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Persons from racial and ethnic minority groups are disproportionately affected by COVID-19, including experiencing increased risk for infection (1), hospitalization (2,3), and death (4,5). Using administrative discharge data, CDC assessed monthly trends in the proportion of hospitalized patients with COVID-19 among racial and ethnic groups in the United States during March-December 2020 by U.S. Census region. Cumulative and monthly age-adjusted COVID-19 proportionate hospitalization ratios (aPHRs) were calculated for racial and ethnic minority patients relative to non-Hispanic White patients. Within each of the four U.S. Census regions, the cumulative aPHR was highest for Hispanic or Latino patients (range = 2.7-3.9). Racial and ethnic disparities in COVID-19 hospitalization were largest during May-July 2020; the peak monthly aPHR among Hispanic or Latino patients was >9.0 in the West and Midwest, >6.0 in the South, and >3.0 in the Northeast. The aPHRs declined for most racial and ethnic groups during July-November 2020 but increased for some racial and ethnic groups in some regions during December. Disparities in COVID-19 hospitalization by race/ethnicity varied by region and became less pronounced over the course of the pandemic, as COVID-19 hospitalizations increased among non-Hispanic White persons. Identification of specific social determinants of health that contribute to geographic and temporal differences in racial and ethnic disparities at the local level can help guide tailored public health prevention strategies and equitable allocation of resources, including COVID-19 vaccination, to address COVID-19-related health disparities and can inform approaches to achieve greater health equity during future public health threats.

Soil-transmitted helminth (STH) infections and diarrheal illness affect billions of people yearly. We conducted a cross-sectional survey in Nueva Santa Rosa, Guatemala to identify factors associated with STH infections and diarrhea using univariable and multivariable logistic regression models. On multivariable analyses, we found associations between STH infections and two factors: school-aged children (odds ratio (OR) vs. adults: 2.35, 95% CI 1.10–4.99) and household drinking water supply classified as ‘other improved’ (OR vs. ‘improved’: 7.00, CI 1.22–40.14). Finished floors in the household vs. natural floors were highly protective (OR 0.16, CI 0.05–0.50) for STH infection. In crowded households (>2.5 people/bedroom), observing water present at handwashing stations was also protective (OR 0.32, CI 0.11–0.98). When adjusted for drying hands, diarrhea was associated with preschool-age children (OR vs. adults: 3.33, CI 1.83–6.04), spending >10 min per round trip collecting water (OR 1.90, CI 1.02–3.56), and having a handwashing station ≤10 m near a sanitation facility (OR 3.69, CI 1.33–10.21). Our study indicates that familiar WASH interventions, such as increasing drinking water quantity and water at handwashing stations in crowded homes, coupled with a hygiene intervention like finished flooring may hold promise for STH and diarrhea control programs. HIGHLIGHTS School-aged children had over 2× the odds of STH infection than adults in our study.; ‘Other improved’ water as household drinking water was associated with 7× the odds of developing STH infection compared with ‘improved’ water.; Households with finished floors were protective for STH infection compared with natural floors.; Improved WASH interventions need consideration for STH and diarrheal disease control programs.

Provision of safe drinking water in the United States is a great public health achievement. However, new waterborne disease challenges have emerged (e.g., aging infrastructure, chlorine-tolerant and biofilm-related pathogens, increased recreational water use). Comprehensive estimates of the health burden for all water exposure routes (ingestion, contact, inhalation) and sources (drinking, recreational, environmental) are needed. We estimated total illnesses, emergency department (ED) visits, hospitalizations, deaths, and direct healthcare costs for 17 waterborne infectious diseases. About 7.15 million waterborne illnesses occur annually (95% credible interval [CrI] 3.88 million-12.0 million), results in 601,000 ED visits (95% CrI 364,000-866,000), 118,000 hospitalizations (95% CrI 86,800-150,000), and 6,630 deaths (95% CrI 4,520-8,870) and incurring US $3.33 billion (95% CrI 1.37 billion-8.77 billion) in direct healthcare costs. Otitis externa and norovirus infection were the most common illnesses. Most hospitalizations and deaths were caused by biofilm-associated pathogens (nontuberculous mycobacteria, Pseudomonas, Legionella), costing US $2.39 billion annually.

Naegleria fowleri is a free-living ameba that causes primary amebic meningoencephalitis (PAM), a rare but usually fatal disease. We analyzed trends in recreational water exposures associated with PAM cases reported during 1978–2018 in the United States. Although PAM incidence remained stable, the geographic range of exposure locations expanded northward.

Areas of rural Alabama may be at risk for re-emergence of soil-transmitted helminthiasis (STH) where environmental conditions are favorable for STH transmission, including in the agricultural Black Belt region. We describe pediatric Medicaid STH visits in Alabama and compare STH visit rates in Black Belt counties with those of non-Black Belt counties. Alabama Medicaid visit claims among children aged 0–18 years who received an STH diagnosis during January 2010–December 2018 were examined. STH-related pediatric visits were uncommon, but several counties with higher STH rates were identified. Visit rates did not differ meaningfully when comparing Black Belt with non-Black Belt region counties (rate ratio: 1.10; 95% CI: 0.73–1.64). Additional studies examining STH prevalence among children living in communities at risk for STH in Alabama can further clarify STH burden and identify communities experiencing environmental and sanitation conditions favorable to STH endemicity.

