Candidiasis

It is the most common cause of fungal infections in HIV infected children. Oral thrush, esophageal candidiasis and systemic candidiasis are common manifestations.

Clinical features

Oral thrush :

 It is one of the first clinical indicators of HIV infection in infants more than 6 months of age. Patients may have creamy white curd like patches with inflamed underlying mucosa in the oropharynx, palate and tonsils. It may also present as erythematous lesions (atrophic), hyperplastic (hypertrophic) and angular cheilitis. At times there may be nappy rash accompanying.

Esophageal candidiasis :

 Esophageal candidiasis is seen in patients with low CD4 cell count (< 100/cumm), high viral load and neutropenia (< 500/cumm) (52, 53) and those with concomitant oropharyngeal candidiasis. Patients present with odynophagia, dysphagia, retrosternal pain, nausea and vomiting.

Systemic candidiasis may be seen in patients on prolonged antibiotics and can cause endophthalmitis, hepatic, splenic, renal and bone involvement. Patients present in shock and with sepsis.

Diagnosis

Oral thrush can be diagnosed clinically. KOH preparation and culture with demonstration of budding yeast cells in wet mounts or biopsy specimen under microscope can be used for confirming the diagnosis as well as in vitro susceptibility testing can be used as a guide for antifungal treatment.
Esophageal candidiasis has classic cobblestoning appearance on barium swallow. It should be suspected in a child with oral candidiasis who has refusal to feeds, swallowing difficulty, drooling, hoarse voice or stridor. Endoscopy shows white raised plaques with extensive ulceration and biopsy will prove candida on KKOH preparation. Endoscopy is required in resistant cases to rule out other infections such as HSV, CMV, MAC and azole resistant candida.

Treatment
Systemic candidiasis is diagnosed on isolation of candida from blood culture.
Early oral thrush can be treated with topical application of clotrimazole applied 4-6 hourly to oral mucosa for 7-14 days. Alternatively nystatin suspension administered as 4,00,000 - 6,00,000 U/ml (4-6 mL 4 times daily after feed for 1-10 days may be given. Only if nystatin or clotrimazole trouche/mouth paint is not available, then gentian violet may be used. In patients who fail topical therapy, oral fluconazole (3-6 mg/kg/day OD) for 7-14 days or itraconazole (2-5 mg/kg/dose OC BD) for 7-14 days may be given. Ketoconazole also can be used as a second-line therapy in dose of 5-10 mg/kg/day in BD doses for 14 days but is less effective than fluconazole or itraconazole. Intravenous amphotericin B (0.3-0.5 mg/kg/day) may be used as a last resort.

Esophageal candidiasis : For esophageal candidiasis, fluconazole is the drug of choice. It is given at dose of 3 mg/kg/day IV for 21 days changing to oral route once the child starts tolerating food. Itraconazole capsule is not useful for treatment of esophageal candidiasis, however oral solution may be given for 14-21 days. Variconazole and caspofungin have been used for a limited number of children and thus not recommended for esophageal or disseminated candidiasis.
Systemic candidiasis : Amphotericin B is the drug of choice in dose of 0.5-1.5 mg/kg OD IV over 1-2 hours for 14 to 21 days after the last positive blood culture and signs and symptoms have resolved. Flucytosine (100-1560 mg/kg/day in 4 doses) may be used in combination with amphotericin B in patients with severe invasive disease. Fluconazole may be used as an alternative to amphotericin B in stable patients who have not recently received azole therapy. Lipid amphotericin B can be used in patients who are intolerant to conventional Amphotericin B or have a pre-existing renal disease (54).

Prophylaxis