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Global Health, Immunology, Infectious Disease, Microbiology, Research, Stanford News

Discovered: Why so many people with schistosomiasis (there’s a lot of them) are so vulnerable to bacterial co-infection

Discovered: Why so many people with schistosomiasis (there's a lot of them) are so vulnerable to bacterial co-infection

More than a billion people worldwide – almost all of them in developing countries – are infected by worm-like parasitic organisms called helminths. Organisms making up just a single genus of helminth, Schistosoma, account for one-quarter of those infections, which damage different body parts depending on what schistosomal species is doing the infecting. Some go for the lung. Others (card-carrying members of the species Schistosoma haematobium) head for the urinary tract, with one in ten infected patients suffering severe physical consequences.

People with schistosomiasis of the urinary tract are especially vulnerable to bacterial co-infections. Worse, these co-infections exacerbate an already heightened risk of bladder cancer in infected individuals, it’s believed. Unfortunately, considering the massive numbers of cases, surprisingly little is understood about the molecular aspects of the infection’s course.

A big reason for that relative ignorance has been the absence of an effective animal model enabling the detailed study of urinary-tract schistosomiasis. A couple of years ago, Stanford schistosomiasis expert Mike Hsieh, MD, PhD, developed the world’s first decent mouse model for the disease, allowing him to explore the molecular pathology that occurs early in the course of infection. Now, in a just-published study in Infection and Immunity, Hsieh has put that mouse model to work in coaxing out the cause of the curious collegiality of S. haematobium and co-infecting bacteria.

The secret, the scientists learned, is that S. haemotobium infection induces a spike in levels of a circulating immune-system signaling protein, or cytokine, called IL-4. That excess, in turn, results in a drop in the number and potency of a subset of immune cells that are important in fighting off bacterial infections. The discovery opens a pathway toward the development of new, non-antibiotic drug treatments for co-infected patients that won’t wreak havoc with their microbiomes, as antibiotics typically do.

Previously: Is the worm turning? Early stages of schistosomiasis bladder infection charted, Neglected story of schistosomiasis in Ghana, as told in a  sand animation and A good mouse model for a bad worm

Global Health, HIV/AIDS, Infectious Disease, Stanford News

Stanford study: South Africa could save millions of lives through HIV prevention

Stanford study: South Africa could save millions of lives through HIV prevention

South Africa could save the lives of some 4.5 million people over the next 20 years by using a double-barreled approach to HIV prevention.

That’s the result of a new study by Stanford researchers who looked at two methods for helping contain the epidemic in South Africa. According to the latest figures from the United Nations Joint Programme on HIV/AIDS, South Africa is the world’s hardest-hit country with 6.1 million people infected with HIV and most new infections happening via heterosexual transmission.

Effectively targeting people who don’t use condoms and have many sexual partners would prevent many infections and avert the costs of having to treat people down the road

One way to prevent sexual transmission of the disease is to give antiretroviral therapy to individuals as soon as they are found to be HIV-positive, said Sabina Alistar, PhD, first author of the new study. The World Health Organization now recommends that people go on ARV treatment when their CD4 counts – a measure of their immune system function – fall below 500. But a landmark study, published in 2011, showed that if infected individuals are effectively taking ARV treatment, the chance of their passing on the virus falls by a staggering 96 percent. So the greater the number of infected people on treatment, the less the virus will spread through the population.

“It’s much more cost-effective to put people in treatment as you find them, regardless of how far along they’ve progressed, rather than wait until they get really sick and put them on treatment,” said Alistar, who did the study while a PhD candidate in Management Science and Engineering at Stanford.

That idea isn’t new, but in this latest study from Stanford, the researchers examined the benefits of combining that universal approach to therapy with another tool, creating a powerful, cost-effective strategy for preventing millions of infections over time. The added tool, known as pre-exposure prophylaxis, or PrEP, involves daily use of a pill containing an antiretroviral drug. The pill is taken by people who may be at risk for HIV but are not infected. A landmark 2010 trial found that PrEP, if used faithfully, can reduce the risk of acquiring the virus by up to 73 percent.

“If you could focus on getting PrEP to people who engage in risky behaviors, then you could get quite significant results,” Alistar said. “Effectively targeting people who do not use condoms and have many sexual partners would prevent many infections and avert the costs of having to treat people down the road.”

