High Public Health Impact Research Articles

RE-AIM analysis of a randomized school-based nutrition intervention among fourth-grade classrooms in California.

Childhood overweight and obesity are major health problems. School-based programs enable intervening with large groups of children, but program overall health impact is rarely completely assessed. A RE-AIM (Reach, Efficacy, Adoption, Implementation, Maintenance) analysis tested the overall public health impact of the fourth-grade "Nutrition Pathfinders" school-based nutrition-education program. A randomized controlled trial in 47 fourth-grade California classrooms (1713 students) tested program efficacy, and a secondary analysis of archival data tested program dissemination. Desired effects were seen in child nutrition knowledge, attitudes, consumption of low-nutrient high-density foods, sugar-sweetened beverages, proteins, grains, and parent willingness to serve new foods. The program was disseminated to ∼25% of public school fourth-grade classrooms in California and cost about $1.00 per student to implement. The Nutrition Pathfinders program demonstrates potential for moderate to high public health impact due to its wide dissemination, effectiveness in altering attitudes and behaviors, and its relatively inexpensive cost of implementation.

NIH inventions translate into drugs and biologics with high public health impact

Compared with other US public-sector research institutions, the US National Institutes of Health has contributed inventions that have had a disproportionately greater impact on the overall number of products produced, drugs granted orphan status and drugs granted priority review.

Prevention of Traumatic Stress in Mothers With Preterm Infants: A Randomized Controlled Trial

The current study evaluates a treatment intervention developed with the goal of reducing symptoms of posttraumatic stress, depression, and anxiety in parents of premature infants. A total of 105 mothers of preterm infants (25-34 weeks' gestational age; >600 g) were randomized to receive a 6-session intervention developed to target parental trauma as well as facilitate infant redefinition (n = 62) or to an active comparison group (n = 43). Mothers in the intervention group received a combination of trauma-focused treatments, including psychoeducation, cognitive restructuring, progressive muscle relaxation, and development of their trauma narrative. The intervention also incorporated material targeting infant redefinition, defined as the process of changing the mother's negative perceptions of her infant and the parenting experience. Mothers in the intervention group reported a greater reduction in both trauma symptoms (Cohen's d = 0.41, P = .023) and depression (Cohen's d = 0.59, P < .001) compared with the comparison group. Patients under both conditions improved significantly in terms of anxiety, with no differences between groups. Results of the moderator analysis showed that mothers with higher ratings of baseline NICU stress benefited more from the intervention compared with mothers who had lower ratings (P = .036). This short, highly manualized intervention for mothers of preterm infants statistically significantly reduced symptoms of trauma and depression. The intervention is feasible, can be delivered with fidelity, and has high ratings of maternal satisfaction. Given that improvements in mothers' distress may lead to improved infant outcomes, this intervention has the potential for a high public health impact.

Vertebral compression fractures: a review of current management and multimodal therapy

Vertebral compression fractures are a prevalent disease affecting osteoporotic patients. When symptomatic, they cause significant pain and loss of function and have a high public health impact. In this paper we outline the diagnosis and management of these patients, with evidence-based review of treatment outcomes for the various therapeutic options. Diagnosis involves a clinical history focusing on the nature of the patient’s pain as well as various imaging studies. Management is multimodal in nature and starts with conservative therapy consisting of analgesic medication, medication for osteoporosis, physical therapy, and bracing. Patients who are refractory to conservative management may be candidates for vertebral augmentation through either vertebroplasty or kyphoplasty.

Immunization with tegument nucleotidases associated with a subcurative praziquantel treatment reduces worm burden following Schistosoma mansoni challenge.

Schistosomiasis is a debilitating disease caused by flatworm parasites of the Schistosoma genus and remains a high public health impact disease around the world, although effective treatment with Praziquantel (PZQ) has been available since the 1970s. Control of this disease would be greatly improved by the development of a vaccine, which could be combined with chemotherapy. The sequencing of the Schistosoma mansoni transcriptome and genome identified a range of potential vaccine antigens. Among these, three nucleotidases from the tegument of the parasite, presumably involved in purinergic signaling and nucleotide metabolism, were proposed as promising vaccine candidates: an alkaline phosphatase (SmAP), a phosphodiesterase (SmNPP-5) and a diphosphohydrolase (SmNTPDase). Herein, we evaluate the potential of these enzymes as vaccine antigens, with or without subcurative PZQ treatment. Immunization of mice with the recombinant proteins alone or in combination demonstrated that SmAP is the most immunogenic of the three. It induced the highest antibody levels, particularly IgG1, associated with an inflammatory cellular immune response characterized by high TNF-α and a Th17 response, with high IL-17 expression levels. Despite the specific immune response induced, immunization with the isolated or combined proteins did not reduce the worm burden of challenged mice. Nonetheless, immunization with SmAP alone or with the three proteins combined, together with subcurative PZQ chemotherapy was able to reduce the worm burden by around 40%. The immunogenicity and relative exposure of SmAP to the host immune system are discussed, as key factors involved in the apparently synergistic effect of SmAP immunization and subcurative PZQ treatment.

