Fatal cardiotoxicity related to halofantrine: a review based on a worldwide safety data base

<p>Abstract</p> <p>Background</p> <p>Halofantrine (HF) was considered an effective and safe treatment for multi-drug resistant falciparum malaria until 1993, when the first case of drug-associated death was reported. Since then, numerous studies have confirmed cardiac arrythmias, possibly fatal, in both adults and children. The aim of the study was to review fatal HF related cardiotoxicity.</p> <p>Methods</p> <p>In addition, to a systematic review of the literature, the authors have had access to the global safety database on possible HF related cardiotoxicity provided by GlaxoSmithKline.</p> <p>Results</p> <p>Thirty-five cases of fatal cardiotoxicity related to HF, including five children, were identified. Females (70%) and patients from developing countries (71%) were over-represented in this series. Seventy-four percent of the fatal events occurred within 24 hours of initial exposure to HF. Twenty six patients (74%) had at least one predisposing factor for severe cardiotoxicity, e.g., underlying cardiac disease, higher than recommended doses, or presence of a concomitant QT-lengthening drug. All (100%) of the paediatric cases had either a contraindication to HF or an improper dose was given. In six cases there was no malaria.</p> <p>Conclusion</p> <p>A distinction should be made between common but asymptomatic QT-interval prolongation and the much less common ventricular arrhythmias, such as torsades de pointes, which can be fatal and seem to occur in a very limited number of patients. The majority of reported cardiac events occurred either in patients with predisposing factors or with an improper dose.</p> <p>Therefore, in the rare situations in which HF is the only therapeutic option, it can still be given after carefully checking for contraindications, such as underlying cardiac disease, bradycardia, metabolic disorders, personal or family history of long QT-interval or concomitant use of another QT-prolonging drug (e.g., mefloquine), especially in females.</p

Adverse drug reactions in Ghanaian children: review of reports from 2000 to 2012 in VigiBase

Objective: The aim of this article is to describe adverse drug reactions (ADRs) reported for children aged 0 - 17 years in Ghana. Methods: Paediatric reports submitted by the Ghana National Centre for Pharmacovigilance to the World Health Organisation (WHO) Global ADR database, VigiBase up to December 2012 were extracted. The data were analysed for number of reports per year, types of reporters and suspected ADRs and drugs. Results: A total of 343 reports for children were received during the period. The drug classes most frequently reported were vaccines (115, 31%), antimalarials (106, 28%) and antibiotics (57, 15%). Of the top 20 individual drugs, 19 were anti-infectives. The most frequently reported ADRs were injection site infection, fever and rash. There were 23 deaths reported, and antimalarials were implicated in 12 cases. Conclusions: Vaccines, antimalarials and antibiotics are the leading medicines reported to cause ADRs in Ghanaian children. There was a high mortality rate, with many of the deaths due to causes explained in the individual case safety reports

Pattern of drug utilization for treatment of uncomplicated malaria in urban Ghana following national treatment policy change to artemisinin-combination therapy

<p>Abstract</p> <p>Background</p> <p>Change of first-line treatment of uncomplicated malaria to artemisinin-combination therapy (ACT) is widespread in Africa. To expand knowledge of safety profiles of ACT, pharmacovigilance activities are included in the implementation process of therapy changes. Ghana implemented first-line therapy of artesunate-amodiaquine in 2005. Drug utilization data is an important component of determining drug safety, and this paper describes how anti-malarials were prescribed within a prospective pharmacovigilance study in Ghana following anti-malarial treatment policy change.</p> <p>Methods</p> <p>Patients with diagnosis of uncomplicated malaria were recruited from pharmacies of health facilities throughout Accra in a cohort-event monitoring study. The main drug utilization outcomes were the relation of patient age, gender, type of facility attended, mode of diagnosis and concomitant treatments to the anti-malarial regimen prescribed. Logistic regression was used to predict prescription of nationally recommended first-line therapy and concomitant prescription of antibiotics.</p> <p>Results</p> <p>The cohort comprised 2,831 patients. Curative regimens containing an artemisinin derivative were given to 90.8% (n = 2,574) of patients, although 33% (n = 936) of patients received an artemisinin-based monotherapy. Predictors of first-line therapy were laboratory-confirmed diagnosis, age >5 years, and attending a government facility. Analgesics and antibiotics were the most commonly prescribed concomitant medications, with a median of two co-prescriptions per patient (range 1–9). Patients above 12 years were significantly less likely to have antibiotics co-prescribed than patients under five years; those prescribed non-artemisinin monotherapies were more likely to receive antibiotics. A dihydroartemisinin-amodiaquine combination was the most used therapy for children under five years of age (29.0%, n = 177).</p> <p>Conclusion</p> <p>This study shows that though first-line therapy recommendations may change, clinical practice may still be affected by factors other than the decision or ability to diagnose malaria. Age, diagnostic confirmation and suspected concurrent conditions lead to benefit:risk assessments for individual patients by clinicians as to which anti-malarial treatment to prescribe. This has implications for adherence to policy changes aiming to implement effective use of ACT. These results should inform education of health professionals and rational drug use policies to reduce poly-pharmacy, and also suggest a potential positive impact of increased access to testing for malaria both within health facilities and in homes.</p

