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1.
Cornea ; 41(5): 609-615, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34176916

RESUMO

PURPOSE: To report clinical presentation, in vivo confocal microscopic features, and corneal phenotype in patients with trachomatous keratopathy (TK) and secondary amyloidosis. METHODS: Histopathological records of all patients undergoing keratoplasty at the Dr. Rajendra Prasad Centre for Ophthalmic Sciences over a 3-year period were scanned retrospectively for a diagnosis of TK and amyloidosis. Demographic profile and details of preoperative comprehensive ophthalmic assessment were extracted. The histopathology was freshly reviewed. RESULTS: Fifteen patients (29 eyes) with TK and atypical corneal involvement due to amyloid deposition were identified. Herbert's pits and upper palpebral conjunctival scarring were present in all cases. Central or total diffuse corneal scarring was present involving the anterior stroma in 5 (31%) and the full thickness of the cornea in 11 (69%) of the eyes. Eight (73%) of 11 patients with deep stromal amyloid deposits revealed bilateral, discrete, blue-white opacities at the level of deep stroma and Descemet membrane (DM). Endothelial cells were atrophic and flattened with gutta formation. Confoscans revealed hyperreflective, needle-shaped crystalline deposits of extracellular amyloid at various depths of the corneal stroma up to DM. All host corneal buttons demonstrated Congo red-positive amyloid deposits on histopathological examination. CONCLUSIONS: We describe a distinct form of TK unlike the usual presentation of dense, leucomatous, vascularized corneal scarring in trachoma. We believe that amyloid deposits in DM and the corneal endothelium have not previously been reported in patients with trachoma.


Assuntos
Amiloidose , Tracoma , Amiloidose/complicações , Amiloidose/diagnóstico , Córnea/patologia , Células Endoteliais/patologia , Humanos , Fenótipo , Estudos Retrospectivos , Tracoma/complicações , Tracoma/diagnóstico , Tracoma/patologia
2.
PLoS One ; 15(5): e0229297, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32427995

RESUMO

OBJECTIVES: The objectives of the study were to estimate the prevalence of different clinical signs of trachoma and identify possible factors associated with TF. METHODOLOGY: Following the approval of the study protocol by the ethics committee, a cross-sectional study was conducted in Vaupés, a department of the Colombian Amazon, between the years 2012 and 2013 in two districts. Based on the records obtained from a standardized format for the clinical evaluation of the participants and the factors associated with follicular trachoma, an excel database was built and debugged, which was analyzed using IBM SPSS, Statistics Version 23 and Stata STATA (Version 14, 2015, StataCorp LLC, Texas, USA). RESULTS: The records of 13,091 individuals was collected from 216 rural indigenous communities, of which 12,080 were examined (92.3%); 7,274 in the Western and 4,806 in the Eastern districts. A prevalence of trachomatous inflammation-follicular (TF) of 21.7% (n = 599; 95% CI 20.2-23.3) in the Western and 24.9% (n = 483; 95% CI 23.1-26.9) in the Eastern district was found in children aged 1 to 9 years. Regarding trachomatous trichiasis (TT), 77 cases were found, of which 14 belonged to the Western district (prevalence 0.3%, CI 95% 0.2-0.5) and 63 to the Eastern district (1.8%, CI 95% 1.4-2.4). Children aged between 1 to 9 years were significantly more likely to have TF when there was the presence of secretions on the face (OR: 3.2; 95% CI: 2.6-3.9). CONCLUSIONS: Trachoma is a public health problem in Vaupés that requires the implementation of the SAFE strategy (S = Surgery, A = Antibiotics, F = Face Washing, E = Environment) in the Eastern and Western districts, for at least 3 consecutive years, in accordance with WHO recommendations.


Assuntos
Inquéritos Epidemiológicos , Grupos Populacionais , Saúde Pública , Tracoma/epidemiologia , Censos , Criança , Pré-Escolar , Chlamydia trachomatis/patogenicidade , Colômbia/epidemiologia , Feminino , Humanos , Lactente , Masculino , Fatores de Risco , População Rural , Tracoma/microbiologia , Tracoma/patologia
3.
Infect Immun ; 88(4)2020 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-31964744

RESUMO

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.


