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Parasitic Infections: Clinical Manifestations, Diagnosis and Treatment Lennox K. Archibald, MD, PhD, FRCP, DTM&H  Hospital...
The Reality <ul><li>1.3 billion persons infected with Ascaris (1: 4 persons on earth) </li></ul><ul><li>300 million with s...
Case1  <ul><li>42-yr-old previously healthy, UF professor </li></ul><ul><li>6-week history of intermittent diarrhea, flatu...
Case 1 <ul><li>His 8-yr-old son had had a mild course of watery diarrhea—ascribed to viral gastroenteritis by general prac...
 
 
Diagnosis?
Giardiasis ( G. lamblia ) <ul><li>Should be suspected in prolonged diarrhea </li></ul><ul><li>Contaminated water often imp...
Giardiasis  Tests of choice <ul><li>Examination of concentrated stools for cysts (90% yield after 3 samples) </li></ul><ul...
Case 2 <ul><li>40 y/o male vicar returned from 2 years of missionary work in South Africa </li></ul><ul><li>Excellent heal...
Case 2 <ul><li>Physical examination: </li></ul><ul><ul><li>Acutely ill </li></ul></ul><ul><ul><li>Distended abdomen </li><...
Sigmoidoscopy revealed… <ul><li>Multiple punctate bleeding sites at 7 to 15 cm with  normal  appearing mucosa between site...
Case 2 <ul><li>Diagnosed with ulcerative colitis </li></ul><ul><li>Started on corticosteroids </li></ul><ul><li>Temperatur...
 
 
Diagnosis?
Entamoeba histolytica <ul><li>One of 7 amoebae commonly found in humans </li></ul><ul><li>Only one that causes significant...
Trophozoites with ingested RBC
Trophozoites in colon tissue (H & E stain)
Cyst (wet mount)
Amoebiasis: Clinical Manifestations <ul><li>Symptoms depend on degree of bowel invasion </li></ul><ul><ul><li>Superficial:...
Amoebiasis: Clinical Manifestations <ul><li>Can be mistaken for ulcerative colitis </li></ul><ul><li>Steroids can dramatic...
Amoebic abscess—remember… <ul><li>Can occur in lung, brain, spleen </li></ul>
Amoebic Abscess <ul><li>Liquefaction of liver cells </li></ul><ul><li>Do not contain pus </li></ul><ul><li>Anchovy paste s...
 
 
Remember… <ul><li>That stool is merely a convenient vehicle passing by </li></ul><ul><li>Amoebae live the bowel wall </li>...
Amoebiasis  Treatment <ul><li>Most respond to metronidazole </li></ul><ul><li>Open surgical drainage should be avoided, if...
Case 3 <ul><li>Previously healthy 3-year-old girl </li></ul><ul><li>Attends day-care center </li></ul><ul><li>7 day histor...
 
Case 4 <ul><li>34 year-old AIDS patient </li></ul><ul><li>Debilitating, cholera-like diarrhea  </li></ul><ul><li>Severe ab...
 
Diagnosis? Case 3 & 4
Three cysts stained pale red are seen in the center with this acid fast stain
Modified acid-fast stain of stool showing red oocysts of  Cryptosporidium parvum  against the blue background of coliforms...
Cryptosporidium parvum <ul><li>Causes secretory diarrhea: 10 liter/day </li></ul><ul><li>Significant cause of death in HIV...
Cryptosporidium parvum <ul><li>Infants & young children in day-care  </li></ul><ul><li>Unfiltered or untreated drinking wa...
Diagnosis and Treatment <ul><li>Best diagnosed by stool exam </li></ul><ul><li>No known effective treatment </li></ul><ul>...
Case 5 <ul><li>Mr. & Mrs. R. were sailing with their 3 children in Jamaica </li></ul><ul><li>Living primarily on the boat ...
Case 5 <ul><li>Two days later, Mr. R. became jaundiced and passed dark urine </li></ul><ul><li>He progressively worsened, ...
Case 5 <ul><li>None of the children were sick despite having eaten the same fruits and other foods. </li></ul><ul><li>The ...
 
 
Falciparum vs. Vivax <ul><li>Location: Falciparum confined to tropics and subtropics; vivax more temperate </li></ul><ul><...
 
 
Malaria: Genetic susceptibility <ul><li>Two genetic traits associated with decreased susceptibility to malaria </li></ul><...
Malaria: Clinical manifestations <ul><li>Non-specific, flu-like illness </li></ul><ul><li>Incubation </li></ul><ul><ul><li...
Malaria: Clinical manifestations <ul><li>Febrile paroxysms have 3 classic stages </li></ul><ul><ul><li>Cold stage </li></u...
Malaria: Clinical manifestations <ul><li>Other symptoms depend on malaria strain </li></ul><ul><li>P. vivax, ovale  and  m...
Malaria: Clinical manifestations <ul><li>Always suspect malaria in travelers from developing countries who present with: <...
Diagnosis <ul><li>Giemsa-stained blood smear </li></ul><ul><ul><li>Thick and thin smears </li></ul></ul><ul><li>P. falcipa...
Differences in strains <ul><li>P. falciparum </li></ul><ul><ul><li>No dormant phase in liver </li></ul></ul><ul><ul><li>Mu...
Differences in strains <ul><li>P. vivax  and  ovale </li></ul><ul><ul><li>Dormant liver phase </li></ul></ul><ul><ul><li>S...
Differences in strains <ul><li>P. malariae </li></ul><ul><ul><li>No dormant stage </li></ul></ul><ul><ul><li>Single signet...
Treatment <ul><li>P. falciparum  malaria can be fatal if not promptly diagnosed and treated </li></ul><ul><li>Non-  P. fal...
Treatment Uncomplicated malaria <ul><li>P. vivax, ovale, malariae,  chloroquine-susceptible  falciparum </li></ul><ul><ul>...
Treatment Severe malaria <ul><li>Drug options </li></ul><ul><ul><li>Quinidine gluconate—only approved parenteral agent in ...
Prevention <ul><li>Mefloquine </li></ul><ul><li>Doxycycline </li></ul><ul><li>Nets </li></ul><ul><li>30-35% DEET </li></ul...
And don’t forget baggage malaria!
Case 5 <ul><li>Mrs. R. was treated with IV quinidine and improved rapidly. </li></ul><ul><li>In retrospect, Mr. R. had die...
Case 6 <ul><li>A 24-year-old white male army officer </li></ul><ul><li>Referred to the VA ID clinic with a 3-month history...
Case 6  <ul><li>Physical examination essentially normal except for: </li></ul><ul><li>Non-tender (20 × 15 mm) scaly erythe...
 
Diagnosis?
 
An intact macrophage practically filled with amastigotes (arrows),
Leishmaniasis <ul><li>Tropical areas where phlebotomine sandfly is common: South America, India, Bangladesh, Middle East, ...
Leishmaniasis <ul><li>Cutaneous  </li></ul><ul><ul><li>Most common among farmers, settlers, troops and tourists in Mid Eas...
Leishmaniasis: Diagnosis <ul><li>Biopsy and Giemsa stain with amastigotes </li></ul><ul><li>Species most prevalent in diff...
Visceral Leishmaniasis <ul><li>Dissemination of amastigotes throughout the reticulendothelial system of the body </li></ul...
Hepatosplenomegaly
Splenic aspirate <ul><li>Most satisfactory method </li></ul><ul><li>Spleen must be at least 3cm below LCM </li></ul><ul><l...
Leishmaniasis: treatment <ul><li>Only drug approved in US is Amphotericin B </li></ul><ul><li>Treatment of cutaneous disea...
 
