| Literature DB >> 29428183 |
Oriol Mitjà1, Charmie Godornes2, Wendy Houinei3, August Kapa4, Raymond Paru4, Haina Abel4, Camila González-Beiras5, Sibauk V Bieb3, James Wangi6, Alyssa E Barry7, Sergi Sanz8, Quique Bassat9, Sheila A Lukehart10.
Abstract
BACKGROUND: Yaws is a substantial cause of chronic disfiguring ulcers in children in at least 14 countries in the tropics. WHO's newly adopted strategy for yaws eradication uses a single round of mass azithromycin treatment followed by targeted treatment programmes, and data from pilot studies have shown a short-term significant reduction of yaws. We assessed the long-term efficacy of the WHO strategy for yaws eradication.Entities:
Mesh:
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Year: 2018 PMID: 29428183 PMCID: PMC5920722 DOI: 10.1016/S0140-6736(18)30204-6
Source DB: PubMed Journal: Lancet ISSN: 0140-6736 Impact factor: 79.321
Prevalence of skin ulcers and active yaws
| Time post | No. of | No. of | All Clinically Suspected Lesions | Active Yaws Lesions | Clinically Suspected Lesions with | |||
|---|---|---|---|---|---|---|---|---|
| No. of cases | Prevalence ratio | No. of | Prevalence ratio | No. of cases | Prevalence ratio | |||
| Baseline | 16,092 | 13,490 (84%) | 690 (5·1) | 1 | 238 (1·8) | 1 | 323 (2·4) | 1 |
| 6 mo. | 16,092 | 13,166 (82%) | 121 (0·9) | 0·18 (0·15; 0·22) | 59 (0·4) | 0·25 (0·19; 0·34) | 44 (0·3) | 0·14 (0·10; 0·19) |
| 12 mo. | 17,339 | 13,204 (76%) | 114 (0·9) | 0·17 (0·14; 0·21) | 19 (0·1) | 0·08 (0·05; 0·13) | 34 (0·3) | 0·11 (0·08; 0·15) |
| 18 mo. | 17,339 | 15,977 (92%) | 88 (0·6) | 0·11 ( 0·09; 0·13) | 17 (0·1) | 0·06 (0·04; 0·10) | 38 (0·2) | 0·10 (0·07; 0·14) |
| 24 mo. | 17,555 | 11,792 (67%) | 68 (0·6) | 0·11 (0·09; 0·14) | 13 (0·1) | 0·06 (0·04; 0·11) | 24 (0·2) | 0·09 (0·06; 0·13) |
| 30 mo. | 17,555 | 14,935 (85%) | 120 (0·8) | 0·16 (0·13; 0·19) | 31 (0·2) | 0·12 (0·08; 0·17) | 52 (0·3) | 0·15 (0·11; 0·19) |
| 36 mo. | 18,836 | 14,765 (78%) | 107 (0·7) | 0·14 ( 0·12; 0.17) | 36 (0·2) | 0·14 (0·10; 0·20) | 53 (0·4) | 0·15 (0·11; 0·20) |
| 42 mo. | 18,836 | 13,601 (72%) | 107 (0·8) | 0·15 ( 0·13; 0.19) | 51 (0·4) | 0·21 (0·16; 0·29) | 63 (0·5) | 0·19 (0·15; 0·25) |
Active yaws refers to the estimated number of participants with lesional PCR positive results in either tpN47 (tp0574) or tp0548, and in which the pertenue subspecies was confirmed by TprL PCR amplicon size.
The prevalence ratio was calculated by means of the log-binomial model. The baseline prevalence is the reference value.
P<0.0001 for the significance of the model overall.
At baseline, a random sample of 90 (out of 690) clinically suspected yaws lesions were tested by PCR; the number of active yaws cases in the entire population were estimated using the proportion of PCR-positive specimens among the subset of PCR-tested lesions (34·4% [31/90]) multiplied by the total number of clinically suspected yaws lesions detected (n 690).
At 6 months, the same approach as taken for baseline was used to estimate the number of active yaws cases. The proportion of PCR-positive specimens (48·8% [41/84]) was multiplied by the total number of clinically suspected yaws lesions detected (n 121).
