Trachoma, Anti-Pgp3 Serology, and Ocular Chlamydia trachomatis Infection in Papua New Guinea.

BACKGROUND: In Melanesia, the prevalence of trachomatous inflammation-follicular (TF) suggests that public health-level interventions against active trachoma are needed. However, the prevalence of trachomatous trichiasis is below the threshold for elimination as a public health problem and evidence of conjunctival infection with trachoma's causative organism (Chlamydia trachomatis [CT]) is rare. Here, we examine the prevalence of ocular infection with CT and previous exposure to CT in three evaluation units (EUs) of Papua New Guinea. METHODS: All individuals aged 1-9 years who were examined for clinical signs of trachoma in 3 Global Trachoma Mapping Project EUs were eligible to take part in this study (N = 3181). Conjunctival swabs were collected from 349 children with TF and tested by polymerase chain reaction to assess for ocular CT infection. Dried blood spots were collected from 2572 children and tested for anti-Pgp3 antibodies using a multiplex assay. RESULTS: The proportion of children with TF who had CT infection was low across all 3 EUs (overall 2%). Anti-Pgp3 seroprevalence was 5.2% overall and there was no association between anti-Pgp3 antibody level and presence of TF. In 2 EUs, age-specific seroprevalence did not increase significantly with increasing age in the 1- to 9-year-old population. In the third EU, there was a statistically significant change with age but the overall seroprevalence and peak age-specific seroprevalence was very low. CONCLUSIONS: Based on these results, together with similar findings from the Solomon Islands and Vanuatu, the use of TF to guide antibiotic mass drug administration decisions in Melanesia should be reviewed.

Conjunctival Scarring, Corneal Pannus, and Herbert's Pits in Adolescent Children in Trachoma-endemic Populations of the Solomon Islands and Vanuatu.

BACKGROUND: In the Solomon Islands and Vanuatu, the sign trachomatous inflammation-follicular (TF) is common, but ocular infection with Chlamydia trachomatis is not. It is therefore debatable whether azithromycin mass drug administration (MDA), the recommended antibiotic treatment strategy for trachoma's elimination as a public health problem, is necessary in this setting. We set out to estimate what proportion of adolescents were at risk of progression of trachomatous scarring. METHODS: A cross-sectional survey was undertaken of all children aged 10-14 years resident in communities identified as high-TF clusters during previous population-based mapping. Graders examined children for clinical evidence of trachomatous scarring, pannus, and Herbert's pits (HPs) or limbal follicles in both eyes. A dried blood spot was collected from each child and tested for antibodies to C. trachomatis. RESULTS: A total of 492 children in 24 villages of the Solomon Islands and Vanuatu were examined. In total, 35/492 (7%) of children had limbal signs (pannus and/or HPs) plus any conjunctival scarring. And 9/492 (2%) had limbal signs and moderate or severe conjunctival scarring; 22% of children were anti-Pgp3 seropositive. CONCLUSIONS: Few adolescents here are at risk of future complications from trachoma, supporting the conclusion that further antibiotic MDA is not currently required for trachoma elimination purposes in these settings.

Antibody Responses to Two Recombinant Treponemal Antigens (rp17 and TmpA) before and after Azithromycin Treatment for Yaws in Ghana and Papua New Guinea.

WHO and its partners aim to interrupt yaws transmission in countries of endemicity and to certify others as being yaws-free. Transmission can be assessed using rapid plasma reagin (RPR) tests, reflecting current or recent infection, but RPR is operationally impractical. We evaluated changes in antibody levels against two recombinant treponemal antigens, rp17 (also known as Tp17) and TmpA, after antibiotic treatment given as part of a randomized controlled trial for yaws in Ghana and Papua New Guinea. Paired serum samples from children aged 6 to 15 years with confirmed yaws, collected before and after treatment, were tested for antibodies to rp17 and TmpA using a semiquantitative bead-based immunoassay. Of 344 baseline samples, 342 tested positive for anti-rp17 antibodies and 337 tested positive for anti-TmpA antibodies. Six months after treatment, the median decrease in anti-rp17 signal was 3.2%, whereas the median decrease in anti-TmpA was 53.8%. The magnitude of change in the anti-TmpA response increased with increasing RPR titer fold change. These data demonstrate that responses to TmpA decrease markedly within 6 months of treatment whereas (as expected) those to rp17 do not. Incorporating responses to TmpA as a marker of recent infection within an integrated sero-surveillance platform could provide a way to prioritize areas for yaws mapping.

