DOCSLIB.ORG

Tafenoquine for Prevention of Malaria

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Tafenoquine for Prevention of Malaria Tafenoquine for Prevention of Malaria July 26, 2018 60 Degrees Pharmaceuticals, LLC Antimicrobial Drugs Advisory Committee Meeting 1 Overview Geoffrey Dow, PhD Chief Scientific Officer & CEO 60 Degrees Pharmaceuticals, LLC 2 Global Burden of Malaria P. falciparum 216,000,000 cases annually P. vivax 8,550,000 cases annually Tatem (2017). Malaria Impact and Burden WHO (2017). World Malaria Report 3 Current Approaches to Malaria Elimination Fall Short Number of cases 2010 2011 2012 2013 2014 2015 2016 Lower 95% Cl 218,000,000 207,000,000 199,000,000 191,000,000 191,000,000 192,000,000 196,000,000 Estimated total 237,000,000 225,000,000 217,000,000 210,000,000 210,000,000 211,000,000 216,000,000 Upper 95% Cl 278,000,000 267,000,000 262,000,000 256,000,000 256,000,000 257,000,000 263,000,000 New Therapeutics With Different Labeling Required? . Multiple dosing . Longer duration of dosing . Asymptomatic & non-immune subjects WHO (2017). World Malaria Report 4 US Malaria Burden 1973-2013 Cullen KA, Mace KE, Arguin PM. Malaria Surveillance — United States, 2013. MMWR Surveill Summ 2016;65(No. SS-2)(No. SS-2):1–22. DOI: http://dx.doi.org/10.15585/mmwr.ss6502a1 96% of malaria cases due to failure to comply with malaria chemoprophylaxis 5 This just isn’t good enough! Severe malaria is entirely preventable 6 Vision: Malaria Prevention with ARAKODA 0 0 malaria cases pediatric deaths amongst deployed from falciparum malaria U.S. service members 0 malaria cases in U.S. 0 outbreaks in returning travelers elimination regions 7 ARAKODA – Target Label Claims Description & Target Label Claims Attribute Description API Name ● Tafenoquine succinate Presentation ● 100 mg tablets Indication ● Prevention of malaria in adults for up to six months dosing Dosing ● Loading dose: 200 mg once per day for 3 days within one week of travel ● During travel: 200 mg once per week ● Following travel: 200 mg once within 1 week of return from travel Efficacy ● During travel: Protective efficacy (95% CI) = 100% (93-100%) ● Post exposure: Protective efficacy equivalent to primaquine (30 mg x 14 days) Common AEs ● GI distress, back pain, certain infections Contraindications ● Severe G6PD deficiency ● Pregnancy - G6PD status of fetus cannot be determined “All parasites, everywhere, with a safe, simple dosing regimen” 8 ARAKODA Compared to Standard of Care Kills all Pf Single Dose Global # Tabs for 1 Neurologic G6PD Test Drug Dosing and Pv Post- use MO trip* Liability Required stages Exposure Daily No Yes No 72 No No Weekly No No No 25 Yes No Daily No Yes No 51 No No ARAKODA Weekly Yes Yes Yes 16 No Yes * Includes loading or pre-travel doses, post-travel doses, and 14 days of post-exposure primaquine (the latter only for Malarone®, Doxycycline, and Lariam®) 9 Malaria Lifecycle 10 Malaria Lifecycle & Mode of Action of ARAKODA ARAKODA is active against all the mammalian stages of malaria • Exact mechanism of action is not known 11 Tolerability of Primaquine for Malaria Prophylaxis 6 MO Baird (1992) 12 MO Fryauff (1995) • Primaquine and placebo equally well tolerated following daily administration up to 12MO 12 Adverse Event Labeling for Primaquine Prophylaxis Adverse drug reactions. Most common mild/moderate adverse drug reactions (ADRs): abdominal pain, nausea, vomiting. Severe hemolysis in persons with G6PD deficiency. Met- hemoglobinemia occurs, but is not reported to be clinically significant at dosages used for prophylaxis. In studies, 0-2% of persons have reported a severe reaction and 0-2% have discontinued prophylaxis