A Case of Zika Virus - Or Is It?
March  2016


A 35 year-old man applied for life insurance with waiver of premium for disability benefit. His medical records indicate that he was previously in good health when he presented to his doctor about one month prior to the application. He was complaining of a 103o F fever, a headache, and muscle aches. There was no evidence of a stiff neck, rash, gastrointestinal or respiratory complaints.

He admitted that he started feeling bad three days earlier while on a return flight from Honduras, where he had been on a church mission in the rural countryside. His doctor recommended fluids, rest, antipyretics and analgesics. He also ordered a CBC and a sample for Zika virus testing to be sent to the state health department.

The doctor suggested that the proposed insured isolate himself until the fever had resolved for five days and return for follow up if he worsened, or in one week for test results. This was the last entry in the medical record.


What are the implications of Zika virus infection for mortality and morbidity risks?
Zika virus (ZKV) is an emerging mosquito-borne virus (Flavivirus) that was first identified in Uganda in 1947. It was subsequently identified in humans in 1952 in Uganda and the United Republic of Tanzania. Outbreaks of Zika virus disease have been recorded in Africa, the Americas, Asia and the Pacific.

The most recent outbreak reported in Latin America and the Caribbean is an immediate health concern for the region, and news continues to develop on this topic rapidly. We present what is known at the time of publication and encourage our colleagues in client companies to contact us for further discussion.

Figure 1 – American/Caribbean Countries with Confirmed ZKV Cases


Cases of the Zika virus have been reported throughout Latin America and the Caribbean. Many cases in the US involve foreign travelers.


Outbreak and Transmission
ZKV in the Americas was first identified in Brazil in April 2015. Since then, the number of infections and complications have increased and the infection has been reported by almost all American countries. Incubation for Zika virus is likely to be a few days to a week.

The ZKV natural transmission cycle involves mosquitoes, especially A.aegypti and A.albopictus. However, ZKV transmission by sexual intercourse has been reported and transfusion-transmitted ZKV infections have also been demonstrated.

Signs and Symptoms
About 80% of people infected with ZKV are asymptomatic. When people are symptomatic, the illness is usually mild with symptoms lasting for several days to a week. The main symptoms are headache, low-grade fever, mild joint pain, skin rash (exanthema) and conjunctivitis. Other less common symptoms are sore throat, cough and vomiting. Joint pain may persist for approximately one month.  Deaths are rare.


Diagnosis and Treatment
Zika virus is diagnosed through PCR (polymerase chain reaction) and virus isolation from blood samples.

Zika virus disease is usually relatively mild and requires no specific treatment. No medications or vaccines currently are available to prevent or treat Zika infections, though several labs are testing interventions.

Complications
Increased incidence of neurological syndromes and microcephaly were reported in Brazil since the beginning of the outbreak.

This increase in the incidence of rare pathologies during Zika virus outbreak is consistent with a temporal and spatial link with the Zika virus outbreak. However, the etiopathogenesis and associated risk factors have not yet been well established.

Pathological complications include neurological syndromes, increased risk of microcephaly and other birth defects and ophthalmological anomalies.

Neurological syndromes – The rate of neurological syndromes in adults increased during the last Zika virus outbreak. Observed incidence of Gullain Barré syndrome and other neurological anomalies is about 10-20 times expected.

Microcephaly – The association between Zika virus infection and the increased number of reports of congenital microcephaly and other birth defects is a serious issue. The average of annual incidence of microcephaly in the 4 last years in Brazil was 163 (SD 16.9) cases. Since the beginning of the outbreak the incidence of microcephaly has increased dramatically. Since the epidemiological 1st week of 2016, 3530 cases of microcephaly in Brazil have been reported.

Ophthalmological anomalies – Ophthalmological lesions have been reported in newborns. Ocular findings commonly involve the macular region, such as macular neuroretinal atrophy.

