Zika Virus: An Emerging Arboviral Threat of 2016

Editor's Notes

• #2: Hello everyone. Our presentation is on Zika Virus, an Emerging Arboviral Threat of 2016.
• #3: BACKGROUND ZIKV is a viral mosquito borne disease transmitted to humans, which was initially identified in the blood of a rhesus monkey in the Zika Forest of Uganda in 1947. It is a single-stranded RNA virus, of which there are 3 known, distinct lineages (Nigerian Cluster, MR766 Cluster, and the Asian Genotype). It is primarily Transmitted by the bite of the Aedes Aegypti and Albopictus mosquitoes which are aggressive daytime biters. Other possible transmission routes are: mother to child (in utero), sexual transmission. Mosquito to human, and infected human to non-infected mosquito. Approximately 80% of individuals are asymptomatic and 20% will experience: a mild fever similar to dengue fever, rash, joint pain, and conjunctivitis lasting several days to a week. To date, there is no treatment or vaccine for ZIKV. Treatment only focuses on relieving pain and symptoms associated with the disease. Supportive therapy including rest, getting plenty of fluids, applying cold compresses to inflamed joined, and use of NSAIDS is recommended. However, aspirin use is discouraged due to risk of hemorrhage and Reye’s Syndrome.
• #4: A yellow fever study in 1947 led to the isolation of the virus from the blood of a macaque in the Zika forest of Uganda. Human infection was suggested because serosurveys indicated the presence of Zika antibodies in some African and Asian population The first human illnesses occurred in Nigeria during 1953. Zika virus remained silent for almost 70 years until a 2007 outbreak on several Pacific islands including the Federated States of Micronesia resulted in approximately 5, 000 infections among the total population of 6,700. Outbreaks continued in French Polynesia from 2012-2014 which involved 32,000 individuals and cases of Guillain–Barré syndrome were observed during that time. ZIKV was initially identified in the Americas in Brazil in March 2015, where an ongoing outbreak is occurring. By March 2016, the virus subsequently spread to at least 33 countries and territories in the Americas as depicted in Figure 1. By September 2015, investigators in Brazil also noted an increase in the number of infants born with microcephaly in the same areas in which Zika virus was first reported,38 and by mid-February 2016, more than 4300 cases of microcephaly had been recorded. Later, in French Polynesian investigators retrospectively identified an increased number of fetal abnormalities, including microcephaly, after the Zika virus outbreak occurred in that country.
• #5: The primary reservoir are humans and other reservoirs in Africa includes non-human primates. Although the human incubation period for ZIKV is unknown, if it is similar to other arboviruses, it has an average incubation of: 2-7 days following the bite of an infected mosquito. The Mosquito Incubation Period ranges from: an average of 7-10 days between intake of an infected blood meal to when mosquitos can transmit the virus to humans The primary mode of transmission is through a mosquito to human to mosquito transmission cycle. Other reported modes of transmission includes: intrabirth transmission (mother to fetus), sexual transmission, and transfusion of infected blood products occurring in 3% of donated samples were infected with ZIKV during a 2013 outbreak occurring in French Polynesia. Sexual transmission has been reported in males travelling abroad to disease endemic countries and returning back to non-endemic areas. In one instance, sexual intercourse and transmission of ZIKV occurred only before the onset of symptoms, whereas in other cases sexual intercourse occurred during the development of symptoms. To date, transmission via breast milk is not documented. Although, breast milk of a symptomatic woman with ZIKV on day of delivery consisted of infective ZIIKV particles in high titer. Please note that the duration of symptoms after sexual transmission and other modes of transmission are not documented in the literature yet.
• #6: This image to the left depicts the life cycle of ZIKV virus in Africa showing the connection b/t the sylvatic cycle on the left and the urban cycle on the right. In Africa, ZIKV circulates in a sylvatic cycle among forest-dwelling Aedes mosquitoes and monkeys. In this setting, sporadic infections could occur. In urban settings including the Americas, ZIKV is primarily transmitted by Ae. aegypti through a mosquito to human to mosquito transmission cycle. In this cycle, mosquitoes bite an infected person, infected mosquitos bite healthy individuals, and then healthy individuals become sick/infectious-cycle continues. Aedes aegypti mosquitoes can infect multiple humans (approximately 4-5 people) within a single blood meal and they reside in close proximity to human populations.
• #7: 80% of individuals infected with ZIKV are asymptomatic while 20% of those exposed will develop flu-like symptoms including: rash being the most common symptom seen in 90 to 95% of all symptomatic cases, a mild fever, joint pain, and conjunctivitis. However, in some cases Congenital Microcephaly in ZIKV infected mothers during the first two trimesters of pregnancy and Guillian-Barre Syndrome has been observed. Substantial evidence now indicates that Zika virus can be transmitted from the mother to the fetus during pregnancy and result in adverse birth defects including: microcephaly. Microcephaly is …… The timing of the Zika virus and microcephaly epidemics in Brazil and French Polynesia indicate that the greatest risk of microcephaly is in the first trimester. In addition, a number of cases in past outbreaks as well as recently infected cases have reported: Guillian-Barre Syndrome.
