Goals for girls: a cluster-randomized trial to investigate a school-based sexual health programme amongst female learners in South Africa.

The delivery of comprehensive sexuality education to adolescents at school is recognized as a long-term strategy to support adolescent health. Suboptimal sexual and reproductive health (SRH) outcomes among South African adolescents necessitate the ongoing development and optimization of SRH education and promotion models. We conducted a cluster-randomized controlled trial amongst secondary schools (n = 38) in Cape Town, South Africa, to evaluate a sport-based, near-peer-led SRH curriculum, SKILLZ, amongst female learners (n = 2791). Biomedical (sexually transmitted infections [STIs], human immunodeficiency virus [HIV] and pregnancy) and socio-behavioural (social support, gender norms and self-concept) outcomes were assessed pre and post intervention. Attendance at SKILLZ was low and intervention participants did not show an improvement in SRH outcomes, with HIV and pregnancy incidence remaining stable and STI prevalence remaining high and increasing in both control and intervention arms. Although evidence of positive socio-behavioural measures was present at baseline, participants with high attendance showed further improvement in positive gender norms. SKILLZ did not demonstrate the capacity to significantly impact clinical SRH outcomes. Modest improvements in outcomes amongst high attenders suggest that the impact may be possible with improved attendance; however, in the absence of optimal attendance, alternative intervention strategies may be required to improve SRH outcomes amongst adolescents.

Relationship between environmental exposure to pesticides and anthropometric outcomes of boys in the rural Western Cape, South Africa.

BACKGROUND: Rural residents in the Western Cape (WC), South Africa (SA) are highly exposed to agricultural pesticides that could impact their reproductive development. However, epidemiological evidence of the effect of pesticides on pubertal growth is contradictory. OBJECTIVE: To investigate the effect of pesticide exposure measured using indices of environmental exposure to pesticides on the pubertal growth of boys in rural WC, SA. METHODS: A cross-sectional study of 269 boys (177 of whom gave a history of residing on farms) was conducted. A questionnaire was administered, height and weight were measured and body mass index was calculated. A proximity index (PI) and spraying index (SI) was developed, measuring the lifetime average home distance from pesticide spraying and average frequency of spraying pesticides on a farm, respectively. RESULTS: Median age of boys was 12.4 years (interquartile range 9.5 - 13.3). More than 60% boys had height and weight <50th percentile for age. After adjusting for confounders, PI was significantly associated with shorter stature and lower weight (-1.7 cm/10-fold decrease, p=0.02 and -1.24 kg/10-fold decrease, p=0.04; respectively) and SI was non-significantly associated (-1.4 cm/10-fold increase, p=0.05 and -1.1 cm/10-fold increase, p=0.06; respectively). Associations were stronger for boys aged <11 years and were weaker when excluding non- farm boys. There were no other associations between outcome and exposure. CONCLUSIONS: The use of quantitative exposure indices showed that lower heights and weights might be associated with pesticide exposure in farm boys v. non-farm boys, but not among farm boys. Lower anthropometric measurements among farm boys v. non-farm boys appear stronger at a younger age. The indices of environmental exposure to pesticides require further development.

Nourishing networks: an interprofessional learning model and its application to the Australian rural health workforce.