The objective of this study was to determine sources of Shiga toxin-producing Escherichia coli O157 (STEC O157) infection among visitors to Farm X and develop public health recommendations. A case-control study was conducted. Case-patients were defined as the first ill child (aged ; of these, 62% (18 of 29) yielded STEC O157 highly related by WGS to patient isolates. STEC O157 environmental contamination and fecal shedding by goats at Farm X was extensive. Farms should provide handwashing stations with soap, running water, and disposable towels. Access to animal areas, including animal pens and enclosures, should be limited for young children who are at risk for severe outcomes from STEC O157 infection. National recommendations should be adopted to reduce disease transmission.

Acanthamoeba keratitis (AK) is a painful, potentially blinding eye disease associated with contact lens use and corneal injury. AK, caused by the free-living amoeba Acanthamoeba, is ubiquitous in the environment and has been isolated from municipal water supplies. It can be tolerant of normal chlorine levels in drinking water. An AK outbreak investigated in 2003–2005 in five Illinois counties showed a lower AK age-standardized rate ratio in Cook County than in surrounding counties and was hypothesized to be due in part to reductions in residual disinfectant levels (RDLs) in drinking water. We evaluated RDLs in public water systems in the same five Illinois counties over eight years (2002–2009) using a multivariable model of water system RDL measurements. Fitted RDLs for each county were in the acceptable range by United States Environmental Protection Agency standards for the entire study period. After correcting for multiple testing, two of the surrounding counties had fitted RDLs that differed from Cook County for one year—this pattern differed from the epidemiologic pattern of cases observed in the AK outbreak. Our findings do not support the hypothesis that the development of AK was associated with changes in RDLs in the five Illinois counties.

Urinary tract infections (UTIs) are common and may occur in foodborne Salmonella outbreaks. Using data from PulseNet, the U.S. national molecular subtyping network for foodborne disease surveillance, we analyzed the 9781 Salmonella isolates associated with the 110 outbreaks from 2004 to 2013 that included at least one urine isolate. Within each outbreak, we calculated standardized isolation dates, using these dates in a linear mixed model to estimate the difference in incubation period for infections yielding stool versus urine isolates. We estimate that the incubation period for Salmonella UTIs is on average 10.6 (95% confidence interval 6.0-15.2) days longer than for gastrointestinal illness, suggesting that outbreak investigators should interview UTI patients about a longer time period before illness onset to identify sources of infection.

On October 6, 2017, the Zambia Ministry of Health declared a cholera outbreak in Lusaka. By December, 1,462 cases and 38 deaths had occurred (case fatality rate, 2.6%). We conducted a case-control study to identify risk factors and inform interventions. A case was any person with acute watery diarrhea (≥ 3 loose stools in 24 hours) admitted to a cholera treatment center in Lusaka from December 16 to 21, 2017. Controls were neighbors without diarrhea during the same time period. Up to two controls were matched to each case by age-group (1-4, 5-17, and ≥ 18 years) and neighborhood. Surveyors interviewed cases and controls, tested free chlorine residual (FCR) in stored water, and observed the presence of soap in the home. Conditional logistic regression was used to generate matched odds ratios (mORs) based on subdistricts and age-groups with 95% CIs. We enrolled 82 cases and 132 controls. Stored water in 71% of case homes had an FCR > 0.2 mg/L. In multivariable analyses, those who drank borehole water (mOR = 2.4, CI: 1.1-5.6), had close contact with a cholera case (mOR = 6.2, CI: 2.5-15), and were male (mOR = 2.5, CI: 1.4-5.0) had higher odds of being a cholera case than their matched controls. Based on these findings, we recommended health education about household water chlorination and hygiene in the home. Emergency responses included providing chlorinated water through emergency tanks and maintaining adequate FCR levels through close monitoring of water sources.

Improved water quality reduces diarrhea, but the impact of improved water quality on Ascaris and Trichuris, soil-transmitted helminths (STH) conveyed by the fecal-oral route, is less well described. To assess water quality associations with diarrhea and STH, we conducted a cross-sectional survey in households of south-eastern Guatemala. Diarrhea was self-reported in the past week and month. STH was diagnosed by stool testing using a fecal parasite concentrator method. We explored associations between Escherichia coli-positive source water (water quality) and disease outcomes using survey logistic regression models. Overall, 732 persons lived in 167 households where water was tested. Of these, 79.4% (581/732) had E. coli-positive water, 7.9% (58/732) had diarrhea within the week, 14.1% (103/732) had diarrhea within the month, and 6.6% (36/545) tested positive for Ascaris or Trichuris, including 1% (6/536) who also reported diarrhea. Univariable analysis found a statistically significant association between water quality and STH (odds ratio [OR] = 5.1, 95% confidence interval [CI] = 1.1–24.5) but no association between water quality and diarrhea. Waterborne transmission and effects of water treatment on STH prevalence should be investigated further. If a causal relationship is found, practices such as household water treatment including filtration might be useful adjuncts to sanitation, hygiene, and deworming in STH control programs.

