Maternal Zika virus infection and newborn microcephaly—an analysis of the epidemiological evidence

Purpose

To evaluate whether existing data and evidence support a causal link between maternal Zika virus (ZIKV) infection and newborn microcephaly.

The Epidemic of Zika Virus–Related Microcephaly in Brazil: Detection,Control, Etiology,and Future Scenarios

We describe the epidemic of microcephaly in Brazil, its detection and attempts to control it, the suspected causal link with Zika virus infection during pregnancy, and possible scenarios for the future. In October 2015, in Pernambuco, Brazil, an increase in the number of newborns with microcephaly was reported. Mothers of the affected newborns reported rashes during pregnancy and no exposure to other potentially teratogenic agents. Women delivering in October would have been in the first trimester of pregnancy during the peak of a Zika epidemic in March. By the end of 2015, 4180 cases of suspected microcephaly had been reported. Zika spread to other American countries and, in February 2016, the World Health Organization declared the Zika epidemic a public health emergency of international concern. This unprecedented situation underscores the urgent need to establish the evidence of congenital infection risk by gestational week and accrue knowledge. There is an urgent call for a Zika vaccine, better diagnostic tests, effective treatment, and improved mosquito-control methods.Less than a year after the first identification, in April 2015, of Zika virus (ZIKV) in Brazil,1 there was an outbreak of an exanthematous disease in its northeastern region tentatively attributed to ZIKV. ZIKV was later detected in 20 of the 27 states in Brazil2 and in 18 countries in America.3 A sharp increase in microcephaly is expected among the offspring of women who were pregnant and infected during the subsequent outbreaks give birth.Microcephaly is an abnormally small head at birth because of defective brain development. It can have genetic or environmental causes. Environmental exposures include radiation, drugs, fetal alcohol syndrome, and infections. Well-known agents of congenital infections include toxoplasmosis, rubella, cytomegalovirus, herpesvirus, and syphilis (TORCHES).4,5 Until November 2015, ZIKV has never been considered to be a cause of congenital infections or microcephaly.6ZIKV is an RNA arbovirus, Flaviviridae family (genus Flavivirus), transmitted by the Aedes mosquito (which is also the vector for dengue). Because dengue and Zika share a vector, Zika could establish itself in any country where dengue is present. ZIKV is genetically close to dengue, West Nile, yellow fever, and Japanese encephalitis viruses.7 One study suggests that most (80%) ZIKV infections appear to be asymptomatic.8 When clinical features are present, they are similar to those of dengue and chikungunya7—both arboviruses that are circulating in Brazil.8 The force of transmission of ZIKV can be very high, as 73% of the population was estimated to have been infected in the 2007 outbreak in Yap, Federated States of Micronesia8; the rate of clinical cases was estimated to be 12% in the 2013–2014 outbreak in French Polynesia.9ZIKV was isolated in Uganda in 1947, and only sporadic cases and small outbreaks were reported in Africa and Asia during the 1960s until early in the 21st century.7,10 In 2007, an outbreak was detected on Yap Island8; in 2013, an outbreak was detected in French Polynesia.9 In April 2015, ZIKV was identified in Brazil, and assessed to be the etiological agent of outbreaks of an acute exanthematous illness, which started in late 2014 in many cities of the northeast region.1,11     

Zika病毒全球首次“女传男”,专家担忧其成下一个HIV

<正>7月15日,美国纽约市健康与心理卫生局(New York City Department of Health and Mental Hygiene)报告了首例通过"性传播"(由女性传染给男性)的寨卡(Zika)病毒的报道。在此之前,所有报道经性传播的寨卡病毒,都是男性传染给女性。     

Integrated prevention of mother-to-child transmission for human immunodeficiency virus,syphilis and hepatitis?B virus in China

ProblemChina continues to face challenges in eliminating mother-to-child transmission of human immunodeficiency virus (HIV), syphilis and hepatitis B virus (HBV).ApproachIn 2010, a programme that integrated and standardized prevention of mother-to-child transmission (PMTCT) efforts for HIV, syphilis and HBV was implemented in 1156 counties. At participating antenatal care clinics, pregnant women were offered all three tests concurrently and free of charge. Further interventions such as free treatment, prophylaxis and testing for mothers and their children were provided for HIV and syphilis.

