1. Slide 1 Unit 5 Persistent Diarrhoea
Unit 5 should take approximately 40 minutes to implement (total of 28 slides)
Step 1: Learning Objectives & Definition (Slides 1-3) – 2 minutes
Step 2: Dehydration & Rehydration (Slides 4-11) – 5 minutes
Step 3: Clinical Categories of Diarrhoea (Slides 12-20) – 8 minutes
Step 4: Treatment (Slides 21-26) – 10 minutes
Step 5: Diarrhoea Summary & Key Points (Slides 27-28) – 5 minutes
Step 6: Question and Answer (No Slides) – 10 minutes
NOTE: These facilitation notes provide information on timing, items to emphasize, and background information to help the facilitator understand and explain the slide content. These notes are not meant to be read aloud by the speaker.
It may be necessary to darken the lighting in the training room so that participants can see sufficient detail in the photographs contained in this unit.

2. Learning Objectives Participants will be able to:
Slide 2
Participants will be able to:
Provide empirical treatment for persistent diarrhoea
Use and interpret stool exams in patients who do not respond to empirical therapy
Provide appropriate treatment for identified infections
Step 1: Learning Objectives & Definition (Slides 1-3) – 2 minutes
ASK participants if they have any questions about the learning objectives before continuing.
Training on Clinical Care of HIV, AIDS and Opportunistic Infections

3. Definition: Persistent Diarrhoea
Slide 3
Liquid stools
3 or more times per day
Continuous or intermittent
At least 2 weeks duration
HIV positive
Defined in the MoHSS Guidelines for the Clinical Management of HIV and AIDS, 2001.
Republic of Namibia, Ministry of Health and Social Services (MoHSS), Guidelines for the Clinical Management of HIV and AIDS. (2001?)
Training on Clinical Care of HIV, AIDS and Opportunistic Infections

4. Case History - Nangura
Slide 4
Nangura is a 28 year old woman with HIV who presents with diarrhoea and nausea. She has had 4 liquid stools per day most days for about 2 weeks. She otherwise feels well and is urinating normally. She thinks the symptoms may be improving over the past 2 or 3 days.
Step 2: Dehydration & Rehydration (Slides 4-11) – 5 minutes
Training on Clinical Care of HIV, AIDS and Opportunistic Infections

5. Case History (2)
Slide 5
Nangura was diagnosed with HIV 6 months ago. Her most recent CD4 count 4 months ago was 46.
Her opportunistic infection history includes tuberculosis treated last year, and oral candidiasis 6 months ago that resolved with nystatin suspension.
She developed hepatitis when she started nevirapine and HAART was discontinued until she recovered. Three weeks ago, she began stavudine (d4T) + lamivudine (3TC) + Lopinavir/ritonavir. She has taken cotrimoxazole daily for 6 months.
Aluvia® (lopinavir 200mg / ritonavir 50 mg) tablets have replaced Kaletra® (lopinavir mg / ritonavir 33.3 mg) capsules because of Aluvia®’s favourable qualities
Does not need to be stored in a refrigerator
Can be taken with or without food
Reduced pill burden
Training on Clinical Care of HIV, AIDS and Opportunistic Infections

6. Case Exam
Slide 6
On exam, Nangura is afebrile. She appears agitated, but she relates this to her long wait to see you. BP 110/60. Pulse 94. RR 16. Weight 50 kg. Her mouth appears mildly dry with some chapping of the lips. Her skin retracts promptly on pinching.
Training on Clinical Care of HIV, AIDS and Opportunistic Infections

7. Additional History - Nangura
Slide 7
She reports no fevers.
She reports no visible blood in the stools.
She has no recent sick contacts.
She reports no recent antibiotic use besides cotrimoxazole.
Training on Clinical Care of HIV, AIDS and Opportunistic Infections

