Characterizing measles transmission in India: a dynamic modeling study using verbal autopsy data

Abstract

Background: Decreasing trends in measles mortality have been reported in recent years. However, such estimates of measles mortality have depended heavily on assumed regional measles case fatality risks (CFRs) and made little use of mortality data from low- and middle-income countries in general and India, the country with the highest measles burden globally, in particular.

Methods: We constructed a dynamic model of measles transmission in India with parameters that were empirically inferred using spectral analysis from a time series of measles mortality extracted from the Million Death Study, an ongoing longitudinal study recording deaths across 2.4 million Indian households and attributing causes of death using verbal autopsy. The model was then used to estimate the measles CFR, the number of measles deaths, and the impact of vaccination in 2000-2015 among under-five children in India and in the states of Bihar and Uttar Pradesh (UP), two states with large populations and the highest numbers of measles deaths in India.

Results: We obtained the following estimated CFRs among under-five children for the year 2005: 0.63% (95% confidence interval (CI): 0.40-1.00%) for India as a whole, 0.62% (0.38-1.00%) for Bihar, and 1.19% (0.80-1.75%) for UP. During 2000-2015, we estimated that 607,000 (95% CI: 383,000-958,000) under-five deaths attributed to measles occurred in India as a whole. If no routine vaccination or supplemental immunization activities had occurred from 2000 to 2015, an additional 1.6 (1.0-2.6) million deaths for under-five children would have occurred across India.

Conclusions: We developed a data- and model-driven estimation of the historical measles dynamics, CFR, and vaccination impact in India, extracting the periodicity of epidemics using spectral and coherence analysis, which allowed us to infer key parameters driving measles transmission dynamics and mortality.

Keywords: Case fatality risk; Child health; Immunization; India; Mathematical modeling; Measles; Supplementary immunization activities; Vaccine-preventable diseases.

Fig. 1

Weekly measles deaths recorded over the period 2000–2003, for India (a), Bihar (b), and Uttar Pradesh (c), since the day of the first measles death (source Million Death Study), with their associated frequency spectra with strength of harmonic on y-axis and period up to 2 years on x-axis. The black lines correspond to the raw data and corresponding spectra, while the red line denotes the data and spectra post-detrending with the Baxter-King filter

Fig. 2

Pooled coherence estimate across five periods (0.5, 0.6, 0.75, 1.0, 1.5 years) for India (a), Bihar (b), and Uttar Pradesh (c), plotted against estimated basic reproduction number (R ₀) and amplitude of the forcing term (Amp or a ₀). Pink indicates a better match to periodicity in the mortality data. The location of the maximum coherence is identified with an asterisk (*), and the 95% significance contour (coherence = 0.11) is marked in dark blue

Fig. 3

Pooled coherence across five periods (0.5, 0.6, 0.75, 1.0, and 1.5 years) plotted against estimated case fatality risk (CFR) calculated from corresponding R ₀ and a ₀ for India (a), Bihar (b), and Uttar Pradesh (c). The left and right green lines delimit the range of the CFR where coherence is above the 95% significance level. The middle green line indicates the CFR for which the highest pooled coherence was estimated. The bottom red line indicates the upper 95% significance limit for the coherence function