Emerging Infections and Medical Procedures
By:Lennox K. Archibald, MD, PhD, FRCP
Hospital Epidemiologist, University of Florida
Parasitic Infections:
Clinical Manifestations, Diagnosis and Treatment
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
Infections Deaths
Parasites
* Organisms that cannot survive outside their host, AND they cause some harm to the host.
* Contrast with commensal organisms
* Incredibly complex organisms
* Consider the struggle for survival from the perspective of a parasite
Giardia
Giardiasis (G. lamblia)
* Should be suspected in prolonged diarrhea
* Contaminated water often implicated—outbreaks
* Campers who fail to sterilize mountain stream water
* Person-person in day care centers
* MSM
* Symptoms usually resolve spontaneously in 4-6 weeks
* Tests of choice
o Examination of concentrated stools for cysts (90% yield after 3 samples); usually no PMNs
o Stool ELISA, IF Antigen (up to 98% sensitive/90-100% specific)
o Consider aspiration of duodenal contents--trophozoites
* Treatment: Metronidazole for 5-7 days
Entamoeba histolytica
* One of 7 amoebae commonly found in humans
* Only one that causes significant disease
* Causes intestinal disease (diarrhea and dysentery) and extra-intestinal disease (liver primarily)
* In US, often seen in institutionalized patients, MSM, tourists returning from developing countries, patients with depressed cell mediated immunity
Cyst (wet mount)
* Diagnostic smear: trophozoites in liquid stools, cysts in formed stools
* IHA important in liver abscess
o Intestinal: 95% predictive of active infection
o Extra-intestinal: 100% predictive of active I infection
Amoebiasis: Clinical Manifestations
* Symptoms depend on degree of bowel invasion
o Superficial: watery diarrhea and nonspecific GI complaints
o Invasive: gradual onset (1-3 weeks) of abdominal pain, bloody diarrhea, tenesmus
* Fever is seen in minority of patients
* Can be mistaken for ulcerative colitis
* Steroids can dramatically worsen and precipitate toxic megacolon
* Amebic liver abscesses
o RUQ pain, pain referred to right shoulder
o High fever
o Hepatomegaly (50%)
Amoebic abscess—remember…
* Can occur in lung, brain, spleen
* 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
* Liquifaction of liver cells
* Do not contain pus
* Anchovy paste sauce
* Culture of contents usually sterile
* Liver affected
o 53%--right lobe
o 8%--left lobe
Amoebiasis (Entamoeba histolytica)
Treatment
* Most respond to metronidazole
* Open surgical drainage should be avoided, if at all possible
Cryptosporidium
Cryptosporidium parvum
* Causes secretory diarrhea: 10 liter/day
* Significant cause of death in HIV/AIDS
* Animal reservoirs
* Incubation period: 5-10 days
* Infants and younger children in day-care centers
* Unfiltered or untreated drinking water
* Farming practices: lambing, calving, and muck-spreading
* Sexual practices that brings a person into oral contact with feces 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)
Diagnosis and Treatment
* Best diagnosed by stool exam
* There is no known effective treatment-nitazoxamide shortens duration of diarrhea
o Infectious disease specialist - for consideration of antiparasitic and antiretroviral therapy
o Gastroenterologist - ERCP and sphincterotomy; endoscopy sometimes required for diagnosis
o General surgeon - suspected acalculous cholecystitis
Malaria
Falciparum vs. Vivax
* Location: Falciparum confined to tropics and subtropics; vivax more temperate
* Falciparum infects RBC of any age; others like reticulocytes; only 2% infected cells
* Falciparum infected RBCs stick to vascular endothelium causing capillary blockage; fewer schizonts in the periphery, heavy pigment deposition, cerebral and renal disease
* Vivax and Ovale may reinfect hepatocytes, leading to a persisting tissue phase, causing relapses
* Sickle cell trait protects against Falciparum
Malaria: Genetic susceptibility
* Two genetic traits associated with decreased susceptibility to malaria
o Absence of Duffy blood group antigen blocks invasion of Plasmodium vivax
+ Significant number of Africans
o Persons with sickle cell hemoglobin are resistant to P. falciparum
+ Sickle cell disease and trait
Malaria: Clinical manifestations
* Non-specific, flu-like illness
* Incubation
* Fever is the hallmark of malaria
* Fever occurs after the lysis of RBCs and release of merozoites
* Febrile paroxysms have 3 classic stages
* Other symptoms depend upon the strain of malaria
* P. vivax, ovale and malariae: few other sxs
* P. falciparum:
* Always suspect malaria in travelers from developing countries who present with:
o Influenza-like illness
o Jaundice
o Confusion or obtundation
Diagnosis
* Giemsa-stained blood smear
* P. falciparum:
* Others:
* Examine blood on 3-4 successive days
* Key of diagnosis is to identify P. falciparum
* New assays: o ELISA for antigen, immunoassay for LDH, PCR
* Anemia, elevated LDH, increased reticulocytes, thrombocytopenia
* Elevated unconjugated bilirubin without increases in hepatic enzymes
* Elevated serum creatinine, proteinuria, hemoglobinuria, hypoglycemia
Differences in strains
* P. falciparum
* P. vivax and ovale
* P. malariae
Early troph--ring
Mature troph
Schizont
Gametocyte
Treatment
* P. falciparum malaria can be fatal if not promptly diagnosed and treated
* Pts with no immunity against P. falciparum require hospitalization
o Pregnant women, young children, elderly
* Non- P. falciparum malaria rarely requires hospitalization
* Widespread drug resistance dictates regimen (www.cdc.gov/travel; CDC malaria hot line: 770-488-7788).