On October 6, 2017, an outbreak of cholera was declared in Zambia after laboratory confirmation of Vibrio cholerae O1, biotype El Tor, serotype Ogawa, from stool specimens from two patients with acute watery diarrhea. The two patients had gone to a clinic in Lusaka, the capital city, on October 4. Cholera cases increased rapidly, from several hundred cases in early December 2017 to approximately 2,000 by early January 2018 (Figure). In collaboration with partners, the Zambia Ministry of Health (MoH) launched a multifaceted public health response that included increased chlorination of the Lusaka municipal water supply, provision of emergency water supplies, water quality monitoring and testing, enhanced surveillance, epidemiologic investigations, a cholera vaccination campaign, aggressive case management and health care worker training, and laboratory testing of clinical samples. In late December 2017, a number of water-related preventive actions were initiated, including increasing chlorine levels throughout the city's water distribution system and placing emergency tanks of chlorinated water in the most affected neighborhoods; cholera cases declined sharply in January 2018. During January 10-February 14, 2018, approximately 2 million doses of oral cholera vaccine were administered to Lusaka residents aged ≥1 year. However, in mid-March, heavy flooding and widespread water shortages occurred, leading to a resurgence of cholera. As of May 12, 2018, the outbreak had affected seven of the 10 provinces in Zambia, with 5,905 suspected cases and a case fatality rate (CFR) of 1.9%. Among the suspected cases, 5,414 (91.7%), including 98 deaths (CFR = 1.8%), occurred in Lusaka residents.

In 2016, a multijurisdictional team investigated an outbreak of Shiga toxin-producing Escherichia coli (STEC) serogroup O121 and O26 infections linked to contaminated flour from a large domestic producer.A case was defined as infection with an outbreak strain in which illness onset was between December 21, 2015, and September 5, 2016. To identify exposures associated with the outbreak, outbreak cases were compared with non-STEC enteric illness cases, matched according to age group, sex, and state of residence. Products suspected to be related to the outbreak were collected for STEC testing, and a common point of contamination was sought. Whole-genome sequencing was performed on isolates from clinical and food samples.A total of 56 cases were identified in 24 states. Univariable exact conditional logistic-regression models of 22 matched sets showed that infection was significantly associated with the use of one brand of flour (odds ratio, 21.04; 95% confidence interval [CI], 4.69 to 94.37) and with tasting unbaked homemade dough or batter (odds ratio, 36.02; 95% CI, 4.63 to 280.17). Laboratory testing isolated the outbreak strains from flour samples, and whole-genome sequencing revealed that the isolates from clinical and food samples were closely related to one another genetically. Trace-back investigation identified a common flour-production facility.This investigation implicated raw flour as the source of an outbreak of STEC infections. Although it is a low-moisture food, raw flour can be a vehicle for foodborne pathogens.

Background Enteric fever in the United States has been primarily associated with travel and with worrisome changes in global patterns of antimicrobial resistance. We present the first comprehensive report of National Typhoid and Paratyphoid Fever Surveillance System (NTPFS) data for a 5-year period (2008-2012). Methods We reviewed data on laboratory-confirmed cases reported to NTPFS, and related antimicrobial susceptibility results of Salmonella Typhi and Paratyphi A isolates sent for testing by participating public health laboratories to the Centers for Disease Control and Prevention's National Antimicrobial Resistance Monitoring System laboratory. Results During 2008-2012, 2341 enteric fever cases were reported, 80% typhoid and 20% paratyphoid A. The proportion caused by paratyphoid A increased from 16% (2008) to 22% (2012). Foreign travel within 30 days preceding illness onset was reported by 1961 (86%) patients (86% typhoid and 92% paratyphoid A). Travel to southern Asia was common (82% for typhoid, 97% for paratyphoid A). Among 1091 (58%) typhoid and 262 (56%) paratyphoid A isolates tested for antimicrobial susceptibility, the proportion resistant to nalidixic acid (NAL-R) increased from 2008 to 2012 (Typhi, 60% to 68%; Paratyphi A, 91% to 94%). Almost all NAL-R isolates were resistant or showed decreased susceptibility to ciprofloxacin. Resistance to at least ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole (multidrug resistant [MDR]) was limited to Typhi isolates, primarily acquired in southern Asia (13%). Most MDR isolates were also NAL-R. Conclusions Enteric fever in the United States is primarily associated with travel to southern Asia, and increasing resistance is adding to treatment challenges. A bivalent typhoid and paratyphoid vaccine is needed.

Diarrheal illness, a common occurrence among people living with human immunodeficiency virus (PLHIV), is largely preventable through access to safe drinking water quality, sanitation, and hygiene (WASH) facilities. We examined WASH characteristics among households with and without HIV-positive residents enrolled in the Global Enteric Multicenter Study (GEMS) in rural Western Kenya. Using univariable logistic regression, we examined differences between HIV-positive and HIV-negative households in regard to WASH practices. Among HIV-positive households, we explored the relationship between the length of time knowing their HIV status and GEMS enrollment. No statistically significant differences were apparent in the WASH characteristics among HIV-positive and HIV-negative households. However, we found differences in the WASH characteristics among HIV-positive households who were aware of their HIV status ≥ 30 days before enrollment compared with HIV-positive households who found out their status < 30 days before enrollment or thereafter. Significantly more households aware of their HIV-positive status before enrollment reported treating their drinking water (odds ratio [OR] confidence interval [CI]: 2.34 [1.12, 4.86]) and using effective water treatment methods (OR [CI]: 9.6 [3.09, 29.86]), and had better drinking water storage practices. This suggests that within this region of Kenya, HIV programs are effective in promoting the importance of practicing positive WASH-related behaviors among PLHIV.

