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• W3084928471 abstract "In the past decade, many tropical regions have had arboviruses epidemics, including of Zika, dengue, and chikungunya viruses. Factors related to arboviral infection epidemics include population growth, unplanned urbanisation, increased travel, climate change, and decline of vector control programmes. The geographical distribution of Zika, dengue, and chikungunya viruses overlap and co-circulation became a serious concern in regions where Aedes spp mosquito vectors are endemic. Particularly, the Americas suffered from simultaneous outbreaks and co-circulation of these arthropod-borne viruses.1Mercado-Reyes M Acosta-Reyes J Navarro-Lechuga E et al.Dengue, chikungunya and Zika virus coinfection: results of the national surveillance during the Zika epidemic in Colombia.Epidemiol Infect. 2019; 147: e77Crossref PubMed Scopus (29) Google Scholar However, our knowledge about co-transmission and co-infection processes and the consequences of dual infection is scarce. Laboratory studies have shown that mosquito vectors can be simultaneously or sequentially infected with multiple arboviruses, and a combination of Zika, dengue, and chikungunya viruses was detected in the saliva of Aedes egypti mosquitoes.2Rückert C Weger-Lucarelli J Garcia-Luna SM et al.Impact of simultaneous exposure to arboviruses on infection and transmission by Aedes aegypti mosquitoes.Nat Commun. 2017; 815412Crossref PubMed Scopus (109) Google Scholar Data from epidemiological surveillance of the Zika outbreak in Colombia showed that among 23 871 processed samples only 0·14% had evidence of co-infection.1Mercado-Reyes M Acosta-Reyes J Navarro-Lechuga E et al.Dengue, chikungunya and Zika virus coinfection: results of the national surveillance during the Zika epidemic in Colombia.Epidemiol Infect. 2019; 147: e77Crossref PubMed Scopus (29) Google Scholar However, co-infections were found in 71 (27%) of 263 patients with confirmed arboviral infection in Nicaragua, and mean viraemia in those patients was significantly lower in comparison with that of monoinfections.3Waggoner JJ Gresh L Vargas MJ et al.Viremia and clinical presentation in Nicaraguan patients infected with Zika virus, chikungunya virus, and dengue virus.Clin Infect Dis. 2016; 63: 1584-1590Crossref PubMed Scopus (160) Google Scholar Chikungunya and dengue co-infection is commonly found, very likely because of the high number of outbreaks associated with these viruses.3Waggoner JJ Gresh L Vargas MJ et al.Viremia and clinical presentation in Nicaraguan patients infected with Zika virus, chikungunya virus, and dengue virus.Clin Infect Dis. 2016; 63: 1584-1590Crossref PubMed Scopus (160) Google Scholar Concurrent co-infection with two or more arboviruses was previously reported in small case-series of patients with neurological disease,4Zambrano H Waggoner JJ Almeida C Rivera L Benjamin JQ Pinsky BA Zika virus and Chikungunya virus coinfections: a series of three cases from a single center in Ecuador.Am J Trop Med Hyg. 2016; 95: 894-896Crossref PubMed Scopus (58) Google Scholar, 5Acevedo N Waggoner J Rodriguez M et al.Zika virus, chikungunya virus, and dengue virus in cerebrospinal fluid from adults with neurological manifestations, Guayaquil, Ecuador.Front Microbiol. 2017; 8: 42Crossref PubMed Scopus (50) Google Scholar including those with Guillain-Barré syndrome and encephalitis.5Acevedo N Waggoner J Rodriguez M et al.Zika virus, chikungunya virus, and dengue virus in cerebrospinal fluid from adults with neurological manifestations, Guayaquil, Ecuador.Front Microbiol. 2017; 8: 42Crossref PubMed Scopus (50) Google Scholar However, the full spectrum of neurological complications associated with these arboviruses and the role of dual infection and co-infections has not been systematically evaluated before in a prospective study. In The Lancet Neurology, Maria L Brito Ferreira and colleagues6Brito Ferreira ML Militão de Albuquerque MFP de Brito CAA et al.Neurological disease in adults with Zika and chikungunya virus infection in Northeast Brazil: a prospective observational study.Lancet Neurol. 2020; 19: 826-839Summary Full Text Full Text PDF PubMed Scopus (28) Google Scholar report the neurological complications associated with arboviral disease in patients from Northeast Brazil. Patients in this study were aged 18 years or older, with suspected acute neurological disease, and a history of suspected arboviral infection. Brito Ferreira and colleagues assessed for evidence of Zika, chikungunya, or dengue infection by viral RNA or specific IgM antibodies in serum or CSF. Patients were classified as having co-infection when more than one virus was detected at the same time by RT-PCR and dual infection when they had more than one virus on PCR or IgM testing. In 148 patients who had laboratory evidence of arbovirus infection, CNS disease was significantly associated with chikungunya infection (26 [47%] of 55 patients vs six [15%] of 41 with Zika infection; p=0·0008), especially myelitis (12 [22%] patients with chikungunya infection vs one [2%] with Zika infection; p=0·006). Zika infection was associated with peripheral neurological disease (26 [63%] of 41 patients with Zika