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The incidence of HIV infection among female sex workers and their clients in the Middle East and north Africa is not well known. We aimed to assess HIV incidence, the contribution of heterosexual sex work networks to these numbers, and the effect of interventions by use of mathematical modelling.

In April, 2019, an HIV outbreak predominantly affecting children occurred in Larkana District, Sindh, Pakistan. By December, 2019, 881 (4·0%) of 21 962 children screened for HIV had tested positive. We aimed to assess factors associated with HIV infection in this outbreak.

Index-linked HIV testing, whereby children of individuals with HIV are targeted for testing, increases HIV yield but relies on uptake. Community-based testing might address barriers to testing access. In the Bridging the Gap in HIV testing and care for children in Zimbabwe (B-GAP) study, we investigated the uptake and yield of index-linked testing in children and the uptake of community-based vsfacility-based HIV testing in Zimbabwe.

Mental health problems are a leading cause of disability in adolescents worldwide. Problem solving is a well-tested mental health intervention in many populations. We aimed to investigate the effectiveness of a brief, transdiagnostic problem-solving intervention for common adolescent mental health problems when delivered by non-specialist school counsellors in New Delhi, India.

Germline variants in the melanocortin 1 receptor gene (MC1R)might increase the risk of childhood and adolescent melanoma, but a clear conclusion is challenging because of the low number of studies and cases. We assessed the association of MC1Rvariants with childhood and adolescent melanoma in a large study comparing the prevalence of MC1Rvariants in child or adolescent patients with melanoma to that in adult patients with melanoma and in healthy adult controls.

School environments affect health and academic outcomes. With increasing secondary school retention in low-income and middle-income countries, promoting quality school social environments could offer a scalable opportunity to improve adolescent health and wellbeing.

HIV testing is the important entry point for HIV care and prevention service, but uptake of HIV testing and thus coverage of antiretroviral therapy are much lower in older children and adolescents than in adults. We investigated the effect of economic incentives provided to caregivers of children aged 8–17 years on uptake of HIV testing and counselling in Harare, Zimbabwe.

The interactions between antiretroviral therapy (ART) and high-risk human papillomavirus (HPV) and cervical lesions in women living with HIV are poorly understood. We reviewed the association of ART with these outcomes.

Children and adolescents have poorer HIV treatment outcomes than adults. We aimed to assess the effect of community-based support for caregivers of HIV-infected children and adolescents, who are key mediators to children engaging with care, on treatment outcomes.

IMPORTANCE: The incidence of age-related macular degeneration (AMD) is unknown in Africa. OBJECTIVE: To estimate the 6-year cumulative incidence and progression of AMD in older adults (≥50 years old) in Nakuru, Kenya. DESIGN, SETTING, AND PARTICIPANTS: This study assessed a population-based cohort with 6-year follow-up of 4414 participants who had a complete assessment. Random cluster sampling with probability proportionate to size procedures was used to select a representative, cross-sectional sample of adults 50 years and older from January 26, 2007, through November 11, 2008. A 6-year follow-up was undertaken from January 7, 2013, through March 12, 2014. On both occasions, a comprehensive ophthalmic examination was performed that included logMAR visual acuity, digital retinal photography, and grading of images at Moorfields Eye Hospital Reading Centre. Data were collected on general health and risk factors. MAIN OUTCOMES AND MEASURES: Incident AMD in participants with no AMD at baseline and progression from early to late AMD. RESULTS: A total of 1453 of the 2900 individuals (50.1%) at risk for AMD were followed up after 6 years (mean [SD] age, 60.7 [8.2] years; 635 female [49.5%]; 799 Kikuyu [62.3%], 324 Kalenjin [25.3%], and 159 other [12.4%]); 1282 had data on AMD status at follow-up. Of these, 202 developed early AMD, and no participants developed late AMD. The 6-year weighted (for loss to follow-up) cumulative incidence of early AMD was 164.2 per 1000 persons (95% CI, 136.7-195.9 per 1000 persons). Two individuals with baseline early AMD from the 142 at risk had developed late AMD at follow-up, with a 6-year cumulative incidence of progression from early to late AMD of 24.5 per 1000 persons (95% CI, 5.0-111.7 per 1000 persons). Cumulative incidence of AMD increased with age (≥80 years old vs 50-59 years old: 1.8; 95% CI, 0.9-3.5) and was higher in women (female vs male: 1.6; 95% CI, 1.2-2.1) and persons with diabetes (diabetes vs no diabetes: 1.7; 95% CI, 1.0-2.8). CONCLUSIONS AND RELEVANCE: In Kenya, more than 100 000 estimated new cases of AMD, mainly early AMD, will develop every year in individuals 50 years or older, although a 50% loss to follow-up and wide CIs for progression to late AMD limit definitive conclusions from these findings.

