Tropical diseases and the
Gastrointestinal system
Ahmed Laving
ESPGHAN Post Graduate Course 2013
Case 1
• 3 yr old girl from Western Kenya
• c/o diarrhoea for 6 wks
• Stools x6-10/day (x3 at night), mucoid,
occasionally bloody, foul smelling, tenesmus
• Intermittent fevers, mouth sores, rashes, joint
pains but no joint swelling
• No h/o contact with PTB
• Weight gain appropriate
Case 1 (..2)
• PMH: first episode of mucoid stools at 6
months of age; intermittent symptoms
• Repeated courses of antibiotics, metronidazole
• Positive family h/o atopy and had multiple
food allergies (milk, wheat, bananas)
• Had been on elemental milk with initial
response but with periodic flares
• Diagnosis?
Case 1: (..3)
• Fair GC, P°, J°, afebrile, not dehydrated
• Wt: 14 kg, Ht: 91 cm, MUAC 17.5 cm
• Aphthuous mouth sores, healed skin lesions, perianal
erythema, no anal tags or fissures
• Hb: 10.1, MCV 60, ESR 28, Eos: 6%, Albumin 40
• Stool: occult blood +ve, few pus cells + RBC’s,
Campylobacter sensitive to azithromicin
• Endoscopy: oesophagitis, gastritis, pancolitis (nonspecific, normal eosinophil counts)
Case 1: Diagnosis?
• Infectious enteropathy (Campylobacter)
• Allergic enteropathy
• ?Inflammatory Bowel Disease (IBD)
Case 1: Final diagnosis
• Management:
– Azithromicin: no response, repeat stool c/s -ve
– Dietary elimination of dairy, wheat products
– Prednisone (tapered off), sulfasalazine (?IBD)
• Recurring episodes of fever, bloody, mucoid stools
(compliant to dietary elimination, drugs)
• Inadvertent finding: Father of child on ARV’s!
• Elisa for HIV: positive
• Child started on ARV’s with resolution of symptoms
• Final Diagnosis: HIV enteropathy
Tropical diseases and GIT
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HIV and the GIT
Malnutrition associated enteropathy
Tropical sprue
Sickle cell hepatopathy
Amoebic liver abscess
Schistosomal liver disease
HIV and the GIT
HIV and the GIT
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Uncommon if CD4 >200
Oropharynx: Thrush, hairy leukoplakia, ulcers
Oesophagus: Candida, HSV, CMV
Small/large intestines: chronic diarrhoea
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Bacterial: Salmonella, Shigella, Campylobacter, TB
Fungal: Histoplasma, Coccidiomycosis
Protozoa: Cryptosporidia, Microsporidia, Isospora
Others: CMV colitis, C. difficile, bacterial overgrowth
• Rectum: Kaposi’s Sarcoma, HSV, condylomata,
Non-Hodgkins lymphoma
Oesophagus
• Oesophagitis-Burning retrosternal pain,
odynophagia.
• Candida
• HSV-Multiple small ulcers
• CMV-Solitary large ulcer
Oesophagitis
HIV: Small/Large Intestine disease
• Usual presentation: diarrhoea with colicky
abdominal pain ± fever and weight loss
• Bacterial causes are common
• Salmonella
– 20x more likely to get non-typhoid salmonella
– Severe disease with relapses
– Long term ciprofloxacin may be necessary
• Shigella, Campylobacter, Mycobacteria (MAC)
Protozoal Infections
• Usually manifest with fever, watery diarrhea, nausea,
vomiting, abdominal pain, dehydration, weight loss
• Cryptosporidia
1% per yr in those with CD4< 300
50% respond to Nitazoxanide (long courses)
• Microsporidia
May require stool EM, intestinal aspirate or biopsy
Extra-intestinal features: eye, muscle and liver
• Isospora
Peripheral eosinophilia
Septrin, Ciprofloxacin
• Giardiasis: chronic diarrhoea with malabsorption
Other Causes of Diarrhoea
• CMV colitis
– Nonbloody diarrhoea
– Endoscopy: multiple ulcerative lesions
– Biopsy: intranuclear inclusion bodies
– May induce vasculitis in the colon/distal small
bowel resulting in GI bleeding.
