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Biomedical subjects

D C Mabey

Publications and source records attributed to D C Mabey.

At least 19 recordsLinked to original sources

Rationale and design of the MEMA kwa Vijana adolescent sexual and reproductive health intervention in Mwanza Region, Tanzania.

Large-scale innovative, integrated, multifaceted adolescent sexual and reproductive health (ASRH) interventions are urgently needed in sub-Saharan Africa. Implementation through schools and health facilities may maximize intervention coverage and sustainability, however the impact of the use of these structures on intervention content and delivery is not well documented. This paper describes the rationale and design of a large-scale multifaceted ASRH intervention, which was developed and evaluated over three years in rural communities in Mwanza Region, North West Tanzania. The intervention comprised community mobilization, participatory reproductive health education in primary schools, youth-friendly reproductive health services and community-based condom provision for youth. We examine the effect of socioeconomic, cultural and infrastructural factors on intervention content and implementation. This paper demonstrates the means by which such interventions can be feasibly and sustainably implemented to a high standard through existing government health and school structures. However, the use of these structures involves compromise on some key aspects of intervention design and requires the development of complementary strategies to access out-of-school youth and the wider community.

Adolescent↗

Distance to water source and altitude in relation to active trachoma in Rombo district, Tanzania.

OBJECTIVES: To investigate the relationship between distance to water source, altitude and active trachoma in children in Rombo district, Tanzania. METHODS: In each of Rombo's 64 villages, 10 balozis (groups of 8-40 households) were selected at random and all resident children aged 1-9 years were examined for clinical signs of active trachoma. The households of these children and village water sources were mapped using differentially corrected global positioning system data to determine each household's altitude and distance to the nearest water supply. RESULTS: We examined 12 415 children and diagnosed 1171 cases of active trachoma (weighted prevalence=9.1%, 95% CI: 8.0, 10.2%). Active trachoma prevalence ranged from 0% to 33.7% across villages. Increasing distance to the nearest water source was significantly associated with rising trachoma prevalence (age-adjusted odds ratio for infection (OR) for highest quartile compared to lowest=3.56, 95% CI 2.47, 5.14, P for trend <0.0001). Altitude was significantly inversely associated with trachoma prevalence (age-adjusted OR for highest quartile compared to lowest=0.55, 95% CI 0.41, 0.75, P for trend <0.0001). These associations remained significant after adjustment in multivariate analysis. CONCLUSIONS: Trachoma is endemic in Rombo district, although the prevalence varies considerably between villages. Spatial mapping is a useful method for analysing risk factors for active trachoma.

Age Distribution↗

The household distribution of trachoma in a Tanzanian village: an application of GIS to the study of trachoma.

The distribution of active trachoma in Kahe Mpya, Tanzania, an endemic village of approximately 1000 people, was mapped spatially and analysed for associated risk factors and evidence of clustering. An association between distance to water source and active disease was demonstrated, although this was reduced after accounting for the lack of independence between cases in the same household. Significant clustering of active trachoma within households was demonstrated, adding support to the hypothesized importance of intra-familial transmission. The spatial distribution of trachoma was analysed using the spatial scan statistic, and evidence of clustering of active trachoma cases detected. Understanding the distribution of the disease has implications for understanding the dynamics of transmission and therefore appropriate control activities. The demonstrated spatial clustering suggests inter-familial as well as intra-familial transmission of infection may be common in this setting. The association between active trachoma and geographical information system (GIS) measured distance to water may be relevant for planning control measures.

Adolescent↗

Pilot study of the use of community volunteers to distribute azithromycin for trachoma control in Ghana.

