Assessment of Long-Term Health Effects of Antimalarial Drugs When Used for Prophylaxis (2020) / Chapter Skim
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2 Background
2 Background
Pages 25-56
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From page 25... ...
It then provides an overview of how the antimalarials under consideration interrupt the life cycle of the Plasmodium parasites and discusses the differences among causal prophylaxis, suppressive prophylaxis, presumptive anti-relapse therapy, and the treatment of malaria. An overview of differences among the classes of antimalarial drugs and their mechanisms of action is also provided.
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Disease Infection with the Plasmodium parasite occurs after an infected female nopheles mosquito takes a blood meal from a human host. Once the parasite A infects a human, it migrates to the liver and enters into an incubation period during which the parasite establishes itself within the body and continues its life cycle.
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Because it is difficult to differentiate between the symptoms caused by high fever and those caused by severe malaria, removing fever from the case definition allows for more precise diagnostic criteria in which fever is removed as a potential confounder. Although WHO's case definition for severe malaria no longer includes neurologic symptoms not directly associated with coma, several studies have found that many survivors of severe malaria can develop long-term physiologic damage resulting in neurologic and cognitive deficits (Idro et al., 2006, 2010, 2016; John et al., 2008)
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PROPHYLACTIC ANTIMALARIAL DRUGS As described in Chapter 1, the antimalarial drugs covered by this report are those that are currently available and approved by the Food and Drug Administration (FDA) as of 2019 for malaria prophylaxis in adults and that are currently being used, or that have been used in the past 25 years by U.S.
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. e e s Merozoites infect red blood cells .
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Suppressive prophylaxis refers to drugs that act only on parasites within the red blood cells (Schwartz, 2012)
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, mefloquine, chloroquine, and doxycycline are defined exclusively as suppressive antimalarial prophylactic drugs. Suppressive prophylaxis has no effect on Plasmodium parasites until the liver phase of the life cycle is complete and the parasite has invaded red blood cells.
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. The adverse events of a given drug are often difficult to predict a priori, but sometimes the compounds of a certain drug class result in common adverse events.
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ovale malaria. It is the most widely used 8-aminoquinoline for malaria prophylaxis, but its exact mechanism of action is still unknown.
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G6PD deficiency causes an increased susceptibility of rythrocytes to hydrogen peroxide and other reactive oxygen species which e can lead to hemolysis (the rupture of red blood cells and release of their contents into the plasma) and hemolytic anemia (red blood cells being destroyed faster than they can be replaced)
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As a result, heterozygous females may express G6PD-deficient characteristics that are not detected by the currently available field testing procedures (Ley et al., 2017) ; the presentation of these false-negative results may lead to inadvertent exposure to 8-aminoquinoline antimalarial drugs and their subsequent adverse events (Peters and Van Noorden, 2009)
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Furthermore, as numerous non-antimalarial drugs also contain quinoline substructures, overgeneralizations about adverse events of quinolines as a group are unwarranted (Dorwald, 2012)
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The electron transport system of the Plasmodium species is 1,000 times more sensitive to atovaquone than this system in mammals, which is thought to explain the selective action and limited adverse events of the drug (Schlagenhauf et al., 2019)
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military deployments, actions, and overseas exercises since the American Civil War (see Table 2-1) , and despite advances in antimalarial drugs and improvements in preventive equipment and supplies, it remains an ongoing threat (IOM, 2006)
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falciparum Action primarily in Panama City Persian Gulf 1991 P vivax Few cases in northern Iraq, Kurdish area Somalia 1992–1994 P
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. The military began testing doxycycline for malaria prophylaxis in 1985, but it was not used routinely for prophylaxis until 1992 in Somalia (Sánchez et al., 1993; Wallace et al., 1996)
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However, while ordinary travelers are encouraged to adhere to malaria prophylaxis, military personnel are required to do so. Moreover, military personnel often use malaria prophylaxis for longer periods than travelers (many deployments are for 1 year or more)
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Studies specifically examining adherence in the case of drugs used for malaria prophylaxis have reported several reasons for the low rates of adherence, including forgetfulness, fear of adverse events, discomfort of swallowing or of swallowng i too many pills, receiving inaccurate pre-travel advice from nonmedical or medical professionals, incorrect risk perception, failure to take any prophylaxis, and inaccurate understanding of malaria transmission (Adshead, 2014; Behrens et al., 1998; Cunningham et al., 2014; Goodyer et al., 2011; Hopperus Buma et al., 1996; Huzly et al., 1996; Landman et al., 2015; Laver et al., 2001; Ollivier et al., 2008; Phillips and Kass, 1996; Ropers et al., 2008; Saunders et al., 2015)
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. While real or perceived side effects and adverse events of drugs used for malaria prophylaxis are common reasons given for the lack of adherence to them, other factors may contribute, especially during deployments.
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, and these are antimalarial drugs that VA considers to be of high interest. Some of the potentially confounding exposures were unique to specific conflicts, such as the numerous oil-well fires and their smoke, the release of the nerve agents sarin and cyclosarin, and the use of pyridostigmine bromide as a prophylaxis for the nerve agents in the 1990–1991 Persian Gulf War.
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For example, during the 1990– 1991 Persian Gulf War, about 150,000 troops received anthrax vaccine and about 8,000 troops received botulinum toxoid vaccine, although medical records from this period are notably lacking information regarding who received these vaccines, how frequently the vaccines were administered, or the timing of vaccinations relative to other putative exposures (IOM, 2000)
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Many surveys have been conducted to assess veterans' combat experiences and exposures (e.g., Millennium Cohort Study, National Health Survey of Gulf War Era Veterans and Their Families, National Health Study for a New Generation of U.S. Veterans)
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In addition, several studies of deployment experiences found that female military personnel were more likely to experience sexual harassment and assault than male personnel (Goldzweig et al., 2006; Kang et al., 2005; Vogt et al., 2005; Wolfe et al., 1998)
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For example, a person who is a poor metabolizer of a particular substance, depending on his or her genetic makeup, might be at higher or lower risk for specific health effects if exposed to the substance. All antimalarial drugs used for prophylaxis in adults are prescribed as fixed dose regimens in which the amount of drug (e.g., one tablet)
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For example, among people who use mefloquine, more women report adverse events than men. Because in general women weigh less than men and have a smaller vascular volume, a fixed dose tablet of an antimalarial may result in higher plasma levels of the drug in people of lower weight (women)
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2014. Compliance with long term malaria prophylaxis in British expatriates.
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Am J Trop Med Hyg 69(6)
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2005. The role of sexual assault on the risk of PTSD among Gulf War veterans.
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Travel Med Infect Dis 12:61-68. Laver, S
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Am J Trop Med Hyg 100(1)
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1999. Health of UK servicemen who served in Persian Gulf War.
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female Persian Gulf War military personnel. J Interpers Violence 13(1)
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