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FUNGAL AND PROTOZOAL DISEASES

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					39         Human Diseases Caused by Fungi and Protists




CHAPTER OVERVIEW

This chapter discusses some of the more important fungal and protist diseases of humans. The clinical
manifestations, diagnosis, epidemiology, pathogenesis, and treatment of selected diseases are presented.

CHAPTER OBJECTIVES

After reading this chapter you should be able to:

     discuss the five types of diseases caused by fungi (mycoses) and give examples of each
     discuss some of the more important diseases caused by protists

CHAPTER OUTLINE

I.    Pathogenic Fungi and Protists
      A. Medical mycology—discipline that deals with fungi that cause human disease; fungal diseases are
           called mycoses
      B. Systemic mycoses are caused by dimorphic fungi (except for Cryptococcus neoformans, which has
           only a yeast form); usually acquired by inhalation of spores from soil; infection begins as lung
           lesions, becomes chronic, and disseminates through the bloodstream to other organs
      C. Protists are transmitted by arthropod vectors or by food and water vehicles; fewer than 20 protist
           genera cause human disease; however, malaria, trypanosomes, and amoeba account for hundreds of
           millions of cases
II.   Airborne Diseases
      A. Blastomycosis—Blastomyces dermatitidis
           1. Occurs in three clinical forms: cutaneous, pulmonary, and disseminated
           2. Diagnosis is aided by serological tests; antifungal agents are effective; surgery may be
                 necessary to drain large abscesses; no prevention or control measures
      B. Coccidiomycosis—Coccidioides immitis
           1. Acquired by inhalation of spores
           2. Usually an asymptomatic or mild respiratory infection that spontaneously resolves in a few
                 weeks; occasionally progresses to chronic pulmonary disease
           3. Diagnosis is by culturing; serological tests also are available; treatment with several antifungal
                 agents; prevention involves reduction of exposure to dust in endemic areas
      C. Cryptococcosis—Cryptococcus neoformans or C. gattii
           1. Aged, dried pigeon droppings are a source of infection; fungus enters by the respiratory tract
           2. Minor transitory pulmonary infection that can disseminate and cause meningitis; more serious
                 and chronic disease in HIV/AIDS patients and the immunocompromised
           3. Diagnosis is by microscopic examination of specimens and immunological procedures;
                 treatment includes amphotericin B and/or fluconazole; no prevention or control measures
      D. Histoplasmosis—Histoplasma capsulatum