* Uncomplicated malaria
o Drug options
+ Chloroquine phosphate
+ Mefloquine
+ Quinine sulfate plus doxycycline
+ Atovaquone plus proguanil (AP)
+ Artemisin derivatives
* P. vivax, ovale, malariae, chloroquine-susceptible falciparum
+ Chloroquine
+ Primaquine
Prevention
* Chloroquine
* Mefloquine
* Doxycycline
* Atovaquone plus proguanil (AP)
* Screens, nets
* 30-35% DEET
* permethrin spray for clothing and nets
And don’t forget baggage malaria!
Leishmaniasis
* Tropical areas where phlebotomine sandfly is common:
o South America
o India
o Bangladesh
o Middle East
o East Africa
* Sandfly introduces flagellated promastigote into human ingested by macrophages develops into nonflagellated amastigote
* Intracellular parasite controlled by Th1-type CD8+ response
Leishmaniasis: Clinical Manifestations
* 3 forms: visceral, cutaneous, mucosal
* A single species can produce more than one syndrome, and each syndrome is caused by multiple different species
* Visceral (kala azar)
o Species most prevalent in different places
# L. donovani – India
# L. infantum – Mid East
# L. chagasi – Latin America
# L. amazonensis -- Brazil
* Cutaneous
* Mucosal
Visceral Leishmaniasis
* Dissemination of amastigotes throughout the reticulendothelial system of the body
* Opportunistic infection in AIDS patients
* Ineffective humeral response
Hepatosplenomegaly
Splenic aspirate
* Most satisfactory method
* Spleen must be at least 3cm below LCM
* PT not more than 5 secs longer than controls
* Platelets >40,000
* 21 gauge needle
* Aspirate stained with Giemsa
Leishmaniasis: treatment
* Only drug approved in US is Amphotericin B
* Outside US: pentavalent antimony (sodium stibogluconate)
* Treatment of cutaneous disease depends on anatomic location
* Many spontaneously heal and do not require treatment
* If no mucosal disease and areas of no cosmetic concern:
o 15% paromomycin or 12% methylbenzethonium chloride
* Mucosal, progressive lesions or cosmetically sensitive locations:
o Pentavalent antimony or ketoconazole
Remember..
* The factors determining the form of leishmaniasis:
o Leishmanial species
o Geographic location
o Immune response of the host
Toxoplasmosis
Toxoplasma gondii
* Worldwide distribution
* Human infection
* Prevalence of latent infection in US about 10%; France about 75%
o Generally higher in less-developed world
Transmission
* Eating oocysts excreted by cats harboring sexual stages of parasite
* Outbreaks traced to inadequately cooked meat of herbivores (raw beef)
* Mutton
Toxoplasma gondii: life cycle
Immunocompetent hosts
* Latent infection (persistence of cysts) is generally asymptomatic
* Cervical lymphadenopathy (10-20%)
* Mono-like presentation (<1% of all mono-like illnesses)
* Chorioretinitis
* Very rare: myocarditis, myositis
Toxoplasma gondii: Immunocompromised hosts
* Often life-threatening
* Almost always reactivation of latent infection
* AIDS
o Encephalitis most common manifestation
o Usually subacute onset/focal (if CD4< 200)
o Mental status changes, seizures, weakness, cranial nerve abnormalities, cerebellar signs,
o Can present as acute hemiparesis/language deficit
o Usually multiple ring-enhancing lesions on CT/MRI
* Pneumonitis
* Chorioretinitis
Toxoplasma gondii: Clinical manifestations
* Immunocompromised hosts
o Non-AIDS (transplants, hematologic malignancies)
* Congenital
* Acute infection asymptomatic in mother
* Clinical manifestations range: no sequelae to sequelae that develop at various times after birth
o Chorioretinitis
o Strabismus
o Blindness
o Epilepsy, mental retardation, pneumonitis, microcephaly, hydrocephalus, spontaneous abortion, stillbirth
Toxoplasma gondii: diagnosis
* Clinical suspicion crucial
* Serology is primary method of diagnosis
o IgM, IgG
* Histopathology
o Tachyzoites in tissue sections or body fluid (difficult to stain)
o Multiple cysts near necrotic, inflammatory lesions
Toxoplasma gondii: Treatment
* Immunocompetent adults are usually not treated unless visceral disease is overt or symptoms are severe and persistent
* Immunodeficient patients
* Congenital:
Ascaris lubricoides
Ascaris lumbricoides
* In GI tract, few symptoms in light infectionst.
