine (PCV) introduction has reduced pneumococcal meningitis incidence. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project described the serotype distribution of remaining pneumococcal meningitis in countries using PCV10/13 for least 5-7 years with primary series uptake above 70%. The distribution was estimated using a multinomial Dirichlet regression model, stratified by PCV product and age. In PCV10-using sites (N = 8; cases = 1141), PCV10 types caused 5% of cases <5 years of age and 15% among ≥5 years; the top serotypes were 19A, 6C, and 3, together causing 42% of cases <5 years and 37% ≥5 years. In PCV13-using sites (N = 32; cases = 4503), PCV13 types caused 14% in <5 and 26% in ≥5 years; 4% and 13%, respectively, were serotype 3. Among the top serotypes are five (15BC, 8, 12F, 10A, and 22F) included in higher-valency PCVs under evaluation. Other top serotypes (24F, 23B, and 23A) are not in any known investigational product. In countries with mature vaccination programs, the proportion of pneumococcal meningitis caused by vaccine-in-use serotypes is lower (≤26% across all ages) than pre-PCV (≥70% in children). Higher-valency PCVs under evaluation target over half of remaining pneumococcal meningitis cases, but questions remain regarding generalizability to the African meningitis belt where additional data are needed. |
Changes in invasive pneumococcal disease caused by streptococcus pneumoniae serotype 1 following introduction of pcv10 and pcv13: Findings from the PSERENADE project
Bennett JC , Hetrich MK , Quesada MG , Sinkevitch JN , Knoll MD , Feikin DR , Zeger SL , Kagucia EW , Cohen AL , Ampofo K , Brandileone MCC , Bruden D , Camilli R , Castilla J , Chan G , Cook H , Cornick JE , Dagan R , Dalby T , Danis K , de Miguel S , De Wals P , Desmet S , Georgakopoulou T , Gilkison C , Grgic‐vitek M , Hammitt LL , Hilty M , Ho PL , Jayasinghe S , Kellner JD , Kleynhans J , Knol MJ , Kozakova J , Kristinsson KG , Ladhani SN , Macdonald L , Mackenzie GA , Mad’arová L , McGeer A , Mereckiene J , Morfeldt E , Mungun T , Muñoz‐almagro C , Nuorti JP , Paragi M , Pilishvili T , Puentes R , Saha SK , Khan AS , Savrasova L , Scott JA , Skoczyńska A , Suga S , Linden M , Verani JR , von Gottberg A , Winje BA , Yildirim I , Zerouali K , Hayford K , Pserenade Team . Microorganisms 2021 9 (4) Streptococcus pneumoniae serotype 1 (ST1) was an important cause of invasive pneumococ-cal disease (IPD) globally before the introduction of pneumococcal conjugate vaccines (PCVs) con-taining ST1 antigen. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERE‐ NADE) project gathered ST1 IPD surveillance data from sites globally and aimed to estimate PCV10/13 impact on ST1 IPD incidence. We estimated ST1 IPD incidence rate ratios (IRRs) compar-ing the pre‐PCV10/13 period to each post‐PCV10/13 year by site using a Bayesian multi‐level, mixed-effects Poisson regression and all‐site IRRs using a linear mixed‐effects regression (N = 45 sites). Following PCV10/13 introduction, the incidence rate (IR) of ST1 IPD declined among all ages. After six years of PCV10/13 use, the all‐site IRR was 0.05 (95% credibility interval 0.04–0.06) for all ages, 0.05 (0.04–0.05) for <5 years of age, 0.08 (0.06–0.09) for 5–17 years, 0.06 (0.05–0.08) for 18–49 years, 0.06 (0.05–0.07) for 50–64 years, and 0.05 (0.04–0.06) for ≥65 years. PCV10/13 use in infant immunization programs was followed by a 95% reduction in ST1 IPD in all ages after approximately 6 years. Limited data availability from the highest ST1 disease burden countries using a 3+0 schedule constrains generalizability and data from these settings are needed. |
Digital auscultation in PERCH: Associations with chest radiography and pneumonia mortality in children
McCollum ED , Park DE , Watson NL , Fancourt NSS , Focht C , Baggett HC , Abdullah Brooks W , Howie SRC , Kotloff KL , Levine OS , Madhi SA , Murdoch DR , Scott JAG , Thea DM , Awori JO , Chipeta J , Chuananon S , DeLuca AN , Driscoll AJ , Ebruke BE , Elhilal M , Emmanouilidou D , Githua LP , Higdon MM , Hossain L , Jahan Y , Karron RA , Kyalo J , Moore DP , Mulindwa JM , Naorat S , Prosperi C , Verwey C , West JE , Knoll MD , Brien KLO , Feikin DR , Hammitt LL . Pediatr Pulmonol 2020 55 (11) 3197-3208 BACKGROUND: Whether digitally recorded lung sounds are associated with radiographic pneumonia or clinical outcomes among children in low-income and middle-income countries is unknown. We sought to address these knowledge gaps. METHODS: We enrolled 1-59 month old children hospitalized with pneumonia at eight African and Asian Pneumonia Etiology Research for Child Health sites in six countries, recorded digital stethoscope lung sounds, obtained chest radiographs, and collected clinical outcomes. Recordings were processed and reclassified into binary categories positive or negative for adventitial lung sounds. Listening and reading panels classified recordings and radiographs. Recording classification associations with chest radiographs with World Health Organization (WHO)-defined primary endpoint pneumonia (radiographic pneumonia) or mortality were evaluated. We also examined case fatality among