Comparison of Tuberculin Skin Testing and Interferon-γ Release Assays in Predicting Tuberculosis Disease.

Importance: Elimination of tuberculosis (TB) disease in the US hinges on the ability of tests to detect individual risk of developing disease to inform prevention. The relative performance of 3 available TB tests-the tuberculin skin test (TST) and 2 interferon-γ release assays (IGRAs; QuantiFERON-TB Gold In-Tube [QFT-GIT] and SPOT.TB [TSPOT])-in predicting TB disease development in the US remains unknown. Objective: To compare the performance of the TST with the QFT-GIT and TSPOT IGRAs in predicting TB disease in high-risk populations. Design, Setting, and Participants: This prospective diagnostic study included participants at high risk of TB infection (TBI) or progression to TB disease at 10 US sites between 2012 and 2020. Participants of any age who had close contact with a case patient with infectious TB, were born in a country with medium or high TB incidence, had traveled recently to a high-incidence country, were living with HIV infection, or were from a population with a high local prevalence were enrolled from July 12, 2012, through May 5, 2017. Participants were assessed for 2 years after enrollment and through registry matches until the study end date (November 15, 2020). Data analysis was performed in June 2023. Exposures: At enrollment, participants were concurrently tested with 2 IGRAs (QFT-GIT from Qiagen and TSPOT from Oxford Immunotec) and the TST. Participants were classified as case patients with incident TB disease when diagnosed more than 30 days from enrollment. Main Outcomes and Measures: Estimated positive predictive value (PPV) ratios from generalized estimating equation models were used to compare test performance in predicting incident TB. Incremental changes in PPV were estimated to determine whether predictive performance significantly improved with the addition of a second test. Case patients with prevalent TB were examined in sensitivity analysis. Results: A total of 22 020 eligible participants were included in this study. Their median age was 32 (range, 0-102) years, more than half (51.2%) were male, and the median follow-up was 6.4 (range, 0.2-8.3) years. Most participants (82.0%) were born outside the US, and 9.6% were close contacts. Tuberculosis disease was identified in 129 case patients (0.6%): 42 (0.2%) had incident TB and 87 (0.4%) had prevalent TB. The TSPOT and QFT-GIT assays performed significantly better than the TST (PPV ratio, 1.65 [95% CI, 1.35-2.02] and 1.47 [95% CI, 1.22-1.77], respectively). The incremental gain in PPV, given a positive TST result, was statistically significant for positive QFT-GIT and TSPOT results (1.64 [95% CI, 1.40-1.93] and 1.94 [95% CI, 1.65-2.27], respectively). Conclusions and Relevance: In this diagnostic study assessing predictive value, IGRAs demonstrated superior performance for predicting incident TB compared with the TST. Interferon-γ release assays provided a statistically significant incremental improvement in PPV when a positive TST result was known. These findings suggest that IGRA performance may enhance decisions to treat TBI and prevent TB.

Mumps vaccine effectiveness of a 3rd dose of measles, mumps, rubella vaccine in school settings during a mumps outbreak -- Arkansas, 2016-2017.

Objectives: The largest mumps outbreak in the United States since 2006 occurred in Arkansas during the 2016-17 school year. An additional dose (third dose) of measles-mumps-rubella vaccine (MMR3) was offered to school children. We evaluated the vaccine effectiveness (VE) of MMR3 compared with two doses of MMR for preventing mumps among school-aged children during the outbreak. Study design: A generalized linear mixed effects model was used to estimate the incremental vaccine effectiveness (VE) of a third dose of MMR compared with two doses of MMR for preventing mumps. Methods: We obtained school enrollment, immunization status and mumps case status from school registries, Arkansas's immunization registry, and Arkansas's mumps surveillance system, respectively. We included students who previously received 2 doses of MMR in schools with ≥1 mumps case after the MMR3 clinic. We used a generalized linear mixed model to estimate VE of MMR3 compared with two doses of MMR. Results: Sixteen schools with 9272 students were included in the analysis. Incremental VE of MMR3 versus a two-dose MMR regimen was 52.7% (95% confidence interval [CI]: -3.6%‒78.4%) overall and in 8 schools with high mumps transmission it was 64.0% (95% CI: 1.2%‒86.9%). MMR3 VE was higher among middle compared with elementary school students (68.5% [95% CI: -30.2%‒92.4%] vs 37.6% [95% CI: -62.5%‒76.1%]); these differences were not statistically significant. Conclusion: Our findings suggest MMR3 provided additional protection from mumps compared with two MMR doses in elementary and middle school settings during a mumps outbreak.