She and her colleagues calculated that combining the two strategies – universal therapy for all those with HIV and targeted PrEP therapy for uninfected, high-risk individuals – would cost $150 per quality-adjusted life year gained (a QALY is measure of how much health benefit is gained for every dollar invested). That is a highly valuable bargain for South Africa, she said, which has significant resources to invest in the epidemic.

Eran Bendavid, MD, an assistant professor of medicine at Stanford and senior author of the paper, said scientists are now developing an approach to PrEP that only requires an injection every three or four months, rather than a daily pill.

When that therapy becomes available, “That has the potential to become a game-changer, since the Achilles heel of PrEP is low adherence,” Bendavid said.

The paper appears online today in the journal BMC Medicine.

Previously: U.S. AIDS Czar tells Stanford audience that witnessing death is a powerful motivatorTask force recommends HIV screening for all people aged 15 to 65International AIDS conference ends on an optimistic note and Using family planning counseling to reduce number of HIV-positive children in Africa

Clinical Trials, Global Health, Infectious Disease, Pediatrics, Stanford News

Life-saving dollar-a-dose rotavirus vaccine attains clinical success in advanced India trial

Life-saving dollar-a-dose rotavirus vaccine attains clinical success in advanced India trial

dollar bill 2Nearly every child in the world has been infected with rotavirus at least once by the age of five. But kids in poor countries get the worst of it. Rotavirus mortality is low in the developed world, but in low-income countries it’s a killer, accounting for 85 percent of the estimated 180,000 to 400,000 annual deaths caused by the pathogen.

The disparity exists for at least two reasons.

First, widespread malnutrition results in a different epidemiology. For example, 70 percent of rotavirus hospitalizations in India happen the first year of life, compared with 40 percent in high- and middle-income countries.

Second, price. Vaccination is second only to gaining access to potable water as a low-cost, high-payoff  strategy for ensuring children’s health. But many vaccines are far too pricey for families living on incomes in the neighborhood of $1,500 per year. As a result, most childhood deaths from vaccine-preventable diseases happen in low-income countries. India has the most rotavirus deaths in the world, estimated at about 75,000-122,000 per year (close to a quarter of the worldwide total.)

So it’s great news that a new rotavirus vaccine developed by Indians for Indians has leaped the safety and efficacy thresholds of a late-stage clinical trial, in which more than 6,500 Indian infants were inoculated, and will likely become available in that country for less than a dollar a dose. (The full immunization procedure requires three separate doses.)

The results appear in a study just published in The Lancet and co-authored by a team including veteran rotavirus-vaccine developer Harry Greenberg, MD. An accompanying perspective piece co-written by Greenberg, who also directs the Stanford Center for Clinical and Translational Research and Education, states:

[P]roof of the efficacy of the… vaccine against a disease that affects almost every child in India, leads to millions of clinic visits and hundreds of thousands of hospital admissions, and kills roughly one child in every 175-200 born in India before their fifth birthday is cause for celebration.

The new vaccine was the first to be fully tested for efficacy in a randomized, double-blind, placebo-controlled clinical trial in India. Interestingly, its development began with the discovery, by an Indian pediatrician, that newborns were getting rotavirus infections in the hospital but not getting sick. The strain they were infected with turned out to be an attenuated mutant virus that turns on the body’s immune response without causing symptoms: in short, the ideal vaccine candidate.

Ultimately spearheaded by a young Indian biotechnology company, Bharat Biotech, the effort to capitalize on this promising episode of serendipity drew financial support from the Bill & Melinda Gates Foundation and technical assistance from the Government of India’s Department of Biotechnology, the United States’ Centers for Disease Control and Prevention, and Stanford, among others.  This international team of collaborators then spent more than 15 years turning the promise into a reality.

Previously: Trials, and tribulations, of a rotavirus vaccine
Photo by David Guo

Applied Biotechnology, Bioengineering, Global Health, Stanford News

Free DIY microscope kits to citizen scientists with inspiring project ideas

Free DIY microscope kits to citizen scientists with inspiring project ideas

foldscope-paper-microscope-620x406

Stanford bioengineer Manu Prakash, PhD, is giving away 10,000 build-your-own paper microscope kits to citizen scientists with the most inspiring ideas for things to do with this new invention.

