Bertrand Graz

A “reverse pharmacology” approach for developing an anti-malarial phytomedicine

A “reverse pharmacology” approach to developing an anti-malarial phytomedicine was designed and implemented in Mali, resulting in a new standardized herbal anti-malarial after six years of research. The first step was to select a remedy for development, through a retrospective treatment-outcome study. The second step was a dose-escalating clinical trial that showed a dose-response phenomenon and helped select the safest and most efficacious dose. The third step was a randomized controlled trial to compare the phytomedicine to the standard first-line treatment. The last step was to identify active compounds which can be used as markers for standardization and quality control. This example of “reverse pharmacology” shows that a standardized phytomedicine can be developed faster and more cheaply than conventional drugs. Even if both approaches are not fully comparable, their efficiency in terms of public health and their complementarity should be thoroughly considered.

Argemone mexicana decoction versus artesunate-amodiaquine for the management of malaria in Mali: Policy and public-health implications

A classic way of delaying drug resistance is to use an alternative when possible. We tested the malaria treatment Argemone mexicana decoction (AM), a validated self-prepared traditional medicine made with one widely available plant and safe across wide dose variations. In an attempt to reflect the real situation in the home-based management of malaria in a remote Malian village, 301 patients with presumed uncomplicated malaria (median age 5 years) were randomly assigned to receive AM or artesunate-amodiaquine [artemisinin combination therapy (ACT)] as first-line treatment. Both treatments were well tolerated. Over 28 days, second-line treatment was not required for 89% (95% CI 84.1-93.2) of patients on AM, versus 95% (95% CI 88.8-98.3) on ACT. Deterioration to severe malaria was 1.9% in both groups in children aged </=5 years (there were no cases in patients aged >5 years) and 0% had coma/convulsions. AM, now government-approved in Mali, could be tested as a first-line complement to standard modern drugs in high-transmission areas, in order to reduce the drug pressure for development of resistance to ACT, in the management of malaria. In view of the low rate of severe malaria and good tolerability, AM may also constitute a first-aid treatment when access to other antimalarials is delayed.

Blood glucose and prognosis in children with presumed severe malaria: is there a threshold for 'hypoglycaemia'?

Objectives  Hypoglycaemia (glucose <2.2 mmol/l) is a defining feature of severe malaria, but the significance of other levels of blood glucose has not previously been studied in children with severe malaria.

To what extent can traditional medicine contribute a complementary or alternative solution to malaria control programmes

Recent studies on traditional medicine (TM) have begun to change perspectives on TM effects and its role in the health of various populations. The safety and effectiveness of some TMs have been studied, paving the way to better collaboration between modern and traditional systems. Traditional medicines still remain a largely untapped health resource: they are not only sources of new leads for drug discoveries, but can also provide lessons and novel approaches that may have direct public-health and economic impact. To optimize such impact, several interventions have been suggested, including recognition of TMs economic and medical worth at academic and health policy levels; establishing working relationships with those prescribing TM; providing evidence for safety and effectiveness of local TM through appropriate studies with malaria patients; spreading results for clinical recommendations and health policy development; implementing and evaluating results of new health policies that officially integrate TM.

Ethnopharmacology, sustainable development and cooperation: The importance of gathering clinical data during field surveys

This commentary aims to focus, among the “multiple roles ofdata generated in ethnopharmacological field studies” (Heinrichet al., 2009, p. 1), on the systematic collection of clinical data.Even if this issue may somewhat resemble what has long beensaid (Martin, 1996), recent experiences with clinical assessmentof the effectiveness of medicinal plants may shed some new light.This commentary is also a call for better cooperation betweenethnopharmacologists,physicians,traditionalhealersandthepop-ulationsconcerned:thatistheconditionforethnopharmacologicalwork to be useful at the level of local populations and, if includedin a development project, for the design of sound health policies(Elisabetsky and Nunes, 1990).A common research process is to go from field survey to phy-tochemistry, with the idea that the research can contribute toeconomic development if a new drug can eventually be found andmarketed while appropriate and ethical relationships are main-tained with the owners of the traditional knowledge (ten Kate andLaird, 2002). However, the road to development of a new drug isexcessively long, even in the rare cases where it is successful (e.g.Hoodia gordonii: see van Heerden, 2008). In the example of a phy-tochemical and pharmacological review on Garcinia mangostana,the authors concluded that “a serious weakness in our knowledgeis the lack of clinical data and it is not yet clear to what extent thefindings about pharmacological activities are of potential clinicalrelevance” (Obolskiy et al., 2009, p. 1047).In the meantime, local traditional treatments continue to beused. In our experience, local users are always interested in theresults of ethnopharmacology research and insist on the system-atic organisation of restitution sessions. They are interested in theanalysisofclinicaldatacollectedduringthesurveys,becauseitpro-vides indices of treatment quality and has implications for local

