Clinical Diagnosis of Bordetella Pertussis Infection: A Systematic Review

Mark H. Ebell; Christian Marchello; Maria Callahan

doi:10.3122/jabfm.2017.03.160330

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Figure 1.
Preferred Reporting Items for Systematic Reviews and Meta-analyses flow diagram. Only the first identified reason for excluding an article is listed. In some cases >1 reason was identified.
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Figure 2.
Summary receiver operating characteristic curves for overall impression (A), whooping cough (B), posttussive vomiting (C), and apnea or cyanosis (D), stratified by age.
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Figure 3.
Summary receiver operating characteristic curves for overall impression (A), whooping cough (B), paroxysmal cough (C), and posttussive vomiting (D), stratified by vaccination status.

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Table 1.

Characteristics of Included Studies

Studies	Patient Population	Patients (n)	Age	Adult or Child	Reference Standard	Country	Year(s) Recruited
Teepe et al,¹³ 2015	Adults presenting with cough of <28 days' duration	3074	Mean, 50 years	Adult	PCR	12 European countries	2007–2010
Karagul, et al,¹⁴ 2015	Consecutive patients between ages 10 and 39 years admitted to a hospital with at least 2 weeks of cough illness	214	Mean, 26.6 years; range, 10–39 years	Both	PCR^*	Turkey	2010–2011
Park et al,¹⁵ 2014	Patients with cough of <30 days' duration presenting to a hospital or outpatient clinic	490	Mean, 44.3 years	Both	PCR or culture	South Korea	2011–2012
Gentile et al,¹⁶ 2014	Consecutive children with clinically suspected pertussis based on typical symptoms, prolonged cough (older children), or apnea (infants)	620	Median, 3 months; range, 15 days to 8 years	Child	PCR	Argentina	2003–2011
Philipson et al,¹⁷ 2013	Consecutive patients aged 5–49 years with at least 2 weeks of cough	222	5–16 years (n = 70); 17–49 years (n = 156)	Child	Single IgG in oral fluid samples	New Zealand	2011
Miyashita et al,¹⁸ 2013	Consecutive adolescents and adults with cough	1315	Mean, 37.5 years; range, 16–79 years	Adult	PCR and paired serology	Japan	2005–2012
Ghanaie et al,¹⁹ 2010	Population-based sample of children with at least 2 weeks of cough	328	Mean, 11 years, range, 6–14 years	Child	PCR or culture	Iran	2007–2008
Harnden et al,²⁰ 2006	Children presenting to a primary care physician with at least 2 weeks of cough	172	Mean, 9.4 years; range, 5–16 years	Child	Single or paired IgG serology^{^†}	England	2001–2005
Park et al,²¹ 2005	Persons aged ≥16 years presenting to an outpatient clinic with cough of 1–12 weeks' duration	102	Mean, 30 years; range, 19–83 years	Adult	PCR and culture	Korea	2002–2003
Narkeviciute et al,²² 2005	Immunized children with prolonged cough referred for evaluation in a hospital	32	Median, 11; range, 4–15 years	Child	Single IgM or IgA serology	Lithuania	2001
Liese et al,²³ 2003	Children with cough for at least 7 days	116	Mean, 4.2 years; range, 2.2–6.0 years	Child	PCR or culture^{^‡}	Germany	1997–1999
Preziosi and Halloran,²⁴ 2003	Children aged 6 months to 8 years with cough of >7 days' duration	989	Range, 6 months to 8 years	Child	Culture or serology	Senegal	1993
Gilberg et al,²⁵ 2002	Adults with cough of 7–31 days' duration, without fever or other clear cause	123	Median, 49 years; range, 18–88 years	Both	≥2-fold anti-PT IgG, PCR, or culture	France	1999
Senzilet et al,²⁶ 2001	Adults and adolescents with cough from 1–8 weeks' duration referred from a primary care sentinel surveillance network	442	Mean, 37.2 years; range, 12–90 years	Both	PCR, culture, and/or serology	Canada	1996–1997
Strebel et al,²⁷ 2001	Persons aged 10–49 years with acute paroxysmal cough or persistent cough 7–34 days' duration	212	Median, 35 years; range, 10–49 years	Both	PCR, culture, or serology	United States	1995–1996
Heininger et al,²⁸ 2000	Patients enrolled in a vaccine trial or family members with at least 7 days of cough	392	NR	Both	PCR, culture, and/or serology	Germany	1991–1994
Heininger et al,²⁹ 1997	All children presenting to a pediatrician with cough of ≥7 days' duration	2045	Mean, 4.3 years; range, 6 days to 41 years	Both	Culture	Germany	1990–1991
Schlapfer et al,³⁰ 1995	Patients enrolled in a vaccine trial or family members with at least 7 days of cough	546	Mean, 4.7 years; range, child up to 47 years	Both	PCR or culture	Germany	1993–1994
Postels-Multani et al,³¹ 1995	Adult members in a family with a child who has confirmed pertussis and who have a respiratory symptom	79	Mean, 36 years; median, 33 years; range, 19–83 years	Adult	Culture or serology^{^§}	Germany	1992–1994
Granstrom et al,³² 1991	Consecutive patients with suspected pertussis seen at the outpatient clinic of a hospital	285	Median, 3.7 years; range, 0.3–63.2 years	Both	Culture or serology	Sweden	1986–1987
He et al,³³ 1998	Adults and children with a complaint of paroxysmal cough of any duration	584	Median, 9 years; range, 7 days to 74 years	Both	PCR or culture	Finland	1994–1997
Heininger et al,³⁴ 1993	Children and household contacts with cough illness	3629	Almost all (98%) aged ≤15 years	Child	Culture	Germany	1991–1992

