1. CLINICAL CASE
โข A 26 year old male comes to the ER for
SHORTNESS OF BREATH.
โข He says this has been going on for about 3
weeks already. It started with feeling more
tired than usual when climbing up the stairs.
โข Today he feels almost unable to walk anymore
from bed to bathroom.
2. CLINICAL CASE
โข Our patient admits to having a cough of about 4
weeks already. Itโs a dry cough, almost no
phlegm.
โข He also has on and off fever through all this
period, which would go away if he took
paracetamol.
โข When asked he says he also has loose stools
which he attributes to the new supplements he
has been taking. He would go to the bathroom 5x
a day. The stools are watery.
3. CLINICAL CASE
โข Our patient was a school athlete when he was
in college.
โข He now works for a start up company but has
been unable to go to work for the last week.
โข He does not smoke, nor drink alcohol.
โข He denies using drugs.
โข He has had 3 partners in the past: 2 males and
one female.
4. CLINICAL CASE
โข On exam, our patient looks ill and tired.
โข His VS: BP 110/80; HR 110; RR 36; T 38.5
โข He is awake and can talk in brief sentences.
โข He has no jaundice. His skin appears dry and
rough with scattered papules.
โข He has several cervical lymph nodes. His
mouth has a thick layer of white thrush over
upper palate and tongue.
5. CLINICAL CASE
โข His lung sounds have crackles and rhonchi
over all lung fields. His heart sounds are
tachycardic but no murmurs.
โข His abdomen is scaphoid. Mild area of
tenderness in the lower abdomen.
โข All extremities are moving full range. No focal
neurologic deficits.
โข No edema. No joint effusions. No cyanosis.
13. OPPORTUNISTIC INFECTIONS (OI)
โข Ois are a heterogenous group of infection that
occur more in immunocompromised states
โข Caused by viruses, bacteria, fungi, protozoans,
helminths & other life forms
โข OIs tend to be more severe and disseminated
โข OIs usually require longer RX
โข OIs in HIV assoc with specific CD4 counts
17. Typical Relationship of Clinical Manifestations to
CD4 Count in HIV Infected Patients
50
Lymphoma
Tuberculosis
Kaposi Sarcoma
Herpes Zoster
18. In the Philippines: TOP 9 OIs
(n=478)
RANK OI % Prevalence Mean CD4 Mortality %
1 PTB 15.3 161 6.8
2 PCP 10.5 86 8
3 ePTB 5.7 160 0
4 disseminated TB 2.3 30 9.1
5 oral Thrush 2.3 136 9.1
6 CMV 1.9 48 11.1
7 Cryptococcal
Meningitis
1.3 35 16.7
8 Esophageal
Candidiasis
1.2 64 0
9 Toxoplasmosis 0.8 13 0
Salvana et al 2012
19. Approach to Patients with Cough:
DIAGNOSTIC CLUES
PARAMETER PRESENTATION
Duration of Symptoms Acute : bacterial pneumonia
Chronic: TB, PCP
Presence of fever Often present
If absent: non infectious cause like CA
Character of phlegm Purutent: Bacterial pneumonia, TB
Scanty: PCP, Viral pneumonia, Atypical
Pneumonia, TB
Chest Xray Typical: Bacterial pneumonia, TB
Atypical: TB, PCP
20. Approach to Patients with Cough
โข Chest Xray
โข Sputum tests:
โ Gram stain, CS
โ Sputum for GenXpert MTB
โ Induced Sputum for PCP PCR or PCP Antigen
โ Bronchoalveolar Lavage (BAL) studies
โข Other Labs: CBC, LDH, ABG
โข CT Scan Chest
21. EMPIRIC THERAPY FOR PATIENTS WITH COUGH
EVALUATE THE PATIENT AND COVER FOR
INFECTIONS YOU ARE HIGHLY CONSIDERING:
โข Always prudent to cover for bacterial CAP
(PSMID guidelines) โ lifesaving
โข TMP-SMX is drug of choice if PCP is strongly
suspected (+ Prednisone if hypoxemic)
โข HRZE best started when more information
becomes available.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31. GenXpert MTB
โข Sensitivity approaches 100%
โข Specificity for Rifampicin resistance: 92%
โข Turn around time: 1 hr 40 min
โข Takes cartridges loaded with
sputum and reagents.
