CASE 45 INTRODUCTION An 8-year-old boy, a child of immigrants from El Salvador who moved to the southwestern United States three months ago, presents to the emergency room with abdominal pain and vomiting. He was ill for a day, but his symptoms have worsened in the past few hours, and his parents became panicked when they saw a worm in his vomitus. He has no significant medical history and has taken no medications. On examination, he appears very ill and in obvious pain. His temperature is 37.7°C (99.9°F), his pulse is 110 beats per minute, and his blood pressure is normal. His mucous membranes are dry, but his head and neck exam is otherwise normal. He is tachycardiac, and his lungs are clear. His abdomen has high-pitched, tinkling bowel sounds on auscultation and is diffusely tender to palpation. There is, however, no rebound tenderness. An abdominal x-ray shows air-fluid levels consistent with a small bowel obstruction. His parents saved and brought in the worm that he vomited. It is 5 inches long and reddish-yellow in color. · What organism is most likely responsible for the patient's illness? · How did the patient become infected? ANSWERS TO CASE 45: Ascaris · Most likely organism responsible for the patient's illness: The nematode, Ascaris lumbricoides. · How did the patient become infected: By ingesting eggs of the parasite that have matured to contain a larval form. Summary: An 8-year-old boy with a small bowel obstruction and who vomited a worm. CLINICAL CORRELATION Introduction Infections with Ascaris are frequently asymptomatic or may be accompanied by numerous symptoms. The pathology that underlies symptoms is conditioned by the number of worms harbored and the sequential location of larvae in the lungs and adult worms in the intestine. Larvae released when ingested eggs hatch make a so-called "heart-lung circuit" in which they are carried via the blood to various tissues (Figure 45-1). Migrating larvae elicit eosinophilia and granulomatous lesions. During the larval migration stage, symptoms are associated mainly with larvae present in the liver and lungs. Larvae that reach the lungs may cause pneumonitis. Patients may cough up exudates that are blood-tinged and contain polymorphonuclear leukocytes, mainly eosinophils. Fever may accompany pneumonitis, which disappears when the larvae move to the small intestine. Ascaris is highly allergenic, stimulating inordinately high IgE levels. Therefore, pneumonitis may be especially severe in individuals who are sensitized by a prior infection and encounter a challenge or secondary infection. Increased severity is caused by immune-mediated inflammation. Gastrointestinal (GI) symptoms depend on the number and location of adult worms. Light infection may cause GI upset, colic, and loss of appetite and impair digestion or absorption of nutrients. In heavy infections, the adult worms may ball up in the small intestine, resulting in physical obstruction, a rare but serious occurrence. From their location in the small intestine, adult worms infrequently migrate down and out of the anus or up and through the mouth or nose. Adult worms may cause symptoms by migrating to obstruct the bile ducts or penetrate the gallbladder or liver. Adult worms may be seen in the stool or vomitus. Figure 45-1. Life Cycle of Parasitic Nematodes, including Ascaris lumbricoides. With permission from Barron S, ed. Medical microbiology, 4th ed. Galveston: University of Texas Medical Branch, 1996. Approach to Suspected Ascaris Infection Definitions Nematode: A helminth characterized by a cylindrical body and separate sexes, in contrast to cestodes and trematodes that are flatworms and generally hermaphroditic. "Giant intestinal roundworm": common name for Ascaris lumbricoides. Egg (ova), larva, and adult: sequential developmental stages in life cycle of helminths. Larva: preadult or juvenile stage of helminths; nematodes have four larval stages in their life cycle prior to reaching the adult stage. Each stage is preceded by a molt. Objectives 1. Learn the life cycle of A. lumbricoides and the epidemiology and clinical course of infection. 2. Be able to describe three basic aspects of infection: transmission, diagnosis, and treatment/prevention. Discussion Characteristics of Ascaris Ascaris is one of several nematodes that infect the GI tract and, like all of these, develops through egg, larva, and adult stages. Ascaris lumbricoides is very similar in size and life cycle to Ascaris suum, which is found in pigs. If a human ingests eggs of A. suum, the larvae will migrate to the lungs and die, but in the process can cause a serious form of "ascaris pneumonia." Adult worms of this species do not develop in the human intestine. Parasitologists debate the point that there is only one species of Ascaris that infects both pigs and humans. Other ascarids that infect humans are Toxocara canis and Toxocara cati, which are parasites of dogs and cats, respectively. Although humans can become infected by ingesting eggs of these species, neither worm develops to maturity. After hatching in the intestine, Toxocara larvae migrate chronically in visceral tissue, giving rise to the condition termed "visceral larvae migrans." Infection Transmission Typical of nematodes, A. lumbricoides has separate sexes and a life cycle that involves egg, larva, and adult stages. Growth involves four larval stages. Transition from one stage to another and to the adult stage is preceded by a molt or shedding of the cuticle or "skin." A person becomes infected by ingesting eggs that are usually acquired through hand-to-mouth transmission from the soil or via contaminated food or water. Eggs hatch in the duodenum, releasing larvae that penetrate the small intestine to enter the blood stream. Larvae are carried hematogenously to various organs. On reaching the lungs, they penetrate into the alveoli. Larvae reside in the lung for approximately three weeks, growing and advancing to a subsequent larval stage. They then migrate up the bronchi and trachea, where they are then swallowed and returned to the small intestine. In the intestine, larvae develop to the adult stage and reach reproductive maturity in about 2 months. Adults can survive for up to 2 years and grow to 15-35 cm in length. A single female worm lays about 200,000 eggs daily that are passed in the feces. Eggs can survive for years in the soil, tolerating a wide range of temperatures and other environmental variables. Under optimal conditions, eggs reach an infective, larvated stage in 2-3 weeks. Development is arrested at this stage until the egg is ingested. Ascariasis is a chronic disease of the small intestine and can be transmitted as long as adult worms are in the intestine and feces containing ascaris eggs are allowed to contaminate the environment. Ascariasis is more prevalent in tropical climates but is found in temperate regions of the world. It is most common where sanitation is poor and where human feces are used as fertilizer in agricultural practices. Infections occur in all ages but are more common in children. In endemic areas, most of the population has some worm burden. With the exception of pinworm infection, ascariasis is the most common helminthic infection of humans. Diagnosis A presumptive diagnosis may be based on clinical symptoms. However, symptoms are not pathognomonic. The pneumonitis phase of infection cannot be diagnosed as Ascaris-induced because it precedes the intestinal phase by several weeks. Intestinal symptoms are normally absent or mild and, in most cases, go undetected. A definitive diagnosis is based on identifying egg or adult stages. As in this case (Case 45), the first clue of infection may be adult worms that are vomited or passed in a stool. Intestinal obstruction, especially in children, often prompts medical attention. Because of its uniquely large size, an adult A. lumbricoides is unmistakable. The adult females are reddish yellow in color and can measure up to 12-15 inches long (males are generally shorter) and one-fourth of an inch in diameter. Although a definitive diagnosis can be made by identifying adult worms, ascariasis is more commonly diagnosed by identifying eggs in the stool. Both fertile and infertile eggs are passed in the stool. Because female worms pass thousands of eggs daily, diagnosis can be made by direct examination of a stool sample without the need for techniques to concentrate eggs. The eggs are ovoid, measure 45 by 75 um and have a thick transparent inner shell covered by an albuminous coat that is wrinkled and usually stained light brown by bile pigments. Unfertilized eggs are commonly seen in a stool. These are more elongated, measuring 40 by 90 mm. The inside of the unfertilized egg is amorphous instead of containing a well defined single cell of the fertilized egg. Treatment and Prevention