CONTEXT: Access to continuing professional development for rural health clinicians requires strategies to overcome barriers associated with finances, travel and a lack of resources. Approaches to providing professional development need to transcend conventional educational methods and consider interprofessional educational opportunities to meet the diverse needs of the rural health workforce. Rural clinicians often work in professional isolation and frequently work collaboratively with clinicians from a range of other health disciplines. Interprofessional learning and practice is therefore important in a rural areas as clinicians working in these settings are often more reliant on each other and require an understanding of other's roles to provide effective health care. In addition, specialist services are limited in rural areas, with health professionals increasingly required to perform extended roles at an advanced-practice level. ISSUES: A model for interprofessional learning has been developed to attempt to address the barriers related to the delivery of interprofessional education in the rural health setting in Australia. This model demonstrates a flexible approach to interprofessional learning which meets different educational needs across a number of health disciplines, and is tailored to varying levels of expertise. It incorporates three learning approaches: traditional learning, flexible learning and advanced practice. Each of these components of the model are described and the Nourishing Networks program is provided as an example of the application of the model in a rural setting, utilising 'eating disorders' as the educational topic. LESSONS LEARNED: Interprofessional learning can be delivered effectively in a rural setting by utilising technology to help bridge the isolation experienced in rural practice. Challenges in delivering the interprofessional learning program included: engaging rural general practitioners, utilising technology and maintaining participant engagement. The use of technology is essential to access a broad group of rural clinicians however, there are limitations in its use that must be acknowledged. The pilot of the Stepped Interprofessional Rural Learning Model and its application to eating disorders has scope for use in delivering education for other health topics.

Multiplexed, rapid point of care platform to quantify allergen-specific IgE.

Variation of probe immobilization on microarrays hinders the ability to make high quality, assertive and statistically relevant conclusions needed in the healthcare setting. To address this problem, we have developed a calibrated, compact, inexpensive, multiplexed, dual modality point-of-care detection platform that calibrates and correlates surface probe density measured label-free to captured labeled secondary antibody, is independent of chip-to-chip variability, and improves upon existing diagnostic technology. We have identified four major technological advantages of our proposed platform: the capability to perform single spot analysis based on the fluorophore used for detection, a 10-fold gain in fluorescence signal due to optimized substrate, a calibrated, quantitative method that uses the combined fluorescent and label-free modalities to accurately measure the density of probe and bound target for a variety of systems, and a compact measurement platform offering reliable and rapid results at the doctor's office. Already, we have formulated over a 90% linear correlation between the amount of probe bound to surface and the resulting fluorescence of captured target for IgG, ß-lactoglobulin, Ara h 1 peanut allergen, and Phl 5a Timothy grass allergen.

Three years of erlotinib in routine practice for non-small cell lung cancer in South East Scotland.

We present a review of 111 patients who were treated over an initial 3-year period with erlotinib. The median treatment time was 68 days and 59% of patients had stopped treatment within the first 3 months. However, 20 patients were on erlotinib for more than 12 months. Performance status and smoking history were the significant prognostic factors. The overall 3-year survival in patients who had never smoked was 26%.

Pharmacokinetics of sulfadoxine and pyrimethamine in intermittent preventive treatment of malaria in pregnancy.

Malaria during pregnancy is associated with maternal and fetal morbidity and mortality. In order to minimize the burden, sulfadoxine-pyrimethamine (SP) is widely used in Africa as an intermittent preventive treatment of malaria in pregnancy (IPTp). However, only limited data are available on the pharmacokinetics of sulfadoxine and pyrimethamine during pregnancy. We conducted a prospective, self-matched, multicenter study of 98 pregnant women in four African countries in order to determine the effects of pregnancy on SP pharmacokinetics. After adjusting for the effects of potential confounders, blood concentrations (associated with therapeutic efficacy) of pyrimethamine were higher (geometric mean ratio (GMR) 1.33; 95% confidence interval (CI) 1.18-1.51; P < 0.001) and those of sulfadoxine were lower (GMR 0.91; 95% CI 0.84-0.98; P = 0.013) on day 7 after SP administration during pregnancy than after the postpartum period. SP pharmacokinetic parameters differed significantly among the study sites. Given the inconsistency of changes in pharmacokinetic parameters between sulfadoxine and pyrimethamine as well as among the study sites, it is not possible to recommend any dose adjustment to prolong the therapeutic life span of the fixed dose combination of SP for IPTp on the basis of our study findings.

Alveolar macrophage activation and an emphysema-like phenotype in adiponectin-deficient mice.