Prevalence of Scabies and Impetigo 3 Years After Mass Drug Administration With Ivermectin and Azithromycin.

BACKGROUND: Ivermectin-based mass drug administration has emerged as a promising strategy for the control of scabies and impetigo in settings where the diseases are endemic. Current follow-up data are limited to 12 months for the majority of studies. Longer-term data are vital to inform the sustainability of interventions. METHODS: We conducted a prevalence survey for scabies and impetigo in 10 villages in Choiseul Province of the Solomon Islands 36 months after a single round of ivermectin and azithromycin mass drug coadministration. In the primary analysis, we compared the prevalence of scabies and impetigo at 36 months to the prevalence at baseline. RESULTS: At 36 months, the prevalence of scabies was 4.7% (95% confidence interval [CI], 3.6-6.1), which was significantly lower than at baseline (18.7%; relative reduction, 74.9%; 95% CI, 61.5%-87.7%; P < .001). The prevalence of impetigo was 9.6% (95% CI, 8.1%-11.4%), significantly lower than at baseline (24.7%; relative reduction, 61.3%; 95% CI, 38.7%-100%; P < .001). The highest prevalence of scabies was among children aged <5 years (12.5%; adjusted odds ratio, 33.2; 95% CI, 6.6-603.2), and the highest prevalence of impetigo was among children aged 5-9 years (16.4%; adjusted odds ratio, 8.1; 95% CI, 3.6-21.8). CONCLUSIONS: There was a sustained impact of a single round of ivermectin and azithromycin mass drug coadministration on the prevalence of scabies and impetigo 3 years after the intervention. Our data provide further support to adopt this intervention as a central component of global scabies control efforts. CLINICAL TRIALS REGISTRATION: Australian and New Zealand Trials Registry (ACTRN12615001199505).

Impact of Community Treatment With Ivermectin for the Control of Scabies on the Prevalence of Antibodies to Strongyloides stercoralis in Children.

The prevalence of antibodies to Strongyloides stercoralis was measured in 0-12-year-olds using a bead-based immunoassay before and after ivermectin mass drug administration (MDA) for scabies in the Solomon Islands. Seroprevalence was 9.3% before and 5.1% after MDA (P = .019), demonstrating collateral benefits of ivermectin MDA in this setting.

Modeling Treatment Strategies to Inform Yaws Eradication.

Yaws is a neglected tropical disease targeted for eradication by 2030. To achieve eradication, finding and treating asymptomatic infections as well as clinical cases is crucial. The proposed plan, the Morges strategy, involves rounds of total community treatment (i.e., treating the whole population) and total targeted treatment (TTT) (i.e., treating clinical cases and contacts). However, modeling and empirical work suggests asymptomatic infections often are not found in the same households as clinical cases, reducing the utility of household-based contact tracing for a TTT strategy. We use a model fitted to data from the Solomon Islands to predict the likelihood of elimination of transmission under different intervention schemes and levels of systematic nontreatment resulting from the intervention. Our results indicate that implementing additional treatment rounds through total community treatment is more effective than conducting additional rounds of treatment of at-risk persons through TTT.

Estimating the Intracluster Correlation Coefficient for the Clinical Sign "Trachomatous Inflammation-Follicular" in Population-Based Trachoma Prevalence Surveys: Results From a Meta-Regression Analysis of 261 Standardized Preintervention Surveys Carried Out in Ethiopia, Mozambique, and Nigeria.

Sample sizes in cluster surveys must be greater than those in surveys using simple random sampling in order to obtain similarly precise prevalence estimates, because results from subjects examined in the same cluster cannot be assumed to be independent. Therefore, a crucial aspect of cluster sampling is estimation of the intracluster correlation coefficient (ρ): the degree of relatedness of outcomes in a given cluster, defined as the proportion of total variance accounted for by between-cluster variation. In infectious disease epidemiology, this coefficient is related to transmission patterns and the natural history of infection; its value also depends on particulars of survey design. Estimation of ρ is often difficult due to the lack of comparable survey data with which to calculate summary estimates. Here we use a parametric bootstrap model to estimate ρ for the ocular clinical sign "trachomatous inflammation-follicular" (TF) among children aged 1-9 years within population-based trachoma prevalence surveys. We present results from a meta-regression analysis of data from 261 such surveys completed using standardized methods in Ethiopia, Mozambique, and Nigeria in 2012-2015. Consistent with the underlying theory, we found that ρ increased with increasing overall TF prevalence and smaller numbers of children examined per cluster. Estimates of ρ for TF were independently higher in Ethiopia than in the other countries.