Although structured psychological treatments are recommended as first-line interventions for harmful drinking, only a small fraction of people globally receive these treatments because of poor access in routine primary care. We assessed the effectiveness and cost-effectiveness of Counselling for Alcohol Problems (CAP), a brief psychological treatment delivered by lay counsellors to patients with harmful drinking attending routine primary health-care settings.

Although structured psychological treatments are recommended as first-line interventions for depression, only a small fraction of people globally receive these treatments because of poor access in routine primary care. We assessed the effectiveness and cost-effectiveness of a brief psychological treatment (Healthy Activity Program [HAP]) for delivery by lay counsellors to patients with moderately severe to severe depression in primary health-care settings.

IMPORTANCE: Visualization and interpretation of the optic nerve and retina are essential parts of most physical examinations. OBJECTIVE: To design and validate a smartphone-based retinal adapter enabling image capture and remote grading of the retina. DESIGN, SETTING, AND PARTICIPANTS: This validation study compared the grading of optic nerves from smartphone images with those of a digital retinal camera. Both image sets were independently graded at Moorfields Eye Hospital Reading Centre. Nested within the 6-year follow-up (January 7, 2013, to March 12, 2014) of the Nakuru Eye Disease Cohort in Kenya, 1460 adults (2920 eyes) 55 years and older were recruited consecutively from the study. A subset of 100 optic disc images from both methods were further used to validate a grading app for the optic nerves. Data analysis was performed April 7 to April 12, 2015. MAIN OUTCOMES AND MEASURES: Vertical cup-disc ratio for each test was compared in terms of agreement (Bland-Altman and weighted κ) and test-retest variability. RESULTS: A total of 2152 optic nerve images were available from both methods (also 371 from the reference camera but not the smartphone, 170 from the smartphone but not the reference camera, and 227 from neither the reference camera nor the smartphone). Bland-Altman analysis revealed a mean difference of 0.02 (95% CI, −0.21 to 0.17) and a weighted κ coefficient of 0.69 (excellent agreement). The grades of an experienced retinal photographer were compared with those of a lay photographer (no health care experience before the study), and no observable difference in image acquisition quality was found. CONCLUSIONS AND RELEVANCE: Nonclinical photographers using the low-cost smartphone adapter were able to acquire optic nerve images at a standard that enabled independent remote grading of the images comparable to those acquired using a desktop retinal camera operated by an ophthalmic assistant. The potential for task shifting and the detection of avoidable causes of blindness in the most at-risk communities makes this an attractive public health intervention.

