Does Intra-Uterine Exposure to the Zika Virus Increase Risks of Cognitive Delay at Preschool Ages? Findings from a Zika-Exposed Cohort from Grenada, West Indies.

Maternal infection with Zika virus (ZIKV) is associated with a distinct pattern of birth defects, known as congenital Zika syndrome (CZS). In ZIKV-exposed children without CZS, it is often unclear whether they were protected from in utero infection and neurotropism. Early neurodevelopmental assessment is essential for detecting neurodevelopmental delays (NDDs) and prioritizing at-risk children for early intervention. We compared neurodevelopmental outcomes between ZIKV-exposed and unexposed children at 1, 3 and 4 years to assess exposure-associated NDD risk. A total of 384 mother-child dyads were enrolled during a period of active ZIKV transmission (2016-2017) in Grenada, West Indies. Exposure status was based on laboratory assessment of prenatal and postnatal maternal serum. Neurodevelopment was assessed using the Oxford Neurodevelopment Assessment, the NEPSY® Second Edition and Cardiff Vision Tests, at 12 (n = 66), 36 (n = 58) and 48 (n = 59) months, respectively. There were no differences in NDD rates or vision scores between ZIKV-exposed and unexposed children. Rates of microcephaly at birth (0.88% vs. 0.83%, p = 0.81), and childhood stunting and wasting did not differ between groups. Our results show that Grenadian ZIKV-exposed children, the majority of whom were without microcephaly, had similar neurodevelopmental outcomes to unexposed controls up to at least an age of 4 years.

Zoonotic helminths of dogs and risk factors associated with polyparasitism in Grenada, West Indies.

Canine soil-transmitted helminths (STHs) cause important zoonoses in the tropics, with varying degrees of intensity of infection in humans and dogs. This study aimed to investigate the prevalence and associated risk factors for STHs in community dogs residing in Grenada, West Indies. In May 2021, 232 canine fecal samples were examined for zoonotic helminths by microscopy (following flotation), and genomic DNA from a subset of 211 of these samples were subjected to multiplex qPCR for the detection and specific identification of hookworms, Toxocara spp. and Strongyloides. Microscopic examination revealed that 46.5% (108/232, 95% CI 40­52.9), 9% (21/232, 95% CI 5.35­12.7) and 5.2% (12/232, 95% CI 2.3­8) of the samples contained eggs of Ancylostoma spp., Toxocara spp. and Trichuris vulpis, respectively. Multiplex qPCR revealed that, 42.2% (89/211, 95% CI 35.5­48.8) were positive for at least 1 zoonotic parasite. Of these, 40.8% (86/211, 95% CI 34.1­47.3) of samples tested positive for Ancylostoma spp., 36% (76/211, 95% CI 29.5­42.9) were positive for A. caninum, 13.3% (28/211, 95% CI 9­18.6) for A. ceylanicum, 5.7% for T. canis (12/211, 95% CI 2.97­8.81) and 1% (2/211, 95% CI 0­2.26) for Strongyloides spp. (identified as S. stercoralis and S. papillosus by conventional PCR-based Sanger sequencing). Using a multiple logistic regression model, a low body score and free-roaming behaviour were significant predictors of test-positivity for these parasitic nematodes in dogs (P < 0.05). Further studies of zoonotic STHs in humans should help elucidate the public health relevance of these parasites in Grenada.

Factors Associated with Chikungunya Infection among Pregnant Women in Grenada, West Indies.

Neonates are vulnerable to vector-borne diseases given the potential for mother-to-child congenital transmission. To determine factors associated with chikungunya virus (CHIKV) infection among pregnant women in Grenada, West Indies, a retrospective cohort study enrolled women who were pregnant during the 2014 CHIKV epidemic. In all, 520/688 women (75.5%) were CHIKV IgG positive. Low incomes, use of pit latrines, lack of home window screens, and subjective reporting of frequent mosquito bites were associated with increased risk of CHIKV infection in bivariate analyses. In the multivariate modified Poisson regression model, low income (adjusted relative risk [aRR]: 1.05 [95% CI: 1.01-1.10]) and frequent mosquito bites (aRR: 1.05 [95% CI: 1.01-1.10]) were linked to increased infection risk. In Grenada, markers of low socioeconomic status are associated with CHIKV infection among pregnant women. Given that Grenada will continue to face vector-borne outbreaks, interventions dedicated to improving living conditions of the most disadvantaged will help reduce the incidence of arboviral infections.

