Conditions of the Gastrointestinal System

2. Objectives Describe the various infectious agents that cause chronic diarrhea Describe the clinical presentation of each infection List the recommended diagnostics and common findings for each infection Understand the treatment and management of chronic diarrhea Discuss hepatitis, including management, treatment, and prevention Make a differential diagnosis using a case study approach

3. Overview Chronic diarrhea is a very frequent and frustrating problem in PLHA: at least 50% experience it sometime during the evolution of the disease Often accompanied by nausea, weight loss, abdominal cramps, and dehydration Often an intermittent watery diarrhea, without blood or mucous In one-third to two-thirds of cases, no cause is identified In high HIV prevalence areas, chronic diarrhea is invariably due to symptomatic HIV infection.

5. Major Pathogens Bacterial infection Campylobacter, Shigella, and Salmonella Protozoal infection Cryptosporidium species, Giardia lamblia, Isospora belli, Entamoeba histolitica, Microsporidium species Toxin induced E. coli and Clostridium difficile Mycobacterial infection M. tuberculosis, M. Avium complex Helminthic infection Strongyloides stercoralis Fungal infection Candida species (seldom a cause of diarrhea)

7. Bacterial infection: Campylobacter Clinical Symptoms may evolve Fever and general malaise, sometimes without GI symptoms When present, GI symptoms include bloody diarrhea, abdominal pain and weight loss.

8. Campylobacter bacilli found in stool culture 

9. Erythromycin 500 mg bid x 5 days (1st choice) � Fluoroquinolones are also effective, but resistance rates of 30-50% have been reported in some developing countries

10. It is clinically impossible to distinguish the different etiological agents of bacterial gastroenteritis without a stool culture If empiric therapy with TMP/SMX is not effective in patients with bacillary dysentery, try fluoroquinolones If symptoms of bloody diarrhea persist , try erythromycin

11. Bacterial infection: Salmonella Clinical Symptoms may evolve Fever; general malaise Sometimes no GI symptoms If there are GI symptoms, will see: Bloody diarrhea Abdominal pain Weight loss

12. Stool culture Salmonella bacilli may be found in stool/blood cultures Serology: positive Widal test with increased titers Bacterial infection: Salmonella Diagnostics

13. Management and Treatment TMP/SMX 960 mg bid or Chloramphenicol 250 mg qid for 3 weeks In case of sepsis, IV therapy is necessary � Shorter regimens are: ciprofloxacin 500 mg bid or ofloxacin 400 mg bid or ceftriaxone 2 g IV for 7-10 days Many patients often relapse after treatment and chronic maintenance therapy (TMP/SMX 1 DD daily) is sometimes necessary.

14. Unique features, Caveats Salmonellosis is a frequent cause of bacteremia in PLHA

15. Bacterial infection: Shigella Presenting Signs and Symptoms Clinical Symptoms may evolve High fever Abdominal pain Bloody diarrhea

16. Stool microscopy� fresh examination and after concentration Multiple stool samples may be necessary Shigella bacillus found in stool

17. ShigellaManagement and Treatment TMP/SMX 960 mg bid x 5 days or amoxicillin 500 mg tid x 5 days If resistant to the above, give ciprofloxacin 500 mg bid or norfloxacin 400 mg bid x 5 days or nalidixic acid 1 g qid x 10 days

18. Unique features, Caveats In many developing countries resistance of Shigella (and Salmonella) to TMP/SMX has increased.

19. Protozoal infection: Clostridium difficile Clinical Symptoms may evolve Diarrhea Fever

20. Stool microscopy and culture 

21. May be underestimated as a cause of diarrhea in AIDS patients in the tropics because of the difficulty in making the diagnosis. Frequent hospitalization and exposure to antibiotics puts patients at high risk of infection As in HIV-negative patients, 5-30% of patients with C. difficile-associated diarrhea experience relapse

22. Protozoal infection: Cryptosporidium Clinical Symptoms may evolve Recent and prolonged history of severe diarrhea�usually large volume, watery stools with a lot of abdominal pain, bowel noise and activity Severe weight loss/wasting in those with longer history

23. Stool samples x 3 for staining/AFB smear Oocysts present in stool exam No fecal WBCs 

24. Rehydration (IV and/or ORS) Paromomycin 500 mg qid for 2-3 weeks; maintenance with 500 mg bid often required Codeine phosphate 30-60 mg tid until under control (or other anti-diarrheal agents such as loperamide 2-4 mg tid or qid�maximum of 32 mg in 24 hours) The use of ARV is protective against cryptosporidiosis

26. Highly infectious Transmitted through water, food, animal-to-human and human-to-human contact Special precautions should be taken to prevent exposure: people with HIV and a CD4<200 should boil tap water for at least 1 minute to reduce risk of ingestion of oocysts in potentially contaminated drinking water.� May be the AIDS-defining presentation in patients who previously had few symptoms of HIV infection