IMPORTANCE: Clinical features are unreliable for distinguishing ocular surface squamous neoplasia (OSSN) from benign conjunctival lesions. OBJECTIVE: To evaluate the adverse effects, accuracy, and interobserver variation of toluidine blue 0.05% vital staining in distinguishing OSSN, confirmed by histopathology, from other conjunctival lesions. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study in Kenya from July 2012 through July 2014 of 419 adults with suspicious conjunctival lesions. Pregnant and breastfeeding women were excluded. EXPOSURES: Comprehensive ophthalmic slitlamp examination was conducted. Vital staining with toluidine blue 0.05% aqueous solution was performed before surgery. Initial safety testing was conducted on large tumors scheduled for exenteration looking for corneal toxicity on histology before testing smaller tumors. We asked about pain or discomfort after staining and evaluated the cornea at the slitlamp for epithelial defects. Lesions were photographed before and after staining. MAIN OUTCOMES AND MEASURES: Diagnosis was confirmed by histopathology. Six examiners assessed photographs from a subset of 100 consecutive participants for staining and made a diagnosis of OSSN vs non-OSSN. Staining was compared with histopathology to estimate sensitivity, specificity, and predictive values. Adverse effects were enumerated. Interobserver agreement was estimated using the κ statistic. RESULTS: A total of 143 of 419 participants (34%) had OSSN by histopathology. The median age of all participants was 37 years (interquartile range, 32-45 years) and 278 (66%) were female. A total of 322 of the 419 participants had positive staining while 2 of 419 were equivocal. There was no histological evidence of corneal toxicity. Mild discomfort was reported by 88 (21%) and mild superficial punctate keratopathy seen in 7 (1.7%). For detecting OSSN, toluidine blue had a sensitivity of 92% (95% CI, 87%-96%), specificity of 31% (95% CI, 25%-36%), positive predictive value of 41% (95% CI, 35%-46%), and negative predictive value of 88% (95% CI, 80%-94%). Interobserver agreement was substantial for staining (κ = 0.76) and moderate for diagnosis (κ = 0.40). CONCLUSIONS AND RELEVANCE: With the high sensitivity and low specificity for OSSN compared with histopathology among patients with conjunctival lesions, toluidine blue 0.05% vital staining is a good screening tool. However, it is not a good diagnostic tool owing to a high frequency of false-positives. The high negative predictive value suggests that a negative staining result indicates that OSSN is relatively unlikely.

IMPORTANCE: There is a trend toward treating conjunctival lesions suspected to be ocular surface squamous neoplasia (OSSN) based on the clinical impression. OBJECTIVE: To describe the presentation of OSSN and identify clinical features that distinguish it from benign lesions and subsequently evaluate their recognizability. DESIGN, SETTING, AND PARTICIPANTS: Prospective multicenter study in Kenya from July 2012 through July 2014 of 496 adults presenting with conjunctival lesions. One histopathologist examined all specimens. Six additional masked ophthalmologists independently examined photographs from 100 participants and assessed clinical features. EXPOSURES: Comprehensive history, slitlamp examination, and photography before excision biopsy. MAIN OUTCOMES AND MEASURES: Frequency of clinical features in OSSN and benign lesions were recorded. Proportions and means were compared using χ2, Fisher exact test, or t test as appropriate. Interobserver agreement was estimated using the κ statistic. Examiners’ assessments were compared with a reference. RESULTS: Among 496 participants, OSSN was the most common (38%) histological diagnosis, followed by pterygium (36%) and actinic keratosis (19%). Patients with OSSN were slightly older (mean [SD] age, 41 [11.6] vs 38 [10.9] years; P = .002) and tended to have lower levels of education than patients with benign lesions (P = .001). Females predominated (67% of OSSN vs 64% of benign lesions; P = .65). Human immunodeficiency virus infection was common among patients with OSSN (74%). The most common location was the nasal limbus (61% OSSN vs 78% benign lesions; P < .001). Signs more frequent in OSSN included feeder vessels (odds ratio [OR], 5.8 [95% CI, 3.2-10.5]), moderate inflammation (OR, 3.5 [95% CI, 1.8-6.8]), corneal involvement (OR, 2.7 [95% CI, 1.8-4.0]), leukoplakia (OR, 2.6 [95% CI, 1.7-3.9]), papilliform surface (OR, 2.1 [95% CI, 1.3-3.5]), pigmentation (OR, 1.5 [95% CI, 1.0-2.2]), temporal location (OR, 2.0 [95% CI, 1.2-3.2]), circumlimbal location (6.7% vs 0.3%; P < .001), severe inflammation (6.7% vs 0.3%; P < .001), and larger mean (SD) diameter (6.8 [3.2] vs 4.8 [2.8] mm; P < .001). All OSSN signs were also observed in benign lesions. There was slight to fair interobserver agreement in assessment of most signs and diagnosis (κ, 0.1-0.4). The positive predictive value of clinical appearance in identifying OSSN was 54% (interquartile range, 51%-56%) from photographs in which prevalence was 32%. CONCLUSIONS AND RELEVANCE: With overlapping phenotypes and modest interobserver agreement, OSSN and benign conjunctival lesions are not reliably distinguished clinically. Point-of-care diagnostic tools may help.

