OBJECTIVES: After respiratory syncytial virus (RSV), human metapneumovirus (hMPV) was the second-ranked pathogen attributed to severe pneumonia in the PERCH study. We sought to characterize hMPV-positive cases in high-burden settings, which have limited data, by comparing with RSV-positive and other cases. METHODS: Children aged 1-59 months hospitalized with suspected severe pneumonia and age/season-matched community controls in seven African and Asian countries had nasopharyngeal/oropharyngeal swabs tested by multiplex PCR for 32 respiratory pathogens, among other clinical and lab assessments at admission. Odds ratios adjusted for age and site (adjusted OR [aOR]) were calculated using logistic regression. Aetiologic probability was estimated using Bayesian nested partial latent class analysis. Latent class analysis identified syndromic constellations of clinical characteristics. RESULTS: hMPV was detected more frequently among cases (267/3887, 6.9%) than controls (115/4976, 2.3%), among cases with pneumonia chest X-ray findings (8.5%) than without (5.5%), and among controls with respiratory tract illness (3.8%) than without (1.8%; all p ≤ 0.001). HMPV-positive cases were negatively associated with the detection of other viruses (aOR, 0.18), especially RSV (aOR, 0.11; all p < 0.0001), and positively associated with the detection of bacteria (aORs, 1.77; p 0.03). No single clinical syndrome distinguished hMPV-positive from other cases. Among hMPV-positive cases, 65.2% were aged <1 year and 27.5% had pneumonia danger signs; positive predictive value for hMPV aetiology was 74.5%; mortality was 3.9%, similar to RSV-positive (2.4%) and lower than that among other cases (9.6%). DISCUSSION: HMPV-associated severe paediatric pneumonia in high-burden settings was predominantly in young infants and clinically indistinguishable from RSV. HMPV-positives had low case fatality, similar to that in RSV-positives.

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.

Background: Effective prevention, detection, and response to disease threats at the human-animal-environment interface rely on a multisectoral, One Health workforce. Since 2009, the U.S. Centers for Disease Control and Prevention (CDC) has supported Field Epidemiology Training Programs (FETPs) to train veterinarians and veterinary paraprofessionals (VPPs) alongside their human health counterparts in the principles of epidemiology, disease surveillance, and outbreak investigations. We aim to describe and evaluate characteristics of CDC-supported FETPs enrolling veterinarians/VPPs to understand these programs contribution to the strengthening of the global One Health workforce. Methods: We surveyed staff from CDC-supported FETPs that enroll veterinarians and VPPs regarding cohort demographics, graduate retention, and veterinary and One Health relevant curriculum inclusion. Descriptive data was analyzed using R Version 3.5.1. Results: Forty-seven FETPs reported veterinarian/VPP trainees, 68% responded to our questionnaire, and 64% reported veterinary/VPP graduates in 2017. The veterinary/VPP graduates in 2017 made up 12% of cohorts. Programs reported 74% of graduated veterinarians/VPPs retained employment within national ministries of agriculture. Common veterinary and One Health curriculum topics were specimen collection and submission (93%), zoonotic disease (90%) and biosafety practices (83%); least covered included animal/livestock production and health promotion (23%) and transboundary animal diseases (27%). Less than half (41%) of programs reported the curriculum being sufficient for veterinarians/VPPs to perform animal health specific job functions, despite most programs being linked to the ministry of agriculture (75%) and providing veterinary-specific mentorship (63%). Conclusions: Our results indicate that FETPs provide valuable training opportunities for animal health sector professionals, strengthening the epidemiology capacity within the ministries retaining them. While veterinary/VPP trainees could benefit from the inclusion of animal-specific curricula needed to fulfill their job functions, at present, FETPs continue to serve as multisectoral, competency-based, in-service training important in strengthening the global One Health workforce by jointly training the animal and human health sectors. © 2022

