Laboratory investigations

Levels of blood haemoglobin, leukocytes, differential counts, and thrombocytes may be lowered by the HIV infection, but are normally unaffected by the P. carinii infection. Decreasing levels of these haematological parameters are common during high-dose therapy with co-trimoxazole, while adjunct treatment with corticosteroids - which may be life saving in patients with hypoxaemia (Bozzette et al. 1990) - may induce blood leukocytosis. Monitoring the levels of blood lactate dehydrogenase (LDH) is much more helpful: more than 90% of patients with PCP have elevated LDH, and if above 450 International Units, the prognosis is poor (Leoung and Hopewell 1990a).

If the patient is not manifest hypoxaemic, exercise biking may reveal latent hypoxaemia, and prompt further examination for the causative agent. As mentioned earlier, very discrete symptoms and a normal chest X-ray may change to life-threatening PCP within a day or two. Computed tomography (CT) scanning of the chest may disclose early diffuse infiltrates, but the diagnosis should be based on demonstration of P. carinii.

BAL +/- trans-bronchial biopsy via a flexible fibre bronchoscope was recommended as the standard procedure early on in the AIDS epidemic (Broaddus et al. 1985); it has a high sensitivity, about 90%, even without biopsy, which is no longer routine. Sputum induced by inhalation of hypertonic saline, in the hands of experienced clinicians and laboratory technicians, may attain almost 80% sensitivity (Leoung and Hopewell 1990b). Staining techniques, including toluidine blue, Giemsa, and methenamine silver have been described in previous chapters, as has the use of fluorescent monoclonal antibodies. Improved diagnosis can be obtained by polymerase chain reaction (PCR) on sputum (Lipschik et al. 1992), while PCR on serum has been disappointing (Wagner et al. 1997).

Demonstration of fluorescing serum antibodies to crude P. carinii antigens is not helpful in diagnosing PCP in AIDS (Hofmann et al. 1985), while IgG antibodies against gp95 antigens are increased in 66% of patients with PCP; IgM antibodies are only raised in 4% (Lundgren et al. 1992a). Some patients may be too ill to co-operate to induced sputum or bronchoscopy. These may benefit from non-invasive procedures like PCR on mouth washings. However, there may not be time to await the results, and presumptive treatment with co-trimoxazole should be instituted. As mentioned above, the mortality rises from 10% to more than 40% if the patient becomes so ill that mechanical ventilation may be required. When improving, the patient may undergo BAL, since P. carinii is demonstrable even after several days' or weeks' treatment. Therefore, re-examination after treatment is normally not helpful. Patients not responding to standard treatment should, however, be re-examined to exclude important differential diagnostic conditions, including cytomegalovirus infection, bacterial infection

Page 275

(streptococci, styphylococci, H. influenzae), mycobacteria, fungi, and disseminated Kaposi's sarcoma, which may be indistinguishable clinically and radiologically. PCP not responding to standard treatment may be treated with alternative regimens, including trimetrexate, pentamidine, clindamycin with primaquine, atovaquone and others.

Recently, successful in vitro culture of P. carinii has been reported (Merali et al. 1999), but routine testing for drug resistance in vitro is not possible. However, mutations in dihydropteroate synthase, the enzyme essential for folate biosynthesis in P. carinii, which is blocked by sulphonamides, may be demonstrated by PCR and may be associated with impaired prognosis (Helweg-Larsen et al. 1999). Further details on the management of PCP should be sought in standard textbooks on AIDS.

0 0

Post a comment