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Tropical Medicine > Gastroenterology > Flashcards

Gastroenterology Flashcards

1
Q
  • What is this?
  • What is the geographical distribution, who is at risk?
  • i.e. who would you consider screening?
A
  • Entamoeba histolytica or E. dispar
  • E. dispar is 4 times as common as E. histolytica but non-pathogenic
  • worldwide
  • situations of poor hygeine and sanitation, common in developing countries
    • immigrants
    • travellers
    • residential institutions
    • men having sex with men
    • immunosuppressed
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2
Q

What non-pathogenic protozoa reside in human intestine and the cysts of which of these can be confused with those of E. hystolitica?

A
  • Entamoeba dispar: 3 times as common as E. histolytica in developing countries, 10 times as common in industrialized countries
  • Entameba moshkovskii (cysts identical to E. dispar and E. histolytica)
  • Entameba coli, Entameba hartmanni and Endolimax nana
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3
Q
  • What disease causing ameba are found in humans?
A
  • E. hystolytica
  • E. gingivalis (periodontal disease)
  • E. polecki and Dientameba fragilis (diarrhea)
  • Acanthameba sp and Balamuthia mandrillaris (acanthamebic keratitis/granulomatous amebic encephalitis)
  • Naegleria fowleri (primary amebic meningoencephalitis)
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4
Q
  • What 3 entamoebi look identical?
  • Which cause disease?
  • How are they distinguished?
A
  • E. histolytica - pathological
  • E. moshkovski - possibly pathological, some recorded cases associated with GI symptoms
  • Not causing disease:
    • E. dispar
  • Microscopically identical. Need PCR to distinguish.
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5
Q

What are the 7 species of human entameba?

A
  • E. histolytica
  • E. dispar
  • E. polecki
  • E. moshkovskii
  • E. gingivalis
  • E. coli
  • E. hartmanni
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6
Q
  • Draw E. histolytica trophozoite and cyst.
  • What are distinguishing characteristics?
A
  • Trophozoites
    • size 15-60 microns
    • nucleus with karyosome and peripheral chromatin
    • may see ingested RBC’s (about 5 microns)
    • pseudopod
  • Cysts
    • 10-15 micron diameter
    • immature cysts
      • may have < 4 nuclei
      • glycogen mass
      • chromatoidal body
    • Nuclei
      • 4 nuclei when mature (also in E. dispar)
      • E. coli non-pathogenic, has up to 8 nuclei
      • have numerous pores, lined with peripheral chromatin
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7
Q
  • What is E. dispar and why is it important?
A
  • morphologically identical to E. histolytica but non-pathogenic
  • much more common than E. histolytica
  • distinct on basis of genetic and biochemical differences
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8
Q
  • What is the incubation period for intestinal amebiasis?
A
  • may range from few days to many years depending on size of the inoculum and host response
  • can have prolonged latent period and may present more than a decade following exposure
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9
Q
  • Which patients are at risk for more severe clinical course of amebiasis?
A
  • neonates
  • children
  • pregnancy
  • elderly
  • immunosuppressed
  • alcoholics
  • malnourishment
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10
Q

What factors affect the severity of amebiasis?

A
  • strain of E. hystolytica
  • dose of inoculum
  • status of patient’s immune system
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11
Q
  • Is intestinal amebiasis a zoonosis? Explain.
A
  • principally an infection of humans
  • (some monkeys may harbour the parasite)
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12
Q
  • What is the ‘bind-lyse-eat’ model for invasive amebiasis?
A
  1. E. histolytica binds to host intestine by means of galactose-binding lectin
  2. amoebapores (pore forming molecules) and other enzymes trigger cell apoptosis
  3. ameba phagocytoses the dead cell leading to development of undermined mucosal ulcers with typical “flask-shaped”ulcers.
  • However, invasion also appears to involve cytoskeleton motility, secretion of proteases that degrade extracellular matrix and antibodies. Host inflammatory response also important
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13
Q
  • Describe the pathogenesis of amebic dysentery
A
  • four-nucleated cyst ingested in contaminated food or water
  • cyst digested in gut releasing eight amoebic trophozoites
  • trophozoites live on surface of mucosa, feeding on bacteria and other food residues
  • multiply be binary fission
  • become invasive bind-lyze-eat their way into mucosa
  • gradually ascend the colon and as contents of colon become more solid, amebae stop feeding and encyst
  • amebic cysts are passed in formed stool of people with asymptomatic amebiasis
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14
Q
  • Can E. histolytica cysts survive outside body?
  • If so under what conditions and for how long?
A
  • yes under permissive conditions
    • more than 12 days in cool feces and several weeks in water
    • killed by
      • drying at temps above 50oC and
      • freezing below -5oC
      • standard treatment of water supplies
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15
Q

Can humans develop immunity to E. histolytica?

A
  • some evidence of mucosal immunity to recurrent infections
  • protective immunity does not follow amebic liver abscess
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16
Q

What are the clinical features of intestinal amebiasis?

A
  • wide range from
    • majority of infections asymptomatic through
    • mild disease to
    • fulminant amebic colitis
  • onset may be precipitated by another gi infection or other illness, debility or immunosuppression
  • sx usually insidious with
    • abd discomfort
    • loose stools sometimes containing mucous and blood
    • Mild to moderate
      • pts may be afebrile and ambulatory despite 5-15 bloody stools per day
    • Severe disease
      • debilitated or immunosuppressed pts more likely to have rapid onset abd pain, vomiting, dysuria, tenesmus and frequent bloody stools
      • may be febrile, toxic, dehydrated, anemic, with evidence of peritonitis
    • Most extreme: fulminant necrotizing colitis in minority, usually immunosuppressed
      • often fatal
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17
Q
  • How do you make diagnosis of amebic dysentery? What studies?
A
  • stool exam & endoscopy
    • mild disease may reveal scanty trophozoites in feces, few ulcers on endoscopy
    • moderate disease may have mumerous trophozoites, obvious rectal ulceration on endoscopy
    • severe disease in immunosuppressed patients: COLONOSCOPY CONTRAINDICATED for fear of bowel perforation
  • microscopy
    • MUST SEE trophozoites containing ingested RBC’s in fresh stool
    • ideally examined within 15 min of passing stool or kept at body temp until examined
    • trophozoites may also be seen in scrapings of ulcers at endoscopy
    • leukocytes usually scanty (opposite of bacillary dysentery)
  • E. hist copro-Ag test
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18
Q
  • What are potential complications of amebiasis?
A
  • amebic abscess, most commonly liver
  • ameboma
    • chronic inflammatory mass or masses, most commonly ileocecal presenting as acute/subacute obstruction or causing an intussusception
  • hemorrhage causing anemia or shock
  • peritonitis
    • abrupt/insidious onset, may occur after pt has started treatment
  • post-dysenteric ulcerative colitis
    • usually resolves without treatment
    • rarely progresses to massive necrosis and toxic megacolon
  • skin ulceration
    • usually perinal and anogenital, may occur e.g. ileostomy/colostomy sites, surgical wounds
  • stricture
    • esp of colon and rectum
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19
Q
  1. What is the differential diagnosis of amebic colitis?
A
  • shigella
  • typhoid or other salmonella
  • enteroinvasive and enterohemorrhagic escherischia coli
  • schistosomiasis (esp. S. mansoni and S. japonicum)
  • Balantidium coli
  • trichuris trichiuria
  • tb
  • ca
  • ischemic colitis
  • av malformation
  • diverticulitis
  • Any other cause of acute or chronic abd pain
  • Other causes of dysentery or bloody stools
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20
Q

What is the differential diagnosis of ameboma?

A
  • tb
  • ca
  • actinomycosis
  • antibioma
  • appendiceal mass
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21
Q

How do amebic liver abscesses form?

A
  • trophozoites invade liver via portal vein and destroy hepatocytes
  • microabscesses form and coalesce to form
    • single abscess (65-75%)
    • multiple abscesses (25-35%)
  • surrounding tissue becomes edematous and enflamed
  • secondary bacterial infection unusual
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22
Q

Where do liver abscess form?

A
  • right lobe abscesses 4 times more common than left
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23
Q

Who gets amebic liver abscesses?

A
  • Men 10 times as common as women
  • all age groups from neonates to elderly BUT
    • ​ALA most common in males aged 20-40 yrs
    • < 50% have hx of dysentery within 1 month prior to presentation
    • many have no hx of dysentery at all
  • may present many years after expsure with transition from latent infection to clinical disease triggered by illness or immune suppression
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24
Q

What are the clinical features of amebic liver abscess?

