By Paul Nicolaus
September 12, 2017 | It’s a scorcher, and the cool of the nearby water beckons as a research group collects stool samples from Kenyans this past April. If he didn’t know better, one of those researchers would gladly jump into Lake Victoria to beat the heat.
But Mark Lim, PhD PMP, diagnostics program officer with the Bill and Melinda Gates Foundation, is well aware that schistosomiasis—a disease caused by parasitic worms—is transmitted, at least in part, by fresh water.
“It’s a weird disease because it requires three different things,” he said. “It requires fresh water, it requires a person to actually pee in the water, and it requires a specific snail in there.”
At first glance, it might seem like a simple sickness to defeat. All you need to do is remove one of those three variables from the equation. Easier said than done.
As Africa’s largest lake, the water isn’t going anywhere. Eliminating the aquatic snail would be incredibly difficult, Lim explained, and the process would cause significant environmental damage. Preventing urination (or defecation) by those who are infected is no small feat, either.
Imagine, for example, an impoverished farmer working along Lake Victoria. If the choice is to stop and travel back home to use the latrine or quickly relieve himself in the lake and get right back to work, the latter option is likely. And that singular act by one infected individual can wind up impacting thousands.
The worm eggs spread by human waste hatch and release larvae that enter snail hosts. From there, free-swimming larvae are released by the snails and penetrate human skin during contact with contaminated water. Inside the body, the parasites develop into adult worms that live in blood vessels, remain in tissues, trigger immune reactions, and damage organs.
As Lim and his colleagues observe the Kenyans fishing, bathing, and washing their dishes and clothing in the lake, one of them looks down at his feet and picks up the snail responsible for catalyzing the disease.
“Right now,” he said, “you’re looking at people actively getting infected.”
Global Goals
For Lim, the memory serves as a powerful reminder of the difficulty of dealing with schistosomiasis, which affects over 200 million people worldwide and is second only to malaria as the most devastating parasitic disease, according to the Centers for Disease Control and Prevention (CDC).
And schistosomiasis is just one of a whole array of Neglected Tropical Diseases (NTDs)—a group of ailments referred to as neglected because they have been largely wiped out in the more developed parts of the world.
Caused by bacteria or parasites, NTDs are most prevalent in low and middle-income countries within parts of Africa, Asia, and Latin America where people have little access to clean water or modern ways to dispose of human waste.
Various NTDs cause anemia and blindness, stunt children’s growth, lead to cognitive impairments, complicate pregnancies, and result in thousands of deaths each year. They also keep kids out of school and make it hard to earn a livig, which perpetuates the cycle of poverty and disease.
Although over 1 billion people suffer from one or more of these diseases, researchers have traditionally been unable to attract donor funding. In recent years, though, global health and development organizations have stepped up. The World Health Organization (WHO) targeted 17 NTDs for control, elimination, or eradication by the year 2020 in its 2012 roadmap, Accelerating Work To Overcome The Global Impact Of Neglected Tropical Diseases.
The WHO Roadmap helped inspire the 2012 signing of the London Declaration on Neglected Tropical Diseases—a pledge made by a group of foundations, pharmaceutical companies, governments, and other global health organizations to speed progress toward meeting the 2020 goals for 10 of the NTDs.
Anniversary Celebrates, Looks Ahead
The 5th anniversary of the WHO Roadmap and the London Declaration was celebrated in April at the NTDs Summit in Geneva, Switzerland, where strides made in recent years were highlighted. Sixty percent of those in need have now been treated for at least one NTD. Some diseases, like lymphatic filariasis (LF) and Guinea worm disease, are moving in the direction of elimination.
There have been substantial contributions that have spurred these achievements. In the five years since the 2012 London Declaration, pharmaceutical companies have collectively donated over 7 billion treatments, and foreign aid for NTDs amounted to roughly $200 to $300 million a year between 2012 and 2014, according to a WHO report.
As the collaborative effort continues, a number of financial and other commitments were announced or confirmed at the NTD Summit to continue work toward 2020 targets and the elimination of many diseases by 2030.
The Bill & Melinda Gates Foundation promised $335 million in grants over the next four years, which builds upon its $1 billion in donations made during the past decade. The U.K. government promised $460 million over the course of the next five years, and $27 million was pledged by the Belgian government to support the elimination of sleeping sickness in the Democratic Republic of the Congo by 2025.
But additional resources will be needed for the next stage of the ongoing struggle against NTDs. WHO has estimated that $750 million a year would be needed up to 2020, and $460 million a year between 2020 and 2030 to sustain progress.
When this financial picture is considered within the context of diagnostics, it is useful to make comparisons, Lim said. In the realm of HIV or Malaria, PEPFAR and the Global Fund exist. The NTD community, on the other hand, lacks a procurement mechanism and funding for the use of diagnostic tests. END Fund is the primary fundraiser, but the organization doesn’t necessarily have a diagnostic bent.
Because diagnostics are a decision-making tool and not a direct intervention, they don’t tend to carry the same weight as a pill, he pointed out. And unlike the pharma community, which is donating mainly off-patent drugs, the diagnostic community would have to pay for a test de novo, covering all R&D and clinical trial expenses.
Narrowed Focus
While the Bill and Melinda Gates Foundation has targeted the 10 NTDs outlined in the London Declaration, the organization’s most recent efforts have zeroed in on soil-transmitted helminths (STH) and schistosomiasis.
“For both STH and schistosomiasis, there’s just nothing beyond the microscope,” Lim said. “That’s our tour de force right now.” And that’s the technology available after the labor-intensive process of collecting stool samples.