OBJECTIVE: To assess the skills of community health volunteers in diagnosing active trachoma and distributing azithromycin in the Northern Region of Ghana. METHODS: Six community health volunteers from Daboya were trained to diagnose trachoma and to treat the disease using azithromycin. They were also informed of the drug's possible side-effects. Under supervision, each volunteer then examined, and if necessary treated, 15 households. The dose of azithromycin was determined by weight; height was also measured. Tablets were given in preference to suspension when possible. RESULTS: The volunteers' diagnostic sensitivity for active trachoma was 63%; their specificity was 96%. At the household level, their "decision to treat" was correct in 83% of households. In 344 treatment episodes, volunteers planned a dose of azithromycin outside the range 15-30 mg/kg on only seven occasions (2.0% of all planned treatments). The volunteers' drug management skills were good, the response of the community was excellent, and adverse reactions were infrequent. Diagnosis of active trachoma, record-keeping skills, and knowledge of side-effects were found to need greater emphasis in any future education programme. Most people aged four years or older were able to swallow tablets. For those taking tablets, the correlation between the data gathered for height and weight shows that calculating azithromycin doses by height is a valid alternative to calculating it by weight. CONCLUSION: Trained community health volunteers have a potential role in identifying active trachoma and distributing azithromycin. To simplify training and logistics, it may be better to base dosage schedules on height rather than weight for those taking tablets, which included most people aged four years or more in the population studied.

Adolescent↗

Polymorphisms in the IkappaB-alpha promoter region and risk of diseases involving inflammation and fibrosis.

The transcription factor NFkappaB regulates inflammatory and other cellular responses. In non-stimulated cells, NFkappaB is linked to its inhibitor IkappaB, which plays a major role in controlling NFkappaB activity. Here, the gene promoter region of the major inducible IkappaB component (IkappaB-alpha) was studied to identify single nucleotide polymorphisms (SNPs), and to test if these are associated with risk of two diseases involving inflammation and fibrosis (trachoma and silicosis). Three SNPs were identified at positions -881, -826 and -297 relative to the transcription start site. The position -297 is close to two NFkappaB binding sites, kappaB2 and kappaB3, but the alleles were not associated with either disease. Alleles at positions -881 and -826 were in complete linkage disequilibrium with each other, and the rare haplotype was significantly less frequent among patients with trachoma compared to controls, although there was no difference in frequencies between silicosis patients and controls.

Base Sequence↗

Failure to detect HLA-A*6802-restricted CD8+ T cells specific for Chlamydia trachomatis antigens in subjects from trachoma-endemic communities.

The role of HLA-A*6802-restricted CD8+ T cells in chlamydial disease was investigated in human ocular infections. Peptides with predicted binding motifs for HLA-A*6802 were synthesized using sequences based on chlamydial antigens, major outer membrane protein (MOMP), macrophage infectivity potentiator (MIP) and heat shock protein (hsp70). Peptides were pooled according to Chlamydia trachomatis protein type and serovar, and were tested in 51Cr-release cytotoxic T lymphocyte (CTL) and enzyme-linked immunospot (ELISPOT) assays, using peripheral blood mononuclear cells (PBMC) isolated from subjects living in trachoma-endemic communities in The Gambia. Significant CTL activity or interferon-gamma release was not detected in any of the subjects, suggesting either that HLA-A*6802 CD8+ T cells may not be important in ocular infections or that the peptides chosen did not represent epitopes.

Adolescent↗

Prevalence of HIV and Chlamydia trachomatis infection in 15--19-year olds in rural Tanzania.

OBJECTIVE: To estimate the prevalence of HIV and Chlamydia trachomatis (CT) infections amongst adolescents in rural Mwanza Region, Tanzania and their association with demographic variables. DESIGN: Population-based cross-sectional survey. METHODS: All 15--19-year olds living in households selected by random cluster sampling were invited to participate. After interview, urine was tested for HIV and CT. RESULTS: 9445 15--19-year olds were enrolled. HIV prevalence was 0.6% (95% CI: 0.4--0.8%) in males and 2.4% (95% CI: 2.0--2.8%) in females, and increased steeply with age (trend: P < 0.006 and P < 0.001, respectively). After adjustment for age, risk of HIV infection was significantly associated with female sex (OR=4.3), never having been to primary school in males (OR=2.7), and current symptoms of genital discharge (OR=2.3) or genital ulcer (OR=5.3) in females. The prevalence of CT was 1.0% (95% CI: 0.8--1.4%) in males and 2.4% (95% CI: 2.0-2.9%) in females. After adjustment for age, CT infection was associated with female sex (OR=2.4), reported current symptoms of STD (males OR=2.5, females OR=1.9) and positive leucocyte esterase (LE) test (males OR=3.1, females OR=2.6). Eighty-two percent of males and 79% of females with CT were asymptomatic. There was no association between CT and HIV infection in either sex. CONCLUSIONS: There is a high prevalence of HIV and CT amongst adolescents, especially young women, in this rural population, highlighting the need for effective interventions to improve adolescent reproductive health. The high rates of asymptomatic infection imply that innovative strategies are needed to reach and treat young people with STD.

