Clinical Symptoms and Complications of Dengue, Zika and Chikungunya Infections in Pacific Island Countries: A Systematic Review and Meta-Analysis

Background: Dengue fever (DENV), Zika virus (ZIKV) and chikungunya (CHIKV) pose a significant public health risk to Pacific Island countries. However, there is limited existing research that compares the clinical manifestations of these arboviruses.

Methods: We searched PubMed, Embase and Scopus for epidemiological studies that presented quantitative data for symptoms or complications of DENV, ZIKV or CHIKV in a Pacific Island country. Risk of bias assessment was conducted using the Newcastle-Ottawa Scale (NOS). For each arbovirus, we used descriptive statistics and performed random-effects meta-analysis to calculate pooled prevalence estimates with 95% confidence intervals. Heterogeneity was assessed using the I2 statistic and was further investigated through subgroup analysis. Publication bias was assessed via Egger’s test.

Findings: We found that fever, headache, arthralgia, myalgia, rash and gastrointestinal symptoms were common in all three arboviruses. Complications for ZIKV included Guillain-Barré syndrome (GBS) (0.5%) and microcephaly (56%), and for CHIKV, were shock or organ failure (3%), liver disease (1%), myocarditis (0.1%) and neurological complications (1%). Through meta-analysis, we estimated the rates of hospitalisation (12.45% [7.88-17.87]), mortality (0.25% [0.05-0.54]) and severe dengue (4.47% [0.97-10.17]) in DENV. Subgroup analysis revealed clinical heterogeneity based on age, geographical location, study design and whether studies only examined hospitalised patients. Publication bias was also detected for studies assessing complications of DENV.

Interpretation: We identified overlapping symptoms as well as clinical features that were specific to each arbovirus: For DENV, haemorrhagic symptoms, flushed face and taste alteration; and for ZIKV, limb oedema, Guillain-Barré syndrome and microcephaly. Despite CHIKV being recognised as a classically mild disease, we also identified the potential for severe complications such as myocarditis, encephalitis and shock or organ failure. We proposed updated clinical criteria for DENV, ZIKV and CHIKV to guide clinicians in Pacific Island countries. Our review was limited by lack of data availability and consequently we advocate for efforts to improve the transparency and consistency of disease reporting systems in the region. Overall, our research will assist healthcare providers in Pacific Island countries to better understand these clinically challenging arboviruses.