Picture the process of traveling into what are often remote communities and knocking on doors to request this type of sample. By the time a home has been reached, it isn’t practical to return later if a sample cannot be produced.
Considering that field perspective, it is unrealistic to think of bringing back thousands of samples at a time. For each field team, Lim said, it is more likely that each person would gather five or six at best.
Smearing human waste on a slide and counting worm eggs is a method that fails to provide reliable data, however, and this is especially true as disease levels taper off thanks to mass drug administration (MDA) given to entire communities at risk of disease.
“We’re kind of the victims of our own success,” Lim said. Because this method of diagnosis involves searching for an egg or a worm, fewer eggs and fewer worms mean a more difficult hunt and the possibility of false negatives.
As NTD programs are ramped up and infection levels continue to fall, there is a clear need for more sensitive diagnostics that are low-cost and easy to use in the field.
Recent Developments
There have been some recent signs of advancement in this regard.
One case in point is the collaborative effort between the Bill and Melinda Gates Foundation, PATH, Standard Diagnostics (SD), and the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH) that led to a biplex point-of-care rapid test that addresses both onchocerciasis and LF.
Onchocerciasis (river blindness) is caused by a parasitic worm transmitted to humans through the bite of the blackfly, and LF is spread by mosquitos. Some communities, particularly in Africa, are commonly affected by both. Because of this overlap, diagnostic efforts have taken on an integrative approach with an eye on better using resources across diseases.
Control and elimination programs use the drug ivermectin, and in the case of LF, a second drug in combination, to stop transmission. Surveillance data are needed to inform program decisions, and this need led to the creation of the SD BIOLINE Onchocerciasis and Lymphatic Filariasis IgG4.
Field evaluations are currently being performed on the test, which was made available in 2016, explained Helen Storey, MS PhD, public health scientist in PATH’s diagnostics program, and WHO is actively reviewing that data to determine if the product is, in fact, able to make an impact.
Also released in 2016 was the SD BIOLINE Lymphatic Filariasis IgG4 rapid test, a monoplex test based on the detection of antibodies to Wb123, which is best suited for the Asian countries that are affected by LF but not onchocerciasis.
These two tests joined the previously released SD BIOLINE Onchocerciasis IgG4 rapid test, an antibody-detection test for the post-elimination surveillance of onchocerciasis and the Alere Filariasis Test Strip, an antigen-detection test used for LF disease mapping and informing MDA stopping decisions.
These are all inexpensive tests, Storey said, which is a crucial component of any of the diagnostic tools required for NTDs. They are also easy to use, requiring just a finger prick blood sample, and they produce rapid results similar to a home pregnancy test.
“The more tools that we have available to measure and combat the diseases, the greater the success is going to be for these programs,” she added.
Thinking Ahead
Although Lim views any new diagnostic tool that works as a breakthrough considering the current lack of available tests, he also believes new and emerging solutions need to head in a different direction.
“We have these rapid diagnostic tests, but we only use them once and we kind of throw them away,” he said, “and that’s kind of the one time we touch these communities.” The desire to move away from rapid diagnostics also relates to inherent quality issues and an inability to gather data right away.
Although newly developed diagnostics won’t necessarily play a vital role in reaching the 2020 goals for most NTDs, they may play a more central role when it comes to meeting post-2020 objectives. The key will be replacing the microscope, which remains the gold standard for many NTDs, with molecule-based tests.
To head in that direction, the Bill and Melinda Gates Foundation is working with GlaxoSmithKline and Johnson & Johnson—the drug donors for STH and schistosomiasis—to identify diagnostic needs and potentially work together on funding their development and deployment.
The tests envisioned would send data directly to a cloud-based system so that a program manager could see what’s happening in real time and make intervention related decisions. “That’s an area we’re actively exploring right now,” he said, “particularly in STH and schistosomiasis.”
Once diagnostic tools are created and made available, thinking about how programs can purchase and implement them is also a crucial element of the big picture. The communities impacted by NTDs typically have, at best, someone who could operate a rapid diagnostic test or a very simple sample in, sample out test.
Therein lies the Catch-22. “We’d love to have a much more sophisticated test,” he said, “but we can’t deploy sophisticated tests in the communities that need them.” That doesn’t keep Lim from thinking big, though.
Diagnostic Dreams
One of his fears is that funding will be devoted to the development of a test that fizzles due to lack of use. If a test is only used for one or two samplings of a population, for example, then five years down the road a company that has dedicated itself to making this test might no longer exist.
“We want to place our bet on the right test that has the most power and then the most impact,” Lim said. Because of this, sustainability needs to be part of the conversation. As he peers into the future, he hopes that forthcoming diagnostics will be conceptually different from existing options.
Considering the close link between NTDs and poverty as well as the global agenda to reduce poverty, moving toward a test that could detect more than just NTDs could be a solution to the sustainability dilemma.
Imagine a test that looks over multiple diseases, he said. It could handle an STH or schistosomiasis survey, but the instrument would be routinely used, it would be well-maintained, and operators would know how to use it.
Ideally, it would also become part of a broader health system strengthening. Although large diagnostic companies are often scared off by the logistical challenges and lack of incentive in this space, plans of putting a test into a community health system that is continually being used could be a way to lower the barrier to entry.
“This is very, very aspirational,” he acknowledged. “That’s my moonshot right now.”
Paul Nicolaus is a freelance writer specializing in health and medicine. Learn more at www.nicolauswriting.com.