because of ADRs. No specific warnings for neuropsychiatric events Hill (2006) 13 ARAKODA is an Improved Primaquine Analog F3C O CH3 5 4 5 4 O 6 3 O 6 3 2 2 8 N 8 N OMe HN HN NH2 NH2 PRIMAQUINE ARAKODA ● Half-Life: 6h ● Half-Life: 14 days ● Kills hepatic stages ● Kills hepatic stages ● Weak activity against blood stages ● Kills blood stages in vivo ● No evidence of neurologic liability ● No evidence of neurologic from clinical literature liability from Sponsor database 14 Primaquine and Mefloquine Act Differently Defining Structural Feature Activation in vivo ACTIVE OXIDATIVE SPECIES DIRECT ACTION PRIMAQUINE MEFLOQUINE (8-AMINOQUINOLINE) (4-QUINOLINE METHANOL) ● Kills parasites following activation ● Direct antiparasitic effect ● Kills hepatic stages ● No effect on hepatic stages ● Weak activity against blood stages ● Potent blood schizonticide ● No evidence of neurologic liability ● Increases frequency of neuropsychiatric from clinical literature events relative to standard of care 15 Important Clinical Studies of ARAKODA Study 030 043 045 033 057 60PH02 60PH04 Year(s) Conducted 2000 1997 1998 1999-2000 2003-2006 2017 Ongoing Study Design* PC, MQ MQ PC, MQ MQ PC PC PC Efficacy & Parameters Assessed Safety & Efficacy Safety & Efficacy Safety & Efficacy Safety & Efficacy Safety Safety Safety Non-immune military Population Residents of Residents of Residents of population (deployed Residents of Residents of Residents of Characteristics malaria- malaria-endemic malaria- to malaria-endemic US and UK Australia Australia endemic area area endemic area (all Healthy Adults) area) Bobonaro District and Kassena Maryland, USA Nyanza Nyanza Province, capitol (Dili) of East Brisbane, Multiple sites in Study Location Nankana and Berkshire, Province, Kenya Kenya Timor (now Timor Queensland Australia and US District, Ghana UK Leste) Number of Subjects 300 104 ARAKODA 55 ARAKODA 93 ARAKODA 492 ARAKODA 81 ARAKODA 12 ARAKODA (ARAKODA; ARAKODA** 101 MQ 0 MQ 46 MQ 162 MQ 0 MQ 0 MQ Mefloquine (M); 0 MQ 101 PC 61 PC 94 PC 0 PC 39 PC 4 PC Placebo (P)) 300 PC Duration of Study 24 weeks 10-15 weeks 13 weeks 26±4 weeks 24 weeks 10 days 52 weeks Drug Dosing Safety Follow-up after 4 weeks 4 weeks 4 weeks 24 weeks 24 weeks 21 days 12 weeks Study Drug Dosing *All studies were randomized and double blinded, comparators were PC = placebo or MQ = mefloquine **Size of Safety Database at filing: 825; Size of Safety Database at 60PH04 Completion: 1125 16 Deployment is a Risk Factor for Neuropsychiatric Events Psychologically-attributed war-related illnesses have included (Hyams (1996), Jones (2002)): . “nostalgia” (US Civil War); . shell shock or trench neurosis (World War I); . battle fatigue, combat exhaustion, or operational fatigue (World War II and the Korean Conflict); . post-traumatic stress disorder (PTSD) (Vietnam War and Persian Gulf War) Diagnoses of mental illnesses, especially PTSD and depression, increased substantially among returned US military personnel who had been deployed to Iraq or Afghanistan (Seal (2009), Plumb (2014), McGlinchey (2017), Nissen (2017), Primack (2017), Qi (2016)). In almost all studies of war-related illnesses, a suitable control population is unavailable, and the single unifying theme is that a unique (military) population is intensely scrutinized after experiencing an exceptional, life- threatening set of exposures (Hyams (1996)). In the rare studies that do report on comparisons deployed and non-deployed personnel, or comparisons between pre- and post-deployment mental health status, these studies support a negative effect of deployment on mental health (Hermes (2014), Hom (2017), Jaksic (2017)). 