risk strata. RESULTS: Among children without WHO danger signs, wheezing (without crackles) had a lower adjusted odds ratio (aOR) for radiographic pneumonia (0.35, 95% confidence interval (CI) 0.15, 0.82), compared to children with normal recordings. Neither crackle only (no wheeze) (aOR 2.13, 95%CI 0.91, 4.96) or any wheeze (with or without crackle) (aOR 0.63, 95%CI 0.34, 1.15) were associated with radiographic pneumonia. Among children with WHO danger signs no lung recording classification was independently associated with radiographic pneumonia, although trends towards greater odds of radiographic pneumonia were observed among children classified with crackle only (no wheeze) or any wheeze (with or without crackle). Among children without WHO danger signs, those with recorded wheezing had a lower case fatality than those without wheezing (3.8% vs 9.1%, p=0.03). CONCLUSIONS: Among lower risk children without WHO danger signs digitally recorded wheezing is associated with a lower odds for radiographic pneumonia and with lower mortality. Although further research is needed, these data indicate that with further development digital auscultation may eventually contribute to child pneumonia care. This article is protected by copyright. All rights reserved. |
Upper airways colonisation of Streptococcus pneumoniae in adults aged 60 years and older: A systematic review of prevalence and individual participant data meta-analysis of risk factors
Smith EL , Wheeler I , Adler H , Ferreira DM , Sá-Leão R , Abdullahi O , Adetifa I , Becker-Dreps S , Esposito S , Farida H , Kandasamy R , Mackenzie GA , Nuorti JP , Nzenze S , Madhi SA , Ortega O , Roca A , Safari D , Schaumburg F , Usuf E , Sanders EAM , Grant LR , Hammitt LL , O'Brien KL , Gounder P , Bruden DJT , Stanton MC , Rylance J . J Infect 2020 81 (4) 540-548 BACKGROUND: Colonisation with Streptococcus pneumoniae can lead to invasive pneumococcal disease and pneumonia. Pneumococcal acquisition and prevalence of colonisation are high in children. In older adults, a population susceptible to pneumococcal disease, colonisation prevalence is reported to be lower, but studies are heterogeneous. METHODS: This is a systematic review and meta-analysis of prevalence of, and risk factors for, pneumococcal colonisation in adults ≥ 60 years of age (PROSPERO #42016036891). We identified peer-reviewed studies reporting the prevalence of S. pneumoniae colonisation using MEDLINE and EMBASE (until April 2016), excluding studies of acute disease. Participant-level data on risk factors were sought from each study. FINDINGS: Of 2202 studies screened, 29 were analysable: 18 provided participant-level data (representing 6290 participants). Prevalence of detected pneumococcal colonisation was 0-39% by conventional culture methods and 3-23% by molecular methods. In a multivariate analysis, colonisation was higher in persons from nursing facilities compared with the community (odds ratio (OR) 2•30, 95% CI 1•26-4•21 and OR 7•72, 95% CI 1•15-51•85, respectively), in those who were currently smoking (OR 1•69, 95% CI 1•12-2•53) or those who had regular contact with children (OR 1•93, 95%CI 1•27-2•93). Persons living in urban areas had significantly lower carriage prevalence (OR 0•43, 95%CI 0•27-0•70). INTERPRETATION: Overall prevalence of pneumococcal colonisation in older adults was higher than expected but varied by risk factors. Future studies should further explore risk factors for colonisation, to highlight targets for focussed intervention such as pneumococcal vaccination of high-risk groups. FUNDING: No funding was required. |
Does respiratory syncytial virus lower respiratory illness in early life cause recurrent wheeze of early childhood and asthma Critical review of the evidence and guidance for future studies from a World Health Organization-sponsored meeting
Driscoll AJ , Arshad SH , Bont L , Brunwasser SM , Cherian T , Englund JA , Fell DB , Hammitt LL , Hartert TV , Innis BL , Karron RA , Langley GE , Mulholland EK , Munywoki PK , Nair H , Ortiz JR , Savitz DA , Scheltema NM , Simoes EAF , Smith PG , Were F , Zar HJ , Feikin DR . Vaccine 2020 38 (11) 2435-2448 Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI) and hospitalization in infants and children globally. Many observational studies have found an association between RSV LRTI in early life and subsequent respiratory morbidity, including recurrent wheeze of early childhood (RWEC) and asthma. Conversely, two randomized placebo-controlled trials of efficacious anti-RSV monoclonal antibodies (mAbs) in heterogenous infant populations found no difference in physician-diagnosed RWEC or asthma by treatment group. If a causal association exists and RSV vaccines and mAbs can prevent a substantial fraction of RWEC/asthma, the full public health value of these interventions would markedly increase. The primary alternative interpretation of the observational data is that RSV LRTI in early life is a marker of an underlying predisposition for the development of RWEC and asthma. If this is the case, RSV vaccines and mAbs would not necessarily be expected to impact these outcomes. To evaluate