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Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing remains essential for early identification and clinical management of cases. We compared the diagnostic performance of 3 specimen types for characterizing SARS-CoV-2 in infected nursing home residents. Methods A convenience sample of 17 residents were enrolled within 15 days of first positive SARS-CoV-2 result by real-time reverse transcription polymerase chain reaction (RT-PCR) and prospectively followed for 42 days. Anterior nasal swabs (AN), oropharyngeal swabs (OP), and saliva specimens (SA) were collected on the day of enrollment, every 3 days for the first 21 days, and then weekly for 21 days. Specimens were tested for presence of SARS-CoV-2 RNA using RT-PCR and replication-competent virus by viral culture. Results Comparing the 3 specimen types collected from each participant at each time point, the concordance of paired RT-PCR results ranged from 80% to 88%. After the first positive result, SA and OP were RT-PCR-positive for ≤48 days; AN were RT-PCR–positive for ≤33 days. AN had the highest percentage of RT-PCR–positive results (21/26 [81%]) when collected ≤10 days of participants’ first positive result. Eleven specimens were positive by viral culture: 9 AN collected ≤19 days following first positive result and 2 OP collected ≤5 days following first positive result. Conclusions AN, OP, and SA were effective methods for repeated testing in this population. More AN than OP were positive by viral culture. SA and OP remained RT-PCR-positive longer than AN, which could lead to unnecessary interventions if RT-PCR detection occurred after viral shedding has likely ceased.

Virus shedding in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can occur before onset of symptoms; less is known about symptom progression or infectiousness associated with initiation of viral shedding. We investigated household transmission in 5 households with daily specimen collection for 5 consecutive days starting a median of 4 days after symptom onset in index patients. Seven contacts across 2 households implementing no precautionary measures were infected. Of these 7, 2 tested positive for SARS-CoV-2 by reverse transcription PCR on day 3 of 5. Both had mild, nonspecific symptoms for 1-3 days preceding the first positive test. SARS-CoV-2 was cultured from the fourth-day specimen in 1 patient and from the fourth- and fifth-day specimens in the other. We also describe infection control measures taken in the households that had no transmission. Persons exposed to SARS-CoV-2 should self-isolate, including from household contacts, wear a mask, practice hand hygiene, and seek testing promptly.

Background The evidence base for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is nascent. We sought to characterize SARS-CoV-2 transmission within US households and estimate the household secondary infection rate (SIR) to inform strategies to reduce transmission. Methods We recruited patients with laboratory-confirmed SARS-CoV-2 infection and their household contacts in Utah and Wisconsin during 22 March 2020–25 April 2020. We interviewed patients and all household contacts to obtain demographics and medical histories. At the initial household visit, 14 days later, and when a household contact became newly symptomatic, we collected respiratory swabs from patients and household contacts for testing by SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) and sera for SARS-CoV-2 antibodies testing by enzyme-linked immunosorbent assay (ELISA). We estimated SIR and odds ratios (ORs) to assess risk factors for secondary infection, defined by a positive rRT-PCR or ELISA test. Results Thirty-two (55%) of 58 households secondary infection among household contacts. The SIR was 29% (n = 55/188; 95% confidence interval [CI], 23%–36%) overall, 42% among children (aged Conclusions We found substantial evidence of secondary infections among household contacts. People with COVID-19, particularly those with immunocompromising conditions or those with household contacts with diabetes, should take care to promptly self-isolate to prevent household transmission.

There is growing evidence for the decline of cryptic species across the planet as a result of human activities. Accurate data regarding patterns of poorly known or hard-to-find species diversity is essential for the recognition and conservation of threatened species and ecosystems. Casey’s June beetle Dinacoma caseyi is a federally listed endangered species restricted to the Coachella Valley in southern California, where rapid development is leading to habitat fragmentation. This fragmentation may be disproportionately impacting a wide-range of poorly-dispersing, cryptic species, including Casey’s June beetle, which has flightless females. We characterized 1876 single nucleotide polymorphisms from across the genome along with 1480 bp of mitochondrial DNA of all confirmed extant Dinacoma populations. We found that Dinacoma is isolated into three distinct species, including evidence for a previously undescribed species revealed during this study. Each is restricted to a small part of the inland desert region. Our results suggest unappreciated and fine scale diversity, which may be reflected in the other cryptic species of the region. Patterns of diversity in non-vagile species should guide ongoing conservation planning in the region. These results show that genetic exchange within the one remaining island of beetle habitat (Palm Canyon Wash) is not limited. However, non-vagile species, such as Casey’s June beetle, may not colonize suitable but fragmented habitat islands which presents risks to the species due to habitat loss and periodic natural events that may put the single population at risk of extirpation.

Introduction Endemic measles persists in China, despite >95% reported coverage of two measles-containing vaccine doses and nationwide campaign that vaccinated >100 million children in 2010. An increasing proportion of infections now occur among adults and there is concern that persistent susceptibility in adults is an obstacle to measles elimination in China. We performed a case-control study in six Chinese provinces between January 2012 to June 2013 to identify risk factors for measles virus infection and susceptibility among adults. Methods Persons ≥15 years old with laboratory-confirmed measles were age and neighborhood matched with three controls. Controls had blood specimens collected to determine their measles IgG serostatus. We interviewed case-patients and controls about potential risk factors for measles virus infection and susceptibility. Unadjusted and adjusted matched odds ratios and 95% confidence intervals (CIs) were calculated via conditional logistic regression. We calculated attributable fractions for infection for risk factors that could be interpreted as causal. Results 899 cases and 2498 controls were enrolled. Among controls, 165 (6.6%) were seronegative for measles IgG indicating persistent susceptibility to infection. In multivariable analysis, hospital visit and travel outside the prefecture in the prior 1–3 weeks were significant risk factors for measles virus infection. Occupation and reluctance to accept measles vaccination were significant risk factors for measles susceptibility. The calculated attributable fraction of measles cases from hospital visitation was 28.6% (95% CI: 20.6–38.8%). Conclusions Exposure to a healthcare facility was the largest risk factor for measles virus infection in adults in China. Improved adherence to hospital infection control practices could reduce risk of ongoing measles virus transmission and increase the likelihood of achieving and sustaining measles elimination in China. The use of control groups stratified by serological status identified distinct risk factors for measles virus infection and susceptibility among adults.