Remember.. <ul><li>The factors determining the form of leishmaniasis: </li></ul><ul><ul><li>Leishmanial species </li></ul>...
Case 7 <ul><li>38-year-old businessman </li></ul><ul><li>Previously fit  </li></ul><ul><li>2-week history of fever since r...
Case 8 <ul><li>A 29-yr-old man with AIDS (CD4 count=59) presents with a 2 week history of headache, fevers and new onset s...
Cases 7 & 8 <ul><li>What parasite could  </li></ul><ul><li>cause this picture? </li></ul>
AIDS Patient
AIDS Patient
Toxoplasma gondii  cyst in brain tissue with H & E stain (100x)
For the businessman… <ul><li>Toxoplasma  serology was positive at a very high titer  </li></ul><ul><li>Responded to treatm...
Transmission <ul><li>Eating oocysts excreted by cats harboring sexual stages of parasite </li></ul><ul><li>Outbreaks trace...
Toxoplasma gondii <ul><li>Worldwide distribution </li></ul><ul><li>Human infection </li></ul><ul><ul><li>Ingestion of cyst...
Toxoplasma gondii:    Immunocompetent hosts <ul><li>Latent infection (persistence of cysts) is generally asymptomatic </li...
Toxoplasma gondii:  Immunocompromised hosts <ul><li>Often life-threatening </li></ul><ul><li>Almost always reactivation of...
Toxoplasma gondii:  Clinical manifestations <ul><li>Immunocompromised hosts </li></ul><ul><ul><li>Non-AIDS  (transplants, ...
Toxoplasma gondii:  Clinical manifestations <ul><li>Congenital </li></ul><ul><li>Acute infection asymptomatic in mother </...
Toxoplasma gondii:  diagnosis <ul><li>Clinical suspicion crucial </li></ul><ul><li>Serology is primary method of diagnosis...
Toxoplasma gondii:  Treatment <ul><li>Immunocompetent adults are usually not treated unless visceral disease is overt or s...
Toxoplasma gondii:  Treatment <ul><li>Congenital: </li></ul><ul><ul><li>Treatment of acute infected pregnant women decreas...
Case 22 <ul><li>25-year-old Caucasian woman presented with 1-week history of fever, chills, sweating, myalgias, fatigue </...
Thick smear
Thin smear Maltese cross
Diagnosis??
Babesiosis <ul><li>Babesiosis caused by hemoprotozoan parasites of the genus  Babesia </li></ul><ul><li>> 100 species repo...
Babesiosis <ul><li>Babesia microti   </li></ul><ul><li>Life cycle involves two hosts:  </li></ul><ul><ul><li>Deer tick,  I...
Babesiosis <ul><li>Deer are the hosts upon which the adult ticks feed and are indirectly part of the  Babesia  cycle as th...
Babesiosis <ul><li>Clindamycin* plus quinine  </li></ul><ul><li>Atovaquone* plus azithromycin*  </li></ul><ul><li>Exchange...
Case 9 <ul><li>6-year-old son of seasonal farm worker </li></ul><ul><li>Presents with cough and fever, wheeze </li></ul><u...
 
Diagnosis?
Ascaris lumbricoides <ul><li>In GI tract, few symptoms in light infections </li></ul><ul><ul><li>Nausea </li></ul></ul><ul...
Effects of Adult  Ascaris  Worms <ul><li>Depends on worm load </li></ul><ul><li>Effects </li></ul><ul><ul><li>Mechanical: ...
Ascaris lumbricoides Diagnosis <ul><li>Characteristic eggs on direct smear examination </li></ul><ul><li>If treating mixed...
 
Case 10 <ul><li>11-year-old female </li></ul><ul><li>Doing poorly in school </li></ul><ul><li>Not sleeping well </li></ul>...
 
 
 
Diagnosis?
Enterobius (Pinworm) <ul><li>18 million infections in U.S. </li></ul><ul><li>Incidence higher in whites </li></ul><ul><li>...
<ul><li>69-year-old male was admitted to VA Hospital </li></ul><ul><li>Far East Prisoner of War (FEPOW) </li></ul><ul><li>...
On the day of admission… <ul><li>Fever, confusion, and not able to get out of bed---transported to the hospital </li></ul>...
 
Diagnosis
Strongyloides: Crucial Aspects of Life Cycle <ul><li>Infection acquired through penetration of intact skin </li></ul><ul><...
Disseminated Strongyloidiasis <ul><li>High mortality  75% </li></ul><ul><li>Penetration of gut wall by infective larvae <...
Summary—Clinical Findings <ul><li>Defective cell-meditated immunity: steroids, burns, lymphomas, AIDS (?) </li></ul><ul><l...
Summary—Clinical Findings <ul><li>Skin rash or pruritis in  ~ one-third   </li></ul><ul><ul><li>Larva currens (racing larv...
Summary-Clinical Findings <ul><li>Eosinophilia 60-95% </li></ul><ul><li>Less if on steroids  </li></ul>
Case 12 <ul><li>57 year old farmer from Dixie County </li></ul><ul><li>Presents with profound SOB </li></ul><ul><li>Physic...
 
Diagnosis?
 
Hookworm <ul><li>Hookworm responsible for development of USPHS </li></ul><ul><li>Caused by two different species (North Am...
 
 
Case 13 <ul><li>8-yr-old schoolgirl visiting the U.S. from Malaysia </li></ul><ul><li>1 week history of epigastric pain, f...
 
Diagnosis?
Trichuris trichiura  (Whipworm) <ul><li>Common in Southeast U.S.  </li></ul><ul><li>Frequently coexists with ascaris </li>...
 
 
 
Case 14 <ul><li>18-year-old trailer park handyman seen in ER </li></ul><ul><li>Worked under trailers wearing shorts and no...
 
Case 15 <ul><li>An 8 year old boy </li></ul><ul><li>Presents with skin lesions and itching after spending the summer at a ...
 
Diagnosis ?
Cutaneous Larva Migrans <ul><li>Caused by filariform larvae of dog or cat hookworm ( Ancylostoma braziliense  or  Ancylost...
Cutaneous larva migrans  (creeping eruption) <ul><li>More common in children </li></ul><ul><ul><li>Larvae penetrate skin a...
Cutaneous larva migrans  (creeping eruption) <ul><ul><li>Usually not associated with systemic symptoms  </li></ul></ul>
Cutaneous larva migrans  (creeping eruption) <ul><li>Diagnosis and treatment </li></ul><ul><li>Skin lesions are readily re...
 
 
Visceral Larva Migrans  <ul><li>Infection with dog or cat  round worms </li></ul><ul><li>Toxocara canis; Toxocara catis </...
Case 17 <ul><li>A 34 yr-old woman from Saudi Arabia </li></ul><ul><li>Radiation and cyclophosphamide, adriamycin, vincrist...
Case 17 <ul><li>No evidence of lymphoma found on re-staging </li></ul><ul><li>Completed chemo, was deemed to be in complet...
 
Chronic intestinal schistosomiasis
Case 17 <ul><li>The patient was treated with praziquantel and did not have relapse of symptoms at 2-year follow-up </li></...
Schistosomiasis: Epidemiology  and life cycle <ul><li>Cercariae in fresh water penetrate human skin. </li></ul><ul><li>Cer...
Schistosomiasis: Epidemiology  and life cycle <ul><li>Worms release eggs for many years into stool or urine, resulting in ...
Schistosomiasis: Clinical manifestations <ul><li>Three stages of disease, corresponding to life cycle within human hosts <...
Chronic Schistosomiasis <ul><li>Granulomatous reaction to egg deposition in intestine, liver, bladder, lungs  </li></ul><u...
Schistosomiasis:  Diagnosis and Treatment <ul><li>Detection of characteristic eggs in stool, urine or tissue biopsy is dia...
 
S. mansoni Stool S. haematobium Urine S. japonicum
Case 18 <ul><li>15-yr-old girl  </li></ul><ul><li>Fever, rash, swelling around the eye and hands, severe headaches </li></...
Diagnosis?
Investigations <ul><li>Blood films </li></ul><ul><li>Lumbar puncture </li></ul>
Blood smear
African trypanosomiasis Trypanosoma brucei gambiense
Tsetse fly
Treatment <ul><li>Suramin </li></ul><ul><li>Melasoprol </li></ul>
Case 19 <ul><li>6-yr-old boy recently arrived from Brazil </li></ul><ul><li>Swelling around the eye </li></ul><ul><li>Conj...
 
Diagnosis?
Blood smear
Reduviid bug (assassin bug)
Chagas disease:  Clinical manifestations  <ul><li>Local edema is followed by fever, malaise, anorexia </li></ul><ul><ul><l...
Chagas disease: Diagnosis  and treatment <ul><li>Acute disease is diagnosed by seeing trypomastigotes on peripheral blood ...
Chagas Disease <ul><li>Public health implications in the US </li></ul><ul><li>Chronic  </li></ul><ul><ul><li>Cardiomyopath...
Case 20 <ul><li>20-yr-old male </li></ul><ul><li>Abdominal pain and nausea for several months  </li></ul><ul><li>More comm...
 
Diagnosis?
Taenia saginata <ul><li>Ingestion of raw or poorly cooked beef </li></ul><ul><li>Cows infected via the ingestion of human ...
Beef Tapeworm
Treatment <ul><li>Praziquantel </li></ul><ul><li>Albendazole </li></ul><ul><li>Niclosamide </li></ul>
Tapeworms (Cestodes) <ul><li>Adult worms inhabit GI tract of definitive vertebrate host </li></ul><ul><li>Larvae inhabit t...
Case 21 <ul><li>A 33 year-old Indian man was admitted with a grand mal seizure </li></ul><ul><li>2 yrs PTA, he had vertigo...
Case 21 <ul><li>Difficulty speaking and loss of consciousness while on the phone </li></ul><ul><li>Co-workers noticed gene...
 
Case 21 <ul><li>ELISA titer was positive for antibodies against  Taenia solium. </li></ul><ul><li>The neurosurgeons tell y...
Cystercercosis <ul><li>Human infected with the larval stage of  Taenia solium </li></ul><ul><li>Humans can serve as defini...
Cystercercosis <ul><li>Symptoms depend on location of cysts, but frequently include motor spasms, seizures, confusion, irr...
Cysticercosis <ul><li>Clinical manifestations </li></ul><ul><ul><li>Adult worms rarely cause sxs </li></ul></ul><ul><ul><l...
Cysticercosis <ul><li>Diagnosis </li></ul><ul><ul><li>CT and MRI preferred studies </li></ul></ul><ul><ul><ul><li>Discrete...
Cysticercosis <ul><li>Treatment </li></ul><ul><ul><li>Complex and controversial </li></ul></ul><ul><ul><li>Praziquantel an...
 