Local setting

China’s national PMTCT HIV programme started in 2003, at which time there were no national programmes for perinatal syphilis and HBV. In 2009, the rate of maternal-to-child transmission of HIV was 8.1% (57/702). Reported congenital syphilis was 60.8 per 100 000 live births. HBV infection was 7.2% of the overall population infected.

Relevant changes

Between 2010 and 2013 the number of pregnant women attending antenatal care clinics with integrated PMTCT services increased from 5.5 million to 13.1 million. In 2013, 12.7 million pregnant women were tested for HIV, 12.6 million for syphilis and 12.7 million for HBV. Mother-to-child transmission of HIV fell to 6.7% in 2013. Data on syphilis transmission are not yet available.

Lessons learnt

Integrated PMTCT services proved to be feasible and effective, and they are now part of the routine maternal and child health services provided to infected women. The services are provided through a collaboration between maternal and child health clinics, the national and local Centers for Disease Control and Prevention, and general hospitals.     

Seroepidemiological survey for influenza virus in Belém, Pará, Brazil, 1992-1993

A seroepidemiological study was carried out from 1992 to 1993 to estimate the prevalence of antibody to prevailing influenza virus strains circulating among patients attending the IEC Virology Laboratory in Belem, Northern Brazil. A total of 179 (11%) of serum samples were obtained during the post-epidemic period and processed by the hemagglutination inhibition test against the A/Taiwan/1/86 (H1N1), A/Beijing/353/89 (H3N2), and B/Yamagata/16/88 types of influenza virus. The serological results indicate circulation of viruses antigenically related to all three strains during the two-year study period. In 1992, the overall prevalence rates of HI antibodies to H1N1 and H3N2 were 84% and 56%, respectively. Presence of antibodies to both strains was detected in all age groups, suggesting intense viral activity that year. Antibodies to influenza B were detected at lower levels in all patients during this period. Similar prevalence to the H1N1 virus was noted in 1993, indicating that this strain occurred in both years. However, an increase in prevalence rates for the H3N2 virus was seen in 1993, suggesting that this strain (or a related virus) circulated intensively during this year. Influenza B activity also increased in 1993, causing infection mainly among young adults.     

Rabies virus maintained by dogs in humans and terrestrial wildlife, Ceará State, Brazil

Rabies viruses circulating in Ceará, Brazil, were identified by molecular analysis to be related to variants maintained by dogs, bats, and other wildlife. Most of these viruses are associated with human rabies cases. We document the emergence of a rabies virus variant responsible for an independent epidemic cycle in the crab-eating fox (Cerdocyon thous).     

Human T-cell lymphotropic virus type II in Guaraní Indians, Southern Brazil

Human T-cell lymphotropic virus type II (HTLV-II) is found in many New World Indian groups on the American continent. In Brazil, HTLV-II has been found among urban residents and Indians in the Amazon region, in the North. Guaraní Indians in the South of Brazil were studied for HTLV-I/II infection. Among 52 individuals, three (5.76%) showed positive anti-HTLV-II antibodies (enzyme-linked immunosorbent assay and Western blot). This preliminary report is the first seroepidemiological study showing HTLV-II infection among Indians in the South of Brazil.     

Both human immunodeficiency virus–infected and human immunodeficiency virus–exposed,uninfected children living in Brazil,Argentina, and Mexico have similar rates of low concentrations of retinol, β-carotene,and vitamin E

Our objective was to describe the prevalence of low concentrations of retinol, β-carotene, and vitamin E in a group of human immunodeficiency virus (HIV)-infected Latin American children and a comparison group of HIV-exposed, uninfected children. Our hypothesis was that the rates of low concentrations of these micronutrients would be higher in the HIV-infected group than those in the HIV-exposed, uninfected group. This was a cross-sectional substudy of a larger cohort study at clinical pediatric HIV centers in Latin America. Serum levels of micronutrients were measured in the first stored sample obtained after each child's first birthday by high-performance liquid chromatography. Low concentrations of retinol, β-carotene, and vitamin E were defined as serum levels below 0.70, 0.35, and 18.0 μmol/L, respectively. The population for this analysis was 336 children (124 HIV-infected, 212 HIV-exposed, uninfected) aged 1 year or older to younger than 4 years. Rates of low concentrations were 74% for retinol, 27% for β-carotene, and 89% for vitamin E. These rates were not affected by HIV status. Among the HIV-infected children, those treated with antiretrovirals were less likely to have retinol deficiency, but no other HIV-related factors correlated with micronutrient low serum levels. Low concentrations of retinol, β-carotene, and vitamin E are very common in children exposed to HIV living in Brazil, Argentina, and Mexico, regardless of HIV-infection status.     