The cartridges consist of a
syringe barrel, a sonicator dome,
a reverse-transcriptase PCR tube
and a rotary valve
32. HIV/AIDS and TB:
A Deadly Combination
โข HIV suppresses the human immune system.
โข TB suppresses the human immune system.
โข Each makes the other worse synergistically.
โข The number of new cases of TB has more than
doubled in countries with high HIV prevalence in
the past decade
One in four HIV
deaths is linked to TB
+
33. Pneumocystis Jiroveci
(Formerly P. carinii)
โข Taxonomy
โ Fungus (before was considered) Protozoan
โข Epidemology
โ Environmental source
โข Transmission
โ Respiratory
โข Usually in HIV with CD4 less than 200
โข Recommended Prophylaxis- TMP/SMX (160/800)
โข Alternative agents- Dapsone
34.
35.
36. PCP Pneumonia: Treatment
โข Drug of CHOICE for PCP:
- Typical oral dose TMP/SMX or Cotrimoxazole Forte
160/800 2tablets 3x a day for 21 days
- If IV formulation is available give as 5mg/kg IV q 8
of the trimethoprim component for severe disease
+/- Corticosteroids are added for patients with
hypoxemia.
โข Alternative Drugs if with hypersentivity
- Clindamycin 300-450mg po/IV q6-q8 +
Primaquine 30mg qday for 21 days
37. Toxicities to watch out for when
treating for PCP
Drug Issues
TMP-SMX Toxicities: โWBC, โPlat, โLFT
โCreat, โAmylase, rash, fever
Cross reactivity: dapsone (+/-
50%)
Clindamycin + Primaquine Rash, LFT, diarrhea
Methemoglobinemia
Hemolytic anemia (G-6-PD)
Dapsone Rash, fever, โLFT, Hemolytic
anemia (G-6-PD), peripheral
neuropathy
38. CLINICAL CASE
Our 26 patient was found to have a CD4 = 23
and bilateral interstitial infiltrates on CXR has
been started on treatment with cotrimoxazole
forte plus prednisone for presumptive PCP.
On the 5th day he still dyspnea and reports
that his symptoms have not improved since
admission to the hospital.
What can you do?
39. Management of Patients with AIDS Related PCP
Not improving on TMP-SMX
โข Add corticosteroids if not already done
โข Send sputum specimens if not yet done
โข Reassess diagnosis
โ Is PCP correct?
โ Are there any other pathogens? TB?
โข Explain to patient and family
โ Realistic assessment of prognosis
โ May need home oxygen
43. CLINICAL CASE: Other Problems
โข Lesions in the mouth: Oral Candidiasis
โ Usually CD4 < 200
โ Associated with high viral loads
โข Diagnosis: Clinical
โ If there is doubt, KOH stain
โ If esophageal candidiasis is suspected: scope
โ If resistance to usual treatment is suspected: Fungal
CS
โข Treatment: Fluconazole 100-200mg once daily for
7-14 days
44.
45.
46. Evaluation of HIV-patient with
Diarrhea
โข Diarrhea due to multitude of etiologies
โข Infectious, Malignancy or medication-induced
โข Incidence decrease with use of potent ARVs
47. Causes of Diarrhea in Patients suspected to have HIV
Protozoal Gut neoplasms Bacterial
Microsporidium*
Cryptosporidium*
Isospora belli
Giardia lamblia
Entamoeba histolytica
Leishmania donovani
Blastocystis hominis
Cyclospora sp
Lymphoma
Kaposi's sarcoma
Salmonella*
Campylobacter*
Mycobacterium avium compl
Clostridium difficile
Shigella
Small bowel bact overgrowth
Vibrio sp
Tumor invasion
Lymphoma
Kaposi's sarcoma
Viral Pancreatic insuff Fungal
Cytomegalovirus*
Herpes simplex
Adenovirus
Rotavirus
Norwalk
HIV
Infectious pancreatitis
Cytomegalovirus
Mycobacterium avium
complex
Drug-induced pancreatitis
Didanosine
Pentamidine
Histoplasmosis
Coccidiomycosis
Idiopathic
"AIDS enteropathy"
49. Diagnostic Studies
Stool
Exam
๏งculture of bacteria
๏งC. difficile toxin assay
๏งexamination for ova and parasites
๏งAFB or immunofluorescent stain
(Cryptosporidium, Isospora, and Cyclospora)
๏ง trichrome staining (Microsporidium)
Blood
culture
๏ง Bacterial
๏ง Fungal
Endoscopy ๏ง small bowel biopsies looking for MAC, lymphoma, or
microsporidiosis
๏ง colonoscopy and biopsy: CMV or other inflammatory
enteridites, Kaposiโs sarcoma
๏ง Lower endoscopy: classic features of colitis
๏ง Upper endoscopy: symptoms suggesting enteritis
Imaging ๏ง abdominal computed tomography (CT) using oral and
intravenous contrast
50.
