Marks Michael, Sokana Oliver, Nachamkin Eli, Puiahi Elliot, Kilua Georgina, Pillay Allan, Bottomley Christian, Solomon Anthony W, Mabey David C
Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
The Hospital for Tropical Diseases, London, United Kingdom.
PLoS Negl Trop Dis. 2016 Aug 23;10(8):e0004927. doi: 10.1371/journal.pntd.0004927. eCollection 2016 Aug.
Both yaws and trachoma are endemic in the Pacific. Mass treatment with azithromycin is the mainstay of the WHO strategy for both the eradication of yaws and the elimination of trachoma as a public health problem, but the dose recommended for trachoma is lower than that for yaws. In countries where both diseases are endemic, there is a potential for synergy between yaws and trachoma control programs if mass treatment with the lower dose of azithromycin was shown to be effective for the treatment of yaws. In an earlier study, we demonstrated a profound reduction in the clinical and serological prevalence of yaws following a single round of mass treatment with azithromycin 20 mg/kg undertaken for the purposes of trachoma elimination.
This survey was conducted 18 months following a single round of azithromycin mass treatment in the same communities in which we had conducted our previous six-month follow-up survey. We examined children aged 1-14 years and took blood and lesion samples for yaws diagnosis using the Treponema pallidum particle agglutination assay (TPPA) and the non-treponemal Rapid Plasma Reagin (RPR) test.
A total of 1,284 children were enrolled in the study. Amongst children aged 5-14 years, 223 had a positive TPPA (27.5%, 95% CI 13.6-47.7%). The TPPA seroprevalence amongst this age group did not differ significantly from either our pre-mass treatment survey or our initial follow-up survey. Thirty-five children had positive TPPA and positive RPR (4.3%, 95% CI 2.1-8.7%), and this did not differ significantly from our initial post-mass drug administration (MDA) follow-up survey (4.3% versus 3.5%, p = 0.43) but remained significantly lower than our initial pre-MDA survey (4.3% vs 21.7%, p <0.0001). Village-level MDA coverage was strongly associated with dual-seropositivity (p = 0.005). Amongst children aged 1-4 years, 16 had a positive TPPA (3.5%, 95% CI 1.6-7.1%). This did not differ significantly from the seroprevalence in this age group that had been predicted based on our previous surveys (3.5% vs 5%, p = 0.11). Fourteen children (1.1%) were considered to have a skin lesion clinically consistent with yaws, but none of these individuals was seropositive for yaws. Of nine cases where a swab could be collected for PCR, all were negative for Treponema pallidum subsp. pertenue DNA.
In this study we have shown that the benefit of a single round of mass treatment with azithromycin 20mg/kg appears to extend to 18 months without any further intervention. The lack of a significant change in seroprevalence from 6 to 18 months after mass treatment might suggest that interventions could be spaced at yearly intervals without a significant loss of impact, and that this might facilitate integration of yaws eradication with other neglected tropical disease (NTD) control programmes. MDA coverage above 90% was associated with significantly better outcomes than coverages lower than this threshold, and strategies to improve coverage at all stages of yaws eradication efforts should be investigated.
雅司病和沙眼在太平洋地区均为地方病。使用阿奇霉素进行大规模治疗是世界卫生组织根除雅司病和消除沙眼这一公共卫生问题战略的主要支柱,但推荐用于沙眼的剂量低于雅司病。在这两种疾病均为地方病的国家,如果低剂量阿奇霉素大规模治疗被证明对雅司病治疗有效,那么雅司病和沙眼控制项目之间就有可能产生协同效应。在一项早期研究中,我们证明,为消除沙眼目的进行一轮20毫克/千克阿奇霉素大规模治疗后,雅司病的临床和血清学患病率大幅降低。
本次调查在我们之前进行为期六个月随访调查的相同社区进行一轮阿奇霉素大规模治疗18个月后开展。我们检查了1至14岁的儿童,并采集血液和病变样本,使用梅毒螺旋体颗粒凝集试验(TPPA)和非梅毒螺旋体快速血浆反应素(RPR)试验进行雅司病诊断。
共有1284名儿童参与了该研究。在5至14岁的儿童中,223名TPPA呈阳性(27.5%,95%置信区间13.6 - 47.7%)。该年龄组的TPPA血清阳性率与我们大规模治疗前的调查或初始随访调查相比,差异均无统计学意义。35名儿童TPPA和RPR均呈阳性(4.3%,95%置信区间2.1 - 8.7%),这与我们大规模药物给药(MDA)后的初始随访调查(4.3%对3.5%,p = 0.43)相比差异无统计学意义,但仍显著低于我们大规模药物给药前的初始调查(4.3%对21.7%,p <0.0001)。村级MDA覆盖率与双血清阳性密切相关(p = 0.005)。在1至4岁的儿童中,16名TPPA呈阳性(3.5%,95%置信区间1.6 - 7.1%)。这与根据我们之前调查预测的该年龄组血清阳性率相比差异无统计学意义(3.5%对5%,p = 0.11)。14名儿童(1.1%)被认为有临床上与雅司病相符的皮肤病变,但这些个体中没有一人雅司病血清呈阳性。在可采集拭子进行PCR的9例病例中,所有病例梅毒螺旋体 pertenue亚种DNA均为阴性。
在本研究中,我们表明一轮20毫克/千克阿奇霉素大规模治疗的益处似乎可延续至18个月,无需任何进一步干预。大规模治疗后6至18个月血清阳性率无显著变化,这可能表明干预措施可以每年进行一次,而不会显著降低效果,并且这可能有助于将雅司病根除与其他被忽视热带病(NTD)控制项目相结合。MDA覆盖率高于90%与低于该阈值的覆盖率相比,结局显著更好,应研究在雅司病根除工作的各个阶段提高覆盖率的策略。