Objective:To characterize and compare severe acute respiratory coronavirus virus 2 (SARS-CoV-2)–specific immune responses in plasma and gingival crevicular fluid (GCF) from nursing home residents during and after natural infection.Design:Prospective cohort.Setting:Nursing home.Participants:SARS-CoV-2–infected nursing home residents.Methods:A convenience sample of 14 SARS-CoV-2–infected nursing home residents, enrolled 4–13 days after real-time reverse transcription polymerase chain reaction diagnosis, were followed for 42 days. After diagnosis, plasma SARS-CoV-2–specific pan-Immunoglobulin (Ig), IgG, IgA, IgM, and neutralizing antibodies were measured at 5 time points, and GCF SARS-CoV-2–specific IgG and IgA were measured at 4 time points.Results:All participants demonstrated immune responses to SARS-CoV-2 infection. Among 12 phlebotomized participants, plasma was positive for pan-Ig and IgG in all 12 participants. Neutralizing antibodies were positive in 11 participants; IgM was positive in 10 participants, and IgA was positive in 9 participants. Among 14 participants with GCF specimens, GCF was positive for IgG in 13 participants and for IgA in 12 participants. Immunoglobulin responses in plasma and GCF had similar kinetics; median times to peak antibody response were similar across specimen types (4 weeks for IgG; 3 weeks for IgA). Participants with pan-Ig, IgG, and IgA detected in plasma and GCF IgG remained positive throughout this evaluation, 46–55 days after diagnosis. All participants were viral-culture negative by the first detection of antibodies.Conclusions:Nursing home residents had detectable SARS-CoV-2 antibodies in plasma and GCF after infection. Kinetics of antibodies detected in GCF mirrored those from plasma. Noninvasive GCF may be useful for detecting and monitoring immunologic responses in populations unable or unwilling to be phlebotomized.

Measles and rubella microarray patches (MR-MAPs) are critical in achieving measles and rubella eradication, a goal highly unlikely to meet with current vaccines presentations. With low commercial incentive to MAP developers, limited and uncertain funding, the need for investment in a novel manufacturing facility, and remaining questions about the source of antigen, product demand, and regulatory pathway, MR-MAPs are unlikely to be prequalified by WHO and ready for use before 2033. This article describes the current progress of MR-MAPs, highlights challenges and opportunities pertinent to MR-MAPs manufacturing, regulatory approval, creating demand, and timelines to licensure. It also describes activities that are being undertaken by multiple partners to incentivise investment in and accelerate the development of MR-MAPs.

Background Bloodstream infection (BSI) surveillance is essential to characterize the public health threat of bacteremia. We summarize BSI epidemiology in rural Thailand over an eight year period. Methods Population-based surveillance captured clinically indicated blood cultures and associated antimicrobial susceptibility results performed in all 20 hospitals in Nakhon Phanom (NP) and Sa Kaeo (SK) provinces. BSIs were classified as community-onset (CO) when positive cultures were obtained ≤2 days after hospital admission and hospital-onset (HO) thereafter. Hospitalization denominator data were available for incidence estimates for 2009–2014. Results From 2007 to 2014 a total of 11,166 BSIs were identified from 134,441 blood cultures. Annual CO BSI incidence ranged between 89.2 and 123.5 cases per 100,000 persons in SK and NP until 2011. Afterwards, CO incidence remained stable in SK and increased in NP, reaching 155.7 in 2013. Increases in CO BSI incidence over time were limited to persons aged ≥50 years. Ten pathogens, in rank order, accounted for > 65% of CO BSIs in both provinces, all age-groups, and all years: Escherichia coli, Klebsiella pneumoniae, Burkholderia pseudomallei, Staphylococcus aureus, Salmonella non-typhi spp., Streptococcus pneumoniae, Acinetobacter spp., Streptococcus agalactiae, Streptococcus pyogenes, Pseudomonas aeruginosa. HO BSI incidence increased in NP from 0.58 cases per 1000 hospitalizations in 2009 to 0.91 in 2014, but were higher (ranging from 1.9 to 2.3) in SK throughout the study period. Extended-spectrum beta-lactamase production among E. coli isolates and multi-drug resistance among Acinetobacter spp. isolates was common (> 25% of isolates), especially among HO cases (> 50% of isolates), and became more common over time, while methicillin-resistance among S. aureus isolates (10%) showed no clear trend. Carbapenem-resistant Enterobacteriaceae were documented in 2011–2014. Conclusions Population-based surveillance documented CO BSI incidence estimates higher than previously reported from Thailand and the region, with temporal increases seen in older populations. The most commonly observed pathogens including resistance profiles were similar to leading pathogens and resistance profiles worldwide, thus; prevention strategies with demonstrated success elsewhere may prove effective in Thailand. Electronic supplementary material The online version of this article (10.1186/s12889-019-6775-4) contains supplementary material, which is available to authorized users.

Escherichia coli and Klebsiella pneumoniae are two of the most common causes of bloodstream infections (BSIs) worldwide.1,2 β-Lactam antibiotics are the preferred treatment because of their selective toxicity, broad spectrum of activity, and low cost.3,4 However, E. coli and K. pneumoniae, and other Enterobacteriaceae, have developed extended-spectrum β-lactamase (ESBL)–producing capability and can hydrolyze penicillins, cephalosporins, and monobactams, rendering them clinically ineffective.5 Extended-spectrum β-lactamase–producing E. coli and K. pneumoniae are increasingly reported worldwide in hospital and community settings, resulting in prolonged and more expensive hospitalizations and increased morbidity and mortality.6,7 Prompt identification is essential for appropriate treatment and improved patient outcomes.8,9 Extended-spectrum β-lactamase–producing E. coli have been identified throughout Thailand,10–13 with the first documented case in 1994,14 and a prevalence among different clinical specimens ranging from 22% to 59%, and evidence that they are becoming more common.10–13,15 However, representative estimates of the incidence of ESBL-producing E. coli and K. pneumoniae and longitudinal trends in antimicrobial resistance are currently limited in Southeast Asia. This study aimed to expand our understanding of ESBL-producing pathogen disease burden by estimating trends in population-based E. coli and K. pneumoniae bacteremia incidence, changes over time in the proportion of these cases due to ESBL-producing organisms, susceptibility profiles to other antibiotics, and the probability of recurrent infections. This study used the same well-established surveillance database that was previously used to estimate the incidence and susceptibility profiles of several other pathogens in rural Thailand.16–19