whether the available evidence supports a causal association between RSV LRTI and RWEC/asthma and to provide guidance for future studies, the World Health Organization convened a meeting of subject matter experts on February 12-13, 2019 in Geneva, Switzerland. After discussing relevant background information and reviewing the current epidemiologic evidence, the group determined that: (i) the evidence is inconclusive in establishing a causal association between RSV LRTI and RWEC/asthma, (ii) the evidence does not establish that RSV mAbs (and, by extension, future vaccines) will have a substantial effect on these outcomes and (iii) regardless of the association with long-term childhood respiratory morbidity, severe acute RSV disease in young children poses a substantial public health burden and should continue to be the primary consideration for policy-setting bodies deliberating on RSV vaccine and mAb recommendations. Nonetheless, the group recognized the public health importance of resolving this question and suggested good practice guidelines for future studies. |
The predictive performance of a pneumonia severity score in HIV-negative children presenting to hospital in seven low and middle-income countries
Gallagher KE , Knoll MD , Prosperi C , Baggett HC , Brooks WA , Feiken DR , Hammitt LL , Howie SRC , Kotloff KL , Levine OS , Madhi SA , Murdoch DR , O'Brien KL , Thea DM , Awori JO , Baillie VL , Ebruke BE , Goswami D , Kamau A , Maloney SA , Moore DP , Mwananyanda L , Olutunde EO , Seidenberg P , Sissoko S , Sylla M , Thamthitiwat S , Zaman K , Scott JAG . Clin Infect Dis 2019 70 (6) 1050-1057 BACKGROUND: In 2015, pneumonia remained the leading cause of mortality in children between 1-59 months old. METHODS: Data from 1802 HIV-negative children between 1-59 months old enrolled in the Pneumonia Etiology Research for Child Health (PERCH) study with severe or very severe pneumonia during 2011-14 were used to build a parsimonious multivariable model predicting mortality using backwards stepwise logistic regression. The PERCH severity score, derived from model coefficients, was validated on a second, temporally discrete dataset of a further 1819 cases and compared to other available scores using the c-statistic. RESULTS: Predictors of mortality, across seven low and middle-income countries, were: age <1 year, female sex, 3 or more days of illness prior to presentation to hospital, low weight-for-height, unresponsiveness, deep breathing, hypoxemia, grunting and the absence of cough. The model discriminated well between those who died and those who survived (c-statistic: 0.84), but the predictive capacity of the PERCH 5-stratum score derived from the coefficients was moderate (c=0.76). The performance of the Respiratory Index of Severity in Children (RISC) score was similar (c=0.76). The number of WHO danger signs demonstrated the highest discrimination (c=0.82; 1.5% died if no danger signs, 10% if 1 danger sign and 33% if 2 or more danger signs). CONCLUSIONS: The PERCH severity score could be used to interpret geographic variations in pneumonia mortality and etiology. The number of WHO danger signs on presentation to hospital could be the most useful, of the currently available tools, to aid clinical management of pneumonia. |
Water quality, availability, and acute gastroenteritis on the Navajo Nation - a pilot case-control study
Grytdal SP , Weatherholtz R , Esposito DH , Campbell J , Reid R , Gregoricus N , Schneeberger C , Lusk TS , Xiao L , Garrett N , Bopp C , Hammitt LL , Vinje J , Hill VR , O'Brien KL , Hall AJ . J Water Health 2018 16 (6) 1018-1028 The Navajo Nation includes approximately 250,000 American Indians living in a remote high desert environment with limited access to public water systems. We conducted a pilot case-control study to assess associations between acute gastroenteritis (AGE) and water availability, use patterns, and quality. Case patients with AGE and non-AGE controls who presented for care to two Indian Health Service hospitals were recruited. Data on demographics and water use practices were collected using a standard questionnaire. Household drinking water was tested for presence of pathogens, coliforms, and residual chlorine. Sixty-one subjects (32 cases and 29 controls) participated in the study. Cases and controls were not significantly different with respect to water sources, quality, or patterns of use. Twenty-one percent (n = 12) of study participants resided in dwellings not connected to a community water system. Eleven percent (n = 7) of subjects reported drinking hauled water from unregulated sources. Coliform bacteria were present in 44% (n = 27) of household water samples, and 68% (n = 40) of samples contained residual chlorine concentrations of <0.2 mg/L. This study highlights issues with water availability, quality, and use patterns within the Navajo Nation, including sub-optimal access to community water systems, and use of water hauled from unregulated sources. |
Detection of Pneumococcal DNA in Blood by Polymerase Chain Reaction for Diagnosing Pneumococcal Pneumonia in Young Children From Low- and Middle-Income Countries.
