Cholera. Our studies of the devastating 1853 cholera epidemics in Denmark is a good example of how historical epidemiology research can inform contemporary public health. In the absence of population immunity and effective interventions, we were able to measure key parameters (Ro, serial interval, case fatality) and to compare with the 2010 Haiti outbreak, seeing many similarities. Across Denmark we found that cholera was not the quintessential waterborne illness. Rather, our uniquely detailed transmission chains told a tale of short-cycle transmission at the household level. Typically, cholera was introduced by a traveler who arrived by boat or foot from a city with an ongoing cholera outbreak; secondary cases occurred within days among close contacts and care givers – some of whom brought cholera to their own household. We next carefully modeled the spread of cholera within neighborhoods in Copenhagen, and reached the same conclusion: cholera did not travels along contaminated waterways. Rather, cholera spreads more like Ebola in West Africa: through close personal contact with seriously ill persons. These findings are important clues for control of cholera in contemporary low-income settings; specifically, our findings suggest that broad hygiene measures are key, rather than a focus on drinking water. This study was only possible due to an interdisciplinary team; two papers have been published and the PhD student (M. Phelps) will defend in spring 2018.
Pandemic Influenza patterns & impact, from 1889 to 2009. Our work on the 1889 “Russian” pandemic, the 1918 “Spanish” pandemic, the 1957 “Asian” pandemic and the 2009 pandemic “signature” patterns were also good illustrations of the insights that can be gained to inform pandemic preparedness going forward. Our quantitative study of weekly morbidity and mortality data for influenza and other major epidemic diseases in the 1889-1892 pandemic period led to an epidemiological demonstration of this being a pandemic event (R0>2), and that pandemic deaths occurred in the elderly and mostly in the 3rd wave. This solidifies the fact that in future pandemic events it is prudent to expect multiple waves and possible a delayed mortality impact, leaving ample time to deploy pandemic vaccine. Another lesson is that context such as background mortality levels is critical when comparing pandemic impact across age groups, time and geography. For example, in young children the pandemic mortality impact was small compared to diphtheria and diarrhea. Meanwhile, we conducted further research on the 1918 “herald wave”, and global patterns of the 1957 pandemic and saw a 1918-like age pattern in the 2009 pandemic, confirming the antigenic recycling hypothesis we had previously proposed to explain senior sparing in the 1918 pandemic. I have presented the pandemic work at several international conferences, and our 1889 manuscript was invited back by Lancet Inf Dis for publication (it will be resubmitted shortly) and our 1918 herald wave paper was accepted for publication, while the 1957 and 2009 papers were already published.
Patterns and key factors explaining the Epidemiological Transition: In Copenhagen, the road to long life expectancy was reached through sharp reductions in childhood mortality due to infectious diseases. Before 1900, more than 90% of all deaths in infants and toddlers were related to epidemic diseases like measles, diphtheria, pertussis, smallpox and diarrhea. In long morbidity and mortality time series it became clear that what happened over time was a sharp reduction in the case fatality ratio for each disease – and that this probably came about as a result of improved immune systems due to better nutrition and access to care plus social services. We are planning to study epidemiological transitions at 3 time scales: Europe 150 years ago, S.America 50 years ago and Africa now. In contemporary settings, researchers tend to attribute these reductions to biomedical interventions such as vaccines and antibiotics – but as the same pattern was observed in Europe decades before vaccines and antibiotics it is evident that other environmental and societal improvements are key determinants. This work is in progress, but already fascinating patterns emerge. Two students have completed their thesis work on this topic with me, and a comprehensive database of mortality patterns in Copenhagen during 1880-2930 is under development.
