Biomedical subjects

Anthony W Solomon

Publications and source records attributed to Anthony W Solomon.

7 recordsLinked to original sources

PubMed2003

Strategies for control of trachoma: observational study with quantitative PCR.

BACKGROUND: Antibiotics are an important part of WHO's strategy to eliminate trachoma as a blinding disease by 2020. At present, who needs to be treated is unclear. We aimed to establish the burden of ocular Chlamydia trachomatis in three trachoma-endemic communities in Tanzania and The Gambia with real-time quantitative PCR. METHODS: Conjunctival swabs were obtained at examination from 3146 individuals. Swabs were first tested by the qualitative Amplicor PCR, which is known to be highly sensitive. In positive samples, the number of copies of omp1 (a single-copy C trachomatis gene) was measured by quantitative PCR. FINDINGS: Children had the highest ocular loads of C trachomatis, although the amount of pooling in young age groups was less striking at the site with the lowest trachoma frequency. Individuals with intense inflammatory trachoma had higher loads than did those with other conjunctival signs. At the site with the highest prevalence of trachoma, 48 of 93 (52%) individuals with conjunctival scarring but no sign of active disease were positive for ocular chlamydiae. INTERPRETATION: Children younger than 10 years old, and those with intense inflammatory trachoma, probably represent the major source of ocular C trachomatis infection in endemic communities. Success of antibiotic distribution programmes could depend on these groups receiving effective treatment.

Adolescent↗

PubMed2003

Trachoma.

Trachoma is the most common infectious cause of blindness. It is caused by ocular serovars of Chlamydia trachomatis. Transmission is favoured in poor communities, where crowding is common and access to water and sanitation inadequate. Repeated reinfection over many years causes dense scarring of the upper eyelid. The resultant inversion of the lashes abrades the eyeball, and the abrasion leads to corneal opacification and visual impairment. The host immune response is probably at least partly the cause of this process. The "SAFE" strategy is used for the control of trachoma: surgery for in-turned lashes, antibiotics for active disease, facial cleanliness, and environmental improvement. The demonstration that a single oral dose of the antibiotic azithromycin is as effective as 6 weeks of topical tetracycline was an important advance in trachoma control. By means of the SAFE strategy, WHO and its partners aim to eliminate trachoma as a public-health problem by the year 2020.

Chlamydia trachomatis↗

PubMed2003

A critical review of the SAFE strategy for the prevention of blinding trachoma.

Trachoma is an ocular disease caused by repeated infection with Chlamydia trachomatis. It is the leading cause of infectious blindness globally, responsible for 5.9 million cases of blindness. Although trachomatous blindness is untreatable, it is eminently possible to prevent and the World Health Organization promotes the use of the SAFE strategy (surgery to treat end-stage disease, antibiotics to reduce the reservoir of infection, facial cleanliness, and environmental improvement to reduce transmission of C trachomatis) for this purpose. In this review we have assessed the evidence base supporting the elements of the SAFE strategy. We find strong support for the efficacy of the surgery and antibiotics components, although the optimal antibiotic regimens have not yet been established. The evidence for an effect of health education and environmental improvement is weaker, and depends mostly on cross-sectional observational studies.

Anti-Bacterial Agents↗

PubMed2003

Impact of azithromycin administration for trachoma control on the carriage of antibiotic-resistant Streptococcus pneumoniae.

Community distribution of azithromycin has an important role to play in trachoma control. Previous studies have suggested that this may increase the prevalence of macrolide-resistant Streptococcus pneumoniae. S. pneumoniae was isolated from children under 7 years of age in Rombo District, northern Tanzania, before and 2 and 6 months after community-wide administration of azithromycin. Overall carriage rates were 11, 12, and 7%, respectively. Only one macrolide-resistant isolate carrying the mef gene was obtained 6 months after azithromycin administration. This contrasted with cotrimoxazole and penicillin resistance, both of which were common (cotrimoxazole resistance, 42, 43, and 47%, and penicillin resistance, 21, 17, and 16% at baseline, 2 months, and 6 months, respectively). There was a significant association between cotrimoxazole and penicillin resistance (P < 0.0001, Fisher's exact). These data suggest that in communities where macrolide resistance is rare, azithromycin distribution for trachoma control is unlikely to increase the prevalence of resistant organisms.