Using Electronic Health Record Data to Measure the Latent Tuberculosis Infection Care Cascade in Safety-Net Primary Care Clinics.

Introduction: Prevention of tuberculosis disease through diagnosis and treatment of latent tuberculosis infection is critical for achieving tuberculosis elimination in the U.S. Diagnosis and treatment of latent tuberculosis infection in safety-net primary care settings that serve patients at risk for tuberculosis may increase uptake of this prevention effort and accelerate progress toward elimination. Optimizing tuberculosis prevention in these settings requires measuring the latent tuberculosis infection care cascade (testing, diagnosis, and treatment) and identifying gaps to develop solutions to overcome barriers. We used electronic health record data to describe the latent tuberculosis infection care cascade and identify gaps among a network of safety-net primary care clinics. Methods: Electronic health record data for patients seen in the OCHIN Clinical Network, the largest network of safety-net clinics in the U.S., between 2012 and 2019 were extracted. electronic health record data were used to measure the latent tuberculosis infection care cascade: patients who met tuberculosis screening criteria on the basis of current recommendations were tested for tuberculosis infection, diagnosed with latent tuberculosis infection, and prescribed treatment for latent tuberculosis infection. Outcomes were stratified by diagnostic test and treatment regimen. Results: Among 1.9 million patients in the analytic cohort, 43.5% met tuberculosis screening criteria, but only 21.4% were tested for latent tuberculosis infection; less than half (40.4%) were tested using an interferon-gamma release assay. Among those with a valid result, 10.5% were diagnosed with latent tuberculosis infection, 29.1% of those were prescribed latent tuberculosis infection treatment, and only 33.6% were prescribed a recommended rifamycin-based regimen. Conclusions: Electronic health record data can be used to measure the latent tuberculosis infection care cascade. A large proportion of patients in this safety-net clinical network are at high risk for tuberculosis infection. Addressing identified gaps in latent tuberculosis infection testing and treatment may have a direct impact on improving tuberculosis prevention in primary care clinics and accelerate progress toward elimination.

Variability of interferon-γ release assays in people at high risk of tuberculosis infection or progression to tuberculosis disease living in the United States.

OBJECTIVES: Interferon-γ release assays, including T-SPOT.TB (TSPOT) and QuantiFERON Gold In-Tube (QFT), are important diagnostic tools for tuberculosis infection, but little work has been done to study the performance of these tests in populations prioritized for tuberculosis testing in the United States, especially those other than health care personnel. METHODS: Participants were enrolled as part of a large, prospective cohort of people at high risk of tuberculosis infection or progression to tuberculosis disease. All participants were administered a tuberculin skin test, TSPOT, and QFT test. A subset of participants had their QFT (n = 919) and TSPOT (n = 885) tests repeated when they returned to get their tuberculin skin test read 2 to 3 days later (repeat study). A total of 531 participants had a TSPOT performed twice on the same sample taken at the same time (split study). RESULTS: The QFT repeat test interpretations were discordant (one test positive and the other negative) for 6.4% of participants (59 of 919), and the TSPOT tests were discordant for 60 of 885 participants in the repeat study (6.8%) and 41 of 531 participants in the split study (7.7%). There was a high degree of variability in the quantitative test results for both QFT and TSPOT, and discordance was not associated with both test results being near the established cut-offs. Furthermore, the proportion of discordance was similar when comparing participants in both the TSPOT repeat and TSPOT split studies. DISCUSSION: Both QFT and TSPOT were 6% to 8% discordant. The results should be interpreted with caution, particularly when seeing a conversion or reversion in serial testing.

Prevalence of Latent Tuberculosis Infection Among Non-US-Born Persons by Country of Birth-United States, 2012-2017.

