Introduction In low-resource settings, empiric case management of febrile illness is routine as a result of limited access to laboratory diagnostics. The use of comprehensive fever syndromic surveillance, with enhanced clinical microbiology, advanced diagnostics and more robust epidemiologic investigation, could enable healthcare providers to offer a differential diagnosis of fever syndrome and more appropriate care and treatment. Methods We conducted a year-long exploratory study of fever syndrome among patients >= 1 year if age, presenting to clinical settings with an axillary temperature of >= 37.5 degrees C and symptomatic onset of <= 5 days. Blood and naso-pharyngeal/oral-pharyngeal (NP/OP) specimens were collected and analyzed, respectively, using AFI and respiratory TaqMan Array Cards (TAC) for multi-pathogen detection of 57 potential causative agents. Furthermore, we examined numerous epidemiologic correlates of febrile illness, and conducted demographic, clinical, and behavioral domain-specific multivariate regression to statistically establish associations with agent detection. Results From 15 September 2014-13 September 2015, 1007 febrile patients were enrolled, and 997 contributed an epidemiologic survey, including: 14% (n = 139) 1<5yrs, 19% (n = 186) 5-14yrs, and 67% (n = 672) >= 15yrs. AFI TAC and respiratory TAC were performed on 842 whole blood specimens and 385 NP/OP specimens, respectively. Of the 57 agents surveyed, Plasmodium was the most common agent detected. AFI TAC detected nucleic acid for one or more of seven microbial agents in 49% of AFI blood samples, including: Plasmodium (47%), Leptospira (3%), Bartonella (1%), Salmonella enterica (1%), Coxiella burnetii (1%), Rickettsia (1%), and West Nile virus (1%). Respiratory TAC detected nucleic acid for 24 different microbial agents, including 12 viruses and 12 bacteria. The most common agents detected among our surveyed population were: Haemophilus influenzae (67%), Streptococcus pneumoniae (55%), Moraxella catarrhalis (39%), Staphylococcus aureus (37%), Pseudomonas aeruginosa (36%), Human Rhinovirus (25%), influenza A (24%), Klebsiella pneumoniae (14%), Enterovirus (15%) and group A Streptococcus (12%). Our epidemiologic investigation demonstrated both age and symptomatic presentation to be associated with a number of detected agents, including, but not limited to, influenza A and Plasmodium. Linear regression of fully-adjusted mean cycle threshold (Ct) values for Plasmodium also identified statistically significant lower mean Ct values for older children (20.8), patients presenting with severe fever (21.1) and headache (21.5), as well as patients admitted for in-patient care and treatment (22.4). Conclusions This study is the first to employ two syndromic TaqMan Array Cards for the simultaneous survey of 57 different organisms to better characterize the type and prevalence of detected agents among febrile patients. Additionally, we provide an analysis of the association between adjusted mean Ct values for Plasmodium and key clinical and demographic variables, which may further inform clinical decision-making based upon intensity of infection, as observed across endemic settings of sub-Saharan Africa.

Background: Hepatitis E (HEV) is an emerging cause of viral hepatitis mainly transmitted through the fecal-oral route. Residents of the Kibera slum of Nairobi, Kenya are at risk for fecal-orally transmitted infections.Objective: To quantify the incidence and prevalence of HEV infection among acute febrile illness (AFI) cases using a population-based infectious disease surveillance network. Study design: Cross-sectional serum samples from AFI case-patients between 2009 and 2012 were matched to the age and gender distribution of the Kibera population and tested by IgM and IgG enzyme immunoassays (EIA) and nucleic acid testing (NAT). Serum from healthy residents was also tested by EIA.Results: Of the 482 AFI serum samples tested, 124 (25.7%) and 182 (37.8%) were IgM and IgG reactive, respectively. On multivariate analysis, IgM reactivity was associated with HIV (RR 1.66, 95% CI 1.07, 2.60; p = 0.024) while IgG reactivity was associated with increasing age (p < 0.001) and HIV (RR 1.93, 95%CI 1.52, 2.46; p<0.001). AFI case-patients were more likely to be IgM (p = 0.002) and IgG (p<0.001) reactive compared to healthy residents. The seroincidence by HEV-specific IgM was 84.0 per 1000 person years, however, all 482 samples were negative by NAT.Conclusions: Serologic evidence for HEV in Kibera suggests a high burden of infection, but NAT did not confirm HEV viremia. Additional testing is needed to determine whether EIAs are susceptible to false positivity in undifferentiated AFI populations before their widespread use. (C) 2016 Elsevier B.V. All rights reserved.

