Looking beyond drug treatments for parasitic disease

A Stanford study investigates the barriers to controlling parasitic disease and possible interventions beyond mass drug and education campaigns.

Just two doses of praziquantel can effectively treat adults and children for schistosomiasis — a disease caused by parasitic worms that develop and multiply inside infected freshwater snails, and then enter the water and penetrate the skin of people who are bathing or fishing.

So why are 200 million people worldwide, mostly in sub-Saharan Africa, still suffering from schistosomiasis despite widespread administration of this antiparasitic drug? Why are people in some “hot spot” regions re-infected over and over?

A new study explored these questions by surveying 74 residents from four rural villages along the Senegal River, a region with very high rates of schistosomiasis despite mass drug administration campaigns. In each village, the field team conducted focused discussion groups separately for adult men, adult women and mixed-gender youth to facilitate open conversation among peers. These different groups are known to have varied activities involving contact with the parasite-infested water

The study made three key findings. First, the researchers learned that many residents have a fairly sophisticated understanding of schistosomiasis risk, including knowing where and when infections occur, even though they don’t understand the underlying biological details. For example, the villagers realize infection risk increases midday — an observation supported by studies, which show snails tend to shed parasites in daily cycles that peak around noon.

Second, the scientists determined that residents use their knowledge to develop strategies to reduce their exposure to the parasite, such as avoiding the river at certain times or forbidding urination and defecation near the river or lake. In addition to personal strategies, some villages adopt written village-wide rules for water use that are enforced with fines.

Lastly, despite having translated knowledge into strategies to reduce disease risk, the researchers found that the residents are still consistently exposed to the parasite because their rural livelihoods depend on the river and lakes — even in villages with limited piped water. They use surface water to cultivate crops. They wade in the water to fish and do laundry. They harvest the cattail reeds to use for roofs, fences or floor mats. And children play in the water.

“There is a feeling of inevitability around schistosomiasis infection, given the constraints of poverty,” said Susanne Sokolow, PhD, a Stanford disease ecologist and study author with the Woods Institute for the Environment, in a recent Stanford news release. “That jibes with the experience of the many years of efforts to distribute pills and carry out educational campaigns in the regions without a huge drop in schisto transmission or infection.”

Instead of focusing exclusively on mass praziquantel distribution, the researchers also recommend using local community input to develop diverse environmental strategies for reducing infection risk. Possible interventions include chemical or biological snail control, provision of sanitation facilities and laundry platforms, removal of vegetation to reduce snail habitats and behavioral change interventions.

According to the study authors, the key is to work with the local communities to select interventions that take into account their specific social and environmental factors.

Photo by eutrophication&hypoxia / Fundraising | Wikimedia Commons   

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Designing an inexpensive surgical headlight: A Q&A with a Stanford surgeon

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Photo by Jared Forrester / © Lifebox 2017

For millions of people throughout the world, even the simplest surgeries can be risky due to challenging conditions like frequent power outages. In response, Stanford surgeon Thomas Weiser, MD, is part of a team from Lifebox working to develop a durable, affordable and high-quality surgical headlamp for use in low-resource settings. Lifebox is a nonprofit that aims to make surgery safer throughout the world.

Why is an inexpensive surgical headlight important?

“The least expensive headlight in the United States costs upwards of $1000, and most cost quite a bit more. They are very powerful and provide excellent light, but they’re not fit for purpose in lower-resource settings. They are Ferraris when what we need is a Tata – functional, but affordable.

Jared Forrester, MD, a third-year Stanford surgical resident, lived and worked in Ethiopia for the last two years. During that time, he noted that 80 percent of surgeons working in low- and middle-income countries identify poor lighting as a safety issue and nearly 20 percent report direct experience of poor-quality lighting leading to negative patient outcomes. So there is a massive need for a lighting solution.”

How did you develop your headlamp specifications?

“Jared started by passing around a number of off-the-shelf medical headlights with surgeons in Ethiopia. We also asked surgeons in the U.S. and the U.K. to try them out to see how they felt and evaluate what was good and bad about them.

We performed some illumination and identification tests using pieces of meat in a shoebox with a slit cut in it to mimic a limited field of view and a deep hole. We asked surgeons to use lights at various power with the room lights off, with just the room lights on and with overhead surgical lights focused on the field. That way we could evaluate the range of light needed in settings with highly variable lighting, something that does not really exist here in the U.S.”

How do they differ from recreational headlamps?

