A LITERATURE REVIEW AND SURVEY OF CHILDHOOD PNEUMONIA ETIOLOGY STUDIES: 2000 -­‐ 2010 Zunera Gilani1, YuenDng D. Kwong2, Orin S. Levine3, Maria Deloria-­‐Knoll3, J. Anthony G. ScoQ4,5, Katherine L. O’Brien3, and Daniel R. Feikin3,6 1 Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, BalAmore, Maryland, USA; 2 School of Medicine, Johns Hopkins University, BalAmore, Maryland, USA; 3 InternaAonal Vaccine Access Center, Bloomberg School of Public Health, Johns Hopkins University, BalAmore, Maryland, USA; 4 KEMRI–Wellcome Trust Research Programme, Kilifi, Kenya; 5Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom; 6 Division of Preparedness and Emerging InfecAons, NaAonal Center for Emerging and ZoonoAc InfecAous Diseases, Centers for Disease Control and PrevenAon, Atlanta, Georgia, USA INTRODUCTION • 
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TABLE 1 Approximately 1.6 million children die from pneumonia annually [1]. The Pneumonia EAology Research for Child Health (PERCH) study is the largest mulA-­‐site study of childhood pneumonia since the Board of Science and Technology for InternaAonal Development (BOSTID) studies were done in the 1980’s [2]. PERCH undertaken to idenAfy the expected eAologies of pneumonia in 2015. In recent years many developed and developing country sites have iniAated pneumonia studies that provide eAology data. These studies will provide useful complementary data to the PERCH study. METHODS • 
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PubMed literature review to idenAfy pneumonia eAology studies in children under five. Search terms included key words, MeSH terms, synonyms or truncaAons; 8 separate search strategies were conducted. Titles and abstracts were screened and perAnent informaAon was obtained from eligible studies. Studies were grouped by category and summary staAsAcs were calculated. A web-­‐based survey conducted to capture informaAon on unpublished ongoing or recently completed studies (Survey Monkey™, Palo Alto, California). Emailed to ~5000 pneumonia community members subscribing to PneumoFOCUS [3], a bulleAn providing news about pneumonia, pneumococcal disease, and pneumococcus. We also contacted: researchers responding to the PERCH Request for Proposals for Sites, other known pneumonia surveillance researchers and researchers idenAfied through our contacts. Inclusion criteria: study of acute community-­‐acquired pneumonia or acute lower respiratory tract infecAon; consistent tesAng for at least one specific eAology in enrolled paAents; enrollment of children <5 years old; published between June 2005 and June 2010; data collecAon from year 2000 onwards; ≥10 pneumonia/ALRI cases; ≥ 1 calendar year of surveillance; English language. Exclusion criteria: exclusive enrollment of bronchioliAs paAents or paAents with a specific complicaAon or sequelae of pneumonia; inability to disAnguish eAology of pneumonia cases from other syndromes; eAology inferred from upper airway carriage alone; focus only on anAbioAc resistance among pneumococcal isolates; exclusive enrollment of hospital-­‐acquired pneumonia paAents RESULTS • 
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We idenAfied 88 published studies in 52 countries ranging from 10 to 21,239 pneumonia paAents (median 260 paAents) (Figure 1) . MulAple studies were done in 26 countries. Our survey idenAfied 65 ongoing or recently completed studies in 41 countries ranging from 12 to 27,778 pneumonia paAents (median 780 paAents). MulAple studies were being conducted in 16 countries. Literature review and survey results are not mutually exclusive. Study characterisAcs reported in Table 1 illustrate large variaAons in the methods used. CONCLUSIONS • 
