Etiology of Pulmonary Infections in Human Immunodeficiency Virus-infected Inpatients Using Sputum Multiplex Real-time Polymerase Chain Reaction

Abstract

Background: There are limited data on the etiology of respiratory infections in human immunodeficiency virus (HIV)-infected patients in resource-limited settings.

Methods: We performed quantitative multiplex real-time polymerase chain reaction (PCR) for Pneumocystis jirovecii and common bacterial and viral respiratory pathogens on sputum samples (spontaneous or induced) from a prospective cohort study of HIV-infected inpatients with World Health Organization danger signs and cough. Mycobacterial culture was done on 2 sputum samples, blood cultures, and relevant extrapulmonary samples.

Results: We enrolled 284 participants from 2 secondary-level hospitals in Cape Town, South Africa: median CD4 count was 97 cells/μL, 64% were women, and 38% were on antiretroviral therapy. One hundred forty-eight had culture-positive tuberculosis, 100 had community-acquired pneumonia (CAP), 26 had P. jirovecii pneumonia (PJP), and 64 had other diagnoses. Probable bacterial infection (>105 copies/mL) was detected in 133 participants; the prevalence was highest in those with CAP (52%). Haemophilus influenzae and Streptococcus pneumoniae were the commonest bacterial pathogens detected; atypical bacteria were uncommon. Viruses were detected in 203 participants; the prevalence was highest in those with PJP (85%). Human metapneumovirus was the commonest virus detected. Multiple coinfections were commonly detected.

Conclusions: Sputum multiplex PCR could become a useful diagnostic tool for bacterial respiratory infections in HIV-infected inpatients, but its value is limited as quantitative cutoffs have only been established for a few bacterial pathogens and validation has not been done in this patient population. We found a high prevalence of respiratory viruses, but it is unclear whether these viruses were causing infection as there are no accepted quantitative PCR cutoffs for diagnosing respiratory viral infections.

Keywords: Pneumocystis jirovecii pneumonia; HIV; bacterial pneumonia; respiratory viral infections; tuberculosis.

Figure 1.

Flow diagram for participant enrollment into the study. Abbreviations: CCF, congestive cardiac failure; COPD, chronic obstructive pulmonary disease; HIV, human immunodeficiency virus; PCR, polymerase chain reaction.

Figure 2.

The distribution of genome copy number by virus is shown in box and whisker plots for viruses detected in ≥10 participants (different species of coronavirus and parainfluenza virus, respectively, were combined for this analysis). The horizontal line indicates the median, the box indicates the interquartile range, and the bars indicate the range.

Figure 3.

Venn diagrams of pathogen detection in all 284 participants (A) and in 100 participants fulfilling the case definition of community-acquired pneumonia (B). Abbreviations: CAP, community-acquired pneumonia; PCR, polymerase chain reaction; PJP, Pneumocystis jirovecii pneumonia.