Adolescent↗

The interrelation of HIV, cervical human papillomavirus, and neoplasia among antenatal clinic attenders in Tanzania.

OBJECTIVES: To determine the prevalence and interrelation of cervical human papillomavirus (HPV) genotypes, squamous intraepithelial lesions (SIL), HIV, and other reproductive tract infections (RTIs) among urban antenatal clinic attenders in Mwanza, Tanzania. METHODS: Genital swabs were collected from 660 pregnant women and tested for a range of RTIs and for cervical cytology. Cervical HPV-DNA was detected by PCR and genotyped. HIV and syphilis serologies were performed. RESULTS: HPV prevalence was 34% (209/612 women). Of the 144 typeable samples, 83% were high risk (HR-HPV) oncogenic strains (56% HPV 16 related types). SIL was detected in 43 women (7%), with high grade SIL in 3%. There was a high prevalence of HIV (15%), and of any RTI (83%). Genital warts were detected in 20 women (3%). HPV infection was associated with some behavioural factors (short duration of relationship, single status, not using condoms) and gonorrhoea. There was no overall association between HPV and HIV (OR=1.02, 95% CI 0.6-1.6), but a non-significant trend towards a stronger association with HR-HPV in women aged 15-19 (OR=2.79, 95% CI 0.8-9.5) and women aged > or =30 (OR=3.20, 95% CI 0.7-15). SIL was associated with HPV (OR=3.66, 95% CI 1.9-7.0), but not significantly with HIV (OR=1.54, 95% CI 0.7-3.4). Prevalence of SIL was higher among women dually positive for HPV/HIV compared to HPV infection only (21% v 12%), although this difference was not statistically significant (p=0.17). CONCLUSIONS: HPV infection was highly prevalent in this young antenatal population. The association of HIV with HR-HPV types in older women may suggest that the principal HIV/HPV interaction in this population is for HIV to upregulate HPV persistence, leading to subsequent development of SIL.

Adolescent↗

Efficacy of oral azithromycin versus topical tetracycline in mass treatment of endemic trachoma.

OBJECTIVE: To compare the impact of mass treatment with oral azithromycin and topical tetracycline on the prevalence of active trachoma. METHODS: A total of 1803 inhabitants from 106 households of eight Gambian villages were randomized, in pairs, to receive either three doses of azithromycin at weekly intervals, or daily topical tetracycline over 6 weeks. Ocular examinations were conducted before treatment, and 2, 6 and 12 months after treatment. FINDINGS: Prior to treatment, 16% of the study participants had active trachoma. Two months after treatment, the prevalence of trachoma was 4.6% and 5.1% in the azithromycin and the tetracycline groups, respectively (adjusted odds ratio (OR) = 1.09; 95% confidence interval (CI) = 0.53, 2.02). Subsequently, the prevalence rose to 16% in the tetracycline group, while remaining at 7.7% in the azithromycin group (adjusted OR at 12 months = 0.52; 95% CI = 0.34, 0.80). At 12 months post-treatment, there were fewer new prevalent cases in the azithromycin group, and trachoma resolution was significantly better for this group (adjusted OR = 2.02; 95% CI = 1.42, 3.50). CONCLUSION: Oral azithromycin therefore appears to offer a means for controlling blinding trachoma. It is easy to administer and higher coverages may be possible than have been achieved hitherto.

Administration, Oral↗

Polymorphisms in candidate genes and risk of scarring trachoma in a Chlamydia trachomatis--endemic population.

Genes involved in regulating antimicrobial immunity and inflammation may modulate the risk of tissue scarring and fibrosis in chlamydial diseases such as trachoma. By use of a large case-control study of scarring trachoma in The Gambia, the importance of single-nucleotide polymorphisms in several candidate genes was investigated. Overall, no significant differences were found between patients and control subjects in genotype frequencies for polymorphisms in cytokine promoters interleukin (IL)-10 (positions -1082, -819, -592), IL-4 (-590), or tumor necrosis factor-alpha (-376) or for codon 57 of the mannose-binding protein. Among the ethnic groups in the study, Mandinkas had the highest frequency of the IL-10-1082G allele (0.36). Within this ethnic group, the IL-10-1082G homozygote genotype was significantly more common among case patients than control subjects (odds ratio, 5.10; 95% confidence interval, 1.24-24.2; P=.009). This single association is consistent with data indicating that the IL-10-1082G allele is associated with higher levels of IL-10 transcription and that Th2-type immune responses are associated with risk of chlamydial disease.