IMPORTANCE: Visual acuity is the most frequently performed measure of visual function in clinical practice and most people worldwide living with visual impairment are living in low- and middle-income countries. OBJECTIVE: To design and validate a smartphone-based visual acuity test that is not dependent on familiarity with symbols or letters commonly used in the English language. DESIGN, SETTING, AND PARTICIPANTS: Validation study conducted from December 11, 2013, to March 4, 2014, comparing results from smartphone-based Peek Acuity to Snellen acuity (clinical normal) charts and the Early Treatment Diabetic Retinopathy Study (ETDRS) logMAR chart (reference standard). This study was nested within the 6-year follow-up of the Nakuru Eye Disease Cohort in central Kenya and included 300 adults aged 55 years and older recruited consecutively. MAIN OUTCOMES AND MEASURES: Outcome measures were monocular logMAR visual acuity scores for each test: ETDRS chart logMAR, Snellen acuity, and Peek Acuity. Peek Acuity was compared, in terms of test-retest variability and measurement time, with the Snellen acuity and ETDRS logMAR charts in participants’ homes and temporary clinic settings in rural Kenya in 2013 and 2014. RESULTS: The 95% CI limits for test-retest variability of smartphone acuity data were ±0.029 logMAR. The mean differences between the smartphone-based test and the ETDRS chart and the smartphone-based test and Snellen acuity data were 0.07 (95% CI, 0.05-0.09) and 0.08 (95% CI, 0.06-0.10) logMAR, respectively, indicating that smartphone-based test acuities agreed well with those of the ETDRS and Snellen charts. The agreement of Peek Acuity and the ETDRS chart was greater than the Snellen chart with the ETDRS chart (95% CI, 0.05-0.10; P = .08). The local Kenyan community health care workers readily accepted the Peek Acuity smartphone test; it required minimal training and took no longer than the Snellen test (77 seconds vs 82 seconds; 95% CI, 71-84 seconds vs 73-91 seconds, respectively; P = .13). CONCLUSIONS AND RELEVANCE: The study demonstrated that the Peek Acuity smartphone test is capable of accurate and repeatable acuity measurements consistent with published data on the test-retest variability of acuities measured using 5-letter-per-line retroilluminated logMAR charts.

This systematic review summarizes evidence on the effectiveness of strategies to increase men's HIV-testing in sub-Saharan Africa.

Observational evidence suggests that community-based services for people with schizophrenia can be successfully provided by community health workers, when supervised by specialists, in low-income and middle-income countries. We did the COmmunity care for People with Schizophrenia in India (COPSI) trial to compare the effectiveness of a collaborative community-based care intervention with standard facility-based care.

Little is known about the impact of HIV infection on biological ageing in sub-Saharan Africa. The study aimed to assess biological ageing in South African HIV-infected adults and HIV-seronegative individuals using two validated biomarkers, telomere length and CDKN2A expression (a mediator of cellular senescence).

Background:There is conflicting evidence on the relationship between war trauma and suicidal behavior. Some studies point to an increased risk of suicidal behavior while others do not, with a paucity of such data from sub-Saharan Africa. Aims:To investigate the prevalence and risk factors of attempted suicide in war-affected Eastern Uganda. Method:A cross-sectional survey was carried out in two districts of Eastern Uganda where 1,560 respondents (15 years and older) were interviewed. Multivariable logistic regression was used to assess risk factors of attempted suicide in this population. Results:Lifetime attempted suicide was 9.2% (n= 142; 95% CI, 7.8%–10.8%), and 12-month attempted suicide was 2.6% (n= 41; 95% CI, 1.9–3.5%). Lifetime attempted suicide was significantly higher among females 101 (11.1%) than among males 43 (6.5%; OR = 1.80, 95% CI 1.21–2.65). Factors independently associated with lifetime rate of attempted suicide among females were subcounty, being a victim of intimate partner violence, having reproductive health complaints, and having major depressive disorder. Among males these were belonging to a war-vulnerable group, having a surgical complaint, and having a major depressive disorder. Conclusions:In both sexes, the lifetime rate of attempted suicide was not independently directly related to experiences of war trauma. It was, however, indirectly related to war trauma through its association with psychological, somatic, and psychosocial sequelae of war.

The HIV epidemic has carved contrasting trajectories around the world with sub-Saharan Africa (SSA) being most affected. We hypothesized that mean HIV-1 plasma RNA viral loads are higher in SSA than other areas, and that these elevated levels may contribute to the scale of epidemics in this region.

