Globally, parasitic diseases cause enormous mortality and morbidity among children. Pediatricians working in many areas of the developing world are commonly challenged with chloroquine-resistant Plasmodium falciparum malaria. Schistosomiasis, the parasitic disease associated with the greatest human morbidity after malaria, is most prevalent among the 8- to 14-year-old age group and can cause liver or urinary tract damage. One in four persons on earth harbor the intestinal round worm Ascaris lumbricoides; a similar rate occurs for human infection with the protozoan G lamblia. In iact, infection with intestinal parasites is so common among the children of the developing world that it often is difficult to distinguish parasitic infection from true parasitic disease.
Compared with the tropics, pediatrie parasitic infections are rare in the United States. There are only about 1000 US malaria cases per year reported to the Centers for Disease Control and Prevention (CDC), and only 15% of these occur in children under 15 years of age.1 Intestinal parasitosis is more common and occurs widely throughout the country (Table I).2 Giardia lamblia was found in more than 15 000 stool specimens submitted to state laboratories in 1987 (7% of all specimens examined). This represented an increase in the Giardia positivity rate by 75% over that of the last state laboratory report in 1978. One explanation for the increase in Giardia is that a greater number of children now attend day-care centers, where there is increased risk of acquiring intestinal infections.2,3
Pinworm (Enterobius vermicularis) remains the most common helminthic infection in the United States. Eleven percent of 9500 adhesive tape examinations in the state laboratory survey were positive for pinworm eggs (Table 1); this percentage is similar to other reports based on surveys in asymptomatic school children.4 The scope of parasitic infections can be appreciated by the list of conditions in Table 2.
Results From 216 275 "Stool for O & P" Specimens Performed at 49* State Public Health Laboratories, United States, 1987
THE SETTINGS OF PEDIATRIC PARASITIC DISEASE: WHAT'S OLD?
Although parasitic diseases often are considered "exotic" infections, in reality they are commonly diagnosed and treated by physicians in routine clinical practice. For example, without hesitation the differential diagnostic considerations of an adolescent with vaginal discharge would include Trichomonas vaginaíis. Giardiasis is a common cause of persistent diarrhea in a toddler enrolled in a day-care center.5 Pinworm immediately comes to mind in a child with pruritus ani.6 And most clinicians would not be surprised at receiving a report that multiple parasites were found on a screening stool examination of an asymptomatic immigrant child.7
Aside from these relatively routine clinical settings, the following are examples of parasitic infections that are common topics in general pediatrie journals or weekly grand rounds:
* a 6-month-old infant with previously unrecognized congenital human immunodeficiency virus infection presents with Pneumocystis carinii pneumonia (PCP),
* a newborn with cerebral calcifications, thrombocytopenia, hepatosplenomegaly, and chorioretinitis in whom ToxopiosrnagonOK infection is considered the likely diagnosis,
* Toxocara can«, the dog roundworm, causing visceral larva migrans in a child with pica, eosinophilia, and hepatomegaly,8 and
* neurocysticercosis in a child presenting with headache, seizures, and multiple ring enhancing lesions on magnetic resonance imaging or computed tomography scan.
THE SETTINGS OF PEDIATRIC PARASITIC DISEASE: WHAT'S NEW?
Diarrhea and Day Care
Cryptosporidiosis is emerging as an important cause of watery diarrhea in children attending day-care centers.9 The diagnosis may be missed since laboratories must specially stain (Kinyoun acid-fast stain) for Cryptosporidium, and some will not automatically do so unless the physician specifically requests it. When Giardia or Cryptosporidium enteritis is suspected, the order should be written "Stool for ova and parasites (O & P) and Cryptosparidium."
Cryptosporidiosis is a self-limited disease in immunocompetent children, but can be life-threatening in patients with acquired immunodeficiency syndrome. Since transmission may occur from infected children to other family members, children with cryptosporidiosis acquired in a day-care center are a potential risk to any immunocompromised persons who might live in their homes. Human immunodeficiency virus- infected family members should probably avoid diaper changing and related activities until the child no longer has diarrhea.9'11 A sample information sheet for parents of children with cryptosporidiosis has been published.10
Fever and the Tick Bite
The differential diagnosis of fever and tick bite should include babesiosis (in addition to Lyme disease, Rocky Mountain spotted fever, and ehrlichiosis). Babesiosis may be acquired in Washington, California, Wisconsin, New York, and the New England states. Both babesiosis and Lyme disease are transmitted by the same deer tick (Ixodes dammini) and have as reservoirs the same white-footed mouse (Peromyscus leucopus). The diagnosis of babesiosis is made by finding intraerythrocytic parasites in Wright's- or Giemsa-stained blood smears (Babesia protoza often are misdiagnosed as malaria parasites by laboratory technologists). Serological testing also is available at the CDC, but some newly recognized US Babesia species may not react in available serologie tests.