Assuntos
Cicatriz/patologia , Cicatriz/fisiopatologia , Túnica Conjuntiva/patologia , Imunidade Inata , Fatores Imunológicos/biossíntese , Tracoma/patologia , Tracoma/fisiopatologia , Criança , Chlamydia trachomatis/crescimento & desenvolvimento , Feminino , Perfilação da Expressão Gênica , Humanos , Fatores Imunológicos/genética , Estudos Longitudinais , Masculino , Tanzânia
4.
Ophthalmic Epidemiol ; 27(2): 155-164, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31916887

RESUMO

Purpose: Previous phases of trachoma mapping in Pakistan completed baseline surveys in 38 districts. To help guide national trachoma elimination planning, we set out to estimate trachoma prevalence in 43 suspected-endemic evaluation units (EUs) of 15 further districts.Methods: We planned a population-based trachoma prevalence survey in each EU. Two-stage cluster sampling was employed, using the systems and approaches of the Global Trachoma Mapping Project. In each EU, residents aged ≥1 year living in 30 households in each of 26 villages were invited to be examined by trained, certified trachoma graders. Questionnaires and direct observation were used to evaluate household-level access to water and sanitation.Results: One EU was not completed due to insecurity. Of the remaining 42, three EUs had trichiasis prevalence estimates in ≥15-year-olds ≥0.2%, and six (different) EUs had prevalence estimates of trachomatous inflammation-follicular (TF) in 1-9-year-olds ≥5%; each EU requires trichiasis and TF prevalence estimates below these thresholds to achieve elimination of trachoma as a public health problem. All six EUs with TF prevalences ≥5% were in Khyber Pakhtunkhwa Province. Household-level access to improved sanitation ranged by EU from 6% to 100%. Household-level access to an improved source of water for face and hand washing ranged by EU from 37% to 100%.Conclusion: Trachoma was a public health problem in 21% (9/42) of the EUs. Because the current outbreak of extremely drug-resistant typhoid in Pakistan limits domestic use of azithromycin mass drug administration, other interventions against active trachoma should be considered here.


Assuntos
Antibacterianos/provisão & distribuição , Tracoma/epidemiologia , Tracoma/prevenção & controle , Triquíase/epidemiologia , Adolescente , Cegueira/epidemiologia , Cegueira/etiologia , Criança , Pré-Escolar , Farmacorresistência Bacteriana , Feminino , Inquéritos Epidemiológicos , Humanos , Lactente , Inflamação/patologia , Masculino , Paquistão/epidemiologia , Prevalência , Saúde Pública/estatística & dados numéricos , Saneamento/estatística & dados numéricos , Tracoma/complicações , Tracoma/patologia , Febre Tifoide/tratamento farmacológico , Febre Tifoide/epidemiologia , Abastecimento de Água/estatística & dados numéricos
6.
Am J Trop Med Hyg ; 99(4): 858-863, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30039782

RESUMO

In collaboration with the health ministries that we serve and other partners, we set out to complete the multiple-country Global Trachoma Mapping Project. To maximize the accuracy and reliability of its outputs, we needed in-built, practical mechanisms for quality assurance and quality control. This article describes how those mechanisms were created and deployed. Using expert opinion, computer simulation, working groups, field trials, progressively accumulated in-project experience, and external evaluations, we developed 1) criteria for where and where not to undertake population-based prevalence surveys for trachoma; 2) three iterations of a standardized training and certification system for field teams; 3) a customized Android phone-based data collection app; 4) comprehensive support systems; and 5) a secure end-to-end pipeline for data upload, storage, cleaning by objective data managers, analysis, health ministry review and approval, and online display. We are now supporting peer-reviewed publication. Our experience shows that it is possible to quality control and quality assure prevalence surveys in such a way as to maximize comparability of prevalence estimates between countries and permit high-speed, high-fidelity data processing and storage, while protecting the interests of health ministries.