↵* Pertussis positive: positive for insertion sequence 481(IS481) and pertussis toxin promoter (ptxA-Pr); Bordetella spp: positive for IS481 with a cycle threshold (Ct) value <35 and negative for ptxA-Pr; indeterminate: positive for IS481 with a Ct between 35 and 40, and negative for ptxA-Pr; negative: cycle threshold >=40.
↵† >100 Enzyme-linked immunosorbant assay units in a single sample, or a 4-fold change in titers.
↵‡ Polymerase chain reaction (PCR) or culture from nasopharyngeal swab (cough >7 days) or serology (cough >21 days).
↵§ Culture, >=100% increase in immunoglobulin (Ig) G or IgA antibodies to pertussis toxin (PT), filamentous hemagglutinin (FHA), and/or pertactin, or IgA antibody levels to PT, FHA, and/or pertactin at least 2 standard deviations above normal.
NR, not reported.

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Table 2.

Assessment of Study Quality Using the QUADAS-2 Framework

Study	Consecutive or Random Sample Enrolled (Y/N/U)	Avoided Case-Control Design (Y/N/U)	Avoided Inappropriate Exclusion Criteria (Y/N/U)	Likelihood That Patient Selection Could Have Introduced Bias (H/L/U)	Concerns Exist That Included Patients and Setting Do Not Match the Review Question (Y/N/U)	Index Test Results Were Interpreted Without Knowledge of Reference Standard (Y/N/U)	Likelihood That Conduct or Interpretation of Index Test Introduced Bias (H/L/U)	Applicability: Concerns Exist That the Index Test Differs from the Review Question (Y/N/U)	Reference Standard Is Likely to Correctly Classify Patients as Having Pertussis (Y/N/U)	Reference Standard Was Interpreted without Knowledge of Index Test (Y/N/U)	Likelihood That Conduct or Interpretation of Reference Standard Introduced Bias (H/L/U)	Applicability: Concerns Exist That the Target Conditions Defined By the Reference Standard Do Not Match the Review Question (Y/N/U)	All Patients Received a Reference Standard (Y/N/U)	All Patients Received the Same Reference Standard (Y/N/U)	All Patients Were Included in the Analysis (Y/N/U)	Patient Flow Could Have Introduced Bias (H/L/U)	Overall Assessment of Risk of Bias (L/M/H)
Teepe, 2015	Y	Y	Y	L	N	Y	L	N	Y	Y	L	N	Y	Y	Y	L	L
Karagul, 2015	Y	Y	Y	L	N	Y	L	N	Y	U	L	N	Y	Y	Y	L	L
Park, 2014	Y	Y	Y	L	N	Y	L	N	Y	U	L	N	Y	Y	Y	L	L
Gentile, 2014	Y	Y	Y	L	N	Y	L	N	Y	U	L	N	Y	N	Y	L	L
Miyashita, 2013	Y	Y	Y	L	N	Y	L	N	Y	U	L	N	Y	Y	Y	L	L
Ghanaie RM, 2010	Y	Y	Y	L	N	Y	L	N	Y	U	L	N	Y	Y	Y	L	L
Park, 2005	Y	Y	Y	L	N	Y	L	N	Y	U	L	N	Y	Y	Y	L	L
Heininger, 2000	Y	Y	Y	L	N	Y	L	N	Y	U	L	N	Y	Y	Y	L	L
Heininger, 1997	Y	Y	Y	L	N	Y	L	N	Y	U	L	N	Y	Y	Y	L	L
Granstrom, 1991	Y	Y	Y	L	N	Y	L	N	Y	U	L	N	Y	Y	Y	L	L
Strebel, 2001	Y	Y	Y	L	N	Y	L	N	Y	U	L	N	Y	N	Y	L	L
Gilberg, 2002	Y	Y	Y	L	N	Y	L	N	Y	U	L	N	Y	N	Y	L	L
He, 1998	Y	Y	Y	L	N	Y	L	N	Y	U	L	N	Y	Y	Y	L	L
Heininger, 1993	Y	Y	Y	L	N	Y	L	N	Y	U	L	N	Y	Y	Y	L	L
Schlapfer, 1995	N	Y	Y	H	N	Y	L	N	Y	U	L	N	Y	Y	Y	L	M
Philipson K, 2013	Y	Y	Y	L	N	Y	L	N	N	U	H	N	Y	Y	Y	L	M
Harnden, 2006	Y	Y	Y	L	N	Y	L	N	N	U	H	N	Y	Y	Y	L	M
Senzilet, 2001	U	Y	Y	U	N	Y	L	N	Y	U	L	N	Y	Y	Y	L	M
Narkeviciute I, 2005	Y	Y	Y	L	N	Y	H	N	N	U	H	N	Y	Y	N	H	H
Liese JG, 2003	Y	Y	Y	L	N	Y	L	N	N	U	H	N	Y	N	N	H	H
Postels-Multani, 1995	N	Y	Y	H	N	Y	L	N	N	U	H	N	Y	N	N	H	H
Preziosi and Halloran, 2003	Y	Y	Y	L	N	Y	L	N	N	U	H	N	Y	N	N	H	H

H, high; L, low; M, medium; N, no; U, unknown; Y, yes.

