Prevalence of microcephaly and Zika virus infection in a pregnancy cohort in Kenya, 2017-2019.

BACKGROUND: Zika virus (ZIKV), first discovered in Uganda in 1947, re-emerged globally in 2013 and was later associated with microcephaly and other birth defects. We determined the incidence of ZIKV infection and its association with adverse pregnancy and fetal outcomes in a pregnancy cohort in Kenya. METHODS: From October 2017 to July 2019, we recruited and followed up women aged ≥ 15 years and ≤ 28 weeks pregnant in three hospitals in coastal Mombasa. Monthly follow-up included risk factor questions and a blood sample collected for ZIKV serology. We collected anthropometric measures (including head circumference), cord blood, venous blood from newborns, and any evidence of birth defects. Microcephaly was defined as a head circumference (HC) < 2 standard deviations (SD) for sex and gestational age. Severe microcephaly was defined as HC < 3 SD for sex and age. We tested sera for anti-ZIKV IgM antibodies using capture enzyme-linked immunosorbent assay (ELISA) and confirmed positives using the plaque reduction neutralization test (PRNT90) for ZIKV and for dengue (DENV) on the samples that were ZIKV neutralizing antibody positive. We collected blood and urine from participants reporting fever or rash for ZIKV testing. RESULTS: Of 2889 pregnant women screened for eligibility, 2312 (80%) were enrolled. Of 1916 recorded deliveries, 1816 (94.6%) were live births and 100 (5.2%) were either stillbirths or spontaneous abortions (< 22 weeks of gestation). Among 1236 newborns with complete anthropometric measures, 11 (0.9%) had microcephaly and 3 (0.2%) had severe microcephaly. A total of 166 (7.2%) participants were positive for anti-ZIKV IgM, 136 of whom became seropositive during follow-up. Among the 166 anti-ZIKV IgM positive, 3 and 18 participants were further seropositive for ZIKV and DENV neutralizing antibodies, respectively. Of these 3 and 18 pregnant women, one and 13 (72.2%) seroconverted with antibodies to ZIKV and DENV, respectively. All 308 samples (serum and urine samples collected during sick visits and samples that were anti-ZIKV IgM positive) tested by RT-PCR were negative for ZIKV. No adverse pregnancy or neonatal outcomes were reported among the three participants with confirmed ZIKV exposure. Among newborns from pregnant women with DENV exposure, four (22.2%) were small for gestational age and one (5.6%) had microcephaly. CONCLUSIONS: The prevalence of severe microcephaly among newborns in coastal Kenya was high relative to published estimates from facility-based studies in Europe and Latin America, but little evidence of ZIKV transmission. There is a need for improved surveillance for microcephaly and other congenital malformations in Kenya.

Investigations on Potential Applications of CaMg(CO3)2 Nanoparticles.

Calcium magnesium carbonate nanoparticles (CaMg(CO3)2 NPs), well-known as dolomite, are formed by the replacement of half of the calcite minerals of limestone. The dolomite (CaMg(CO3)2) nanoparticles are composed of calcite (CaCO3) and magnesium carbonate (MgCO3), both of which offer promising strategies for maintaining growth and development in mammals and agricultural plants. A grounded mixture of dolomite limestone was prepared via colloidal precipitates for the synthesis of CaMg(CO3)2 NPs, and their characteristics were examined using XRD, particle size analysis by DLS, and surface morphology by SEM and TEM. X-ray photoelectron spectroscopy was used to investigate the binding energy of each element of the dolomite NPs. Spectroscopy revealed that colloidal precipitation is the ideal method for producing NPs. We assessed the numerous beneficial impacts of CaMg(CO3)2 NPs in diverse sectors such as agriculture, cancer treatment, and microbiology in this study. Furthermore, an in vivo study was also carried out on chickens to observe the effects of CaMg(CO3)2 NPs. The obtained results showed that the treated group with CaMg(CO3)2 NPs maintained a more uniform calcium absorption rate than the control group did. The findings of this study suggest that CaMg(CO3)2 NPs operate as a stimulant for plants and as an inhibitory agent for bacteria and cancer cells.

Inappropriate use of antibiotics for childhood diarrhea case management - Kenya, 2009-2016.

