Pneumonia Caused by Coinfection with Cytomegalovirus and Pneumocystis jirovecii in an HIV-Negative Infant Diagnosed by Metagenomic Next-Generation Sequencing

Abstract

Background: Pneumonia produced by coinfection with Pneumocystis jirovecii (PJ) and cytomegalovirus (CMV) in infants and young children without timely diagnosis and treatment is often fatal due to the limitations of traditional tests. More accurate and rapid diagnostic methods for multiple infections are urgently needed.

Case presentation: Here, we report a case of a 2-month-old boy with pneumonia caused by Pneumocystis jirovecii (PJ) and cytomegalovirus (CMV) without HIV infection. Chest computed tomography (CT) showed massive exudative consolidation in both lungs. Microscopic examination of stained sputum and smear specimens and bacterial and fungal culture tests were all negative, and CMV nucleic acid and antibody tests were positive. After a period of antiviral and anti-infective therapy, pulmonary inflammation was not relieved. Subsequently, sputum and venous blood samples were analysed by metagenomic next-generation sequencing (mNGS), and the sequences of PJ and CMV were acquired. The patient was finally diagnosed with pneumonia caused by PJ and CMV coinfection. Anti-fungal combined with anti-viral therapy was given immediately. mNGS re-examination of bronchoalveolar lavage fluid (BALF) also revealed the same primary pathogen. Therapy was stopped due to the request of the patient's guardian. Hence, the child was discharged from the hospital and eventually died.

Conclusion: This case emphasizes the combined use of mNGS and traditional tests in the clinical diagnosis of mixed lung infections in infants without HIV infection. mNGS is a new adjunctive diagnostic method that can rapidly discriminate multiple causes of pneumonia.

Keywords: HIV-negative; Pneumocystis jirovecii; cytomegalovirus; metagenomic next-generation sequencing; pneumonitis.

Figure 1

Timeline of the patient’s clinical manifestations and treatment.

Figure 2

Imaging data of lungs. (A) on the 1st day of admission, CR showed exudation in both lungs and large effusion in the right pleural cavity. (B) CR indicated a large amount of diffuse patchy exudation in both lung fields on the 4th day. (C and D) Chest CT scans showed dense shadow and consolidation were diffused in both lungs on the 12th day. (E and F) on the day before discharge day, CR showed exudation and consolidation still existed in large areas of the lungs.

Figure 3

Blood mGNS gene sequence coverage depth map for PJ (A) and CMV (B); sputum mGNS gene sequence coverage depth map for PJ (C) and CMV (D). Multiple Mapping: Multiple comparing 2 or more species. Unique Mapping: unique comparison to a certain species. Identity: the identity of the sequence compared to the reference genome. The abscissa is the size and location of the genome; the ordinate on the left is the number of sequenced sequences of the reference genome; the ordinate on the right is the consistency of the sequenced sequence with the reference genome. Peak map of PJ nucleic acid by Sanger sequencing (E).