Assuntos
Coleta de Dados/métodos , Saúde Global/estatística & dados numéricos , Inquéritos Epidemiológicos/normas , Doenças Negligenciadas/epidemiologia , Tracoma/epidemiologia , Chlamydia trachomatis/patogenicidade , Humanos , Armazenamento e Recuperação da Informação , Cooperação Internacional , Doenças Negligenciadas/microbiologia , Doenças Negligenciadas/patologia , Prevalência , Controle de Qualidade , Tracoma/microbiologia , Tracoma/patologia
7.
Am J Trop Med Hyg ; 99(1): 150-154, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29848403

RESUMO

Trachoma surveillance is typically performed via random sampling of endemic districts. This strategy minimizes bias and allows examination of preschool children, but is also expensive. Surveillance for some other neglected tropical diseases is carried out in schools, which is logistically easier. In the present study, the prevalence of trachomatous inflammation-follicular (TF) from a population-based sample of children from each of 70 communities in Ethiopia was compared with the corresponding school-based estimate, which was calculated for each community by performing examinations in all primary schools in the district. The overall prevalence of TF was 39.1% (95% confidence interval [CI]: 35.0-43.1%) among children aged 1-9 years in the community-based sample and 18.8% (95% CI: 15.9-21.7%) among children in grades 1-3 of the school-based sample. School-based estimates of TF explained 35% of the variation in the community-based prevalences (P < 0.001). When TF prevalence was used as a diagnostic test for detecting a community with > 5% prevalence of ocular chlamydia, the area under the receiver operating characteristic curve was 0.73 (95% CI: 0.60-0.85) for the school-based sample and 0.71 (0.58-0.83) for the community-based sample (P = 0.76). Thus, although school-based monitoring was necessarily biased relative to population-based monitoring of 1- to 9-year olds, the two methods provided a similar amount of information about the community burden of ocular chlamydia in this trachoma-hyperendemic setting. The generalizability of these findings to areas with less prevalent trachoma is unclear.


Assuntos
Chlamydia trachomatis/patogenicidade , Doenças Endêmicas , Monitoramento Epidemiológico , Estudantes , Tracoma/diagnóstico , Criança , Pré-Escolar , Chlamydia trachomatis/isolamento & purificação , Estudos Transversais , Etiópia/epidemiologia , Feminino , Humanos , Lactente , Masculino , Prevalência , Instituições Acadêmicas , Tracoma/patologia
8.
Cornea ; 37(4): 416-420, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29504955

RESUMO

PURPOSE: To study the effect of trachoma on meibomian glands using infrared meibography and to correlate the results with tear film parameters. METHODS: This is a prospective cohort study in which 86 eyes of healthy volunteers and 90 eyes with trachoma were included. Clinical assessment was performed including the following: slit-lamp examination looking for signs of sequelae of trachoma, tear breakup time (TBUT), superficial punctate keratopathy (SPK), Schirmer II test (with anesthesia), and meibum score. Noncontact meibography was performed on both upper and lower eyelids separately using the meibograde system, which involved distortion of the meibomian gland, shortening, and dropout. RESULTS: Lid margin abnormalities (telangiectasia, lid margin swelling, and hyperemia) were all significantly higher in the trachoma group. The mean SPK (1.36), meibum score (1.76), meibography dropout, distortion, shortening, and total meibography (8.19 for upper eyelids and 3.81 for lower eyelids) were all significantly higher in the trachoma group (P < 0.001) compared with the normal group were SPK (0.88), meibum score (0.16), and total meibography (1.24 for upper eyelids and 0.92 for lower eyelids). Mean TBUT (4.2 s) was significantly shorter in the trachoma group than in the normal group (10.3 s) (P < 0.001). There was no significant difference between both groups in the Schirmer II test. CONCLUSIONS: Meibography of patients with sequelae of trachoma was in agreement with the histopathologic studies. Upper eyelids were much more affected than the lower eyelids. TBUT, SPK, and meibum score were correlated with the status of meibomian glands and meibography, which were significantly different in the trachoma group.