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          1.  A facultative fungus that grows intracellularly; can be found as a budding yeast and in a mold
              form
          2. Found worldwide in soils; spores are easily spread by air currents and inhaled; the spores are
              most prevalent where bird droppings have accumulated
          3. Inhaled microsporidia are transformed into budding yeasts within alveolar spaces and are
              eventually observed within the cells of the monocyte-macrophage system; symptoms are
              usually those of mild respiratory involvement; it rarely disseminates
          4. Diagnosis by immunological tests and culture; most effective treatment is amphotericin B,
              ketoconazole, or intraconazole; prevention and control by using protective clothing and masks
              and by soil decontamination where feasible
III. Arthropod-Borne Diseases
     A. Malaria—Plasmodium falcipurum, P. malariae, P. vivax, P. ovale
          1. Transmitted to humans by bite of an infected female Anopheles mosquito; sporozoites in blood
              move to and reproduce in the liver (asexual schizogony), producing merozoites; these enter
              erythrocytes and form large trophozoites that undergo schizogony and the schizonts produce
              merozoites; the cycle repeats every 48 to 72 hours
          2. Periodic sudden release of merozoites, toxins, cell debris from the infected erythrocytes; and
              TNF- and interleukin-1 from macrophages trigger the characteristic attack of chills and fever;
              anemia can result, and the spleen and liver often hypertrophy
          3. Diagnosis is by microscopic examination of blood smears; serological tests are also available;
              treatment is by chloroquine or related drugs; no effective vaccine is available and prevention is
              through bed netting and insecticides
     B. Leishmaniasis—Leishmania tropica, L. mexicana, L. braziliensis, L. donovani
          1. Caused by flagellated protists (hemoflagellates) transmitted by sandflies from canines and
              rodents
          2. Can be mucocutaneous, cutaneous, or visceral; symptoms vary with the particular etiological
              organism involved
          3. Treated with pentavalent antimonial compounds; recovery usually confers permanent
              immunity; vector and reservoir control and epidemiological surveillance are the best options
              for control
     C. Trypanosomiasis—Trypanosoma brucei, T. cruzi
          1. T. brucei, a hemoflagellate, causes African trypanosomiasis; transmitted by tsetse flies; causes
              interstitial inflammation and necrosis of the lymph nodes, brain, and heart; causes sleeping
              sickness (uncontrollable lethargy)
          2. T. cruzi causes American trypanosomiasis (Chagas' disease); transmitted when bite of
              triatomid (kissing) bug is contaminated with insect feces; symptoms are similar to those caused
              by T. brucei
          3. Trypanosomiasis is diagnosed by microscopic examination of blood and by serological tests;
              treatment with antibiotics is specific for type of trypanosome and stage of disease; vaccines are
              not useful because the parasite can change its protein coat to avoid the immune response
IV. Direct Contact Diseases
     A. Superficial mycoses
          1. Most occur in the tropics
          2. The fungi that cause the disease are limited to the outer surface of the hair and the skin
              a. Piedras are infections of hair shaft that result in formation of a hard nodule
              b. Tineas are infections of the outer layer of skin, nails, and hair
          3. Treatment involves removal of skin scales and infected hairs; prevention is by good personal
              hygiene
     B. Cutaneous mycoses—dermatomycoses, ringworms, tineas
          1. Occur worldwide; most common fungal diseases
          2. Three genera, Epidermophyton, Microsporum, and Trichophyton, are involved
          3. Diagnosed by microscopic examination of skin biopsies and by culture on Sabouraud's glucose
              agar
          4. Treatment—topical ointments, oral griseofulvin, or oral itraconazole (sporanox)

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          5.  Different diseases are distinguished according to the causative agent and the area of the body
              affected (tinea barbae—beard hair, tinea capitis—scalp hair, tinea corporis—any part of skin,
              tinea cruris—groin, tinea pedis—athlete's foot, tinea mannum—hands, tinea unguium—nail
              bed)
     C. Subcutaneous mycoses
         1. The fungi that cause these diseases are saprophytes in soil; they gain entry by puncture wounds
         2. Disease develops slowly over a period of years, during which time nodule develops and then
              ulcerates; organisms spread along lymphatic channels, producing more nodules at other
              locations
         3. Treatment is with 5-fluorocytosine, iodides, amphotericin B, and surgical excision; diagnosis
              is by culture of the infected tissue
         4. Examples include chromoblastomycosis, maduromycosis, and sporotrichosis
     D. Toxoplasmosis—Toxoplasma gondii
         1. Fecal-oral transmission from infected animals; also transmitted by ingestion of undercooked
              meat and by congenital transfer, blood transfusion, or tissue transplant
         2. Most cases are asymptomatic; can be fatal in immunocompromised individuals; leads to severe
              congenital effects for pregnant women; associated with exposure to cat feces containing
              oocytes
         3. Acute disease is characterized by lymphadenopathy, enlargement of reticular cells, pulmonary
              necrosis, myocarditis, hepatitis, and retinitis; a major cause of death in AIDS patients
         4. Diagnosis is by serological tests; chemotherapeutic agents are available for treatment;
              prevention and control require minimizing exposure by not eating raw meat and eggs, washing
              hands after working in soil, cleaning cat litter boxes daily, keeping cats indoors, and feeding
              cats commercial food
     E. Trichomoniasis—Trichomonas vaginalis; a sexually transmitted disease; host accumulates
         leukocytes at the site of infection; in females, this leads to a yellow purulent discharge and itching;
         in males, most infections are asymptomatic; treatment is with metronidazole
V.   Food-Borne and Waterborne Diseases
     A. Amebiasis (amebic dysentery)—Entamoeba histolytica
         1. Ingested cysts excyst in the intestine and proteolytically destroy the epithelial lining of the
              large intestine
         2. Disease severity ranges from asymptomatic to fulminating dysentery, exhaustive diarrhea, and
              abscesses of the liver, lungs, and brain
         3. Diagnosis is based on finding trophozoites in fresh, warm stools and cysts in ordinary stools;
              serological testing also should be done; treatment with several drugs is possible; prevention
              and control involves avoiding contaminated water; hyperchlorination or iodination can destroy
              waterborne cysts
     B. Amebic meningoencephalitis—caused by Naegleria and Acanthamoebae; facultative parasites that
         cause granulomatous amoebic encephalitis and keratitis (particularly among wearers of soft contact
         lenses); found in freshwater and soil; diagnosis is by microscopic examination of clinical specimens;
         most are resistant to common antimicrobial agents
     C. Cryptosporidiosis—Cryptosporidium parvum
         1. Found in the intestines of many birds and mammals, which shed oocysts into the environment
              in fecal material; when oocysts are ingested, they excyst in the small intestine; the released
              sporozoites parasitize intestinal epithelial cells
         2. Major symptom of infection is diarrhea; diagnosis is by microscopic examination of feces;
              treatment with nitazoxanide and rehydration; patients will usually recover, but the disease can
              be fatal in late stage AIDS patients
     D. Cyclospora—Cyclospora cayetanensis
         1. Mainly in tropical regions; linked to contaminated produce
         2. Frequent, explosive diarrhea with fever, fatigue, and weight loss; infects intestines and shed
              cyst oocysts in feces; these must differentiate into sporozoites to be infectious