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Table 3.

Summary Estimates of the Diagnostic Accuracy of Signs and Symptoms for Bordetella pertussis Infection^*

Sign or Symptom	Studies^*	Sensitivity (95% CI)		Specificity (95% CI)	LR+ (95% CI)^{^‡}	LR− (95% CI)^{^‡}	DOR (95% CI)^{^‡}	AUROCC^{^‡}
Sign or Symptom	Studies^*	Studies Reporting Sensitivity and Specificity	All Studies^{^†}	Specificity (95% CI)	LR+ (95% CI)^{^‡}	LR− (95% CI)^{^‡}	DOR (95% CI)^{^‡}	AUROCC^{^‡}
Overall clinical impression	4/5	0.47 (0.36–0.59)	0.48 (0.39–0.58)	0.85 (0.71–0.93)	3.3 (1.9–5.5)^{^§}	0.63 (0.56–0.70)^{^§}	5.3 (3.3–8.1)^{^§}	0.659
Whooping cough
All	12/17	0.31 (0.23–0.41)	0.31 (0.24–0.40)	0.84 (0.74–0.91)	1.9 (1.2–3.1)^{^§}	0.83 (0.73–0.95)^{^§}	2.5 (1.4–4.2)^{^§}	0.545
Children	5/6	0.41 (0.24–0.61)	0.43 (0.29–0.57)	0.84 (0.52–0.96)	2.9 (1.2–7.3)	0.72 (0.60–0.84)	4.1 (1.4–9.8)	0.593
Adults	7/8	0.21 (0.16–0.28)	0.17 (0.11–0.23)	0.82 (0.70–0.90)	1.2 (0.81–1.8)	0.97 (0.81–1.8)	1.3 (0.75–2.0)	0.349
Posttussive vomiting
All	14/19	0.42 (0.33–0.52)	0.45 (0.35–0.54)	0.75 (0.68–0.80)	1.7 (1.4–1.9)^{^§}	0.77 (0.68–0.86)^{^§}	2.2 (1.7–2.7)^{^§}	0.646
Children	5/7	0.56 (0.39–0.72)	0.55 (0.41–0.68)	0.66 (0.52–0.78)	1.7 (1.3–2.2)	0.67 (0.49–0.84)	2.6 (1.6–3.9)	0.650
Adults	7/8	0.34 (0.26–0.43)	0.35 (0.27–0.42)	0.80 (0.74–0.84)	1.7 (1.3–2.3)	0.83 (0.73–0.93)	2.0 (1.3–3.0)	0.602
Paroxysmal cough
All	13/16	0.80 (0.71–0.86)	0.79 (0.73–0.86)	0.35 (0.24–0.49)	1.2 (1.1–1.4)^{^§}	0.58 (0.49–0.68)^{^§}	2.2 (1.7–2.7)^{^§}	0.653
Children	5/7	0.72 (0.60–0.81)	0.75 (0.65–0.84)	0.47 (0.32–0.62)	1.4 (1.2–1.7)	0.61 (0.52–0.72)	2.3 (1.6–3.1)	0.644
Adults	6/6	0.88 (0.80–0.92)	=	0.26 (0.12–0.47)	1.2 (1.04–1.6)	0.50 (0.33–0.75)	2.6 (1.4–4.4)	0.774
Sputum production	4/4	0.79 (0.52–0.93)	—	0.34 (0.18–0.56)	1.2 (1.1–1.3)^{^§}	0.63 (0.39–0.89)^{^§}	2.0 (1.3–3.0)^{^§}	0.555
Wheezing absent	4/4	0.75 (0.34–0.95)	—	0.36 (0.17–0.62)	1.1 (0.90–1.3)	0.69 (0.31–1.1)	1.9 (0.83–3.8)	0.514
CDC clinical criteria	3/3	0.90 (0.82–0.95)	—	0.16 (0.13–0.19)	1.07 (0.97–1.1)	0.66 (0.33–1.1)	1.8 (0.86–3.4)	0.19
Headache absent	3/3	0.60 (0.38–0.85)	—	0.54 (0.24–0.81)	1.3 (1.05–1.8)^{^§}	0.76 (0.51–0.95)^{^§}	1.8 (1.1–2.7)^{^§}	0.588
Sleep disturbed by cough	5/6	0.55 (0.21–0.85)	0.56 (0.31–0.80)	0.54 (0.19–0.85)	1.2 (1.0–1.5)^{^§}	0.83 (0.69–0.95)^{^§}	1.5 (1.1–1.9)^{^§}	0.557
Dyspnea	4/4	0.21 (0.09–0.42)	—	0.84 (0.57–0.95)	1.3 (0.92–1.9)	0.96 (0.90–1.05)	1.4 (0.89–2.1)	0.467
Sneezing	4/4	0.78 (0.58–0.90)		0.23 (0.13–0.36)	1.00 (0.87–1.09)	0.97 (0.63–1.4	1.1 (0.65–1.7)	0.423
Apnea	5/6	0.07 (0.02–0.22)	0.10 (0.03–0.17)	0.93 (0.83–0.97)	1.0 (0.64–1.5)	0.99 (0.94–1.02)	1.0 (0.64–1.5)	0.606
Cyanosis	4/4	0.05 (0.01–0.24)	—	0.95 (0.79–0.99)	0.99 (0.66–1.4)	1.0 (0.96–1.02)	1.0 (0.67–1.4)	0.545
Chest pain	3/3	0.25 (0.16–0.37)		0.74 (0.67–0.80)	0.96 (0.72–1.2)	1.01 (0.92–1.1)	0.95 (0.67–1.3)	0.55
Fever	7/8	0.13 (0.05–0.29)	0.17 (0.05–0.29)	0.82 (0.71–0.90)	0.76 (0.45–1.2)	1.0 (0.95–1.1)	0.73 (0.41–1.2)	0.549