51. Common Opportunistic Infections presenting with diarrhea
Causative
Organism
Transmission Presentation Diagnostic study Treatment
Microsporidia
-obligate
intracellular
Protozoan
fecal-oral route
via ingestion of
spores
anorexia, nausea,
weight loss,
abdominal pain,
malabsorption,
fever and chronic
non-bloody
diarrhea
Stool exams using
light microscopy
with Kinyoun
staining
Albendazole (400
mg PO BID x 3
weeks)
Cyclospora
-coccidian
protozoan
consumption of
untreated water
and
contaminated
food
Acute or chronic
diarrhea, fatigue,
weight loss,
nausea, fever,
vomiting
Stool modified
Kinyoun staining
TMP-SMX
160/800 mg
orally four times a
day for 7โ10 days
Cryptosporidiu
m
-intracellular,
protozoan
ingestion of
oocysts from
contaminated
drinking
or recreational
water, sexual
contact
acute, chronic, or
fulminant
diarrhea,
acid-fast staining
modified
AFB/Kinyoun
stains
No antibiotics are
currently
recommended
Started on
ARV therapy
immediately to
improve
Philippine Clinical Practice Guidelines for the Prevention, Diagnosis, and Treatment of Opportunistic Infections in Human
Immunodeficiency Virus-Infected Adults and Adolescents in the Philippines
52. CLINICAL CASE 2
A 28 y/o man is brought to the ER after a
witnessed seizure. Family members report
that he has had some memory loss and
unusual behavior for the past 2 weeks.
The patient is an English teacher.
On PE he is confused and disoriented. Weakness
was noted in the R upper and lower
extremities.
53.
54.
55.
56. Evaluation of CNS Mass Lesions in
Suspected HIV Patients
Toxoplasmosis
Lymphoma
PML
Tuberculosis
Fungus
Nocardia
Bacterial
Syphilis
Kaposi Sarcoma
Glioblastoma
Radiologic
non specific
extra CNS lesions
Laboratory
Serology โ Toxo IgG, crypt Ag
Blood culture โ AFB, fungus
CSF โ Crypt Ag, CMV PCR, EBV PCR
Urine โ Histo Ag
Empiric Therapy
57. Toxoplasmosis
โข Toxoplasma gondii
โข Carried by cats, birds and other domesticated
animals; soil contaminated by cat feces, and in meat
โข Most common site is the brain
โข It can infect lungs, retina of the eyes, heart, pancreas,
liver, colon and testes
58. Toxoplasmosis - Diagnosis
โข Definite diagnosis: Biopsy with demonstration
of tachyzoites
โข Stereotactic biopsy of the brain often difficult
to do
โข Presumptive diagnosis acceptable when
โ CD4 < 100
โ Compatible neurologic disease
โ No prophylaxis
โ Serology: positive toxo IgG
63. Cryptococcal Infections
โข Cryptococcus neoformans
โข Areas heavily contaminated with bird excrement.
โข Infects meninges, skin and lungs
โข Signs and symptoms
โข Diagnosis and prognosis
โข Therapy: - Amphotericin-B +/- Flucytosine
- Fluconazole +/- Flucytosine
- Itraconazole
64.
65.
66. CLINICAL CASE 3
โข A 40 year male diagnosed HIV + 3 years ago and
lost to followup.
โข He now complains of headache for the last 2
months
โข Two days ago now with behavioral changes, fever,
vomitting.
โข He has lost over 20kg in the last 6mos.
โข He has no cough.
โข His CD4 count is 200.
67.
