The Burden of Chikungunya Virus Infection: The Need for Systematic and Geriatric-Specific Epidemiological Monitoring.

Abstract

To the Editor: In their letter in response to our review,1 Godeart and colleagues2 have underlined the way by which we have estimated the potential burden of Chikungunya virus (CHIKV) infection in older people. Evidence from epidemiological, clinical, and laboratory studies suggest an age-related defect in the immune system inducing a state of susceptibility and vulnerability to new or emerging pathogens.3 With respect to arboviral diseases, in addition to infants, older adults are often the first affected with the highest incidence of severe and atypical cases.4, 5 For example, in the first outbreak of West Nile Virus in the United States in 1999, the median age was 71, with 73% of those affected aged 60 and older.6 In 2000 in Israel, all of the victims were aged 78 and older.7 Similar trends can be drawn in the United States with California encephalitis, dengue, Eastern equine encephalitis, St. Louis encephalitis, yellow fever, and Zika, which are also spread by mosquitoes.5 For CHIKV, data are less abundant and conclusive. As detailed by Godeart and colleagues2 and in our review,1 the effect of the age-associated remodeling of the immune system probably contributes to the highest incidence of atypical presentation at the acute stage of CHIKV infection.8 In the absence of serological confirmation or more specific diagnostic criteria for older adults, all unrecognized cases globally contribute to underestimation of the burden of CHIKV. This state of immune vulnerability also favors a high incidence of chronic cases,1 which is another factor that increases the burden of disease in this population more than in younger individuals. Female mosquitoes, particularly the domestic forms of Aedes aegypti and albopictus, have evolved to specialize in biting humans. They are worldwide vectors of CHIKV but also dengue, yellow fever, and Zika virus, and a functional genetic variation in an odorant receptor that recognizes specific components of human body odor induces their preference for human blood.9 Host immunity and genetic factors that model vector-host contact also enhance the invasiveness of both species, as well as their public health threats as vectors.10 Except for the greater amount of carbon dioxide in the breath associated with poor health conditions, there is no evident reason that mosquitoes’ scent receptors specifically target older adults. As Godeart and colleagues underline in their letter,2 it was not hazardous to consider the burden of CHIKV as high. By merely extrapolating data from younger to older adults. We have probably, on the contrary, underestimated the exact burden of this infectious disease in this vulnerable population. This is true particularly when considering CHIKV as a disease with low mortality but high rates of postinfection morbidity and long-term disability. Moreover, the indirect effect of CHIKV in exacerbating comorbid health conditions should be also considered (Figure 1).1, 2 Thus, the associated disability-adjusted life years (DALYs) that can be used to estimate the global or regional burden of CHIKV infection should be, at least, the sum of, for mortality, years of healthy life lost from a standard expected years of life lost and, for nonlethal, disease-specific disability, years lived with disability times a disability weight reflecting the proportion of impairment,4 which should be considered for acute and chronic phase but also with respect to the direct effect of CHIKV and the indirect effect on comorbid and potentially disabling conditions as depicted in Figure 1. To further complicate the burden estimate, it is also important to estimate annualized incidence rates, case fatality rates, and acute-to-chronic-disease case conversion rates based on systematic reported numbers of cases of CHIKV-related symptomatic disease (according to specific criteria for older adults) and not on serological evidence only. We thank Godeart and colleagues2 for drawing attention to the need to specifically assess the burden of CHIKV infection in older adults. There are considerable epidemiological and methodological challenges in estimating the exact burden of CHIKV infection. At the individual level, systematic epidemiological monitoring and recording using not only CHIKV-specific, but also geriatric-specific outcome measures must first be designed, which will lead to accurate estimation of case-fatality rates (including delayed mortality rates), acute-to-chronic-CHIKV case conversion rates, and case-morbidity and -disability rates, but all cases should be precisely identified according to specific clinical criteria1, 8 and only after that the question of the burden of CHIKV infection on society and the healthcare system is addressed. Conflict of Interest: The authors have no conflicts of interest. Author Contributions: Lang, Aspinall: Drafting the reply letter. Sponsor's Role: There was no role of the sponsor in any aspect of this manuscript.