Assuntos
Doenças Palpebrais/diagnóstico por imagem , Pálpebras/patologia , Glândulas Tarsais/diagnóstico por imagem , Tracoma/diagnóstico por imagem , Idoso , Doenças Palpebrais/patologia , Feminino , Seguimentos , Voluntários Saudáveis , Humanos , Masculino , Glândulas Tarsais/patologia , Pessoa de Meia-Idade , Estudos Prospectivos , Lâmpada de Fenda , Lágrimas/metabolismo , Tracoma/patologia
9.
Genome Med ; 10(1): 15, 2018 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-29482619

RESUMO

BACKGROUND: Chlamydia trachomatis (Ct) is the most common infectious cause of blindness and bacterial sexually transmitted infection worldwide. Ct strain-specific differences in clinical trachoma suggest that genetic polymorphisms in Ct may contribute to the observed variability in severity of clinical disease. METHODS: Using Ct whole genome sequences obtained directly from conjunctival swabs, we studied Ct genomic diversity and associations between Ct genetic polymorphisms with ocular localization and disease severity in a treatment-naïve trachoma-endemic population in Guinea-Bissau, West Africa. RESULTS: All Ct sequences fall within the T2 ocular clade phylogenetically. This is consistent with the presence of the characteristic deletion in trpA resulting in a truncated non-functional protein and the ocular tyrosine repeat regions present in tarP associated with ocular tissue localization. We have identified 21 Ct non-synonymous single nucleotide polymorphisms (SNPs) associated with ocular localization, including SNPs within pmpD (odds ratio, OR = 4.07, p* = 0.001) and tarP (OR = 0.34, p* = 0.009). Eight synonymous SNPs associated with disease severity were found in yjfH (rlmB) (OR = 0.13, p* = 0.037), CTA0273 (OR = 0.12, p* = 0.027), trmD (OR = 0.12, p* = 0.032), CTA0744 (OR = 0.12, p* = 0.041), glgA (OR = 0.10, p* = 0.026), alaS (OR = 0.10, p* = 0.032), pmpE (OR = 0.08, p* = 0.001) and the intergenic region CTA0744-CTA0745 (OR = 0.13, p* = 0.043). CONCLUSIONS: This study demonstrates the extent of genomic diversity within a naturally circulating population of ocular Ct and is the first to describe novel genomic associations with disease severity. These findings direct investigation of host-pathogen interactions that may be important in ocular Ct pathogenesis and disease transmission.


Assuntos
Chlamydia trachomatis/genética , Genoma Bacteriano , Índice de Gravidade de Doença , Tracoma/microbiologia , Túnica Conjuntiva/patologia , Doenças Endêmicas , Marcadores Genéticos , Guiné-Bissau , Humanos , Funções Verossimilhança , Fenótipo , Filogenia , Polimorfismo de Nucleotídeo Único/genética , Tracoma/patologia , Sequenciamento Completo do Genoma
10.
PLoS Negl Trop Dis ; 12(2): e0006289, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29432434