This invention, called Foldscope, is a print-and-fold optical microscope that can be assembled from a flat sheet of paper. Although it costs less than a dollar in parts, it can magnify objects over 2,000 times and is small enough to fit in a pocket.

Prakash initiated The Ten Thousand Microscopes Project, funded by the Gordon and Betty Moore Foundation, as a way to open up the wonders of the microscopic world to future generations of scientists and engineers. Prakash, who entered and won science fairs as a child in India, clearly wishes that he had a tool like this when growing up.

“Many children around the world have never used a microscope, even in developed countries like the United States,” said Prakash. “A universal program providing a microscope for every child could foster deep interest in science at an early age.”

kid-sketches

Through this project, he and his team will assemble a crowd-sourced biology microscopy manual that includes examples of creative uses for his microscope, collected from the scientists, teachers, tinkerers, thinkers, hackers and kids who participate.

“So many times people use a tool for one specific purpose and don’t realize the rich potential for other uses,” said Prakash. “This online manual will inspire further explorations.”

To apply for a Foldscope kit, submit ideas on how you would use your microscope to signup (at) foldscope (dot) com. Recipients must pledge to document their experiments in a way that could be replicated by anyone. Submission details and sample proposals are posted at Foldscope.com. Kits will be shipped in August 2014 to the applicants with the best ideas.

“My dream is that someday, every kid will have a Foldscope in their back pocket,” said Prakash.

Previously: Stanford bioengineer develops a 50-cent paper microscope, Stanford microscope inventor featured on TED Talk, Stanford bioengineer developing an “Electric Band-Aid Worm Test and Stanford bioengineers create an ultra-low-cost oral cancer screening tool
Photos by TED and Prakash Lab

Applied Biotechnology, Bioengineering, Global Health, Stanford News, Videos

Stanford microscope inventor featured on TED Talk

Stanford microscope inventor featured on TED Talk

Earlier today I wrote about the 50-cent paper microscope developed by Stanford bioengineering professor Manu Prakash, PhD. You can now watch a video of him building and demonstrating the microscope on TED.com. This TED “Talk of Week” has already been viewed almost 300,000 times.

Prakash, who grew up in the mega-cities of India without a refrigerator, is a leader in the frugal design movement. His lab is currently developing a number of global health solutions, leveraging the cost savings of emerging manufacturing techniques such as 3D printers, laser cutters and conductive ink printing.

Previously: Stanford bioengineer develops a 50-cent paper microscope, Stanford bioengineer developing an “Electric Band-Aid Worm Test and Stanford bioengineers create an ultra-low-cost oral cancer screening tool

Applied Biotechnology, Bioengineering, Global Health, Stanford News, Videos

Stanford bioengineer develops a 50-cent paper microscope

Stanford bioengineer develops a 50-cent paper microscope

UPDATE: A second blog entry, including a link to Prakash’s TED talk on this topic, can be found here. And this entry discusses Prakash’s plans to give away 10,000 build-your-own paper microscope kits to citizen scientists with the most inspiring ideas for things to do with this new invention.

***

When Manu Prakash, PhD, wants to impress lab visitors with the durability of his Origami-based paper microscope, he throws it off a three-story balcony, stomps on it with his foot and dunks it into a water-filled beaker. Miraculously, it still works.

Even more amazing is that this microscope — a bookmark-sized piece of layered cardstock with a micro-lens — only costs about 50 cents in materials to make.

In the video posted above, you can see his “Foldscope” being built in just a few minutes, then used to project giant images of plant tissue on the wall of a dark room.

Prakash’s dream is that this ultra-low-cost microscope will someday be distributed widely to detect dangerous blood-borne diseases like malaria, African sleeping sickness, schistosomiasis and Chagas.

“I wanted to make the best possible disease-detection instrument that we could almost distribute for free,” said Prakash. “What came out of this project is what we call use-and-throw microscopy.”

The Foldscope can be assembled in minutes, includes no mechanical moving parts, packs in a flat configuration, is extremely rugged and can be incinerated after use to safely dispose of infectious biological samples. With minor design modifications, it can be used for bright-field, multi-fluorescence or projection microscopy.