Background Urinary tract infections (UTI) are common bacterial infections that may occur as a part of foodborne outbreaks. Salmonella, a less common cause of UTI, has been identified during foodborne outbreaks, but the epidemiology and pathogenesis are poorly understood. Methods PulseNet, the United States national molecular subtyping network for foodborne disease surveillance, was used to identify Salmonella isolates associated with outbreaks from 2004 to 2013 containing at least one urine and one stool isolate in which the duration was ≤1 year and a food vehicle was suspected or confirmed. We standardized isolation dates across outbreaks by calculating the mean date for stool isolation within an outbreak and subtracting this from the date of each stool/urine isolate in that outbreak. A linear-mixed model with random effect for stool/urine was used to estimate the difference in incubation periods between stool/urine isolates. We also surveyed patients from a 2012 Salmonella Cubana outbreak with many urinary isolates and associated with sprouts, to ask about diarrhea, UTI symptoms, diagnosis, and treatment. Descriptive statistics were calculated. Results Urine isolates had later isolation dates than stool isolates for 102 of the 110 outbreaks identified. The average difference between stool and urine isolates was 10.6 days (95% CI: 6.0, 15.2). Seven women from the Salmonella Cubana outbreak were reached. All women were diagnosed with either a UTI (6/7 = 86%) and/or kidney infection (2/7 = 29%) and were treated with antibiotics (7/7 = 100%). All six women completing the survey reported multiple signs and/or symptoms including frequency, urgency, dysuria, and hematuria with only two women reporting diarrhea prior to UTI. Conclusion Salmonella UTI seen during foodborne outbreaks are symptomatic foodborne infections not associated with diarrhea and appear to have a longer incubation period than Salmonella gastrointestinal (GI) illness. A 13- to 16-day incubation period for Salmonella UTI may be more appropriate, calculated by adding a 3- to 4-day GI illness incubation period plus delay in obtaining a stool isolate. Foodborne UTI investigation may need to change as the current method of obtaining a food history for the 6–72 hours prior to illness does not accurately reflect the incubation period for Salmonella UTI. Disclosures All authors: No reported disclosures.

Background Diarrheal disease remains among the leading causes of global mortality in children younger than 5 years. Exposure to domestic animals may be a risk factor for diarrheal disease. The objectives of this study were to identify animal-related exposures associated with cases of moderate-to-severe diarrhea (MSD) in children in rural western Kenya, and to identify the major zoonotic enteric pathogens present in domestic animals residing in the homesteads of case and control children. Methodology/Principal findings We characterized animal-related exposures in a subset of case and control children (n = 73 pairs matched on age, sex and location) with reported animal presence at home enrolled in the Global Enteric Multicenter Study in western Kenya, and analysed these for an association with MSD. We identified potentially zoonotic enteric pathogens in pooled fecal specimens collected from domestic animals resident at children’s homesteads. Variables that were associated with decreased risk of MSD were washing hands after animal contact (matched odds ratio [MOR] = 0.2; 95% CI 0.08–0.7), and presence of adult sheep that were not confined in a pen overnight (MOR = 0.1; 0.02–0.5). Variables that were associated with increased risk of MSD were increasing number of sheep owned (MOR = 1.2; 1.0–1.5), frequent observation of fresh rodent excreta (feces/urine) outside the house (MOR = 7.5; 1.5–37.2), and participation of the child in providing water to chickens (MOR = 3.8; 1.2–12.2). Of 691 pooled specimens collected from 2,174 domestic animals, 159 pools (23%) tested positive for one or more potentially zoonotic enteric pathogens (Campylobacter jejuni, C. coli, non-typhoidal Salmonella, diarrheagenic E. coli, Giardia, Cryptosporidium, or rotavirus). We did not find any association between the presence of particular pathogens in household animals, and MSD in children. Conclusions and significance Public health agencies should continue to promote frequent hand washing, including after animal contact, to reduce the risk of MSD. Future studies should address specific causal relations of MSD with sheep and chicken husbandry practices, and with the presence of rodents., Author summary Diarrheal disease is one of the leading causes of death worldwide in children younger than 5 years. Exposure to animals in homes may be a risk factor for diarrhea in children. To test this, we studied a subset of children in the Global Enteric Multicenter Study (GEMS) in rural western Kenya, whose caretakers reported the presence of animals in the children’s homesteads. In GEMS, children with moderate-to-severe diarrhea (MSD) were matched with children without MSD, who were of the same sex, similar age and who lived in the same area. We asked questions about the presence and management of animals in the children’s homesteads. We also collected fecal specimens from domestic animals present at homesteads and tested these for microbes that could cause diarrheal disease in children. We found that children who reportedly washed their hands after animal contact, and who lived in a homestead with adult sheep that were not confined to a pen overnight, had a lower risk of MSD. Children who lived in homesteads that owned more adult sheep, or in which fresh rodent droppings were observed frequently, had a higher risk of MSD, as did children who reportedly participated in providing water to chickens in the homestead. We did not find any association between the presence of particular pathogens in household animals, and MSD in children.

