HIV - AIDS. Associated Infections and Invasions

THEME:
AIDS-ASSOCIATED INFECTIONS
AND INVASIONS
Department of infectious diseases
Infectious diseases

AIDS- indicator diseases
The infectious process at a HIV-INFECTION is very individual.
The patient losses the immunity gradually and each stage of
illness the manifestations are peculiar. In the beginning the
patient has "«usual" diseases, but which proceed unusually:
more long-lived current, unusual localization of the patho-
logical process, often relapses, more often combined damage
of many bodies and systems is simultaneous etc.
But only at considerable lowering of immunity (decrease of
quantity of СD 4-lymphocytes up to 200 in mсl. of the blood)
for the patient occur diseases, which for the persons with
valuable immunity do not arise even at often infection, that has
allowed the doctors to attribute them to AIDS - indicators,
having detected which the doctor should think of
probability HIV for the patient!!!!

ALL INDICATOR DISEASES ARE
DISTRIBUTED:
1. On localization of the struck body:
- skin and mucous membranes
- lungs and upper respiratory tract
- gastrointestinal tract
- peripheral and CNS
- heart
- eyes
- system (constitutional) damage
2. On an etiology:
- viruses - protozoa
- bacterium - tumour
- funguses

CNS ILLNESSES WITH HIV INFECTION
Toxoplasmosis
HSV Encephalitis
Cytomegalovirus Encephalitis
Cryptococcal meningitis
Dementia
Primary CNS Lymphoma
Progressive Multifocal Leukoencephalopathy

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TOXOPLASMOSIS
 CAUSE: Latent T. gondii infection
 In HIV-infected persons toxoplasmosis mainly
appears as encephalitis or as disseminated
disease
 FREQUENCY: 30% of AIDS patients with latent
T. gondii infection (positive serology) and no
prophylaxis
WHO HIV/AIDS Treatment and Care Protocols for countries of the Commonwealth of Independent States. March. 2004.

PRESENTATION OF TOXOPLASMOSIS
Toxoplasmosis may be suspected by the
clinical findings:
 altered mental status
 fever
 seizures
 headaches
 focal neurologic findings, including motor deficits,
cranial nerve palsies, movement disorders,
dysmetria, visual-field loss, and aphasia
 over 80% have CD4 <100 cells/mm3

TOXOPLASMOSIS DIAGNOSIS
 CT or MRI scans: multiple ring enhancing lesions
 IgG for toxoplasma may help in establishing the
diagnosis in the absence of neuroimaging
techinques (T. gondii serology is positive in >95%)
 PCR for T. gondii in CSF is 50% sensitive and
96% to 100% specific.
 Can be confirmed by histologic examination of
tissue obtained by brain biopsy
 Response to therapy is characteristically prompt
and impressive

TOXOPLASMOSIS TREATMENT
Pyrimethamine 200mg Single PO Single dose
THEN
Pyrimethamine 25-50mg TID PO 6-8 weeks
PLUS
Folinic acid 15mg OD PO 6-8 weeks
PLUS
Sulphadiazine 1g Every 6 h PO 6-8 weeks
 Instead of sulphadiazine in this regimen, the following may be
used:
- Clindamycin 600mg every 6 h IV/PO for 6 weeks then 300-450mg QID
PO for life, OR
- Azithromycin 1200mg OD PO for 6 weeks then 600mg OD PO for life,
OR
- Clarithromycin 1g BID PO for 6 weeks then 500mg BID PO for life, OR
- Atovaquone 750mg QID PO for 6 weeks then 750mg BID PO for life

HERPES SIMPLEX VIRUS
 HSV may also cause meningoencephalitis and
meningitis
 HSV encephalitis leads to the development of
multiple lesions in different parts of the brain and
typical changes may be seen on CT scan studies
of the brain
 First line treatment: Aciclovir 10mg/kg every 8
hours IV 14-21 days OR
 Second line treatment: Foscarnet (suspected
resistance to aciclovir) 40 mg/kg every 8 to 12 h IV
14 d

CYTOMEGALOVIRUS ENCEPHALITIS
 CAUSE: CMV + CD4 count <50 cells/mm3
 FREQUENCY: <0.5% of AIDS patients
 PRESENTATION: Rapid progressive delirium, cranial
nerve deficits, nystagmus, ataxia, headache with fever
± CMV retinitis
 DIAGNOSIS:
- MRI shows periventricular confluent lesions with enhancement
- CMV PCR in CSF shows sensitivity of >80% and specificity of
90%
- Cultures of CSF for CMV are usually negative
 TREATMENT: Ganciclovir, foscarnet, or both IV

CRYPTOCOCCAL MENINGITIS
 INCIDENCE: 8% to 10%
 PRESENTATION: Fever, headache, alert (75%),
less common are visual changes, stiff neck,
cranial nerve deficits, seizures (10%); no focal
neurologic deficits
 CD4 count <100 cells/mm3
 CT, MRI: Usually normal
 DIAGNOSIS: Culture positive (95-100%), Crypt
Ag (>95% sensitive and specific)
- Definitive diagnosis: CSF antigen and/or positive
culture
 TREATMENT: see handout D4-2

PRIMARY CNS LYMPHOMA
 CAUSE: Virtually all are EBV-associated
 FREQUENCY: 2% to 6% in pre-HAART era –
1000x higher than in the general population
 PRESENTATION: Focal or non-focal signs
 CD4 count is usually <50 cells/mm3
 DIAGNOSIS:
- MRI (single lesion or multiple lesions that are isodense or
hypodense and usually homogeneous, but sometimes
ring forms)
- CSF EBV DNA is >94% specific and 80% sensitive
- brain biopsy

FACTORS FAVORING CNS LYMPHOMA
1. Typical neuro imaging results (above)
2. Negative T. gondii serology
3. Failure to respond to empiric treatment of
toxoplasmosis within 1 to 2 weeks
4. Lack of fever
5. Thallium SPECT scan with early thallium
uptake
John G. Bartlett. Medical management of HIV infection, 2003

