Wednesday, November 30, 2016

Further down the trail....Mary has died of typhoid

"Mary has died of typhoid." Yet another disease you may remember encountering on The Oregon Trail in childhood, typhoid fever, or simply typhoid, is also still a major public health concern today. Affecting an estimated 20.6 million people and causing 223,000 deaths a year, typhoid is caused by the bacterium Salmonella enterica serovar Typhi (S. Typhi). The bacteria is often spread through contaminated water or from person-to-person contact. In places where clean water and sanitation are standard, the disease has been essentially eliminated. But in developing countries, it remains a major threat.

The most recent outbreak of typhoid occurred just last week in the city of Masvingo, Zimbabwe. Areas where the disease is endemic and can lead to outbreaks include Southeast Asia, Africa, and South America.  Travel to and from these areas also allows for the transmission of the bacteria to industrialized nations and can cause local outbreaks. Although there are currently two approved vaccines against S. Typhi, both have drawbacks that prevent them from being used en masse. The protective efficacy of the vaccines is sub-optimal and ranges from 40%-70%, largely dependent upon age and location. Additionally, the protection from the vaccines is short-lived, averaging 2-3 years for one vaccine and 5-7 years for the other. A further complication is that both vaccines need to be stored with refrigeration until they are used. Transport and storage under these conditions are major difficulties in countries where electricity is a supreme luxury.

Without a reliable vaccine, the major way to fight the disease is through the use of antibiotics. Chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole, very common antibiotics, have historically been used to stop the infection, and this strategy was highly successful for many years. However, in recent years, a new threat has emerged to thwart these efforts. In the 1970s, cases of S. Typhi that were resistant to these antibiotics began to emerge. We now face the threat of multi-drug resistant S. Typhi, making disease treatment much more difficult.

In light of the rising drug resistance, many have begun to see wide-spread vaccination as the best strategy to fight typhoid. Others argue that improving water sanitation will have the greatest effect on decreasing disease prevalence. One thing is certain: either strategy will require a large investment of funds to be achieved.

The Bill & Melinda Gates Foundation is leading the way in the funding arena and has identified the elimination of typhoid as a public health problem by 2035 as a goal. The Gates Foundation recently gave over half a million dollars to Yale University to explore and determine the cost-effectiveness of typhoid vaccination strategies. Additionally, The Gates Foundation gave a $36.9 million grant earlier this month to a collaboration between the Maryland School of Medicine Center for Vaccine Development, the Oxford Vaccine Group, and PATH, a non-profit public health organization, to accelerate the development of a new vaccine to be used in young children. The goal is to develop a vaccine with more long-lasting protection than the two currently available. The Gates Foundation is also providing funds to increase surveillance for typhoid in South Asia and Africa.

While the Gates Foundation is leading the way to fund the vaccination strategy, other groups are focusing on improving water sanitation. The United States Agency for International Development (USAID) features water and sanitation as one of its main avenues of focus, with sponsored projects underway in large portions of Africa and Southeast Asia. The World Bank has also been sponsoring projects to improve water quality and health throughout the world. Additionally, UNICEF has been a major player in the increased access to clean water that has over the past decade. Many other smaller non-profits have also played a role in this endeavor.

As both vaccine and water and sanitation improvements occur, our ability to battle this age-old pathogen will increase. Using both strategies simultaneously allows for the most rapid and sustainable progress toward S. Typhi elimination. With the continued investment of groups like the Gates Foundation and USAID, the goal of typhoid elimination as a public health problem by 2035 might just be achievable.

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