Yaws recurrence in children at continued risk of infection.

BACKGROUND: In yaws-endemic areas, children with Treponema pallidum subsp. pertenue infection may suffer recurrent episodes due to either reinfection or relapse. However, the possibility of infection with other cutaneous ulcer causative agents and difficulties in interpreting standard laboratory results challenges the estimation of yaws recurrence rates. METHODS: We estimated the rates of yaws recurrences in the Lihir Island (Papua New Guinea) using two approaches: passive surveillance based on a retrospective screening of electronic medical records of cutaneous ulcers diagnosed using serological testing between 2005 and 2016, and active surveillance conducted during a cross-sectional prevalence study which included PCR analyses of ulcers of all suspected cases of yaws. The risk of recurrent infection was assessed based on data from the passive surveillance analysis and using two Cox regression models (crude and multivariate), stratified by year of index episode. Data gathered from the active surveillance was used to characterize the recurrences and no hypothesis testing was performed. RESULTS: The electronic medical records included 6,125 patients (7,889 ulcer episodes) with documented serological results of cutaneous ulcers of which1,486 were diagnosed with yaws. Overall, 1,246/6,125 patients (20.3%) presented more than once with a cutaneous ulcer, and 103/1,486 (6.7%) patients had multiple episodes of yaws. The risk of yaws recurrence significantly increased with age and was higher in patients with ≥3 recurrent episodes. In the active surveillance, we identified 50 individuals with recurrent cutaneous ulcer that had PCR results available for both the index and recurrent episode. Of 12 individuals with T. pallidum in the index ulcer, 8 (66%) had T. pallidum in subsequent assessments, relapse related to macrolide-resistance was identified in two of these cases. CONCLUSIONS: Our results confirm the need for active follow-up of yaws patients after treatment, particularly children and individuals with a history of recurrence

Analytical and clinical performance of the panbio COVID-19 antigen-detecting rapid diagnostic test

info:eu-repo/semantics/submittedVersio

Transmission of COVID-19 in 282 clusters in Catalonia, Spain: a cohort study.

BACKGROUND: Scarce data are available on what variables affect the risk of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the development of symptomatic COVID-19, and, particularly, the relationship with viral load. We aimed to analyse data from linked index cases of COVID-19 and their contacts to explore factors associated with transmission of SARS-CoV-2. METHODS: In this cohort study, patients were recruited as part of a randomised controlled trial done between March 17 and April 28, 2020, that aimed to assess if hydroxychloroquine reduced transmission of SARS-CoV-2. Patients with COVID-19 and their contacts were identified by use of the electronic registry of the Epidemiological Surveillance Emergency Service of Catalonia (Spain). Patients with COVID-19 included in our analysis were aged 18 years or older, not hospitalised, had quantitative PCR results available at baseline, had mild symptom onset within 5 days before enrolment, and had no reported symptoms of SARS-CoV-2 infections in their accommodation or workplace within the 14 days before enrolment. Contacts included were adults with a recent history of exposure and absence of COVID-19-like symptoms within the 7 days preceding enrolment. Viral load of contacts, measured by quantitative PCR from a nasopharyngeal swab, was assessed at enrolment, at day 14, and whenever the participant reported COVID-19-like symptoms. We assessed risk of transmission and developing symptomatic disease and incubation dynamics using regression analysis. We assessed the relationship of viral load and characteristics of cases (age, sex, number of days from reported symptom onset, and presence or absence of fever, cough, dyspnoea, rhinitis, and anosmia) and associations between risk of transmission and characteristics of the index case and contacts. FINDINGS: We identified 314 patients with COVID-19, with 282 (90%) having at least one contact (753 contacts in total), resulting in 282 clusters. 90 (32%) of 282 clusters had at least one transmission event. The secondary attack rate was 17% (125 of 753 contacts), with a variation from 12% when the index case had a viral load lower than 1 × 106 copies per mL to 24% when the index case had a viral load of 1 × 1010 copies per mL or higher (adjusted odds ratio per log10 increase in viral load 1·3, 95% CI 1·1-1·5). Increased risk of transmission was also associated with household contact (3·0, 1·59-5·65) and age of the contact (per year: 1·02, 1·01-1·04). 449 contacts had a positive PCR result at baseline. 28 (6%) of 449 contacts had symptoms at the first visit. Of 421 contacts who were asymptomatic at the first visit, 181 (43%) developed symptomatic COVID-19, with a variation from approximately 38% in contacts with an initial viral load lower than 1 × 107 copies per mL to greater than 66% for those with an initial viral load of 1 × 1010 copies per mL or higher (hazard ratio per log10 increase in viral load 1·12, 95% CI 1·05-1·20; p=0·0006). Time to onset of symptomatic disease decreased from a median of 7 days (IQR 5-10) for individuals with an initial viral load lower than 1 × 107 copies per mL to 6 days (4-8) for those with an initial viral load between 1 × 107 and 1 × 109 copies per mL, and 5 days (3-8) for those with an initial viral load higher than 1 × 109 copies per mL. INTERPRETATION: In our study, the viral load of index cases was a leading driver of SARS-CoV-2 transmission. The risk of symptomatic COVID-19 was strongly associated with the viral load of contacts at baseline and shortened the incubation time of COVID-19 in a dose-dependent manner. FUNDING: YoMeCorono, Generalitat de Catalunya. TRANSLATIONS: For the Catalan translation of the abstract see Supplementary Materials section