Recently, health measurements have broadened to include the assessment of quality of life (QOL). This study was conducted to assess whether the short form of the World Health Organization (WHO) QOL questionnaire (WHOQOL-BREF) was an effective tool for measuring morbidity due to Schistosoma mansoni infection and whether it could detect an impact of treatment with praziquantel. A total of 724 adults 18–85 years of age were enrolled. At baseline, S. mansoni prevalence was 73.2% by stool examination and 75.4% by circulating cathodic antigen, and there was no association between infection status and WHOQOL-BREF scores. Six months after treatment, S. mansoni prevalence was lower and the proportion of persons with higher WHOQOL-BREF scores significantly increased among persons who were infected at baseline. However, a similar increase was observed in persons not infected at baseline. In areas of high prevalence, the WHOQOL-BREF may not be able to detect the benefits of schistosomiasis control programs.

Cryptosporidium is a common cause of sporadic diarrheal disease and outbreaks in the United States. Increasingly, immunochromatography-based rapid cartridge assays (RCAs) are providing community laboratories with a quick cryptosporidiosis diagnostic method. In the current study, the Centers for Disease Control and Prevention (CDC), the Association of Public Health Laboratories (APHL), and four state health departments evaluated RCA-positive samples obtained during routine Cryptosporidium testing. All samples underwent "head to head" re-testing using both RCA and direct fluorescence assay (DFA). Community level results from three sites indicated that 54.4% (166/305) of Meridian ImmunoCard STAT! positives and 87.0% (67/77) of Remel Xpect positives were confirmed by DFA. When samples were retested by RCA at state laboratories and compared with DFA, 83.3% (155/186) of Meridian ImmunoCard STAT! positives and 95.2% (60/63) of Remel Xpect positives were confirmed. The percentage of confirmed community results varied by site: Minnesota, 39.0%; New York, 63.9%; and Wisconsin, 72.1%. The percentage of confirmed community results decreased with patient age; 12.5% of community positive tests could be confirmed by DFA for patients 60 years of age or older. The percentage of confirmed results did not differ significantly by sex, storage temperature, time between sample collection and testing, or season. Findings from this study demonstrate a lower confirmation rate of community RCA positives when compared to RCA positives identified at state laboratories. Elucidating the causes of decreased test performance in order to improve overall community laboratory performance of these tests is critical for understanding the epidemiology of cryptosporidiosis in the United States (US).

Nuclear magnetic resonance (NMR) spectroscopy, traditionally used in analytical chemistry, has recently been introduced to studies of metabolite composition of biological fluids and tissues. Metabolite levels change over time, and providing a tool for better extraction of NMR peaks exhibiting periodic behavior is of interest. We propose a method in which NMR peaks are clustered based on periodic behavior. Periodic regression is used to obtain estimates of the parameter corresponding to period for individual NMR peaks. A mixture model is then used to develop clusters of peaks, taking into account the variability of the regression parameter estimates. Methods are applied to NMR data collected from human blood plasma over a 24-hour period. Simulation studies show that the extra variance component due to the estimation of the parameter estimate should be accounted for in the clustering procedure.

Integrated vector management is a pillar of the South Asian visceral leishmaniasis (VL) elimination program, but the best approach remains a matter of debate. Sand fly seasonality was determined in 40 houses sampled monthly. The impact of interventions on Phlebotomus argentipes density was tested from 2006–2007 in a cluster-randomized trial with four arms: indoor residual spraying (IRS), insecticide-treated nets (ITNs), environmental management (EVM), and no intervention. Phlebotomus argentipes density peaked in March with the highest proportion of gravid females in May. The EVM (mud plastering of wall and floor cracks) showed no impact. The IRS and ITNs were associated with a 70–80% decrease in male and female P. argentipes density up to 5 months post intervention. Vector density rebounded by 11 months post-IRS, whereas ITN-treated households continued to show significantly lower density compared with households without intervention. Our data suggest that both IRS and ITNs may help to improve VL control in Bangladesh.

We assessed the performance characteristics of two rK39 immunochromatographic tests, a direct agglutination test (DAT), and an indirect immunofluorescent antibody test (IFAT) in the site of a new epidemic of visceral leishmaniasis (VL) in northwestern Ethiopia. The study population was composed of 179 patients with suspected VL and 67 controls. The sensitivities of Kalazar Detect(®), DiaMed-IT Leish(®), DAT, and IFAT in 35 polymerase chain reaction-confirmed VL cases were 94.3%, 91.4%, 91.4%, and 100%, respectively, and the specificities were 98.5%, 94%, 98.5%, and 98.5%, respectively. In a Bayesian latent class analysis of all 246 specimens, the estimated sensitivities were 90.5%, 89%, 88.8%, and 96% for Kalazar Detect(®), DiaMed-IT Leish(®), DAT, and IFAT, respectively; DAT showed the highest estimated specificity (97.4%). Both rK39 immunochromatographic tests perform as well as DAT, and are suitable for VL diagnosis in first-level health centers in this area of Ethiopia. Sí