In 12-month to 42-month surveys, we tested all clinically suspicious lesions by PCR; therefore we obtained a direct measurement of the number of active yaws cases in the entire population.
Baseline, 6, and 12 month data were previously published (Ref. 7) and are included here for comparison to later time points.
Figure 1Characteristics of PCR-confirmed active yaws by epidemiological history, molecular type, and macrolide resistance mutation
PCR-confirmed active yaws refers to samples with positive results in either tpN47 (tp0574) or tp0548, and in which the pertenue subspecies was confirmed by TprL PCR amplicon size.
*A random sample of 90 (out of 690) clinically suspected yaws cases at baseline and 84 (out of 121) at 6 months were tested by PCR; we provide data on the characteristics of lesions that were actually PCR-positive among the subset of PCR-tested lesions (31 at baseline and 41 at 6-months). In 12-month to 42-month surveys, we tested all clinically suspected lesions by PCR; therefore we provide data on the characteristics of all lesions detected for these time-points.
†Not all T. p. pertenue positive samples could be fully typed for all three typing targets.
§ P<0.0001 for the estimate of the mean evolutionary diversity of T. p. pertenue isolates at 24-month survey compared to baseline.
¶ Estimate of the mean evolutionary diversity of T. p. pertenue isolates at each round.
‡Not all T. p. pertenue positive samples could be amplified for 23S rRNA by PCR.
Proportion of non-travelling vs travelling participants with yaws in the post-MDA period according to genotypes
| Genotypes of yaws strains | No Amplification | Total | |||||||
|---|---|---|---|---|---|---|---|---|---|
| JG8 (n=149) | SE7 (n=11) | TG8 (n=1) | TD6 (n=11) | TG6 (n=3) | SD6 (n=1) | JD8 (n=1) | |||
| Non-travelling resident | 125 (83·9%) | 2 (18·2%) | 0 (0·0%) | 11 (100%) | 3 (100%) | 0 (0·0%) | 1 (100%) | 26 (83·9%) | 168 (80·8%) |
| Travelling or in-migrated participant | 24 (16·1%) | 9 (81·8%) | 1 (100%) | 0 (0·0%) | 0 (0·0%) | 1 (100%) | 0 (0·0%) | 5 (16·1%) | 40 (19.2%) |
All non-travelling residents either absent or present at Mass Drug Administration.
Travel history was assessed by self-reported travel out of Lihir Island to a yaws endemic area in the preceding 6 months, regardless of compliance to MDA.
History of in-migration was assessed by self-reported migration to Lihir Island in the preceding 6 months and verified by non-appearance at the previous year census, regardless of compliance to MDA.
Figure 2Yaws lesions in a patient with treatment failure associated with macrolide-resistant Treponema pallidum subsp. pertenue
(A) Primary lesion (red, moist 2·5 cm ulcer) on the left leg of an 11-year-old patient with yaws observed at the 30 months survey. Lesional swab PCR was positive for T. p. pertenue with wild-type 23S rRNA. (B) Secondary yaws papillomas (multiple nodules with yellow-colour granular surface) seen at 36 months survey. These lesions were PCR positive for T. p. pertenue with A2059G mutation in 23SrRNA. (C) Photomicrograph of skin biopsy of the larger papilloma lesion in Panel B with abundant spirochete organisms stained bright red by the Treponema pallidum immunohistochemical stain (×400 magnification).
