The state and future of research at the University of Cape Town’s Faculty of Health Sciences

The nature of research has continued to change considerably over the last century. Our Faculty’s challenge has been to keep abreast of those changes to remain at the cutting edge, while contributing meaningfully to the scientific literature which informs clinical and public health practice in South Africa and beyond. The Faculty must possess an agreed-on research strategy that is dynamic and responsive. Over the years our Faculty has ‘grown’ such a strategy document. This article, summarising its main thrusts, is offered because we feel that while it applies specifically to UCT, the issues raised surely apply to all similar faculties in our country and on the continent, to varying degrees

a systematic review protocol

Introduction Varicella zoster virus (VZV) causes varicella (chicken pox) and herpes zoster (shingles). Worldwide, these diseases are associated with significant morbidity. Most of the epidemiological data on VZV come from high income countries. There are few data on VZV in Africa, where tropical climates and high HIV/AIDS prevalence rates are expected to impact the epidemiology of VZV. Safe and effective vaccinations for both varicella and herpes zoster exist, but are not routinely used in Africa. There are very few data available on VZV disease burden in Africa to guide the introduction of these vaccines on the continent. Our aim is to conduct a systematic review of the VZV-associated morbidity and mortality in Africa, which will provide critical information that could be used to develop vaccination policies against these diseases in Africa. Methods and analysis Electronic databases will be searched and all studies published after 1974 that meet predefined criteria will be assessed. The primary outcomes for the study are VZV incidence/prevalence, hospitalisation rates and total death rates. The secondary outcome for this study is the proportion of VZV hospitalisations and/or deaths associated with HIV/AIDS. Two reviewers will screen the titles and abstracts, and then independently review the full texts, to determine if studies are eligible for inclusion. A risk of bias and quality assessment tool will be used to score all included studies. Following standardised data extraction, a trend analysis using R-programming software will be conducted to investigate the trend of VZV. Depending on the characteristics of included studies, subgroup analyses will be performed. This review will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Ethics and dissemination As this is a protocol for a systematic review, which will use already published data, no ethics approval is required. Findings will be disseminated in peer-reviewed journals. Trial registration number CRD4201502614

The Christmas Cove Dyke of coastal Maine, USA, and regional sources for Early Mesozoic flood basalts in northeastern North America

 A large Early Mesozoic quartz tholeiite dyke has been mapped discontinuously for 190 km in southern coastal Maine, USA. Including its type locality at Christmas Cove (South Bristol, Maine, USA), the dyke has features of a generally ENE strike; dip usually steep to the SSE but abruptly turning very shallow in short sections; and widths of 9 to 35 m. The dyke rock has a distinctive cross-columnar field appearance, and a subophitic to micro-porphyritic texture with abundant Ti-bearing augite, calcic plagioclase, scattered euhedral orthopyroxene phenocrysts, and coarse-grained glomerophyric clumps of augite with plagioclase. Several 40Ar/39Ar whole-rock dates for this and associated regional dykes are close to 201 Ma, in agreement with ages of other Early Mesozoic dykes and basalts of the Central Atlantic Magmatic Province (CAMP). The geographic position, age, whole-rock chemistry, and petrography indicate that the Christmas Cove Dyke is co-magmatic or contiguous with the Higganum-Holden Dyke of southern New England, which was a source for the Talcott Basalt of the Early Mesozoic Hartford rift basin. The dyke system is a 700-km long fissure source for the earliest rift basin basalts preserved in northeastern North America, and it virtually connects the Hartford Basin and the Fundy Basin in Atlantic Canada. The Caraquet Dyke of New Brunswick and central Maine may be co-magmatic with the Buttress Dyke and Holyoke Basalt of southern New England, but lava from it is not preserved in Atlantic Canada or Maine.

Oral trimethoprim-sulphamethoxazole levels in stable HIV-infected children

Background. Effective treatment of Pneumocystis jiroveci pneumonia (PCP) requires therapeutic serum concentrations of 5 - 10 µg/ml trimethoprim (TMP); consequently intravenous trimethoprim-sulphamethoxazole (TMP-SMZ) is recommended therapy. However, oral therapy is desirable as the intravenous route is costly, time-consuming, more difficult to administer and carries a risk of needlestick injury. Objective. To investigate whether therapeutic TMP levels for treatment of PCP can be attained with oral therapy in HIVinfected children. Methods. A prospective dose-escalation study was undertaken of serum TMP levels attained following oral doses of TMP of 5 mg/kg, 10 mg/kg or 20 mg/kg in stable HIV-infected children. Children who received a 20 mg/kg dose were randomised to get a second dose (5 or 10 mg/kg TMP) at 6 hours. TMP levels were measured at baseline, peak (3 hours), and trough (6 hours) using liquid chromatography. An additional TMP level was taken at 9 hours in those who received a second TMP dose. Results. Median (25th - 75th percentile) peak serum TMP levels following a 5 mg/kg, 10 mg/kg or 20 mg/kg oral loading dose were 0.93 (0.5 - 1.5) µg/ml, 1.94 (1.4 - 2.2) µg/ml and 7.68 (6.1- 7.8) µg/ml respectively. Peak TMP levels at 9 hours after a second TMP dose of 5 or 10 mg/kg were 6.98 (3.4 - 8.8) µg/ml and 9.25 (8.2 - 10.3) µg/ml respectively. Conclusion. Therapeutic concentrations of TMP for treatment of P. jiroveci can be attained with an oral loading dose of 20 mg/kg and sustained with a second dose at 6 hours of either 5 mg or 10 mg/kg in stable HIV-infected children