8. First Assess for Dehydration
Slide 8
Clinical Feature
Moderate
Severe
General
Irritable
Cold, Sweaty
Pulse
Rapid
Rapid, Feeble
Respiration
Deep
Deep, Rapid
Skin Elasticity
Poor
Very Poor
Eyes
Sunken
Deeply Sunken
Mucous Membranes
Dry
Very Dry
Urine Flow
Reduced
None > 6 hours
Table 3 of the Republic of Namibia, Ministry of Health and Social Services (MoHSS), Guidelines for the Clinical Management of HIV and AIDS. (2001?)
Table 3 - MoHSS, Guidelines for the Clinical Management of HIV and AIDS, 2001.
Training on Clinical Care of HIV, AIDS and Opportunistic Infections

9. Rehydration in Primary Care Setting
Slide 9
Mild or moderate dehydration – Oral rehydration
Oral Rehydration Solution (ORS) packets preferred
‘Home’ recipe
½ tsp salt with
8 tsp sugar in
1 liter boiled water
Severe dehydration – initial IV rehydration preferred
If unable to correct, refer to level 2
Oral rehydration salts (ORS) are especially important for children. Adults without severe dehydration can use other fluids, including some sodium and potassium intake.
Research has shown that home preparation of oral rehydration is not very accurate, and the resulting solution has very variable electrolyte concentrations. Also, glucose based solutions do not provide as rapid GI absorption of liquid as some other carbohydrate sources. Therefore, if available, oral rehydration solution (ORS) is preferred.
Training on Clinical Care of HIV, AIDS and Opportunistic Infections

10. Potassium Replacement
Slide 10
Oral rehydration solution (ORS)
Fruits – like bananas, oranges, etc.
Vegetables including potatoes and leafy greens like spinach
Training on Clinical Care of HIV, AIDS and Opportunistic Infections

11. Nutrition
Slide 11
Maintain intake of healthy balanced diet during episodes of diarrhoea
Remind clinicians that it is important for patients to maintain a healthy diet in settings of diarrhoea; that reducing oral intake over time does not reduce the illness causing diarrhoea but does lead to malnutrition and more disease.
The second half of the unit gives more information on nutrition counselling.
Training on Clinical Care of HIV, AIDS and Opportunistic Infections

12. Some Clinical Categories of Diarrhoea
Slide 12
Bloody with fever
Bloody without fever
Any CD4 count
CD4 < 200
Non-bloody with fever
Non-bloody without fever
Step 3: Clinical Categories of Diarrhoea (Slides 12-20) – 8 minutes
One widely used method for developing a differential diagnosis for diarrhoea starts by characterizing diarrhoea by the presence or absence of blood, and the presence or absence of fever, leading to 4 categories.
We further divide these by the presence or absence of severe immunosuppression.
In the next few slides, we will examine the common causes of diarrhoea that occur within each category.
Causative agent is not found in 15 to 46% of cases in a review study. Ref; The Clinical Practice of HIV Medicine, 2005, Dr. D.C Spencer pg 150
Training on Clinical Care of HIV, AIDS and Opportunistic Infections

13. Bloody Diarrhoea with Fever
Slide 13
Any CD4 count
Bacillary dysentery
Shigella*
Salmonella*
Campylobacter*
Invasive E. coli*
Clostridium difficile colitis*
Schistosoma mansoni
Ulcerative colitis*
CD4 < 200
CMV**
The common causes of bloody diarrhoea with fever are the organisms that cause bacillary dysentery, and the toxin of clostridium difficile.
Shigella sp: very common. Watery diarrhoea , mucus +/- blood, fever, WBCs in stool, not related to CD4 count. Rx: CTX 960 mg (1 DS) bd x 3 d OR nalidixic acid 1 g qds x 5 days OR ciprofloxacin 500 mg bd x 3 d
Non-typhi salmonella: watery diarrhoea, fever, prostration, confusion, may have WBCs in stool, any CD4 count. Rx: CTX mg bd x 14d or longer OR ciprofloxacin 500 mg bd x 14 d or longer
Campylobacter: watery diarrhoea sometimes with blood, fever, stool may contain WBCs, any CD4 count. Rx: erythromycin 500 mg qid x 5 days or longer
Invasive E. coli: low CD4 counts. Rx: ciprofloxacin 500 mg bd x 7 days
C. difficile: watery diarrhoea in context of hospitalisation and prior antibiotic use (penicillins, clindamycin), fever, increased WBC, stool may contain WBCs. Rx: metronidazole 400 mg po tds x 10 days (“Orange” book)
Schistosoma mansoni: abdominal pain and blood-streaked stool. Rx: praziquantel 20 mg/kg po bd for one day
Ulcerative colitis, non-infectious inflammatory bowel disease, may also cause chronic and recurrent bloody diarrhoea with fever. Diagnosis of exclusion; not specifically related to HIV - may be less frequent in persons with advanced immunosuppression.
CMV colitis only occurs with severe immunosuppression, typically the CD4 count is <50. It can be difficult to diagnose. Abdominal pain bloating, flatus, diarrhoea may be bloody. Gancyclovir and foscarnet not available. Restore immunity with HAART.
Ref: The Clinical Practice of HIV Medicine, Dr. D. Spencer, 2005, p
*Specific treatment available
** May respond to HAART
Training on Clinical Care of HIV, AIDS and Opportunistic Infections