 
Case 21 <ul><li>He was not treated with praziquantel or albendazole </li></ul><ul><li>He continued to receive dilantin for...
Classification of Parasitic Diseases <ul><li>Protozoa: amoeba; flagellates; ciliates </li></ul><ul><li>Metazoa (two phyla)...
General rules of treatment <ul><li>Protozoa: require species-specific treatment </li></ul><ul><li>Metozoa: species-specifi...
General rules of treatment of metazoa Nematodes Intestinal Mebendazole or Albendazole Tissue Albendazole Filiariae Ivermec...
This is just the beginning of a great adventure in infectious diseases Sine qua non :  history and physical examination
Thank you Lennox K. Archibald, MD, PhD, FRCP [email_address]
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Transcript of "Clinical Parasitology 08"

  1. 1. Parasitic Infections: Clinical Manifestations, Diagnosis and Treatment Lennox K. Archibald, MD, PhD, FRCP, DTM&H Hospital Epidemiologist University of Florida
  2. 2. The Reality <ul><li>1.3 billion persons infected with Ascaris (1: 4 persons on earth) </li></ul><ul><li>300 million with schistosomiasis </li></ul><ul><li>100 million new malaria cases/yr </li></ul><ul><li>At UCLA, 38% of pediatric and dental clinic children harbored intestinal parasites </li></ul>
  3. 3. Case1 <ul><li>42-yr-old previously healthy, UF professor </li></ul><ul><li>6-week history of intermittent diarrhea, flatus and abdominal cramps </li></ul><ul><li>Diarrhea: x8/day; pale; no blood or mucus </li></ul><ul><li>No tenesmus </li></ul><ul><li>Illness began slowly during camping trip to Colorado with loose stools </li></ul><ul><li>Spontaneously remission for 5-6 days at a time, then recur </li></ul>
  4. 4. Case 1 <ul><li>His 8-yr-old son had had a mild course of watery diarrhea—ascribed to viral gastroenteritis by general practitioner </li></ul><ul><li>Stool smear—no pus cells </li></ul><ul><li>However, wet preps showed… </li></ul>
  5. 7. Diagnosis?
  6. 8. Giardiasis ( G. lamblia ) <ul><li>Should be suspected in prolonged diarrhea </li></ul><ul><li>Contaminated water often implicated—outbreaks </li></ul><ul><li>Campers who fail to sterilize mountain stream water </li></ul><ul><li>Person-person in day care centers </li></ul><ul><li>MSM </li></ul><ul><li>Symptoms usually resolve spontaneously in 4-6 weeks </li></ul>
  7. 9. Giardiasis Tests of choice <ul><li>Examination of concentrated stools for cysts (90% yield after 3 samples) </li></ul><ul><ul><li>Usually no PMNs </li></ul></ul><ul><li>Stool ELISA, IF Antigen (up to 98% sensitive/90-100% specific) </li></ul><ul><li>Consider aspiration of duodenal contents--trophozoites </li></ul><ul><li>Treatment: Metronidazole for 5-7 days </li></ul>
  8. 10. Case 2 <ul><li>40 y/o male vicar returned from 2 years of missionary work in South Africa </li></ul><ul><li>Excellent health throughout stay there </li></ul><ul><li>3 months after returning to U.S. </li></ul><ul><ul><li>Suddenly ill with abdominal distension </li></ul></ul><ul><ul><li>Fever </li></ul></ul><ul><ul><li>Periumbilical pain </li></ul></ul><ul><ul><li>Vomiting </li></ul></ul><ul><ul><li>Blood-tinged diarrheal stools </li></ul></ul><ul><li>Denied arthritis /known exposure to parasites </li></ul><ul><li>Family history of “inflammatory bowel disease” </li></ul>
  9. 11. Case 2 <ul><li>Physical examination: </li></ul><ul><ul><li>Acutely ill </li></ul></ul><ul><ul><li>Distended abdomen </li></ul></ul><ul><ul><li>No hepatomegaly or splenomegaly </li></ul></ul><ul><ul><li>Decreased bowel sounds </li></ul></ul><ul><ul><li>Stool exam </li></ul></ul><ul><ul><ul><li>Gross blood present </li></ul></ul></ul><ul><ul><ul><li>No pus cells </li></ul></ul></ul><ul><ul><ul><li>Negative for O&P, one negative C&S </li></ul></ul></ul>
  10. 12. Sigmoidoscopy revealed… <ul><li>Multiple punctate bleeding sites at 7 to 15 cm with normal appearing mucosa between sites </li></ul><ul><li>This mucosa easily denuded when pressure applied to it, leaving large areas of bleeding submucosa </li></ul>
  11. 13. Case 2 <ul><li>Diagnosed with ulcerative colitis </li></ul><ul><li>Started on corticosteroids </li></ul><ul><li>Temperature rose to 40 °C </li></ul><ul><li>Abdomen distension increased and worsening of symptoms </li></ul><ul><li>Emergency laparotomy for toxic megacolon </li></ul>
  12. 16. Diagnosis?
  13. 17. Entamoeba histolytica <ul><li>One of 7 amoebae commonly found in humans </li></ul><ul><li>Only one that causes significant disease </li></ul><ul><li>Causes intestinal (diarrhea and dysentery) and extraintestinal (liver primarily) disease </li></ul><ul><li>In US </li></ul><ul><ul><li>Institutionalized patients </li></ul></ul><ul><ul><li>MSM </li></ul></ul><ul><ul><li>Tourists returning from developing countries </li></ul></ul><ul><ul><li>Patients with depressed cell mediated immunity </li></ul></ul>
  14. 18. Trophozoites with ingested RBC
  15. 19. Trophozoites in colon tissue (H & E stain)
  16. 20. Cyst (wet mount)
  17. 21. Amoebiasis: Clinical Manifestations <ul><li>Symptoms depend on degree of bowel invasion </li></ul><ul><ul><li>Superficial: watery diarrhea and nonspecific GI complaints </li></ul></ul><ul><ul><li>Invasive: gradual onset (1-3 weeks) of abdominal pain, bloody diarrhea, tenesmus </li></ul></ul><ul><li>Fever is seen in minority of patients </li></ul>
  18. 22. Amoebiasis: Clinical Manifestations <ul><li>Can be mistaken for ulcerative colitis </li></ul><ul><li>Steroids can dramatically worsen and precipitate toxic megacolon </li></ul><ul><li>Amebic liver abscesses </li></ul><ul><ul><li>RUQ pain, pain referred to right shoulder </li></ul></ul><ul><ul><li>High fever </li></ul></ul><ul><ul><li>Hepatomegaly (50%) </li></ul></ul>
  19. 23. Amoebic abscess—remember… <ul><li>Can occur in lung, brain, spleen </li></ul>
  20. 24. Amoebic Abscess <ul><li>Liquefaction of liver cells </li></ul><ul><li>Do not contain pus </li></ul><ul><li>Anchovy paste sauce </li></ul><ul><li>Culture of contents usually sterile </li></ul><ul><li>Liver affected: </li></ul><ul><ul><li>53%-right lobe </li></ul></ul><ul><ul><li>8%-left lobe </li></ul></ul>
  21. 27. Remember… <ul><li>That stool is merely a convenient vehicle passing by </li></ul><ul><li>Amoebae live the bowel wall </li></ul><ul><li>Direct observation preferable to mere examination of stool </li></ul><ul><li>Trophozoites best seen in direct scrapings of ulcers </li></ul>
  22. 28. Amoebiasis Treatment <ul><li>Most respond to metronidazole </li></ul><ul><li>Open surgical drainage should be avoided, if at all possible </li></ul>
  23. 29. Case 3 <ul><li>Previously healthy 3-year-old girl </li></ul><ul><li>Attends day-care center </li></ul><ul><li>7 day history of watery diarrhea </li></ul><ul><li>Nausea </li></ul><ul><li>Vomiting </li></ul><ul><li>Abdominal cramps </li></ul><ul><li>Low-grade fever </li></ul>
  24. 31. Case 4 <ul><li>34 year-old AIDS patient </li></ul><ul><li>Debilitating, cholera-like diarrhea </li></ul><ul><li>Severe abdominal cramps </li></ul><ul><li>Malaise </li></ul><ul><li>Low-grade fever </li></ul><ul><li>Weight loss </li></ul><ul><li>Anorexia </li></ul>
  25. 33. Diagnosis? Case 3 & 4
  26. 34. Three cysts stained pale red are seen in the center with this acid fast stain
  27. 35. Modified acid-fast stain of stool showing red oocysts of Cryptosporidium parvum against the blue background of coliforms and debris
  28. 36. Cryptosporidium parvum <ul><li>Causes secretory diarrhea: 10 liter/day </li></ul><ul><li>Significant cause of death in HIV/AIDS </li></ul><ul><li>Animal reservoirs </li></ul><ul><li>Incubation period: 5-10 days </li></ul>