Adult worms are the target of several drugs available to treat ascariasis. The drug of choice is mebendazole, a benzimidazole derivative that has a high therapeutic index. The effectiveness of treatment can be assessed by the disappearance of eggs in stool samples and allev2ation of symptoms. In cases of intestinal obstruction, the first action should be directed at ridding the patient of worms through the use of chemotherapeutic agents, such as mebendazole. If the worms can be dislodged the patient may void them in the stool. If the bolus of worms cannot be dislodged, surgery may be an option. If surgery is chosen, it is imperative that the worms be killed or paralyzed with a drug such as piperazine prior to physically removing them from the intestine. The reason for this procedure is that a live, active worm releases an aerosol of eggs through its uterine pore. Eggs are invisible to the naked eye. However, if eggs fall on exposed viscera they elicit granulomatous lesions and adhesions that can lead to severe complications. Preventive measures relate to instructing the patient on how the infection was acquired and on the proper disposal of feces to avoid soil contamination and reinfection. COMPREHENSION QUESTIONS [45.1] A definitive diagnosis of ascariasis can be made by observing which of the following? A. An eosinophilia in a differential white blood cell count. B. Motile larvae in a stool sample. C. Larvae in x-ray of lungs. D. An adult worm passed during a bowel movement. [45.2] Ascariasis is most effectively treated with which of the following drugs? A. Mebendazole B. Metronidazole C. Niclosamide D. Praziquantel [45.3] A person presents to his physician complaining of chronic GI symptoms. A diagnosis of Ascaris lumbricoides was made. Human nematodes infect individuals via different routes. This patient was most likely infected by which of the following? A. Larvae penetrating unprotected skin B. Ingesting larvated eggs C. Eating uncooked pork D. Internal autoinfection ANSWERS [45.1] D. Identification of adult worms passed by an individual can ensure a definitive diagnosis. Although an eosinophilia accompanies ascariasis, this condition can be caused by other infections and by various allergic conditions. Motile larvae in a stool are indicative of infection with Strongyloides stercoralis. Nematode larvae cannot be seen in an x-ray. [45.2] A. Mebendazole is a broad spectrum antihelminthic that is the drug of choice for treating Ascaris and several other intestinal nematodes. Metronidazole is used primarily to treat infections with protozoa, such as Giardia lamblia and Trichomonas vaginalis. Niclosamide is the drug of choice in treating most adult cestode or tapeworm infections. Praziquantel is used to treat infections with blood flukes or schistosomes and can also be used to treat adult tapeworms. [45.3] B. Ascaris is acquired by ingesting infective eggs, as are the whip-worm, Trichuris trichiura, and the pinworm, Enterobius vermicularis. Filariform larvae penetrating unprotected skin is the route by which a person becomes infected by other intestinal nematodes, hookworms and Strongyloides; eating uncooked pork could lead to trichinosis; and internal autoinfection is caused only by Strongyloides. MICROBIOLOGY PEARLS · The fertilized eggs are unsegmented when laid by the female worm. · Mebendazole, one of several available benzimidazole compounds used to treat nematodes, is the drug of choice in treating Ascaris infection. REFERENCES Centers for Disease Control. DPDx. Laboratory identification of parasites of public concern. Ascariasis. Centers for Disease Control and Prevention, 2004. Available online at: http://www.dpd.cdc.gov/dpdx/HTML/Ascariasis.htm Graphic Images of Parasites. Ascaris lumbricoides and ascaris suum (intestinal round worms of humans and pigs). Author, 2004. Available online at: http://www.biosci.ohio-state.edu/~parasite/ascaris.html Medical Letter on Drugs and Therapeutics. Drugs for parasitic infections. New Rochelle, NY: Author, 2002. Available online at: http://www.medletter.com/freedocs/parasitic.pdf ============================ CASE 46 INTRODUCTION A 32-year-old man with known HIV is brought to the hospital with diarrhea. He has had between 15 and 25 watery stools a day for the past 2 weeks. He has had a low grade fever and felt very fatigued, but denies vomiting. He has not passed any blood in his stool. He says that he has lost 8 lb in this time frame. He is on a "triple therapy cocktail" of AZT, 3TC, and a protease inhibitor for his HIV. His last CD4 cell count was 150 cells/mm3. On examination, his temperature is 37.2° C (98.9°F), pulse is 110 beats per minute, blood pressure is 95/75 mmHg, and respiratory rate is 24 breaths per minute. In general, he appears cachectic. His eyes are dry and sunken. His mucous membranes are moist. His cardiovascular exam is notable for tachycardia, and he has orthoscopic changes on sitting up from lying down. His abdomen has hyperactive bowel sounds, but is soft and only mildly tender. His stool is heme negative. A modified acid-fast stained stool sample reveals multiple red and pink, round oocysts. · What is the most likely cause of diarrhea? · How is this infection most commonly acquired? ANSWERS TO CASE 46: Cryptosporidium parvum · Most likely etiologic agent: Cryptosporidium parvum · How is this infection most commonly acquired: Ingestion of oocysts in contaminated water or food or fecal-oral transmission from infected animals or person to person. Summary: A 32-year-old man with HIV and diarrhea. A modified acid-fast stained stool sample reveals multiple red and pink, round oocysts. CLINICAL CORRELATION Introduction Cryptosporidium parvum belongs to a group of protozoans known as coccidians. The infective oocyst is about 3-8 um in diameter. The parasite, on emerging from the oocyst, attaches to the surface of intestinal epithelium where it multiplies both asexually and sexually. The parasite causes changes in mucosa that include crypt hyperplasia and villous atrophy. Associated with its presence in the intestine, and after an incubation period of about 2-12 days, is an acute illness characterized by nausea, abdominal cramps, weight loss, anorexia, malaise, low-grade fever, and diarrhea. The frequency of diarrheal episodes and voluminous fluid loss is often debilitating. During infection there, may be periods in which symptoms are absent. In immunocompetent individuals, the disease will resolve on its own, usually within 7 to 14 days. In immunocompromised hosts, the disease is generally more severe and chronic, sometimes lasting for life. Five to ten percent of patients with AIDS acquire infection with Cryptosporidium. Persistence of infection in HIV-infected individuals is closely associated with CD4 lymphocyte counts of less than 180 cells/mm3. Protracted diarrhea may lead to dehydration, wasting, and death. Severe intestinal distress, usually in immunodeficient individuals, is sometimes associated with pulmonary and tracheal cryptosporidiosis that is associated with coughing and low-grade fever. The strains that infect the intestine and lungs are, to date, indistinguishable. Approach to Suspected Cryptosporidium Infection Definitions Coccidian: The specific taxonomic group of protozoans to which C. parvum belongs. Oocyst: The stage in the life cycle of C. parvum that transmits the disease and is also sought in making a definitive diagnosis. Each oocyst contains four sporozoites. Sporozoite: The stage released from the oocyst following ingestion and which initiates infection. Zoonosis: A disease that is transmitted from lower vertebrate hosts to humans. Acid-fast stain: A type of stain that renders oocysts highly visible in a fecal sample. It is used to support the microscopic diagnosis of the parasite. Objectives 1. Learn the life cycle of Cryptosporidium parvum and the epidemiology and clinical course of cryptosporidiosis, and compare this disease with those caused by related organisms, such as Cyclospora and Isospora. 