Download HIV Associated Opportunistic Infections in Ethiopia

HIV Associated Opportunistic Infections
in Ethiopia
Daniel Fekade MD, MSc
Faculty of Medicine, Addis Ababa
University
HIV ASSOCIATED OPPORTUNISTIC
INFECTIONS
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Opportunistic infections are major causes of
morbidity & mortality among HIV infected
patients
Many of the common opportunistic infections
are both preventable/treatable
However, inadequate infrastructures make it
difficult to implement prevention/treatment
programs in many developing countries
Major diagnostic categories among
237 HIV infected medical inpatients
Tikur Anbessa Hospital, Addis Ababa, Jan-Dec,
2000.
Diagnoses, (Number of patients), Percent of total
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Oropharyngeal candidiasis (136), 57.4%
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Tuberculosis (131), 55.3%
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CNS mass lesion (74), 31.2%
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Sepsis (59), 24.9%
Major diagnostic categories of HIV
infected patients (contd.)
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Pneumocystis pneumonia (34) 14.3%
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Bacterial pneumonia (22) 9.3%
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Kaposi's sarcoma (20) 8.4%
Major diagnostic categories of HIV
infected patients (contd.)
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AIDS dementia (14) 5.9%
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Cryptococcal meningitis (14) 5.9%
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Peripheral neuropathy (11) 4.6%
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Myelopathy (11) 4.6%
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Lymphoma (7) 3.0 %
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Others* (82) 34.6%
Causes of hospital death among HIV
positive medical inpatients.
In hospital mortality rate (70) 30%
Cause of death (Number of patients) Percent of
total (%)
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Tuberculosis (41) 56.2%
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Sepsis (41) 56.2%
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CNS mass lesion (26) 35.6%
Causes of hospital death among HIV
medical inpatients (contd.)
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Bacterial pneumonia (10) 13.7%
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Pneumocystis pneumonia (8) 11%
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Cryptococcal meningitis (6) 8%
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Others*(16) 21.9%
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Unknown (4) 5.5%
Management of HIV- associated
tuberculosis
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Tuberculosis is the leading opportunistic
infection in persons infected with HIV in
developing countries.
HIV seroprevalence among tuberculosis
patients in Ethiopia estimated to be 44%
(MOH, unpublished report 1994)
5%-10% of HIV seropositive patients develop
active disease annually (cf. 5% cumulative
lifelong risk in seronegatives).
Clinical presentation of tuberculosis
among 131 HIV infected patients
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Prevalence of TBc among HIV medical
inpatients, (131/237) 55.3%
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Disseminated TBc (66/131) 50.4%
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Pulmonary TB (37/131) 27%
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Smear positive (8/37) 21.8%
Smear negative(29/37) 78.4
Meningitis (11) 8.4%
Clinical presentation of tuberculosis
among 131 HIV infected patients
(contd.)
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Lymphnode (5) 3.8%
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Pleural(5) 3.8%
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Tuberculoma (4) 3.1%
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Spondylitis (3) 2.3%
Problems in the management of HIV
associated tuberculosis:
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High incidence of adverse drug reactions (18%
vs. 5%)
Atypical presentation/extra pulmonary disease
Resistance to any one or more of the first line
anti-TB drugs in Ethiopia, 15% - 33%
MDR TB, resistance to both rifampicin and
INH, among previously untreated patients 5%
Preventive therapy against
tuberculosis in people living with
HIV
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Progression to active disease in persons
latently infected, 3.5-9.7 per 100 person years;
relative risk – 20
TB prophylaxis increases survival of HIV
infected persons at risk of TB e.g. persons
residing in endemic regions.
INH preventive therapy for a year costs US$
5.15 – affordable
However, inadequate infrastructures make it
difficult to be practicable
HIV Associated Cryptococcal
Meningitis
Clinical presentation:
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Occurs in persons with advanced
immunodeficiency, CD4 <100/μl
Subtle clinical presentation, headache, fever,
malaise; absent meningeal signs
Altered sensorium in 25%, and focal signs 5%
HIV Associated Cryptococcal
Meningitis
Diagnosis
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CSF, Indian ink/culture; yield about 75%
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Cryptococcal antigen assays, CSF/serum
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Blood culture
HIV Associated Cryptococcal
Meningitis
Treatment
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Induction: Amphotericine B; 0.7-1mg/kg/day
IV,
 With/without flu cytosine 100mg/kg/day
PO for 14 days,
Consolidation: fluconazole 400mg/day for 810 weeks,
Maintenance: fluconazole 200mg/day, lifelong.