BACKGROUND: Most tuberculosis (TB) disease in the United States (US) is attributed to reactivation of remotely acquired latent TB infection (LTBI) in non-US-born persons who were likely infected with Mycobacterium tuberculosis in their countries of birth. Information on LTBI prevalence by country of birth could help guide local providers and health departments to scale up the LTBI screening and preventive treatment needed to advance progress toward TB elimination. METHODS: A total of 13 805 non-US-born persons at high risk of TB infection or progression to TB disease were screened for LTBI at 16 clinical sites located across the United States with a tuberculin skin test, QuantiFERON Gold In-Tube test, and T-SPOT.TB test. Bayesian latent class analysis was applied to test results to estimate LTBI prevalence and associated credible intervals (CrIs) for each country or world region of birth. RESULTS: Among the study population, the estimated LTBI prevalence was 31% (95% CrI, 26%-35%). Country-of-birth-level LTBI prevalence estimates were highest for persons born in Haiti, Peru, Somalia, Ethiopia, Vietnam, and Bhutan, ranging from 42% to 55%. LTBI prevalence estimates were lowest for persons born in Colombia, Malaysia, and Thailand, ranging from 8% to 13%. CONCLUSIONS: LTBI prevalence in persons born outside the US varies widely by country. These estimates can help target community outreach efforts to the highest-risk groups.

A Cluster Randomized Trial of the Impact of Education through Listening (a Novel Behavior Change Technique) on Household Water Treatment with Chlorine in Vihiga District, Kenya, 2010-2011.

Despite multiple studies demonstrating the effectiveness of household water treatment with chlorine in disinfecting water and preventing diarrhea, social marketing of this intervention in low- and middle-income countries has resulted in only modest uptake. In a cluster randomized trial in Vihiga district, western Kenya, we compared uptake of household water treatment with chlorine among six villages served by community vendors trained in standard social marketing plus education through listening (ETL), an innovative behavior change method, and six villages served by community vendors trained in standard social marketing only. Water treatment uptake, water quality, and childhood diarrhea were measured over 6 months and compared between the two groups of villages. During the 6-month period, we found no association between ETL exposure and reported and confirmed household water treatment with chlorine. In both groups (ETL and comparison), reported use of water treatment was low and did not change during our 6-month follow-up. However, persons confirmed to have chlorinated water had improved bacteriologic water quality. Study findings suggest that ETL implementation was suboptimal, which, along with unexpected changes in the supply and price of chlorine, may have prevented an accurate assessment of the potential impact of ETL on water treatment behavior. Taken together, these observations exemplify the complexities of habits, practices, attitudes, and external factors that can create challenging conditions for implementing behavioral interventions. As a consequence, in this trial, ETL had no measurable impact on water treatment behavior.

Acute Flaccid Myelitis in the United States: 2015-2017.

BACKGROUND: Acute flaccid myelitis (AFM) is a neurologic condition characterized by flaccid limb weakness. After a large number of reports of AFM in 2014, the Centers for Disease Control and Prevention began standardized surveillance in the United States to characterize the disease burden and explore potential etiologies and epidemiologic associations. METHODS: Persons meeting the clinical case criteria of acute flaccid limb weakness from January 1, 2015, through December 31, 2017, were classified as confirmed (spinal cord gray matter lesions on MRI) or probable (white blood cell count >5 cells per mm3 in cerebrospinal fluid [CSF]). We describe clinical, radiologic, laboratory, and epidemiologic findings of pediatric patients (age ≤21 years) confirmed with AFM. RESULTS: Of 305 children reported from 43 states, 193 were confirmed and 25 were probable. Of confirmed patients, 61% were male, with a median age of 6 years (range: 3 months to 21 years; interquartile range: 3 to 10 years). An antecedent respiratory or febrile illness was reported in 79% with a median of 5 days (interquartile range: 2 to 7 days) before limb weakness. Among 153 sterile-site specimens (CSF and serum) submitted to the Centers for Disease Control and Prevention, coxsackievirus A16 was detected in CSF and serum of one case patient and enterovirus D68 was detected in serum of another. Of 167 nonsterile site (respiratory and stool) specimens, 28% tested positive for enterovirus or rhinovirus. CONCLUSIONS: AFM surveillance data suggest a viral etiology, including enteroviruses. Further study is ongoing to better characterize the etiology, pathogenesis, and risk factors of this rare condition.

Diffusion of Handwashing Knowledge and Water Treatment Practices From Mothers in an Antenatal Hygiene Promotion Program to Nonpregnant Friends and Relatives, Machinga District, Malawi.