“Recreational headlights have their uses and I’ve seen them used for providing care — including surgery. However, they tend to be uncomfortable during long cases and not secure on the head. Also, the light isn’t uniformly bright. You can see this when you shine a recreational light on a wall: there is a halo and the center is a different brightness than the outer edge of the light. This makes distinguishing tissue planes and anatomy more difficult.”

What are the barriers to implementation?

“While surgeons working in these settings all express interest in having a quality headlight, there is no reliable manufacturer or distributor for them. Surgeons cannot afford expensive lights, and no one has stepped up to provide a low-cost alternative that is robust, high quality and durable. We’re working to change that.”

What are your next steps?

“We are now evaluating a select number of headlights and engaging manufacturers in discussions about their current devices and what changes might be needed to make a final light at a price point that would be affordable to clinicians and facilities in these settings. By working through our networks and using our logistical capacity, we can connect the manufacturer with a new market that currently does not exist  — but is ready and waiting to be developed.

We believe these lights will improve the ability of surgeons to provide better, safer surgical care and also allow emergency cases to be completed at night when power fluctuations are most problematic. These lights should increase the confidence of the surgeon that the operation can be performed safely.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Blocking Zika: New antiviral may treat and prevent infection, a Stanford study suggests

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Image of the surface of the Zika virus by Purdue University/courtesy of Kuhn and Rossmann research groups

The Zika virus, which made headlines in 2016 following an outbreak in South America, is transmitted by mosquitos and can cause serious birth defects and neurological problems. Researchers are searching for antiviral treatments or effective vaccines to address this global health threat, but there are currently no approved treatments.

Now, Stanford researchers are taking a different approach — investigating cellular factors of humans that are essential for Zika to propagate. One of those factors is a type of protein called Hsp70, which helps proteins fold correctly and performs a wide range of housekeeping and quality-control functions in cells.

Based on a series of experiments in mosquito and human cells, the Stanford study found that certain Hsp70 proteins are required in multiple steps of the Zika virus’ lifecycle. By blocking Hsp70 with an Hsp70 inhibitor drug, the researchers were able to prevent virus replication, as recently reported in Cell Reports.

One advantage of targeting the human host protein to thwart Zika is that it is less likely to promote drug resistance, Judith Frydman, PhD, senior author of the paper and a professor of genetics and of biology at Stanford, told me.

“The emergence of drug-resistant variants is a major obstacle for the development of antiviral therapies,” she continued. “We hypothesize that because Hsp70 is required for several different steps in the Zika virus cycle, it would be difficult for Zika to acquire enough mutations to develop resistance to the Hsp70 inhibitors. This opens the way to both therapeutic and prophylactic use of these drugs for short courses of treatment without losing effectiveness due to resistance.”

In addition, the team found that the Hsp70 inhibitors showed negligible toxicity to the host cells at the concentrations needed to fully block virus production. They demonstrated this lack of toxicity in both human cells and mice.

“The virus has a much higher demand for Hsp70 than the host cellular processes,” Frydman said. “We can exploit the viral ‘addiction’ to Hsp70 for treatment to prevent the virus from producing the proteins it needs to replicate and infect cells. But most importantly, we show Hsp70 inhibitors can be administered to animals at therapeutically effective doses. To my knowledge, this is the first drug that actually works for Zika-infected animals, protecting them from lethal infection and disease symptoms.”

The researchers believe their new approach could serve to create broad-spectrum antivirals that work against other existing and emerging viruses. In fact, this class of drugs could also treat other insect-borne viruses including Dengue virus and Yellow Fever, Frydman said.

“Our findings provide new strategies to develop a novel class of antivirals that will not be rendered ineffective by the emergence of drug resistance,” Frydman said. “This unique property of targeting host factors used for viral protein folding therapeutically may close a fundamental gap in antiviral drug development.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

A look at the cigarette epidemic in China

Image by Dimhou

The imagery of a cuddly panda bear has often been used to sell tobacco products in China. So a new book that examines China’s cigarette industry seems aptly titled: Poisonous Pandas: Chinese Cigarette Manufacturing in Critical Historical Perspectives.

The book brings together an interdisciplinary group of scholars — including Stanford editors Matthew Kohrman, PhD, a professor of anthropology, and Robert Proctor, PhD, a professor of history. Together the team has investigated how transnational tobacco companies have worked to triple the world’s annual cigarette consumption since the 1960s. They focus on the China National Tobacco Corporation, which currently produces forty percent of cigarettes sold globally.

In a recent Freeman Spolgi Institute Q&A, Kohrman discusses how he got involved in this work. “When I began my ethnographic fieldwork on tobacco in China, I initially studied mostly consumer behavior. But I quickly realized that focusing solely on cigarette consumption, without considering the relationship between supply and demand, was like studying obesity while ignoring food,” he says.

