HIV Associated Opportunistic Infections in Ethiopia

1
HIV Associated Opportunistic Infections in
Ethiopia

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

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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

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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

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Major diagnostic categories of HIV infected
patients (contd.)

• Pneumocystis pneumonia (34) 14.3
• Bacterial pneumonia (22) 9.3
• Kaposi's sarcoma (20) 8.4

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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

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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

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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

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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  Ethiopia estimated to be 44 (MOH, unpublished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).

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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

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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

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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

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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

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HIV Associated Cryptococcal Meningitis

• Clinical presentation
• Occurs in persons with advanced immunodeficiency,
  CD4 lt100/µl
• Subtle clinical presentation, headache, fever,
  malaise absent meningeal signs
• Altered sensorium in 25, and focal signs 5

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HIV Associated Cryptococcal Meningitis

• Diagnosis
• CSF, Indian ink/culture yield about 75
• Cryptococcal antigen assays, CSF/serum
• Blood culture

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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.

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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.

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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

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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

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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

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Management of toxoplasma encephalitis

• Two major regimens
• Pyrimethamine plus sulfadiazine
• OR
• Pyrimethamine plus clindamycin
• both with folinic acid
• duration of treatment six weeks
• Suppressive/maintenance treatment continued for
  life

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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.

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Preventive therapies for toxoplasmosis

• Indications
• CD4 count lt 100 cells/µl
• Positive T gondii serology
• Regimens
• TMP-SMX two tablets per day (single strength)
• Alternative regimens
• Dapsone 50mg daily, plus pyrimethamine 50 mg po
  weekly

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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?

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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

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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

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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

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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

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Pneumocystis pneumonia, preventive therapies

• Prevention is strongly recommended for HIV
  infected person with significant immune
  deficiency
• Indications
• CD4 count lt 200/µl
• Prior episode of PCP
• HIV associated thrush
• Unexplained fever

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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