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           3. Diagnosis is by observation of oocysts in feces; treatment is with trimethoprim and
              sulfamethoxazole and fluid replacement; prevention is through avoidance of contaminated
              food and water
    E. Giardiasis—Giardia intestinalis
        1. Most common cause of waterborne epidemic diarrheal disease; commonly found in daycare
              facilities with diapered children
        2. Transmission is usually by cyst-contaminated water supplies, and disease is common in
              wilderness areas where animal carriers shed cysts into otherwise "clean" water
        3. Disease varies in severity; asymptomatic carriers are common; may be chronic or acute
        4. Diagnosis is by identification of trophozoites; immunological tests also are available; treatment
              is with quinacrine or metronidazole; prevention involves avoiding contaminated water and the
              use of slow-sand filters in the processing of drinking water
VI. Opportunistic Diseases
        1. Opportunistic organisms are normally harmless but can cause disease in a compromised host
        2. Aspergillosis—Aspergillus fumigatus or A. flavus
              a. Portal of entry is respiratory tract; inhalation can lead to several types of pulmonary
                    aspergillosis; the fungus can spread to other tissues and organs; in immunocompromised
                    patients, invasive aspergillosis (mycelia in lungs) may occur
              b. Diagnosis depends on examination of specimens or isolation and characterization of
                    fungus or immunological methods; treated with voriconazole and intraconazole
        3. Candidiasis—Candida albicans
              a. C. albicans is part of normal microbiota and can be transmitted sexually
              b. Exhibits a diverse spectrum of disease:
                    i.    Oropharyngeal candidiasis (thrush)—mouth; common in newborns
                    ii. Paronychia—subcutaneous tissues of the digits
                    iii. Onychomycosis—subcutaneous tissues of the nails
                    iv. Intertriginous candidiasis—warm, moist areas such as axillae, groin, and skin folds
                          (e.g., diaper candidiasis, candidal vaginitis, and balanitis)
              c. Diagnosis is difficult; no satisfactory treatment; cutaneous lesions can be treated with
                    topical agents; oral antibiotics are used for systemic candidiasis
        4. Microsporidia—obligate intracellular Microspora
              a. Infect a wide range of animal hosts that act as reservoirs; highly resistant spores (with
                    characteristic polar tube structure) survive long periods in the environment; mainly seen
                    in AIDS patients
              b. Spores inject intraspore contents (sporoplasm) into host cells using polar body; the
                    sporoplasm multiplies asexually and generates more spores; symptoms include hepatitis,
                    pneumonia, skin lesions, weight loss, diarrhea, and wasting syndrome
              c. Diagnosis is based on stained microsporidia, if possible with electron microscopy, and
                    via PCR; treatment is not well defined
        5. Pneumocystis pneumonia
              a. Caused by a fungus (Pneumocystis jeroveci) that was once thought to be a protozoan
              b. Disease occurs almost exclusively in immunocompromised hosts including more than
                    80% of AIDS patients; the fungus remains localized in the lungs, even in fatal cases
              c. Definitive diagnosis involves demonstrating the presence of the organism in infected lung
                    material or PCR analysis; treatment is by oxygen therapy and combination drug therapy;
                    prevention and control is through prophylaxis with drugs in susceptible persons

TERMS AND DEFINITIONS
Place the letter of each term in the space next to the definition or description that best matches it.

