Zika virus infection in adults often causes pruritic maculopapular rash, but rarely leads to clinically significant fever, according to two cohort studies in Rio de Janeiro.

The findings raise questions about case definitions of Zika virus disease (ZVD).

“In our opinion, pruritus, the second most common clinical sign presented by the confirmed cases, should be added to the Pan American Health Organization case definition [for Zika virus disease], while fever could be given less emphasis,” Dr. Patricia Brasil of the Oswaldo Cruz Foundation in Rio de Janeiro and her associates wrote online April 12 in PLoS Neglected Tropical Diseases.

Watching for a combination of itching and rash also could help distinguish Zika virus disease from infections of Chikungunya and Dengue, co-circulating arboviruses in Brazil that tend to cause nonpruritic rash, the investigators noted. Distinguishing these infections is crucial because Dengue, in particular, can be devastating without appropriate treatment ( doi: 10.1371/journal.pntd.0004636 ).

Brazil confirmed Zika virus disease in the northeastern state of Bahia in May 2015. Cases in Rio de Janeiro soon followed, triggering worries because of its dense population and status as host of the 2016 Olympic and Paralympic Games. To better characterize Zika virus disease in Rio de Janeiro, Dr. Brasil and her associates studied 364 cases of acute rash, with or without fever, among adults with clinical onset during the first half of 2015. Quantitative reverse transcription–polymerase chain reaction detected Zika viral RNA in blood samples from 119 (45%) of 262 patients tested.

The first 4 days of confirmed ZVD were marked by rash (97%), itching (79%), prostration (73%), headache (66%), arthralgias (63%), and myalgia (61%). Just 36% of patients were febrile, and fevers usually were short-lived and low-grade, in contrast to other arboviral infections. Partial sequencing of the Zika virus gene from 10 randomly selected positive samples showed that it resembled Asian strains of Zika virus, supporting the hypothesis that Pacific Islanders brought Zika to Rio de Janeiro during a canoe championship in 2014, the researchers added.

The researchers also determined that Zika virus was circulating in Rio de Janeiro as early as January 2015 – “at least five months before its detection was announced by the health authorities, which must be taken into consideration for future design and implementation of effective syndromic surveillance systems,” they wrote. Surprisingly, an assay for Dengue was negative in all 250 patients tested, which might indicate “explosive transmission dynamics of Zika virus disease,” the investigators added.

A retrospective cohort study of confirmed Zika virus cases in Rio de Janeiro also reported a much higher prevalence of rash compared with fever (Emerg Infect Dis. 2016 Jul. doi: 10.3201/eid2207.160375 ).

This was a retrospective convenience sample of 57 patients, including 98% with rash, 56% with pruritus, and 67% with measured or self-reported fever. Most fevers were low-grade, and the median recorded temperature was 30.0 degrees Celsius (within normal limits). Other common presentations included headache (67%), arthralgias (58%), myalgias (49%), and joint swelling (23%), according to Dr. Jose Cerbino-Neto of the Oswaldo Cruz Foundation in Rio de Janeiro and his associates. Their findings support emphasizing rash, fever, or both as “primary characteristics” of ZVD, they added. Currently, the interim case definition from the World Health Organization defines a suspected Zika virus disease case as rash, fever, or both, plus at least one of three other symptoms – arthralgia, arthritis, or conjunctivitis.

The study by Dr. Brasil and her associates was funded by Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, the Fundacao de Amparo a Pesquisa no Estado do Rio de Janeiro, and the European Commission. Dr. Brasil and her coinvestigators had no disclosures. Dr. Cerbino-Neto reported no funding sources or conflicts of interest.