THERAPY OF PRIMARY CNS LYMPHOMA
- Standard: Radiation + corticosteroids
- Chemotherapy: May be +Standard. Usually for
patients with elevated CD4 counts. Preliminary results
with methotrexate without radiation were promising
RESPONSE: Response rates to radiation
treatment plus corticosteroids is 20% to
50%, but these results are temporary

PROGRESSIVE MULTIFOCAL
LEUKOENCEPHALOPATHY
 CAUSE: Activation of JC virus (which is
ubiquitous) in patients who are immunodeficient
 FREQUENCY: 1% to 2%
 PRESENTATION: Cognitive impairment, visual
field deficits, hemiparesis speech defects,
incoordination with no fever.
 CD4 count is usually 35-100 cells/mm3, but a
subset of 7% to 25% have CD4 counts >200
cells/mm3

PROGRESSIVE MULTIFOCAL
LEUKOENCEPHALOPATHY (CONTINUED)
 DIAGNOSIS
- MRI shows hypodense lesions of white matter without
edema or enhancement
- PCR for JCV in CSF with sensitivity of 80% and
specificity of 95%
 TREATMENT: None with established merit
 PROGNOSIS: Median duration of survival is 1 to
6 months

THE COMMON SKIN AND MUCOUS MEMBRANE
DISORDERS IN PATIENTS WITH HIV
 Aphthous Ulcers
 Gingivitis
 Esophagitis
 Candidiasis
 Kaposi’s Sarcoma
 Seborrhoic Dermatitis
 Dermatophytic
Infections
 Molluscum Contagiosum
 Oral Hairy Leukoplakia
 Prurigo Nodularis
 Salivary Gland
Enlargement
 Staphylococcal
Folliculitis

APHTHOUS ULCERS
CAUSE: Unknown
 Minor: <1 cm diameter, usually self-limiting
(usually heals in 10 to 14 days)
 Major: >1 cm, deep, prolonged, heals slowly,
causes pain, and may prevent oral intake
(John G. Bartlett, Medical Management of HIV Infection, 2003)

GINGIVITIS
 CAUSE: Anaerobic bacteria
 PHASES: Linear gingival erythema > necrotizing
gingivitis > necrotizing periodontitis > necrotizing
stomatitis
 TREATMENT:
1. Routine dental care: Brush and floss ±
topical antiseptics: Listerine swish x 30-60
seconds bid, Peridex, etc.
2. Dental consultation: Curettage and
debridement
3. Antibiotics (necrotizing stomatitis):
Metronidazole; alternatives – clindamycin
and amoxicillin-clavulanate

ESOPHAGITIS IN PATIENTS WITH HIV
INFECTION
 Candidosis 50% to 70%
 CMV 10% to 20%
 HSV 2% to 5%
 Aphthous Ulcers 10% to 20%
 Other diagnostic considerations:
 Drug-induced dysphagia, including AZT and ddC (rare);
 infection, including M. avium, TB, Cryptosporidia, P. carinii, primary HIV infection
(acute retroviral syndrome), histoplasmosis, and tumor, including KS or lymphoma

CANDIDIASIS
 The facts about Candida albicans in healthy people:
- colonizes most body cavities
- the gastrointestinal tract of both men and women, and
the genital tract in women are the sites most
commonly colonized by the fungus
- generally produces no symptoms at all
- 1/3 of all normal women carry C. albicans in the
vagina

CANDIDIASIS (CONTINUED)
 Vulvovaginal/genital
candidiasis
 Women:
vaginal discharge and
vulvovaginal pruritus
 Men:
balanitis or balanoposthitis
and will complain of a
subpreputial discharge and
itchiness of the penis and
foreskin

 Cutaneous candidiasis: pruritic dermatitis

 Oropharyngeal candidiasis: involved buccal mucosa,
tongue, oropharynx, gums and the hard and soft palate

CANDIDIASIS: TREATMENT
 Localized disease:
 relatively inexpensive topical drugs (nystatin,
miconazole, or clotrimazole)
 Disseminated candidiasis or topical therapy
has failed:
 systemic antifungal agents
(ketoconazole, fluconazole, itraconazole, or
amphotericin B)

KAPOSI’S SARCOMA
 CAUSE:
 Human Herpesvirus Type 8 (HHV-8,
KSHV);
 associated with HIV
immunosuppressive
 PRESENTATION:
 Firm, purple to brown-black colored
macules, patches, plaques, papules,
nodules, or tumors; usually
asymptomatic.
 LOCALISATION:
 Face, chest, genitals, oral mucosa,
and feet;
 Usually multiple; symmetric
distribution
 Visceral involvement and lymphatic
obstruction are frequent

KAPOSI’S SARCOMA (CONTINUED)
 DIAGNOSIS:
 clinical suspicion
 confirmed by histological examination
 Chest X-ray
 TREATMENT: by oncologist and infectiologist!
 A. HAART - often induces resolution
 B.
1. Liposomal Doxorubicin IV
2. Surgical excision
3. Intralesional vinblastine
4. Intralesional 3% Na tetradecyl sulfate
5. Radiation (may cause severe mucositis)
6. Cryotherapy
7. Laser oblation

RegionalKnowledgeHubfortheCareand
TreatmentofHIV/AIDSinEurasia
www.aidsknowledgehub.org
Kaposi Sarkoma

SEBORRHEIC DERMATITIS
 CAUSE: Pityrosporum
yeast?
 PRESENTATION:
Erythematous plaques
with greasy scales and
indistinct margins on
scalp, central face, post
auricular area, trunk, and
occasionally pubic area
Regional Knowledge Hub for the Care and Treatment of HIV/AIDS in Eurasia
(John G. Bartlett, Medical Management of HIV Infection, 2

SEBORRHEIC DERMATITIS (CONTINUED)
 DIAGNOSIS: Clinical features
 TREATMENT:
- Topical steroids
- Shampoos

DERMATOPHYTIC INFECTIONS
 DEFINITION:
 Fungal infection of skin, hair, and nails
 CAUSE:
 Infection of skin by T. rubrum, T. mentagrophytes, M.
canis, E. floccosum, T. tonsurans, T. verrucosum, T.
soudanense.
 Candida causes typical nail and skin lesions;
 Malassezia furfur causes tinea versicolor.
 (Note: Candida and M. furfur are not
dermatophytes.)