Pharmacology of myopia and potential role for intrinsic retinal circadian rhythms

Despite the high prevalence and public health impact of refractive errors, the mechanisms responsible for ametropias are poorly understood. Much evidence now supports the concept that the retina is central to the mechanism(s) regulating emmetropization and underlying refractive errors. Using a variety of pharmacologic methods and well-defined experimental eye growth models in laboratory animals, many retinal neurotransmitters and neuromodulators have been implicated in this process. Nonetheless, an accepted framework for understanding the molecular and/or cellular pathways that govern postnatal eye development is lacking. Here, we review two extensively studied signaling pathways whose general roles in refractive development are supported by both experimental and clinical data: acetylcholine signaling through muscarinic and/or nicotinic acetylcholine receptors and retinal dopamine pharmacology. The muscarinic acetylcholine receptor antagonist atropine was first studied as an anti-myopia drug some two centuries ago, and much subsequent work has continued to connect muscarinic receptors to eye growth regulation. Recent research implicates a potential role of nicotinic acetylcholine receptors; and the refractive effects in population surveys of passive exposure to cigarette smoke, of which nicotine is a constituent, support clinical relevance. Reviewed here, many puzzling results inhibit formulating a mechanistic framework that explains acetylcholine's role in refractive development. How cholinergic receptor mechanisms might be used to develop acceptable approaches to normalize refractive development remains a challenge. Retinal dopamine signaling not only has a putative role in refractive development, its upregulation by light comprises an important component of the retinal clock network and contributes to the regulation of retinal circadian physiology. During postnatal development, the ocular dimensions undergo circadian and/or diurnal fluctuations in magnitude; these rhythms shift in eyes developing experimental ametropia. Long-standing clinical ideas about myopia in particular have postulated a role for ambient lighting, although molecular or cellular mechanisms for these speculations have remained obscure. Experimental myopia induced by the wearing of a concave spectacle lens alters the retinal expression of a significant proportion of intrinsic circadian clock genes, as well as genes encoding a melatonin receptor and the photopigment melanopsin. Together this evidence suggests a hypothesis that the retinal clock and intrinsic retinal circadian rhythms may be fundamental to the mechanism(s) regulating refractive development, and that disruptions in circadian signals may produce refractive errors. Here we review the potential role of biological rhythms in refractive development. While much future research is needed, this hypothesis could unify many of the disparate clinical and laboratory observations addressing the pathogenesis of refractive errors.

State-wide dissemination of a school-based nutrition education programme: a RE-AIM (Reach, Efficacy, Adoption, Implementation, Maintenance) analysis.

The current study evaluated the overall public health impact of the 'Shaping Up My Choices' (SMC) programme, a 10-week school-based nutrition education curriculum developed for third-grade students, using the RE-AIM (Reach, Efficacy, Adoption, Implementation, Maintenance) framework. Randomized controlled trial to evaluate the programme and secondary analysis of archival data to describe dissemination. Data were collected from programme records, teacher surveys and student pre-, post- and 3-month follow-up surveys. Public elementary schools in California. An evaluation sample (938 students and nineteen teachers) and a dissemination sample (195 245 students and 7359 teachers). In the evaluation sample, differences between the control and intervention groups were observed for nutrition knowledge, self-efficacy, outcome expectancies, and intakes of vegetables, fruit (girls only), soda, and low-nutrient high-energy foods from pre- to post-survey. Group differences in change in knowledge, outcome expectancies and vegetable intake were sustained through the 3-month follow-up (efficacy). One hundred per cent of intervention teachers in the evaluation sample implemented all of the lessons (implementation). The dissemination sample represented 42% of third-grade students (reach) and 39% of third-grade classrooms in public elementary schools in California during 2010-2011 (adoption). Thirty-seven per cent of third-grade teachers in the dissemination sample reordered SMC materials during the subsequent school year (2011-2012; maintenance). The SMC programme demonstrates the potential for moderate to high public health impact.

