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Biomedical subjects

David Mabey

Publications and source records attributed to David Mabey.

At least 37 records · Page 2Linked to original sources

Participatory evaluations of trachoma control programmes in eight countries.

OBJECTIVES: Trachoma is a major cause of blindness. The objective of this initiative was to conduct participatory process evaluations of the trachoma control programmes receiving support from the International Trachoma Initiative in eight countries. METHODS: During each 2- to 4-week evaluation we analysed information collected at the central, district and community level through interviews, focus groups, questionnaires, direct observation of trachoma control activities, and existing data. RESULTS: Mapping and assessment of disease prevalence had been completed in four of eight countries. Integration of trachoma control activities into national planning and district-level service provision varied. Intersectoral partnerships to implement the SAFE strategy (i.e. surgery, antibiotics, facial cleanliness and environmental change) were well established in a few countries. In all eight countries, the number of surgeries performed annually was insufficient; and quality of surgery was rarely monitored. Mass distribution of antibiotics was carried out well in extremely resource-poor settings and good coverage was achieved, although the strategy for antibiotic distribution varied. Inadequate water and sanitation remained a major problem in all programme areas. Monitoring of programme activities was generally inadequate. The Morocco programme is an example from which lessons and processes can be learnt and adapted to other programme countries. CONCLUSIONS: Significant achievements have been made in implementing the SAFE strategy. Scaling up of activities to true national coverage should be planned and implemented provided the resources can be made available. Further standardization of how to assess, implement and monitor trachoma control activities will facilitate expansion of the programme.

Africa↗

Antenatal syphilis screening in sub-Saharan Africa: lessons learned from Tanzania.

UNLABELLED: OBJECTIVES; To synthesise data from four recent studies in Tanzania examining maternal syphilis screening and its operational implementation in routine antenatal clinics (ANC), drawing lessons for strengthened antenatal services for the prevention of mother-to-child transmission (PMTCT) of HIV. METHODS: The impact of untreated maternal syphilis was examined in a retrospective cohort of 380 Tanzanian women. Effectiveness and cost-effectiveness of screening and single dose benzathine penicillin treatment were prospectively examined in 1688 pregnant women. Observation, interviews and facility audits were carried out in health facilities within nine districts to determine the operational reality of syphilis screening. RESULTS: Overall, 49% of women with untreated high titre syphilis experienced an adverse pregnancy outcome compared with 11% of uninfected women. Stillbirth and low birthweight rates among those treated for high- or low-titre syphilis were reduced to rates similar to those for uninfected women. The economic cost was $1.44 per woman screened and $10.56 per disability-adjusted life year saved. In the operational study, only 43% of 2256 ANC attenders observed were screened and only 61% of seroreactive women and 37% of their partners were treated. Adequate training, continuity of supplies, supervision and quality control are critical elements for strengthened antenatal services, but are frequently overlooked. CONCLUSIONS: Maternal syphilis has a severe impact on pregnancy outcome. Same-day screening and treatment strategies are clinically effective and highly cost-effective, but there are significant challenges to implementing syphilis screening programmes in sub-Saharan Africa. Current PMTCT interventions present an opportunity to reinforce and improve syphilis screening. Increasing PMTCT coverage will involve similar operational challenges to those faced by syphilis screening programmes.

Anti-Bacterial Agents↗

In vitro effects of spectinomycin and ceftriaxone alone or in combination with other antibiotics against Chlamydia trachomatis.

The in vitro effects of spectinomycin and ceftriaxone, alone or in combination with erythromycin, ofloxacin, and doxycycline, against Chlamydia trachomatis were investigated by the checkerboard method and compared by Ridit (reference identical unit) analysis. A combination of spectinomycin with erythromycin or doxycycline was found to be more effective than that of ceftriaxone.

Anti-Bacterial Agents↗

Mass treatment and the effect on the load of Chlamydia trachomatis infection in a trachoma-hyperendemic community.

