Cases of Leishmaniasis Increasing in the United States, Vaccine in Development

Leishmaniasis is a neglected tropical disease that is transmitted by phlebotomine sand flies infected with Leishmania parasites.¹ The disease affects more than 12 million people worldwide, with the highest prevalence rates observed in Africa, Asia, South America, and the Middle East.² Most human cases of leishmaniasis in the United States occur in Texas, where sand flies and animals known to harbor leishmaniasis are found, and additional cases are attributed to immigration and international travel.²

As Texas is the only state required to report new cases, there is a dearth of data regarding rates of infection in the United States, and US doctors may not recognize the symptoms of the disease.³ However, the incidence of leishmaniasis in the US has risen in recent years, partly because of increasing travel to high-prevalence regions.⁴ This trend prompted the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH) to publish clinical guidelines in 2017 pertaining to the diagnosis and treatment of cutaneous, mucosal, and visceral leishmaniasis, the 3 main forms of the disease.⁴

While cutaneous leishmaniasis is the most common form of infection, visceral leishmaniasis is the most life-threatening form of the disease and has the second highest fatality rate of parasitic infections, following malaria.² Symptoms of visceral leishmaniasis may include fever, weight loss, low blood cell and platelet count, and enlarged spleen and liver.^4,1

The only medications approved by the US Food and Drug Administration (FDA) for leishmaniasis treatment include intravenous liposomal amphotericin B for visceral leishmaniasis and oral miltefosine for select cases of cutaneous, mucosal, and visceral leishmaniasis.⁴ There have been numerous efforts to develop leishmaniasis vaccines, including the work of Abhay Satoskar, MD, PhD, a researcher and professor in the division of experimental pathology at The Ohio State University Wexner Medical Center in Columbus.^5,2

“Our research team has been able to generate genetically-modified live, weakened leishmaniasis parasites that have been proven safe and effective at inducing protective immunity against infection in preclinical studies,” Dr Satoskar explained in a press release.² “The dogs in our trials have had the immune response we expected, so I believe we have a good shot at a human prophylactic vaccine as well as a vaccine for dogs to reduce their risk as carriers.”

To further these endeavors, Dr Satoskar was recently awarded grant funding totaling $4.25 million, including $650,000 from The Wellcome Trust based in the United Kingdom and $3.6 million from the Global Health Innovative Technology Fund in Japan. These funds will support testing of a visceral leishmaniasis vaccine for dogs and the production of clinical-grade materials for subsequent human trials, respectively. The National Institutes of Health, the FDA, Gennova Biopharmaceuticals Ltd, and Johns Hopkins University are among Dr Satoskar’s international research partners for these investigations.

“Dr. Satoskar’s research has placed a spotlight on a pressing global health issue,” K. Craig Kent, MD, dean of the College of Medicine at Ohio State University, stated in the press release. “He has dedicated his career to the elimination of leishmaniasis and these funding awards will further his research efforts.”

Infectious Disease Advisor interviewed Dr Satoskar to learn more about his work in this area.

Infectious Disease Advisor: What is the relevance of leishmaniasis to physicians in the US?

Abhay Satoskar, MD, PhD: Nearly 10% of the world population lives in leishmaniasis-endemic regions, including Central and South America and other parts of the world.⁶ Americans traveling to these regions are at increased risk for infection. Due to globalization, we are now seeing more cases of this disease in the US. Of more importance, an endemic focus has now been reported for leishmaniasis in the US in humans.³

Additionally, dogs are the zoonotic reservoir for infection, and several thousand dogs in the US have tested positive for leishmaniasis.⁷ US military personnel deployed abroad in leishmaniasis-endemic countries such as Iraq, Afghanistan, and Syria are at high risk of acquiring the infection.

Infectious Disease Advisor: What do you hope to accomplish in your upcoming research?

Dr Satoskar: There is no licensed vaccine for human use against any parasitic disease. Vaccinations are an essential component of the success of elimination programs for any zoonotic disease including leishmaniasis. We have developed a live attenuated prophylactic vaccine and we hope to manufacture and test it in humans and license it for clinical use.

Infectious Disease Advisor: How did you become interested in focusing on leishmaniasis, and how did your pursuit of a vaccine come about?

Dr Satoskar: I am originally from India, which is an endemic country for leishmaniasis. During my clinical training in India, I encountered patients suffering from leishmaniasis, some of whom were dying from the visceral form of disease — which is fatal without treatment. These deaths would have been totally preventable if suitable prophylactic intervention such as a vaccine had been available.

Infectious Disease Advisor: What are additional needs in this area in terms of research and education?

Dr Satoskar: We need a vaccine, but also better tests for early detection of infection. Also, current therapies for this disease are suboptimal because they involve prolonged injection of toxic drugs. Healthcare providers and others in non-endemic countries need to be educated and made aware of tropical diseases such as leishmaniasis as they are emerging in these settings. Other issues such as global warming are likely to increase rates of these diseases due to the emergence of new foci for vectors.⁸

References

1. Centers for Disease Control and Prevention (CDC). Parasites – Leishmaniasis. https://www.cdc.gov/parasites/leishmaniasis/ Accessed September 20, 2019
2. The Ohio State University Wexner Medical Center. $4.25 million grants fund research on vaccine for tropical disease affecting US. August 13, 2019. https://wexnermedical.osu.edu/mediaroom/pressreleaselisting/4-million-grants-fund-research-on-vaccine-for-tropical-disease-affecting-us. Accessed December 6, 2019.
3. McIlwee BE, Weis SE, Hosler GA. Incidence of endemic human cutaneous leishmaniasis in the United States. JAMA Dermatol. 2018;154(9):1032-1039.
4. Aronson N, Herwaldt BL, Libman M, et al. Diagnosis and treatment of leishmaniasis: clinical practice guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Am J Trop Med Hyg. 2017;96(1):24-45.
5. Gillespie PM , Beaumier CM , Strych U  , Hayward T , Hotez PJ , Bottazzi ME. Status of vaccine research and development of vaccines for leishmaniasis. Vaccine. 2016;34(26):2992-2995.
6. McGwire BS, Satoskar AR. Leishmaniasis: clinical syndromes and treatment. QJM. 2014;107(1):7-14.
7. Petersen CA. Leishmaniasis, an emerging disease found in companion animals in the United States. Top Companion Anim Med. 2009;24(4):182-188.
8. González C, Wang O, Strutz SE, González-Salazar C, Sánchez-Cordero V, Sarkar S. Climate change and risk of leishmaniasis in North America: Predictions from ecological niche models of vector and reservoir species. PLoS Negl Trop Dis. 2010;4(1):e585.