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 Zambia HIV National Guidelines
 


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 Guide Editors
 Editor In Chief
    Joel E. Gallant, MD, MPH

Pharmacology Editor
    Paul Pham, PharmD, BCPS

Zambia Guideline Team
   Peter Mwaba MMed PhD FRCP
   Alywn Mwinga MMed
   Isaac Zulu MMed MPH
   Velepie Mtonga MMed
   Albert Mwango MBChB
   Jabbin Mulwanda MMed FCS
 

 

 

Diagnosis>Opportunistic Infections>
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Pneumocystis carinii pneumonia

Noah Lechtzin, M.D., M.H.S.
08-06-2008

  • PCP less common in Africa than US or Europe (3-10% of individuals hospitalized with fever in Africa) & less common than pulmonary TB or bacterial pneumonia in Africa
  • Sx: fever, progressive dyspnea on exertion, dry cough
  • Differential diagnosis: TB, bacterial pneumonia, KS
  • Multiple diagnoses more likely in Zambia; consider empiric treatment if Sx consistent with PCP even if another process has also been diagnosed (e.g. TB)
  • Diagnostic capacity limited in Zambia, thus empiric therapy should be relied on

REFERENCES

Zambia Information Author: Christopher Hoffmann, MD, MPH

PATHOGENS

  • Pneumocystis jiroveci or jirovecii (formerly P. carinii), a fungal organism previously classified as a protozoan
  • Ubiquitous organism, respiratory transmission.
  • Active cases due to both reactivation of old and acquisition of new infection (N Engl J Med 2004;350:2487).

CLINICAL

  • Incidence peaked 1987-1988, with subsequent decrease due to prophylaxis and HAART.
  • Occurs when CD4 <200; risk increases with decreasing CD4 count.
  • Hx: gradual/subacute onset of cough (usually non-productive), dyspnea, fever in most pts. Chills, fatigue, chest pain, weight loss less common.
  • PE: fever, normal lung exam in ~50%. May have crackles and/or rhonchi.
  • Extrapulmonary involvement rare but can occur.
  • Hypoxemia and low DLCO common. Oxygen saturation may be normal at rest, but decreases with exercise

DIAGNOSIS

  • CXR: diffuse interstitial and/or alveolar infiltrates. 25% are normal with early disease.
  • CXR findings variable: Can have lobar infiltrates, nodules, masses, dense infiltrates, blebs, spontaneous pneumothorax and possibly pleural effusions.
  • Induced sputum diagnostic in 60%; BAL diagnostic in >90%.
  • Elevated LDH common but nonspecific.
  • Molecular based diagnostic tests on sputum or oral washings hold promise
  • Definitive Dx (by sputum or BAL) preferred over presumptive Dx, as presentation similar for other OIs, toxicity common during 3-week treatment course, and adjunctive corticosteroids may exacerbate other conditions.

TREATMENT

Initial Therapy

  • Preferred: TMP-SMX 5 mg/kg (of TMP component) q8h x21 days.
  • Alternative: clindamycin 600 mg q8h & primaquine 15-30 mg once-daily.
  • Alternative: dapsone 100 mg once-daily & TMP 5 mg/kg q8h x 21 days (mild-to-moderate PCP only).
  • Alternative: atovaquone 750 mg three times a day x 21 days (mild-to-moderate PCP only).
  • Alternative: pentamidine 4 mg/kg/day IV (high rate of side effects: ARF, hypotension, pancreatitis, hypo- and hyperglycemia, and electrolyte abnormalities).
  • Alternative: trimetrexate 45 mg/m2/day IV & leucovorin 20mg/m2 IV (moderate-to-severe PCP). Not as effective as regimen 2. Side effects include myelosuppression, hepatic and renal toxicity.
  • Regimens 1-4 can be given orally. Side effects including rash, anemia, hyperkalemia are common. Check G6PD before using dapsone.
  • Resistance to TMP-SMX described, but not clearly correlated with treatment outcome. Approach to pts failing TMP-SMX controversial.
Adjunctive Therapy

  • If PaO2 <70 mm Hg or A-a gradient > 35 mm Hg add corticosteroids: prednisone 40 mg PO twice-daily x5d, then 40 mg once-daily x5d, then 20 mg once-daily x11d (or IV equivalent).
Prophylaxis

  • Indications: CD4 <200 or history of thrush. Consider for CD4% <14 or history of AIDS-defining illness.
  • TMP-SMX, 1 SS or 1 DS tab once-daily. Alternative is 1 DS tab 3 x/wk. (1 DS once-daily preferred for toxo-seropositives with CD4<100).
  • Alternative: dapsone 100 mg once-daily.
  • Alternative: pentamidine 300 mg in 6 mL sterile water aerosolized monthly.
  • Alternative: Atovaquone suspension 750 mg twice-daily or 1500 mg once-daily.
  • Discontinue if CD4 >200 x >3 mos   on HAART.
Infection Control

  • Need for isolation of pts from other immunosuppressed pts controversial.

Drug Comments

DrugRecommendations/Comments
Atovaquone Less effective than TMP-SMX but has fewer adverse reactions. Expensive compared to other oral alternatives. Absorption variable if diarrhea. For mild-to-moderate cases only. Also effective (at treatment doses) for prophylaxis, but very expensive.
Clindamycin Effective when combined with primaquine in mild-to-moderate disease and can be given orally. Some trials using clinda/primaquine had pts with PO2 <70.
Dapsone Used as single agent only for prophylaxis; effective for mild-to-moderate PCP when combined with TMP, with fewer side effects than TMP-SMX.
Pentamidine Best 2nd line agent for severe PCP in pts who cannot tolerate TMP-SMX. Azotemia, hypo- and hyperglycemia common. Aerosolized form should not be used to treat active infection but is alternative agent for prophylaxis.
Primaquine Effective when combined with clindamycin in mild-to-moderate disease and can be given orally. Some trials using clinda/primaquine had pts with PO2 <70.
Trimethoprim + Sulfamethoxazole 1st line agent for treatment and prophylaxis of PCP. Can be given PO or IV. Adverse reactions common.
Trimetrexate Less effective than clindamycin & primaquine and has low success rate in TMP-SMX failures.

REFERENCES

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