Background To estimate the infectious period of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adults with underlying conditions, we assessed duration of coronavirus disease 2019 (COVID-19) symptoms, reverse-transcription polymerase chain reaction (RT-PCR) positivity, and culture positivity among nursing home residents. Methods We enrolled residents within 15 days of their first positive SARS-CoV-2 test (diagnosis) at an Arkansas facility from July 7 to 15, 2020 and instead them for 42 days. Every 3 days for 21 days and then weekly, we assessed COVID-19 symptoms, collected specimens (oropharyngeal, anterior nares, and saliva), and reviewed medical charts. Blood for serology was collected on days 0, 6, 12, 21, and 42. Infectivity was defined by positive culture. Duration of culture positivity was compared with duration of COVID-19 symptoms and RT-PCR positivity. Data were summarized using measures of central tendency, frequencies, and proportions. Results We enrolled 17 of 39 (44%) eligible residents. Median participant age was 82 years (range, 58–97 years). All had ≥3 underlying conditions. Median duration of RT-PCR positivity was 22 days (interquartile range [IQR], 8–31 days) from diagnosis; median duration of symptoms was 42 days (IQR, 28–49 days). Of 9 (53%) participants with any culture-positive specimens, 1 (11%) severely immunocompromised participant remained culture-positive 19 days from diagnosis; 8 of 9 (89%) were culture-positive ≤8 days from diagnosis. Seroconversion occurred in 12 of 12 (100%) surviving participants with ≥1 blood specimen; all participants were culture-negative before seroconversion. Conclusions Duration of infectivity was considerably shorter than duration of symptoms and RT-PCR positivity. Severe immunocompromise may prolong SARS-CoV-2 infectivity. Seroconversion indicated noninfectivity in this cohort.

BACKGROUND AND OBJECTIVES: Limited data exist on severe acute respiratory syndrome coronavirus 2 in children. We described infection rates and symptom profiles among pediatric household contacts of individuals with coronavirus disease 2019. METHODS: We enrolled individuals with coronavirus disease 2019 and their household contacts, assessed daily symptoms prospectively for 14 days, and obtained specimens for severe acute respiratory syndrome coronavirus 2 real-time reverse transcription polymerase chain reaction and serology testing. Among pediatric contacts ( RESULTS: Among 58 households, 188 contacts were enrolled (120 adults; 68 children). Secondary infection rates for adults (30%) and children (28%) were similar. Among households with potential for transmission from children, child-to-adult transmission may have occurred in 2 of 10 (20%), and child-to-child transmission may have occurred in 1 of 6 (17%). Pediatric case patients most commonly reported headache (79%), sore throat (68%), and rhinorrhea (68%); symptoms had low positive predictive values, except measured fever (100%; 95% confidence interval [CI]: 44% to 100%). Compared with symptomatic adults, children were less likely to report cough (odds ratio [OR]: 0.15; 95% CI: 0.04 to 0.57), loss of taste (OR: 0.21; 95% CI: 0.06 to 0.74), and loss of smell (OR: 0.29; 95% CI: 0.09 to 0.96) and more likely to report sore throat (OR: 3.4; 95% CI: 1.04 to 11.18). CONCLUSIONS: Children and adults had similar secondary infection rates, but children generally had less frequent and severe symptoms. In two states early in the pandemic, we observed possible transmission from children in approximately one-fifth of households with potential to observe such transmission patterns.

Background Improved understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spectrum of disease is essential for clinical and public health interventions. There are limited data on mild or asymptomatic infections, but recognition of these individuals is key as they contribute to viral transmission. We describe the symptom profiles from individuals with mild or asymptomatic SARS-CoV-2 infection. Methods From 22 March to 22 April 2020 in Wisconsin and Utah, we enrolled and prospectively observed 198 household contacts exposed to SARS-CoV-2. We collected and tested nasopharyngeal specimens by real-time reverse-transcription polymerase chain reaction (rRT-PCR) 2 or more times during a 14-day period. Contacts completed daily symptom diaries. We characterized symptom profiles on the date of first positive rRT-PCR test and described progression of symptoms over time. Results We identified 47 contacts, median age 24 (3–75) years, with detectable SARS-CoV-2 by rRT-PCR. The most commonly reported symptoms on the day of first positive rRT-PCR test were upper respiratory (n = 32 [68%]) and neurologic (n = 30 [64%]); fever was not commonly reported (n = 9 [19%]). Eight (17%) individuals were asymptomatic at the date of first positive rRT-PCR collection; 2 (4%) had preceding symptoms that resolved and 6 (13%) subsequently developed symptoms. Children less frequently reported lower respiratory symptoms (21%, 60%, and 69% for Conclusions Household contacts with laboratory-confirmed SARS-CoV-2 infection reported mild symptoms. When assessed at a single timepoint, several contacts appeared to have asymptomatic infection; however, over time all developed symptoms. These findings are important to inform infection control, contact tracing, and community mitigation strategies.