  29. 37. Cryptosporidium parvum <ul><li>Infants & young children in day-care </li></ul><ul><li>Unfiltered or untreated drinking water </li></ul><ul><li>Farming practices: lambing, calving, and muck-spreading </li></ul><ul><li>Sexual practices: oral contact with stool of an infected individual </li></ul><ul><li>Nosocomial setting with other infected patients or health-care employees </li></ul><ul><li>Veterinarians: contact with farm animals </li></ul><ul><li>Travelers to areas with untreated water </li></ul><ul><li>Living in densely populated urban areas </li></ul><ul><li>Owners of infected household pets (rare) </li></ul>
  30. 38. Diagnosis and Treatment <ul><li>Best diagnosed by stool exam </li></ul><ul><li>No known effective treatment </li></ul><ul><li>Nitazoxamide shortens duration of diarrhea </li></ul>
  31. 39. Case 5 <ul><li>Mr. & Mrs. R. were sailing with their 3 children in Jamaica </li></ul><ul><li>Living primarily on the boat with several day trips to a small coastal island </li></ul><ul><li>On island, ate several types of tropical fruit </li></ul><ul><li>Both became suddenly ill with fevers, chills, muscle aches, and loss of appetite. </li></ul><ul><li>Sought treatment locally, and were diagnosed with hepatitis, likely due to ingestion of toxic fruit </li></ul>
  32. 40. Case 5 <ul><li>Two days later, Mr. R. became jaundiced and passed dark urine </li></ul><ul><li>He progressively worsened, became comatose and died </li></ul><ul><li>In the meantime, Mrs. R. was transferred to SUF for liver transplant </li></ul>
  33. 41. Case 5 <ul><li>None of the children were sick despite having eaten the same fruits and other foods. </li></ul><ul><li>The family had taken chloroquine prophylaxis against malaria, but the parents stopped the medicine 2 weeks prior to becoming ill because of side effects. </li></ul>
  34. 44. Falciparum vs. Vivax <ul><li>Location: Falciparum confined to tropics and subtropics; vivax more temperate </li></ul><ul><li>Falciparum infects RBC of any age; others like reticulocytes </li></ul><ul><li>Falciparum-infected RBCs stick to vascular endothelium causing capillary blockage </li></ul>
  35. 47. Malaria: Genetic susceptibility <ul><li>Two genetic traits associated with decreased susceptibility to malaria </li></ul><ul><li>Absence of Duffy blood group antigen blocks invasion of Plasmodium vivax </li></ul><ul><ul><li>Significant number of Africans </li></ul></ul><ul><li>Persons with sickle cell hemoglobin are resistant to P. falciparum </li></ul><ul><li>Sickle cell disease and trait </li></ul>
  36. 48. Malaria: Clinical manifestations <ul><li>Non-specific, flu-like illness </li></ul><ul><li>Incubation </li></ul><ul><ul><li>P. falciparum : 9-40 days </li></ul></ul><ul><ul><li>Non-P. falciparum : may be prolonged </li></ul></ul><ul><ul><ul><li>P. vivax : 6-12 months </li></ul></ul></ul><ul><ul><ul><li>P. malariae and ovale : years </li></ul></ul></ul><ul><li>Fever is the hallmark of malaria </li></ul><ul><ul><li>Classically, 2-3 day intervals in P. vivax and malariae </li></ul></ul><ul><ul><li>More irregular pattern in P. falciparum </li></ul></ul><ul><li>Fever occurs after the lysis of RBCs and release of merozoites </li></ul>
  37. 49. Malaria: Clinical manifestations <ul><li>Febrile paroxysms have 3 classic stages </li></ul><ul><ul><li>Cold stage </li></ul></ul><ul><ul><ul><li>Pt feels cold and has shaking chills </li></ul></ul></ul><ul><ul><ul><li>15-60 mins. prior to fever </li></ul></ul></ul><ul><ul><li>Hot stage </li></ul></ul><ul><ul><ul><li>39-41 °C </li></ul></ul></ul><ul><ul><ul><li>Lassitude, loss of appetite, bone and joint aches </li></ul></ul></ul><ul><ul><ul><li>Tachycardia, hypotension, cough, HA, back pain, N/V, diarrhea, abdo pain, altered consciousness </li></ul></ul></ul><ul><ul><li>Sweating stage </li></ul></ul><ul><ul><ul><li>Marked diaphoresis followed by resolution of fever, profound fatigue, and sleepiness </li></ul></ul></ul><ul><ul><ul><li>2-6 hours after onset of hot stage </li></ul></ul></ul>
  38. 50. Malaria: Clinical manifestations <ul><li>Other symptoms depend on malaria strain </li></ul><ul><li>P. vivax, ovale and malariae : few other sxs </li></ul><ul><li>P. falciparum : </li></ul><ul><ul><li>Dependent upon host immune status </li></ul></ul><ul><ul><li>No prior immunity/splenectomy  high levels of parasitemia  profound hemolysis </li></ul></ul><ul><ul><li>Vascular obstruction and hypoxia </li></ul></ul><ul><ul><ul><li>Kidneys: renal failure </li></ul></ul></ul><ul><ul><ul><li>Brain: (CNS) ― hypoxia, coma, seizures </li></ul></ul></ul><ul><ul><ul><li>Lungs: pulmonary edema </li></ul></ul></ul><ul><ul><li>Jaundice & hemoglobinuria (blackwater fever) </li></ul></ul>
  39. 51. Malaria: Clinical manifestations <ul><li>Always suspect malaria in travelers from developing countries who present with: </li></ul><ul><ul><li>Influenza-like illness </li></ul></ul><ul><ul><li>Jaundice </li></ul></ul><ul><ul><li>Confusion or obtundation </li></ul></ul>
  40. 52. Diagnosis <ul><li>Giemsa-stained blood smear </li></ul><ul><ul><li>Thick and thin smears </li></ul></ul><ul><li>P. falciparum: </li></ul><ul><ul><li>Best just after fever peak </li></ul></ul><ul><li>Others: </li></ul><ul><ul><li>Smears can be performed at any time </li></ul></ul><ul><li>Examine blood on 3-4 successive days </li></ul>
  41. 53. Differences in strains <ul><li>P. falciparum </li></ul><ul><ul><li>No dormant phase in liver </li></ul></ul><ul><ul><li>Multiple signet ring trophs per cell </li></ul></ul><ul><ul><li>High percentage (>5%) parasitized RBCs considered severe </li></ul></ul>
  42. 54. Differences in strains <ul><li>P. vivax and ovale </li></ul><ul><ul><li>Dormant liver phase </li></ul></ul><ul><ul><li>Single signet ring trophs per cell </li></ul></ul><ul><ul><li>Schuffner’s dots in cytoplasm </li></ul></ul><ul><ul><li>Low percent (< 5%) of parasitized RBCs </li></ul></ul>
  43. 55. Differences in strains <ul><li>P. malariae </li></ul><ul><ul><li>No dormant stage </li></ul></ul><ul><ul><li>Single signet ring trophs per cell </li></ul></ul><ul><ul><li>Very low parasitemia </li></ul></ul>
  44. 56. Treatment <ul><li>P. falciparum malaria can be fatal if not promptly diagnosed and treated </li></ul><ul><li>Non- P. falciparum malaria rarely requires hospitalization </li></ul><ul><li>Widespread drug resistance dictates regimen ( www.cdc.gov/travel ; CDC malaria hot line: 770-488-7788). </li></ul>
  45. 57. Treatment Uncomplicated malaria <ul><li>P. vivax, ovale, malariae, chloroquine-susceptible falciparum </li></ul><ul><ul><li>Chloroquine </li></ul></ul><ul><ul><li>Primaquine for dormant liver forms </li></ul></ul><ul><li>Chloroquine-resistant falciparum </li></ul><ul><ul><li>Quinine plus doxycycline </li></ul></ul><ul><ul><li>Mefloquine </li></ul></ul><ul><ul><li>Atovaquone plus proguanil (AP) </li></ul></ul><ul><ul><li>Artemisins (common in SE Asia due to multi-drug resistance) </li></ul></ul>
  46. 58. Treatment Severe malaria <ul><li>Drug options </li></ul><ul><ul><li>Quinidine gluconate—only approved parenteral agent in US </li></ul></ul><ul><ul><li>Artemisin </li></ul></ul>
  47. 59. Prevention <ul><li>Mefloquine </li></ul><ul><li>Doxycycline </li></ul><ul><li>Nets </li></ul><ul><li>30-35% DEET </li></ul><ul><li>Permethrin spray for clothing and nets </li></ul>
  48. 60. And don’t forget baggage malaria!
  49. 61. Case 5 <ul><li>Mrs. R. was treated with IV quinidine and improved rapidly. </li></ul><ul><li>In retrospect, Mr. R. had died from untreated blackwater fever </li></ul><ul><ul><li>Few parasites in peripheral blood </li></ul></ul><ul><ul><li>Acute renal failure </li></ul></ul>
  50. 62. Case 6 <ul><li>A 24-year-old white male army officer </li></ul><ul><li>Referred to the VA ID clinic with a 3-month history of a lesion on his right leg, developing approximately 2 weeks after returning from Iraq </li></ul><ul><li>Recent travel history: 1 month in Kuwait and 2 months traveling between Kuwait and Iraq </li></ul><ul><li>Recalled being bitten numerous times by small flying insects and other nasty “bugs” </li></ul>