Adiponectin is an adipocyte-derived collectin that acts on a wide range of tissues including liver, brain, heart, and vascular endothelium. To date, little is known about the actions of adiponectin in the lung. Herein, we demonstrate that adiponectin is present in lung lining fluid and that adiponectin deficiency leads to increases in proinflammatory mediators and an emphysema-like phenotype in the mouse lung. Alveolar macrophages from adiponectin-deficient mice spontaneously display increased production of tumor necrosis factor-alpha (TNF-alpha) and matrix metalloproteinase (MMP-12) activity. Consistent with these observations, we found that pretreatment of alveolar macrophages with adiponectin leads to TNF-alpha and MMP-12 suppression. Together, our findings show that adiponectin leads to macrophage suppression in the lung and suggest that adiponectin-deficient states may contribute to the pathogenesis of inflammatory lung conditions such as emphysema.

Incidence of seropositive myasthenia gravis in Cape Town and South Africa.

BACKGROUND: Myasthenia gravis (MG) is a treatable autoimmune disease characterised by fatiguable weakness of skeletal muscles. More than 85% of MG patients have antibodies to the acetylcholine receptor (AChR) at the neuromuscular junction or are seropositive for MG (SPMG). In the developed world the incidence of MG has increased, particularly among older individuals, but no epidemiological studies have been done on SPMG in Africa. OBJECTIVES: To determine the annual incidence rate (IR) of SPMG in the Cape Town (CT) municipality, and the crude annual IR of SPMG for the whole of South Africa (SA). METHODS: Positive AChR antibody tests were identified between 1 January 2003 and 1 January 2005 for patients living in CT, and the age- and sex-specific incidences were calculated. To determine the national crude annual IR over the same period, positive assays were identified from the laboratories that process AChR assays for SA. National Census 2001 population statistics formed the denominators. RESULTS: There were 65 positive assays in CT, and 230 nationwide. Based on these figures the annual IR for CT was 11.2 per million per year (95% confidence interval (CI) 8.7 - 14.3), and for South Africa 2.6 per million/year (95% CI 2.2 - 2.9). After a questionnaire response from CT neurologists regarding the routine use of the AChR antibody assay, the annual IR for CT was adjusted to 12.6 per million (95% CI 9.9 - 15.9) to incorporate those presumed to have SPMG without a confirmatory test. In CT, the IR in females was 15.3 per million/year (95% CI 11.2 - 20.4), and in males, 6.8 per million/year (95% CI 4.1 - 10.7). The CT IRs for blacks, coloureds and whites were not statistically different after adjusting for age and gender. The IR of SPMG in CT was 6 times greater in those presenting after the age of 50 years than in those with earlier disease onset (95% CI 3.7 - 9.7). CONCLUSIONS: The annual IR of SPMG in CT is much the same as rates recorded recently in other developed countries, but the rest of SA has a much lower IR. A preponderance of MG starting after the age of 50 years reflects a worldwide trend, although the CT data showed a relatively lower-than-expected incidence for older males. IRs for SPMG vary widely in different regions in SA; this is likely to be related to differences in regional health care delivery, and underdiagnosis.

Myasthenia gravis in South Africans: racial differences in clinical manifestations.

We present data on the phenotypic variation in myasthenia gravis of 205 subjects from a multi-racial South African cohort. Consecutive subjects seen more than twice from 1996 to 2006, were included. Documented observational data included a myasthenia gravis and extra-ocular eye muscle score. Results showed Black subjects were more likely than Whites to develop treatment-resistant complete ophthalmoplegia and ptosis (18% vs. 2%; p=0.041). Of the 14 patients with this phenotype, 13 had generalised disease and positive AChR antibodies. Despite similar sized cohorts, White subjects were more likely than Blacks to develop generalised myasthenia poorly responsive to therapy (p=0.005). There were no significant racial differences in the time between diagnosis to initiation of therapy, or the performance and timing of thymectomy. The racial variation in some phenotypic features of myasthenia gravis and outcome to therapy, highlights the need to study biological factors in different subgroups to develop a more rational approach to immuno-suppressive therapy.

Improving outcomes for limited stage small cell lung cancer patients in Scotland with concomitant chemoradiation.