Access to safe drinking water and improved hygiene are essential for preventing diarrheal diseases in low- and middle-income countries. Integrating water treatment and hygiene products into antenatal clinic care can motivate water treatment and handwashing among pregnant women. Free water hygiene kits (water storage containers, sodium hypochlorite water treatment solution, and soap) and refills of water treatment solution and soap were integrated into antenatal care and delivery services in Machinga District, Malawi, resulting in improved water treatment and hygiene practices in the home and increased maternal health service use. To determine whether water treatment and hygiene practices diffused from maternal health program participants to friends and relatives households in the same communities, we assessed the practices of 106 nonpregnant friends and relatives of these new mothers at baseline and 1-year follow-up. At follow-up, friends and relatives were more likely than at baseline to have water treatment products observable in the home (33.3% vs. 1.2%, p < 0.00001) and detectable free chlorine residual in their water, confirming water treatment (35.7% vs. 1.4%; p < 0.00001). Qualitative data from in-depth interviews also suggested that program participants helped motivate adoption of water treatment and hygiene behaviors among their friends and relatives.

Water, Sanitation, and Hygiene Characteristics among HIV-Positive Households Participating in the Global Enteric Multicenter Study in Rural Western Kenya, 2008-2012.

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.

Clinical, environmental, and behavioral characteristics associated with Cryptosporidium infection among children with moderate-to-severe diarrhea in rural western Kenya, 2008-2012: The Global Enteric Multicenter Study (GEMS).

BACKGROUND: Cryptosporidium is a leading cause of moderate-to-severe diarrhea (MSD) in young children in Africa. We examined factors associated with Cryptosporidium infection in MSD cases enrolled at the rural western Kenya Global Enteric Multicenter Study (GEMS) site from 2008-2012. METHODOLOGY/PRINCIPAL FINDINGS: At health facility enrollment, stool samples were tested for enteric pathogens and data on clinical, environmental, and behavioral characteristics collected. Each child's health status was recorded at 60-day follow-up. Data were analyzed using logistic regression. Of the 1,778 children with MSD enrolled as cases in the GEMS-Kenya case-control study, 11% had Cryptosporidium detected in stool by enzyme immunoassay; in a genotyped subset, 81% were C. hominis. Among MSD cases, being an infant, having mucus in stool, and having prolonged/persistent duration diarrhea were associated with being Cryptosporidium-positive. Both boiling drinking water and using rainwater as the main drinking water source were protective factors for being Cryptosporidium-positive. At follow-up, Cryptosporidium-positive cases had increased odds of being stunted (adjusted odds ratio [aOR] = 1.65, 95% CI: 1.06-2.57), underweight (aOR = 2.08, 95% CI: 1.34-3.22), or wasted (aOR = 2.04, 95% CI: 1.21-3.43), and had significantly larger negative changes in height- and weight-for-age z-scores from enrollment. CONCLUSIONS/SIGNIFICANCE: Cryptosporidium contributes significantly to diarrheal illness in young children in western Kenya. Advances in point of care detection, prevention/control approaches, effective water treatment technologies, and clinical management options for children with cryptosporidiosis are needed.

A Randomized Controlled Trial to Assess the Impact of Ceramic Water Filters on Prevention of Diarrhea and Cryptosporidiosis in Infants and Young Children-Western Kenya, 2013.

Cryptosporidium is a leading cause of diarrhea among Kenyan infants. Ceramic water filters (CWFs) are used for household water treatment. We assessed the impact of CWFs on diarrhea, cryptosporidiosis prevention, and water quality in rural western Kenya. A randomized, controlled intervention trial was conducted in 240 households with infants 4-10 months old. Twenty-six weekly household surveys assessed infant diarrhea and health facility visits. Stool specimens from infants with diarrhea were examined for Cryptosporidium. Source water, filtered water, and filter retentate were tested for Cryptosporidium and/or microbial indicators. To estimate the effect of CWFs on health outcomes, logistic regression models using generalized estimating equations were performed; odds ratios (ORs) and 95% confidence intervals (CIs) are reported. Households reported using surface water (36%), public taps (29%), or rainwater (17%) as their primary drinking water sources, with no differences in treatment groups. Intervention households reported less diarrhea (7.6% versus 8.9%; OR: 0.86 [0.64-1.16]) and significantly fewer health facility visits for diarrhea (1.0% versus 1.9%; OR: 0.50 [0.30-0.83]). In total, 15% of intervention and 12% of control stools yielded Cryptosporidium (P = 0.26). Escherichia coli was detected in 93% of source water samples; 71% of filtered water samples met World Health Organization recommendations of < 1 E. coli/100 mL. Cryptosporidium was not detected in source water and was detected in just 2% of filter rinses following passage of large volumes of source water. Water quality was improved among CWF users; however, the short study duration and small sample size limited our ability to observe reductions in cryptosporidiosis.