DERMATOPHYTIC INFECTIONS
(CONTINUED)
 FORMS:
 Tinea corporis (ringworm)
 Tinea cruris (jock itch)
 Tinea pedis (athlete’s
foot)
 Tinea unguium or
onychomycosis (nail
involvement)
 Tinea captis (ringworm of
scalp)

MOLLUSCUM CONTAGIOSUM
 CAUSE: A poxvirus
 PRESENTATION: Flesh
colored, pink, or whitish,
dome-shaped papules with
central umbilication
(dimpling). Occur anywhere
on the body, except palms
and soles.

MOLLUSCUM CONTAGIOSUM
(CONTINUED)
 DIAGNOSIS: Clinical presentation
 TREATMENT:
 curettage, cryotherapy, electrocauterization,
chemical cauterization, imiquimod, topical
cidofovir
 lesions usually disappear in patients
responding to HAART

ORAL HAIRY LEUKOPLAKIA
 CAUSE: Intense replication of EBV
 PRESENTATION:
 Unilateral or bilateral adherent white/gray patches on lingual
lateral margins ± dorsal or ventral surface of tongue
 IMPLICATIONS:
 Found almost exclusively with HIV,
 indicates low CD4 count, predicts AIDS, and responds to
immune reconstitution with HAART

Oral Hairy Leukoplakia

ORAL HAIRY LEUKOPLAKIA (CONTINUED)
 TREATMENT - Rarely symptomatic and
rarely treated, but:
1) HAART (preferred)
2) Topical podophyllin
3) Surgical excision
4) Cryotherapy
5) Anti-EBV treatment

STAPHYLOCOCCAL FOLLICULITIS
- a skin infection localized to the hair follicle
 Perifolliculitis occurs commonly in HIV infected
persons
 Diagnosis: clinical findings
 Treatment:
 Antibiotics:
(cephalexin or cloxacillin 500mg PO QID for 7-21
days)

HERPES INFECTIONS
 HSV
 CMV infection
 CMV neurological disorders (including CMV
retinitis, encephalitis)
 Chronic diarrhea
 CMV pulmonary disorders
 VZV
 EBV

HERPES SIMPLEX VIRUS (HSV) INFECTION
 Commonly encountered in clinical practice
 Usually presents with vesicles and painful superficial sores
around the mouth, nose, lips and genitals
 Following an initial attack of herpes simplex infection
recurrences occur frequently
 In immunosuppressed persons the infection may be
extensive and persistent and may become disseminated
 Dissemination may lead to infection of the lungs, the
oesophagus, and the brain
WHO HIV/AIDS Treatment and Care Protocols for countries of the Commonwealth of
Independent States, March 2004

HSV MENINGOENCEPHALITIS
 HSV may also cause meningoencephalitis and
meningitis
 HSV encephalitis leads to the development of
multiple lesions in different parts of the brain and
typical changes may be seen on CT scan studies
of the brain
 First line treatment:
 Aciclovir 10mg/kg every 8 hours IV 14-21 days
 OR
 Second line treatment:
 Foscarnet (suspected resistance to aciclovir) 40 mg/kg every 8 to 12
h IV 14 d
WHO HIV/AIDS Treatment and Care Protocols for countries of the Commonwealth of Independent States, March 2004

CMV INFECTION
CMV neurological disorders
(including CMV retinitis, encephalitis)
Chronic diarrhea
CMV pulmonary disorders

CMV ENCEPHALITIS
 CAUSE: CMV + CD4 count <50 cells/mm3
 FREQUENCY: <0.5% of AIDS patients
 PRESENTATION: Rapid progressive delirium, cranial nerve
deficits, nystagmus, ataxia, headache with fever ± CMV
retinitis
 DIAGNOSIS:
- MRI shows periventricular confluent lesions with
enhancement
- CMV PCR in CSF shows sensitivity of >80% and
specificity of 90%
- Cultures of CSF for CMV are usually negative

CMV CHRONIC DIARRHEA
 FREQUENCY: 15% to 40% of chronic diarrhea in
AIDS patients
 CLINICAL FEATURES:
- Colitis and/or enteritis;
- fecal WBC and/or blood; cramps;
- fever;
- watery diarrhea & blood;
- may cause perforation;
- hemorrhage, toxic megacolon, ulceration;
- CD4 cell count <50/mm3

CMV CHRONIC DIARRHEA (CONTINUED)
 DIAGNOSIS:
 Biopsy
 CT scan
 Cannot establish this diagnosis with CMV
markers in blood or stool; need biopsy
 RESPONSE: variable; foscarnet and
ganciclovir are equally effective or
ineffective
(John G. Bartlett, Medical Management of HIV Infection, 20

CMV: PULMONARY DISORDERS
 Course: Subacute or chronic
 Frequency: Common isolate, rare cause of pulmonary
disease
 Setting: Advanced HIV infection (median CD4 count 20
cells/mm3)
 Typical findings: Interstitial infiltrates
 Diagnosis:
 Yield with FOB is 20% to 50%, culture requires more
than 1 week; shell culture 1 to 2 days; diagnosis of
CMV pneumonitis (disease) requires CMV seen on
cytopath or biopsy, progressive disease, and no
alternative pathogen

CMV: TREATMENT OF GI DISEASE,
NEUROLOGIC DISEASE AND RETINITIS
Dose Frequency Route Duration
Ganciclovir 5mg/kg BID IV 2-3 weeks
 Long term treatment with ganciclovir 5mg/kg
given IV daily may be necessary

CMV: TREATMENT OF GI DISEASE AND
NEUROLOGIC DISEASE
Second line treatment
Foscarnet 90mg/kg BID IV 3 weeks
 Long term treatment with foscarnet 90mg/kg
given IV daily may be necessary

