robin j green phd, dsc new insights into the bugs in the airway of hiv-infected children with lung...
DESCRIPTION
PCP as a Syndrome Pj CMV Bacteria TB VirusesTRANSCRIPT
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Robin J GreenPhD, DSc
New Insights into the Bugs in the Airway of HIV-infected Children with Lung Disease
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The Diseases to Consider
PCPALRTIHIV-associated bronchiectasisBronchiolitis / Pneumonia
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* No mention of TB
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PCP as a Syndrome
Pj
CMV
Bacteria
TB
Viruses
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Bacteria (blood culture): • 5 (7.9%) non-survivors • 8 (12.7%) survivors (p=0.508)
Bacteria (NBBAL): • 6 (9.5%) non-survivors • 13 (20.6%) survivors (p=1.00)
Bacterial Co-infection in PCP
Kitchin O, et al. Pediatr Crit Care Med 2012;13:517-9
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Respiratory viruses: • 1 (1.6%) non-survivors • 8 (12.7%) survivors (p=0.256)
Viral Co-infection in PCP
Kitchin O, et al. Pediatr Crit Care Med 2012;13:517-9
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Cytomegalovirus and Risk of Death
Kitchin O, et al. Pediatr Crit Care Med 2012;13:517-9
CMV Status Alive Dead Total
CMV (-) 25 (56.82) 3 (15.79) 28 (44.44)
CMV <log 4 8 (18.18) 3 (15.79) 11 (17.46)
CMV >log 4 11 (25) 13 (68.42) 24 (38.10)
Total 44 (100) 19 (100) 63 (100)
Fisher’s exact 0.002
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Zampoli M, et al1 Goussard P, et al2 Kitchin P, et al3
n 202 25 63Age(months) 3,2 3.3 3,7HIV 61.4% 100% 84%Mortality 38% 72% 30%PJP(+)/CMV 36% 32% 33%Other viruses RSV, Adeno, PIV PIV3 RSV,PIV3, IV, Adeno
CMV(+) 66% 63% 55%CMV VL>log 4Culture(+)
35/47 (74%) 15/25 (60%) 24/63 (38%)
CMV> log4 (survived) 17/47(36%) ? 11/63(25%)
Treated 23/44 1/24 all IPPV in days ? 14.4 (5-31) 14.1 (10.4-17.9)CMV pn(deaths) ? 13.5 days 12.9 days
1. Zampoli M, et al. Pediatr Infect Dis J 2011;30:413–417 2. Goussard P, et al. Pediatr Pulmonol 2010; 45:650–655 3. Kitchin O, et al. Pediatr Crit Care Med 2012;13:517-9
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Serum Cytokines
IL-10 IL-1B IP-10 TNFa0
1000
2000
3000
4000
5000
6000
PCPBronchiectasis
P<.001
P=.0078
Green RJ, et al. J Antiviral Antiretroviral 2012;13:516-519
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New Data from SBAH
Survival 5% in 2005Survival 70% in 2009Survival 82% in 2012 - 2015
Reasons for improved survival:Lung protective ventilationOral steroidsGanciclovirEarly ARV introduction (BUT NOT WITHOUT PRICE)
Cloete J, et al. S Afr J Child Health 2015;in press
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ALRTI’sPneumonian = 58 (54.7%)
Bronchiolitisn = 48 (45.3%)
X2 p value
Cough 53 (91.4%) 46 (95.8%) 0.358Wheeze 14 (24.1%) 27 (56.3%) 0.001Shortness of breath 45 (77.6%) 38 (79.2%) 0.844
Fever 31 (53.4%) 29 (60.4%) 0.471Runny nose 22 (37.9%) 25 (52.1%) 0.144Nasal congestion 36 (62.1%) 31 (64.6%) 0.789Sneeze 18 (31.%) 18 (37.5%) 0.484Current antibiotics 49 (84.5%) 25 (52.1%) 0.001
HIV status 14 (24.1%) 1 (2.1%) 0.001
Abbott S, et al. SATS 2014
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Viral Results
Abbott S, et al. SATS 2014
NS for all comparisonsRespiratory viruses identified in nasopharyngeal aspirates of cases and controls (n=158)
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HRV Prevalence
Abbott S, et al. SATS 2014
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Abbott S, et al. SATS 2014
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HRV
Adeno
virus
RSV
Bocav
irus
Corona
virus
Parainf
luenz
a viru
s
Influe
nza v
irus
Metapn
uemov
irus
0.0
10.0
20.0
30.0
40.0
50.0
60.053.3
20.0
0.0
13.3
20.0 20.0
0.0
6.7
49.4
34.1 30.6
24.7
10.68.2 9.4
7.1
HIV-Infected (n=15)
HIV-Uninfected (n=85)
Per
cent
(%) w
ithin
HIV
-infe
cted
and
uni
nfec
ted
case
s P<0.001
Abbott S, et al. SATS 2014
Respiratory viruses identified in nasopharyngeal aspirates of HIV-infected and HIV-uninfected cases (n=100)
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P<0.001
Sikazwe CT, et al. 9th International Respiratory Syncytial Virus Symposium 2014
RSV Viral Load
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Sikazwe CT, et al. 9th International Respiratory Syncytial Virus Symposium 2014
RSV Subtypes and Disease
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16s rRNA Bacterial Load in ALRTI’s
HIV-infected HIV-uninfected P HRV + HRV - P
7.22 X 106 4.93 X 106 0.047 5.95 X 106 3.96 X 106 0.049
Annamaly A, et al. ATS 2014
68% higher in HIV-infected children
67% higher in HRV-positive children
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Abbott S, et al. SATS 2015
Cytokines in ALRTI’s HIV-infected vs. Uninfected• IL-13, IL-4, IL-5, TNF-α, IFN-α, IFN-γ,
MIP-1α significantly lower in HIV-infected cases
• IP-10 and MIG significantly higher in HIV-infected cases
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HIV-associated Bronchiectasis
Masekela R, et al. SAMJ 2009;99:822-825 Masekela R, et al. IJTBLD 2012;16:114-119
Only one viral culture of Parainfluenza type 2
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23
Haemophilus influenzae
Pseudomonas sp.
Vosloo S, et al 2015;unpublished
Bronchiectasis Airway Microbiome
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Serum TREM-1
Masekela R, et al. Ped Pulmonol 2015;50:333-339
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Conclusion
• Many childhood ALRTI’s have identifiable viral and bacterial organisms
• The relative contribution of each species to disease is not clear
• In HIV-infected children there is a greater relative abundance of bacteria, even in obvious viral disease
• Acute viral bronchiolitis (RSV) occurs less commonly in HIV-infected children …..
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Conclusion• … But many normal children harbor viruses and bacteria
• Organisms in HIV-associated bronchiectasis are different to CF-associated bronchiectasis, possibly reflecting different immune responses
• Cytokine data does not support the pro/anti-inflammatory model (but IP-10 important in ALRTI’s)
All these conclusions may have implications for management and vaccine prevention
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Thank You• Prof Refiloe Masekela
• Dr Teshni Moodley
• Dr Omolemo Kitchin
• Dr Salome Abbott
• Dr Alicia Annamaly / Prof Peter le Souef
• Dr Jeane Cloete
• Ms Solize Vosloo / Prof Fanus Venter
• Prof Max Klein