Helminths, parasites and flukes, oh my! A review of treatments for common NTDs
Neglected tropical diseases, or NTDs, are a group of chronic, debilitating, communicable diseases that predominantly affect those living in poverty in developing countries in Latin America, Africa and South Asia. They affect more than 1 billion people and are a major cause of morbidity and mortality worldwide. These conditions are poverty-promoting, leaving those most prone to acquiring them trapped in a cycle of poverty and disease.
Besides being concentrated primarily in developing countries, these infections often are overlooked because they cause disability rather than death. Their worldwide burdens are typically assessed by disability-adjusted life years (DALYs), a measure of the gap between current and ideal health status. DALYs are calculated by adding years of life lost and years lost due to disability. One DALY can be considered equivalent to 1 lost year of healthy life.
Most of these infections, which can be parasitic, bacterial, viral or fungal in nature, are easily and inexpensively prevented and treated. However, as developing countries are the primary sites of these diseases, many of those affected cannot afford the necessary medications.
While many of the NTDs can be found on multiple continents, each has unique infections most prevalent in that area.
South Asia — helminth infections
Soil-transmitted helminth infections include those caused by roundworms (ascariasis), whipworms (trichuriasis) and hookworms. They often chronically infect humans concomitantly. They cause illness through skin contact with the eggs or larvae in warm soil.
These parasitic infections are prevalent worldwide in developing countries and are the most common NTDs affecting India and South Asia, at nearly 300 million current cases. Soil-transmitted helminth infections are a major cause of malnutrition, intellectual retardation and cognitive deficits in the world. The estimated number of DALYs in South Asia for this type of NTD is up to 10.1 million.
Soil-transmitted helminth infections are typically easily treated with a single dose of a broad-spectrum benzimidazole anthelminthic, either 400 mg Albenza (albendazole, Amedra Pharmaceuticals) or 500 mg mebendazole. Albendazole is preferred for hookworm, while mebendazole is more effective for trichuriasis, and either agent can be used for ascariasis. Sometimes, particularly for trichuriasis, up to three doses are needed to achieve the goal of complete worm removal.
These antimicrobials block glucose uptake in parasites by causing degeneration of their microtubules, leading to decreased glycogen storage and reduced formation of adenosine triphosphate needed for survival. They are generally well-tolerated, and the most commonly experienced adverse effect is gastrointestinal distress.
Prevention also can be achieved by once- or twice-yearly mass medication administration of either of these agents in a single dose. Preventive efforts are often targeted at school-aged children, as they are particularly susceptible to helminth infections. A human hookworm vaccine is currently undergoing development as well.
Both albendazole and mebendazole can be purchased for less than $1 per treatment, making the goal of controlling the massive morbidity of this disease a definite possibility.
Latin America — Chagas disease
Chagas disease affects 8 million to 9 million people in Latin American countries, second in prevalence only to helminth infections. This illness is estimated to cause a disease burden of 662,000 DALYs. The protozoan parasite (Trypanosoma cruzi) is most commonly transmitted through vectors living in the cracks of mud walls and thatched roofs of rural houses, but can also be spread through the feces of an infected vector and by vertical transmission. Transmission is considered to be more common through prolonged exposure.
The acute phase of Chagas disease consists of mild, nonspecific infectious symptoms lasting 4 to 8 weeks and is often undiagnosed. The chronic phase results in a lifelong infection if not treated. Many patients may remain asymptomatic, but Chagas cardiomyopathy results in 20% to 30% of patients. This is mediated by an inflammatory immune response and progresses to dilated cardiomyopathy and congestive heart failure. Another less common manifestation of chronic Chagas disease affects the esophagus or colon and can lead to esophageal reflux, weight loss, aspiration and sometimes megacolon.
The FDA has not approved any drugs for the treatment of Chagas disease. However, two medications, nifurtimox and benznidazole, have been proven effective and can be obtained from the CDC under investigational protocols. The process involves a physician confirming the diagnosis of a patient with two positive tests, followed by a call to the CDC to discuss whether the patient meets eligibility for inclusion. If the joint decision is made that the patient is eligible, the physician must apply to be a subinvestigator, and the CDC will provide the medication free of charge.
Benznidazole (3-10 mg/kg/day for 30-90 days) is considered first-line treatment over nifurtimox (8-10 mg/kg/day in four divided doses for 120 days) because it has a better side-effect profile and has more evidence for efficacy. It is a nitroimidazole derivative, which inhibits protein and ribonucleic acid synthesis in T. cruzi cells. Common adverse effects include mild rash and reversible, dose-dependent peripheral neuropathy. Nifurtimox, a 5-nitrofuran derivative, works by reducing reactive radicals that accumulate to cytotoxic levels in T. cruzi, leading to membrane injury, enzyme inactivation, DNA damage, and mutagenesis. It commonly causes nausea, vomiting, vertigo and rash.
Africa — schistosomiasis
Schistosomiasis, sometimes referred to as “snail fever,” is a parasitic disease found mainly in those living near bodies of water that are contaminated with freshwater snails carrying schistosomes. More than 90% of the world’s 207 million cases occur in sub-Saharan Africa. The disease burden is approximately 1.6 million to 4.2 million DALYs.
Schistosomiasis is caused by blood flukes, a type of flatworm whose larvae emerge from their snail hosts until they contact a human host and penetrate the skin. Once in the body, eggs are produced and often settle in the urinary tract, where they cause chronic irritation and inflammation. This results in hyperplasia, sometimes leading to renal failure or bladder cancer. Schistosomiasis can also manifest in the form of genital ulcers, bloody diarrhea or liver dysfunction.
The treatment of choice for schistosomiasis is a 1-day course of Biltricide (praziquantel, Bayer Healthcare; 25 mg/kg orally three times over 1 day), which exhibits a cure rate of over 85% and decreases egg burden in those who are not cured. Praziquantel depletes the parasite’s intracellular calcium, which causes massive contraction and paralysis of its musculature, creating blebs in the membrane that burst and disintegrate. This medication is most effective against the adult worm, so it is preferentially given 6 to 8 weeks post-exposure. Common adverse effects include nausea, dizziness and fever. The average cost of treatment is approximately 20 cents to 30 cents.
Helminth infections, Chagas disease and schistosomiasis are just a few of many NTDs that affect millions of people in developing countries around the world. Despite their high disease burdens, in general, these debilitating disease states can be treated easily and inexpensively by pharmacologic means.
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- For more information:
- Rachel S. Bacher, PharmD, is a PGY1 pharmacy resident at Denver Health Medical Center.
- Katherine C. Shihadeh, PharmD, is a clinical pharmacy specialist in infectious diseases at Denver Health Medical Center. Shihadeh can be reached at email@example.com.
Disclosures: Bacher and Shihadeh report no relevant financial disclosures.