TREATMENT OF CMV RETINITIS
Second line treatment
Ganciclovir intraocular implant
PLUS
Valganciclovir 900mg BID PO 21 days
 Long term treatment with valganciclovir 900mg
OD PO may be given after successful treatment
WHO HIV/AIDS Treatment and Care Protocols for countries of the Commonwealth of
Independent States, March 2004

VARICELLA ZOSTER VIRUS (VZV)
 The virus lays dormant in the paraspinal ganglia
for years after initial infection
 Causes disseminated infection after initial
exposure
 With immune suppression from whatever cause
(eg. HIV), the virus replicates and produces
lesions along the length of a cutaneous nerve in
a dermatomal distribution
 Diagnosis: The diagnosis is usually made on
clinical grounds

VARICELLA ZOSTER VIRUS (VZV) (CONTINUED)
Post-herpetic VZV neuralgia:
 common and serious debilitating problem
 causes severe pain
 control with Non-Steroid Anti-
Inflammatory Drugs. If pain control is not
achieved, amitryptiline, cabamazepine or
phenytoin may be tried.

VZV INFECTION: TREATMENT
 Dermatomal zoster
 1st line treatment:
 Aciclovir 800mg 5 times a day PO 7-10 days or until lesions crust
 OR
 Famciclovir 500mg TID PO 7-10 days
 Disseminated, visceral, ophthalmic zoster
 1st line treatment:
- Aciclovir 10mg/kg every 8 hours IV 7-10 days OR
- Famciclovir 500mg TID PO 7-10 days
- 2nd line treatment:
- Foscarnet 60 mg/kg (Q12h) or 40 mg/kg (Q8h) IV 7-10 days

THE COMMON GASTROINTESTINAL
DISORDERS IN PATIENTS WITH HIV
 Anorexia, Nausea,
Vomiting
 Acute Diarrhea
- medication-related acute
diarrhea
- campylobacter jejuni
- clostridium difficile
- enteric viruses
- salmonella
- shigella
- escherichia coli
- idiopathic (pathogen-
negative)
 Chronic Diarrhea
- cytomegalovirus
- entamoeba histolytica
- giardia lamblia
- cryptosporidia
- microsporidia
- mycobacterium avium
complex (mac)
- idiopathic (pathogen-
negative)
 Cholangiopathy
 Pancreatitis

ANOREXIA, NAUSEA, VOMITING
 MAJOR CAUSES:
- Medications (especially antiretrovirals,
antibiotics, opiates, and NSAIDs)
- Depression
- Intracranial pathology
- GI disease
- Hypogonadism
- Pregnancy
- Lactic acidosis
- Acute gastroenteritis

ANOREXIA, NAUSEA, VOMITING
(CONTINUED)
 EVALUATION:
- Drug holiday
- Lactic acid level
- Fasting testosterone level
- GI evaluation (endoscopy, CT scan)
- Intracranial evaluation (head CT scan or MRI)
 TREATMENT: Treat underlying condition.

DIARRHEA
Acute
- as ≥3 loose or watery stools for 3 to 10
days
Chronic
- as >2 loose or watery stools/day for ≥30
days in advanced HIV infection

MEDICATION-RELATED ACUTE DIARRHEA
Main antiretroviral agents:
 Nelfinavir
 Lopinavir/ritonavir
 Saquinavir
Management:
 Loperamide
 Pancreatic enzymes

PATHOGEN DETECTION
Blood culture: MAC, Salmonella
Stool culture: Salmonella, Shigella, C.
jejuni, Vibrio, Yersinia, E. Coli 0157
Stool assay for C. difficile toxin A and B
Ova & Parasite examination + AFB
(Cryptosporidia, Cyclospora, Isospora),
trichrome or other stain for Microsporidia
and antigen detection (Giardia)

MAIN PATHOGENS OF ACUTE DIARRHEA
 BACTERIAL: Campylobacter jejuni, Clostridium
difficile, Escherichia coli, Salmonella, Shigella
 ENTERIC VIRUSES: Adenovirus, Astrovirus,
Picornavirus, Calicivirus
 IDIOPATHIC

ACUTE DIARRHEA:
CAMPYLOBACTER JEJUNI
 FREQUENCY: 4% to 8% of HIV infected patients
with acute diarrhea
 CLINICAL FEATURES: Watery diarrhea or
bloody flux, fever, fecal leukocytes variable; any
CD4 count
 DIAGNOSIS: Stool culture; most laboratories
cannot detect C. cinaedi, C. fennelli, etc.

ACUTE DIARRHEA: CLOSTRIDIUM DIFFICILE
 FREQUENCY: 10% to 15% of HIV infected patients with acute
diarrhea
 CLINICAL FEATURES: Watery diarrhea, fecal WBCs variable;
fever and leukocytosis common; prior antibacterial agents
(especially clindamycin, ampicillin, and cephalosporins); any
CD4 count
 DIAGNOSIS:
- Endoscopy: pseudomembranous colitis, colitis, or normal
(this procedure is not usually indicated)
- Stool toxin assay
- CT scan: Colitis with thickened mucosa
 TREATMENT: Metronidazole, Vancomycin.
!!! Antiperistaltic agents are contraindicated.
 RESPONSE:
- fever resolves within 24 h
- diarrhea resolves within 5 days
- 20% to 25% have relapses at 3 to 14 days after treatment
stopped.