BACKGROUND: Antibiotics are essential to treat for many childhood bacterial infections; however inappropriate antibiotic use contributes to antimicrobial resistance. For childhood diarrhea, empiric antibiotic use is recommended for dysentery (bloody diarrhea) for which first-line therapy is ciprofloxacin. We assessed inappropriate antibiotic prescription for childhood diarrhea in two primary healthcare facilities in Kenya. METHODS: We analyzed data from the Kenya Population Based Infectious Disease Surveillance system in Asembo (rural, malaria-endemic) and Kibera (urban slum, non-malaria-endemic). We examined records of children aged 2-59 months with diarrhea (≥3 loose stools in 24 h) presenting for care from August 21, 2009 to May 3, 2016, excluding visits with non-diarrheal indications for antibiotics. We examined the frequency of antibiotic over-prescription (antibiotic prescription for non-dysentery), under-prescription (no antibiotic prescription for dysentery), and inappropriate antibiotic selection (non-recommended antibiotic). We examined factors associated with over-prescription and under-prescription using multivariate logistic regression with generalized estimating equations. RESULTS: Of 2808 clinic visits with diarrhea in Asembo, 2685 (95.6%) were non-dysentery visits and antibiotic over-prescription occurred in 52.5%. Of 4697 clinic visits with diarrhea in Kibera, 4518 (96.2%) were non-dysentery and antibiotic over-prescription occurred in 20.0%. Antibiotic under-prescription was noted in 26.8 and 73.7% of dysentery cases in Asembo and Kibera, respectively. Ciprofloxacin was used for 11% of dysentery visits in Asembo and 0% in Kibera. Factors associated with over- and under-prescription varied by site. In Asembo a discharge diagnosis of gastroenteritis was associated with over-prescription (adjusted odds ratio [aOR]:8.23, 95% confidence interval [95%CI]: 3.68-18.4), while malaria diagnosis was negatively associated with antibiotic over-prescription (aOR 0.37, 95%CI: 0.25-0.54) but positively associated with antibiotic under-prescription (aOR: 1.82, 95%CI: 1.05-3.13). In Kibera, over-prescription was more common among visits with concurrent signs of respiratory infection (difficulty breathing; aOR: 3.97, 95%CI: 1.28-12.30, cough: aOR: 1.42, 95%CI: 1.06-1.90) and less common among children aged < 1 year (aOR: 0.82, 95%CI: 0.71-0.94). CONCLUSIONS: Inappropriate antibiotic prescription was common in childhood diarrhea management and efforts are needed to promote rational antibiotic use. Interventions to improve antibiotic use for diarrhea should consider the influence of malaria diagnosis on clinical decision-making and address both over-prescription, under-prescription, and inappropriate antibiotic selection.

Characteristics, risk factors, and outcomes related to Zika virus infection during pregnancy in Northeastern Thailand: A prospective pregnancy cohort study, 2018-2020.

BACKGROUND: In response to the 2015-2016 Zika virus (ZIKV) outbreak and the causal relationship established between maternal ZIKV infection and adverse infant outcomes, we conducted a cohort study to estimate the incidence of ZIKV infection in pregnancy and assess its impacts in women and infants. METHODOLOGY/PRINCIPAL FINDINGS: From May 2018-January 2020, we prospectively followed pregnant women recruited from 134 participating hospitals in two non-adjacent provinces in northeastern Thailand. We collected demographic, clinical, and epidemiologic data and blood and urine at routine antenatal care visits until delivery. ZIKV infections were confirmed by real-time reverse transcriptase polymerase chain reaction (rRT-PCR). Specimens with confirmed ZIKV underwent whole genome sequencing. Among 3,312 women enrolled, 12 (0.36%) had ZIKV infections, of which two (17%) were detected at enrollment. Ten (83%, 3 in 2nd and 7 in 3rd trimester) ZIKV infections were detected during study follow-up, resulting in an infection rate of 0.15 per 1,000 person-weeks (95% CI: 0.07-0.28). The majority (11/12, 91.7%) of infections occurred in one province. Persistent ZIKV viremia (42 days) was found in only one woman. Six women with confirmed ZIKV infections were asymptomatic until delivery. Sequencing of 8 ZIKV isolates revealed all were of Asian lineage. All 12 ZIKV infected women gave birth to live, full-term infants; the only observed adverse birth outcome was low birth weight in one (8%) infant. Pregnancies in 3,300 ZIKV-rRT-PCR-negative women were complicated by 101 (3%) fetal deaths, of which 67 (66%) had miscarriages and 34 (34%) had stillbirths. There were no differences between adverse fetal or birth outcomes of live infants born to ZIKV-rRT-PCR-positive mothers compared to live infants born to ZIKV-rRT-PCR-negative mothers. CONCLUSIONS/SIGNIFICANCE: Confirmed ZIKV infections occurred infrequently in this large pregnancy cohort and observed adverse maternal and birth outcomes did not differ between mothers with and without confirmed infections.