The public health control of scabies: priorities for research and action.

Scabies is a parasitic disease of the skin that disproportionately affects disadvantaged populations. The disease causes considerable morbidity and leads to severe bacterial infection and immune-mediated disease. Scientific advances from the past 5 years suggest that scabies is amenable to population-level control, particularly through mass drug administration. In recognition of these issues, WHO added scabies to the list of neglected tropical diseases in 2017. To develop a global control programme, key operational research questions must now be addressed. Standardised approaches to diagnosis and methods for mapping are required to further understand the burden of disease. The safety of treatments for young children, including with ivermectin and moxidectin, should be investigated. Studies are needed to inform optimum implementation of mass treatment, including the threshold for intervention, target, dosing, and frequency. Frameworks for surveillance, monitoring, and evaluation of control strategies are also necessary.

Comprehensive global genome dynamics of Chlamydia trachomatis show ancient diversification followed by contemporary mixing and recent lineage expansion.

Chlamydia trachomatis is the world's most prevalent bacterial sexually transmitted infection and leading infectious cause of blindness, yet it is one of the least understood human pathogens, in part due to the difficulties of in vitro culturing and the lack of available tools for genetic manipulation. Genome sequencing has reinvigorated this field, shedding light on the contemporary history of this pathogen. Here, we analyze 563 full genomes, 455 of which are novel, to show that the history of the species comprises two phases, and conclude that the currently circulating lineages are the result of evolution in different genomic ecotypes. Temporal analysis indicates these lineages have recently expanded in the space of thousands of years, rather than the millions of years as previously thought, a finding that dramatically changes our understanding of this pathogen's history. Finally, at a time when almost every pathogen is becoming increasingly resistant to antimicrobials, we show that there is no evidence of circulating genomic resistance in C. trachomatis.

The simplified trachoma grading system, amended.

A simplified grading system for trachoma was published by the World Health Organization (WHO) in 1987. Intended for use by non-specialist personnel working at community level, the system includes five signs, each of which can be present or absent in any eye: (i) trachomatous trichiasis; (ii) corneal opacity; (iii) trachomatous inflammation-follicular; (iv) trachomatous inflammation-intense; and (v) trachomatous scarring. Though neither perfectly sensitive nor perfectly specific for trachoma, these signs have been essential tools for identifying populations that need interventions to eliminate trachoma as a public health problem. In 2018, at WHO's 4th global scientific meeting on trachoma, the definition of one of the signs, trachomatous trichiasis, was amended to exclude trichiasis that affects only the lower eyelid. This paper presents the amended system, updates its presentation, offers notes on its use and identifies areas of ongoing debate.

En 1987, l'Organisation mondiale de la Santé a publié un système de codage simplifié du trachome. Destiné au personnel non qualifié travaillant au sein des communautés, il comporte cinq signes, chacun pouvant être présent ou absent dans l'un ou l'autre œil: (i) le trichiasis trachomateux; (ii) l'opacité cornéenne; (iii) l'inflammation trachomateuse ­ folliculaire; (iv) l'inflammation trachomateuse ­ intense; et enfin, (v) la cicatrice trachomateuse. Bien qu'ils ne soient ni parfaitement précis, ni totalement spécifiques au trachome, ces signes constituent des outils essentiels pour identifier les populations qui nécessitent une intervention afin d'éliminer le trachome en tant que problème de santé publique. En 2018, lors de la quatrième réunion scientifique mondiale sur le trachome, la définition de l'un des signes, le trichiasis trachomateux, a été modifiée pour exclure du système de codage le trichiasis qui n'affecte que la paupière inférieure. Ce document expose le nouveau système, actualise sa présentation, formule des remarques sur son utilisation et identifie les domaines qui font encore l'objet de débats.