Mycoplasma genitaliumis an emerging sexually transmitted infection (STI) and has been associated with reproductive tract infections and HIV in cross-sectional studies. In this longitudinal study, we assess whether M. genitaliumis associated with risk of acquiring HIV-1 infection.

ABSTRACTTrachoma is the most common infectious cause of blindness and a major public health problem in many developing countries. It is caused by recurrent ocular infection with Chlamydia trachomatisin childhood, with conjunctival scarring seen later in life. The pathogenesis of trachomatous scarring, however, is poorly understood, and this study was carried out to investigate the immunofibrogenic correlates of trachomatous conjunctival scarring. A case-control study of 363 cases with conjunctival scarring and 363 control participants was conducted. Investigations included in vivoconfocal microscopy (IVCM) assessment, quantitative real-time PCR gene expression, C. trachomatisdetection, and nonchlamydial bacterial culture. Trachomatous scarring was found to be strongly associated with a proinflammatory, innate immune response with increased expression of psoriasin, interleukin-1β, tumor necrosis factor alpha, defensin-β4A, chemokine ligand 5, and serum amyloid A1. There was also differential expression of various modifiers of the extracellular matrix, including metalloproteinases 7, 9, 10, and 12, tissue inhibitor of matrix metalloproteinase 1, and secreted protein acidic cystein-rich-like 1. The expression of many of these genes was also significantly associated with the presence of nonchlamydial bacterial infection. These infections had a marked effect on conjunctival immune processes, including an increased inflammatory infiltrate and edema seen with IVCM. This study supports the possibility that the immunofibrogenic response in scarring trachoma is partly stimulated by nonchlamydial bacterial infection, which is characterized by the expression of innate factors.

Trachoma is the most common infectious cause of blindness and a major public health problem in many developing countries. It is caused by recurrent ocular infection with Chlamydia trachomatis in childhood, with conjunctival scarring seen later in life. The pathogenesis of trachomatous scarring, however, is poorly understood, and this study was carried out to investigate the immunofibrogenic correlates of trachomatous conjunctival scarring. A case-control study of 363 cases with conjunctival scarring and 363 control participants was conducted. Investigations included in vivo confocal microscopy (IVCM) assessment, quantitative real-time PCR gene expression, C. trachomatis detection, and nonchlamydial bacterial culture. Trachomatous scarring was found to be strongly associated with a proinflammatory, innate immune response with increased expression of psoriasin, interleukin-1β, tumor necrosis factor alpha, defensin-β4A, chemokine ligand 5, and serum amyloid A1. There was also differential expression of various modifiers of the extracellular matrix, including metalloproteinases 7, 9, 10, and 12, tissue inhibitor of matrix metalloproteinase 1, and secreted protein acidic cystein-rich-like 1. The expression of many of these genes was also significantly associated with the presence of nonchlamydial bacterial infection. These infections had a marked effect on conjunctival immune processes, including an increased inflammatory infiltrate and edema seen with IVCM. This study supports the possibility that the immunofibrogenic response in scarring trachoma is partly stimulated by nonchlamydial bacterial infection, which is characterized by the expression of innate factors.

The immunological basis of scarring trachoma is not well understood. It is unclear whether it is driven primarily through cell-mediated adaptive or epithelial-cell-derived innate responses. The purpose of this study was to investigate the expression of the inflammatory and fibrogenic mediators which may be involved. We conducted a cross-sectional survey of children living in an untreated trachoma-endemic community in Tanzania. The children were examined for signs of trachoma, and swabs were collected for bacteriological culture and RNA and DNA isolation. Chlamydia trachomatis was detected by the Amplicor PCR test. The expression of the following genes was measured by quantitative reverse transcription-PCR (RT-PCR): S100A7, IL1B, IL17A, IL23A, CXCL5, CCL18, TLR2, NLRP3, KLRD1, CTGF, and MMP9. Four hundred seventy children under the age of 10 years were included. Follicular trachoma (TF) was detected in 65 children (14%), C. trachomatis was detected in 25 (5%), and bacterial pathogens were cultured in 161 (34%). TF was associated with significantly increased expression of S100A7, IL17A, CCL18, CXCL5, and CTGF. Expression was increased further in the presence of papillary inflammation. Nonchlamydial bacterial infection was associated with increased expression of IL17A, CXCL5, CCL18, and KLRD1. IL17A expression was associated with increased expression of S100A7, CXCL5, CCL18, KLRD1, and CTGF. These data are consistent with a role for IL-17A in orchestrating the proinflammatory response in trachoma. Its activity may be promoted either as part of the cell-mediated response or through innate pathways. It may drive a range of proinflammatory factors leading to excessive tissue damage and repair involving fibrosis.