17 Timor Deployment Considered “Warlike” by Australian Government - Waller (2012) . Psychologically-attributed Study 033 – ADF deployed to East Timor (2000-2001), a “warlike” military operation. Australian government: “Warlike operations” = military activities where force is authorized and casualties are expected . Specific traumatic exposures reported by ADF deployed to East Timor: . danger of being injured or killed (71% of ADF reported this); . witness to human degradation and misery on a large scale (58%); . saw dead bodies (49%) or handled dead bodies (28%); . feared you had been exposed to a toxic agent, contagious disease, or injury (31%); . heard of a close friend or co-worker injured or killed (30%); . present when a close friend or co-worker was injured or killed (13%). Other stressors: threat of danger (67%) and health concerns (52%). Among all ADF personnel deployed to East Timor: 7.2% developed PTSD and 6.9% had a long-term high level of psychological stress at 7-9 years after deployment 18 Burden of Diagnosed Neuropsychiatric Illness Following Mefloquine and Malarone Administration in US Military Personnel Antimalarial Mefloquine Malarone Deployment Status Not Deployed Deployed Not Deployed Deployed Total Incidence of Neuropsychiatric 58.59/ 98.27/ 57.92/ 98.46/ Adverse Reactions per 1000 Person 10,847 25,691 10,261 2,620 Years/Number of Personnel* Increase Associated With Deployment (%) 68% 70% Individual Neuropsychiatric Endpoints: . No statistical difference amongst deployed individuals . Incidence of PTSD higher amongst non-deployed individuals administered mefloquine relative to Malarone *Excluding tinnitus Eick-Cost (2017) 19 Important Nonclinical Studies of ARAKODA Key Findings: . Comprehensive nonclinical safety package. All available information submitted to FDA and TGA for review. In the 35 in vivo acute and chronic dose toxicology studies (with mice – 2 years; rats – 2 years; dogs – 1 year) as well as 15 pharmacology studies (mice, rats, dogs, and monkeys), no neurotoxicity observed . Major organ risk is lung (phospholipodosis, dog only), liver (centrilobular inflammation, apoptosis and fatty change, increased plasma transaminases) and kidney (tubular nephrosis, necrosis, and dilation [rat only, 13 wks]) . ARAKODA: . has no safety pharmacology risk for lung and brain. No clinical risk to the heart from QT prolongation.
Load more

Recommended publications
  • Stevelinkbjpauthors Reply
    King’s Research Portal Link to publication record in King's Research Portal Citation for published version (APA): Stevelink, S., Jones, M. M., Greenberg, N., Rona, R. J., & Fear, N. T. (2019). Mental health outcomes at the end of the British involvement in the Iraq and Afghanistan conflicts: a cohort study - Authors' reply. British Journal of Psychiatry. Citing this paper Please note that where the full-text provided on King's Research Portal is the Author Accepted Manuscript or Post-Print version this may differ from the final Published version. If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections. General rights Copyright and moral rights for the publications made accessible in the Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognize and abide by the legal requirements associated with these rights. •Users may download and print one copy of any publication from the Research Portal for the purpose of private study or research. •You may not further distribute the material or use it for any profit-making activity or commercial gain •You may freely distribute the URL identifying the publication in the Research Portal Take down policy If you believe that this document breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim.