Water treatment and handwashing practices in rural Kenyan health care facilities and households six years after the installation of portable water stations and hygiene training.

Many health care facilities (HCFs) and households in low-and-middle-income countries have inadequate access to water for hygiene and consumption. To address these problems, handwashing and drinking water stations were installed in 53 HCFs with prevention-of-mother-to-child-transmission of HIV programs in Kenya in 2005, and hygiene education was provided to health workers and clinic clients. To assess this program, we selected a random sample of 30 HCFs, observed the percentage of handwashing and drinking water stations that were functional and in use, and after that interviewed health providers and clients about hygiene and water treatment. Results indicated that, six years after implementation, 80.0% of HCFs had at least one functional handwashing station and 83.3% had at least one functional drinking water station. In addition, 60% of HCFs had soap at ≥ one handwashing stations, and 23.3% had ≥ one container with detectable free chlorine. Of 299 clients (mothers with ≥ one child under five), 57.2% demonstrated proper water treatment knowledge, 93.3% reported ever using water treatment products, 16.4% had detectable chlorine residual in stored water, and 89.0% demonstrated proper handwashing technique. Six years after program implementation, although most HCFs had water stations and most clients could demonstrate proper handwashing technique, water stored in most clinics and homes was not treated.

Safe Water and Hygiene Integration with Human Immunodeficiency Virus and Antenatal Services: Leveraging Opportunities for Public Health Interventions and Improved Service Uptake.

Integrating public health interventions with antenatal clinic (ANC) visits may motivate women to attend ANC, thereby improving maternal and neonatal health, particularly for human immunodeficiency virus (HIV)-infected persons. In 2009, in an integrated ANC/Preventing Mother-to-Child Transmission program, we provided free hygiene kits (safe storage containers, WaterGuard water treatment solution, soap, and oral rehydration salts) to women at their first ANC visit and refills at subsequent visits. To increase fathers' participation, we required partners' presence for women to receive hygiene kits. We surveyed pregnant women at baseline and at 12-month follow-up to assess ANC service utilization, HIV counseling and testing (HCT), test drinking water for residual chlorine, and observe handwashing. We conducted in-depth interviews with pregnant women, partners, and health workers. We enrolled 106 participants; 97 (92%) were found at follow-up. During the program, 99% of pregnant women and their partners received HCT, and 99% mutually disclosed. Fifty-six percent of respondents had ≥ 4 ANC visits and 90% delivered at health facilities. From baseline to follow-up, the percentage of women who knew how to use WaterGuard (23% versus 80%, P < 0.0001), had residual chlorine in stored water (0% versus 73%, P < 0.0001), had confirmed WaterGuard use (0% versus 70%, P < 0.0003), and demonstrated proper handwashing technique (21% versus 64% P < 0.0001) increased. Program participants showed significant improvements in water treatment and hygiene, and high use of ANC services and HCT. This evaluation suggests that integration of hygiene kits, refills, and HIV testing during ANC is feasible and may help improve household hygiene and increase use of health services.

Assessment of water, sanitation and hygiene interventions in response to an outbreak of typhoid fever in Neno District, Malawi.

On May 2, 2009 an outbreak of typhoid fever began in rural villages along the Malawi-Mozambique border resulting in 748 illnesses and 44 deaths by September 2010. Despite numerous interventions, including distribution of WaterGuard (WG) for in-home water treatment and education on its use, cases of typhoid fever continued. To inform response activities during the ongoing Typhoid outbreak information on knowledge, attitudes, and practices surrounding typhoid fever, safe water, and hygiene were necessary to plan future outbreak interventions. In September 2010, a survey was administered to female heads in randomly selected households in 17 villages in Neno District, Malawi. Stored household drinking water was tested for free chlorine residual (FCR) levels using the N,N diethyl-p-phenylene diamine colorimetric method (HACH Company, Loveland, CO, USA). Attendance at community-wide educational meetings was reported by 56% of household respondents. Respondents reported that typhoid fever is caused by poor hygiene (77%), drinking unsafe water (49%), and consuming unsafe food (25%), and that treating drinking water can prevent it (68%). WaterGuard, a chlorination solution for drinking water treatment, was observed in 112 (56%) households, among which 34% reported treating drinking water. FCR levels were adequate (FCR ≥ 0.2 mg/L) in 29 (76%) of the 38 households who reported treatment of stored water and had stored water available for testing and an observed bottle of WaterGuard in the home. Soap was observed in 154 (77%) households, among which 51% reported using soap for hand washing. Educational interventions did not reach almost one-half of target households and knowledge remains low. Despite distribution and promotion of WaterGuard and soap during the outbreak response, usage was low. Future interventions should focus on improving water, sanitation and hygiene knowledge, practices, and infrastructure. Typhoid vaccination should be considered.

