Tropical diseases and the Gastrointestinal system

Ahmed LavingESPGHAN 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 (non-

specific, 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

• 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• Uncommon if CD4 >200• Oropharynx: Thrush, hairy leukoplakia, ulcers• Oesophagus: Candida, HSV, CMV• Small/large intestines: chronic diarrhoea– 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< 30050% respond to Nitazoxanide (long courses)

• MicrosporidiaMay require stool EM, intestinal aspirate or biopsyExtra-intestinal features: eye, muscle and liver

• IsosporaPeripheral eosinophiliaSeptrin, 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 KJ Acquir Immune Defic Syndr. 2006;43(2):197

Malnutrition Associated Enteropathy(Environmental Enteropathy)

Malnutrition and Diarrhoea

Reduced food input

Malnutrition

Reduced immunity

Diarrhoeal disease

Increased nutritional demand

Convalescent period not enough to catch up nutrients

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

Ultrasonography90% sensitivity – user dependant

CT scanUsually 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 childrenin 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

• 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

• 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!