    [Show full text]
  • Rediscovery of Fexinidazole
    New Drugs against Trypanosomatid Parasites: Rediscovery of Fexinidazole INAUGURALDISSERTATION zur Erlangung der Würde eines Doktors der Philosophie vorgelegt der Philosophisch-Naturwissenschaftlichen Fakultät der Universität Basel von Marcel Kaiser aus Obermumpf, Aargau Basel, 2014 Originaldokument gespeichert auf dem Dokumentenserver der Universität Basel edoc.unibas.ch Dieses Werk ist unter dem Vertrag „Creative Commons Namensnennung-Keine kommerzielle Nutzung-Keine Bearbeitung 3.0 Schweiz“ (CC BY-NC-ND 3.0 CH) lizenziert. Die vollständige Lizenz kann unter creativecommons.org/licenses/by-nc-nd/3.0/ch/ eingesehen werden. 1 Genehmigt von der Philosophisch-Naturwissenschaftlichen Fakultät der Universität Basel auf Antrag von Prof. Reto Brun, Prof. Simon Croft Basel, den 10. Dezember 2013 Prof. Dr. Jörg Schibler, Dekan 2 3 Table of Contents Acknowledgement .............................................................................................. 5 Summary ............................................................................................................ 6 Zusammenfassung .............................................................................................. 8 CHAPTER 1: General introduction ................................................................. 10 CHAPTER 2: Fexinidazole - A New Oral Nitroimidazole Drug Candidate Entering Clinical Development for the Treatment of Sleeping Sickness ........ 26 CHAPTER 3: Anti-trypanosomal activity of Fexinidazole – A New Oral Nitroimidazole Drug Candidate for the Treatment
    [Show full text]
  • Australian Public Assessment Report for Tafenoquine (As Succinate)
    Australian Public Assessment Report for Tafenoquine (as succinate) Proprietary Product Name: Kozenis Sponsor: GlaxoSmithKline Australia Pty Ltd November 2018 Therapeutic Goods Administration About the Therapeutic Goods Administration (TGA) • The Therapeutic Goods Administration (TGA) is part of the Australian Government Department of Health and is responsible for regulating medicines and medical devices. • The TGA administers the Therapeutic Goods Act 1989 (the Act), applying a risk management approach designed to ensure therapeutic goods supplied in Australia meet acceptable standards of quality, safety and efficacy (performance) when necessary. • The work of the TGA is based on applying scientific and clinical expertise to decision- making, to ensure that the benefits to consumers outweigh any risks associated with the use of medicines and medical devices. • The TGA relies on the public, healthcare professionals and industry to report problems with medicines or medical devices. TGA investigates reports received by it to determine any necessary regulatory action. • To report a problem with a medicine or medical device, please see the information on the TGA website <https://www.tga.gov.au>. About AusPARs • An Australian Public Assessment Report (AusPAR) provides information about the evaluation of a prescription medicine and the considerations that led the TGA to approve or not approve a prescription medicine submission. • AusPARs are prepared and published by the TGA. • An AusPAR is prepared for submissions that relate to new chemical entities, generic medicines, major variations and extensions of indications. • An AusPAR is a static document; it provides information that relates to a submission at a particular point in time. • A new AusPAR will be developed to reflect changes to indications and/or major variations to a prescription medicine subject to evaluation by the TGA.
    [Show full text]
  • A Novel Disease Affecting US Veterans
    Identifying and Evaluating Sources of Evidence of Quinism: A Novel Disease Affecting U.S. Veterans Remington Nevin, MD, MPH, DrPH Executive Director Neuropsychiatric Quinism • Significant empirical evidence of a common set of symptoms and signs developing after exposure to quinoline drugs – Quinine, quinacrine, clioquinol, primaquine, chloroquine, mefloquine, tafenoquine, and others – 100+ years of case reports, pharmacovigilance reports, and accumulated clinical observations • Significant in vitro and in vivo evidence of a common pathophysiology – Chronic encephalopathy from focal brainstem and limbic neurotoxicity – Idiosyncratic effects at prophylactic doses Nevin RL. Neuropsychiatric Quinism: Chronic Encephalopathy Caused by Poisoning by Mefloquine and Related Quinoline Drugs. In: Ritchie EC, Llorente M, eds. Veteran Psychiatry in the US. Cham, Switzerland: Springer Nature; 2019. doi:10.1007/978-3-030-05384-0. In press. “Psychiatric symptoms such as insomnia, abnormal dreams/nightmares, acute anxiety, depression, restlessness or confusion have to be regarded as prodromal for a more serious event.” Roche UK. Lariam product documentation, June 2018. Emphasis added. Confounding Insomnia Exposure assumed causation Nightmares to Traumas Depression independent causation Anxiety correlation Confounder Confounding Insomnia Exposure assumed causation Nightmares to Traumas Depression actual causation Anxiety correlation Disequilibrium Mefloquine Vertigo Nevin RL. Mefloquine Exposure May Confound Associations and Limit Inference in Military Studies of Posttraumatic Stress Disorder. Military Medicine. 2017;182(11/12):1757. WRMI-2 • “Have you ever taken the weekly drug mefloquine (also known as Lariam®) to prevent malaria?" • If yes, “At any time while taking the drug, did you experience abnormal dreams or nightmares, insomnia, anxiety, depression, restlessness, or confusion?” © 2018 Remington Nevin. Under license to The Quinism Foundation.
