Snakebite envenoming is a common but neglected public health problem, particularly in impoverished rural regions of sub-Saharan Africa, Asia and Latin America. The only validated treatment for this condition is passive immunotherapy with safe and effective animal-derived antivenoms. However, there is a long-lasting crisis in the availability of these life-saving medications, particularly in sub-Saharan Africa and parts of Asia. We herein advocate a multicomponent strategy to substantially improve the availability of safe and effective antivenoms at the global level. This strategy is based on: (i) preparing validated collections of representative venom pools from the most medically dangerous snakes in high-risk regions of the world; (ii) strengthening the capacity of national antivenom manufacturing and quality control laboratories and their regulatory authorities and establishing new facilities in developing countries through technology transfer, as an integral part of efforts to develop their biological products industry; (iii) getting established laboratories to generate antivenoms for various regions of the world; and (iv) getting governments and relevant organizations to give snakebite envenoming due recognition within national and international public health policy frameworks. These ways of making antivenom available should be complemented by actions to improve health information systems, the accessibility of antivenoms, the training of medical and nursing staff, and community-based education. Such a multicomponent strategy involving stakeholders on many levels could help consolidate sustainable improvements in antivenom availability worldwide.

Resumen El envenenamiento por mordedura de serpiente es un problema de salud pública común pero desatendido, especialmente en las regiones rurales más pobres de África subsahariana, Asia y América Latina. El único tratamiento reconocido contra estas mordeduras es la inmunoterapia pasiva con sueros antiofídicos de origen animal seguros y eficaces. Sin embargo, la disponibilidad de estos medicamentos esenciales para salvar vidas lleva mucho tiempo en crisis, en particular en África subsahariana y en algunas zonas de Asia. En el presente documento, abogamos por una estrategia multicomponente para mejorar de forma sustancial la disponibilidad de sueros antiofídicos seguros y eficaces en todo el mundo. La estrategia se basa en: (i) preparar colecciones reconocidas de sueros antiofídicos representativos de las serpientes más peligrosas en zonas de alto riesgo del mundo; (ii) reforzar la capacidad nacional de producción de sueros antiofídicos y la calidad de los laboratorios de control y sus autoridades normativas, así como crear instalaciones nuevas en los países en desarrollo por medio de la transferencia de tecnología como parte integral de los esfuerzos por desarrollar su industria de productos biológicos; (iii) conseguir que los laboratorios consolidados fabriquen sueros antiofídicos para varias regiones del mundo; y (iv) conseguir que los gobiernos y las organizaciones pertinentes otorguen al envenenamiento por mordedura de serpiente el reconocimiento debido dentro del marco de las políticas nacionales e internacionales de salud pública. Estas tareas dirigidas a facilitar el suero antiofídico deben complementarse con acciones para mejorar los sistemas de información sobre la salud, la accesibilidad de los antiofídicos, la formación del personal médico y de enfermería, y la educación comunitaria. Una estrategia multicomponente de ese tipo, que incluye a los interesados a varios niveles, podría ayudar a consolidar mejoras sostenibles en la disponibilidad de antiofídicos en todo el mundo.