Prevalence of HPV infection among Thai schoolgirls in the north-eastern provinces in 2018: implications for HPV immunization policy.

Objective: The aim of this study was to determine the prevalence of high-risk (HR) and vaccine-type human papillomavirus (HPV) infection among Thai schoolgirls who were not included in the national HPV immunization program. Methods: Cross-sectional surveys were conducted among grade 10 (15-16 years old) and grade 12 (17-18 years old) schoolgirls in two provinces of Thailand. Urine samples were collected using the Colli-PeeⓇ device from November 2018 to February 2019. The samples were initially tested using CobasⓇ 4800. Subsequently, all Cobas-positive samples and 1:1 matched Cobas-negative samples were tested by AnyplexⓇ assay. Prevalences of any HPV, any HR HPV, vaccine-type HPV, and individual HR HPV types were estimated by school grade. Results: Prevalences of any HPV and any HR HPV were 11.6% and 8.6% for grade 10, and 18.5% and 12.4% for grade 12 schoolgirls, respectively. Prevalences of bivalent vaccine-type HPV infection in grades 10 and 12 were 3.4% and 4.5%, respectively. Prevalences of quadrivalent and nonavalent vaccine-type HPV infections were 4.0%/6.6% and 6.4%/10.4% in grades 10 and 12, respectively. HPV16 was the most common type detected, followed by HPV58, 51, and 52. Circulating HR HPV types were similar between the school grades. Conclusion: A substantial burden of HR HPV infections was found among unvaccinated high school girls in Thailand.

A community intervention effectiveness study of single dose or two doses of bivalent HPV vaccine (CERVARIX®) in female school students in Thailand.

Human papillomavirus (HPV) is a common infection principally spread through sexual activity. Most HPV infections are asymptomatic and resolve spontaneously. However, persistent infection may progress to cervical cancer. Highly efficacious HPV vaccines have been available since 2006, yet uptake into national programs has been slow in part due to cost. WHO guidelines call for a two-dose (0,6 month) schedule for girls 9-14 years of age. Post-hoc analyses of randomized trials have found high vaccine effectiveness following a single dose of vaccine. In order to provide additional data on the potential impact of single dose HPV vaccination in a real-world setting, we are conducting an effectiveness study among Thai schoolgirls. This is an observational study of a single dose (SD) or two doses (2D) of the bivalent HPV vaccine CERVARIX® (GlaxoSmithKline plc.) administered in a school-based program to 8-9,000 Grade 8 female students in two provinces of Thailand beginning in 2018; one province is assigned the SD, and the other the standard 2D regimen. The reduction in HPV vaccine-type prevalence will be assessed in each province two and four years after vaccination by comparing HPV prevalence in urine samples obtained through cross-sectional surveys of the immunized grade cohort as they age and compared to a historical "baseline" HPV prevalence of same age students.

Complementing conventional infectious disease surveillance with national health insurance claims data in the Republic of Korea.

Surveillance remains an important tool for timely outbreak detection and response. Many countries, including Korea, have established national infectious disease surveillance systems with clinical notification. We aimed to evaluate the National Health Insurance Claims-based Surveillance (NHICS) compared to conventional passive report-based National Infectious Diseases Surveillance (NIDS). Reported to claimed cases ratios (R/C ratio) were evaluated from monthly notifiable disease cases captured by NIDS and NHICS. The relationships between 26 infectious diseases and each surveillance system were analysed using Pearson's correlation analysis and linear regression. There was an overall increase in R/C ratio from 2010-2017 (0.37 to 0.78). In 22 infectious diseases, there was a correlation between NIDS and NHICS. Moreover, claim-based surveillance showed less fluctuating disease incidence rates than report-based surveillance for specific infectious diseases, such as varicella, mumps, and scarlet fever. However, for infectious diseases with episodic outbreaks or low incidence, it was difficult to assess NHICS usefulness. Claim-based surveillance is less affected by limitations of conventional report-based surveillance systems, such as reporting rate. Given delays in claim systems, a claim-based surveillance is expected to be complementary to conventional systems for the detection of various infectious diseases with the advancement of bio-information technology.