Ancylostoma ceylanicum Hookworms in Dogs, Grenada, West Indies.

Ancylostoma ceylanicum hookworms are recognized agents of human infection in the Asia-Pacific region. We investigated prevalence of zoonotic hookworm infections in dogs in Grenada in 2021; 40.8% were infected by hookworms, including Ancylostoma ceylanicum. Surveillance of this parasite in dogs and humans is needed in tropical/subtropical countries in the Americas.

Toxoplasma gondii clonal type III is the dominant genotype identified in Grenadian pigs.

BACKGROUND: Toxoplasma gondii is a widespread zoonotic protozoan parasite capable of infecting all warm-blooded animals. Although the genotypes of T. gondii in pigs have been reported worldwide, there is no information on the genotypes and diversity of T. gondii in pigs in Grenada, West Indies. OBJECTIVES: The aims of the present study were to isolate, genotype and determine the diversity of T. gondii genotypes in pigs. METHODS: We carried out a modified agglutination test (MAT) on blood from 149 pig hearts collected from a local meat market. Myocardial tissue homogenate from pigs that tested positive for T. gondii was homogenized and inoculated into mice for isolation of the parasite. We collected mouse tissues and extracted DNA for genotyping based on 11 polymerase chain reaction-restriction fragment length polymorphism markers (SAG1, SAG2, alt. SAG2, SAG 3, BTUB, GRA6, L358, PK1, C22-8, C 29-2 and Apico). RESULTS: Out of the 149 pig hearts, 31 (20.8%) tested positive for T. gondii on MAT. Bioassays in mice yielded 12 isolates designated TgpgGr1 to TgpgGr12. Molecular characterisation of T. gondii revealed four genotypes as follows: ToxoDB #2-clonal type III (seven isolates); ToxoDB #7 (three isolates); ToxoDB #13 (one isolate); ToxoDB #30 (1 isolate). Overall, ToxoDB #2 was the most common (58%). Toxo database (DB) # 13, which causes interstitial pneumonia in affected mice, has also been reported. CONCLUSION: The genetic diversity of T. gondii in pigs in Grenada is lower than that in other surrounding Caribbean areas.

The epidemiology and control of Toxocara canis in puppies.

Toxocara canis is a helminth zoonosis that is estimated to infect more than 100 million dogs and 1 billion people, mostly in the tropics. Humans can be infected by accidentally ingesting embryonated T. canis eggs from the environment or occasionally after ingesting L3 larvae from paratenic hosts. This study investigated the importance of vertical transmission and the role of puppies in the epidemiology of T. canis through the examination of fecal samples from dogs less than one year of age in Grenada, West Indies, a small island tropical developing country. Samples were stored at 4 °C or in 10% formalin until microscopic examination for helminth eggs or using a rapid antigen test for the presence of protozoan species. A knowledge, attitudes and practices study was completed among dog owners, physicians and veterinary students. Of 306 dogs less than one year of age, 147 (48%) were found to have T. canis eggs. Vertical transmission was indicated by the proportion of infected dogs increasing from 50% at two weeks of age (from in utero transmission) to 70% by 12 weeks (in utero and lactogenic transmission). After 12 weeks the positivity rate dropped rapidly with no dogs over 40 weeks of age being infected. As T. canis eggs were found in puppy feces at two weeks of age, initial treatment of puppies should begin earlier, at twelve days post-partum, than currently recommended to prevent shedding of eggs. Perhaps even more importantly, treatment of pregnant dogs, preventing vertical transmission, would have a major impact on the control of T. canis infection. Knowledge of T. canis and other zoonotic helminths such as Ancylostoma caninum was found to be low among dog owners, physicians and veterinary students. None of the dog owners treated their dogs for helminths, all were unaware of the risk of zoonoses, and only 9% picked up dog feces. Efforts to prevent vertical transmission and to increase awareness and knowledge of these zoonoses could result in reducing their public health impact.