IntroductionEtiology studies of severe acute respiratory infections (SARI) in adults are limited. We studied potential etiologies of SARI among adults in six countries using multi-pathogen diagnostics.MethodsWe enrolled both adults with SARI (acute respiratory illness onset with fever and cough requiring hospitalization) and asymptomatic adults (adults hospitalized with non-infectious illnesses, non-household members accompanying SARI patients, adults enrolled from outpatient departments, and community members) in each country. Demographics, clinical data, and nasopharyngeal and oropharyngeal specimens were collected from both SARI patients and asymptomatic adults. Specimens were tested for presence of 29 pathogens utilizing the Taqman® Array Card platform. We applied a non-parametric Bayesian regression extension of a partially latent class model approach to estimate proportions of SARI caused by specific pathogens.ResultsWe enrolled 2,388 SARI patients and 1,135 asymptomatic adults from October 2013 through October 2015. We detected ≥1 pathogen in 76% of SARI patients and 67% of asymptomatic adults. Haemophilus influenzae and Streptococcus pneumoniae were most commonly detected (≥23% of SARI patients and asymptomatic adults). Through modeling, etiology was attributed to a pathogen in most SARI patients (range among countries: 57.3-93.2%); pathogens commonly attributed to SARI etiology included influenza A (14.4-54.4%), influenza B (1.9-19.1%), rhino/enterovirus (1.8-42.6%), and RSV (3.6-14.6%).ConclusionsUse of multi-pathogen diagnostics and modeling enabled attribution of etiology in most adult SARI patients, despite frequent detection of multiple pathogens in the upper respiratory tract. Seasonal flu vaccination and development of RSV vaccine would likely reduce the burden of SARI in these populations.

Background Multiplex bead assays (MBA) that measure IgG antibodies to the carboxy-terminal 19-kDa sub-unit of the merozoite surface protein 1 (MSP119) are currently used to determine malaria seroprevalence in human populations living in areas with both stable and unstable transmission. However, the species specificities of the IgG antibody responses to the malaria MSP119 antigens have not been extensively characterized using MBA. Methods Recombinant Plasmodium falciparum (3D7), Plasmodium malariae (China I), Plasmodium ovale (Nigeria I), and Plasmodium vivax (Belem) MSP119 proteins were covalently coupled to beads for MBA. Threshold cut-off values for the assays were estimated using sera from US citizens with no history of foreign travel and by receiver operator characteristic curve analysis using diagnostic samples. Banked sera from experimentally infected chimpanzees, sera from humans from low transmission regions of Haiti and Cambodia (N = 12), and elutions from blood spots from humans selected from a high transmission region of Mozambique (N = 20) were used to develop an antigen competition MBA for antibody cross-reactivity studies. A sub-set of samples was further characterized using antibody capture/elution MBA, IgG subclass determination, and antibody avidity measurement. Results Total IgG antibody responses in experimentally infected chimpanzees were species specific and could be completely suppressed by homologous competitor protein at a concentration of 10 μg/ml. Eleven of 12 samples from the low transmission regions and 12 of 20 samples from the high transmission area had antibody responses that were completely species specific. For 7 additional samples, the P. falciparum MSP119 responses were species specific, but various levels of incomplete heterologous competition were observed for the non-P. falciparum assays. A pan-malaria MSP119 cross-reactive antibody response was observed in elutions of blood spots from two 20–30 years old Mozambique donors. The antibody response from one of these two donors had low avidity and skewed almost entirely to the IgG3 subclass. Conclusions Even when P. falciparum, P. malariae, P. ovale, and P. vivax are co-endemic in a high transmission setting, most antibody responses to MSP119 antigens are species-specific and are likely indicative of previous infection history. True pan-malaria cross-reactive responses were found to occur rarely. Electronic supplementary material The online version of this article (10.1186/s12936-018-2566-0) contains supplementary material, which is available to authorized users.

Melioidosis incidence and mortality have reportedly been increasing in endemic areas of Thailand, but little population-based data on culture-confirmed Burkholderia pseudomallei infections exist. We provide updated estimates of melioidosis bacteremia incidence and in-hospital mortality rate using integration of two population-based surveillance databases in Nakhon Phanom, Thailand, since automated blood culture became available in 2005. From 2009 to 2013, 564 hospitalized bacteremic melioidosis patients were identified. The annual incidence of bacteremic melioidosis ranged from 14 to 17 per 100,000 persons, and average population mortality rate was 2 per 100,000 persons per year. In-hospital mortality rate declined nonsignificantly from 15% (15/102) to 13% (15/118). Of 313 (56%) bacteremic melioidosis patients who met criteria for acute lower respiratory infection and were included in the hospital-based pneumonia surveillance system, 65% (202/313) had a chest radiograph performed within 48 hours of admission; 46% (92/202) showed radiographic evidence of pneumonia. Annual incidence of bacteremic melioidosis with pneumonia was 2.4 per 100,000 persons (95% confidence intervals; 1.9–2.9). In-hospital death was more likely among bacteremic melioidosis patients with pneumonia (34%; 20/59) compared with non-pneumonia patients (18%; 59/321) (P-value = 0.007). The overall mortality could have been as high as 46% (257/564) if patients with poor clinical condition at the time of discharge had died. The continued high incidence of bacteremic melioidosis, pneumonia, and deaths in an endemic area highlights the need for early diagnosis and treatment and additional interventions for the prevention and control for melioidosis.

Introduction Vectorborne diseases are major causes of death and illness worldwide. In the United States, the most common vectorborne pathogens are transmitted by ticks or mosquitoes, including those causing Lyme disease; Rocky Mountain spotted fever; and West Nile, dengue, and Zika virus diseases. This report examines trends in occurrence of nationally reportable vectorborne diseases during 2004-2016. Methods Data reported to the National Notifiable Diseases Surveillance System for 16 notifiable vectorborne diseases during 2004-2016 were analyzed; findings were tabulated by disease, vector type, location, and year. Results A total 642,602 cases were reported. The number of annual reports of tickborne bacterial and protozoan diseases more than doubled during this period, from >22,000 in 2004 to >48,000 in 2016. Lyme disease accounted for 82% of all tickborne disease reports during 2004-2016. The occurrence of mosquitoborne diseases was marked by virus epidemics. Transmission in Puerto Rico, the U.S. Virgin Islands, and American Samoa accounted for most reports of dengue, chikungunya, and Zika virus diseases; West Nile virus was endemic, and periodically epidemic, in the continental United States. Conclusions and implications for public health practice Vectorborne diseases are a large and growing public health problem in the United States, characterized by geographic specificity and frequent pathogen emergence and introduction. Differences in distribution and transmission dynamics of tickborne and mosquitoborne diseases are often rooted in biologic differences of the vectors. To effectively reduce transmission and respond to outbreaks will require major national improvement of surveillance, diagnostics, reporting, and vector control, as well as new tools, including vaccines.