Background: Asymptomatic individuals (AIs) serve as reservoirs of pathogens associated with disease transmission. The objective of this study was to identify the presence and diversity of selected viral respiratory and gastrointestinal (GI) pathogens in AIs among residents of an informal settlement in Nairobi, Kenya. Methods & Materials: In 2006, KEMRI/CDC established a population-based infectious disease surveillance site within Kibera in Nairobi, Kenya. AIs (healthy controls) were enrolled as part of the system among persons who presented to the study's referral facility (Tabitha Medical Clinic). Persons presenting without current or previous 2 weeks history of fever, respiratory or diarrheal symptoms were eligible for enrollment as healthy controls. Following consent, participants provided stool and nasopharyngeal/oropharyngeal (NP/OP) specimens. Stool samples were tested by culture for bacterial pathogens and rotavirus by enzyme-linked immunoassay. Respiratory viruses were detected in NP/OP swabs by real time PCR. Results: Between 01st November 2008 and 31st December 2011, 384 stool samples and 779 NP/OP swabs were obtained from AIs. Pathogens were found in 23 (6.0%) of the 384 stool samples. Shigella, 10 (43.5%), was the predominant bacterial pathogen isolated; S. dysenteriae (10%), S. flexneri (70%), and 2 unsubtypable Shigella species. Other bacterial species identified included Campylobacter coli (4.3%) and C. jejuni (17.3%). Rotavirus was the only viral pathogen targeted for isolation; however, it was only detected in <2% of the participants (n=384; 1.8%). Of the 779 NP/OP swabs, adenovirus (11%), respiratory syncytial virus (RSV) (2.8%), human metapnuemovirus (hMPV) (2.7%), influenza virus type A and B (2.3 and 0.5%, respectively), parainfluenza (PIV) type 1, 2 and 3 (0.9, 1.0 and 1.9%, respectively) were detected. Adenovirus, hMPV, RSV, and influenza B were found more frequently in ages 5-17 years (28.1%, 33.3%, 45.5%, and 75% respectively). Adenovirus (78.9%) and all cases of RSV and PIV 1-3 in 18-34 years were identified more among females. Within the same age group Influenza A (85.7%) and hMPV (60%) were more common among males. Conclusion: AIs did show evidence of infection and could serve as reservoirs for these pathogens through close contact in this urban settlement especially among immunocompromised individuals.

SUMMARYWe investigated a mixed outbreak of Legionnaires' disease (LD) and Pontiac fever (PF) at a military base to identify the outbreak's environmental source as well as known legionellosis risk factors. Base workers with possible legionellosis were interviewed and, if consenting, underwent testing for legionellosis. A retrospective cohort study collected information on occupants of the buildings closest to the outbreak source. We identified 29 confirmed and probable LD and 38 PF cases. All cases were exposed to airborne pathogens from a cooling tower. Occupants of the building closest to the cooling tower were 6·9 [95% confidence interval (CI) 2·2–22·0] and 5·5 (95% CI 2·1–14·5) times more likely to develop LD and PF, respectively, than occupants of the next closest building. Thorough preventive measures and aggressive responses to outbreaks, including searching for PF cases in mixed legionellosis outbreaks, are essential for legionellosis control.

SUMMARYTravel is a risk factor for Legionnaires' disease. In 2008, two cases were reported in condominium guests where we investigated a 2001 outbreak. We reinvestigated to identify additional cases and determine whether ongoing transmission resulted from persistent colonization of potable water. Exposures were assessed by matched case-control analyses (2001) and case-series interviews (2008). We sampled potable water and other water sources. Isolates were compared using sequence-based typing. From 2001 to 2008, 35 cases were identified. Confirmed cases reported after the cluster in 2001–2002 were initially considered sporadic, but retrospective case-finding identified five additional cases. Cases were more likely than controls to stay in tower 2 of the condominium [matched odds ratio (mOR) 6·1, 95% confidence interval (CI) 1·6–22·9]; transmission was associated with showering duration (mOR 23·0, 95% CI 1·4–384). We characterized a clinical isolate as sequence type 35 (ST35) and detected ST35 in samples of tower 2's potable water in 2001, 2002, and 2008. This prolonged outbreak illustrates the importance of striving for permanent Legionella eradication from potable water.

