Andrea N. DeLuca

The Pneumonia Etiology Research for Child Health Project: A 21st Century Childhood Pneumonia Etiology Study

The Pneumonia Etiology Research for Child Health (PERCH) project is a 7-country, standardized, comprehensive evaluation of the etiologic agents causing severe pneumonia in children from developing countries. During previous etiology studies, between one-quarter and one-third of patients failed to yield an obvious etiology; PERCH will employ and evaluate previously unavailable innovative, more sensitive diagnostic techniques. Innovative and rigorous epidemiologic and analytic methods will be used to establish the causal association between presence of potential pathogens and pneumonia. By strategic selection of study sites that are broadly representative of regions with the greatest burden of childhood pneumonia, PERCH aims to provide data that reflect the epidemiologic situation in developing countries in 2015, using pneumococcal and Haemophilus influenzae type b vaccines. PERCH will also address differences in host, environmental, and/or geographic factors that might determine pneumonia etiology and, by preserving specimens, will generate a resource for future research and pathogen discovery.

The Definition of Pneumonia, the Assessment of Severity, and Clinical Standardization in the Pneumonia Etiology Research for Child Health Study

To develop a case definition for the Pneumonia Etiology Research for Child Health (PERCH) project, we sought a widely acceptable classification that was linked to existing pneumonia research and focused on very severe cases. We began with the World Health Organization’s classification of severe/very severe pneumonia and refined it through literature reviews and a 2-stage process of expert consultation. PERCH will study hospitalized children, aged 1–59 months, with pneumonia who present with cough or difficulty breathing and have either severe pneumonia (lower chest wall indrawing) or very severe pneumonia (central cyanosis, difficulty breastfeeding/drinking, vomiting everything, convulsions, lethargy, unconsciousness, or head nodding). It will exclude patients with recent hospitalization and children with wheeze whose indrawing resolves after bronchodilator therapy. The PERCH investigators agreed upon standard interpretations of the symptoms and signs. These will be maintained by a clinical standardization monitor who conducts repeated instruction at each site and by recurrent local training and testing.

A cluster randomized trial of provider-initiated (Opt-out) HIV counseling and testing of tuberculosis patients in South Africa

Objective:To determine whether implementation of provider-initiated human immunodeficiency virus (HIV) counseling would increase the proportion of tuberculosis (TB) patients who received HIV counseling and testing. Design:Cluster-randomized trial with clinic as the unit of randomization. Setting:Twenty, medium-sized primary care TB clinics in the Nelson Mandela Metropolitan Municipality, Port Elizabeth, Eastern Cape Province, South Africa. Subjects:A total of 754 adults (18 years and older) newly registered as TB patients in the 20 study clinics. Intervention:Implementation of provider-initiated HIV counseling and testing. Main Outcome Measures:Percentage of TB patients HIV counseled and tested. Secondary:Percentage of patients with HIV test positive, and percentage of those who received cotrimoxazole and who were referred for HIV care. Results:A total of 754 adults newly registered as TB patients were enrolled. In clinics randomly assigned to implement provider-initiated HIV counseling and testing, 20.7% (73/352) patients were counseled versus 7.7% (31/402) in the control clinics (P = 0.011), and 20.2% (n = 71) versus 6.5% (n = 26) underwent HIV testing (P = 0.009). Of those patients counseled, 97% in the intervention clinics accepted testing versus 79% in control clinics (P = 0.12). The proportion of patients identified as HIV infected in intervention clinics was 8.5% versus 2.5% in control clinics (P = 0.044). Fewer than 40% of patients with a positive HIV test were prescribed cotrimoxazole or referred for HIV care in either study arm. Conclusions:Provider-initiated HIV counseling significantly increased the proportion of adult TB patients who received HIV counseling and testing, but the magnitude of the effect was small. Additional interventions to optimize HIV testing for TB patients urgently need to be evaluated.

Lower Respiratory Infections Among Hospitalized Children in New Caledonia: A Pilot Study for the Pneumonia Etiology Research for Child Health Project

Abstract We conducted a prospective pilot study over a 1-year period in New Caledonia in preparation for the Pneumonia Research for Child Health (PERCH) project. The pathogens associated with hospitalized lower respiratory infections in children were identified through the use of culture of induced sputum and blood, urinary antigen detection, polymerase chain reaction (PCR) on respiratory specimens, and serology on paired sera. Respiratory viruses were detected on respiratory specimens by immunofluorescence and PCR, and by serology on paired sera. Pathogens were detected in 87.9% of the 108 hospitalized cases. Viruses represented 81.6% of the 152 pathogens detected. Respiratory syncytial virus and rhinovirus were the most frequent, accounting for 32.2% and 24.3% of the pathogens identified, respectively. Only 26.3% of 99 induced sputum specimens collected were determined to be of good quality, which may be a consequence of the collection method used.

