Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study

Background Pneumonia is the leading cause of death among children younger than 5 years. In this study, we estimated causes of pneumonia in young African and Asian children, using novel analytical methods applied to clinical and microbiological findings. Methods We did a multi-site, international case-control study in nine study sites in seven countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. All sites enrolled in the study for 24 months. Cases were children aged 1–59 months admitted to hospital with severe pneumonia. Controls were age-group-matched children randomly selected from communities surrounding study sites. Nasopharyngeal and oropharyngeal (NP-OP), urine, blood, induced sputum, lung aspirate, pleural fluid, and gastric aspirates were tested with cultures, multiplex PCR, or both. Primary analyses were restricted to cases without HIV infection and with abnormal chest x-rays and to controls without HIV infection. We applied a Bayesian, partial latent class analysis to estimate probabilities of aetiological agents at the individual and population level, incorporating case and control data. Findings Between Aug 15, 2011, and Jan 30, 2014, we enrolled 4232 cases and 5119 community controls. The primary analysis group was comprised of 1769 (41·8% of 4232) cases without HIV infection and with positive chest x-rays and 5102 (99·7% of 5119) community controls without HIV infection. Wheezing was present in 555 (31·7%) of 1752 cases (range by site 10·6–97·3%). 30-day case-fatality ratio was 6·4% (114 of 1769 cases). Blood cultures were positive in 56 (3·2%) of 1749 cases, and Streptococcus pneumoniae was the most common bacteria isolated (19 [33·9%] of 56). Almost all cases (98·9%) and controls (98·0%) had at least one pathogen detected by PCR in the NP-OP specimen. The detection of respiratory syncytial virus (RSV), parainfluenza virus, human metapneumovirus, influenza virus, S pneumoniae, Haemophilus influenzae type b (Hib), H influenzae non-type b, and Pneumocystis jirovecii in NP-OP specimens was associated with case status. The aetiology analysis estimated that viruses accounted for 61·4% (95% credible interval [CrI] 57·3–65·6) of causes, whereas bacteria accounted for 27·3% (23·3–31·6) and Mycobacterium tuberculosis for 5·9% (3·9–8·3). Viruses were less common (54·5%, 95% CrI 47·4–61·5 vs 68·0%, 62·7–72·7) and bacteria more common (33·7%, 27·2–40·8 vs 22·8%, 18·3–27·6) in very severe pneumonia cases than in severe cases. RSV had the greatest aetiological fraction (31·1%, 95% CrI 28·4–34·2) of all pathogens. Human rhinovirus, human metapneumovirus A or B, human parainfluenza virus, S pneumoniae, M tuberculosis, and H influenzae each accounted for 5% or more of the aetiological distribution. We observed differences in aetiological fraction by age for Bordetella pertussis, parainfluenza types 1 and 3, parechovirus–enterovirus, P jirovecii, RSV, rhinovirus, Staphylococcus aureus, and S pneumoniae, and differences by severity for RSV, S aureus, S pneumoniae, and parainfluenza type 3. The leading ten pathogens of each site accounted for 79% or more of the site's aetiological fraction. Interpretation In our study, a small set of pathogens accounted for most cases of pneumonia requiring hospital admission. Preventing and treating a subset of pathogens could substantially affect childhood pneumonia outcomes

Feasibility of Using HIV Care-Continuum Outcomes to Identify Geographic Areas for Targeted HIV Testing.

BACKGROUND: Improved detection and linkage to care of previously undiagnosed HIV infections requires innovative approaches to testing. We sought to determine the feasibility of targeted HIV testing in geographic areas, defined by continuum of care parameters, to identify HIV-infected persons needing linkage or engagement in care. METHODS: Using HIV surveillance data from Washington, DC, we identified census tracts (CTs) that had an HIV prevalence >1% and were either above (higher risk areas--HRAs) or below (lower risk areas--LRAs) the median for three indicators: monitored viral load, proportion of persons out of care (OOC) and never in care. Community-based HIV rapid testing and participant surveys were conducted in the twenty CTs meeting the criteria. Areas were mapped using ArcGIS and descriptive and univariate analyses were conducted comparing the areas and participants. RESULTS: Among 1,471 persons tested, 28 (1.9%) tested HIV-positive; 2.1% in HRAs vs. 1.7% in LRAs (p=0.57). Higher proportions of males (63.7% vs. 56.7%, p=0.007) and fewer blacks (91.0% vs. 94.6%, p=0.008) were tested in LRAs vs. HRAs; no differences were observed in risk behaviors between the areas. Among HIV-positive participants, 54% were new diagnoses (n=9) or OOC (n=6), all were black, 64% were male with a median age of 51 years. CONCLUSIONS: While significant differences in HIV seropositivity were not observed between testing areas, our approach proved feasible and enabled identification of new diagnoses and OOC HIV-infected persons. This testing paradigm could be adapted in other locales to identify areas for targeted HIV testing and other re-engagement efforts

Measuring Unmet Needs among Persons Living with HIV at Different Stages of the Care Continuum

Unmet needs can impede optimal care engagement, impacting the health and well-being of people living with HIV (PLWH); yet, whether unmet needs differ by care engagement status is not well understood. Using surveys and qualitative interviews, we examined and compared unmet needs for PLWH (n = 172) at different levels of care engagement. Unmet needs varied only slightly by care status. Survey findings revealed that provision of housing, emergency financial assistance, employment assistance, and food security were the greatest unmet need; for those in care, housing was the greatest unmet need, whereas for those sporadically in care or out of care, employment assistance was the greatest unmet needs. Qualitative interviews likewise illustrated that a lack of financial resources including insurance, housing, employment, and transportation presented barriers to care engagement across all care groups. Our findings indicate that unmet needs among PLWH are complex and multi-faceted across care engagement status

The Etiology of Childhood Pneumonia in Bangladesh

BACKGROUND: Pneumonia remains the leading infectious cause of death among children <

The Etiology of Pneumonia From Analysis of Lung Aspirate and Pleural Fluid Samples: Findings From the Pneumonia Etiology Research for Child Health (PERCH) Study.

BACKGROUND: An improved understanding of childhood pneumonia etiology is required to inform prevention and treatment strategies. Lung aspiration is the gold standard specimen for pneumonia diagnostics. We report findings from analyses of lung and pleural aspirates collected in the Pneumonia Etiology Research for Child Health (PERCH) study. METHODS: The PERCH study enrolled children aged 1-59 months hospitalized with World Health Organization-defined severe or very severe pneumonia in 7 countries in Africa and Asia. Percutaneous transthoracic lung aspiration (LA) and pleural fluid (PF) aspiration was performed on a sample of pneumonia cases with radiological consolidation and/or PF in 4 countries. Venous blood and nasopharyngeal/oropharyngeal swabs were collected from all cases. Multiplex quantitative polymerase chain reaction (PCR) and routine microbiologic culture were applied to clinical specimens. RESULTS: Of 44 LAs performed within 3 days of admission on 622 eligible cases, 13 (30%) had a pathogen identified by either culture (5/44) or by PCR (11/29). A pathogen was identified in 12/14 (86%) PF specimens tested by either culture (9/14) or PCR (9/11). Bacterial pathogens were identified more frequently than viruses. All but 1 of the cases with a virus identified were coinfected with bacterial pathogens. Streptococcus pneumoniae (9/44 [20%]) and Staphylococcus aureus (7/14 [50%]) were the predominant pathogens identified in LA and PF, respectively. CONCLUSIONS: Bacterial pathogens predominated in this selected subgroup of PERCH participants drawn from those with radiological consolidation or PF, with S. pneumoniae and S. aureus the leading pathogens identified