ACUTE DIARRHEA: ENTERIC VIRUSES
 FREQUENCY: 15% to 30% of HIV infected
patients with acute diarrhea
 CLINICAL FEATURES: Watery diarrhea, acute,
but one-third become chronic; any CD4 cell
count
 DIAGNOSIS: clinical laboratories cannot detect
most viruses
 TREATMENT: Supportive treatment (Lomotil or
Loperamide) + rehydration

ACUTE DIARRHEA: SALMONELLA
 CLINICAL FEATURES: Watery diarrhea, fever,
fecal WBCs variable; any CD4 count
 DIAGNOSIS: Stool culture, blood culture

ACUTE DIARRHEA: SHIGELLA
 FREQUENCY: 1% to 3% of HIV infected patients
with acute diarrhea
 CLINICAL FEATURES: Watery diarrhea or
bloody flux, fever, fecal WBCs common; any
CD4 count
 DIAGNOSIS: Stool culture

ACUTE DIARRHEA: ESCHERICHIA COLI
Agent Clinical Presentation
Enterotoxigenic (ETEC) Traveler’s diarrhe
Enterohemorrhagic
0157:H7 (EHEC)
Bloody diarrhea
Enteroinvasive (EIEC) Dysentery
Enteropathic (EPEC) Watery diarrhea
!!! EHEC - Antibiotics contraindicated

TREATMENT OF ACUTE DIARRHEA
Non-typhoid
salmonelloses
Ciprofloxacin 500mg PO BID for > 2 weeks
+ Rehydration
Shigelloses Ciprofloxacin 500mg PO BID for 5 days, OR
Nalidixic acid 500mg PO QID for 5 days, OR
Sulphamethoxazole/trimethoprim 800mg/160mg PO BID for
5 days
+ Rehydration
Campylobac-
teriosis
Erythromycin 500 mg PO qid x 5 days; fluoroquinolone
resistance rates are >20%
+ Rehydration
Virus diarrhea Rehydration
ETEC Cipro 500 mg bid x 3 days or TMP-SMX DS bid x 3 days
+ Rehydration
EIEC Cipro 500 mg bid x 5 days or TMP-SMX DS bid x 5 days
+ Rehydration

ACUTE DIARRHEA: IDIOPATHIC DIARRHEA
 CLINICAL FEATURES: Variable noninfectious
causes; rule out medications, dietary, irritable
bowel syndrome; any CD4 cell count
 DIAGNOSIS: Negative studies including culture,
O&P examination, and C. difficile toxin assay
 TREATMENT (sever acute idiopathic diarrhea):
empiric antibiotic treatment

 CYTOMEGALOVIRUS
 ENTAMOEBA HISTOLYTICA
 GIARDIA LAMBLIA
 CRYPTOSPORIDIA
 MICROSPORIDIA
 MYCOBACTERIUM AVIUM COMPLEX (MAC)
 IDIOPATHIC (PATHOGEN-NEGATIVE)
MAIN PATHOGENS OF CHRONIC DIARRHEA

CHRONIC DIARRHEA: CRYPTOSPORIDIA
 FREQUENCY: 10% to 30% of chronic diarrhea in AIDS patients
 CLINICAL FEATURES: Enteritis; watery diarrhea; no fecal
WBCs; fever variable; malabsorption; wasting; large stool volume
with abdominal pain; remitting symptoms for months; CD4 cell
count <150/mm3 is associated with recurrent or chronic disease.
 DIAGNOSIS: AFB smear of stool to show oocyst of 4-6 µm
 TREATMENT:
- Best results are with HAART
- Paromomycin 1000 mg bid or 500 mg PO bid x 7 days; efficacy
is marginal
- Azithromycin 600 mg/day + paromomycin (above doses) x ≥4w
- Nutritional support plus Lomotil
 RESPONSE: The most effective treatment is immune
reconstitution; even small rises in CD4 count often succeed in
controlling diarrhea

CHRONIC DIARRHEA: CYTOMEGALOVIRUS
 FREQUENCY: 15% to 40% of chronic diarrhea in AIDS patients
 CLINICAL FEATURES: Colitis and/or enteritis; fecal WBC
and/or blood; cramps; fever; watery diarrhea ± blood; may
cause perforation; hemorrhage, toxic megacolon, ulceration;
CD4 cell count <50/mm3
 DIAGNOSIS:
- Biopsy
- CT scan
- Cannot establish this diagnosis with CMV markers in blood or
stool; need biopsy
 TREATMENT:
1) HAART
2) Valganciclovir 900 mg PO bid x 3 weeks, then 900 mg qd
3) Ganciclovir 5 mg/kg IV bid x 2 weeks, then valganciclovir 900
mg/day
4) Foscarnet 40-60 mg/kg IV q8h 2 x weeks, then 90 mg/kg/day
 RESPONSE: variable; foscarnet and ganciclovir are equally
effective or ineffective

CHRONIC DIARRHEA: ENTAMOEBA HISTOLYTICA
AIDS patients
 CLINICAL FEATURES: Colitis; bloody stools;
cramps; no fecal WBCs (bloody stools); most are
asymptomatic carriers; any CD4 cell count
 DIAGNOSIS: Stool O&P examination.
 TREATMENT: Metronidazole 500-750 mg PO or
IV tid x 5 to 10 days, then iodoquinol 650 mg PO
tid x 21 days or paromomycin 500 mg PO qid x 7
days

CHRONIC DIARRHEA: GIARDIA LAMBLIA
AIDS patients
 CLINICAL FEATURES: Enteritis; watery
diarrhea ± malabsorption, bloating; flatulence;
any CD4 cell count
 DIAGNOSIS: Antigen detection
 TREATMENT: Metronidazole 250 mg PO tid x 10
days

CHRONIC DIARRHEA: CYCLOSPORA
 FREQUENCY: <1% of chronic diarrhea in AIDS
patients
diarrhea; CD4 cell count <100/mm3
 DIAGNOSIS: Stool AFB smear: Resembles
cryptosporidia
 TREATMENT: TMP-SMX 1 DS bid x 3 days

CHRONIC DIARRHEA: ISOPORA BELLI
AIDS patients
diarrhea; no fecal WBCs; no fever; wasting;
malabsorption; CD4 cell count <100/mm3
 DIAGNOSIS: AFB smear of stool; oocysts: 20 to
30 µm
 TREATMENT: TMP-SMX 3-4 DS/day;
Pyrimethamine 50-75 mg/day PO x 7 to 10 days

