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The frequency and duration of Chlamydia trachomatis (Ct) ocular infections decrease with age, suggesting development of partial immunity. However, there is a lack of clear correlates of immunity to Ct infection in humans. We screened sera from a cohort of Gambian children followed for six-months against a Ct-proteome microarray. At genome sequence level, we detected signatures of selection from a population of ocular Ct isolates from Guinea-Bissau. Together these approaches allowed us to highlight the focus of humoral responses and hypothesise new modes of pathogen immune evasion. Children who were susceptible to frequent and/or prolonged Ct infection had a less focussed antibody response, including preferential recognition of forty-two antigens. There was evidence of positive and purifying selection across the genome, but little balancing selection. In contrast, most antigens that were associated with susceptibility were under neutral selection. These data suggest an evasion strategy in which Ct presents a large panel of irrelevant antigens to the immune system to block or misdirect protective responses. Development of a focused immune response, possibly induced through vaccination, may be an effective strategy to promote protection to Ct infection.

BackgroundThe World Health Organization has recommended three rounds of mass drug administration (MDA) with antibiotics in districts where the prevalence of follicular trachoma (TF) is ≥10% in children aged 1-9 years, with treatment coverage of at least 80%. For districts at 5-10% TF prevalence it was recommended that TF be assessed in 1-9 year olds in each community within the district, with three rounds of MDA provided to any community where TF≥10%. Worldwide, over 40 million people live in districts whose TF prevalence is estimated to be between 5 and 10%. The best way to treat these districts, and the optimum role of testing for infection in deciding whether to initiate or discontinue MDA, are unknown.MethodsIn a community randomized trial with a factorial design, we randomly assigned 48 communities in four Gambian districts, in which the prevalence of trachoma was known or suspected to be above 10%, to receive annual mass treatment with expected coverage of 80-89% ("Standard"), or to receive an additional visit in an attempt to achieve coverage of 90% or more ("Enhanced"). The same 48 communities were randomised to receive mass treatment annually for three years ("3×"), or to have treatment discontinued if Chlamydia trachomatis (Ct) infection was not detected in a sample of children in the community after mass treatment (stopping rule("SR")). Primary outcomes were the prevalence of TF and of Ct infection in 0-5 year olds at 36 months.ResultsThe baseline prevalence of TF and of Ct infection in the target communities was 6.5% and 0.8% respectively. At 36 months the prevalence of TF was 2.8%, and that of Ct infection was 0.5%. No differences were found between the arms in TF or Ct infection prevalence either at baseline (Standard-3×: TF 5.6%, Ct 0.7%; Standard-SR: TF 6.1%, Ct 0.2%; Enhanced-3×: TF 7.4%, Ct 0.9%; and Enhanced-SR: TF 6.2%, Ct 1.2%); or at 36 months (Standard-3×: TF 2.3%, Ct 1.0%; Standard-SR TF 2.5%, Ct 0.2%; Enhanced-3× TF 3.0%, Ct 0.2%; and Enhanced-SR TF 3.2%, Ct 0.7% ). The implementation of the stopping rule led to treatment stopping after one round of MDA in all communities in both SR arms. Mean treatment coverage of children aged 0-9 in communities randomised to standard treatment was 87.7% at baseline and 84.8% and 88.8% at one and two years, respectively. Mean coverage of children in communities randomized to enhanced treatment was 90.0% at baseline and 94.2% and 93.8% at one and two years, respectively. There was no evidence of any difference in TF or Ct prevalence at 36 months resulting from enhanced coverage or from one round of MDA compared to three.ConclusionsThe Gambia is close to the elimination target for active trachoma. In districts prioritised for three MDA rounds, one round of MDA reduced active trachoma to low levels and Ct infection was not detectable in any community. There was no additional benefit to giving two further rounds of MDA. Programmes could save scarce resources by determining when to initiate or to discontinue MDA based on testing for Ct infection, and one round of MDA may be all that is necessary in some settings to reduce TF below the elimination threshold.

