Now is the time for the Zika virus

In April 1947 it was discovered through an experimental animal model a jungle fever. During the experiment, monkeys (macaques) were placed in cages and left exposed in the Zika forest (Uganda); one of the monkeys became ill and died. They filtered postmortem monkey tissues were inoculated into mouse brain and from there, a virus called Zika (ZIKV) was cultured. In 1948 ZIKV was also isolated from mosquitoes Aedes africanus captured in the Zika forest. In 1956 ZIKV transmission in mosquitoes Ae. aegypti was found, as well as a monkey. Between 1968 and 1975, ZIKV was subsequently isolated from humans (Nigeria); 40% of those patients analized by PRNT shown antibodies

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June 21, 2016, 1140 EDT (11:40 AM EDT)CDCHAN-00392Testing for Zika virus infection using real-time reverse-transcription polymerase chain reaction (rRT-PCR) molecular assays is now commercially available. When requesting Zika rRT-PCR testing from a commercial laboratory, providers should be aware that commercial laboratories performing rRT-PCR currently do not also offer Zika IgM enzyme-linked immunosorbent assay (ELISA) or confirmatory serologic testing (plaque reduction neutralization test, or PRNT). Therefore, if possible, providers should store a serum aliquot for subsequent Zika IgM ELISA testing if the rRT-PCR assay is negative. Otherwise, collection of an additional serum sample may be necessary.Recommendations\u2022 rRT-PCR (molecular) testing should be performed for patients possibly exposed to Zika virus who have symptoms consistent with Zika virus infection\u2022 Providers who request molecular testing for Zika virus infection from a commercial testing laboratory are advised to retain and store in a refrigerator (2-8\ub0C) an aliquot of the patient's serum for subsequent Zika IgM ELISA testing if the rRT-PCR is negative\u2022 For specimens that are rRT-PCR negative from the commercial laboratory and no stored serum specimen is available, another serum specimen should be collected within 12 weeks of symptom onset for Zika IgM ELISA testing\u2022 Appropriate samples for molecular testing are serum samples collected <7 days and urine samples collected <14 days after symptom onset. Urine should always be collected with a patient-matched serum specimen.FINAL HAN 392 CDC Recommendations for Subsequent Zika IgM Antibody Testing_06 21 2016.pdf2016Zika VirusVirusZika Viru