Strengths, pitfalls, and lessons learned in implementing electronic collection of childhood vaccination data in Zambia: The SmartCare experience.

BACKGROUND: Despite widespread interest in computerized vaccination information systems, evaluation of the data quality in these systems and their acceptability to frontline healthcare workers in low and middle-income countries aren't well addressed in the literature. OBJECTIVES: Evaluation of vaccination data quality and facility-level staff perspectives on the strengths and challenges of a vaccination data module in a widely used electronic health record (EHR) system in Zambia. METHODS: After a desk review of data from two provinces, a cross-sectional mixed methods study was designed, including quantitative analysis of data quality and qualitative analysis of the module's acceptability to facility staff, using the Information System Success model as the framework for evaluation of system quality, service quality, and information quality. Data were collected from 10 purposively sampled health facilities. RESULTS: There was low current use of the vaccination module by facilities in the study area (2%). Daily power outages presented a practical challenge. Staff who had used previous EHRs had concerns about sustainability. SYSTEM QUALITY: While the module was user-friendly, there were concerns about EHR compatibility with vaccination workflow and outreach settings, where vaccines are commonly administered to older children. SERVICE QUALITY: The module was viewed as dependable; perceptions were influenced by computer literacy. INFORMATION QUALITY: The database contained incomplete and incongruous data. Staff perceived data as accurate but incomplete; easy access to data was a strength. CONCLUSIONS: Potential benefits of the vaccination module were frequently unrealized due to infrastructure, workflow, and data flow challenges that resulted in low module use and poor information quality. Elements to optimize vaccination information system implementation could include robust engagement of facility-level staff in system design, system suitability to the vaccination setting and workflow, and comprehensive planning for data flow, sustainability, data monitoring and feedback. Adaptability to the outreach setting might be increasingly important as vaccination schedules extend past infancy.

Global knowledge gaps in acute febrile illness etiologic investigations: A scoping review.

BACKGROUND: Acute febrile illness (AFI), a common reason for people seeking medical care globally, represents a spectrum of infectious disease etiologies with important variations geographically and by population. There is no standardized approach to conducting AFI etiologic investigations, limiting interpretation of data in a global context. We conducted a scoping review to characterize current AFI research methodologies, identify global research gaps, and provide methodological research standardization recommendations. METHODOLOGY/FINDINGS: Using pre-defined terms, we searched Medline, Embase, and Global Health, for publications from January 1, 2005-December 31, 2017. Publications cited in previously published systematic reviews and an online study repository of non-malarial febrile illness etiologies were also included. We screened abstracts for publications reporting on human infectious disease, aimed at determining AFI etiology using laboratory diagnostics. One-hundred ninety publications underwent full-text review, using a standardized tool to collect data on study characteristics, methodology, and laboratory diagnostics. AFI case definitions between publications varied: use of self-reported fever as part of case definitions (28%, 53/190), fever cut-off value (38·0°C most commonly used: 45%, 85/190), and fever measurement site (axillary most commonly used: 19%, 36/190). Eighty-nine publications (47%) did not include exclusion criteria, and inclusion criteria in 13% (24/190) of publications did not include age group. No publications included study settings in Southern Africa, Micronesia & Polynesia, or Central Asia. We summarized standardized reporting practices, specific to AFI etiologic investigations that would increase inter-study comparability. CONCLUSIONS: Wider implementation of standardized AFI reporting methods, with multi-pathogen disease detection, could improve comparability of study findings, knowledge of the range of AFI etiologies, and their contributions to the global AFI burden. These steps can guide resource allocation, strengthen outbreak detection and response, target prevention efforts, and improve clinical care, especially in resource-limited settings where disease control often relies on empiric treatment. PROSPERO: CRD42016035666.

Syndromic Surveillance System for Korea-US Joint Biosurveillance Portal: Design and Lessons Learned.

