Stanford Assistant Professor of Medicine Marcella Alsan had always wondered why the mineral-rich African continent — with so many natural resources, diverse climates and arable land — remains so poor.

She launched into extensive research while working on her PhD in economics and has now come up with an intriguing theory: A pesky parasite prevented many precolonial Africans from adopting progressive agricultural methods, a phenomenon that still impacts parts of the continent today.

The tsetse fly has plagued Africa for centuries — having sent millions of people into the confusing stupor of sleeping sickness, while killing the cows and other livestock needed to plough their fields and feed their families.

Alsan writes in a paper published in The American Economic Review that the tsetse fly, which today is found only in Africa, drove precolonial Africans to use slaves instead of domesticated animals for agriculture. This limited their crop yields and the ability to transport goods.

“Communicable disease has often been explored as a cause of Africa’s underdevelopment,” writes Alsan, who is the only infectious-disease trained economist in the United States and a core faculty member of the Center for Health Policy/Center for Primary Care and Outcomes Research.

“Although the literature has investigated the role of human pathogens on economic performance, it is largely silent on the impact of veterinary disease,” she notes. “This is peculiar, given the role that livestock played in agriculture and as a form of transport throughout history.”

The economic impact caused by the parasite of the trypanosome vector is estimated to be as much as $4 billion a year. The Food and Agricultural Organization estimates 37 African countries are affected by the tsetse fly and that its trypanosomosis kills around 3 million livestock per year.

The World Health Organization reports that the sleeping sickness delivered by the tsetse bite in humans is hard to diagnose and treat. Some 60 million people were once at risk with an estimated 300,000 new cases each year.

Sleeping sickness causes headaches, fatigue and weight loss; confusion and personality disorders occur as the illness progresses. If left untreated, people typically die after several years of infection.

Fortunately, sustained control efforts have reduced the number of new cases, dropping below 10,000 annual cases annual for the first time in 50 years in 2009. This is in part to an eradication effort using radiation sterilization techniques adopted by the International Atomic Energy Agency.

But the lingering economic impact from the tsetse has been monumental.

For her research, Alsan used geospatial-mapping software to mine data gathered by missionaries and anthropologists in the 1800s. She found that farming methods used in other developing regions of the world — such as the agricultural revolution in England — were not widely adopted in Africa.

“Livestock were really important for development in many places, such as Europe and North America and in some parts of Africa like the highlands of Ethiopia,” Alsan said in an interview. “They pulled plows and carried carts, their manure was used for fertilizer. They helped transport people and goods across land.”

She found that ethnic groups inhabiting tsetse-prone African regions were less likely to use domesticated animals to plow their fields, turning instead to the slash-and-burn technique still used in many parts of the continent today.

The same people were also less likely to be politically centralized, due to lack of transportation by livestock, and had a lower population density.

“These correlations are not found in the tropics outside of Africa, where the fly does not exist,” she writes. “The evidence suggests current economic performance is affected by the tsetse through the channel of precolonial political centralization.”

The FAO estimates that the tsetse fly infects nearly 10 million square kilometers in sub-Saharan Africa. Much of this large area is fertile but left uncultivated, a so-called green desert not used by humans and cattle. Most of the tsetse-infected countries are poor, debt-ridden and underdeveloped.

And this is what triggered Alsan’s interest in the tsetse fly: How its deadly bite has altered the socioeconomic impact of a continent.

“I am an infectious disease doctor, so part of my work is looking at neglected infectious diseases much like this one,” she said. “And it is

incredibly important to shine light on issues that are Africa-specific and therefore may not garner as much attention as those economic and medical issues that affect wealthier regions of the world.” 

Alsan, who sees patients at the Stanford University Medical Center and is an investigator at the VA Palo Alto Health Care Systems, is now launching work in India, Ghana and the San Francisco Bay Area. She hopes to better understand how socioeconomic and health disparities interact, and the important role that history plays in understanding those interactions.

Video of A career in Economics...it's much more than you think

Marcella Alsan, an assistant professor of Medicine and CHP/PCOR core faculty member, shows how economics is a broader field than most people realize in this video produced by the American Economic Association (AEA).  Along with other top economists, she discusses the interdisciplinary nature of economics, specifically as it relates to global health.  Alsan states that "without understanding economic principals and economic forces, [there is] a real gaping hole in actually practicing medicine."  Understanding economics can help us to understand policy decisions and to tackle the broad problems of society.

Foreign aid to the public health sectors of developing countries often appears to be allocated backwards: The global burden of non-communicable diseases such as diabetes or heart disease is enormous – yet they receive little health aid. 

By comparison, the global burden of HIV is much smaller, yet it receives more health aid than any other single disease.

So will a wholesale reversal in health aid priorities improve global health? The answer, according to a new study by Stanford researchers, is that if the goal is to maximize the health benefits from each donor dollar, health aid is actually allocated pretty well.

Still, reallocating foreign aid to step up the fight against malaria and TB could lead to greater overall health improvements in developing nations. And it could be done without spending more money, the researchers have found.