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August 19, 2016, 1515 ET (3:15 PM ET)CDCHAN-00394CDC has previously issued travel, testing, and other guidance for local mosquito-borne Zika virus transmission (active Zika virus transmission) for a one-square-mile area in the Wynwood area of Miami that the Florida Department of Health (FL DOH) identified. The guidance for those who live in or traveled to this area any time after June 15, 2016, remains in effect. FL DOH continues to investigate active Zika virus transmission in South Florida. Investigation has revealed a new area of active transmission in a 1.5-square-mile section of Miami Beach. In addition, FL DOH has identified multiple other individual instances of mosquito-borne Zika virus infection and an increase in travel-related cases. Because the incubation period for Zika infection is up to two weeks, a high proportion of infected people have no symptoms, and the diagnosis and investigation of cases takes several weeks, coupled with these individual instances of mosquito-borne Zika virus infection and increase in travel-related cases, it is possible that other neighborhoods in Miami-Dade County have active Zika virus transmission that is not yet apparent. For the identified area of active transmission in Miami Beach, CDC advises that the recommendations outlined below be followed. Based on the earliest time of symptom onset and a maximal two-week incubation period for Zika virus, this guidance applies to pregnant women, women of reproductive age, and their partners who live in or traveled to Miami Beach after July 14, 2016. For all other areas of Miami-Dade County, while further investigations are underway, CDC advises strict adherence to precautions to prevent mosquito bites. Consistent with the August 3 recommendation of the Florida Governor, pregnant women in these areas should be assessed for potential exposure to Zika virus and, when indicated, obtain laboratory testing. Pregnant women and partners of pregnant women who are concerned about potential Zika virus exposure may also consider postponing nonessential travel to all parts of Miami-Dade County.This is an ongoing investigation, and FL DOH and CDC are working together to rapidly learn more about the extent of active Zika virus transmission in Miami-Dade County. CDC will update these recommendations as more information becomes available.Recommendations1. Pregnant women should avoid travel to the designated area of Miami Beach (http://www.cdc.gov/zika/intheus/florida-update.html), in addition to the designate)d area of Wynwood, both located in Miami-Dade County, because active Zika virus transmission has been confirmed in both of these areas.2. Pregnant women and their partners living in or traveling to the designated areas should be aware of active Zika virus transmission and should follow steps to prevent mosquito bites (http://www.cdc.gov/zika/prevention/prevent-mosquito-bites.html). Healthcare providers caring for pregnant women and their partners should visit CDC Zika website (http://www.cdc.gov/zika/) frequently for the most up-to-date recommendations.3. Women and men who live in or who have traveled to the designated area of Miami Beach since July 14, 2016, should be aware of active Zika virus transmission, and those who have a pregnant sex partner should consistently and correctly use condoms or other barriers to prevent infection during sex or not have sex for the duration of the pregnancy. The same recommendation applies for women and men who live in or who have traveled to the designated area in Wynwood since June 15, 2016.4. Pregnant women and partners of pregnant women who are concerned about potential Zika virus exposure may also consider postponing nonessential travel to all parts of Miami-Dade County.5. All pregnant women in the United States should be assessed for possible Zika virus exposure and signs or symptoms consistent with Zika virus disease at each prenatal care visit. Women with ongoing risk of possible Zika virus exposure include those who live in or frequently travel to the designated areas of Miami Beach and Wynwood due to the possibility of active Zika virus transmission. Women with limited risk of Zika virus exposure include those who traveled to the designated areas of Miami Beach and Wynwood or had sex without using condoms or other barrier methods to prevent infection by a partner who lives in or traveled to the designated areas of Miami Beach and Wynwood. Each prenatal evaluation should include an assessment of signs and symptoms of Zika virus disease (acute onset of fever, rash, arthralgia, conjunctivitis), travel history, and sexual exposure to determine whether Zika virus testing is indicated. Limitations of laboratory tests used to diagnose Zika virus infection should also be discussed with pregnant women and their partners.6. Pregnant women with possible exposure to Zika virus and signs or symptoms consistent with Zika virus disease should be tested for Zika virus infection based on time of evaluation relative to symptom onset in accordance with CDC guidance (http://www.cdc.gov/mmwr/volumes/65/wr/mm6529e1.htm?s_cid=mm6529e1_e).7. Pregnant women with ongoing risk of possible Zika virus exposure and who do not report symptoms of Zika virus disease should be tested in the first and second trimesters of pregnancy in accordance with CDC guidance (http://www.cdc.gov/mmwr/volumes/65/wr/mm6529e1.htm?s_cid=mm6529e1_e).8. Pregnant women with limited risk of possible Zika virus exposure and who do not report symptoms should consult with their healthcare providers to obtain testing for Zika virus infection based on the elapsed interval since their last possible exposure in accordance with CDC guidance (http://www.cdc.gov/mmwr/volumes/65/wr/mm6529e1.htm?s_cid=mm6529e1_e).9. Women with Zika virus disease should wait at least eight weeks after symptom onset to attempt conception, and men with Zika virus disease should wait at least six months after symptom onset.10. Women and men with ongoing risk of possible Zika virus exposure who do not have signs or symptoms consistent with Zika virus disease and are considering pregnancy should consult their healthcare provider. Due to the ongoing risk of possible Zika virus exposure, healthcare providers should discuss the risks of Zika, emphasize ways to prevent Zika virus infection, and provide information about safe and effective contraceptive methods. As part of their pregnancy planning and counseling with their healthcare providers, some women and their partners living either of the two designated areas (Miami Beach and Wynwood) might consider if now is the right time to get pregnant due to the possibility of exposure to Zika virus during pregnancy or the periconceptional period.11. Women and men with limited risk of possible Zika virus exposure and who do not report signs or symptoms consistent with Zika virus disease should wait at least eight weeks after last possible exposure to attempt conception.Final HAN 394_CDC Expands Guidance for Travel and Testing of Pregnant Wo....pdf2016Zika VirusVirusZika Viru