The estimates presented here include only signs and symptoms for which at least 3 studies reported both sensitivity and specificity. Entries are sorted by diagnostic odds ratios.
↵* Data are the number of studies with reported values for both sensitivity and specificity among the total studies found.
↵† When studies reported sensitivity only, sensitivity was calculated using a random effects model.
↵‡ These values were calculated using only data from studies that were able to calculate both sensitivity and specificity.
↵§ Value is significantly different from 1.0.
CDC, Centers for Disease Control and Prevention; CI, confidence interval; DOR, diagnostic odds ratio; LR+, positive likelihood ratio; LR−, negative likelihood ratio; AUROCC, area under the receiver operating characteristic curve (also known as the c-statistic).

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Appendix

Individual patient data. Continuity correction applied to avoid division by zero where necessary

Study	Sign or symptom	Age Group	Vaccinated	TP	FP	FN	TN	Sens	Spec	LR+	LR-
Preziosi, 2003	Alternation of consciousness or seizures	Children	No	0	0	243	30	0.00	0.97	0.13	7.66
Preziosi, 2003	Alternation of consciousness or seizures	Children	Yes	0	0	594	122	0.00	0.99	0.21	4.81
Schlapfer, 1995	Antibiotic use	Both	Yes	13	36	91	359	0.13	0.91	1.37	0.96
Karagul, 2015	Antibiotic use	Adult	NR	29	116	11	58	0.73	0.33	1.09	0.83
Preziosi, 2003	Apnea	Children	No	3	0	240	30	0.02	0.97	0.52	1.91
Preziosi, 2003	Apnea	Children	Yes	0	0	594	122	0.00	0.99	0.21	4.81
Philipson K, 2013	Apnea	Children	NR	1	1	11	53	0.08	0.98	4.50	0.93
Harndon A, 2006	Apnea	Children	Yes	14	12	50	96	0.22	0.89	1.97	0.88
Philipson K, 2013	Apnea	Adult	NR	2	20	9	125	0.18	0.86	1.32	0.95
Gentile, 2014	Apnea	Children	Yes	41	52	142	243	0.22	0.82	1.27	0.94
Senzilet, 2001	Apnea	Adult	Partial	12	55	76	299	0.14	0.84	0.88	1.02
Narkeviciute I, 2005	Apnea	Children	Yes	1		31		0.03
Gilberg, 2002	CDC clinical criteria	Adults	Partial	55	42	7	5	0.89	0.11	0.99	1.06
Strebel, 2001	CDC clinical criteria	Both	Yes	27	153	0	32	1.00	0.17	1.21	0.00
Ghanaie RM, 2010	CDC clinical criteria	Children	Yes	20	261	1	46	0.95	0.15	1.12	0.32
Philipson K, 2013	Chest pain	Children	NR	2	11	10	43	0.17	0.80	0.82	1.05
Philipson K, 2013	Chest pain	Adult	NR	3	40	8	105	0.27	0.72	0.99	1.00
Park, 2014	Chest pain	Adult	Partial	6	93	28	363	0.18	0.80	0.87	1.03
Miyashita, 2013	Chest pain	Adult	NR	66	382	117	750	0.36	0.66	1.07	0.96
Park, 2014	Chills	Adult	Partial	0	26	34	430	0.00	0.94	0.00	1.06
Preziosi, 2003	Conjunctival injection	Children	No	222	25	21	5	0.91	0.17	1.10	0.52
Preziosi, 2003	Conjunctival injection	Children	Yes	389	60	205	62	0.65	0.51	1.33	0.68
Gentile, 2014	Cough (any)	Children	Yes	176	269	7	26	0.96	0.09	1.05	0.43
Narkeviciute I, 2005	Cough (any)	Children	Yes	32		0		1.00
Postels-Multani, 1995	Cough (any)	Adults	No	72		7		0.91
Schlapfer, 1995	Cough < 14 days	Both	Yes	90	362	20	71	0.82	0.16	0.98	1.11
Heininger, 1997	Cough > 14 days	Both	No	421		1624		0.21
Narkeviciute I, 2005	Cough > 21 days	Children	Yes	22		10		0.69
Postels-Multani, 1995	Cough > 21 days	Adults	No	63		16		0.80
Schlapfer, 1995	Cough > 28 days at follow-up	Both	Yes	67	139	25	239	0.73	0.63	1.98	0.43
Liese JG, 2003	Cough > 42 days	Children	No	35		0		1.00
Liese JG, 2003	Cough > 42 days	Children	Yes	74		7		0.91
Narkeviciute I, 2005	Cough 15 - 21 days	Children	Yes	3		29		0.09
