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.

Immunopathogenesis of Progressive Scarring Trachoma: Results of a 4-Year Longitudinal Study in Tanzanian Children.

Trachoma is initiated during childhood following repeated conjunctival infection with Chlamydia trachomatis, which causes a chronic inflammatory response in some individuals that leads to scarring and in-turning of the eyelids in later life. There is currently no treatment to halt the progression of scarring trachoma due to an incomplete understanding of disease pathogenesis. A cohort study was performed in northern Tanzania in 616 children aged 6 to 10 years at enrollment. Every 3 months for 4 years, children were examined for clinical signs of trachoma, and conjunctival swabs were collected for C. trachomatis detection and to analyze the expression of 46 immunofibrogenic genes. Data were analyzed in relation to progressive scarring status between baseline and the final time point. Genes that were significantly associated with scarring progression included those encoding proinflammatory chemokines (CXCL5, CCL20, CXCL13, and CCL18), cytokines (IL23A, IL19, and IL1B), matrix modifiers (MMP12 and SPARCL1), immune regulators (IDO1, SOCS3, and IL10), and a proinflammatory antimicrobial peptide (S100A7). In response to C. trachomatis infection, IL23A and PDGF were significantly upregulated in scarring progressors relative to in nonprogressors. Our findings highlight the importance of innate proinflammatory signals from the epithelium and implicate interleukin 23A (IL-23A)-responsive cells in driving trachomatous scarring, with potential key mechanistic roles for PDGFB, MMP12, and SPARCL1 in orchestrating fibrosis.

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.

Advancing the understanding of treponemal disease in the past and present.

Syphilis was perceived to be a new disease in Europe in the late 15th century, igniting a debate about its origin that continues today in anthropological, historical, and medical circles. We move beyond this age-old debate using an interdisciplinary approach that tackles broader questions to advance the understanding of treponemal infection (syphilis, yaws, bejel, and pinta). How did the causative organism(s) and humans co-evolve? How did the related diseases caused by Treponema pallidum emerge in different parts of the world and affect people across both time and space? How are T. pallidum subspecies related to the treponeme causing pinta? The current state of scholarship in specific areas is reviewed with recommendations made to stimulate future work. Understanding treponemal biology, genetic relationships, epidemiology, and clinical manifestations is crucial for vaccine development today and for investigating the distribution of infection in both modern and past populations. Paleopathologists must improve diagnostic criteria and use a standard approach for recording skeletal lesions on archaeological human remains. Adequate contextualization of cultural and environmental conditions is necessary, including site dating and justification for any corrections made for marine or freshwater reservoir effects. Biogeochemical analyses may assess aquatic contributions to diet, physiological changes arising from treponemal disease and its treatments (e.g., mercury), or residential mobility of those affected. Shifting the focus from point of origin to investigating who is affected (e.g., by age/sex or socioeconomic status) and disease distribution (e.g., coastal/ inland, rural/urban) will advance our understanding of the treponemal disease and its impact on people through time.

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.

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.

A Cluster-Randomized Trial to Assess the Efficacy of Targeting Trachoma Treatment to Children.

Background: The World Health Organization recommends annual treatment of entire trachoma-endemic communities, although children typically have a higher load, longer duration, and greater likelihood of infection. Methods: Forty-eight communities in Matameye, Niger, were randomized to annual oral azithromycin treatment of the entire community or biannual treatment of children aged 0-12 years only. Both children and adults were monitored for ocular chlamydial infection by polymerase chain reaction. Results: The prevalence of childhood infection was reduced in the annually treated arm from 21.2% (95% confidence interval [CI], 15.2%-28.0%) at baseline to 5.8% (95% CI, 3.2%-9.0%) at 36 months (P < .001) and in the biannual arm from 20.2% (95% CI, 15.5%-25.3%) to 3.8% (95% CI, 2.2%-6.0%; P < .001). Adult infection in the annual arm was reduced from 1.7% (95% CI, .9%-2.7%) to 0.3% (95% CI, .0%-.7%) and in the biannual arm from 1.2% (95% CI, .5%-2.2%) to 0.0% (95% CI, .0%-.7%; P = .005). The effect of biannual treatment of children compared with annual treatment of the entire community in both children (95% CI, -.04% to .02%) and adults (95% CI, .9%-2.7%) excluded the prespecified noninferiority threshold of 6% (P = .003 and P < .001, respectively). Conclusions: Periodic distribution of antibiotics to children in trachoma-endemic communities reduces chlamydial infection in both children and untreated adults, suggesting a form of herd protection. Biannual treatment of children was comparable to (specifically, noninferior to) annual treatment of the entire community, and may offer lower antibiotic use and other logistical advantages. Clinical Trials Registration: NCT00792922.