Scope of Knowledge About Zika Among Women in US–Mexico Border Communities

Maternal Zika virus infection (ZIKV) has serious health consequences for unborn offspring. Knowledge about prevention is critical to reducing risk, yet what women in the high-risk US–Mexico border region know about protecting themselves and their babies from ZIKV is mostly unknown. This study aimed to assess knowledge of ZIKV among pregnant and inter-conception women and to identify sources of information that might address knowledge gaps. Clients in five federally-funded, border region Healthy Start programs (N?=?326) were interviewed in late 2016 about their knowledge of ZIKV prevention methods and whether they believed themselves or their babies to be at risk. Sources of information about ZIKV and demographic characteristics were also measured. Chi square tests identified important associations between variables; adjusted odds ratios (AOR) and 95% confidence intervals for knowledge and beliefs were calculated. Among the 305 women aware of ZIKV, 69.5% could name two ways to prevent infection. Only 16.1% of women named using condoms or abstaining from sex as a prevention method. While 75.3% heard about ZIKV first from TV/radio, just 9.5% found the information helpful. Women who received helpful information from health care providers had greater odds of knowing two prevention methods (AOR?=?2.0; 1.1–3.7), when to test for ZIKV (AOR?=?5.2; 2.1–13.2), and how long to delay pregnancy after infection in a male partner (AOR?=?1.9; 1.1–3.2). Those who said web-based and social media sources were helpful had greater odds of knowing when to test for ZIKV (AOR?=?2.8; 1.3–6.3). Results can inform messaging for safe pregnancy and ZIKV prevention.     

Economic Evaluation of the Zika Contraception Access Network—A Primary Public Health Intervention to Increase Access to Contraception in Puerto Rico during the 2016–17 Zika Virus Outbreak

To use modeling and simulation to analyze the interplay of factors and interventions on maternal mortality rates and to empower decision makers with the necessary data to make informed decisions to reduce maternal mortality rates, particularly among non-Hispanic black women. The interactive dashboard is fed by the results of a simulation model—a computer representation of a system meant to observe the effect of changes onto the system through time (ie, dynamic) using a synthetic population. A synthetic population is a reproduced representation of a population (eg, women of childbearing potential) that replicates the statistical variable distributions of a population. With the use of Synthetic Populations and Ecosystems of the World (SPEW), Healthcare Cost and Utilization Project (HCUP), Institute for Health Metrics and Evaluation (IHME), and March of Dimes PeriStats, we sample a synthetic population representing women of childbearing age to assess the risk of maternal mortality at the individual level. Then, users can analyze how budgeting, social determinants of health, and the application of quality improvement toolkits address the leading causes of pregnancy-related deaths. The toolkits were designed by the California Maternal Quality Care Collaboration (CMQCC) to address conditions such as obstetric hemorrhage and preeclampsia. Various runs of the simulation allow the user to see how the selected interventions might reduce the rates of maternal mortality in various states. Women of childbearing age between the ages of 14 and 44 within the state of California and Georgia to ensure varying economic, racial, and political diversity. The intention is to expand the scope nationally following validation. The MITRE Maternal Mortality Interactive Dashboard (3MID), a microsimulation and policy simulator, allows users to set parameters and evidence-based interventions to understand the influence and the most impactful interventions to reduce maternal mortality rates, particularly among non-Hispanic black women. The outputs of a simulation are predicted number of maternal deaths, simulated program cost, and mortality risk assessment score. The risk of mortality is calculated as a linear regression model of the individual’s race, age, and county of residence. These results are based off mortality trends derived from high-level reports from AHRQ that are based on the HCUP data. The 3MID prototype allows users to maximize the allocation of their resources to reduce maternal mortality. This sets the foundation to explore the additional social determinants of health and expand the scope to include severe maternal morbidity, additional variables, and more states. The United States is the only developed nation in the world with an increasing maternal mortality rate. Policy makers currently do not have the data needed to understand the impact of interventions. By using this evidence-based approach, decision makers can use 3MID to make informed decisions to reduce the maternal deaths within their states and lower the United States’ overall maternal mortality rate. ©2020 The MITRE Corporation. ALL RIGHTS RESERVED. This study was supported by the Internal MITRE Research Program.     