OBJECTIVES: The success of National Public Health Institutes (NPHIs) in low-income and middle-income countries (LMICs) is critical to countries' ability to deliver public health services to their populations and effectively respond to public health emergencies. However, empirical data are limited on factors that promote or are barriers to the sustainability of NPHIs. This evaluation explored stakeholders' perceptions about enabling factors and barriers to the success and sustainability of NPHIs in seven countries where the U.S. Centers for Disease Control and Prevention (CDC) has supported NPHI development and strengthening. DESIGN: Qualitative study. SETTING: Cambodia, Colombia, Liberia, Mozambique, Nigeria, Rwanda and Zambia. PARTICIPANTS: NPHI staff, non-NPHI government staff, and non-governmental and international organisation staff. METHODS: We conducted semistructured, in-person interviews at a location chosen by the participants in the seven countries. We analysed data using a directed content analysis approach. RESULTS: We interviewed 43 NPHI staff, 29 non-NPHI government staff and 24 staff from non-governmental and international organisations. Participants identified five enabling factors critical to the success and sustainability of NPHIs: (1) strong leadership, (2) financial autonomy, (3) political commitment and country ownership, (4) strengthening capacity of NPHI staff and (5) forming strategic partnerships. Three themes emerged related to major barriers or threats to the sustainability of NPHIs: (1) reliance on partner funding to maintain key activities, (2) changes in NPHI leadership and (3) staff attrition and turnover. CONCLUSIONS: Our findings contribute to the scant literature on sustainability of NPHIs in LMICs by identifying essential components of sustainability and types of support needed from various stakeholders. Integrating these components into each step of NPHI development and ensuring sufficient support will be critical to strengthening public health systems and safeguarding their continuity. Our findings offer potential approaches for country leadership to direct efforts to strengthen and sustain NPHIs.

BACKGROUND: Field epidemiology training programs (FETPs) have trained field epidemiologists who strengthen global capacities for surveillance and response to public health threats. We describe how FETP residents and graduates have contributed to COVID-19 preparedness and response globally. METHODS: We conducted a cross-sectional survey of FETPs between March 13 and April 15, 2020 to understand how FETP residents or graduates were contributing to COVID-19 response activities. The survey tool was structured around the eight Pillars of the World Health Organization's (WHO) Strategic Preparedness and Response Plan for COVID-19. We used descriptive statistics to summarize quantitative results and content analysis for qualitative data. RESULTS: Among 88 invited programs, 65 (74%) responded and indicated that FETP residents and graduates have engaged in the COVID-19 response across all six WHO regions. Response efforts focused on country-level coordination (98%), surveillance, rapid response teams, case investigations (97%), activities at points of entry (92%), and risk communication and community engagement (82%). Descriptions of FETP contributions to COVID-19 preparedness and response are categorized into seven main themes: conducting epidemiological activities, managing logistics and coordination, leading risk communication efforts, providing guidance, supporting surveillance activities, training and developing the workforce, and holding leadership positions. CONCLUSIONS: Our findings demonstrate the value of FETPs in responding to public health threats like COVID-19. This program provides critical assistance to countries' COVID-19 response efforts but also enhances epidemiologic workforce capacity, public health emergency infrastructure and helps ensure global health security as prescribed in the WHO's International Health Regulations.

National Public Health Institutes (NPHIs) can strengthen countries' public health capacities to prevent, detect, and respond to public health emergencies. This qualitative evaluation assessed the role of the US Centers for Disease Control and Prevention (CDC) in NPHI development and strengthening of public health functions. We interviewed NPHI staff (N = 43), non-NPHI government staff (N = 29), and non-governmental organization staff (N = 24) in seven countries where CDC has supported NPHI development: Cambodia, Colombia, Liberia, Mozambique, Nigeria, Rwanda, and Zambia. Participants identified four areas of support that were the most important: workforce capacity building, technical assistance for key public health functions, identifying institutional gaps and priorities, and funding to support countries' priorities. Participants underscored the need for capacity building directed toward country-driven priorities during planning and implementation. Continued support for NPHI development from CDC and other partners is vital to building stronger public health systems, improving population health, and strengthening global health security.

