Pulmonary Infection in HIV AIDS Patients.

Pulmonary Infection in HIV AIDS Patients

Anak Agung Ayu Yuli Gayatri, Tuti Parwati Merati Division of Tropical and Infectious Disease

Department of Internal Medicine

Udayana University School of Medicine-Sanglah Hospital Denpasar

Abstract

The immune dysregulation associated with HIV result in an increased incidence of respiratory infection at all CD4 T-cell count. The type of pulmonary condition to be developed by AIDS patients will depend on the stage of disease, which is generally determine based on the CD4 lymphocytes count. Some of the most common opportunistic infectious lung diseases seen in HIV-positive or AIDS patients are pneumocystis carinii pneumonia, tuberculosis and bacterial pneumonia. A simple patient risk assessment allows the clinician to determine the likelyhood that other opportunistic infections are the cause of severe respiratory disease and that further pathogens may need to be considered. 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, severity of the illness and the resources available locally.

Keywords :

Introduction

Human Immunodeficiency virus (HIV) is the virus that causes acquired immunodeficiency syndrome (AIDS). HIV targets an important kind of white blood cell called CD-4 T Lymphocyte or T cells. T cells belong to the immune system and protect the body from germs and other disease-causing agents. Germs take this opportunity to invade the body and cause infections. People may be infected with HIV for years before developing AIDS. The lung is a major area of opportunistic infection in people living with HIV and AIDS. Some of the most common opportunistic infectious diseases seen in HIV-positive or AIDS patients are pneumocystis carinii pneumonia, tuberculosis and bacterial pneumonia. (Dockrell DH et al. 2011)

A simple patient risk assessment allows the clinician to determine the likelyhood that other opportunistic infections are the cause of severe respiratory disease and that further pathogens may need to be considered. Relevant factors include: (1) patient use of effective opportunistic infection prophylaxis or HAART; (2) 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 increase risk of bacterial pneumonia and TB; (5) level of host immunity; (6) neutropenia; (7) use of prolong course of immune modulator (e.g. corticosteroids).

Pneumocystis carinii pneumonia (PCP)

Pneumocystis carinii pneumonia (PCP) is the first sign of illness in more than half of all persons with AIDS in the United States. This is caused by the Pneumocyctis jiroveci germ, formerly known as Pneumocystis carinii. Pneumocystis jirovecii is a fungus that causes infection specific to humans. The great majority occur in immunocompromised subjects and are associated with respiratory symptoms. Many people who are HIV positive take medication to prevent PCP; frequent blood tests help health care provider decided when such treatment should begin.

Presentation

Without preventive medicine, over 80% of people with HIV will likely get PCP. Common symptoms include coughing, fever and trouble breathing. 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 high plasma HIV load. (Dunleavy A et al. 2009)

apparent. Rarer presentation include a more rapid onset, haemoptysis and pleuritic chest pain. Physical examination reveals tachypnoea, normal breath sounds or less frequently, and-inspiratory crackles. Wheezing and sign of focal consolidation or pleural effusion are less common presentation. Spontaneous or infection-associated pneumothorax in an HIV-seropositive individual should prompt exclusion of PCP. 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 up to 39% of patient and should , there fore, not distract from pursuing the diagnosis of PCP clinically suspected. (Dockrell DH et al. 2011)

Diagnosis

There are no clinical features specific to PCP. Radiology and nuclear medicine test are not particularly sensitive or specific. Other opportunistic infections may mimic the typical radiological features of PCP. Demonstration of 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, but is not reliable enough to make a diagnosis without confirmatory microbiology. If induced sputum (IS) is routinely available, this can be performed initially(sensitivity 50-90%). If IS result are negative or inconclusive, then the patient should be assessed for bronchoscopy with bronco-alveolar lavage (BAL; diagnostic sensitivity>90%). 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. Spontaneously expectorated sputum is not an adequate alveolar sample and should not be processed. (Beck. 2005; Dockrell DH et al. 2011)

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 immune-flourescent stains.

Treatment

duration; many switch individuals showing a good initial response to oral therapy at doses equivalent to those used for mild-moderate severity disease. Individuals with a PaO2 <9.3kPa(<70mm Hg)or SpO2<92%, should receive prednisolon 40 mg bd po days 1-5, 40mg od po, days 6-10, 20mg od po days 11-21, or if unable to take oral medications, methylprednisolone at 75% of this dose. The benefit of corticosteroid therapy is documented only where it has been commenced within 72 h starting specific anti-PCP therapy. (Dunleavy A. et al. 2009; Dockrell DH et al. 2011). A favourable treatment response may take 7 days or more. The decision to switch from one drug to another is driven by either treatment-limiting toxicity or lack of efficacy. (Dunleavy A. et al. 2009)

Tabel 1. Stratification of disease severity in PCP (Dunleavy A.et al. 2009)