Narkeviciute I, 2005	Cough 7–14 days	Children	Yes	7		25		0.22
Park, 2014	Crackles	Adult	Partial	0	23	34	433	0.00	0.95	0.00	1.05
Preziosi, 2003	Cyanosis	Children	No	0	0	243	30	0.00	0.97	0.13	7.66
Preziosi, 2003	Cyanosis	Children	Yes	0	0	594	122	0.00	0.99	0.21	4.81
Philipson K, 2013	Cyanosis	Children	NR	1	4	11	50	0.08	0.93	1.13	0.99
Harndon A, 2006	Cyanosis	Children	Yes	6	6	58	102	0.09	0.94	1.69	0.96
Philipson K, 2013	Cyanosis	Adult	NR	0	6	11	139	0.00	0.96	0.00	1.04
Gentile, 2014	Cyanosis	Children	Yes	106	150	77	145	0.58	0.49	1.14	0.86
Philipson K, 2013	Dizziness	Children	NR	3	10	9	44	0.25	0.81	1.35	0.92
Philipson K, 2013	Dizziness	Adult	NR	3	30	8	115	0.27	0.79	1.32	0.92
Philipson K, 2013	Dyspnea	Children	NR	0	1	12	53	0.00	0.98	0.00	1.02
Philipson K, 2013	Dyspnea	Adult	NR	0	12	11	133	0.00	0.92	0.00	1.09
Park, 2014	Dyspnea	Adult	Partial	4	50	30	406	0.12	0.89	1.07	0.99
Gentile, 2014	Dyspnea	Children	Yes	102	189	81	106	0.56	0.36	0.87	1.23
Miyashita, 2013	Dyspnea	Adult	NR	56	297	127	835	0.31	0.74	1.17	0.94
Philipson K, 2013	Epistaxis	Adult	NR	0	1	11	144	0.00	0.99	0.00	1.01
Philipson K, 2013	Epistaxis	Children	NR	0	3	12	51	0.00	0.94	0.00	1.06
Philipson K, 2013	Exercise intolerance	Children	NR	9	37	3	17	0.75	0.31	1.09	0.79
Philipson K, 2013	Exercise intolerance	Adult	NR	9	92	2	53	0.82	0.37	1.29	0.50
Miyashita, 2013	Exposed to cough by family member or colleague	Adult	NR	97	273	86	859	0.53	0.76	2.20	0.62
Preziosi, 2003	Facial swelling	Children	No	115	11	128	19	0.47	0.63	1.29	0.83
Preziosi, 2003	Facial swelling	Children	Yes	148	16	446	106	0.25	0.87	1.90	0.86
Park, 2014	Female sex	Adult	Partial	27	329	7	127	0.79	0.28	1.10	0.74
Granstrom, 1991	Fever	Both	No	7	15	156	107	0.04	0.88	0.35	1.09
Park, 2014	Fever	Adult	Partial	2	21	32	435	0.06	0.95	1.28	0.99
Schlapfer, 1995	Fever	Both	Yes	12	53	62	244	0.16	0.82	0.91	1.02
Karagul, 2015	Fever	Adult	NR	24	56	16	118	0.60	0.68	1.86	0.59
Gentile, 2014	Fever	Children	Yes	53	122	130	173	0.29	0.59	0.70	1.21
Miyashita, 2013	Fever	Adult	NR	27	234	156	898	0.15	0.79	0.71	1.07
Heininger, 1993	Fever	Children	No	32	369	569	2659	0.05	0.88	0.44	1.08
Heininger, 1997	Fever	Both	No	87		1439		0.06
Philipson K, 2013	Headache	Children	NR	7	42	5	12	0.58	0.22	0.75	1.88
Harndon A, 2006	Headache	Children	Yes	29	63	35	44	0.45	0.41	0.77	1.33
Park, 2014	Headache	Adult	Partial	3	68	31	388	0.09	0.85	0.59	1.07
Philipson K, 2013	Headache	Adult	NR	7	102	4	43	0.64	0.30	0.90	1.23
Philipson K, 2013	Headache absent	Children	NR	5	12	7	42	0.42	0.78	1.88	0.75
Philipson K, 2013	Headache absent	Adult	NR	4	43	7	102	0.36	0.70	1.23	0.90
Harndon A, 2006	Headache absent	Children	Yes	35	44	29	63	0.55	0.59	1.33	0.77
Park, 2014	Headache absent	Adult	Partial	31	388	3	68	0.91	0.15	1.07	0.59
Park, 2014	Hemoptysis	Adult	Partial	1	8	33	448	0.03	0.98	1.68	0.99
Gilberg, 2002	History of whooping cough	Adults	Partial	16	5	32	24	0.33	0.83	1.93	0.81
Gilberg, 2002	Hoarseness	Adults	Partial	31	20	34	28	0.48	0.58	1.14	0.90
Philipson K, 2013	Malaise	Children	NR	1	2	11	52	0.08	0.96	2.25	0.95
Philipson K, 2013	Malaise	Adult	NR	0	13	11	132	0.00	0.91	0.00	1.10
Park, 2014	Malaise	Adult	Partial	2	14	32	442	0.06	0.97	1.92	0.97
Strebel, 2001	Male sex	Both	Yes	11	61	16	124	0.41	0.67	1.24	0.88
Narkeviciute I, 2005	Male sex	Children	Yes	11		21		0.34
Preziosi, 2003	Mechanical complication	Children	No	4	0	239	30	0.02	0.97	0.65	1.53
Preziosi, 2003	Mechanical complication	Children	Yes	7	0	587	122	0.01	0.99	1.66	0.60