Severe Morbidity Due to Opisthorchis viverrini and Schistosoma mekongi Infection in Lao People's Democratic Republic

We assessed morbidity due to Opisthorchis viverrini and Schistosoma mekongi infections in 243 individuals in Lao People's Democratic Republic. Morbidity was associated with O. viverrini infection intensity. Coinfection with S. mekongi resulted in excess risk of liver fibrosis and left liver lobe enlargement. The high public health impact of opisthorchiasis warrants control.

Antidepressant Combinations: Widely Used, but Far from Empirically Validated

This paper reviews the evidence on combining antidepressants (ADs) for treatment of major depressive disorder. Although widely used and usually safe, the efficacy of even the most widely prescribed combinations of ADs has not been established by properly controlled, adequately powered, clinical trials. This stands in contrast to several adjunctive strategies for AD nonresponders, including adjunctive lithium, thyroid hormone, or newer-generation antipsychotics. The wide use of AD combinations no doubt reflects the limited efficacy of commonly used ADs and the unmet need for effective strategies for patients with treatment-resistant depression. Although of unproven efficacy, potential merits of combining selected ADs include: (1) avoiding discontinuation-emergent symptoms and cross-titration schedules, (2) at worst, the second AD should be as effective in combination as it would be as a monotherapy following a switch, and (3) the possibility of complementary neuropharmacologic effects that may enhance efficacy or improve tolerability. The dearth of controlled studies of such a commonly used strategy for such a highly prevalent condition is symptomatic of shortcomings in the way clinically relevant research is funded, points to the need for industry-academic-federal collaborations, and underscores the need for large, practice-based, research groups that can efficiently complete publicly funded studies of high public health impact.

Quantitative Mass Spectrometry for Bacterial Protein Toxins — A Sensitive, Specific, High-Throughput Tool for Detection and Diagnosis

Matrix-assisted laser-desorption time-of-flight (MALDI-TOF) mass spectrometry (MS) is a valuable high-throughput tool for peptide analysis. Liquid chromatography electrospray ionization (LC-ESI) tandem-MS provides sensitive and specific quantification of small molecules and peptides. The high analytic power of MS coupled with high-specificity substrates is ideally suited for detection and quantification of bacterial enzymatic activities. As specific examples of the MS applications in disease diagnosis and select agent detection, we describe recent advances in the analyses of two high profile protein toxin groups, the Bacillus anthracis toxins and the Clostridium botulinum neurotoxins. The two binary toxins produced by B. anthracis consist of protective antigen (PA) which combines with lethal factor (LF) and edema factor (EF), forming lethal toxin and edema toxin respectively. LF is a zinc-dependent endoprotease which hydrolyzes specific proteins involved in inflammation and immunity. EF is an adenylyl cyclase which converts ATP to cyclic-AMP. Toxin-specific enzyme activity for a strategically designed substrate, amplifies reaction products which are detected by MALDI-TOF-MS and LC-ESI-MS/MS. Pre-concentration/purification with toxin specific monoclonal antibodies provides additional specificity. These combined technologies have achieved high specificity, ultrasensitive detection and quantification of the anthrax toxins. We also describe potential applications to diseases of high public health impact, including Clostridium difficile glucosylating toxins and the Bordetella pertussis adenylyl cyclase.

Meta-analysis: Circulating vitamin D and ovarian cancer risk

ObjectiveTo review and summarize evidence from longitudinal studies on the association between circulating 25 hydroxyvitamin D (25(OH)D) and the risk of ovarian cancer (OC). MethodsRelevant prospective cohort studies and nested case-control studies were identified by systematically searching Ovid Medline, EMBASE, and ISI Web of Knowledge databases and by cross-referencing. The following data were extracted in a standardized manner from eligible studies: first author, publication year, country, study design, characteristics of the study population, duration of follow-up, OC incidence according to circulating vitamin D status and the respective relative risks, and covariates adjusted for in the analysis. Due to the heterogeneity of studies in categorizing circulating vitamin D levels, all results were recalculated for an increase of circulating 25(OH)D by 20ng/ml. Summary relative risks (RRs) were calculated using meta-analysis methods. ResultsOverall, ten individual-level studies were included that reported on the association between circulating vitamin D levels and OC incidence. Meta-analysis of studies on OC incidence resulted in a summary RR (95% confidence interval, CI) of 0.83 (0.63–1.08) for an increase of 25(OH)D by 20ng/ml (P=0.160). No indication for heterogeneity and publication bias was found. ConclusionsA tentative inverse association of circulating 25(OH)D with OC incidence was found, which did not reach statistical significance but which requires clarification by additional studies due to potentially high clinical and public health impact.

