Follicular trachoma and trichiasis prevalence in an urban community in The Gambia, West Africa: is there a need to include urban areas in national trachoma surveillance?

OBJECTIVES: Urban areas are traditionally excluded from trachoma surveillance activities, but due to rapid expansion and population growth, the urban area of Brikama in The Gambia may be developing social problems that are known risk factors for trachoma. It is also a destination for many migrants who may be introducing active trachoma into the area. This study aimed to determine the prevalence and risk factors for follicular trachoma and trichiasis in Brikama. METHODS: A community-based cross-sectional prevalence survey including 27 randomly selected households in 12 randomly selected enumeration areas (EAs) of Brikama. Selected households were offered eye examinations, and the severity of trachoma was graded according to WHO's simplified grading system. Risk factor data were collected from each household via a questionnaire. RESULTS: The overall prevalence of trachomatous inflammation-follicular (TF) in children aged 1-9 years was 3.8% (95% CI 2.5-5.6), and the overall prevalence of trichiasis in adults aged ≥15 years was 0.46% (95% CI 0.17-1.14). EA prevalence of TF varied from 0% to 8.4%. The major risk factors for TF were dirty faces (P < 0.01, OR = 9.23, 95% CI 1.97-43.23), nasal discharge (P = 0.039, OR = 5.11, 95% CI 1.08-24.10) and residency in Brikama for <1 year (P = 0.047, OR = 7.78, 95% CI 1.03-59.03). CONCLUSIONS: Follicular trachoma can be considered to have been eliminated as a public health problem in Brikama according to WHO criteria. However, as the prevalence in some EAs is >5%, it may be prudent to include Brikama in surveillance programmes. Trichiasis remains a public health problem (>0.1%), and active case finding needs to be undertaken.

Writhed Analytical Magnetic Flux Rope Model.

Observations of magnetic clouds, within interplanetary coronal mass ejections (ICMEs), are often well described by flux rope models. Most of these assume either a cylindrical or toroidal geometry. In some cases, these models are also capable of accounting for non-axisymmetric cross-sections but they generally all assume axial invariance. It can be expected that any ICME, and its flux rope, will be deformed along its axis due to influences such as the solar wind. In this work, we aim to develop a writhed analytical magnetic flux rope model which would allow us to analytically describe a flux rope structure with varying curvature and torsion so that we are no longer constrained to a cylindrical or toroidal geometry. In this first iteration of our model we will solely focus on a circular cross-section of constant size. We describe our flux rope geometry in terms of a parametrized flux rope axis and a parallel transport frame. We derive expressions for the axial and poloidal magnetic field components under the assumption that the total axial magnetic flux is conserved. We find an entire class of possible solutions, which differ by the choice of integration constants, and present the results for a specific example. In general, we find that the twist of the magnetic field locally changes when the geometry deviates from a cylinder or torus. This new approach also allows us to generate completely new types of in situ magnetic field profiles which strongly deviate from those generated by cylindrical or toroidal models.

Literacy, education and adherence to antiretroviral therapy in The Gambia.

We examined the relationship of patients' literacy and education to antiretroviral therapy (ART) adherence in an urban treatment centre in The Gambia. Information on education and literacy systematically collected before ART initiation was compared against selected adherence outcomes. Formally educated patients were significantly more likely to achieve virological suppression at both six and 12 months (87% vs. 67%, OR=3.13, P=0.03; 88% vs. 63%, OR=4.49, P=0.007, respectively). Literate patients had similar benefit at 12 months (OR=3.39 P=0.03), with improved virological outcomes associated with degree of literacy (P=0.003). A trend towards similar results was seen at 6 months for Koranically educated patients; however, this was no longer apparent at 12 months. No significant correlation was seen between socio-demographic characteristics and missed appointments. Our study suggests that literacy, formal education and possibly Koranic education may impact favourably on adherence to ART.

Population-based analysis of ocular Chlamydia trachomatis in trachoma-endemic West African communities identifies genomic markers of disease severity.

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.

An index of community ocular Chlamydia trachomatis load for control of trachoma.

