Enlisting mHealth in the Fight Against River Blindness

Monday, June 22, 2015

When it comes to devising new ways to provide state-of-the art medical care to people living in remote areas of the world, smartphones truly are helping scientists get smarter. For example, an NIH-supported team working in Central Africa recently turned an iPhone into a low-cost video microscope capable of quickly testing to see if people infected with a parasitic worm called Loa loa can safely receive a drug intended to protect them from a different, potentially blinding parasitic disease.

As shown in the video above, the iPhone’s camera scans a drop of a person’s blood for the movement of L. loa worms. Customized software then processes the motion to count the worms (see the dark circles) in the blood sample and arrive at an estimate of the body’s total worm load. The higher the worm load, the greater the risk of developing serious side effects from a drug treatment for river blindness, also known as onchocerciasis.

This work represents the latest advance in biomedical research’s long, ongoing battle against river blindness, which affects about 25 million people in Africa, Latin America, and the Middle East. Major progress was made starting in the late 1980s, when the pharmaceutical firm Merck discovered that its drug ivermectin (Mectizan®) kills the parasitic worm that causes river blindness (Onchocerca volvulus)  and then took the bold step of donating an unlimited supply of the drug to needy nations that requested it.

Nearly three decades and a billion pills later, the ivermectin distribution campaign has made a big difference in fighting river blindness. Still, in the Republic of Cameroon and other countries in Central and West Africa, the campaign ran into an unexpected problem: a small, but significant, fraction of people who received ivermectin fell severely ill or even died from neurological complications. Researchers later determined that patients who suffered such adverse reactions not only were infected with O. volvulus worms, but also had unusually heavy loads of L. loa worms in their bodies. By itself, L. loa infection, called loiasis, usually isn’t serious. However, when large numbers of L. loa worms are suddenly killed by ivermectin, they incite an inflammatory reaction that can block tiny blood vessels, leading to devastating complications in the brain, liver, and other organs.

Laboratory and field-based blood tests exist that can determine which individuals have too many L. loa worms in their blood to receive ivermectin safely. But due to the logistics and requirements for trained personnel and sophisticated equipment, these have proven to be too impractical to administer on a wide-scale basis in remote areas. So, by the early 2000s, annual ivermectin treatments to combat river blindness were halted in this area of Africa.

To get at the problem, Thomas Nutman, an immunologist with NIH’s National Institute of Allergy and Infectious Diseases (NIAID), and his colleagues first tried to simplify standard screening tests, with mixed results. Then, a few years ago, Nutman heard about the work that bioengineer Daniel Fletcher was doing in adapting smartphones for use as mobile microscopes. Already, Fletcher’s group at the University of California, Berkeley had reconfigured smartphones to test for tuberculosis and malaria, with other applications on the drawing board.

So, the Nutman and Fletcher labs began talking, and their conversations led to a re-engineered iPhone 5s, which they’ve dubbed CellScope Loa. What’s innovative about their new screening test is its reliance on the phone’s built-in video camera and processors.

Here’s how the process works: A person’s finger is pricked and a drop of his or her blood is loaded into a thin, roughly four-inch capillary—the equivalent of a glass slide for a standard microscope. The capillary inserts into a slot on the side of the phone, and the “go” button is punched. That prompts the phone’s video camera to image the sample briefly from five different fields of view with the help of two lenses that have been repositioned to focus on the capillary. An image-processing algorithm programmed into the phone automatically identifies disturbances to red blood cells caused by wriggling of immature L. loa worms, called microfilariae. Based on this motion detection, the phone estimates the individual’s worm load. If the count is under 30,000 microfilariae per microliter of blood, a person can safely receive ivermectin treatment.  But if the count is above 30,000, treatment is not recommended due to risk of adverse reactions.

In their pilot study, just published in Science Translational Medicine [1], the researchers used CellScope Loa to test 33 people living in the Republic of Cameroon. Compared to traditional microscopy, CellScope Loa was successful 94 percent of the time at identifying individuals eligible for ivermectin treatment, and, most importantly for purposes of preventing adverse reactions, it was nearly 100 percent successful at detecting individuals with microfilariae counts above the recommended level for treatment. In fact, researchers calculated that using their new smartphone-based test, only 1 in 10 million people at high risk for adverse reactions would mistakenly receive the green light for ivermectin treatment. Since the phone is reusable, what’s really nice is each test costs less than three cents, mainly to cover the cost of the capillary, swabs, and other testing materials.

Nutman and his colleagues plan to return to the Republic of Cameroon this summer to use their smartphone test to screen 60,000 people. If their preliminary findings are confirmed by the larger study, this system may provide an efficient, cost-effective way to enable resumption of ivermectin campaigns in Central and West Africa, helping to reduce the suffering and disability still being caused by river blindness in this area of the world.

Reference:

[1] Point-of-care quantification of blood-borne filarial parasites with a mobile phone microscope. D’Ambrosio MV, Bakalar M,Nutman TB, Fletcher DA, et al.  Sci Transl Med. 2015 May 6;7(286):286re4.

Links:

Onchocerciasis (Centers for Disease Control and Prevention)

Loiasis (CDC)

Thomas Nutman (National Institute of Allergy and Infectious Diseases/NIH)

Fletcher Lab (University of California, Berkeley)

25 Years: The Mectizan® Donation Program (Merck, Kenilworth, New Jersey)

NIH Support: National Institute of Allergy and Infectious Diseases

Category: Science

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