Update: Interim guidance for health care providers caring for pregnant women with possible Zika virus exposure \u2014 United States (including U.S. Territories), July 2017

On July 24, 2017, this report was posted online as an MMWR Early Release.CDC has updated the interim guidance for U.S. health care providers caring for pregnant women with possible Zika virus exposure in response to 1) declining prevalence of Zika virus disease in the World Health Organization\u2019s Region of the Americas (Americas) and 2) emerging evidence indicating prolonged detection of Zika virus immunoglobulin M (IgM) antibodies. Zika virus cases were first reported in the Americas during 2015\u20132016; however, the incidence of Zika virus disease has since declined. As the prevalence of Zika virus disease declines, the likelihood of false-positive test results increases. In addition, emerging epidemiologic and laboratory data indicate that, as is the case with other flaviviruses, Zika virus IgM antibodies can persist beyond 12 weeks after infection. Therefore, IgM test results cannot always reliably distinguish between an infection that occurred during the current pregnancy and one that occurred before the current pregnancy, particularly for women with possible Zika virus exposure before the current pregnancy. These limitations should be considered when counseling pregnant women about the risks and benefits of testing for Zika virus infection during pregnancy. This updated guidance emphasizes a shared decision-making model for testing and screening pregnant women, one in which patients and providers work together to make decisions about testing and care plans based on patient preferences and values, clinical judgment, and a balanced assessment of risks and expected outcomes.For these recommendations, the definition of possible Zika virus exposure has not changed and includes travel to, or residence in an area with risk for mosquito-borne Zika virus transmission or sex with a partner who has traveled to or resides in an area with risk for mosquito-borne Zika virus transmission. These areas can be found on the CDC \u201cZika Travel Information\u201d webpage.Key recommendations include the following:1) All pregnant women in the United States and U.S. territories should be asked about possible Zika virus exposure before and during the current pregnancy, at every prenatal care visit. CDC recommends that pregnant women not travel to any area with risk for Zika virus transmission. It is also recommended that pregnant women with a sex partner who has traveled to or lives in an area with risk for Zika virus transmission use condoms or abstain from sex for the duration of the pregnancy.2) Pregnant women with recent possible Zika virus exposure and symptoms\u2020 of Zika virus disease should be tested to diagnose the cause of their symptoms. The updated recommendations include concurrent Zika virus nucleic acid test (NAT) and serologic testing as soon as possible through 12 weeks after symptom onset.3) Asymptomatic pregnant women with ongoing possible Zika virus exposure\ua7 should be offered Zika virus NAT testing three times during pregnancy. IgM testing is no longer routinely recommended because IgM can persist for months after infection; therefore, IgM results cannot reliably determine whether an infection occurred during the current pregnancy. The optimal timing and frequency of testing of asymptomatic pregnant women with NAT alone is unknown. For pregnant women who have received a diagnosis of laboratory\u2013confirmed Zika virus infection (by either NAT or serology [positive/equivocal Zika virus or dengue virus IgM and Zika virus plaque reduction neutralization test (PRNT) 6510 and dengue virus PRNT <10 results]) any time before or during the current pregnancy, additional Zika virus testing is not recommended. For pregnant women without a prior laboratory-confirmed diagnosis of Zika virus, NAT testing should be offered at the initiation of prenatal care, and if Zika virus RNA is not detected on clinical specimens, two additional tests should be offered during the course of the pregnancy coinciding with prenatal visits.4) Asymptomatic pregnant women who have recent\ub6 possible Zika virus exposure (i.e., through travel or sexual exposure) but without ongoing possible exposure are not routinely recommended to have Zika virus testing. Testing should be considered using a shared patient-provider decision-making model, one in which patients and providers work together to make decisions about testing and care plans based on patient preferences and values, clinical judgment, a balanced assessment of risks and expected outcomes, and the jurisdiction\u2019s recommendations. Based on the epidemiology of Zika virus transmission and other epidemiologic considerations (e.g., seasonality), jurisdictions might recommend testing of asymptomatic pregnant women, either for clinical care or as part of Zika virus surveillance. With the decline in the prevalence of Zika virus disease, the updated recommendations for the evaluation and testing of pregnant women with recent possible Zika virus exposure but without ongoing possible exposure are now the same for all areas with any risk for Zika virus transmission.5) Pregnant women who have recent possible Zika virus exposure and who have a fetus with prenatal ultrasound findings consistent with congenital Zika virus syndrome should receive Zika virus testing to assist in establishing the etiology of the birth defects. Testing should include both NAT and IgM tests.6) The comprehensive approach to testing placental and fetal tissues has been updated. Testing placental and fetal tissue specimens can be performed for diagnostic purposes in certain scenarios (e.g., women without a diagnosis of laboratory-confirmed Zika virus infection and who have a fetus or infant with possible Zika virus-associated birth defects**). However, testing of placental tissues for Zika virus infection is not routinely recommended for asymptomatic pregnant women who have recent possible Zika virus exposure but without ongoing possible exposure and who have a live born infant without evidence of possible Zika virus\u2013associated birth defects.7) Zika virus IgM testing as part of preconception counseling to establish baseline IgM results for nonpregnant women with ongoing possible Zika virus exposure is not warranted because Zika virus IgM testing is no longer routinely recommended for asymptomatic pregnant women with ongoing possible Zika virus exposure.CDC continues to evaluate all available evidence and will update recommendations as new information becomes available.2874992