____ 1.    The discipline that deals with fungi that cause human               ____ 4.    Fungi that cause
           disease                                                                        cutaneous infections
____ 2.    General term for diseases caused by fungi                           ____ 5.    A tumorlike deformity
____ 3.    Fungal infections of the hair shaft                                            that results from a
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         subcutaneous fungal infection                                            a.   dermatophytes
____ 6.  A microorganism that is generally harmless in its own                    b.   eumycota mycetoma
         environment but becomes pathogenic in a                                  c.   hemoflagellates
         compromised host                                                         d.   keratitis
____ 7. Candidal infection of the digits                                          e.   medical mycology
____ 8. Candidal infection of the nails                                           f.   mycoses
____ 9. An inflammation of the cornea                                             g.   onychomycosis
____ 10. Transmitted by the bites of infected arthropods;                         h.   opportunistic microorganism
         protozoans that infect the blood and tissues of humans                   i.   paronychia
                                                                                  j.   piedras

FILL IN THE BLANK
    1.   Cutaneous mycoses, which are also called __________, are distinguished in part by the area of the body
         infected. Infections of beard hair are called tinea ____________; those of scalp hair are called tinea
         ____________; infections of any part of the skin are called tinea ____________; those of the groin are
         called tinea ____________ (commonly called __________ __________); and those of the feet, hands,
         and nail beds are called tinea ____________ (commonly called __________ __________), tinea
         __________, and tinea ____________, respectively.
    2.   An ____________ microorganism is one that is generally harmless in its normal environment but that can
         become pathogenic in a ____________ host.
    3.   The most important opportunistic mycoses are ____________ and ____________. A third important
         opportunistic mycosis is __________ __________, which is caused by an organism that was thought to
         be a protozoan but is now classified as a fungus.
4.       Candidiasis takes many forms. If the disease involves the mouth, it is referred to as ____________
         candidiasis or ____________. Infections in areas of the body that are warm and moist (e.g., axillae and
         groin) are called __________ candidiasis. One example of this type of candidiasis is __________
         candidiasis, which is observed in infants whose diapers are changed infrequently. Candidiasis can also
         involve the female genital tract, in which case it is referred to as __________ __________. If C. albicans
         is sexually transmitted to a male, the resulting infection of the glans penis is referred to as ____________.
    5.   Flagellated protozoa that infect the blood and tissues of humans fall into two major groups of organism:
         __________ and __________. A major disease caused by Plasmodium is __________.

MULTIPLE CHOICE
For each of the questions below select the one best answer.