• Clostridium difficile- drugs
• Neoplastic disease: Kaposis/NHL
• Small bowel bacterial overgrowth
Bacterial Overgrowth
• A syndrome of diarrhoea with attendant
malabsorption
• Uncommon in immuno-competent individuals
• Predisposing factors: Impaired intestinal
immunity, motility and gastric hypoacidity
• Rx: broad spectrum antibiotics
• Duration of Rx unknown
HIV Enteropathy
• Syndrome of non-infective diarrhoea
• Possible pathogenetic mechanisms:
– direct infection of the enterocyte by HIV
– infection of the lymphoid tissue of the GIT with
dysregulation of local cytokine production
– Secondary damage due to opportunistic infections
•Prevalence and impact of diarrhea on health-related quality of life in HIV-infected patients in the era of highly active antiretroviral therapy.
•Siddiqui U, Bini EJ, Chandarana K, Leong J, Ramsetty S, Schiliro D, Poles M J Clin Gastroenterol. 2007;41(5):484.
**A prospective study of diarrhea and HIV-1 infection among 429 Zairian infants.Thea DM, St Louis ME, Atido U, Kanjinga K, Kembo B
, Matondo M, Tshiamala T, Kamenga C, Davachi F, Brown C N Engl J Med. 1993;329(23):1696
HIV Enteropathy (2)
• Diagnostic workup:
– Stools: mcs, AAFB staining (cryptosporidia,
cyclospora), trichrome staining (microspora)
– Blood cultures: if suspect disseminated disease
– Endoscopy: colitis, multiple ulcers, lymphoma
– CT abdomen
• >50% of diarrhoeal illnesses in HIV-infected
individuals no identifiable pathogen
*Physiological effects of HIV infection on human intestinal epithelial cells: an in vitro model for HIV enteropathy.Asmuth DM,
Hammer SM, Wanke CA AIDS. 1994;8(2):205
**Diagnostic strategies in HIV-infected patients with diarrhea. Mayer HB, Wanke CA AIDS. 1994;8(12):1639.
HIV Enteropathy: Treatment
• Antiretroviral therapy: early initiation with
reduced incidence of diarrhoea
• Empiric antimicrobial use: nitazoxanide,
metronidazole, ciprofloxacin (2-3 weeks)
• Specific Rx: antivirals, pyrimethamine
• ?Antimotility agents, ?probiotics
• Zinc supplementation not shown to alter
duration or severity in adults
*Malabsorption and wasting in AIDS patients with microsporidia and pathogen-negative diarrhea.Lambl BB, Federman M,
Pleskow D, Wanke CA AIDS. 1996;10(7):739.
**Randomized controlled trial of zinc supplementation for persistent diarrhea in adults with HIV-1 infection.
Cárcamo C, Hooton T, Weiss NS, Gilman R, Wener MH, Chavez V, Meneses R, Echevarria J, Vidal M, Holmes K
J Acquir Immune Defic Syndr. 2006;43(2):197
Malnutrition Associated Enteropathy
(Environmental Enteropathy)
Malnutrition and Diarrhoea
Reduced food input
Convalescent period
not enough to catch
up nutrients
Reduced immunity
Malnutrition
Diarrhoeal disease
Increased nutritional demand
Infant Diets
• Review of 42 infant feeding studies published
1996-2006: (Dewey and Adu-Afarwuah, 2008)
• Children who received interventions gained
•0-760 g more weight (0.0 – 0.76 WAZ)
•0 – 1.7 cm taller (0.0 – 0.64 LAZ)
• The very best of these interventions produced a
0.7 Z-score improvement
• BUT, the average growth deficit of African and
Asian children is –2.0 Z-score
• At best, diet solved 1/3 of the problem
Environmental Enteropathy (EE)
• A major cause of child undernutrition may be
a subclinical inflammation of small intestine
• EE: Chronic inflammation of the gut,
characterised by:
– Villous flattening
– Modest malabsorption
– Inflammatory cell infiltrate
– Increased permeability
– Bacterial overgrowth
Environmental enteropathy (2)
• Starved infants pass frequent green liquid stools
of small volume (less than 10 grams)
• Pathogenesis
– Impaired development and function of the immune
system, therefore increase in enteric infection
– generalized increase in inflammatory mediators
– impaired tissue repair mechanisms
– Specific nutrient deficiencies, such as vitamin A and
zinc deficiencies
EE: Management
• Inpatient or outpatient management of
malnutrition
• Multivitamin (and zinc) supplementation
• Empiric use of antibiotics
• Improve hygiene and sanitation
• Role of anti-inflammatory agents
(?mesalamine)
Tropical Sprue
Tropical sprue
• A syndrome of acute or chronic diarrhoea,
weight loss and malabsorption.
