SCHISTOSOMIASIS ( BLOOD FLUKE INFECTION ) : CLINICAL ASPECTS
Within 24 hours of penetrating the skin, a large proportion of the schistosomula die. In S. mansoni and S. haematobium infections, immediate and delayed hypersensitivity to parasitic antigens results in an intensely pruritic papular skin rash that increases in severity with repeated exposures to cercariae. As the viable schistosomula begin their migration to the liver, the rash disappears and the patient experiences fever, headache, and abdominal pain for 1 to 2 weeks.
Note: In the United States, cercariae of avian schistosomes can penetrate human skin and die, producing an intensely pruritic, transient rash known as “swimmers’ itch.” No further disease occurs.
One to two months after primary exposure, patients with severe S. mansoni or S. japon-icum infections may experience the onset of an acute febrile illness that bears a strikingresemblance to serum sickness. The onset of oviposition leads to a state of relative anti-gen excess, the formation of soluble immune complexes, and the deposition of these in the tissues of the host. Indeed, high levels of such complexes have been demonstrated in the peripheral blood and correlate well with the severity of illness. In addition to the fever and chills, patients experience cough, urticaria, arthralgia, lymphadenopathy, splenomegaly, abdominal pain, and diarrhea. Sigmoidoscopic examination reveals an in-flamed colonic mucosa and petechial hemorrhages; occasionally, patients with S. japon-icum infection develop clinical manifestations of encephalitis. Typically, leukocytosis;marked peripheral eosinophilia; and elevated levels of IgM, IgG, and IgE immunoglobu-lins are present. This symptom complex is commonly termed the Katayama syndrome. It is more common and more severe in visitors to endemic areas in whom it may persist for 3 months or more, occasionally resulting in death.
Approximately one half of all deposited eggs reach the lumen of the bowel or bladder and are shed from the body. Those retained induce inflammation and scarring, initiating the fi-nal and most morbid phase of schistosomiasis. Soluble antigens excreted by the eggs stimulate the formation of T lymphocyte – mediated eosinophilic granulomas. Early in the infection, the inflammatory response is vigorous, producing lesions more than 100-fold larger than the inciting egg itself. Obstruction of blood flow is common. With time, the host’s inflammatory response moderates, leading to a significant decrease in granuloma size. Fibroblasts stimulated by factors released by both retained eggs and the granulomas lay down scar tissue, rendering the earlier, granuloma-induced vascular obstruction per-manent. As would be expected, the severity of tissue damage is directly related to the to-tal number of eggs retained.
In S. haematobium infection, the bladder mucosa becomes thickened, papillated, and ulcerated. Hematuria and dysuria result; repeated hemorrhages produce anemia. In severe infections the muscular layers of the bladder are involved, with loss of bladder capacity and contractibility. Vesicoureteral reflux, ureteral obstruction, and hydronephrosis may follow. Progressive obstruction leads to renal failure and uremia. Calcification of the bladder wall is occasionally seen, and approximately 10% of patients harbor urinary tract calculi. Secondary bacterial infections are common. Chronic Salmonella bacteriuria with recurrent bouts of bacteremia have been reported from Egypt. In the same country, blad-der carcinoma is frequently seen as a late complication of disease.
In S. mansoni and S. japonicum infections, the bowel mucosa is congested, thickened, and ulcerated. Polyposis has been reported from Egypt but nowhere else. Patients experi-ence abdominal pain, diarrhea, and blood in the stool. Eggs deposited in the larger intestinal veins may be carried by the portal blood flow back to the liver, where they lodge in the presinusoidal capillaries. The resulting inflammatory reaction leads to the development of periportal fibrosis and hepatic enlargement. The frequency and severity with which the liver is involved are genetically determined and associated with the human leukocyte anti-gen (HLA) type of the patient. In most cases, liver function is well preserved. Infected in-dividuals who subsequently acquire hepatitis B or C viruses develop chronic active hepatitis more frequently than those free of schistosomes. The presinusoidal obstruction to blood flow can result in the serious manifestations of portal obstruction. Eggs carried around the liver in the portosystemic collateral vessels may lodge in the small pulmonary arterioles, where they produce interstitial scarring, pulmonary hypertension, and right ventricular failure. Immune complexes shunted to the systemic circulation may induce glomerulonephritis. Occasionally, eggs may be deposited in the central nervous system, where they may cause epilepsy or paraplegia.