Morpeth SC , Deloria Knoll M , Scott JAG , Park DE , Watson NL , Baggett HC , Brooks WA , Feikin DR , Hammitt LL , Howie SRC , Kotloff KL , Levine OS , Madhi SA , O'Brien KL , Thea DM , Adrian PV , Ahmed D , Antonio M , Bunthi C , DeLuca AN , Driscoll AJ , Githua LP , Higdon MM , Kahn G , Karani A , Karron RA , Kwenda G , Makprasert S , Mazumder R , Moore DP , Mwansa J , Nyongesa S , Prosperi C , Sow SO , Tamboura B , Whistler T , Zeger SL , Murdoch DR . Clin Infect Dis 2017 64 S347-s356 Background.: We investigated the performance of polymerase chain reaction (PCR) on blood in the diagnosis of pneumococcal pneumonia among children from 7 low- and middle-income countries. Methods.: We tested blood by PCR for the pneumococcal autolysin gene in children aged 1-59 months in the Pneumonia Etiology Research for Child Health (PERCH) study. Children had World Health Organization-defined severe or very severe pneumonia or were age-frequency-matched community controls. Additionally, we tested blood from general pediatric admissions in Kilifi, Kenya, a PERCH site. The proportion PCR-positive was compared among cases with microbiologically confirmed pneumococcal pneumonia (MCPP), cases without a confirmed bacterial infection (nonconfirmed), cases confirmed for nonpneumococcal bacteria, and controls. Results.: In PERCH, 7.3% (n = 291/3995) of cases and 5.5% (n = 273/4987) of controls were blood pneumococcal PCR-positive (P < .001), compared with 64.3% (n = 36/56) of MCPP cases and 6.3% (n = 243/3832) of nonconfirmed cases (P < .001). Blood pneumococcal PCR positivity was higher in children from the 5 African countries (5.5%-11.5% among cases and 5.3%-10.2% among controls) than from the 2 Asian countries (1.3% and 1.0% among cases and 0.8% and 0.8% among controls). Among Kilifi general pediatric admissions, 3.9% (n = 274/6968) were PCR-positive, including 61.7% (n = 37/60) of those with positive blood cultures for pneumococcus. Discussion.: The utility of pneumococcal PCR on blood for diagnosing childhood pneumococcal pneumonia in the 7 low- and middle-income countries studied is limited by poor specificity and by poor sensitivity among MCPP cases. |
Evaluation of Pneumococcal Load in Blood by Polymerase Chain Reaction for the Diagnosis of Pneumococcal Pneumonia in Young Children in the PERCH Study.
Deloria Knoll M , Morpeth SC , Scott JAG , Watson NL , Park DE , Baggett HC , Brooks WA , Feikin DR , Hammitt LL , Howie SRC , Kotloff KL , Levine OS , O'Brien KL , Thea DM , Ahmed D , Antonio M , Awori JO , Baillie VL , Chipeta J , Deluca AN , Dione M , Driscoll AJ , Higdon MM , Jatapai A , Karron RA , Mazumder R , Moore DP , Mwansa J , Nyongesa S , Prosperi C , Seidenberg P , Siludjai D , Sow SO , Tamboura B , Zeger SL , Murdoch DR , Madhi SA . Clin Infect Dis 2017 64 S357-s367 Background.: Detection of pneumococcus by lytA polymerase chain reaction (PCR) in blood had poor diagnostic accuracy for diagnosing pneumococcal pneumonia in children in 9 African and Asian sites. We assessed the value of blood lytA quantification in diagnosing pneumococcal pneumonia. Methods.: The Pneumonia Etiology Research for Child Health (PERCH) case-control study tested whole blood by PCR for pneumococcus in children aged 1-59 months hospitalized with signs of pneumonia and in age-frequency matched community controls. The distribution of load among PCR-positive participants was compared between microbiologically confirmed pneumococcal pneumonia (MCPP) cases, cases confirmed for nonpneumococcal pathogens, nonconfirmed cases, and controls. Receiver operating characteristic analyses determined the "optimal threshold" that distinguished MCPP cases from controls. Results.: Load was available for 290 of 291 cases with pneumococcal PCR detected in blood and 273 of 273 controls. Load was higher in MCPP cases than controls (median, 4.0 x 103 vs 0.19 x 103 copies/mL), but overlapped substantially (range, 0.16-989.9 x 103 copies/mL and 0.01-551.9 x 103 copies/mL, respectively). The proportion with high load (≥2.2 log10 copies/mL) was 62.5% among MCPP cases, 4.3% among nonconfirmed cases, 9.3% among cases confirmed for a nonpneumococcal pathogen, and 3.1% among controls. Pneumococcal load in blood was not associated with respiratory tract illness in controls (P = .32). High blood pneumococcal load was associated with alveolar consolidation on chest radiograph in nonconfirmed cases, and with high (>6.9 log10 copies/mL) nasopharyngeal/oropharyngeal load and C-reactive protein ≥40 mg/L (both P < .01) in nonconfirmed cases but not controls. Conclusions.: Quantitative pneumococcal PCR in blood has limited diagnostic utility for identifying pneumococcal pneumonia in individual children, but may be informative in epidemiological studies. |
Colonization Density of the Upper Respiratory Tract as a Predictor of Pneumonia-Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pneumocystis jirovecii.