• Occurs in the tropics and subtropics
• Aetiology unknown, but intestinal microbial
infection may cause the initial insult
• Coliform bacteria (E.coli, Klebsiella,
Enterobacter) usual organisms isolated
Tropical sprue (2)
• Pathogenesis:
– Infection results in enterocyte injury, intestinal
stasis and possible bacterial overgrowth
– Results in malabsorption with deficiencies of Iron,
Folate, B12
• Affects people who live in areas with sprue as
well as travellers who stay for > 1 month
Tropical sprue (3)
• CBC: megaloblastic anaemia, Iron deficiency
• Diagnosis: endoscopy
– Tropical sprue involves the entire small bowel
– Gross findings at endoscopy include flattening of
duodenal folds and "scalloping”
– Histology: shortened, blunted villi and elongated
crypts with increased inflammatory cells
• Must rule out other causes of diarrhoea,
especially infective
Tropical Sprue: Management
• Antibiotics for 3-6 months
• Folate, Vitamin B12, Iron supplements
• No role for antibiotic prophylaxis to prevent
sprue
Giardiasis (2)
• clinical manifestations*:
– 50 %: asymptomatic and clear the infection
– 5 to 15% asymptomatic shed cysts
– 35 to 45% of individuals have symptomatic
infection:
• Acute disease
• Chronic disease
• Diagnosis:
– Stool microscopy
* 2012 UpToDate ,Release: 20.9 - C20.24
Amoebic Liver Abscess
Epidemiology
• Amoebic liver abscesses (ALA) most common
extraintestinal site of infection of E histolytica
• occur in fewer than 1% infections
• ALA is 10 times more common in adult males
than females while colonic infection is
identical in males and females
Pathogenesis:
Amoeba cysts ingested and
Trophozoites released
Infect intestines and cause necrosis
with formation of flask shaped ulcers
Gain access to the portal vein system
and liver
Cause necrosis of the hepatocytes
which results in abscess formation
Clinical Presentation:
• Subacute fever
• Right upper quadrant pain
• May have protracted diarrhoea, abdominal
pain, with weight loss
• Up to 50% patients have evidence of colonic
disease
• Jaundice – uncommon, presence suggests
multiple abscesses/severe disease
Investigations: laboratory
• Hemogram:
– Increased WBC (≤75% cases), no eosinophillia
• Liver Enzymes:
– Increased liver transaminases (≤ 75% cases)
• Stool microscopy:
– Neither sensitive nor specific
• Serology:
– Up to 90% positive after 1 week of symptoms
Investigations: Imaging
Ultrasonography
90% sensitivity –
user dependant
CT scan
Usually solitary
involve right lobe of
the liver
Treatment:
• Metronidazole 35-50mg/kg/d for 7-10 days
• Luminal amoebicide to control intestinal cysts
(diloxanide furoate, iodoquinol) – present in ≤
60% patients following treatment of ALA
• Cure rates of up to 90% with metronidazole
• No advantage of percutaneous drainage of an
uncomplicated abscess
Schistosomal liver disease
Schistosomal liver disease (2)
• One of the most common causes of
noncirrhotic portal hypertension in the world
• S. Japonicum, S. Mansoni and S. Hematobium
• Schistosomal eggs induce periportal fibrosis,
by inducing chronic inflammation once they
are trapped in terminal portal veins
• Clinical features: of portal hypertension, and
of growth retardation
Hepatic schistosomiasis. Dunn MA, Kamel R Hepatology. 1981;1(6):653.