14. Bloody Diarrhoea without Fever
Slide 14
Any CD4 count
Amebic dysentery*
Entameba histolytica
Bacillary dysentery*
Strongyloides stercoralis*
Ulcerative colitis*
CD4 < 200
CMV**
E histolytica is present in some areas of Namibia. It is not increased with HIV. Bloody diarrhoea with cramps and colitis. Rx: metronidazole 400 mg po tds x 5-10 days
Strongyloides stercoralis: pain, diarrhoea, acute steatorrhea described, may get “creeping eruption” skin lesions often on the back produced by migrating larvae. Hyperinfection syndrome can occur following severe immunosuppression, giving diffuse mucosal injury with dysentery, septicaemia, dyspnea and even larval invasion of the brain. Rx: thiabendazole 50 mg/kg/day divided in 2 doses x 2 days, maximum 3 g/d BUT this is not in NEMlist – guidelines for the clinical management of HIV and AIDS, MoHSS “Orange book” p. 18, recommends albendazole 400 mg daily x 3 days, repeat after 3 weeks.
*Specific treatment available
** May respond to HAART
Training on Clinical Care of HIV, AIDS and Opportunistic Infections

15. Non-Bloody Diarrhoea with Fever
Slide 15
CD4 < 200
CMV**
MTB* or MOTT**
KS* ** and Lymphoma*
HIV enteropathy**
Any CD4 count
Bacillary dysentery*
Crohn’s* Disease
C. difficile*
KS can involve the bowel so extensively that it can block water re-absorption and can also cause secretions
HIV enteropathy described in 15-60% of patients with severe refractory diarrhoea in era prior to HAART. Villous atrophy on small bowel biopsy and evidence of small bowel dysfunction. Diarrhoea and wasting with fat malabsorption. Alternative diagnoses should be excluded. Rx: HAART (subsequent improvement diagnostic)
*Specific treatment available
** May respond to HAART
Training on Clinical Care of HIV, AIDS and Opportunistic Infections

