PCP: management of co-infection Dr. Immaculate Kariuki Consultant Paediatrician Nairobi, Kenya

Intended Learning Outcomes To appreciate the diversity and significance of co-infections in patients with PCP

Significance of co-infections Common A frequent cause of clinical failure Present at initial presentation or acquired in critical care units Bias towards respiratory pathogens Lowe D. et al Plos One 2013; 8 (8): 1425 patients from 49 studies, bias towards respiratory pathogens. Lowe D. Pneumocystis jirovecii  Pneumonia in Tropical and Low and Middle Income Countries: A Systematic Review and Meta-Regression.Plos One 2013; 8(8):

Aetiology of co-infections Bacteria: eg S. aureus, S. pneumoniae, K. pneumoniae Mycobacterium tuberculosis Viruses: eg RSV, adenovirus, CMV Morrow et al. The Pediatric Infectious Disease Journal. 29(6):535-539. Morrow pneumonia in South African children with PCP 2006-2008. Of 43 South African children with PCP, 30 (69.8%) were co-infected with another organism. Seventeen (56.7%) were co-infected with CMV, 4 (13.3%) with another virus

Co-infections in non HIV Mainly pulmonary Present in 28-71% of patients Multiple pathogens eg Staphylococcus aureus, gram negative bacteria, Aspergillus sp, CMV CMV still significant In allogeneic hematopoietic stem cell transplant (HSCT) recipients, PCP is associated with CMV pneumonia in around 50% of cases1 1 Slides from ECIL-5 (European council on Infections in Leukemia) 2013

Co-infection with viruses Present in up to 16-40% of HIV infected children with severe all-cause pneumonia Viruses identified include CMV, RSV, influenza, human metapneumovirus, parainfluenza and adenovirus Difficult to make diagnosis out of research settings in low and middle income areas

Cytomegalovirus (1) CMV co-infection has been reported in HIV children with pneumonia on autopsy studies & in 1 out 5 adults with RTI in an autopsy study¹ It is more common in HIV-infected than uninfected children CMV viraemia peaks at age 3-6 months. It is found in high proportion of HIV exposed infants with pneumonia² CMV detectable DNA can be an independent predictor of HIV transmission and mortality in infected individuals and may be an indicator of moderate or severe immunosuppression Mudenda et al Curr Opin Pulm Med2013 May;19(3):229-37 Deaths due to respiratory tract infections in Africa: a review of autopsy studies. 2. Hsiao NYJ Clin Virol. 2013 Sep;58(1):74-8.Cytomegalovirus viraemia in HIV exposed and infected infants: prevalence and clinical utility for diagnosing CMV pneumonia. 

Cytomegalovirus (2) 48% co-infection with PCP in pre ART era and 36% dual infection in ventilated patients¹ CMV pneumonia may be considered in ventilated PCP paediatric patients failing treatment² Histological diagnosis maybe required because its role in pulmonary disease is difficult to assess Treatment : IV gancyclovir 5mg/kg every 12 hours for 14 to 21 days then maintenance at 5mg/kg/day References: Williams AJ, et al. Pneumocystis carinii pneumonia and cytomegalovirus infection in children with vertically acquired HIV infection. AIDS. 2001;15:335–33 2. Goussard P. CMV pneumonia in HIV-infected ventilated infants. Pediatr Pulmonol. 2010 Jul;45(7):650-5.

Bacterial co-infections (1) In most studies of children with severe pneumonia, PCP is a co- infection of bacterial pneumonia Polymicrobial disease associated with higher mortality Blood culture and appropriate antibiotics necessary Higher rates of resistant organisms on nasopharyngeal swabs have been found in association with PCP

Bacterial co-infections (2) Commonly isolated: Streptococcus pneumoniae Staphylococcus aureus Haemophilus influenza Other gram negative bacteria like Klebsiella spp & Escherichia Coli

Tuberculosis (TB) co-infection (1) TB may present as an acute severe pneumonia in infants and young children PCP treatment with steroids has potential to worsen untreated TB Gastric washings and induced sputums routinely done for TB diagnosis can be used for PCP microscopy

Tuberculosis co-infection (2) 5.8% of the patients (2651 adults) had concurrent TB and PCP Low and middle income data on TB/PCP co-infections missing Refence: Castro JG et al Scand J Infect Dis. 2007;39(11-12):1054-8 PCP diagnosis was presumptive & microbiological ( IF & PCR) while TB diagnosis was based on PCR & culture

Summary Pneumocystis pneumonia commonly occurs as a co-infection Other than bacteria co-infections, CMV pneumonia is increasingly being reported in pediatric patients Co-infections compound both diagnosis and management