infection vs nine [16%] of 55 with chikungunya infection). In 46 patients with dual infection with Zika and chikungunya, 13 (28%) had CNS disease and 15 (33%) peripheral neurological disease. This single-centre hospital-based study from a highly endemic area for multiple arboviral infections provided confirmatory information regarding Zika and chikungunya neurotropism; however, its results require replication in other geographical settings. Co-infection can enhance the severity of neurological complications compared with monoinfection. Arboviruses have neurovirulent and neurotropism properties, and co-infection with Zika and chikungunya might lead to the occurrence of more severe neurological disease. The authors reported severe neurological complications in patients with dual infection, and more of these patients (five [36%] of 14) were admitted to the intensive care unit than those with mono-infection (two [6%] of 32). Four potential outcomes of co-infection have been proposed, including the enhancement or inhibition of both arboviruses, the competition between them, or the absence of effect.7Vogels CBF Rückert C Cavany SM Perkins TA Ebel GD Grubaugh ND Arbovirus coinfection and co-transmission: a neglected public health concern?.PLoS Biol. 2019; 17e3000130Crossref PubMed Scopus (53) Google Scholar Competition between multiple infecting arboviruses might happen as they replicate in monocytes, and the faster-replicating virus could infect cells first and use cellular resources for its replication. A study showed that not all patients who were PCR positive for co-infected arboviruses at initial presentation might have produced antibodies, and chikungunya replicates quicker and might outcompete dengue and Zika viruses.7Vogels CBF Rückert C Cavany SM Perkins TA Ebel GD Grubaugh ND Arbovirus coinfection and co-transmission: a neglected public health concern?.PLoS Biol. 2019; 17e3000130Crossref PubMed Scopus (53) Google Scholar An exacerbated immune response or susceptibility when co-infection occurs could explain the more severe neurological disease. However, the role of dual infection on the severity of neurological complications and its effect on vulnerable populations—such as pregnant women, neonates, older people, and people with comorbidities—is still unclear. The host's immune response might be affected during dual infections and co-infections and the role of pre-existing cross-reactive antibodies from previous flavivirus infections requires further investigation. Previous dengue infection and the presence of pre-existing dengue antibodies might reduce the risk of Zika infection,8Rodriguez-Barraquer I Costa F Nascimento EJM et al.Impact of preexisting dengue immunity on Zika virus emergence in a dengue endemic region.Science. 2019; 363: 607-610Crossref PubMed Scopus (132) Google Scholar although this might not be the case for severe CNS Zika infection. Brito Ferreira and colleagues found a higher prevalence of cerebrovascular events among individuals co-infected with Zika and chikungunya viruses, which could be due to either immune-mediated endothelial damage, meningovasculitis, or platelet dysfunction, as in dengue infection.9Carod-Artal FJ Wichmann O Farrar J Gascón J Neurological complications of dengue virus infection.Lancet Neurol. 2013; 12: 906-919Summary Full Text Full Text PDF PubMed Scopus (251) Google Scholar, 10Estofolete CF de Oliveira Mota MT Bernardes Terzian AC Unusual clinical manifestations of dengue disease—real or imagined?.Acta Trop. 2019; 199105134Crossref PubMed Scopus (8) Google Scholar This association was not significant when adjusted for comorbidities, so additional studies should clarify the link between stroke and multiple arbovirus co-infections. Our understanding of the pathogenesis and consequences of arboviral dual infections and co-infections is insufficient, and the question of whether dual infections and co-infections affect the clinical course or the severity of neurological disease needs to be elucidated. Arboviral mono-infection, sequential mono-infection, and concurrent co-infections could be linked to a different clinical course of neurological disease. The question of whether arbovirus dual infection might result in no clinical effect, synergism, or one virus outcompeting the other, resulting in symptoms consistent with a single infection, needs to be clarified. Arboviruses should be considered within the differential diagnosis of any myelitis, encephalitis, or Guillain-Barré syndrome in the tropics, and concurrent co-infection should be routinely ruled out. We declare no competing interests. Neurological disease in adults with Zika and chikungunya virus infection in Northeast Brazil: a prospective observational studyThere is a wide and overlapping spectrum of neurological manifestations caused by Zika or chikungunya mono-infection and by dual infections. The possible increased risk of acute cerebrovascular disease in patients with dual infection merits further investigation. Full-Text PDF" @default.
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• W3084928471 title "Neurological complications in adults with Zika and chikungunya virus infection" @default.
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