En 1987, la Organización Mundial de la Salud (OMS) publicó un sistema de clasificación simplificado para el tracoma. Este sistema fue diseñado para que lo utilice el personal no especializado que trabaja a nivel comunitario e incluye cinco signos, cada uno de los cuales puede estar presente o ausente en los ojos: i) la triquiasis tracomatosa; ii) la opacidad corneal; iii) la inflamación tracomatosa-folicular; iv) la inflamación tracomatosa-intensa; y v) la cicatrización tracomatosa. Si bien no son perfectamente sensibles ni muy específicos del tracoma, estos signos han sido herramientas esenciales para identificar a las poblaciones que requieren intervenciones para eliminar el tracoma como problema de salud pública. En 2018, se modificó la definición de uno de los signos, la triquiasis tracomatosa, en la 4.ª Reunión Científica Mundial sobre el Tracoma de la OMS, para descartar la triquiasis que solo afecta al párpado inferior. En el presente documento se describe el sistema modificado, se actualiza su presentación, se ofrecen observaciones sobre su aplicación y se identifican los ámbitos de debate en curso.

Systematic review of the incidence of post-operative trichiasis in Africa.

BACKGROUND: Surgery for trichiasis is one of the pillars of the World Health Organization's strategy for global elimination of trachoma as a public health problem. A high incidence of post-operative trichiasis or other poor surgical outcomes could jeopardize these efforts. In this review, we aimed to summarize the reported incidence of post-operative trichiasis and other poor outcomes of trichiasis surgery in Africa. METHODS: We conducted a systematic literature search using PubMed, Academic Search Premier, Africa-Wide Information, CINAHL and Health Source Nursing through EBSCOhost, Web of Science, and the Cochrane Central Register of Controlled Trials. Reference lists of included studies were also reviewed to identify further potentially relevant publications. All observational and interventional studies that measured post-operative trichiasis in Africa as an outcome of trichiasis surgery were included. RESULTS: Thirty-five papers reporting on 22 studies (9 interventional,13 observational; total 13,737 participants) met the inclusion criteria. The reported incidence of post-operative trichiasis in the included studies ranged from 2% (at 6 weeks after bilamellar tarsal rotation) to 69% (at 3 weeks after anterior lamellar repositioning). The incidence varied by surgical procedure, study design, and length of follow-up. CONCLUSION: Trichiasis surgical outcomes should be improved. National trachoma programmes could benefit from identifying and adopting strategies to improve the performance and quality of their surgical service.

Randomized Trial of Community Treatment With Azithromycin and Ivermectin Mass Drug Administration for Control of Scabies and Impetigo.

BACKGROUND: Scabies is a public health problem in many countries, with impetigo and its complications important consequences. Ivermectin based mass drug administration (MDA) reduces the prevalence of scabies and, to a lesser extent, impetigo. We studied the impact of co-administering azithromycin on the prevalence of impetigo and antimicrobial resistance. METHODS: Six communities were randomized to receive either ivermectin-based MDA or ivermectin-based MDA co-administered with azithromycin. We measured scabies and impetigo prevalence at baseline and 12 months. We collected impetigo lesions swabs at baseline, 3 and 12 months to detect antimicrobial resistance. RESULTS: At baseline, scabies and impetigo prevalences were 11.8% and 10.1% in the ivermectin-only arm and 9.2% and 12.1% in the combined treatment arm. At 12 months, the prevalences had fallen to 1.0% and 2.5% in the ivermectin-only arm and 0.7% and 3.3% in the combined treatment arm. The proportion of impetigo lesions containing Staphylococcus aureus detected did not change (80% at baseline vs 86% at 12 months; no significant difference between arms) but the proportion containing pyogenic streptococci fell significantly (63% vs 23%, P < .01). At 3 months, 53% (8/15) of S. aureus isolates were macrolide-resistant in the combined treatment arm, but no resistant strains (0/13) were detected at 12 months. CONCLUSIONS: Co-administration of azithromycin with ivermectin led to similar decreases in scabies and impetigo prevalence compared to ivermectin alone. The proportion of impetigo lesions containing pyogenic streptococci declined following MDA. There was a transient increase in the proportion of macrolide-resistant S. aureus strains following azithromycin MDA. CLINICAL TRIALS REGISTRATION: clinicaltrials.gov (NCT02775617).

Impact of mass drug administration of azithromycin for trachoma elimination on prevalence and azithromycin resistance of genital Mycoplasma genitalium infection.