16. Non-Bloody Diarrhoea without Fever
Slide 16
CD4 < 200
Opportunistic protozoa
Isospora*
Cryptosporidia**
Microsporidia**
Opportunistic viruses
CMV**
Adenovirus**
HIV enteropathy**
KS**
Any CD4 count
Protozoa
Giardia*
Helminths
Ascaris*
(Hookworm*)
Strongyloides *
Schistosomiasis (Bilharzia)*
Non-invasive bacteria*
Intestinal viruses
Drug toxicity
Other causes
Giardia is present in Namibia. It is not increased with HIV disease. Rx: metronidazole
Helminths:
Ascaris lumbricoides: may be asymotpmatic; large worm loads can cause episodes of recurrent colic. Rx: albendazole 400 mg po stat
Hookworm: large infestations can produce severe anaemia as parasite feeds on human blood in GIT. Usually no abdominal symptoms. Rx: albendazole 400 mg po stat
Strongyloides stercoralis: pain, diarrhoea, acute steatorrhea described, may get “creeping eruption” skin lesions often on the back produced by migrating larvae. Hyperinfection syndrome can occur following severe immunosuppression, giving diffuse mucosal injury with dysentery, septicaemia, dyspnea and even larval invasion of the brain. Rx: thiabendazole 50 mg/kg/day divided in 2 doses x 2 days, maximum 3 g/d BUT this is not in NEMlist – guidelines for the clinical management of HIV and AIDS, MoHSS “Orange book” p. 18, recommends albendazole 400 mg daily x 3 days, repeat after 3 weeks.
Schistosoma mansoni: abdominal pain and blood-streaked stool. Rx: praziquantel 20 mg/kg po
Ref: Manual of Tropical Pediatrics, M.D. Seear, Cambridge University Press, 2000, p
HIV enteropathy described in 15-60% of patients with severe refractory diarrhoea in era prior to HAART. Villous atrophy on small bowel biopsy and evidence of small bowel dysfunction. Diarrhoea and wasting with fat malabsorption. Alternative diagnoses should be excluded. Rx: HAART (subsequent improvement diagnostic)
*Specific treatment available
** May respond to HAART
Training on Clinical Care of HIV, AIDS and Opportunistic Infections

17. Non-Bloody Diarrhoea without Fever (2)
Slide 17
Lactose intolerance and fat malabsorption
Can cause diarrhoea or occur following diarrhoea from another cause
Irritable bowel syndrome
Colonic malignancy
Training on Clinical Care of HIV, AIDS and Opportunistic Infections

18. Empiric Therapy of Severe or Persistent Diarrhoea
Slide 18
Bloody with fever
Bloody without fever
Nalidixic acid (bacillary dysentery) +/-metronidazole
(C. difficile)
Metronidazole
(Amebic dysentery or C. difficile colitis)
Non-bloody with fever
Persistent non-bloody without fever
Nalidixic acid
(bacillary dysentery)
Metronidazole +/- albendazole
(Giardia +/- helmiths)
Training on Clinical Care of HIV, AIDS and Opportunistic Infections

19. Stool Examinations
Slide 19
Can be done at same time as empiric therapy where available
Can be done if empiric therapy at primary care level is not successful
Can be done for chronic diarrhoea
Training on Clinical Care of HIV, AIDS and Opportunistic Infections

20. Stool Examinations (2) Gram Stain (1 sample) For WBC
Slide 20
Gram Stain (1 sample)
For WBC
Bacterial Culture (1 sample)
Salmonella, Shigella, Campylobacter, Clostridium
Wet Mount (3 samples)
Motile protozoa
Helminth eggs
Acid Fast Stain (3 samples)
MTB, MOTT, Isospora, Cryptosporidium
C. difficile toxin (sent to South Africa only)
Send 3 samples on 3 separate days
Training on Clinical Care of HIV, AIDS and Opportunistic Infections

