Parasitic Infections Among Immigrants and Immunodeficient Patients

Tsieh Sun, M.D.

          I have selected these two groups of patients for my presentation because most parasitic infections are detected in these groups of people.

 The first parasite I want to introduce to you is Ascaris lumbricoides. I am quite sure everybody knows this worm very well because it is the largest round worm in humans. Unlike humans, the female parasites are generally larger than the male parasites. Stool examination may not show any eggs if only male worms or a single female worm is present. The patient usually have no or mild clinical symptoms mainly GI symptoms. The most severe complication is due to intestinal or biliary obstruction. The life span of this worm is between 6 months and 1 year, so that infection is self limited.

 The second common parasite is hookworm. There are two major species of hookworm, the Ancylostoma and the Necator. Their eggs are indistinguishable. Infection is due to the penetration of the filariform larva into the skin of the host. Therefore the earliest symptom is called creeping eruption. However, most patients may not notice it and they are asymptomatic until they become anemic. Anemia is due to the adult worm which can suck 0.04 to 0.30 ml of blood a day. So that in mild infection, the patient may lose 3 ml a day, while in severe infection, the patient may lose as much as 100 ml a day.

 The third parasite is usually not diagnosed by stool examination. It causes itching anus because the female worm crawls out to the perianal region to lay eggs at night. As a result, the patient, usually children, may have secondary infection or dermatitis because of scratching. The diagnostic technique is the use of a Scotch tape swab to make a smear on the perianal region at night or early morning.  The Scotch tape is then stretched on a glass slide for microscopic examination. You can usually see the eggs with characteristic asymmetric configuration and a larva inside. Occasionally, you may even see a female worm.

About twenty five years ago, a Cornell student named Ken Mott, who did a survey in New York Chinatown, paying one dollar for a stool specimen. He found that the most common parasite was Clonorchis sinensis. He later became a tropical medicine expert and now is the chief of parasitology division in the WHO heatquarters in Geneva. I went to Canton, China 15 years ago and found that there were still many patients with hepatomegaly due to clonorchiasis. When I visited the fishing village, the answer was clear. The fishman built toilets at the shore of the fish pond, with the idea that the feces may serve as the food source for the fish. It is econmonically sound but then if a patient uses the toilet, his feces may contaminate the fish pond. The fish pond has snail and fish, so that the life cycle of Clonorchis can be completed conveniently. Clonorchis has a life span of 25-30 years, so that the immigrants may carry the infection to the United States. Of course, they cannot transmit the disease, because there is no suitable snail host in this country. However, the patients may have clinical symptoms after a long time infection. The most common manifestation is recurrent pyogenic cholangitis. Fortunately, this parasitic disease is now curable with a drug called Praziquentel.

 The most severe parasitic infection in China is shistosomiasis. Here is an egg of Schistosoma japonicum, the species endemic in China. However, we see more cases infected with Schistosoma mansoni in the United States, because this parasitic infection is endemic in South America, particularly Puerto Rico. The infection is cause by the cercaria which penetrates human skin and go to the mesenteric vein. The eggs may travel to the liver and cause portal fibrosis. Here are two patients with ascites, one of them shows prominent umbilical hernia, another one shows varicosis. The colon biopsy in a Puerto Rican shows the characteristic egg with a prominent lateral spine.

A less severe parasitic infection is taeniasis. There are two major species of Taenia: T. solium, or pork tapeworm, and T. saginata, or beef tapeworm. They are contracted by eating raw port or raw beef, respectively. To distinguish of T.solium from T.saginata is important because T.solium can cause cysticercosis. Morphologically, T.solium has less than 10 uterine branches and T.saginata has more than 15 branches. They have more than 1000 proglottids. In the old days, parasitologists have to search the scolex and the neck segment painstakingly in the stool after the worm is expelled. However, with Praziquantel treatment, the entire worm is disintegrated and the search becomes unnecessary. Patients with adult worm in the intestine may ingest the eggs due to reverse peristalsis of the proglottids into the stomach, but most likely they swallow eggs form contaminated water or food. The ingestion of eggs has a more severe consequence than eating raw pork, because it causes cysticercosis. Most cases of cysticercosis occur in the brain, which lead to seizures, such as Jacksonian epilepsy. Cysticercosis can be diagnosed by demonstrating the scolex in a biopsy as seen in this unusual case of myocardial infection.

 Marlaria is one of the most important protozoal infections in terms of morbidity and mortality. However, in the United States, endogenous outbreaks of malaria have been brought under control, most recent cases are immigrants. Although most malaria cases are due to P. vivax or P. falciparum, P. malariae infection is most relevant in terms of transmission through blood donation, because this parasite can persist in asymptomatic carriers for as long as 47 years. P. vivax and P. ovale are believed to die out within 3-4 years after the acute attack, and P. falciparum rarely persists in the blood beyond 1 year. Besides the malarial paroxysm, the major clinical signs for malaria is splenomegaly. The pigmented spleen and liver as seen in this picture is due to the deposition of the malarial pigment, hemozoin. The most severe clinical implication is cerebral malaria, which is invariably due to P. falciparum infection and is frequently fatal if not treated in time. The second fatal complication is renal failure, clinically referred to as blackwater fever.