RESUMO

BACKGROUND: In 2009, three years after stopping mass treatment with azithromycin, a trachoma impact survey in four health districts in the Kayes region of Mali found a prevalence of trachomatous inflammation-follicular (TF) among children aged 1 to 9 years of >5% and a trachomatous trichiasis (TT) prevalence within the general population (≥1-year-old) of <1%. As a result, the government's national trachoma program expanded trichiasis surgery and related activities required to achieve trachoma elimination. METHODOLOGY/PRINCIPAL FINDINGS: In 2015, to assess progress towards elimination, a follow-up impact survey was conducted in the Kayes, Kéniéba, Nioro and Yélimané health districts. The survey used district level two-stage cluster random sampling methodology with 20 clusters of 30 households in each evaluation unit. Subjects were eligible for examination if they were ≥1 year. TF and TT cases were identified and confirmed by experienced ophthalmologists. In total 14,159 people were enumerated and 11,620 (82%) were examined. TF prevalence (95% confidence interval (CI)) was 0.5% (0.3-1%) in Kayes, 0.8% (0.4-1.7%) in Kéniéba, 0.2% (0-0.9%) in Nioro and 0.3% (0.1-1%) in Yélimané. TT prevalence (95% CI) was 0.04% (0-0.25%) in Kayes, 0.29% (0.11-0.6%) in Kéniéba, 0.04% (0-0.25%) in Nioro and 0.07% (0-0.27%) in Yélimané. CONCLUSIONS/SIGNIFICANCE: Eight years after stopping MDA and intensifying trichiasis surgery outreach campaigns, all four districts reached the TF elimination threshold of <5% and three of four districts reached the TT elimination threshold of <0.1%.


Assuntos
Controle de Doenças Transmissíveis/métodos , Educação em Saúde/métodos , Administração Massiva de Medicamentos/métodos , Tracoma/epidemiologia , Tracoma/prevenção & controle , Adolescente , Brasil/epidemiologia , Criança , Técnicas de Laboratório Clínico , Feminino , Imunofluorescência , Humanos , Masculino , Prevalência , Instituições Acadêmicas , Estudantes , Tracoma/diagnóstico , Tracoma/patologia
11.
J Med Biogr ; 26(1): 59-67, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27316693

RESUMO

Arthur Ferguson MacCallan was an ophthalmic surgeon who undertook his pioneering work in Egypt between 1903 and 1923. He established the Egyptian ophthalmic infrastructure which, on his departure, consisted of 23 operational hospital units, treating 134,000 new patients, having trained some 100 ophthalmic surgeons. He also established the Memorial Ophthalmic Laboratory at Giza which is still operational today. MacCallan became a world authority on trachoma. He pioneered the 'MacCallan Classification' which was the first grading system to standardise the stages of trachoma. He used this grading internally from 1905, continuing his research into trachoma over the ensuing years. In 1952, the WHO adopted the 'MacCallan Classification' as its standard. There has recently been a revival of interest in MacCallan's work. First, the International Coalition for Trachoma Control (ICTC) inaugurated the 'ICTC MacCallan Medal' in 2014 as a contribution towards achieving the WHO's target date for the Global Elimination of Blinding Trachoma ('GET 2020'). Second, MacCallan's work with the military hospitals has been recognised by Moorfields Eye Hospital on their World War I Commemorative History Board. Thus, MacCallan's pioneering spirit, his humanitarian campaign for the relief of suffering and his accomplishments of over a century ago continue to resonate with the profession today.


Assuntos
Oftalmologia/história , Tracoma/história , Egito , História do Século XX , Tracoma/diagnóstico , Tracoma/patologia
12.
Parasit Vectors ; 10(1): 624, 2017 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-29282126

RESUMO

BACKGROUND: Trachoma, a neglected tropical disease, is caused by ocular infection with Chlamydia trachomatis (Ct). The World Health Organization (WHO) recommends three annual rounds of community mass drug treatment with azithromycin (MDA) if the prevalence of follicular trachoma in 1-9 year olds (TF1-9) exceeds 10% at district level to achieve an elimination target of district-level TF1-9 below 5% after. To evaluate this strategy in treatment-naïve trachoma-endemic island communities in Guinea Bissau, we conducted a cross-sectional population-based trachoma survey on four islands. The upper tarsal conjunctivae of each participant were clinically assessed for trachoma and conjunctival swabs were obtained (n = 1507). We used a droplet digital PCR assay to detect Ct infection and estimate bacterial load. We visited the same households during a second cross-sectional survey and repeated the ocular examination and obtained conjunctival swabs from these households one year after MDA (n = 1029). RESULTS: Pre-MDA TF1-9 was 22.0% (136/618). Overall Ct infection prevalence (CtI) was 18.6% (25.4% in 1-9 year olds). Post-MDA (estimated coverage 70%), TF1-9 and CtI were significantly reduced (7.4% (29/394, P < 0.001) and 3.3% (34/1029, P < 0.001) (6.6% in 1-9 year olds, P < 0.001), respectively. Median ocular Ct load was reduced from 2038 to 384 copies/swab (P < 0.001). Following MDA cases of Ct infection were highly clustered (Moran's I 0.27, P < 0.001), with fewer clusters of Ct infection overall, fewer clusters of cases with high load infections and less severe disease. CONCLUSIONS: Despite a significant reduction in the number of clusters of Ct infection, mean Ct load, disease severity and presence of clusters of cases of high load Ct infection suggesting the beginning of trachoma control in isolated island communities, following a single round of MDA we demonstrate that transmission is still ongoing. These detailed data are useful in understanding the epidemiology of ocular Ct infection in the context of MDA and the tools employed may have utility in determining trachoma elimination and surveillance activities in similar settings.