Résumé L'envenimation par morsure de serpent est un problème de santé publique fréquent, mais négligé, en particulier dans les régions rurales pauvres de l'Afrique subsaharienne, de l'Asie et de l'Amérique latine. Le seul traitement validé pour soigner cet état est l'immunothérapie passive avec des sérums antivenimeux d'origine animale sûrs et efficaces. Cependant, une crise durable limite actuellement la disponibilité de ces médicaments vitaux, surtout en Afrique subsaharienne et dans certaines parties de l'Asie. Nous préconisons ici une stratégie à composants multiples pour améliorer considérablement la disponibilité des sérums antivenimeux sûrs et efficaces à l'échelle mondiale. Cette stratégie repose sur: (i) la préparation de collections validées de groupes représentatifs de venins prélevés sur les serpents les plus dangereux sur le plan médical dans les régions à haut risque du monde; (ii) le renforcement de la capacité de production nationale des sérums antivenimeux, des laboratoires de contrôle qualité et de leurs organismes de réglementation, et la création de nouvelles installations dans les pays en développement par transfert de technologies, en tant que partie intégrante de la stratégie de développement de leur industrie de produits biologiques; (iii) la production par les laboratoires déjà établis de sérums antivenimeux pour les différentes régions du monde; et (iv) la reconnaissance officielle par les gouvernements et les organisations compétentes de l'envenimation par morsure de serpent dans le cadre des politiques de santé publique nationales et internationales. Ces façons de rendre disponibles les sérums antivenimeux devraient être complétées par des actions visant à améliorer les systèmes d'informations sanitaires, l'accessibilité des sérums antivenimeux, la formation du personnel médical et infirmier et les programmes communautaires d'éducation. Une telle stratégie à composants multiples impliquant des acteurs à différents niveaux pourrait contribuer à consolider les améliorations durables en matière de disponibilité des sérums antivenimeux dans le monde entier.

Background and Objectives: Safety and tolerability of atomoxetine were studied in the largest double-blind, placebo-controlled, randomised withdrawal trial of atomoxetine (80 or 100 mg/day) in adults with attention-deficit/hyperactivity disorder (ADHD). Methods: Patients (N = 2017), 18 to 50 years of age, with ADHD were enrolled from 18 countries. Patients who responded to atomoxetine during a 12-week open-label treatment phase and maintained that response during a 12-week double-blind maintenance phase were randomised to atomoxetine (N = 266) or placebo (N = 258) for 25 weeks of double-blind treatment. Treatment differences were compared for serious adverse events (AEs), treatment-emergent AEs (TEAEs), discontinuation due to AEs, vital signs, body weight, and electrocardiograms. Results: During the 25-week double-blind treatment phase, discontinuations due to AEs were similar between atomoxetine and placebo (3.4% vs. 1.9%; P = .418). The percentage of patients experiencing >1 TEAE(s) was significantly higher for atomoxetine than placebo (47.0% vs. 37.6%; P = .034), but there were no significant differences for any individual TEAE. Diastolic blood pressure (-0.1 vs. -2.3 mmHg), heart rate (-1.4 vs. -5.3 bpm), and weight (-0.2 vs. 1.1 kg) were significantly different between atomoxetine and placebo (P <.001). There were no significant differences between atomoxetine and placebo in the frequencies of patients showing an increase from baseline >30 ms in Fridericia's QT correction (QTcF; 1.4% vs. 2.6%) or Bazett's QT correction (QTcB; 2.8% vs. 2.6%). During the entire study, no patient had a QTcF or QTcB >500 ms, or an increase from baseline >60 ms. Conclusions: This study demonstrated that atomoxetine exhibited an acceptable safety profile in adults with ADHD after 1 year of treatment, and no clinically meaningful safety-related rebound effects were observed following abrupt discontinuation after 24 weeks of treatment.

OBJECTIVES: An association between intimate partner violence and adverse physical health outcomes and health-risk behaviours among women has been established, most scientific research having been conducted in the USA and other developed countries. There have been few studies in developing countries, including South Africa, which has one of the highest rates of intimate partner violence in the world. We therefore sought to study the association between physical intimate partner violence and physical health outcomes and behaviours among South African women. METHODS: Using data from the cross-sectional, nationally representative South African Stress and Health Study, we assessed exposure to intimate partner violence, health-risk behaviours, health-seeking behaviours and chronic physical illness among a sample of 1 229 married and cohabiting women. RESULTS: The prevalence of reported violence was 31%. This correlated with several health-risk behaviours (smoking, alcohol consumption, and use of non-medical sedatives, analgesics and cannabis) and health-seeking behaviours (recent visits to a medical doctor or healer). Intimate partner violence was not significantly associated with chronic physical illness, although rates of headache, heart attack and high blood pressure reached near-significance. CONCLUSIONS: Partner violence against women is a significant public health problem in South Africa, associated with health risk behaviours and increased use of medical services. Public health programmes should incorporate interventions to mitigate the impact of violence on victims and reduce the risk of negative behavioural outcomes. Further investigation of the pathways between violence exposure and health behaviours is needed to inform the design of such programming.

