Quantifying the consequences of measles-induced immune modulation for whooping cough epidemiology

Abstract

Measles, an acute viral disease, continues to be an important cause of childhood mortality worldwide. Infection with the measles virus is thought to be associated with a transient but profound period of immune suppression. Recently, it has been claimed that measles-induced immune manipulation lasts for about 30 months and results in increased susceptibility to other co-circulating infectious diseases and more severe disease outcomes upon infection. We tested this hypothesis using model-based inference applied to parallel historical records of measles and whooping cough mortality and morbidity. Specifically, we used maximum likelihood to fit a mechanistic transmission model to incidence data from three different eras, spanning mortality records from 1904 to 1912 and 1922 to 1932 and morbidity records from 1946 to 1956. Our aim was to quantify the timing, severity and pathogenesis impacts of measles-induced immune modulation and their consequences for whooping cough epidemiology across a temporal gradient of measles transmission. We identified an increase in susceptibility to whooping cough following recent measles infection by approximately 85-, 10- and 36-fold for the three eras, respectively, although the duration of this effect was variable. Overall, while the immune impacts of measles may be strong and clearly evident at the individual level, their epidemiological signature in these data appears both modest and inconsistent. This article is part of the theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes'. This issue is linked with the subsequent theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control'.

Keywords: immune suppression; maximum likelihood; measles; polymicrobial system; transmission model; whooping cough.

Figure 1.

Weekly notification of whooping cough and measles fatality cases in London during (a) 1904–1912 and (b) 1922–1932 and (c) weekly incidence of whooping cough and measles during 1946–1956.

Figure 2.

Schematic of the whooping cough transmission model. Individuals progress from compartments S to I and I to R at rates of λ and γ, respectively. Individuals recently infected with measles progress from compartments S_M to I_M and I_M to R at rates of θλ and γ, respectively. Disease-induced mortality owing to whooping cough and measles are represented by α₁ and α₂, respectively. Here, M(t) is number of measles cases at week t. Immune mediation parameters are coloured red; θ quantifies the susceptibility to whooping cough after measles infection, α^M represents the risk of disease-induced mortality owing to whooping cough after measles infection, and n is the immune modulation duration. The slice size does not represent the actual size of S_M.

Figure 3.

Log-likelihood profiles for parameters n, θ, α^M and α₁ for eras 1904–1912 (a–d), 1922–1932 (e–h), 1946–1956 (i,j) in London. The profiles are constructed by fitting a smooth curve through the log-likelihood points. Vertical dashed dotted lines represent the maximum-likelihood estimate (MLE). The horizontal dashed lines represent the approximately 2 log-likelihood units below the MLE. The shaded areas represent the estimated 95% confidence interval.