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.

Short-term increase in prevalence of nasopharyngeal carriage of macrolide-resistant Staphylococcus aureus following mass drug administration with azithromycin for trachoma control.

BACKGROUND: Mass drug administration (MDA) with azithromycin is a corner-stone of trachoma control however it may drive the emergence of antimicrobial resistance. In a cluster-randomized trial (Clinical trial gov NCT00792922), we compared the reduction in the prevalence of active trachoma in communities that received three annual rounds of MDA to that in communities that received a single treatment round. We used the framework of this trial to carry out an opportunistic study to investigate if the increased rounds of treatment resulted in increased prevalence of nasopharyngeal carriage of macrolide-resistant Staphylococcus aureus. Three cross-sectional surveys were conducted in two villages receiving three annual rounds of MDA (3 × treatment arm). Surveys were conducted immediately before the third round of MDA (CSS-1) and at one (CSS-2) and six (CSS-3) months after MDA. The final survey also included six villages that had received only one round of MDA 30 months previously (1 × treatment arm). RESULTS: In the 3 × treatment arm, a short-term increase in prevalence of S. aureus carriage was seen following MDA from 24.6% at CSS-1 to 38.6% at CSS-2 (p < 0.001). Prevalence fell to 8.8% at CSS-3 (p < 0.001). A transient increase was also seen in prevalence of carriage of azithromycin resistant (AzmR) strains from 8.9% at CSS-1 to 34.1% (p < 0.001) in CSS-2 and down to 7.3% (p = 0.417) in CSS-3. A similar trend was observed for prevalence of carriage of macrolide-inducible-clindamycin resistant (iMLSB) strains. In CSS-3, prevalence of carriage of resistant strains was higher in the 3 × treatment arm than in the 1 × treatment (AzmR 7.3% vs. 1.6%, p = 0.010; iMLSB 5.8% vs. 0.8%, p < 0.001). Macrolide resistance was attributed to the presence of msr and erm genes. CONCLUSIONS: Three annual rounds of MDA with azithromycin were associated with a short-term increase in both the prevalence of nasopharyngeal carriage of S. aureus and prevalence of carriage of AzmR and iMLSB S. aureus. TRIAL REGISTRATION: This study was ancillary to the Partnership for the Rapid Elimination of Trachoma, ClinicalTrials.gov NCT00792922 , registration date November 17, 2008.

Population-based prevalence survey of follicular trachoma and trachomatous trichiasis in the Casamance region of Senegal.

BACKGROUND: Trachoma, caused by ocular infection with Chlamydia trachomatis, is the leading infectious cause of blindness worldwide. We conducted the first population-based trachoma prevalence survey in the Casamance region of Senegal to enable the Senegalese National Eye Care Programme (NECP) to plan its trachoma control activities. The World Health Organization (WHO) guidelines state that any individual with trachomatous trichiasis (TT) should be offered surgery, but that surgery should be prioritised where the prevalence is >0.1%, and that districts and communities with a trachomatous inflammation, follicular (TF) prevalence of ≥10% in 1-9 year-olds should receive mass antibiotic treatment annually for a minimum of three years, along with hygiene promotion and environmental improvement, before re-assessing the prevalence to determine whether treatment can be discontinued (when TF prevalence in 1-9 year-olds falls <5%). METHODS: Local healthcare workers conducted a population-based household survey in four districts of the Bignona Department of Casamance region to estimate the prevalence of TF in 1-9 year-olds, and TT in ≥15 year-olds. Children's facial cleanliness (ocular and/or nasal discharge, dirt on the face, flies on the face) was measured at time of examination. Risk factor questionnaires were completed at the household level. RESULTS: Sixty communities participated with a total censused population of 5580 individuals. The cluster-, age- and sex-adjusted estimated prevalence of TF in 1-9 year-olds was 2.5% (95% Confidence Interval (CI) 1.8-3.6) (38/1425) at the regional level and <5% in all districts, although the upper 95%CI exceeded 5% in all but one district. The prevalence of TT in those aged ≥15 years was estimated to be 1.4% (95%CI 1.0-1.9) (40/2744) at the regional level and >1% in all districts. CONCLUSION: With a prevalence <5%, TF does not appear to be a significant public health problem in this region. However, TF monitoring and surveillance at sub-district level will be required to ensure that elimination targets are sustained and that TF does not re-emerge as a public health problem. TT surgery remains the priority for trachoma elimination efforts in the region, with an estimated 1819 TT surgeries to conduct.

