Epidemiological Profile of Children Infected with Bordetella pertussis at Varela Santiago Children’s Hospital: a Retrospective Study

Abstract Background: Pertussis, also called whooping cough, is an acute infectious disease of high transmissibility transmitted through aerosol particles released during the catarrhal phase and paroxysmal cough. Since the 1990s its incidence has increased and atypical clinical forms have been identified, mainly in newborns and adults. We hypothesized that there is a relationship between the high incidence of pertussis infection in children up to 6 months of age and genetic changes in the circulating strains of B. pertussis leading to inefficacy of diphtheria, tetanus, and pertussis vaccine (DTP). Methods: Data were obtained from the medical records of hospitalized patients at the Varela Santiago Children’s Hospital in Brazil from January 1, 2013 to December 31, 2013. Results: A total of 33 cases of pertussis hospitalizations were found, where 75.7% (25/33) of the patients were 6 months of age or younger (6 patients were 30 days old or younger while 19 ranged in age from 31 days to 6 months). Of these, 54.5% (14/25) were in exclusive breastfed children. Only 18.2% (6/33) of the patients had the appropriate administration of DTP doses according to their age. Signs and symptoms were: cough 100%, cyanosis 63.6%, fever 48.5% and inspiratory winch 33.3%. Azithromycin was used as monotherapy in 90% (30/33) of the cases and the mean time of hospitalization was 9.48 days ranging from 6 to 30 days. No patient died. Conclusion: We identified a high prevalence (75.7%) of B. pertussis infection in children up to 6 months of age. This is likely explained by the low vaccination rate (18.2%) and the low percentage of exclusive breastfeeding of the studied population. The low rate of vaccination is unexpected, given that there has been greater access to vaccination in recent decades in Brazil. In addition, the cases evolved with an atypical clinical presentation, since the classic symptoms of the catarrhal stage were absent or had a such short duration that such symptoms were no longer present at the time of hospitalization. Our study does not exclude the possibility that genetic changes are occurring in the circulating strains of B. pertussis and that DTP seems to have less efficacy on these new strains, but future studies will be needed to specifically test this hypothesis. Disclosures All authors: No reported disclosures

Perinatal Case Fatality Rate Related to Congenital Zika Syndrome in Brazil: a Cross-Sectional Study

Abstract Background: Many studies have demonstrated a causal link between Zika virus (ZIKV) infection, microcephaly (MCP), and other congenital abnormalities (CA). This study aimed to determine perinatal case fatality rate in cases of Congenital Zika Syndrome (CZS) in the Rio Grande do Norte State (RN), a Brazilian Northeast State highly impacted by the Zika virus outbreak. Methods: A cross-sectional study was conducted using data obtained through the State Health Department (SHD) for cases of MCP and CA in Rio Grande do Norte from April 2015 to February 5, 2016. Definition of perinatal period: commences at 22 completed weeks (154 days) of gestation and ends seven completed days after birth. Results: During the study period, there were 486 cases of MCP and others CA notified in RN, of which 142 were confirmed and 108 remain under investigation. The remaining 236 cases have been ruled out by presenting normal examinations or due to presenting microcephaly by noninfectious causes. Of the total confirmed cases, 26.7% (38/142) died after birth or during pregnancy. 15.78% (06/38) of confirmed deaths had ZIKV infection during pregnancy and 2.63% (01/38) had a positive TORCH blood test. The six cases related to ZIKV were confirmed by RT–PCR and/or IgM/IgG antibodies against ZIKV. The remaining cases of deaths remain either under investigation or have been ruled out. Conclusion: This study highlights a high rate of perinatal lethality (15.78%) in cases of CZS. Despite the growing number of CZS cases, the real incidence and prevalence might be higher due to the underreporting and lack of resources for confirmatory diagnostic tests (laboratory and imaging). Due to the high rate of lethality and the ongoing uncontrolled ZIKV outbreak, this study predicts an increase in the infant mortality rate in Brazil and highlights the need for developing public health programs to control the ZIKV outbreak. Disclosures All authors: No reported disclosures