A
  • “amebic hepatitis”
    • in early precoalescence phase may present with low grade fever, ruq discomfort and tenderness
    • however, AST, ALT, GGT, bili usually normal
  • “mature” abscess
    • gradually increasing, sometimes acute pain RUQ
    • sometimes referred pain to shoulder
    • pain may be pleuritic, localize to lower chest wall
    • fever, sweats, rigor common
    • maybe cough, SOB, evidence of pleural effusion leading to wrong dx pneumonia
    • weight loss, wasting, anemia more frequent in chronic picture, may be afebrile
    • most have tender hepatomegaly, tender ic space (Durban’s sign)
    • CXR may show raised hemidiaphragm or pleural effusion
    • jaundice uncommon, <1/2 have elevated transaminases or bili
    • Most have increase alk phos
    • neutrophil leucocytosis in ~80%
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25
Q

What are the complications of amebic liver abscess?

A
  • rupture through
    • skin
    • peritoneum
    • lung
    • pleura
    • pericardium and poss cardiac tamponade (esp with left lobe abscess)
  • hematogenous seeding causing abscesses anywhere, e.g.
    • brain
    • muscle
    • kidney
    • spleen
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26
Q

What is the differential diagnosis of amebic liver abscess?

A
  • pyogenic abscess
  • hepatocellular ca
  • liver mets
  • hydatid cyst
  • hepatitis
  • tb
  • syphilitic gumma
  • lung pathology
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27
Q

How do you distinguish pathogenic and non-pathogenic amebic trophozoites by microscopy?

A
  • non-pathogenic amebae do not contain ingested RBC’s
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28
Q

How do you confirm the dx of amebic liver abscess (ALA)?

A
  • Primarily clinical diagnosis, with imaging findings
    • CXR, US, CT
    • rare to have trophozoites in stool
  • less than half have cysts
  • Abscess aspiration
    • pink to dark brown, darkens on exposure to air
    • “Anchovy sauce”
    • Microscopy
      • trophozoites can be seen in pus
      • more reliably trophozoites can be seen in scrapings from the wall of an ALA
      • cysts never found in abscesses
      • leukocytes scanty unless 2o infection
    • Antigen detection more sensitive
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29
Q

What are the 4 different technologies for detection of E. histolytica and what about them?

A
  • microscopy
    • in resource-poor settings, remains principal method of investigation
  • stool ag detection more sensitive and specific, in affluent countries
    • reliably differentiates E. histolytica from E. dispar but does not guarantee that E. histolytica is cause of sx
    • Ag detectable in pus from abscess
  • PCR recent
  • serology
    • Enzyme immunoassay (EIA) most widely recommended
    • Ab in 95% of extraintestinal disease and 70% of active intestinal disease
    • EIA becomes neg 6-12 months after recovery
    • EIA may be neg in early stages of amebic liver abscess and should be repeated after a week if necessary
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30
Q

What is the role of endoscopy in dx of intestinal amebiasis?

A
  • may be helpful if suspected but microscopy or ag tests neg
  • no bowel prep: reduces yield
  • amebic colitis looks like ulcerative colitis
  • may invade other pathology e.g. carcinoma
  • scrapings or biopsies from ulcer edge should be examined immediately for erythrophagocytic trophozoites
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31
Q
  • What is the role of serology in confirming Amebic liver abscess?
A
  • current serology screening tests do not differentiate current from past infections. Therefore not useful in endemic area
    • Indirect Hemagluttanin Assay (IHA)
    • Fluorescent Ab (sometimes for screening)
    • Gel diffusion (for invasive disease)
    • Cellulose Acetate Precipitin (CAP) very specific
    • ELISA (very specific)
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32
Q
  • What is the General Basic Approach to dx of Intestinal Amebiasis?
A
  1. stool trophs (hematophagocytic)
  2. stool Ag
  3. endoscopy
  4. serology
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33
Q
  • What is the General Basic approach to diagnosis of amebic liver abscess (ALA)?
A
  1. Imaging: US/CXR/CT
  2. Serology
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34
Q
  • How do you treat Intestinal Amebiasis?
A
  • Imidazoles: for tissue cure:
    • Metranidazole 800 mg tid x 5-10 days
    • Tinidazole
  • Luminal amebacides: for cyst eradication
    • Diloxanide furoate
    • Quinfamide
  • Other drugs:
    • ​Nitazoxanide
    • ​Luminal
      • ​Tetracycline
      • Paromomycin
      • Iodoquinol
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35
Q
  • How do you treat ALA?
A
  • Imidazoles
    • Metronidazole
    • Tinidazole
  • Other:
    • Nitazoxanide
  • Aspiration only if impending rupture/failed conservative treatment
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36
Q
  • What is the usual clinical presentation of Giardiasis?
A
  • mostly assymptomatic, very variable
  • anorexia, nausea, lassitude, “eggy” tast
  • chronic diarrhea, cramps, bloating, nausea, wt loss, FTT
  • severe diarrhea + malabsorption (usually if low immunity)
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37
Q
  • How do you make diagnosis of Giardia?
A
  • cysts in stool
  • string (antiquated)
  • aspirate
  • Crosby Capsule (for upper small bowel biopsy)
    • antiquated largely replaced by upper gi endoscopy except rarely in kids
  • endoscopy
  • stool antigen detection
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38
Q
  • How do you treat Giardia? (Basic)
A
  • First Line: imidazoles
    • metronidazole
    • tinidazole
  • Reserve:
    • quinacrine, mepacrine
    • furazolidine
    • paromomycin
    • albendazole
    • nitazoxanide
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39
Q
  • How do you approach refractory Giardia?
  • Treatment?
A
  • Causal considerations
    • adherence?
    • any pets? i.e. reinfection
    • IgA deficiency?
    • consider treating whole family
    • consider possible resistance
  • Combination treatment
    • Albendazole x 7 days + Tinidazole on Day 1 & Day 7
    • if persistent try Mepacrine 100 mg tid x 7 days
    • other combinations include
      • albendazole + metronidazole
      • quinacrine + metronidazole
      • albendazole + nitazoxanide
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40
Q
  • What is the proposed Liverpool treatment ladder for resistant Giardia?
A
  • 1st line: Tinidazole - 2 gm stat
  • 2nd line: Tinidazole - 2 gm stat
      • Albendazole 400 mg bid x 7 days
  • 3rd line: Tinidazole - 2 gm stat
      • Albendazole 400 mg bid x 7 days
      • mepacrine 100 mg tid x 7 days
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41
Q
  • What is this?
  • In what clinical settings is this found?
A
  • Cryptosporidium cysts
  • People who swim regularly in pools with insufficient sanitation (certain strains of Cryptosporidium are chlorine-resistant)
  • Child-care workers
  • Parents of infected children
  • People caring for other people with cryptosporidiosis
  • Backpackers, hikers, and campers who drink unfiltered, untreated water
  • People, including swimmers, who swallow water from contaminated sources
  • People handling infected cattle
  • People exposed to human feces
  • may chronically sicken immunocompromised
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42
Q

What are the symptoms/clinical picture of cryptosporidium infections?

A
  • watery diarrhea, cramps, gas, wt loss, fever, malaise
  • usually self limiting
  • chronic/fulminant in immunocompromised (eg HIV)
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43
Q
  • What is this?
  • How is the diagnosis made?
    • microscopic appearance?
    • size?
A
  • cryptosporidium parvum
  • acid fast oocysts in stool by ZN stain
  • stain bright red to pink, some dark granules, central clearing
  • small 3-6 µm diameter
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44
Q

How do you treat cryptosporidium?

A
  • symptomatic (e.g. ORS) as it is usually self-limiting, mild
  • ?paromomycin, ?Azithromycin
  • Nitazonoxanide
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45
Q

What is this?

What organism does it need to be distinguished from?

How?

clinical setting, where found?

A
  • Cyclospora
  • distinguish from cryptosporidium, which looks similare and stains similarly on ZN stain. (ZN cyclospora below)
  • But cyclospora is LARGER - 8-10 µm vs 4-5 µm
  • found mostly in contaminated water, fruit, herbs
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46
Q

Cyclospora: clinical picture

A
  • similar to cryptosporidium and Isospora
    • prolonged watery diarrhea, cramps, fever, fatigue
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47
Q

Cyclospora: how diagnosed?

A
  • Stool microscopy: modified acid-fast stain
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48
Q

Isosporiasis:

  • Species
  • geographic dystribution
  • human disease
  • microscopy
A
  • Isospora (cystoispora) belli
  • worldwide, but generally from tropics & subtropics
  • causes watery diarrhhea and wt loss, malabsorption, usually self-limited but
  • immunocompromised at risk for debilitating and chronic illness
  • disease via ingestion of mature oocysts, which must sporulate outside the host for 1-2 days
  • acquired by ingestion of contaminated food or water
  • dx by finding Isospora oocysts (dimensions, 23–36 µm by 12–17 µm)
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49
Q

Isosporiasis: pathological and clinical picture?

A
  • similar to cryptosporidium
  • watery diarrhea +/- blood +/- pus, pain, malabsorption
  • self-limiting
  • chronic/relapsing in immunocompromised
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50
Q

Isosporiasis: how is the diagnosis made?