CHRONIC DIARRHEA:
MICROSPORIDIA (ENTEROCYTOZOON BIENEUSI OR
ENTEROCYTOZOON (SEPTATA) INTESTINALIS)
 FREQUENCY: 15% to 30% of chronic diarrhea in AIDS
patients
 CLINICAL FEATURES: Enteritis, watery diarrhea, no fecal
WBCs; fever uncommon; remitting disease over months;
malabsorption; wasting; CD4 cell count <100/mm3
 DIAGNOSIS:
 Special trichrome stain
 Alternative: Fluorescent stains with similar sensitivity
 TREATMENT:
 Albendazole 400-800 mg PO bid x ≥3 weeks; efficacy is established
only for Septata intestinalis
 Fumagillin 60 mg PO qd x 14 days for E. bieneusi; monitor for
neutropenia and thrombocytopenia

CHRONIC DIARRHEA: MYCOBACTERIUM AVIUM
COMPLEX (MAC)
patients
 CLINICAL FEATURES: Enteritis; watery diarrhea; no
fecal WBCs; fever and wasting common; diffuse
abdominal pain in late stage; CD4 cell count <50/mm3
 DIAGNOSIS:
 Positive blood cultures for MAC
 Biopsy
 CT scan
 TREATMENT:
 Clarithromycin 500 mg PO bid + EMB 15 mg/kg/day
 Azithromycin 600 mg/day + EMB 15 mg/kg/day ± rifabutin 300
mg/day
 RESPONSE: Slow response over several weeks

CHRONIC DIARRHEA: IDIOPATHIC (PATHOGEN-
NEGATIVE)
patients, who undergo a full diagnostic evaluation
including endoscopy
 CLINICAL FEATURES:
 Usually low-volume diarrhea that resolves spontaneously or is
controlled with antimotility agents
 Typically not associated with significant weight loss and often
resolves spontaneously
 DIAGNOSIS:
 Biopsy
 With pathogen-negative, persistent, large volume diarrhea, must
rule out KS and lymphoma
 TREATMENT: Supportive care

CHOLANGIOPATHY
 CAUSE:
main - Cryptosporidiosis
other - Microsporidia, CMV, and Cyclospora
idiopathic – 20-40%
 Seen primarily in late stage AIDS (CD4 count
<100 cells/mm3)
 PRESENTATION: Right upper quadrant pain,
LFTs show cholestasis
 DIAGNOSIS: ERCP (preferred); ultrasound is
75% to 95% specific
 TREATMENT: Based on cause

PANCREATITIS IN PATIENTS WITH HIV
INFECTION
 MAJOR CAUSES
- Drugs: ddI or ddI + d4T ± hydroxyurea
- CMV
- Alcoholism
 DIAGNOSIS
- Amylase
- Lipase (same sensitivity but more specificity)
- CT Scan
 TREATMENT: Supportive

RESPIRATORY ILLNESSES IN PERSONS WITH
HIV INFECTION & AID
Bacterial infections:
Pneumococcal pneumonia
H. influenzae pneumoniae
Klebsiella pneumonia
Staphylococcal pneumonia
M. tuberculosis
pneumoniae
MAC pneumonia
Possible complications:
·Lung abscess
·Empyema
·Pleural effusion
·Pericardial effusion
·Pneumothorax
Viral infections:
Cytomegalovirus
Herpes simplex virus
Possible complications:
Lymphocytic interstitial pneumonitis
Fungal infections:
Pneumocystis pneumonia
Cryptococcosis
Histoplasmosis
Aspergillosis
Other conditions:
Kaposi's sarcoma
Lymphoma

CAUSE OF PULMONARY DISODERS
WITH HIV
 The single major prospective study of
pulmonary complications of HIV was
discontinued in the pre-HAART era – 1995. Data
from 3 years (1992-1995) showed 521
infections:
- PCP – 232 (45%),
- Pyogenic bacteria – 220 (42%),
- Tuberculosis – 25 (5%),
- CMV – 19 (4%),
- Aspergillus – 12 (2%), and
- Cryptococcosis – 7 (1%)

PNEUMONIA ETIOLOGY CORRELATED WITH
CD4 COUNT
CD4 count
>200
cells/mm3
S. pneumoniae, M. tuberculosis, S.
aureus (IDU), Influenza
CD4 count
50-200
cells/mm3
Above + P. carinii, cryptococcosis,
histoplasmosis, coccidioidomycosis,
Nocardia, M. kansasii, Kaposi’s sarcoma
CD4 count
<50
cells/mm3
Above + P. aeruginosa, Aspergillus,
MAC, CMV

UNCOMMON ASSOCIATION OF CHEST X-RAY
CHANGES AND ETIOLOGY OF PNEUMONIA
Consolidation Nocardia, M. tuberculosis, M. kansasii,
Legionella,
B. Bronchiseptica
Reticulonodular
infiltrates
Kaposi’s sarcoma, toxoplasmosis, CMV,
leishmania, lymphoid interstital pneumonitis
Nodules Kaposi’s sarcoma, Nocardia
Cavity M. kansasii, MAC, Legionella, P. carinii,
lymphoma, Klebsiella, Rhodococcus equi
Hilar nodes M. kansasii, MAC
Pleural effusion Cryptococcosis, MAC, histoplasmosis,
coccidioidomycosis, aspergillosis,
anaerobes, Nocardia, lymphoma,
toxoplasmosis, primary effusion lymphoma

CORRELATION OF CHEST X-RAY CHANGES AND
ETIOLOGY OF PNEUMONIA
Consolidation Pyogenic bacteria, Kaposi’s sarcoma, cryptococcosis
Reticulonodular
infiltrates
P. carinii, M. tuberculosis, histoplasmosis,
coccidioidomycosis
Nodules M. tuberculosis, cryptococcosis
Cavity M. tuberculosis, S. Aureus (IDU), Nocardia, P.
aeruginosa, cryptococcosis, coccidioidomycosis,
histoplasmosis, aspergillosis, anaerobes
Hilar nodes M. tuberculosis, histoplasmosis,
coccidioidomycosis, lymphoma, Kaposi’s sarcoma
Pleural effusion Pyogenic bacteria, Kaposi’s sarcoma, M. tuberculosis
(congestive heart failure, hypoalbuminemia)