There are few data from South Africa and other low- and middle-income countries on how mental disorders in childhood and adolescence may influence different aspects of socio-economic position, including educational attainment. We examined the association between early-onset disorders and subsequent educational achievement in a nationally representative sample of 4 351 South African adults. After adjusting for participant demographic characteristics and traumatic life events, post-traumatic stress disorder, major depressive disorder and substance-related disorders were each associated with increased odds of failing to complete secondary education (odds ratios and 95% confidence intervals 2.3, 1.0 - 5.1; 1.7, 1.2 - 2.5, and 1.7, 1.2 - 2.5, respectively). These data point to the role that early-life mental disorders may play in educational achievement and subsequent socio-economic position over the life course.

BACKGROUND: Although stressful life events (SLEs) are associated with psychopathology, the contribution from distal and proximal events and the specificity of their association with common mental disorders require further exploration. We examined the association of recent life events and past adversities to mood, anxiety, substance use and impulse control disorders in South Africa. METHODS: Data were analysed from the South African Stress and Health study, a population-based study of mental disorders in a nationally representative sample of 4 351 adults. Psychiatric disorders were assessed with the Composite International Diagnostic Interview (CIDI). This included questions covering early and later SLEs (negative life events, relationship stress, partner violence, social strain and adverse events during childhood) and various socio-demographic variables. Logistic regression models were constructed for 3 957 respondents (2 371 female, 1 586 male) with no missing covariate data, to assess life stress and socio-demographic predictors of 12-month and lifetime disorder. RESULTS: Recent negative life events and relationship problems were significant predictors of any 12-month disorder and any lifetime disorder. Physical partner violence predicted any lifetime disorder. There was evidence of specificity for the prediction of mood versus anxiety disorders, with childhood adversity specifically associated with mood disorders but not anxiety disorders. Single marital status was the strongest socio-demographic predictor of any 12-month and any lifetime disorder. CONCLUSIONS: Stressful life events, distal and proximal, contribute significantly and independently to the prediction of major psychiatric disorders among South Africans, underscoring the importance of screening adversities in adults with common mental disorders, and of providing appropriate adjunctive interventions.

BACKGROUND: A nationally representative study of psychiatric disorders in South Africa provided an opportunity to study the association between perpetration of human rights violations (HRVs) during apartheid and psychiatric disorder. Prior work has suggested an association between perpetration and post-traumatic stress disorder (PTSD), but this remains controversial. METHODS: Subjects reported on their perpetration of human rights violations, purposeful injury, accidental injury and domestic violence. Lifetime and 12-month prevalence of DSM-IV (Diagnostic and Statistical Manual, 4th edition) disorders were assessed with Version 3.0 of the World Health Organization Composite International Diagnostic Interview (CIDI 3.0). Socio-demographic characteristics of these groups were calculated. Odds ratios for the association between the major categories of psychiatric disorders and perpetration were assessed. RESULTS: HRV perpetrators were more likely to be male, black and more educated, while perpetrators of domestic violence ( DV) were more likely to be female, older, married, less educated and with lower income. HRV perpetration was associated with lifetime and 12-month anxiety and substance use disorders, particularly PTSD. Purposeful and DV perpetration were associated with lifetime and 12-month history of all categories of disorders, whereas accidental perpetration was associated most strongly with mood disorders. CONCLUSION: Socio-demographic profiles of perpetrators of HRV and DV in South Africa differ. While the causal relationship between perpetration and psychiatric disorders deserves further study, it is possible that some HRV and DV perpetrators were themselves once victims. The association between accidental perpetration and mood disorder also deserves further attention.