Identification and selection of cases and controls in the Pneumonia Etiology Research for Child Health project.

Methods for the identification and selection of patients (cases) with severe or very severe pneumonia and controls for the Pneumonia Etiology Research for Child Health (PERCH) project were needed. Issues considered include eligibility criteria and sampling strategies, whether to enroll hospital or community controls, whether to exclude controls with upper respiratory tract infection (URTI) or nonsevere pneumonia, and matching criteria, among others. PERCH ultimately decided to enroll community controls and an additional human immunodeficiency virus (HIV)–infected control group at high HIV-prevalence sites matched on age and enrollment date of cases; controls with symptoms of URTI or nonsevere pneumonia will not be excluded. Systematic sampling of cases (when necessary) and random sampling of controls will be implemented. For each issue, we present the options that were considered, the advantages and disadvantages of each, the rationale for the methods selected for PERCH, and remaining implications and limitations.

Evaluation of Risk Factors for Severe Pneumonia in Children: The Pneumonia Etiology Research for Child Health Study

As a case-control study of etiology, the Pneumonia Etiology Research for Child Health (PERCH) project also provides an opportunity to assess the risk factors for severe pneumonia in hospitalized children at 7 sites. We identified relevant risk factors by literature review and iterative expert consultation. Decisions for inclusion in PERCH were based on comparability to published data, analytic plans, data collection costs and logistic feasibility, including interviewer time and subject fatigue. We aimed to standardize questions at all sites, but significant variation in the economic, cultural, and geographic characteristics of sites made it difficult to obtain this objective. Despite these challenges, the depth of the evaluation of multiple risk factors across the breadth of the PERCH sites should furnish new and valuable information about the major risk factors for childhood severe and very severe pneumonia, including risk factors for pneumonia caused by specific etiologies, in developing countries.

Safety of Induced Sputum Collection in Children Hospitalized With Severe or Very Severe Pneumonia

Abstract 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.

South African TB nurses' experiences of provider-initiated HIV counseling and testing in the Eastern Cape Province: a qualitative study

Abstract This study addressed factors that played a role in the limited but effective implementation of provider-initiated HIV counseling in tuberculosis (TB) clinics in the Eastern Cape Province, South Africa, as part of a clinical trial. The Eastern Cape is a region with some of the highest TB and HIV rates in the world. The parent study was a pragmatic, cluster-randomized trial designed to measure the impact of provider-initiated (“opt-out”) counseling on the uptake of HIV counseling and testing in newly registered TB patients. Key informants were interviewed and clinic nurses who participated in the study were invited to participate in focus group discussions (FGDs). Thematic content analysis of transcriptions was conducted on data collected during interviews and FGDs. Three major themes regarding nurse experiences were derived from analysis, indicating that multiple structural and personal factors influence the success of provider-initiated HIV counseling of TB patients in primary care settings: (1) chronic frustration with knowing what TB tasks need to be accomplished but not having the resources, including staff, to accomplish them; (2) conflict between the appreciation of the need and importance of HIV counseling and testing and the health systems recognition of their difficulties implementing it; and (3) ambivalence in their roles as care providers and educators in the context of HIV counseling and testing. Innovative and coordinated strategies are needed in this environment to facilitate greater number of patients receiving HIV counseling and testing services.

Intensified case finding for tuberculosis in prevention of mother-to-child transmission programs: a simple and potentially vital addition for maternal and child health.

The intersection of HIV and tuberculosis (TB) poses a serious threat to HIV-infected women and their children. The majority of patients with TB in sub-Saharan Africa are infected with HIV and together the overlapping epidemics synergistically accelerate illness and death. Escalating case rates increased mortality and the recent emergence of extensively drug-resistant TB highlights how catastrophic a once preventable and curable disease has become among people with HIV/AIDS. The HIV epidemic requires new strategies to control TB in high-burden areas especially as women of reproductive age are disproportionately affected by the epidemic. Intensified case finding for TB has the potential to reduce morbidity and mortality for people living with HIV especially pregnant women their families and infants. (excerpt)

Chest Radiograph Findings in Childhood Pneumonia Cases From the Multisite PERCH Study

Summary In the Pneumonia Etiology Research for Child Health study, abnormal chest radiographs (CXRs) in cases were associated with hypoxemia, crackles, tachypnea, and fever. Overall, 54% of CXRs were abnormal (site range, 35%–64%). Consolidation on CXR was associated with an increased risk of mortality.