Unrecognized babesiosis probably occurs frequently. A recent serosurvey among 52 children in Rhode Island showed that 12% were immunoglobulin (Ig) G seropositive for Babesia by indirect fluorescent antibody testing. None of these children had detectable parasitemia or splenomegaly, although many had a history of a recent febrile illness.12 Splenectomized patients with Babesia infections are at particular risk for becoming very ill with fever, hemolysis, and thrombocytopenia.
A Tropical Disease With No History of Travel
Schantz et al13 reported a cluster of neurocysticercosis (infection with larval stages of the pork tapeworm Taenia so/ium) among six New Yorkers, five of whom had not traveled out of the United States. Four of the six patients were in the pediatric age group (one 2 year old, two 6 year olds, and one 16 year old); three affected children had seizures. Because all were from Orthodox Jewish families, none of the patients had consumed pork. The major risk factor for infection was determined to be contact with domestic workers who had immigrated from countries in which T solium intestinal tapeworm infection is endemic. Neurocysticercosis is acquired from ingestion of infectious tapeworm eggs passed in feces, not by eating pork. The presence of tapeworm carriers in the United States means that an epidemiologie history of travel to, or origin from, a disease-endemic area is not required to consider a diagnosis of neurocysticercosis.
TREATMENT: WHAT'S OLD? WHAT'S NEW?
Intestinal parasites are either considered to be potential pathogens (treat) or nonpathogenic coinhabitants (do not treat). Coinhabitant agents that do not require treatment include EndoUmax nana, Entamoeba coli, Entamoeba hartmanni, Entamoeba polecki, lodamoeba buetschlii, Chuiomastix mesni, and Trichomonas hominis. It remains controversial as to whether BIostocystis hominis should be considered a coinhabitant or a pathogen.14 Symptomatic patients having infections with Entamoeba histolytica, G lambiia, Dientamoeba iragilis, or Jsospora belii should be treated. Asymptomatic E histolytica infections also require treatment, and therapy should be offered to children with asymptomatic intestinal helminthic infections. Children without diarrhea who are excreting Giardia or Cryptosporidium do not have to be excluded from day-care centers, and asymptomatic giardiasis does not always require treatment.5'9 The value of treating an asymptomatic child with positive Toxocara titers (with or without eosinophilia) is unknown. Table 3 lists important agents in the three classes of antiparasitic drugs: antimalarials, antiprotozoals, and anthelmintics.
Drugs for Malaria
The classic antimalarials include chloroquine, primaquine, quinine, doxycyline, and Fansidar (sulfadoxine and pyrimethamine, Roche Laboratories, Nutley, New Jersey). Plosmodium falciparum infections usually are chloroquine-resistant and so must be treated with quinine, Fansidai; or doxycyline. Intravenous quinine is not available in the United States, but the antiarrhythmia drug quinidine gluconate is equally effective should a parenteral preparation be required. The so-called relapsing malarias caused by PIosmoadium vivax or Piasmotfium ovale can be treated with chloroquine (for the red blood cell malaria parasites), followed by primaquine (for the liver malaria parasites). Patients should be tested for glucose-6-phosphate dehydrogenase deficiency before primaquine is administered.
The new antimalarial drug mefloquine (Lariam, Roche Laboratories, Nutley, New Jersey) is now the recommended chemoprophylactic antimalarial agent to be used in most areas where P falciporum occurs; the drug is given weekly starting 1 week before departure and continued for 4 weeks after leaving the malariaendemic area. Mefloquine should not be used in children under 30 lbs body weight, patients with a history of epilepsy, pregnant women, or persons taking beta blockers.15'16 Since the only alternative to mefloquine is daily doxycycline, no good options are available for P falcipantm malaria prophylaxis in young children. Furthermore, lactating mothers do not excrete sufficient amounts of any antimalarial drug into the breast milk to provide effective malaria prophylaxis to the nursing child. Parents who plan to take infants and toddlers to areas where chloroquineresistant malaria occurs should be encouraged to defer travel until the child weighs enough to take mefloquine. If the child must travel, consultation should be obtained to discuss other chemoprophylactic options. A child who develops fever during or after the trip should be taken immediately for medical consultation, and blood smears should be obtained to rule out malaria. Remember that bed nets, screened rooms, and insect repellents/sprays while in the endemic area also are important in reducing the risk of malaria infection.