PURPOSE: Trachoma remains a leading cause of blindness. Determining the most effective antibiotic treatment strategy is essential for the success of country-based trachoma control programs. METHODS: Baseline and 2-month follow-up examinations were performed in a trachoma-hyperendemic village. All residents were offered azithromycin for trachoma after baseline was determined. Infection with Chlamydia trachomatis and chlamydial load were determined by PCR. Clinical trachoma status was evaluated. A high chlamydial load was defined as a higher than median chlamydial load among those with infection. Risk factors were examined in multiple logistic regression models. Associations are presented as odds ratios and 95% confidence intervals. RESULTS: At baseline, 57% of participants were infected with C. trachomatis. Although clinical trachoma correlated with infection, 23% of participants with high chlamydial loads showed no clinical signs. Adults represented only 10% of the population with high loads. Treatment significantly decreased the proportion positive in the community and the load in the community. However, 27% of individuals with high loads at baseline who received treatment also were infected at 2 months. Of those, 93% with high loads at 2 months were aged < or =10 years. CONCLUSIONS: Although most of the chlamydial load in this community resided in children, 10% of the high load resided in adults, most of whom did not have follicular trachoma and in whom the infection would be missed under treatment strategies that focus on clinical disease or children. These data support a mass treatment strategy for hyperendemic communities, at least as a first approach. In addition, treatment of children age < or =2 years should be reexamined, as >30% with high loads at baseline remained infected at 2 months, despite monitored treatment according to weight.

Adolescent↗

Risk factors for postsurgical trichiasis recurrence in a trachoma-endemic area.

PURPOSE: The World Health Organization recommends trichiasis surgery to prevent blindness caused by trachoma; however, recurrence is common. Risk factors for recurrence have not been widely studied, particularly in trachoma hyperendemic areas. METHODS: Three hundred ninety-four persons with trichiasis in Tanzania were examined. Participants had undergone surgery >18 months before the study. Trichiasis recurrence and active trachoma at study visit were assessed. Ocular swabs were collected and tested for Chlamydia trachomatis. Household members were examined for active trachoma. RESULTS: Of the surgical eyes, 28% had recurrence; 40% of patients had recurrence in one or both eyes. Rates did not vary by time since surgery. Eye-level recurrence rates varied significantly across districts, ranging from 16% to 38%. Current chlamydial infection among surgical cases was low (6%) and was not associated with recurrence. Recurrence was associated with tarsal conjunctival inflammation (OR: 2.4; 95% confidence interval [CI]: 1.6-3.8) and residence in the Kongwa district (OR: 2.3; 95% CI: 1.2-4.6). CONCLUSIONS: Recurrence after trichiasis surgery is high, suggesting that vigilant follow-up in surgical cases is needed to reduce blindness. Recurrence is associated with evidence of inflammation in the tarsal conjunctiva, although it is not clear whether the inflammation contributes to recurrence, or is a result of the recurrence. Longitudinal studies of trichiasis patients after surgery are needed.

Aged↗

Detection of gonococcal infection : pros and cons of a rapid test.

WHO estimates that 62 million cases of gonorrhea occur annually worldwide. Untreated infection can cause serious long-term complications, especially in women. In addition, Neisseria gonorrheae infection can facilitate HIV transmission, and babies born to infected mothers are at risk of ocular infection, which can lead to blindness. Where diagnostic facilities are lacking, gonorrhea can be treated syndromically. However, this inevitably leads to over-treatment, especially in women in whom the syndrome of vaginal discharge may be due not to N. gonorrheae infection but to several other more prevalent conditions. Over-treatment is a major concern because of widespread N. gonorrheae antibiotic resistance. Moreover, a high proportion of gonorrhea cases are asymptomatic and so do not present for syndromic management. Such cases will only be detected by screening tests. The gold standard test for the detection of N. gonorrheae is culture, which has high sensitivity and specificity. However, it requires well trained staff and its performance is affected by specimen transport conditions. Other options include microscopy and tests that detect gonococcal antigen or nucleic acid. Nucleic acid amplification tests (NAATs) have higher sensitivity and can be used on non-invasive samples (urine). However, they can cross-react with other Neisseria species and are expensive, requiring highly trained staff and sophisticated equipment. In settings where patients are asked to return for laboratory results, some infected patients never receive treatment as they fail to return for their test results. This reduction in treatment, and the possible onward transmission of N. gonorrheae during any delay in treatment, means that a rapid test of lower sensitivity may be more effective if it results in patients being treated at the initial visit. Indeed, even with the low sensitivity of currently available rapid tests (50-70%), modeling shows that they can outperform gold standard tests in populations with high sexual activity and/or low return rates. Unfortunately, however, most of the rapid tests currently available are immunoassays that are quite expensive and involve many steps, which limit their current usefulness. In summary, the pros and cons of using a rapid test are dependent on the setting. Culture or NAATs remain the best choice in an ideal setting. However, in settings where laboratory facilities are not available, or in high-risk populations where return rates are low, rapid tests may be the most effective way of diagnosing gonorrhea. Their optimal use in these settings requires the development of simpler and cheaper rapid tests.