    [Show full text]
  • Injectable Anti-Malarials Revisited: Discovery and Development of New Agents to Protect Against Malaria
    Macintyre et al. Malar J (2018) 17:402 https://doi.org/10.1186/s12936-018-2549-1 Malaria Journal REVIEW Open Access Injectable anti‑malarials revisited: discovery and development of new agents to protect against malaria Fiona Macintyre1, Hanu Ramachandruni1, Jeremy N. Burrows1, René Holm2,3, Anna Thomas1, Jörg J. Möhrle1, Stephan Duparc1, Rob Hooft van Huijsduijnen1 , Brian Greenwood4, Winston E. Gutteridge1, Timothy N. C. Wells1* and Wiweka Kaszubska1 Abstract Over the last 15 years, the majority of malaria drug discovery and development eforts have focused on new mol- ecules and regimens to treat patients with uncomplicated or severe disease. In addition, a number of new molecular scafolds have been discovered which block the replication of the parasite in the liver, ofering the possibility of new tools for oral prophylaxis or chemoprotection, potentially with once-weekly dosing. However, an intervention which requires less frequent administration than this would be a key tool for the control and elimination of malaria. Recent progress in HIV drug discovery has shown that small molecules can be formulated for injections as native molecules or pro-drugs which provide protection for at least 2 months. Advances in antibody engineering ofer an alternative approach whereby a single injection could potentially provide protection for several months. Building on earlier profles for uncomplicated and severe malaria, a target product profle is proposed here for an injectable medicine providing long-term protection from this disease. As with all of such profles, factors such as efcacy, cost, safety and tolerability are key, but with the changing disease landscape in Africa, new clinical and regulatory approaches are required to develop prophylactic/chemoprotective medicines.
    [Show full text]
  • Data Sheet of Clinical Trial C.T
    DATA SHEET OF CLINICAL TRIAL C.T. No 048-14 CLINICAL TRIAL REGISTRATION (EC) I. SPONSOR INFORMATION Foreign National 2. LEGAL PERSON 2.1 FOREIGN SPONSOR Registered Name: GlaxoSmithKline Registered Tradename: GlaxoSmithKline FOREIGN SPONSOR REPRESENTATIVE IN PERU SUBSIDIARY: BRANCH: CRO: OTHER: _________ Tradename: N/A TYPE OF INSTITUTION Laboratorio (Industria Farmacéutica) II. CLINICAL TRIAL GENERAL INFORMATION 1. CLINICAL TRIAL IDENTIFICATION Scientific Title: A RANDOMIZED, DOUBLE-BLIND, DOUBLE DUMMY, COMPARATIVE, MULTICENTER STUDY TO ASSESS THE INCIDENCE OF HEMOLYSIS, SAFETY, AND EFFICACY OF TAFENOQUINE (SB-252263, WR238605) VERSUS PRIMAQUINE IN THE TREATMENT OF SUBJECTS WITH PLASMODIUM VIVAX MALARIA Public Title: A RANDOMIZED, DOUBLE-BLIND, DOUBLE DUMMY, COMPARATIVE, MULTICENTER STUDY TO ASSESS THE INCIDENCE OF HEMOLYSIS, SAFETY, AND EFFICACY OF TAFENOQUINE (SB-252263, WR238605) VERSUS