ZIKA VIRUS DISEASE Prof Hilda T Matarira and Dr R I.L.Glavintcheva :Harare and Parirenyatwa Teaching Hospitals

Between 1 January 2007 and 25 February 2016, a total of 52 countries and territories have reported autochthonous (local) transmission of Zika virus, including those where the outbreak is now over and countries and territories that provided indirect evidence of local transmission. Among the 52 countries and territories, Marshall Islands, Saint Vincent and the Grenadines, and Trinidad and Tobago are the latest to report autochthonous transmission of Zika virus.

Zika fever is a mosquito-borne viral illness caused by Zika virus (ZIKV). Zika fever is a mosquito-borne viral illness caused by Zika virus (ZIKV). The clinical course of Zika fever is similar to that of Dengue fever, and is characterized by fever, joint pain, myalgia, headache and rash The clinical course of Zika fever is similar to that of Dengue fever, and is characterized by fever, joint pain, myalgia, headache and rash

Zika virus was discovered in 1946 in Zika Forest, Uganda in febrile rhesus monkeys Zika virus was discovered in 1946 in Zika Forest, Uganda in febrile rhesus monkeys Mice were inoculated- Virus in the brain Mice were inoculated- Virus in the brain 1952 – Humans in Uganda and UR Tanzania 1952 – Humans in Uganda and UR Tanzania In 1948 was found in Aedes Africanus, forest relative of Aedes aegypti In 1948 was found in Aedes Africanus, forest relative of Aedes aegypti Aedes albopictus can spread it as well Aedes albopictus can spread it as well Many scientists believe the 2007 strain of ZIKV has mutated from the original virus, with increased virulence Many scientists believe the 2007 strain of ZIKV has mutated from the original virus, with increased virulence

Genre: Flavivirus - related to yellow fever, dengue, West Nile, and Japanese encephalitis viruses. Genre: Flavivirus - related to yellow fever, dengue, West Nile, and Japanese encephalitis viruses. Vector: Aedes mosquitoes (which usually bite during the morning and late afternoon/evening hours) Vector: Aedes mosquitoes (which usually bite during the morning and late afternoon/evening hours) High Flying Mosquitoes High Flying Mosquitoes Live around buildings in urban areas Reservoir: Unknown Reservoir: Unknown

Distribution of Dengue fever & Aedes Egypti

Approximate known distribution of ZIKV 1947–2007. Red - represents Yap Island. Yellow - human serologic evidence; Red - virus isolated from humans; Green - mosquito isolates.

Countries, territories and areas with local (autochthonous) Zika virus circulation,

Countries and territories in the Americas with autochthonous, confirmed Zika virus cases, (as of 3 March 2016) Countries and territories in the Americas with autochthonous, confirmed Zika virus cases, (as of 3 March 2016)

US States – Travel associated Zika – 153 US Territories – Travel associated Zika – 1, Locally aquired- 107

, serologic evidence of human ZIKV infection was reported from: , serologic evidence of human ZIKV infection was reported from: Uganda, Tanzania, Egypt, Central Uganda, Tanzania, Egypt, Central African Republic, Sierra Leone, and Gabon African Republic, Sierra Leone, and Gabon Later in Senegal (humans), Cote D’Ivoire (mosquitoes) Later in Senegal (humans), Cote D’Ivoire (mosquitoes) and in: India, Malaysia, the Philippines, Thailand, Vietnam, and Indonesia and in: India, Malaysia, the Philippines, Thailand, Vietnam, and Indonesia 9/71 (13%) human volunteers in Lombok, Indonesia, had neutralizing antibody to ZIKV 9/71 (13%) human volunteers in Lombok, Indonesia, had neutralizing antibody to ZIKV

Transmission ZIKV disease outbreaks: ZIKV disease outbreaks: 2007 and 2013 Pacific - Yap Island, Micronesia (75% of the population), French Polynesia 2007 and 2013 Pacific - Yap Island, Micronesia (75% of the population), French Polynesia 2015: 2015: The Americas (Brazil and Colombia) The Americas (Brazil and Colombia) Africa: (Cape Verde) Africa: (Cape Verde) In addition, more than 13 countries in the Americas reported sporadic ZIKV infections - rapid geographic expansion of ZIKV. In addition, more than 13 countries in the Americas reported sporadic ZIKV infections - rapid geographic expansion of ZIKV.

There is to date no solid evidence of non primate reservoirs of ZIKV, but 1 study did find antibody to ZIKV in rodents There is to date no solid evidence of non primate reservoirs of ZIKV, but 1 study did find antibody to ZIKV in rodents ?other arthropod vectors/reservoir hosts ?other arthropod vectors/reservoir hosts ?the possibility of congenital infection ?the possibility of congenital infection ?transmission through blood transfusion. ?transmission through blood transfusion.

