3 Pulmonary opportunistic infections

The PubMed database was searched under the following headings: HIV or AIDS and lung or pneumonia or pneumonitis and/or Pneumocystis carinii, Pneumocystis jirovecii, Pneumocystis pneumonia, PCP, Cryptococcus neoformans, cryptococci, Cryptococcus, Aspergillus, aspergillosis, CMV, influenza A virus, influenza B virus, parainfluenza virus, respiratory syncytial virus, bacteria and vaccination. The immune dysregulation associated with HIV results in an increased incidence of respiratory infection at all CD4 T-cell counts. Early reports of the dramatic increased risk of Pneumocystis pneumonia (PCP) in advanced HIV disease have tended to overshadow the finding that other respiratory pathogens are also more common in HIV disease (Table 3.1). The widespread use of prophylaxis against opportunistic infections together with HAART has reduced the risk of life-threatening infection, though it has not returned to the background levels present in HIV-sero negative populations [1]. Mycobacterial disease is not discussed in this section as Mycobacterium tuberculosis is the focus of separate guidelines [2]. Pulmonary symptoms may arise from infection with a wide variety of organisms although PCP and bacterial pneumonia predominate. A simple patient risk assessment allows the clinician to determine the likelihood that other opportunistic infections (OI) are the cause of severe respiratory disease and that further pathogens may need to be considered. Relevant factors include: (1) patient use of effective OI prophylaxis or HAART; (2) recent discharge from hospital or current hospital admission >5 days (nosocomial infections); (3) country/place of residence and travel history; (4) history of active injecting drug use, since these individuals are at increased risk of bacterial pneumonia and TB; (5) level of host immunity; (6) neutropenia; and (7) use of prolonged courses of immune modulators (e.g. corticosteroids). Treatment is often started prior to laboratory confirmation of diagnosis. The intensity with which investigation is undertaken is usually determined by the patient risk assessment, the severity of the illness and the resources available locally. While empirical therapy (usually directed against bacterial pathogens) may be appropriate for patients with CD4 counts >200 cells/μL, every effort should be made to confirm a specific diagnosis in the more immunocompromised individual (category IV recommendation). Pneumocystis jirovecii is a fungus that causes infection specific to humans [3]. The great majority occur in immunocompromised subjects and are associated with respiratory symptoms [4]. Current evidence suggests that PCP arises by re-infection from an exogenous source [5]. Evidence for nosocomial transmission exists but is limited [5]. Before the advent of preventative therapy and HAART, PCP occurred in up to 80% of HIV-seropositive individuals with AIDS [6]. In the UK this has declined considerably. Almost 90% of cases occur in HIV-seropositive persons with CD4 T-cell counts <200 cells/μL (or a CD4 T-cell percentage <14%). Other predictive factors for PCP in subjects not receiving effective HAART, include non-adherence to prophylaxis, oral candidiasis, oral hairy leukoplakia, unintentional weight loss, recurrent bacterial pneumonia, previous PCP and a high plasma HIV load [6–12]. The typical presentation of PCP is with exertional dyspnoea, which progresses over several weeks, malaise and a dry cough. An inability to take a deep breath and fever are often apparent [13]. Rarer presentations include a more rapid onset, haemoptysis and pleuritic chest pain. Purulent sputum production suggests bacterial infection – although this can be present as a co-pathogen in around one-sixth of cases [14]. Physical examination reveals tachypnoea, normal breath sounds or, less frequently, end-inspiratory crackles. Wheezing and signs of focal consolidation or pleural effusion are less common presentations [13]. Spontaneous or infection-associated pneumothorax in an HIV-seropositive individual should prompt exclusion of PCP [15]. Radiological findings in the chest include perihilar haze, interstitial infiltrates (characteristically sparing the apices and costo-phrenic angles), pneumatocoeles and pneumothoraces. Upper lobe infiltrates alone have been reported to occur in individuals who are receiving inhaled pentamidine prophylaxis. A normal chest radiograph has been reported to occur in up to 39% of patients and should, therefore, not distract from pursuing the diagnosis of PCP if clinically suspected [16,17]. There are no clinical features specific to PCP. Radiology and nuclear medicine tests are not particularly sensitive or specific [18,19]. Other opportunistic infections may mimic the typical radiological features of PCP [20,21]. Demonstration of a fall in oxygenation between rest and exercise has been validated as a reasonably specific test for PCP in cases with a normal or near-normal chest radiograph who have no previous history of PCP [22], but is not reliable enough to make a diagnosis without confirmatory microbiology. In conclusion, whilst PCP remains a very common AIDS diagnosis in the UK [23] and the clinical and radiological presentation may be classical, neither clinical nor radiological presentation are sufficiently specific and further microbiological investigations are required to confirm PCP and exclude alternative diagnoses or co-pathology. It is important to obtain either tissue samples or body fluid in which the organism can be identified (category III recommendation). In view of the current reduction in PCP presentations, all cases should undergo investigation and not just receive treatment empirically for presumed PCP (category IV recommendation). If induced sputum (IS) is routinely available, this can be performed initially (sensitivity 50–90%). If IS results are negative or inconclusive, then the patient should be assessed for bronchoscopy with broncho-alveolar lavage (BAL; diagnostic sensitivity >90%) [24–27]. Some may choose BAL as