 The next disease is commonly seen in both immigrants and immunodeficient patients. Strongyloides stercoralis is the only round worm that only larvae are seen in the stool specimens. The absence of eggs in stool is because they are hatched rapidly in the intestine of the host as demonstrated in this endoscopic aspirate. The rhabdatiform larvae are generally detected. If many filariform larvae are found, it indicates hyperinfection, which is seen in immunodeficient patients. The filariform larvae can penetrate the intestinal wall and migrate to the lungs or to the brain, the later frequently is the cause of death. Therefore, before cancer patients receiving chemotherapy, stool examination should be performed to check if Strongyloides parasite is present. If the filariform larva only penetrates the perianal skin, it may be presented as long-standing cutaneous infection, known as larva currens. In 1980, a few former prisoners of war were found to have this form, contracted during the second world war. 

 The leading cause of death in HIV infected patients is pneumocystosis. It is usually presented as pulmonary infection. However, because of the frequent use of aerosolized pentamidine for prophylaxis, extrapulmonary pneumocytosis are more frequently seen. This is frequently a challenge for the pathologists to make the diagnosis. Illustrated here are a case of hepatic granuloma and a case of splenic pneumocystosis. The later was originally considered as lymphoma or metastatic carcinoma.

 Toxoplasmosis is the second common protozoal infection that may lead to death of the patient, because it usually involves the brain. Many cases were first diagnosed by a CT scan showing the ring enhancing lesions. Autopsy frequently demonstrate the lesion as brain abscess. A touch preparation of the brain and stain with Giemsa stain may facilitate a prompt diagnosis. In immunodeficient patients, serologic tests should be routinely performed to rule out this potentially fatal complication.

After the AIDS outbreak, several intestinal protozoa have been discovered. The first one is cryptosporidiosis. The oocysts of the parasite can be detected in the stool with the modified acid fast stain, the Kinyoun stain. It can also be demonstrated in intestinal biopsy, usually seen in the surface of the intestinal villi or in the lumen of the crypts. In case of doubt, electronic microscopic examination can demonstrate the typical intramembrane, extracytoplasmic organism. Clinical symptoms in this infection is usually protracted diarrhea in immunocompromised patients. AIDS patients with a CD4 cell count lower than 200 cell/ml may also have biliary and respiratory infections. However, this infection may also affect immunocompetant people. In 1989, a large waterborne outbreak in Milwauki affecting 400,000 people.

 The second new protozoan disease is microsporidiosis. Microsporidia belong to the phylum Microspora, but there are eight genera and 13 species of this phylum that are pathogenic to humans. These species have various names but not Microsporidium. These include Enterocytozoon bieneusi, Encephalitozoon intestinalis, Encephalitozoon hellem, Nosema conorii, Nosema corneum, and Pleistophora species. Most species are transmitted through ingestion of the infective spores, but E. hellem is contracted by inhalation and Nosema corneum by invasion of the conjunctiva. Infections are mainly seen in HIV infected patients with extremely low CD4 cell counts. Clinical symptoms may involve multiple systems. Chromotrope-2R modified trichrome stain is used to identified the spores in fecal smears and the Brown and Brenn stain (tissue Gram stain) is the preferred stain for tissue sections. A definitive diagnosis can be established by electron microscopic studies.

The most recent discovery is cyclosporiasis caused by Cyclospora cayetanensis. Its life cycle was partially elucidated in 1996. The first outbreak in the United States was in Chicago during 1990, but the largest outbreak was in 1996 when 14,654 cases were reported from 20 states in USA and two provinces in Canada. It was later found out that the infective source was raspberries imported from Guatemala. Subsquently, fresh basil and baby lettuce were also incriminated as the sources of infection. The clinical symptoms of cyclosporiasis are similar to cryptosporidiosis and isosporiasis. The major distinction is the protracted clinical course. The median duration of diarrhea is 7 weeks. The stain of choice for stool smears is Kinyoun acid-fast stain. Again, a final diagnosis depends on electron microscopic studies.

 The last disease to be presented is lieshmaniasis. This is an ancient disease, but recently it has been found in many immunodeficient patients. Therefore, it is an opportunistic infection. It has visceral and mucocutaneous forms. There are two new forms recognized recently. The first one is called the concurrent HIV infection and leishmaniasis. This form is predominantly visceral leishmaniasis involving the gastrointestinal tract without hepatosplenomegaly. Another form is called viscerotropic leishmaniasis. This form was first discovered in the soldiers returning from Saudi Arabia after the Gulf war. These patients have systemic symptoms, such as low-grade fever, malaise, fatigue and diarrhea, but no hepatosplenomegaly. Leishmania tropica, an organism usually causes cutaneous leishmaniasis, has been isolated from the bone marrow or lymph nodes of these patients.

Reference

Sun T: Parasitic Disorders: Pathology, Diagnosis and Management. Second edition, Baltimore, Williams & Wilkins, 1999.

 (Dr. Sun is Professor of Pathology, University of Colorado. The above lecture was prepared for the 2003 CAMS Annual Scientific Meeting. Because of sudden illness the lecture was not delivered.)