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Greater depth of available data than convenAonal wisdom might have suggested. Challenges in interpreAng various pneumonia eAology studies, parAcularly when comparing or combining results. Different studies employ different case definiAons, levels of clinician involvement, facility types, specimens collected and laboratory tests. Use of a common protocol in a mulA-­‐site study with broad geographic and epidemiologic representaAon will offer some anchor on which to draw inferences about the similariAes and differences from other studies. • 
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FIGURE 1: Map of Countries with Recent or Ongoing Child Pneumonia EAology Studies IdenAfied in Literature Review and Survey REFERENCES 1.Black RE, Cousens S, Johnson HL, et al. Global, regional, and naAonal causes of child mortality in 2008: a systemaAc analysis. Lancet 2010 Jun 5;375(9730):1969-­‐87. 2.Selwyn BJ. The epidemiology of acute respiratory tract infecAon in young children: comparison of findings from several developing countries. Coordinated Data Group of BOSTID Researchers. Rev Infect Dis 1990 Nov-­‐Dec;12 Suppl 8:S870-­‐88. 3.PneumoACTION. PneumoFOCUS. 2011 [cited; Available from: htp://www.preventpneumo.org/news/pneumofocus/index.cfm Study CharacterisDc
Literature Review (N=88)
WHO Region
AFRO
EMRO
EURO
PAHO
SEARO
WPRO
MulA-­‐Region
Case DefiniDonb
WHO very severe pneumonia
WHO severe pneumonia
WHO pneumonia
Other Clinical +/-­‐ laboratory definiAon
Clinical + Radiologic definiAon
Other Unknown
Wheeze Included in Case DefiniDon
Included
Excluded
Excluded if clears with bronchodilator
Other
Unknown
Facility Typeb
District/Provincial hospital
Subdistrict/Mission hospital
Health center/clinic
University hospital
Other
Unknown
Type of PaDent
InpaAents only
InpaAents and outpaAents
OutpaAents only
Community only
InpaAents, outpaAents, community
Other
Unknown
Age Grouping
<5 years
<3 years
< 1 year
Other
MulA-­‐age Unknown
Includes Neonates
Yes
No
Unknown
Eligibility DeterminaDonb
Physicians
Clinical officers/physician assistants
Nurses
Other
Unknown
Specimens Collectedb
NP swabs/nasal wash/nasal aspirate
Blood
Sera
Induced sputum
Lung aspirates
Pleural fluid
Post mortem specimens
Other
Unknown
Lab testsb
Blood culture
PCR
Serology
Urine anAgen tesAng
Blood anAgen tesAng
Other
Unknown
Data CollecDon Start Date
2005 or earlier
2006 to 2010
Unknown
Number of Studies
% of studiesa Survey (N=65)
Number of % of
Studies studiesa
12
3
13
18
20
18
4
14
3
15
20
23
20
5
17
5
5
12
19
6
1
26
8
8
18
29
9
2
5
13
10
25
47
41
2
6
15
11
28
52
47
-­‐-­‐
3
36
26
22
30
11
0
5
55
40
34
46
17
-­‐-­‐
9
5
2
5
67
43
24
10
24
-­‐-­‐
22
26
9
1
7
38
45
16
2
-­‐-­‐
9
0
2
29
35
18
13
0
3
41
50
-­‐-­‐
29
3
13
7
24
0
45
5
20
11
37
-­‐-­‐
40
29
0
0
2
1 16
56
40
0
0
3
1
-­‐-­‐
30
26
4
2
2
0
1
47
41
6
3
3
0
-­‐-­‐
32 4 5 47 0
0
36
5
6
53
0
-­‐-­‐
24
9
2
27
2
1
38
14
3
42
3
-­‐-­‐
24 47 17
34
66
-­‐-­‐
41
24
0
63
37
-­‐-­‐
16
1 3 5 66
64
4
12
44
-­‐-­‐
51
20
12
7
0
79
31
19
11
-­‐-­‐
43 67 33 9 5 13
3
21
1
49
77
38
10
6
15
3
24
-­‐-­‐
48
51
19
6
8
23
2
17
0
74
79
29
9
12
35
3
26
-­‐-­‐
54 38 44 6 6 24 5
64
45
52
7
7
29
-­‐-­‐ 53
44
14
14
6
8
0
82
68
22
19
9
12
-­‐-­‐
77
9
2
90
10
-­‐-­‐
14
40
11
26
74
-­‐-­‐
a Percentages do not include unknowns b QuesAon allowed mulAple items to be checked so percentages may exceed 100% NOTE: Due to rounding, totals may not sum to 100%; Literature Review and Survey results not mutually exclusive © InternaAonal Vaccine Access Center (IVAC) at the Johns Hopkins Bloomberg School of Public Health 2012 Al Rights Reserved