Pneumocystis Carinii (PCP)

It is the most common opportunistic infection (OI) in infants (children less than 1 year of age) with a high mortality rate of about 35% (1, 2, 3). Pneumocystis is an organism with biological characteristics similar to that of fungi and protozoa. It is now renamed as pneumocystis jiroveci (for the human strain) (4). P. carinii is now referred to the organism found in rats. PCP is a common AIDS - defining illness.

Mechanism of action

PCP is usually acquired in childhood. Serum antibodies are found in over 80% of children by 4 years of age (5). In immunocompetent infants, it may lead to mild respiratory symptoms or children are usually asymptomatic (6). In immunodeficient individuals it infects the alveoli leads to interstitial edema and results in progressive hypoxemia and respiratory failure (7). Extrapulmonary affection is rare in children and include ear, eye, thyroid, spleen, GI tract, peritoneum, liver, pancreas, bone marrow, meninges, heart and muscle (6).

Clinical features

Patients present with fever, tachypnea, dyspnea and cough. On examination, there may be bilateral basal crepts with respiratory distress and hypoxia.

Investigations

1. X-ray chest
2. Arterial blood gas
3. Lactic dehydrogenase (Serum LDH)
4. Isolation of organism by gastric lavage / Bronchoalveolar lavage (BAL) / Bronchoscopy with transbronchial biopsy or open lung biopsy.

X-Ray Chest

• Common findings - Bilateral diffuse parenchymal infiltrates with "ground-glass" or reticulogranular appearance.

• Less common - Mild parenchymal infiltrates predominantly perihilar and progressing peripherally to reach the apical portion of the lung.

• Rarely - Lobar, cavitatory or miliary lesions

Stains

• Gomori's methenamine - Silver stain: Stains the cyst wall brown or black.
• T?oluidine blue: Stains the cyst wall blue or lavender.
• Giemsa or Wright stain: Stains the trophozoites and intracystic sporozoites pale blue with a punctate red nucleus. Does not stain the cyst wall.
• Monoclonal immunoflorescent antibodies:- Stain the cyst wall. Most specific compared to other methods.

Treatment for PCP

Drugs that can be used:

• Trimethoprim/Sulfamethoxazole (TMP/SMX).
• Pentamidine
• Dapsone/Trimethoprim
• Atovaquone (Recommended in adults)
• Clindamycin/Primaquine

TMP/SMX: It is the drug of choice
Dose : 15-20 mg/kg/day of the TMP component (75-100 mg/kg of SMX component) IV in 3-4 divided doses infused over 1 hour for 21 days.

If the acute symptoms resolve and child has no malabsorption, oral treatment with same dose of TMP/SMX can be given to complete the 21 day course.

Adverse effects :

 Erythema Multiforme, Stevens Johnson Syndrome (SJS), bone marrow suppression, hepatitis and interstitial nephrites. For mild rash, TMP/SMX can be temporarily discontinued and restarted when rash resolves. If SJS occurs, it should be discontinued and not restarted (9, ¹⁰⁾.

Pentamidine :

It is used in patients intolerant to TMP/SMX or who show no improvement after 5-7 days of TMP/SMX therapy. Combined therapy with TMP/SMX and pentamidine is not recommended due to potential increased toxicity.

Dose : 4 mg/kg/day OD IV over 1-1½ hours.

On clinical improvement after 7-10 days, patient can be shifted to oral atovaquone for a complete 21 day course.

Atovaquone :

Limited data in children. It is used in patients intolerant to TMP/SMX or have failure of response with TMP/SMX. May be substituted for IV pentamidine on clinical response.

Dose : 30-40 mg/kg/day in 2 divided doses PO with fatty food (max: 750 mg/dose). For children between 3-24 months - dose may increase to 45 mg/kg/day (12).

Adverse effects : Skin rash, nausea, Diarrhea, elevated liver enzymes. Most adverse effects occur after first week of therapy. Administer with care in patients on fluconazole, prednisolone, acyclovir, cephalosporins and rifampicin.

Clindamycin / Primaquine :

Primaquine is contraindicated in patients with G-6-PD deficiency. It can be used as alternative therapy in patients in who TMP/SMX or pentamidine treatment fails or causes adverse effects.

Dose : Primaquine base - 0.3 mg/kg OD (max 30 mg/day) for 21 days.
                                                                      +
Trimethoprim - 15 mg/kg/day in 3 divided doses PO for 21 days

Adverse effects : Reversible neutropenia, skin rash, elevated liver enzymes, anemia and thrombocytopenia.

Indications for corticosteroids :

Early use of corticosteroids decreases mortality due to acute respiratory failure and decreases need for ventilation. It is indicated if the PaO2 < 70 mm Hg at room air

Dose :

Oral Prednisolone - 2 mg/kg/day PO in 2 divided doses for 5 days

                           then 1 mg/kg/day PO for next 5 days

                           and lastly 0.5 mg/kg/day PO for 11-21 days.

Alternative : IV methyl Prednisolone

• 1 mg/kg every 6 hours for 7 days
• 1 mg/kg every 12 hours on day 8 & 9
• 0.5 mg/kg every 12 hours on day 10 & 11
• 1 mg/kg every 24 hours on days 12-16.

• All HIV exposed infants from 4 weeks of age (Infants born to HIV infected mothers) till prove to be negative
• All HIV infected asymptomatic infants till 1 year of age
• All symptomatic HIV infected children
• All HIV infected children with CD4 % less than 15% irrespective of symptoms

Indications (Primary prophylaxis)

Secondary prophylaxis

• All HIV infected children who are symptomatic should receive till started on ART and there is evidence of immune reconstitution. i.e., in a CD4 count of > 15% on 2 occasions no less than 3 months apart. If CD4 count not available, then stop TMP/SMX only after 6 months of ART with clinical evidence of immune reconstitution.
• Life-long suppressive therapy is recommended for children after initial therapy for treatment of PCP.

Drugs recommended for prophylaxis :

• TMP-SMX
  

Dose : 150 mg of TMP/m2/day orally in 2 divided doses on alternating days

                                                              OR

             5 mg/kg/day of TMP orally as night dose every day

• Dapsone

Dose : 2 mg/kg/day PO (max - 100 mg/day)

• Pentamidine

Dose : 300 mg inhaler every 28 days (for children over 5 years of age)

                                              OR

             4 mg/kg/day IV OD every 2-4 weeks.