53 Favism
Fasciolopsiasis is caused by the giant intestinal fluke, Fasciolopsis buski. Discovered in 1843, the organism occurs in China, Korea, Southeast Asia, and parts of India and Indonesia.
The adult worm, which has a life-span of only 6 months, attaches itself to the wall of the small intestine of humans. Pigs and dogs can also be infected, and sometimes are important reservoir hosts. Eggs produced by the hermaphroditic adults pass out in the feces and, if they reach fresh water, produce motile larvae that penetrate into the tissues of certain planorbid snails. After two generations of reproduction, another motile form leaves the snail, finds a plant like the water chestnut, water caltrop, or water bamboo, and encysts on it. Humans become infected with cysts by peeling raw fruits of plants with their teeth or eating them uncooked. The disease can become very prevalent in areas where these plants are cultivated with human feces as fertilizer.Mild infections are often asymptomatic, but flukes can irritate and even ulcerate the intestinal mucosa. Abdominal pain, diarrhea, anemia, and fluid accumulation in the abdomen are common symptoms. Extreme cases can be fatal. Diagnosis is made by discovery of the eggs in the feces. Drug therapy is usually effective. Prevention includes better rural sanitation and control of swine reservoir hosts. Cooking vegetables would also be very beneficial, but drastic changes in long-established culinary habits are unlikely.
K. David Patterson
Bibliography
Kean, B. H., Kenneth E. Mott, and Adair J. Russell, eds. 1978. Tropical medicine and parasitology: Classic investigations, Vol. II, 584-99. Ithaca and London.
Sadun, E. H., and C. Maiphoom. 1953. Studies on the epidemiology of the human intestinal fluke. Fasciolop- sis buski (Lankester) in central Thailand. American Journal of Tropical Medicine and Hygiene 2:1070—84.
Favism is an acute hemolytic reaction triggered by exposure either to fava beans (Vicia faba) or to certain drugs (e.g., sulfa-based antibiotics and the antimalarial primaquine) in people with an inherited deficiency of the enzyme glucose-6 -phosphate dehydrogenase (G6PD). In favism, the patient can suffer from destruction of red blood cells, severe anemia, and possibly death. There are two necessary conditions for the disease: (1) genetic inheritance of the “Mediterranean” variant of the abnormal gene trait for G6PD deficiency; and (2) ingestion of fava beans, usually fresh, or exposure to some drugs. The bean is a dietary staple in areas where favism is reported. Only an estimated 20 percent of those with the genetic trait for G6PD are likely to experience episodes of favism. Under modem medical conditions the hemolytic anemia caused by favism is only rarely fatal. Strong evidence suggests that both the gene for G6PD deficiency and the cultural practice of fava bean consumption are evolutionarily adaptive traits that protect against death from all types of malaria. Favism, then, could be described as a negative outcome of the interaction of the positive adaptive qualities of both the gene and the bean.Distribution and Incidence
Favism is found primarily in the Mediterranean and Middle East regions where fava beans are a staple food and the Mediterranean variant of G6PD deficiency gene is relatively common. Mark Belsey (1973) reports that it is frequently encountered in Greece, Sardinia, Italy, Cyprus, Egypt, Lebanon, Israel, Iran, Iraq, Algeria, and Bulgaria, and is particularly common among Sephardic Jews. Favism has also been sporadically reported in China, Germany, France, Poland, Romania, Yugoslavia, Great Britain, and the United States. The disease is considered a serious public health problem in contemporary Greece (Trakas 1981).
The incidence of favism has been estimated for few areas. The most complete study in two Iranian provinces on the Caspian coast found an annual incidence that ranged between 0.65 and 6.39 cases per 10,000 population, with some areas reporting incidences as high as 9.27 cases per 10,000 (Lapeys- sonnie and Keyhan 1966).
William Crosby (1956), on the other hand, estimated 50 cases per 10,000 for Sardinia. Mortality is generally rare, with rates ranging between 1 and 4 percent of the reported cases.Epidemiology and Etiology
Favism is generally a pediatric illness in which the majority of victims are between 2 and 5 years of age, although cases as young as 6 months and as old as 65 years have been reliably reported. The disease has a marked seasonal cycle corresponding to the harvest of fresh fava beans, a 4- to 5-week period between April and July, although in areas where the bean is dried for later consumption, cases can occur all year. There is evidence that the toxic factor that induces the favism crisis has four characteristics:
1. It is located in the skin of the bean.
2. It is heat stable.
3. It is able to enter the breast milk of lactating women.
4. Its toxicity decreases when the beans are dried and the skin changes color.
Active biochemical agents in the skin of the bean - the pyrimidine oxidant compounds vicine, isoura- mil, divicine, and L-dopa - are probably responsible. These same biochemical agents are believed to provide some protection against malaria for people with normal genotypes when they eat fresh fava beans. Although it is widely believed that inhalation of pollen of the V. faba can trigger cases of favism, recent studies indicate that this is not true.
Boys are much more likely to suffer favism attacks than girls, with male/female case ratios varying from 2.1:1 to 2.7:1. The reason for the increased risk for males is that G6PD deficiency is a sex-linked trait; the gene is located on the X chromosome. Only carrier males (hemizygotes) and homozygous females can suffer from favism. Heterozygote females appear to be at an evolutionary advantage because they have no risk of favism and also enjoy a degree of protection against the malaria protozoa Plasmodium.