Obstructive sleep apnea and type 2 diabetes

Type 2 diabetes and obstructive sleep apnea (OSA) are diseases with high prevalence and major public health impact. There is evidence that regular snoring and OSA are independently associated with alterations in glucose metabolism. Thus, OSA might be a risk factor for the development of type 2 diabetes. Possible causes might be intermittent hypoxia and sleep fragmentation, which are typical features of OSA. OSA might also be a reason of ineffective treatment of type 2 diabetes. There is further evidence that the treatment of OSA by continuous positive airway pressure (CPAP) therapy might correct metabolic abnormalities in glucose metabolism. It is assumed that this depends on therapy compliance to CPAP. On the other hand, there are also hints in the literature that type 2 diabetes per se might induce sleep apnea, especially in patients with autonomic neuropathy. Pathophysiological considerations open up new insights into that problem. Based on the current scientific data, clinicians have to be aware of the relations between the two diseases, both from the sleep medical and the diabetological point of view. The paper summarizes the most important issues concerning the different associations of OSA and type 2 diabetes.

Prioritization of diseases for work-related health monitoring by multidimensional ranking

AimAlthough working life issues are subject to European health monitoring schemes, not many routine data sources include information on occupations or working conditions. Additional in-depth analysis is therefore necessary for diseases with high public health impact. The aim of this paper is to introduce a multidimensional ranking procedure for priority setting of diseases based on European and national data.Subject and methodsMultidimensional ranking was carried out on ten disease-specific indicators. First, suitable data sources were identified and information on indicators was retrieved. Second, the diseases were sorted by their ranks according to each indicator. Third, all ranks were added to a rank sum. Finally, the diseases were sorted by their rank sum.ResultsDiseases of the circulatory system account for the highest rank sum. The high public health impact is visible in regard to most criteria, particularly to mortality, hospital discharges, and costs. Diseases of the digestive system rank second mainly because of high ranks for hospital discharges and costs. The third place is assigned to diseases of the musculoskeletal system.ConclusionA multidimensional ranking procedure has advantages when used for priority setting of diseases. The procedure leads to an overall rank as a summary measure for the public health impact but information for each indicator is still retrieved. Furthermore, the procedure uses ranks and is therefore scale invariant. However, ranking procedures do not lead to a selection of diseases but a rank order. So, there is still a decision rule required to determine which diseases are selected e.g. for in-depth health reporting.

Impact of Obstructive Sleep Apnoea on Type 2 Diabetes and Vice Versa.

Type 2 diabetes and obstructive sleep apnoea (OSA) are diseases with high prevalence and major public health impact. There is evidence that OSA is independently associated with alterations in glucose metabolism. Furthermore, OSA is a significant risk factor for the development of type 2 diabetes. Possible causes might be intermittent hypoxaemia and sleep fragmentation with increased oxidative stress and sympathetic activity, which are typical features of OSA. OSA might also be a reason for ineffective treatment of type 2 diabetes. There is further evidence that the treatment of OSA by continuous positive airway pressure (CPAP) therapy might improve glucose metabolism. On the other hand, there are also hints in the literature that type 2 diabetes might induce sleep apnoea, especially in patients with autonomic neuropathy, but that OSA also facilitates the development of neuropathy in terms of mutual interactions between OSA, type 2 diabetes and diabetic neuropathy. Based on the current scientific data, clinicians have to be aware of the relations between OSA and type 2 diabetes, both from the sleep medical and the diabetological point of view.