Quantitative PCR (Q-PCR) technology has recently been applied to the measurement of ocular loads of Chlamydia trachomatis. We present an index called the community ocular C. trachomatis load (COCTL) which is similar to the community microfilarial load (CMFL) of onchocerciasis. Our index has the advantage of being scale-independent so that, for example, percentage changes are the same whether calculated per eye swab or per Q-PCR capillary. The COCTL for a population or subgroup is formed by adding the arbitrary concentration of 1 organism per ml to each individual Q-PCR quantification, calculating the geometric mean, and finally subtracting 1 per ml again. The use of the COCTL is illustrated in a study of trachoma in northern Tanzania. The COCTL is higher in people with clinical trachoma than those without (5.8 organisms per swab vs. 0.1), and in children aged six months to ten years than in the overall population (1.1 vs. 0.4). The COCTL index is potentially useful for sentinel sites, operational research and calibration of clinical measures of trachoma.

Long term outcome of trichiasis surgery in the Gambia.

BACKGROUND: Trichiasis surgery is believed to reduce the risk of losing vision from trachoma. There are limited data on the long term outcome of surgery and its effect on vision and corneal opacification. Similarly, the determinants of failure are not well understood. METHODS: A cohort of people in the Gambia who had undergone surgery for trachomatous trichiasis 3-4 years earlier was re-assessed. They were examined clinically and the conjunctiva was sampled for Chlamydia trachomatis polymerase chain reaction (PCR) and general bacterial culture. RESULTS: In total, 141/162 people were re-examined. Recurrent trichiasis was found in 89/214 (41.6%) operated eyes and 52 (24.3%) eyes had five or more lashes touching the globe. Corneal opacification improved in 36 of 78 previously affected eyes. There was a general deterioration in visual acuity between surgery and follow up, which was greater if new corneal opacification developed or trichiasis returned. Recurrent trichiasis was associated with severe conjunctival inflammation and bacterial infection. C trachomatis was detected in only one individual. CONCLUSIONS: Recurrent trichiasis following surgery is a common potentially sight threatening problem. Some improvement in the cornea can occur following surgery and the rate of visual loss tended to be less in those without recurrent trichiasis. The role of conjunctival inflammation and bacterial infection needs to be investigated further. Follow up of patients is advised to identify individuals needing additional surgical treatment.

A randomised controlled trial of azithromycin following surgery for trachomatous trichiasis in the Gambia.

BACKGROUND/AIM: Trachomatous trichiasis frequently returns following surgery. Several factors may promote recurrence: preoperative disease severity, surgeon ability, surgical procedure, healing responses, and infection. This study investigates whether enhanced control of infection, both of Chlamydia trachomatis and other bacteria, with azithromycin can improve surgical outcome in a trachoma control programme. METHODS: Individuals with trachomatous trichiasis were examined and operated. After surgery patients were randomised to the azithromycin or control group. The azithromycin group and children in their household were given a dose of azithromycin. Antibiotic treatment was repeated at 6 months. All patients were reassessed at 6 months and 12 months. Samples were collected for C trachomatis polymerase chain reaction and general microbiology at each examination. RESULTS: 451 patients were enrolled. 426 (94%) were reassessed at 1 year, of whom 176 (41.3%) had one or more lashes touching the eye and 84 (19.7%) had five or more lashes. There was no difference in trichiasis recurrence between the azithromycin and control group. Recurrent trichiasis was significantly associated with more severe preoperative trichiasis, bacterial infection, and severe conjunctival inflammation at 12 months. Significant variability in outcome was found between surgeons. Visual acuity and symptoms significantly improved following surgery. CONCLUSION: In this setting, with a low prevalence of active trachoma, azithromycin did not improve the outcome of trichiasis surgery conducted by a trachoma control programme. Audit of trichiasis surgery should be routine.

Adrenalectomy attenuates stimulation-produced analgesia.

Ablation of the adrenal glands potentiates analgesia induced by morphine and attenuates an opioid form of stress-induced analgesia. the adrenal cortex has been implicated in analgesia induced by morphine and enkephalin-like peptides in the adrenal medulla have been suggested to modulate stress-induced analgesia. The effect of adrenalectomy upon analgesia produced by stimulation of the brain has not been investigated. The present investigations demonstrated that antinociception (measured with the tail-flick test) from focal stimulation of the periaqueductal grey was attenuated or abolished after adrenal ablation. These results implicate adrenal hormones in the regulation of the endogenous pain inhibitory system in the brain.