BACKGROUND: Mass drug administration (MDA) of 20 mg/kg (maximum 1 g in adults) azithromycin for ocular Chlamydia trachomatis (CT) infection is a key component of the WHO trachoma elimination strategy. However, this dose may be suboptimal in Mycoplasma genitalium infection and may encourage emergence of antimicrobial resistance (AMR) to azithromycin. OBJECTIVES: To determine the effect of MDA for trachoma elimination on M. genitalium prevalence, strain type and azithromycin resistance. METHODS: A secondary analysis of CT-negative vulvovaginal swabs from three outpatient antenatal clinics (Honiara, Solomon Islands) from patients recruited either pre-MDA, or 10 months post-MDA in two cross-sectional surveys was carried out. Swabs were tested for M. genitalium infection using Fast Track Diagnostics Urethritis Plus nucleic acid amplification assay. M. genitalium-positive samples were subsequently tested for azithromycin resistance by sequencing domain V of the 23S rRNA DNA region of M. genitalium and underwent phylogenetic analysis by dual locus sequence typing. RESULTS: M. genitalium prevalence was 11.9% (28/236) in women pre-MDA and 10.9% (28/256) 10 months post-MDA (p=0.7467). Self-reported receipt of azithromycin as part of MDA was 49.2% in women recruited post-MDA and 17.9% (5/28) in those who tested M. genitalium positive. Of samples sequenced (21/28 pre-MDA, 22/28 post-MDA), all showed a macrolide susceptible genotype. Strain typing showed that sequence types diverged into two lineages, with a suggestion of strain replacement post-MDA. CONCLUSION: A single round of azithromycin MDA in an island population with high baseline M. genitalium prevalence did not appear to impact on either prevalence or azithromycin resistance, in contrast to reported decreased genital CT prevalence in the same population. This may be due to limitations such as sample size, including CT-negative samples only, and low MDA coverage. Further investigation of the impact of multiple rounds of MDA on M. genitalium azithromycin AMR in antibiotic experienced and naïve populations is warranted.

Understanding the spatial distribution of trichiasis and its association with trachomatous inflammation-follicular.

BACKGROUND: Whilst previous work has identified clustering of the active trachoma sign "trachomatous inflammation-follicular" (TF), there is limited understanding of the spatial structure of trachomatous trichiasis (TT), the rarer, end-stage, blinding form of disease. Here we use community-level TF prevalence, information on access to water and sanitation, and large-scale environmental and socio-economic indicators to model the spatial variation in community-level TT prevalence in Benin, Cote d'Ivoire, DRC, Guinea, Ethiopia, Malawi, Mozambique, Nigeria, Sudan and Uganda. METHODS: We fit binomial mixed models, with community-level random effects, separately for each country. In countries where spatial correlation was detected through a semi-variogram diagnostic check we then fitted a geostatistical model to the TT prevalence data including TF prevalence as an explanatory variable. RESULTS: The estimated regression relationship between community-level TF and TT was significant in eight countries. We estimate that a 10% increase in community-level TF prevalence leads to an increase in the odds for TT ranging from 20 to 86% when accounting for additional covariates. CONCLUSION: We find evidence of an association between TF and TT in some parts of Africa. However, our results also suggest the presence of additional, country-specific, spatial risk factors which modulate the variation in TT risk.

Antibiotics for trachoma.