Soil-transmitted helminth (STH) infections affect persons living in areas with poor water, sanitation, and hygiene (WASH). Preschool-aged children (PSAC) and school-aged children (SAC) are disproportionately affected by STH infections. We aimed to identify WASH factors associated with STH infection among PSAC and SAC in Kibera, Kenya. In 2012, households containing a PSAC or SAC were randomly selected from those enrolled in the International Emerging Infections Program, a population-based surveillance system. We administered a household questionnaire, conducted environmental assessments for WASH, and tested three stools from each child for STH eggs using the Kato-Katz method. WASH factors were evaluated for associations with STH infection using univariable and multivariable Poisson regression. Any-STH prevalence was 40.8% among 201 PSAC and 40.0% among 475 SAC enrolled. Using the Joint Monitoring Programme water and sanitation classifications, 1.5% of households reported piped water on premises versus 98.5% another improved water source; 1.3% reported improved sanitation facilities, while 81.7% used shared sanitation facilities, 13.9% had unimproved facilities, and 3.1% reported no facilities (open defecation). On univariable analysis, STH infection was significantly associated with a household toilet located off-premises (prevalence ratio (PR) = 1.33; p = 0.047), while always treating water (PR = 0.81; p = 0.04), covering drinking water containers (PR = 0.75; p = 0.02), using clean towels during hand drying (PR = 0.58; p

We evaluated the performance of a point-of-contact circulating cathodic antigen assay (POC-CCA) to detect schistosome infections in primary school children (N = 1,801) living in areas with low, moderate, and high Schistosoma mansoni prevalence in western Kenya. The commercially available assay (CCA-1) and a second, experimental formulation (CCA-2) were compared against Kato-Katz stool examinations and an anti-schistosome enzyme-linked immunosorbent assay (ELISA). A latent class model based on the four tests was used to establish “true infection status” in three different zones based on their distance from Lake Victoria. As a screening tool for community treatment according to World Health Organization (WHO) guidelines, the Kato-Katz examination was in closest agreement with the latent class model, followed by the experimental CCA-2, soluble adult worm antigen preparation (SWAP) ELISA, and CCA-1, which had high sensitivity compared with the other tests but was consistently the least specific. Our experience suggests that POC-CCA tests offer a field-friendly alternative to Kato-Katz, but need further interpretation for appropriate field use.

We conducted a longitudinal analysis of 117 lymphedema patients in a filariasis-endemic area of Haiti during 1995-2008. No difference in lymphedema progression between those who received or did not receive mass drug administration (MDA) was found on measures of foot (P = 0.24), ankle (P = 0.87), or leg (P = 0.46) circumference; leg volume displacement (P = 0.09), lymphedema stage (P = 0.93), or frequency of adenolymphangitis (ADL) episodes (P = 0.57). Rates of ADL per year were greater after initiation of MDA among both groups (P < 0.01). Nevertheless, patients who received MDA reported improvement in four areas of lymphedema-related quality of life (P ≤ 0.01). Decreases in foot and ankle circumference and ADL episodes were observed during the 1995-1998 lymphedema management study (P ≤ 0.01). This study represents the first longitudinal, quantitative, leg-specific analysis examining the clinical effect of diethylcarbamazine on lymphedema progression and ADL episodes.

Nuclear magnetic resonance (NMR) spectroscopy, traditionally used in analytical chemistry, has recently been introduced to studies of metabolite composition of biological fluids and tissues. Metabolite levels change over time, and providing a tool for better extraction of NMR peaks exhibiting periodic behavior is of interest. We propose a method in which NMR peaks are clustered based on periodic behavior. Periodic regression is used to obtain estimates of the parameter corresponding to period for individual NMR peaks. A mixture model is then used to develop clusters of peaks, taking into account the variability of the regression parameter estimates. Methods are applied to NMR data collected from human blood plasma over a 24-hour period. Simulation studies show that the extra variance component due to the estimation of the parameter estimate should be accounted for in the clustering procedure.

Immunoglobulin (Ig) GM and KM allotypes, genetic markers of γ and κ chains, are associated with humoral immune responsiveness. Previous studies have shown the relationships between GM6-carrying haplotypes and susceptibility to malaria infection in children and adults; however, the role of the genetic markers in placental malaria (PM) infection and PM with HIV co-infection during pregnancy has not been investigated. We examined the relationship between the gene polymorphisms of Ig GM6 and KM allotypes and the risk of PM infection in pregnant women with known HIV status. DNA samples from 728 pregnant women were genotyped for GM6 and KM alleles using polymerase chain reaction-restriction fragment length polymorphism method. Individual GM6 and KM genotypes and the combined GM6 and KM genotypes were assessed in relation to PM in HIV-1 negative and positive women, respectively. There was no significant effect of individual GM6 and KM genotypes on the risk of PM infection in HIV-1 negative and positive women. However, the combination of homozygosity for GM6(+) and KM3 was associated with decreased risk of PM (adjusted OR, 0.25; 95% CI, 0.08-0.8; P = 0.019) in HIV-1 negative women while in HIV-1 positive women the combination of GM6(+/-) with either KM1-3 or KM1 was associated with increased risk of PM infection (adjusted OR, 2.10; 95% CI, 1.18-3.73; P = 0.011). Hardy-Weinberg Equilibrium (HWE) tests further showed an overall significant positive F(is) (indication of deficit in heterozygotes) for GM6 while there was no deviation for KM genotype frequency from HWE in the same population. These findings suggest that the combination of homozygous GM6(+) and KM3 may protect against PM in HIV-1 negative women while the HIV-1 positive women with heterozygous GM6(+/-) combined with KM1-3 or KM1 may be more susceptible to PM infection. The deficit in heterozygotes for GM6 further suggests that GM6 could be under selection likely by malaria infection.

