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The whole iceberg: estimating the incidence of yellow fever virus infection from the number of severe cases.

ABSTRACT: Like many infectious agents, yellow fever (YF) virus only causes disease in a proportion of individuals it infects and severe illness only represents the tip of the iceberg relative to the total number of infections, the more critical factor for virus transmission.We compiled data on asymptomatic infections, mild disease, severe disease (fever with jaundice or hemorrhagic symptoms) and fatalities from 11 studies in Africa and South America between 1969 and 2011. We used a Bayesian model to estimate the probability of each infection outcome.For YF virus infections, the probability of being asymptomatic was 0.55 (95% credible interval [CI] 0.37-0.74), mild disease 0.33 (95% CI 0.13-0.52) and severe disease 0.12 (95% CI 0.05-0.26). The probability of death for people experiencing severe disease was 0.47 (95% CI 0.31-0.62).In outbreak situations where only severe cases may initially be detected, we estimated that there may be between one and seventy infections that are either asymptomatic or cause mild disease for every severe case identified. As it is generally only the most severe cases that are recognized and reported, these estimates will help improve the understanding of the burden of disease and the estimation of the potential risk of spread during YF outbreaks.

SUBMITTER: Johansson MA

PROVIDER: S-EPMC4632853 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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The whole iceberg: estimating the incidence of yellow fever virus infection from the number of severe cases.

Johansson Michael A MA Vasconcelos Pedro F C PF Staples J Erin JE

Transactions of the Royal Society of Tropical Medicine and Hygiene 20140630 8

<h4>Background</h4>Like many infectious agents, yellow fever (YF) virus only causes disease in a proportion of individuals it infects and severe illness only represents the tip of the iceberg relative to the total number of infections, the more critical factor for virus transmission.<h4>Methods</h4>We compiled data on asymptomatic infections, mild disease, severe disease (fever with jaundice or hemorrhagic symptoms) and fatalities from 11 studies in Africa and South America between 1969 and 2011 ...[more]

PMID: 24980556

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Project description:BackgroundCase fatality risk (CFR), commonly referred to as a case fatality ratio or rate, represents the probability of a disease case being fatal. It is often estimated for various diseases through analysis of surveillance data, case reports, or record examinations. Reported CFR values for Yellow Fever vary, offering wide ranges. Estimates have not been found through systematic literature review, which has been used to estimate CFR of other diseases. This study aims to estimate the case fatality risk of severe Yellow Fever cases through a systematic literature review and meta-analysis.MethodsA search strategy was implemented in PubMed and Ovid Medline in June 2019 and updated in March 2021, seeking reported severe case counts, defined by fever and either jaundice or hemorrhaging, and the number of those that were fatal. The searches yielded 1,133 studies, and title/abstract review followed by full text review produced 14 articles reporting 32 proportions of fatal cases, 26 of which were suitable for meta-analysis. Four studies with one proportion each were added to include clinical case data from the recent outbreak in Brazil. Data were analyzed through an intercept-only logistic meta-regression with random effects for study. Values of the I2 statistic measured heterogeneity across studies.ResultsThe estimated CFR was 39 % (95 % CI: 31 %, 47 %). Stratifying by continent showed that South America observed a higher CFR than Africa, though fewer studies reported estimates for South America. No difference was seen between studies reporting surveillance data and studies investigating outbreaks, and no difference was seen among different symptom definitions. High heterogeneity was observed across studies.ConclusionsApproximately 39 % of severe Yellow Fever cases are estimated to be fatal. This study provides the first systematic literature review to estimate the CFR of Yellow Fever, which can provide insight into outbreak preparedness and estimating underreporting.

Project description:BackgroundYellow fever is a viral hemorrhagic fever caused by yellow fever virus, a mosquito-borne flavivirus. Despite an effective vaccine, major outbreaks continue to occur around the world. Even though it is not a proven neurotropic virus, neurological symptoms in more severe clinical forms are frequent. The understanding of this apparent paradox is still rarely addressed in literature.MethodsThe brains of thirty-eight patients with yellow fever confirmed by RT-PCR, who underwent autopsy, were analyzed morphologically to identify and characterize neuropathological changes. The data were compared with brains collected from individuals without the disease, as a control group. Both cases and controls were subdivided according to the presence or absence of co-concurrent septic shock, to exclude changes of the sepsis associated encephalopathy. To verify possible morphological differences between the yellow fever cases groups, between the control groups, and between the cases and the controls, we applied the statistical tests Fisher's exact test and chi-square, with p values < 0.05 considered statistically significant.ResultsAll cases and controls presented, at least focally, neuropathological changes, which included edema, meningeal and parenchymal inflammatory infiltrate and hemorrhages, and perivascular inflammatory infiltrate. We did not find an unequivocal aspect of encephalitis. The only parameter that, after statistical analysis, can be attributed to yellow fever was the perivascular inflammatory infiltrate.ConclusionsThe neuropathological findings are sufficient to justify the multiple clinical neurologic disturbances detected in the YF cases. Since most of the parameters evaluated did not show statistically significant difference between cases and controls, an explanation for most of the neuropathological findings may be the vascular changes, consequent to shock induced endotheliopathy, associated with stimulation of the immune system inherent to systemic infectious processes. The statistical difference obtained in yellow fever cases regarding perivascular infiltrate can be can be explained by the immune activation inherent to the condition.

Project description:Understanding the impact of non-pharmaceutical interventions as well as accounting for the unascertained cases remain critical challenges for epidemiological models for understanding the transmission dynamics of COVID-19 spread. In this paper, we propose a new epidemiological model (eSEIRD) that extends the widely used epidemiological models such as extended Susceptible-Infected-Removed model (eSIR) and SAPHIRE (initially developed and used for analyzing data from Wuhan). We fit these models to the daily ascertained infected (and removed) cases from March 15, 2020 to Dec 31, 2020 in South Africa that reported the largest number of confirmed COVID-19 cases and deaths from the WHO African region. Using the eSEIRD model, the COVID-19 transmission dynamics in South Africa was characterized by the estimated basic reproduction number (R0) starting at 3.22 (95%CrI: [3.19, 3.23]) then dropping below 2 following a mandatory lockdown implementation and subsequently increasing to 3.27 (95%CrI: [3.27, 3.27]) by the end of 2020. The initial decrease of effective reproduction number followed by an increase suggest the effectiveness of early interventions and the combined effect of relaxing strict interventions and emergence of a new coronavirus variant in South Africa. The low estimated ascertainment rate was found to vary from 1.65% to 9.17% across models and time periods. The overall infection fatality ratio (IFR) was estimated as 0.06% (95%CrI: [0.04%, 0.22%]) accounting for unascertained cases and deaths while the reported case fatality ratio was 2.88% (95% CrI: [2.45%, 6.01%]). The models predict that from December 31, 2020, to April 1, 2021, the predicted cumulative number of infected would reach roughly 70% of total population in South Africa. Besides providing insights on the COVID-19 dynamics in South Africa, we develop powerful forecasting tools that enable estimation of ascertainment rates and IFR while quantifying the effect of intervention measures on COVID-19 spread.

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The whole iceberg: estimating the incidence of yellow fever virus infection from the number of severe cases.

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The whole iceberg: estimating the incidence of yellow fever virus infection from the number of severe cases.

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