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Rotavirus in the United States and other developed countries

credit: CDC
Prior to the introduction of routine vaccination in 2006, rotavirus was estimated to cause around 60,000 hospitalizations per year in the United States, primarily in children <5 years old. Epidemics of rotavirus-associated gastroenteritis (RVGE) occurred each winter, beginning in the southwestern states and “spreading” to the northeast. We were able to link this pattern of epidemics to underlying variation in birth rates across the US. Vaccination has had a profound impact on rotavirus in the US and other developed countries, both decreasing the incidence of RVGE and altering the pattern and timing of epidemics. The mathematical models we developed were instrumental in helping to understand and anticipate these changes. We are currently working the refine our models to better evaluate post-vaccination changes to the epidemiology of rotavirus.

Rotavirus vaccination in developing countries

In 2009, WHO recommended the global use of rotavirus vaccines, and many developing countries have recently begun or will soon begin vaccinating against rotavirus. However, the impact of vaccination may differ in developing countries, where immunity from natural infection is weaker, vaccine efficacy is considerably reduced, and seasonal patterns of incidence and genotypes causing infection differ. Modeling the dynamics of rotavirus is essential for understanding the dynamical consequences and potential indirect, or “herd immunity”, effects of vaccination. We are in the process of extending our models for the transmission dynamics of rotavirus to explain differences in pre-vaccination patterns of epidemics in developing countries, including Bangladesh, Malawi, and Ghana. We will then examine the potential impact of vaccination on the incidence, age distribution, and seasonal pattern of epidemics in these settings.

Controlling endemic typhoid transmission

Improvements in sanitation and the provision of clean drinking water led to the elimination of typhoid fever from developed countries in the beginning of the 20th century. However, Salmonella Typhi and Paratyphi A remain a major source of morbidity and mortality in many developing countries today. The dynamics of typhoid transmission are poorly understood. Two vaccines against typhoid are currently licensed and used worldwide, and new and improved conjugate vaccines are on the horizon, but there is conflicting evidence as to whether these vaccines are expected to confer a potential herd immunity benefit for the population. Using mathematical models fit to hospital surveillance data, we are comparing the transmission dynamics of typhoid in present-day endemic settings, including Vellore, India; Dhaka, Bangladesh; Kathmandu, Nepal; and Blantyre, Malawi. We will use these models to evaluate the feasibility and impact of different methods of typhoid control, including vaccination, improved treatment strategies, and investment in clean water and sanitation.

Historical analysis of typhoid fever in US cities

Cartoon by Zim
Cities across the United States exhibited different timing in terms of the decline in typhoid mortality during the late 19th and early 20th centuries, and also exhibited very different patterns of seasonality that did not follow a clear geographic pattern. For example, typhoid dynamics in New York are characterized by strong seasonal oscillations and a gradual decline in mortality beginning around 1900, while Philadelphia exhibits multiannual typhoid oscillations with no clear seasonality and higher overall incidence rate prior to the staged introduction of filtration and chlorination beginning in 1904. We are using mathematical models to examine the correlation between data on financial investments into the water supply and sanitation systems and changes in the transmission rate estimated by fitting dynamic models to the typhoid mortality data. This approach will also allow us to quantify the degree of herd immunity exhibited by typhoid dynamics and gain a better understanding of the underlying epidemiology.