ABSTRACTThe immunological basis of scarring trachoma is not well understood. It is unclear whether it is driven primarily through cell-mediated adaptive or epithelial-cell-derived innate responses. The purpose of this study was to investigate the expression of the inflammatory and fibrogenic mediators which may be involved. We conducted a cross-sectional survey of children living in an untreated trachoma-endemic community in Tanzania. The children were examined for signs of trachoma, and swabs were collected for bacteriological culture and RNA and DNA isolation. Chlamydia trachomatiswas detected by the Amplicor PCR test. The expression of the following genes was measured by quantitative reverse transcription-PCR (RT-PCR): S100A7, IL1B, IL17A, IL23A, CXCL5, CCL18, TLR2, NLRP3, KLRD1, CTGF, and MMP9. Four hundred seventy children under the age of 10 years were included. Follicular trachoma (TF) was detected in 65 children (14%), C. trachomatiswas detected in 25 (5%), and bacterial pathogens were cultured in 161 (34%). TF was associated with significantly increased expression of S100A7, IL17A, CCL18, CXCL5, and CTGF.Expression was increased further in the presence of papillary inflammation. Nonchlamydial bacterial infection was associated with increased expression of IL17A, CXCL5, CCL18, and KLRD1. IL17Aexpression was associated with increased expression of S100A7, CXCL5, CCL18, KLRD1, and CTGF.These data are consistent with a role for IL-17A in orchestrating the proinflammatory response in trachoma. Its activity may be promoted either as part of the cell-mediated response or through innate pathways. It may drive a range of proinflammatory factors leading to excessive tissue damage and repair involving fibrosis.

Depression and anxiety disorders are common mental disorders worldwide. The MANAS trial aimed to test the effectiveness of an intervention led by lay health counsellors in primary care settings to improve outcomes of people with these disorders.

ABSTRACTHerpes simplex virus type 2 (HSV-2) is the most common cause of genital ulcer disease and is a cofactor for HIV-1 acquisition and transmission. We analyzed specimens from three separate phase III trials of acyclovir (ACV) for prevention of HIV-1 acquisition and transmission to determine if failure of ACV to interrupt HIV acquisition and transmission was associated with genotypic ACV resistance. Acyclovir (400 mg twice daily) or placebo was provided to HSV-2-infected persons at risk of HIV-1 infection in the Mwanza and HPTN 039 trials and to persons dually infected with HSV-2 and HIV-1 who had an HIV-negative partner in the Partners in Prevention study. We extracted HSV DNA from genital ulcer swabs or cervicovaginal lavage fluids from 68 samples obtained from 64 participants randomized to ACV and sequenced the HSV-2 UL23 gene encoding thymidine kinase. The UL23 sequences were compared with published and unpublished data. Variants were observed in 38/1,128 (3.4%) nucleotide positions in the UL23 open reading frame, with 58% of these encoding amino acid changes. No deletions, insertions, or mutations known to be associated with resistance were detected. Thirty-one of the variants (81.5%) are newly reported, 15 of which code for amino acid changes. Overall, UL23 is highly polymorphic compared to other loci in HSV-2, but no drug resistance mutations were detected that could explain the failure to reduce HIV incidence or to prevent HIV-1 transmission in these studies.