Eran Bendavid, an assistant professor in the Department of Medicine and a core faculty member at the Center for Health Policy and Center for Primary Care and Outcomes Research, and three Stanford research assistants write in the July issue of Health Affairs that more health aid is going to disease categories with more cost-effective interventions.

"What we found, somewhat to our surprise, is that in nearly all countries, more aid was flowing to finance priorities with more cost-effective options,” Bendavid said in an interview. “That is partly because more aid was flowing to the treatment and prevention of infectious diseases such as HIV and malaria, and their management can be relatively inexpensive, even if the burden of these diseases is lower than that of non-communicable diseases.”

Bendavid, an infectious disease physician, added: “Conversely, even though the burden of non-communicable diseases is high and growing, addressing these chronic conditions such as diabetes and heart disease is, broadly, more costly than the unfinished infectious disease agenda.”

The authors also show that just because health aid is broadly allocated toward better cost-effectiveness does not mean that it cannot be better allocated.

The biggest gains would come from taking some of the foreign aid earmarked for HIV or maternal, newborn or child health, and putting it toward programs to treat malaria and tuberculosis, they write.

The Stanford research team reviewed the literature for cost-effectiveness of interventions targeting five disease categories: HIV, malaria, tuberculosis, non-communicable disease and maternal, newborn and child health.

What they found was that aid from wealthy nations to developing ones might be allocated efficiently, but that the money is not always spent in the best interest of curbing the communicable diseases that would improve the overall health of a nation.

It is crucial, therefore, to further study the consequences of realignment of donor funds.

Public health aid is critical to most developing countries. Development assistance from high-income countries to public health sectors of low- and middle-income countries amounts to nearly 40 percent of public health spending in countries with a per capita GDP of less than $2,000.

The researchers focused on 20 countries that received the greatest total amount of aid between 2008 and 2011, a period of historically unprecedented growth in health aid. Development assistance has since flattened, however, so the authors believe it’s increasingly important to consider best value when investing limited resources.

The 20 countries studied ­– from Afghanistan to Zambia – received $58 billion out of the total $103.2 billion in recorded health aid disbursements to 170 countries between 2001 and 2011.

“Over the period of 2001-2011, a greater amount of disbursements flowed to HIV programs than any other disease category,” the authors write. “On average, interventions addressing malaria and had the lowest incremental cost-effectiveness ratio (ICER), which indicates that malaria interventions could yield greater health improvements from each dollar compared with the interventions having a higher ICER.”

The authors analyzed the data and determined that the alignment improves if up to 61 percent of HIV aid is reallocated for TB control and up to 80 percent is reallocated for malaria control.

“Our evidence suggests that the greatest improvements in the efficiency of global health dollars could result from reallocating funds to malaria and TB control programs,” the authors write.

“This study shows, for the first time, that the current allocation of health aid is generally aligned with the cost-effectiveness of targeted interventions. Contrary to common views that advocate for reprioritization toward non-communicable diseases, our data suggest that the alignment could best be improved by focusing on malaria and TB, especially where addressing those diseases is highly cost effective.”

The other authors of the study are Andrew Duong and Gillian Raikes, both research assistants in the Program of Human Biology; and Charlotte Sagan, a RA in the School of Medicine.

The increasing resistance to antimicrobial drugs is a growing public health concern, particularly in low- and middle-income countries that require high out-of-pocket payments for prescription drugs.

“Understanding the drivers of antibiotic resistance in low- to middle-income countries is important for wealthier nations because antibiotic-resistant pathogens, similar to other communicable diseases, do not respect national boundaries,” said Marcella Alsan, MD, PhD, MPH, the lead author of the study, which was published July 9 in The Lancet Infectious Disease.

Alsan is an assistant professor of medicine at Stanford, an investigator at the Veterans Affairs Palo Alto Health Care System and a core faculty member at the Center for Health Policy/Center for Primary Care and Outcomes Research.

“Out-of-pocket health expenditures are a major source of health-care financing in the developing world,” said Jay Bhattacharya, MD, PhD, senior author of the study and a professor of medicine, a senior fellow at the Freeman Spogli Institute for International Studies and another core faculty member at CHP/PCOR.

Read the full article here.

“I am the first child of my parents. I have a small brother at home. If the first child were a son, my parents might be happy ... but I am a daughter. I complete all the household tasks, go to school, again do the household activities in the evening … my parents do not give value or recognition to me.”

Stanford Assistant Professor of Medicine Marcella Alsan often refers to this comment by a 15-year-old girl from Nepal when she talks about how the division of labor among men and women starts at a young age in the developing world.

“Anecdotally, girls must sacrifice their education to help out with domestic tasks, including taking care of children, a job that becomes more onerous if their younger siblings are ill,” said, Alsan, a core faculty member at the Center for Health Policy/Center for Primary Care and Outcomes Research (CHP/PCOR) within the Freeman Spogli Institute of International Studies, and the Department of Medicine.

More than 100 million girls worldwide fail to complete secondary school, despite research that shows a mother’s literacy is the most robust predictor of child survival. So Alsan is analyzing whether medical interventions in children under 5 tend to lead their older sisters back to school.