Operational comparison of single-dose azithromycin and topical tetracycline for trachoma.

PURPOSE: World Health Organization guidelines for antibiotic treatment of trachoma currently include a 6-week course of tetracycline eye ointment twice daily or a single dose of oral azithromycin. Previous trials have shown similar efficacy of these two alternatives when administration of the ointment was carefully supervised. It is believed, however, that azithromycin may be a more effective treatment in practice, and the purpose of this study was to test that hypothesis. METHODS: A masked randomized controlled trial was conducted to compare azithromycin and tetracycline under practical operational conditions-i.e., without supervision of the administration of the ointment. Three hundred fourteen children aged 6 months to 10 years with clinically active trachoma were recruited and individually randomized to receive one of the two treatments. Follow-up visits were conducted at 10 weeks and 6 months. The outcome was resolution of disease (clinical "cure"). RESULTS: Children allocated to azithromycin were significantly more likely to have resolved disease than those allocated to tetracycline, both at 10 weeks (68% versus 51%; cure rate ratio, 1.31; 95% confidence interval [CI], 1.08-1.59; P = 0.007) and at 6 months (88% versus 73%; cure rate ratio, 1.19; 95% CI, 1.06-1.34; P = 0.004). Azithromycin was particularly effective for intense inflammation (P = 0.023, Fisher's exact test). CONCLUSIONS: Single-dose oral azithromycin was a more effective treatment for active trachoma than tetracycline ointment as applied by caregivers. The high cure rate achieved with tetracycline in this study in the absence of supervision and the significantly higher costs of azithromycin, suggest that in the absence of donation programs, switching routine treatment from tetracycline to azithromycin would not be a good use of resources.

Expression of MHC class II antigens by conjunctival epithelial cells in trachoma: implications concerning the pathogenesis of blinding disease.

In an attempt to understand the pathogenesis of corneal changes and conjunctival scarring in trachoma, which are responsible for blindness in some 7 million people worldwide, the surface expression of major histocompatibility complex class II antigens on conjunctival epithelial cells was sought in patients with different clinical features of the disease. Class II expression was significantly associated with active (inflammatory) trachoma, but an independent association with corneal pannus or conjunctival scarring could not be shown. Longitudinal data suggest that class II expression may antedate clinically active disease and persist after it has resolved.

Transmission ecology of the fly Musca sorbens, a putative vector of trachoma.

Recent evidence suggests that eye-seeking flies are important trachoma vectors. We conducted a series of investigations to identify which species of synanthropic flies are potential vector(s) of this blinding disease in The Gambia. Several species of fly were caught in fish-baited attractant traps placed in villages throughout the year (1997/98) but only 2 species, Musca sorbens and M. domestica, were caught from the eyes of children. M. sorbens comprised < 10% of the total number of flies caught with attractant traps but was responsible for > 90% of fly-eye contacts, the remainder were made by M. domestica. All fly species were more numerous in the wet season than the dry season. Eyes of young children are considered to be the main reservoir of Chlamydia trachomatis, the causative agent of trachoma. Collections of eye-seeking flies from children showed frequent fly-eye contacts (median [interquartile range], 3 [1.5-7] every 15 min). Children with potentially infective ocular or nasal discharge had twice as many fly-eye contacts than children with no discharge (P < 0.001). There was no difference in exposure to fly-eye contacts if a child sat inside or outside a house (P = 0.273). Female flies were more commonly caught from eyes than male (P < 0.001). The presence of Chlamydia DNA was demonstrated by PCR on 2 of 395 flies caught from the eyes of children with a current active trachoma infection. Both positive flies were M. sorbens, one male and the other female. Further elucidation of M. sorbens behavioural ecology and the development of sustainable strategies to control these flies should be a priority. It is likely that M. sorbens is the principal insect vector of trachoma in The Gambia.

Molecular epidemiology of trachoma in a Gambian village.