  51. 63. Case 6 <ul><li>Physical examination essentially normal except for: </li></ul><ul><li>Non-tender (20 × 15 mm) scaly erythematous plaque with a moist central erosion of the left popliteal area. </li></ul><ul><li>There was no lymphadenopathy and no mucosal lesions were noted </li></ul>
  52. 65. Diagnosis?
  53. 67. An intact macrophage practically filled with amastigotes (arrows),
  54. 68. Leishmaniasis <ul><li>Tropical areas where phlebotomine sandfly is common: South America, India, Bangladesh, Middle East, East Africa </li></ul><ul><li>Sandfly introduces flagellated promastigote into human  ingested by macrophages  develops into nonflagellated amastigote </li></ul>
  55. 69. Leishmaniasis <ul><li>Cutaneous </li></ul><ul><ul><li>Most common among farmers, settlers, troops and tourists in Mid East (L. major and tropica), Central and South America (L. mexicana, braziliensis, amazonensis, and panamensis) </li></ul></ul><ul><ul><li>L. mexicana reported in Texas </li></ul></ul><ul><li>Visceral (kala azar) </li></ul><ul><ul><li>Anemia, leukopenia, thrombocytopenia, hypergammaglobulinemia common </li></ul></ul>
  56. 70. Leishmaniasis: Diagnosis <ul><li>Biopsy and Giemsa stain with amastigotes </li></ul><ul><li>Species most prevalent in different places </li></ul><ul><ul><ul><ul><li>L. donovani – India </li></ul></ul></ul></ul><ul><ul><ul><ul><li>L. infantum – Mid East </li></ul></ul></ul></ul><ul><ul><ul><ul><li>L. chagasi – Latin America </li></ul></ul></ul></ul><ul><ul><ul><ul><li>L. amazonensis -- Brazil </li></ul></ul></ul></ul>
  57. 71. Visceral Leishmaniasis <ul><li>Dissemination of amastigotes throughout the reticulendothelial system of the body </li></ul><ul><ul><li>Spleen </li></ul></ul><ul><ul><li>Bone marrow </li></ul></ul><ul><ul><li>Lymph nodes </li></ul></ul><ul><li>Opportunistic infection in AIDS patients </li></ul><ul><li>Ineffective humeral response </li></ul>
  58. 72. Hepatosplenomegaly
  59. 73. Splenic aspirate <ul><li>Most satisfactory method </li></ul><ul><li>Spleen must be at least 3cm below LCM </li></ul><ul><li>Aspirate stained with Giemsa </li></ul>
  60. 74. Leishmaniasis: treatment <ul><li>Only drug approved in US is Amphotericin B </li></ul><ul><li>Treatment of cutaneous disease depends on anatomic location </li></ul><ul><li>Many spontaneously heal and do not require treatment </li></ul>
  61. 76. Remember.. <ul><li>The factors determining the form of leishmaniasis: </li></ul><ul><ul><li>Leishmanial species </li></ul></ul><ul><ul><li>Geographic location </li></ul></ul><ul><ul><li>Immune response of the host </li></ul></ul>
  62. 77. Case 7 <ul><li>38-year-old businessman </li></ul><ul><li>Previously fit </li></ul><ul><li>2-week history of fever since returning from Brazil business trip </li></ul><ul><li>Flu-like symptoms and myalgia </li></ul><ul><li>Had consumed steak tartare in Brazil </li></ul><ul><li>Results all unremarkable---normal WBC and ESR; negative smears; CXR and urine OK </li></ul><ul><li>Continued to have fever, tachycardia and myalgia </li></ul>
  63. 78. Case 8 <ul><li>A 29-yr-old man with AIDS (CD4 count=59) presents with a 2 week history of headache, fevers and new onset seizures </li></ul><ul><li>He had not been taking any antiretroviral medications </li></ul>
  64. 79. Cases 7 & 8 <ul><li>What parasite could </li></ul><ul><li>cause this picture? </li></ul>
  65. 80. AIDS Patient
  66. 81. AIDS Patient
  67. 82. Toxoplasma gondii cyst in brain tissue with H & E stain (100x)
  68. 83. For the businessman… <ul><li>Toxoplasma serology was positive at a very high titer </li></ul><ul><li>Responded to treatment with sulphonamide + pyrimethamine </li></ul><ul><li>No relapse </li></ul>
  69. 84. Transmission <ul><li>Eating oocysts excreted by cats harboring sexual stages of parasite </li></ul><ul><li>Outbreaks traced to inadequately cooked meat of herbivores (raw beef) </li></ul><ul><li>Mutton </li></ul>
  70. 85. Toxoplasma gondii <ul><li>Worldwide distribution </li></ul><ul><li>Human infection </li></ul><ul><ul><li>Ingestion of cysts in undercooked meat of herbivores </li></ul></ul><ul><ul><li>Water/food contaminated with oocysts </li></ul></ul><ul><ul><li>Congenitally </li></ul></ul><ul><ul><li>Infected organs, blood (less common) </li></ul></ul><ul><li>Prevalence of latent infection in US about 10%; France about 75% </li></ul><ul><ul><li>Generally higher in less-developed world </li></ul></ul><ul><ul><li>50% in AIDS patients; up to 90% of AIDS patients in developing world </li></ul></ul>
  71. 86. Toxoplasma gondii: Immunocompetent hosts <ul><li>Latent infection (persistence of cysts) is generally asymptomatic </li></ul><ul><li>Cervical lymphadenopathy (10-20%) </li></ul><ul><li>Mono-like presentation (<1% of all mono-like illnesses) </li></ul><ul><li>Chorioretinitis </li></ul><ul><li>Very rare: myocarditis, myositis </li></ul>
  72. 87. Toxoplasma gondii: Immunocompromised hosts <ul><li>Often life-threatening </li></ul><ul><li>Almost always reactivation of latent infection </li></ul><ul><li>AIDS </li></ul><ul><ul><li>Encephalitis most common manifestation </li></ul></ul><ul><ul><li>Usually subacute onset/focal (if CD4< 200) </li></ul></ul><ul><ul><li>Mental status changes, seizures, weakness, cranial nerve abnormalities, cerebellar signs, </li></ul></ul><ul><ul><li>Can present as acute hemiparesis/language deficit </li></ul></ul><ul><ul><li>Usually multiple ring-enhancing lesions on CT/MRI </li></ul></ul><ul><li>Pneumonitis </li></ul><ul><li>Chorioretinitis </li></ul>
  73. 88. Toxoplasma gondii: Clinical manifestations <ul><li>Immunocompromised hosts </li></ul><ul><ul><li>Non-AIDS (transplants, hematologic malignancies) </li></ul></ul><ul><ul><ul><li>CNS 75% </li></ul></ul></ul><ul><ul><ul><li>Myocardial 40% </li></ul></ul></ul><ul><ul><ul><li>Pulmonary 25% </li></ul></ul></ul>
  74. 89. Toxoplasma gondii: Clinical manifestations <ul><li>Congenital </li></ul><ul><li>Acute infection asymptomatic in mother </li></ul><ul><li>Clinical manifestations range: no sequelae to sequelae that develop at various times after birth </li></ul><ul><ul><li>Chorioretinitis </li></ul></ul><ul><ul><li>Strabismus </li></ul></ul><ul><ul><li>Blindness </li></ul></ul><ul><ul><li>Epilepsy, mental retardation, pneumonitis, microcephaly, hydrocephalus, spontaneous abortion, stillbirth </li></ul></ul>
  75. 90. Toxoplasma gondii: diagnosis <ul><li>Clinical suspicion crucial </li></ul><ul><li>Serology is primary method of diagnosis </li></ul><ul><ul><li>IgM, IgG </li></ul></ul><ul><li>Histopathology </li></ul><ul><ul><li>Tachyzoites in tissue sections or body fluid (difficult to stain) </li></ul></ul><ul><ul><li>Multiple cysts near necrotic, inflammatory lesions </li></ul></ul>
  76. 91. Toxoplasma gondii: Treatment <ul><li>Immunocompetent adults are usually not treated unless visceral disease is overt or symptoms are severe and persistent </li></ul><ul><li>Immunodeficient patients </li></ul><ul><ul><li>Latent disease: not treated </li></ul></ul><ul><ul><li>Active disease: pyrimethamine + sulfadiazone + folinic acid </li></ul></ul>
  77. 92. Toxoplasma gondii: Treatment <ul><li>Congenital: </li></ul><ul><ul><li>Treatment of acute infected pregnant women decreases but does not eliminate transmission </li></ul></ul><ul><ul><ul><li>Spiramycin </li></ul></ul></ul><ul><ul><li>If fetal infection is documented, treat with pyrimethamine + sulfadiazone + folinic acid </li></ul></ul><ul><ul><li>Postnatal treatment: pyrimethamine + sulfadiazone + folinic acid </li></ul></ul>