21. Parasites and Their Treatment
Slide 21
Aetiology
Treatment
Giardia lamblia
Metronidazole
400 mg tds x 5d
E. histolytica
400 mg tds x 10d
Strongyloides stercoralis
Albendazole
400 mg bd X 2-7d
Ascaris, hookworm
400 mg once
Isospora belli
Cotrimoxazole (80/400)
2 tab bd or qds x 7-21 d
Cryptosporidium
Immune Restoration with ARVs
Microsporidium
Step 4: Treatment (Slides 21-26) – 10 minutes
Doses are from Table 4 of the Republic of Namibia, Ministry of Health and Social Services (MoHSS), Guidelines for the Clinical Management of HIV and AIDS. (2001?) except as noted.
Source: Mandell, G.L., J.E. Bennett, R. Dolin. Principles and Practice of Infectious Disease. Sixth Edition, Elseiver, Inc.
Strongyloides- although increased with other immunodeficiencies, it is not increased in HIV disease. It is normally treated with albendazole for 2-7 days depending on if there is hyperinfection or not (longer course than in guidelines). Hyperinfection is more common in immunosuppressed patients.
Ascaris, hookworm are treated with a single 400 mg dose of albendazole, whipworm (trichuris) requires 3 days of therapy
Isospora is diagnosed on a (modified) acid fast stain of stool. It is treated with cotrimoxazole, but often recurs unless chronic suppressive therapy is used.
Cryptosporidia is diagnosed on a modified acid fast stain of stool: the test is not generally performed in Namibia. Cyrptosporidia usually improves with HAART. A new drug, nitazoxanide or Alinia, is licensed for cryptosporidiosis in children. The manufacturer is seeking FDA approval for use in adults and HIV patients
Microsporidia, a group of related tiny parasites, are found on electron microscopy of intestinal biospies (not available) and by a modified trichrome stain (probably not available in Namibia currently). So a specific diagnosis of microsporidia may not be possible. The microsporidium that most often causes diarrhoea, Enterocytozoon beineusi, is not effectively treated by albendazole but often improves with HAART. Encephalitozoon intestinalis, a rare cause of diarrhea, responds to albendazole 400 mg bd x 3 weeks. Eye disease, kidney disease, disseminated microsporidiosis caused by other related parasites may respond to albendazole but are even less likely to be diagnosed.
Training on Clinical Care of HIV, AIDS and Opportunistic Infections

22. Bacteria and Their Treatment
Slide 22
Aetiology
Treatment
Salmonella
Chloramphenicol
mg qid x 7-14 d
OR Nalidixic Acid
1g qid x 5d
Shigella
Nalidixic Acid
Campylobacter
Erythromycin
500mg qid x 7d
Clostridium difficile
Stop other antibiotics
Metronidazole
400mg tds x 10d
E. coli
Doses are from Table 4 of the Republic of Namibia, Ministry of Health and Social Services (MoHSS), Guidelines for the Clinical Management of HIV and AIDS. (2001?)
Salmonella was 85% susceptible to nalidixic acid and 100% susceptible to chloramphenicol (500 mg qd for 7-14 days) per NIP. Ciprofloxacin, used in other countries, was not tested. Ceftriaxone IV is also effective. (Guideline recommends chloramphenicol; this was been a treatment for typhoid fever prior to quinolones].
Shigella was % susceptible to nalidixic acid, depending on the species.
Campylobacter was not tested by NIP, but is usually susceptible to erythromycin. Susceptibility to flouroquinolones is decreasing worldwide.
C difficile colitis may improve when other antibiotics are stopped. If that is not sufficient, the treatment of choice is metronidazole
E coli in Namibia are usually susceptible to nalidixic acid. The guidelines recommend cefuroxime, but it is rarely available.
MoHSS, Guidelines for the Clinical Management of HIV and AIDS, 2001.
Training on Clinical Care of HIV, AIDS and Opportunistic Infections

23. Persistent Diarrhoea: No Organism Identified
Slide 23
Consider empiric C. difficile treatment if:
Patient is toxic
History of recent antibiotic use
Stool sent for culture
ELISA for C. difficile toxin available in South Africa
Consider cotrimoxazole for isospora
Consider albendazole 400 mg bd for 2-3 weeks for one type of microsporidia
For isospora treatment see slide 21
This dose of albendazole, 400 mg bd for 3 weeks, is the treatment of a rare cause of diarrhea in AIDS patients, the microsporidium parasite Encephalitozoon intestinalis. [Drugs for parasitic infections, Medical Letter on Drugs and Therapeutics, August 2004.]
A study in Zambia used 800 mg bd for 3 weeks as empiric therapy in a randomized controlled trial of AIDS patients with chronic diarrhea. There were 29% fewer days with diarrhea in albendazole arm compared with placebo arm. These patients did not receive antiretroviral therapy. [ Kelly P et al, BMJ 1996;312: ]
Training on Clinical Care of HIV, AIDS and Opportunistic Infections