the first-line investigation employed. Open lung biopsy (diagnostic sensitivity 95–98%) is reserved for the occasional patient, with negative initial tests, and who is not improving on empirical treatment [28,29]. Spontaneously expectorated sputum is not an adequate alveolar sample and should not be processed. Pneumocystis jirovecii cannot be cultured in vitro; diagnosis relies on visualization of the organism using either histochemical (typically with silver stains such as Grocott–Gomori methenamine silver stain) or immunofluorescent stains. Nucleic acid amplification techniques (NAAT) using a variety of primers have been reported with induced sputum, BAL and oral wash specimens [30–33]. In general NAAT-based tests have increased sensitivity but reduced specificity compared to visualization; and the specificity varies by protocol. In one study comparing two NAAT-based assays the sensitivities were 97–98% but specificities ranged from 68% to 96% [30]. The sensitivity is lower using samples that are obtained from more easily obtained specimens such as sputum or oral washes. NAAT-based assays, although not widely available, can provide information on the molecular epidemiology of PCP and the frequency of mutations in Pneumocystis' dihydropteroate synthase gene (which is associated with previous exposure to sulpha- drugs – see later). Currently, no definitive recommendations concerning NAAT-based assays can be made. Where centres use them as part of a diagnostic algorithm they must be interpreted with input from the testing laboratory in the light of their sensitivity and specificity. They should be combined with a definitive visualization technique (category IV recommendation). Treatment should not be delayed in a presumed case, by having to wait for a diagnostic procedure, as adequate pulmonary samples can be obtained up to 7–10 days after starting specific anti-pneumocystis therapy [34]. First-line treatment for moderate–severe PCP [PaO2≤9.3 kPa (≤70 mmHg)] is with high-dose intravenous (iv) trimethoprim-sulphamethoxazole for 21 days (co-trimoxazole, TMP-SMX) (category Ib recommendation). Some clinicians will continue with iv therapy for the duration; many switch individuals a initial to oral therapy at to for severity disease (category IV recommendation). or intravenous should be started in all cases of suspected moderate–severe PCP with a kPa or (category Ib recommendation). 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In cases further lung either by sputum or bronchoscopy with BAL should not be but bronchoscopy must be in cases that to to initial therapy and induced sputum or bronchoscopy in all cases with risk factors for PCP or treatment is usually empirical and should be pneumonia the likelihood of pathogens as by risk the for and A of guidelines to the of in individuals and the in these guidelines are from them HIV-seropositive individuals with pneumonia should be as populations (category IV recommendation). prophylaxis is not for bacterial The against The of HIV-seropositive individuals the for is and are discussed in the HIV guidelines The of HAART have been in a reduced risk of bacterial pneumonia in individuals using has been less for opportunistic infections [1]. and epidemiology section Cryptococcus The symptoms may be from PCP, with (which may be exertional and pleuritic chest often present interstitial or pleural interstitial which may or have a are common in with advanced or with with PCP, may disease is the common presentation section Cryptococcus is identified in induced sputum, BAL or pleural fluid by (which reveals an or by with can be in sensitivity and specificity The can be cultured from BAL or biopsy specimens using or such as usually of the with or without a test or of on BAL or pleural specimens can be with stains such as Grocott–Gomori methenamine or is and disease but may be Pulmonary is usually as infection (category III recommendation). Pulmonary focal and not associated with or may be initially with (category III recommendation). In cases with pulmonary a examination should be performed to determine is present (category III recommendation). In treatment is with a B section Cryptococcus If the is and (1) is no other evidence of (2) radiological infiltrates are focal and (3) is no treatment with for the initial and after is an alternative (category III and of HAART section Cryptococcus the in of individuals with lung the fungus the and to other may occur in HIV-seropositive individuals in individuals with infection in the of other risk factors such as or and are features of and are often in chest may is A alternative in individuals with infection is to individuals have or in the and usually have risk factors for such as or symptoms include dyspnoea, and cases may to of the of a of radiological and microbiological of the chest provide of and or pulmonary is identified either a clinical is associated with a biopsy that by or or is associated with a clinical radiological and with a microbiological sample from sputum or to can be by stains such as stains of sputum or BAL and Grocott–Gomori methenamine silver stains or on biopsy specimens should be obtained on all respiratory specimens from HIV-seropositive individuals with pulmonary of (category IV recommendation). should be on all samples as the definitive of (category IV recommendation). The test is an that the of a of It is in patients but are available in the of HIV may in a variety of in individuals receiving to the incidence of the such as and have not been compared or in an HIV-seropositive with the of but of HIV-seropositive therapy for pulmonary is with (category IV is at as a for and then for at by to is to B in treatment of as by and though the for this is a study that not with B and the was evidence of B iv is the alternative to and iv is an alternative if neither nor B can be and is the if or disease is present or is alternative to or In individuals will usually receive in often with to They then can switch to the and to a which is to at the oral an alternative for individuals