Park DE , Baggett HC , Howie SRC , Shi Q , Watson NL , Brooks WA , Deloria Knoll M , Hammitt LL , Kotloff KL , Levine OS , Madhi SA , Murdoch DR , O'Brien KL , Scott JAG , Thea DM , Ahmed D , Antonio M , Baillie VL , DeLuca AN , Driscoll AJ , Fu W , Gitahi CW , Olutunde E , Higdon MM , Hossain L , Karron RA , Maiga AA , Maloney SA , Moore DP , Morpeth SC , Mwaba J , Mwenechanya M , Prosperi C , Sylla M , Thamthitiwat S , Zeger SL , Feikin DR . Clin Infect Dis 2017 64 S328-s336 Background.: There is limited information on the association between colonization density of upper respiratory tract colonizers and pathogen-specific pneumonia. We assessed this association for Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pneumocystis jirovecii. Methods.: In 7 low- and middle-income countries, nasopharyngeal/oropharyngeal swabs from children with severe pneumonia and age-frequency matched community controls were tested using quantitative polymerase chain reaction (PCR). Differences in median colonization density were evaluated using the Wilcoxon rank-sum test. Density cutoffs were determined using receiver operating characteristic curves. Cases with a pathogen identified from lung aspirate culture or PCR, pleural fluid culture or PCR, blood culture, and immunofluorescence for P. jirovecii defined microbiologically confirmed cases for the given pathogens. Results.: Higher densities of H. influenzae were observed in both microbiologically confirmed cases and chest radiograph (CXR)-positive cases compared to controls. Staphylococcus aureus and P. jirovecii had higher densities in CXR-positive cases vs controls. A 5.9 log10 copies/mL density cutoff for H. influenzae yielded 86% sensitivity and 77% specificity for detecting microbiologically confirmed cases; however, densities overlapped between cases and controls and positive predictive values were poor (<3%). Informative density cutoffs were not found for S. aureus and M. catarrhalis, and a lack of confirmed case data limited the cutoff identification for P. jirovecii. Conclusions.: There is evidence for an association between H. influenzae colonization density and H. influenzae-confirmed pneumonia in children; the association may be particularly informative in epidemiologic studies. Colonization densities of M. catarrhalis, S. aureus, and P. jirovecii are unlikely to be of diagnostic value in clinical settings. |
Limited Utility of Polymerase Chain Reaction in Induced Sputum Specimens for Determining the Causes of Childhood Pneumonia in Resource-Poor Settings: Findings From the Pneumonia Etiology Research for Child Health (PERCH) Study.
Thea DM , Seidenberg P , Park DE , Mwananyanda L , Fu W , Shi Q , Baggett HC , Brooks WA , Feikin DR , Howie SRC , Knoll MD , Kotloff KL , Levine OS , Madhi SA , O'Brien KL , Scott JAG , Antonio M , Awori JO , Baillie VL , DeLuca AN , Driscoll AJ , Higdon MM , Hossain L , Jahan Y , Karron RA , Kazungu S , Li M , Moore DP , Morpeth SC , Ofordile O , Prosperi C , Sangwichian O , Sawatwong P , Sylla M , Tapia MD , Zeger SL , Murdoch DR , Hammitt LL . Clin Infect Dis 2017 64 S289-s300 Background.: Sputum examination can be useful in diagnosing the cause of pneumonia in adults but is less well established in children. We sought to assess the diagnostic utility of polymerase chain reaction (PCR) for detection of respiratory viruses and bacteria in induced sputum (IS) specimens from children hospitalized with severe or very severe pneumonia. Methods.: Among children aged 1-59 months, we compared organism detection by multiplex PCR in IS and nasopharyngeal/oropharyngeal (NP/OP) specimens. To assess whether organism presence or density in IS specimens was associated with chest radiographic evidence of pneumonia (radiographic pneumonia), we compared prevalence and density in IS specimens from children with radiographic pneumonia and children with suspected pneumonia but without chest radiographic changes or clinical or laboratory findings suggestive of pneumonia (nonpneumonia group). Results.: Among 4232 cases with World Health Organization-defined severe or very severe pneumonia, we identified 1935 (45.7%) with radiographic pneumonia and 573 (13.5%) with nonpneumonia. The organism detection yield was marginally improved with IS specimens (96.2% vs 92.4% for NP/OP specimens for all viruses combined [P = .41]; 96.9% vs 93.3% for all bacteria combined [P = .01]). After accounting for presence in NP/OP specimens, no organism was detected more frequently in the IS specimens from the radiographic pneumonia compared with the nonpneumonia cases. Among high-quality IS specimens, there were no statistically significant differences in organism density, except with cytomegalovirus, for which there was a higher quantity in the IS specimens from cases with radiographic pneumonia compared with the nonpneumonia cases (median cycle threshold value, 27.9 vs 28.5, respectively; P = .01). Conclusions.: Using advanced molecular methods with IS specimens provided little additional diagnostic information beyond that obtained with NP/OP swab specimens. |
Density of Upper Respiratory Colonization With Streptococcus pneumoniae and Its Role in the Diagnosis of Pneumococcal Pneumonia Among Children Aged <5 Years in the PERCH Study.