• #9: Clinically, the disease is very similar to dengue. Misdiagnosis is not unusual. Therefore differential diagnosis of illness includes: dengue fever, WNV, and Chikungunya viruses. The virus can be detected via RT-PCR testing within the first week of clinical illness up to day 8 from initial onset of symptoms. The diagnosis can also be confirmed by a four-fold or greater rise in antibody titres to ZIKV virus antigen in paired serum samples. Also, presence of ZIKV IgM antibody, which is usually detectable in serum collected from day 5 after onset, provides a presumptive diagnosis. The considerable cross-reactivity of flavivirus antibodies presents major challenges for the interpretation of serologic test results. For example, Zika virus infection may also evoke a positive ELISA result for dengue. The plaque reduction neutralization test (PRNT), is the most specific test used to differentiate antibodies of closely related viruses, and can be used to help verify the ELISA results. Testing is performed at CDC Arboviral Diseases Branch and several reference labs located in state health departments throughout the country.
• #10: In 2016, ZIKV become a nationally notifiable disease in the US and the Council of State and Territorial Epidemiologists (CSTE) developed the following case definition for a suspected case: “a patient with rash or elevated body temperature (> 37.2 C) with one or more of the following symptoms (not explained by other medical conditions): joint pain, conjunctivitis, headache or malaise” in someone who resides in or has visited epidemic or endemic areas within two weeks prior to the onset of symptoms (PAHO). A probable ZIKV case is defined as a “suspected case with presence of IgM antibody against ZIKV and an epidemiological link” (WHO, 2016). A confirmed case of ZIKV infection is defined as: “a suspected case with a laboratory confirmed diagnosis of ZIKV, which includes the presence of ZIKV RNA or antigen in serum or other samples (e.g. urine, saliva, tissues, whole blood) or IgM antibody against ZIKV and exclusion of other flaviviruses identified through one or more tests” (PAHO, 2016). Surveillance also includes: Informing and evaluating women who traveled to areas with ZIKV transmission while they are pregnant. Evaluating fetuses of women infected during pregnancy for microcephaly.
• #11: ZIKV currently affects approximately 2 million residents in 62 countries and territories since the beginning of 2016. To date, local transmission has been identified in 43 countries or regions throughout the Americas (including Puerto Rico, Caribbean Islands, Central and South American countries & the Pacific Islands. Zika virus has been found in total of 62 countries, including countries where only sexual transmission has taken place. Zika is now found in North and South America, Asia, Africa and the Pacific Islands. ZIKV associated Microcephaly has been reported in Brazil, the United States, Cabo Verde, Colombia, French Polynesia, and Panama.
• #12: As of April 20, 2016, a total of 426 laboratory confirmed Zika virus disease cases have been reported from 50 U.S. states between 2015-2016. To date, no locally acquired cases have been reported in the continental US. All of the cases were travel-associated to disease endemic countries. Of the 426 cases, 33 (9%) were reported in pregnant women, 8 (2%) were sexually transmitted, and one resulted in Guillian Barre Syndrome. The State of Florida reported the largest number of cases (N=84, 20%) followed by New York State with 60 cases. In US territories including: Puerto Rico, US Virgin Islands, and the American Samoa, a total of 500 lab confirmed locally acquired Zika cases were identified and a total of 3 travel associated cases were reported. Zika virus became a notifiable disease in 2016 and establish case definitions were established by CSTE.
• #13: To date, Florida reports largest number of travel associated ZIKV cases in the Continental United States (N=94), (January-April 27, 2016). The top three counties reporting the largest number of reported cases were: Miami-Dade (N=39), Broward (N=15), & Palm Beach (N=5).
• #14: Brazil leads the world with the greatest incidence of ZIKV, as nearly 440,000-1,300,000 cases occurred in 2015, and to date a total of 1,046 cases were reported in 2016 ( Brazil has a total population of: 202 million residents and the country is divided up into 5 regions as depicted on the image at the top right. The Nordeste or Northeast region has reported the highest number of ZIKV & Microcephaly cases and this is the epicenter of our proposed research study. In 2015, approximately 440,000-1,300,000 laboratory confirmed ZIKV cases were reported in Brazil. To date in 2016, a total of 1,046 ZIKV cases were reported.
• #15: Brazil has reported the first Zika outbreak in the Americas in 2015 and the first and largest number of Zika virus associated microcephaly cases. Based on the epidemiological curve in this slide, the Brazil Ministry of Health has identified a total of 3,050 microcephaly cases in the country in 2015 and during the first two weeks of January 2016, a total of 728 cases were reported. Of the 3,778 cases reported in 2015 and early 2016, a total of 3,003 (79%) cases were identified within the Northeast Region of Brazil, one of the nation’s poorest areas that has overall poverty rate of 58%. The second highest number of cases during this time period were reported in the Southeast region of Brazil with a total of 483, making up 13% of all cases. The southeast region is another area marked by poverty as compared to the northern and Midwest regions of the country.