One of the unique design features of the microscope is the use of inexpensive spherical lenses rather than the precision-ground curved glass lenses used in traditional microscopes. These poppy-seed-sized lenses were originally mass produced in various sizes as an abrasive grit that was thrown into industrial tumblers to knock the rough edges off metal parts. In the simplest configuration of the Foldscope, one 17-cent lens is press-fit into a small hole in the center of the slide-mounting platform. Some of his more sophisticated versions use multiple lenses and filters.

To use a Foldscope, a sample is mounted on a microscope slide and wedged between the paper layers of the microscope. With a thumb and forefinger grasping each end of the layered paper strip, a user holds the micro-lens close enough to one eye that eyebrows touch the paper. Focusing and locating a target object are achieved by flexing and sliding the paper platform with the thumb and fingers.

microbes

Because of the unique optical physics of a spherical lens held close to the eye, samples can be magnified up to 2,000 times. (To the right are two disease-causing microbes, Giardia lamblia and Leishmania donovani, photographed through a Foldscope.)

The Foldscope can be customized for the detection of specific organisms by adding various combinations of colored LED lights powered by a watch battery, sample stains and fluorescent filters. It can also be configured to project images on the wall of a dark room.

In addition, Prakash is passionate about mass-producing the Foldscope for educational purposes, to inspire children — our future scientists — to explore and learn from the microscopic world.

In a recent Stanford bioengineering course, Prakash used the Foldscope to teach students about the physics of microscopy. He had the entire class build their own Foldscope. Then teams wrote reports on microscopic observations or designed Foldscope accessories, such a smartphone camera attachment.

For more on Foldscope optics, a materials list and construction details, read Prakash’s technical paper.

Previously: Stanford bioengineer developing an “Electric Band-Aid Worm TestStanford bioengineers create an ultra-low-cost oral cancer screening tool,
Related: Prakash wins Gates grant for paper microscope development

Global Health, Health Disparities

In Uganda, offering support for those born with indeterminate sex

Kaggwa - smallWhen most adolescent boys in his Ugandan village were lobbing soccer balls, Julius Kaggwa was sidelined by an unusual phenomenon: He began to develop the breasts of a girl. His mother took this as a sign from the spirits that young Julius was intended to be female and she began to send him to school in girls’ dresses. The boy was mortified and became afraid to show his face in public. Life became so unbearable that he contemplated suicide.

Today, Kaggwa, 44, is the founder and director of Support Initiative for People with Congenital Disorders, the first group of its kind in East Africa to serve the intersex population. Intersex individuals are those born with indeterminate sex because of hormonal, physiologic or other medical anomalies.

In Uganda, where children are cherished and celebrated by the community in the month after birth, he said the arrival of an intersex child is a mother’s “nightmare.”

“Our work starts in the delivery ward where children are mutilated or their lives are terminated,” he said. The mother may be reviled by the community: “There are people who will say, ‘What is the use of this woman?’ So the mother will kill that child to avoid the stigma.”

I met Kaggwa in February at the group’s headquarters in Kampala, Uganda’s bustling capital city. I had traveled to the East African country as a Global Justice Fellow with the American Jewish World Service, an international organization that aims to end poverty and support human rights in the developing world. Fifteen of us fellows spent nine days in Uganda last month meeting with organizations that support women, girls and members of the LGBTI community.

We headed down a long dirt road to the headquarters for SIPD, located in a building that remained unidentified for security reasons. Since the Ugandan Parliament passed a harsh anti-gay law in December, there had been a rise in arrests, beatings and public assaults on members of the LGBTI community, and there were concerns that the anti-gay sentiment would spill over into the organization.

The group focuses on changing cultural attitudes so that intersex children are more accepted in the community. SIPD also facilitates referrals to a hospital in Kampala where they can receive appropriate medical treatment, the only site in Uganda where physicians are equipped to deal with their specialized medical problems, Kaggwa said.

The group also does educational outreach in schools so that intersex youngsters don’t experience the kind of stigma and emotional trauma that he did.

“So they don’t have to kill themselves, drop out of school or sell their souls to seek asylum in other countries,” he said.