Anti-Bacterial Agents↗

PubMed2003

Antibiotic dosage in trachoma control programs: height as a surrogate for weight in children.

PURPOSE: National programs for trachoma control are implementing mass treatment programs in which azithromycin is used as part of the control strategy. Dose is determined by weight, which can be difficult to determine in field conditions. The purposes of this study were to determine whether an accurate dose could be determined by using height as a surrogate for weight and whether a single model of height-based dosage would be applicable in more than one setting. METHODS: Data on height, weight, age, and gender of 5558 children aged 6 months to15 years were obtained from Kongwa and Rombo, Tanzania; Malakal, Sudan; Jareng, The Gambia; and Daboya, Ghana. Models for predicting weight by measuring height were developed that incorporated country-specific parameters. Doses of azithromycin assumed suspension of 40 mg/mL and 250-mg tablets that could be halved. Tolerance limits were defined as 15 to 30 mg/kg. RESULTS: A regression model, predicting log weight as a function of log height, was the best fit and explained 94% of the variance. In children less than 1 year of age or 60 cm in height, dose determined by weight was preferred. Dosage by height resulted in more than 97% of children receiving doses within the tolerance limits. Children aged 1 to 2 years were the group most likely to be over- or undermedicated, but this occurred in only 6% of this age group. CONCLUSIONS: Height-based determination of dosage of azithromycin in trachoma control programs appears to be feasible, using the height-based schedule proposed. One model was adequate for all the countries in the study. Further expansion to other countries is warranted.

Adolescent↗

PubMed2003

Polymorphisms in Chlamydia trachomatis tryptophan synthase genes differentiate between genital and ocular isolates.

We previously reported that laboratory reference strains of Chlamydia trachomatis differing in infection organotropism correlated with inactivating mutations in the pathogen's tryptophan synthase (trpBA) genes. Here, we have applied functional genomics to extend this work and find that the paradigm established for reference serovars also applies to clinical isolates - specifically, all ocular trachoma isolates tested have inactivating mutations in the synthase, whereas all genital isolates encode a functional enzyme. Moreover, functional enzyme activity was directly correlated to IFN-gamma resistance through an indole rescue mechanism. Hence, a strong selective pressure exists for genital strains to maintain a functional synthase capable of using indole for tryptophan biosynthesis. The fact that ocular serovars (serovar B) isolated from the genital tract were found to possess a functional synthase provided further persuasive evidence of this association. These results argue that there is an important host-parasite relationship between chlamydial genital strains and the human host that determines organotropism of infection and the pathophysiology of disease. We speculate that this relationship involves the production of indole by components of the vaginal microbial flora, allowing chlamydiae to escape IFN-gamma-mediated eradication and thus establish persistent infection.

Antigens, Bacterial↗

PubMed2003

Application of molecular tools in the control of blinding trachoma.

The use of anti-chlamydial antibiotics for trachoma control is based on the assumption that most people with clinically active disease have conjunctival infection with Chlamydia trachomatis. In high prevalence areas, this is generally true. As prevalence decreases, however, the positive predictive value of clinical signs for C. trachomatis infection also decrease. In this paper, the case for using laboratory assays to guide trachoma control strategies is presented, molecular methods for diagnosis (such as a ligase chain reaction and a polymerase chain reaction [PCR]) are compared with earlier techniques, and recent findings of ongoing studies using a quantitative PCR are reviewed. In addition, the contribution of genotyping to our understanding of the epidemiology and biology of C. trachomatis is considered.

Anti-Bacterial Agents↗