Response to Imported Case of Marburg Hemorrhagic Fever, the Netherlands

On July 10, 2008, Marburg hemorrhagic fever was confirmed in a Dutch patient who had vacationed recently in Uganda. Exposure most likely occurred in the Python Cave (Maramagambo Forest), which harbors bat species that elsewhere in Africa have been found positive for Marburg virus. A multidisciplinary response team was convened to perform a structured risk assessment, perform risk classification of contacts, issue guidelines for follow-up, provide information, and monitor the crisis response. In total, 130 contacts were identified (66 classified as high risk and 64 as low risk) and monitored for 21 days after their last possible exposure. The case raised questions specific to international travel, postexposure prophylaxis for Marburg virus, and laboratory testing of contacts with fever. We present lessons learned and results of the follow-up serosurvey of contacts and focus on factors that prevented overreaction during an event with a high public health impact.

Response to Imported Case of Marburg Hemorrhagic Fever, the Netherlands

On July 10, 2008, Marburg hemorrhagic fever was confirmed in a Dutch patient who had vacationed recently in Uganda. Exposure most likely occurred in the Python Cave (Maramagambo Forest), which harbors bat species that elsewhere in Africa have been found positive for Marburg virus. A multidisciplinary response team was convened to perform a structured risk assessment, perform risk classification of contacts, issue guidelines for follow-up, provide information, and monitor the crisis response. In total, 130 contacts were identified (66 classified as high risk and 64 as low risk) and monitored for 21 days after their last possible exposure. The case raised questions specific to international travel, postexposure prophylaxis for Marburg virus, and laboratory testing of contacts with fever. We present lessons learned and results of the follow-up serosurvey of contacts and focus on factors that prevented overreaction during an event with a high public health impact.

Recent Trends in Breast Cancer Incidence and Mortality in Germany

Background: Breast cancer is the most common cancer among women in Germany with high public health impact. In the last decade rapid changes in risk factor patterns, early breast cancer detection, and therapy have taken place. Their effects on breast cancer epidemiology in Germany are described. Materials and Methods: A register-based survey using recent incidence data from German cancer registries was performed. Mortality data were provided by the Central Federal Statistical Office. We calculated age-standardized rates and 5- and 10-year trends. Results: Breast cancer incidence increased until the year 2002, thereafter a discreet decline occurred until 2005 (– 6.8%). In the age group 50–59 years this reduction was most pronounced (– 12%). Mortality declined from 1996/7 to 2004/5 by 19%, with the strongest effect in women younger than 55 years (approximately 30%). Regional patterns of breast cancer incidence and mortality revealed differences within Germany of greater than 30%. Conclusion: Declining hormone replacement therapy prescription is the most likely factor to explain the drop in breast cancer incidence. The reduction in mortality might be caused by better therapy and enhanced early detection during the last decade. Differences in breast cancer incidence and mortality between Eastern and Western Germany give reason for further research and discussion.

Using the RE-AIM Framework to Evaluate the Statewide Dissemination of a School-Based Physical Activity and Nutrition Curriculum: “Exercise Your Options”

Examine the reach, efficacy, adoption, implementation, and maintenance of a physical activity and nutrition curriculum for middle-school students. Nonexperimental pilot evaluation of a statewide dissemination trial. California middle schools during the 2006 to 2007 school year. Sixteen classes (N = 668 students and 16 teachers) sampled from the statewide pool who used the program. An eight-lesson nutrition and physical activity curriculum, "Exercise Your Options" (EYO), including a teacher guide, video clips, a student activity booklet, and ancillary materials was made available to teachers. Program records, classroom observations, teacher surveys, and student presurveys and postsurveys (assessing physical activity, sedentary behaviors, and dietary intake). Descriptive statistics and multilevel random-coefficient modeling. The EYO program reached 234,442 middle-school students in California. During the program, total physical activity increased (p < .001), whereas watching TV/DVDs and playing electronic games/computer use decreased (p < .05). Intake of dairy products increased (p < .05), whereas consumption of sugars/sweets decreased (p < .001). Forty-two percent of eligible middle-school classrooms ordered the program materials. Eighty-six percent of sampled teachers implemented all of the lessons. Over the past 5 years, 51% of all middle-school students in California were exposed to the program. The EYO program showed its potential for moderate to high public health impact among California middle-school students.

