Study | Study design | Median follow-up time (months) | Re-infection | Initial N (HIV-/HIV+)* | Stage (HIV status) | Follow-up N† | Treatment | Serological failures | Clinical failures | |
Dowell (1992)10 | Retrospective series | ≥6 | Y | 56 (0/56) | L (+) | 49 | 13 | BPG X 3 | 4 | 0 |
36 | Cef X 10–14 doses | 9 | 0 | |||||||
N (+) | 7 | 7 | Cef X 10–14 doses | 1 | 1 | |||||
Gourevitch (1993)11 | Retrospective cohort | 11.4 | N | 50 (19/31) | E (−) | 4 | 1 | BPG X 1 | 0 | 0 |
3 | BPG X 1 enhanced§ | 0 | 0 | |||||||
L (−) | 12 | 7 | BPG X 3 | 0 | 0 | |||||
3 | Less than BPG X 3 | 0 | 0 | |||||||
1 | Doxy X 28d | 0 | 0 | |||||||
1 | Tetra X 14d | 1 | 0 | |||||||
N (−) | 1 | 1 | APG X 10–14d | 0 | 0 | |||||
E (+) | 11 | 1 | BPG X1 | 0 | 0 | |||||
10 | BPG X 1 enhanced§ | 0 | 0 | |||||||
L (+) | 13 | 9 | BPG X 3 | 0 | 0 | |||||
1 | Less than BPG X 3 | 0 | 0 | |||||||
2 | BPG X 3 enhanced§ | 0 | 0 | |||||||
1 | Erythro X 28d | 0 | 0 | |||||||
N (+) | 2 | 2 | APG X 10–14d | 0 | 0 | |||||
Caumes (1994)12 | Prospective series | 24 | N | 13 (0/13) | E (+) | 12 | 5 | BPG X 2 | 0 | 0 |
5 | BPG X 3 | 0 | 0 | |||||||
1 | Doxy X 14–15d | 0 | 0 | |||||||
1 | Erythro X 21d | 0 | 0 | |||||||
N (+) | 1 | 1 | APG X 10–14d | 0 | 0 | |||||
Gordon (1994)13 | Prospective series | 10 | N | 11 (0/11) | N (+) | 11 | 11 | APG X 10d | 3 | 1 |
Hutchinson (1994)14 | Case–control | <12 | N | 309 (239/70) | E (−) | 78 | 78 | BPG X 1 or Doxy X 14d | 11 | 0 |
E (+) | 28 | 28 | BPG X 1 or Doxy | 5 | 0 | |||||
Goeman (1995)15 | Prospective cohort | 24 | N | 120 (73/47) | U (−) | 34 | 34 | BPG X 3 | 11 | NA |
U (+) | 26 | 26 | BPG 2.4 X 3 | 13 | NA | |||||
Malone (1995)16 | Retrospective series | 24 (mean) | N | 59 (0/59) | E (+) | 21 | 11 | BPG 2.4 X 3 | 3 | 3 |
7 | CPG + P X 10–14d | 0 | 0 | |||||||
3 | APG X 10–14d | 0 | 0 | |||||||
L (+) | 30 | 19 | BPG X 3 | 4 | 1 | |||||
1 | Cef? Dose | 0 | 0 | |||||||
2 | CPG +P X 10–14d | 0 | 0 | |||||||
8 | APG X 10–14d | 0 | 0 | |||||||
N (+) | 5 | 5 | APG X 10–14d | 3 | 1 | |||||
Marra (1996)17 | Retrospective series | ∼3–6 | N | 22 (9/13) | N (−) | 9 | 5 | APG X 10d | 0 | 0 |
3 | CPG + P X 10–14d | 0 | 0 | |||||||
1 | CPG + P X 9d | 0 | 0 | |||||||
N (+) | 13 | 9 | APG X 10d | 2 | 0 | |||||
4 | CPG + P X 10–14d | 1 | 0 | |||||||
Yinnon (1996)18 | Case–control | ∼12 (mean) | N | 128 (64/64) | E (−) | 26 | 22 | BPG X 1 | ||
1 | BPG X 3 | |||||||||
3 | Other | 15 of 52 | 0 | |||||||
L (−) | 26 | 24 | BPG X 3 | |||||||
2 | other | |||||||||
E (+) | 26 | 4 | BPG X 1 | |||||||
18 | BPG X 3 | |||||||||
4 | other | 21 of 48 | ||||||||
L (+) | 21 | 2 | BPG X 1 | 0 | ||||||
19 | BPG X 3 | |||||||||
N (+) | 1 | 5 | other | |||||||