BACKGROUND: Trachoma is the world's leading infectious cause of blindness. In 1996, WHO launched the Alliance for the Global Elimination of Trachoma by the year 2020, based on the 'SAFE' strategy (surgery, antibiotics, facial cleanliness, and environmental improvement). OBJECTIVES: To assess the evidence supporting the antibiotic arm of the SAFE strategy by assessing the effects of antibiotics on both active trachoma (primary objective), Chlamydia trachomatis infection of the conjunctiva, antibiotic resistance, and adverse effects (secondary objectives). SEARCH METHODS: We searched relevant electronic databases and trials registers. The date of the last search was 4 January 2019. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that satisfied either of two criteria: (a) trials in which topical or oral administration of an antibiotic was compared to placebo or no treatment in people or communities with trachoma, (b) trials in which a topical antibiotic was compared with an oral antibiotic in people or communities with trachoma. We also included studies addressing different dosing strategies in the population.  DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We identified 14 studies where individuals with trachoma were randomised and 12 cluster-randomised studies. Any antibiotic versus control (individuals)Nine studies (1961 participants) randomised individuals with trachoma to antibiotic or control (no treatment or placebo). All of these studies enrolled children and young people with active trachoma. The antibiotics used in these studies included topical (oxy)tetracycline (5 studies), doxycycline (2 studies), and sulfonamides (4 studies). Four studies had more than two study arms. In general these studies were poorly reported, and it was difficult to judge risk of bias.These studies provided low-certainty evidence that people with active trachoma treated with antibiotics experienced a reduction in active trachoma at three months (risk ratio (RR) 0.78, 95% confidence interval (CI) 0.69 to 0.89; 1961 people; 9 RCTs; I2 = 73%) and 12 months (RR 0.74, 95% CI 0.55 to 1.00; 1035 people; 4 RCTs; I2 = 90%). Low-certainty evidence was available for ocular infection at three months (RR 0.81, 95% CI 0.63 to 1.04; 297 people; 4 RCTs; I2 = 0%) and 12 months (RR 0.25, 95% CI 0.08 to 0.78; 129 people; 1 RCT). None of these studies assessed antimicrobial resistance. In those studies that reported harms, no serious adverse effects were reported (low-certainty evidence).Oral versus topical antibiotics (individuals)Eight studies (1583 participants) compared oral and topical antibiotics. Only one study included people older than 21 years of age. Oral antibiotics included azithromycin (5 studies), sulfonamides (2 studies), and doxycycline (1 study). Topical antibiotics included (oxy)tetracycline (6 studies), azithromycin (1 study), and sulfonamide (1 study). These studies were poorly reported, and it was difficult to judge risk of bias.There was low-certainty evidence of little or no difference in effect between oral and topical antibiotics on active trachoma at three months (RR 0.97, 95% CI 0.81 to 1.16; 953 people; 6 RCTs; I2 = 63%) and 12 months (RR 0.93, 95% CI 0.75 to 1.15; 886 people; 5 RCTs; I2 = 56%). There was very low-certainty evidence for ocular infection at three or 12 months. Antimicrobial resistance was not assessed. In those studies that reported adverse effects, no serious adverse effects were reported; one study reported abdominal pain with azithromycin; one study reported a couple of cases of nausea with azithromycin; and one study reported three cases of reaction to sulfonamides (low-certainty evidence).Oral azithromycin versus control (communities)Four cluster-randomised studies compared antibiotic with no or delayed treatment. Data were available on active trachoma at 12 months from two studies but could not be pooled because of reporting differences. One study at low risk of bias found a reduced prevalence of active trachoma 12 months after a single dose of azithromycin in communities with a high prevalence of infection (RR 0.58, 95% CI 0.52 to 0.65; 1247 people). The other, lower quality, study in low-prevalence communities reported similar median prevalences of infection at 12 months: 9.3% in communities treated with azithromycin and 8.2% in untreated communities. We judged this moderate-certainty evidence for a reduction in active trachoma with treatment, downgrading one level for inconsistency between the two studies. Two studies reported ocular infection at 12 months and data could be pooled. There was a reduction in ocular infection (RR 0.36, 0.31 to 0.43; 2139 people) 12 months after mass treatment with a single dose compared with no treatment (moderate-certainty evidence). There was high-certainty evidence of an increased risk of resistance of Streptococcus pneumoniae, Staphylococcus aureus, and Escherichia coli to azithromycin, tetracycline, and clindamycin in communities treated with azithromycin, with approximately 5-fold risk ratios at 12 months. The evidence did not support increased resistance to penicillin or trimethoprim-sulfamethoxazole. None of the studies measured resistance to C trachomatis. No serious adverse events were reported. The main adverse effect noted for azithromycin (˜10%) was abdominal pain, vomiting, and nausea.Oral azithromycin versus topical tetracycline (communities)Three cluster-randomised studies compared oral azithromycin with topical tetracycline. The evidence was inconsistent for active trachoma and ocular infection at three and 12 months (low-certainty evidence) and was not pooled due to considerable heterogeneity. Antimicrobial resistance and adverse effects were not reported.Different dosing strategiesSix studies compared different strategies for dosing. There were: mass treatment at different dosing intervals; applying cessation or stopping rules to mass treatment; strategies to increase mass treatment coverage. There was no strong evidence to support any variation in the recommended annual mass treatment. AUTHORS' CONCLUSIONS: Antibiotic treatment may reduce the risk of active trachoma and ocular infection in people infected with C trachomatis, compared to no treatment/placebo, but the size of the treatment effect in individuals is uncertain. Mass antibiotic treatment with single dose oral azithromycin reduces the prevalence of active trachoma and ocular infection in communities. There is no strong evidence to support any variation in the recommended periodicity of annual mass treatment. There is evidence of an increased risk of antibiotic resistance at 12 months in communities treated with antibiotics.