SUMMARYAlthough pneumonia is a leading cause of death from infectious disease worldwide, comprehensive information about its causes and incidence in low- and middle-income countries is lacking. Active surveillance of hospitalized patients with pneumonia is ongoing in Thailand. Consenting patients are tested for seven bacterial and 14 viral respiratory pathogens by PCR and viral culture on nasopharyngeal swab specimens, serology on acute/convalescent sera, sputum smears and antigen detection tests on urine. Between September 2003 and December 2005, there were 1730 episodes of radiographically confirmed pneumonia (34·6% in children aged <5 years); 66 patients (3·8%) died. A recognized pathogen was identified in 42·5% of episodes. Respiratory syncytial virus (RSV) infection was associated with 16·7% of all pneumonias, 41·2% in children. The viral pathogen with the highest incidence in children aged <5 years was RSV (417·1/100 000 per year) and in persons aged ⩾50 years, influenza virus A (38·8/100 000 per year). These data can help guide health policy towards effective prevention strategies.

SUMMARY Legionnaires' disease (LD) is caused by Legionella species, most of which live in water. The Mid-Atlantic region experienced a sharp rise in LD in 2003 coinciding with a period of record-breaking rainfall. To investigate a possible relationship, we analysed the association between monthly legionellosis incidence and monthly rainfall totals from January 1990 to December 2003 in five Mid-Atlantic states. Using negative binomial model a 1-cm increase in rainfall was associated with a 2·6% (RR 1·026, 95% CI 1·012–1·040) increase in legionellosis incidence. The average monthly rainfall from May to September 1990–2002 was 10·4 cm compared to 15·7 cm from May to September 2003. This change in rainfall corresponds to an increased risk for legionellosis of approximately 14·6% (RR 1·146, 95% CI 1·067–1·231). Legionellosis incidence increased during periods of increased rainfall; identification of mechanisms that increase exposure and transmission of Legionella during rainfall might lead to opportunities for prevention.

Legionella pneumophila will infect biofilm-associated protozoa, and in this way might be protected from disinfectants in potable water systems. A base biofilm containing Pseudomonas aeruginosa, Klebsiella pneumoniae, and Flavobacterium spp. was grown on steel coupons in potable water prior to the addition of L. pneumophila and the protozoan H. vermiformis. After 7 d, coupons were removed and treated with 0.5 mg 1(-1) free residual chlorine (FRC) or 0.5 mg l(-1) monochloramine (MCA) for 15, 60, or 180 min or 24 h. In a second experiment, only L. pneumophila and the base biofilm organisms were present but with an identical treatment protocol. Treatment of L. pneumophila for 180 min in a system without H. vermiformis resulted in log reductions of 2.07 and 2.11 for FRC and MCA, respectively. When H. vermiformis was present, however, the treatment resulted in log reductions of 0.67 and 0.81 for FRC and MCA, respectively. A similar pattern was observed for 15 and 60 min contact times. These results indicate that L. pneumophila was less susceptible to MCA or FRC when associated with biofilm-associated H. vermiformis in a model potable water biofilm.

Background and Purpose— Serologic evidence of infection with Chlamydia pneumoniae has been associated with cardiovascular disease, but its relationship with stroke risk remains uncertain. The objective of this study is to determine whether serological evidence of C pneumoniae infection is associated with risk of ischemic stroke. Methods— A population-based case-control study was performed in an urban, multiethnic population. Cases (n=246) had first ischemic stroke, and controls (n=474) matched for age, sex, and race–ethnicity were derived through random-digit dialing. Titers of C pneumoniae –specific IgG and IgA antibodies were measured using microimmunofluorescence, and positive titers were prospectively defined. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% CIs adjusting for medical, behavioral, and socioeconomic factors. Results— Mean age among cases was 72.3±9.7 years; 50.8% were women. Elevated C pneumoniae IgA titers were associated with increased risk of ischemic stroke after adjusting for hypertension, diabetes mellitus, current cigarette use, atrial fibrillation, and levels of high-density lipoprotein and low-density lipoprotein (adjusted OR, 1.5; 95% CI, 1.0 to 2.2). Elevated IgG titers were not associated with stroke risk (adjusted OR, 1.2; 95% CI, 0.8 to 1.8). There was a trend toward an association of elevated IgA titers with atherosclerotic and lacunar stroke but less so cardioembolic or cryptogenic subtypes. Conclusions— Serologic evidence of C pneumoniae infection is associated with ischemic stroke risk. IgA titers may be a better marker of risk than IgG. This association is independent of other stroke risk factors and is present for atherosclerotic, lacunar, and cardioembolic subypes. Further studies of the effect of C pneumoniae on stroke risk are warranted.