27. Toxin induced: E. coli Clinical Symptoms may evolve Diarrhea Fever

28. Stool microscopy and culture Toxin induced: E. coli

29. Entamoeba histolytica Clinical Symptoms may evolve Colitis Bloody stools Cramps Can be asymptomatic

30. Stool for ova and parasite exam O&P present in stool exam No fecal WBC�s Entamoeba histolytica

31. Entamoeba histolyticaManagement and Treatment metronidazole 500-700 mg po or IV tid x 5-10 days or paromomycin 500 mg po qid x 7 days

32. Entamoeba histolytica E. histolytica may be common in the general population in developing countries, but may be recurrent or more severe in HIV patients

33. Giardia lamblia Clinical Symptoms may evolve Enteritis Watery diarrhea ? malabsorption Bloating Flatulence

34. Stool for ova and parasites O&P in stool exam Giardia lamblia

35. Giardia lamblia Metronidazole 250 mg po tid x 10 days

36. Giardia lamblia Common cause of diarrhea in general population, but may be recurrent or more severe in HIV patients

37. Isospora belli Clinical Symptoms may evolve Enteritis; watery diarrhea No fever Wasting; malabsorption ** Symptoms similar to what occurs with Cryptosporidium

38. Stool x 3: unstained wet preparation Isospora belli oocysts are relatively big (2030 ?m) and can be easily identified in unstained wet stool preparation No fecal WBCs Giardia lamblia Diagnostics

39. Giardia lamblia  Most cases are readily treated with sulfamethoxazole/ trimethoprim (960 mg qid for 10 days) followed by 1 double strength tablet (960 mg bid for 3 weeks), then chronic suppression with sulfamethoxazole/ trimethoprim (960mg daily) High dose of pyrimethamine with calcium folinate to prevent myelosuppression Long-term maintenance therapy may be required to prevent relapse

41. Microsporidium Clinical Symptoms may evolve Profuse watery, non-bloody diarrhea Abdominal pain and cramping Nausea Vomiting Weight loss

42. Fresh stool microscopy with modified trichrome stain Spores present in stool exam Giardia lamblia Diagnostics

43. Giardia lamblia Unique features, Caveats Species of microsporidia have been linked to disseminated disease, e.g., cholangitis, keratoconjunctivitis, hepatitis, peritonitis, and infections of the lungs, muscles, and brain However, the presence of microsporidia does not always correlate with symptomatic disease Most microsporidial infections are not treatable

44. Helminthic infection: Strongyloides stercoralis Presenting Signs and Symptoms Clinical Symptoms may evolve Serpiginous erythematous skin lesions (larva currens) Diarrhea Abdominal pain Cough Full-blown hyper-infection syndrome has the characteristics of a gram-negative sepsis, with acute respiratory distress syndrome, disseminated intravascular coagulation, and secondary peritonitis, cough

45. Chest x-ray: The chest x-ray may reveal diffuse pulmonary infiltrates. Stool microscopy, (multiple stool samples may be necessary) Sputum sample In disseminated strongyloidiasis, filariform larvae can be found in stool, sputum, broncho-alveolar lavage fluid, pleural fluid, peritoneal fluid and surgical drainage fluid Strongyloides stercoralis Diagnostics

46. Strongyloides stercoralis Management and Treatment Ivermectin 12 mg daily for 3 days. This drug is also the drug of choice for the treatment of systemic strongyloidiasis An alternative treatment is albendazole 400 mg bid x 5 days � A maintenance therapy once a month is necessary to suppress symptomatic infection (albendazole 400 mg or ivermectin 6 mg once monthly)

47. Strongyloides stercoralis Unique features, Caveats In immuno-compromised patients, strongyloides can cause overwhelming infection.This serious complication is called strongyloides hyper-infection syndrome and has a high case-fatality rate Disseminated strongyloidiasis and heavy worm loads can occur in patients with HIV, but the full-blown hyper-infection syndrome is less common The likelihood of developing the hyper-infection syndrome is also increased in patients taking high-dose steroids

48. Other: Hepatitis Clinical Symptoms may evolve Flu-like symptoms of lassitude, weakness, drowsiness, anorexia, nausea, abdominal discomfort, fever, headache, jaundice (including dark urine, gray stools, and mild pruritis), Hepatomegaly

49. HepatitisManagement and Treatment Symptomatic and supportive care. Where available, Interferon for treatment of Hepatitis B and C and Havrix as a preventive measure for patients at risk for hepatitis A; Interferon for treatment of Hepatitis B and C. Epivir-HBV for Hep B Alcohol consumption should be discouraged during convalescence

50. HepatitisPrevention Frequent hand-washing and good hygiene are important as Hepatitis A is spread by oral-fecal route and often by food contamination Hepatitis B and C are transmitted through contact with blood or through sexual contact Condoms can reduce risk of transmission It is important to discourage needle sharing

51. Comments Vaccines are very expensive and may not be available Co-infection of HIV and Hepatitis C signifies probability of acceleration of HIV disease and Hepatitis C disease The hepatotoxic effect of some ARVs (e.g., Nevirapine) and other drugs (e.g., Ketoconazole) is significant