or to therapy for therapy should be clinical and radiological evidence of a is for at should then be with an oral such as for a of A prolonged of therapy with an such as oral or should be for in which is no evidence of have drug and drug should be performed to of or prophylaxis for pulmonary is not (category IV recommendation). There is information concerning in pulmonary but the incidence to have declined reports of individuals who have pulmonary as an following HAART is a and of the and individuals with can severe disease to or of is common in with advanced and not cause of in or BAL without evidence of infection but not in BAL or is common in individuals with HIV infection, who have CD4 T-cell counts symptoms are dry and exertional with and this presentation is to many other pulmonary is often The chest radiograph and often interstitial infiltrates or but alveolar pleural or or may occur There may be evidence of and a examination should be performed to The diagnostic is to in respiratory from cases with or for from BAL or biopsy not from and must be interpreted with A negative with high negative predictive reasonably exclude pneumonia of pneumonia a biopsy to provide evidence of pulmonary in with a clinical (category III recommendation). Evidence of or for or of by molecular techniques such as in on a pulmonary biopsy the diagnosis in the of a clinical in the respiratory is a of and not of The majority of individuals in microbiological tests on or should not receive treatment for (category III recommendation). with a clinical for in BAL or biopsy and on biopsy or BAL without an alternative microbiological cause of respiratory disease should receive treatment (category III recommendation). is by evidence that treatment is in individuals with evidence of on BAL or clinical is not the of treatment to the of individuals who have evidence of a clinical and for and no alternative diagnosis have been by that clinical with treatment The of individuals with for but of a pulmonary is also In individuals it is to by the co-pathogen and to the if is a of clinical (category IV recommendation). therapy for pneumonitis is with (category III recommendation). is at iv for 21 days or are in who are not or who are to therapy although in pneumonia in HIV-seropositive individuals are limited is an alternative for individuals to oral therapy or for a switch from intravenous therapy is is no clinical evidence to the use of prophylaxis, in the patient with a CD4 and no HIV treatment prophylaxis may be considered. The majority of patients with CD4 T-cell counts will not prophylaxis. prophylaxis or can be in individuals the CD4 remains cells/μL, is of or with a risk of prompt immune by HAART and is no evidence of disease (category IV since of is a risk for in this over and the risk of CD4 T-cell or HIV therapy with is not initially required after treatment of pneumonia but may be if pneumonia or if disease is may be as prophylaxis in patients with and or as prophylaxis in with of pneumonia after appropriate therapy (category IV recommendation). HAART has the incidence of all of disease and pneumonia is more as an although reports of in the lung of HIV-seropositive individuals have not a incidence of they a risk of more severe disease but this an with In suspected cases diagnosis is by of or from or HIV-seropositive individuals should receive the the majority of in a (category IV recommendation). HIV-seropositive individuals should be is and fever has been present for less although for individuals with T-cell <200 treatment may be if or if symptoms have been present for more recommendations are made in view of the increased incidence of in HIV-seropositive individuals but are no of treatment in HIV-seropositive from treatment of patients at of of in in cases associated with treatment has often been of for days is the by for days is an alternative and has been as the for HIV-seropositive with in guidelines on the of increased of in this in to but with reduced to have been reported in individuals with HIV In in were and the of the appropriate must be made in light of the of the in a in with While many of these to at have been reported in other immunocompromised Some have therapy will be particularly for immunocompromised in the and clinical are this in patients HIV-seropositive with severe infection individuals of available for use or include iv and but are no on their use in HIV-seropositive have against in individuals at high risk of It is that immunocompromised patients also receive then or with as an all for days an of but no specific are available for HIV-seropositive populations If pneumonia should be as the guidelines for pneumonia but if patients to are that or may be bacterial or is a incidence of bacterial with then therapy should also these should be to all HIV-seropositive individuals every (category Ib in by the may in increased levels of HIV-seropositive individuals HIV-seropositive individuals should receive (category Ib immunocompromised individuals have prolonged of but are limited on the of in HIV-seropositive individuals this should be and appropriate infection for and with advanced for have no evidence for prolonged in a of HIV-seropositive with CD4 T-cell counts cells/μL receiving HAART but not compared to was it the of treatment may transmission in HIV-seropositive of symptoms and treatment of cases may be as a preventative (category IV recommendation). In with recommendations for the general the use of prophylaxis is not routinely required in HIV-seropositive individuals to individuals who are (1) T-cell <200 (2) have not or are to be at risk of to either or recent and (3) have been the prophylaxis may be although are no on which to this (category IV recommendation). is often for use in the general using for days although in more individuals or in the of inhaled for days may be Some the of these to levels to treatment or by for days in more immunocompromised treatment recommendations discussed from to are to on which varies from to In the UK these guidelines are by the