Assuntos
Antibacterianos/administração & dosagem , Azitromicina/administração & dosagem , Carga Bacteriana , Chlamydia trachomatis/efeitos dos fármacos , Administração Massiva de Medicamentos , Tracoma/tratamento farmacológico , Tracoma/patologia , Túnica Conjuntiva/microbiologia , Estudos Transversais , Guiné-Bissau , Reação em Cadeia da Polimerase , Índice de Gravidade de Doença , Tracoma/microbiologia , Resultado do Tratamento
13.
Pathog Dis ; 75(5)2017 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-28472466

RESUMO

Chlamydia trachomatis (Ct) is the most common cause of bacterial sexually transmitted infection and infectious cause of blindness (trachoma) worldwide. Understanding the spatial distribution of Ct infection may enable us to identify populations at risk and improve our understanding of Ct transmission. In this study, we sought to investigate the spatial distribution of Ct infection and the clinical features associated with high Ct load in trachoma-endemic communities on the Bijagós Archipelago (Guinea Bissau). We collected 1507 conjunctival samples and corresponding detailed clinical data during a cross-sectional population-based geospatially representative trachoma survey. We used droplet digital PCR to estimate Ct load on conjunctival swabs. Geostatistical tools were used to investigate clustering of ocular Ct infections. Spatial clusters (independent of age and gender) of individuals with high Ct loads were identified using local indicators of spatial association. We did not detect clustering of individuals with low load infections. These data suggest that infections with high bacterial load may be important in Ct transmission. These geospatial tools may be useful in the study of ocular Ct transmission dynamics and as part of trachoma surveillance post-treatment, to identify clusters of infection and thresholds of Ct load that may be important foci of re-emergent infection in communities.


Assuntos
Carga Bacteriana , Chlamydia trachomatis/isolamento & purificação , Análise por Conglomerados , Topografia Médica , Tracoma/epidemiologia , Tracoma/patologia , Túnica Conjuntiva/microbiologia , Estudos Transversais , Guiné-Bissau/epidemiologia , Reação em Cadeia da Polimerase , Análise Espacial , Tracoma/microbiologia
15.
Hum Genet ; 135(8): 939-51, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27312142

RESUMO

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.


Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Subfamília C de Receptores Semelhantes a Lectina de Células NK/genética , Tracoma/genética , Adolescente , Adulto , África Ocidental , Idoso , Idoso de 80 Anos ou mais , Alelos , Criança , Pré-Escolar , Feminino , Genótipo , Homozigoto , Humanos , Lactente , Recém-Nascido , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Deleção de Sequência/genética , Tracoma/epidemiologia , Tracoma/patologia
16.
Sci Rep ; 6: 28261, 2016 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-27321784