2. Be able to describe the three basic aspect of infection: transmission, diagnosis, and treatment/prevention. Discussion Characteristics of Cryptosporidium that Impact Transmission Misdiagnosis with cyclosporiasis may be made, in part because clinical symptoms are similar. Protracted, watery diarrhea is the hallmark of infection. Cyclospora cayetanensis, which infects humans, has a worldwide distribution. Another related organism that causes diarrhea in humans is Isospora belli. Cryptosporidium species are ubiquitous, worldwide enteric pathogens of humans and multiple other animal species. Of the many species of the genus, C. parvum is responsible for most clinical disease in humans and other mammals. The life cycle of C. parvum occurs within a single host and, like other coccidian, involves sexual and asexual reproduction. The small intestine is the usual host habitat for Cryptosporidium, where it lives in a unique intraepithelial niche. The life cycle is initiated with the ingestion of oocysts that contain four sporozoites. When oocysts are ingested, they undergo excystation as the outer wall is removed by digestive processes. Sporozoites that are released attach to the host's intestinal epithelial cells and become surrounded by a host-derived membrane, making them intracellular but extracytoplasmic. Sporozoites undergo multiple fission to form meronts that contain multiple merozoites. The merozoites are released to infect other cells. Following another round of asexual division and on release of the second and subsequent generations of merozoites, they penetrate new cells to form gametes. Most gametes undergo enlargement into macrogametes (female). Some become microgametocytes that undergo fission multiple times to form sperm-like microgametes (male). Microgametes leave the microgametocyte and fertilize a macrogamete to form a zygote. The zygote then becomes covered by a wall, forming an oocyst that is highly resistant to chemical and physical changes in the internal and external environment. Sporozoites develop within the oocyst that are sloughed, along with intestinal epithelial cells, and voided in the feces. Because oocysts are passed in the feces in a sporulated stage (i.e., contain sporozoites), they are immediately infective and can retain infectivity for long periods because of their protective wall. In having oocysts that are immediately infective, Cryptosporidium is different from Cyclospora, which has oocysts that require 1-2 weeks to develop to an infective stage. Presumably ingestion of one oocyst can initiate an infection that can be contracted by eating contaminated food or drinking contaminated water. Touching the stool of infected individuals or animals or anything contaminated with feces and then not washing your hands before touching your mouth can also initiate infection. Infection can be transmitted by ingestion of oocysts passed in feces of infected humans or animals. Thus, infection can be transmitted from one person to another or from animals to humans, from eating and drinking food or water contaminated with fecal material or from transfer of oocysts from contaminated material to the mouth or from person-to person. Diagnosis A definitive diagnosis is based on identifying oocysts in a fecal sample. A technique, such as sugar flotation, is used to concentrate the oocysts and acid-fast staining is used to identify them. A fluorescent antibody technique is also available to stain the isolated oocysts, augmenting visualization. Oocysts contain four sporozoites. It is important to make a differential diagnosis with Cyclospora oocysts, which are similar in size but are not sporulated when passed. Cryptosporidium oocysts contain four sporozoites and are about 8 um in diameter. When sporulated, the oocysts of Cyclospora are the same size, but contain two sporocysts, each with two sporozoites. Isospora oocysts can also be found in the stool; however, they can be differentiated by their larger size, 15 by 30 um ovoid. Like Cyclospora, oocysts of Isospora are excreted in an unsporulated stage, and, after becoming sporulated, contain two sporocysts, each with two sporozoites. Pulmonary infections of Cryptosporidium are diagnosed by biopsy and staining (Table 46-1). Treatment and Prevention No specific chemotherapeutic agent is available to effectively treat cryptosporidiosis. As noted, infection is self-limiting in immunocompetent hosts and chronic in immunosuppressed individuals. HIV infection makes a person vulnerable to infection with Cryptosporidium. Because of massive fluid loss due to diarrhea, infected individuals may require rehydration therapy. Because there are no effective agents to treat infection, the best measure to control infection is avoidance of situations that are conducive to transmission. Thus, knowledge about sources of infection and how infection is transmitted is the key to prevention. Most surface water, such as streams, lakes, and rivers contain some Cryptosporidium oocysts. Many public supplies of treated and filtered water derived from these sources are contaminated with low lev2ls of oocysts. Although any individual may acquire infection, children in daycare centers and individuals with AIDS or HIV infection represent populations that are especially vulnerable to infection. Cryptosporidiosis can be prevented by thoroughly washing hands before eating and after any contact with animals or soil or after changing diapers. In people with weakened immune systems, cryptosporidiosis can be life-threatening. These individuals must take extra precautions to drink only water that has been purified; wash with purified water; cook all food; do not swim in lakes, rivers, streams, or public pools; avoid sexual practices that might involve contact with stool; and avoid touching farm animals. COMPREHENSION QUESTIONS [46.1] A 33-year-old woman has chronic diarrhea. A fecal sample is obtained. Microscopic identification of which of the following stages of the organism would provide the strongest evidence for cryptosporidiosis? A. Cyst B. Oocyst C. Egg D. Sporozoites E. Merozoites [46.2] A 24-year-old male scientist is diagnosed with chronic cryptosporidiosis. He asks about the epidemiology of this disorder. Which of the following accurately describes the disease or the etiologic agent? A. Is self-limiting in immunocompromised patients B. Reproduces sexually and asexually in different hosts C. Can be acquired through sporozoites transmitted by an insect vector D. Is transmitted through drinking water contaminated with animal feces E. Is the only human parasite that produces oocysts [46.3] Chronic, debilitating cryptosporidiosis is most likely to affect which of the following individuals? 1. Dairy farmers 2. Individuals with AIDS 3. Infants placed in daycare centers 4. Zoo animal handlers 5. Hikers who drink from streams and lakes ANSWERS [46.1] B. Oocyst is the correct answer. Egg and cyst stages are not part of the life cycle of Cryptosporidium. Eggs are produced by helminths, and cyst stages are produced by other intestinal protozoans, such as Entamoeba and Giardia. Merozoites occur within infected epithelial cells but are not the target of diagnostic tests or procedures. Sporozoites are part of the life cycle and occur inside the oocyst but are not the object of the microscopic examination. [46.2] D. Infection can be acquired from oocysts transferred from farm animals. In immunocompromised individuals, such as those with AIDS or cancer patients being treated with immunosuppressive agents, infection is not self-limiting but rather chronic and sometimes life-threatening. The life cycle of Cryptosporidium involves both asexual and sexual reproduction, but both forms occur in a single host. Sporozoites are stages in the life cycle that are released from ingested oocysts. There is no insect that serves as a biological or mechanical vector in the life cycle. Oocysts are also produced by other species of coccidians that infect humans Isospora, Cyclospora, Toxoplasma, and Plasmodium. Toxoplasma oocysts only occur in feline hosts; Plasmodium species cause malaria in which only the mosquito definitive host harbors oocysts; Isospora and Cyclospora are intestinal coccidian parasites that produce oocysts that are passed in the feces and must be considered in making a differential diagnosis. [46.3] B. All individuals (A-E) are susceptible to infection. However, persons that are at high risk of severe, protracted infection are those with AIDS, or those who have cancer or organ transplants who are treated with drugs that weaken the immune system, or individuals who are genetically immunodeficient. MICROBIOLOGY PEARLS · Often there is misdiagnosis between cryptosporidiosis and cyclosporiasis. · Cryptosporidiosis does not respond to specific therapy, whereas cyclosporiasis responds well to a combination of trimethoprim and sulfamethoxazole. REFERENCES Centers for Disease Control. DPDx. Laboratory identification of parasites of public concern. Cryptosporidiosis. Author, 2004. Available online at: http://www.dpd.cdc.gov/dpdx/HTML/Cryptosporidiosis.htm Graphic Images of Parasites. Cryptosporidium parvum (cryptosporidiosis). Author, 2004. Available online at: http://www.biosci.ohio-state.edu/~parasite/cryptosporidium.html Medical Letter on Drugs and Therapeutics. Drugs for parasitic infections. New Rochelle, NY: The Medical Letter, 2002. Available online at: http://www.medletter.com/freedocs/parasitic.pdf ============================ CASE 47 INTRODUCTION A 4-year-old girl is brought to the office by her mother because of anal itching. The mother has noticed her daughter scratching and rubbing her anal area