Global Pharmacovigilance for Antiretroviral Drugs: Overcoming Contrasting Priorities

Jur Strobos and colleagues describe the deliberations of a recent multi-stakeholder meeting discussing the creation of a sustainable global pharmacovigilance system for antiretroviral drugs that would be applicable in resource limited settings

Self-reported use of anti-malarial drugs and health facility management of malaria in Ghana

<p>Abstract</p> <p>Objective</p> <p>To assess the appropriateness of self-reported use of anti-malarial drugs prior to health facility attendance, and the management of malaria in two health facilities in Ghana.</p> <p>Method</p> <p>A structured questionnaire was used to collect data from 500 respondents who were diagnosed clinically and/or parasitologically for malaria at Agogo Presbyterian Hospital and Suntreso Polyclinic, both in the Ashanti Region of Ghana. Collected information included previous use of anti-malarial drugs prior to attending the health facilities, types of drugs used, how the drugs were used, and the sources of the drugs. In addition, the anti-malarial therapy given and outcomes at the two health facilities were assessed.</p> <p>Results</p> <p>Of the 500 patients interviewed, 17% had severe malaria, 8% had moderate to severe malaria and 75% had uncomplicated malaria. Forty three percent of the respondents had taken anti-malarial drugs within two weeks prior to hospital attendance. The most commonly used anti-malarials were chloroquine (76%), sulphadoxine-pyrimethamine (9%), herbal preparations (9%) and amodiaquine (6%). The sources of these medicines were licensed chemical sellers (50%), pharmacies (21%), neighbouring clinics (9%) or "other" sources (20%) including left-over medicines at home. One hundred and sixty three (77%) of the 213 patients who had used anti-malarial drugs prior to attending the health facilities, used the drugs inappropriately. At the health facilities, the anti-malarials were prescribed and used according to the national standard treatment guidelines with good outcomes.</p> <p>Conclusion</p> <p>Prevalence of inappropriate use of anti-malarials in the community in Ghana is high. There is need for enhanced public health education on home-based management of malaria and training for workers in medicine supply outlets to ensure effective use of anti-malaria drugs in the country.</p

Cellular responses to modified Plasmodium falciparum MSP119 antigens in individuals previously exposed to natural malaria infection

<p>Abstract</p> <p>Background</p> <p>MSP1 processing-inhibitory antibodies bind to epitopes on the 19 kDa C-terminal region of the <it>Plasmodium falciparum </it>merozoite surface protein 1 (MSP1₁₉), inhibiting erythrocyte invasion. Blocking antibodies also bind to this antigen but prevent inhibitory antibodies binding, allowing invasion to proceed. Recombinant MSP1₁₉had been modified previously to allow inhibitory but not blocking antibodies to continue to bind. Immunization with these modified proteins, therefore, has the potential to induce more effective protective antibodies. However, it was unclear whether the modification of MSP1₁₉would affect critical T-cell responses to epitopes in this antigen.</p> <p>Methods</p> <p>The cellular responses to wild-type MSP1₁₉and a panel of modified MSP1₁₉antigens were measured using an <it>in-vitro </it>assay for two groups of individuals: the first were malaria-naïve and the second had been naturally exposed to <it>Plasmodium falciparum </it>infection. The cellular responses to the modified proteins were examined using cells from malaria-exposed infants and adults.</p> <p>Results</p> <p>Interestingly, stimulation indices (SI) for responses induced by some of the modified proteins were at least two-fold higher than those elicited by the wild-type MSP1₁₉. A protein with four amino acid substitutions (Glu27→Tyr, Leu31→Arg, Tyr34→Ser and Glu43→Leu) had the highest stimulation index (SI up to 360) and induced large responses in 64% of the samples that had significant cellular responses to the modified proteins.</p> <p>Conclusion</p> <p>This study suggests that specific MSP1₁₉variants that have been engineered to improve their antigenicity for inhibitory antibodies, retain T-cell epitopes and the ability to induce cellular responses. These proteins are candidates for the development of MSP1-based malaria vaccines.</p