The G6PD enzyme, found in all tissues, plays important housekeeping functions in red blood cell metabolism.
The cells of enzyme-deficient individuals tend to become oxidant-sensitive, and any exogenous sources of increased oxidants (malaria parasites, antimalaria drugs, or fava beans) can result in the lysis (explosion) of the cell (Katz and Schall 1979). In enzyme-deficient individuals, this process can result in either favism or protection from a severe malaria infection, depending on the context.The geographic distribution of the many varieties of G6PD-deficient genes has been exceptionally well studied by population biologists. Over 200 varieties of the gene have been identified. Both population genetic data and in vitro studies indicate that the distribution of these genes is correlated with the historical distribution of malaria. Favism occurs in only a small proportion of individuals with the Mediterranean variant of G6PD deficiency, and within that population it follows familial lines. It has been recently recognized that there is substantial genetic variation within the Mediterranean variant (Luz- zatto and Battistuzzi 1985).
Clinical Manifestations
Favism is characterized by five general Sjnnptoms: weakness, fatigue, pallor, jaundice, and hemoglobinuria (blood in the urine). The anemia caused by hemolysis is severe. In a clinical study in Greece, one- third of favism cases had hemocrit levels below 4 grams of hemoglobin per 100 milliliters of blood (Katt- amis, Kyriazakov, and Chidas 1969). In populations at risk, this set of symptoms is recognized as a distinct illness, often referred to as “fava bean poisoning.”
History and Geography
The historical puzzle of favism is that peoples of Mediterranean and Middle Eastern societies would continue to eat a food that regularly causes illness and even death. From an evolutionary perspective, both fava bean consumption and G6PD deficiency appear to be retained in populations because they provide some protection from malaria. The correlation between the geographic distribution of these traits and malaria is one line of evidence for this relationship.
Fava bean cultivation dates back to the Neolithic period in areas that have favism. Ancient Indo-European culture, and particularly Greek culture, placed remarkable emphasis on the symbolic rather than nutritional qualities of the fava bean. Alfred Andrews (1949) argues that “no plant or animal known to the Indo-Europeans has produced a more luxuriant growth of benefits than fava beans.”Fava beans have had three primary Sjnnbolic associations: the life principle, the souls of the dead, and the generative powers of male sexuality, and they are Iitualistically eaten at certain times of the year, a practice that continues in European folk cultures. On the other hand, taboos against the consumption of fava beans for certain groups, particularly priests, have been reported in ancient Greece, Egypt, India, and Africa. The most famous case of such a taboo was among the Pjfthagoreans, who had the maxim, “It is an equal crime to eat beans and the heads of one’s parents.” Although many historical analyses for this taboo have been suggested, a medically informed hypothesis based on the risk of favism appears most reasonable (Brumbaugh and Schwartz 1979).
In the history of medicine, the early clinical descriptions by the Italian physician Antonio Gasbar- rini were a landmark for the diagnosis and treatment of favism attacks of varying severity. Within the tradition of Galenic medicine, treatment, although not always for favism attacks, emphasized the reinforcement of the blood with red wine among other things. Understanding the evolutionary history of favism has been a recent development that paralleled the discovery of the malaria connection with other genetic polymorphisms like thalassemia and sickle-cell anemia. The analytical connection with G6PD deficiency was first suggested in 1956, by Crosby, and the development of a genetic screening technique for the trait created a wealth of population genetic data during the 1960s. Such data on genetic markers in populations - for example, the variants of G6PD deficiency - have a potential for historical reconstruction of population movements and culture contact (Brown 1981).
Peter J. Brown
Bibliography
Andrews, Alfred C. 1949. The bean and Indo-European totemism. American Anthropologist 51: 274-92.
Belsey, Mark A. 1973. The epidemiology of favism. Bulletin of the World Health Organization 48: 1-13.
Brown, Peter J. 1981. New considerations on the distribution of thalassemia, glucose-6-phosphate dehydrogenase deficiency and malaria in Sardinia. Human Biology 53: 367-82.
Brumbaugh, Robert, and Jessica Schwartz. 1979. Pythagoras and beans: A medical explanation. Classical World 73: 421-2.
Crosby, William H. 1956. Favism in Sardinia. Blood 11: 91-2.
Kattamis, C. A., M. Kyriazakov, and S. Chidas. 1969. Favism: Clinical and biochemical data. Journal of Medical Genetics 6: 34—41.
Katz, Solomon, and Jean Schall. 1979. Fava bean consumption and biocultural evolution. Medical Anthropology 3: 459-76.
Lapeyssonnie, L., and R. Keyhan. 1966. Favism in the Caspian littoral area. In Proceedings of the first seminar on favism in Iran. Teheran.
Luzzatto, L. 1969. Glucose-6-phosphate dehydrogenase deficient red cells: Resistance to infection by malarial parasites. Science 164: 839—42.
Luzzatto, L., and G. Battistuzzi. 1985. Glucose-6-phos- phate dehydrogenase. Advances in Human Genetics 14: 217-327.
Trakas, Deanna. 1981. Favism and G6PD deficiency in Rhodes, Greece. Ph.D. thesis, Michigan State University.