For >60 years, Zika virus (ZIKV) has been recognized as an arthropod-borne virus with Aedes species mosquitoes as the primary vector. However in the past 10 years, multiple alternative routes of ZIKV transmission have been identified. We review the available data on vector and non-vector-borne modes of transmission and interventions undertaken, to date, to reduce the risk of human infection through these routes. Although much has been learned during the outbreak in the Americas on the underlying mechanisms and pathogenesis of non-vector-borne ZIKV infections, significant gaps remain in our understanding of the relative incidence of, and risk from, these modes compared to mosquito transmission. Additional research is urgently needed on the risk, pathogenesis, and effectiveness of measures to mitigate non-vector-borne ZIKV transmission.

CDC has updated the interim guidance for U.S. health care providers caring for pregnant women with possible Zika virus exposure in response to 1) declining prevalence of Zika virus disease in the World Health Organization's Region of the Americas (Americas) and 2) emerging evidence indicating prolonged detection of Zika virus immunoglobulin M (IgM) antibodies. Zika virus cases were first reported in the Americas during 2015-2016; however, the incidence of Zika virus disease has since declined. As the prevalence of Zika virus disease declines, the likelihood of false-positive test results increases. In addition, emerging epidemiologic and laboratory data indicate that, as is the case with other flaviviruses, Zika virus IgM antibodies can persist beyond 12 weeks after infection. Therefore, IgM test results cannot always reliably distinguish between an infection that occurred during the current pregnancy and one that occurred before the current pregnancy, particularly for women with possible Zika virus exposure before the current pregnancy. These limitations should be considered when counseling pregnant women about the risks and benefits of testing for Zika virus infection during pregnancy. This updated guidance emphasizes a shared decision-making model for testing and screening pregnant women, one in which patients and providers work together to make decisions about testing and care plans based on patient preferences and values, clinical judgment, and a balanced assessment of risks and expected outcomes.

Introduction Endemic measles persists in China, despite >95% reported coverage of two measles-containing vaccine doses and nationwide campaign that vaccinated more than 100 million children in 2010. We performed a case–control study in six Chinese provinces during January 2012 through June 2013 to identify risk factors for measles infection among children aged 0–7 months. Methods Children with laboratory-confirmed measles were neighborhood matched with three controls. We interviewed parents of case and control infants on potential risk factors for measles. Adjusted matched odds ratios (mOR) and 95% confidence intervals (CIs) were calculated by multivariable conditional logistic modeling. We calculated attributable fractions for risk factors that could be interpreted as causal. Results Eight hundred thirty cases and 2303 controls were enrolled. In multivariable analysis, male sex (mOR 1.6 [1.3, 2.0]), age 5–7 months (mOR 3.9 [3.0, 5.1]), migration between counties (mOR 2.3 [1.6, 3.4]), outpatient hospital visits (mOR 9.4 [6.6, 13.3]) and inpatient hospitalization (mOR 107.1 [48.8, 235.1]) were significant risk factors. The calculated attributable fractions for hospital visits was 43.1% (95% CI: 40.1, 47.5%) adjusted for age, sex and migration. Conclusions Hospital visitation was the largest risk factor for measles infection in infants. Improved hospital infection control practices would accelerate measles elimination in China.

Background The etiology of severe pneumonia is frequently not identified by routine disease surveillance in Thailand. Since 2010, the Thailand Ministry of Public Health (MOPH) and US CDC have conducted surveillance to detect known and new etiologies of severe pneumonia. Methods Surveillance for severe community-acquired pneumonia was initiated in December 2010 among 30 hospitals in 17 provinces covering all regions of Thailand. Interlinked clinical, laboratory, pathological and epidemiological components of the network were created with specialized guidelines for each to aid case investigation and notification. Severe pneumonia was defined as chest-radiograph confirmed pneumonia of unknown etiology in a patient hospitalized ≤48 h and requiring intubation with ventilator support or who died within 48 h after hospitalization; patients with underlying chronic pulmonary or neurological disease were excluded. Respiratory and pathological specimens were tested by reverse transcription polymerase chain reaction for nine viruses, including Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and 14 bacteria. Cases were reported via a secure web-based system. Results Of specimens from 972 cases available for testing during December 2010 through December 2015, 589 (60.6%) had a potential etiology identified; 399 (67.8%) were from children aged

Background Determining the etiology of pneumonia is essential to guide public health interventions. Diagnostic test results, including from polymerase chain reaction (PCR) assays of upper respiratory tract specimens, have been used to estimate prevalence of pneumococcal pneumonia. However limitations in test sensitivity and specificity and the specimen types available make establishing a definitive diagnosis challenging. Prevalence estimates for pneumococcal pneumonia could be biased in the absence of a true gold standard reference test for detecting Streptococcus pneumoniae. Methods We conducted a case control study to identify etiologies of community acquired pneumonia (CAP) from April 2014 through August 2015 in Thailand. We estimated the prevalence of pneumococcal pneumonia among adults hospitalized for CAP using Bayesian latent class models (BLCMs) incorporating results of real-time polymerase chain reaction (qPCR) testing of upper respiratory tract specimens and a urine antigen test (UAT) from cases and controls. We compared the prevalence estimate to conventional analyses using only UAT as a reference test. Results The estimated prevalence of pneumococcal pneumonia was 8% (95% CI: 5–11%) by conventional analyses. By BLCM, we estimated the prevalence to be 10% (95% CrI: 7–16%) using binary qPCR and UAT results, and 11% (95% CrI: 7–17%) using binary UAT results and qPCR cycle threshold (Ct) values. Conclusions BLCM suggests a > 25% higher prevalence of pneumococcal pneumonia than estimated by a conventional approach assuming UAT as a gold standard reference test. Higher quantities of pneumococcal DNA in the upper respiratory tract were associated with pneumococcal pneumonia in adults but the addition of a second specific pneumococcal test was required to accurately estimate disease status and prevalence. By incorporating the inherent uncertainty of diagnostic tests, BLCM can obtain more reliable estimates of disease status and improve understanding of underlying etiology. Electronic supplementary material The online version of this article (10.1186/s12879-019-4067-3) contains supplementary material, which is available to authorized users.