Are slum dwellers at heightened risk of HIV infection than other urban residents? Evidence from population-based HIV prevalence surveys in Kenya

In 2008, the global urban population surpassed the rural population and by 2050 more than 6 billion will be living in urban centres. A growing body of research has reported on poor health outcomes among the urban poor but not much is known about HIV prevalence among this group. A survey of nearly 3000 men and women was conducted in two Nairobi slums in Kenya between 2006 and 2007, where respondents were tested for HIV status. In addition, data from the 2008/2009 Kenya Demographic and Health Survey were used to compare HIV prevalence between slum residents and those living in other urban and rural areas. The results showed strong intra-urban differences. HIV was 12% among slum residents compared with 5% and 6% among non-slum urban and rural residents, respectively. Generally, men had lower HIV prevalence than women although in the slums the gap was narrower. Among women, sexual experience before the age of 15 compared with after 19 years was associated with 62% higher odds of being HIV positive. There was ethnic variation in patterns of HIV infection although the effect depended on the current place of residence

Maternal health in resource-poor urban settings: how does women's autonomy influence the utilization of obstetric care services?

Background: Despite various international efforts initiated to improve maternal health, morethan half a million women worldwide die each year as a result of complications arising frompregnancy and childbirth. This research was guided by the following questions: 1) How doeswomen's autonomy influence the choice of place of delivery in resource-poor urban settings? 2)Does its effect vary by household wealth? and 3) To what extent does women's autonomy mediatethe relationship between women's education and use of health facility for delivery?Methods: The data used is from a maternal health study carried out in the slums of Nairobi, Kenya.A total of 1,927 women (out of 2,482) who had a pregnancy outcome in 2004–2005 were selectedand interviewed. Seventeen variable items on autonomy were used to construct women's decisionmaking,freedom of movement, and overall autonomy. Further, all health facilities serving the studypopulation were assessed with regard to the number, training and competency of obstetric staff;services offered; physical infrastructure; and availability, adequacy and functional status of suppliesand other essential equipment for safe delivery, among others. A total of 25 facilities weresurveyed.Results: While household wealth, education and demographic and health covariates had strongrelationships with place of delivery, the effects of women's overall autonomy, decision-making andfreedom of movement were rather weak. Among middle to least poor households, all threemeasures of women's autonomy were associated with place of delivery, and in the expecteddirection; whereas among the poorest women, they were strong and counter-intuitive. Finally, thestudy showed that autonomy may not be a major mediator of the link between education and useof health services for delivery.Conclusion: The paper argues in favor of broad actions to increase women's autonomy both asan end and as a means to facilitate improved reproductive health outcomes. It also supports thecall for more appropriate data that could further support this line of action. It highlights the needfor efforts to improve households' livelihoods and increase girls' schooling to alter perceptions ofthe value of skilled maternal health care

Urban-rural differences in the socioeconomic deprivation-Sexual behavior link in Kenya

We compare the impact of socioeconomic deprivation on risky sexual outcomes in rural and urban Kenya. Quantitative data are drawn from the Demographic & Health Surveys (DHS) and qualitative data from the Sexual Networking and Associated Reproductive and Social Health Concerns study. Using two separate indicators of deprivation we show that, although poverty is significantly associated with the examined sexual outcomes in all settings, the urban poor are significantly more likely than their rural counterparts to have an early sexual debut and a greater incidence of multiple sexual partnerships. The disadvantage of the urban poor is accentuated for married women; those in Nairobi's slums are at least three times as likely to have multiple sexual partners as their rural counterparts. The implications of these findings are discussed.Poverty Rural-urban differences Sexual outcomes Multiple partners Condom use Kenya