Risk Factors for Acanthamoeba Keratitis-A Multistate Case-Control Study, 2008-2011.

OBJECTIVE: To identify modifiable risk factors contributing to Acanthamoeba keratitis (AK) infection. METHODS: A case-control investigation was conducted. Case patients were soft contact lens wearers with laboratory-confirmed AK. Control were soft contact lens wearers ≥12 years of age, with no history of AK. Case patients were recruited from 14 ophthalmology referral centers and a clinical laboratory. Control were matched on state of residence and type of primary eye care provider (ophthalmologist or optometrist). Participants were interviewed using a standardized questionnaire. Univariable and multivariable conditional logistic regression analyses were conducted. Matched odds ratios (mORs) were calculated. RESULTS: Participants included 88 case patients and 151 matched control. Case patients were more likely to be aged <25 years (unadjusted mOR 2.7, 95% confidence interval 1.3-5.5) or aged >53 years (mOR 2.5, 1.1-5.7), and more likely to be men (mOR 2.6, 1.4-4.8). Unadjusted analyses identified multiple risk factors: rinsing (mOR 6.3, 1.3-29.9) and storing lenses in tap water (mOR 3.9, 1.2-12.3), topping off solution in the lens case (mOR 4.0, 2.0-8.0), having worn lenses ≤5 years (mOR 2.4, 1.3-4.4), rinsing the case with tap water before storing lenses (mOR 2.1, 1.1-4.1), and using hydrogen peroxide (mOR 3.6, 1.1-11.7) versus multipurpose solution. Significant risk factors in multivariable modeling included age >53 years, male sex, topping off, and using saline solution. CONCLUSIONS: Numerous modifiable risk factors for AK were identified, mostly involving hygiene practices. To reduce the risk of AK, lens wearers should observe recommended lens care practices.

An evaluation of a bucket chlorination campaign during a cholera outbreak in rural Cameroon.

Bucket chlorination (where workers stationed at water sources manually add chlorine solution to recipients' water containers during collection) is a common emergency response intervention with little evidence to support its effectiveness in preventing waterborne disease. We evaluated a bucket chlorination intervention implemented during a cholera outbreak by visiting 234 recipients' homes across five intervention villages to conduct an unannounced survey and test stored household drinking water for free chlorine residual (FCR). Overall, 89 per cent of survey respondents reported receiving bucket chlorination, and 80 per cent reported receiving the intervention in the previous 24 hours. However, only 8 per cent of stored household water samples that were reportedly treated only with bucket chlorination in the previous 24 hours had FCR ≥0.2 mg/l. Current international guidelines for bucket chlorination recommend an empirically derived dosage determined 30 minutes after chlorine addition, and do not account for water storage in the home. In controlled investigations we conducted, an initial FCR of 1.5 mg/l resulted in FCR ≥0.5 mg/l for 24 hours in representative household plastic and clay storage containers. To ensure reduction of the risk of waterborne disease, we recommend revising bucket chlorination protocols to recommend a chlorine dosage sufficient to maintain FCR ≥0.2 mg/l for 24 hours in recipients' household stored drinking water.

Factors Associated with the Duration of Moderate-to-Severe Diarrhea among Children in Rural Western Kenya Enrolled in the Global Enteric Multicenter Study, 2008-2012.