Prevention
The first line of prevention is effective mosquito control, including reducing the risk of mosquito bites: using an insect repellent; wearing clothing (preferably light colored) that covers most of the body; using physical barriers such as screens, closed doors and windows; and sleeping under mosquito nets. It is very important to identify and eliminate potential mosquito breeding sites. This is especially true for travelers. Some agencies recommend pregnant women against travelling to epidemic countries.

Vaccines
No vaccines are available currently. However, a vaccine for the Zika virus is in development by US and Canadian scientists with Inovio Pharmaceuticals Inc (INO.O) and South Korea’s GeneOne Life Science Inc. The first approved vaccination could be available for emergency use before the end of the year, with  clinical trials scheduled to start by September 2016.

Figure 2 - Comparison of Zika, Chikungunya and Dengue Viruses

​Zika Virus​Chikungunya Virus​Dengue Virus
​TransmissionAedes mosquitoes, blood transfusion, sexAedes mosquitoes​Aedes mosquitos
​From infection to disease in...​1 in 5 people​3 in 4 people​1 in 4 people
​Incubation (range)​2-12 days​2-12 days​3-14 days
​Symptoms​Low grade fever, maculopapular rash, arthritis (smaller joints of the hands and feet), conjunctivitis​Fever, joint pain in multiple joints, headache, muscle pain, rash, joint swelling​Fever, headache, retro-orbital pain, joint pain, muscle and/or bone pain, rash, mild bleeding (nose or gums, easy bruising), nauseau, vomiting, diarrhea
​Typically resolves​2-7 days​7-10 days

​Febrile phase:
2-7 days
Critical phase:
1-2 days
Recovery phase:
2-3 days

​Complications (associations)​Perinatal infection: fetal loss; microencephaly Guillian-Barre syndrome​Joint swelling and pain may recur for several months​Bleeding, neutropenia, thrombocytopenia, liver enlargement, shock can occur
​Mortality​Very rare​Rare, mostly in adults​Severe Dengue - 2.5% CFR

The Zika, chikungunya and dengue viruses present common symptoms. It is advisable that physicians test for the presence of all three when infection is suspected. (* CFR = Case fatality rate. Severe defined as requiring hospitalization.)
 

Returning to the Case
It is not clear that this case is a Zika virus infection. The Center for Disease Control (CDC) recommends that all samples tested for Zika virus also be tested for dengue virus and chikungunya virus as all three are present in Latin America, they share the same mosquito vector (aedes aegypti, aedes albopictus), and the initial presentations are all very similar (Figure 2).

Given the mortality implications of dengue infection and the possible post-infection morbidity with any of the infections it would be prudent to postpone issuing any policy for at least 6 months, and then reconsider with results of testing and an up-to-date evaluation for complications.


References
CDC. Symptoms, Diagnosis, & Treatment http://www.cdc.gov/zika/symptoms/index.html
ECDC. Rapid Risk Assessment. Zika virus. First update January 2016. http://ecdc.europa.eu/en/publications/Publications/rapid-risk-assessment-zika-virus-first-update-jan-2016.pdf
WHO. Zika virus. http://www.who.int/mediacentre/factsheets/zika/en/
CIDRAP. Zika news. http://www.cidrap.umn.edu/infectious-disease-topics/zika#news
PAHO. “Epidemiological Update Neurological syndrome, congenital anomalies, and Zika virus infection.” 17 January 2016
Ministerio da Saude. Dengue, Chikungunya, Zika.  http://combateaedes.saude.gov.br/
Musso D, Roche C, Robin E and colls. “Potential Sexual Transmission of Zika Virus.” Emerging Infectious Diseases, Vol. 21, No. 2, February 2015 359-361.
WHO. Dengue. http://www.who.int/mediacentre/factsheets/fs117/en/
CDC. “Distribution of Aedes mosquitoes, US.” http://www.cdc.gov/chikungunya/resources/vector-control.html