A
  • Stool, modified acid-fast stain
  • nb may cause eosinophilia, the only one of GI parasites commonly doing this
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51
Q

Cyclospora/Isospora: How treated?

A
  • TMP-SMX (160/800 mg po bid x 7-10 days)
    • then maintenance 3 doses/week if HIV +ve or
      • fansidar weekly

OR

  • Pyrimethamin alone if sulphonamide allergic
  • cipro for cyclospora
  • Nitazoxanide
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52
Q

Microsporidia: what is the clinical significance?

A
  • various species pathogenic in humans
  • increasingly recognized as important, esp HIV-infected persons
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53
Q

What is the commonest microsporidium in a clinical setting?

A
  • Enterocytozoon bieneusi
    • occurs in 7-50% of HIV-infected persons with chronic diarrhea
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54
Q

Microsporidia: how identified?

A
  • Stool microscopy: Weber’s chromotrope or chemofluorescent stain.
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55
Q

Microsporidia, how treated?

A
  • Albendazole, Nitazoxanide
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56
Q

What are the causes of malabsorption in the tropics?

A
  • Parasites:
    • giardiasis
    • fasciolopsis
    • capillariasis
    • stongyloidiasis
    • isosporiasis
    • cryptosporidiosis
  • Tropical sprue
  • Celiac disease
  • Hypolactasia
  • chronic calcific pancreatitis
  • malnutrition
  • Intestinal TB
  • alpha-chain disease (variant of heavy chain disease, lymphoproliferative)
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57
Q
  • What are the four groups or species of Shigella, how many suptypes and what are the clinical settings they are found in?
A
  • Group A: Shigella dysenteriae
    • tends to cause epidemics, (esp subtype 1)
    • no major outbreaks since 1990
    • 15 serotypes
  • Group B: Sh. flexneri
    • commonly causes endemic dysentery in developing countries
    • however nb outbreak in England & Wales with MSM sex (cell phone sex, chemsex, fisting etc.)
    • 8 serotypes with 15 subtypes
  • Group C: Sh. boydii
    • common on Indian subcontinent
    • 120 serotypes
  • Group D: Sh. Sonnei
    • important cause of dysentery in industrialized world
    • 1 serotype
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58
Q

Which strains of shigella have been described as sexually transmitted?

A
  • MSM sex
  • Sh. flexnerii
  • Sh. sonnei
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59
Q
  • How many deaths globally in 2015 in chilren under 5 from Diarrhea?
  • What organisms are the most common causes?
A
  • about 500,000 deaths
  • rotavirus
  • Cryptosporidium spp
  • Shigella spp
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60
Q

What organisms cause the most deaths due to diarrhea globally (any age) in the total population?

A
  • rotavirus
  • shigella
  • salmonella
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61
Q

What role does shigella play in diarrheal disease in children <5 in Asia and Africa?

(GEMS study)

A
  • commonest cause of dysentery
  • 2nd most common cause of watery diarrhea (after rotavirus)
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62
Q
  • What is best treatment for shigella dysentery and ETEC?
  • Against what antibiotics are shigella frequently resistant?
A
  • Best: cipro or norfloxacin (little resistance until recently, emergence of cipro resistance in SE Asia & India)
  • azithromycin
  • TMP-SMX (80% Shigella resistant, 40% ETEC
  • Tetracyline
  • Ampicillin
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63
Q

How common is cholera?

A
  • globally 3-5 million cases
  • 100-120 thousand deaths annually
  • however, may represent only 10% of all cases!
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64
Q

Cholera: What are the only animal hosts/reservoirs of infection?

A
  • Man
      • shellfish and plankton
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65
Q

What is the incubation period for cholera?

A
  • few hours to 5 days
  • most 12-24 hours
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66
Q
  • Cholera Epidemiology
    • what is the reservoir?
    • how does it enter the human population?
A
  • warm brackish water favour growth of plankton and V. cholerae and expression of virulence, taken up by copepods and crustaceans
  • consumed via uncooked shellfish and enters human population, thereafter transferred via fecal-oral route and spreads via contaminated food or water
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67
Q
  • Cholera Bacteriology
    • Basic description
    • implications for diagnosis
A
  • comma shaped
  • aerobic
  • Gram negative
  • Disease-causing cholera are divided into strains based on O antigen: (O1 and 0139)
  • classically 01 strain was predominant, recent emergence of 0139 poses issues for effectiveness of vaccines
  • 01 Strain divided into Biotypes El Tor & Classical and these into
  • Serotypes Inaba and Ogawa, each of which may or may not produce toxin
  • Therefore diagnosis requires identification of strain and identification of toxin antigen
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68
Q

Cholera: How well does it survive outside host?

A
  • survives saline at low temp ~ 60 days, 12 days at ambient temp
  • killed by heating at 55oC for 15 min
  • killed by hypochlorite etc
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69
Q

What is Vibrio Cholera 0139 and what is it’s significance?

A
  • a new strain appeared in S. India in 1992
  • high attack rate in adults
  • prev exposure to 01 doesn’t confer immunity to 0139
  • vaccines based on 01 Ag likely not effective
  • likely to cause next cholera pandemic
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70
Q

Describe the pathogenesis of cholera disease?

A
  • adherence to small bowel mucosa via Outer Membrane Protein and flagellar adhesins
  • Toxin: 2 subunits
    • B=binding
    • A=active
    • ⇒enters cell
    • ⇒stimulates cAMP
    • ⇒inhibits NaCl absorption
    • ⇒stimulates Cl excretion (water, K & bicarb follow Cl)
    • ⇒net loss of water, NaCl, K, bicarb
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71
Q

What are the factors affecting severity of Cholera infection?

A
  • local intestinal immunity (previous infection Vibrio)
  • infecting dose
  • Gastric acidity (drugs or prior gastrectomy or age)
  • blood group - more severe if gp ‘O’
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72
Q
  • Describe the clincial presentation of cholera
  • mortality rate?
A
  • Varies from
    • Assymptomatic
    • ⇒ mild diarrhea
    • ⇒’rice water stools’ +/- bloating +/- vomiting
    • ⇒severe dehydration, acidosis, Elyte disturbance
    • ⇒ileus, muscle weakness, cramps, arrhythmias
    • ⇒Acute Renal Failure (ATN), shock coma death
  • Adults may lose 500 to 1000 ml/hr
  • hypoglycemia, esp in children
  • most cases mild, self-limiting
  • Mortality 5-15%
  • ‘Cholera sicca’: little d&v, rapid collapse, high mortality
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73
Q

Cholera Diagnosis

A
  • presumptive in epidemics, subsequent confirmation
  • dark field microscopy ⇒ darting vibrios
  • movement inhibited by antisera (01 or 0139)
  • transport in alkaline peptone water or CaryBlair medium
  • Stool culture (stool/rectal swab) on TCBS agar
  • send for biotyping, serotyping, sensitivity
  • recently immunodiagnostic dipsticks for rapid diagnosis in field conditions
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74
Q

What is the role of the Rapid Diagnostic Test?

A
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75
Q

Cholera Management

A
  • Fluids, fluids, fluids
  • ORS usually sufficient
  • IV if severe dehydration/shock (Ringer’s Lactate/Hartman’s)
  • Antibiotics: shorten period of diarrhea and reduce fluid loss
    • antibiotic resistance common
      • doxycycline
      • SMT-TMP
      • cipro
      • azithromycin or erythromycin (if pregnant)
      • nb resistance to SMT-TMP and erythromycin common
  • ​Zinc- reduces diarrhea volume and duration in children
  • chlorpromazine - anti-secretory, rarely used
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76
Q

How do you make ORS for cholera?

A
  • one litre water
    • 2.6 gm NaCl
    • 2.9 gm trisodium citrate
    • 1.5 gm KCl
    • 13.5 gm glucose (or 50 gm boiled and cooled rice powder instead of glucose

OR

  • one level teaspoon salt
  • eight level teaspoons of sugar
  • one litre of clean water
  • remember 1 thumb for salt, the other for the litre of water and the 8 fingers for 8 level teaspoons of sugar.

nb standard ORS better than reduced osmolarity

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77
Q

Cholera Case Management

A
  • Severe
    • lethargic, unconscious, floppy, very sunken eyes
    • drinks poorly or unable to drink, mouth very dry
    • Skin pinch goes back very slowly
    • No tears (only for kids)
      • ⇒IV therapy + antibiotics + ORS
  • Moderate
    • restless and irritable, sunken eyes
    • dry mouth but thirsty, drinks eagerly
    • skin pinch goes back slowly
    • No tears (kids)
      • ⇒ ORS + very close surveillance
  • No dehydration
    • none of the above signs
      • ⇒ ORS at home
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78
Q

Cholera IV Management: How much fluid?