Prenatal USS Images and Coronal Slices of Brain Panel A - numerous calcifications in various parts of the brain (arrows) and the dilated occipital horn of the lateral ventricle (Vp, marked with a measurement bar), transverse USS. Panel B - numerous calcifications in the placenta. Panel C - multifocal cortical and subcortical white calcifications (arrows) and almost complete loss of gyration of the cortex. Basal ganglia developed but poorly delineated (black asterisks), sylvian fissures are widely open on both sides (arrowheads on the left). The third ventricle is not dilated (white asterisk). Panel D - dilated lateral ventricles (white arrowheads); the left - collapsed. Temporal horns of the lateral ventricles (black arrowheads) are also dilated. The thalami (black asterisks) and the left hippocampus (white asterisk) are well developed, but the contralateral structure is not recognisable due to autolysis.

Virology and Pathogenesis ZIKV is an RNA virus ZIKV is an RNA virus Family flaviviruses Family flaviviruses Next Closest Relatives: Ilheus, Rocio and St. Louis encephalitis viruses Next Closest Relatives: Ilheus, Rocio and St. Louis encephalitis viruses Yellow fever virus is the prototype of the family, which also includes Dengue, Japanese encephalitis, and West Nile viruses Yellow fever virus is the prototype of the family, which also includes Dengue, Japanese encephalitis, and West Nile viruses

Information regarding pathogenesis of ZIKV is scarce but mosquito-borne flaviviruses are thought to replicate initially in dendritic cells near the site of inoculation then spread to lymph nodes and the bloodstream Information regarding pathogenesis of ZIKV is scarce but mosquito-borne flaviviruses are thought to replicate initially in dendritic cells near the site of inoculation then spread to lymph nodes and the bloodstream ZIKV has been detected in human blood as early as the day of illness onset; viral nucleic acid has been detected as late as 11 days after onset ZIKV has been detected in human blood as early as the day of illness onset; viral nucleic acid has been detected as late as 11 days after onset Detected in the sperm, sexual transmission confirmed in Texas, France & Italy Detected in the sperm, sexual transmission confirmed in Texas, France & Italy

Clinical Manifestations The first well-documented report of human ZIKV disease was in 1964, Simpson described his own occupationally acquired ZIKV illness at age 28: The first well-documented report of human ZIKV disease was in 1964, Simpson described his own occupationally acquired ZIKV illness at age 28: Headache at onset Headache at onset Next day - maculopapular rash - face, neck, trunk, and upper arms, spread to his palms and soles. Transient fever, malaise, and back pain developed. Next day - maculopapular rash - face, neck, trunk, and upper arms, spread to his palms and soles. Transient fever, malaise, and back pain developed. By the evening of the second day of illness he was afebrile, the rash was fading, and he felt better. By the evening of the second day of illness he was afebrile, the rash was fading, and he felt better. By day three, he felt well and had only the rash, which disappeared over the next 2 days. By day three, he felt well and had only the rash, which disappeared over the next 2 days. ZIKV was isolated from serum collected while he was febrile. ZIKV was isolated from serum collected while he was febrile.

Symptoms and signs ❖ ❖ 1 in 5 infected persons develop symptoms ❖ ❖ Symptoms nonspecific – –may be confused with dengue – –mild and self limiting – –consist of low grade fever, maculopapular rash, myalgia, athralgia, conjunctivitis, headache ❖ ❖ Severe disease uncommon except with underlying comobidities ❖ ❖ Possible link with neurological complications observed in Brazil and French Polynesia – –microcephaly for babies born to infected mothers – –Guillain Barre Syndrome

Diagnosis PCR tests on acute-phase serum samples (viral DNA) PCR tests on acute-phase serum samples (viral DNA) PCR in urine PCR in urine ZIKV Ab tests ZIKV Ab tests IgM to ZIKV IgM to ZIKV Cross-reactivity with: dengue virus < yellow fever, Japanese encephalitis, Murray Valley encephalitis, or West Nile viruses Cross-reactivity with: dengue virus < yellow fever, Japanese encephalitis, Murray Valley encephalitis, or West Nile viruses Acute serum ASAP, 2 nd sample 2-3/52 later Acute serum ASAP, 2 nd sample 2-3/52 later

Management Usually no tx needed Prevention One in 5 people has symptoms, usually mild illness Supportive treatment: Bed rest, Antipyretics, Pain Killers, Rehydration, Antihistamines, Antibiotics if secondary bacterial infection Treat co-morbidities No vaccine yet, may be in 18/12

WHO REG. OFFICE COUNTRY/TERRITORY WHO REG. OFFICE COUNTRY/TERRITORY Reported autochthonous transmission (40)AFRO Cape Verde AMRO/PAHO(31) Aruba, Barbados, Bolivia, Bonaire, Brazil, Colombia, Costa Rica, Curaçao, Dominican Republic, Ecuador, El Salvador, French Guiana, Guadeloupe, Guatemala, Guyana, Haiti, Honduras, Jamaica, Martinique, Mexico, Nicaragua, Panama, Paraguay, Puerto Rico, Saint Martin, Sint Maarten, Saint Vincent and the Grenadines, Suriname, Trinidad and Tobago, United States Virgin Islands, Venezuela SEARO Maldives, Thailand WPRO American Samoa, Samoa, Solomon Island, Tonga, Vanuatu Indication of viral circulation (6) AFROGabon SEAROIndonesia WPRO Cambodia, Fiji, Philippines, Malaysia, Countries with outbreaks terminated (5) AMRO/PAHO Eastern Islands WPRO Cook Islands, French Polynesia, New Caledonia, Yap Locally acquired without vector borne transmission (1) AMRO/PAHOUSA Countries and territories with autochthonous transmission of ZIKV, 2007 – 2016 Countries and territories with autochthonous transmission of ZIKV, 2007 – 2016