  78. 93. Case 22 <ul><li>25-year-old Caucasian woman presented with 1-week history of fever, chills, sweating, myalgias, fatigue </li></ul><ul><li>No travel abroad </li></ul><ul><li>Had gone cranberry picking in Massachusetts approx 3 weeks earlier </li></ul><ul><li>PE: anemic, hepatosplenomegaly </li></ul><ul><li>Blood workup: hemolytic anemia, reduced platelets  </li></ul>
  79. 94. Thick smear
  80. 95. Thin smear Maltese cross
  81. 96. Diagnosis??
  82. 97. Babesiosis <ul><li>Babesiosis caused by hemoprotozoan parasites of the genus Babesia </li></ul><ul><li>> 100 species reported </li></ul><ul><li>Few actually cause human infection </li></ul>
  83. 98. Babesiosis <ul><li>Babesia microti </li></ul><ul><li>Life cycle involves two hosts: </li></ul><ul><ul><li>Deer tick, Ixodes dammini, (definitive host) introduces sporozoites into white-footed mouse </li></ul></ul><ul><li>Once ingested by an appropriate tick gametes unite and undergo a sporogonic cycle resulting in sporozoites </li></ul><ul><li>Humans enter cycle when bitten by infected ticks </li></ul>
  84. 99. Babesiosis <ul><li>Deer are the hosts upon which the adult ticks feed and are indirectly part of the Babesia cycle as they influence the tick population </li></ul>
  85. 100. Babesiosis <ul><li>Clindamycin* plus quinine </li></ul><ul><li>Atovaquone* plus azithromycin* </li></ul><ul><li>Exchange transfusion in severely ill patients with high parasitemia </li></ul><ul><li>* Approved by FDA </li></ul>
  86. 101. Case 9 <ul><li>6-year-old son of seasonal farm worker </li></ul><ul><li>Presents with cough and fever, wheeze </li></ul><ul><li>CXR reveals a lobar pneumonia </li></ul><ul><li>Admitted for initial therapy </li></ul><ul><li>After 2 days of antibiotics, with good defervescence, a worm is found in his bed </li></ul><ul><li>Stool exam reveals … </li></ul>
  87. 103. Diagnosis?
  88. 104. Ascaris lumbricoides <ul><li>In GI tract, few symptoms in light infections </li></ul><ul><ul><li>Nausea </li></ul></ul><ul><ul><li>Vomiting </li></ul></ul><ul><ul><li>Obstruction of small bowel or common bile duct. </li></ul></ul><ul><li>Pulmonary: symptoms due to migration </li></ul><ul><ul><li>Alveoli (verminous pneumonia)—cough, fever wheeze, dyspnea, X-ray changes, eosinophilia </li></ul></ul>
  89. 105. Effects of Adult Ascaris Worms <ul><li>Depends on worm load </li></ul><ul><li>Effects </li></ul><ul><ul><li>Mechanical: obstruction, volvulus, intussusception, appendicitis, obstructive jaundice, liver abscesses, pancreatitis, asphyxia </li></ul></ul><ul><li>Toxic and Metabolic </li></ul><ul><ul><li>Malnutrition (complex) </li></ul></ul>
  90. 106. Ascaris lumbricoides Diagnosis <ul><li>Characteristic eggs on direct smear examination </li></ul><ul><li>If treating mixed infections, treat Ascaris first </li></ul><ul><ul><li>Mebendazole </li></ul></ul><ul><ul><li>Pyrantel </li></ul></ul><ul><li>Control: </li></ul><ul><ul><li>Periodic mass treatment of children, health education, environmental sanitation </li></ul></ul>
  91. 108. Case 10 <ul><li>11-year-old female </li></ul><ul><li>Doing poorly in school </li></ul><ul><li>Not sleeping well </li></ul><ul><li>Anorectic </li></ul><ul><li>Complains of itching in rectal region throughout the day </li></ul><ul><li>A Scotch-tape test reveals… </li></ul>
  92. 112. Diagnosis?
  93. 113. Enterobius (Pinworm) <ul><li>18 million infections in U.S. </li></ul><ul><li>Incidence higher in whites </li></ul><ul><li>Preschool and elementary school most often </li></ul><ul><li>Mostly asymptomatic </li></ul><ul><li>Nocturnal anal pruritis cardinal feature due to migration and eggs </li></ul><ul><li>May have insomnia, possible emotional symptoms </li></ul><ul><li>DS-eggs or adults on perineum {scotch tape} </li></ul><ul><li>Mebendazole 100 mg. Repeat in 2 weeks. Pyrantel pamoate 11 mg/kg; repeat 2 weeks </li></ul>
  94. 114. <ul><li>69-year-old male was admitted to VA Hospital </li></ul><ul><li>Far East Prisoner of War (FEPOW) </li></ul><ul><li>COPD--steroids for 3 years </li></ul><ul><li>2-month history of nausea, vomiting and anorexia </li></ul><ul><li>25 pounds weight loss </li></ul>Case 11
  95. 115. On the day of admission… <ul><li>Fever, confusion, and not able to get out of bed---transported to the hospital </li></ul><ul><li>Initial blood work: </li></ul><ul><ul><li>Elevated WBC </li></ul></ul><ul><ul><li>Raised eosinophil count 4 times normal </li></ul></ul><ul><li>Underwent UGI endoscopy </li></ul><ul><li>Duodenal biopsy obtained </li></ul>
  96. 117. Diagnosis
  97. 118. Strongyloides: Crucial Aspects of Life Cycle <ul><li>Infection acquired through penetration of intact skin </li></ul><ul><li>Infection may persist for many years via autoinfection </li></ul><ul><li>In immunocompromised patients, there is risk of dissemination or hyperinfection </li></ul><ul><ul><li>Hyperinfection syndrome </li></ul></ul>
  98. 119. Disseminated Strongyloidiasis <ul><li>High mortality  75% </li></ul><ul><li>Penetration of gut wall by infective larvae </li></ul><ul><li>Gut organisms carried on the surface of larvae results in polymicrobial sepsis, meningitis </li></ul><ul><li>Larvae disseminate into all parts of body: CNS, lungs, bladder, peritoneum </li></ul>
  99. 120. Summary—Clinical Findings <ul><li>Defective cell-meditated immunity: steroids, burns, lymphomas, AIDS (?) </li></ul><ul><li>Gl symptoms in about two-thirds: </li></ul><ul><ul><li>Abdominal pain </li></ul></ul><ul><ul><li>Bloating </li></ul></ul><ul><ul><li>Diarrhea </li></ul></ul><ul><ul><li>Constipation </li></ul></ul><ul><li>Wheezing, SOB, hemoptysis </li></ul>
  100. 121. Summary—Clinical Findings <ul><li>Skin rash or pruritis in ~ one-third </li></ul><ul><ul><li>Larva currens (racing larva) </li></ul></ul><ul><ul><li>Intensely pruritic </li></ul></ul><ul><ul><li>Linear or serpiginous urticaria with flare that moves 5-15 cm/hr </li></ul></ul><ul><ul><li>Usually buttocks, groin, and trunk </li></ul></ul><ul><ul><li>In dissemination, diffuse petechiae and purpura </li></ul></ul>
  101. 122. Summary-Clinical Findings <ul><li>Eosinophilia 60-95% </li></ul><ul><li>Less if on steroids </li></ul>
  102. 123. Case 12 <ul><li>57 year old farmer from Dixie County </li></ul><ul><li>Presents with profound SOB </li></ul><ul><li>Physical examination: anemic otherwise unremarkable </li></ul><ul><li>Laboratory examination reveals a profound anemia (hct 24) with aniso and poikilocytosis </li></ul><ul><li>Remainder of laboratory examination normal. </li></ul>
  103. 125. Diagnosis?
  104. 127. Hookworm <ul><li>Hookworm responsible for development of USPHS </li></ul><ul><li>Caused by two different species (North American and Old World) </li></ul><ul><li>Very similar to strongyloides in life cycle </li></ul><ul><li>Attaches to duodenum, feeds on blood </li></ul><ul><li>Elaborates anticoagulant, attaches and reattaches many times </li></ul><ul><li>Loss of around 0.1 ml/d of blood per worm </li></ul>
  105. 130. Case 13 <ul><li>8-yr-old schoolgirl visiting the U.S. from Malaysia </li></ul><ul><li>1 week history of epigastric pain, flatulence, anorexia, bloody diarrhea </li></ul><ul><li>No eosinophilia noted </li></ul><ul><li>Clinical diagnosis of amoebic dysentery made </li></ul><ul><li>However, microscopy of stool prep… </li></ul>
  106. 132. Diagnosis?
  107. 133. Trichuris trichiura (Whipworm) <ul><li>Common in Southeast U.S. </li></ul><ul><li>Frequently coexists with ascaris </li></ul><ul><li>Entirely intraluminal life cycle—eggs are ingested </li></ul><ul><li>Frequently asymptomatic </li></ul><ul><li>Severe infections: diarrhea, abdominal pain and tenesmus </li></ul><ul><li>Rectal prolapse in children </li></ul><ul><li>DS-eggs in stool </li></ul><ul><li>Mebendazole 100 mg bid x 3 days </li></ul>