68. HIV and EPTB
โข Immunosuppression increases infection and makes
its symptoms become atypical
โข TB: most cause of death in 24-44 y/o AIDS
โข EPTB occur in 40-80% in HIV(+).
โข Lymph node involvement is the most
โข Miliary, CNS or cutaneous TB are more than HIV(-)
โข Multi drug-resistant TB
69. Mycobacterium tuberculosis: EPTB
โข CD4 count threshold: - Any CD4 count
โข For TST (+) > 5 mm
- Anergic but with high risk
- Known exposure to active case
โข Recommended prophylaxis - INH 300mg/day
+ Vitamin B6 x 6months
70. Mycobacterium tuberculosis
Therapy:
First line drugs: Second line drugs:
- Isoniazid - Ethionamide
- Rifampin - Ofloxacin, Ciprofloxacin
- Ethambutol - Streptomycin
- Pyrazinamide - Cycloserine
- Capreomycin
- Kanamycin
82. Diagnosis of CMV Disease
โข Serology (IgG, IgM)
โข Viremia common in asymptomatic persons with
low CD4/ CMV Antigenemia)
โข Histology required for diagnosis of colitis and
pneumonitis
โข โowlโs eye โ intranuclear inclusion bodies pathognomonic
โข Rare cells in the absence of clinical disease insignificant
โข Retinitis clinical diagnoses
โข Fluffy exudate
โข CNS โ CMV PCR
83. Cytomegalovirus Infections
โข CD4 count threshold: <50 cell per uL
< 100 cells per uL if prior OI
<CMV antibody positivity
โข Ophthalmologic evaluations should be done
90. Mycobacterial Infections Other than TB
(MOTT)
โข Atypical mycobacteria
โข Can cause a wide variety of infections such as
abscesses, masses, sinus infections.
โข They can also can infect the lungs, lymph
nodes, bones, gastrointestinal tract, skin and
soft tissues.
โข Nosocomial infections
91. Mycobacterium avium intracellulare
โข Mycobacterium avium complex and
immunosupression
โข Sources are food, water, and soil
โข Localized or disseminated infection
โข Symptoms of fever, weight loss, night sweats, fatigue,
anemia, loss of appetite, loose stools or diarrhea,
abdominal pain, enlarged liver or spleen
92. Mycobacterium avium
โข CD4 count threshold - 50 cells per uL.
โข Recomm. prophylaxis - Azithromycin or
- Clarithromycin
โข Alternative agents - Rifabutin
- Azithromycin + Rifabutin
93. Symptoms and Diagnosis
โข Variety of symptoms
โข Diagnosis based on isolation of MOTT from
site affected
94. Mycobacterium Avium
Therapy:
โข Clarithromycin + Ethambutol +/- Rifabutin
โข Azithromycin + Ethambutol +/- Rifabutin
โข Alternatives as second line drugs:
Ciprofloxacine,
Ofloxacine, Amikacin, Kanamycin.
95. How patients with advanced HIV infection/AIDS
may present to our clinics
โข Pulmonary diseases
โ Pneumocystis pneumonia
โ Tuberculosis
โ Pneumococcal pneumonia
โข Central nervous system
โ Toxoplasmosis
โ Cryptococcosis
โ Cytomegalovirus
โข Gastrointestinal diseases
โ Salmonella
โ Cryptosporidiosis
โ Other parasitic infections
โข Eyes
โ Cytomegalovirus
โข Disseminated diseases
โ Disseminated TB
โ Mycobacterium avium
intracellulare
โ Bacterial infections (e.g.
salmonellosis)
โข Skin
โ Candidiasis
โ Kaposiโs sarcoma
โข Immune system
โ Non-Hodgkinโs lymphoma
96. Common Infections of advanced HIV
infection/AIDS by pathogen
โข Fungal diseases
โ Pneumocystis pneumonia
โ Oral and esophageal
candidiasis
โ Cryptococcosis
โข Mycobacterial diseases
โ Mycobacterium tuberculosis
โ Mycobacterium avium
intracellulare
โข Protozoal diseases
โ Toxoplasmosis
โ Various gastrointestinal
pathogens
โข Viral diseases
โ Cytomegalovirus
โ Epstein-Barr virus
โ Human herpes virus 8
โข Bacterial diseases
โ Streptococcus pneumoniae
โ Salmonellosis