She is one of two winners of this year’s Rosenkranz Prize for Health Care Research in Developing Countries, awarded by CHP/PCOR to promising young Stanford researchers.

Her Stanford Department of Medicine colleague, Jason Andrews, is the other recipient of the $100,000 prize given to young Stanford researchers to investigate ways to improve access to health care in developing countries.

Andrews is looking at cheap, effective diagnostic tools for infectious diseases, while Alsan is researching how older girls in poorer countries are impacted by the health of their younger siblings.

“My proposed work lays the foundation for a more comprehensive understanding of how illness in households and early child health interventions impact a critical determinant of human development: an older girl’s education,” she said.

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Alsan, the only infectious-disease trained economist in the United States, said Stanford is the ideal place to carry out her interdisciplinary global health research.

“I am humbled and honored to receive this prize, since Dr. Rosenkranz has done so much for women’s health worldwide,” she said.

Alsan – an MD with a specialty in infectious disease who has a PhD in economics from Harvard – said she intends to estimate the impact that illnesses in under-5 children have on older girls’ schooling using econometric tools.

She will compile data from more than 100 Demographic and Health Surveys (DHS) covering nearly 4 million children living in low- and middle-income countries.

The surveys ask about episodes of diarrhea, pneumonia and fever in children under 5 and record data on literacy and school enrollment for every child in the household.

Alsan also intends to collaborate with partners in sub-Saharan Africa to study the gendered effect of household illness on time use, using culturally appropriate questionnaires.

Douglas K. Owens, a Stanford professor of medicine and director of CHP/PCOR, called Alsan’s work “groundbreaking.”

“Although training is critical, more importantly, her work to date shows a degree of innovation, creativity and rigor that led us to conclude she was likely to become one of the top investigators in her field worldwide,” he said.

Low-Cost Diagnostic Tools

Andrews, also an assistant professor of medicine, has been working on ways to bring low-cost diagnostic tools to impoverished communities that bear the brunt of disability and death from infectious disease.

“I began working in rural Nepal as an undergraduate student and as a medical student founded a nonprofit organization that provides free medical services in one of the most remote and impoverished parts of the country,” Andrews said. “As I became a primary physician, and then an infectious diseases specialist, one of the consistent and critical challenges I encountered in this setting was routine diagnosis of infectious disease.”

He said those routine diagnostics were typically hindered by lack of electricity, limited laboratory infrastructure and lack of trained lab personnel.

“In my experiences working throughout rural Nepal – and in India, South Africa, Brazil, Peru and Ethiopia – I found these challenges to be common across rural resource-limited settings,” said Andrews, who founded a nonprofit Nyaya Health – recently renamed Possible Health – which provides modern, low-cost healthcare to rural Nepal.

Andrews has been collaborating with engineers to develop an electricity-free, culture-based incubation and identification system for typhoid; low-cost portable microscopes to detect parasitic worm infections; and most recently an easy-to-use molecular diagnostic tool that does not require electricity.

“The motivation for these projects was not to develop fundamentally new diagnostic approaches, but rather to find simple, low-cost means to make established laboratory techniques affordable and accessible,” he said.

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“We then perform isothermal amplification heated by a reusable, solar-heated, phase-change material,” Andrews said, adding that the entire process is completed in less than 20 minutes and can be performed by anyone with minimal training.

Andrews will enroll 250 patients with suspected cases of cholera in Nepal, using the new diagnostic tools and adapting as many local supplies as possible.

Andrews also intends to establish and curate a website to gather open-source ideas and evidence on diagnostic techniques for use in the developing world.

“Stanford is one of the world’s greatest hubs for innovation and information sharing as pertains to science and technology and is an ideal home for this venture,” he said.

In the current scientific climate, most National Institutes of Health grants go to established researchers. The Rosenkranz Prize aims to stimulate the work of Stanford’s bright young stars – researchers who have the desire to improve health care in the developing world, but lack the resources.

The award’s namesake, George Rosenkranz, first synthesized cortisone in 1951, and later progestin, the active ingredient in oral birth control pills. He went on to establish the Mexican National Institute for Genomic Medicine, and his family created the Rosenkranz Prize in 2009.

The award embodies Dr. Rosenkranz’s belief that young scientists hold the curiosity and drive necessary to find alternative solutions to longstanding health-care dilemmas.

“As in past years, the competition was extremely tough,” said Grant Miller, a senior fellow at the Freeman Spogli Institute and associate professor of medicine who chaired the prize committee this year.

“It’s exciting to see all of the truly innovative global health research being done by junior scholars at Stanford,” he said. “Both Jason and Marcella really exemplify this – and the legacy of George Rosenkranz.”

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Dr. Marcella Alsan finds that disease associated with the tsetse fly continues to influence development in Africa.

Tsetse fly castration may reduce sickness in animals and help increase animal-based farming in Africa.  The Guardian interviews Dr. Marcella Alsan regarding her research on the tsetse fly's relationship to African agriculture.

Dr. Marcella Alsan argues that the tsetse fly contributed to Africa's historically low population density.