    1.   Which of the following terms is used to refer                   c. systemic sporotrichosis
         to cutaneous mycoses?                                           d. fulminating sporotrichosis
         a. dermatomycoses                                          4.   Which of the following systemic mycoses is
         b. ringworms                                                    caused by a fungus that is NOT dimorphic?
         c. tineas                                                       a. Blastomyces dermatitidis
         d. All of the above refer to cutaneous                          b. Coccidioides immitis
               mycoses.                                                  c. Cryptococcus neoformans
    2.   Which of the following is NOT a                                 d. Histoplasma capsulatum
         subcutaneous mycosis?                                      5.   Which of the following statements about
         a. chromoblastomycosis                                          Pneumocystis pneumonia (PCP) is NOT
         b. coccidiomycosis                                              true?
         c. maduromycosis                                                a. It occurs almost exclusively in
         d. sporotrichosis                                                     immunocompromised hosts.
    3.   Which term refers to sporotrichosis that has                    b. It remains localized in the lungs, even
         spread throughout the body?                                           in fatal cases.
         a. extracutaneous sporotrichosis                                c. It occurs in 80% of AIDS patients.
         b. disseminated sporotrichosis                                  d. All of the above are true about PCP.
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    6.   Which of the following diseases is caused by                  a. giardiasis
         trypanosomes?                                                 b. toxoplasmosis
         a. sleeping sickness                                          c. trichomoniasis
         b. Chagas' disease                                            d. sporotrichosis
         c. Both (a) and (b) are caused by                         9. Which of the following is NOT caused by a
              trypanosomes.                                            protozoan?
         d. Neither (a) nor (b) is caused by                           a. cryptosporidiosis
              trypanosomes.                                            b. cryptococcosis
    7.   Why aren’t vaccines effective against                         c. Both (a) and (b) are caused by a
         trypanosomiasis?                                                   protozoan.
         a. because the organisms are never                            d. Neither (a) nor (b) is caused by a
              exposed to the immune system                                  protozoan.
         b. because the organism is only weakly                    10. Which of the following is a superficial
              immunogenic                                              mycosis?
         c. because the organism can change its                        a. black piedra
              protein coat and thereby evade the                       b. white piedra
              immune response                                          c. tinea versicolor
         d. All of the above are correct.                              d. All of the above are superficial
    8.   What is one of the leading causes of death in                      mycoses.
         AIDS patients?




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FUNGAL AND PROTOZOAL DISEASES

                                        Causative Agent(s) and Mode of       Type of Organism (Fungus or
Disease                                 Transmission                         Protozoan)
amebiasis (amebic dysentery)
American trypanosomiasis
(Chaga’s disease)
aspergillosis

blastomycosis

coccidiomycosis

cryptococcosis

cryptosporidiosis

giardiasis

histoplasmosis

leishmaniasis

malaria

Pneumocystis pneumonia
primary amebic
meningoencephalitis
sporotrichosis

toxoplasmosis

trichomoniasis

African trypanosomiasis


TRUE/FALSE

____ 1.      Jock itch and athlete's foot are caused by the same set of fungi.
____ 2.      Subcutaneous mycoses are caused by soil-inhabiting fungi that can easily penetrate the skin.
____ 3.      Candida albicans is normally found in the vagina but does not usually cause disease because the
             acidic pH created by Lactobacilli prevents its overgrowth.
____ 4.      The impact of protozoan diseases worldwide is great even though there are relatively few genera
             associated with human diseases.
____   5.    Asymptomatic cyst shedders of Entamoeba histolytica do not need treatment.
____   6.    Entamoeba histolytica cysts can be destroyed by hyperchlorination and iodination.
____   7.    Giardia lamblia is the most common cause of epidemic waterborne diarrheal disease in the U.S.
____   8.    Trichomoniasis is frequently asymptomatic in males, but seldom is asymptomatic in females.


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CRITICAL THINKING

    1.   One of the apparent paradoxes associated with giardiasis is that outbreaks occur more frequently in the
         Rocky Mountain and New England states where the raw water is considered to be of fairly high quality,
         whereas outbreaks are less frequent in the South, Southwest, and Midwest, where quality of raw water is
         actually considered much poorer. Explain. (Consider the types of treatment used in the two types of
         areas.)




    2.   Describe the life cycle of Plasmodium vivax and discuss how it is related to the symptoms associated with
         malaria.




ANSWER KEY

Terms and Definitions

1. e, 2. f, 3. j, 4. a, 5. b, 6. h, 7. i, 8. g, 9. d, 10. c

Fill in the Blank

1. dermatomycoses; barbae; capitis; corporis; cruris; jock itch; pedis; athlete’s foot; mannum, unguium
2. opportunistic; compromised; 3. aspergillosis; candidiasis; Pneumocystis pneumonia 4. oral; thrush;
intertriginous; napkin (diaper); candidal vaginitis; balanitis 5. leishmanias; trypanosomes; malaria

Multiple Choice

1. d, 2. b, 3. a, 4. c, 5. d, 6. c, 7. c, 8. b, 9. b, 10. d

True/False

1. T, 2. F, 3. T, 4. T, 5. F, 6. T, 7. T, 8. T




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