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.

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.

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.

The covid-19 pandemic reminds us yet again of the critical importance of an effective field epidemiology workforce to safeguard and promote the health of countries' citizens, prevent the spread of infectious disease, and strengthen global health security. For the past 4 decades, field epidemiology training programs (FETPs)1,2 have worked to address precisely this need in countries throughout the world. FETPs are service-based, hands-on programs that emphasize learning by doing. They are designed to develop skilled and experienced field epidemiologists who can detect, investigate, and control disease outbreaks; conduct surveillance; analyze epidemiological data; measure the impact of interventions; and carry out applied epidemiological studies. Today, more than 85 FETPs are providing invaluable field epidemiology services to ministries of health in more than 165 countries and territories,3 and, as cases surge, the COVID-19 pandemic offers myriad examples of impactful contributions of FETP trainees and graduates to the response around the globe.4

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.

Transmission of SARS-CoV-2, the virus that causes COVID-19, is common in congregate settings such as correctional and detention facilities (1-3). On September 17, 2020, a Utah correctional facility (facility A) received a report of laboratory-confirmed SARS-CoV-2 infection in a dental health care provider (DHCP) who had treated incarcerated persons at facility A on September 14, 2020 while asymptomatic. On September 21, 2020, the roommate of an incarcerated person who had received dental treatment experienced COVID-19-compatible symptoms*; both were housed in block 1 of facility A (one of 16 occupied blocks across eight residential units). Two days later, the roommate received a positive SARS-CoV-2 test result, becoming the first person with a known-associated case of COVID-19 at facility A. During September 23-24, 2020, screening of 10 incarcerated persons who had received treatment from the DHCP identified another two persons with COVID-19, prompting isolation of all three patients in an unoccupied block at the facility. Within block 1, group activities were stopped to limit interaction among staff members and incarcerated persons and prevent further spread. During September 14-24, 2020, six facility A staff members, one of whom had previous close contact(†) with one of the patients, also reported symptoms. On September 27, 2020, an outbreak was confirmed after specimens from all remaining incarcerated persons in block 1 were tested; an additional 46 cases of COVID-19 were identified, which were reported to the Salt Lake County Health Department and the Utah Department of Health. On September 30, 2020, CDC, in collaboration with both health departments and the correctional facility, initiated an investigation to identify factors associated with the outbreak and implement control measures. As of January 31, 2021, a total of 1,368 cases among 2,632 incarcerated persons (attack rate = 52%) and 88 cases among 550 staff members (attack rate = 16%) were reported in facility A. Among 33 hospitalized incarcerated persons, 11 died. Quarantine and monitoring of potentially exposed persons and implementation of available prevention measures, including vaccination, are important in preventing introduction and spread of SARS-CoV-2 in correctional facilities and other congregate settings (4).

The Zambia Field Epidemiology Training Program (ZFETP) was established by the Ministry of Health (MoH) during 2014, in order to increase the number of trained field epidemiologists who can investigate outbreaks, strengthen disease surveillance, and support data-driven decision making. We describe the ZFETP´s approach to public health workforce development and health security strengthening, key milestones five years after program launch, and recommendations to ensure program sustainability. Program description: ZFETP was established as a tripartite arrangement between the Zambia MoH, the University of Zambia School of Public Health, and the U.S. Centers for Disease Control and Prevention. The program runs two tiers: Advanced and Frontline. To date, ZFETP has enrolled three FETP-Advanced cohorts (training 24 residents) and four Frontline cohorts (training 71 trainees). In 2016, ZFETP moved organizationally to the newly established Zambia National Public Health Institute (ZNPHI). This re-positioning raised the program´s profile by providing residents with increased opportunities to lead high-profile outbreak investigations and analyze national surveillance data-achievements that were recognized on a national stage. These successes attracted investment from the Government of Republic of Zambia (GRZ) and donors, thus accelerating field epidemiology workforce capacity development in Zambia. In its first five years, ZFETP achieved early success due in part to commitment from GRZ, and organizational positioning within the newly formed ZNPHI, which have catalyzed ZFETP´s institutionalization. During the next five years, ZFETP seeks to sustain this momentum by expanding training of both tiers, in order to accelerate the professional development of field epidemiologists at all levels of the public health system.

