121 - SECTION 17 Protozoal and Helminthic Infections- General Considerations

SECTION 17 Protozoal and Helminthic Infections: General Considerations

appear to be particularly susceptible to PCP. The glucocorticoid exposure threshold that warrants chemoprophylaxis is ill-defined, but such preventive therapy should be strongly considered for any patient who is receiving more than the equivalent of 20 mg of pred­ nisone daily for 30 days or who is receiving glucocorticoids in con­ junction with other immunosuppressive agents. Clinical experience also suggests that chemoprophylaxis is useful for patients receiving certain immunosuppressive agents (e.g., tumor necrosis factor inhibi­ tors, antithymocyte globulin, rituximab, and alemtuzumab). The duration of such chemoprophylaxis is empirically estimated based on prior clinical experience and immunologic factors that would plausi­ bly relate to immunity, such as CD4+ T-cell counts, recognizing that such estimates are not precise. TMP-SMX is the most effective prophylactic drug; few patients experience a PCP breakthrough when they are reliably taking a recom­ mended TMP-SMX chemoprophylactic regimen. Several TMP-SMX regimens have been used successfully. Regimens of one single-strength or double-strength tablet daily are the regimens with which there is the most experience, but one double-strength tablet two or three times weekly also has been recommended for various PLWH and non-HIVinfected populations of patients. For patients who cannot tolerate TMP-SMX (usually because of hypersensitivity or bone marrow suppression), alternative drugs include daily dapsone, weekly dapsone-pyrimethamine, atovaquone, and monthly aerosol pentamidine. Patients who develop hypersensi­ tivity to TMP-SMX can sometimes tolerate the drug if a gradual doseescalation protocol is used. Atovaquone is effective and well tolerated; however, this drug is available only as an oral preparation, and gastro­ intestinal absorption is unpredictable in patients with abnormal gas­ trointestinal motility or function. Aerosolized pentamidine is effective, but it is not as effective as TMP-SMX and may not provide protection in areas of the lung that are not well-ventilated. Dapsone cross-reacts with sulfonamides in a substantial fraction of patients and is rarely use­ ful in patients with a history of life-threatening reactions to TMP-SMX. ■ ■FURTHER READING Buchacz K et al: Incidence of AIDS-defining opportunistic infections in a multicohort analysis of HIV-infected persons in the United States and Canada, 2000–2010. J Infect Dis 214:862, 2016. Del Corpo O et al: Diagnostic accuracy of serum (1-3)-β-D-glucan for Pneumocystis jirovecii pneumonia: A systematic review and metaanalysis. Clin Microbiol Infect 26:1137, 2020. Lécuyer R et al: Characteristics and prognosis factors of Pneumocystis jirovecii pneumonia according to underlying disease. Chest 165:1319, 2024. Le Gal S et al: Pneumocystis infection outbreaks in organ trans­ plantation units in France: A nation-wide survey. Clin Infect Dis 70:2216, 2020. Ma L et al: Genome analysis of three Pneumocystis species reveals adaptation mechanisms to life exclusively in mammalian hosts. Nat Commun 7:10740, 2016. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents: Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adoles­ cents: Recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medi­ cine Association of the Infectious Diseases Society of America. Available at https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinicalguidelines-adult-and-adolescent-opportunistic-infections/pneumocystis0?view=full.  Accessed December 21, 2024. Wills NK et al: The prevalence of laboratory-confirmed Pneumocystis jirovecii in HIV-infected adults in Africa: A systematic review and meta-analysis. Med Mycol 59:802, 2021. Zolopa A et al: Early antiretroviral therapy reduces AIDS progression/ death in individuals with acute opportunistic infections: A multicenter randomized strategy trial. PLoS One 4:e5575, 2009.

Section 17 Protozoal and Helminthic Infections: General Considerations Sharon L. Reed, Charles E. Davis

Introduction to

Parasitic Infections The word parasite comes originally from the Greek parasitos (para, alongside of; and sitos, food), meaning someone who eats at another’s table or lives at another’s expense. Although the same is true of many bacteria and viruses, the designation parasite is reserved, by conven­ tion, for helminths and protozoa. These organisms are larger and more complex than bacteria, with a eukaryotic cell structure similar to that of human host cells. Historically, this similarity has made it difficult to find effective antiparasitic agents that do not cause unacceptable toxicity to human cells. Fortunately, intensive research and modern techniques have now provided suitable agents for safe and effective treatment of most parasitic infections. See Chap. S12 for details on diagnostic procedures and Chap. 229 for details on treatment. Internal parasites of human beings are divided into two types: hel­ minths (worms) and protozoa. Helminths are multicellular organisms that can often be seen with the naked eye (Chap. 237). There are two phyla: Platyhelminthes (flat worms) and Nemathelminthes (round­ worms). Both phyla include some genera that mature in the gastroin­ testinal tract and others that migrate through the tissue after ingestion or skin penetration. Tables S12-1 and S12-2 present the helminthic genera, their definitive and intermediate hosts, their geographic distri­ butions, and the parasitic stages in the human body. CHAPTER 228 Introduction to Parasitic Infections The key to understanding which helminths use humans as defini­ tive hosts is to remember that helminth ova develop into larvae, and larval stages develop into adults. Humans serve as the definitive host when they ingest helminth larvae, which develop into adults in the intestine and usually cause mild disease, often without any symptoms. (The exception is ingestion of the late-stage larvae of the somatic or tissue flukes, as shown in Table S12-1.) In contrast, if humans ingest helminth ova and serve as the intermediate host, the ova develop into larvae, which penetrate the intestine, migrate through the tissue, and invade organs where they mature into adults. Intermediate hosts with parasitic invasion of organs may experience severe disease. Protozoa are microscopic single-celled organisms. Among the many differences between helminths and protozoans, the most important is the ability of protozoa (like bacteria) to multiply within the human body and cause overwhelming infections. A major mechanism pro­ moting unrestrained growth is evasion of the host immune response either by antigenic variation (Trypanosoma brucei) or by survival inside host cells (e.g., Plasmodium, Babesia, Cryptosporidium, Leishmania, and Toxoplasma). In contrast, almost all helminths require stages in other hosts to complete their life cycles and multiply. As a result, except for Strongyloides and Capillaria, which can complete their life cycle in humans, increases in the burden of infection with helminths require repeated exogenous reinfections. Thus, permanent residents of endemic countries, who are exposed repeatedly, may have heavy severe infections, while most travelers with one or two exposures are unlikely to experience the full spectrum of chronic helminthic infections. In contrast to helminthic infections, naïve patients with their first protozoal infection usually are the most severely affected because partial immunity often limits the number of parasites during recurrent infections. Protozoan replication to large numbers in the host also pro­ motes the development of drug-resistant forms, especially in malaria (Chap. 229). Because protozoa belong to many different phyla, it is easier to understand the pathogenesis and management of protozoal infections when they are classified by the site of infection (intestinal protozoans, free-living amebae, and blood and tissue protozoans)