• #17: To date, no vaccine is available but several research groups are investigating potential vaccines which are under the planning phases of development as depicted in Table 1.
• #18: An effective ZIKV response strategy involves policy change, federal funding, aggressive testing of potentially infected ZIKV cases, proactive vector control measures, and targeted public health messaging towards high risk groups. Targeted public health messages includes issuing travel advisories encouraging women of reproductive age not to travel to disease endemic countries, avoiding mosquito bites by: wearing long sleeved clothing, remaining indoors, applying deet, and using air conditioning versus window screens. Multiple prevention efforts vary by country and the majority are focusing on: reduction of mosquito breeding sites and reducing adult mosquito population density. The strategies employed by Brazil are depicted in the bottom images.
• #19: Statement of Problem: This is the first time in history that ZIKV has been associated with the development of adverse birth outcomes and has been linked to perinatal transmission. Little is known regarding the exposures that may be associated with development in adverse birth outcomes in some ZIKV infected pregnant mothers versus those that do not develop any outcomes. We are proposing a case control study to evaluate risk factors and exposures associated with the development of adverse birth outcomes (microcephaly) in pregnant women with a laboratory confirmed diagnosis of ZIKV and gain insight into the development of future vaccination recommendation, screening guidelines, and interventions for women of childbearing age. The risk factors include: Multiple exposures will be measured to explore associations among the risk of developing adverse birth outcomes among infected pregnant women including: a previous arboviral infection with dengue and/or chikungunya, co-infections with one or more illnesses including: chronic hypertension, diabetes, sexually transmitted diseases (gonorrhea, HIV, syphilis) and/or arboviral diseases (dengue and chikungunya), travel within the past 14 days of illness onset, age at pregnancy, smoking, alcohol and/or drug use during any stage of pregnancy etc., and socioeconomic variables (e.g., type of employment, household income, marital status, etc.). The primary outcome measure for this study is the development of adverse pregnancy outcomes among women infected with Zika virus. We will attempt to answer the research question: Do ZIKV pregnant infected women different in their exposure status (e.g., have concurrent infection with one or more chronic, sexual, arboviral infections or have a lower socioeconomic status) than those ZIKV infected pregnant mothers who did not develop an adverse birth outcome upon delivery? An example of one exposure we will look at is: presence of a pre-existing comorbidity such as diabetes or dengue with ZIKV in a pregnant mother and the development of an adverse birth outcome. The study sample consists of a total of 411 Pregnant Laboratory Confirmed ZIKV patients admitted for delivery into one of several maternal health facilities located in three Brazilian low-income regions: Bahia, Rio de Grande Norte, and Rio de Janeiro. Cases will include 211 ZIKV infected pregnant mothers that developed an adverse birth outcome upon delivery. Controls includes 200 ZIKV infected pregnant women that did not develop an adverse birth outcome upon delivery. Medical record abstraction and brief telephone interviews will be conducted to recruit participants. Telephone interviews will be conducted by culturally competent, trained community health workers. The training of field staff will encompass a week long work shop covering topics in cultural competence, safety, and ethics in conducting research with women of reproductive age, and resources to redirect the women to access counseling and support services.
• #20: The individuals in our study population experience a vulnerable socioeconomic situation that can further exacerbate their overall health. Some of the cultural factors to consider are the demographics of our study population. 58% of residents in Northeast Region reside in poverty and they are of the most socially disadvantaged groups residing in the nation. There are overall high morbidity and mortality rates for all diseases in this region. The women typically receive very little marital support in raising a child as the majority of households consist of women heading a single-parent family (40%). Women were typically housewives while their husbands remained unemployed (32%), educational levels, and literacy rates are low. The majority of women residing in these regions do not own public transportation and their closest health center is typically located within a 20-mile radius Inequality and discrimination against women is significant as the incidence of poor maternal health outcomes remains high, and many women do not have adequate resources or support to raise a healthy child further exacerbating the cycle of poor health and poverty in low-income regions of Brazil. A thorough understanding of these factors are important as they will inform our research team on whether inequalities and barriers are resulting in a significant disproportion of poor, minority women facing the greatest maternal health challenges and placing them at an increased risk for developing ZIKV associated microcephaly.
• #23: This program deserves to be funded for a number of reasons. Not only is ZIKV considered a public health emergency of international concern by the World Health Organization, but these adverse birth effects that have been associated with the virus can possibly be prevented. It is also evident that the disease can continue to spread to other parts of the world, as seen by the increasing number of cases. Infectious diseases are preventable and that means that no one should have to suffer when something is avoidable. It is important to fund this program not only to prevent the effects seen in newborns, but also to help their families. No one should have to suffer from a preventable disease, which is why this study should be funded.
• #24: -Here are a list of references we used to compile our presentation and we encourage you to peruse them for further information.