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.

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.

OBJECTIVE: To identify the etiology of an outbreak of spastic paraparesis among women and children in the Western Province of Zambia suspected to be konzo. METHODS: We conducted an outbreak investigation of individuals from Mongu District, Western Province, Zambia, who previously developed lower extremity weakness. Cases were classified with the World Health Organization definition of konzo. Active case finding was conducted through door-to-door evaluation in affected villages and sensitization at local health clinics. Demographic, medical, and dietary history was used to identify common exposures in all cases. Urine and blood specimens were taken to evaluate for konzo and alternative etiologies. RESULTS: We identified 32 cases of konzo exclusively affecting children 6 to 14 years of age and predominantly females >14 years of age. Fourteen of 15 (93%) cases >/=15 years of age were female, 11 (73%) of whom were breastfeeding at the time of symptom onset. Cassava was the most commonly consumed food (median [range] 14 [4-21] times per week), while protein-rich foods were consumed <1 time per week for all cases. Of the 30 patients providing urine specimens, median thiocyanate level was 281 (interquartile range 149-522) mumol/L, and 73% of urine samples had thiocyanate levels >136 mumol/L, the 95th percentile of the US population in 2013 to 2014. CONCLUSION: This investigation revealed the first documented cases of konzo in Zambia, occurring in poor communities with diets high in cassava and low in protein, consistent with previous descriptions from neighboring countries.

The World Health Organization monitoring and evaluation framework for the International Health Regulations (IHR, 2005) describes the targets for the Joint External Evaluation (JEE) indicators. For workforce development, the JEE defines the optimal target for attaining and complying with the IHR (2005) as 1 trained field epidemiologist (or equivalent) per 200,000 population. We explain the derivation and use of the current field epidemiology workforce development target and identify the limitations and lessons learned in applying it to various countries' public health systems. This article also proposes a way forward for improvements and implementation of this workforce development target.

Background: The etiology of severe pneumonia is frequently not identified by routine disease surveillance in Thailand. Since 2010, the Thailand Ministry of Public Health (MOPH) and US CDC have conducted surveillance to detect known and new etiologies of severe pneumonia. Methods: Surveillance for severe community-acquired pneumonia was initiated in December 2010 among 30 hospitals in 17 provinces covering all regions of Thailand. Interlinked clinical, laboratory, pathological and epidemiological components of the network were created with specialized guidelines for each to aid case investigation and notification. Severe pneumonia was defined as chest-radiograph confirmed pneumonia of unknown etiology in a patient hospitalized ≤48 h and requiring intubation with ventilator support or who died within 48 h after hospitalization; patients with underlying chronic pulmonary or neurological disease were excluded. Respiratory and pathological specimens were tested by reverse transcription polymerase chain reaction for nine viruses, including Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and 14 bacteria. Cases were reported via a secure web-based system. Results: Of specimens from 972 cases available for testing during December 2010 through December 2015, 589 (60.6%) had a potential etiology identified; 399 (67.8%) were from children aged < 5 years. At least one viral agent was detected in 394 (40.5%) cases, with the most common of single vial pathogen detected being respiratory syncytial virus (RSV) (110/589, 18.7%) especially in children under 5 years. Bacterial pathogens were detected in 341 cases of which 67 cases had apparent mixed infections. The system added MERS-CoV testing in September 2012 as part of Thailand's outbreak preparedness; no cases were identified from the 767 samples tested. Conclusions: Enhanced surveillance improved the understanding of the etiology of severe pneumonia cases and improved the MOPH's preparedness and response capacity for emerging respiratory pathogens in Thailand thereby enhanced global health security. Guidelines for investigation of severe pneumonia from this project were incorporated into surveillance and research activities within Thailand and shared for adaption by other countries.

