Summary 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 f...

In this well-functioning cohort, several cognitive tasks were associated with gait speed cross-sectionally and predicted longitudinal gait speed decline. These data are consistent with a shared pathology underlying cognitive and motor declines but do not suggest that specific executive cognitive deficits account for slowing of usual gait in aging.

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.

SummaryBackgroundDespite WHO recommendations to offer pregnant women treatment with praziquantel, many nations continue to withhold treatment, awaiting data from controlled trials addressing safety and efficacy. The objectives of the study were to 1) assess whether treatment of pregnant women with schistosomiasis at 12–16 weeks gestation leads to improved maternal and newborn outcomes and 2) collect maternal and newborn safety data.MethodsWomen who were otherwise healthy and infected with S. japonicum (N=370) were enrolled and randomized 1:1 to receive either over-encapsulated praziquantel (60 mg/kg in split dose) or placebo. The following efficacy outcomes were ascertained: maternal hemoglobin, iron status, and gestational weight gain, birth weight (primary outcome), newborn hemoglobin and iron status. Safety data were collected including immediate reactogenicity, post dosing toxicology ascertained 24 hours after study agent administration, and maternal and newborn serious adverse events.FindingsMost women harbored low intensity infections (90.9%). Treatment with praziquantel did not have a significant impact on birth weight (2.85 kg in both groups, Beta −0.002, [0.88, 0.083]) or the incidence of low birth weight (OR 1.319 [0.729, 2.387]. Lack of treatment success may be due to the lack of difference in measures of maternal inflammation at 32 weeks gestation. Treatment with praziquantel resulted in a higher likelihood of treatment success (OR 5.815, [3.52, 9.61], P < 0.0001). Treatment was well tolerated with reactogenicity rates similar to that observed in non-pregnant subjects. There were no significant differences in key safety outcomes including abortion, fetal death in utero and congenital anomalies.InterpretationResults from this study provide important data from a controlled trial in support of the expansion of treatment policies to include pregnant women as recommended by WHO.FundingThe trial was funded by the United States National Institutes of Health, National Institute of Allergy and Infectious Diseases (U01AI066050).

In well-functioning older adults, central arterial stiffness may contribute to cognitive decline independent of hypertension and other vascular risk factors.

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.

Background. Maternal GBS colonization is associated with early-onset neonatal sepsis and extensive efforts are directed to preventing this complication. Less is known about maternal risks of GBS colonization. We seek to provide a modern estimate of the incidence and impact of maternal GBS colonization and invasive GBS disease. Methods. A single center historical cohort study of all births between 2003 and 2015 was performed. Data was collected via electronic health record abstraction using an institutional specific tool. Descriptive statistics were performed regarding GBS status. Inferential statistics were performed comparing risk of adverse pregnancy outcomes in cohorts with and without GBS colonization as well as cohorts with GBS colonization and invasive GBS disease. Results. A total of 60,029 deliveries were included for analysis. Overall, 21.6% of the population was GBS colonized and 0.1% had invasive GBS disease. GBS colonization was associated with younger maternal age, Black race, non-Hispanic ethnicity, chronic hypertension, preexisting diabetes, and tobacco use (p<0.01). In the adjusted analyses, there was an increased risk of gestational diabetes (aRR 1.21, 95% CI 1.11-1.32) in colonized pregnancies and a decreased incidence of short cervix (aRR 0.64, 95% CI 0.52-0.79), chorioamnionitis (aRR 0.76, 95% CI 0.66-0.87), wound infection (aRR 0.75, 95% CI 0.64-0.88), and operative delivery (aRR 0.85, 95% CI 0.83-0.88). Conclusions. This modern-day large cohort of all births over a 12-year period demonstrates a GBS colonization rate of 21.6%. This data reflects a need to assess maternal and perinatal outcomes in addition to neonatal GBS sepsis rates to inform decisions regarding the utility of maternal vaccination.

While the cross-sectional relationship of arterial stiffness with cerebral small vessel disease is consistently shown in middle-aged and young-old adults, its less clear if these associations remain significant over time in very old adults. We hypothesize that arterial stiffness is longitudinally associated with white matter characteristics and associations are stronger within watershed areas. Neuroimaging was obtained in 2006–08 from 303 elderly (mean age 82.9 years, 59% women, 41% black) with pulse wave velocity measures in 1997–98. Multivariable regression models estimated the coefficients for pulse wave velocity (cm/sec) in relationship to presence, severity and spatial distribution of white matter hyperintensities, gray matter volume and fractional anisotropy from diffusion tensor, adjusting for demographic, cardiovascular risk factors and diseases from 1997–98 to 2006–08. Higher pulse wave velocity in 1997–98 was associated with greater white matter hyperintensities volume in 2006–08 within the left superior longitudinal fasciculus (age and total brain white matter hyperintensities-adjusted p=0.023), but not with white matter hyperintensities in other tracts, or with fractional anisotropy or gray matter volume from total brain (p>0.2). Associations were stronger in blacks than in whites remaining significant in fully adjusted models. Elderly with white matter hyperintensities in tracts related to processing speed and memory are more likely to have had higher pulse wave velocity values ten years prior, before neuroimaging data being available. Future studies should address whether arterial stiffness can serve as an early biomarker of covert brain structural abnormalities and whether early arterial stiffness control can promote successful brain aging, especially in black elderly.