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

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

3. 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):

4. 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):
Morrow pneumonia in South African children with PCP
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

5. 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

6. 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

7. 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): Deaths due to respiratory tract infections in Africa: a review of autopsy studies.
2. Hsiao NYJ Clin Virol Sep;58(1):74-8.Cytomegalovirus viraemia in HIV exposed and infected infants: prevalence and clinical utility for diagnosing CMV pneumonia. 

8. 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 Jul;45(7):650-5.

9. 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

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

11. 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

12. 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

13. 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