Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae) and the more recently discovered Mycobacterium lepromatosis (M. lepromatosis). The two leprosy bacilli cause similar pathologic conditions. They primarily target the skin and the peripheral nervous system. Currently it is considered a Neglected Tropical Disease, being endemic in specific locations within countries of the Americas, Asia, and Africa, while in Europe it is only rarely reported. The reason for a spatial inequality in the prevalence of leprosy in so-called endemic pockets within a country is still largely unexplained. A systematic review was conducted targeting leprosy transmission research data, using PubMed and Scopus as sources. Publications between January 1, 1945 and July 1, 2019 were included. The transmission pathways of M. leprae are not fully understood. Solid evidence exists of an increased risk for individuals living in close contact with leprosy patients, most likely through infectious aerosols, created by coughing and sneezing, but possibly also through direct contact. However, this systematic review underscores that human-to-human transmission is not the only way leprosy can be acquired. The transmission of this disease is probably much more complicated than was thought before. In the Americas, the nine-banded armadillo (Dasypus novemcinctus) has been established as another natural host and reservoir of M. leprae. Anthroponotic and zoonotic transmission have both been proposed as modes of contracting the disease, based on data showing identical M. leprae strains shared between humans and armadillos. More recently, in red squirrels (Sciurus vulgaris) with leprosy-like lesions in the British Isles M. leprae and M. lepromatosis DNA was detected. This finding was unexpected, because leprosy is considered a disease of humans (with the exception of the armadillo), and because it was thought that leprosy (and M. leprae) had disappeared from the United Kingdom. Furthermore, animals can be affected by other leprosy-like diseases, caused by pathogens phylogenetically closely related to M. leprae. These mycobacteria have been proposed to be grouped as a M. leprae-complex. We argue that insights from the transmission and reservoirs of members of the M. leprae-complex might be relevant for leprosy research. A better understanding of possible animal or environmental reservoirs is needed, because transmission from such reservoirs may partly explain the steady PLOS NEGLECTED TROPICAL DISEASES
ContextRecent public outcry has highlighted the rising cost of prescription drugs worldwide, which in several disease areas outpaces other health care expenditures and results in a suboptimal global availability of essential medicines.MethodA systematic review of Pubmed, the Financial Times, the New York Times, the Wall Street Journal and the Guardian was performed to identify articles related to the pricing of medicines.FindingsChanges in drug life cycles have dramatically affected patent medicine markets, which have long been considered a self-evident and self-sustainable source of income for highly profitable drug companies. Market failure in combination with high merger and acquisition activity in the sector have allowed price increases for even off-patent drugs. With market interventions and the introduction of QALY measures in health care, governments have tried to influence drug prices, but often encounter unintended consequences. Patent reform legislation, reference pricing, outcome-based pricing and incentivizing physicians and pharmacists to prescribe low-cost drugs are among the most promising short-term policy options. Due to the lack of systematic research on the effectiveness of policy measures, an increasing number of ad hoc decisions have been made with counterproductive effects on the availability of essential drugs. Future challenges demand new policies, for which recommendations are offered.ConclusionA fertile ground for high-priced drugs has been created by changes in drug life-cycle dynamics, the unintended effects of patent legislation, government policy measures and orphan drug programs. There is an urgent need for regulatory reform to curtail prices and safeguard equitable access to innovative medicines.
Prospective parents in the Dutch population seem interested in newborn screening for untreatable childhood-onset disorders; therefore, we argue that additional debate of pros and cons is needed among policy makers, health care professionals, and consumers.
BackgroundIn 2003–2004 and 2007–2008, the regulatory banning of SSRI use in pediatrics and young adults due to concerns regarding suicidality risk coincided with negative media coverage. SSRI use trends were analyzed from 2000–2010 in the Netherlands (NL) and the UK, and whether trend changes might be associated with media coverage of regulatory warnings.MethodsMonthly SSRIs sales were presented as DDDs/1000 inhabitants/day. SSRI-use trends were studied using time-series segmented regression analyses. Timing of trend changes was compared with two periods of media coverage of warnings. Annual Dutch SSRI prescription data were analyzed by age group.ResultsTrend changes in SSRI use largely corroborated with the periods of media coverage of warnings. British SSRI use declined from 3.9 to 0.7 DDDs/month (95%CI 3.3;4.5 & 0.5;0.9, respectively) before the first warning period (2003–2004). A small decrease of −0.6 DDDs/month (−1.2; −0.05) was observed in Dutch SSRI use shortly after 2003–2004. From 2007–2008, British SSRI use stabilized, whilst Dutch SSRI use diminished to −0.04 DDDs/month (−0.4;0.3). Stratified analyses showed a rapid decrease of −1.2 DDDs/month (−2.1; −1.7) in UK paroxetine use before 2003–2004, but only a minimal change in Dutch paroxetine use (−0.3 DDDs/month −0.8;0.2). Other SSRI use, especially (es)citalopram, increased during 2003–2004 in both countries. Significant reductions in Dutch paroxetine use were observed in pediatrics, adolescents, and young adults after 2003–2004.ConclusionChanges in SSRI use (NL & UK) were associated with the timing of the combined effect of media coverage and regulatory warnings. Our long-term assessment illustrates that changes in SSRI use were temporal, drug-specific and more pronounced in pediatrics and young adults. The twofold increase in SSRI use over one decade indicates that regulatory warnings and media coverage may come and go, but they do not have a significant impact on the overall upward trend of SSRI use as a class in both countries.
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