A
  • Fluids + frequently assess response
  • In all patients with hypovolemic shock, initial fluid deficit will be at least 10% of body weight
    • rule of thumb: give 1/3 total estimated deficit in first 20-30 min
  • Severe dehydration: 100 ml/kg over 3-6 hrs
    • Age < 1yr 30 ml/kg over 60 min
      • then 70 ml/kg over 5 hrs
    • Age > 1 yr 30 ml/kg over 30 min then 70 ml/kg over 2.5 hrs
  • Mild-mod dehydration
    • ORS 75 ml/kg over 4 hrs
  • No dehydration
    • start giving ORS as soon as diarrhea starts.
    • Give ORS after each loose stool
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79
Q

What is the case definition for Cholera (MSF and WHO)?

A
  • MSF
    • any pt developid rapid onset severe watery diarrhea (usually with vomiting), resulting in severe dehydration
  • WHO
    • In area where cholera known to be present
      • patient > 5 yrs develops severe dehydration or dies from acute watery diarrhea
    • In area where there is a cholera outbreak
      • any patient > 5 yrs develops acute watery diarrhea with or without vomiting
80
Q

How many cases of cholera to expect in a refugee camp?

and

How many will require IV tx?

A
  • MSF:
    • if camp population 50,000
      • expect 2500 cases (attack rate 5%)
      • 1875 may require IV (75%)
81
Q

Which parasites are important gut pathogens?

A
  • Entameba histolytica
  • Giardia Duodenalis (lamblia)
  • Cryptosporidium hominis
  • Cryposporidium parvum
82
Q
  • What is Entameba Polecki?
  • Disease?
  • Animal Reservoir?
  • Distribution?
  • Microscopic and how diagnosed?
A
  • Entamoeba similar to Ent. Histolytica in appearance
  • Causes GI symptoms, much less common than E. Histolytica, debatable.
  • Reservoir: pigs
  • Distribution: where pigs and humans live closely togeter
    • Papua New Guinea
    • Cambodia etc.
    • Venezuala
83
Q
  • What is Acanthamoeba?
    • Where? Distribution, prevalence?
    • Disease?
    • Treatment?
A
  • Widespread Eukaryote found in soil, water, contact lens cases, swimming pools, sewage, seawater etc
  • 2 forms of disease:
    • Granulomatous amoebic encephalitis
      • generally in immunosuppressed pts (HIV, alcoholics, diabetes, sle, malignancies) after ameba enters through break in skin or inhalation via upper respiratory tract
      • leptomeningeal picture, high fatality rate
    • Acanthamoebic keratitis
      • contact lens wearers
  • May harbour symbiotic bacteria species: legionella, e coli, staph
  • Treatment is difficult
84
Q
  • What is Balamuthia mandralis?
A
  • Free-living ameba widespread in soil and water, widespread in temperate climates
  • First isolated from infected baboon in San Diego Zoo.
  • Causes rare disease granulomatous amoebic encephalitis
  • Enters body through wounds, lower resp tract infections, documented spread in organ donation
  • Diff to treat, but survival possible using antibiotics and antifungals.
85
Q
  • What is Naegleria fowleri?
    • disease, distribution, who infected
    • treatment?
A
  • Free living, fresh water ameba (warm ponds, lakes, hot springs)
  • Enters via nasal passage in trophozoite form, through cribriform plate
  • Causes Acute amebic encephalomyelitis with high (>95%) fatality rate.
  • treatment Amphotericin B but not very effective
86
Q
  • What is the mode of transmission of cholera?
A
  • contaminated food and water
  • source usually feces of cholera patient
  • Vibrio Cholera O1 has zooplankton reservoir via warm brackish waters, may enter population via contaminated seafood.
  • Person to person contact via shaking hands or caring for cholera patient has NOT been shown to occur.
87
Q
  • When did the current cholera pandemic start?
  • What is the strain and biotype of this pandemic?
A
  • 1961 Sulawesi
  • Strain 01, Biotype El Tor
88
Q

Describe the spectrum of severity of cholera.

A
  • 75% are assymptomatic
  • 25% symptomatic, most of whom will have mild illness
  • 5% of those infected will have moderate illness causing presentation to hospital but treatment as outpatient with ORS
  • 2% of those infected will have severe cholera (‘cholera gravis’) requiring IV therapy
89
Q
  • What is the role of Rapid Diagnostic Test for cholera?
    • What is it and when used?
A
  • Ag test identifying 01 and 0139 strains
  • not for individual diagnosis
  • in outbreaks of watery diarrhea test up to 10 people with onset < 4 days
  • if >30% are positive, send samples to lab for confirmation
  • does not detect cholera toxin, biotype, serotype or PFGE (pulsed field gel electrophoresis) or antimicrobial sensitivity profiles
90
Q
  • What complications during rehydration from cholera?
    • How treated?
A
  • hypoglycemia, esp in kids
    • tx 1ml/kg d50W by slow IV
  • overhydration, pul edema
    • tx according to severity, sit up with legs down slow IV rate
  • watch for anuria, renal failure, consider if no urine output after rehydration
  • repeated muscle cramps may suggest hypokalemia after IV rehydration
    • use ORS to replace K
91
Q
  • What cholera vaccines are available?
    • Dosing?
    • Protective efficacy?
A
  • Dukoral (Sweden)
    • killed V cholerae O1 plus recominant B subunit
      • 2-6 yrs old: 3 oral doses
      • >6: 2 oral doses 1-6 wks apart (WHO 10-14 days)
      • protection 10 days after 2nd dose
      • Booster after 2 yrs (after 6 months if age 2-6)
    • adults 85-90% after 6 months, falling to 62% at 1 yr
    • kids age 2-5 yrs 100% at 4-6 months f/u
    • refugee camps: 78% protection + herd effect
  • Shanchol (India)
    • based on serogroups O1 & O139
    • does not contain bacterial toxin B subunit so won’t protect against ETEC
    • dose: >1 yr 2 liquid doses po 14 days apart, booster at 2 yr
    • 67% efficacy after 2 doses
  • both effective up to 2 years
92
Q

What is WHO position on cholera vaccines?

A
  • cholera control a priority where endemic
  • vaccination should not disrupt other control effors
  • vaccines provide short term benefit while longer term interventions started
  • where resources limited target high risk kids
    • > 1 yr (Shancol) or
    • >2 yr (Dukoral)
  • In case of epidemic: pre-emptive or reactive vaccination should cover as many eligible people as possible
93
Q
  • What is the role of vaccines in controlling endemic cholera?
  • Is there a role in outbreaks?
A
  • target high risk groups (eg preschool and school aged children, pregnant women and HIV +ve people)
  • possibly also older people
  • need boosters q 2 yrs
  • possibly also a role in pre-emptive chontrol of outbreaks
    • study suggests one dose of Shanchol may protect
94
Q
  • What is dysentery?
  • What are the 2 commonest causes?
  • Others?
A
  • Bloody diarrhea
    • usually with fever
  • Bacillary dysentery
    • Shigella Species
    • Much less common: campylobacter
  • Amoebic dysentery
    • Entamoeba histolytica
95
Q
  • Globally what organisms are the leading causes of diarrheal deaths?
  • How many deaths annually?
  • Geographically where do most of these deaths occur?
A
  • Rotavirus
  • Shigella
  • Salmonella
  • 1.3 to 1.4 million deaths total
  • Most occur in Sub-Saharan Africa or South Asia
96
Q
  • How many deaths does Shigella cause per year?
  • What percentage of diarrheal deaths?
A
  • 164,300 deaths or
  • 12.5% of total 1.31 million deaths per year due to diarrhea
97
Q
  • What spectrum of disease does Shigella cause?
  • What is the GEMS study and what were its main conclusions?
A
  • Although known as a cause of dysentery (bloody) diarrhea, Shigella species are also a common cause of watery diarrhea.
  • GEMS a study of diarrheal illness in children, using PCR to identify the organism
    • In children aged 12-23 months it was the 2nd most common pathogen (after rotavirus)
    • In children aged 24-59 months it was the most common pathogen
    • culture based diagnostics likely missed a lot of children with Shigella
    • IN CHILDREN UNDER 5, SHIGELLA WAS THE 2ND MOST COMMON PATHOGEN ASSOCIATED WITH WATERY DIARRHEA
98
Q

When was Shigella first recognized as an STI?

A

1971

99
Q
  • What species of Shigella have been associated with STI’s?
A
  • Shigella flexneri
  • Shigella Sonnei
100
Q
  • In an outbreak of sexually transmitted Shigella in England and Wales in 2009-2012 what behaviours were associated with transmission of strain 3a of S. flexneri?
A
  • condomless sex
  • chemsex
  • oral-anal contact
  • fisting
101
Q

In a study of gulf war soldiers in Iraq in the 1990’s what species of Shigella were identified as causes of dysentery?