The application of a diagnostic and genotyping technique based on the polymerase chain reaction (PCR) to the study of trachoma epidemiology in the Gambian village of Jali is reported. PCR based on the major outer membrane protein (MOMP) gene of Chlamydia trachomatis appears to be more sensitive than either isolation or antigen detection by enzyme immunoassay; it had a specificity of 95% and sensitivity of 51% against clinical signs. PCR genotyping identified genotypes A and B of Chlamydia trachomatis circulating in Jali. Sequencing revealed a Pst1 restriction endonuclease site in the amplified MOMP gene of some B strains but not others; Pst1 digestion of the PCR product proved an easy method of distinguishing these strains. The distribution of serotypes and B strain variants shows a significant degree of household clustering (p < 0.001). PCR based genotyping combined with strain typing provides a new and powerful epidemiological tool for the study of transmission events in trachoma.

Longitudinal study of trachomatous trichiasis in the Gambia.

AIM: Investigation of the natural history of trachomatous trichiasis in the Gambia and of the outcome of self epilation and surgery for the condition. METHODS: A 1 year longitudinal study of 190 subjects with trichiasis was performed. Major trichiasis cases (five lashes or more) were referred for surgery and minor trichiasis cases were advised to epilate. Outcome measures included progression of trichiasis and corneal scarring; attendance for and results of surgery. RESULTS: 34 of 148 (23%, 95% CI 16 to 31) subjects with major trichiasis attended for surgery over the year. Progression from minor to major trichiasis occurred in 18 of 55 subjects (33%, 95% CI 21 to 47). Progression of corneal scarring occurred in 60 of 167 patients (36%, 95% CI 29 to 44). Clinically active trachoma and conjunctival bacterial isolation predicted progression of corneal opacity. Surgery was successful in 39 of 54 (72%) eyes. CONCLUSIONS: Despite the overall decline in trachoma in the Gambia, patients with both minor and major trichiasis remain at risk of developing corneal opacity. Active trachomatous inflammation and additional infection with bacteria may accelerate this process. Antibiotic treatment for trichiasis patients (in addition to surgery) should be investigated. Surgery for minor trichiasis may be indicated. Regular audit of surgical results is necessary with retraining where needed.

Azithromycin for the treatment and control of trachoma.

Trachoma, a recurrent follicular conjunctivitis caused by Chlamydia trachomatis, is the leading cause of preventable blindness worldwide. Efforts to control this disease have met with limited success. This failure is due in part to the limitations of conventional antibiotic treatment, a prolonged course of topical tetracycline. Azithromycin, an azalide antibiotic, is effective against chlamydial infections when given as a single oral dose. Recent research from Africa has shown azithromycin to be as effective as tetracycline in the treatment of trachoma. Under operational conditions azithromycin proved to be more effective. This success is attributed to a much-improved compliance with treatment. Community-wide mass treatment with azithromycin is advocated as a means of controlling trachoma in endemic countries. Questions still remain over the use of azithromycin for this purpose. The frequency and target population of mass distribution campaigns need to be defined. A few countries are beneficiaries of a philanthropic donation by the manufacturer of azithromycin, Pfizer Inc. However, in the absence of a drug donation programme the cost-effectiveness of this measure is unclear.

Lymphoma of the stomach.

A retrospective review revealed 17 lymphomas in a 25-year period (1960-84). Presenting features did not allow differentiation from carcinoma. Preoperative diagnosis was made in 3 patients by endoscopic biopsy. Treatment included apparent complete resection of 12 patients. Incomplete removal following biopsy with or without a drainage procedure was performed on five patients. Radiation therapy was used on ten patients and chemotherapy was used on three patients. There were three 5-year survivors and four others with survival greater than 2 years. All patients surviving more than 2 years had apparent complete resection while five patients also had radiation. One also had chemotherapy. Analysis of our patients with review of other series suggests complete resection with adjacent nodes to be the best approach. Appropriate node sampling, liver biopsy, and removal of the spleen if it appears clinically involved should be done. Postoperative radiation and/or chemotherapy may be indicated only when apparent complete resection is not feasible.

Is diagnostic peritoneal lavage for blunt trauma obsolete?