Drugs for Other Protozoal Diseases
Metronidazole (Flagyl, G. D. Searle & Co, Chicago, Illinois) is the antiprotozoal agent most familiar to the practicing pediatrician. In the United States, it is the drug of choice for treating vaginal trichomoniasis and E histolytica amebiasis. Metronidazole may be used to treat giardiasis, but furazolidone (Furoxone, Roberts Pharmaceutical Corp, Eatontown, New Jersey) is more convenient because it is available in a liquid preparation. The antigiardia drug quinacrine (Atabrine, Sanofi Winthrop Pharmacetuicals, New York, New York) is no longer available on the US market, lodoquinol Yodoxin, Glenwood Ine, Tenafly, New Jersey) and paromomycin (Humatin, Parke-Davis, Morris Plains, New Jersey) are poorly absorbed drugs that may be used to treat asymptomatic E histolytica "cyst passers" or thentamoebiasis. lodoquinol or paromomycin should be administered immediately following a course of metronidazole for amebic colitis to reduce the risk of relapse. Tinidazole (Fasigyn, Pfizei; New York), an intestinal antiprotozoal agent not available in the United States, is an excellent agent for amebiasis and giardiasis that is often purchased overseas by travelers with diarrhea. Compared to metronidazole, tinidazole is effective in shorter courses and has fewer side effects.15 There is still no effective treatment for cryptosporidiosis.
Toxoplasmosis is treated with pyrimethamine and sulfediazine (the latter currently available only from the CDC), although clindamycin, spiramycin (not available in the United States except through the manufacturer, Rhône Poulenc Rorer, Collegeville, Pennsylvania), and steroids are indicated in certain clinical situations. Treatment of severe forms of toxoplasmosis (congenital, ocular, or cerebral) probably merits consultation with an infectious disease subspecialist. Pnewmocystis carina pneumonia is treated with trimethoprim sulfamethoxazole, or, when that cannot be used, pentamidine. Steroids are indicated in hypoxemic PCP patients. The Food and Drug Administration (FDA) recently has licensed two new agents for the treatment of PCP. Trimetrexate glucuronate is a patenterai antifolate that must be given with leucovorin. Atovaquone is an oral drug used to treat mild to moderate PCP. There is little experience in the use of either drug in children. In addition, since pediatrie PCP is almost always severe, opportunities to use atovaquone are rare.
Important Drugs for Parasitic Infections
Drugs for Helminthic Infections
Mebendazole (Vermox, Janssen Phamnaceuticals, Piscataway, New Jersey) and pyrantel pamoate (Antiminth, Pfizer, New York) are the most frequently prescribed antihelminthic agents in the United States. Both are effective against pinworms, hookworms, and ascarids. Pyrantel pamoate, however, is not effective treatment for trichuriasis. Hymenolepis rumo, and other intestinal tapeworm infections can be treated with niclosamide (Niclocide, Miles Ine Pharmaceutical Division, West Haven, Connecticut) or praziquantel (Biltricide, Miles Ine Pharmaceutical Division, West Haven, Connecticut); neurocysticercosis can be treated with praziquantel or albendazole. Alberiamole (Zentel), a broad-spectrum antiparasitic agent related to mebendazole, is not available on the US market, but can be obtained through a "compassionate release" mechanism from the manufacturer, SmithKline Beecham. Thiabendazole (Mintezol, Merck Sharp & Dohme, West Point, Pennsylvania) is used to treat cutaneous larva migrans, strongyloidiasis, and visceral larva migrans. Nausea, vomiting, and headache are common during an oral thiabendazole treatment course. Thiabendazole oral suspension may be applied topically to treat cutaneous larva migrans, or pharmacists can prepare a 10% to 15% cream using thiabendazole pills.
DIAGNOSIS: WHAT'S NEW? WHAT'S OLD?
For the diagnosis of giardiasis or cryptosporidiosis, the faithful "Stool for O &. P" is being challenged by several recently marketed fecal antigen tests. A monoclonal fluorescent antibody test that detects both Giordia and Cryptosporidium is available Meridian Diagnostics Ine, Cincinnati, Ohio), as are capture enzyme-linked immunosorbent assay tests for Giardia (LMD Ine, Carlsbad, California; Alexicon Ine, Sunnyvale, California) and Cryptosporidium (Seradyn, Indianapolis, Indiana; Alexicon Ine, Sunnyvale, California). These "high-tech" tests appear to be both sensitive and specific, and may reduce our dependence on skilled laboratory microscopists, who can vary considerably in competence between laboratories. However, antigen detection tests cannot recognize other protozoal or helminthic pathogens, so standard O & P examinations will still be required in certain clinical situations.