A
  • Shigella sonnei
  • S. flexneri
  • S. boydii
102
Q

In a study of gulf war soldiers in Iraq in the 1990’s, what empiric treatment was used for dysentery caused by Shigella species and what was the resistance pattern like?

A
  • SMT-Trimethoprim : high rates of resistance
  • Cipro: no resistance
103
Q
  • Compare and contrast Small bowel diarrhea and large bowel diarrhea wrt:
    • appearance of stool
    • volume
    • frequency
    • presence of blood
    • WCC in stool
    • Typical pathogens
A
  • Small bowel diarrhea
    • watery
    • high volume
    • lower frequency
    • blood not usually seen (?microscopic?)
    • <5 WBC/high power field
    • Typical pathogens:
      • Rotavirus
      • Giardiasis
      • Adenovirus
      • Norovirus
      • Cholera
      • E. coli (ETEC)
  • Large Bowel diarrhea
    • appearance mucoid, bloody, thicker, dysenteric
    • smaller volumes
    • higher frequency
    • blood commonly in stool
    • WCC in stool very high
    • Causes of acute dysentery
      • Acute
        • Shigella
        • E. coli (EHEC)
        • Campylobacter
      • Chronic (> 2wk)
        • Amebiasis
104
Q
  • What is the differential diagnosis for bloody diarrhea with fever?
A
  • Bacterial
    • Gm negative
      • Shigella
      • E. coli
      • Salmonella
      • Campylobacter (curved gm neg)
    • Gm Positive
      • C. dificil
  • Protozoa
    • E. histolytica and (?E. moschovskii)
    • Balantidium coli
  • Helminths
    • Schistosoma
    • Ascariasis
    • Trichuriasis
  • Non-infectious
    • Inflammatory Bowel Disease
105
Q
  • What complications of bacterial dysentery should I look out for?
A
  • Intestinal
    • prolapse, megacolon, perforation, obstruction, appendicitis
    • persistent diarrhea
  • Extra-intestinal
    • seizures
    • dehydration
    • hyponatremia
    • hypoglycemia
    • focal infections - meningitis, osteomyelitis, arthritis
    • sepsis
    • leukemoid reaction
  • post-infectious
    • HUS
    • Reactive arthritis
106
Q
  • Compare bacillar dysentery and amebic dysentery with respect to:
    1. the organism(s)
    2. their survival outside the organism
    3. infectious dose
    4. incubation period
A
  1. Shigella spp Enterobacteriacae vs E. histolytica
  2. resistant to gastric acid but sensitive to chlorine vs E. histo able to survive up to 7 days in chlorine
  3. 10-20 orgs vs > 1000 orgs
  4. 1-8 days (med 5) vs 7-10 days
107
Q
  • Compare bacillary dysentery and amebic dysentery wrt:
    1. incubation period
    2. complications and
    3. diagnostic tools
A
  1. incubation 1-8 days (med 5) vs 7-10 days
  2. complications including seizures, focal infections and leukemoid reactions vs liver abscesses, skin ulceration and amoeboma
  3. dx via culture and rectal swab, serology not useful for bacterial dysentery vs rapid fecal ag tests and ELISA (coproantigen)
108
Q
  • Outline a general treatment plan for bacillary dysentery.
A
  1. Diagnostics? - if available - consider culture vs treat empirically
    • in high resource setings NAAT (PCR)
  2. Supportive care?
    • ORS, hydration, avoid antimotility agents - complications
  3. Antibiotic choice?
    1. Cipro first line treatment, but in UK usually avoided in children due to theoretical concern re risk of arthopathy in wt bearing joints
    2. Ceftriaxone
  4. Micronutrients
    1. Zinc
    2. ?Vitamin A
109
Q
  • Comment on the presentation of Shigella in children
A

Dysentery is NOT a reliable tool for identifying Shigella infection:

Shigella is common in children with dysentery

BUT

Most children infected with Shigella do not present with dysentery.

110
Q

What are protozoa? What proportion of parasitic protozoa in humans are found in the gut.

A
  • single celled eukaryotic organisms
  • about half
111
Q
  • What protozoa may be found in fecal samples?
A
  • Entamoeba histolytica/dispar
  • Entamoeba coli
  • Giardia lamblia
  • Trichomonas hominis
  • Cryptosporidium
  • Balantidium
112
Q

Amebiasis: treatment

  • What drugs are used and why?
A
  • nitroimidazoles first line
    • metronidazole
    • tinidazole
    • ornidazole
  • Asymptomatic & luminal treatmets include
    • Highly absorbed in gut, therefore luminal conc. falls below therapeutic
    • Paromomycin
    • Iodoquinol
    • diloxanide furoate
  • When metronidazole is contraindicated
    • poorly absorbed in gut so used to “mop up” luminal trophozoites
    • dihydroemetine
    • chloroquine
113
Q
  • Describe Entamoeba Histolytica trophozoites & cysts: size, shape, movement, nucleus etc.
    *
A
  • wide variation in size and shape: 12-25 microns
  • active directional movement, pushing forward pseudopodia, engulfing bacteria and rbc’s
  • each nucleus bound by nuclear membrane with chromatin on inner surface
  • mature cysts have 4 nuclei; immature cysts fewer and glygoten present
  • Cysts have less size variation: 10-15 microns, smooth uniform outer membrane
114
Q
  • Entameba dispar:
    • appearance?
    • how can it be distinguished from Ent Histolytica
    • what does it’s presence indicate?
A
  • morphologically identical to Ent. Histolytica
  • Antigenically different so can be distinguished using specific monoclonal antibodies
  • poor hygeine and sanitation
115
Q
  • What is this?
  • How and from what is it distinguished.
A
  • Ent. coli trophozoite
  • Non-pathogenic, no invasive stage, does not ingest RBC’s
  • trophozoite larger (15-50 microns) than Ent. Histolytic (12-25 µm)
    • single large eccentric nucleus with chromatin clumped on nuclear membrane
116
Q
  • What is it?
  • What are the distinguishing features
A
  • cysts
  • 15-25 microns (cw E. histolytica) 10-15 microns
  • contain 1-8 nuclei with irregular peripheral chromatin (E. histolytica up to 4 nuclei)
117
Q
  • What is this?
  • Distinctive characteristics?
A
  • Endolimax nana cyst
    • non-pathogenic species
    • trophozoite seldom seen in fecal samples
    • cyst small (7.5-10 microns) (cw E. hist 10-15 microns)
      • round or oval in shape
      • up to four hole-like nuclei, each with large eccentric karyosome
      • important to differentiate from Ent. histolytica based on smaller size and differences in nuclear detail, best seen in iodine stain
118
Q

​

  • what is it?
  • describe.
A
  • Iodamoeba butschlii cyst
  • considered to be non-pathogenic amoeba
  • trophozoite 12-15 µm, single large nucleus, large karyosome
  • cyst oval 10-12µm
    • uninucleate with large karyosome, often situated against nuclear membrane
    • large glycogen mass diagnostic, stains rich red-brown colour with iodine in fresh feces
119
Q

What is a karyosome?

A

Karyosome refers to the chromatin material inside cell nucleus when the cell is not undergoing mitotic division

120
Q

What is this?

Characteristics?

Distribution?

Human disease?

A
  • Blastocystis homininis cyst-like form
  • protozoan parasite of large intestine (classification controversial)
    • round, oval or irregular, measures 8-12 µm.
    • cyst-like forms have large central body that looks like large vacuole surrounded by multiple granules within periphery of cytoplasm
  • Human Disease: controversial, often found in assymptomatic persons. Sometimes associated with watery diarrhea
121
Q

Giardia Lamblia

  • geographic distribution
A
  • worldwide
  • more common tropics and subtopics
  • in areas where water supplies and environment are contaminated with feces
122
Q

What is this?

  • What are the usual symptoms?
A
  • Giardia cyst
    • no blood
    • often assymptomatic
    • abd pain
    • flatulence
    • diarrhea
    • steatorrhea
123
Q

Giardia lamblia

  • stool appearance
A
  • offensive odour
  • pale, fatty, floating, steatorrheic
124
Q

Giardia lamblia

  • trophozoites
A
  • small, pear shaped
  • flagellae
  • 12-15 µm
  • fresh stool, duodenal/jejunal aspirate, stained smear
125
Q

What is this?

Characteristics?

A
  • fresh stool or concentrate
  • oval in shape, 10-15 µm
  • 4 nuclei, 2-4 visible, often grouped at one end
    • not always visible in saline, better with iodine
    • axostyle down centre of cyst refractive
    • 1-2 median bodies may be present
126
Q

Giardia epidemiology

  • distribution
  • role of assymptomatic carriers
  • what social settings common
  • what clinical condition predisposes
A
  • worldwide
    • feces contaminated water source
  • assymptomatic carriers may pass cysts for years
  • day care and mental institutions common
  • IgA deficiency predisposes
    *
127
Q

Giardia

Mode of transmission?