RESUMO

Trachoma is a conjunctiva scarring disease, which is the leading infectious cause of blindness worldwide. Yet, the molecular mechanisms underlying progressive fibrosis in trachoma are unknown. To investigate the contribution of local resident fibroblasts to disease progression, we isolated conjunctival fibroblasts from patients with scarring trachoma and matching control individuals, and compared their gene expression profiles and functional properties in vitro. We show that scarring trachoma fibroblasts substantially differ from control counterparts, displaying pro-fibrotic and pro-inflammatory features matched by an altered gene expression profile. This pro-inflammatory signature was exemplified by increased IL-6 expression and secretion, and a stronger response to macrophage-mediated stimulation of contraction. We further demonstrate that scarring trachoma fibroblasts can promote Akt phosphorylation in macrophages in an IL-6 -dependent manner. Overall this work has uncovered a distinctive molecular fingerprint for scarring trachoma fibroblasts, and identified IL-6- as a potential contributor to the chronic conjunctival fibrosis, mediating reciprocal pro-fibrotic/pro-inflammatory interactions between macrophages and fibroblasts.


Assuntos
Cicatriz/metabolismo , Fibroblastos/metabolismo , Interleucina-6/metabolismo , Macrófagos/metabolismo , Transdução de Sinais , Tracoma/metabolismo , Cicatriz/patologia , Túnica Conjuntiva/metabolismo , Túnica Conjuntiva/patologia , Feminino , Fibroblastos/patologia , Fibrose , Humanos , Macrófagos/patologia , Masculino , Tracoma/patologia , Células U937
17.
PLoS One ; 10(12): e0144380, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26656797

RESUMO

Trachoma, caused by the intracellular bacterium Chlamydia trachomatis (Ct), remains the world's leading preventable infectious cause of blindness. Recent attempts to develop effective vaccines rely on modified chlamydial antigen delivery platforms. As the mechanisms engaged in the pathology of the disease are not fully understood, designing a subunit vaccine specific to chlamydial antigens could improve safety for human use. We propose the delivery of chlamydia-specific antigens to the ocular mucosa using particulate carriers, bacterial ghosts (BGs). We therefore characterized humoral and cellular immune responses after conjunctival and subcutaneous immunization with a N-terminal portion (amino acid 1-893) of the chlamydial polymorphic membrane protein C (PmpC) of Ct serovar B, expressed in probiotic Escherichia coli Nissle 1917 bacterial ghosts (EcN BGs) in BALB/c mice. Three immunizations were performed at two-week intervals, and the immune responses were evaluated two weeks after the final immunization in mice. In a guinea pig model of ocular infection animals were immunized in the same manner as the mice, and protection against challenge was assessed two weeks after the last immunization. N-PmpC was successfully expressed within BGs and delivery to the ocular mucosa was well tolerated without signs of inflammation. N-PmpC-specific mucosal IgA levels in tears yielded significantly increased levels in the group immunized via the conjunctiva compared with the subcutaneously immunized mice. Immunization with N-PmpC EcN BGs via both immunization routes prompted the establishment of an N-PmpC-specific IFNγ immune response. Immunization via the conjunctiva resulted in a decrease in intensity of the transitional inflammatory reaction in conjunctiva of challenged guinea pigs compared with subcutaneously and non-immunized animals. The delivery of the chlamydial subunit vaccine to the ocular mucosa using a particulate carrier, such as BGs, induced both humoral and cellular immune responses. Further investigations are needed to improve the immunization scheme and dosage.


Assuntos
Adesinas Bacterianas/imunologia , Chlamydia trachomatis/imunologia , Portadores de Fármacos/química , Olho/imunologia , Mucosa/imunologia , Material Particulado/química , Vacinas de Subunidades/imunologia , Animais , Western Blotting , Proliferação de Células , Túnica Conjuntiva/imunologia , Modelos Animais de Doenças , Epitopos , Escherichia coli/metabolismo , Olho/microbiologia , Olho/patologia , Feminino , Cobaias , Imunização , Imunoglobulina A/metabolismo , Imunoglobulina G/sangue , Injeções Subcutâneas , Interferon gama/metabolismo , Interleucina-4/metabolismo , Camundongos Endogâmicos BALB C , Mucosa/microbiologia , Mucosa/patologia , Proteínas Recombinantes/metabolismo , Baço/patologia , Lágrimas/metabolismo , Tracoma/imunologia , Tracoma/microbiologia , Tracoma/patologia , Tracoma/prevenção & controle
19.
Sci Rep ; 5: 18532, 2015 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-26687891