Prevalence of latent yaws in subgroups determined by age
| Time | Children aged 1 – 5 years | Children aged 6 – 15 years | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| No. of | All Cases of Latent Yaws | High-titre Latent Yaws | No. of | All Cases of Latent Yaws | High-titre Latent Yaws | |||||
| no. of | Adjusted | no. of | Adjusted | no. of | Adjusted | no. of | Adjusted | |||
| Baseline | 117 | 26 (22·2) | 1 | 16 (13·7) | 1 | 874 | 299 (34·2) | 1 | 165 (18·9) | 1 |
| 6 mo | 77 | 10 (13·0) | 0·58 (0·20; 1·74) | 6 (7·8) | 0·57 (0·15; 2·19) | 797 | 251 (31·5) | 0·92 (0·55; 1·53) | 117 (14·7) | 0·78 (0·40; 1·53) |
| 12 mo | 114 | 6 (5·3) | 0·24 (0·09; 0·63) | 1 (0·9) | 0·06 (0·01; 0·48) | 796 | 143 (18·0) | 0·53 (0·35; 0·79) | 58 (7·3) | 0·39 (0·19; 0·77) |
| 18 mo | 81 | 9 (11·1) | 0·50 (0·22; 1·12) | 1 (1·2) | 0·09 (0·02; 0·52) | 462 | 129 (27·9) | 0·82 (0·55; 1·22) | 50 (10·8) | 0·57 (0·34; 0·98) |
| 24 mo | 69 | 6 (8·7) | 0·39 (0·17; 0·88) | 1 (1·4) | 0·11 (0·01; 0·75) | 445 | 113 (25·4) | 0·74 (0·48; 1·15) | 24 (5·4) | 0·29 (0·16; 0·52) |
| 30 mo | 65 | 4 (6·2) | 0·28 (0·10; 0·79) | 0 (0·0) | -- | 416 | 136 (32·7) | 0·96 (0·62; 1·48) | 33 (7·9) | 0·42 (0·18; 0·97) |
| 36 mo | 66 | 3 (4·5) | 0·20 (0·05; 0·80) | 1 (1·5) | 0·11 (0·02; 0·78) | 470 | 130 (27·7) | 0·81 (0·47; 1·40) | 22 (4·7) | 0·25 (0·08; 0·81) |
| 42mo. | 68 | 6 (8·8) | 0·40 (0·17; 0·94) | 0 (0·0) | -- | 422 | 84 (19·9) | 0·58 (0·37; 0·91) | 28 (6·6) | 0·35 (0·20; 0·62) |
The analysis included all seropositive children with a reactive TPHA and RPR titre of at least 1:2.
The analysis included children with a reactive TPHA and RPR titre of at least 1:16.
The adjusted prevalence ratio was calculated with the use of the cluster option of a log-binomial regression model. The baseline prevalence is the reference value.
P = 0·0165 for the significance of the model overall.
P = 0·0014 for the significance of the model overall
P = 0·0024 for the significance of the model overall
P = 0·0002 for the significance of the model overall.
Baseline, 6 and 12 month data were previously published (Ref. 7) and are included here for comparison to later time points
Aetiology of skin ulcers prior to MDA of azithromycin and in subsequent rounds of targeted treatment *†
| Time (month) | Participants | Both | Negative | ||
|---|---|---|---|---|---|
| no. | no. of participants (%) | ||||
| Baseline | 90 | 19 (21·1) | 12 (13·3) | 42 (46·7) | 17 (18·9) |
| 6 mo. | 84 | 14 (16·7) | 27 (32·1) | 32 (38·1) | 11 (13·1) |
| 12 mo. | 114 | 12 (10·5) | 7 (6·1) | 53 (46·5) | 42 (36·8) |
| 18 mo. | 88 | 12 (13·6) | 5 (5·7) | 35 (39·8) | 36 (40·9) |
| 24 mo. | 68 | 6 (8·8) | 7 (10·3) | 28 (41·2) | 27 (39·7) |
| 30 mo. | 120 | 19 (15·8) | 12 (10·0) | 63 (52·5) | 26 (21·7) |
| 36 mo. | 107 | 24 (22·4) | 12 (11·2) | 49 (45·8) | 22 (20·6) |
| 42mo. | 107 | 37 (34·6) | 14 (13·1) | 30 (28·0) | 26 (24·3) |
Data of PCR-confirmed yaws cases for baseline and 6 months represent a random sample of 90 and 84 ulcers that were tested by PCR from a total of 690 and 121 participants with skin ulcers detected, respectively. Data from 12 months to 42 months represent all ulcers detected.
P<0.0001 by the chi-square test for the between-group comparison within each type of infection.