Neurodevelopment in normocephalic children with and without prenatal Zika virus exposure.

OBJECTIVE: Zika virus (ZIKV) targets neural stem cells in the developing brain. However, the majority of ZIKV-exposed children are born without apparent neurological manifestations. It remains unclear if these children were protected from ZIKV neurotropism or if they harbour subtle pathology that is disruptive to brain development. We assess this by comparing neurodevelopmental outcomes in normocephalic ZIKV-exposed children relative to a parallel control group of unexposed controls. DESIGN: Cohort study. SETTING: Public health centres in Grenada, West Indies. PATIENTS: 384 mother-child pairs were enrolled during a period of active ZIKV transmission (April 2016-March 2017) and prospectively followed up to 30 months. Child exposure status was based on laboratory assessment of prenatal and postnatal maternal serum. MAIN OUTCOME MEASURES: The INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) package and Cardiff Vision Tests, administered and scored by research staff masked to child's exposure status. RESULTS: A total of 131 normocephalic ZIKV exposed (n=68) and unexposed (n=63) children were assessed between 22 and 30 months of age. Approximately half of these children completed vision testing. There were no group differences in sociodemographics. Deficits in visual acuity (31%) and contrast sensitivity (23%) were apparent in the ZIKV-exposed infants in the absence of cognitive, motor, language or behavioural delays. CONCLUSIONS: Overall neurodevelopment is likely to be unaffected in ZIKV-exposed children with normal head circumference at birth and normal head growth in the first 2 years of life. However, the visual system may be selectively vulnerable, which indicates the need for vision testing by 3 years of age.

Defining the Need for Dermatologic Surgery Global Health in an Afro-Caribbean Country.

BACKGROUND: Dermatologic surgery services are largely absent in Africa and in Afro-Caribbean counties. In the USA, studies of people of African ancestry have demonstrated health care gaps, but there are no data for Africa nor a Afro-Caribbean country. Dermatology surgery has been largely absent from global health because there are few data to demonstrate the need. We sought to determine skin cancer tumor types, and local knowledge and perception in an Afro-Caribbean country. OBJECTIVE: We sought to determine whether there exist knowledge gaps and whether a dermatology surgery medical missions program would improve the health of Afro-Caribbean people. METHODS: First, we conducted a survey of knowledge and behaviors related to skin cancer. Second, we analyzed the number and types of tumors treated during a multi-year surgical dermatology project. RESULTS: In the survey, 62% did not know what melanoma was. Eighty-one percent did not think skin cancer is preventable. Of 163 surgical specimens, 64 were malignancies with 91% related to UV exposure. CONCLUSION: There is a need for a skin cancer treatment and education program in a country of mostly African-ancestry people.

Focal epilepsy features in a child with Congenital Zika Syndrome.

Zika virus (ZIKV) is a mosquito-borne, single-stranded DNA flavivirus that is teratogenic and neurotropic. Similar to the teratogenic effects of other TORCH infections, ZIKV infection during pregnancy can have an adverse impact on fetal and neonatal development. Epilepsy is detected in 48-96% of children with Congenital Zika Syndrome (CZS) and microcephaly. Early epilepsy surveillance is needed in children with prenatal ZIKV exposure; yet, most ZIKV-endemic regions do not have specialist epilepsy care. Here, we describe the demographic, clinical, imaging, and EEG characteristics of a 2-year-old child with CZS and microcephaly who presented with focal epileptiform activity, suboptimal growth, and severe neurodevelopmental delays. Administration of a brief seizure questionnaire by allied health professionals to the patient's caregiver helped to characterize the child's seizure semiology and differentiate focal from generalized seizure features. A telemedicine EEG interpretation platform provided valuable diagnostic information for the patient's local pediatrician to integrate into her treatment plan. This case illustrates that CZS can present with focal epilepsy features and that a telemedicine approach can be used to bridge the gap between epilepsy specialists and local care providers in resource limited ZIKV-endemic regions to achieve better seizure control in children with CZS.