Bloodstream infection surveillance conducted from 2008 to 2014 in all 20 hospitals in Sa Kaeo and Nakhon Phanom provinces, Thailand, allowed us to look at disease burden, antibiotic susceptibilities, and recurrent infections caused by extended-spectrum β-lactamase (ESBL)–producing Escherichia coli and Klebsiella pneumoniae. Of 97,832 blood specimens, 3,338 were positive for E. coli and 1,086 for K. pneumoniae. The proportion of E. coli isolates producing ESBL significantly increased from 19% to 22% in 2008–2010 to approximately 30% from 2011 to 2014 (P-value for trend = 0.02), whereas ESBL production among K. pneumoniae cases was 27.4% with no significant trend over time. Incidence of community-onset ESBL-producing E. coli increased from 5.4 per 100,000 population in 2008 to 12.8 in 2014, with the highest rates among persons aged ≥ 70 years at 79 cases per 100,000 persons in 2014. From 2008 to 2014, community-onset ESBL-producing K. pneumoniae incidence was 2.7 per 100,000, with a rate of 12.9 among those aged ≥ 70 years. Although most (93.6% of E. coli and 87.6% of K. pneumoniae) infections were community-onset, hospital-onset infections were twice as likely to be ESBL. Population-based surveillance, as described, is vital to accurately monitor emergence and trends in antimicrobial resistance, and in guiding the development of rational antimicrobial therapy recommendations.

Background Surveillance data from a large measles outbreak in Mongolia suggested increased case fatality ratio (CFR) in the second of 2 waves. To confirm the increase in CFR and identify risk factors for measles death, we enhanced mortality ascertainment and conducted a case-control study among infants hospitalized for measles. Methods We linked national vital records with surveillance data of clinically or laboratory-confirmed infant (aged Results Infant measles deaths increased from 3 among 2224 cases (CFR: 0.13%) in wave 1 to 113 among 4884 cases (CFR: 2.31%) in wave 2 (P < .001). Inpatient admission, 7–21 days before measles rash onset, for pneumonia or influenza (amOR: 4.5; CI, 2.6–8.0), but not other diagnoses, was significantly associated with death. Discussion Measles infection among children hospitalized with respiratory infections likely increased deaths due to measles during wave 2. Preventing measles virus nosocomial transmission likely decreases measles mortality.

BACKGROUND Prior to 2010, the clinical management of dengue in Puerto Rico was inconsistent with World Health Organization guidelines. A 4-hour classroom-style course on dengue clinical management was developed in 2009 and mandated for Puerto Rico medical licensure in 2010. Fifty physicians were trained as "master trainers" and gave this course to 7638 physicians. This study evaluated the effect of the course on the clinical management of hospitalized dengue patients. METHODS Pre- and post-course test responses were compared. Changes in physician practices were assessed by reviewing medical records of 430 adult and 1075 pediatric dengue patients at the 12 hospitals in Puerto Rico that reported the most cases during 2008-2009 (pre-intervention) and 2011 (post-intervention). Mixed-effects logistic regression was used to compare key indicators of dengue management. RESULTS Physician test scores increased from 48% to 72% correct. Chart reviews showed that the percentage of adult patients who did not receive corticosteroids increased from 30% to 68% (odds ratio [OR], 5.9; 95% confidence interval [CI], 3.7-9.5) and from 91% to 96% in pediatric patients (OR, 2.7; 95% CI, 1.5-4.9). Usage of isotonic intravenous saline during the critical period increased from 57% to 90% in adult patients (OR, 6.2; 95% CI, 1.9-20.4) and from 25% to 44% in pediatric patients (OR, 3.4; 95% CI, 2.2-5.3). CONCLUSIONS Management of dengue inpatients significantly improved following implementation of a classroom-style course taught by master trainers. An online version of the course was launched in 2014 to expand its reach and sustainability.

To monitor progress toward maternal and neonatal tetanus elimination (MNTE) in Cambodia, we conducted a nationwide serosurvey of tetanus immunity in 2012. Multistage cluster sampling was used to select 2,154 women aged 15 to 39 years. Tetanus toxoid antibodies in serum samples were measured by gold-standard double-antigen enzyme-linked immunosorbent assay (DAE) and a novel multiplex bead assay (MBA). Antibody concentrations of ≥0.01 IU/ml by DAE or the equivalent for MBA were considered seroprotective. Estimated tetanus seroprotection was 88% (95% confidence interval [CI], 86 to 89%); 64% (95% CI, 61 to 67%) of women had antibody levels of ≥1.0 IU/ml. Seroprotection was significantly lower ( P < 0.001) among women aged 15 to 19 years (63%) and 20 to 24 years (87%) than among those aged ≥25 years (96%), among nulliparous women than among parous women (71 versus 97%), and among those living in the western region than among those living in other regions (82 versus 89%). The MBA showed high sensitivity (99% [95% CI, 98 to 99%]) and specificity (92% [95% CI, 88 to 95%]) compared with DAE. Findings were compatible with MNTE in Cambodia (≥80% protection). Tetanus immunity gaps should be addressed through strengthened routine immunization and targeted vaccination campaigns. Incorporating tetanus testing in national serosurveys using MBAs, which can measure immunity to multiple pathogens simultaneously, may be beneficial for monitoring MNTE.