Bacteriological Techniques↗

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↗

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↗

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↗

Geographical variations in the prevalence of HIV and other sexually transmitted infections in rural Tanzania.

The prevalence and incidence of HIV and other sexually transmitted infections (STIs) were recorded in two lake-island and eight rural mainland communities in Mwanza, Tanzania. The prevalence and incidence of HIV and syphilis were lower on the islands, but this pattern was not seen for herpes simplex virus type-2, gonorrhoea, chlamydia, male urethritis or antenatal prevalences of Trichomonas vaginalis. Island men reported fewer sexual partners than mainland men but no differences were found for women. Island men were more likely to be circumcised, island women less mobile and there were differences in marriage patterns. Possible explanations for the differences in HIV and syphilis include: slower introduction of HIV into the islands because of geographical isolation, more core-group sexual contact on the mainland, higher prevalence of male circumcision on the islands and differences in marital status. Differences in transmission dynamics may lead to geographical patterns that vary between STIs.

Female↗

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↗

Syphilis in pregnancy in Tanzania. II. The effectiveness of antenatal syphilis screening and single-dose benzathine penicillin treatment for the prevention of adverse pregnancy outcomes.

Treatment for maternal syphilis with single-dose benzathine penicillin (2.4 million units intramuscularly) is being implemented in many parts of sub-Saharan Africa. To examine the effectiveness of this regimen, a prospective cohort of 1688 pregnant women was recruited in Tanzania. Birth outcomes were compared among women treated for high-titer (n=133; rapid plasma reagin [RPR] titer > or = 1:8 and Treponema pallidum hemagglutination assay [TPHA]/fluorescent treponemal antibody [FTA] positive) and low-titer (n=249; RPR titer <1:8 and TPHA/FTA positive) active syphilis and 950 uninfected women. Stillbirth or low-birth-weight live births were observed in 2.3% and 6.3%, respectively, of women treated for high-titer active syphilis and in 2.5% and 9.2%, respectively, of seronegative women. There was no increased risk for adverse pregnancy outcome for women treated for high-titer active syphilis (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.4-1.4) or low-titer active syphilis (OR, 0.95; 95% CI, 0.6-1.5), compared with seronegative women. Single-dose treatment is effective in preventing adverse pregnancy outcomes attributable to maternal syphilis.

Adolescent↗

Syphilis in pregnancy in Tanzania. I. Impact of maternal syphilis on outcome of pregnancy.

To measure the impact of maternal syphilis on pregnancy outcome in the Mwanza Region of Tanzania, 380 previously unscreened pregnant women were recruited into a retrospective cohort at delivery and tested for syphilis. Stillbirth was observed in 18 (25%) of 73 women with high-titer active syphilis (i.e., women with a rapid plasma reagin titer > or = 1 :8 and a positive Treponema pallidum hemagglutination assay or indirect fluorescent treponemal antibody test result), compared with 3 (1%) of 233 uninfected women (risk ratio [RR], 18.1; P<.001). Women with high-titer active syphilis were also at the greatest risk of having low-birth-weight or preterm live births (RR, 3.0 and 6.1, respectively), compared with women with other serological stages of syphilis. Among unscreened women, 51% of stillbirths, 24% of preterm live births, and 17% of all adverse pregnancy outcomes were attributable to maternal syphilis. Syphilis continues to be a major cause of pregnancy loss and adverse pregnancy outcome among women who do not receive antenatal syphilis screening and treatment.

Adult↗

Comparison of HIV prevalences in community-based and antenatal clinic surveys in rural Mwanza, Tanzania.

