Three new conditions were added today to the list of tropical diseases for purposes of obtaining a tropical disease Priority Review Voucher (PRV) from the US Food and Drug Administration (FDA). The agency added brucellosis to the list, as well as two foodborne trematode infections, opisthorchiasis and paragonimiasis.
The agency determined that two other diseases, coccidioidomycosis and clonarchiasis, did not meet statutory criteria for tropical disease designation under the PRV program.
In the final order adding the two trematode, or fluke, infections to the tropical diseases list, FDA noted that opisthorchiasis infection is currently treatable by praziquantel, the only FDA-approved treatment for the condition. Infection with Opisthorchis species is associated with increased risk for cholangiosarcoma. No treatment exists for paragonimiasis, which can cause severe central neurologic symptoms when the flukes migrate to the brain.
Also, noted the agency, no significant market for opisthorchiasis or paragonimiasis treatment exists in developed nations because of the limited geographic range of the flukes and the low rate of infection in the few developed countries where the trematodes are found. Infection with each of the trematodes disproportionately affects poor and marginalized populations, another statutory criterion for tropical disease designation under Section 524 of the Food, Drug and Cosmetic (FD&C) Act.
The agency’s interpretation of the statutory criteria contained in Section 524 was laid out in an August 2015 final order (80 FR 50559). The FDA has applied the dual criteria of “no significant market in developed nations” and “disproportionately affects poor and marginalized populations” since that time.
In declining to designate chlonorchiasis – another fluke infection – as a tropical disease, FDA noted that chlonarchiasis has significant prevalence in many developed Asian countries and far eastern Russia. Prevalence is thought to be especially high in South Korea, reaching 1.4 million individuals infected in 2008. Therefore, concluded FDA, a significant potential market for prevention or treatment of chlonorchiasis does exist in a developed nation, so that statutory requirement for tropical disease designation was not met.
Though clonarchiasis does disproportionately affect poor and marginalized populations, both statutory criteria must be met for tropical disease designation.
Brucellosis is among the most common zoonotic infections, with more than 500,000 cases globally per year. Including this common condition on the tropical diseases list was a decision made by FDA after taking into account the continuing burden of brucellosis disease still seen in developing countries, where severe disease can cause meningitis, endocarditis, osteomyelitis, and pneumonitis. Chronic infection can cause multi-organ granulomatous disease, and infection in pregnant women is associated with adverse fetal outcomes.
Existing treatment options, said FDA, “have changed little in 30 years,” and include doxycycline, streptomycin and tetracycline. No human brucellosis vaccine is licensed in the United States. Since livestock-directed efforts at brucellosis control have been largely effective in the US, human incidence is low; also, said FDA, even in high-income countries where brucellosis is endemic, the incidence falls below the statutory threshold of 0.1 percent of the population. “These markets are unlikely to provide sufficient incentive to encourage development of products to treat or prevent brucellosis,” said the agency in its final rule.
Successful animal vaccination programs for brucellosis have not been achieved by many less developed countries, where human infection disproportionately affects poor and marginalized populations.
In declining to add coccidioidomycosis, or Valley Fever, to the tropical diseases list, FDA noted that the incidence of the disease increased greater than 8-fold in the desert Southwest, where the fungus is endemic, over the 20-year period ending in 2011. Clinical manifestations of coccidioidomycosis can range from asymptomatic infection to acute illness, to disease with life-threatening complications. FDA noted that up to 30% of community-acquired pneumonia may be coccidioidomycosis-related in endemic areas.
“In the current analysis, FDA has found that a sizeable direct market may exist for products to prevent coccidioidomycosis (e.g. vaccines) in developed nations, depending upon the specific attributes of the product and the recommended population,” according to the final rule, so the statutory criterion for “no significant market for prevention or treatment” is not met.
Because this criterion was not met, the fact that the disease does disproportionately affect poor and marginalized populations is not sufficient reason to grant tropical diseases designation to brucellosis for purposes of obtaining PRVs.
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