Continue Reading »

Global Health, In the News, Medicine and Society, Rural Health

From the Stanford Medicine archives: A Q&A with actor Matt Damon on water and health

Water, water, every where,
And all the boards did shrink;
Water, water, every where,
Nor any drop to drink.

Old it may be, but The Rhime of the Ancient Mariner reminds us of our current global water crisis. As Californians batten down the hatches in the face of severe drought, progress is being made to distribute clean water elsewhere in the world.

Actor Matt Damon was recently honored by the World Economic Forum for his work with fellow Water.org co-founder Gary White to make clean water more accessible in developing countries. Last year, the two talked about their efforts and the connection between water and disease in a Stanford Medicine  Q&A. Read on to learn how their organization empowers women and girls to lead clean-water initiatives.

Previously: Factoring in the environment: A report from Stanford Medicine magazine and “Contagion” spreads across the nation on Friday. Will Hollywood get the science right?

Global Health, Orthopedics, Pediatrics, Rural Health, Stanford News, Technology, Videos

Two Stanford students’ $20 device to treat clubfoot in developing countries

In the video above, Stanford graduate students Jeff Yang and Ian Connolly demo their design for a brace to correct clubfoot in a way that’s comfortable and functional for the children who need it, and reasonable for their families to afford. The $20 device uses injection molded plastic attached to cleats to hold a child’s legs in an upright position so that they can strengthen the muscles they need eventually to maintain the posture without assistance. It also allows them to stand and move around with ease, and the device looks more like a toy than a restraint.

Yang and Connelly visited Brazil to learn more about the birth defect that affects one in 1,000 children whose feet appear to be rotated internally. There, clubfoot is commonly treated using rigid, ineffective metal braces, notes this video and an article on Wired.com. The students began working with the organization Miraclefeet during a Stanford D.School course titled “Design for Extreme Affordability” and put their design into action at a hospital in São Paulo.

Previously: Support for robots that assist people with disabilities, New documentary focuses on Stanford’s Design for Extreme Affordability courseBiotech start-up builds artful artificial limbs and Improving treatment for infant respiratory distress in developing countries
Photo in featured entry box from Design for Extreme Affordability

Global Health, Stanford News

Researchers challenge conventional wisdom to identify source of lead contamination in Bangladesh

Researchers challenge conventional wisdom to identify source of lead contamination in Bangladesh

What could be causing lead contamination in one of the poorest corners of the world – a place where roads are scarce and there are almost no vehicles emitting gas exhaust? That’s the question that an interdisciplinary team of Stanford researchers hopes to answer as part of an effort to stop the spread of lead contamination in parts of rural Bangladesh.

A recent Stanford Report story explains how the team began to suspect the Bangladesh’s agriculture sector as the culprit of the contamination and why their theory challenges conventional wisdom:

Based on the evidence of higher lead levels in farm land compared with levels in nearby homes, [Stephen Luby, MD,] speculated that the contamination was coming from an agricultural product, possibly pesticide, and being absorbed by plants.

A similar story played out in the U.S. apple industry during the late 19th century and early 20th century when the use of lead arsenate pesticides contributed to the contamination of thousands of acres and sickened many field workers.

When he floated his hypothesis to other experts in the field, Luby was met with skepticism. Responding to an email from Luby, one wrote that he was “perplexed” by the idea, while another scientist wrote he “would be very surprised” if Luby’s theory proved correct. “They thought I was crazy,” Luby said. “It was pretty direct and troubling because it came from people who have been in Bangladesh a long time.”

Despite the doubts, Luby pushed on. With colleagues, he collected hundreds of blood samples from residents of agricultural areas. Luby didn’t have the funding, however, to test the samples for lead, carry out surveys and do other related work. “Then EVP came along,” Luby said. With the program’s support, Luby and his fellow project investigators, Assistant Professor of Economics Pascaline Dupas and Woods senior fellows Scott Fendorf (Earth sciences) and Roz Naylor (Earth sciences, FSI), plan to look for lead in blood and soil samples, examine evidence of past contamination and develop ways to test pesticides for the dangerous metal.

Previously: Arsenic responsible for 20 percent of Bangladeshi deaths and Using soils science to tackle Asia’s arsenic problem

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