Macrophage migration inhibitory factor (MIF) is a pluripotent factor produced by a variety of cells. It plays an important biological role in the regulation of pregnancy and has been shown to influence malaria pathogenesis. In this study, the levels of MIF in the peripheral, cord and placental intervillous blood (IVB) plasma collected from women residing in a malaria endemic region of Central India was determined and its association with malaria in pregnancy and birth outcomes was investigated. MIF levels were significantly different in IVB, peripheral, and cord plasma, with IVB plasma having the highest MIF levels and peripheral plasma having the lowest. Placental malaria positive women had significantly higher IVB plasma MIF levels than placental malaria negative women, but this relationship was not seen in peripheral or cord plasma MIF levels. In addition, the odds of stillbirth and low birth weight deliveries for the uppermost placental MIF quartile (irrespective of placental malaria status) was significantly higher than that of the lowest placental MIF quartile, supporting the hypothesis that elevated concentrations of placental MIF may be associated with an increased risk of adverse birth outcome.

Pregnant women have abundant natural killer (NK) cells in their placenta, and NK cell function is regulated by polymorphisms of killer cell immunoglobulin-like receptors (KIRs). Previous studies report different roles of NK cells in the immune responses to placental malaria (PM) and human immunodeficiency virus (HIV-1) infections. Given these references, the aim of this study was to determine the association between KIR gene content polymorphism and PM infection in pregnant women of known HIV-1 status. Sixteen genes in the KIR family were analyzed in 688 pregnant Kenyan women. Gene content polymorphisms were assessed in relation to PM in HIV-1 negative and HIV-1 positive women, respectively. Results showed that in HIV-1 negative women, the presence of the individual genes KIR2DL1 and KIR2DL3 increased the odds of having PM, and the KIR2DL2/KIR2DL2 homozygotes were associated with protection from PM. However, the reverse relationship was observed in HIV-1 positive women, where the presence of individual KIR2DL3 was associated with protection from PM, and KIR2DL2/KIR2DL2 homozygotes increased the odds for susceptibility to PM. Further analysis of the HIV-1 positive women stratified by CD4 counts showed that this reverse association between KIR genes and PM remained only in the individuals with high CD4 cell counts but not in those with low CD4 cell counts. Collectively, these results suggest that inhibitory KIR2DL2 and KIR2DL3, which are alleles of the same locus, play a role in the inverse effects on PM and PM/HIV co-infection and the effect of KIR genes on PM in HIV positive women is dependent on high CD4 cell counts. In addition, analysis of linkage disequilibrium (LD) of the PM relevant KIR genes showed strong LD in women without PM regardless of their HIV status while LD was broken in those with PM, indicating possible selection pressure by malaria infection on the KIR genes.

Although accurate assessment of the prevalence of Schistosoma mansoni is important for the design and evaluation of control programs, the most widely used tools for diagnosis are limited by suboptimal sensitivity, slow turn-around-time, or inability to distinguish current from former infections. Recently, two tests that detect circulating cathodic antigen (CCA) in urine of patients with schistosomiasis became commercially available. As part of a larger study on schistosomiasis prevalence in young children, we evaluated the performance and diagnostic accuracy of these tests—the carbon test strip designed for use in the laboratory and the cassette format test intended for field use. In comparison to 6 Kato-Katz exams, the carbon and cassette CCA tests had sensitivities of 88.4% and 94.2% and specificities of 70.9% and 59.4%, respectively. However, because of the known limitations of the Kato-Katz assay, we also utilized latent class analysis (LCA) incorporating the CCA, Kato-Katz, and schistosome-specific antibody results to determine their sensitivities and specificities. The laboratory-based CCA test had a sensitivity of 91.7% and a specificity of 89.4% by LCA while the cassette test had a sensitivity of 96.3% and a specificity of 74.7%. The intensity of the reaction in both urine CCA tests reflected stool egg burden and their performance was not affected by the presence of soil transmitted helminth infections. Our results suggest that urine-based assays for CCA may be valuable in screening for S. mansoni infections., Author Summary Control efforts for schistosomiasis have in part been hampered by the lack of a sensitive and accurate test that can be utilized to rapidly map the prevalence of the disease in different areas. Recently, new tests have become commercially available that may address this problem. This study was designed to compare the new tests, which detect a schistosome antigen in patients' urine, with more traditional tests that look for parasite eggs in stool or anti-parasite antibodies in serum. We found that the new tests performed very well to detect schistosomiasis in children in western Kenya, an area with a high prevalence of Schistosoma mansoni infections. There was no apparent effect of soil transmitted helminth infections on the performance of the tests and the intensity of the antigen detection assays correlated well with the levels of S. mansoni eggs in the stool and schistosome-specific antibody in serum. Additional evaluation is needed in areas with lower schistosomiasis prevalence and intensity levels but we believe that point of contact testing of urine for schistosome antigen could be an effective tool in schistosomiasis mapping and control efforts.