BACKGROUND: Europe and North America have low rates of mental health service use despite high rates of mental disorder. Little is known about mental health service use among South Africans. DESIGN: A nationally representative survey of 4 351 adults. Twelve-month DSM-IV (Diagnostic and Statistical Manual, 4th edition) diagnoses, severity, and service utilisation were determined using the World Health Organization Composite International Diagnostic Interview (CIDI). Twelve-month treatment was categorised by sector and province. South Africans in households and hostel quarters were interviewed between 2002 and 2004 in all nine provinces. OUTCOME MEASURES: 4 317 respondents 18 years and older were analysed. Bivariate logistic regression models predicted (i) 12-month treatment use of service sectors by gender, and (ii) 12-month treatment use by race by gender. RESULTS: Of respondents with a mental disorder, 25.2% had sought treatment within the previous 12 months; 5.7% had used any formal mental health service. Mental health service use was highest for adults with mood and anxiety disorders, and among those with a mental disorder it varied by province, from 11.4% (Western Cape) to 2.2% (Mpumalanga). More women received treatment, and this was largely attributable to higher rates of treatment in women with mood disorders. Age, income, education and marital status were not significantly associated with mental health service use. Race was associated with the treatment sector accessed in those with a mental disorder. CONCLUSIONS: There is a substantial burden of untreated mental disorders in the South African population, across all provinces and even in those with substantial impairment. Greater allocation of resources to mental health services and more community awareness initiatives are needed to address the unmet need.

BACKGROUND: The South African Stress and Health (SASH) study is the first large-scale population-based study of common mental disorders in the country. This paper provides data on the 12-month and lifetime prevalence of these conditions. METHODS: Data from a nationally representative sample of 4 351 adults were analysed. Mental disorders were assessed with the Composite International Diagnostic Interview (CIDI). An extensive survey questionnaire detailed contextual and socio-demographic factors, onset and course of mental disorders, and risk factors. Simple weighted cross-tabulation methods were used to estimate prevalence, and logistic regression analysis was used to study correlates of 12-month and lifetime prevalence. RESULTS: The lifetime prevalence for any disorder was 30.3%, and the most prevalent 12-month and lifetime disorders were the anxiety disorders. The Western Cape had the highest 12-month and lifetime prevalence rates, and the lowest rates were in the Northern Cape. CONCLUSIONS: The SASH study shows relatively high 12-month and lifetime prevalence rates. These findings have significant implications for planning mental health services.

BACKGROUND: There are few reports from South Africa on how common mental disorders may be associated with HIV-related perceptions and behaviours. METHODS: Between 2002 and 2004, 4 351 South African adults were interviewed. Psychiatric diagnoses of depression, anxiety and substance abuse disorders were based on the Diagnostic and Statistical Manual, 4th edition (DSM-IV). HIV-related fears, perceived risk and behaviour change were measured using multi-item scales. We analysed forms of behaviour change that were appropriate for risk reduction (such as changes in sexual behaviour) separately from behaviour changes that were inappropriate to prevent HIV (such as care over things touched or avoiding certain social situations). RESULTS: The presence of any DSM-IV-defined disorder during the previous 12 months was associated with previous HIV testing, increased HIV-related fears, and high levels of perceived risk of HIV. There were no associations between depression, anxiety and substance abuse disorders and appropriate forms of behaviour change for HIV risk reduction. However, individuals with an anxiety or a depressive disorder were more likely to report inappropriate forms of behaviour change. For example, individuals with any depressive and/or anxiety disorders were 1.57 and 1.47 times more likely, respectively, to report avoiding certain social situations to prevent HIV/AIDS compared with those who did not have such disorders (p<0.01 for both associations). DISCUSSION: The lack of appropriate forms of behaviour change to prevent HIV transmission, despite increased levels of HIV-related fear and perceived risk, underscores the need for HIV risk reduction interventions for individuals living with common mental disorders in South Africa.