BACTERIAL INFECTION: GRAM-NEGATIVE BACILLI
 Course: Acute, purulent sputum
 Frequency: uncommon (except with nosocomial
infection or neutropenia)
 Setting: P. auruginosa is relatively common in
late-stage disease, cavitary disease, or chronic
antibiotic exposure (median CD4 50 cells/mm3)
 Typical findings: Lobar or bronchopneumonia
 Diagnosis: Sputum GS and culture (sensitivity is
>80%, but specificity is poor)

BACTERIAL INFECTION: HAEMOPHILUS INFLUENZAE
 Frequency: 100-fold higher then healthy
controls
 Setting: most infections are caused by
unencapsulated strains
 Typical findings: bronchopneumonia
 Diagnosis: Sputum GS and culture (sensitivity
of culture is 50%; prior antibiotics usually
preclude growth)

BACTERIAL INFECTION: LEGIONELLA
 Course: Acute mucopurulent sputum
 Frequency: uncommon.
 Setting: HIV-associated is debated
 Typical findings: bronchopneumonia;
sometimes multiple infiltrates in noncontiguous
segments
 Diagnosis: Sputum culture; urinary antigen

BACTERIAL INFECTION: NOCARDIA
 Course: Chronic or asymptomatic; sputum
production
 Frequency: Uncommon
 Setting: Frequency higher with chronic
corticosteroid use (median CD4 50 cells/mm3)
 Typical findings: Nodule or cavity
 Diagnosis: Sputum or fiberoptic bronchoscopy;
GS

BACTERIAL INFECTION: STAPH. AUREUS
 Course: Acute, subacute, or chronic purulent
sputum
 Frequency: Uncommon, except with injected
drug use and tricuspid valve endocarditis with
septic emboli
 Typical findings: Bronchopneumonia, cavitary
disease, septic emboli with cavities ± effusion
 Diagnosis: Blood, sputum GS and
culture(sputum culture is sensitive, but specificity
is poor). Blood cultures are nearly always
positive with endocarditis

BACTERIAL INFECTION: STREPT. PNEUMONIAE
 Course: Acute, purulent sputum ±pleurisy
 Frequency: common, all stages; 100-fold higher
then healthy controls
 Setting: higher with low CD4 and with smoking
 Typical findings: Lobar or bronchopneumonia
±pleural effusion
 Diagnosis: Blood cultures often positive, sputum
GS, Quellung, culture (sensitivity of culture is
50%; prior antibiotics usually preclude growth)

FUNGAL INFECTION: ASPERGILLUS
 Course: Acute or subacute
 Frequency: Up to 4% of AIDS patients
 Setting: usually advanced HIV infection (median
CD4 count 30 cells/mm3); about 50% have
severe neutropenia (ANC <500/mm3) ± chronic
steroids; disseminated disease is uncommon
 Typical findings: Focal infiltrate; cavity - often
pleural-based, diffuse infiltrates or
reticulonodular infiltrates
 Diagnosis: Sputum stain and culture;
falsepositive and false-negativecultures
common. Best tests:Tissue pathology or sputum
smear and typical CT and clinical features

FUNGAL INFECTION: CANDIDA
 Course: Chronic or subacute
 Frequency: Common isolate, rare cause of
pulmonary disease (median CD4 count 50
cells/mm3)
 Typical findings: Bronchitis; rare cause of
pneumonia (some say it does not exist)
 Diagnosis: Recovery in sputum or FOB
specimen is meaningless (up to 30% of all
expectorated sputumand FOB cultures in
unselected patients yield Candida sp.); must
have histologic evidence of invasion on biopsy

FUNGAL INFECTION: COCCIDIOIDES IMMITIS
 Frequency: Up to 10% of AIDS patients in
endemic area
 Setting: usually advanced HIV infection (median
CD4 count 50 cells/mm3); disseminated disease
in 20% to 40%
 Typical findings: Diffuse nodular infiltrates, focal
infiltrate, cavity; hilar adenopathy
 Diagnosis: Sputum, induced sputum, or FOB
stain and culture; KOH of expectorated sputum is
rarely positive; serology positive in 70%; blood
cultures positive in 10%

FUNGAL INFECTION: CRYPTOCOCCUS
 Course: Chronic, subacute, or symptomatic
 Frequency: Up to 8% to 10% in AIDS patients
 Setting: late-stage HIV infection (median CD4
count 50 cells/mm3); 80% have cryptococcal
meningitis
 Typical findings: Nodule, cavity, diffuse or
nodular infiltrates
 Diagnosis: Sputum, induced sputum, or FOB
stain and culture; serum cryptococcal antigen
usually positive; CSF analysis indicated if
antigen or organism found at any site

FUNGAL INFECTION: HISTOPLASMA
CAPSULATUM
 Frequency: Up to 15% of AIDS patients in endemic area
 Setting: usually advanced HIV infection with
disseminated histoplasmosis (median CD4 count 50
cells/mm3)
 Common features: Fever, weight loss,
hepatosplenomegaly, lymphadenopathy
 Typical findings: Diffuse nodular infiltrates, nodule, focal
infiltrate, cavity, hilar adenopathy
 Diagnosis: Best test for diagnosis and followup of
treatment is serum and urine polysaccharide antigen
assay, with yield of 85% (blood) and 97% (urine).
Serology positive in 50% to 70%; yield with culture of
sputum – 80%, marrow – 80%; blood cultures positive in
60% to 85%

FUNGAL INFECTION: PNEUMOCYSTIS JIROVECI
(PREVIOUSLY KNOWN AS PNEUMOCYSTIS CARINII)
 Course: Acute or subacute
 Presentation:
- Usually present with cough, shortness of breath and
fever
- Often patients have features of respiratory failure
(shortness of breath and cyanosis)
- Occasionally patients have no chest signs
 Frequency: Very common in late stages of HIV
infection (>95% have CD4 <200 cell/mm3)
 Setting: infrequent in patients compliant with
TMP-SMX prophylaxis