Diarrheal disease is a leading cause of death among young children worldwide. As rates of acute diarrhea (AD; 1-6 days duration) have decreased, persistent diarrhea (PD; > 14 days duration) accounts for a greater proportion of the diarrheal disease burden. We describe factors associated with the duration of moderate-to-severe diarrhea in Kenyan children < 5 years old enrolled in the Global Enteric Multicenter Study. We found 587 (58%) children experienced AD, 360 (35%) had prolonged acute diarrhea (ProAD; 7-13 days duration), and 73 (7%) had PD. We constructed a Cox proportional hazards model to identify factors associated with diarrheal duration. Risk factors independently associated with longer diarrheal duration included infection with Cryptosporidium (hazard ratio [HR]: 0.868, P = 0.035), using an unimproved drinking water source (HR: 0.87, P = 0.035), and being stunted at enrollment (HR: 0.026, P < 0.0001). Diarrheal illness of extended duration appears to be multifactorial; given its association with adverse health and development outcomes, effective strategies should be implemented to reduce the duration and severity of diarrheal illness. Effective treatments for Cryptosporidium should be identified, interventions to improve drinking water are imperative, and nutrition should be improved through exclusive breastfeeding in infants ≤ 6 months and appropriate continued feeding practices for ill children.

Recurrence of Guinea Worm Disease in Chad after a 10-Year Absence: Risk Factors for Human Cases Identified in 2010-2011.

A decade after reporting its last case of Guinea worm disease (GWD), a waterborne parasitic disease targeted for eradication, Chad reported 20 confirmed human cases from 17 villages-10 cases in 2010 and 10 cases in 2011. In 2012, the first GWD dog infections were diagnosed. We conducted a case-control study during April-May 2012 to identify human transmission risk factors and epidemiologic links. We recruited 19 cases and 45 controls matched by age, sex, time, and location of exposure based on the case patients' periods of infection 10-14 months earlier. Data were analyzed with simple conditional logistic regression models using Firth penalized likelihood methods. Unusually, GWD did not appear to be associated with household primary water sources. Instead, secondary water sources, used outside the village or other nonprimary sources used at home, were risk factors (matched odds ratio = 38.1, 95% confidence interval = 1.6-728.2). This study highlights the changing epidemiology of GWD in Chad-household primary water sources were not identified as risk factors and few epidemiologic links were identified between the handfuls of sporadic cases per year, a trend that continues. Since this investigation, annual dog infections have increased, far surpassing human cases. An aquatic paratenic host is a postulated mode of transmission for both dogs and humans, although fish could not be assessed in this case-control study due to their near-universal consumption. GWD's evolving nature in Chad underscores the continued need for interventions to prevent both waterborne and potential foodborne transmission until the true mechanism is established.

Epidemiology, Seasonality and Factors Associated with Rotavirus Infection among Children with Moderate-to-Severe Diarrhea in Rural Western Kenya, 2008-2012: The Global Enteric Multicenter Study (GEMS).

OBJECTIVE: To evaluate factors associated with rotavirus diarrhea and to describe severity of illness among children <5 years old with non-dysenteric, moderate-to-severe diarrhea (MSD) in rural western Kenya. METHODS: We analyzed data from children <5 years old with non-dysenteric MSD enrolled as cases in the Global Enteric Multicenter Study (GEMS) in Kenya. A non-dysenteric MSD case was defined as a child with ≥3 loose stools in 24 hrs. and one or more of the following: sunken eyes, skin tenting, intravenous rehydration, or hospitalization, who sought care at a sentinel health center within 7 days of illness onset. Rotavirus antigens in stool samples were detected by ELISA. Demographic and clinical information was collected at enrollment and during a single follow-up home visit at approximately 60 days. We analyzed diarrhea severity using a GEMS 17 point numerical scoring system adapted from the Vesikari score. We used logistic regression to evaluate factors associated with rotavirus infection. RESULTS: From January 31, 2008 to September 30, 2012, among 1,637 (92%) non-dysenteric MSD cases, rotavirus was detected in stools of 245 (15.0%). Rotavirus-positive compared with negative cases were: younger (median age, 8 vs. 13 months; p<0.0001), had more severe illness (median severity score, 9 vs 8; p<0.0001) and had to be hospitalized more frequently (37/245 [15.1%] vs. 134/1,392 [9.6%]), p <0.013). Independent factors associated with rotavirus infection included age 0-11 months old (aOR = 5.29, 95% CI 3.14-8.89) and presenting with vomiting ≥3 times/24hrs (aOR = 2.58, 95% CI [1.91-3.48]). Rotavirus was detected more commonly in warm and dry months than in the cool and rainy months (142/691 [20%] vs 70/673 [10%]) p<0.0001). CONCLUSIONS: Diarrhea caused by rotavirus is associated with severe symptoms leading to hospitalization. Consistent with other settings, infants had the greatest burden of disease.