Araçatuba virus: a vaccinialike virus associated with infection in humans and cattle

We describe a vaccinialike virus, Araçatuba virus, associated with a cowpoxlike outbreak in a dairy herd and a related case of human infection. Diagnosis was based on virus growth characteristics, electron microscopy, and molecular biology techniques. Molecular characterization of the virus was done by using polymerase chain reaction amplification, cloning, and DNA sequencing of conserved orthopoxvirus genes such as the vaccinia growth factor (VGF), thymidine kinase (TK), and hemagglutinin. We used VGF-homologous and TK gene nucleotide sequences to construct a phylogenetic tree for comparison with other poxviruses. Gene sequences showed 99% homology with vaccinia virus genes and were clustered together with the isolated virus in the phylogenetic tree. Araçatuba virus is very similar to Cantagalo virus, showing the same signature deletion in the gene. Araçatuba virus could be a novel vaccinialike virus or could represent the spread of Cantagalo virus.     

Vaccination of sheep with Maedi-visna virus gag gene and protein, beneficial or harmful?

In spite of intense efforts no vaccine is yet available that protects against lentiviral infections. Sheep were immunised eight times over a period of 2.5 years with the maedi-visna (MVV) gag gene on two different vectors, 2 sheep with VR1012-gag-CTE and 2 sheep with pcDNA3.1-gag-CTE. All sheep responded to some of the mature MVV Gag proteins in Western blot (WB). Three of them responded to the virus in lymphocyte proliferation test. The sheep received a boost with recombinant Gag protein resulting in elevated antibody response. However, when they were challenged intratracheally with MVV they all became immediately infected as judged by a strong rise in antibody titer and virus isolation from blood. It is therefore clear that the vaccination gave no protection. It is even possible that it facilitated infectivity since virus was isolated earlier from all the vaccinated sheep than from any of the unvaccinated sheep infected in the same way with the same dose.     

Invasive pneumococcal and meningococcal disease: association with influenza virus and respiratory syncytial virus activity?

Few studies have examined the relationship between viral activity and bacterial invasive disease, considering both influenza virus and respiratory syncytial virus (RSV). This study aimed to assess the potential relationship between invasive pneumococcal disease (IPD), meningococcal disease (MD), and influenza virus and RSV activity in The Netherlands. Correlations were determined between population-based data on IPD and MD during 1997-2003 and influenza virus and RSV surveillance data. Incidence rate ratios of disease during periods of high influenza virus and RSV activity over the peri-seasonal and summer baseline periods were calculated. The analyses comprised 7266 and 3072 cases of IPD and MD. When data from all seasons were included, the occurrence of pneumococcal bacteraemia and MD correlated significantly with influenza virus and RSV activity both in children and adults. Periods of increased influenza virus and RSV activity showed higher rates of pneumococcal bacteraemia in older children and adults than the peri-season period. Rates of MD in children were also higher during periods of increased influenza virus activity; the same appeared true for MD in older children during periods of increased RSV activity. Although no causal relationship may be inferred from these data, they support a role for influenza virus and RSV in the pathogenesis of IPD and MD.     

Molecular epidemiological investigation of Mayaro virus in febrile patients from Goiania City, 2017–2018

Mayaro virus (MAYV) has historically been associated with sylvatic transmission; however, urban outbreaks have been reported in Brazil, including cases of co-detection with dengue virus (DENV). Therefore, we performed a molecular survey to investigate MAYV circulation and cocirculation with DENV within Goiania, a major city in Central-West Brazil. Among 375 subjects with arbovirus-like symptoms, 259 were positive for DENV and 26 for MAYV. Of these, 17 were coinfected with DENV-2, suggesting co-transmission of the viruses. The most common complaints at the time of inclusion were myalgia, headache, fever, arthralgia, retro-orbital pain, and skin rash. No specific symptoms were associated with MAYV when either detected alone or co-detected with DENV, compared to that when DENV was detected alone. Most MAYV-infected subjects were women with no recent travel history to rural/sylvatic areas. Phylogenetic reconstruction indicated that the MAYV identified in this study is closely related with a lineage observed in Peru, belonging to genotype D. Our results corroborate the growing circulation of MAYV in urban environments in Brazil and reinforce the need to implement laboratory diagnosis in the Unified Health System, considering that the clinical manifestations of Mayaro fever are similar to those of other arboviruses, particularly dengue. Furthermore, most cases occurred in association with DENV-2. Further phylogenetic studies are needed to evaluate MAYV, which has not been widely examined.