Monochloramine disinfection of municipal water supplies is associated with decreased risk for Legionnaires' disease. We conducted a 2-year, prospective, environmental study to evaluate whether converting from chlorine to monochloramine for water disinfection would decrease Legionella colonization of hot water systems. Water and biofilm samples from 53 buildings were collected for Legionella culture during 6 intervals. Prevalence ratios (PRs) comparing Legionella colonization before and after monochloramine disinfection were adjusted for water system characteristics. Legionella colonized 60% of the hot water systems before monochloramine versus 4% after conversion (PR 0.07, 95% confidence interval 0.03-0.16). The median number of colonized sites per building decreased with monochloramine disinfection. Increased prevalence of Legionella colonization was associated with water heater temperatures < 50 degrees C, buildings taller than 10 stories, and interruptions in water service. Increasing use of monochloramine in water supplies throughout the United States may reduce Legionella transmission and incidence of Legionnaires' disease.

Background: Leukocyte count has been associated with cardiovascular and cerebrovascular disease in several studies. We hypothesized that white blood cell count is associated with endothelial reactivity.Methods and results: Leukocyte count was measured in a sample of stroke-free community participants undergoing brachial artery testing for endothelial reactivity. How-mediated dilation (FMD) during reactive hyperemia was assessed in each subject using high-resolution B-mode ultrasound. Multivariate linear regression was used to calculate the effect of leukocyte count on endothelial reactivity after adjusting for potential confounding factors. Mean age of the 868 participants was 66.7 +/- 8.8 years; 57% were women. Mean leukocyte count was (6.1 +/- 1.8) x 10(9)/L. Each unit increase in leukocyte count was associated with a mean 0.18% decrease in FMD (p = 0.01). After adjusting for other atherosclerosis risk factors, including age, sex, hypertension, diabetes, hyperlipidemia, and smoking, the relationship persisted (mean decrease in FMD per unit leukocyte count = 0.17%, p = 0.02). There was a linear decrease in FMD by quartile of leukocyte count (p = 0.0014). The effect of leukocyte count on FMD was greater for women, those under age 70, and non-diabetics.Conclusions: Relative elevations in leukocyte count are associated with a reduction in brachial artery endothelial reactivity. These findings are consistent with current hypotheses regarding the inflammatory or infectious etiology of risk of atherosclerosis and stroke, but also suggest interactions with demographic and other risk factors. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

We investigated 3 cases of legionnaires disease (LD) that developed in travelers who stayed at a hotel in the United States Virgin Islands where cases of LD occurred in 1981-1982 and in 1998. The temperature of the potable water at the hotel was in a range that could optimally support the growth of Legionella species, and the potable water was colonized with Legionella pneumophila in 1981-1982 and in 2002-2003.

Eighty-five cases community-acquired pneumonia (CAP) in children 5 years or younger, confirmed by chest X-ray, and 185 age-matched control patients with diarrhea or dermatitis from the Outpatient Department at Beijing Children's Hospital were enrolled into this study. Nasopharyngeal swab specimens were obtained from all subjects. Real-time PCR-based fluorescence assays were performed for Chlamydia pneumoniae and Mycoplasma pneumoniae. A nested PCR was also run for C. pneumoniae for comparison of assays. C. pneumoniae was found in 3 (3.5%) of CAP cases and in 4 (2.1%) of controls (P = 0.51). M. pneumoniae was found in 6 (7.1%) of CAP cases and in none of the controls (P = 0.001). The agreement rate of the 2 applied PCR methods used for C. pneumoniae detection was 98.5%. Our study demonstrates that M. pneumoniae may play a significant role in CAP affecting children up to 5 years in China, whereas C. pneumoniae in nasopharyngeal specimens was not associated with CAP in this age group.

Financial support: Ministry of Education, Culture, Sports, Science, and Technology (grant-in-aid for exploratory research no. 14657179). Reprints and correspondence: Dr. Hideaki Kikuta, Dept. of Pediatrics, Hokkaido University Graduate School of Medicine, N15, W-7, Kita-ku, Sapporo 060-8638, Japan (hide-ki@med .hokudai.ac.jp). The Journal of Infectious Diseases 2005;192:351–2 2005 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2005/19202-0022$15.00