frequently for the past few days. Her anal area has been getting red and raw from all the scratching. Mother has used some petrolatum and hydrocortisone cream, but it hasn't helped much. The child has not had any obvious skin rashes and is not scratching any other part of her body. She has not had diarrhea. She takes no medications and has no significant medical history. She attends daycare 4 days a week. On examination, she is a well-appearing child. Her vital signs and general examination are normal. Examination of her perianal area reveals some erythema and excoriation from scratching. You perform a microscopic examination of a sample collected by touching the perianal region with a piece of clear cellophane tape. · What diagnostic finding are you likely to see on this microscopic examination? · What is the organism responsible for this infection? ANSWERS TO CASE 47: Pinworms · Diagnostic finding likely to see on this microscopic examination: Thin-walled, ovoid eggs that are flattened on one side and contain a nematode larva. · Organism responsible for this infection: Enterobius vermicularis Summary: A 4-year-old girl has perianal pruritus. The diagnosis is made by microscopic examination of a sample collected by touching the perianal region with a piece of clear cellophane tape. CLINICAL CORRELATION Introduction Enterobius vermicularis, commonly called the pinworm, is the most common cause of helminthic infections in the United States and is endemic around the world. Humans are the only known host with E. vermicularis, but other vertebrates can be infected with different species of this nematode. Adult worms, approximately 1 cm in length, white and thread-like in appearance, inhabit the large intestine. Gravid females migrate to the perianal and perineal regions at night to lay eggs that are immediately infective. Infection is more common in children than adults and is often asymptomatic. However, a variety of symptoms are ascribed to pinworms. Atypically, worms are sometimes found in an inflamed appendix and there are rare reports of worms reaching the genital tract and producing vaginitis. By far the most common signs of infection occur in children and include restless sleep and tiredness during the day. However, more common symptoms consist of anal or perianal itching because of the adult worms crawling on the skin. The eggs can also cause local itching, which may be more intense in secondary infections as a result of allergic reactions to their coating. Frequent scratching results in transfer to the hands and areas under the fingernails. Eggs are frequently transferred to clothing, bedding, toys, and dust, where they can survive for several weeks. Through hand-to-mouth transmission, the eggs are ingested and hatch in the duodenum. Larvae released from eggs reach adult stage in about a month. Infections are acute, generally lasting 4-8 weeks. Considering the relatively short duration of a single infection, chronic enterobiasis is caused by reinfection. Approach to the Suspected Enterobius Infection Definitions Pinworm: Common name for Enterobius vermicularis. Cervical alae: An extension of a lateral cuticular protuberance or lateral line on the body surface of the pinworm that extends to the head region and appears microscopically as a "flared" region or collar. Cervical alae help in the identification of adult worms. Nocturnal migration: Refers to the tendency of pinworms to migrate at night from the colon, out the anus, to the perianal and perineal regions to deposit eggs. Larvated egg: Refers to eggs that contain a larval stage and are deposited by pinworms on the skin. Objectives 1. Learn the life cycle of E. vermicularis and the epidemiology and clinical course of infection. 2. Be able to describe three basic aspects of infection: transmission, diagnosis, and treatment/prevention. Discussion Characteristics of Enterobiasis that Impact Transmission A patient acquires infection by ingesting the pinworm eggs containing infective larvae. Ingested eggs hatch in the small intestine releasing larvae that migrate to the cecal area and mature into adult male and female worms that are free or insecurely attached to the mucosa. The period between ingestion of eggs to maturation takes about 3-4 weeks. Following copulation, the female pin-worms produce eggs. Rather than release eggs in the colon, the female worms migrate out the anus onto the surrounding skin and release eggs. Worm migration usually occurs at night. Each female will lay 10,000-20,000 microscopic, larvated eggs. Pinworm eggs are infective within a few hours after being deposited on the skin. They can survive up to 2 weeks on clothing, bedding, or other objects. Individuals can become infected after accidentally swallowing infective pinworm eggs from contaminated surfaces or fingers. The duration of a single infection is 4-8 weeks. Diagnosis Although Enterobius is an intestinal parasite, eggs are rarely found during lab examinations of stools. If a person is suspected of having pinworms, the so-called "scotch tape test" should be used to identify the parasite. Transparent adhesive tape, sometime attached to the end of tongue depressor or "pinworm paddle," is pressed in the anal region. This procedure involves the help of a patient or parents of suspected children. The tape is then transferred to a glass slide, sticky side down. The slide should then be examined microscopically by an expert for eggs. Pinworm eggs are about 20 ' 50 m characteristically flattened on one side and usually contain an active larva. Because bathing or having a bowel movement may remove eggs, the scotch tape impression should be made on awakening in the morning. In children, samples taken from under the fingernails may also contain eggs because scratching of the anal area is common. A definitive diagnosis may also be made on recovery and identification of adult worms seen directly in bedclothes or around the anal area. The female pinworm has a sharply pointed tail and anterior alae that form a collar-like structure around the mouth. The female worm is about 1 cm long with a diameter about .5 mm. In female worms that are gravid, the uterus filled with eggs is a common feature. Treatment and Prevention A highly effective drug in the treatment of enterobiasis is mebendazole, given as a single dose, with a repeat dose administered 2 weeks later. This is a broad spectrum antinematode agent that has a high therapeutic index. Close family contacts should be treated as well. If reinfection occurs, the source of the infection should be identified. Therefore, playmates, schoolmates, close contacts outside the house, and household members should be considered. Each infected person should receive the two-dose treatment and, if necessary, more than two doses. In short, the importance of determining infection in the entire family or contacts should be explained in terms of the life cycle of the worm and personal, and group hygiene should be stressed. COMPREHENSION QUESTIONS [47.1] In which of the following life cycle stages is enterobiasis transmitted? A. Larva B. Egg C. Adult D. Cyst E. Oocyst [47.2]Which of the following is the drug of choice in treating enterobiasis? A. Mebendazole B. Metronidazole C. Piperazine D. Praziquantel E. Chloroquine [47.3] A parent of a child suffering from disturbed sleep and restlessness calls the family physician and states that her child is once again infected with pinworms and asks if she can administer the same medicine that was used to cure an earlier infection. After the physician is convinced that the pinworm infection is the problem, she advises on giving the same treatment and provides direction on how to clean up the environment to prevent further reinfection. The physician should have been convinced by the fact that the parent: A. Knew that reinfection was a possibility B. Had collected worms from bed linen and accurately described them C. Described symptoms of enterobiasis D. Had the child's stool examined by her veterinarian who identified tell-tale eggs E. Noted that the family's pet cat continued to sleep on the child's bed. ANSWERS [47.1] B. The egg stage is the stage transmitted from person to person. A larval form (A) is found inside the egg but does not escape to initiate infection until the egg is ingested. Adult forms (C) live in the intestine but are not the stage directly responsible for transmission of the infection. Cyst (D) and oocyst (D) stages are not a part of the life cycle of E. vermicularis. [47.2] A. Mebendazole is the most appropriate of several available benzimidazole compounds to treat enterobiasis. This drug of choice is a highly effective, broad-spectrum antihelminthic. Metronidazole (B) is used to treat various protozoan infections, but is not efficacious in treating pinworms. Piperazine (C) is an anthelminthic