Parasitic Infections: Clinical Manifestations, Diagnosis and Treatment Part I

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Parasitic InfectionsClinical Manifestations,
Diagnosis and TreatmentPart I

• Lennox K. Archibald, MD, PhD, FRCP, DTMH
• Hospital Epidemiologist
• University of Florida

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The Reality

• 1.3 billion persons infected with Ascaris (1 4
  persons on earth)
• 300 million with schistosomiasis
• 100 million new malaria cases/yr
• At UCLA, 38 of pediatric and dental clinic
  children harbored intestinal parasites

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Chronic Diarrhea
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Case1

• 42-yr-old previously healthy, UF professor
• 6-week history of intermittent diarrhea, flatus
  and abdominal cramps
• Diarrhea x8/day pale no blood or mucus
• No tenesmus
• Illness began slowly during camping trip to
  Colorado with loose stools
• Spontaneously remission for 5-6 days at a time,
  then recur

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Case 1

• His 8-yr-old son had had a mild course of watery
  diarrheaascribed to viral gastroenteritis by
  general practitioner
• Stool smearno pus cells
• However, wet preps showed

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Giardiasis (G. lamblia)

• Should be suspected in prolonged diarrhea
• Contaminated water often implicatedoutbreaks
• Campers who fail to sterilize mountain stream
  water
• Person-person in day care centers
• MSM
• Symptoms usually resolve spontaneously in 4-6
  weeks

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Giardiasis Tests of choice

• Examination of concentrated stools for cysts (90
  yield after 3 samples)
• Usually no PMNs
• Stool ELISA, IF Antigen (up to 98
  sensitive/90-100 specific)
• Consider aspiration of duodenal
  contents--trophozoites
• Treatment Metronidazole for 5-7 days

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Case 2

• 40 y/o male vicar returned from 2 years of
  missionary work in South Africa
• Excellent health throughout stay there
• 3 months after returning to U.S.
• Suddenly ill with abdominal distension
• Fever
• Periumbilical pain
• Vomiting
• Blood-tinged diarrheal stools
• Denied arthritis /known exposure to parasites
• Family history of inflammatory bowel disease

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Case 2

• Physical examination
• Acutely ill
• Distended abdomen
• No hepatomegaly or splenomegaly
• Decreased bowel sounds
• Stool exam
• Gross blood present
• No pus cells
• Negative for OP, one negative CS

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Sigmoidoscopy revealed

• Multiple punctate bleeding sites at 7 to 15 cm
  with normal appearing mucosa between sites
• This mucosa easily denuded when pressure applied
  to it, leaving large areas of bleeding submucosa

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Case 2

• Diagnosed with ulcerative colitis
• Started on corticosteroids
• Temperature rose to 40C
• Abdomen distension increased and worsening of
  symptoms
• Emergency laparotomy for toxic megacolon

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Entamoeba histolytica

• One of 7 amoebae commonly found in humans
• Only one that causes significant disease
• Causes intestinal (diarrhea and dysentery) and
  extraintestinal (liver primarily) disease
• In US
• Institutionalized patients
• MSM
• Tourists returning from developing countries
• Patients with depressed cell mediated immunity

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Trophozoites with ingested RBC
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Trophozoites in colon tissue (H E stain)
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Cyst (wet mount)
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Amoebiasis Clinical Manifestations

• Symptoms depend on degree of bowel invasion
• Superficial watery diarrhea and nonspecific GI
  complaints
• Invasive gradual onset (1-3 weeks) of abdominal
  pain, bloody diarrhea, tenesmus
• Fever is seen in minority of patients

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Amoebiasis Clinical Manifestations

• Can be mistaken for ulcerative colitis
• Steroids can dramatically worsen and precipitate
  toxic megacolon
• Amebic liver abscesses
• RUQ pain, pain referred to right shoulder
• High fever
• Hepatomegaly (50)

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Amoebic Abscess

• Liquefaction of liver cells
• Do not contain pus
• Anchovy paste sauce
• Culture of contents usually sterile
• Liver affected
• 53-right lobe
• 8-left lobe