The methyltransferase and helicase enzymes as therapeutic targets of Zika virus : a bio- computational analysis of interactions with potential inhibitors.

Doctoral of Philosophy in Pharmaceutical Sciences. University of KwaZulu-Natal, Westville, 2019.The rampant Zika virus has received worldwide attention after becoming a global crisis following the Brazilian epidemic in 2015. From an obscure and neglected pathogen, Zika virus is now a notorious virus associated with neurological disorders in infants and adults. Since 2016, the rapid research response from the global scientific community have led to the discovery of numerous potential small molecule inhibitors and vaccines against the Zika virus. Although, in spite of this massive research initiative, there is still no effective antiviral nor vaccine that has made it out of clinical trials. The design and development of new chemical entities demands excessive cost, time and resources. Therefore, this study applies computer-aided drug design techniques, which accelerates the rational drug design process. Computational approaches including molecular docking, virtual screening, molecular modeling and molecular dynamics facilitate the filtration of large databases of compounds to sift out potential lead compounds. Furthermore, research has dedicated several resources toward FDA-approved drug repurposing. Generally, drugs have similar effects on viruses of the same family; hence drugs that have previously been effective in treating other flaviviruses, such as Dengue virus and West Nile virus, are being tested for its potential inhibition of Zika virus. However, the ability of these drugs to pass the bloodbrain barrier to treat infected neurons poses a challenge to anti-Zika virus drug discovery. This study proposes innovative strategies to design drugs that are capable of passing the blood-brain barrier, and to be able to use drugs that are impermeable via drug delivery mechanisms. This study also assesses the bioavailability and blood-brain barrier permeability of screened drugs to scrutinize the list of potential Zika virus inhibitors. Apart from identifying potential inhibitors, understanding the structural dynamics of viral targets and molecular mechanisms underlying potential inhibition of the virus is imperative. This study explores the structural and molecular dynamics of key targets of the Zika virus, the NS3 helicase and the NS5 methyltransferase enzymes, using computational approaches mentioned above and several others elaborated in this thesis. These computational methods also allowed the identification of precise interactions, amino acid residues, inhibitory mechanisms and pharmacophoric features involved in binding of lead compounds to these enzymes. IX Chapter 4 represents the first study of this thesis, which presents a concise literature background of Zika virus and identifies blood-brain barrier permeability as a core challenge in anti-Zika virus drug development. This study also provides approaches that may enable researchers to create effective anti-Zika virus drugs. Chapter 5 is the subsequent study of this thesis, which applies molecular dynamics to comparatively investigate the mechanism of inhibition and binding mode of two potential inhibitors, sinefungin and compound 5, to the NS5 methyltransferase. The specific pharmacophoric moieties of the most stable inhibitor are also identified in this study. Chapter 6 is the final study of this thesis, which examines the structural dynamics of the Zika virus NS3 helicase enzyme upon binding of ATPase inhibitor and flavivirus lead compound, resveratrol, and reports the key interactions and amino acid residues of the NS3 helicase that contribute highly to binding of resveratrol. This thesis presents an all-inclusive in silico assessment to advance research in drug design and development of Zika virus inhibitors, thus providing a greater understanding of the structural dynamics that occur in unbound and inhibitor-bound Zika virus target enzymes. Therefore, the constituents of this thesis are considered an essential platform in the progression of research toward anti-ZIKV drug design, discovery and delivery against Zika virus