that was used prior to the discovery of mebendazole to treat enterobiasis and is less effective, and its dose regimens are more complicated. Praziquantel (D) is effective in treating tapeworm and fluke (flatworms) infections but is not useful against pinworms or other nematodes. Chloroquine is a potent antimalarial drug but of no use against helminths. [47.3] B. Finding and identifying adult pinworms is one way to make a definitive diagnosis. Reinfection (A) is a definite possibility but not convincing evidence that the child is actually infected. Symptoms described (C) are associated with enterobiasis but are only presumptive, not definitive, evidence of infection. A stool exam (D) is not an appropriate or effective method to diagnose enterobiasis. Cats (E) are in no way associated with transmission of infection. MICROBIOLOGY PEARLS · The egg (larvated) is the infective stage. · The life cycle is direct, meaning that the adults develop from larvae without leaving the gastrointestinal tract. Adult worms are the primary cause of pathology. · Mebendazole, a broad spectrum antihelminthic, is the drug of choice. REFERENCES Centers for Disease Control. DPDx. Laboratory identification of parasites of public concern. Enterobiasis. Author, 2004. Available online at: http://www.dpd.cdc.gov/dpdx/HTML/Enterobiasis.htm Graphic Images of Parasites. Pinworms (Enterobius vermicularis, Oxyuris species). Author, 2004. Available online at: http://www.biosci.ohio-state.edu/~parasite/enterobius.html Medical Letter on Drugs and Therapeutics. Drugs for parasitic infections. New Rochelle, NY: Author, 2002. Available online at: http://www.medletter.com/freedocs/parasitic.pdf ===================== CASE 48 INTRODUCTION A 50-year-old woman presents to your office with the complaints of fever, chills, nausea, and vomiting for the past 5 days. She is especially concerned because she just returned from a 3-week long church mission trip to central Africa during which she did not take the recommended malaria prophylaxis. She was careful about using insect repellent and wearing long-sleeved clothing, but she did not take the recommended weekly dose of mefloquine because it made her nauseous. Starting a few days after her return, she has had episodes of shaking chills followed by fever spikes as high as 39.7°C (103.5°F) and then profuse sweating. After these episodes she would feel so exhausted that she would sleep for hours. These severe episodes have been occurring every other day. In between these episodes, she has had low-grade fever, myalgias, nausea, vomiting, and diarrhea. On examination, she appears very fatigued and pale. Her temperature is 37.7°C (99.9°F), pulse 100 beats per minute, blood pressure 110/80 mmHg, and respiratory rate 18 breaths per minute. Other than signs of dehydration, her examination is unremarkable. A complete blood count shows her to be anemic. She has elevated blood urea nitrogen, creatinine, and lactate dehydrogenase levels. A thin-blood smear is sent to the laboratory, which shows erythrocytes with ring forms at the periphery of the cell and multiple erythrocytes with three or four ring forms present. · What is the most likely etiology of her infection? · What findings on the thin blood smear are specific for this organism? ANSWERS TO CASE 48: Plasmodium species · Most likely etiology of her infection: Plasmodium falciparum. · Findings on the thin blood smear are specific for this organism: Multiple ring forms in a single erythrocyte and ring forms located at the periphery of the erythrocytes. Summary: A 50-year-old woman has fever and body aches. A thin-blood smear shows erythrocytes with ring forms at the periphery of the cell and multiple erythrocytes with three or four ring forms. CLINICAL CORRELATION Introduction Malaria is caused by one of the four species of plasmodia and involve a mosquito-human-mosquito life cycle. Plasmodia are coccidian parasites of erythrocytes. Their life cycle involves asexual reproduction in humans and sexual reproduction in the mosquito. Human infection is initiated by the bite of an infected mosquito, which introduces sporozoites into the blood stream. The sporozoites travel to the liver where they mature and reproduce asexually by schizogony. Plasmodium ovale and P. vivax may also establish a dormant¾hypnozoite¾stage in the liver; P. falciparum and P. malariae are incapable of this. On completion of the hepatic growth and reproductive stage, merozoites are released from hepatocytes and infect erythrocytes, initiating the erythrocytic cycle. Asexual reproduction continues, resulting in rupture of erythrocytes and release of more infectious merozoites. The classic symptoms of malaria relate to the paroxysm of shaking chills, fever, and sweating and correspond with the cyclical lysis of erythrocytes and release of merozoites, although the actual cause of these symptoms is unknown. Plasmodium vivax, P. ovale, and P. falciparum species of malaria tend to produce paroxysms in 48 hour cycles (tertian malaria), whereas P. malariae causes paroxysms in 72 hour cycles (quartan malaria). A series of paroxysms of decreasing intensity constitutes a primary malarial attack. After the primary attack, parasites tend to disappear from the blood. In infections with P. falciparum or P. malariae this would constitute a cure. In P. vivax and P. ovale infections, relapses may occur as a result of hypnozoites persisting in the liver. Complicating pathologic changes such as anemia, hepatomegaly, and splenomegaly may occur. In the case of falciparum malaria, capillaries are blocked by infected erythrocytes that typically tend to become "sticky" and sequestered in capillary beds. Erythrocyte destruction leads to anemia. Capillary blockage leads to ischemia, anoxia, and subsequent organ damage. This is the basis for cerebral symptoms and kidney damage that leads to black water fever, a condition in which hemoglobin and erythrocytes appear in the urine and is associated with a poor prognosis. Falciparum malaria is the most virulent and lethal form of malaria, sometimes called malignant tertian malaria. Approach to the Suspected Malaria Infection Definitions Relapse malaria: Infection derived from hypnozoites (hypnos = sleeping; zoites = animals) or residual liver stages that persist after a primary infection with P. vivax and P. ovale. Applique form: Parasite on the periphery of erythrocytes, as in P. falciparum infection. Ring stage: Stage in the life cycle of Plasmodium in an erythrocyte consisting of a thin ring of protoplasm with a nucleus at one side. Schizogony: Asexual division or "splitting" carried out by all Plasmodium species. Blackwater fever: A dangerous complication of malaria, especially falciparum, characterized by passage of red to black urine and associated with high mortality. Objectives 1. Learn the life cycle of Plasmodium species and the epidemiology and clinical course of infection. 2. Be able to describe the three basic aspects of infection: transmission, diagnosis, and treatment/prevention. Discussion Characteristics of Plasmodium that Impact Transmission Plasmodium is a genus in the phylum Apicomplexa, which contains other human parasites such as Toxoplasma, Cryptosporidium, Cyclospora, and Isospora. All of these organisms belong to a phylogenetic class in which all species are parasitic. Malaria infections are endemic in tropical developing countries. Although endogenous malaria has occurred in the United States, most cases are imported by travelers. There are numerous species of Plasmodium, but only four species cause human malaria ¾ P. falciparum, P. vivax, P. malariae, and P. ovale. All species are transmitted by an infected anopheline mosquito. Plasmodium sporozoites are the infective forms injected into the blood stream when the mosquito takes a blood meal. The sporozoites circulate in the blood stream and then invade hepatocytes to initiate a preerythrocytic cycle. In the liver parenchymal cells the parasite multiplies asexually by a process called schizogony or splitting. Asexual reproduction gives rise to multiple individual stages or merozoites. These merozoites become blood-borne and invade erythrocytes to initiate the erythrocytic cycle. In the case of P. vivax and P. ovale, the liver phase can be sustained for years by sporozoite-derived dormant stages known as hypnozoites. It is the prevalence of the hypnozoites that leads to relapses of malarial symptoms, possibly occurring several years after the first acute disease has been cured. When merozoites parasitize erythrocytes, their development takes two routes. Some merozoites develop into micro (male) and macro (female) gametocytes. When a female anopheline mosquito bites an infected person and ingests the gametocytes, fertilization of the macrogametocyte by the microgametocyte takes place in the mosquito with