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Remember

• That stool is merely a convenient vehicle passing
  by
• Amoebae live the bowel wall
• Direct observation preferable to mere examination
  of stool
• Trophozoites best seen in direct scrapings of
  ulcers

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Amoebiasis Treatment

• Most respond to metronidazole
• Open surgical drainage should be avoided, if at
  all possible

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Case 3

• Previously healthy 3-year-old girl
• Attends day-care center
• 7 day history of watery diarrhea
• Nausea
• Vomiting
• Abdominal cramps
• Low-grade fever

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Case 4

• 34 year-old AIDS patient
• Debilitating, cholera-like diarrhea
• Severe abdominal cramps
• Malaise
• Low-grade fever
• Weight loss
• Anorexia

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Three cysts stained pale red are seen in the
center with this acid fast stain
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Modified acid-fast stain of stool showing red
oocysts of Cryptosporidium parvum against the
blue background of coliforms and debris
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Cryptosporidium parvum

• Causes secretory diarrhea 10 liter/day
• Significant cause of death in HIV/AIDS
• Animal reservoirs
• Incubation period 5-10 days

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Cryptosporidium parvum

• Infants young children in day-care
• Unfiltered or untreated drinking water
• Farming practices lambing, calving, and
  muck-spreading
• Sexual practices oral contact with stool of an
  infected individual
• Nosocomial setting with other infected patients
  or health-care employees
• Veterinarians contact with farm animals
• Travelers to areas with untreated water
• Living in densely populated urban areas
• Owners of infected household pets (rare)

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Diagnosis and Treatment

• Best diagnosed by stool exam
• No known effective treatment
• Nitazoxamide shortens duration of diarrhea

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Blood Protozoa
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Case 5

• Mr. Mrs. R. were sailing with their 3 children
  in Jamaica
• Living primarily on the boat with several day
  trips to a small coastal island
• On island, ate several types of tropical fruit
• Both became suddenly ill with fevers, chills,
  muscle aches, and loss of appetite.
• Sought treatment locally, and were diagnosed with
  hepatitis, likely due to ingestion of toxic fruit

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Case 5

• Two days later, Mr. R. became jaundiced and
  passed dark urine
• He progressively worsened, became comatose and
  died
• In the meantime, Mrs. R. was transferred to SUF
  for liver transplant

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Case 5

• None of the children were sick despite having
  eaten the same fruits and other foods.
• The family had taken chloroquine prophylaxis
  against malaria, but the parents stopped the
  medicine 2 weeks prior to becoming ill because of
  side effects.

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Falciparum vs. Vivax

• Location Falciparum confined to tropics and
  subtropics vivax more temperate
• Falciparum infects RBC of any age others like
  reticulocytes
• Falciparum-infected RBCs stick to vascular
  endothelium causing capillary blockage

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Malaria Genetic susceptibility

• Two genetic traits associated with decreased
  susceptibility to malaria
• Absence of Duffy blood group antigen blocks
  invasion of Plasmodium vivax
• Significant number of Africans
• Persons with sickle cell hemoglobin are resistant
  to P. falciparum
• Sickle cell disease and trait

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Malaria Clinical manifestations

• Non-specific, flu-like illness
• Incubation
• P. falciparum 9-40 days
• Non-P. falciparum may be prolonged
• P. vivax 6-12 months
• P. malariae and ovale years
• Fever is the hallmark of malaria
• Classically, 2-3 day intervals in P. vivax and
  malariae
• More irregular pattern in P. falciparum
• Fever occurs after the lysis of RBCs and release
  of merozoites

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Malaria Clinical manifestations

• Febrile paroxysms have 3 classic stages
• Cold stage
• Pt feels cold and has shaking chills
• 15-60 mins. prior to fever
• Hot stage
• 39-41C
• Lassitude, loss of appetite, bone and joint aches
• Tachycardia, hypotension, cough, HA, back pain,
  N/V, diarrhea, abdo pain, altered consciousness
• Sweating stage
• Marked diaphoresis followed by resolution of
  fever, profound fatigue, and sleepiness
• 2-6 hours after onset of hot stage