2012 UpToDate ,Release: 20.9 - C20.24
Schistosomal liver disease (3)
• Underlying hepatic function remains preserved
• Diagnosis
– detection of schistosomal ova in the stool
– biopsies of the rectal mucosa or the liver
– immunologic assays
• Treatment
– Praziquantel (20mg/kg/dose TID for 1 day) in acute
stage
– Treating complications of portal hypertension
•Immunopathogenesis of schistosomiasis. Wynn TA, Thompson RW, Cheever AW, Mentink-Kane MM Immunol Rev. 2004;201:156.
Praziquantel side effects and efficacy related to Schistosoma mansoni egg loads and morbidity in primary school children
in north-east Ethiopia. Berhe N, Gundersen SG, Abebe F, Birrie H, Medhin G, Gemetchu TActa Trop. 1999;72(1):53.
Sickle cell hepatopathy
Sickle cell hepatopathy (2)
• Clinical syndrome characterized by marked
hyperbilirubinaemia, not explained by severe
haemolysis, viral hepatitis, hepatic sequestration
or extra-hepatic obstruction
• Classified into two categories:
– a milder self-limited form without severe hepatic
dysfunction
– a severe form characterized by fulminant liver failure
with coagulopathy and encephalopathy
Pediatr Blood Cancer 2005;45:184-190
Sickle cell hepatopathy (3)
Complications
• Due to disease itself:
– Sickle cell vasculopathy
– Pigment gall stones due to chronic haemolysis
– Acute hepatic crises
– Hepatic sequestration
• Due to treatment :
– Chronic blood transfusions: iron overload
2012 UpToDate ,Release: 20.9 - C20.24
Sickle cell hepatopathy (4)
• Evaluation recommended in any child with
jaundice > 13 mg/dl ( >220 μmol/L) without
evidence of acute severe haemolysis
• complete blood count
• coagulopathy panel
• viral hepatitis serology
• appropriate imaging (abdominal ultrasound or
CT scan) to r/o biliary sludge, stones
• Renal function (hepato-renal syndrome)
Sickle cell hepatopathy - biopsy
Sickle cell hepatopathy: Treatment
• Non-severe disease:
– Simple transfusion
– Supportive management for sickle cell disease
• Severe Disease:
– Exchange transfusion: only effective therapy
– Supportive treatment
– ? Role of hydroxyurea, ursodeoxycholic acid
Case 2
• 14 year old boy with blood per rectum for 6
months
• Frank blood, tablespoon full, not associated
with pain
• No h/o constipation
• No h/o bleeding disorder
• Boarding school in Eastern Kenya
Case 2
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Examination: NAD!
Diagnosis?
Management?
Colonoscopy: 1 pedunculated polyp at 25cm,
removed
• Histology: juvenile retention polyp with
multiple eggs of Schistosoma!
Case 3
• 4 yr old Kenyan Asian girl, known “asthmatic” child
with recurrent chest infections since birth
• c/o: loose stools since late infancy (1st mention!)
– X1-2/day, oily, bulky stools, foul smelling, worse with
fatty foods, not readily flushable
– No abdominal pain, vomiting, jaundice, pruritus
– Poor weight gain, normal milestones
• Strong family h/o atopy, consanguineous parents
Case 3: cont’d
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Fair GC, P°, J°, afebrile, no pedal oedema
Malnourished: Wt: 9.5 kg (<3SD), Ht: 90 cm (<3SD)
ENT: rhinorrhoea, Chest clear
Abdomen: soft , not distended, non tender, no
masses/organomegally
• Stool: fecal fat present, pH/reducing substances not
done, occult blood negative
• Hb: 10.3, MCV: 70, WBC: 8.5, Platelet 195, Albumin:
28
Case 3: Diagnosis?
• FTT (9.5 kg at 4 yrs)
• Malabsorption
• Differential diagnosis:
– Immune suppression: HIV, Ig deficiency
– Allergic enteropathy
– Shwachman Diamond Syndrome, ?CF
Case 3: Final Diagnosis
• Self-referred to India:
– Upper endoscopy: reportedly normal
– Sweat chloride test: suggestive of Cystic Fibrosis
– Confirmatory test (DNA): not done
• Started on pancreatic enzyme supplements
– Good response to GI symptoms, stools normal
– Weight and height gain still not optimal,
respiratory symptoms continue
• Final Diagnosis: Cystic Fibrosis
Thank You!
Asante!
Enkosi!