* Pulmonary: symptoms due to migration
Effects of Adult Ascaris Worms
* Depends on worm load
* Effects
* Toxic and Metabolic
Ascaris lumbricoides Diagnosis
* Characteristic eggs on direct smear examination
* If treating mixed infections, treat Ascaris first
o Mebendazole 100 mg bid x 3 days
o Pyrantel 10 mg/kg single dose
* Control:
o Periodic mass treatment of children, health education, environmental sanitation
Enterobius (Pinworm)
* 18 million infections in U.S.
* Incidence higher in whites
* Preschool and elementary school most often
* Mostly asymptomatic
* Nocturnal anal pruritis cardinal feature due to migration and eggs
* May have insomnia, possible emotional symptoms
* DS-eggs or adults on perineum {scotch tape}
* Mebendazole 100 mg. Repeat in 2 weeks. Pyrantel pamoate 11 mg/kg; repeat 2 weeks
Strongyloides
Strongyloides: Crucial Aspects of Life Cycle
* Infection acquired through penetration of intact skin
* Infection may persist for many years via autoinfection
* In immunocompromised patients, there is risk of dissemination or hyperinfection
o Hyperinfection syndrome
Disseminated Strongyloidiasis
* High mortality 75%
* Penetration of gut wall by infective larvae
* Gut organisms carried on the surface of larvae results in polymicrobial sepsis, meningitis
* Larvae disseminate into all parts of body: CNS, lungs, bladder, peritoneum
Summary—Clinical Findings
* Defective cell-meditated immunity: steroids, burns, lymphomas, AIDS (?)
* Gl symptoms in about two-thirds:
o Abdominal pain
o Bloating
o Diarrhea
o Constipation
* Wheezing, SOB, hemoptysis
Summary—Clinical Findings
* Skin rash or pruritis in ~ one-third
* Eosinophilia 60-95%
* Less if on steroids
Hookworm
* Hookworm responsible for development of USPHS
* Caused by two different species (North American and Old World)
* Very similar to strongyloides in life cycle
* Attaches to duodenum, feeds on blood
* Elaborates anticoagulant, attaches and reattaches many times
* Loss of around 0.1 ml/d of blood per worm
Cutaneous larva migrans (creeping eruption)
* Caused by filariform larvae of dog or cat hookworm (Ancylostoma braziliense or Ancylostoma duodenale
* Common in Southeast U.S.
* Red papule at entry with serpiginous tunnel
* Intense pruritis
* Self limiting condition
* Diagnosis clinical
* Topical or oral thiabendazole 25 mg/kg bid for 3-5 days
* May use ethyl chloride topically
* More common in children
o Larvae penetrate skin and cause tingling followed by intense itching.
* Eggs shed from dog and cat bowels develop into infectious larvae outside the body in places protected from desiccation and extremes of temperature
* Shady, sandy areas under houses, at beach, etc.