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Malaria Clinical manifestations

• Other symptoms depend on malaria strain
• P. vivax, ovale and malariae few other sxs
• P. falciparum
• Dependent upon host immune status
• No prior immunity/splenectomy ? high levels of
  parasitemia ? profound hemolysis
• Vascular obstruction and hypoxia
• Kidneys renal failure
• Brain (CNS) ? hypoxia, coma, seizures
• Lungs pulmonary edema
• Jaundice hemoglobinuria (blackwater fever)

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Malaria Clinical manifestations

• Always suspect malaria in travelers from
  developing countries who present with
• Influenza-like illness
• Jaundice
• Confusion or obtundation

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Diagnosis

• Giemsa-stained blood smear
• Thick and thin smears
• P. falciparum
• Best just after fever peak
• Others
• Smears can be performed at any time
• Examine blood on 3-4 successive days

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Differences in strains

• P. falciparum
• No dormant phase in liver
• Multiple signet ring trophs per cell
• High percentage (gt5) parasitized RBCs considered
  severe

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Differences in strains

• P. vivax and ovale
• Dormant liver phase
• Single signet ring trophs per cell
• Schuffners dots in cytoplasm
• Low percent (lt 5) of parasitized RBCs

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Differences in strains

• P. malariae
• No dormant stage
• Single signet ring trophs per cell
• Very low parasitemia

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Treatment

• P. falciparum malaria can be fatal if not
  promptly diagnosed and treated
• Non- P. falciparum malaria rarely requires
  hospitalization
• Widespread drug resistance dictates regimen
  (www.cdc.gov/travel CDC malaria hot line
  770-488-7788).

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TreatmentUncomplicated malaria

• P. vivax, ovale, malariae, chloroquine-susceptible
  falciparum
• Chloroquine
• Primaquine for dormant liver forms
• Chloroquine-resistant falciparum
• Quinine plus doxycycline
• Mefloquine
• Atovaquone plus proguanil (AP)
• Artemisins (common in SE Asia due to multi-drug
  resistance)

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TreatmentSevere malaria

• Drug options
• Quinidine gluconateonly approved parenteral
  agent in US
• Artemisin

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Prevention

• Mefloquine
• Doxycycline
• Nets
• 30-35 DEET
• Permethrin spray for clothing and nets

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And dont forget baggage malaria!
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Case 5

• Mrs. R. was treated with IV quinidine and
  improved rapidly.
• In retrospect, Mr. R. had died from untreated
  blackwater fever
• Few parasites in peripheral blood
• Acute renal failure

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Case 6

• 25-year-old Caucasian woman presented with 1-week
  history of fever, chills, sweating, myalgias,
  fatigue
• No travel abroad
• Had gone cranberry picking in Massachusetts
  approx 3 weeks earlier
• PE anemic, hepatosplenomegaly
• Blood workup hemolytic anemia, reduced
  platelets 

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Thick smear
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Thin smear
Maltese cross
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Babesiosis

• Babesiosis caused by hemoprotozoan parasites of
  the genus Babesia
• gt100 species reported
• Few actually cause human infection

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Babesiosis

• Babesia microti
• Life cycle involves two hosts
• Deer tick, Ixodes dammini, (definitive host)
  introduces sporozoites into white-footed mouse
• Once ingested by an appropriate tick gametes
  unite and undergo a sporogonic cycle resulting in
  sporozoites
• Humans enter cycle when bitten by infected ticks

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Babesiosis

• Deer are the hosts upon which the adult ticks
  feed and are indirectly part of the Babesia cycle
  as they influence the tick population

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Babesiosis

• Clindamycin plus quinine
• Atovaquone plus azithromycin
• Exchange transfusion in severely ill patients
  with high parasitemia
• Approved by FDA

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Summary

• Chronic diarrhea caused by
• Amoeba
• Giardia
• Cryptosporidum
• Isospora belli
• Microsporidium
• Malaria - P. falciparum clinical manifestations.
  Differentiation from P. vivax by peripheral smear
• Babesiosis - tickborne, Northeast USA