Philipson K, 2013	Myalgia	Children	NR	0	8	12	46	0.00	0.85	0.00	1.17
Park, 2014	Myalgia	Adult	Partial	2	28	32	428	0.06	0.94	0.96	1.00
Philipson K, 2013	Myalgia	Adult	NR	2	45	9	100	0.18	0.69	0.59	1.19
Philipson K, 2013	Nausea or retching	Children	NR	2	11	10	43	0.17	0.80	0.82	1.05
Philipson K, 2013	Nausea or retching	Adult	NR	2	26	9	119	0.18	0.82	1.01	1.00
Granstrom, 1991	Overall clinical impression	Both	No	73	0	90	122	0.45	0.99	55.61	0.02
Heininger, 2000	Overall clinical impression	Both	Partial	37	28	47	266	0.44	0.90	4.63	0.62
Schlapfer, 1995	Overall clinical impression	Both	Yes	36	38	69	370	0.34	0.91	3.68	0.72
Heininger, 1993	Overall clinical impression	Children	No	343	995	200	1637	0.63	0.62	1.67	0.59
Heininger, 1997	Overall clinical impression	Both	No	1055		943		0.53
Preziosi, 2003	Paroxysmal cough	Children	No	176	10	67	20	0.72	0.67	2.17	0.41
Preziosi, 2003	Paroxysmal cough	Children	Yes	281	28	313	94	0.47	0.77	2.06	0.68
Park, 2005	Paroxysmal cough	Adult	Yes	3	64	0	35	1.00	0.35	1.54	0.03
Gilberg, 2002	Paroxysmal cough	Adults	Partial	64	50	5	3	0.93	0.06	0.98	1.28
Karagul, 2015	Paroxysmal cough	Adult	NR	30	55	10	119	0.75	0.68	2.37	0.37
Harndon A, 2006	Paroxysmal cough	Children	Yes	55	82	9	26	0.86	0.24	1.13	0.58
Schlapfer, 1995	Paroxysmal cough	Both	Yes	60	158	44	230	0.58	0.59	1.42	0.71
Strebel, 2001	Paroxysmal cough	Both	Yes	27	162	0	23	1.00	0.12	1.14	0.00
Ghanaie RM, 2010	Paroxysmal cough	Children	Yes	17	177	4	130	0.81	0.42	1.40	0.45
Gentile, 2014	Paroxysmal cough	Children	Yes	140	178	43	117	0.77	0.40	1.27	0.59
Senzilet, 2001	Paroxysmal cough	Adult	Partial	82	318	6	36	0.93	0.10	1.04	0.67
Park, 2014	Paroxysmal cough	Adult	Partial	27	328	7	128	0.79	0.28	1.10	0.73
Miyashita, 2013	Paroxysmal cough	Adult	NR	165	849	18	283	0.90	0.25	1.20	0.39
Heininger, 1993	Paroxysmal cough	Children	No	409	1670	192	1358	0.68	0.45	1.23	0.71
Heininger, 1997	Paroxysmal cough	Both	No	1605		343		0.82
Liese JG, 2003	Paroxysmal cough	Children	No	33		2		0.94
Liese JG, 2003	Paroxysmal cough	Children	Yes	54		27		0.67
Narkeviciute I, 2005	Paroxysmal cough	Children	Yes	27		5		0.84
Karagul, 2015	Paroxysmal cough + whooping	Adult	NR	6	5	34	169	0.15	0.97	5.22	0.88
Gilberg, 2002	Paroxysmal cough > 21 days	Adults	Partial	50	39	12	8	0.81	0.17	0.97	1.14
Liese JG, 2003	Paroxysmal cough > 21 days	Children	No	29		6		0.83
Liese JG, 2003	Paroxysmal cough > 21 days	Children	Yes	33		48		0.41
Postels-Multani, 1995	Paroxysmal cough > 21 days	Adults	No	50		29		0.63
He, 1998	Paroxysmal cough > 7 days	Both	Yes	66	35	300	163	0.18	0.82	1.02	1.00
Heininger, 2000	Paroxysmal cough OR whooping cough OR post-tussive vomiting	Both	Partial	65	187	19	107	0.77	0.36	1.22	0.62
Gentile, 2014	Pneumonia	Children	Yes	11	29	172	266	0.06	0.90	0.61	1.04
Miyashita, 2013	Post-tussive gagging	Adult	NR	90	259	93	873	0.49	0.77	2.15	0.66
Gilberg, 2002	Post-tussive inspiratory effort	Adults	Partial	38	25	31	17	0.55	0.40	0.93	1.11
Preziosi, 2003	Post-tussive sticky sputum	Children	No	228	25	15	5	0.94	0.17	1.13	0.37
Preziosi, 2003	Post-tussive sticky sputum	Children	Yes	513	95	81	27	0.86	0.22	1.11	0.62
Gilberg, 2002	Post-tussive vomiting	Adults	Partial	17	11	52	42	0.25	0.79	1.19	0.95
Granstrom, 1991	Post-tussive vomiting	Both	No	28	16	135	106	0.17	0.87	1.31	0.95
Preziosi, 2003	Post-tussive vomiting	Children	No	180	16	63	14	0.74	0.47	1.39	0.56
Karagul, 2015	Post-tussive vomiting	Adult	NR	16	19	24	155	0.40	0.89	3.66	0.67
