The clinical spectrum of Zika virus had, to date, been described in small series from endemic/epidemic countries and is not well established.
Methods
We describe the clinical manifestations of laboratory-proven Zika virus infection in Israeli travelers during December 2015-February 2016, and review all published cases of travel-related Zika virus.
Results
During the study period, 8 returning Israeli travelers were diagnosed with Zika virus infection. In addition, 41 published cases were included, mostly from Latin America to Europe and North America. Overall, 65.3% were diagnosed by polymerase chain reaction. Rash was the most frequent symptom, present in 95.7% of cases, followed by fever and arthralgia. Conjunctivitis was present in 53.1%; however, only 40.3% presented with a triad of conjunctivitis, fever, and rash. Less frequent symptoms included dysgeusia and nightmares, which, together with arthralgia, persisted for several weeks in some travelers.
Conclusions
Zika virus clinical picture in travelers is diverse. Prolonged symptoms may occur.
The Zika virus outbreak in Latin America and the Caribbean region appears to be growing rapidly in scale. This, and the concerns raised as to a possible causative association of Zika virus with both microcephaly and Guillain-Barré syndrome, had caused the World Health Organization to designate it as a Public Health Emergency of International Concern. Surprisingly, only a few studies describe the clinical manifestations of Zika virus infection.2,3 In addition, because in all epidemic/endemic regions, Zika virus co-circulates with other arboviruses including dengue and chikungunya, and because few clinically suspected cases are in fact laboratory confirmed, accurate information about the clinical manifestations is lacking. Returning travelers provide a unique opportunity to study the clinical features of Zika virus because all cases have laboratory confirmation, and are followed in a modern health care environment.
Methods
This was a nationwide, case series study.
In Israel, Zika virus diagnostic tests had become available in December 2015, and all tests are performed in the Central Virology Laboratory of the Israeli Ministry of Health at the Sheba Medical Center.
Serology involved an enzyme-linked immunosorbent assay immunoglobulin M and immunoglobulin G kit (Euroimmun AG, Luebeck, Germany), which detects antibodies against Zika virus NS1 protein and is considered very specific for Zika virus infection (Jonas Chanasit-Schmidt, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany; personal communication). Zika virus reverse transcription polymerase chain reaction (RT-PCR) was adopted from the method established during the Zika virus outbreak in Micronesia.
In addition, we performed a literature review: a PubMed search for the period of January 2000-February 2016 was performed, using the search term “Zika virus”; all studies reporting on Zika virus in humans were evaluated. Included were cases in returning travelers (including secondary cases in nonendemic countries) that were laboratory proven: either by positive PCR or viral culture or by seroconversion documented with specific serology. To compare Zika virus findings in travelers with those described in epidemic settings, we extracted symptom data from 3 well-described outbreaks (Yap, Rio De Janeiro, and Puerto Rico).
Results
During December 2015-February 2016, 8 returning Israeli travelers were diagnosed with Zika virus infection. There were 5 cases returning from Colombia, and one case each from the Dominican Republic, Mexico, and Vietnam. In addition, reports of 41 travelers with Zika virus infection, in which clinical details were described, were included in the analysis.
The epidemiological data of these 49 cases is described in Table 1. Age was reported in 45/49 cases: exact age in 28 cases, and in 17 cases only by decade. Overall, 55% were aged between 20 and 39 years, 43% above 40 years, and there was one child (2%) aged 2 years. The male/female ratio was 0.88.
Most cases were in European and North American travelers (Table 1). The country of Zika virus acquisition was reported in all studies except one.24 Travel-related cases were acquired in all areas of known Zika virus circulation, including Africa and Asia, but most frequently in Latin America and the Caribbean (Table 1). Two cases involved sexually transmitted secondary cases, where a male traveler transmitted Zika virus to a nontraveler female partner.
Clinical features of these 49 cases are described in Table 2. The most prevalent symptoms were rash and fever, reported in 95.7% and 81.6%, respectively. The rash was usually nonpruritic, with only 5 cases (10.6%) reporting disturbing itch. Arthralgia or myalgia was present in 76.6%, whereas conjunctivitis was reported in only 53.1%. The symptom triad of fever, rash, and conjunctivitis was reported in 20/49 (40.8%) cases, whereas the triad of fever, rash and arthralgia/myalgia (reminiscent of dengue or chikungunya) was reported in 28/49 (57.1%) cases. There were no definite cases of meningitis/encephalitis. One child had suffered from seizures during acute presentation; neurological examination was normal, as was examination of the cerebrospinal fluid. She was considered to have had a first occurrence of febrile convulsions, however, 3 months later, nonfebrile seizures recurred, with localizing findings in electroencephalogram; brain magnetic resonance imaging did not reveal any pathological findings. Headache was frequent (40.8%), and symptoms that may suggest neural effects were occasionally present: 2 patients reported transient dysgeusia and in one, there was also altered hearing; 2 cases reported recurring nightmares that lasted well after the resolution of fever.
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-Eyal Meltzer, MD, DTM&H, Eyal Leshem, MD, Yaniv Lustig, PhD, Giora Gottesman, MD, Eli Schwartz, MD, DTM&H
This article originally appeared in the October 2016 issue of The American Journal of Medicine.