PRIMAQUINE IN THE TREATMENT OF SUBJECTS WITH PLASMODIUM VIVAX MALARIA Secundary ID(s): WHO UTN: PER-048-14 Protocol Code: TAF116564 Clinicaltrials.gov: NA EUDRACT N°: NA 1 1-2 2 2-3 Study clinical phase: 3 4 Clinical Trial Total Duration: 24 months No Aplica 0(exploratory trials) Enrolment start date in Peru (Initial) 30/12/2014 Worldwide enrolment start date (dd/ (dd/mm/aaaa): 18/09/2014 mm/aaaa): Enrolment start date in Peru (Posterior) (dd/mm/aaaa): Without starting enrollment In enrollment Peru enrolment status : Enrollment stopped Enrollment closed Other 2. CLINICAL TRIAL GOALS AND DESIGN Randomnized Simple Non randomnized Double Assignation method Type of blinding No aplica Triple Open Single arm Parallel Crossed Factorial Assignation Others: ____________________ Study Design In this prospective, double-blind, double-dummy design, a total of 300 subjects will be randomized to treatment on Day 1, of which a minimum of 50 female subjects must be enrolled that display moderate G6PD deficiency (&#8805;40% - <70% of the site median G6PD value).
    [Show full text]
  • How to Protect Yourself Against Malaria 1 Fig
    From our Whitepaper Files: How to > See companion document Protect Yourself Against Malaria World Malaria Risk Chart 2015 Edition Canada 67 Mowat Avenue, Suite 036 Toronto, Ontario M6K 3E3 (416) 652-0137 USA 1623 Military Road, #279 Niagara Falls, New York 14304-1745 (716) 754-4883 New Zealand 206 Papanui Road Christchurch 5 www.iamat.org | [email protected] | Twitter @IAMAT_Travel | Facebook IAMATHealth THE ENEMY area. Of the 460 Anopheles species, approximately 100 can transmit malaria Sunset — the hunt for human blood begins. parasites. From dusk to dawn the female Anopheles, Mosquitoes prey on a variety of hosts — the malaria-carrying mosquito searches for a host humans, monkeys, lizards, birds — carrying to supply her with blood. Blood is an absolute different species of malaria parasites which in necessity for her because it provides the protein turn infect only specific hosts. Of the approxi- needed for the development of her eggs which mately 50 different species of malaria parasites she later deposits in her breeding place. sharing the genetic name Plasmodium, only She has a tiny, elegant body, measuring 5 infect humans: Plasmodium falciparum, from 8 mm to 1 cm. She has dark spots on the killer; Plasmodium vivax; Plasmodium ovale, her wings, three pairs of long, slender legs and Plasmodium malariae and Plasmodium knowlesi. a prominent tubular proboscis with which The latter, a malaria parasite of Old World she draws blood. monkeys, has been identified to infect humans Fig. 1 Female Anopheles mosquito. The Anopheles enters your room at night. in Southeast Asia. In the past this parasite has Image source: World Health Organization You may recognize her by the way she rests been misdiagnosed as Plasmodium malariae.