Rolfs (1997)19 | RCT | 6 | Y | 541 (440/101) | E (−) | 257 | NA | BPG X1 | 42 of 257 | 0 |
NA | BPG X 1+ amox/P X 10d | |||||||||
E (+) | 69 | NA | BPG X1 | 15 of 69 | 1 | |||||
NA | BPG X1 + amox/P X 10d | |||||||||
Bordón (1999)20 | Prospective series | 21 | N | 13 (0/13) | E (+) | 4 | 4 | BPG X 3 | 0 | 0 |
L (+) | 5 | 1 | CPG X 14d | 1 of 5 | 0 | |||||
4 | BPG X 3 | |||||||||
N (+) | 4 | 4 | APG X 14d | 0 | 0 | |||||
Hook (2002)21 | Randomised open label | 6 | Y | 74 (71/3) | E (−) | 71 | 19 | BPG X 1 or 2 | 0 | 0 |
21 | Azithro X 1 | 0 | 0 | |||||||
31 | Azithro X 2 | 3 | 0 | |||||||
E (+) | 3 | 2 | BPG X 1 or 2 | 0 | 0 | |||||
1 | Azithro X 2 | 0 | 0 | |||||||
Tattevin (2002)22 | Prospective cohort | ∼6 | N | 23 (0/23) | L (+) | 11 | 11 | Biclinocilline 2MU IM X1 daily X 10d | ||
N (+) | 1 | 1 | Biclinocilline 2MU IM X1 daily X 10d | 7 of 12‡ | 0 | |||||
Smith (2004)23 | Randomised open label | 18–32 | N | 31 (0/31) | L (+) | 15 | 8 | CPG + P X 15d | 1 | 0 |
7 | Cef X 15d | 1 | 0 | |||||||
N (+) | 9 | 2 | CPG +P X 15d | 1 | 0 | |||||
7 | Cef X 15d | 2 | 0 | |||||||
Guitierrez-Galhardo (2005)24 | Prospective series | 24 | Y | 24 (0/24) | E (+) | 5 | 4 | BPG X3 | 0 | |
1 | Erythro? duration | 0 | 0 | |||||||
L (+) | 5 | 5 | BPG X 3 | 0 | 0 | |||||
N (+) | 14 | 3 | APG X 14d | |||||||
10 | Cef X 14d | 4 of 14 | 0 | |||||||
1 | BPG X 3 | |||||||||
Kiddugavu (2005)25 | Prospective cohort | ∼9 (mean) | N | 952 (754/198) | E (−) | 88 | 136 | BPG X 1 | ||
L (−) | 666 | 135 | Azithro X 1 | 303 of 754 | NA | |||||
483 | BPG X 1 + Azithro | |||||||||
E (+) | 45 | 32 | BPG X 1 | |||||||
L (+) | 152 | 30 | Azithro X 1 | 69 of 198 | NA | |||||
136 | BPG X 1 + Azithro | |||||||||
Nnoruka (2005)26 | Prospective series | 12 | N | 31 (0/31) | E (+) | 9 | 9 | BPG X 3 | 5 of 10 | 2 of 10 |
L (+) | 1 | 1 | Doxy X 15d | |||||||
Riedner (2005)27 | Randomised double-blinded | 9 | N | 328 (157/171) | E (−) | 157 | 78 | BPG X 1 | 3 | 0 |
79 | Azithro X 1 | 0 | 0 | |||||||
E (+) | 171 | 87 | BPG X 1 | 6 | 0 | |||||
84 | Azithro X 1 | 4 | 0 | |||||||
Chauhan (2006)28 | Retrospective series | 12 | N | 40 (34/6) | E (−) | 31 | 2 | BPG X 1 | 0 | 0 |
24 | BPG X 2 | 0 | 0 | |||||||
2 | BPG X1 + Doxy X 14d | 0 | 0 | |||||||
2 | Doxy X 14d | 0 | 0 | |||||||
1 | CPG X 10d | 0 | 0 | |||||||
E (+) | 5 | 3 | BPG X 3 | 0 | 0 | |||||
2 | Doxy X 14d | 0 | 0 | |||||||
N (+) | 1 | 1 | CPG + P X 17d | 0 | 0 | |||||
Kofoed (2006)29 | Prospective series | 7 | N | 41 (0/41) | E (+) | 28 | 4 | BPG X 3 | 0 | 0 |
15 | Doxy X 14d | 1 | 0 | |||||||
9 | CPG X 10d | 1 | 0 | |||||||
L (+) | 12 | 3 | BPG X 3 | 0 | 0 | |||||
9 | Doxy X 14d | 2 | 2 | |||||||