Some differences between the clinical presentation of schistosomiasis mansoni and that of schistosomiasis japonicum have been noted. Manifestations of the latter disease typically occur earlier in the course of the infection and tend to be more severe. When in-volvement of the central nervous system develops, it is more likely to occur in the brain than the spinal cord. On the other hand, immune complex nephropathy and recurrent Sal-monella bacteremia are more likely to be seen in hepatosplenic S. mansoniinfections.The latter phenomenon is apparently related to the ability of Salmonella to parasitize the gut and integument of the adult fluke, providing a persistent bacterial focus within the portal system of the infected patient. This focus cannot be eradicated without treatment of the schistosomal infection.
Definitive diagnosis requires the recovery of the characteristic eggs in urine, stool, or biopsy specimens. In S. haematobium infections, eggs are most numerous in urine sam-ples obtained at midday. When examination of the sediment yields negative results, eggs may sometimes be recovered by filtering the urine through a membrane filter. Cystoscopy with biopsy of the bladder mucosa may be required for the diagnosis of mild infection. Eggs of S. mansoni and S. japonicum are passed in the stool. Concentration techniques such as formalin – ether or gravity sedimentation are necessary when the ova are scanty. Results of rectal biopsy may be positive when those of repeated stool examinations are negative.
Because dead eggs may persist in tissue for a long time after the death of the adult worms, active infection is confirmed only if the eggs are shown to be viable. This confir-mation may be obtained by observing the eggs microscopically for movement of flame cell cilia or by hatching them in water. Quantitation of egg output is useful in estimating the severity of infection and in following response to treatment.
Conventional serologic tests detect circulating antibodies with sensitivities exceeding 90% but cannot distinguish active from inactive infection. Recently introduced enzyme immunoassay (EIA)–based reagent strip (dipstick) tests capable of detecting circulating, genus-specific, adult-worm antigens in blood and urine are rapid, simple and sensitive. They are particularly helpful in the diagnosis of the Katayama syndrome in individuals re-turning from endemic areas. Moreover, because antigen levels drop rapidly after successful therapy, these tests may prove helpful in distinguishing active from inactive disease.
No specific therapy is available for the treatment of schistosomal dermatitis or the Katayama syndrome. Antihistamines and corticosteroids may be helpful in ameliorating their more severe manifestations. In the late stage of schistosomiasis, therapy is directed at interrupting egg deposition by killing or sterilizing the adult worms. Because the sever-ity of clinical and pathologic manifestations is related to the intensity of infection, ther-apy of long-term residents of endemic areas is often reserved for patients with moderate or severe active infections.
Several anthelmintic agents may be used. Praziquantel, which is active against all three species of schistosomes, is the agent of choice. Unfortunately, several recent reports have suggested increased resistance to this single-dose oral agent in areas where it has been used in mass therapy programs. S. mansoni infections acquired in such areas may be treated with oxamniquine. Use of this agent is contraindicated in pregnancy.
It has proved both difficult and expensive to control this deadly disease. Programs aimed at interrupting transmission of the parasite by the provision of pure water supplies and the sanitary disposal of human feces are often beyond the economic reach of the nations most seriously affected. Similarly, measures to deny snails access to newly irrigated lands are expensive. Chemical molluscicides have been shown effective in limited trials, but have been less successful when used over large areas for prolonged periods. Mass therapy of the infected human population has, until recently, been severely limited by the toxicity of effective agents. Newer agents, particularly praziquantel, has proven more suitable for this purpose. Nevertheless, discontinuation of mass therapy, in the absence of other control measures, can result in a rapid rebound of active disease. At present, programs that have incorporated all of these control measures have been the most successful.
Currently, there is intense interest in developing a vaccine suitable for human use. A vaccine made from irradiated S. bovis cercariae, developed for cattle, appears to confer a significant degree of protection against infection. Although the use of a similar live accine would not be suitable for human populations, the success of the animal vaccine has
provided clues to potential immunoprotective mechanisms in human schistosomiasis. Monoclonal antibodies have been used to identify a number of schistosomula and adult antigens thought to be capable of inducing protective immunity; the World Health Organization has selected six of these for further evaluation.
Copyright © 2018-2020 BrainKart.com; All Rights Reserved. Developed by Therithal info, Chennai.