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.

Background: Bloodstream infection (BSI) surveillance is essential to characterize the public health threat of bacteremia. We summarize BSI epidemiology in rural Thailand over an eight year period. Methods: Population-based surveillance captured clinically indicated blood cultures and associated antimicrobial susceptibility results performed in all 20 hospitals in Nakhon Phanom (NP) and Sa Kaeo (SK) provinces. BSIs were classified as community-onset (CO) when positive cultures were obtained ≤2 days after hospital admission and hospital-onset (HO) thereafter. Hospitalization denominator data were available for incidence estimates for 2009-2014. Results: From 2007 to 2014 a total of 11,166 BSIs were identified from 134,441 blood cultures. Annual CO BSI incidence ranged between 89.2 and 123.5 cases per 100,000 persons in SK and NP until 2011. Afterwards, CO incidence remained stable in SK and increased in NP, reaching 155.7 in 2013. Increases in CO BSI incidence over time were limited to persons aged ≥50 years. Ten pathogens, in rank order, accounted for > 65% of CO BSIs in both provinces, all age-groups, and all years: Escherichia coli, Klebsiella pneumoniae, Burkholderia pseudomallei, Staphylococcus aureus, Salmonella non-typhi spp., Streptococcus pneumoniae, Acinetobacter spp., Streptococcus agalactiae, Streptococcus pyogenes, Pseudomonas aeruginosa. HO BSI incidence increased in NP from 0.58 cases per 1000 hospitalizations in 2009 to 0.91 in 2014, but were higher (ranging from 1.9 to 2.3) in SK throughout the study period. Extended-spectrum beta-lactamase production among E. coli isolates and multi-drug resistance among Acinetobacter spp. isolates was common (> 25% of isolates), especially among HO cases (> 50% of isolates), and became more common over time, while methicillin-resistance among S. aureus isolates (10%) showed no clear trend. Carbapenem-resistant Enterobacteriaceae were documented in 2011-2014. Conclusions: Population-based surveillance documented CO BSI incidence estimates higher than previously reported from Thailand and the region, with temporal increases seen in older populations. The most commonly observed pathogens including resistance profiles were similar to leading pathogens and resistance profiles worldwide, thus; prevention strategies with demonstrated success elsewhere may prove effective in Thailand.

BACKGROUND: Determining the etiology of pneumonia is essential to guide public health interventions. Diagnostic test results, including from polymerase chain reaction (PCR) assays of upper respiratory tract specimens, have been used to estimate prevalence of pneumococcal pneumonia. However limitations in test sensitivity and specificity and the specimen types available make establishing a definitive diagnosis challenging. Prevalence estimates for pneumococcal pneumonia could be biased in the absence of a true gold standard reference test for detecting Streptococcus pneumoniae. METHODS: We conducted a case control study to identify etiologies of community acquired pneumonia (CAP) from April 2014 through August 2015 in Thailand. We estimated the prevalence of pneumococcal pneumonia among adults hospitalized for CAP using Bayesian latent class models (BLCMs) incorporating results of real-time polymerase chain reaction (qPCR) testing of upper respiratory tract specimens and a urine antigen test (UAT) from cases and controls. We compared the prevalence estimate to conventional analyses using only UAT as a reference test. RESULTS: The estimated prevalence of pneumococcal pneumonia was 8% (95% CI: 5-11%) by conventional analyses. By BLCM, we estimated the prevalence to be 10% (95% CrI: 7-16%) using binary qPCR and UAT results, and 11% (95% CrI: 7-17%) using binary UAT results and qPCR cycle threshold (Ct) values. CONCLUSIONS: BLCM suggests a > 25% higher prevalence of pneumococcal pneumonia than estimated by a conventional approach assuming UAT as a gold standard reference test. Higher quantities of pneumococcal DNA in the upper respiratory tract were associated with pneumococcal pneumonia in adults but the addition of a second specific pneumococcal test was required to accurately estimate disease status and prevalence. By incorporating the inherent uncertainty of diagnostic tests, BLCM can obtain more reliable estimates of disease status and improve understanding of underlying etiology.