Ghanem (2007)30 | Retrospective series | 9 | Y | 297 (168/129) | E (−) | 152 | 151 | BPG X 1 | 4 | 0 |
1 | Doxy X 14d | 0 | 0 | |||||||
L (−) | 14 | 14 | BPG X 3 | 1 | 0 | |||||
E (+) | 32 | 31 | BPG X 1 | 4 | 0 | |||||
1 | Doxy X 14d | 0 | 0 | |||||||
L (+) | 96 | 93 | BPG X 3 | 18 | 0 | |||||
3 | Doxy X 28d | 0 | 0 | |||||||
Manavi (2007)31 | Retrospective series | 24 | Y | 371 (242/129) | E (−) | 181 | 23 | BPG X 1 | ||
L (−) | 61 | 39 | BPG X 2 | |||||||
113 | BPG X 3 | 58 of 161 | ||||||||
41 | Doxy X 21d | HIV- @ 24m | ||||||||
5 | CPG X 17d | |||||||||
21 | Unknown | |||||||||
E (+) | 67 | 4 | BPG X 1 | |||||||
L (+) | 62 | 13 | BPG X 2 | |||||||
61 | BPG X 3 | |||||||||
16 | Doxy X21d | 30 of 100 | ||||||||
1 | Azithr1 g X15d | HIV+ | ||||||||
16 | CPG X 17d | @ 24 m | ||||||||
1 | APG x 14d | |||||||||
15 | Unknown | |||||||||
Ghanem (2008)32 | Retrospective cohort | 63.6 | Y | 231 (0/231) | E (+) | 62 | 49 | BPG X 1 | 11 | 0 |
1 | BPG X 2 | 4 of 11 | 0 | |||||||
10 | BPG X 3 | |||||||||
1 | Doxy X 14d | 0 | 0 | |||||||
1 | APG X 10–14d | 0 | 0 | |||||||
L (+) | 128 | 5 | BPG X 1 | 0 | 0 | |||||
4 | BPG X 2 | 0 | 0 | |||||||
103 | BPG X 3 | 32 | 0 | |||||||
7 | Doxy X 21d | 2 | 0 | |||||||
1 | Cef X 10d | 0 | 0 | |||||||
7 | Unknown | 0 | 0 | |||||||
N (+) | 41 | 36 | APG X 10–14d | 10 | 1 | |||||
5 | Cef X 10d | 1 | 0 | |||||||
Warwick (2008)33 | Retrospective series | 6 | N | 257 (132/125) | E (−) | 132 | 132 | BPG X 1 | 3 | N/A |
E (+) | 125 | 105 | CPG+P X 17d | 1 | N/A | |||||
20 | Other | 1 | N/A |
↵* Total number of people who completed follow-up.
↵† N=the subset of people who had follow-up data available.
↵‡ Serological failure in this study was defined as complete rapid plasma reagin seroreversion. No data on fourfold decline were provided.
↵§ Enhanced with additional doses of penicillin (but dose not provided).
Re-infection, the study examined whether failure might have been due to re-infection.
E, early-stage syphilis (primary, secondary, or early latent); L, late latent syphilis stage or syphilis stage of unknown duration; N, neurosyphilis. Amox, amoxicillin 2 g daily orally; APG, aqueous penicillin 18–24 million units intravenously daily; Azithro, azithromycin 2 g orally unless otherwise noted; BPG, benzathine penicillin G 2.4 million units given intramuscularly; Cef, ceftriaxone 1–2 g intramuscularly or intravenously; CPG, procaine penicillin 2.4 million units intramuscularly; d, days; Doxy, doxycycline 100 mg orally twice a day; erythro, erythromycin 3 g daily orally; IM, intramuscularly; m, months; MU, million units; P, probenecid 500 mg orally four times daily; Tetra, tetracycline 500 mg orally four times daily; U, unknown stage.