Mapping HIV/STI behavioural surveillance in Europe

BackgroundUsed in conjunction with biological surveillance, behavioural surveillance provides data allowing for a more precise definition of HIV/STI prevention strategies. In 2008, mapping of behavioural surveillance in EU/EFTA countries was performed on behalf of the European Centre for Disease prevention and Control.MethodNine questionnaires were sent to all 31 member States and EEE/EFTA countries requesting data on the overall behavioural and second generation surveillance system and on surveillance in the general population, youth, men having sex with men (MSM), injecting drug users (IDU), sex workers (SW), migrants, people living with HIV/AIDS (PLWHA), and sexually transmitted infection (STI) clinics patients. Requested data included information on system organisation (e.g. sustainability, funding, institutionalisation), topics covered in surveys and main indicators.ResultsTwenty-eight of the 31 countries contacted supplied data. Sixteen countries reported an established behavioural surveillance system, and 13 a second generation surveillance system (combination of biological surveillance of HIV/AIDS and STI with behavioural surveillance). There were wide differences as regards the year of survey initiation, number of populations surveyed, data collection methods used, organisation of surveillance and coordination with biological surveillance. The populations most regularly surveyed are the general population, youth, MSM and IDU. SW, patients of STI clinics and PLWHA are surveyed less regularly and in only a small number of countries, and few countries have undertaken behavioural surveys among migrant or ethnic minorities populations. In many cases, the identification of populations with risk behaviour and the selection of populations to be included in a BS system have not been formally conducted, or are incomplete. Topics most frequently covered are similar across countries, although many different indicators are used. In most countries, sustainability of surveillance systems is not assured.ConclusionAlthough many European countries have established behavioural surveillance systems, there is little harmonisation as regards the methods and indicators adopted. The main challenge now faced is to build and maintain organised and functional behavioural and second generation surveillance systems across Europe, to increase collaboration, to promote robust, sustainable and cost-effective data collection methods, and to harmonise indicators.

Is parasite clearance clinically important after malaria treatment in a high transmission area? A 3-month follow-up of home-based management with herbal medicine or ACT

Argemone mexicana (AM), a validated herbal medicine for uncomplicated malaria, seems to prevent severe malaria without completely clearing parasites in most patients. This study, in a high transmission area of South Mali, explores whether residual parasitaemia at day 28 was associated with subsequent malaria episodes and/or anaemia. Three hundred and one patients were randomly assigned to AM or artesunate/amodiaquine as first line treatment, of whom 294 were followed up beyond the standard 28 days, to 84 days. From day 29 to day 84, there were no significant differences between treatment groups in new clinical episodes of uncomplicated malaria (0.33 vs 0.31 episodes/patient), severe malaria (< 6% per month of patients aged ≤ 5 years) or moderate anaemia (hematocrit < 24%: 1.1% in both groups at day 84). Total parasite clearance at day 28 was not correlated with incidence of uncomplicated or severe malaria or of moderate anaemia over the subsequent two months. Total parasite clearance at day 28 was not clinically important in the context of high transmission. If this finding can be confirmed, some antimalarials which are clinically effective but do not completely clear parasites could nevertheless be appropriate in high transmission areas. Such a policy could be tested as a way to delay resistance to artemisinin combination therapies.

Reverse pharmacology for developing an anti-malarial phytomedicine. The example of Argemone mexicana.

Graphical abstract

Characteristics of victims of violence admitted to a specialized medico-legal unit in Switzerland

To improve care and services to victims of interpersonal violence, a medico-legal consultation unit was set up at the Lausanne University Hospital, Switzerland in 2006. Adult victims of violence are referred to the consultation by the emergency department. Patients are received by forensic nurses for support, forensic examination and community orientation. A descriptive study of medical reports filled for the 2006 population was conducted in 2007 with the aim to explore characteristics of this specific population and to better orient prevention. Among the 422 patients in 2006, 57% were men and 43% women, with a median age of 31 years old. Violent episodes took place in a public place for 90% of male victims and at home for 70% of female victims. The perpetrators were mostly unknown to male victims (62% of all men victims) and mostly known (usually the partner or a former partner) to female victims (90% of all women victims). For 80% of the women and 47% of the men, the violent event which brought them to the consultation, was not the first one. Because 90% of all patients under study were victimized by men., not only is it necessary to target prevention program to match the potential victims, prevention messages must also focus on potential offenders, especially on young men.

Rapid Assessment of Alternative Medicine Through a Comparison of the Expected and Observed Progress of Patients: A Feasibility Study of the Prognosis/Follow-Up Method

OBJECTIVE AND METHOD To test an unusual research design in assessing alternative care, in a classic Arabic medicine clinic in Mauritania. The need for a common language between alternative and standard (modern) practitioners, as well as patients, led to the development of a relative patient progress scale. Patient-observed progress under alternative treatment was compared to expected progress (prognosis) by alternative and standard practitioners. RESULTS With a follow-up rate of 55 of 80 patients, alternative and standard practitioners had 86% agreement in judging patient progress (kappa = 0.46). Sixty-two percent (62%) of patients progressed as well or better than expected with standard medicine, according to standard practitioners. Classic Arabic medicine was found to be safe; standard practitioners observed signs of imminent danger in two patients only, one of whom was referred to the modern hospital, and the other not, by his own will. In the course of this study, CAM and standard practitioners started a weekly joint consultation. CONCLUSION The prognosis/follow-up method is useful for the assessment of alternative medicine, especially when a study with a control group is impractical. It provides practitioners from different medical systems with elements of a common language. It may facilitate collaboration and appropriate referral between alternative and standard practitioners.