Diagnostic peritoneal lavage was 97 percent accurate, with a 2 percent false positive rate and a 1 percent false negative rate in this series of 414 patients. The ease, safety, and accuracy of diagnostic peritoneal lavage justify its continued use in evaluating these patients. Recent studies show computerized tomography (CT) can be highly accurate in detecting intra-abdominal injuries after blunt trauma. We reviewed our experience with diagnostic peritoneal lavage (DPL) to evaluate whether the accuracy, safety, speed, and cost justified its continued use. Four hundred fifteen DPLs were performed on 414 patients from February 1, 1983, through December 31, 1987. All DPLs were done by the open technique. The lavage was considered grossly positive if 10 cc gross blood were aspirated. If there were greater than 100,000 red blood cells (RBC)/mm3, greater than 500 white blood cells (WBC)/mm3, elevated amylase or bilirubin, or bacteria or vegetable fibers the lavage was microscopically positive. There were no cases with elevated bilirubin, amylase, or presence of bacteria. All four cases with "rare vegetable fibers" were false positive. Six DPLs were for penetrating trauma to the lower chest or back. There were 291 negative lavages, including five false negatives (1%), and 124 positive DPLs, including seven false positives (2%), resulting in a crude accuracy of 97 percent. Three of the five false negative lavages had a ruptured diaphragm as the only intra-abdominal injury. There was one minor complication. DPL was usually performed in the trauma resuscitation room during the secondary survey. At our institution, the total fees for DPL are +185 less than the fees for CT. DPL is accurate, rapid, safe, and avoids the disruption of patient care that results in the radiology suite. DPL remains our procedure of choice for evaluating blunt abdominal trauma in the adult.

Quantitative cytochemistry of lysosomal structures in rat incisor maturation enamel organ.

Trimetaphosphatase was used as a lysosomal marker in the ruffle-ended maturation ameloblasts and associated papillary cells. Morphometric analysis was carried out of the percentage area of these cells (density) occupied by the various enzyme-reactive lysosomal structures. The density of total TMPase-positive lysosomal structures, tubular lysosomes and multivesicular bodies in ruffle-ended ameloblasts were all significantly greater (p less than or equal to 0.05) in early than in late maturation enamel formation. In papillary cells the same was true of tubular lysosomes, whereas the greater density of enzyme-positive total structures in early maturation was not statistically significant when compared to late maturation. These findings demonstrate a corresponding pattern between enamel-organ lysosomal activity and the period of early enamel maturation when most enamel protein is lost. They support the likely involvement by ruffle-ended ameloblasts and papillary cells in absorption and degradation of exogenous enamel proteins.

Host genetic studies in human ocular Chlamydial infection.

Several human and animal models and methods have been used to dissect genetic contributions to immunity and pathogenesis of chlamydial diseases. Considerable achievements have been made in this field of host genetics. The hope is that these studies will lead to medical applications by helping to elicit the function of genes that are involved in host defense against chlamydia and in progression to severe sequelae. In the present article, we review a selection of findings in the forward genetics of ocular Chlamydia trachomatis infection in humans.

Host genetic contribution to the cellular immune response to Chlamydia trachomatis: Heritability estimate from a Gambian twin study.

If the cellular immune response to Chlamydia trachomatis is subject to genetic influences, the degree and mechanisms of such genetic control may have important implications for vaccine development. We estimated the relative contribution of host genetics to the total variation in lymphoproliferative responses to C. trachomatis antigen by analyzing these responses in 64 Gambian twin pairs from trachoma endemic areas. Zygosity was determined by restriction fragment length polymorphism analysis of minisatellite probes and microsatellite typing. Proliferative responses to serovar A elementary body antigen were estimated in monozygotic (MZ) and dizygotic (DZ) twin pairs. We found a stronger correlation and lower within-pair variability in these responses in MZ than in DZ twin pairs. The heritability estimate was 0.39 (P = 0.07) suggesting that host genetic factors contributed 39% of the variation. A better understanding of these genetic influences will contribute to the elucidation of preventive therapies for ocular C. trachomatis infection and may identify important mechanisms in protection for rational vaccine construction.