Trachoma is a poorly understood immunofibrogenic disease process, initiated by Chlamydia trachomatis. Differences in conjunctival gene expression profiles between Ethiopians with trachomatous trichiasis (with [TTI] or without [TT] inflammation) and controls (C) were investigated to identify relevant host responses. Tarsal conjunctival swab samples were collected for RNA isolation and C. trachomatis PCR. Transcriptome-wide microarray experiments were conducted on 42 samples (TTI, n = 13; TT, n = 15; C, n =14). Specific results were confirmed by using multiplex quantitative reverse transcription-PCR for 16 mRNA targets in an independent collection of case-control samples: 386 case-control pairs (TTI, n = 244; TT, n = 142; C, n = 386). The gene expression profiles of cases were consistent with squamous metaplasia (keratins, SPRR), proinflammatory cytokine production (IL1β, CXCL5, and S100A7), and tissue remodeling (MMP7, MMP9, MMP12, and HAS3). There was no difference in the level of IFN between cases and controls. However, cases had increased INDO, NOS2A, and IL13RA2 and reduced IL13. C. trachomatis was detected in 1/772. Cases show evidence of ongoing inflammation and tissue remodeling, which were more marked where clinical inflammation was also present. Significantly, these processes appear to be active in the absence of current C. trachomatis infection. There was limited evidence of a TH1 response (INDO and NOS2A) and no association between a TH2 response and cases. The epithelium appears to be actively involved in late cicatricial stages of trachoma through the production of proinflammatory factors (IL1β, CXCL5, and S100A7). Longitudinal studies are needed to investigate which etiological factors and pathways are associated with progressive scarring and whether simply controlling chlamydial infection will halt progression in people with established cicatricial disease.

ABSTRACTTrachoma is a poorly understood immunofibrogenic disease process, initiated by Chlamydia trachomatis. Differences in conjunctival gene expression profiles between Ethiopians with trachomatous trichiasis (with [TTI] or without [TT] inflammation) and controls (C) were investigated to identify relevant host responses. Tarsal conjunctival swab samples were collected for RNA isolation and C. trachomatisPCR. Transcriptome-wide microarray experiments were conducted on 42 samples (TTI, n= 13; TT, n= 15; C, n=14). Specific results were confirmed by using multiplex quantitative reverse transcription-PCR for 16 mRNA targets in an independent collection of case-control samples: 386 case-control pairs (TTI, n= 244; TT, n= 142; C, n= 386). The gene expression profiles of cases were consistent with squamous metaplasia (keratins, SPRR), proinflammatory cytokine production (IL1β, CXCL5, and S100A7), and tissue remodeling (MMP7, MMP9, MMP12, and HAS3). There was no difference in the level of IFNγ between cases and controls. However, cases had increased INDO, NOS2A, and IL13RA2and reduced IL13. C. trachomatiswas detected in 1/772. Cases show evidence of ongoing inflammation and tissue remodeling, which were more marked where clinical inflammation was also present. Significantly, these processes appear to be active in the absence of current C. trachomatisinfection. There was limited evidence of a TH1 response (INDOand NOS2A) and no association between a TH2 response and cases. The epithelium appears to be actively involved in late cicatricial stages of trachoma through the production of proinflammatory factors (IL1β, CXCL5, and S100A7). Longitudinal studies are needed to investigate which etiological factors and pathways are associated with progressive scarring and whether simply controlling chlamydial infection will halt progression in people with established cicatricial disease.

ABSTRACTThe performances of commercial enzyme-linked immunosorbent assays (ELISAs) in detecting herpes simplex virus type 2 (HSV-2) antibodies have been inconsistent for African and human immunodeficiency virus (HIV)-positive populations. We compared the performances of the HerpeSelect and Kalon glycoprotein G2 ELISAs for patients with genital ulcer disease in Ghana and the Central African Republic. Sera from 434 women were tested with the HerpeSelect assay, and a subsample (n= 199) was tested by the Kalon assay. Ulcer swabs and cervicovaginal lavage samples were tested for HSV-2 DNA by PCR. HSV-2-seronegative women with detectable genital HSV-2 DNA were retested for HSV-2 antibodies 14 and 28 days later by the two ELISAs. A total of 346 (80%) women were positive by HerpeSelect at baseline, and 225 (54%) had detectable genital (lesional or cervicovaginal) HSV-2 DNA. Sixty-six (19%) HerpeSelect-positive samples had low-positive index values (1.1 to 3.5), and 58% of these samples had detectable genital HSV-2 DNA. Global agreement between the two serological assays was 86%. Concordance was high (99%) for sera that were negative by HerpeSelect or had high index values (>3.5). Defining infection detected by HSV-2 DNA PCR and/or Kalon assay as true infection, 71% of sera with low-positive index values were associated with true HSV-2 infection. Twenty-five women were identified as having nonprimary first-episode genital HSV-2 infection. Rates of HSV-2 seroconversion at day 14 were 77% (10/13 patients) by HerpeSelect assay and 23% (3/13 patients) by Kalon assay, with four additional seroconversions detected by Kalon assay at day 28. HIV serostatus did not influence assay performance. Low index values obtained with the HerpeSelect assay may correspond to true HSV-2 infection, in particular to nonprimary first episodes of genital HSV-2 infection, and need to be interpreted in the context of clinical history.