Oral trimethoprim-sulphamethoxazole levels in stable HIV-infected children

Background. Effective treatment of Pneumocystis jiroveci pneumonia (PCP) requires therapeutic serum concentrations of 5 - 10 µg/ml trimethoprim (TMP); consequently intravenous trimethoprim-sulphamethoxazole (TMP-SMZ) is recommended therapy. However, oral therapy is desirable as the intravenous route is costly, time-consuming, more difficult to administer and carries a risk of needlestick injury. Objective. To investigate whether therapeutic TMP levels for treatment of PCP can be attained with oral therapy in HIVinfected children. Methods. A prospective dose-escalation study was undertaken of serum TMP levels attained following oral doses of TMP of 5 mg/kg, 10 mg/kg or 20 mg/kg in stable HIV-infected children. Children who received a 20 mg/kg dose were randomised to get a second dose (5 or 10 mg/kg TMP) at 6 hours. TMP levels were measured at baseline, peak (3 hours), and trough (6 hours) using liquid chromatography. An additional TMP level was taken at 9 hours in those who received a second TMP dose. Results. Median (25th - 75th percentile) peak serum TMP levels following a 5 mg/kg, 10 mg/kg or 20 mg/kg oral loading dose were 0.93 (0.5 - 1.5) µg/ml, 1.94 (1.4 - 2.2) µg/ml and 7.68 (6.1- 7.8) µg/ml respectively. Peak TMP levels at 9 hours after a second TMP dose of 5 or 10 mg/kg were 6.98 (3.4 - 8.8) µg/ml and 9.25 (8.2 - 10.3) µg/ml respectively. Conclusion. Therapeutic concentrations of TMP for treatment of P. jiroveci can be attained with an oral loading dose of 20 mg/kg and sustained with a second dose at 6 hours of either 5 mg or 10 mg/kg in stable HIV-infected children. No Abstract. South African Medical Journal Vol. 96(7) 2006: 627-62

Mobile phone text messaging for promoting adherence to anti-tuberculosis treatment: a systematic review protocol

BACKGROUND: In 2010, there were approximately 8.8 million incident cases of tuberculosis (TB) worldwide. The treatment of TB is at least six months long and may be complicated by a high pill burden. In addition, TB patients often do not take their medication on schedule simply because they forget. Mobile phone text messaging has the potential to help promote TB treatment adherence. We, therefore, propose to conduct a review of current best evidence for the use of mobile phone text messaging to promote patient adherence to TB treatment. METHODS: This is a systematic review of the literature. We will preferably include randomized controlled trials (RCTs). However, non-randomized studies (NRS) will be considered if there is an inadequate number of RCTs.We will search PubMed, EMBASE, CINAHL, CENTRAL, Science Citation Index, Africa-Wide Information, and WHOLIS electronic databases for eligible studies available by 30 November 2012 regardless of language or publication status. We will also check reference lists for additional studies, identify abstracts from conference proceedings and communicate with authors for any relevant material.At least two authors will independently screen search outputs, select studies, extract data and assess the risk of bias (using separate criteria for RCTs and NRS); resolving discrepancies by discussion and consensus. We will assess clinical heterogeneity by examining the types of participants, interventions and outcomes in each study and pool studies judged to be clinically homogenous. We will also assess statistical heterogeneity using the chi-square test of homogeneity and quantify it using the I-square statistic. If study results are found to be statistically homogeneous (that is heterogeneity P > 0.1), we will pool them using the fixed-effect meta-analysis. Otherwise, we will use random-effects meta-analysis. We will calculate risk ratios and their corresponding 95% confidence intervals for dichotomous outcomes, and mean differences for continuous outcomes. For other outcomes without quantitative data, a descriptive analysis will be used.DISCUSSION:Our results can be used by researchers and policy-makers to help inform them of the efficacy of mobile phone text messaging interventions to promote patient adherence to TB treatment

Initial experience of a public sector antiretroviral treatment programme for HIV-infected children and their infected parents

Objective. To describe the initial experience of treating HIVinfected children and their infected parents with antiretroviral therapy. Design. Prospective, cohort study. Setting. Tertiary, referral hospital. Patients. HIV-infected children and their parents. Methods. This report focuses on the early response of children to highly active antiretroviral therapy (HAART). Children were followed up at 4-weekly intervals. Monitoring included initial and yearly viral load measurements, baseline and 6- monthly CD4 counts and 4-weekly adherence checks. Results. Between August 2002 and June 2003, 80 children were enrolled in the programme, representing a follow-up period of 23.9 patient-years. Seventy-five children had severe clinical disease, severe immune suppression, or a combination of the two. The response of children who had received HAART for ≥ 6 months (N = 17) was assessed. There was no change in mass z-score (p = 0.11) or length z-score (p = 0.37), but a significant increase in CD4 percentage (p < 0.0001) during the first 6 months of therapy. Six-month viral loads were available for 12 children. There was a significant drop in viral load (p = 0.001) and 9 achieved undetectable levels by 6 months. Most children achieved ≥ 85% adherence. By June 2002, 67 children (84%) were relatively well, 1 had B-cell lymphoma, 7 (8.8%) had died, 4 (5%) were lost to follow-up and 1 was withdrawn from the programme. Of 57 children who completed 3 months of HAART, 12 were admitted a total of 17 times for infectious complications. There were no severe drug reactions. Three of 7 mothers on HAART received treatment through the programme. Conclusion. These initial results suggest that many HIVinfected children in the public sector will benefit from antiretroviral therapy. However, both ambulatory and inpatient facilities are required to manage children on HAART comprehensivel