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)