Metaanalysis of the Performance of a Combined Treponemal and Nontreponemal Rapid Diagnostic Test for Syphilis and Yaws.

BACKGROUND: The human treponematoses are important causes of disease. Mother-to-child transmission of syphilis remains a major cause of stillbirth and neonatal death. There are also almost 100 000 cases of endemic treponemal disease reported annually, predominantly yaws. Rapid diagnostic tests (RDTs) would improve access to screening for these diseases. Most RDTs cannot distinguish current and previous infection. The Dual Path Platform (DPP) Syphilis Screen & Confirm test includes both a treponemal (T1) and nontreponemal (T2) component and may improve the accuracy of diagnosis. METHODS: We conducted a metaanalysis of published and unpublished evaluations of the DPP-RDT for the diagnosis of syphilis and yaws. We calculated the sensitivity, specificity, and overall agreement of the test compared with reference laboratory tests. RESULTS: Nine evaluations, including 7267 tests, were included. Sensitivity was higher in patients with higher titer rapid plasma reagin (≥1:16) for both the T1 (98.2% vs 90.1%, P < .0001) and the T2 component (98.2% vs 80.6%, P < .0001). Overall agreement between the DPP test and reference serology was 85.2% (84.4%-86.1%). Agreement was highest for high-titer active infection and lowest for past infection. CONCLUSIONS: The RDT has good sensitivity and specificity of the treponemal and nontreponemal components both in cases of suspected syphilis and yaws, although the sensitivity is decreased at lower antibody titers.

Differential frequency of NKG2C/KLRC2 deletion in distinct African populations and susceptibility to Trachoma: a new method for imputation of KLRC2 genotypes from SNP genotyping data.

NKG2C is an activating receptor that is preferentially expressed on natural killer (NK) cells. The gene encoding NKG2C (killer cell lectin-like receptor C2, KLRC2) is present at different copy numbers in the genomes of different individuals. Deletion at the NKG2C locus was investigated in a case-control study of 1522 individuals indigenous to East- and West-Africa and the association with the ocular Chlamydia trachomatis infection and its sequelae was explored. The frequency of homozygous KLRC2 deletion was 13.7 % in Gambians and 4.7 % in Tanzanians. A significantly higher frequency of the deletion allele was found in West-Africans from the Gambia and Guinea-Bissau (36.2 % p = 2.105 × 10(-8), 26.8 % p = 0.050; respectively) in comparison to East-African Tanzanians where the frequency of the deletion is comparable to other human populations (20.9 %). We found no evidence for an association between the numbers of KLRC2 gene copies and the clinical manifestations of trachoma (follicular trachoma or conjunctival scarring). A new method for imputation of KLRC2 genotypes from single nucleotide polymorphism (SNP) data in 2621 individuals from the Gambia further confirmed these results. Our data suggest that NKG2C does not play a major role in trachomatous disease. We found that the deletion allele is present at different frequencies in different populations but the reason behind these differences is currently not understood. The new method offers the potential to use SNP arrays from genome wide association studies to study the frequency of KLRC2 deletion in other populations and its association with other diseases.

Inverse relationship between microRNA-155 and -184 expression with increasing conjunctival inflammation during ocular Chlamydia trachomatis infection.

BACKGROUND: Trachoma, a preventable blinding eye disease, is initiated by ocular infection with Chlamydia trachomatis (Ct). We previously showed that microRNAs (miR) -147b and miR-1285 were up-regulated in inflammatory trachomatous scarring. During the initial stage of disease, follicular trachoma with current Ct infection, the differential expression of miR has not yet been investigated. METHODS: Conjunctival samples were collected from 163 children aged 1-9 years old living in a trachoma-endemic region of Guinea Bissau, West Africa. Small RNA sequencing (RNAseq) was carried out on samples from five children with follicular trachoma and current Ct infection and five children with healthy conjunctivae and no Ct infection. Small RNAseq was also carried out on human epithelial cell lines infected with ocular Ct strains A2497 and isogenic plasmid-free A2497 in vitro. Results were validated by quantitative PCR (qPCR) in 163 clinical samples. RESULTS: Differential expression of RNAseq data identified 12 miR with changes in relative expression during follicular trachoma, of which 9 were confirmed as differentially expressed by qPCR (miR-155, miR-150, miR-142, miR-181b, miR-181a, miR-342, miR-132, miR-4728 and miR-184). MiR-155 and miR-184 expression had a direct relationship with the degree of clinical inflammation. MiR-155 was up-regulated (OR = 2.533 ((95 % CI = 1.291-4.971); P = 0.0069) and miR-184 was down-regulated (OR = 0.416 ((95 % CI = 0.300-0.578); P = 1.61*10(-7)) as the severity of clinical inflammation increased. Differential miR expression was not detected in HEp-2 or HCjE epithelial cells 48 h post infection with Ct in vitro. HCjE cells, a conjunctival epithelial cell line, had a markedly different miR background expression compared to HEp-2 cells. CONCLUSIONS: In follicular trachoma, expression of miR-155 and miR-184 is correlated with the severity of inflammation. This likely reflects host regulation of the immune response and a prolonged period of wound healing following the clearance of Ct. Prolonged healing may be associated with subsequent development of scarring trachoma.