Usually not associated with systemic symptoms
* Diagnosis and treatment
* Skin lesions are readily recognized
* Usually diagnosed clinically
* Generally do not require biopsy
# Reveal eosinophilia inflammatory infiltrate
# Migrating parasite is generally not seen
* Stool smear will reveal eggs
Visceral Larva Migrans
* Infection with dog or cat round worms
* Toxocara canis; Toxocara catis
* Underdiagnosed based on seroprevalence surveys
* Heavy infections associated with fever, cough, nausea, vomiting, hepatomegaly, and eosinophilia
* Uncommon in adults
* Ocular type more common in adults
* Diagnosis-ELISA
* Thiabendazole: 25 mg/kg bid X 5 days
Echinococcosis Hydatid Disease
Echinococcosis
* Clinical manifestations:
o Most patients are asymptomatic
+ Dx’d incidentally on an imaging study
o Sxs generally develop when the hydatid cyst reaches 8-10 cm (often over decades)
+ Compress vital structures
+ Erode into biliary tract or bronchus
o Cysts can become superinfected
o Leakage or rupture can result in anaphylactic reaction fever, hypotension
Echinococcosis
* Diagnosis:
o US, CT or MRI
+ Characteristic hydatid cyst with septated daughter cysts
+ May see head of the tapeworm
o ELISA
+ Highly sensitive for liver cysts, less so for other organs
Echinococcosis (Treatment)
* Surgical resection of cyst
* To reduce risk of spread:
o Aspirate cyst
o Instill hypertonic saline, iodophor, 95% ethanol to kill germinal layer and daughter cysts
o No cidal agents in cases with biliary communication risk of sclerosing cholangitis
* Percutaneous aspiration-injection-reaspiration (PAIR)
* Albendazole before and after surgery or PAIR
Schistosomiasis
Schistosomiasis: Epidemiology and life cycle
Schistosomiasis: Clinical manifestations
Schistosomiasis: Diagnosis and treatment
* Detection of characteristic eggs in stool, urine or tissue biopsy is diagnostic
o Urine is best between 12N and 2Pm, passed through 10 µm filter to concentrate eggs
* Antibody tests are available, but limited by sensitivity, specificity
* Praziquantel is the drug of choice
S. mansoni
Stool
S. haematobium
Urine
S. japonicum
African trypanosomiasis
Trypanosoma brucei gambiense
Blood smear
Tsetse fly
Treatment
* Suramin
* Melasoprol
American trypanosomiasis
Blood smear
Reduviid bug
(assassin bug)
Chagas disease:
Clinical manifestations
Chagas disease: Diagnosis and treatment
* Acute disease is diagnosed by seeing trypomastigotes on peripheral blood smear
* Chronic disease is diagnosed by ELISA detecting IgG antibody to T. cruzi
* Both acute and chronic disease can be treated with nifurtimox or benznidazole
* Treatment slows the progression of heart disease
Chagas Disease
* Public health implications in the US
* Chronic
o Cardiomyopathy
o Megaesophagus
o Magacolon
* Blood transfusion
* Transplant
o Solid organ
o Musculoskeletal allograft tissue
Tapeworms (Cestodes)
* Adult worms inhabit GI tract of definitive vertebrate host
* Larvae inhabit tissues of intermediate host
* Humans
o Definitive for T. saginata
o Intermediate for Echinococcus granulosus (hydatid)
o Both definitive and intermediate for T. solium
* Adult worms shed egg-containing segments in stool ingested by intermediate host larval form in tissues
Taenia saginata
* Ingestion of raw or poorly cooked beef
* Cows infected via the ingestion of human waste containing the eggs of the parasite
* Cows contain viable cysticercus larvae in the muscle
* Humans act as the host only to the adult tapeworms
* Up to 25 meters in the lumen of intestine
* Found all over the world, including the U.S.
Beef Tapeworm
Treatment
* Praziquantel
* Albendazole
* Niclosamide
Cystercercosis
* Human infected with the larval stage of Taenia solium
* Humans can serve as definitive or intermediate host
* Eggs are ingested, or possibly get to stomach by reverse peristalsis
* Probably much more common than is reported, since most infections are asymptomatic
Cystercercosis
* Symptoms depend on location of cysts, but frequently include motor spasms, seizures, confusion, irritability, and personality change
* In the eye, often subretinal or in vitreous. Movement may be seen by the patient. Pain, amaurosis, and loss of vision may occur.
* Clinical manifestations
Cysticercosis * Diagnosis
o CT and MRI preferred studies
+ Discrete cysts that may enhance
+ Usually multiple lesions
# Single lesions especially common in cases from India
+ Older lesions may calcify
o CSF
+ Lymphs or eos, low glucose, elevated protein
o Serology
+ Especially in cases with multiple cysts
Cysticercosis * Treatment
o Complex and controversial
o Praziquantel and albendazole may kill cysts, but death of larvae can increase inflammation, edema and exacerbate sxs
o When possible, surgical resection of symptomatic cyst is preferred
o Corticosteroids vs. edema and inflammation; antiseizure meds
Babesiosis
* Babesiosis caused by hemoprotozoan parasites of the genus Babesia
* >100 species reported
* Few actually cause human infection
* Babesia microti
* Life cycle involves two hosts:
o 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
Deer are the hosts upon which the adult ticks feed and are indirectly part of the Babesia cycle as they influence the tick population
* Clindamycin* plus quinine
* Atovaquone* plus azithromycin*
* Exchange transfusion in severely ill patients with high parasitemia
Classification of Parasitic Diseases
* Protozoa: amoeba; flagellates; ciliates; apicomplexa; microspors (primitive intracellular parasites)
* Metazoa (two phyla)
o Helminths (worms)
+ Nematodes
# Intestinal
# Extra-intestinal
+ Flatworms (platyhelminths)
# Cestodes (tapeworms)
# Trematodes (flukes)
o Arthopods (ectoparasites): scabies, lice, fly larvae
General rules of treatment
* Protozoa: require species-specific treatment
* Metozoa: species-specific
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
This is just the beginning of a great adventure in infectious diseases
Sine qua non:history and physical examination
Emerging Infections and Medical Procedures.ppt
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