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September 20, 2016, 11:45 ET (11:45 AM ET)CDCHAN-00396CDC previously issued travel, testing, and other guidance related to local mosquito-borne Zika virus transmission (active Zika virus transmission) that the Florida Department of Health (FL DOH) identified in two areas of Miami-Dade County: (1) a one-square-mile area in Wynwood, and (2) a 1.5-square-mile area in Miami Beach. CDC has updated the guidance for people who live in or traveled to these areas.FL DOH continues to investigate active Zika virus transmission in South Florida. Investigation has shown an expanded area of active transmission in Miami Beach, now measuring 4.5 square miles, which includes the original 1.5-square-mile area.The FL DOH has determined that active Zika virus transmission is no longer ongoing in the one-square-mile area of Wynwood after three mosquito incubation periods have passed without any new cases of local transmission. As of September 19, 2016, CDC has modified recommendations for the Wynwood area. CDC no longer recommends pregnant women and their partners avoid travel to the Wynwood area. However, pregnant women and partners of pregnant women who are concerned about potential Zika virus exposure may consider postponing nonessential travel to all parts of Miami-Dade County, including areas without identified active transmission. For all of Miami-Dade County, CDC advises strict adherence to precautions to prevent mosquito bites.Because the incubation period for Zika virus infection is up to two weeks and many people infected with Zika virus won\u2019t have symptoms or will only have mild symptoms, it is likely that there are additional people infected in the population. In addition, because the diagnosis and investigation of cases may take several weeks, coupled with additional cases of local mosquito-borne Zika virus infection and increase in travel-related cases in Miami-Dade County, it is possible that other neighborhoods besides Miami Beach in Miami-Dade County have active Zika virus transmission that is not yet apparent.For the newly expanded area of active transmission in Miami Beach, CDC advises that the recommendations outlined below be followed. As outlined in prior guidance, based on the earliest time of symptom onset and a maximal two week incubation period for Zika virus infection, these recommendations apply to pregnant women, women of reproductive age, and their partners who live in or traveled to the designated 4.5-square-mile area of Miami Beach after July 14, 2016.This is an ongoing investigation, and FL DOH and CDC are working together to rapidly learn more about the extent of active Zika virus transmission in Miami-Dade County. CDC will update these recommendations as more information becomes available.Final HAN 396_CDC Updates Guidance for Travel and Testing of Pregnant Women and Women of Reproductive Age Related to Zika_FL_09 20 16_.pdf2016Zika VirusVirusZika Viru

The Zika outbreak of the 21st century.