  108. 137. Case 14 <ul><li>18-year-old trailer park handyman seen in ER </li></ul><ul><li>Worked under trailers wearing shorts and no shirt </li></ul><ul><li>Developed intensely pruritic skin rash </li></ul><ul><li>Unable to sleep </li></ul><ul><li>WBC 18,000 </li></ul><ul><li>65% eosinophils. </li></ul>
  109. 139. Case 15 <ul><li>An 8 year old boy </li></ul><ul><li>Presents with skin lesions and itching after spending the summer at a beach condo in St. Augustine with his family (mother, father, younger sister, dog and cat). </li></ul><ul><li>Legs show several raised, reddened, serpiginous lesions that are intensely pruritic. </li></ul>
  110. 141. Diagnosis ?
  111. 142. Cutaneous Larva Migrans <ul><li>Caused by filariform larvae of dog or cat hookworm ( Ancylostoma braziliense or Ancylostoma duodenale </li></ul><ul><li>Common in Southeast U.S. </li></ul><ul><li>Red papule at entry with serpiginous tunnel </li></ul><ul><li>Intense pruritis </li></ul><ul><li>Self limiting condition </li></ul><ul><li>Diagnosis clinical </li></ul><ul><li>Topical or oral thiabendazole 25 mg/kg bid for 3-5 days </li></ul><ul><li>May use ethyl chloride topically </li></ul>
  112. 143. Cutaneous larva migrans (creeping eruption) <ul><li>More common in children </li></ul><ul><ul><li>Larvae penetrate skin and cause tingling followed by intense itching. </li></ul></ul><ul><li>Eggs shed from dog and cat bowels develop into infectious larvae outside the body in places protected from desiccation and extremes of temperature </li></ul><ul><li>Shady, sandy areas under houses, at beach, etc. </li></ul>
  113. 144. Cutaneous larva migrans (creeping eruption) <ul><ul><li>Usually not associated with systemic symptoms </li></ul></ul>
  114. 145. Cutaneous larva migrans (creeping eruption) <ul><li>Diagnosis and treatment </li></ul><ul><li>Skin lesions are readily recognized </li></ul><ul><li>Usually diagnosed clinically </li></ul><ul><li>Generally do not require biopsy </li></ul><ul><ul><ul><ul><li>Reveal eosinophilia inflammatory infiltrate </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Migrating parasite is generally not seen </li></ul></ul></ul></ul><ul><li>Stool smear will reveal eggs </li></ul>
  115. 148. Visceral Larva Migrans <ul><li>Infection with dog or cat round worms </li></ul><ul><li>Toxocara canis; Toxocara catis </li></ul><ul><li>Underdiagnosed based on seroprevalence surveys </li></ul><ul><li>Heavy infections associated with fever, cough, nausea, vomiting, hepatomegaly, and eosinophilia </li></ul><ul><li>Uncommon in adults </li></ul><ul><li>Ocular type more common in adults </li></ul><ul><li>Diagnosis-ELISA </li></ul><ul><li>Thiabendazole: 25 mg/kg bid X 5 days </li></ul>
  116. 149. Case 17 <ul><li>A 34 yr-old woman from Saudi Arabia </li></ul><ul><li>Radiation and cyclophosphamide, adriamycin, vincristine and prednisone for diffuse large B cell lymphoma of the neck. </li></ul><ul><li>Mild eosinophilia (AEC=500) at the time of diagnosis </li></ul><ul><li>4 months after initiation of chemo, c/o intermittent diffuse abdominal pain, bloating, constipation and occasional rectal bleeding. </li></ul><ul><li>Absolute eosinophil count: 1000 </li></ul>
  117. 150. Case 17 <ul><li>No evidence of lymphoma found on re-staging </li></ul><ul><li>Completed chemo, was deemed to be in complete remission, but had persistence of GI complaints. </li></ul><ul><li>Upper endoscopy was unrevealing. </li></ul><ul><li>Colonoscopy and biopsy revealed granulomatous inflammation, prominent eosinophilic infiltrate, surrounding a collection of eggs. </li></ul>
  118. 152. Chronic intestinal schistosomiasis
  119. 153. Case 17 <ul><li>The patient was treated with praziquantel and did not have relapse of symptoms at 2-year follow-up </li></ul><ul><li>AEC=250 </li></ul>
  120. 154. Schistosomiasis: Epidemiology and life cycle <ul><li>Cercariae in fresh water penetrate human skin. </li></ul><ul><li>Cercariae mature to schistosomulae, which enter the bloodstream, liver and lung. </li></ul><ul><li>Mature worms migrate to the venous system of the small intestine ( S. japonicum ), large intestine ( S. mansoni ) or bladder venous plexus ( S. haematobium ). </li></ul>
  121. 155. Schistosomiasis: Epidemiology and life cycle <ul><li>Worms release eggs for many years into stool or urine, resulting in fresh water contamination. </li></ul><ul><li>Freshwater snails are infected by miracidia and are necessary for the production of cercariae and human infection. </li></ul><ul><li>S. mansoni </li></ul><ul><ul><li>South America, Caribbean, Africa, Mid East </li></ul></ul><ul><li>S. japonicum </li></ul><ul><ul><li>China and Philippines </li></ul></ul><ul><li>S. haematobium </li></ul><ul><ul><li>Africa, Mid East </li></ul></ul>
  122. 156. Schistosomiasis: Clinical manifestations <ul><li>Three stages of disease, corresponding to life cycle within human hosts </li></ul><ul><li>Swimmer’s itch </li></ul><ul><ul><li>Within 24 hours of cercariae penetration </li></ul></ul><ul><li>Serum sickness syndrome (Katayama fever) </li></ul><ul><ul><li>4 to 8 weeks later when worms mature and release eggs </li></ul></ul><ul><ul><ul><li>Fever, headache, cough, chills, sweating, lymphadenopathy, hepatosplenomegaly  usually resolves spontaneously </li></ul></ul></ul><ul><ul><ul><li>Elevated IgE and eosinophils </li></ul></ul></ul><ul><ul><ul><li>Most common with S. japonicum </li></ul></ul></ul>
  123. 157. Chronic Schistosomiasis <ul><li>Granulomatous reaction to egg deposition in intestine, liver, bladder, lungs </li></ul><ul><li>S. mansoni, japonicum </li></ul><ul><ul><li>Chronic diarrhea, abdominal pain, blood loss, portal hypertension, hepatosplenomegaly, pulmonary hypertension </li></ul></ul><ul><ul><li>Eosinophilia is common </li></ul></ul><ul><ul><li>Liver function tests are usually normal </li></ul></ul><ul><li>S. Haematobium </li></ul><ul><ul><li>Hematuria, bladder obstruction, hydronephrosis, recurrent UTIs, bladder cancer </li></ul></ul>
  124. 158. Schistosomiasis: Diagnosis and Treatment <ul><li>Detection of characteristic eggs in stool, urine or tissue biopsy is diagnostic </li></ul><ul><ul><li>Urine is best between 12N and 2Pm, passed through 10 µm filter to concentrate eggs </li></ul></ul><ul><li>Antibody tests are available, but limited by sensitivity, specificity </li></ul><ul><li>Praziquantel is the drug of choice </li></ul>
  125. 160. S. mansoni Stool S. haematobium Urine S. japonicum
  126. 161. Case 18 <ul><li>15-yr-old girl </li></ul><ul><li>Fever, rash, swelling around the eye and hands, severe headaches </li></ul><ul><li>Fatigue, aching muscles and joints </li></ul><ul><li>Swollen lymph nodes on the back of neck </li></ul><ul><li>Weight loss </li></ul><ul><li>Progressive confusion, personality changes </li></ul><ul><li>Sleeping for long periods of the day </li></ul><ul><li>Insomnia </li></ul><ul><li>Had been on a safari with parents to West Africa </li></ul><ul><li>Dusky red lesion developed within 1 week </li></ul><ul><li>Vaguely remembered being bitten by a fly </li></ul>
  127. 162. Diagnosis?
  128. 163. Investigations <ul><li>Blood films </li></ul><ul><li>Lumbar puncture </li></ul>
  129. 164. Blood smear
  130. 165. African trypanosomiasis Trypanosoma brucei gambiense
  131. 166. Tsetse fly
  132. 167. Treatment <ul><li>Suramin </li></ul><ul><li>Melasoprol </li></ul>
  133. 168. Case 19 <ul><li>6-yr-old boy recently arrived from Brazil </li></ul><ul><li>Swelling around the eye </li></ul><ul><li>Conjunctivitis </li></ul><ul><li>Fever </li></ul><ul><li>Enlarged lymph nodes </li></ul><ul><li>Hepatosplenomegaly </li></ul><ul><li>Had stayed in a hotel—adobe style with thatched roof </li></ul>
  134. 170. Diagnosis?
