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

The global burden of trichiasis in 2016.

BACKGROUND: Trichiasis is present when one or more eyelashes touches the eye. Uncorrected, it can cause blindness. Accurate estimates of numbers affected, and their geographical distribution, help guide resource allocation. METHODS: We obtained district-level trichiasis prevalence estimates in adults for 44 endemic and previously-endemic countries. We used (1) the most recent data for a district, if more than one estimate was available; (2) age- and sex-standardized corrections of historic estimates, where raw data were available; (3) historic estimates adjusted using a mean adjustment factor for districts where raw data were unavailable; and (4) expert assessment of available data for districts for which no prevalence estimates were available. FINDINGS: Internally age- and sex-standardized data represented 1,355 districts and contributed 662 thousand cases (95% confidence interval [CI] 324 thousand-1.1 million) to the global total. Age- and sex-standardized district-level prevalence estimates differed from raw estimates by a mean factor of 0.45 (range 0.03-2.28). Previously non- stratified estimates for 398 districts, adjusted by ×0.45, contributed a further 411 thousand cases (95% CI 283-557 thousand). Eight countries retained previous estimates, contributing 848 thousand cases (95% CI 225 thousand-1.7 million). New expert assessments in 14 countries contributed 862 thousand cases (95% CI 228 thousand-1.7 million). The global trichiasis burden in 2016 was 2.8 million cases (95% CI 1.1-5.2 million). INTERPRETATION: The 2016 estimate is lower than previous estimates, probably due to more and better data; scale-up of trichiasis management services; and reductions in incidence due to lower active trachoma prevalence

Health Beliefs and Perceptions of Trachoma in Communities on the Bijagos Archipelago of Guinea Bissau

PURPOSE: The World Health Organization aims to eliminate blinding trachoma by 2020 using the SAFE strategy: Surgery for trichiasis, Antibiotics, Facial cleanliness and Environmental improvement. Trachoma is hyperendemic on the remote Bijagos Archipelago of Guinea-Bissau, West Africa. Sociocultural factors remain unexplored here, despite their potential impact on disease control, particularly through the "F" and "E" aspects. By examining these, we aim to illuminate this population's unreported health beliefs, hygiene behaviors and disease perceptions. This understanding will help to optimize future public health interventions, and guide the distribution of limited healthcare resources. METHODS: Two unmatched interview series were conducted 1 year apart on Bubaque Island in the Bijagos Archipelago; one in rural villages using purposive snowball sampling, the other in a semi-urban settlement, using random-cluster sampling. Interviews were conducted and recorded in Kriolu, the local dialect, by a supervised local field assistant before translation into English for conventional content analysis. RESULTS: Trachoma was unheard of in either series, despite ongoing local trachoma research. A heterogeneous range of disease etiology and preventative measures were suggested, but the importance of hygiene was more widely reported by semi-urban interviewees. Although western medicine was well regarded, traditional practices continued, particularly in the rural populations. CONCLUSIONS: Differences in knowledge, beliefs and behaviors were apparent between the two series. Despite widespread rudimentary knowledge of disease prevention, targeted education might benefit both communities, particularly basic hygiene education for rural communities. Healthcare access should also be improved for rural populations. The impact of these measures could be assessed by future fieldwork

Can corneal pannus with trachomatous inflammation – follicular be used in combination as an improved specific clinical sign for current ocular Chlamydia trachomatis infection?