Kohrman explains that cigarettes have become the single greatest cause of preventable death in the world today and the problem is getting worse. “Instead of declining as we would expect based on our impressions living here in California, the number of daily cigarette smokers around the world is projected to continue climbing,” he says. In particular, he explains the big tobacco companies are targeting less-educated people from lower- and middle-income countries.

Kohrman does offer some hope in light of the Chinese government’s recent initiatives to restrict tobacco advertising and smoking in public places. But he says that there is a lot more work to do.

“The road towards comprehensive tobacco prevention in China is going to be a long one,” Kohrman concludes.

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

Stanford data analyst’s childhood inspires his research: A Q&A

Photo, of Jonathan Altamarino and collaborators in front of an Asili clinic, by Valery Namuto

Data analysts are critical to medical research — particularly to epidemiology studies that look at the incidence, distribution and determinants of health conditions in specific populations. So I was happy to have the opportunity to speak with Jonathan Altamirano, a research data analyst in Stanford’s Global Child Health Program.

How did you get involved in global health research?

“Growing up, I spent summers with family in Nicaragua in a very poor, rural coastal village called Puerto Cabezas. We would often lose water around noon and power by sunset. Personally,  I was lucky. I had food on the table every night. But I saw kids who didn’t — and that was my biggest impetus for getting into global health. I also got dengue and malaria one summer, which got me interested in science and epidemiology. It’s a weird thing to say: a mosquito almost killed me, so I wanted to go into medicine.

I knew I wanted to help less fortunate populations, but I wasn’t sure how I’d fit into that landscape. As a biology undergraduate at Stanford, I then took an epidemiology class taught by Bonnie Maldonado, MD and I fell in love with it. It looked at how best to approach problems: If you have an intervention, is it effective or not? And how can you tell? That got me interested in statistics and ways to model diseases.

When I was getting my masters in biology at Stanford, I took another class with Dr. Maldonado just after she started her polio project in Mexico, which is investigating vaccine-derived poliovirus transmission. And I was hired as a research data analyst for the project.”

You’re now working on a project in the Democratic Republic of the Congo. What exactly are you studying?

“We’re acting as external evaluators for Asili, a poverty-reduction program launched by the American Refugee Committee and IDEO.org aimed at improving child survival and reducing poverty in South Kivu. They’re bringing clean water and small-format health clinics to help these communities recover from years of civil conflict. I’m working with a team including Rasika Behl, Clea Sarnquist and Bonnie Maldonado to collect and analyze on-site data to measure the impact of these interventions.

We’re looking at household demographics — such as what their house is made of , whether they have land and other indicators of wealth. We’re also collecting various health information on the children — such as the incidence of stunting, wasting, diarrhea, fever and cough. And we’re collecting data on the mothers, looking at women empowerment metrics and views on gender relations.

We collect this data in the field with tablets, which I program and setup. After we provide training, local data collectors go out into the community and survey the households. We collected all the baseline data in 2016 and 2017. We’re now collecting the same data after the interventions to evaluate the effectiveness of Asili’s clean water and health clinic programs. We’re also interested in characterizing this understudied population.”

Why did you recently travel to DRC? What was that like?

“In April, I went to South Kivu to help train Asili data collectors to take the end-line data. It was really great to get to know the American Refugee Committee team.

This was my first time in DRC, and I was struck by similarities with my family’s village in Nicaragua. The colors of the houses were the same and the roofs were made of the same kind of corrugated metal. I saw households with a lot of kids in the same space, and I was like ‘yeah, everyone had that in Nicaragua.’ Also, an older woman was running a small restaurant — consisting of plastic lawn chairs and a giant cooking pot. And I immediately pictured our neighbor lady in Nicaragua who made carne asada every night. Of course, the villages in DRC weren’t exactly the same, but they brought up childhood memories.”

What’s next for you?

“We hope to continue working with American Refugee Committee to evaluate Asili as they roll out the program in new parts of Bukavu over the next several years.

Our team is also completing a randomized clinical trial on a gender-based violence intervention, which was rolled out in schools in Kenyan informal settlements to reduce rates of sexual assault in adolescents. We also recently secured funding to collect pilot data on gender-based violence prevention in Fiji and other Pacific islands, in collaboration with the RISE program and Monash University.

However, I’m hoping to apply to medical school next year, once I have time to study for the MCATs.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.