Mild Moderate Severe

Symptoms and signs

Dyspnoea on exertion with or without cough and sweats

Dyspnoea on minimal exertion and

occasionally at rest; cough and fever with or without sweats

Dypnoea and tachipnoea at rest fever and cough

Oxygen PaO2 room air, at rest in kPa (mmHg)

>11.0 (>83) 8.1-11.0 (61-83) ≤8.0 (≤60)

SaO2 at rest on air

.96 91-96 <91

Chest radiograph

Normal or minor perihilar shadowing

Diffuse interstitial shadowing

Extensive interstitial shadowing with or without diffuse alveolar shadowing Note: for treatment purpose moderate severity is group with severe disease if

PaO2>9.3kPa

The choice of treatment is therefore determined by patient tolerance and ability to take either oral or iv medication. For severe PCP, the other treatment options are clindamycin 600-900mg qid/tid iv or 300-450 mg tid/qid po and primaquine 15-30 mg od or pentamidine 4 mg/kg od iv for 21 days. Many clinician favour clindamycin based therapy in view of the toxicity profile of iv pentamidine. Good bioavailability allows clindamycin to be given by the oral route unless the patient is unable to take oral medicines. A lower rate of methaemoglobinaemia means the 15 mg dose of primaquine recommended. (Dunleavy A. et al. 2009; Dockrell DH et al. 2011)

Prophylaxis

do not provide the additional protection provided by TMP-SMX against other infections and some are not as effective at low CD4 T-cell counts. Early initiation of HAART is favourable in individuals with PCP. The improvement in systemic and local immunity following continous use of HAART translate into very low risk of PCP if profilaxis is discontinued in population with CD4 T cell count >200 cells/µL for more than 3 months.

Tuberculosis

Tuberculosis (TB) infection in HIV patient remains a major global public health challenges, with estimated 1.4 million patients world wide. By the end of 2009, an estimated 2.6 million individuals had become newly infected with HIV and 1.8 million had died of AIDS in that year alone. TB is the most common opportunistic infection among HIV infected individuals, and co-infected individuals are at high risk of death. (Lawn S. et al. 2009)

TB may occur in any stage of HIV disease and is frequently the first recognized presentation of underlying HIV infection. As compared to people without HIV, people living with HIV (PLWH) have 20-fold higher risk of developing TB and the risk continues to increase as CD4 cell counts progressively decline. Although ART can reduced the incidence of TB both at the individual and population level, PLWH on ART still have higher TB incidence rates and a higher risk of dying from TB. This may be due to delayed initiation of ART or the fact that patients present with advance TB or both. Routine TB screening among PLWH offers the opportunity to identify those without TB, prevent TB by chemoprophylaxis as well as to diagnose and promptly treat TB. However co-administration of ART along with anti-TB therapy present several management challenges, including drug-drug interactions, overlapping drug toxicities and immune reconstitution syndrome. (Lawn S et al. 2009)

Presentation

Clinical symptoms of TB pulmonary disease are similar to those caused by other mycobacteria : fever, night sweats, weight loss, productive cough, dyspnea, central chest pain and sometimes hemoptysis.

Diagnosis

Diagnosis of active TB disease in HIV- infected persons is difficult, because patients with HIV-associated TB have fewer bacilli in their sputum than do HIV-uninfected patients with pulmonary TB. In addition it has been observed that presence of a cough for > 3 weeks is not sensitive enough on its own as a symptom of TB in HIV-infected persons.

impact of methods that optimize the use of smear microscopy is not well understood for HIV-infected persons. Mycobacterial culture is the gold standard for TB diagnosis and is routinely recommended to assist the diagnosis of TB in HIV-infected persons, although it is frustratingly slow. HIV infection compromises the validity and effectiveness of chest radiography in the diagnosis of pulmonary TB in HIV-infected persons, and the findings could be normal for up to 14% of HIV- infected persons who have culture confirmed pulmonary TB. However, chest radiography remains an important adjunct in the diagnosis of TB, and its use must be expanded, including the use of advance and innovative technology such as digital imaging. (Padmapriyadarsini C et al. 2011)

The WHO recommends TB screening at the time that HIV infection is diagnosed, before the initiation of antiretroviral therapy and at regular interval during follow up. It was recommended that screening for TB should include asking questions about the present of any one of current cough, fever, night sweats or weight loss. In the hospital setting, bacteriological examination mostly failed to find Mycobacterium TB from sputum smear, and this is not simply just by difficulty to get the specimen. Because of the poor performance of sputum smear microscopy in HIV-infected patients, recently the WHO endorsed the used of GeneXpert-Rif for the rapid diagnosis of TB as well as rifampicin resistance among HIV-infected individuals with clinical suspicion of TB. (WHO report. 2010; Padmapriyadarsini Cet al 2011))

