ZIKA VIRUS Epic and aspects of management
Classification - Belong to the family Flaviviridae which are mosquitoes borne viruses such as Dengue virus ( DEN V ), West Nile virus ( WN V ), Yellow fever Virus ( YF V ),Chicungunya virus (CHIKV ). - The name Zike is a forest in Uganda which is the main habitat of the animal reservoir ( the Macaque monkey). - Zika virus is a positive-sense single stranded RNA contained into capsid and envelope. This means that the virus can use its RNA directly as messenger RNA to start multiplication. -Polymorphism of many important genetic materials are frequent with possibility of recombination. Which is rare among other Flaviviruses. This has important impact on viral spread, zoonotic maintenance and epidemiological potential
Genetic analysis distinguishes between two distinct lineages, African and Asian, both emerged from Africa before spreading in the late 40`s to the to south east Asia and pacific islands (Polynesia ),then to the American continent. - The principal host are Macaque monkeys which live in Zika forest, Uganda.
Pathogenesis - Aedes mosquitoes family ( Egypti and Africanus species ) is implicated as vectors. -Unlike other Arboviruses, mosquitoes does not play any part in Zika virus life cycle, which means the direct transmission from patient to healthy individuals through insect bite. - The virus is inoculated into skin by carrying mosquito, facilitated by specific receptors, then spread to blood stream. -One of the characteristic s of Aedes aegypti is in door resting behavior which make it very efficient vector of Arboviruses (Dingu, Chikungunia, Zika ).
The insect habitat in bedrooms and living rooms is about 1.5 m. height. This is very important in the strategy of insect elimination using insecticide s spraying procedures. The second important route of infection is sexual transmission and genital persistence of the virus is as important as vector transmission. It was found that the time of exposure to the virus is crucial for the infection (during estrus phase,the female genitals are resistant to the virus The viral particles can persist and recovered in vaginal wash for 10 days after exposure.
Inc Severe cases with neurological complications (meningitis,meningioencephetitis, Guillan-Barre ) are not uncommon. Microcephaly in newborns of infected mother is the worst and most common manifestation of the disease. Mitosis abnormalities and Apoptotic death of human progenerator cells ( both in adults and developing nervous system in fetuses ) are frequently disrupted.
Using FISH (Fluorescence In Situ Hybridization )method analysis of chromosomes 12 and 17 showed increased frequency of abnormality ( monosomy,trisomy,polysomy )
-Incubation time is 3-7 days before symptoms appear. - Most cases are asymptomatic with mild self limiting flu like disease. - Similarity of symptoms of other Arboviruses infections confound right diagnosis.
- Rare death cases were reported in patient suffering other immunopathies ( Rheumatoid arthritis, Lupus, sickle cells, chronic corticosteroids use, alcoholism ). - The stage of pregnancy at which the mother becomes infected seems to affect the risk to the fetus. One study estimated the risk of developing microcephaly at about 1 % during the first trimester with less chance during the rest pregnancy time.
In a study on group of pregnant women developed symptoms ( rash, headache ) during pregnancy in Brazil, fetuses development was evaluated: The fetuses presented with brain lesions Amniotic fluid and tissue analysis confirmed Zika infection 27 % of newborns died within two days of life with evidence of cerebral inflammation and focal calcification. Eye Arthrogyrposis seen in few cases. Microcephaly was the prominent feature in most cases
Some cases showed head circumference within normal range although the cerebral tissue was small. This was due to Hydrocephalus symptoms in those cases
-Historically, symptomatic Zika virus infections were limited to sporadic cases or clusters of exposed humans. - Major outbreaks occurred in 2007 in Polynesia to spread later in epic proportions to Americas - Sporadic cases were reported in Europe, restricted to travelers from affected areas. This might due to the lack of vector insects.
Transmission - Viral particles can cross placenta to infect fetus in the uterine. Virus particles detected in fetus tissues from infected mothers - Possible transmission through blood products and organ transplant procedures. -Possible needle sticks injuries. Cases were reported in health workers following accidental instrumental inoculation. -Possible sexual transmission from infected males. Viral particles were detected in seminal fluids after up to 6 months and transmitted to female partner - No convincing evidence yet to support breast feeding transmission to babies although the virus was detected in milk of infected mothers. - Most reported cases of none placental transmission were coincided with contact with or exposure to mosquitoes, which cast some doubts on these routes.
Laboratory findings - Mild elevation in inflammatory markers (CRP, fibrinogen ). -Elevation in Liver enzymes,ld. CBC profile mostly normal with frequent finding of nonspecific changes (thrombocytopenia, leucopenia ) which coincide with viral infections None of these finding are diagnostic.most are found in other viruses in the family ( DENV,CHIKV )
DIAGNOSIS - Clinical diagnosis is unreliable because of symptoms overlaps with other Arboviruses. -Molecular and immunological procedures are available commercially. - Evaluation for Zika. CHIKV, DENV, should be considered concurrently for all patients with acute fever, rash, myalgia or arthralgia after travel to endemic areas. - PCR based assays are available for definitive diagnosis in large reference laboratories. - Serological assays were approved by FDA for restricted use as emergency first line procedures.
- Molecular amplification procedures (Reverse Transcriptase PCR ) are most specific and preferred approach during acute phase with viremia ( 3-7 days from onset ).Saliva samples can be processed with reliable results. Virus particles are detected in urine samples for up to 14 days after onset. The virus has been found to survive longer in urine than serum or saliva. The virus was detected in seminal fluids after 6 months of exposure.the virus can be detected in vaginal secretions for up to 10 daysa after sexual contact with infected male - The virus does not establish any latency phase in the host. -Serological tests for IgM, IgG abs are available commercially.igm abs can be detected within 3 days of onset. - Cross reactions were seen with closely related flaviviruses (DNV, WNV ) as well as vaccines to flaviviruses
Testing strategy Nucleic Acid Tests (NAT ) for patients presented with symptoms onset less than 7 days. Serology and or NAT in patients with symptoms onset more than 7 days with preference to serological procedures because viremea phase drops rapidly after 7 days. Serology tests for other flaviviruses ( DIN. CHIK. ) should be performs concurrently because of cross reactivity between them. A novel serological Elisa based procedure using None structural Protein 1 (NSP 1), to detect Abs to Zika virus with minimum crossreactivity with DIN V abs ( IgG,IgM ).
Management & Prevention 1- Mosquitoes avoidance and control: - Covering skin and exposed areas to prevent biting - Using insects repellant - Controlling breading places ( still water. Ponds ) - Using insecticides 2- Sexual transmission avoidance: - Using condoms for six months after visiting endemic areas - Avoiding pregnancy for at least six weeks after visiting endemic areas. Some studies reported detection of the virus in women after 3.5 months of symptoms.
3- Infecting mosquitoes with bacterial sp. (Wollbachia ) which make them resistant to Zika virus 4- Spreading sterile male mosquitoes 5- Spreading genetically modified strain of insects developed in Brazil (Oxitec OX513 A ) 7- Vaccination: No available successful vaccines until now. A new approach using DNA based vaccine for Fliviviruses. The DNA coding for immunogenic protein and when injected in tissues, will generates hummoral and cellular immune non specific response to the viruses. Preliminary results show that it prevent infection after exposure to the virus