Introduction: Mumps is a vaccine-preventable viral disease that may cause deafness, orchitis, encephalitis or death. However, mumps vaccine is not included in Zambia's Expanded Program for Immunization. In January 2015, Integrated Disease Surveillance and Response data revealed an increase in reported mumps cases in Luanshya District. We investigated to confirm the etiology and generate epidemiological data on mumps in Zambia. Method(s): We conducted active case finding, examined possible case-patients, and administered a standard questionnaire. A suspected mumps case was defined as acute onset of salivary gland swelling in a Luanshya resident during January-June 2015. Eight case-patients provided serum samples to test for mumps-specific immunoglobulin IgM, and buccal swabs to test for mumps viral RNA by RT-PCR, and genotyping of mumps virus at the Centers for Disease Control and Prevention, Atlanta, Georgia, USA. Result(s): From January - June 2015, a total of 283 mumps cases were reported in Luanshya, peaking in April (71 cases) and clustering (81%) in two townships. Of 72 suspected case-patients interviewed, 81% were aged < 15 years (29%, 1-4 years) and 61% were female. Common clinical characteristics were buccal tenderness (29%) and fever > 37.5C (29%). Mumps virus genotype D was confirmed in five case-patients who tested positive by RT-PCR; six case-patients were sero-positive for anti-mumps IgM antibodies (total seven lab-confirmed cases). Conclusion(s): Our findings represent the first reported epidemiologic description of mumps in Zambia. While the epidemiology is consistent with prior descriptions of mumps in unimmunized populations and no serious complications arose, this report provides data to inform policy discussions regarding mumps vaccination in Zambia.

INTRODUCTION: Invasive salmonellosis is a common cause of bloodstream infection in Southeast Asia. Limited epidemiologic and antimicrobial resistance data are available from the region. METHODS: 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 (bioMerieux, Thailand) and isolates were identified using standard microbiological techniques; all Salmonella isolates were classified to at least the serogroup level. Antimicrobial resistance was assessed using disk diffusion. RESULTS: Salmonella 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 Salmonella serovar Enteritidis. Serogroup C predominated in SK (166/314) with 84.3% of this serogroup being Salmonella 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%). CONCLUSIONS: 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.

Staphylococcus aureus is a common cause of bloodstream infection and methicillin-resistant S. aureus (MRSA) is a growing threat worldwide. We evaluated the incidence rate of S. aureus bacteremia (SAB) and MRSA from population-based surveillance in all hospitals from two Thai provinces. Infections were classified as community-onset (CO) when blood cultures were obtained </= 2 days after hospital admission and as hospital-onset (HO) thereafter. The incidence rate of HO-SAB could only be calculated for 2009-2014 when hospitalization denominator data were available. Among 147,524 blood cultures, 919 SAB cases were identified. Community-onset S. aureus bacteremia incidence rate doubled from 4.4 (95% confidence interval [CI]: 3.3-5.8) in 2006 to 9.3 per 100,000 persons per year (95% CI: 7.6-11.2) in 2014. The highest CO-SAB incidence rate was among adults aged 50 years and older. Children less than 5 years old had the next highest incidence rate, with most cases occurring among neonates. During 2009-2014, there were 89 HO-SAB cases at a rate of 0.13 per 1,000 hospitalizations per year (95% CI: 0.10-0.16). Overall, MRSA prevalence among SAB cases was 10% (90/911) and constituted 7% (55/736) of CO-SAB and 20% (22/111) of HO-SAB without a clear temporal trend in incidence rate. In conclusion, CO-SAB incidence rate has increased, whereas MRSA incidence rate remained stable. The increasing CO-SAB incidence rate, especially the burden on older adults and neonates, underscores the importance of strong SAB surveillance to identify and respond to changes in bacteremia trends and antimicrobial resistance.