A
  • cyst ingestion (fecal-oral)
  • oral-anal sexual transmission
128
Q

Giardia

Pathophysiology

A
  • cysts attach but don’t invade
  • inflammation leads to malabsorption of proteins and fat, leading to steatorrhea, fatty foul stools
129
Q

Giardia:

Clinical presentation

A
  • many assymptomatic
  • non-bloody, foul smelling diarrhea
  • nausea, anorexia, flatulence and cramping lasting weeks to months
  • no fever
130
Q

Giardia:

lab diagnosis

A
  • observation of trophozoites or cysts in stool
  • in assymptomatic carriers, only cysts may be found
  • duodenal fluid or biopsy material may reveal pear-shaped trophozoites
    • obtained by string test or endoscopy
    • useful when giardia suspected but undetected in stool samples
  • other staining methods include
    • enzyme immunoassay
    • immunofluorescence
  • also Giardia/Cryptosporidium Quik Chek
  • PCR (see image)
131
Q

Giardia:

Treatment and prevention

A
  • Tx: metronidazole
  • Prevention:
    • boiling water
    • filter sterilization
    • chlorination NOT effective in eliminating cysts from water
132
Q

What is this?

How is it read?

A
  • Giardia/Cryptosporidium Quik Chek
  • rapid immunoassay for giardia and cryptosporidium cyst antigen
  • blue line on right side pos for giardia
  • blue line on left pos for cryptosporidium
  • control dots must also be positive
133
Q
  • What is this?
  • What is it’s clinical significance?
  • What does it look like?
    • trophozoites?
    • cysts?
A
  • Chylomastix mesnili cyst
    • non-pathogenic protozoa
    • trophozoite to be distinguished from giardia
    • cysts to be distinguished from giardia and entamoeba cysts
  • trophozoite (below)
    • lemon shaped org 10-15µm
    • large single nucleus with small karyosome, often pushed to anterior of trophozoite
    • presence of a cytosome, “shepherd’s crook” shape near nucleus is diagnostic
  • cysts
    • small, lemon-shaped cysts 8-10 µm
    • single large nucleus, karyosome large and centrally placed
134
Q
  • What is this?
  • Clinical significance?
  • Morphology?
A
  • Trichomonas hominis
  • flagellate thought to be non-pathogenic but has been associated with diarrhoeic stools
    • to be distinguished from Giardia lamblia
  • trophozoite tear shaped, 8-14µ
    • single nucleus at anterior end with small central karyozome
    • axostyle runs from nucleus down centre of body extending to end
    • undulating membrane extends along entire length of body projecting from the body like a free flagellum
    • there are 4 free flagellae at anterio end
  • cyst: there is no cyst stage
135
Q
  • What is this?
    • What is clinical significance?
    • Morphology
A
  • Balantidium coli trophozoite
  • causes Balantidiasis
    • characterized by diarrhea and abdominal pain, colitis similar to amebiasis
    • esp in populations living in close proximity to pigs
  • trophozoites large (40-70 µm)
    • cilia on cell surface
  • cysts circular, 50-60 µm, thick wall (below)
    • contains a single parasite from which cilia and food vacuoles have disappeard
      • although cilia occ seen in young cyst
      • large macronucleus stains well with iodine
136
Q
  • Cryptosporidium and cyclospora
    • Clinical significance and symptoms?
    • morphology?
      • what stain?
    • how can they be distinguished?
A
  • both cause abd pain and diarrhea
  • Cryptosporidium leads to watery diarrhea accompanied by dehydration, weight loss, abd pain, fever and nausea
    • low infective dose: only 2 to 10 orgs cause infection
    • symptoms may be severe in immuno-compromised pt
    • oocysts stained by modified acid-fast method (ZN stain)
  • cyclospora oocysts in wet preps appear round with distinct wall
    • ZN stain similar to Cryptosporidium but larger 8-19 µm
137
Q

How long can an Entamoeba Histolytica cyst last in the environment.

A

Up to 30 days.

(lab book p13)

138
Q

Describe the life cycle of Entamoeba histolytica

A
139
Q

Which parasite causes eosinophilia?

A

Isosporiasis

140
Q
  • Which are the most common disease causing strains and biotypes of cholera?
  • Briefly outline their epidemiologic significance.
A
  • 01 was major strain initially.
    • El Tor has supplanted Classical biotype as major pathogen of public health importance
      • First identified in Egypt in 1905, emerged as pandemic starting in 1963 (with outbreak at Sulawesi)
      • has largely replaced classical cholera as major pathogen of public health importance
      • Most current outbreaks of cholera are caused by 01 El Tor, serotypes Ogawa or Inaba
      • El-Tor has improved environmental survival compared with classical and higher ratio of assymptomatic carriers:cases, leading it to displace classical as dominant disease causing strain
      • Although generally causing less severe disease than Classical, in last decade El Tor variants having some characteristics of Classical have been described, with higher severity of disease and higher case fatality rates
  • 0139 emerged in 1992 in Bangladesh with outbreaks in South Asia since then
    • complicates vaccine development which have primarily targeted 01
141
Q

What is the infective dose of cholera?

A
  • relatively high (102 to 106)
  • less in achlorhydria and chronic gastritis
142
Q

Is there a role for antibiotics in management of cholera?

A
  • WHO guidance:
    • Appropriate antibiotics can reduce the volume of diarrhoea due to cholera, reduce the volume of rehydration fluids needed, and shorten the duration of V. cholerae excretion.
    • give antibiotics only to cholera cases with severe dehydration.
    • Children under 12 years of age should be given a 3-day course of erythromycin (12.5 mg/kg – 4 times a day).
    • Children under 5 years of age should also be given zinc for 10 days (10 mg per day under 6 months, 20 mg per day above 6 months).
    • For older children and adults, a 3-day course of tetracycline (12.5 mg/kg – 4 times a day) or a single dose of doxycycline (300 mg) is recommended.
    • furazoledine also useful but not as effective as tetracyclines
143
Q
  • La Crosse Virus
A
  • arbovirus
  • Genus Bunyavirus
  • Family Bunyaviridae
  • Vectors: Aedes species esp Aedes triseriatus, Aedes albopictus
  • Geography: US, midwest, Appalachia, ?Eastern US
  • Human Disease: viral encephalitis
144
Q
A
  • amebic cysts
145
Q

What is this?

Characteristics?

A
  • Giardia cysts
146
Q

Which protozoa may be found in fecal samples?

A
  • Entamoeba histolytica/dispar
  • Entamoeba coli
  • Giardia lamblia
  • Trichomonas hominis
  • Cryptosporidium
  • Balantidium
147
Q

What is this?

A
  • arrows indicate cysts of E. Histolytica
    • well defined wall
    • 10-15 µm
    • mature cysts have 4 nuclei; immature cysts have fewer and glycogen present
    • single nucleus bounded by nuclear membrane with chromatin on inner surface
    • smooth uniform outer membrane
  • also E. coli larger
    • 15-30 µm
    • up to 8 nuclei (if >than 4, dist from E. histolytica)
148
Q

What is it?

Characteristics?

A
  • cysts of E. Histolytica
  • arrows indicate nuclei
  • smooth uniform outer membrane
  • 10-15 µm
  • mature cysts have 4 nuclei; immature cysts have fewer and glycogen present
  • single nucleus bounded by nuclear membrane with chromatin on inner surface
149
Q

What is it?

Characteristics?

A
  • mature cyst of E. Histolytica
  • smooth uniform outer membrane
  • 10-15 µm
  • mature cysts have 4 nuclei; immature cysts have fewer and glycogen present
  • single nucleus bounded by nuclear membrane with chromatin on inner surface
150
Q

What is it?

Characteristics

A
  • immature cyst of E. Histolytica
  • smooth uniform outer membrane
  • 10-15 µm
  • mature cysts have 4 nuclei; immature cysts have fewer and glycogen present
  • single nucleus bounded by nuclear membrane with chromatin on inner surface
151
Q

What is it?

Characteristics?

Distinguish btw. two possible amebae.

What other ameba must be distinguished morphologically?

A
  • cyst of E. Histolytica or Ent dispar
  • E. dispar is non-pathogenic but identical, can be distinguished using specific monoclonal Ab tests
  • also absence of hemophagocytic trophozoites
  • smooth uniform outer membrane
  • 10-15 µm
  • mature cysts have 4 nuclei; immature cysts have fewer and glycogen present
  • single nucleus bounded by nuclear membrane with chromatin on inner surface
  • Ent. coli, Endolimax nana, Iodameba butschlii
152
Q

What is this?

Distinctive characteristics?