Spatio-Temporal Patterns of Barmah Forest Virus Disease in Queensland, Australia

Background Barmah Forest virus (BFV) disease is a common and wide-spread mosquito-borne disease in Australia. This study investigated the spatio-temporal patterns of BFV disease in Queensland, Australia using geographical information system (GIS) tools and geostatistical analysis. Methods/Principal Findings We calculated the incidence rates and standardised incidence rates of BFV disease. Moran's I statistic was used to assess the spatial autocorrelation of BFV incidences. Spatial dynamics of BFV disease was examined using semi-variogram analysis. Interpolation techniques were applied to visualise and display the spatial distribution of BFV disease in statistical local areas (SLAs) throughout Queensland. Mapping of BFV disease by SLAs reveals the presence of substantial spatio-temporal variation over time. Statistically significant differences in BFV incidence rates were identified among age groups (χ2 = 7587, df = 7327,p<0.01). There was a significant positive spatial autocorrelation of BFV incidence for all four periods, with the Moran's I statistic ranging from 0.1506 to 0.2901 (p<0.01). Semi-variogram analysis and smoothed maps created from interpolation techniques indicate that the pattern of spatial autocorrelation was not homogeneous across the state. Conclusions/Significance This is the first study to examine spatial and temporal variation in the incidence rates of BFV disease across Queensland using GIS and geostatistics. The BFV transmission varied with age and gender, which may be due to exposure rates or behavioural risk factors. There are differences in the spatio-temporal patterns of BFV disease which may be related to local socio-ecological and environmental factors. These research findings may have implications in the BFV disease control and prevention programs in Queensland

Effects of Cu/Zn Superoxide Dismutase (sod1) Genotype and Genetic Background on Growth, Reproduction and Defense in Biomphalaria glabrata

Resistance of the snail Biomphalaria glabrata to the trematode Schistosoma mansoni is correlated with allelic variation at copper-zinc superoxide dismutase (sod1). We tested whether there is a fitness cost associated with carrying the most resistant allele in three outbred laboratory populations of snails. These three populations were derived from the same base population, but differed in average resistance. Under controlled laboratory conditions we found no cost of carrying the most resistant allele in terms of fecundity, and a possible advantage in terms of growth and mortality. These results suggest that it might be possible to drive resistant alleles of sod1 into natural populations of the snail vector for the purpose of controlling transmission of S. mansoni. However, we did observe a strong effect of genetic background on the association between sod1 genotype and resistance. sod1 genotype explained substantial variance in resistance among individuals in the most resistant genetic background, but had little effect in the least resistant genetic background. Thus, epistatic interactions with other loci may be as important a consideration as costs of resistance in the use of sod1 for vector manipulation

Impact of early life exposures to geohelminth infections on the development of vaccine immunity, allergic sensitization, and allergic inflammatory diseases in children living in tropical Ecuador: the ECUAVIDA birth cohort study.

Background Geohelminth infections are highly prevalent infectious diseases of childhood in many regions of the Tropics, and are associated with significant morbidity especially among pre-school and school-age children. There is growing concern that geohelminth infections, particularly exposures occurring during early life in utero through maternal infections or during infancy, may affect vaccine immunogenicity in populations among whom these infections are endemic. Further, the low prevalence of allergic disease in the rural Tropics has been attributed to the immune modulatory effects of these infections and there is concern that widespread use of anthelmintic treatment in high-risk groups may be associated with an increase in the prevalence of allergic diseases. Because the most widely used vaccines are administered during the first year of life and the antecedents of allergic disease are considered to occur in early childhood, the present study has been designed to investigate the impact of early exposures to geohelminths on the development of protective immunity to vaccines, allergic sensitization, and allergic disease. Methods/Design A cohort of 2,403 neonates followed up to 8 years of age. Primary exposures are infections with geohelminth parasites during the last trimester of pregnancy and the first 2 years of life. Primary study outcomes are the development of protective immunity to common childhood vaccines (i.e. rotavirus, Haemophilus influenzae type B, Hepatitis B, tetanus toxoid, and oral poliovirus type 3) during the first 5 years of life, the development of eczema by 3 years of age, the development of allergen skin test reactivity at 5 years of age, and the development of asthma at 5 and 8 years of age. Potential immunological mechanisms by which geohelminth infections may affect the study outcomes will be investigated also. Discussion The study will provide information on the potential effects of early exposures to geohelminths (during pregnancy and the first 2 years of life) on the development of vaccine immunity and allergy. The data will inform an ongoing debate of potential effects of geohelminths on child health and will contribute to policy decisions on new interventions designed to improve vaccine immunogenicity and protect against the development of allergic diseases