  135. 171. Blood smear
  136. 172. Reduviid bug (assassin bug)
  137. 173. Chagas disease: Clinical manifestations <ul><li>Local edema is followed by fever, malaise, anorexia </li></ul><ul><ul><li>More rarely: myocarditis, encephalitis </li></ul></ul><ul><li>Years later: chronic Chagas Disease (10-30%) </li></ul><ul><ul><li>Heart: primary target </li></ul></ul><ul><ul><ul><li>Cardiomyopathy associated with CHF, emboli, arrythmias </li></ul></ul></ul><ul><ul><li>GI tract: mega-esophagus, megacolon </li></ul></ul>
  138. 174. Chagas disease: Diagnosis and treatment <ul><li>Acute disease is diagnosed by seeing trypomastigotes on peripheral blood smear </li></ul><ul><li>Chronic disease is diagnosed by ELISA detecting IgG antibody to T. cruzi </li></ul><ul><li>Treatment slows the progression of heart disease </li></ul>
  139. 175. Chagas Disease <ul><li>Public health implications in the US </li></ul><ul><li>Chronic </li></ul><ul><ul><li>Cardiomyopathy </li></ul></ul><ul><ul><li>Megaesophagus </li></ul></ul><ul><ul><li>Megacolon </li></ul></ul><ul><li>Blood transfusion </li></ul><ul><li>Transplant </li></ul><ul><ul><li>Solid organ </li></ul></ul><ul><ul><li>Musculoskeletal allograft tissue </li></ul></ul>
  140. 176. Case 20 <ul><li>20-yr-old male </li></ul><ul><li>Abdominal pain and nausea for several months </li></ul><ul><li>More common in the morning </li></ul><ul><li>Relieved by eating small amounts of food </li></ul><ul><li>Some diarrhea and irritability </li></ul><ul><li>Weight loss </li></ul><ul><li>Pruritus ani </li></ul><ul><li>Passage of white “bits” </li></ul>
  141. 178. Diagnosis?
  142. 179. Taenia saginata <ul><li>Ingestion of raw or poorly cooked beef </li></ul><ul><li>Cows infected via the ingestion of human waste containing the eggs of the parasite </li></ul><ul><li>Cows contain viable cysticercus larvae in the muscle </li></ul><ul><li>Humans act as the host only to the adult tapeworms </li></ul><ul><li>Up to 25 meters in the lumen of intestine </li></ul><ul><li>Found all over the world, including the U.S. </li></ul>
  143. 180. Beef Tapeworm
  144. 181. Treatment <ul><li>Praziquantel </li></ul><ul><li>Albendazole </li></ul><ul><li>Niclosamide </li></ul>
  145. 182. Tapeworms (Cestodes) <ul><li>Adult worms inhabit GI tract of definitive vertebrate host </li></ul><ul><li>Larvae inhabit tissues of intermediate host </li></ul><ul><li>Humans </li></ul><ul><ul><li>Definitive for T. saginata </li></ul></ul><ul><ul><li>Intermediate for Echinococcus granulosus (hydatid) </li></ul></ul><ul><ul><li>Both definitive and intermediate for T. solium </li></ul></ul><ul><li>Adult worms shed egg-containing segments in stool ingested by intermediate host larval form in tissues </li></ul>
  146. 183. Case 21 <ul><li>A 33 year-old Indian man was admitted with a grand mal seizure </li></ul><ul><li>2 yrs PTA, he had vertigo and CT revealed an enhancing calcified lesion in left temporal-parietal region </li></ul><ul><li>FHx: Brother had grand mal seizure several years earlier </li></ul><ul><li>Throughout his life, he has eaten a diet heavy in pork </li></ul>
  147. 184. Case 21 <ul><li>Difficulty speaking and loss of consciousness while on the phone </li></ul><ul><li>Co-workers noticed generalized tonic-clonic seizures lasting 10 minutes. </li></ul><ul><li>CT revealed new localized edema around the previously identified lesion and a second contiguous ring enhancing lesion. </li></ul><ul><li>He received phenytoin (Dilantin, an antiseizure med) and 5 days of corticosteroids. </li></ul>
  148. 186. Case 21 <ul><li>ELISA titer was positive for antibodies against Taenia solium. </li></ul><ul><li>The neurosurgeons tell you that resection is impossible because of the extent and location of the lesion </li></ul>
  149. 187. Cystercercosis <ul><li>Human infected with the larval stage of Taenia solium </li></ul><ul><li>Humans can serve as definitive or intermediate host </li></ul><ul><li>Eggs are ingested, or possibly get to stomach by reverse peristalsis </li></ul><ul><li>Probably much more common than is reported, since most infections are asymptomatic </li></ul>
  150. 188. Cystercercosis <ul><li>Symptoms depend on location of cysts, but frequently include motor spasms, seizures, confusion, irritability, and personality change </li></ul><ul><li>In the eye, often subretinal or in vitreous. Movement may be seen by the patient. Pain, amaurosis, and loss of vision may occur. </li></ul>
  151. 189. Cysticercosis <ul><li>Clinical manifestations </li></ul><ul><ul><li>Adult worms rarely cause sxs </li></ul></ul><ul><ul><li>Larvae penetrate intestine, enter blood, and eventually encyst in the brain. </li></ul></ul><ul><ul><ul><li>Cerebral ventircles  hydrocephalus </li></ul></ul></ul><ul><ul><ul><li>Spinal cord  compression, paraplegia </li></ul></ul></ul><ul><ul><ul><li>Subarachnoid space  chronic meningitis </li></ul></ul></ul><ul><ul><ul><li>Cerebral cortex  seizures </li></ul></ul></ul><ul><ul><li>Cysts may remain asymptomatic for years, and become clinically apparent when larvae die </li></ul></ul><ul><ul><li>Larvae may encyst in other organs, but are rarely symptomatic </li></ul></ul>
  152. 190. Cysticercosis <ul><li>Diagnosis </li></ul><ul><ul><li>CT and MRI preferred studies </li></ul></ul><ul><ul><ul><li>Discrete cysts that may enhance </li></ul></ul></ul><ul><ul><ul><li>Usually multiple lesions </li></ul></ul></ul><ul><ul><ul><ul><li>Single lesions especially common in cases from India </li></ul></ul></ul></ul><ul><ul><ul><li>Older lesions may calcify </li></ul></ul></ul><ul><ul><li>CSF </li></ul></ul><ul><ul><ul><li>Lymphs or eos, low glucose, elevated protein </li></ul></ul></ul><ul><ul><li>Serology </li></ul></ul><ul><ul><ul><li>Especially in cases with multiple cysts </li></ul></ul></ul>
  153. 191. Cysticercosis <ul><li>Treatment </li></ul><ul><ul><li>Complex and controversial </li></ul></ul><ul><ul><li>Praziquantel and albendazole may kill cysts, but death of larvae can increase inflammation, edema and exacerbate sxs </li></ul></ul><ul><ul><li>When possible, surgical resection of symptomatic cyst is preferred </li></ul></ul><ul><ul><li>Corticosteroids vs. edema and inflammation; antiseizure meds </li></ul></ul>
  154. 194. Case 21 <ul><li>He was not treated with praziquantel or albendazole </li></ul><ul><li>He continued to receive dilantin for seizures and was treated with corticosteroids for edema </li></ul>
  155. 195. Classification of Parasitic Diseases <ul><li>Protozoa: amoeba; flagellates; ciliates </li></ul><ul><li>Metazoa (two phyla) </li></ul><ul><ul><li>Helminths (worms) </li></ul></ul><ul><ul><ul><li>Nematodes </li></ul></ul></ul><ul><ul><ul><ul><li>Intestinal </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Extra-intestinal </li></ul></ul></ul></ul><ul><ul><ul><li>Flatworms (platyhelminths) </li></ul></ul></ul><ul><ul><ul><ul><li>Cestodes (tapeworms) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Trematodes (flukes) </li></ul></ul></ul></ul><ul><ul><li>Arthopods (ectoparasites): scabies, lice, fly larvae </li></ul></ul>
  156. 196. General rules of treatment <ul><li>Protozoa: require species-specific treatment </li></ul><ul><li>Metozoa: species-specific </li></ul>
  157. 197. General rules of treatment of metazoa Nematodes Intestinal Mebendazole or Albendazole Tissue Albendazole Filiariae Ivermectin, doxycycline Cestodes Praziquantel, Albendazole, Niclosamide Trematode Praziquantel Ectoparasites Permethrin, Ivermectin
  158. 198. This is just the beginning of a great adventure in infectious diseases Sine qua non : history and physical examination
  159. 199. Thank you Lennox K. Archibald, MD, PhD, FRCP [email_address]
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