Park, 2005	Post-tussive vomiting	Adult	Yes	1	17	2	82	0.33	0.83	1.90	0.81
Philipson K, 2013	Post-tussive vomiting	Children	NR	7	20	5	34	0.58	0.63	1.58	0.66
Harndon A, 2006	Post-tussive vomiting	Children	Yes	45	42	19	66	0.70	0.61	1.81	0.49
Philipson K, 2013	Post-tussive vomiting	Adult	NR	5	43	6	102	0.45	0.70	1.53	0.78
Gentile, 2014	Post-tussive vomiting	Children	Yes	40	45	143	250	0.22	0.85	1.43	0.92
Strebel, 2001	Post-tussive vomiting	Both	Yes	15	59	12	126	0.56	0.68	1.74	0.65
Ghanaie RM, 2010	Post-tussive vomiting	Children	Yes	13	60	8	247	0.62	0.80	3.17	0.47
Preziosi, 2003	Post-tussive vomiting	Children	Yes	367	62	227	60	0.62	0.49	1.22	0.78
Park, 2014	Post-tussive vomiting	Adult	Partial	11	76	23	380	0.32	0.83	1.94	0.81
Senzilet, 2001	Post-tussive vomiting	Adult	Partial	40	101	48	253	0.45	0.71	1.59	0.76
Schlapfer, 1995	Post-tussive vomiting	Both	Yes	49	108	55	280	0.47	0.72	1.69	0.73
Miyashita, 2013	Post-tussive vomiting	Adult	NR	46	228	137	904	0.25	0.80	1.25	0.94
He, 1998	Post-tussive vomiting	Both	Yes	26		62		0.30
Heininger, 1997	Post-tussive vomiting	Both	No	741		649		0.53
Liese JG, 2003	Post-tussive vomiting	Children	No	26		9		0.74
Liese JG, 2003	Post-tussive vomiting	Children	Yes	32		49		0.40
Narkeviciute I, 2005	Post-tussive vomiting	Children	Yes	10		22		0.31
Postels-Multani, 1995	Post-tussive vomiting	Adults	No	33		46		0.42
Karagul, 2015	Post-tussive vomiting + paroxysmal cough	Adult	NR	15	18	25	156	0.38	0.90	3.63	0.70
Karagul, 2015	Post-tussive vomiting + whooping	Adult	NR	4	0	36	174	0.12	0.99	20.95	0.05
Liese JG, 2003	Post-tussive vomiting > 21 days	Children	No	6		29		0.17
Liese JG, 2003	Post-tussive vomiting > 21 days	Children	Yes	3		78		0.04
Miyashita, 2013	Preceding RTI	Adult	NR	83	561	100	571	0.45	0.50	0.92	1.08
Schlapfer, 1995	Previous immunization	Both	Yes	26	185	44	135	0.37	0.42	0.64	1.49
Preziosi, 2003	Pulmonary sign	Children	No	29	2	214	28	0.12	0.93	1.79	0.94
Preziosi, 2003	Pulmonary sign	Children	Yes	57	13	537	109	0.10	0.89	0.90	1.01
Park, 2014	Rhinorrhea	Adult	Partial	12	173	22	283	0.35	0.62	0.93	1.04
Park, 2014	Rhonchi	Adult	Partial	7	31	27	425	0.21	0.93	3.03	0.85
Preziosi, 2003	Runny nose	Children	No	200	20	43	10	0.82	0.33	1.23	0.53
Preziosi, 2003	Runny nose	Children	Yes	501	95	93	27	0.84	0.22	1.08	0.71
Gentile, 2014	Seizures	Children	Yes	4	7	179	288	0.02	0.98	0.92	1.00
Harndon A, 2006	Sinus pain	Children	Yes	9	23	55	84	0.14	0.79	0.65	1.09
Philipson K, 2013	Sinus pain	Children	NR	6	23	6	31	0.50	0.57	1.17	0.87
Philipson K, 2013	Sinus pain	Adult	NR	4	66	7	79	0.36	0.54	0.80	1.17
Philipson K, 2013	Sleep disturbed by cough	Children	NR	1	3	11	51	0.08	0.94	1.50	0.97
Philipson K, 2013	Sleep disturbed by cough	Adult	NR	1	10	10	135	0.09	0.93	1.32	0.98
Gilberg, 2002	Sleep disturbed by cough	Adults	Partial	60	46	9	7	0.87	0.13	1.00	0.99
Senzilet, 2001	Sleep disturbed by cough	Adult	Partial	74	276	14	78	0.84	0.22	1.08	0.72
Miyashita, 2013	Sleep disturbed by cough	Adult	NR	133	747	50	385	0.73	0.34	1.10	0.80
Postels-Multani, 1995	Sleep disturbed by cough	Adults	No	41		38		0.52
Preziosi, 2003	Sneezing	Children	No	224	26	19	4	0.92	0.13	1.06	0.59
Philipson K, 2013	Sneezing	Children	NR	8	43	4	11	0.67	0.20	0.84	1.64
Harndon A, 2006	Sneezing	Children	Yes	29	59	35	49	0.45	0.45	0.83	1.21
Preziosi, 2003	Sneezing	Children	Yes	525	104	69	18	0.88	0.15	1.04	0.79
Philipson K, 2013	Sneezing	Adult	NR	8	107	3	38	0.73	0.26	0.99	1.04