AIMS: To determine whether the introduction of early concomitant chemoradiotherapy for patients with limited stage small cell lung cancer (LS-SCLC) has resulted in acceptable outcomes and toxicity in a UK practice. MATERIALS AND METHODS: The case records of all patients with LS-SCLC treated with chemoradiotherapy from July 2001 to 2004 were reviewed, and subjected to descriptive statistics and proportional hazards analysis. RESULTS: Concomitant chemoradiotherapy was delivered to 30 patients and sequential chemoradiotherapy was delivered to 36 patients. The former patients tended to be younger (mean 58.9 vs 64.1 years, P=0.01); the latter patients tended to have bulkier disease. There was no difference in performance status, but cisplatin was given more often in the former group (90% vs 44%, P<0.0001). Grade 3 acute oesophagitis occurred in less than 10% of either group and there were no cases of grade 3 or greater pneumonitis. Two-year actuarial survival for the concomitant group was 53% (95% confidence interval 36-71%) and 36% (95% confidence interval 20-52%) for the sequential group (P=0.018). Proportional hazards analysis showed an increased hazard of death with increasing performance status and age, sequential therapy and the use of cisplatin with sequential therapy. CONCLUSION: Concomitant chemoradiotherapy can be safely given in a UK population with outcomes comparable with those reported in North American series.

Comparison of mantoux skin test with three generations of a whole blood IFN-gamma assay for tuberculosis infection.

SETTING: A rural town in South Africa. OBJECTIVE: To compare the performance of Quanti-FERON assays with the tuberculin skin test (TST) for identifying latent tuberculosis infection (LTBI) in a high TB burden community. DESIGN: In a cross-sectional study in healthy adults, we applied the TST and took blood for the three generations of QuantiFERON assays. RESULTS: Of 358 participants whose results were analysed, 291 (81%) had a TST result of > or = 10 mm induration, and 187 (52%) > or = 15 mm. QuantiFERON-TB was positive in 215 (60%), QuantiFERON-TB Gold in 137 (38%), and QuantiFERON-TB Gold (In-Tube method) in 201 (56%). There was poor agreement between TST and QuantiFERON tests, and between the different generations of QuantiFERON tests (kappa = 0.12-0.50). Of the subset with TST indurations > or = 15 mm, 30-56% had negative QuantiFERON tests. However, positive Quanti-FERON tests were associated with males, who have a higher incidence of TB in this area. CONCLUSION: We showed poor agreement between TST and the different QuantiFERON tests in diagnosing LTBI. The surprising discordance between the Quanti-FERON TB Gold and QuantiFERON TB Gold (In-Tube method) tests needs to be investigated further.

The first 5 years of the family clinic for HIV at Tygerberg Hospital: family demographics, survival of children and early impact of antiretroviral therapy.

BACKGROUND: Family clinics address the problems of HIV-infected children and their families. The aims were to document demographics of the children and caregivers attending the Family Clinic for HIV at Tygerberg Academic Hospital (TAH) and to investigate factors affecting disease progression in children. METHODS: A retrospective folder review of children and parents attending the Family Clinic at TAH between January 1997 and December 2001, a period noted for its lack of antiretroviral treatment. RESULTS: Of 432 children seen for testing, 274 children, median age 16.9 months, were HIV-infected. During follow-up, 46 children died (median age 23 months) and 113 were lost to follow-up. The majority of children were malnourished. Those <2 years of age had lower weight for age Z-scores (WAZ) than older children (p<0.001). At presentation, 47 per cent were in clinical stage B and two-thirds had moderate or severe CD4+ T cell depletion. Seventeen children had received highly active antiretroviral therapy (HAART), 12 dual and 31 monotherapy. HAART was associated with improved survival compared to dual or monotherapy. Risk of death was reduced from eleven-fold for a WAZ <-4 to four-fold between -2 and -3. There was no association with immunological and clinical classification at entry and risk of mortality. Only 18 per cent of parents were evaluated in the clinic. Non-parental care was documented for 25 per cent of families. CONCLUSIONS: A low WAZ is associated with poor survival in children. Nutritional status should receive more attention in HIV disease classification in children. Parent utilization of the clinic was inadequate. Even in the absence of HAART, extended survival in children is possible.

