HIV Associated Opportunistic Infections in Ethiopia

Daniel Fekade MD, MSc Faculty of Medicine, Addis Ababa University

HIV ASSOCIATED OPPORTUNISTIC INFECTIONS

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

Oropharyngeal candidiasis (136), 57.4%

Tuberculosis (131), 55.3%

CNS mass lesion (74), 31.2%

Sepsis (59), 24.9%

Major diagnostic categories of HIV infected patients (contd.)

Pneumocystis pneumonia (34) 14.3%

Bacterial pneumonia (22) 9.3%

Kaposi's sarcoma (20) 8.4%

Major diagnostic categories of HIV infected patients (contd.)

AIDS dementia (14) 5.9%

Cryptococcal meningitis (14) 5.9%

Peripheral neuropathy (11) 4.6%

Myelopathy (11) 4.6%

Lymphoma (7) 3.0 %

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 (%)

Tuberculosis (41) 56.2%

Sepsis (41) 56.2%

CNS mass lesion (26) 35.6%

Causes of hospital death among HIV medical inpatients (contd.)

Bacterial pneumonia (10) 13.7%

Pneumocystis pneumonia (8) 11%

Cryptococcal meningitis (6) 8%

Others*(16) 21.9%

Unknown (4) 5.5%

Management of HIV- associated tuberculosis

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HIV seroprevalence among tuberculosis patients in Ethiopia estimated to be 44% (MOH, unpublished report 1994)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

Prevalence of TBc among HIV medical inpatients, (131/237) 55.3%

Disseminated TBc (66/131) 50.4%

Pulmonary TB (37/131) 27%

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.)

Lymphnode (5) 3.8%

Pleural(5) 3.8%

Tuberculoma (4) 3.1%

Spondylitis (3) 2.3%

Problems in the management of HIV associated tuberculosis:

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

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:

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

CSF, Indian ink/culture; yield about 75%

Cryptococcal antigen assays, CSF/serum

Blood culture

HIV Associated Cryptococcal Meningitis

Treatment

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

8-10 weeks,

Maintenance: fluconazole 200mg/day, lifelong.

Management of Toxoplasmosis in Patients with HIV Infection

Epidemiology:

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 anti-toxoplasma antibodies.

Toxoplasmosis, clinical presentation:

Typical presentation is an altered mental state, seizures, weakness, and cranial nerve abnormalities

Onset is usually subacute, nearly 90% of cases develop focal neurologic signs

Commonly affected areas, basal ganglia, brain stem and cerebellum

Extracranial sites may occur, retina, myocardium, and lungs

Diagnosis of toxoplasmosis:

Neuro- radiologic imaging:

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:

A negative Toxoplasma antibody test makes the diagnosis of toxoplasmosis less likely.

Histologic diagnosis:

Brain biopsy; Wright-Giemsa, fluorescent antibody staining

Management of toxoplasma encephalitis

Two major regimens:

Pyrimethamine plus sulfadiazineOR

Pyrimethamine plus clindamycin

both with folinic acid

duration of treatment six weeks

Suppressive/maintenance treatment continued for life

Management of toxoplasmosis (contd.)

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 serologyRegimens

TMP-SMX two tablets per day (single strength)

Alternative regimens

Dapsone 50mg daily, plus pyrimethamine 50 mg po weekly

The management Pneumocystis pneumonia in patients with HIV infection

Epidemiology:

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:

Onset, subacute

Dyspnea, non-productive cough, fever

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:

Demonstration of the organism in bronchoalveolar lavage (BAL), sensitivity 95-100%

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:

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).

Adverse drug reactions in 25-50%, primarily skin rash +/- fever

Patients with moderate/severe disease should receive corticosteroids

Pneumocystis pneumonia, alternative regimens:

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

Prevention is strongly recommended for HIV infected person with significant immune deficiency:

Indications:

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 weekAlternative 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