A
  • Endolimax nana trophozoite & cyst
  • non-pathogenic species
  • trophozoite seldom seen in fecal samples
  • cyst small (7.5-10 microns) (cw E. hist 10-15 microns)
  • round or oval in shape
  • up to four hole-like nuclei, each with large eccentric karyosome
  • important to differentiate from Ent. histolytica based on smaller size and differences in nuclear detail, best seen in iodine stain
153
Q

What is this?

Characteristics.

A
  • fresh stool or concentrate
  • oval in shape, 10-15 µm
  • 4 nuclei, 2-4 visible, often grouped at one end
  • not always visible in saline, better with iodine
  • axostyle down centre of cyst refractive
  • 1-2 median bodies may be present
154
Q

What is this?

Characteristics of cyst and troph?

A
  • Balantidium coli cyst
  • causes Balantidiasis
  • characterized by diarrhea and abdominal pain, colitis similar to amebiasis
  • esp in populations living in close proximity to pigs
  • trophozoites large (40-70 µm) (below)
  • cilia on cell surface
  • cysts circular, 50-60 µm, thick wall
  • contains a single parasite from which cilia and food vacuoles have disappeard
  • although cilia occ seen in young cyst
  • large macronucleus stains well with iodine
155
Q

What is this?

Characteristics?

A

Symmetrical

2 nuclei

sucker disk visible

central axostyle

8 flagellae

10-15 µm long

156
Q

What is this?

A
157
Q

What is Löffler’s syndrome?

A
  • Ascaris pneumonitis accompanied by eosinophilia.
  • pneumonitis commoner in children
  • tends to be more severe on reinfection
158
Q

Describe some clinical features of ascaris infections.

A
  • pneumonitis, Löffler’s syndrome
  • intestinal obstruction (more common in kids), volvulus, perforation, granulomatous peritonitis
  • biliary tract invasion (more common in adults), cholangitis, liver abscess
  • vitamin A deficiency (associated with steatorrhea)
  • ectopic worms kidneys
159
Q

Ascaris lumbricoides: how treated?

How about pneumonitis.

A
  • Albendazole
  • Mebendazole
  • Piperazine
  • Pyrantel Pamoate
  • Nitazoxanide
  • pneumonitis is treated with steroids and bronchodilators.
160
Q

Hookworm infections:

(Which worms?)

Clinical features.

A
  • Necator americanus
  • Ancylostoma duodenales
  • Usually assymptomatic, but can cause Fe def anemia particularly if Fe content of diet is low. Associated hypoalbuminemia, hypoproteinemia and in severe cases CHF
  • rarely cut. larva migrans (more common with cat or dog hookworm)
  • Wakana syndrome: N, V, retching, cough, dyspnea if hookworm larvae are swallowed
161
Q

What is treatment for hookworm?

A
  • Albendazole 400 mg one dos
  • Mebendazole 100 mg bid x 3 days
  • pyrantel pamoate
  • levimazole
  • treat Fe deficiency
162
Q

Treatment of whipworm?

(What parasite?)

A
  • Trichuris trichiuria
  • Mebendazole 500 mg one dose more effective than Albendazole 400 mg
  • If severe may need mebendazole 100 mg bid x 3 days or Albendazole 400 mg daily x 3 days
  • Albendazole + ivermectin
  • nitazoxanide also effective
163
Q

What are the clinical features of Toxocariasis?

(What parasites?)

What lab tests, how dx’d?

How treated?

A
  • Toxocara catis and T. cani - the dog and cat roundworm
  • infection following ingestion of eggs in soil, larvae released in intestine then ‘prolonged safari’ through tissues. never mature and release eggs
  • Visceral larva migrans: pneumonitis, fever, abd pain, myalgia, lymphadenopathy, hepatosplenomegaly, sleep and behavioural problems, seizures
    • Treatment: albendazole or mebendazole
    • bronchodilators, steroids, antihistamines as needed
  • Ocular larva migrans: larva invades eye produces granulomatous reaction in retina causing visual disturbance or blindness, may be mistaken for retinoblastoma
    • Treatment: no evidence for antihelminthics in eye disease
    • steroids, surgery as needed
  • Lab: eosinophilia, hypergammaglobulinemia, elevated titres of isohemagluttanins. Serological dx by ELISA
164
Q

Do Soil-transmitted helminths multiply within thier final host?

A
  • No
  • Soil-transmitted helminths do not multiply within their final host. They live in a state of balanced parasitism and achieve this by depressing immune responses within the host. This probably accounts for the increased susceptibility of those with such helminths to HIV, TB and malaria.
165
Q

Describe the life-cycle of ascariasis

A
  • Ingested eggs release larvae in the duodenum, jejunum and upper ileum. These larvae penetrate the mucosa and are carried to the liver and ultimately to the lungs. Here they penetrate into the alveoli and are coughed or creep up the bronchi to be swallowed with other normal bronchial secretions. Having reached the small intestine for a second time, they maturate into adult males and females. These readily attach to the mucosa of the small intestine where fertilization occurs. Egg production probably starts once the female reaches a minimum weight of 1.1 g. The number of eggs produced by each female is inversely related to the total worm load.

When one is infected with female-only worms, infertile eggs that do not develop into the infectious stage are produced. With male-only worm infections, no eggs are formed.

  • Ascaris eggs can survive in an unfavourable milieu outside the body for many years. They have a thick lipid coating, which makes them very resistant to desiccation, UVL, low temperatures and most chemicals including acids and alkalis. While they can be inactivated in minutes by temperatures above 60 °C they can survive for more than 1 year at 40 °C.

They thrive best in warm, shaded, moist soil and these conditions favour embryonation of fertilized eggs. They normally develop into infective larvae in 2–3 weeks. A single female can produce over 200 000 eggs each day.

166
Q
A
167
Q

What are the causes of liver diseases in tropics?

(from Beeching & Dassanayake 2015)

5 Main syndromes

A
  1. Jaundice/hepatitis/hepatosplenomegaly
    • Inherited haemolytic disorders Acute viral hepatitis A, B, C, D, E Biliary flukes
    • Brucellosis
    • Dengue
    • Enteric fever
    • Hepatobiliary ascariasis
    • HIV related (e.g. cryptococcosis)
    • Leptospirosis
    • Malaria
    • Rickettsial infection
    • Secondary syphilis
    • Sepsis
    • Tuberculosis
    • Viral haemorrhagic fevers
    • Yellow fever
  2. Toxins and drugs
    • Ackee poisoning
    • Aflatoxins
    • Amanita phalloides (death cap mushroom)
    • Bantu siderosis (iron)
    • Bush teas
    • Illicit alcohol (methanol)
    • Industrial toxins
    • Indian childhood cirrhosis (copper)
    • Paraquat
    • Traditional herbal remedies (pyrrolizidine alkaloids)
  3. Cirrhosis and/or fibrosis
    • Alcohol
    • Chronic hepatitis B, D, C
    • Non-alcoholic fatty liver disease (NAFLD) Schistosomiasis (fibrosis)
  4. Hepatomegaly
    • Alveolar hydatid
    • Amoebic liver abscess
    • Cholangiocarcinoma
    • Cystic hydatid
    • Hepatocellular carcinoma
    • Liver fluke Fasciola hepatica
    • Pyogenic liver abscess
  5. Massive hepatosplenomegaly
    • Hyper-reactive malarial splenomegaly
    • Late stage schistosomiasis
    • Tropical splenic lymphoma
    • Visceral leishmaniasis
168
Q

What is this?

A
  • Ackee apple fruit is a native fruit to Jamaica and some parts of west Africa. Its toxicity known as “Jamaican vomiting sickness” dates back to the nineteenth century.
  • only toxic when unripe, when it can cause prolonged hypoglycemia, encephalopathy and lever toxicity
  • Found in Caribbean and Africa, esp Jamaica and Nigeria
169
Q

What is an aflatoxin?

A
  • any of a class of toxic compounds produced by certain moulds found in food, which can cause liver damage and cancer.
170
Q

What is Budd Chiari syndrome?

A
  • Budd–Chiari syndrome is a very rare condition, affecting 1 in a million adults.[1] The condition is caused by occlusion of the hepatic veins that drain the liver. It presents with the classical triad of abdominal pain, ascites, and liver enlargement. The formation of a blood clot within the hepatic veins can lead to Budd–Chiari syndrome. The syndrome can be fulminant, acute, chronic, or asymptomatic.
171
Q

What is tropical sprue and where is it found?

A
  • Tropical sprue is a general malabsorption syndrome usually associated with persistent non-bloody diarrhoea and sometimes with steatorrhoea. Considerable bloating, weight loss and a general failure to fight infections satisfactorily occur in the majority of cases. It is thought that the condition is initiated by failure of the gut mucosa to recover adequately after an initial or early bout of diarrhoea, but this does not explain why it is found predominantly in India rather than in Africa where diarrhoea in children is the norm. On histology, villi are stunted and often atrophied. Experience shows that folic acid and tetracyclines yield excellent results.
172
Q

What are the differential for massive splenomegaly in the tropics? (from Lecture Notes)

For Splenomegaly?

