Neglected tropical diseases: Fascioliasis

Fascioliasis belongs to the group of foodborne trematode infections and is a zoonosis, meaning an animal infection that may be transmitted to humans. It is caused by two species of parasitic flatworms or trematodes that mainly affect the liver.

The two species of trematodes that cause fascioliasis (Fasciola hepatica and F. gigantica) are leaf-shaped worms, large enough to be visible to the naked eye (adult F. hepatica measure 20–30 mm x 13 mm; adult F. gigantica measure 25–75 mm x 12 mm). The disease they both cause is similar.

Until recently, human cases occurred occasionally but are now increasingly reported from Europe, the Americas and Oceania (where only F. hepatica is transmitted) and from Africa and Asia (where the two species overlap). WHO estimates that at least 2.4 million people are infected in more than 75 countries worldwide, with several million at risk. No continent is free from fascioliasis, and it is likely that where animal cases are reported, human cases also exist.

The epidemiological pattern of fascioliasis is quite varied: the infection usually has a hypo-endemic pattern, with low and stable levels of prevalence among a defined population. Sporadic outbreaks may occur among such populations: these are usually related to sudden changes in climatic conditions that boost the life-cycle of either the parasite or the snail, or both. Scientists have also found that the epidemiology of fascioliasis is strictly linked to the geographical and environmental characteristics of the area where transmission occurs, and different patterns can be distinguished: this suggests that fascioliasis may adapt to different ecological niches.

In Africa and Asia, where both F. hepatica and F. gigantica are present, mixed infections are possible. In Asia, hybridization among the two species occurring in co-infected humans or animals has been described. The offspring resulting from such hybridization is characterized by intermediate morphological characteristics between the two species as well as by different ploidies (diploid, triploid, and mixoploid); such worms are frequently non-fertile.

The life-cycle of fascioliasis is complex. It involves a final host (where the adult worm lives), an intermediate host (where the larval stages of the worm develop) and a carrier (entailing suitable aquatic plants).

The process starts when infected animals (cattle, sheep, buffaloes, donkeys and pigs but also horses, goats, dromedaries, camels, llamas and other herbivores) defecate in fresh-water sources. Since the worm lives in the bile ducts of such animals, its eggs are evacuated in faeces and hatch into larvae that lodge in a particular type of water snail (the intermediate host).

Once in the snail, the larvae reproduce and eventually release more larvae into the water. These larvae swim to nearby aquatic or semi-aquatic plants, where they attach to the leaves and stems and form small cysts (metacercariae). When the plants with the small cysts attached are ingested, they act as carriers of the infection. Watercress and water-mint are good plants for transmitting fascioliasis, but encysted larvae may also be found on many other salad vegetables. Ingestion of free metacercariae floating on water (possibly detached from carrier plants) may also be a possible mode of transmission.

Transmission of the infection in the environment is usually perpetuated by animals. Humans do not typically contribute to the parasite's life-cycle; they are only occasionally infected after failure to observe basic hygiene measures (consuming larvae-contaminated uncooked vegetables or drinking larvae-infected water). Moreover, Fasciola worms are not well adapted to humans and, in some cases, fail to develop into mature adult worms and produce eggs.

In some areas, transmission to humans is constant and intense, and a geographical aggregation of cases may be observed. This pattern is possibly explained by a human-to-snail-to-plant-to-human transmission cycle, without the involvement of any animal. Indigenous communities in the South American highlands represent well known "hot spots" for fascioliasis: here, highly prevalent infection has been reported and may be explained by such transmission pathway.

Where it occurs sporadically, fascioliasis affects people from all age-groups, and there is no specific risk group. Where the infection is highly endemic, the prevalence and intensity of infection tend to peak in school-age children. People living in rural areas are typically more likely to become infected; however, cases may occur anywhere and can follow the trade routes of the carrier plants, which are part of the usual diet in many countries.