Improving access to diagnostics: an evaluation of a satellite laboratory service in the emergency department.

OBJECTIVES: To measure the impact of a satellite laboratory upon laboratory result turnaround times and clinical decision making times. DESIGN: A prospective cohort study, the intervention group had blood tests sent Monday to Friday 12 noon to 8 pm and the control group had blood tests sent outside these hours. The data were collected over a six week period before the laboratory was opened, and a subsequent six week period. SETTING: An urban teaching hospital emergency department. PARTICIPANTS: 1065 patients requiring blood tests. MAIN OUTCOME MEASURE: Time from the blood sample being sent to the laboratory to the results being available on the clinician's computer. RESULTS: The time to haematology (blood count) results in the intervention group decreased by 47.2 minutes (95% CI 38.3 to 56.1, p<0.001) after the laboratory was opened. The corresponding control group times were unchanged (0.6 minutes; -13.8 to 15.0, p = 0.94). Similar sized differences were also seen for haemostasis (d-dimer) testing 66.1 (41.8 to 90.4) minutes compared with -14.2 (-47.1 to 18.7) and chemistry 41.3 (30.3 to 52.2) compared with -4.2 (-17.4 to 8.9) testing. Decisions to discharge patients were significantly faster (28.2 minutes, 13.5 to 42.8, p<0.0001) in the intervention group after the laboratory was opened (controls; -2.6 minutes -27.0 to 21.7). No change was seen with decisions to admit patients. There was a trend for earlier laboratory results modifying intravenous drug or fluids orders, or both (p = 0.06) CONCLUSION: A comprehensive satellite laboratory service is an important adjunct to improve the timeliness of care in the emergency department.

Efficacy of rectal artesunate compared with parenteral quinine in initial treatment of moderately severe malaria in African children and adults: a randomised study.

BACKGROUND: Many patients with malaria of increasing severity cannot take medicines orally, and delay in injectable treatment can be fatal. We aimed to assess the reliability of absorption, antimalarial efficacy, and tolerability of a single rectal dose of artesunate in the initial management of moderately severe falciparum malaria. METHODS: 109 children and 35 adults were randomly assigned to rectal artesunate (single dose of about 10 mg/kg) or parenteral quinine treatment (10 mg/kg at 0, 4, and 12 h). The primary endpoint was the proportion of patients with peripheral asexual parasitaemia of less than 60% of that at baseline after 12 h. Secondary endpoints were clinical response and concentrations of drug in plasma. Analysis was by intention-to-treat. FINDINGS: All artesunate-treated patients had pharmacodynamic or pharmacokinetic evidence of adequate drug absorption. 80 (92%) of 87 artesunate-treated children had a 12 h parasite density lower than 60% of baseline, compared with three of 22 (14%) receiving quinine (relative risk 0.09 [95% CI 0.04-0.19]; p<0.0001). In adults, parasitaemia at 12 h was lower than 60% of baseline in 26 (96%) of 27 receiving artesunate, compared with three (38%) of eight receiving quinine (relative risk 0.06 [0.01-0.44]; p=0.0009). These differences were greater at 24 h. Clinical response was equivalent with rectal artesunate and parenteral quinine. INTERPRETATION: A single rectal dose of artesunate is associated with rapid reduction in parasite density in adults and children with moderately severe malaria, within the initial 24 h of treatment. This option is useful for initiation of treatment in patients unable to take oral medication, particularly where parenteral treatment is unavailable.

Exogenous interleukin-16 inhibits antigen-induced airway hyper-reactivity, eosinophilia and Th2-type cytokine production in mice.

