Zika virus how it emerged Pontiano Kaleebu Director MRC/UVRI Uganda Research Unit and Acting Director Uganda Virus Research Institute, Entebbe

2014–16 Zika virus epidemic As early as August 2014, physicians in Brazil began to investigate an outbreak of illness characterized by a flat pinkish rash, bloodshot eyes, fever, joint pain and headaches. While the symptoms resembled dengue fever, testing ruled out this and several other potential causes. Then, in May 2015, researchers in Brazil determined, using the RT-PCR technique, that the illness was an outbreak of Zika virus.

2014–16 Zika virus epidemic… In February 2016, WHO declared the outbreak a Public Health Emergency of International Concern as evidence grew that Zika can cause birth defects as well as neurological problems. The virus can be transmitted from an infected pregnant woman to her fetus, then can cause microcephaly and other severe brain anomalies in the infant.

What is Zika virus and how did it emerged

Uganda Virus Research Institute UVRI at present Yellow fever laboratory in Entebbe, Uganda, est.1936

Zika forest

Zika Virus Single stranded RNA virus Genus Flavivirus, Family Flaviviridea Closely related to dengue, yellow fever, Japanese encephalitis and West Nile viruses Transmitted to humans primarily by Aedes species mosquitoes Zika virus co-discover Alexander Haddow at the Uganda Virus Institute circa 1960 when he was Director

Viral genome organization HIV-1 genome ~9,700 bp

Zika virus vectors: Aedes mosquitoes Aedes species mosquitoes Ae aegypti more efficient vectors for humans Ae albopictus Also transmit dengue and chikungunya viruses Lay eggs in domestic water- holding containers Live in and around households Aggressive daytime biters

Geographical distribution of Zika Virus 2016 Cabo Verde Mexico 2015 Puerto Rico 2013 Canada 1948 Tanzania 1954 Nigeria USA

Genetic diversity of Zika virus lineages Nigeria Senegal African lineage Uganda (1947) Central R. Africa Senegal Indian/Pacific Oceans Asian lineage Americas

What are the symptoms Many people infected with Zika virus don’t have symptoms.  For people with symptoms (20%), the most common symptoms are Fever Rash Joint pain Conjunctivitis (red eyes) Other symptoms include Muscle pain Headache

Zika virus clinical disease course and outcomes Clinical illness usually mild Symptoms last several days to a week Severe disease requiring hospitalization uncommon Fatalities are rare Guillain-Barre Syndrome reported in patients following suspected Zika virus infection GBS is an uncommon sickness of the nervous system in which a person’s own immune system damages the nerve cells, causing muscle weakness, and sometimes paralysis.

Zika virus and microcephaly Reports of a substantial increase in number of babies born with microcephaly in 2015 in Brazil; Zika virus infection identified in several infants born with microcephaly (including deaths) and in early fetal losses Some of the infants with microcephaly have tested negative for Zika virus Incidence of microcephaly among fetuses with congenital Zika infection is unknown

Is the Ugandan Population Vulnerable to a Zika epidemic Is the Ugandan Population Vulnerable to a Zika epidemic? MRC-UK,Wellome Trust and Newton Fund Funded

UVRI Arbovirus Laboratory Testing Flowchart Samples arrive and logged in Non-inactivated aliquot Inactivated aliquot Re-assay any equivocal results IgM ELISAs Virus Isolation Any IgM positive PRNTs Negative Negative or uninformative Positive and definitive Report Results Continue Virus Isolate? Go to next page

Zika genome detection Taqman RT PCR Next Generation Sequencing Miseq system at UVRI

Universal Taqman RT-PCR assay detects both african and asian lineages of ZIKV Ugandan MR766 ZIKV RNA Fluorescence (dRn) Cycle number Brazilian ZIKV RNA – PE strain Brazilian ZIKV RNA – AB strain Fluorescence (dRn) Fluorescence (dRn) Cycle number Cycle number

Prevention New approaches in devp Reduce mosquitoes bites Cover yourself, long sleeves Bed nets Insecticides/repellants Vertical transmission Avoid mosquito bites Pregnant women consider postponing travel to areas where Zika is present Condoms to avoid sexual transmission where the epidemic is New approaches in devp Use of mosquitoes with wolbalchia Genetically modified mosquitoes Vaccines (killed virus, recombinant, in trials appear safe and immugonenic in animal studies)

WHO recent announcement 18 November 2016 – “Zika virus and associated consequences remain a significant public health challenge requiring intense action, but they no longer represent a Public Health Emergency of International Concern”

Final remarks THANK YOU Zika, Ebola etc outbreaks remind us to be prepared for the emerging and re-emerging infections Importance of surveillance and building health systems The importance of building capacity The importance of collaboration THANK YOU