FUNGAL INFECTION: PNEUMOCYSTIS JIROVECI
(PREVIOUSLY KNOWN AS PNEUMOCYSTIS CARINII)
 X-ray findings:
- Interstitial infiltrates with characteristic ground glass
appearance;
- Negative X-ray in early stages, about 15% to 20%;
- Atypical findings in 20% (upper lobe infiltrates, focal
infiltrates, nodules, cavitary disease, or mediastinal
lymphadenopathy)
 Diagnosis: Cytology of induced sputum (mean yield of
60% in proven cases) and bronchoalveolar lavage (mean
yield of 95%)
 Treatment and prophylaxis: see D3-3

VIRUSES INFECTION: CMV
 Course: Subacute or chronic
 Frequency: Common isolate, rare cause of
pulmonary disease
 Setting: Advanced HIV infection (median CD4
count 20 cells/mm3)
 Typical findings: Interstitial infiltrates
 Diagnosis: Yield with FOB is 20% to 50%,
culture requires more than 1 week; shell culture
1 to 2 days; diagnosis of CMV pneumonitis
(disease) requires CMV seen on cytopath or
biopsy, progressive disease, and no alternative
pathogen

VIRUSES INFECTION: HCV, VZV, RSV,
PARAINFLUENZA
 Course: Acute
 Frequency: Rare causes of pneumonia
 Typical findings: Diffuse or nodular pneumonia,
bronchopneumonia
 Diagnosis:
 Culture of sputum or FOB commonly yields HSV as a
contaminant from upper airways
 RSV is rare in adults but has increased frequency in
immunosuppressed host, is easily detected with DFA
stain of respiratory secretions

VIRUSES INFECTION: INFLUENZA
 Frequency: Frequency and course minimally
different from patients without HIV infection
 Setting: Bacterial super-infection is common
with S. pneumoniae, S. aureus and H. influenza
 Typical findings: Bronchopneumonia, interstitial
infiltrates
 Diagnosis: Culture of throat, nasopharyngeal
aspirates, washing, and serology;

MYCOBACTERIUM AVIUM COMPLEX (MAC)
 Course: Chronic or asymptomatic
 Frequency: Moderate for disseminated disease
but uncommon for pulmonary disease
 Setting: late stage HIV (median CD4 20
cells/mm3)
 Typical findings: Variable
 Diagnosis: Sputum, FOB, or induced sputum
AFB stain and culture; must distinguish from
MTB (DNA probe or radiometric culture
technique); MAC may colonize airways without
causing pulmonary disease; requires 1 to 2
weeks for growth in Bactec system

MYCOBACTERIUM KANSASII
 Frequency: Uncommon
 Setting: Late-stage HIV (median CD4 50
cells/mm3)
 Typical findings: Cavitary disease, nodule, cyst,
infiltrate, or normal chest Х-ray
 Diagnosis: Sputum, induced sputum, or FOB,
AFB stain and culture

KAPOSI’S SARCOMA (KS)
 Course: Asymptomatic or chronic progressive
cough and dyspnea
 Frequency: Moderately common in patients with
cutaneous KS and advanced HIV disease
 Typical findings: Interstitial, alveolar, or nodular
infiltrates, hilar adenopathy (25%), scan usually
negative, pleural effusions (40%); gallium
 Diagnosis: FOB often shows discolored
endobronchial nodule(s); yield of histopathology
from transbronchial or transthoracic biopsy is only
20% to 30%. Pulmonary infiltrate on x-ray with
negative gallium scan is highly suggestive

LYMPHOCYTIC INTERSTITIAL PNEUMONIA (LIP)
 Frequency: Uncommon in adults
 Setting: median CD4 - 200-400 cells/mm3
 Typical findings: Diffuse reticulonodular
infiltrates, resembles PCP on chest x-ray
 Diagnosis: Requires tissue for histopathology;
yield with FOB biopsy is 30% to 50%; open lung
biopsy often required

LYMPHOMA
 Frequency: Uncommon, but may be presenting
site
 Typical findings: Interstitial, alveolar, or nodular
infiltrates; cavity, hilar adenopathy, pleural
effusions
 Diagnosis: Requires tissue for histopathology;
yield with FOB biopsy is poor; open lung biopsy
often required

TREATMENT (EXCEPT PNEUMOCYSTIS)
Gram-negative
bacilli
Need in vitro susceptibility tests. Long-term ciprofloxacin
usually results in relapse and resistance to P.
aeruginosa.
Staph.aureus -MSSA: Nafcillin/oxacillin, cefuroxime, TMP-SMX,
clindamycin
-MRSA: Vancomycin
Haemophilus
influenzae
Oral: Amox-CA, azithromycin, TMP-SMX,
fluoroquinolone, cephalosporin; Intravenous: Cefotaxime,
ceftriaxone
Aspergillus Amphotericin B or itraconazole or caspofungin
Candida Fluconazole or amphotericin B
C.immitis Fluconazole, itraconazole, or amphotericin B
Cryptococcus Fluconazole without CNS involvement amphotericin B
H.capsulatum Itraconazole or amphotericin B
Legionella Fluoroquinolone, macrolide, doxycycline

TREATMENT (EXCEPT PNEUMOCYSTIS)
CMV Ganciclovir, foscarnet or cidofovir
HSV, VZV, RSV,
parainfluenza
HSV, VZV: Acyclovir
RSV: Ribavirin (?)
Influenza Amantadine/ramantadine neuramidase inhibitors:
Oseltamivir or zanamivir
Asp.pneumonia 1)Clindamycin 2)Beta-lactam + Betalactamase inhibitor
KS -Liposomal daunorubicin or doxorubicin
-Taxol
-Adriamycin, bleomycin/vincristin, or vinblastin
LIP Prednisone (?)
Lymphoma 1)CHOP 2)BACOD + G-CSF
Str.pneumoniae PO: Amoxicillin, macrolide, cefpodoxime,
fluoroquinolone
IV: Cefotaxime, ceftriaxone, fluoroquinolone

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