BACKGROUND: IL-16 has been described as a natural soluble CD4-ligand with immunosuppressive effects in vitro. However, little is known about the effect of IL-16 on immune responses in vivo. OBJECTIVE: In the present study, we examined the effect of IL-16 administration in a murine model of allergic asthma. Next, we determined whether these effects were mediated by modulation of CD4+ T lymphocytes. METHODS AND RESULTS: Intraperitoneal administration of IL-16 completely inhibits antigen-induced airway hyper-responsiveness and largely decreases the number of eosinophils in bronchoalveolar lavage fluid (> 90%) and airway tissue of ovalbumin-sensitized and challenged mice. Firstly, it appears that thoracic lymph node cells isolated from in vivo IL-16-treated ovalbumin-challenged animals produce less IL-4 (77%) and IL-5 (85%) upon antigenic re-stimulation, when compared to vehicle-treated mice. Secondly, pre-incubation of lymphocytes with IL-16 in vitro reduces antigen-induced proliferation (55%) and Th2-type cytokine production (IL-4; 56%, IL-5; 77%). Thirdly, the presence of IL-16 during priming cultures of TCR transgenic T cells (DO11.10), reduces IL-4 (33%) and IL-5 (35%), but not IL-10 and IFNgamma levels upon re-stimulation. CONCLUSION: It can be concluded that IL-16 has potent immunosuppressive effects on a Th2dominated allergic airway response.

Improving the accessibility of condoms in South Africa: the role of informal distribution.

Lack of access to condoms presents a fundamental barrier to HIV prevention across most of sub-Saharan Africa. One strategy to enhance the accessibility of condoms is to promote their informal distribution outside of health facilities through existing social networks. To investigate the prevalence and practices of informal condom distribution, we administered a questionnaire to individuals procuring condoms at 12 public health facilities in four regions of South Africa. Of the 554 individuals interviewed, 269 (48%) reported either giving or receiving condoms informally in the month before the study. In multivariate analysis, reporting informal condom distribution was associated with increased education, male gender, multiple sex partners and recent condom use. The specific practices involved in giving or receiving condoms differed between males and females, with women more likely to involve family members and men more likely to involve friends. These results indicate that informal condom distribution is surprisingly common among individuals procuring public sector condoms in South Africa, and begin to suggest the gendered nature of informal condom distribution networks. While these findings require confirmation in other populations, the practices of informal condom distribution described here provide an excellent opportunity for enhancing condom accessibility and delivering other interventions for HIV prevention.

Il-9 stimulates release of chemotactic factors from human bronchial epithelial cells.

Interleukin (IL)-9 is a T helper 2 cytokine implicated as a candidate gene and contributor to human asthma. We hypothesized that the inflammatory potential of bronchial epithelium is affected by its local environment and explored this hypothesis with respect to the effect of IL-9 on bronchial epithelium. We investigated the response of primary and immortalized human bronchial epithelial cells to IL-9 stimulation with respect to the release of T-cell chemoattractant factors. In response to IL-9, the HBE4-E6/E7 cell line, but not BEAS-2B cells, released the T-cell chemoattractants IL-16 and regulated on activation, normal T cells expressed and secreted (RANTES) in a dose-dependent fashion. We found a similar dose response to IL-9 in primary cells from bronchial brushings of healthy subjects and that nearly all of the T-cell chemoattraction was attributable to IL-16 and RANTES. Reverse transcriptase/polymerase chain reaction of BEAS-2B, HBE4-E6/E7, and primary cells from two subjects revealed messenger RNA for IL-9 receptor (IL-9R) alpha but not in BEAS-2B cells. Fluorescence-activated cell sorter analysis of HBE4-E6/E7 and primary cells confirmed surface expression of the IL-9 receptor. Costimulation of both cell types with IL-9 and antibody to either gamma-common chain or IL-9Ralpha completely blocked the release of T-cell chemoattractant activity, confirming the primary role of a functioning IL-9 receptor for IL-9 signaling in HBE4-E6/E7 and primary bronchial epithelial cells. We conclude that IL-9 is a stimulus for airway epithelial cell release of T-cell chemoattractant factors, which in turn may modulate the immune response in allergic airway inflammation.