the subsequent and sequential formation of diploid zygotes, oocysts, and, eventually, sporozoites. Sporozoites travel to enter the salivary glands of the mosquito where they are capable of initiating a new infection when the mosquito takes a blood meal. Through the second route in the erythrocytic cycle, the parasite develops successively through ring, trophozoite and schizont stages. As a result of schizogony, the erythrocyte breaks open and releases many new merozoites. These parasites then infect more erythrocytes, repeat the development cycle, ultimately causing the destruction of massive numbers of erythrocytes. The characteristic chill, fever, and sweating paroxysm occurs when the parasites are released from the erythrocytes. Because the release of parasites becomes synchronized and periodic, the paroxysms are also periodic, occurring at 48 or 72 hours depending on the species. The destruction of erythrocytes and release of cell and parasite debris contribute to pathological changes. Diagnosis (see Table 48-1) Diagnosis is made by finding the characteristic organisms on thick and thin blood smears. Differential diagnosis rests on knowing the specific morphological characteristics of each species, which are revealed in a thin blood smear. Plasmodium vivax and P. ovale appear as ring shapes, and in other advanced stages of development in enlarged erythrocytes that contain numerous granules, known as Schuffner dots.Plasmodium malariae has characteristic "band or bar" pattern and do not enlarge the host erythrocytes. Plasmodium falciparum can be identified by the presence of multiple ring forms within a single erythrocyte, in contrast to other plasmodia that will have only one ring form per erythrocyte. Plasmodium falciparum ring forms also tend to occur at the periphery of the erythrocyte; these "applique" forms are distinctive for this species. Mixed infections with more than one species of Plasmodium may occur. Treatment and Prevention From the perspective of patient management, drugs to treat malaria fall into three categories: prophylactic, schizonticidal, and antirelapse. Prophylactics are designed to prevent infection by attacking the sporozoite stages or preventing the development of clinical symptoms by preventing schizogony in the erythrocytic cycle. Schizonticidal compounds may be used in prophylactic measures and to effect a clinical cure in an acute infection. Antirelapse drugs are directed against hypnozoite stages, as in vivax infection. A radical cure in P. vivax and P. ovale infections requires the use of drugs that eradicate both the erythrocytic and exoerythrocytic schizonts in the liver. Chloroquine is a schizonticidal compound and drug of choice in treating clinical cases of malaria. Mefloquine, referred to in the case presentation, is used in prophylaxis and also to treat chloroquine resistant strains of Plasmodium. Drug resistance of certain strains of Plasmodium is a practical problem. In this case, back-up drugs are quinine or chemically related mefloquine, or a combination of sulfadoxine (a sulfonamide) and pyrimethamine (pyrimidine derivative). Antirelapse or tissue schizonticidal drugs are aimed at hypnozoites (liver schizonts). The drug of choice in this category is primaquine. COMPREHENSION QUESTIONS [48.1] Microscopic examination of a thin blood smear from a patient suspected of having malaria reveals numerous normal size erythrocytes without stippling but with ring stages, many with multiple ring stages and applique forms. Several erythrocytes show developing trophozoites that are spread across the erythrocytes in a band fashion. Which of the following is the most likely cause of infection? A. Plasmodium vivax B. Plasmodium malariae C. Plasmodium ovale D. Plasmodium falciparum E. A mixed infection with two plasmodium species [48.2] A patient in California was diagnosed with malaria acquired through a blood transfusion. A discussion of this case by physicians included the following statements. Which statement is correct? A. The infected blood contained sporozoites. B. The patient should be treated with chloroquine and primaquine. C. The patient should be treated to eradicate the stages responsible for symptoms. D. The blood donor had chloroquine-resistant malaria. E. The patient would not be infective to mosquitoes. [48.3] Cerebral malaria most commonly attends infection with which of the following? A. Any two species of Plasmodium B. Plasmodium malariae C. Plasmodium falciparum D. Plasmodium ovale E. Plasmodium vivax ANSWERS [48.1] E. Multiple ring stages and applique forms are indicative of P. falciparum; several erythrocytes show developing trophozoites that are spread across the erythrocytes in a band fashion that is indicative of P. malariae infection. Normal size erythrocytes without stippling (Schuffner dots) would exclude P. vivax and P. ovale. [48.2] C. The primary goal should be to treat the patient to eliminate the erythrocytic cycle that is the cause of symptoms. This would constitute a radical cure because the liver phase only occurs if infection is initiated by sporozoites. Thus, treating with primaquine (B) is not necessary because the patient will not harbor hypnozoites. Likewise, (A) is not correct because sporozoites are only acquired from mosquitoes. Transfusion malaria is caused by schizonts and merozoites present in the transferred blood. There is no way to know that the malaria is chloroquine resistant until after treatment with chloroquine (D) and the patient, although not likely to occur, could transmit the infection to mosquitoes (E) because gametocytes would be present in the blood and susceptible Anopheles species occur in the United States. [48.3] C. Cerebral malaria involves the clinical manifestations of Plasmodium falciparum malaria that induce changes in mental status and coma and is accompanied by fever. Without treatment, cerebral malaria is fatal in 24-72 hours and the mortality ratio is between 25-50 percent. The common histopathological finding is the sequestration of parasitized and nonparasitized red blood cells in cerebral capillaries and venules. MICROBIOLOGY PEARLS · In a laboratory diagnosis, in which blood smears are treated with Giemsa or Wright stain plasmodia can be identified when the nucleus and cytoplasm are seen. · Chemotherapy is directed at erythrocytic stages to provide a clinical cure and hypnozoites in the liver to effect a radical cure. REFERENCES Centers for Disease Control. DPDx. Laboratory identification of parasites of public concern. Malaria. Author, 2004. Available online at: http://www.dpd.cdc.gov/dpdx/HTML/Malaria.htm Graphic Images of Parasites. Plasmodium spp. (malaria). Author, 2004. Available online at: http://www.biosci.ohio-state.edu/~parasite/plasmodium.html Medical Letter on Drugs and Therapeutics. Drugs for parasitic infections. New Rochelle, NY: Author, 2002. Available online at: http://www.medletter.com/freedocs/parasitic.pdf ======================== CASE 49 INTRODUCTION A 40-year-old man presents for a routine examination. He is generally feeling well but complains of some mild dysuria and increasing urinary frequency. He has never had a urinary tract infection (UTI) and thought that the increasing urinary frequency was a normal part of aging. He has not seen any blood in his urine but says that the urine does appear darker than it used to look. He has no other complaints and his review of systems is otherwise entirely negative. He has no significant medical or family history. He smokes a pack of cigarettes a day and denies alcohol use. He is an immigrant from Egypt who has lived in the United States for 3 years. His vital signs and physical examination, including genital and prostate exams, are normal. A urinalysis shows many red blood cells, a few white blood cells, and oval-shaped parasite eggs with terminal spines. · What organism is the likely cause of his hematuria? · How does this organism gain entry into humans? ANSWERS TO CASE 49: Schistosomiasis · Organism likely cause of his hematuria: Schistosoma haematobium. · Method organism gains entry into humans: Penetration through intact skin by the cercarial stage of the organism. Summary: A 40-year-old Egyptian man has hematuria. A urinalysis shows many red blood cells, a few white blood cells, and oval-shaped eggs with terminal spines. CLINICAL CORRELATION Introduction Schistosomiasis is a human disease syndrome caused by infection with one of several parasitic trematodes or flukes of the genus Schistosoma. These parasites are known commonly as blood flukes because the adult worms live in blood vessels of the definitive host. The human disease syndrome is characterized by dermatitis that is caused by entry of the infective stage and by acute and chronic systemic symptoms caused by host responses to eggs deposited by adult worms. Schistosoma