Epilepsy surveillance in normocephalic children with and without prenatal Zika virus exposure.

Children with Congenital Zika Syndrome and microcephaly are at high risk for epilepsy; however, the risk is unclear in normocephalic children with prenatal Zika virus (ZIKV) exposure [Exposed Children (EC)]. In this prospective cohort study, we performed epilepsy screening in normocephalic EC alongside a parallel group of normocephalic unexposed children [Unexposed Children (UC)]. We compared the incidence rate of epilepsy among EC and UC at one year of life to global incidence rates. Pregnant women were recruited from public health centers during the ZIKV outbreak in Grenada, West Indies and assessed for prior ZIKV infection using a plasmonic-gold platform that measures IgG antibodies in serum. Normocephalic children born to mothers with positive ZIKV results during pregnancy were classified as EC and those born to mothers with negative ZIKV results during and after pregnancy were classified as UC. Epilepsy screening procedures included a pediatric epilepsy screening questionnaire and video electroencephalography (vEEG). vEEG was collected using a multi-channel microEEG® system for a minimum of 20 minutes along with video recording of participant behavior time-locked to the EEG. vEEGs were interpreted independently by two pediatric epileptologists, who were blinded to ZIKV status, via telemedicine platform. Positive screening cases were referred to a local pediatrician for an epilepsy diagnostic evaluation. Epilepsy screens were positive in 2/71 EC (IR: 0.028; 95% CI: 0.003-0.098) and 0/71 UC. In both epilepsy-positive cases, questionnaire responses and interictal vEEGs were consistent with focal, rather than generalized, seizures. Both children met criteria for a clinical diagnosis of epilepsy and good seizure control was achieved with carbamazepine. Our results indicate that epilepsy rates are modestly elevated in EC. Given our small sample size, results should be considered preliminary. They support the use of epilepsy screening procedures in larger epidemiological studies of children with congenital ZIKV exposure, even in the absence of microcephaly, and provide guidance for conducting epilepsy surveillance in resource limited settings.

Pre and postnatal exposure to Chikungunya virus does not affect child neurodevelopmental outcomes at two years of age.

BACKGROUND: The 2005-06 chikungunya virus (CHIKV) outbreak in La Réunion suggested that mothers could transmit CHIKV to their neonates while viremic during the intrapartum period, and more than half of the infected neonates showed impaired neurodevelopment at two years of age. However, data sparsity precluded an overview of the developmental impact of vertical infection within the whole prenatal period. OBJECTIVE & METHODS: The current study assessed two-year old children born to mothers who were infected during the 2014 CHIKV outbreak in Grenada to determine the neurodevelopmental impact of perinatal CHIKV infection throughout gestation. Mother and child infection status were confirmed by serologic testing (IgG and IgM) for CHIKV. Cognitive, fine motor, gross motor, language and behavioral outcomes were assessed at two years of age on the INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA). RESULTS: No differences in neurodevelopmental outcomes were observed between two-year-old children born to mothers infected with CHIKV during gestation (n = 149) and those born to mothers not infected with CHIKV (n = 161). No differences were found in INTER-NDA scores between children infected with CHIKV (n = 47) and children not infected with CHIKV (n = 592). Likewise, there were no differences between children infected with CHIKV post-partum (n = 19) versus children not infected with CHIKV (n = 592). CONCLUSION: Our findings suggest that children exposed and/or infected with CHIKV outside of the intrapartum period experience no significant neurodevelopmental delay at two years of age, as measured by the INTER-NDA, compared to their unexposed and/or uninfected peers. These results complement those of previous studies which showed a neurodevelopmental risk only for children infected during the intrapartum period, while the mother was highly viremic. These results might be reassuring for women of childbearing age and public health officials in CHIKV-endemic regions.

Global Prevalence Estimates of Toxascaris leonina Infection in Dogs and Cats.