The Zika virus outbreak has captivated the attention of the global audience and information has spread rapidly and wildly through the internet and other media channels. This virus was first identified in 1947, when it was isolated from a sentinel rhesus monkey placed by British scientists working at the Yellow Fever Research Laboratory located in the Zika forest area of Uganda, hence its name, and is transmitted primarily by the mosquito vector, Aedes aegypti. The fact that the rhesus macaque is an Asian species being placed in an African forest brings to mind the possibility of rapid adaptation of the virus from an African to Asian species, an issue that has not been considered. Whether such adaptation has played any role in acquiring pathogenicity due to cross species transmission remains to be identified. The first human infection was described in Nigeria in 1954, with only scattered reports of about a dozen human infections identified over a 50-year period. It was not until 2007 that Zika virus raised its ugly head with infections noted in three-quarters of the population on the tiny island of Yap located between the Philippines and Papua New Guinea in the western Pacific Ocean, followed by a major outbreak in French Polynesia in 2013. The virus remained confined to a narrow equatorial band in Africa and Asia until 2014 when it began to spread eastward, first toward Oceania and then to South America. Since then, millions of infected individuals have been identified in Brazil, Colombia, Venezuela, including 25 additional countries in the Americas. While the symptoms associated with Zika virus infection are generally mild, consisting of fever, maculopapular rash, arthralgia and conjunctivitis, there have been reports of more severe reactions that are associated with neurological complications. In pregnant women, fetal neurological complications include brain damage and microcephaly, while in adults there have been several cases of virus-associated Guillain-Barre syndrome. The virus was until recently believed to only be transmitted via mosquitoes. But when the Zika virus was isolated from the semen specimens from a patient in Texas, this provided the basis for the recent report of possible sexual transmission of the Zika virus. Due to the neurological complications, various vectors for infection as well as the rapid spread throughout the globe, it has prompted the World Health Organization to issue a global health emergency. Various governmental organizations have recommended that pregnant women do not travel to countries where the virus is epidemic, and within the countries affected by the virus, recommendations were provided for women of childbearing age to delay pregnancy. The overall public health impact of these above findings highlights the need for a rapid but specific diagnostic test for blood banks worldwide to identify those infected and for the counseling of women who are pregnant or contemplating pregnancy. As of this date, there are neither commercially licensed diagnostic tests nor a vaccine. Because cross-reactivity of the Zika virus with dengue and Chikungunya virus is common, it may pose difficulty in being able to quickly develop such tests and vaccines. So far the most effective public health measures include controlling the mosquito populations via insecticides and preventing humans from direct exposure to mosquitoes

Zika Virus: Can Artificial Contraception Be Condoned?

As the Zika virus pandemic continues to bring worry and fear to health officials and medical scientists, Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) have recommended that residents of the Zika-infected countries, e.g., Brazil, and those who have traveled to the area should delay having babies which may involve artificial contraceptive, particularly condom. This preventive policy, however, is seemingly at odds with the Roman Catholic Church’s position on the contraceptive. As least since the promulgation of Paul VI’s 1968 encyclical, Humanae Vitae, the Church has explicitly condemned artificial birth control as intrinsic evil. However, the current pontiff, Pope Francis, during his recent visit to Latin America, remarked that the use of artificial contraception may not be in contradiction to the teaching of Humanae Vitae while drawing a parallel between the current Zika Crisis and the 1960’s Belgian Congo Nun Controversy. The pope mentioned that the traditional ethical principle of the lesser of two evils may be the doctrine that justified the exceptions. The authors of this paper attempt to expand the theological rationale of the pope’s suggestion. In so doing, the authors rely on casuistical reasoning as an analytic tool that compares the Belgian Congo Nun case and the given Zika case, and suggest that the former is highly similar to, if not the same as, the latter in terms of normative moral feature. That is, in both cases the use of artificial contraception is theologically justified in reference to the criteria that the doctrine of the lesser of two evils requires. The authors wish that the paper would provide a solid theological-ethical ground based on which condom-use as the most immediate and effective preventive measure can be recommended in numerous Catholic hospitals as well as among Catholic communities in the world, particularly the most Zika-affected and largest Catholic community in the world, Brazil – 123 million present Brazilian citizens are reported to be Roman Catholic

Outlook Magazine, Winter 2016

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