Distinguishing between Zika and Spondweni Viruses

The Spondweni serogroup includes Zika and Spondweni viruses. Both viruses have been historically misidentified and their diseases have been misdiagnosed due to their serological cross-reactivity and similar clinical presentations. Early case reports indicate a subset of patients present with clinical manifestations suggestive of serious illness. Flaviviruses have a high serological cross-reactivity. Before the advent of genetic sequencing, serological assays such as virus neutralization and hemaglutination-inhibition were used to differentiate virus species. Much of the early work differentiating flaviviruses into various serogroups was later confirmed by sequencing and phylogenetic analyses. Historically, serological assays (neutralization and complement fixation tests) were also used to determine evidence of prior infection and geographic distribution. Both viruses in the Spondweni serogroup exhibit serological cross-reactivity and cause non-specific febrile illness in humans, making diagnosis challenging in regions where both viruses circulate. Zika virus was first isolated in Uganda in 1947 (strain MR-766) (1) and Spondweni virus (strain Chuku) was first isolated in Nigeria in 1952. (2) Cross-reactivity in neutralization tests led to the misidentification of the Spondweni virus Chuku strain as a strain of Zika virus. (2-5) This misidentification led to additional studies where this strain of Spondweni virus was reported as Zika virus, a confusion that continues to the present day, although the misidentification of this isolate was clarified and widely reported in 1964. (3-5) Consequently, early clinical case reports from Nigeria, (2) studies involving the experimental infection of a human volunteer, (6) vector competence studies in Aedes aegypti mosquitoes (6) and experimental infections in non-human primates, (7) all involved Spondweni virus (strain Chuku) rather than Zika virus. This cross-reactivity means that the results of early serosurveys--in which only one serological assay was used to screen. blood samples from people or animals living in regions where both viruses circulate--are difficult to interpret. (2,8) Both Zika and Spondweni viruses are primarily transmitted to humans through the bite of an infective mosquito, and the majority of infections are asymptomatic. In symptomatic Zika and Spondweni virus cases, signs and symptoms appear as early as three days post-infection. (6,9) The typical clinical presentation of a Zika virus infection is now well established. The most commonly reported signs and symptoms from 195 patients between 1964 and 2016 are rash (67.2%), fever (63.6%), arthralgia (28.7%), myalgia (23.6%), headache (21.5%), conjunctivitis (20.5%), retroorbital pain (11.3%), oedema (9.7%), pruritus (7.7%) and fatigue (7.2%). (9) Less is known regarding the clinical presentation of Spondweni virus infections. The six well documented cases of Spondweni virus infections report signs and symptoms of fever (100%), headache (83.3%), nausea (83.3%), myalgia (66. …