Characteristics of Madariaga and Venezuelan Equine Encephalitis Virus Infections, Panama

Abstract

Madariaga virus (MADV) and Venezuelan equine encephalitis virus (VEEV) are emerging arboviruses affecting rural and remote areas of Latin America. However, clinical and epidemiologic reports are limited, and outbreaks are occurring at an increasing frequency. We addressed the data gap by analyzing all available clinical and epidemiologic data of MADV and VEEV infections recorded since 1961 in Panama. A total of 168 human alphavirus encephalitis cases were detected in Panama during 1961‒2023. We described the clinical signs and symptoms and epidemiologic characteristics of those cases, and also explored signs and symptoms as potential predictors of encephalitic alphavirus infection compared with those of other arbovirus infections occurring in the region. Our results highlight the challenges for the clinical diagnosis of alphavirus disease in endemic regions with overlapping circulation of multiple arboviruses.

Keywords: Madariaga virus; Panama; Venezuelan equine encephalitis; alphaviruses; outbreak investigation; vector-borne infections; viruses.

Figure 1

General laboratory algorithm used for diagnosis of MADV and VEEV, Panama. MADV and VEEV diagnosis made on the basis of days since symptom onset. *In paired samples showing 4-fold increase in antibody titers. †Confirmation after IgG or IgM testing. MADV, Madariaga virus; PRNT, plaque-reduction neutralization test; RT-PCR, reverse transcription PCR; VEEV, Venezuelan equine encephalitis virus.

Figure 2

Timeline showing history of VEEV and MADV in humans animals and vectors, Panama. Timeline shows incidence during 1961‒2023. A) VEEV incidence; B) MADV incidence. Ab, antibodies; MADV, Madariaga virus; VEEV, Venezuelan equine encephalitis virus.

Figure 3

Locations of recorded cases in a study of characteristics of MADV and VEEV infections, Panama, 1961–2023. Green squares represent MADV cases and red circles VEEV cases. MADV cases were reported only in the eastern Panama region, in the province of Darien. MADV cases detected outside Darien, in Chiriquí, Comarca Näbe Bugle, and Herrera were reported in members of the border police working in the Darien Province, who at time of symptom onset were in their home region. MADV, Madariaga virus; NA, not applicable; VEEV, Venezuelan equine encephalitis virus.

Figure 4

Heatmap of frequency of signs and symptoms by viral infection in South America used in study of characteristics of MADV and VEEV infections, Panama. Datasets from alphavirus cases in Panama (1961‒2023), and DENV (2009), CHIKV (2015‒2020), and ZIKV (2016) infection cases from Brazil were used to provide more complete symptom data. Gray blocks denote missing data. Neurologic symptoms included seizures, focal sensory or motor deficits, and diminished level of consciousness. CHIKV, chikungunya virus; DENV, dengue virus, MADV, Madariaga virus; VEEV, Venezuelan equine encephalitis virus; ZIKV, Zika virus.

Figure 5

Heatmap of frequency of signs and symptoms by sex and viral infection in study of characteristics of MADV and VEEV infections, Panama. Cases reported during 1961–2023. Neurologic symptoms included seizures, focal sensory or motor deficits, and diminished level of consciousness. MADV, Madariaga virus; VEEV, Venezuelan equine encephalitis virus.

Figure 6

Heatmap of frequency of signs and symptoms by age and viral infection in study of characteristics of MADV and VEEV infections, Panama. Cases reported during 1961–2023. Neurologic symptoms included seizures, focal sensory or motor deficits, and diminished level of consciousness. MADV, Madariaga virus; VEEV, Venezuelan equine encephalitis virus.

Figure 7

Multivariable logistic regression analysis of associated symptoms of encephalitic alphavirus infections and other arbovirus infections in study of characteristics of MADV and VEEV infections, Panama. A) MADV versus VEEV infection; B) MADV and VEEV versus DENV infection; C) MADV and VEEV versus ZIKV infection; D) MADV and VEEV versus CHIKV infection. MADV cases reported during 1961–2023. Dot represents odds ratio and whiskers indicate 95% CI. The red vertical line represents an odds ratio of 1, indicating that the odds of the event are the same in both groups. CHIKV, chikungunya virus; DENV, dengue virus, MADV, Madariaga virus; VEEV, Venezuelan equine encephalitis virus; ZIKV, Zika virus.