Baggett HC , Watson NL , Deloria Knoll M , Brooks WA , Feikin DR , Hammitt LL , Howie SRC , Kotloff KL , Levine OS , Madhi SA , Murdoch DR , Scott JAG , Thea DM , Antonio M , Awori JO , Baillie VL , DeLuca AN , Driscoll AJ , Duncan J , Ebruke BE , Goswami D , Higdon MM , Karron RA , Moore DP , Morpeth SC , Mulindwa JM , Park DE , Paveenkittiporn W , Piralam B , Prosperi C , Sow SO , Tapia MD , Zaman K , Zeger SL , O'Brien KL . Clin Infect Dis 2017 64 S317-s327 Background.: Previous studies suggested an association between upper airway pneumococcal colonization density and pneumococcal pneumonia, but data in children are limited. Using data from the Pneumonia Etiology Research for Child Health (PERCH) study, we assessed this potential association. Methods.: PERCH is a case-control study in 7 countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. Cases were children aged 1-59 months hospitalized with World Health Organization-defined severe or very severe pneumonia. Controls were randomly selected from the community. Microbiologically confirmed pneumococcal pneumonia (MCPP) was confirmed by detection of pneumococcus in a relevant normally sterile body fluid. Colonization density was calculated with quantitative polymerase chain reaction analysis of nasopharyngeal/oropharyngeal specimens. Results.: Median colonization density among 56 cases with MCPP (MCPP cases; 17.28 x 106 copies/mL) exceeded that of cases without MCPP (non-MCPP cases; 0.75 x 106) and controls (0.60 x 106) (each P < .001). The optimal density for discriminating MCPP cases from controls using the Youden index was >6.9 log10 copies/mL; overall, the sensitivity was 64% and the specificity 92%, with variable performance by site. The threshold was lower (≥4.4 log10 copies/mL) when MCPP cases were distinguished from controls who received antibiotics before specimen collection. Among the 4035 non-MCPP cases, 500 (12%) had pneumococcal colonization density >6.9 log10 copies/mL; above this cutoff was associated with alveolar consolidation at chest radiography, very severe pneumonia, oxygen saturation <92%, C-reactive protein ≥40 mg/L, and lack of antibiotic pretreatment (all P< .001). Conclusions.: Pneumococcal colonization density >6.9 log10 copies/mL was strongly associated with MCPP and could be used to improve estimates of pneumococcal pneumonia prevalence in childhood pneumonia studies. Our findings do not support its use for individual diagnosis in a clinical setting. |
Safety of induced sputum collection in children hospitalized with severe or very severe pneumonia
DeLuca AN , Hammitt LL , Kim J , Higdon MM , Baggett HC , Brooks WA , Howie SRC , Deloria Knoll M , Kotloff KL , Levine OS , Madhi SA , Murdoch DR , Scott JAG , Thea DM , Amornintapichet T , Awori JO , Chuananon S , Driscoll AJ , Ebruke BE , Hossain L , Jahan Y , Kagucia EW , Kazungu S , Moore DP , Mudau A , Mwananyanda L , Park DE , Prosperi C , Seidenberg P , Sylla M , Tapia MD , Zaman SMA , O'Brien KL . Clin Infect Dis 2017 64 S301-s308 Background.: Induced sputum (IS) may provide diagnostic information about the etiology of pneumonia. The safety of this procedure across a heterogeneous population with severe pneumonia in low- and middle-income countries has not been described. Methods.: IS specimens were obtained as part a 7-country study of the etiology of severe and very severe pneumonia in hospitalized children <5 years of age. Rigorous clinical monitoring was done before, during, and after the procedure to record oxygen requirement, oxygen saturation, respiratory rate, consciousness level, and other evidence of clinical deterioration. Criteria for IS contraindications were predefined and serious adverse events (SAEs) were reported to ethics committees and a central safety monitor. Results.: A total of 4653 IS procedures were done among 3802 children. Thirteen SAEs were reported in relation to collection of IS, or 0.34% of children with at least 1 IS specimen collected (95% confidence interval, 0.15%-0.53%). A drop in oxygen saturation that required supplemental oxygen was the most common SAE. One child died after feeding was reinitiated 2 hours after undergoing sputum induction; this death was categorized as "possibly related" to the procedure. Conclusions.: The overall frequency of SAEs was very low, and the nature of most SAEs was manageable, demonstrating a low-risk safety profile for IS collection even among severely ill children in low-income-country settings. Healthcare providers should monitor oxygen saturation and requirements during and after IS collection, and assess patients prior to reinitiating feeding after the IS procedure, to ensure patient safety. |
Should controls with respiratory symptoms be excluded from case-control studies of pneumonia etiology? Reflections from the PERCH Study
Higdon MM , Hammitt LL , Deloria Knoll M , Baggett HC , Brooks WA , Howie SRC , Kotloff KL , Levine OS , Madhi SA , Murdoch DR , Scott JAG , Thea DM , Driscoll AJ , Karron RA , Park DE , Prosperi C , Zeger SL , O'Brien KL , Feikin DR . Clin Infect Dis 2017 64 S205-s212 Many pneumonia etiology case-control studies exclude controls with respiratory illness from enrollment or analyses. Herein we argue that selecting controls regardless of respiratory symptoms provides the least biased estimates of pneumonia etiology. We review 3 reasons investigators may choose to exclude controls with respiratory symptoms in light of epidemiologic principles of control selection and present data from the Pneumonia Etiology Research for Child Health (PERCH) study where relevant to assess their validity. We conclude that exclusion of controls with respiratory symptoms will result in biased estimates of etiology. Randomly selected community controls, with or without respiratory symptoms, as long as they do not meet the criteria for case-defining pneumonia, are most representative of the general population from which cases arose and the least subject to selection bias. |