Adolescent↗

Interactions between herpes simplex virus type 2 and human immunodeficiency virus type 1 infection in African women: opportunities for intervention.

Sexually transmitted diseases (STDs) are cofactors for human immunodeficiency virus (HIV) transmission, but the specific role of herpes simplex virus type 2 (HSV-2) is unclear. This study aimed to examine the in vivo relationships between HSV-2 and HIV-1 in 300 women in Bangui, Central African Republic. Sera were tested for syphilis, HIV-1, HSV-2 antibody, and levels of vitamins A and E. Genital specimens were tested for other STDs. HSV-2 DNA and HIV-1 RNA were quantified in cervicovaginal lavage. The prevalences of HSV-2 antibody (91% vs. 78%, P=.02), HSV-2 shedding (43% vs. 22%, P=. 003), and levels of HSV-2 DNA (P=.01) were all significantly higher among HIV-1-seropositive than among HIV-1-seronegative women. There was a significant correlation between genital HIV-1 RNA and HSV-2 DNA levels (P=.02) among the 23 women who were shedding HSV-2 DNA. If confirmed, such associations highlight the urgent need for HSV-2 control measures in populations at high risk of both infections.

Black People↗

Review of the evidence base for the 'F' and 'E' components of the SAFE strategy for trachoma control.

Community control of trachoma as a blinding disease is based on the SAFE strategy of Surgery, Antibiotic therapy, Facial cleanliness and Environmental improvement. Surgery and antibiotic therapy currently dominate most programmes. Blindness from trachoma results from frequent infections repeated over many years, so ultimate success requires the reduction of transmission. This is only likely to be sustainable through the F and E components of SAFE. Environmental improvement with access to water, enhanced hygiene and better sanitation reduces trachoma transmission and the blinding sequelae eventually disappear. Transmission routes and factors that cause this are not known and consequently no single specific tool for F and E is in place. Evidence from intervention studies shows that the promotion of face-washing gave modest gains for intense effort and a pilot study showed that trachoma transmission was reduced in the absence of eye-seeking flies. Other studies have shown that latrines and improved access to water are associated with a lower prevalence of active trachoma. There is likely to be a long-term beneficial effect of a combination of improved water supplies, provision of latrines, facial hygiene promotion through established infrastructure and control of eye-seeking flies. Each of these interventions offers additional public health and other benefits in its own right. Further research on the routes of transmission, the role of hygiene and means of sustainable fly control should be a priority.

Animals↗

Impact of community-based mass treatment for trachoma with oral azithromycin on general morbidity in Gambian children.

BACKGROUND: The World Health Organization has recently targeted the elimination of trachoma as a public health problem by the year 2020. Community-based treatment with antibiotics, including oral azithromycin, is recommended for severely affected communities. The incidence of adverse effects after azithromycin treatment is not known in trachoma endemic communities. METHODS: We compared the effects of azithromycin with those of topical tetracycline given as mass treatment for trachoma on childhood morbidity in eight rural Gambian villages. The entire population of four villages received oral azithromycin suspension (Zithromax, Pfizer) in doses of 20 mg/kg on Days 1, 8 and 15; the other four villages received topical tetracycline eye ointment for 42 days. Morbidity surveys of subjects 3 months to 14 years old were conducted on Days 0, 7, 14, 21 and 28. RESULTS: Of the 804 subjects recruited complete follow-up data were available on 791 (412 azithromycin, 379 tetracycline). Fever and headache were the most common complaints. Apart from cough other symptoms were equally prevalent in both groups at baseline. The azithromycin group had 20% fewer illness, fever and headache episodes and 40% fewer diarrhea and vomiting episodes at follow-up than did the tetracycline group. CONCLUSIONS: Azithromycin treatment for trachoma had favorable short term effects on childhood morbidity in rural Gambian villages, particularly in the high malaria transmission season, and adverse effects were not a problem.

Administration, Oral↗