hematobium, S. mansoni, and S. japonicum are the major species that infect over 200 million humans in Asia, Africa, the Middle East, and South America. Schistosoma japonicum is considered a zoonotic infection. In addition to these three major species, others, such as S. mekongi and S. intercalatum, also with potential zoonotic properties, rarely infect humans. Schistosomes with avian or nonhuman mammalian hosts can cause severe dermatitis or swimmers itch in humans. The disease syndrome parallels the development of the parasite in the definitive host. Swimmers itch, an allergic dermatitis, is caused shortly after humans make skin contact with microscopic, infective larval forms called cercariae that live in an aquatic environment. Following exposure to human schistosomes, the dermatitis is mild and may go unnoticed. However, when exposed to cercariae of schistosomes that normally infect birds, swimmers itch can present as an itchy maculopapular rash. Cercariae penetrate the intact skin, enter the circulation and migrate to the liver where they mature into adult male and female worms. The adult worms migrate via the blood stream to their final locations. Schistosoma mansoni and S. japonicum descend to the mesenteric veins and S. haematobium to the vesical plexus. Gravid female worms may release 300-3,000 eggs per day over a 5-10 year life span. Eggs of S. haematobium can work their way through the wall of the urinary bladder into the lumen and are eliminated in urine, while eggs of S. mansoni and S. japonicum work their way through the walls of the small intestine and colon and are voided in feces. Acute schistosomiasis or Katayama's syndrome develops one to two months after initial infection and includes fever, chills, abdominal pain, lymphadenopathy, and hepatomegaly and splenomegaly. The etiology of acute schistosomiasis is not known. However, the association of its manifestations with heavy infection suggests that it is a form of serum sickness as a result of circulating antigen-antibody complexes. Chronic schistosomiasis results from the inflammatory response to eggs, with granulomas, fibrosis, and scar tissue occurring at the site where eggs are deposited in tissues. Chronic schistosomiasis results from the inflammatory response to the presence of eggs, with granulomas, fibrosis, and scarring around the eggs. Eggs in the bowel wall may result in symptoms of abdominal pain, diarrhea, and blood in the stool. Schistosomiasis of the bladder can cause hematuria, dysuria, frequent urination, and a reduction in bladder capacity. With intestinal schistosomiasis, the liver is frequently involved as a result of eggs being carried by the portal circulation and becoming trapped. Pathology involves inflammation and fibrosis, leading to cirrhosis with resulting portal hypertension, splenomegaly, ascites, and abdominal and esophageal varices. Ectopic lesions may rarely be associated with eggs reaching the brain and lungs. Approach to the Suspected Schistome Infection Definitions Cercaria: Infective, aquatic larval form of schistosomes; characterized by a forked tail. Miracidium: Ciliated larval form of schistosomes (and other flukes) that escapes from the egg and infects a snail intermediate host. Intermediate host: The host in the life cycle of a helminth that harbors the larval stage(s) of the parasite. Bilharziasis: A synonym for schistosomiasis. Swimmer's itch: Dermatitis in humans caused by cercariae penetrating the skin, commonly involving cercariae of schistosomes that parasitize birds or mammals but which cannot complete their life cycle in humans. Dioecious fluke: A fluke that has separate sexes, as opposed to hermaphroditic flukes. Objectives 1. Learn the life cycle of blood flukes and the epidemiology and clinical course of infection. 2. Be able to describe three basic aspects of infection: transmission, diagnosis, and treatment/prevention. Discussion Characteristics of Schistosomes that Impact Transmission The life cycle of all human schistosomes is similar, except in fine details. Eggs voided in feces or urine hatch in fresh water, releasing ciliated miracidia that penetrate a snail intermediate host. The species of snail varies with the species of schistosome. Miracidia undergo morphological development through other larval stages, eventually reproducing asexually. The product is hundreds of cercariae with forked tails that emerge from the snail and swim freely. On contacting humans that enter their environment, the cercariae penetrate the intact skin, losing their tails in the process, and enter the circulation and are disseminated to all parts of the body. The cercariae, now termed schistosomula, are carried via the portal vein into the intrahepatic portal system where they mature in about 3-4 weeks. After maturing, the worms migrate against the blood current and move into branches of veins that drain the urinary bladder (S. hematobium) or the lower ileum and cecum (S. japonicum) or the colon (S. mansoni). Female worms lay several hundred eggs per day. The eggs of each species have characteristic morphology. All eggs leaving the host contain a fully developed miracidium. Diagnosis Infections can be definitively diagnosed by finding characteristic eggs in the urine or feces. Eggs of S. hematobium are in the shape of an elongated oval with a terminal spine; S. mansoni eggs are also oval shaped with a distinct lateral spine; and S. japonicum eggs are round to oval with a short lateral spine or knob that often is unseen. In suspected cases where stools are negative, eggs of S. mansoni may be seen in microscopic examination of a rectal biopsy. Treatment and Prevention Praziquantel is the drug of choice in the treatment of human schistosomiasis and is effective against all human species. Because the drug has been reported to be effective as a prophylactic, larval stages and adult forms are presumed to be susceptible. The treatment of cercarial dermatitis is symptomatic. Prevention is based on avoiding skin exposure to water in endemic areas. COMPREHENSION QUESTIONS [49.1] Which of the following is a host in the life cycle of all trematodes that infect humans? A. Flea B. Mosquito C. Mollusk D. Flour weevil E. Sand fly [49.2] An oil field worker who has lived in Brazil for 10 years has mild gastrointestinal symptoms. Brazil is the only country ever visited by the patient outside of the United States. The patient is diagnosed by his physician of having schistosomiasis mansoni because: A. Round eggs with a prominent terminal spine were observed in a rectal biopsy. B. Blood was detected in the stool. C. Nonoperculated eggs with a miracidium inside were observed in stool samples. D. Eggs were found in a urine sample. E. Symptoms were relieved by treatment with praziquantel. [49.3] A 12-year-old boy reports feeling tingling and itching of his legs 30 minutes after swimming in a lake. Over the next day, small papules develop followed by blisters of the legs. Dermatitis due to schistosome infection is diagnosed. What larval stage most likely caused the infection? A. Filariform larva B. Cysticercus C. Cercaria D. Miracidium E. Sparganum ANSWERS [49.1] C. Snails are mollusks. All flukes have snails as intermediate hosts. Fleas, mosquitoes, flour weevils, and sand flies serve as intermediate or definitive hosts to various helminth and protozoan parasites, but not to flukes. [49.2] C. Eggs with a miracidium inside is indicative of a fluke infection; nonoperculated eggs are characteristic of schistosomes and differentiate them from all other human flukes, which have eggs with opercula. Also, S. mansoni is the only human schistosome endemic to Brazil and to the western hemisphere. A round egg with a terminal spine (A) is characteristic of S. hematobium but would not be expected in a rectal biopsy; furthermore, S. hematobium is not endemic to the western hemisphere. Blood in the stool (B) may be a finding in S. mansoni infection but would not be a definitive diagnosis. Finding eggs in a urine sample (D) is consistent with S. hematobium but not S. mansoni infection; again, S. hematobium is not endemic to the western hemisphere. Vague gastrointestinal symptoms are not pathognomonic of schistosome infections. Praziquantel (E) is used to effectively treat all intestinal tapeworms of humans, as well as schistosomes. Symptoms could have been caused by adult tapeworms. [49.3] C. Forked-tail cercariae are infective for humans. A filariform larva is the infective stage for hookworm and strongyloides, both nematode parasites. A cysticercus larva (B) is the infective stage of Taenia species of tapeworms. A miracidium (D) is the stage of flukes that infects snails, not humans. A sparganum larva (E) is involved in the life cycle of pseudophyllidean tapeworms, such as the broad fish tapeworm. MICROBIOLOGY PEARLS · Swimmers itch is