Performance characteristics of five antigen-detecting rapid diagnostic test (Ag-RDT) for SARS-CoV-2 asymptomatic infection: a head-to-head benchmark comparison.

BACKGROUND: Mass testing for early identification and isolation of infectious COVID-19 individuals is efficacious for reducing disease spread. Antigen-detecting rapid diagnostic tests (Ag-RDT) may be suitable for testing strategies; however, benchmark comparisons are scarce. METHODS: We used 286 nasopharyngeal specimens from unexposed asymptomatic individuals collected between December 2020 and January 2021 to assess five Ag-RDTs marketed by Abbott, Siemens, Roche Diagnostics, Lepu Medical, and Surescreen. RESULTS: For the overall sample, the performance parameters of Ag-RDTs were as follows: Abbott assay, sensitivity 38.6% (95%CI 29.1-48.8) and specificity 99.5% (97-100%); Siemens, sensitivity 51.5% (41.3-61.6) and specificity 98.4% (95.3-99.6); Roche, sensitivity 43.6% (33.7-53.8) and specificity 96.2% (92.4-98.5); Lepu, sensitivity 45.5% (35.6-55.8) and specificity 89.2% (83.8-93.3%); Surescreen, sensitivity 28.8% (20.2-38.6) and specificity 97.8% (94.5-99.4%). For specimens with cycle threshold (Ct) 99% and <50%, respectively. CONCLUSIONS: When screening unexposed asymptomatic individuals, two Ag-RDTs achieved sensitivity ≥80% for specimens with Ct<30 and specificity ≥96%. The estimated negative predictive value suggests the suitability of Ag-RDTs for mass screenings of SARS-CoV-2 infection in the general population

Evaluating the yaws diagnostic gap: A survey to determine the capacity of and barriers to improving diagnostics in all yaws-endemic countries

BACKGROUND: Yaws, caused by Treponema pallidum subsp. pertenue, is a skin neglected tropical disease. It is targeted for eradication by 2030, primarily using mass drug administration (MDA) with azithromycin. Traditionally, diagnosis of yaws has relied on clinical examination and serological testing. However, these approaches have poor diagnostic performance. To achieve eradication, more accurate diagnostics are required to determine whether MDA should be initiated or continued as well as for post-elimination surveillance. Molecular tools will be crucial for detecting antimicrobial resistant cases, which have the potential to derail eradication efforts. In order to determine the feasibility of introducing novel, more accurate, diagnostics for yaws surveillance purposes, it is necessary to understand current in-country diagnostic capacity. This study therefore aimed to understand the current capacity of, and challenges to, improving diagnostics for yaws in all yaws-endemic countries worldwide. METHODOLOGY/ PRINCIPLE FINDINGS: An online survey was sent to all 15 yaws-endemic countries in July 2021. The survey asked about past prevalence estimates, the availability of different diagnostic tools, and perceived barriers to enhancing capacity. Fourteen countries responded to the survey, four of which did not have a current National Policy for yaws eradication in place. Over 95% of reported that yaws cases from the past five years had not been confirmed with serological or molecular tools, largely due to the limited supply of rapid serological tests. Only four countries reported having operational laboratories for molecular yaws diagnosis, with only one of these having a validated assay to detect azithromycin resistance. CONCLUSIONS AND SIGNIFICANCE: This study highlights the diagnostic capacity constraints across all respondent countries. Countries are in need of access to a sustainable supply of serological tests, and development of molecular testing facilities. Sufficient sustainable funding should be made available to ensure that appropriate diagnostic tools are available and utilised