A test is being developed that allows differentiation of the pathogenic strains of E htstotytica from those considered to be nonpathogenic.17 Guidelines are needed for how and when this test should be used to determine if an asymptomatic cyst passer should be treated. Although several new diagnostic techniques for malaria have been introduced (most notable being acridine orange staining of blood smears), the classic method of examining Giemsa-stained thick and thin blood smears may still be the best way to make the diagnosis.1 Repeated thick-smear examinations every 12 to 24 hours for 3 consecutive days are needed to adequately rule out malaria.
Finally, a number of different test kits are marketed in the United States for the serodiagnosis of toxoplasmosis. While results from most IgG test kit systems are qualitatively comparable, the sensitivity and specificity of IgM tests are highly variable.18 Therefore, verification of positive IgM results by a reference laboratory is suggested.
Most general pediatrie texts have good reviews of the life cycles and clinical presentations of common parasitic infections. However, the best reference source to have in the office for answers to questions about the treatment of parasitic infections is the Mediad Letter on Drugs and Therapeutics.16 These treatment recommendations, which include pediatrie doses, are prepared in consultation with internationallyknown experts in tropical infectious diseases. Countryspecific recommendations for malaria prophylaxis are available from the "Yellow Book," Health information for International Travel, I993.19
Perhaps a more convenient (and constantly updated) resource is the CDC Disease Information System (telephone (404) 639-1610 or (404) 3324555), which has detailed health information for international travelers, including recommendations on malaria prevention. You may wish to give the phone number to your patients contemplating travel to the tropics. The Disease Information System also has hundreds of reference documents that can automatically be sent by fax to your office.
There are probably experts in travel medicine/ tropical diseases in your own local medical community. Practicing pediatricians should try to identify this expertise by contacting infectious disease divisions of academic institutions, travel medicine clinics, immigrant clinics, schools of public health, and state and local health departments. Certain organizations and enterprises specialize in providing advice and insurance to international and wilderness travelers. Finally, US government agencies, including the CDC, the National Institutes of Health, and the Armed Forces, have staff capable of helping with difficult patient management issues.
CDC SERVICES IN PARASITIC DISEASES AVAILABLE TO PRACTICING PHYSICIANS
Most CDC activities related to infectious diseases are concentrated at the National Center for Infectious Diseases (NCID). Prevention and control of infectious diseases acquired in day-care settings, infectious diseases transmitted by animals and arthropods, and tropical infectious diseases are among the priority NCID activities. Howevet; the NCID does not have direct hospital access, and patients may not be referred to NCID physicians for consultation or treatment.
The telephone duty officer in the NCID Division of Parasitic Diseases (DPD) (telephone (404) 4887760; fax (404) 488-7761) is available to discuss issues related to the treatment of parasitic diseases or the work-up of patients in whom a parasitic disease is considered likely. Among DPD professional staff are specialists in malaria, filariasis, leishmaniasis, neurocysticercosis, echinococcosis, Chagas' disease, geohelminthiases, and schistosomiasis. Most are involved actively in international projects and have had some hands-on experience in treating these conditions. In some instances, the DPD duty officer will refer the calling physician to another DPD staff member with expertise on the parasite in question. If no such expertise exists at the CDC, the calling physician may be referred to an outside expert.
The CDC Drug Service
The CDC Drug Service (telephone (404) 6393670) stocks certain antiparasitic drugs that are not available in the United States. Currently, CDC has stocks of sulfadiazine, bithionol, dehydroemetine, diloxanide furoate, ivermectin, melarsoprol, nifurtimox, pentostam, and suramin.16 Aside from sulfadiazine (used to treat toxoplasmosis), pediatricians are unlikely to have patients who require any of these agents. The CCXD releases drugs under an FDA Investigational New Drug protocol that requires the responsible physicians to register as investigators and to provide the CDC with information about the success and tolerance of treatment. Some of these drugs are potentially toxic and are released after a DPD duty officer has determined that the drug will be used to treat life-threatening illness. Physicians seeking antiparasitic drugs not available through the CEXD (for example, albendazole for neurocysticercosis or spiramycin for congenital toxoplasmosis) will be referred to the manufacturer of the drug or to the FDA.