Melioidosis incidence and mortality have reportedly been increasing in endemic areas of Thailand, but little population-based data on culture-confirmed Burkholderia pseudomallei infections exist. We provide updated estimates of melioidosis bacteremia incidence and in-hospital mortality rate using integration of two population-based surveillance databases in Nakhon Phanom, Thailand, since automated blood culture became available in 2005. From 2009 to 2013, 564 hospitalized bacteremic melioidosis patients were identified. The annual incidence of bacteremic melioidosis ranged from 14 to 17 per 100,000 persons, and average population mortality rate was 2 per 100,000 persons per year. In-hospital mortality rate declined nonsignificantly from 15% (15/102) to 13% (15/118). Of 313 (56%) bacteremic melioidosis patients who met criteria for acute lower respiratory infection and were included in the hospital-based pneumonia surveillance system, 65% (202/313) had a chest radiograph performed within 48 hours of admission; 46% (92/202) showed radiographic evidence of pneumonia. Annual incidence of bacteremic melioidosis with pneumonia was 2.4 per 100,000 persons (95% confidence intervals; 1.9-2.9). In-hospital death was more likely among bacteremic melioidosis patients with pneumonia (34%; 20/59) compared with non-pneumonia patients (18%; 59/321) (P-value = 0.007). The overall mortality could have been as high as 46% (257/564) if patients with poor clinical condition at the time of discharge had died. The continued high incidence of bacteremic melioidosis, pneumonia, and deaths in an endemic area highlights the need for early diagnosis and treatment and additional interventions for the prevention and control for melioidosis.

More than ever, competent field epidemiologists are needed worldwide. As known, new, and resurgent communicable diseases increase their global impact, the International Health Regulations and the Global Health Security Agenda call for sufficient field epidemiologic capacity in every country to rapidly detect, respond to, and contain public health emergencies, thereby ensuring global health security. To build this capacity, for >35 years the US Centers for Disease Control and Prevention has worked with countries around the globe to develop Field Epidemiology Training Programs (FETPs). FETP trainees conduct surveillance activities and outbreak investigations in service to ministry of health programs to prevent and control infectious diseases of global health importance such as polio, cholera, tuberculosis, HIV/AIDS, malaria, and emerging zoonotic infectious diseases. FETP graduates often rise to positions of leadership to direct such programs. By training competent epidemiologists to manage public health events locally and support public health systems nationally, health security is enhanced globally.

BACKGROUND: We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015. METHODS: We estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity. FINDINGS: We estimated that globally in 2015, 33.1 million (uncertainty range [UR] 21.6-50.3) episodes of RSV-ALRI, resulted in about 3.2 million (2.7-3.8) hospital admissions, and 59 600 (48 000-74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1.4 million (UR 1.2-1.7) hospital admissions, and 27 300 (UR 20 700-36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600-149 400). Incidence and mortality varied substantially from year to year in any given population. INTERPRETATION: Globally, RSV is a common cause of childhood ALRI and a major cause of hospital admissions in young children, resulting in a substantial burden on health-care services. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months. An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group. FUNDING: The Bill & Melinda Gates Foundation.