Hydroxychloroquine for Early Treatment of Adults With Mild Coronavirus Disease 2019: A Randomized, Controlled Trial

No effective treatments for coronavirus disease 2019 (COVID-19) exist. We aimed to determine whether early treatment with hydroxychloroquine (HCQ) would be efficacious for outpatients with COVID-19.The authors thank Gerard Carot-Sans, PhD, for providing medical writing support during the revisions of the subsequent drafts of the manuscript; the personnel from the Fights Aids and Infectious Diseases Foundation for their support in administration, human resources and supply chain management; Eric Ubals (Pierce AB) and Òscar Palao (Opentic) for website and database management; Óscar Camps and OpenArms nongovernmental organization for nursing home operations; and Anna Valentí and the Hospital Germans Trias i Pujol Human Resources Department for telephone monitoring. We thank Consorci Sanitari del Maresme, Centre Sociosanitari El Carme, l'Hospital General de Granollers and occupational hazards department of Hospital Germans Trias i Pujol for their contribution with patient enrollment. We are very grateful to Marc Clotet and Natalia Sánchez who coordinated the JoEmCorono crowd-funding campaign. We thank the Hospital Germans Trias Pujol Institutional Review Board and the Spanish Agency of Medicines and Medical Devices for their prompt action for consideration and approvals to the protocol. Financial support. This work was mainly supported by the crowd-funding campaign JoEmCorono (https://www.yomecorono.com/) with contributions from more than 72 000 citizens and corporations. The study also received financial support from Laboratorios Rubió, Laboratorios Gebro Pharma, Zurich Seguros, SYNLAB Barcelona, and Generalitat de Catalunya. Laboratorios Rubió also contributed to the study with the required doses of hydroxychloroquine (Dolquine®). Foundation Dorneur partly funded lab equipment at Irsi-Caixa.Peer reviewe

Dataset of active ulcer cases included in the analysis

BACKGROUND: In yaws-endemic areas, children with Treponema pallidum subsp. pertenue infection may suffer recurrent episodes due to either reinfection or relapse. However, the possibility of infection with other cutaneous ulcer causative agents and difficulties in interpreting standard laboratory results challenges the estimation of yaws recurrence rates. METHODS: We estimated the rates of yaws recurrences in the Lihir Island (Papua New Guinea) using two approaches: passive surveillance based on a retrospective screening of electronic medical records of cutaneous ulcers diagnosed using serological testing between 2005 and 2016, and active surveillance conducted during a cross-sectional prevalence study which included PCR analyses of ulcers of all suspected cases of yaws. The risk of recurrent infection was assessed based on data from the passive surveillance analysis and using two Cox regression models (crude and multivariate), stratified by year of index episode. Data gathered from the active surveillance was used to characterize the recurrences and no hypothesis testing was performed. RESULTS: The electronic medical records included 6,125 patients (7,889 ulcer episodes) with documented serological results of cutaneous ulcers of which1,486 were diagnosed with yaws. Overall, 1,246/6,125 patients (20.3%) presented more than once with a cutaneous ulcer, and 103/1,486 (6.7%) patients had multiple episodes of yaws. The risk of yaws recurrence significantly increased with age and was higher in patients with ≥3 recurrent episodes. In the active surveillance, we identified 50 individuals with recurrent cutaneous ulcer that had PCR results available for both the index and recurrent episode. Of 12 individuals with T. pallidum in the index ulcer, 8 (66%) had T. pallidum in subsequent assessments, relapse related to macrolide-resistance was identified in two of these cases. CONCLUSIONS: Our results confirm the need for active follow-up of yaws patients after treatment, particularly children and individuals with a history of recurrence

Rapid Serologic Test for Diagnosis of Yaws in Patients with Suspicious Skin Ulcers

The Chembio DPP (Dual Path Platform) Syphilis Screen & Confirm kit (https://chembio.com) is a rapid serologic test that can be used to diagnose yaws. We evaluated its capacity to detect patients with ulcers that tested PCR positive for Treponema pallidum subsp. pertenue. DPP detected 84% of ulcers that were positive by PCR

Low genetic diversity of Treponema pallidum ssp. pertenue (TPE) isolated from patients' ulcers in Namatanai District of Papua New Guinea: Local human population is infected by three TPE genotypes.