Yaws.

INTRODUCTION: Yaws, caused by Treponema pallidum ssp. pertenue, is endemic in parts of West Africa, Southeast Asia and the Pacific. The WHO has launched a campaign based on mass treatment with azithromycin, to eradicate yaws by 2020. SOURCES OF DATA: We reviewed published data, surveillance data and data presented at yaws eradication meetings. AREAS OF AGREEMENT: Azithromycin is now the preferred agent for treating yaws. Point-of-care tests have demonstrated their value in yaws. AREAS OF CONTROVERSY: There is limited data from 76 countries, which previously reported yaws. Different doses of azithromycin are used in community mass treatment for yaws and trachoma. GROWING POINTS: Yaws eradication appears an achievable goal. The programme will require considerable support from partners across health and development sectors. AREAS TIMELY FOR DEVELOPING RESEARCH: Studies to complete baseline mapping, integrate diagnostic tests into surveillance and assess the impact of community mass treatment with azithromycin are ongoing.

Haemophilus ducreyi associated with skin ulcers among children, Solomon Islands.

During a survey of yaws prevalence in the Solomon Islands, we collected samples from skin ulcers of 41 children. Using PCR, we identified Haemophilus ducreyi infection in 13 (32%) children. PCR-positive and PCR-negative ulcers were phenotypically indistinguishable. Emergence of H. ducreyi as a cause of nongenital ulcers may affect the World Health Organization's yaws eradication program.

Integrated care as a means to improve primary care delivery for adults and adolescents in the developing world: a critical analysis of Integrated Management of Adolescent and Adult Illness (IMAI).

BACKGROUND: More than three decades after the 1978 Declaration of Alma-Ata enshrined the goal of 'health for all', high-quality primary care services remain undelivered to the great majority of the world's poor. This failure to effectively reach the most vulnerable populations has been, in part, a failure to develop and implement appropriate and effective primary care delivery models. This paper examines a root cause of these failures, namely that the inability to achieve clear and practical consensus around the scope and aims of primary care may be contributing to ongoing operational inertia. The present work also examines integrated models of care as a strategy to move beyond conceptual dissonance in primary care and toward implementation. Finally, this paper examines the strengths and weaknesses of a particular model, the World Health Organization's Integrated Management of Adolescent and Adult Illness (IMAI), and its potential as a guidepost toward improving the quality of primary care delivery in poor settings. DISCUSSION: Integration and integrated care may be an important approach in establishing a new paradigm of primary care delivery, though overall, current evidence is mixed. However, a number of successful specific examples illustrate the potential for clinical and service integration to positively impact patient care in primary care settings. One example deserving of further examination is the IMAI, developed by the World Health Organization as an operational model that integrates discrete vertical interventions into a comprehensive delivery system encompassing triage and screening, basic acute and chronic disease care, basic prevention and treatment services, and follow-up and referral guidelines. IMAI is an integrated model delivered at a single point-of-care using a standard approach to each patient based on the universal patient history and physical examination. The evidence base on IMAI is currently weak, but whether or not IMAI itself ultimately proves useful in advancing primary care delivery, it is these principles that should serve as the basis for developing a standard of integrated primary care delivery for adults and adolescents that can serve as the foundation for ongoing quality improvement. SUMMARY: As integrated primary care is the standard of care in the developed world, so too must we move toward implementing integrated models of primary care delivery in poorer settings. Models such as IMAI are an important first step in this evolution. A robust and sustained commitment to innovation, research and quality improvement will be required if integrated primary care delivery is to become a reality in developing world.