Incidence of Microcephaly and/or CNS malformations ( ) (Brazil, French Polynesia, El Salvador, Venezuela, Colombia and Suriname): (Brazil, French Polynesia, El Salvador, Venezuela, Colombia and Suriname): Brazil:4783 /76 deaths since January 2015 Brazil:4783 /76 deaths since January 2015 Of 76 deaths to congenital malformations, ZIKV - in foetal tissue in 5 cases Of 76 deaths to congenital malformations, ZIKV - in foetal tissue in 5 cases French Polynesia 2013 – 2014: Increased number of CNS malformations French Polynesia 2013 – 2014: Increased number of CNS malformations Zika virus infection was confirmed in a baby born with microcephaly in Hawaii (1) and in the foetus of a baby in Slovenia after pregnancy termination Zika virus infection was confirmed in a baby born with microcephaly in Hawaii (1) and in the foetus of a baby in Slovenia after pregnancy termination Incidence of Guillain-Barré syndrome (GBS): Brazil, Colombia, El Salvador, Suriname and Venezuela - increase of GBS. Brazil, Colombia, El Salvador, Suriname and Venezuela - increase of GBS. In July 2015 the state of Bahia in Brazil reported 42 cases of GBS, 26 in patients with a history of symptoms of ZIKV infection. In July 2015 the state of Bahia in Brazil reported 42 cases of GBS, 26 in patients with a history of symptoms of ZIKV infection. In November 2015 seven patients presenting GBS were laboratory confirmed for ZIKV infection. In November 2015 seven patients presenting GBS were laboratory confirmed for ZIKV infection. In 2015, a 19% increase in GBS cases was reported in comparison to the previous year. In 2015, a 19% increase in GBS cases was reported in comparison to the previous year. No scientific evidence to date confirms a link between Zika virus and microcephaly or GBS. No scientific evidence to date confirms a link between Zika virus and microcephaly or GBS.

Argentine and Brazilian Doctors Name Larvicide as Potential Cause of Microcephaly ❖ In the area where most sick people live, a chemical larvicide that produces malformations in mosquitoes was introduced into the drinking water supply in ❖ This poison, Pyriproxyfen, is used in a State-controlled programme aimed at eradicating disease-carrying mosquitoes. ❖ Pyriproxyfen is a growth inhibitor of mosquito larvae, alters the development process from larva to pupa to adult, thus generating malformations ❖ It was also noted that ZIKV disease has traditionally a relatively benign disease that has never before been associated with birth defects, even in areas where it infects 75% of the population ❖ From 404 cases with microcephaly only 17% were ZIKV (+)

Countries, territories and areas reporting microcephaly cases potentially associated with Zika virus infection Reporting countryNumber of reported microcephaly cases potentially related to a Zika virus infection Probable location of infection French Polynesia9 Brazil583Brazil Hawaii (United States of America) 1Brazil Slovenia1Brazil

Countries, territories or areas reporting GBS potentially related to Zika virus infection Increased incidence of GBS cases (without biological confirmation of the association with Zika) Increased GBS incidence and biological confirmation of Zika infection in at least some of the cases Reporting GBS with laboratory confirmed Zika virus infection (without increase of GBS incidence BrazilFrench PolynesiaMartinique El SalvadorSurinamePuerto Rico ColombiaVenezuela

Confirmed cases of microcephaly in states of Brazil (583 cases up to 20 February 2016

Countries, territories and areas with Zika virus, microcephaly and GBS,

Potential for transmission in Zim Aedes mosquitoes available in the country - potential for transmission in principle Aedes mosquitoes available in the country - potential for transmission in principle However we need to know: However we need to know: –whether the virus can survive in the environment –whether the mosquito population is sufficient to introduce and sustain transmission The absence of other sister viruses transmitted by Aedes mosquito may give us a ray of hope that Zimbabwe may not be conducive for Zika Virus The absence of other sister viruses transmitted by Aedes mosquito may give us a ray of hope that Zimbabwe may not be conducive for Zika Virus However, need to remain vigilant However, need to remain vigilant

References ❖ ❖ ❖ K. Shinohara et al.,Zika Fever imported from Thailand to Japan and diagnosed by PCR in the urine,JTM, 2016, v1,1-3, ❖ M. Besnard et al.,Evidence of perinatal transmission Zika virus, French Polynesia Decmber 2013 and February 2014, Rapid Communucartuon, 2014, ❖ E. Calves et al. Genetic diversity and Phylogeny of Aedes aegypti, the Main Arbovirus Vector in the Pacific, PLOS NTD, January 22, 2016

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