Standardization of clinical assessment and sample collection across all PERCH study sites
Crawley J , Prosperi C , Baggett HC , Brooks WA , Deloria Knoll M , Hammitt LL , Howie SRC , Kotloff KL , Levine OS , Madhi SA , Murdoch DR , O'Brien KL , Thea DM , Awori JO , Bunthi C , DeLuca AN , Driscoll AJ , Ebruke BE , Goswami D , Hidgon MM , Karron RA , Kazungu S , Kourouma N , Mackenzie G , Moore DP , Mudau A , Mwale M , Nahar K , Park DE , Piralam B , Seidenberg P , Sylla M , Feikin DR , Scott JAG . Clin Infect Dis 2017 64 S228-s237 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. |
Standardization of laboratory methods for the PERCH Study
Driscoll AJ , Karron RA , Morpeth SC , Bhat N , Levine OS , Baggett HC , Brooks WA , Feikin DR , Hammitt LL , Howie SRC , Knoll MD , Kotloff KL , Madhi SA , Scott JAG , Thea DM , Adrian PV , Ahmed D , Alam M , Anderson TP , Antonio M , Baillie VL , Dione M , Endtz HP , Gitahi C , Karani A , Kwenda G , Maiga AA , McClellan J , Mitchell JL , Morailane P , Mugo D , Mwaba J , Mwansa J , Mwarumba S , Nyongesa S , Panchalingam S , Rahman M , Sawatwong P , Tamboura B , Toure A , Whistler T , O'Brien KL , Murdoch DR . Clin Infect Dis 2017 64 S245-s252 The Pneumonia Etiology Research for Child Health study was conducted across 7 diverse research sites and relied on standardized clinical and laboratory methods for the accurate and meaningful interpretation of pneumonia etiology data. Blood, respiratory specimens, and urine were collected from children aged 1-59 months hospitalized with severe or very severe pneumonia and community controls of the same age without severe pneumonia and were tested with an extensive array of laboratory diagnostic tests. A standardized testing algorithm and standard operating procedures were applied across all study sites. Site laboratories received uniform training, equipment, and reagents for core testing methods. Standardization was further assured by routine teleconferences, in-person meetings, site monitoring visits, and internal and external quality assurance testing. Targeted confirmatory testing and testing by specialized assays were done at a central reference laboratory. |
Standardized interpretation of chest radiographs in cases of pediatric pneumonia from the PERCH Study
Fancourt N , Deloria Knoll M , Barger-Kamate B , de Campo J , de Campo M , Diallo M , Ebruke BE , Feikin DR , Gleeson F , Gong W , Hammitt LL , Izadnegahdar R , Kruatrachue A , Madhi SA , Manduku V , Matin FB , Mahomed N , Moore DP , Mwenechanya M , Nahar K , Oluwalana C , Ominde MS , Prosperi C , Sande J , Suntarattiwong P , O'Brien KL . Clin Infect Dis 2017 64 S253-s261 Background.: Chest radiographs (CXRs) are a valuable diagnostic tool in epidemiologic studies of pneumonia. The World Health Organization (WHO) methodology for the interpretation of pediatric CXRs has not been evaluated beyond its intended application as an endpoint measure for bacterial vaccine trials. Methods.: The Pneumonia Etiology Research for Child Health (PERCH) study enrolled children aged 1-59 months hospitalized with WHO-defined severe and very severe pneumonia from 7 low- and middle-income countries. An interpretation process categorized each CXR into 1 of 5 conclusions: consolidation, other infiltrate, both consolidation and other infiltrate, normal, or uninterpretable. Two members of a 14-person reading panel, who had undertaken training and standardization in CXR interpretation, interpreted each CXR. Two members of an arbitration panel provided additional independent reviews of CXRs with discordant interpretations at the primary reading, blinded to previous reports. Further discordance was resolved with consensus discussion. Results.: A total of 4172 CXRs were obtained from 4232 cases. Observed agreement for detecting consolidation (with or without other infiltrate) between primary readers was 78% (kappa = 0.50) and between arbitrators was 84% (kappa = 0.61); agreement for primary readers and arbitrators across 5 conclusion categories was 43.5% (kappa = 0.25) and 48.5% (kappa = 0.32), respectively. Disagreement was most frequent between conclusions of other infiltrate and normal for both the reading panel and the arbitration panel (32% and 30% of discordant CXRs, respectively). Conclusions.: Agreement was similar to that of previous evaluations using the WHO methodology for detecting consolidation, but poor for other infiltrates despite attempts at a rigorous standardization process. |
Microscopic analysis and quality assessment of induced sputum from children with pneumonia in the PERCH Study