Philipson K, 2013	Sore throat	Children	NR	3	10	9	44	0.25	0.81	1.35	0.92
Philipson K, 2013	Sore throat	Adult	NR	2	26	9	119	0.18	0.82	1.01	1.00
Park, 2014	Sore throat	Adult	Partial	8	123	26	333	0.24	0.73	0.87	1.05
Philipson K, 2013	Sputum production	Children	NR	10	45	2	9	0.83	0.17	1.00	1.00
Harndon A, 2006	Sputum production	Children	Yes	44	60	19	48	0.70	0.44	1.26	0.68
Philipson K, 2013	Sputum production	Adult	NR	11	127	0	18	1.00	0.12	1.14	0.00
Park, 2014	Sputum production	Adult	Partial	29	290	5	166	0.85	0.36	1.34	0.40
Miyashita, 2013	Sputum production	Adult	NR	67	378	116	754	0.37	0.67	1.10	0.95
Park, 2014	Stridor	Adult	Partial	1	4	33	452	0.03	0.99	3.35	0.98
Philipson K, 2013	Sweating	Children	NR	8	35	4	19	0.67	0.35	1.03	0.95
Harndon A, 2006	Sweating	Children	Yes	24	56	39	52	0.38	0.48	0.73	1.29
Philipson K, 2013	Sweating	Adult	NR	7	78	4	67	0.64	0.46	1.18	0.79
Philipson K, 2013	Urinary incontinence	Children	NR	0	0	12	54	0.07	0.98	4.00	0.25
Philipson K, 2013	Urinary incontinence	Adult	NR	1	10	10	135	0.09	0.93	1.32	0.98
Philipson K, 2013	URTI symptoms	Children	NR	0	6	12	48	0.00	0.89	0.00	1.13
Philipson K, 2013	URTI symptoms	Adult	NR	1	18	10	127	0.09	0.88	0.73	1.04
Philipson K, 2013	Wheezing	Children	NR	3	29	9	25	0.25	0.46	0.47	1.62
Park, 2014	Wheezing	Adult	Partial	0	30	34	426	0.00	0.93	0.00	1.07
Harndon A, 2006	Wheezing	Children	Yes	19	47	45	61	0.30	0.56	0.68	1.24
Philipson K, 2013	Wheezing	Adult	NR	9	86	2	59	0.82	0.41	1.38	0.45
Philipson K, 2013	Wheezing absent	Children	NR	9	25	3	29	0.75	0.54	1.62	0.47
Philipson K, 2013	Wheezing absent	Adult	NR	2	59	9	86	0.18	0.59	0.45	1.38
Harndon A, 2006	Wheezing absent	Children	Yes	45	61	19	47	0.70	0.44	1.24	0.68
Park, 2014	Wheezing absent	Adult	Partial	34	426	0	30	1.00	0.07	1.07	0.00
Liese JG, 2003	Whooping > 21 days	Children	No	15		20		0.43
Liese JG, 2003	Whooping > 21 days	Children	Yes	11		70		0.14
Preziosi, 2003	Whooping cough	Children	Yes	96	1	498	121	0.16	0.99	19.72	0.85
Preziosi, 2003	Whooping cough	Children	No	83	2	160	28	0.34	0.93	5.12	0.71
Granstrom, 1991	Whooping cough	Both	No	60	5	103	117	0.37	0.96	8.98	0.66
Karagul, 2015	Whooping cough	Adult	NR	6	5	34	169	0.15	0.97	5.22	0.88
Gilberg, 2002	Whooping cough	Adults	Partial	11	11	58	41	0.16	0.79	0.75	1.07
Philipson K, 2013	Whooping cough	Children	NR	4	17	8	37	0.33	0.69	1.06	0.97
Schlapfer, 1995	Whooping cough	Both	Yes	33	27	44	292	0.43	0.92	5.06	0.62
Harndon A, 2006	Whooping cough	Children	Yes	32	29	32	78	0.50	0.73	1.84	0.69
Park, 2005	Whooping cough	Adult	Yes	2	28	1	71	0.67	0.72	2.40	0.46
Philipson K, 2013	Whooping cough	Adult	NR	3	58	8	87	0.27	0.60	0.68	1.21
Park, 2014	Whooping cough	Adult	Partial	4	60	30	396	0.12	0.87	0.89	1.02
Senzilet, 2001	Whooping cough	Adult	Partial	25	96	63	258	0.28	0.73	1.05	0.98
Miyashita, 2013	Whooping cough	Adult	NR	36	156	147	976	0.20	0.86	1.43	0.93
Ghanaie RM, 2010	Whooping cough	Children	Yes	15	167	6	140	0.71	0.46	1.31	0.63
Strebel, 2001	Whooping cough	Both	Yes	7		20	158	0.26
He, 1998	Whooping cough	Both	Yes	23		65		0.26
Liese JG, 2003	Whooping cough	Children	No	25		10		0.71
Liese JG, 2003	Whooping cough	Children	Yes	38		43		0.47
Narkeviciute I, 2005	Whooping cough	Children	Yes	9		23		0.28
Postels-Multani, 1995	Whooping cough	Adults	No	6		73		0.08

FN, false negative; FP, false positive; LR+, positive likelihood ratio; LR−, negative likelihood ratio; NR, not reported; sens, sensitivity; spec, specificity; TP, true positive; TN, true negative.