In 2005, 4.1 million people were infected with HIV. There is an urgent need to intensify and expand HIV prevention methods. Male circumcision is one of several potential approaches. This review summarizes recent evidence for the potential of male circumcision to prevent HIV and other sexually transmitted infections.

ABSTRACTThe accuracy and usefulness of laboratory-developed real-time PCR procedures using a Light Cycler instrument (Roche Diagnostics) for detecting and quantifying human immunodeficiency virus type 1 (HIV-1) RNA and DNA as well as herpes simplex virus type 1 (HSV-1)/HSV-2 DNA in cervicovaginal secretions from women coinfected with HIV and HSV were evaluated. For HIV-1, the use of the NEC152 and NEC131 primer set and the NEC-LTR probe in the long terminal repeat gene allowed us to detect accurately the majority of HIV-1 subtypes of group M circulating in sub-Saharan Africa, including subtypes A, B, C, D, and G as well as circulating recombinant forms 02 and 11. The detection threshold of real-time PCR for HIV in cervicovaginal lavage samples was 5 copies per assay for both RNA and DNA; the intra- and interassay coefficients of variation of CTvalues were 1.30% and 0.69% (HIV-1 RNA) and 1.84% and 0.67% (HIV-1 DNA), respectively. Real-time PCR for HSV using primers and probe targeting the HSV DNA polymerase gene allowed both detection and quantification of HSV DNA and also differentiation between HSV-1 and HSV-2 genotypes. The detection threshold of real-time PCR for HSV was 5 copies per assay; the intra- and interassay coefficients of variation of CTvalues were 0.96% and 1.49%, respectively. Both manual and automated silica-based procedures were appropriate for combined extraction of HIV and HSV genomes from female genital secretions. Taken together, these findings indicate that real-time PCR may be used as a unique nucleic acid amplification procedure to detect and quantify HIV and HSV genomes in cervicovaginal secretions and thus to assess at reduced costs the genital shedding of both viruses in women included in intervention studies.

The accuracy and usefulness of laboratory-developed real-time PCR procedures using a Light Cycler instrument (Roche Diagnostics) for detecting and quantifying human immunodeficiency virus type 1 (HIV-1) RNA and DNA as well as herpes simplex virus type 1 (HSV-1)/HSV-2 DNA in cervicovaginal secretions from women coinfected with HIV and HSV were evaluated. For HIV-1, the use of the NEC152 and NEC131 primer set and the NEC-LTR probe in the long terminal repeat gene allowed us to detect accurately the majority of HIV-1 subtypes of group M circulating in sub-Saharan Africa, including subtypes A, B, C, D, and G as well as circulating recombinant forms 02 and 11. The detection threshold of real-time PCR for HIV in cervicovaginal lavage samples was 5 copies per assay for both RNA and DNA; the intra- and interassay coefficients of variation of CT values were 1.30% and 0.69% (HIV-1 RNA) and 1.84% and 0.67% (HIV-1 DNA), respectively. Real-time PCR for HSV using primers and probe targeting the HSV DNA polymerase gene allowed both detection and quantification of HSV DNA and also differentiation between HSV-1 and HSV-2 genotypes. The detection threshold of real-time PCR for HSV was 5 copies per assay; the intra- and interassay coefficients of variation of CT values were 0.96% and 1.49%, respectively. Both manual and automated silica-based procedures were appropriate for combined extraction of HIV and HSV genomes from female genital secretions. Taken together, these findings indicate that real-time PCR may be used as a unique nucleic acid amplification procedure to detect and quantify HIV and HSV genomes in cervicovaginal secretions and thus to assess at reduced costs the genital shedding of both viruses in women included in intervention studies.