RESUMO

Ocular infection with Chlamydia trachomatis can lead to trachoma, a leading infectious cause of blindness. Trachoma is targeted for elimination by 2020. Clinical grading for ocular disease is currently used for evaluating trachoma elimination programs, but serological surveillance can be a sensitive measure of disease transmission and provide a more objective testing strategy than clinical grading. We calculated the basic reproduction number from serological data in settings with high, medium, and low disease transmission based on clinical disease. The data showed a striking relationship between age seroprevalence and clinical data, demonstrating the proof-of-principle that age seroprevalence predicts transmission rates and therefore could be used as an indicator of decreased transmission of ocular trachoma.


Assuntos
Cegueira/patologia , Chlamydia trachomatis/patogenicidade , Testes Sorológicos , Tracoma/patologia , Antígenos de Bactérias/sangue , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/sangue , Proteínas de Bactérias/imunologia , Cegueira/sangue , Cegueira/epidemiologia , Cegueira/microbiologia , Criança , Pré-Escolar , Chlamydia trachomatis/isolamento & purificação , Olho/microbiologia , Olho/patologia , Feminino , Humanos , Lactente , Masculino , Estudos Soroepidemiológicos , Tracoma/sangue , Tracoma/epidemiologia , Tracoma/microbiologia
20.
Arch. Soc. Esp. Oftalmol ; 90(11): 539-541, nov. 2015. ilus
Artigo em Espanhol | IBECS | ID: ibc-145386

RESUMO

CASO CLÍNICO: Mujer de 84 años con defecto epitelial persistente e infiltrado estromal denso tras trasplante corneal. El análisis microbiológico reveló una Stenotrophomonas maltophilia (S. maltophilia), resistente a todos los antibióticos salvo a trimetoprima-sulfametoxazol (TMP/SMX) Se consiguió su resolución tras 3 semanas de tratamiento con TMP/SMX tópico y oral. DISCUSIÓN: S. maltophilia es un microorganismo oportunista raramente descrito en oftalmología. Se asocia con conjuntivitis, queratitis, escleritis, dacriocistitis, celulitis y endoftalmitis, con importante morbilidad. El tratamiento es complicado por sus múltiples resistencias a antibióticos de amplio espectro. El TMP/SMX en monoterapia puede considerarse como una opción de tratamiento para estas queratitis


CASE REPORT: An 84 year-old woman with persistent epithelial defect and a dense stromal infiltrate post-corneal transplantation. According to the microbiological results, it was due to a Stenotrophomonas maltophilia (S. maltophilia) resistant to all antibiotics except trimethoprim-sulfamethoxazole (TMP/SMX). Healing was achieved after three weeks of treatment with oral and topical TMP/SMX. DISCUSSION: S. maltophilia is an opportunistic microorganism rarely described in ophthalmology. It is associated with conjunctivitis, keratitis, scleritis, dacryrocystitis, cellulitis, and endophthalmitis with significant morbidity. Treatment is complicated because of its resistances to broad-spectrum antibiotics. TMP/SMX monotherapy can be considered an option of treatment for this type of keratitis


Assuntos
Idoso de 80 Anos ou mais , Feminino , Humanos , Ceratite/metabolismo , Ceratite/patologia , Antibacterianos/administração & dosagem , Antibacterianos , Células Epiteliais/citologia , Tracoma/patologia , Esclerite/patologia , Endoftalmite/metabolismo , Terapêutica/métodos , Ceratite/complicações , Ceratite/diagnóstico , Antibacterianos/provisão & distribuição , Antibacterianos/normas , Células Epiteliais/classificação , Tracoma/metabolismo , Esclerite/complicações , Endoftalmite/complicações , Terapêutica
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