Management of Toxoplasmosis in
Patients with HIV Infection
Epidemiology:
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Toxoplasma gondii is a zoonotic infection
Cats are the definitive hosts, and excrete T
gondii oocysts in their feces
T gondii cysts are found in undercooked meat
Prevalence of latent T gondii infection is high
in Ethiopia; 85% seropositive for antitoxoplasma antibodies.
Toxoplasmosis, clinical presentation:
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Typical presentation is an altered mental state,
seizures, weakness, and cranial nerve
abnormalities
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Onset is usually subacute, nearly 90% of cases
develop focal neurologic signs
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Commonly affected areas, basal ganglia, brain
stem and cerebellum
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Extracranial sites may occur, retina,
myocardium, and lungs
Diagnosis of toxoplasmosis:
Neuro- radiologic imaging:
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Contrast enhanced CT, hypodense multiple
lesions with ring-enhancement after IV
contrast
Solitary lesions present with diagnostic
difficulties
Therapeutic trial, clinical / radiological
response in two to three weeks
Toxoplasmosis, diagnosis (contd.)
Serologic assays:
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A negative Toxoplasma antibody test makes
the diagnosis of toxoplasmosis less likely.
Histologic diagnosis:
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Brain biopsy; Wright-Giemsa, fluorescent
antibody staining
Management of toxoplasma
encephalitis
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Two major regimens:
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Pyrimethamine plus sulfadiazine
OR
Pyrimethamine plus clindamycin
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both with folinic acid
duration of treatment six weeks
Suppressive/maintenance treatment
continued for life
Management of toxoplasmosis
(contd.)
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High rates of adverse reactions with
pyrimethamine-sulfadiazine
Experimental therapies: azithromycin,
clarithromycin, trimetrexate, doxycycline,
atovaquoune
Corticosteroids may be used in patients with
cerebral edema and increased intracranial
pressure.
Preventive therapies for
toxoplasmosis:
Indications
 CD4+ count < 100 cells/μl
Positive T gondii serology
Regimens
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TMP-SMX two tablets per day (single strength)
Alternative regimens
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Dapsone 50mg daily, plus pyrimethamine 50
mg po weekly
The management Pneumocystis
pneumonia in patients with HIV
infection
Epidemiology:
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PCP is the most frequent opportunistic
infection in industrialized countries, but less
frequent in Africa.
Infection transmitted from human to human,
or from environmental reservoirs to humans.
Antibody studies suggest that most humans
are infected early in life
Infection transient, or long lived with periods
of latency?
Pneumocystis pneumonia, Clinical
presentation:
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Onset, subacute
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Dyspnea, non-productive cough, fever
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Chest X-rays; diffuse bilateral interstitial
infiltrates
Numerous examples atypical radiographic
presentations e.g. unilateral infiltrates,
cavities, effusions
Hypoxemia, and elevated serum LDH
Pneumocystis pneumonia, diagnosis:
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Demonstration of the organism in
bronchoalveolar lavage (BAL), sensitivity 95100%
Induced sputum, sensitivity 30-90%
Pulmonary biopsy, sensitivity 90-95%,
reserved for unusual cases
Staining; Wright-Giemsa, methenamine silver,
direct immunoflourescence
Treatment of pneumocystis
pneumonia:
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TMP-SMX is the gold standard for the
treatment of PCP
It can be given either IV, or PO
Usual dose, 15mg/kg/day (based on the
trimethoprim component) in 3-4 divided doses
for 14 days (typical oral dosage 2 DS tid).
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Adverse drug reactions in 25-50%, primarily
skin rash +/- fever
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Patients with moderate/severe disease should
receive corticosteroids
Pneumocystis pneumonia,
alternative regimens:
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Clindamycin 600 mg IV q8h or 300-450 mg PO
q6h + primaquine 30 mg base/day, 21 days
Pentamidine 4 mg/kg/day IV, 21 days (usually
reseved for severe cases)
Atovaquone 750 mg suspension PO with bid,
21 days
Pneumocystis pneumonia,
preventive therapies
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Prevention is strongly recommended for HIV
infected person with significant immune
deficiency:
Indications:
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CD4+ count < 200/μl
Prior episode of PCP
HIV associated thrush
Unexplained fever
Preventive therapy, pneumocytis
pneumnia
Regimens:
 TMP-SMX two tablets/day (single strength)
 TMP-SMX two tablets three times per week
Alternative regimens:
 Dapsone 100 mg PO daily
 Dapsone 50 mg PO daily, plus pyrimethamine
50 mg PO weekly, plus leucovirin25 mg Po
weekly
 Aerosolized pentamidine 300 mg monthly via
nebulizer
 Atovaqoune 1500 mg daily