Murdoch DR , Morpeth SC , Hammitt LL , Driscoll AJ , Watson NL , Baggett HC , Brooks WA , Deloria Knoll M , Feikin DR , Kotloff KL , Levine OS , Madhi SA , O'Brien KL , Scott JAG , Thea DM , Ahmed D , Awori JO , DeLuca AN , Ebruke BE , Higdon MM , Jorakate P , Karron RA , Kazungu S , Kwenda G , Hossain L , Makprasert S , Moore DP , Mudau A , Mwaba J , Panchalingam S , Park DE , Prosperi C , Salaudeen R , Toure A , Zeger SL , Howie SRC . Clin Infect Dis 2017 64 S271-s279 Background.: It is standard practice for laboratories to assess the cellular quality of expectorated sputum specimens to check that they originated from the lower respiratory tract. The presence of low numbers of squamous epithelial cells (SECs) and high numbers of polymorphonuclear (PMN) cells are regarded as indicative of a lower respiratory tract specimen. However, these quality ratings have never been evaluated for induced sputum specimens from children with suspected pneumonia. Methods.: We evaluated induced sputum Gram stain smears and cultures from hospitalized children aged 1-59 months enrolled in a large study of community-acquired pneumonia. We hypothesized that a specimen representative of the lower respiratory tract will contain smaller quantities of oropharyngeal flora and be more likely to have a predominance of potential pathogens compared to a specimen containing mainly saliva. The prevalence of potential pathogens cultured from induced sputum specimens and quantity of oropharyngeal flora were compared for different quantities of SECs and PMNs. Results.: Of 3772 induced sputum specimens, 2608 (69%) had <10 SECs per low-power field (LPF) and 2350 (62%) had >25 PMNs per LPF, measures traditionally associated with specimens from the lower respiratory tract in adults. Using isolation of low quantities of oropharyngeal flora and higher prevalence of potential pathogens as markers of higher quality, <10 SECs per LPF (but not >25 PMNs per LPF) was the microscopic variable most associated with high quality of induced sputum. Conclusions.: Quantity of SECs may be a useful quality measure of induced sputum from young children with pneumonia. |
The effect of antibiotic exposure and specimen volume on the detection of bacterial pathogens in children with pneumonia
Driscoll AJ , Deloria Knoll M , Hammitt LL , Baggett HC , Brooks WA , Feikin DR , Kotloff KL , Levine OS , Madhi SA , O'Brien KL , Scott JAG , Thea DM , Howie SRC , Adrian PV , Ahmed D , DeLuca AN , Ebruke BE , Gitahi C , Higdon MM , Kaewpan A , Karani A , Karron RA , Mazumder R , McLellan J , Moore DP , Mwananyanda L , Park DE , Prosperi C , Rhodes J , Saifullah M , Seidenberg P , Sow SO , Tamboura B , Zeger SL , Murdoch DR . Clin Infect Dis 2017 64 S368-s377 Background.: Antibiotic exposure and specimen volume are known to affect pathogen detection by culture. Here we assess their effects on bacterial pathogen detection by both culture and polymerase chain reaction (PCR) in children. Methods.: PERCH (Pneumonia Etiology Research for Child Health) is a case-control study of pneumonia in children aged 1-59 months investigating pathogens in blood, nasopharyngeal/oropharyngeal (NP/OP) swabs, and induced sputum by culture and PCR. Antibiotic exposure was ascertained by serum bioassay, and for cases, by a record of antibiotic treatment prior to specimen collection. Inoculated blood culture bottles were weighed to estimate volume. Results.: Antibiotic exposure ranged by specimen type from 43.5% to 81.7% in 4223 cases and was detected in 2.3% of 4863 controls. Antibiotics were associated with a 45% reduction in blood culture yield and approximately 20% reduction in yield from induced sputum culture. Reduction in yield of Streptococcus pneumoniae from NP culture was approximately 30% in cases and approximately 32% in controls. Several bacteria had significant but marginal reductions (by 5%-7%) in detection by PCR in NP/OP swabs from both cases and controls, with the exception of S. pneumoniae in exposed controls, which was detected 25% less frequently compared to nonexposed controls. Bacterial detection in induced sputum by PCR decreased 7% for exposed compared to nonexposed cases. For every additional 1 mL of blood culture specimen collected, microbial yield increased 0.51% (95% confidence interval, 0.47%-0.54%), from 2% when volume was ≤1 mL to approximately 6% for ≥3 mL. Conclusions.: Antibiotic exposure and blood culture volume affect detection of bacterial pathogens in children with pneumonia and should be accounted for in studies of etiology and in clinical management. |
The enduring challenge of determining pneumonia etiology in children: Considerations for future research priorities
Feikin DR , Hammitt LL , Murdoch DR , O'Brien KL , Scott JAG . Clin Infect Dis 2017 64 S188-s196 Pneumonia kills more children each year worldwide than any other disease. Nonetheless, accurately determining the causes of childhood pneumonia has remained elusive. Over the past century, the focus of pneumonia etiology research has shifted from studies of lung aspirates and postmortem specimens intent on identifying pneumococcal disease to studies of multiple specimen types distant from the lung that are tested for multiple pathogens. Some major challenges facing modern pneumonia etiology studies include the use of nonspecific and variable case definitions, poor access to pathologic lung tissue and to specimens from fatal cases, poor diagnostic accuracy of assays (especially when testing nonpulmonary specimens), and the interpretation of results when multiple pathogens are detected in a given individual. The future of childhood pneumonia etiology research will likely require integrating data from complementary approaches, including applications of advanced molecular diagnostics and vaccine probe studies, as well as a renewed emphasis on lung aspirates from radiologically confirmed pneumonia and postmortem examinations. |
- Page last reviewed:Feb 1, 2024
- Page last updated:May 06, 2024
- Content source:
- Powered by CDC PHGKB Infrastructure