OBJECTIVES: First, to compare the prevalence of HIV infection among women in the general population and antenatal clinic (ANC) attenders in rural Mwanza, Tanzania, and second, to validate a method for adjusting HIV prevalence in ANC attenders to estimate the prevalence in the general female population aged 15-44 years. METHODS: A cross-sectional population survey was conducted in 12 rural communities of Mwanza Region between 1991 and 1992. From the same communities sequential ANC attenders were recruited on two occasions between 1991 and 1993. Consenting subjects were interviewed, examined, treated and a serum sample was tested for HIV. The HIV prevalence in women in the general population was compared with unadjusted and adjusted prevalences in ANC attenders. Parity-adjusted prevalences were obtained by applying correction factors to the observed prevalences in parous and nulliparous ANC attenders. RESULTS: A total of 5675 women aged 15-44 years from the general population and 2265 ANC attenders had complete socio-demographic and laboratory data. Unadjusted HIV prevalence was significantly lower in ANC attenders (3.6%) than women from the general population (4.7%, P = 0.025), but after adjustment there was no significant difference between the two groups (4.6 versus 4.7%, P = 0.95). CONCLUSION: In this rural population, the HIV prevalence in ANC attenders underestimated the prevalence among women in the general population, but this difference was eliminated by applying parity-based correction factors. Information on parity should be routinely collected in ANC-based HIV sentinel surveillance.

Adolescent↗

Herpes simplex virus type 2 infection increases HIV incidence: a prospective study in rural Tanzania.

OBJECTIVES: To quantify the association between prevalent or incident Herpes simplex virus type-2 (HSV2) infection and the incidence of HIV seroconversion among adults in the general population in rural Tanzania. STUDY POPULATION: Adults aged 15-54 years sampled randomly from 12 rural communities in Mwanza Region, Tanzania and recruited to a randomized trial of improved treatment of sexually transmitted diseases. STUDY DESIGN: Unmatched case-control study nested within trial cohort. METHODS: Participants included 127 cases who seroconverted to HIV during the 2-year follow-up period and 636 randomly selected controls who remained HIV negative. Subjects were tested for HSV2 serology at baseline and follow-up, and associations between HIV and HSV2 were analysed with adjustment for socio-demographic and behavioural factors. RESULTS: After adjusting for confounding factors, a strong association between HSV2 infection and HIV seroconversion was observed in men (test for trend: P < 0.001), with adjusted odds ratios (OR) of 6.12 [95% confidence interval (CI), 2.52-14.9] in those HSV2 positive at baseline, and 16.8 (95% CI, 6.06-46.3) in those acquiring HSV2 infection during follow-up. A weaker association was observed in women (tests for trend: P = 0.14), with adjusted OR of 1.32 (95% CI, 0.62-2.78) and 2.36 (95% CI, 0.81-6.84), respectively. Population attributable fractions of incident HIV infection due to HSV2 were estimated as 74% in men and 22% in women. CONCLUSIONS: The results suggest that HSV2 plays an important role in the transmission of HIV infection in this population. There is an urgent need to identify effective HSV2 control measures in order to reduce HIV incidence in Africa.

Adolescent↗

Morbidity and nutritional impairment in relation to CD4 count in a Zambian population with high HIV prevalence.

The HIV epidemic has greatly increased morbidity in many African cities and severe undernutrition is a prominent feature of the clinical presentation. However, there is little information about the relationship of morbidity or nutritional status to immune damage at a population level. We report a cross-sectional study of morbidity and nutritional status in relation to CD4 count in an impoverished urban community in Lusaka, Zambia, at enrollment into a longitudinal study. Over a 2 month period in 1999, 261 (52%) of 506 adults resident in one area were interviewed and examined. Of 186 adults who consented to testing, 33 (51%) of 65 who were HIV seropositive reported symptoms of disease compared to 39 (32%) of 121 who were HIV seronegative (OR 2.2, 95%CI 1.1-4.2; P=0.02). Peripheral blood CD4 counts in HIV seronegative individuals were broadly similar to norms in developed countries, but 8 (7%) had CD4 counts below 500 cells/microl. Morbidity in HIV seropositive adults was dominated by tuberculosis (n=11), other respiratory infections (5) or persistent diarrhoea (4), and affected individuals had a wide range of CD4 counts. Nutritional impairment was evident in HIV seropositive adults with clinical evidence of opportunistic infection (OI), not those with asymptomatic HIV infection. Unexpectedly, we also noted that systolic blood pressure was reduced progressively in HIV infection and in those with OI. In conclusion, HIV-related morbidity was dominated by a small number of treatable infectious diseases occurring over a wide range of CD4 count. Nutritional impairment was associated with OI.

Adult↗