Chest X ray do not show typical feature of lung TB especially in patient with low CD 4 cell count. The spectrum of radiographic manifestation of Pulmonary TB is dependent on the relative level of immunodeficiency. During the early phase of HIV when individuals are not immunosupressed the radiographic pattern is similar to HIV un-infected individuals with more typical lesions-upper lobe infiltrates with or without cavities. With advancing immune-suppression, extra pulmonary involvement, intrathoraxic/ mediastinal lymphadenopathy, lower lobe infiltrates and milliary TB become more common.( Padmapriyadarsini C et al. 2011)

Treatment

symptoms and sign in one or two months after completing in six moths anti TB drugs treatment. (WHO report. 2010; Padmapriyadarsini C et al. 2011)

Bacterial Pneumonia

HIV related bacterial infection of the lower respiratory tract is common and occurs at levels of immunosupression. Risk factors for HIV- related bacterial pneumonia are declining CD4 lymphocyte count, cigarette smoking and injecting drug use. Incidence of bacterial pneumonia is five times greater in HIV positive population than in otherwise similar but HIV-negative population; the incidence of pneumococcal disease, including pneumonia, is 10 times greater and the development of pneumococcal septicemia is 100 times greater. (Beck. 2005)

Recurrent pneumonia (two or more episodes in a 12-month period) is classified as AIDS-defining. The etiology of community-acquired pneumonia (CAP) among HIV-seropositive individuals is similar to that of the general population with Streptococcus pneumonia and Haemophilus influenza predominating. Staphylococcus aureus has been reported at a greater frequency than in the general population. Pseudomonas aeroginosa has been noted more commonly at low CD4 T-cell counts. Although atypical pathogens such as Legionella pneumophila, Mycoplasma pneumonia and Chlamydophila (Chlamidia) pneumonia have not been frequently reported in HIV-related bacterial pneumonia, this may reflect diagnostic difficulties, and there are data to support that these occur at the same frequency in HIV-seropositive and HIV-seronegative populations. As with immunocompetent individuals . Gram-negative pathogens should be considered especially likely in those who develop pneumonia when hospitalized. (Dunleavy A. et al. 2009; Dockrell DH et al. 2011)

Presentation

Presenting symptoms are similar to HIV-seronegative individuals and typically have an acute onset (hours to days).The classical physical signs are those of lung consolidation, although there is an increased tendency to rapid progression: cavitation, parapnemonic effusion and empyema formation The peripheral white blood count (WBC) is usually elevated but may be low in more severe cases.

Diagnosis

suspected a chest radiograph should be obtained. Radiological features are similar to HIV-seronegative individuals. Patchy, lobar or segmental consolidation appears on plain radiograph, although an increased frequency of interstitial infiltrates has been recently reported; cavitation within consolidation, when the infection is cause by gram-negative organisms, as for example pseudomonas and multiple cavitating nodules in case of septic embolism especially in IVDU.

Blood cultures should be routinely performed in these patients because of the high incidence of bacteremia. (Dunleavy A. et al. 2009; Dockrell DH et al. 2011)

Treatment

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. Initial anti-microbial treatment is usually empirical and should be chosen according to; (a) pneumonia severity; (b)the likelyhood of particular pathogens as indicated by risk factors; (c) the potential for antibiotic resistant and (d) potential toxicities. A number of guidelines developed to guide the management of CAP in HIV-seronegative individuals exist and the possible regimens suggested in these guidelines are adapted from them. HIV-seropositive individuals with community-acquired pneumonia should be treated as per HIV-seronegative populations. Antibiotic prophylaxis is not indicated for bacterial pneumonia. The capsular polysaccharide vaccine protects against pneumococcal serotypes. The Departement of Health includes HIV-seropositive individuals amongst the “high- risk” groups for whom vaccination is recommended.

References

Beck J. Immunocompromised Host. Proc Am Thorax Soc 2005;2:423-7

Benson CA et al_{. Treating Opportunistic Infections Among HIV Infected Adults and} Adolescents Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association/ InfectiousDiseases Society of America. Available at: http: //www.cdc.gov/hiv/topics/treatment/index.htm

Dockrell DH, Breen R, Lipman M, Miller RF. Pulmonary Opportunistic infections. 2011. HIV Medicine. 12 (suppl.2) 25-42.

Dunleavy A, Lipman M, Miller R. Infection in the HIV compromised host. In: maskell N, Millar A, eds. Oxford Desk Reference Respiratory Medicine. Oxford, Oxford University Press. 2009: 210-217

Padmapriyadarsini C, Narendran G, Swaminathan S. Diagnosis & Treatment of Tuberculosis in HIV co-invected patients. 2011. Indian J Med Res 134;850-865

Tuberkulosis, Pedoman Diagnosis dan Penatalaksanaan di Indonesia. 2011. Perhimpunan Dokter Paru Indonesia.