often transmitted by bird schistosomes. · Pathology in clinical cases is caused by egg stages. · Praziquantel is effective for all species and is also used to treat intestinal tapeworms. REFERENCES Centers for Disease Control. DPDx. Laboratory identification of parasites of public concern. Schistosomiasis. Author, 2004. Available online at: http://www.dpd.cdc.gov/dpdx/HTML/Schistosomiasis.htm Graphic Images of Parasites. Graphic images of parasites. Schistosoma species (schistosomes or blood flukes; schistosomiasis). Author, 2004. Available online at: http://www.biosci.ohio-state.edu/~parasite/schistosoma.html Medical Letter on Drugs and Therapeutics. Drugs for parasitic infections. New Rochelle, NY: Author, 2002. Available online at: http://www.medletter.com/freedocs/parasitic.pdf =========================== CASE 50 INTRODUCTION A 19-year-old woman presents to the office for the evaluation of an itchy vaginal discharge that she has had for about a week. She has had no fever, abdominal pain, or dysuria. She became involved with a new sexual partner about 3 weeks ago. She takes birth control pills but does not regularly use condoms during intercourse. Her partner is asymptomatic. On examination, her vital signs are normal, and a general physical examination is unremarkable. On pelvic examination, her external genitalia are normal. After inserting a speculum you see a bubbly, thin, yellow vaginal discharge. Her cervix is erythematous but without discharge. She has no cervical motion or uterine or adnexal tenderness. A wet mount of the vaginal discharge examined microscopically reveals numerous motile, flagellated, pear-shaped organisms along with numerous white blood cells. · What is the most likely infectious cause of her vaginal discharge? · What is the most likely source of her infection? ANSWERS TO CASE 50: Trichomonas · Most likely infectious cause of her vaginal discharge:Trichomonas vaginalis. · Most likely source of her infection: Sexual contact with infected but asymptomatic partner. Summary: A 19-year-old woman with vaginal discharge, which on microscopy reveals numerous motile, flagellated, pear-shaped organisms along with numerous white blood cells. CLINICAL CORRELATION Introduction Trichomonas vaginalis is a motile, pear-shaped protozoan with four flagella and an undulating membrane. It multiplies by binary fission and exists only in its trophozoite form; no cyst form has been identified. It is a common cause of both symptomatic and asymptomatic infections. Many infected women are asymptomatic or have only a small amount of thin vaginal discharge. Others develop symptomatic disease with vaginal inflammation, itching, and copious vaginal discharge. The discharge may be white, yellow, or green, and bubbles are often seen. Cervical inflammation with punctate hemorrhages may produce a "strawberry cervix." The vast majority of infections in men are asymptomatic, although urethritis, prostatitis, and epididymitis can occur. The parasite is almost always passed by sexual contact, although fomite transmission has been documented. The diagnosis is most often made by the microscopic evaluation of a sample of vaginal discharge in a saline wet mount. Flagellated, motile trichomonads will be visible in most symptomatic infections. The diagnosis can also be made by the identification of organisms on Pap smears, by culture of the vaginal discharge, or by the use of specific monoclonal antibody stains or nucleic acid probes. This infection is usually treated with oral metronidazole, and both partners should be treated to prevent reinfection. Because of its route of transmission, the identification of infection with Trichomonas should prompt the consideration of evaluation for other sexually transmitted diseases. Approach to the Suspected Trichomonas Infection Definitions Trophozoite: Feeding stage of protozoans. Axostyle: A hyaline rod-like structure that runs through the length of T. vaginalis and exits at the posterior end. Fomite: A substance other than food that may harbor and transmit infectious agents. Objectives 1. Learn the life cycle of Trichomonas vaginalis and the epidemiology and clinical course of infection. 2. Be able to answer the three basic aspects of infection: transmission, diagnosis, and treatment/prevention. Discussion Characteristics of Trichomonas that Impact Transmission The life cycle of trichomonads in general is the simplest of protozoan life cycle because the organism exists only as a trophozoite that divides by binary fission. Transmission is presumed to be by direct transfer of trophozoites because a cyst stage does not exist. Sexual intercourse is considered the usual means of transmitting this infection that is common worldwide. The organism is transmitted cyclically from a woman to a man and back to the same or another woman. Infected men, who play a key role in transmission, are usually asymptomatic. Trichomonas vaginalis trophozoites in vaginal discharge are known to live for 30 minutes or more on toilet seats, supporting the possibility that some infections could be acquired through fomites such as towels and toilet seats. However, this means of transmission is not well supported by evidence. Diagnosis If infection with T. vaginalis is suspected, a first step is to diagnose infection by microscopically examining a wet mount preparation of vaginal discharge from the patient. The live parasite appears as a pear-shaped trophozoite with active flagella that give it motility. Sometime the undulating membrane provides a waving movement. Propagation and concentration of the organism in culture is a possibility if wet mounts are negative. However, examination of wet mounts is usually sufficient to find and identify the organism. Treatment and Prevention Metronidazole is effective in treating T. vaginalis. Treatment of both sexual partners is recommended to prevent reinfection. Using condoms correctly and consistently will lower the risk of individuals contracting trichomoniasis and other sexually transmitted diseases. COMPREHENSION QUESTIONS [50.1] Trichomoniasis is transmitted through this stage: A. Cyst B. Oocyst C. Egg D. Sporozoite E. Trophozoite [50.2] The drug of choice in treating vaginal trichomoniasis is: A. Metronidazole B. Mebendazole C. Mefloquine D. Niclosamide E. Niridazole [50.3] Laboratory diagnosis of vaginal trichomoniasis is most commonly made by: A. Identifying cyst stages in an iodine stained preparation of vaginal secretion. B. Finding trophozoites in a saline wet mount of vaginal discharge. C. Using an acid-fast stain to highlight the parasite. D. Staining a thin blood smear with common blood stains. E. Testing for specific antibodies against T. vaginalis in the patient's serum. ANSWERS [50.1] E.Trichomonas vaginalis exists only as a trophozoite; no cyst stage has been identified. A cyst (A), oocyst (B) and sporozoite (D) are stages involved in transmitting other protozoan infections, and an egg (C) is the means of transmission in a number of helminth infections. [50.2] A. Metronidazole is the drug of choice. Mebendazole (B) is a broad-spectrum antinematode agent. Mefloquine (C) is used as a prophylactic drug to prevent malaria and also used to treat chloroquine-resistant clinical malaria. Niclosamide is a broad-spectrum agent effective in the treatment of adult tapeworm infections. Niridazole (E) is a drug used to treat schistosomiasis if praziquantel is not available. [50.3] B. Trophozoites are usually visible in saline mounts of vaginal scrapings. Cysts (A) are not present in the T. vaginalis life cycle, and iodine is used primarily to observe cysts of intestinal protozoa. Acid-fast stains (D) are used to search for oocysts of coccidian intestinal parasites, such as Cryptosporidium and Cyclospora. Thin blood smears are used to diagnose malaria. Serological diagnoses (E) are helpful in the diagnosis of several "deep tissue" parasites but are not used in diagnosing T. vaginalis. MICROBIOLOGY PEARLS · Trichomonas vaginalis is an important sexually transmitted parasite throughout the world. · Only trophozoite stages occur and frequently are difficult to find in a wet mount. · Males and females are hosts, although males are generally asymptomatic. · Metronidazole is the drug of choice for treating trichomoniasis. REFERENCES Centers for Disease Control. DPDx. Laboratory identification of parasites of public concern. Trichomoniasis. Author, 2004. Available online at: http://www.dpd.cdc.gov/dpdx/HTML/Trichomoniasis.htm Graphic Images of Parasites. Trichomonas vaginalis (trichomoniasis, "trich" or "trick"). 2004. Available online at: http://www.biosci.ohio-state.edu/~parasite/trichomonas.html Medical Letter on Drugs and Therapeutics. Drugs for parasitic infections. New Rochelle, NY: Author, 2002. Available online at: http://www.medletter.com/freedocs/parasitic.pdf