NIAID Now | January 29, 2021
January 30th is World Neglected Tropical Diseases Day, a time to recognize and address the tremendous burden imposed by Neglected Tropical Diseases (NTDs). Comprising parasitic, bacterial, fungal and viral diseases, NTDs affect more than 1 billion people worldwide, and disproportionally impact some of the world’s most impoverished countries and communities. On January 28th the World Health Assembly formally launched the new roadmap for NTDs. Cosponsored by the U.S., it sets global targets to prevent, control, eliminate, and eradicate 20 NTDs by 2030. NIAID has a long-standing research program devoted to better understanding, treating, and preventing NTDs.
Case Study: The Schistosomiasis Research Landscape
NIAID supports both intramural and extramural research efforts across multiple NTDs through research grants and contracts and by providing various resources for researchers. NIAID research repositories, such as the Filariasis Research Reagent Repository Center and Schistosomiasis Resource Center, aid research programs against these diseases by providing researchers with parasite species, standard study protocols, and training. NIAID contractors provide access to sandflies and blackflies, enabling research on those insect disease vectors NIAID-supported investigators are involved in a variety of translational research efforts examining new ways to prevent, treat, or potentially eradicate NTDs.
Schistosomiasis is a serious parasitic disease, second only to malaria in its global impact. Caused by a parasitic flatworm (schistosome) that lives in freshwater snails, the disease is contracted by coming into contact with fresh water infested with the schistosome larvae. Although the worms responsible for human schistosomiasis are not found in the United States, almost 240 million people are affected worldwide and over 700 million people live in endemic areas (WHO). Schistosomiasis leads to chronic illness and can leave people at higher risk of contracting other diseases. Infected women who have female genital schistosomiasis, for example, are at higher risk for contracting HIV/AIDS and human papillomavirus (HPV) infection. Unfortunately, reducing the burden of schistosomiasis has proved difficult. Researchers are developing improved diagnostics, drugs, vaccines, and snail control measures in a multi-pronged approach to combat schistosomiasis.
Praziquantel is the recommended drug treatment for schistosomiasis. Current infection control methods include mass administration of praziquantel to populations in endemic areas as a means of curing disease and temporarily preventing new infections. However, scientists are concerned that the schistosomiasis parasite could mutate and develop resistance to praziquantel. NIAID is engaged in efforts to discover and develop alternative drug treatments for schistosomiasis.
Rapid, accurate detection of infection and point-of-care use are gold standards for a diagnostic tool. This means that the tool would be easily portable, able to detect both high and low levels of infection and could provide results quickly. Effective diagnostic tools are used to measure the level of infection or prevalence of a disease pre- and post-intervention (e.g., before and after a drug or vaccine has been administered). They are critical for determining the efficacy of an intervention. Although several diagnostics for schistosomiasis are available, none fully meet the gold standard. Microscopic examination of a patient’s stool or urine sample to look for parasite eggs is the most widely used method, but this requires specialized trained staff, and it cannot effectively detect low levels of the infection in a patient’s system.
Molecular tests, such as those using the polymerase chain reaction (PCR) technology, are sensitive enough to identify active schistosomiasis infections, even when only low levels of infection are present. Unfortunately, the current PCR diagnostic tool is cumbersome and requires access to electricity, which may not be available in some communities where schistosomiasis is most prevalent. NIAID-supported researcher Dr. Christi Parham from Lynntech, Inc. is currently developing a battery-powered PCR diagnostic for schistosomiasis that is sensitive enough to identify low levels of infection and can distinguish between past and present infections. A rapid and sensitive point-of-care diagnostic tool for schistosomiasis could be critical when researchers are seeking to determine the efficacy of various interventions.
In nature, schistosomes infect only certain snail species in which they reproduce and develop into forms capable of infecting human hosts. These forms are released from the snail into fresh water, effectively contaminating the water and leading to human infection. Implementing an effective intervention targeting the snail intermediate host or the infectious schistosome larvae is another possible strategy to combat schistosomiasis.
Researchers have explored the possibility of using molluscicides—agents that kill snails—to reduce the snail population carrying the schistosomiasis larvae. Although this method is currently used in some areas, effective treatment of vast bodies of water, such as Lake Victoria in Kenya, where this snail population thrives, is challenging. Current molluscicide approaches alone may not be considered a widely deployable and effective method to reduce or control the schistosomiasis-susceptible snail population. In addition, molluscicides may also have undesirable ecological effects. NIAID-funded principal investigator Erik Loker from the University of New Mexico is studying the ecology of schistosomiasis at Lake Victoria and exploring alternative methods of snail control. Dr. Loker’s innovative approach focuses on identifying ways to target the parasite within the infected snail. An important aspect of his research is examining whether non-human infective schistosomes could out-compete the human-infective schistosomes within the snail.
No vaccine for schistosomiasis currently exists, although research is ongoing. A safe and effective vaccine would be an invaluable asset for control of schistosomiasis. NIAID-supported researchers have helped examine the safety and efficacy of candidate vaccines including the SmTSP-2 and Sm-p80 vaccine candidates. NIAID supported preclinical identification and development as well as a Phase 1 and a Phase 1b trial of the SmTSP-2 vaccine. A Phase 2 clinical trial examining the safety and efficacy of SmTSP-2 sponsored by the Baylor College of Medicine is currently ongoing in Uganda. NIAID has also supported various stages of development for the Sm-p80 vaccine over the past several decades. Preliminary study results have found evidence of efficacy in animal models. An NIAID-supported Phase I clinical trial to assess the safety and immunogenicity of the candidate vaccine is in development.
Next Steps: Ending the neglect
Continued progress in prevention, control, and elimination of NTDs will require a multi-pronged approach based on effective drugs, diagnostics, and vaccines. Further research is needed to support development of these public health interventions and to understand how best to utilize them to make continued progress against NTDs. NIAID is dedicated to ending the neglect of NTDs and continuing research to advance the global effort to prevent, control, eliminate, and in some cases, eradicate these diseases.