BackgroundRepeated mass azithromycin distributions are effective in controlling the ocular strains of chlamydia that cause trachoma. However, it is unclear when treatments can be discontinued. Investigators have proposed graduating communities when the prevalence of infection identified in children decreases below a threshold. While this can be tested empirically, results will not be available for years. Here we use a mathematical model to predict results with different graduation strategies in three African countries.MethodsA stochastic model of trachoma transmission was constructed, using the parameters with the maximum likelihood of obtaining results observed from studies in Tanzania (with 16% infection in children pre-treatment), The Gambia (9%), and Ethiopia (64%). The expected prevalence of infection at 3 years was obtained, given different thresholds for graduation and varying the characteristics of the diagnostic test.ResultsThe model projects that three annual treatments at 80% coverage would reduce the mean prevalence of infection to 0.03% in Tanzanian, 2.4% in Gambian, and 12.9% in the Ethiopian communities. If communities graduate when the prevalence of infection falls below 5%, then the mean prevalence at 3 years with the new strategy would be 0.3%, 3.9%, and 14.4%, respectively. Graduations reduced antibiotic usage by 63% in Tanzania, 56% in The Gambia, and 11% in Ethiopia.ConclusionModels suggest that graduating communities from a program when the infection is reduced to 5% is a reasonable strategy and could reduce the amount of antibiotic distributed in some areas by more than 2-fold.

Objective To evaluate the effect of repeated mass drug administration (MDA) of azithromycin in the Gambia on the nasopharyngeal carriage of Streptococcus pneumoniae and on the emergence of antibiotic-resistant strains. Methods This study involved villages that participated in a cluster randomized trial comparing the effect of one versus three azithromycin MDA rounds on the prevalence of trachoma. Only villages In which most children received 7-valent pneumococcal conjugate vaccine were included. Three cross-sectional surveys were performed in two villages that received three annual MDA rounds: the first immediately before the third MDA round and the second and third, 1 and 6 months, respectively, after the third MDA round. The third survey also covered six villages that had received one MDA round 30 months previously. Pneumococcal carriage was assessed using nasopharyngeal swabs and azithromycin resistance was detected using the Etest. Findings The prevalence of pneumococcal carriage decreased from 43.4% to 19.2% between the first and second surveys (P< 0.001) but rebounded by the third survey (45.8%; P=0.591). Being a carrier at the first survey was a risk factor for being a carrier at the second (odds ratio: 3.71; P< 0.001). At the third survey, the prevalence of carriage was similar after one and three MDA rounds (50.3% versus 45.8%, respectively; P=0.170), as was the prevalence of azithromycin resistance (0.3% versus 0.9%, respectively; P=0.340). Conclusion Three azithromycin MDA rounds did not increase the prevalence of nasopharyngeal carriage of azithromycin- resistant 5. pneumoniae strains compared with one round. Objectif Evaluer l'effet de l'administration de medicament massive (AMM) repetee en Gambie sur le portage du Streptococcus pneumoniae dans le nasopharynx et sur Emergence de souches resistantes aux antibiotiques. Methodes Cette etude a implique des villages qui ont participe a un essai randomise par grappes, comparant l'effet d'un cycle d'AMM d'azithromycine par rapport a 3 cycles d'AMM d'azithromycine sur la prevalence du trachome. Seuls les villages dans lesquels la plupart des enfants ont recu le vacan antipneumococdque conjugue heptavalent ont ete Indus dans l'etude. Trois etudes transversales ont ete menees dans 2 villages ayant recu 3 cycles d'AMM: la premiere etude juste avant la troisieme AMM, et les deuxieme et troisieme etudes 1 et 6 mois, respectivement, apres la troisieme AMM. La troisieme etude a egalement couvert 6 villages qui avaient recu une seule AMM 30 mois auparavant. Le portage pneumococcique a ete evalue par le biais de prelevements nasopharynges, et la resistance a l'azithromycine a ete detectee a l'alde de l'Etest. Resultats La prevalence du portage pneumococcique a diminue de 43,4% a 19,2% entre la premiere et la deuxieme etude (P < 0,001), mais elle a rebondi a la troisieme etude (45,8%; P = 0,591). Le fait d'etre porteur lors de la premiere etude etait un facteur de risque pour etre porteur lors de la deuxieme etude (rapport des cotes: 3,71; P < 0,001). Dans la troisieme etude, la prevalence du portage etait similaire apres un et 3 cycles d'AMM (50,3% contre 45,8%, respectivement; P = 0,170). II en est de merme pour la prevalence de la resistance a l'azithromycine (0,3% contre 0,9%, respectivement; P = 0,340). Conclusion Trois cycles d'AMM n'augmentent pas la prevalence du portage de souches Streptococcus pneumoniae resistantes a l'azithromycine dans le nasopharynx, par rapport a un seul cycle. Objetivo Evaluar el efecto de una administracion masiva repetida (MDA) de azitromicina en Gambia sobre el transporte nasofaringeo del Streptococcus pneumoniae y sobre la aparicion de cepas resistentes a los antibioticos. Metodos Este estudio involucro a pueblos que participaron en un ensayo aleatorio por grupos que comparo el efecto de una MDA de azitromicina de una sola ronda frente a una MDA de tres rondas sobre la prevalencia del tracoma. Solo se incluyeron aquellos pueblos en los que la mayoria de ninos habian recibido la vacuna conjugada antineumococica 7-valente. Se realizaron tres encuestas transversales en dos pueblos que recibieron tres rondas anuales de MDA: la primera inmediatamente antes de la tercera ronda de MDA y la segunda y la tercera, 1 y 6 meses, respectivamente, despues de la tercera ronda de MDA. La tercera encuesta tambien incluyo seis pueblos que habian recibido una ronda de MDA 30 meses antes. Se evaluo el transporte neumococlco por medio de frotis nasofaringeos y se detecto la resistencia a la azitromicina por medio del Etest. Resultados La prevalencia del transporte neumococico disminuyo del 43,4 % al 19,2 % entre la p'rimera y la segunda encuesta (P < 0,001), pero se recupero en el momento de la tercera encuesta (45,8 %; P = 0,591). Ser portador en la primera encuesta fue un factor de riesgo para seguir siendo portador de la segunda (cociente de posibilidades: 3,71 ;P< 0,001). En la tercera encuesta, la prevalencia del transporte fue similar tras una y tres rondas de MDA (50,3 % frente a 45,8 %, respectivamente; P = 0,170), al igual que la prevalencia de la resistencia a la azitromicina (0,3 % frente a 0,9 %, respectivamente; P = 0,340). Conclusion Las tres rondas de MDA de azitromicina no aumentaron la prevalencia del transporte nasofaringeo de cepas de S. pneumoniae resistentes a la azitromicina en comparacion con una unica ronda., Introduction Trachoma, which is due to ocular infection with the intracellular bacterium Chlamydia trachomatis, is the leading infectious cause of blindness worldwide. The discovery that ocular C. trachomatis infection can [...]