A look at health care reform — in China

Photo courtesy of Karen Eggleston

The struggles with health insurance reform here in the United States piqued my curiosity about what we could learn from other countries. I reached out to Karen Eggleston, PhD, a senior fellow at the Freeman Spogli Institute for International Studies at Stanford, who researches health care systems and health reform in Asia, especially China.

What is health insurance like in China?

“The original system was linked to the centrally planned economy. Communes in rural areas supported the barefoot doctors and state-owned enterprises provided people with health care coverage in the urban areas. But when China converted to a market-based economy, this had to change. So long story short, they’ve put into place a new system of health coverage based on government subsidized insurance for rural and non-employed urban populations, as well as an employee-based medical insurance for the employed urban population. As I like to tell my US colleagues, if you think providing coverage for 40 million uninsured people is a challenge then think about covering over 800 million uninsured — that’s what China was dealing with.

Many westerners would be surprised to know that Chinese have almost complete freedom when choosing their doctor or hospital.”

How has this expanded coverage impacted health and survival?

“There is a lot of evidence that the expanded health insurance improved access to care and helped protect households from high health care expenditures, but it’s actually pretty difficult to pin down the effects on health and survival.

In a recent study in Health Affairs, we looked at the New Cooperative Medical Scheme that provides health insurance to rural areas. We used the fact that it was introduced over time in different counties to look at the effect it had later, correlating this data with cause-specific mortality data from China’s CDC. We didn’t see a significant impact on mortality rate due to expanded medical coverage.

This was and wasn’t surprising. It may take a long time for the results to manifest. But it’s also quite well known in health economic research that health and survival are often shaped by non-medical factors like lifestyle.”

What are some of the biggest health care challenges in China?

“As China urbanizes hundreds of millions of people at a time, they are changing their diet and living a more sedentary lifestyle. As a result, they’re now getting what are sometimes called the diseases of affluence, such as diabetes. Like many developing countries, China’s healthcare system was setup to deal primarily with acute conditions and to control infectious diseases. Now, they need to sustainably finance and manage programs to prevent and care for people with chronic diseases.

A lot of China’s care is also based in hospitals, so they need to strengthen primary care — ironic for a country so famous for barefoot doctors. Physicians’ career trajectories are better in urban hospitals and patients know that’s where the best physicians are. But new policies are trying to lure patients and doctors to primary care.”

What other factors are affecting health in China?

“China has a rapidly aging population — largely due to their triumph in extending lives by controlling infectious diseases and lifting millions out of poverty, and also related to low fertility. This demographic change reinforces the challenge of preventing and controlling chronic disease.

We also know that people with more education tend to have better health and survival than people with lower education. China’s economic growth has brought a rapid increase in living standards but also a rise in inequality, in both rural and urban areas. One of the best ways to address this is to improve opportunities of education for the disadvantaged. This isn’t typically thought of as a health policy, but actually studies have shown education can have long lasting effects on health and survival.”

This is a reposting of my Scope blog post, courtesy of Stanford School of Medicine.

Sick people are worse for the environment, a study shows

Photo by ryan harvey

Environmental degradation is widely recognized to contribute to human illness. However, little research has been done to investigate the impact of human illness on the environment. This is a critical question particularly for the millions of people around the world who depend on natural resources for food and income while coping with high burdens of infectious diseases.

When people are sick, they often alter their use of natural resources in ways that harm the environment, according to a new study reported in the Proceedings of the National Academy of Sciences.

Specifically, the researchers examined how illness influenced fishing practices in the community around Lake Victoria, Kenya, which has high rates of HIV and other illnesses. They interviewed about 300 households several times over 16 months, collecting and analyzing data about household fishing habits and mental and physical health. They found that healthy people are better for the environment.

“Studies suggest that people will spend less time on their livelihoods when they are sick, but we didn’t see that trend in our study. Instead, we saw a shift toward more destructive fishing methods when people were ill,” said lead author Kathryn Fiorella, PhD, a postdoctoral scholar at Cornell University, in a recent news release.

The study found that sick fishermen were less likely to legally fish in deep waters or overnight to target the more sustainable mature fish. Instead, they used destructive fishing methods that were concentrated along the shoreline — such as using a beach dragnet that captures a high proportion of juvenile fish and disturbs shallow fish breeding habits.

Basically, sick fishermen just wanted to get their catch quickly with less energy. They were focused on their short-term goal and not worried about depleting the fish stock.

In light of this study, the authors suggest that institutions and organizations focused on protecting the environment may need to more deeply consider the health of communities. The paper concludes, “Our study emphasizes the importance of considering health, governance, and ecosystems through an integrative lens.”

This is a reposting of my Scope blog story, courtesy of Stanford School of Medicine.