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Quantiative Study of Major Historic Epidemics and Transitions to longer, healthier lives

Periodic Reporting for period 1 - HistoricEpi (Quantiative Study of Major Historic Epidemics and Transitions to longer, healthier lives)

Reporting period: 2015-10-01 to 2017-09-30

Just 150 years ago, one in five Europeans died in infancy, life expectancy was ~40 years, and infectiosu diseases were the leading causes of death. But during 1880-1910 life expectancy rose dramatically as infectious disease mortality plummeted. This “2nd epidemiological transition,” occurred well before antibiotics and most vaccines. Many factors have been proposed to explain it, including better nutrition, hygiene, sanitation, and the emergence of social support systems.
Although medical historians have made great strides, little had been done to quantitatively study historical data using modern mathematical/statistical tools. As a MC professor, I undertook just that task, taking advantage of uniquely detailed Danish health data and found that the path to longevity went through broad hygiene measures that reduced childhood infectious diseases mortality. Understanding what factors drove this phenomenon will offer helpful lessons to contemporary efforts to combat these “ancient disease” outbreaks that continue to occur following disasters and in low-income settings globally.
I also studied the most serious “killer” epidemic diseases in the pre-vaccination period, including cholera, pandemic influenza. The work involved finding, digitalizing historical epidemiological data and will be used to map the phenomenon of infectious disease mortality decline. The main results of the completed or nearly completed work are as follows:
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 attribut
Wider implications: reintegration accomplished! The intent of the MC senior researcher award is to stimulate re-integration into the European scientific community for researchers who have been abroad. The MC grant allowed me a 24 months visiting professorship at the U. of Copenhagen, and time and opportunity to reintegrate into the European research community and to identify data and interdisciplinary collaborations needed to a broadening of my research focus to the study of all major epidemic infectious diseases and their effect on populations over centuries. Specifically, I have made invaluable connections to existing centers of excellence in my field and create new collaborations with EU researchers and research networks. I have accepted a professorship at the U. of Roskilde, and have already co-written a grant proposal with my colleagues there and researchers at the Dutch National Institutes of Health to obtain funding to our joint historical epidemiology studies – that is, to harness the powers of historical Danish and European health data through a highly interdisciplinary effort that ranges from mathematics to history. Thus, the wider implications of this MC grant will be a continuing EU-based research environment, and with my long-term epidemiology collaborators of researchers in the United States and globally.
Copenhagen Transition to Longevity 1880-193