Driven by the growing importance of situational awareness of bioterrorism threats, the Republic of Korea (ROK) and the United States have constructed a joint military capability, called the Biosurveillance Portal (BSP), to enhance biosecurity. As one component of the BSP, we developed the Military Active Real-time Syndromic Surveillance (MARSS) system to detect and track natural and deliberate disease outbreaks. This article describes the ROK military health data infrastructure and explains how syndromic data are derived and made available to epidemiologists. Queries corresponding to 8 syndromes, based on published clinical effects of weaponized pathogens, were used to classify military hospital patient records to form aggregated daily syndromic counts. A set of ICD-10 codes for each syndrome was defined through literature review and expert panel discussion. A study set of time series of national daily counts for each syndrome was extracted from the Defense Medical Statistical Information System between January 1, 2011, and May 31, 2014. A stratified, adjusted cumulative summation algorithm was implemented for each syndrome group to signal alerts prompting investigation. The algorithm was developed by calculating sensitivity to sets of 1,000 artificial outbreak signals randomly injected in the dataset, with each signal injected in a separate trial. Queries and visualizations were adapted from the Suite for Automated Global bioSurveillance. Findings indicated that early warning of outbreaks affecting fewer than 50 patients will require analysis at subnational levels, especially for common syndrome groups. Developing MARSS to improve sensitivity will require modification of underlying syndromic diagnosis codes, engineering to coordinate alerts among subdivisions, and enhanced algorithms. The bioterrorist threat in the Korean peninsula mandates these efforts.

Clinical Markers Associated with Metabolic Syndrome Among Military Aviators.

BACKGROUND: Due to the recent increase of metabolic syndrome (MetS) in the Korean population, this study was performed to investigate the prevalence of MetS among Republic of Korea (ROK) Air Force military aviators and its relationship with clinical markers. METHODS: A cross-sectional study was performed among 911 aviators who filled out the lifestyle questionnaire and underwent medical examinations at the ROK Air Force Aerospace Medical Center. Clinical markers of aviators with MetS were investigated and odds ratios were calculated. RESULTS: Among the 911 aviators, 90 (9.9%) were found to have MetS and the prevalence of subcomponents were: 31.7% elevated blood pressure, 25.3% elevated waist circumference, 19.0% impaired glucose tolerance, 16.6% elevated triglycerides, 7.9% reduced high density lipoprotein (HDL) cholesterol. Among aviators, a significant statistical association was found between the diagnosis of MetS with the highest quartile of uric acid, white blood cell (WBC) count, and alanine transaminase (ALT) level. Adjusted odds ratio of MetS was 8.88 (3.16 ∼24.99) if all three clinical markers were at highest quartile range. DISCUSSION: Despite the relatively low prevalence of MetS in ROK Air Force aviators, further preventive measures are required as the prevalence is expected to increase in the future. Aviators with high levels of WBC count, uric acid, and ALT should be examined for MetS. Further comprehensive cohort study is required to link the elevation of clinical markers and development of MetS.

Zolpidem use and risk of fracture in elderly insomnia patients.

OBJECTIVES: To evaluate the risk of fractures related with zolpidem in elderly insomnia patients. METHODS: Health claims data on the entire South Korean elderly population from January 2005 to June 2006 were extracted from the Health Insurance Review and Assessment Service database. We applied a case-crossover design. Cases were defined as insomnia patients who had a fracture diagnosis. We set the hazard period of 1 day length prior to the fracture date and four control periods of the same length at 5, 10, 15, and 20 weeks prior to the fracture date. Time independent confounding factors such as age, gender, lifestyle, cognitive function level, mobility, socioeconomic status, residential environment, and comorbidity could be controlled using the case-crossover design. Time dependent confounding factors, especially co-medication of patients during the study period, were adjusted by conditional logistic regression analysis. The odds ratios and their 95% confidence intervals (CIs) were estimated for the risk of fracture related to zolpidem. RESULTS: One thousand five hundred and eight cases of fracture were detected in insomnia patients during the study period. In our data, the use of zolpidem increased the risk of fracture significantly (adjusted odds ratio [aOR], 1.72; 95% CI, 1.37 to 2.16). However, the association between benzodiazepine hypnotics and the risk of fracture was not statistically significant (aOR, 1.00; 95% CI, 0.83 to 1.21). Likewise, the results were not statistically significant in stratified analysis with each benzodiazepine generic subgroup. CONCLUSIONS: Zolpidem could increase the risk of fracture in elderly insomnia patients. Therefore zolpidem should be prescribed carefully and the elderly should be provided with sufficient patient education.