Understanding the relation between Zika virus infection during pregnancy and adverse fetal, infant and child outcomes: a protocol for a systematic review and individual participant data meta-analysis of longitudinal studies of pregnant women and their infants and children

IntroductionZika virus (ZIKV) infection during pregnancy is a known cause of microcephaly and other congenital and developmental anomalies. In the absence of a ZIKV vaccine or prophylactics, principal investigators (PIs) and international leaders in ZIKV research have formed the ZIKV Individual Participant Data (IPD) Consortium to identify, collect and synthesise IPD from longitudinal studies of pregnant women that measure ZIKV infection during pregnancy and fetal, infant or child outcomes.Methods and analysisWe will identify eligible studies through the ZIKV IPD Consortium membership and a systematic review and invite study PIs to participate in the IPD meta-analysis (IPD-MA). We will use the combined dataset to estimate the relative and absolute risk of congenital Zika syndrome (CZS), including microcephaly and late symptomatic congenital infections; identify and explore sources of heterogeneity in those estimates and develop and validate a risk prediction model to identify the pregnancies at the highest risk of CZS or adverse developmental outcomes. The variable accuracy of diagnostic assays and differences in exposure and outcome definitions means that included studies will have a higher level of systematic variability, a component of measurement error, than an IPD-MA of studies of an established pathogen. We will use expert testimony, existing internal and external diagnostic accuracy validation studies and laboratory external quality assessments to inform the distribution of measurement error in our models. We will apply both Bayesian and frequentist methods to directly account for these and other sources of uncertainty.Ethics and disseminationThe IPD-MA was deemed exempt from ethical review. We will convene a group of patient advocates to evaluate the ethical implications and utility of the risk stratification tool. Findings from these analyses will be shared via national and international conferences and through publication in open access, peer-reviewed journals.Trial registration numberPROSPERO International prospective register of systematic reviews (CRD42017068915).</jats:sec

Congenital Neurological Disorders in Children with Microcephaly Related to Exanthematous Diseases During Pregnancy: A Cohort Study

Abstract Background: An increase in the prevalence of microcephaly (MCP) was seen in Rio Grande do Norte State (RN) since September 2015. This Brazilian northeast state was highly impacted by a Zika (ZIKV) outbreak in the last 2 years. The highest rate of MCP was in November 2015 with 20.1 cases per 1,000 live births, compared with 1.8 cases/year in the previous years. Our study aimed to evaluate the neurological disorders in children with microcephaly whose mothers had exanthematous disease (ED) during the pregnancy. Methods: We evaluated children up to 17 months old followed at a children rehabilitation center in RN. Cohort enrollment occurred with children born between January 2015 and May 2016. We interviewed their mothers about the occurrence of ED during their pregnancy. Results: Of the 37 cases of MCP (25 male, 12 girls), 10 mothers did not know how to describe The presence of ED during pregnancy. Of the 24 cases of MCP with maternal ED, 9 patients were classified as having severe spasticity (Ashworth score 3 and 4), 4 patients were classified as mild (Ashworth score 1e 2) and 11 had no spasticity. Eleven patients had seizure disorders and 5 reported irritability. Conclusion: According to this data, there is a high prevalence of neurological complications in children with MCP related to ED. These patients need close follow-up care and intensive medical interventions. Longer follow-up will provide data regarding these chronic neurological complications and how best to intervene. Disclosures All authors: No reported disclosures