BACKGROUND: Trachoma is a blinding disease caused by conjunctival infection with Chlamydia trachomatis (Ct). Mass drug administration (MDA) for trachoma control is administered based on the population prevalence of the clinical sign of trachomatis inflammation - follicular (TF). However, the prevalence of TF is often much higher than the prevalence of Ct infection. The addition of a clinical sign specific for current ocular Ct infection to TF could save resources by preventing unnecessary additional rounds of MDA. METHODS: Study participants were aged between 1-9 years and resided on 7 islands of the Bijagos Archipelago, Guinea Bissau. Clinical grades for trachoma and corneal pannus and ocular swab samples were taken from 80 children with TF and from 81 matched controls without clinical evidence of trachoma. Ct infection testing was performed using droplet digital PCR. RESULTS: New pannus was significantly associated with Ct infection after adjustment for TF (P = 0.009, OR = 3.65 (1.4-9.8)). Amongst individuals with TF, individuals with new pannus had significantly more Ct infection than individuals with none or old pannus (75.0% vs 45.5%, Chi(2) P = 0.01). TF and new pannus together provide a highly specific (91.7%), but a poorly sensitive (51.9%) clinical diagnostic test for Ct infection. CONCLUSIONS: As we move towards trachoma elimination it may be desirable to use a combined clinical sign (new pannus in addition to TF) that is highly specific for current ocular Ct infection. This would allow national health systems to obtain a more accurate estimate of Ct population prevalence to inform further need for MDA without the expense of Ct molecular diagnostics, which are currently unaffordable in programmatic contexts

Plasmid copy number and disease severity in naturally occurring ocular Chlamydia trachomatis infection.

The Chlamydia trachomatis plasmid is a virulence factor. Plasmid copy number, C. trachomatis load and disease severity were assessed in a treatment-naive population where trachoma is hyperendemic. By using droplet digital PCR, plasmid copy number was found to be stable (median, 5.34 [range, 1 to 18]) and there were no associations with C. trachomatis load or disease severity

Multilevel multivariable random effects logistic regression analysis of factors associated with ocular <i>C. trachomatis</i> infection.

a<p>Adjusted Odds Ratio (aOR) using two-level multivariable mixed effects logistic regression modelling; CI = confidence interval.</p>b<p>p-value for Wald test (Wald's Chi²); significant associations (where <i>p≤0.05</i>) are highlighted in bold.</p>c<p>researcher observed.</p

Multilevel univariable random effects logistic regression analysis of factors associated with active trachoma^a.

a<p>Active trachoma defined as TF (inflammatory trachoma-follicular) and/or TI (inflammatory trachoma-intense) using the WHO simplified scoring system <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002900#pntd.0002900-Thylefors1" target="_blank">[23]</a>.</p>b<p>Unadjusted (crude) Odds Ratio (cOR) from two-level univariable mixed effects logistic regression analyses; CI = confidence interval.</p>c<p>p-value for Wald test (Wald's Chi²); significant associations (where <i>p≤0.05</i>) are highlighted in bold.</p>d<p>Continuous numeric variables.</p>e<p>reported by household head.</p>f<p>a ‘vasilha’ is a vessel of capacity ∼30 litres.</p>g<p>researcher observed.</p>h<p>researcher observed within 15 m of the household.</p

The relationship between trachoma and presence of infection with <i>C. trachomatis</i> (<i>Ct</i>).

a<p>N = total number and % = proportion.</p>b<p>Using the WHO Simplified Grading System where TF = trachomatous inflammation-follicular, TI = trachomatous inflammation-intense, TS = trachomatous scarring <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002900#pntd.0002900-Thylefors1" target="_blank">[23]</a>. Individuals may appear in more than one clinical category.</p>c<p><i>Ct</i> DNA detected (<i>Ct</i>+) or absent (<i>Ct</i>−) by Amplicor PCR.</p

Multilevel univariable random effects logistic regression analysis of factors associated with ocular <i>C. trachomatis</i> infection.

a<p>Unadjusted (crude) Odds Ratio (cOR) using two-level univariable mixed effects logistic regression; CI = confidence interval.</p>b<p>p-value for Wald test (Wald's Chi²); significant associations (where <i>p≤0.05</i>) are highlighted in bold.</p>c<p>Continuous numeric variables.</p>d<p>reported by household head.</p>e<p>a ‘vasilha’ is a vessel of capacity ∼30 litres.</p>f<p>researcher observed.</p>g<p>researcher observed within 15 m of the household.</p