Diagnostics for Yaws Eradication: Insights From Direct Next-Generation Sequencing of Cutaneous Strains of Treponema pallidum.

Background: Yaws-like chronic ulcers can be caused by Treponema pallidum subspecies pertenue, Haemophilus ducreyi, or other, still-undefined bacteria. To permit accurate evaluation of yaws elimination efforts, programmatic use of molecular diagnostics is required. The accuracy and sensitivity of current tools remain unclear because our understanding of T. pallidum diversity is limited by the low number of sequenced genomes. Methods: We tested samples from patients with suspected yaws collected in the Solomon Islands and Ghana. All samples were from patients whose lesions had previously tested negative using the Centers for Disease Control and Prevention (CDC) diagnostic assay in widespread use. However, some of these patients had positive serological assays for yaws on blood. We used direct whole-genome sequencing to identify T. pallidum subsp pertenue strains missed by the current assay. Results: From 45 Solomon Islands and 27 Ghanaian samples, 11 were positive for T. pallidum DNA using the species-wide quantitative polymerase chain reaction (PCR) assay, from which we obtained 6 previously undetected T. pallidum subsp pertenue whole-genome sequences. These show that Solomon Islands sequences represent distinct T. pallidum subsp pertenue clades. These isolates were invisible to the CDC diagnostic PCR assay, due to sequence variation in the primer binding site. Conclusions: Our data double the number of published T. pallidum subsp pertenue genomes. We show that Solomon Islands strains are undetectable by the PCR used in many studies and by health ministries. This assay is therefore not adequate for the eradication program. Next-generation genome sequence data are essential for these efforts.

Direct Whole-Genome Sequencing of Cutaneous Strains of Haemophilus ducreyi.

Haemophilus ducreyi, which causes chancroid, has emerged as a cause of pediatric skin disease. Isolation of H. ducreyi in low-income settings is challenging, limiting phylogenetic investigation. Next-generation sequencing demonstrates that cutaneous strains arise from class I and II H. ducreyi clades and that class II may represent a distinct subspecies.

Targeted Treatment of Yaws With Household Contact Tracing: How Much Do We Miss?

Yaws is a disabling bacterial infection found primarily in warm and humid tropical areas. The World Health Organization strategy mandates an initial round of total community treatment (TCT) with single-dose azithromycin followed either by further TCT or active case-finding and treatment of cases and their contacts (the Morges strategy). We sought to investigate the effectiveness of the Morges strategy. We employed a stochastic household model to study the transmission of infection using data collected from a pre-TCT survey conducted in the Solomon Islands. We used this model to assess the proportion of asymptomatic infections that occurred in households without active cases. This analysis indicated that targeted treatment of cases and their household contacts would miss a large fraction of asymptomatic infections (65%-100%). This fraction was actually higher at lower prevalences. Even assuming that all active cases and their households were successfully treated, our analysis demonstrated that at all prevalences present in the data set, up to 90% of (active and asymptomatic) infections would not be treated under household-based contact tracing. Mapping was undertaken as part of the study "Epidemiology of Yaws in the Solomon Islands and the Impact of a Trachoma Control Programme," in September-October 2013.

Mathematical Modeling of Programmatic Requirements for Yaws Eradication.

Yaws is targeted for eradication by 2020. The mainstay of the eradication strategy is mass treatment followed by case finding. Modeling has been used to inform programmatic requirements for other neglected tropical diseases and could provide insights into yaws eradication. We developed a model of yaws transmission varying the coverage and number of rounds of treatment. The estimated number of cases arising from an index case (basic reproduction number [R0]) ranged from 1.08 to 3.32. To have 80% probability of achieving eradication, 8 rounds of treatment with 80% coverage were required at low estimates of R0 (1.45). This requirement increased to 95% at high estimates of R0 (2.47). Extending the treatment interval to 12 months increased requirements at all estimates of R0. At high estimates of R0 with 12 monthly rounds of treatment, no combination of variables achieved eradication. Models should be used to guide the scale-up of yaws eradication.