    [Show full text]
  • The History and Ethics of Malaria Eradication and Control Campaigns in Tropical Africa
    Malaria Redux: The History and Ethics of Malaria Eradication and Control Campaigns in Tropical Africa Center for Historical Research Ohio State University Spring 2012 Seminars: Epidemiology in World History Prof. J.L.A. Webb, Jr. Department of History Colby College DRAFT: NOT FOR CITATION 2 During the 1950s, colonial malariologists, in conjunction with experts from the World Health Organization (WHO), set up malaria eradication pilot projects across tropical Africa. They deployed new synthetic insecticides such as DLD, HCH, and DDT, and new antimalarials, such as chloroquine and pyrimethamine, in an effort to establish protocols for eradication. These efforts ‘protected’ some fourteen million Africans. Yet by the early 1960s, the experts concluded that malaria eradication was not feasible, and the pilot projects were disbanded. The projects had achieved extremely low levels of infection for years at a time, but the experts had to accept with regret that their interventions were unable to reduce malaria transmission to zero. The projects had high recurrent costs, and it was understood that they were financially unsustainable. The pilot projects were allowed to lapse. The malaria eradication pilot projects had reduced the rates of infection to levels so low that the ‘protected’ populations lost their acquired immunities to malaria during the years of the projects. In the immediate aftermath of the projects, the Africans were subject to severe malaria, which sometimes afflicted entire communities in epidemic form, until they regained their immunities. How Should We Understand the Ethics of the Early Eradication Efforts? The ethics of malaria control in the 1950s and 1960s seemed self-evident to the interventionists.
    [Show full text]
  • Prevention of Malaria in Travellers (Pdf 59KB)
    THEME Travel medicine Prevention of malaria in travellers BACKGROUND Malaria remains endemic in over 100 countries worldwide. Travellers to these countries may be at risk of contracting disease. Assessing risk on an individual basis can be challenging. Trish Batchelor OBJECTIVE MBBS, MPH, FRACGP, is This article identifies the traveller at high risk of contracting malaria, outlines preventive methods, including personal Medical Director, Travel Doctor- protection and chemoprophylaxis if indicated, and summarises the risks and benefits of the most commonly used TMVC, Canberra, Australian chemoprophylactic agents. Capital Territory, and Executive Board Member, International DISCUSSION Society of Travel Medicine. Appropriately assessing the risk of malaria in an individual traveller can be complex. A number of factors beyond the trish.batchelor@traveldoctor. com.au country being visited influence the level of risk. These should be identified and taken into account when discussing malaria prevention with individuals. The traveller should be actively involved in the decision making process in order Tony Gherardin to enhance compliance. High risk individuals should be identified. Personal protection methods should always be MBBS, MPH, FRACGP, is emphasised. If chemoprophylaxis is indicated, the contraindications, advantages and side effects should be discussed. National Medical Adviser, Travel Doctor-TMVC, If in doubt, referral to a specialised travel medicine clinic should be considered. Melbourne, Victoria. The malaria parasite, spread via the bite of an infected Risk for travellers female Anopheles mosquito, remains a significant health threat in over 100 countries worldwide. An The risk of contracting malaria varies significantly from estimated 350–500 million cases occur annually, with traveller to traveller, and this is the challenge of providing over a million sub-Saharan Africans, mainly children, quality advice.
    [Show full text]
  • Chemoprophylaxis of Tropical Infectious Diseases
    Pharmaceuticals 2010, 3, 1561-1575; doi:10.3390/ph3051561 OPEN ACCESS pharmaceuticals ISSN 1424-8247 www.mdpi.com/journal/pharmaceuticals Review Chemoprophylaxis of Tropical Infectious Diseases William J. H. McBride School of Medicine and Dentistry, James Cook University, Cairns Base Hospital campus, The Esplanade, Cairns, Queensland 4870, Australia; E-Mail: [email protected]; Tel.: +617-40506530; Fax: +617-40506831 Received: 08 April 2010; in revised form: 28 April 2010 / Accepted: 10 May 2010 / Published: 18 May 2010 Abstract: Travelers to tropical countries are at risk for a variety of infectious diseases. In some cases effective vaccinations are available, but for other infections chemoprophylaxis can be offered. Malaria prevention has become increasingly complex as Plasmodium species become resistant to available drugs. In certain high risk settings, antibiotics can be used to prevent leptospirosis, scrub typhus and other infections. Post-exposure prophylaxis is appropriate for selected virulent infections. In this article the evidence for chemoprophylaxis will be reviewed. Keywords: chemoprophylaxis; malaria; leptospirosis; scrub typhus; diarrhea 1. Introduction Chemoprophylaxis is the administration of drug to prevent the development of a disease. This review will focus on the use of medications to prevent tropical infectious diseases. The use of chemo- prophylactic agents is based on knowledge of the epidemiology and clinical implications of the infectious diseases from which protection is sought. Generally, chemoprophylaxis is taken for diseases that are common, or where the clinical impact of infection is high. Drugs may be taken before exposure (pre-exposure prophylaxis) or after potential exposure to an infectious agent (post-exposure prophylaxis). In addition to the severity and frequency of the disease, the tolerability, toxicity and ecological implications of the medications being used are important considerations in whether drugs are prescribed and taken.
