Pneumocystis jirovecii Pneumonia
Among HIV-Exposed, Uninfected
Infants in Botswana
Letang Gaofiwe, MS Kelly, SC Boiditswe, B Ratshaa,
MI Matsheka, BA Gashe, M Smieja, CK Cunningham,
KA Feemster, AP Steenhoff
FIDSSA Congress
6th November, 2015
Outline
• Background
• Objectives
• Study Design and Methods
• Results
• Implications
Background – HIV in Botswana
• ~33% HIV prevalence among pregnant women
• PMTCT programme decreased vertical HIV
transmission from 20.7% in 1999 to 2.5% in
2013
• ~30% of the Botswana infant population is HIV
exposed, uninfected (HIV-EU)
UNAIDS: Botswana –Global AIDS response report, 2013
Background – HIV-EU Infants
Background – Pneumonia in HIV-EU
• HIV-EU infants tended to have worse pneumonia
treatment outcomes than HIV-unexposed infants
in South African study
• Pneumocystis jirovecii was most common
pathogen identified in HIV-EU infants who failed
first-line pneumonia treatment
• Outcomes and role of PCP in pneumonia among
HIV-EU infants still poorly described
McNally et.al., Effect of age, polymicrobial disease and maternal
HIV status on treatment response, Lancet, 2007:26(6)
Pneumocystis jirovecii pneumonia
• PCP pneumonia mortality in African studies
ranges from 29-67%
• Gold standard: silver staining of lower respiratory
tract specimen
• PCR of lower respiratory specimens widely used
• PCR of nasopharyngeal specimens may be less
invasive alternative
• Serum lactate dehydrogenase (LDH) used in
resource-limited settings
1. To investigate whether HIV-EU infants with
pneumonia have worse outcomes than HIV-
unexposed infants.
2. To examine the role of Pneumocystis
jirovecii in the poor outcomes of HIV-EU infants.
Objectives
Study Design and Methods
• prospective cohort study of
community-acquired pneumonia
• children recruited within 6 hours of
ED triage time, followed until
discharge (or death)
• primary outcome (treatment
failure at 48 hours)
• receive standard medical care -
antibiotic and other treatment
decisions made by clinical team
Inclusion criteria
• 1 – 23 months of age
• WHO pneumonia or severe pneumonia
• pneumonia:
cough OR difficult breathing
AND lower chest wall indrawing
• severe pneumonia:
pneumonia AND danger signs (convulsions,
inability to drink, abnormal
sleepiness, or central cyanosis)
Exclusion criteria
• chronic conditions predisposing to pneumonia
• hospitalization in the prior 2 weeks
• diagnosis of asthma or resolution of chest wall
indrawing after ≤2 β2-agonist treatments
• previous study enrollment with hospital
discharge <30 days ago
Primary Outcome
• Treatment failure defined as any of the following:
- persistent lower chest wall indrawing
- new WHO danger signs
- O2Sat <80% on room air
- requirement for CPAP or mechanical ventilation
- death
• assessed by study team member blinded to HIV
exposure status
Molecular testing for P. jirovecii
• age ≥2 months
• oxygen saturation <85%
• LDH >750 U/L
Case definition for probable PCP
• selected 21 infants PCP suspected by the
clinical team
• PCR on nasopharyngeal swab specimens
Statistical analysis
• Cox-proportional hazards models to estimate
risk ratios for treatment failure and in-hospital
mortality according to HIV exposure status
• analyses adjusted for age and proximity to
health care services
Results : Baseline Characteristics
Results: Treatment failure
• 128 (36%) infants failed treatment at 48 hours
*adjusted for age and proximity to health care services
Results: In-Hospital Mortality
• 24 (7%) children died during the hospitalization
*adjusted for age and proximity to health care services
Results: Probable PCP
• 69 infants had LDH as screening test for PCP
• 3 of 5 HIV-EU children received TMP-SMX
• 5 of 5 HIV-EU children died
N Infants with
probable PCP
% with probable
PCP
HIV-unexposed 12 1* 8%
HIV- EU 38 5 13%
HIV-infected 19 7 37%
* infant with severe malnutrition
Results: Pneumocystis PCR
• Probable PCP: + in 5 of 11 (45%) children
+ in 0 of 1 HIV-unexposed
+ in 1 of 4 HIV-EU
+ in 4 of 6 HIV-infected
• No Probable PCP: + in 1 of 10 (10%) children
Limitations
• single center study
• not obtaining lower respiratory tract
specimens for confirmation of P. jirovecii
• Pneumocystis PCR performed on limited
number of NP specimens to date
• testing for CMV planned but not yet available
Implications
• HIV-EU infants have worse pneumonia
outcomes than HIV-unexposed infants.
• PCP may account for some of the excess
mortality observed in HIV-EU infants.
• Future studies are needed to better define the
role of PCP in the poor outcomes of HIV-EU
infants with pneumonia.
• Department of Pediatrics, Princess Marina Hospital
• Botswana-UPenn Partnership
• Botswana Ministry of Health
• University of Botswana
• Thrasher Research Fund
• International AIDS Society (CIPHER)
Acknowledgements
HIV Exposure Status
• HIV-unexposed
- mother tests negative for HIV during pregnancy, at
delivery, or at enrollment
• HIV-EU
- mother tests positive for HIV before or at delivery
- infant tests negative for HIV at ≥6 weeks of age (if
exclusively formula fed), ≥6 weeks from
discontinuation of breastfeeding, or at enrollment
• HIV-infected
- infant tests positive for HIV by PCR (if <18 months)
or antibody-based test (if ≥18 months)