BACKGROUND: There are limited data on substance use in South Africa. We describe patterns of substance use based on recent, nationally representative data. METHODS: Data were derived from the 2002 - 2004 South African Stress and Health (SASH) study. A nationally representative household probability sample of 4 351 adults was interviewed using the paper and pencil version of the World Health Organization Composite International Diagnostic Interview (CIDI). Data are reported for lifetime use, socio-demographic correlates of use, and age of cohort predicting lifetime use for four classes of drugs. RESULTS: The estimate for cumulative occurrence of alcohol use was 38.7%, of tobacco smoking 30.0%, of cannabis use 8.4%, of other drug use 2.0%, and of extra-medical psychoactive drug use 19.3%. There were statistically significant associations between male gender and alcohol, tobacco, cannabis and other drug use. Coloureds and whites were more likely than blacks to have used alcohol, tobacco and other drugs. Clear cohort variations existed in the age of initiation of drug use; these were most marked for other drugs and for extra-medical drug use. Use of all drug types was much more common in recent cohorts, with a similar cumulative incidence of tobacco, alcohol and cannabis use across age cohorts. CONCLUSIONS: Epidemiological patterns of use for alcohol, tobacco, cannabis, other drugs and extra-medical drugs provide the first nationally representative data. New findings on race and exploratory data on time trends provide a foundation for future epidemiological work on drug use patterns across birth cohorts and population subgroups in South Africa.

BACKGROUND: Mental disorders are a major contributor to the burden of disease in all regions of the world. There are limited data on the epidemiology of major depressive disorder in South Africa. METHODS: A nationally representative household survey was conducted between 2002 and 2004 using the World Health Organization Composite International Diagnostic Interview (CIDI) to establish a diagnosis of depression. The dataset analysed included 4 351 adult South Africans of all racial groups. RESULTS: The prevalence of major depression was 9.7% for lifetime and 4.9% for the 12 months prior to the interview. The prevalence of depression was significantly higher among females than among males. The prevalence was also higher among those with a low level of education. Over 90% of all respondents with depression reported global role impairment. CONCLUSION: In comparison with data from other countries, South Africa has lower rates of depression than the USA but higher rates than Nigeria. The findings are broadly consistent with previous findings in South Africa. These findings are the first step in documenting a level of need for care in a context of significant under-funding of mental health services and research in South Africa.

Blood eosinophilia and tissue infiltration by eosinophils are frequently observed in allergic inflammation and parasitic infections. This selective accumulation of eosinophils suggested the existence of endogenous eosinophil-selective chemoattractants. We have recently discovered a novel eosinophil-selective chemoattractant which we called eotaxin in an animal model of allergic airways disease. Eotaxin is generated in both allergic and non-allergic bronchopulmonary inflammation. The early increase in eotaxin paralled eosinophil infiltration in the lung tissue in both models. An antibody to IL-5 suppressed lung eosinophilia, correlating with an inhibition of eosinophil release from bone marrow, without affecting eotaxin generation. This suggests that endogenous IL-5 is important for eosinophil migration but does not appear to be a stimulus for eotaxin production. Constitutive levels of eotaxin observed in guinea-pig lung may be responsible for the basal lung eosinophilia observed in this species. Allergen-induced eotaxin was present mainly in the epithelium and alveolar macrophages, as detected by immunostaining. In contrast there was no upregulation of eotaxin by the epithelial cells following the injection of Sephadex beads and the alveolar macrophage and mononuclear cells surrounding the granuloma were the predominant positive staining cells. Eotaxin and related chemokines acting through the CCR3 receptor may play a major role in eosinophil recruitment in allergic inflammation and parasitic diseases and thus offer an attractive target for therapeutic intervention.