Introduction Endemic measles persists in China, despite >95% reported coverage of two measles-containing vaccine doses and nationwide campaign that vaccinated more than 100 million children in 2010. In 2011, almost half of the 9943 measles cases in China occurred in children eligible for measles vaccination. We conducted a case-control study during 2012–2013 to identify risk factors for measles infection in children aged 8 months–14 years. Methods Children with laboratory-confirmed measles were age- and neighborhood-matched with three controls. We interviewed parents of case and control infants on potential risk factors for measles. We calculated adjusted matched odds ratios and 95% confidence intervals of risk factors. We calculated attributable fractions for risk factors that could be interpreted as causal and vaccine efficacy (VE) for the measles containing vaccine (MCV) used in the Chinese immunization program. Results In all, 969 case-patients and 2845 controls were enrolled. In multivariable analysis, lack of measles vaccination both overall (mOR 22.7 [16.6, 31.1] and when stratified by region (east region, mOR 74.2 [27.3, 202]; central/western regions mOR 17.4 [12.5, 24.3]), hospital exposure (mOR 63.0, 95% CI [32.8, 121]), and migration among counties (overall mOR 3.0 [2.3, 3.9]) were significant risk factors. The calculated VE was 91.9–96.1% for a single dose of MCV and 96.6–99.5% for 2 doses. Conclusions Lack of vaccination was the leading risk factor for measles infection, especially in children born since the 2010 supplementary immunization activity. Reducing missed vaccination opportunities, improving immunization access for migrant children, and strengthening school/kindergarten vaccine checks are needed to strengthen the routine immunization program and maintain progress toward measles elimination in China.

We reported a case of Escherichia coli with colistin resistance and an extensively drug-resistant phenotype. Molecular analysis revealed that the isolate carried mcr-1 and multiple β-lactamase genes includingblaNDM1, blaCTX-M-15, blaTEM1, and blaCMY-2. This is the first report of a clinical mcr-1 isolate in Thailand highlighting the urgent need for a comprehensive antimicrobial resistance containment strategy to prevent further spread.

Staphylococcus aureus infections are one of the most common bloodstream infections worldwide.1,2 Antimicrobial resistant strains, namely, methicillin-resistant S. aureus (MRSA), are associated with increased mortality, length of hospitalization, and health-care costs3–5; yet, the burden of disease is poorly understood in many countries. A 2014 World Health Organization (WHO) report emphasized the critical need for greater surveillance to more rapidly detect, respond, and control public health threats and therefore enhance global health security. World Health Organization also highlighted major gaps in surveillance in Southeast Asia.6 The few available studies suggest that S. aureus is one of the top causes of bloodstream infections in Thailand and Southeast Asia.7–13 A 2012 review found that methicillin resistance among S. aureus in Southeast Asia varied from 0–39%.14 In two cross-sectional studies in tertiary hospitals in Bangkok and northeast Thailand from 2005 and 2006, MRSA was documented in > 20% of S. aureus isolates.10,11 Since then, significant changes in the epidemiology of S. aureus and methicillin resistance in Thailand and the region may have occurred. The 2011 Jaipur Declaration emphasized the importance of antimicrobial resistance and the need for immediate regional action,15 and infection control efforts in tertiary care centers in Thailand have been intensified.16–18 A better understanding of current trends in S. aureus and MRSA bacteremia is needed to monitor trends and guide prevention and control efforts in Thailand. In 2005, the Thailand Ministry of Public Health, in collaboration with the U.S. Centers for Disease Control and Prevention (CDC), initiated population-based surveillance of bloodstream infections in two rural provinces in Thailand to create a sustainable system to monitor changes in pathogenesis and resistance patterns in rural border provinces where emerging epidemics could occur. This included implementation of automated blood culturing systems and sustained laboratory capacity building activities that were not as developed as in a metropolitan center such as Bangkok. We report incidence rates and trends in S. aureus bacteremia and methicillin resistance from 2006–2014.

Summary Background Outbreak response efforts for the 2014–15 Ebola virus disease epidemic in west Africa brought widespread transmission to an end. However, subsequent clusters of infection have occurred in the region. An Ebola virus disease cluster in Liberia in November, 2015, that was identified after a 15-year-old boy tested positive for Ebola virus infection in Monrovia, raised the possibility of transmission from a persistently infected individual. Methods Case investigations were done to ascertain previous contact with cases of Ebola virus disease or infection with Ebola virus. Molecular investigations on blood samples explored a potential linkage between Ebola virus isolated from cases in this November, 2015, cluster and epidemiologically linked cases from the 2014–15 west African outbreak, according to the national case database. Findings The cluster investigated was the family of the index case (mother, father, three siblings). Ebola virus genomes assembled from two cases in the November, 2015, cluster, and an epidemiologically linked Ebola virus disease case in July, 2014, were phylogenetically related within the LB5 sublineage that circulated in Liberia starting around August, 2014. Partial genomes from two additional individuals, one from each cluster, were also consistent with placement in the LB5 sublineage. Sequencing data indicate infection with a lineage of the virus from a former transmission chain in the country. Based on serology and epidemiological and genomic data, the most plausible scenario is that a female case in the November, 2015, cluster survived Ebola virus disease in 2014, had viral persistence or recurrent disease, and transmitted the virus to three family members a year later. Interpretation Investigation of the source of infection for the November, 2015, cluster provides evidence of Ebola virus persistence and highlights the risk for outbreaks after interruption of active transmission. These findings underscore the need for focused prevention efforts among survivors and sustained capacity to rapidly detect and respond to new Ebola virus disease cases to prevent recurrence of a widespread outbreak. Funding US Centers for Disease Control and Prevention, Defense Threat Reduction Agency, and WHO.

Resurgent outbreaks of vaccine-preventable diseases that have previously been controlled or eliminated have been observed in many settings. Reactive vaccination campaigns may successfully control outbreaks but must necessarily be implemented in the face of considerable uncertainty. Real-time surveillance may provide critical information about at-risk population and optimal vaccination targets, but may itself be limited by the specificity of disease confirmation. We propose an integrated modelling approach that synthesizes historical demographic and vaccination data with real-time outbreak surveillance via a dynamic transmission model and an age-specific disease confirmation model. We apply this framework to data from the 1996–1997 measles outbreak in São Paulo, Brazil. To simulate the information available to decision-makers, we truncated the surveillance data to what would have been available at 1 or 2 months prior to the realized interventions. We use the model, fitted to real-time observations, to evaluate the likelihood that candidate age-targeted interventions could control the outbreak. Using only data available prior to the interventions, we estimate that a significant excess of susceptible adults would prevent child-targeted campaigns from controlling the outbreak and that failing to account for age-specific confirmation rates would underestimate the importance of adult-targeted vaccination.