Yaws is an endemic disease caused by Treponema pallidum subsp. pertenue (TPE) that primarily affects children in rural regions of the tropics. The endemic character of yaws infections and the expected exclusive reservoir of TPE in humans opened a new opportunity to start a yaws eradication campaign. We have developed a multi-locus sequence typing (MLST) scheme for TPE isolates combining the previously published (TP0548, TP0488) and new (TP0858) chromosomal loci, and we compared this typing scheme to the two previously published MLST schemes. We applied this scheme to TPE-containing clinical isolates obtained during a mass drug administration study performed in the Namatanai District of Papua New Guinea between June 2018 and December 2019. Of 1081 samples collected, 302 (28.5%) tested positive for TPE DNA, from which 255 (84.4%) were fully typed. The TPE PCR-positivity in swab samples was higher in younger patients, patients with single ulcers, first ulcer episodes, and with ulcer duration less than six months. Non-treponemal serological test positivity correlated better with PCR positivity compared to treponema-specific serological tests. The MLST revealed a low level of genetic diversity among infecting TPE isolates, represented by just three distinct genotypes (JE11, SE22, and TE13). Two previously used typing schemes revealed similar typing resolutions. Two new alleles (one in TP0858 and one in TP0136) were shown to arise by intragenomic recombination/deletion events. Compared to samples genotyped as JE11, the minor genotypes (TE13 and SE22) were more frequently detected in samples from patients with two or more ulcers and patients with higher values of specific TP serological tests. Moreover, the A2058G mutation in the 23S rRNA genes of three JE11 isolates was found, resulting in azithromycin resistance

Trial of Three Rounds of Mass Azithromycin Administration for Yaws Eradication.

BACKGROUND: Treponema pallidum subspecies pertenue causes yaws. Strategies to better control, eliminate, and eradicate yaws are needed. METHODS: In an open-label, cluster-randomized, community-based trial conducted in a yaws-endemic area of Papua New Guinea, we randomly assigned 38 wards (i.e., clusters) to receive one round of mass administration of azithromycin followed by two rounds of target treatment of active cases (control group) or three rounds of mass administration of azithromycin (experimental group); round 1 was administered at baseline, round 2 at 6 months, and round 3 at 12 months. The coprimary end points were the prevalence of active cases of yaws, confirmed by polymerase-chain-reaction assay, in the entire trial population and the prevalence of latent yaws, confirmed by serologic testing, in a subgroup of asymptomatic children 1 to 15 years of age; prevalences were measured at 18 months, and the between-group differences were calculated. RESULTS: Of the 38 wards, 19 were randomly assigned to the control group (30,438 persons) and 19 to the experimental group (26,238 persons). A total of 24,848 doses of azithromycin were administered in the control group (22,033 were given to the participants at round 1 and 207 and 2608 were given to the participants with yaws-like lesions and their contacts, respectively, at rounds 2 and 3 [combined]), and 59,852 doses were administered in the experimental group. At 18 months, the prevalence of active yaws had decreased from 0.46% (102 of 22,033 persons) at baseline to 0.16% (47 of 29,954 persons) in the control group and from 0.43% (87 of 20,331 persons) at baseline to 0.04% (10 of 25,987 persons) in the experimental group (relative risk adjusted for clustering, 4.08; 95% confidence interval [CI], 1.90 to 8.76). The prevalence of other infectious ulcers decreased to a similar extent in the two treatment groups. The prevalence of latent yaws at 18 months was 6.54% (95% CI, 5.00 to 8.08) among 994 children in the control group and 3.28% (95% CI, 2.14 to 4.42) among 945 children in the experimental group (relative risk adjusted for clustering and age, 2.03; 95% CI, 1.12 to 3.70). Three cases of yaws with resistance to macrolides were found in the experimental group. CONCLUSIONS: The reduction in the community prevalence of yaws was greater with three rounds of mass administration of azithromycin at 6-month intervals than with one round of mass administration of azithromycin followed by two rounds of targeted treatment. Monitoring for the emergence and spread of antimicrobial resistance is needed. (Funded by Fundació "la Caixa" and others; ClinicalTrials.gov number, NCT03490123.)