Over the last 20–30 years, enormous reductions have occurred in the absolute and relative burden of pneumonia mortality in young children around the world. Only 20 years ago, when the population of young children was approximately 625 million, approximately 1.7 million young children died from pneumonia before their 5th birthday (Figure 1) [1–4]. Mortality from pneumonia among children aged <5 years fell to 921 000 in 2015, whereas the population of young children rose to >670 million [1, 2, 5]. This remarkable improvement in child survival and health has resulted from advances in social conditions and economic development [6] but has also been influenced by at least 4 pivotal innovations: (1) the development of a global vaccination program, the World Health Organization’s Expanded Program on Immunizations (begun in 1974), which created the architecture around which country investments, donor funding, program strategies, and outcome measurements could be envisioned and implemented; (2) the global consensus to focus funding, programs, and momentum on 6 development targets articulated by the United Nations General Assembly through the Millennium Development Goals (MDGs, agreed upon in 2000) with MDG4 targeting child survival; (3) the advent of large, health-focused nongovernmental organizations; and (4) the founding of the Global Alliance for Vaccines and Immunization (the Gavi Alliance, formally launched at the World Economic Forum in January 2000), a multilateral funding organization that has allowed for an unprecedented pace of introduction and expanded use of life-saving vaccines in low-income countries. In part, as a result of this multidimensional, multisectoral consensus approach enacted through critical large-scale investments in prevention, protection, and treatment, pneumonia mortality has fallen substantially in many parts of the world because the most fatal of the pathogens and the underlying conditions that put children at risk are being targeted.

Background.: The etiologic inference of identifying a pathogen in the upper respiratory tract (URT) of children with pneumonia is unclear. To determine if viral load could provide evidence of causality of pneumonia, we compared viral load in the URT of children with World Health Organization-defined severe and very severe pneumonia and age-matched community controls. Methods.: In the 9 developing country sites, nasopharyngeal/oropharyngeal swabs from children with and without pneumonia were tested using quantitative real-time polymerase chain reaction for 17 viruses. The association of viral load with case status was evaluated using logistic regression. Receiver operating characteristic (ROC) curves were constructed to determine optimal discriminatory viral load cutoffs. Viral load density distributions were plotted. Results.: The mean viral load was higher in cases than controls for 7 viruses. However, there was substantial overlap in viral load distribution of cases and controls for all viruses. ROC curves to determine the optimal viral load cutoff produced an area under the curve of <0.80 for all viruses, suggesting poor to fair discrimination between cases and controls. Fatal and very severe pneumonia cases did not have higher viral load than less severe cases for most viruses. Conclusions.: Although we found higher viral loads among pneumonia cases than controls for some viruses, the utility in using viral load of URT specimens to define viral pneumonia was equivocal. Our analysis was limited by lack of a gold standard for viral pneumonia.

Background.: Lack of a gold standard for identifying bacterial and viral etiologies of pneumonia has limited evaluation of C-reactive protein (CRP) for identifying bacterial pneumonia. We evaluated the sensitivity and specificity of CRP for identifying bacterial vs respiratory syncytial virus (RSV) pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) multicenter case-control study. Methods.: We measured serum CRP levels in cases with World Health Organization-defined severe or very severe pneumonia and a subset of community controls. We evaluated the sensitivity and specificity of elevated CRP for "confirmed" bacterial pneumonia (positive blood culture or positive lung aspirate or pleural fluid culture or polymerase chain reaction [PCR]) compared to "RSV pneumonia" (nasopharyngeal/oropharyngeal or induced sputum PCR-positive without confirmed/suspected bacterial pneumonia). Receiver operating characteristic (ROC) curves were constructed to assess the performance of elevated CRP in distinguishing these cases. Results.: Among 601 human immunodeficiency virus (HIV)-negative tested controls, 3% had CRP ≥40 mg/L. Among 119 HIV-negative cases with confirmed bacterial pneumonia, 77% had CRP ≥40 mg/L compared with 17% of 556 RSV pneumonia cases. The ROC analysis produced an area under the curve of 0.87, indicating very good discrimination; a cut-point of 37.1 mg/L best discriminated confirmed bacterial pneumonia (sensitivity 77%) from RSV pneumonia (specificity 82%). CRP ≥100 mg/L substantially improved specificity over CRP ≥40 mg/L, though at a loss to sensitivity. Conclusions.: Elevated CRP was positively associated with confirmed bacterial pneumonia and negatively associated with RSV pneumonia in PERCH. CRP may be useful for distinguishing bacterial from RSV-associated pneumonia, although its role in discriminating against other respiratory viral-associated pneumonia needs further study.