International audience; Acute Q fever cases were identified from a hospital-based acute febrile illness study conducted in six community hospitals in rural north and northeast Thailand from 2002 to 2005. Of 1,784 participants that underwent Coxiella burnetii testing, nine (0.5%) participants were identified in this case-series as acute Q fever cases. Eight case-patients were located in one province. Four case-patients were hospitalized. Median age was 13 years (range: 7-69); five were male. The proportion of children with acute Q fever infection was similar to adults (P=0.17). This previously unrecognized at-risk group, school-age children, indicates that future studies and prevention interventions should target this population. The heterogeneity of disease burden across Thailand and milder clinical presentations found in this case-series should be considered in future studies. As diagnosis based on serology is limited during the acute phase of the disease, other diagnostic options, such as polymerase chain reaction, should be explored to improve acute case detection.

The incidence of pneumococcal pneumonia among adults is a key driver for the cost-effectiveness of pneumococcal conjugate vaccine used among children. We sought to obtain more accurate incidence estimates among adults by including results of pneumococcal urine antigen testing (UAT) from population-based pneumonia surveillance in two Thai provinces. Active surveillance from 2006 to 2011 identified acute lower respiratory infection (ALRI)-related hospital admissions. Adult cases of pneumococcal pneumonia were defined as hospitalized ALRI patients aged ≥ 18 years with isolation of Streptococcus pneumoniae from blood or with positive UAT. Among 39,525 adult ALRI patients, we identified 481 pneumococcal pneumonia cases (105 by blood culture, 376 by UAT only). Estimated incidence of pneumococcal pneumonia hospitalizations was 30.5 cases per 100,000 persons per year (2.2 and 28.3 cases per 100,000 persons per year by blood culture and UAT, respectively). Incidence varied between 22.7 in 2007 and 43.5 in 2010, and increased with age to over 150 per 100,000 persons per year among persons aged ≥ 70 years. Viral coinfections including influenza A/B, respiratory syncytial virus (RSV), and adenovirus occurred in 11% (44/409) of pneumococcal pneumonia cases tested. Use of UAT to identify cases of pneumococcal pneumonia among adults in rural Thailand substantially increases estimates of pneumococcal pneumonia burden, thereby informing cost-effectiveness analyses and vaccine policy decisions.

On 29 October 2000, the World Health Organization (WHO) Regional Commission for the Certification of Poliomyelitis Eradication in the Western Pacific certified the WHO Western Pacific Region as free of indigenous wild poliovirus. This status has been maintained to date: wild poliovirus importations into Singapore (in 2006) and Australia (in 2007) did not lead to secondary cases, and an outbreak in China (in 2011) was rapidly controlled. Circulation of vaccine derived polioviruses in Cambodia, China and the Philippines was quickly interrupted. A robust acute flaccid paralysis surveillance system, including a multitiered polio laboratory network, has been maintained, forming the platform for integrating measles, neonatal tetanus, and other vaccine-preventable disease surveillance and their respective control goals. While polio elimination remains one of the most important achievements in public health in the Western Pacific Region, extended delays in global eradication have, however, led to shifting and competing public health priorities among member states and partners and have made the region increasingly vulnerable.

OBJECTIVES To evaluate the effects of ankle taping, bracing, and fibular reposition taping (FRT) on running biomechanics as measured with wearable sensors. APPROACH A randomized crossover study design was employed as 12 young adults (six males, six females) with history of ankle sprain completed four 400 m runs at self-selected pace on an outdoor track. One of four conditions (control, taped, braced, FRT) was applied prior to each run. RunScribe™ sensors were heel-mounted on each shoe and measured kinematic (maximum pronation velocity, pronation excursion), kinetic (braking and impact g) and spatiotemporal (cycle time, contact time, stride length, stride pace) variables. MAIN RESULTS Compared to the control and FRT conditions, both the taped and braced conditions significantly restricted maximum pronation velocity (control: 767.8 ± 228.3° s-1; FRT: 721.2 ± 213.6° s-1; taped: 528.8 ± 193.6° s-1; braced: 562.1 ± 178.3° s-1) and pronation excursion (control: 17.1 ± 6.6°; FRT: 17.2 ± 6.6°; taped:11.9 ± 4.7°; braced: 12.9 ± 5.1°). Braking g were significantly higher in the control condition (12.1 ± 0.9 g) condition compared to the taped (11.6 ± 1.0 g) and braced (11.6 ± 1.2 g) conditions. Cycle time was significantly greater in the braced condition (677.8 ± 43.7 ms) compared to taped (669.3 ± 44.6 ms) and FRT (672.1 ± 44.2 ms) conditions. SIGNIFICANCE Ankle taping and bracing were shown to be comparable in decreasing ankle kinematics and kinetics, while FRT caused minimal changes in running biomechanics. Taping and bracing may be beneficial in stabilizing and protecting the ankle while FRT should not be used to restrict ankle motion during running.

In 2009, an increased proportion of suspected dengue cases reported to the surveillance system in Puerto Rico were laboratory negative. As a result, enhanced acute febrile illness (AFI) surveillance was initiated in a tertiary care hospital. Patients with fever of unknown origin for 2-7 days duration were tested for Leptospira, enteroviruses, influenza, and dengue virus. Among the 284 enrolled patients, 31 dengue, 136 influenza, and 3 enterovirus cases were confirmed. Nearly half (48%) of the confirmed dengue cases met clinical criteria for influenza. Dengue patients were more likely than influenza patients to have hemorrhage (81% versus 26%), rash (39% versus 9%), and a positive tourniquet test (52% versus 18%). Mean platelet and white blood cell count were lower among dengue patients. Clinical diagnosis can be particularly difficult when outbreaks of other AFI occur during dengue season. A complete blood count and tourniquet test may be useful to differentiate dengue from other AFIs.

BACKGROUND: Rotavirus is the leading cause of severe diarrhea among young children worldwide. Rotavirus vaccines have demonstrated substantial benefits in many countries that have introduced vaccine nationally. In China, where rotavirus vaccines are not available through the national immunization program, it will be important to review relevant local and global information to determine the potential value of national introduction. Therefore, we reviewed evidence of rotavirus disease burden among Chinese children