DPD Laboratory Services
The DPD Reference Immunodiagnostic Laboratory (telephone (404) 488-4431; fax (404) 488-4108) can test serum specimens for a number of parasitic conditions, including cysticercosis, strongyloidiasis, toxocariasis, and toxoplasmosis. Immunoglobulin G and IgM testing for toxoplasmosis are performed only for confirmation of positive IgG and IgM test results at an outside laboratory. Serum (3 cc) may be sent at ambient temperature if transit time is less than 1 week. Under special circumstances, DPD laboratories will examine parasite, tissue, or stool specimens. All submissions must be accompanied by a brief clinical history and related laboratory results. In addition, note that all specimens must be submitted tfirougfi your state health department laboratory unless urgent circumstances require direct shipment to the CDC. If direct shipment is anticipated, arrangements should be discussed with DPD staff prior to shipping. It is physicians' responsibility to contact their state laboratory for permission to ship directly to the CDC. The duty DPD officer may be contacted for further information. The CDC laboratory services are free of charge.
1. Zucker JR, Campbell CC. Malaria: principles of prevention and treatment. Infect Dis Clin Nonti Am. 1 993;?: 547 -567.
2. Kappus KK, Juranek DD, Robert JM. Results of testing foi intestinal parasites by state diagnostic laboratories. United States. 1987. MMÏPR CDC Surveiu Summ. 1991;40(suppl):25-46.
3. Addiss DG. DavisJP, Roberts JM, Mast EE. Epidemiology of giardiasis in Wisconsin: increasing incidence of reported cases and unexplained seasonal trends. Am J Trap MedHyg. 1992:47:13-19.
4. Wagner EQ Eby WC. Pinworm prevalence in California elementary school children, and diagnostic methods. Am J Trap Mea Hyg. 1 983 ;3 2:998- 1001.
5. Addiss DG, Juranefc Dd Spencer HC. Treatment of children with asymptomatic and nondiarrheal Giarda infection. Pediarr Infect Di! J. 1991;11843-846.
6. Russell LJ. The pinworm. Enlerofsuj vrrmíruiaris . Prim Care . 199l;18:l3-24.
7. Bass JL, Mehta KA, Eppes B. Parasitoiogy screening of Latin American children in a primary care clinic. Monies. 1992:89:279-283.
8. Taylor MRH, Keane CT, O'Connor P, Girwood RWA, Smith H. The expanded spectrum of toxocaral disease. Lancet. 1988:1:692-694.
9. Cordell R, Addiss DG. Cryptosporidiosis in child care settings: a review of the literature and recommendations for prevention and control. Ptaiair Infect Dis J. 1994; 13:3 10-317.
10. Diekema DS, Martuse EK. Information for parenti and patients: Cryptosporidiosis. Pedian Infect Dis J. 1992;11:689-690.
11. Stoller JS, Adam HM, Weiss B, Winner M. Incidence of intestinal parasitic disease in an acquired immunodeficiency syndrome day-care center, Pediarr Infect Dis J. 1991;10:654-658.
12. Krause PJ. Telford SR H, Pollack RJ, et al. Babesiosis: an underdiagnosed disease of children. Rdiomcs. 1992;89: 1045-1048.
13. Schanc PM, Moore AC, Muñoz JL, et al. Neurocysticercosis m an orthodox Jewish community in New York City. N Engl J Mat. 1992;3 2 7:69 2-695.
14. Marteli EK, Udkow MP Blasiocystis hominis: pathogen or fellow traveler? Am J Trofi MedHyg. 1986:35:1023-1026.
15. While NJ. Antiparasitic drugs in children. Clin Pharmacakrnei. 1989;17(suppl 0:138-155.
16. Drugs for parasitic infections. Med Lett Drugs Ther. 1993;35:111-122.
17. Petti WA, Clark CG, Diamond LS. Host-parasite relationships in amebiasis: conference report. J Infect Du. 1994:169:483-484.
18. Wilson M, McAuley JB. Laboratory diagnosis of toxoplasmosis. Clin Lab Med. 1991;11:923-939.
19. Centeis for Disease Control and Prevention. Heobh Injr/mvuam /or /nwnatwnal Trawl, 1993, Atlanta, Ga: US Department of Health and Human Services; 1993:103-112. US Dept Health and Human Services publication (CDC) 93-8280.
Results From 216 275 "Stool for O & P" Specimens Performed at 49* State Public Health Laboratories, United States, 1987
Important Drugs for Parasitic Infections