A
  • Massive Splenomegaly
    • Malaria or Hyperreactive malaria splenomegaly
    • portal hypertension eg caused by schistosomiasis, cirhossis, etc
    • lymphoma, leukemia, mylodysplasi
    • hemoglobinopathies and hereditary hemolytic anemias
    • Still’s disease
    • glycogen storage and other metabolic diseases
    • amyloidosis
    • visceral leishmaniasis
  • Moderate spleen
    • any of above
    • bacterial endocarditis
    • brucellosis
    • cmv
    • hiv
    • infectious mono
    • leptospirosis
    • lyme disease
    • relapsing fever
    • syphilis
    • toxoplasma
    • trypanosomiasis
    • tb
    • typhoid
    • typhus
173
Q

What is coccidiosis?

A
  • T. gondi is a cocciodiosis
  • Coccidiosis is a parasitic disease of the intestinal tract of animals caused by coccidian protozoa. The disease spreads from one animal to another by contact with infected feces or ingestion of infected tissue. Diarrhea, which may become bloody in severe cases, is the primary symptom. Most animals infected with coccidia are asymptomatic, but young or immunocompromised animals may suffer severe symptoms and death.

While coccidia can infect a wide variety of animals, including humans, birds, and livestock, they are usually species-specific. One well-known exception is toxoplasmosis caused by Toxoplasma gondii.[1][2]

Humans may first encounter coccidia when they acquire a puppy or kitten that is infected. Other than T. gondii, the infectious organisms are canine and feline-specific and are not contagious to humans, unlike the zoonotic diseases.

174
Q

What is the SAAG?

A
  • Serum Albumin Ascites Gradient
  • A high gradient (SAAG >1.1 g/dL) indicates portal hypertension and suggests a nonperitoneal cause of ascites. Such conditions may include the following:
  • Normal Peritoneum (SAAG>1.1)
    • Portal hypertension:
      • hepatic congestion, chf, constrictive pericarditis, tricuspid insufficiency, Budd-Chiari
      • Liver disease, cirhossis, alcoholic hep, massive hepatic mets
    • Hypoalbuminemia
      • nephrotic syndrome, protein losing enteropathy, severe malnutrition with anasarca
    • Misc
      • chylous ascites, pancreatic ascites, bile ascities, nephrogenic ascities, urine ascites, ovarian disease
  • Diseased Peritoneum (SAAG < 1.1)
    • Infectious
      • bacterial, TB, fungal, parasitic or HIV associated peritonitis
      • malignant or other rare conditions
  • *
175
Q

How many deaths due to hepatitis?

Getting better or worse?

A
  • about the same as TB
  • Viral Hepatitis: 1.34 M
  • 66% HBV • 30% HCV • 3.3% HEV • 0.8% HAV
  • TB: 1.37 M
  • HIV: 1.06 M
  • Malaria: 0.44 M
  • Global trend in Mortality from Viral Hepatitis is increasing
176
Q

Hepatitis A

what kind of virus?

transmission?

zoonosis?

course, severity in kds vs older?

no. cases and deaths?

A
  • picornavirus (RNA)
  • transmission water and food
  • humans only
  • solid immunity after one attack
  • Young children assymptomatic
  • prolonged or rarely fatal in older >50 yr
  • early relapse not uncommon, no sequelae
  • 126 million cases and 35000 deaths
177
Q

Hep A

incubation period

relation of severity to age?

A
  • inc period 28 days
  • children generally assymptomatic, adults symptomatic
178
Q

Hep A vaccines

dosing?

booster?

when can the booster be given if miss schedule?

A
  • single dose, booster at 0-36 months
  • but can give up to 5 yrs later and immunity will be lifelong
179
Q

Hep E

when did it emerge and where?

incubation?

mortality?

transmission?

How many genotypes?

A
  • New Delhi 1955
  • point source outbreak, sewage in water tank
  • 40 days
  • low except preg women
  • transmission
    • water borne
    • transfusion
    • shellfish?
  • 4 genotypes
    • G1 & 2 waterborne Africa Asia, Russia
    • G3&4 zoonotic NA and Europe
180
Q

Hep E Virus in High Income Countries

genotype

ecology

prevention and control measures for travellers to HEV endemic regions

A
  • mostly genotype 3
  • zoonotic, raw pork
  • acute disease underrecognized
  • chonic excretino and liver disease in renal transplants, HIV, leukemias
  • Neurological features
    • per neuropathy or spinal cord disease
    • Guillain Barre
  • travellers
    • avoid drinking water, ice of unknown purity, uncooked shellfish, uncooked fruit, veg not peeled or prepared by traveller
    • IG prepared from donors in Western countries does not prevent infection
    • ?future vaccine?
181
Q

Estimated risk of getting Hep B, C and HIV from a contaiminated needle stick.

A
  • Hep B: 30%
  • Hep C: 3%
  • HIV: 0.3%
182
Q

Hepatitis B Overview

how many infected

transmission

fatality rates

A
  • 400 million
  • sexual, parenteral and perinatal
  • slow death: causes death from liver disease in up to 25% of those infected at birth
  • liver cancer very prevalent
183
Q

Hep B Epidemiology

How is it transmitted in tropics?

A
  • 45% of population lives in high endemic areas
  • early childhood infections common
  • most of those will go on to be chronic carriers
  • Transmission
    • perinatal and infant
    • childhood: injections, open sores, saliva, scarification, circumcision, Iatrogenic (epidemic in Egypt and africa due to therapeutic use of dirty needles)
184
Q

Concentration of HBV in various body fluids

In which high, moderate or low/not detectable.

A
  • high
    • blood, serum, wound exudates
  • moderate
    • semen, vag fluid, saliva
  • low/not detectable
    • urine feces sweat tears breast mild
185
Q

Diagnosis of Hep B Virus: pt has the following. What does it mean

  • HBsAg neg
  • anti-HBc neg
  • anti-HBS neg
A
  • Susceptible
186
Q

What does it Mean?

Hep B sAg negative

anti-HBc positive

anti-HBs positive

A

Immune due to natural infection

187
Q

What does it mean?

HBsAg Negative

anti-HBc Negative

anti-HBs Positive

A

Immune by vaccination

188
Q

What does it mean?

HBSAg positive

anti-HBc positive

IgM anti-HBc positive

anti-HBs negative

A

Acutely infected

189
Q

What does it mean?

HBSAg Positive

anti-HBc positive

IgM anti-HBc negative

anti-HBs negative

A

chronically infected

190
Q

What does it mean?

HBSAg negative

anti-HBc positive

anti-HBs negative

How could you resolve the question?

A

Interpretation unclear; four possibilities:

  1. resolved infection (most common)
  2. False-positive anti-HBc, thus susceptible
  3. “Low level” chronic infection
  4. Resolving acute infection
  • wait 3-6 months and repeat or
  • order HBeAg or anti HBeAb, which are surrogate for DNA
  • or order HBV DNA
  • if either of these are positive it is an ongoing infection
  • It may, however be an inactive carrier state which can subsequently reactivate, sho should check HBV DNA yearly
191
Q

What is Hep D?

A
192
Q

In chronically infected patients, how does Hep B viral load relate to survival?

A

HBV DNA>105 strongly correlated with mortality.

Only about 20% alive at 10 yrs compared with 97% for those with VL below this.

193
Q

What therapeutics are available for Chronic Hep B?

A
194
Q

How do you prevent MTCT Hepatitis B?

A
  • Children born to women testing positive for hepatitis B surface antigen were provided with free hepatitis B immunoglobulin (100 IU) within 24 hours after birth and three hepatitis B vaccinations within 24 hours of birth, at 1 month and 6 months of age, in accordance with national guidelines.
  • Currently 84% coverage with 3 doses vaccine has significantly reduced HBV transmission in first 5 years of life
  • But coverage with initial birth dose vaccine is still low at 39%
  • Global prevalence of chronic Hep B is 1.3%
  • WHO plans to scale up and reach 90% vaccination with the aim of eliminating Hep B and Hep C as public health threas by 2030.
195
Q

Hep C virus

what kind?

modes of transmission?

course

immune evasion

A
  • RNA flavivirus
  • mostly blood borne
  • very few get jaundice with acute infection but chronic with substatial hertogeneity due to quesispecies evolution prevents effective neutralization.
196
Q

Define acute and chronic diarrhea and dysentery.

A
  • Diarrhoea is the presence of three or more loose stools within 24 hours. “Loose” stool means that the bowel motion that assumes the shape of the collecting container. Chronic or persistent diarrhoea is defined as having lasted for at least 1 month. Acute diarrhoea lasts less than one month. Dysentery means the presence of visible blood in the stool.

Tropical Medicine (17 decks)

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