Toxascaris leonina is an ascaridoid nematode of dogs and cats; this parasite affects the health of these animals. This study estimated the global prevalence of Ta. leonina infection in dogs and cats using random effects meta-analysis as well as subgroup, meta-regression and heterogeneity analyses. The data were stratified according to geographical region, the type of dogs and cats and environmental variables. A quantitative analysis of 135 published studies, involving 119,317 dogs and 25,364 cats, estimated prevalence rates of Ta. leonina in dogs and cats at 2.9% and 3.4%, respectively. Prevalence was highest in the Eastern Mediterranean region (7.2% for dogs and 10.0% for cats) and was significantly higher in stray dogs (7.0% vs. 1.5%) and stray cats (7.5% vs. 1.8%) than in pets. The findings indicate that, worldwide, ~26 million dogs and ~23 million cats are infected with Ta. leonina; these animals would shed substantial numbers of Ta. leonina eggs into the environment each year and might represent reservoirs of infection to other accidental or paratenic hosts. It is important that populations of dogs and cats as well as other canids and felids be monitored and dewormed for Ta. leonina and (other) zoonotic helminths.

An analysis of time trends for canine heartworm disease in Grenada and its associated risk factors based on veterinary clinical pathology laboratory data base records between 2003 and 2015.

Canine heartworm (CHW) disease is a common parasitic infection in dogs in the Caribbean islands. However, studies on temporal trends and risk factors are limited for this region. This study represents the time trends in laboratory prevalence and risk factors of canine heartworm infections between 2003 and 2015. In this case series, 662 cases of laboratory-diagnosed heartworm were compared to 662 dogs without a laboratory diagnosis of heartworm (controls). One hundred and seventy two frozen serum positive samples were later analyzed for heartworm antigens using Heska solo® Step CH, and all 172 cases of microfilariae were confirmed as Dirofilaria immitis. Annual prevalence, linear trends and odds ratios (OR) for CHW were estimated using EPIINFO version 7 at a significance level of α = 0.05. Logistic regression was used to assess the association of CHW with variables showing a statistically significant univariate relationship. Laboratory prevalence of CHW decreased from 72 cases per 1000 dogs per year in 2003 to 15 cases per 1000 dogs per year in 2015 [X2 for linear trend = 151.8, p < 0.0001], with the occurrence of an epidemic of CHW between 2008 and 2010. The odds of CHW were higher among adult dogs [(OR) = 3.9 (95% CI, 2.9-7.0)] and geriatric dogs [OR = 2.1 (95% CI, 1.1-4.3)] compared to puppies. The odds of CHW were higher [OR = 1.3 (95% CI, 1.1-1.6)] among male dogs than female dogs, but the odds for CHW were lower among neutered dogs [OR = 0.4 (95% CI, 0.2 - 0.6)] compared to intact dogs. The odds of a dog being diagnosed with CHW were elevated [OR = 4.1 (95% CI, 3.2-5.2)] during the dry season compared to the rainy season. Our findings show that canine heartworm is extensive in laboratory submissions in Grenada. However, the laboratory prevalence of CHW decreased between 2003 and 2015, with an epidemic occurring between 2008 and 2010. Age of the dog, sex, neutered status, and seasonality of diagnosis were significantly associated CHW in Grenada.

Global prevalence of Toxocara infection in dogs.

Dogs serve as the most important definitive hosts for Toxocara canis-a causative agent of human toxocariasis and one of the most widespread zoonotic helminth worldwide. The present study was undertaken to assess the global prevalence of T. canis infection in dogs. PubMed, Scopus, Web of Science, EMBASE and SciELO were searched to identify relevant studies. A random-effects model was used to estimate the overall and the subgroup-pooled prevalences across studies, and heterogeneity was assessed via the I2 test. The data were categorized according to WHO-region, different types of dogs, risk factors and environmental variables. From a total of 4370 peer-reviewed publications, 229 articles that studied 13,010,004 dogs in 60 countries met the final inclusion criteria. The overall prevalence of Toxocara infection in dogs was 11.1% (95% CI, 10.6-11.7%). The estimated prevalence in the different WHO-regions ranged from 6.4% to 19.2%: Eastern Mediterranean (19.2%, 13.7-25.5%), Africa (18.5%, 13.7-23.9%), South-East Asia (11.9%, 6.8-18.2%), North America (11.1%, 10.6-11.7%), South America (10.9%, 7.6-14.6%), Europe (10.8%, 8.9-12.9%) and Western Pacific (6.4%, 3.3-10.2%). Young (<1 year of age), stray, rural and male dogs had a significantly (P<0.001) higher prevalence of infection than older, pet, urban or female dogs. The prevalence was higher in low income countries and regions at a low geographical latitude, close to the equator, characterized as having tropical climates. From this review, it is estimated that ≥100 million dogs are infected with Toxocara around the world. This highlights the need for an increased focus on implementing affordable, appropriate control programs to reduce the public health threat of toxocariasis as a zoonosis of global importance.