WHO's Response to Global Public Health Threats: XDR-TB

(This letter appears in response to the May 2007 PLoS Medicine Editorial: “How Is WHO Responding to Global Public Health Threats?” [1]) The travels of a patient with extensively drug-resistant tuberculosis (XDR-TB) from North America to Europe and back have heightened concerns about this growing global disease problem and the possibility of its international transmission through travel. The seriousness of this possibility raises the question of whether XDR-TB cases or outbreaks may constitute public health emergencies of international concern (PHEICs) under the 2005 International Health Regulations (IHR 2005), which became binding international law on June 15, 2007 [2]. XDR-TB may be the first case of a public health problem that tests how States Parties and the World Health Organization (WHO) apply the IHR 2005. We believe that cases or outbreaks of XDR-TB would meet the notification criteria of the IHR 2005 as events that may constitute a PHEIC because they trigger affirmative answers to at least two of the four questions in the IHR 2005's decision instrument (Annex 2, [3]). Thus, as of June 15, 2007, States Parties must report such cases or outbreaks to WHO pursuant to the IHR 2005. XDR-TB triggers an affirmative answer to the decision instrument's question: “Is the public health impact of the event serious?”, both because of the possibility of the event having a high public health impact and, in many instances, the need for external assistance in managing cases. XDR-TB cases would likely produce an affirmative answer to the question: “Is the event unusual or unexpected?”, because of the higher than expected case-fatality rates, particularly where XDR-TB occurs with high prevalence of HIV infection. The disease also may generate a positive answer to the question: “Is there a significant risk of international travel or trade restrictions?”, primarily because of the possibility of international media attention. At present, XDR-TB would arguably not produce a clearly affirmative answer to the question: “Is there a significant risk of international spread?”, because epidemiological data linking XDR-TB outbreaks and cases with the international movement of people are weak. Experience with TB, multi-drug-resistant TB (MDR-TB), and XDR-TB demonstrates, however, that cross-border spread is a very real threat. XDR-TB has already spread from one province to several provinces in South Africa, and has in all likelihood crossed African borders, but confirmation is delayed because of inadequate surveillance capabilities. It remains less certain whether the WHO Director-General would determine that XDR-TB cases or outbreaks notified to WHO would constitute a PHEIC. This would lead to the issuance of temporary recommendations to States Parties, which could include travel restrictions and use of compulsory measures such as quarantine or isolation. In February 2007, the WHO Global Task Force on XDR-TB argued against such a position because “the new regulations are aimed particularly to situations where there is a significant risk of international spread” and that temporary recommendations “are really intended for outbreaks of acute disease, rather than the ‘acute-on-chronic’ situation of MDR-TB and XDR-TB” [4]. The Global Task Force stated that, if international spread of XDR-TB were demonstrated, then standing recommendations should be considered. To some extent, the recommendations and alerts WHO has already issued on XDR-TB suggest that treating XDR-TB as a routine public health risk is not adequate. In addition, the IHR 2005 does not limit its scope of application to “acute disease” [5]. TB has never been an acute risk in the same manner as a pandemic strain of influenza, but history attests to TB's persistence as a lethal global threat, especially for vulnerable populations. As the global XDR-TB problem becomes more severe, more robust and drastic public health actions may be required nationally and globally, including a declaration from the WHO Director-General of the existence of a PHEIC. A window of opportunity may exist now for effective international action to control the spread of the disease, and the IHR 2005 may provide a mechanism to help achieve this objective. A narrow, limited reading of the IHR 2005's scope of application could undermine its ability to contribute to this global health crisis.

Amodiaquine, malaria, pregnancy: the old new drug

In todays Lancet Harry Tagbor and colleagues report on the efficacy safety and tolerability of amodiaquine alone and combined with sulfadoxine-pyrimethamine in the treatment of malaria in pregnant women in Ghana. In endemic countries malaria during pregnancy has a major effect on pregnant womens health birthweight fetal loss infant morbidity and survival. Infections during pregnancy require prompt and effective treatment. Sulfadoxine-pyrimethamine alone is the most commonly used combination for both treatment and prevention of malaria in pregnancy in Africa but resistance is increasing alarmingly4 and the arsenal of alternative antimalarials for use in pregnancy is remarkably limited for a disease with such a high public-health impact. In recent years several new antimalarials have become available or are at an advanced stage of development including several artemisinin-based combination therapies. However little information on the safety pharmacokinetics and efficacy of these new drugs is available in pregnant women because they are systematically excluded from trials for fear of toxicity to the fetus. Amodiaquine is structurally related to chloroquine and has been around for 60 years. The drug was widely used between 1948 and 1990 before being temporarily removed from the essential drug list after reports of serious adverse events in travellers using chemoprophylaxis. (excerpt)