Background Patients with Chagas disease have migrated to cities, where obesity, hypertension and other cardiac risk factors are common. Methodology/Principal Findings The study included adult patients evaluated by the cardiology service in a public hospital in Santa Cruz, Bolivia. Data included risk factors for T. cruzi infection, medical history, physical examination, electrocardiogram, echocardiogram, and contact 9 months after initial data collection to ascertain mortality. Serology and PCR for Trypanosoma cruzi were performed. Of 394 participants, 251 (64%) had confirmed T. cruzi infection by serology. Among seropositive participants, 109 (43%) had positive results by conventional PCR; of these, 89 (82%) also had positive results by real time PCR. There was a high prevalence of hypertension (64%) and overweight (body mass index [BMI] >25; 67%), with no difference by T. cruzi infection status. Nearly 60% of symptomatic congestive heart failure was attributed to Chagas cardiomyopathy; mortality was also higher for seropositive than seronegative patients (p = 0.05). In multivariable models, longer residence in an endemic province, residence in a rural area and poor housing conditions were associated with T. cruzi infection. Male sex, increasing age and poor housing were independent predictors of Chagas cardiomyopathy severity. Males and participants with BMI ≤25 had significantly higher likelihood of positive PCR results compared to females or overweight participants. Conclusions Chagas cardiomyopathy remains an important cause of congestive heart failure in this hospital population, and should be evaluated in the context of the epidemiological transition that has increased risk of obesity, hypertension and chronic cardiovascular disease., Author Summary Latin America is undergoing a transition from disease patterns characteristic of developing countries with high rates of infectious disease and premature deaths to a pattern more like industrialized countries, in which chronic conditions such as obesity, hypertension and diabetes are more common. Many rural residents with Chagas disease have now migrated to cities, taken on new habits and may suffer from both types of disease. We studied heart disease among 394 adults seen by cardiologists in a public hospital in the city of Santa Cruz, Bolivia; 64% were infected with T. cruzi, the parasite that causes Chagas disease. Both T. cruzi infected and uninfected patients had a high rate of hypertension (64%) and overweight (67%), with no difference by infection status. Nearly 60% of symptomatic congestive heart failure was due to Chagas disease; mortality was also higher for infected than uninfected patients. Males and older patients had more severe Chagas heart disease. Chagas heart disease remains an important cause of congestive heart failure in this hospital population, but often occurs in patients who also have obesity, hypertension and/or other cardiac risk factors.

Despite the clear public health benefit of insecticide-treated bednets (ITNs), the impact of malaria transmission-reduction by vector control on the spread of drug resistance is not well understood. In the present study, the effect of sustained transmission reduction by ITNs on the prevalence of Plasmodium falciparum gene mutations associated with resistance to the antimalarial drugs sulfadoxine-pyrimethamine (SP) and chloroquine (CQ) in children under the age of five years was investigated during an ITN trial in Asembo area, western Kenya. During the ITN trial, the national first line antimalarial treatment changed from CQ to SP. Smear-positive samples collected from cross sectional surveys prior to ITN introduction (baseline, n = 250) and five years post-ITN intervention (year 5 survey, n = 242) were genotyped for single nucleotide polymorphisms (SNPs) at dhfr-51, 59, 108, 164 and dhps-437, 540 (SP resistance), and pfcrt-76 and pfmdr1-86 (CQ resistance). The association between the drug resistance mutations and epidemiological variables was evaluated. There were significant increases in the prevalence of SP dhps mutations and the dhfr/dhps quintuple mutant, and a significant reduction in the proportion of mixed infections detected at dhfr-51, 59 and dhps-437, 540 SNPs from baseline to the year 5 survey. There was no change in the high prevalence of pfcrt-76 and pfmdr1-86 mutations. Multivariable regression analysis further showed that current antifolate use and year of survey were significantly associated with more SP drug resistance mutations. These results suggest that increased antifolate drug use due to drug policy change likely led to the high prevalence of SP mutations 5 years post-ITN intervention and reduced transmission had no apparent effect on the existing high prevalence of CQ mutations. There is no evidence from the current study that sustained transmission reduction by ITNs reduces the prevalence of genes associated with malaria drug resistance.

Background The mechanisms underlying the pathogenesis of cerebral malaria (CM) syndrome are not well understood. Previous studies have shown a strong association of inflammatory chemokines, apoptotic markers and angiogenic molecules with CM associated mortality. Recognizing the importance of angiopoietins (ANG) in the pathogenesis of CM, a retrospective investigation was carried out in a hospital cohort of malaria patients with Plasmodium infection in central India to determine if these factors could be suitable markers of CM associated severity. Methods Patients enrolled in the study were clinically characterized as healthy controls (HC), mild malaria (MM), CM survivors (CMS) and CM non-survivors (CMNS) based on their malaria status and hospital treatment outcome. Plasma ANG-1 and ANG-2 levels were assessed using sandwich ELISA. Receiver operating characteristic (ROC) curve analysis was used to calculate area under the curve (AUC) for each biomarker in order to assess predictive accuracy of individual biomarkers. Results The plasma levels of ANG-1 were lower in CMS and CMNS compared to control groups (mild malaria and healthy controls) at the time of hospital admission. On the contrary, ANG-2 levels positively correlated with malaria severity and were significantly higher in CMNS. The ratio of ANG-2/ANG-1 was highest in CMNS compared to other groups. Receiver operating characteristic curves revealed that compared to ANG-1 (AUC = 0.35), ANG-2 (AUC = 0.95) and ratio of ANG-2/ANG-1 (AUC = 0.90) were better markers to discriminate CMNS from MM cases. However, they were less specific in predicting fatal outcome amongst CM cases at the time of hospital admission. Conclusion These results suggest that at the time of admission plasma levels of ANG-2 and ratio of ANG-2/ANG-1 are clinically informative biomarkers to predict fatal CM from MM cases while they have limited usefulness in discriminating fatal CM outcomes in a pool of CM cases in endemic settings of Central India.