Global prevalence of Toxocara infection in cats.

Zoonotic parasites, including Toxocara species, of pet and stray cats are of public health importance. Justification for, and the design and implementation of prevention and control of human toxocariasis may benefit from an understanding of the zoonotic potential and prevalence of parasites in this definitive host species. This is the first systematic review and meta-analysis of cross-sectional studies, conducted to estimate the prevalence of Toxocara infection(s) in cats by geographical location, type (rural vs urban and stray vs pet), gender and age. Pooled data were assessed using a random effects-model as well as several meta-regression and stratified analyses conducted. Of 1733 peer-reviewed articles, 143 were included in this review and represented 2,158,069 cats from 51 countries. The global pooled (95% CI) prevalence of Toxocara infection in cats was 17.0% (16.1-17.8%), being highest in African (43.3%, 28.3-58.4%) and lowest in South American (12.6%, 8.2-17.0%) countries. In other WHO regions, prevalence rates of Toxocara were as follows: Eastern Mediterranean (21.6%, 15.1-28.1%), North America (18.3%, 15.4-21.2%), Europe (17.8%, 15.9-19.7%), Western Pacific (17.3%, 14.7-19.9%), and South-East Asia (14.9%, 9.8-20.1%). Prevalence of Toxocara was higher in low-income tropical countries and also in stray (28.6%, 25.1-32.1%) and young (≤12 months of age) (27.7%, 23.4-32.0%) cats than in pet (11.6%, 10.7-12.5%) and older cats (>12 months of age) (23.8%, 14.8-32.7%). This review indicates that ~118-150 million cats worldwide serve as definitive hosts of Toxocara, shedding eggs and thus contributing to the public health risk of human infection. Prevention and control of this zoonosis in cats should receive greater attention by health officials and cat owners, particularly in countries where risk factors and prevalence are highest.

Human toxocariasis - A look at a neglected disease through an epidemiological 'prism'.

Toxocariasis, a disease caused by infection with larvae of Toxocara canis, T. cati and/or congeners, represents clinical syndromes in humans including visceral and ocular larva migrans, neurotoxocariasis and covert/common toxocariasis. It is reported to be one of the most widespread public health and economically important zoonotic parasitic infections that humans share with dogs, wild canids, including foxes, and possibly other mammals. Humans become infected by accidental ingestion of embryonated Toxocara eggs, or larvae from tissues from domestic or wild paratenic hosts. Most infections are asymptomatic, and human disease may go unnoticed, as clinical investigation is often not pursued and/or diagnostic testing not conducted. Sometimes toxocariasis can be associated with complications, such as allergic and/or neurological disorders, possibly including cognitive or developmental delays in children. There is no anti-toxocariasis vaccine, and chemotherapy in humans varies, depending on symptoms and location of larvae, and may include the administration of albendazole or mebendazole, together with anti-inflammatory corticosteroids. Some recent studies indicate that toxocariasis is having an increased, adverse impact on human health in some, particularly underprivileged, tropical and subtropical communities around the world. Although tens of millions of people, especially children, are expected to be exposed to, or infected with Toxocara species, there is limited precise epidemiological data or information on the relationship between seropositivity and disease (toxocariasis) on a global scale. To gain an improved insight into this area, the present article reviews salient clinical aspects of human toxocariasis and the epidemiology of this disease, with particular reference to seroprevalence, and discusses future research and approaches/measures to understand and prevent/control this socioeconomically important, yet neglected zoonosis.

