An Overview Of Hiv Associated Pneumocystis Pneumonia
Pneumocystis is a fungi which causes opportunistic infection. Species affecting humans are Peumocystis carnii, peumocystis jirovecii. Primanry infection occurs in early childhood, mostly a self limiting upper respiratory tract infection. Animal studies suggested that Pneumocystis is transmitted from animal to animal via an airborn route.
Molecular type of Pneumocystis jirovecii genetic loci from persons with PCP has demonstrated the diversity of P. Jirovecii infecting humans.
PCP is a frequently diagnosed in HIV/AIDS patientsas a frequent opportunistic infectionin USA and Europe. Pneumocystis cannot be cultured, and bronchoscopy with bronchoalveolar is the gold standard test used for diagnosis.
Common symptoms associate with PCP are shortness of breath, non productive cough, low grae fever tachypenia, tachycardia normal finding on lung auscultation. The incidences of HIV and PCP has decreased in the developed countries with the use of antiretroviral therapy and prophylaxis.
The regimen recommended for prophylaxis is trimethoprim and sulphamethoxazole, drug resistance is the cause of concern. Other agents active against Pneumocystis jirovecii are dapsone, pyrimethamine, sulfadoxine, cindamycin and primaquine in combination. TMP/SMX results in 91% reduction in occurance of PCP in HIV patients with prophylaxis compared to patients without prophylaxis.
PCP is a frequently diagnosed in AIDS patients in USA and Europe, it is responsible for diagnosis of 20000 new AIDS cases every year from 1990 to 1993.The presentation differes from the non HIV immunocompromised patients with PCP in them duration of symptoms is shorter. Chest radiography can be used for diagnosis, PCP can be pneumothorax or bilateral pneumothoraces. Pneumothorax with a normal chest radiography is a problem so high resolution computed tomography (HRCT) can be used.
Pneumocystis cannot be cultured, so PCR assay (polymerase chain reaction) can be used in diagnosis of many infectious diseases. Recently serum 1-3 beta D glucan which is present in the cell wall of pneumocystis can be used as a bio marker for PCP diagnosis. 1-3 beta D glucan is elevated in many fungal pneumonias example aspergillus species, PCP.
Trimethoprim sulphamethoxazole combination is recommended for PCP in HIV patients. For inpatients with moderate to severe PCP intravenous therapy is recommended, for outpatientswith milder diseases oral is recommended.
Alternative regimens which can be used are intravenous petamidine, clindamycin plus primaquine, trimethoprim plus dapsone. Patients with moderate to severe PCP are recommended to start with adjuvant corticosteroid therapy it is demonstrated that partial pressure of oxygen less than 70mmHg. Along with adjuvant corticosteroid therapy PCP therapy should be started.the duration of therapy recommended is 21 days. In case the treatment has to be stopped because of toxicity alternative treatment regimen should be considered. Combination of clindamycin and primaquine is an effective alternative to intravenous pentamidine as second line of treatment according to randomized clinical trials and a systematic review.
Trimethoprim sulphamethoxazole is recommended as first line for primary and secondary phrophylaxis. Seven trials which included 707 patients compared daily administration of TMP/SMX prophylaxis verus no intervention, it was observed that there is a significant decrease in the number of incidences out of 335 patients 26 were diagnosed with PCP in the non treatment group whereas one out of 375 patients with TMP/SMX prophylaxis. Alternative regimens are dapsone with or without pyrimethamine and leucovorin, aresolized pentamidine. Adolescent, adults, pregnant women infected with HIV withn CD4 count of less than 200cells per micro liter or history of oral candidiasis (primary prophylaxis) and PCP (secondary prophylaxis).The prophylaxis is given for life but can be discontinued if the CD4 count on treatment with anti retroviral increases to greater than 200 cells per micro liter for atleast 3 months.
The over use of trimethoprim and sulphamethoxazole for prophylaxis is associated with increase in the resistance bacteria. TMP/SMX might also cause resistance to trimethoprim and dapsone. It has raised concern over potential trimethoprim sulphamethoxazole resistance in P jirovecii. The inability to culture P. jirovecii has hindered efforts to document drug resistance in Pneumocystis, but researchers have examining genetic mutations within the dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genes. Six studies were conducted to examine Pjirovecii DHFR mutation underlying HIV infection two studies suggested that the mutations are uncommon and unrelated to TMP/SMX. It was observed that the presence of a mutant DHPS geneotype was not solely responsible for increased mortality 86% patients with PCP containing Pneumocystis DHPS mutated gene survived Independent predictors of mortality are hypoalbuminemia require early hospital admission.
Compared with six DHFR studies, more than 20 studies have examined P. jirovecii DHPS mutations from patients with PCP with and without underlying HIV infection in North America, Europe, Asia, Africa, South America, and Australia. In general, these studies also suggested variation in the proportions of DHPS mutations observed, with the highest proportions reported in the United States (San Francisco) and the lowest number of cases reported in Spain and South Africa. Mutations that result in amino acid substitutions at amino acid position 55 (Thr/Ala) and/or position 57 (Pro/Ser) are almost exclusively reported.
This review discusses the recent advances in the pathogenesis, epidemiology, diagnosis, and management of HIV-associated PCP. The majority of the HIV infected patients with PCP containing mutant Pneumocystis DHPS genotype survived. Mortality was relatted to primarily to the underlying severity of illness.
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