ABSTRACT Background Trachoma, caused by ocular infection with Chlamydia trachomatis, remains the leading infectious cause of blindness and in 2002 was responsible for 3.6% of total global blindness. Although transmission [...]

Conjunctival swabs are collected for quantitative polymerase-chain-reaction assay of Chlamydia trachomatis before and 2, 6, 12, 18, and 24 months after mass treatment with azithromycin in a Tanzanian community. The conclusion states that one-round of very-high-coverage mass treatment with azithromycin can interrupt the transmission of ocular Chlamydia trachomatis infection.

Background: To eliminate trachoma as a public health problem, the World Health Organization recommends the SAFE (surgery, antibiotics, facial cleanliness, and environmental improvement) strategy. As part of the SAFE strategy in the Amhara Region, Ethiopia, the Trachoma Control Program distributed >124 million doses of antibiotics between 2007 and 2015. Despite this, trachoma remained hyperendemic in many districts and a considerable level of Chlamydia trachomatis (Ct) infection was evident.Methods: We utilized residual material from Abbott m2000 Ct diagnostic tests to sequence 99 ocular Ct samples from Amhara and investigated the role of Ct genomic variation in continued transmission of Ct.Results: Sequences were typical of ocular Ct at the whole-genome level and in tissue tropism-associated genes. There was no evidence of macrolide resistance in this population. Polymorphism around the ompA gene was associated with village-level trachomatous inflammation-follicular prevalence. Greater ompA diversity at the district level was associated with increased Ct infection prevalence.Conclusions: We found no evidence for Ct genomic variation contributing to continued transmission of Ct after treatment, adding to evidence that azithromycin does not drive acquisition of macrolide resistance in Ct. Increased Ct infection in areas with more ompA variants requires longitudinal investigation to understand what impact this may have on treatment success and host immunity. [ABSTRACT FROM AUTHOR]