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.

INTRODUCTION: Zika 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 ANALYSIS: We 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 DISSEMINATION: The 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 NUMBER: PROSPERO International prospective register of systematic reviews (CRD42017068915).

Ultrasound and Cystic Echinococcosis.

The introduction of imaging techniques in clinical practice 40 years ago changed the clinical management of many diseases, including cystic echinococcosis (CE). For the first time cysts were clearly seen before surgery. Among the available imaging techniques, ultrasound (US) has unique properties that can be used to study and manage cystic echinococcosis. It is harmless, can image almost all organs and systems, can be repeated as often as required, is portable, requires no patient preparation, is relatively inexpensive and guides diagnosis, treatment and follow-up without radiation exposure and harm to the patient. US is the only imaging technique which can be used in field settings to assess CE prevalence because it can be run even on solar power or a small generator in remote field locations. Thanks to US classifications, the concept of stage-specific treatments was introduced and because US is repeatable, the scientific community has gained a clearer understanding of the natural history of the disease. This paper reviews the scope of US in CE, describes its strengths and weaknesses compared to other imaging techniques and its relationship with serodiagnosis and discusses sonographic features that may be helpful in differential diagnosis.

Clinical, Serological, and Molecular Observations from a Case Series Study during the Asian Lineage Zika Virus Outbreak in Grenada during 2016.

This paper describes the spatial and temporal distribution of cases, demographic characteristics of patients, and clinical manifestations of Zika virus (ZIKV) during the 2016 outbreak in Grenada. The first reported case was recorded in St. Andrew Parish in April, and the last reported case was seen in November, with peak transmission occurring in the last week of June, based on test results. Data were collected from a total of 514 patients, of whom 207 (40%) tested positive for ZIKV. No evidence was found that testing positive for ZIKV infection was related to age, gender, or pregnancy status. Clinical presentation with rash (OR = 2.4, 95% CI = 1.5 to 3.7) or with lymphadenopathy (OR = 1.7, 95% CI = 1.0 to 2.9) were the only reported symptoms consistent with testing positive for ZIKV infection. During the Zika outbreak, the infection rate was 20 clinical cases per 10,000 in the population compared to 41 cases per 10,000 during the chikungunya outbreak in Grenada in 2014 and 17 cases per 10,000 during the dengue outbreak in 2001-2002. Even though the country has employed vector control programs, with no apparent decrease in infection rates, it appears that new abatement approaches are needed to minimize morbidity in future arbovirus outbreaks.

The Identification of Risk Factors for Chronic Chikungunya Arthralgia in Grenada, West Indies: A Cross-Sectional Cohort Study.

BACKGROUND: Chikungunya virus (CHIKV) is a re-emerging arboviral pathogen. In 2014, an explosive CHIKV outbreak occurred in Grenada, West Indies, infecting approximately 60% of the population. In approximately 50% of cases, CHIKV infection transitions to painful arthralgia that can persist for years. Elucidation of the risk factors for chronic disease is imperative to the development of effective risk management strategies and specific therapeutics. METHODS: We conducted a cross-sectional study of 240 people who were tested for CHIKV during the outbreak. We administered questionnaires to examine demographic, behavioral, psychological, social, and environmental factors to identify associations with chronic disease. Physical examinations were performed and persistent symptoms were recorded. RESULTS: Ethnicity and socioeconomic status were not associated with risk of chronic joint pain. Female sex increased risk, and age was demonstrated to be predictive of chronic CHIKV sequelae. Mosquito avoidance behaviors did not reduce risk. Patients suffering joint pains, generalized body ache, and weakness in the extremities during acute infection were more likely to develop chronic arthralgia, and an increased duration of acute disease also increased risk. CONCLUSIONS: These data demonstrate that chronic CHIKV affects people across the ethnic and socioeconomic spectrum, and it is not reduced by vector avoidance activity. Increased duration of acute symptoms, in particular acute joint pain, was strongly correlated with the risk of persistent arthralgia, thus effective clinical management of acute CHIKV disease could reduce burden of chronic CHIKV.