    [Show full text]
  • Mefloquine Poisoning and VA Service Connection
    Mefloquine Poisoning and VA Service Connection Presentation to the State Bar of Texas Military and Veterans Law Section March 29, 2019 Salado, Texas Remington Nevin, MD, MPH, DrPH Executive Director Photo credit: Dr. Remington Nevin Photo credits: Dr. Remington Nevin Background • Mefloquine was developed by the U.S. military as an antimalarial drug – Origins in the late 1960s during a Vietnam War-era program • Widespread use in the U.S. military beginning in the early 1990s (e.g. Somalia, SOCOM, OIF/OEF, AFRICOM) – Tens (hundreds?) of thousands of veterans have been exposed • Recently deprioritized for use by DoD – Followed U.S. and international “black box” warnings and recognition of chronic psychiatric and neurologic effects 2013 “Drug of Last Resort” Policy Memorandum “Mefloquine is the drug of last resort for malaria chemoprophylaxis and should only be used in persons with contraindications to chloroquine, doxycycline and atovaquone- proguanil.” Declining Use of Mefloquine within DoD Woodson J. Memorandum. Subject: Notification for Healthcare Providers of Mefloquine Box Warning. August 12, 2013. Emphasis added. “[Mefloquine] may cause long lasting serious mental problems… Some people who have taken [mefloquine] developed serious neuropsychiatric reactions…” Roche UK. Lariam product documentation, June 2018. Emphasis added. “Psychiatric symptoms such as insomnia, abnormal dreams/nightmares, acute anxiety, depression, restlessness or confusion have to be regarded as prodromal for a more serious event.” Roche UK. Lariam product documentation, June 2018. Emphasis added. “In a small number of patients, it has been reported that neuropsychiatric reactions (e.g. depression, dizziness, or vertigo and loss of balance) may persist for months or longer, even after discontinuation of the drug.” Roche UK.
    [Show full text]
  • Press Release Tafenoquine Approved in Peru
    PRESS RELEASE TAFENOQUINE APPROVED IN PERU Perú becomes second malaria-endemic country in Latin America to approve single- dose tafenoquine for radical cure of P. vivax malaria • Tafenoquine is the first drug approved for the radical cure (relapse prevention) of P. vivax malaria in more than 60 years. • As a single dose, tafenoquine offers a much shorter treatment regimen compared to current standard of care, with the benefit of increasing patient compliance and helping to advance malaria elimination efforts. Lima, January 2021. GSK and Medicines for Malaria Venture (MMV) announced that the General Directorate of Medicines, Supplies and Drugs (DIGEMID) has issued marketing authorization for single-dose tafenoquine for radical cure (prevention relapse) of Plasmodium vivax (P. vivax) malaria in patients 16 years of age or older receiving chloroquine for acute P. vivax infection (blood-stage). Peru becomes the second malaria endemic country in Latin America after Brazil to approve single dose tafenoquine for the prevention of relapse of P. vivax malaria. As a single-dose treatment, tafenoquine facilitates compliance and thus overcomes one of the major limitations of the only other drug approved for the prevention of relapse of P. vivax malaria, primaquine, which needs to be taken for 7 days. “The history of Peru and malaria are deeply entwined. In the nineteenth century, the famous writer Ricardo Palma, made malaria part of his narratives in the book Tradiciones Peruanas. In the same way, the cinchona tree, formerly known to be effective against malaria and from which quinine is derived, is part of the National Emblem”, said Dr José Sandoval, GSK Peru’s Medical Director.
    [Show full text]