After the larvae are ingested with contaminated food or water, a symptomless incubation period starts, lasting for a few days to a few months. This is followed by an acute and a chronic clinical phase.

• Acute phase. The acute phase, lasting 2-4 months, begins when the immature worms penetrate the intestinal wall and the peritoneum, the protective membrane surrounding the internal organs . From here, they puncture the liver's surface and eat their way through its tissues until they reach the bile ducts. This invasion kills the liver's cells and causes intense internal bleeding. Typical symptoms include fever, nausea, a swollen liver, skin rashes and extreme abdominal pain.
• Chronic phase. The chronic phase begins when the worms reach the bile ducts, where they mature and start producing eggs. These eggs are released into the bile and reach the intestine, where they are evacuated in faeces, thereby completing the transmission cycle. Symptoms include intermittent pain, jaundice and anaemia. Pancreatitis, gallstones and bacterial super-infections may also occur. Patients with chronic infections experience hardening of the liver (fibrosis) as a result of the long-term inflammation.

Diagnosis of fascioliasis may be suspected on the basis of the clinical picture, on the anamnestic recall of consuming raw vegetables, on the detection of eosinophilia (blood eosinophil count >500–1000 per μl of blood), and on typical findings at ultrasound or computed tomography scans. Confirmation relies on different types of diagnostic techniques.

• parasitological techniques to detect Fasciola eggs in stool samples; their cost and sensitivity may vary according to the type used; they can only be employed in the chronic phase; some of them allow quantifying intensity of infection (therefore estimating the severity of the infection);
• immunological techniques to detect worm-specific antibodies in serum samples or worm-specific antigens in serum or stool samples; they are usually more sensitive than the commonly used parasitological techniques; detection of antibodies does not allow distinguishing between current, recent and past infections; their ability to quantify intensity of infection is disputed; stool tests are easier to perform and reportedly better accepted by individuals in endemic areas;
• molecular techniques such as the polymerase chain reaction are still at experimental stage.

Triclabendazole, the only medicine recommended by WHO against fascioliasis, is active against both immature and adult parasites, and may therefore be employed during the acute and chronic phases. Cure rates are high , while adverse reactions following treatment are usually temporary and mild. The recommended regimen is 10 mg/kg body weight administered as a single dose in both clinical practice and preventive chemotherapy interventions. In clinical practice, where treatment failure occurs, the dosage may be increased to 20 mg/kg body weight in two divided doses 12-24 hours apart.

From a public health perspective, control of human fascioliasis mainly relies on timely treatment with triclabendazole, a measure that cures infected individuals and prevents development of advanced morbidity.

In areas where cases of fascioliasis occur sporadically, clinical case management of individuals reporting to their local hospital is sufficient to tackle the disease. Diagnostic protocols adapted to the socioeconomic environment of endemic areas should be adopted, and triclabendazole should be made available to peripheral health centres with the aim of increasing access to treatment.

In communities where cases are clustered, possibilities for implementing large-scale anthelminthic distribution (preventive chemotherapy) in subdistricts, villages or communities where the cluster occurs should be considered. Preventive chemotherapy in such foci can be implemented as targeted treatment of school-age children (5–14 years), usually the population with the highest prevalence and intensity of infection, or as universal treatment (mass drug administration, or MDA) of the entire resident population. In such areas, individual-level diagnosis is not necessary; decisions about treatment are rather based on an assessment of the public health relevance of the disease.

Timely treatment with triclabendazole is the quickest way to control morbidity associated with fascioliasis. However, treatment should be complemented, where feasible, by implementing measures that aim to reduce transmission rates, including:

• information, education and communication, promoting cultivation of vegetables in water free from faecal pollution and thorough cooking of vegetables before consumption;
• veterinary public health measures, including treating domestic animals and enforcing separation between husbandry and humans;
• environmental measures such as containment of the snail intermediate hosts and drainage of grazing lands.