24. Persistent Diarrhoea: No Organism Identified (2)
Slide 24
If not on HAART consider starting:
Immune restoration can help improve diarrhoea from Cryptosporidia, Microsporidia, and HIV enteropathy
Unexplained chronic diarrhoea for < 1 month is a WHO Clinical Stage 3 condition
If on HAART or other medications, consider drug toxicity
HAART is likely to be effective, although some persons do develop diarrhea as a drug toxicity, especially on protease inhibitors.
Remember that HIV wasting syndrome includes: unexplained involuntary weight loss (<10%) PLUS unexplained chronic diarrhoea >1 month OR fever or night sweats >1 month. It is a WHO Clinical Stage 4 event and therefore qualifies the patient to receive HAART
Training on Clinical Care of HIV, AIDS and Opportunistic Infections

25. Persistent Diarrhoea: No Organism Identified (3)
Slide 25
Consider colonoscopy with biopsy if available:
Cytomegalovirus (CMV)
Kaposi’s Sarcoma (KS)
Lymphoma
Other malignancy
Inflammatory bowel disease
Consider anti-motility medication (e.g. loperamide) IF:
No organism identified after careful search
Diarrhoea is non-bloody
Patient not elderly or a child
Ref: Guidelines for the clinical management of HIV and AIDS, MoHSS, p. 17
Training on Clinical Care of HIV, AIDS and Opportunistic Infections

26. Persistent Diarrhoea: Nutrition
Slide 26
Continue fluid replacement as needed
Emphasize nutrition to overcome maldigestion or malabsorbtion
Trial of lactose free diet
Trial of reduced fats
But use fats to maximize calories if fat restriction does not reduce diarrhoea
Maximize calories
Every food and drink item should include useful calories
Balanced diet and/or vitamin supplements
Training on Clinical Care of HIV, AIDS and Opportunistic Infections

27. HIV Wasting Syndrome
Slide 27
Unexplained involuntary weight loss (>10% body weight) with obvious wasting or BMI<18.5 PLUS
Unexplained chronic diarrhoea for > 1 month OR
Reports of fever or night sweats for > 1 month (T>37.5°C) without known cause and lack of response to antibiotics or antimalarials
WHO Clinical Stage 4
Diarrhoea is defined as loose or watery stools three or more times daily
Fever should have been investigated at least with blood culture, malaria slide and CXR
Training on Clinical Care of HIV, AIDS and Opportunistic Infections

28. Case Follow-up
Slide 28
Nangura was advised to take more liquids and given nutritional counselling to maintain food intake while minimizing dairy products.
Stool studies were negative for bacteria and parasites.
The diarrhoea was attributed to the recently started lopinavir/ritonavir
She has been given anti-diarrhoeal agents as needed. Despite intermittent diarrhoea and gas pains, she has gained weight and strength.
Step 5: Diarrhoea Summary & Key Points (Slides 27-28) – 5 minutes
Continue with a brief discussion of the follow-up to Nangura’s case of persistent diarrhoea introduced at the beginning of this unit. Sometimes diarrhoea and other GI symptoms are adverse events from antiretroviral therapy. She has few options, is tolerating the side effects with symptomatic treatment and otherwise is improving on HAART.
Training on Clinical Care of HIV, AIDS and Opportunistic Infections

29. Key Points First correct any dehydration
Slide 29
First correct any dehydration
Consider empiric therapy of persistent diarrhoea
If unsuccessful, use stool laboratory studies to identify a cause and guide treatment
Key Points serve as a tool for summarizing and reviewing the main ideas that were discussed in the unit.
Summarize this presentation and review the Key Points for diarrhoea presented.
Step 6: Question and Answer (No Slides) – 10 minutes
Spend 10 minutes answering participant questions about diarrhoea
Collect the questions first, and then answer the most important, avoid repetition, and postpone questions referring to topics to be covered later in the course.
Questions that cannot be answered at the time, or are not immediately relevant, should be written on flip chart paper and answered later (this is often called the ‘parking lot’).
If there are more questions than time allows, remind participants that questions can be asked informally of faculty throughout the day, at breaks, or during the daily review sessions.
Training on Clinical Care of HIV, AIDS and Opportunistic Infections