Classification
RNA virus identification:
Viruses can be classified in many ways. Most viruses, however, will have a genome formed by either DNA or RNA. RNA genome viruses can be further characterized by either a single- or double-stranded RNA. “Enveloped” viruses are covered by a thin coat of cell membrane (usually taken from the host cell). If the coat is absent, the viruses are called “naked” viruses. Viruses with single-stranded genomes are “positive-sense” viruses if the genome is directly used as messenger RNA (mRNA), which is translated into proteins. “Negative-sense,” single-stranded viruses use RNA-dependent RNA polymerase, a viral enzyme, to transcribe their genome into messenger RNA.
General Characteristics and Epidemiology
General characteristics
- Genus: Flavivirus
- Also classified as an arbovirus because it is transmitted by an arthropod
- Structure:
- Positive sense
- Linear ssRNA
- Enveloped
- Icosahedral capsid
Transmission electron microscopic image of Zika virus:
A member of the family Flaviviridae, grown in LLC-MK2 culture cells. Virus particles are 40 nm in diameter, and have an outer envelope and inner dense core. Also note the smooth membrane vesicles, which are recognized as the replication complex for this virus family.
Epidemiology
- 1st identified in Uganda in 1947
- Now widely distributed in the tropical and subtropical zones of:
- Asia
- Africa
- Micronesia
- South and Central America
- Local outbreaks have recently been reported in the United States.
World map showing the distribution of Zika virus (2016)
Image: “CDC map of Zika virus distribution as of 15 January 2016” by CDC. License: Public DomainPathogenesis
Reservoirs
- Humans
- Nonhuman primates
Transmission
- Most commonly transmitted by Aedes aegypti mosquitoes
- Transplacental transmission can occur if pregnant women are infected.
- Sexual transmission possible
Aedes aegypti feeding on human skin
Image: “Aedes aegypti bloodfeeding CDC Gathany” by James Gathany. License: Public DomainHost risk factors
- Recent travel to endemic areas (tropical and subtropical areas)
- Sexual intercourse with a currently infected or recently infected individual
Pathophysiology
- The A. aegypti mosquito serves as a vector:
- Zika virus replicates within the midgut of a mosquito.
- After replication, the virus lives in the salivary glands of the mosquito.
- Mosquito bites a human host, inoculating virus into keratinocytes.
- The virus moves to the lymph nodes before spreading systemically.
- In congenital Zika syndrome, the virus infects the neural progenitor cells of the fetus.
Clinical Presentation
Zika virus infection in adults
- Incubation period: 3–14 days
- The majority of patients remain asymptomatic after the incubation period.
- If symptomatic, the findings are nonspecific:
- Headache
- Arthralgia
- Myalgia
- Fever
- Pruritic rash
- Non-exudative conjunctivitis
- Potential complications:
- Guillain-Barré syndrome
- Meningoencephalitis
- Transverse myelitis
Congenital Zika syndrome
- Most concerning complication of Zika virus infection
- Zika virus infects the neural progenitor cells in the CNS.
- Findings include:
- Subcortical calcifications
- Microcephaly
- Ventriculomegaly
- Ocular defects
- Spasticity
- Seizures
Diagnosis and Management
Diagnosis
- Specific diagnostic studies based on time since infection:
- 0‒14 days after infection: PCR of blood or urine samples to detect Zika RNA
- > 14 days after infection: serology (for antibodies against Zika)
- Nonspecific laboratory abnormalities:
- Leukopenia
- Thrombocytopenia
- Elevated CRP and erythrocyte sedimentation rate (ESR)
- Perform PCR or serologies to rule out coinfection with dengue or yellow fever viruses.
Management
- No curative therapies are available.
- Symptomatic management:
- Oral or IV fluids to maintain adequate hydration
- Acetaminophen to decrease fever and joint pain
- Notify the CDC.
Comparison of Species
| Zika virus | West Nile virus | Dengue virus | |
|---|---|---|---|
| Characteristics |
|
|
|
| Transmission |
|
Culex mosquitoes | Aedes mosquitoes |
| Clinical |
|
|
|
| Diagnosis |
|
|
|
| Management | Symptomatic treatment | ||
| Prevention |
|
|
|
Differential Diagnosis
The following conditions are differential diagnoses for congenital Zika syndrome:
- Congenital toxoplasmosis: a congenital TORCHES infection caused by the protozoa Toxoplasma gondii. Toxoplasmosis is most commonly transmitted by the ingestion of undercooked pork, but can also be transmitted after contact with cat feces. Congenital toxoplasmosis presents with the triad of chorioretinitis, hydrocephalus, and diffuse intracranial (rather than subcortical) calcifications. Diagnosis is made with serology. Treatment is using pyrimethamine-sulfadiazine.
- Congenital cytomegalovirus infection: a congenital TORCHES infection caused by cytomegalovirus, also known as human herpesvirus 5 (HHV-5). Cytomegalovirus is transmitted by urine, blood, saliva, sex, and organ transplantation. Congenital cytomegalovirus presents with hearing loss, seizures, “blueberry muffin” rash, and periventricular (rather than subcortical) calcifications. Diagnosis is made by serology or PCR. Treatment is using ganciclovir or valganciclovir.
- Congenital herpes infection: a congenital TORCHES infection caused by herpes simplex virus (HSV) 2. Herpes simplex virus is transmitted transvaginally from an infected mother to the fetus while the fetus is in contact with lesions in the birth canal. Congenital herpes infection presents with skin and mucous membrane vesicles similar to those seen in adults. Congenital herpes infection can also be disseminated and involve multiple organs. Diagnosis is confirmed using viral PCR, and treatment includes acyclovir.
References
- LaBeaud, A.D. (2021). Zika virus infection: An overview. UpToDate. https://www.uptodate.com/contents/Zika-virus-infection-an-overview
- Nielsen-Saines, K. (2021). Congenital Zika virus infection: Clinical features, evaluation, and management of the neonate. UpToDate. https://www.uptodate.com/contents/congenital-Zika-virus-infection-clinical-features-evaluation-and-management-of-the-neonate
- Navalkele, B.D. (2020). Zika virus: Background, pathophysiology, epidemiology. Medscape. https://emedicine.medscape.com/article/2500035-overview
- Vouga M, et al. (2018). Updated Zika virus recommendations are needed. Lancet. 392(10150), 818–819. https://pubmed.ncbi.nlm.nih.gov/30146329/
- Moreira-Soto, A., et al. (2018). Exhaustive TORCH pathogen diagnostics corroborate Zika virus etiology of congenital malformations in Northeastern Brazil. mSphere, 3(4) https://pubmed.ncbi.nlm.nih.gov/30089647/
- Shehu, N.Y., et al. (2018). Pathogenesis, diagnostic challenges and treatment of Zika virus disease in resource-limited settings. Niger Postgrad Med J. 25(2), 67–72. https://pubmed.ncbi.nlm.nih.gov/30027916/
