Single-Dose Tafenoquine to Prevent Malaria Relapse Interview with:
Malaria CDC imageGavin C.K.W. Koh, MB BChir MA PhD MCRP DTM&H

Department of Drug Discovery Unit for Diseases of the Developing World
GlaxoSmithKline | GSK What is the background for this study?

Response: Malaria still remains one of the greatest global healthcare challenges so, as part of GSK’s efforts to fight diseases that disproportionately impact the poorest, we have been working on tafenoquine as a potential medicine for malaria for over 20 years.  In 2008, GSK entered into a collaboration with the not-for-profit product development partnership, Medicines for Malaria Venture (MMV), to develop tafenoquine as an anti-relapse medicine for patients infected with a particular species of malaria called Plasmodium vivax malaria.

  1. vivaxmalaria is estimated to cause around 7.5 million clinical infections every year. The disease may cause fever, chills, vomiting, malaise, headache and muscle pain, and in some cases, can lead to severe malaria and be fatal.

Unlike other malaria species such as P. falciparumP. vivax also has the ability to lie dormant in the liver from where it may periodically reactivate to cause relapses of P. vivax malaria. A single P. vivax infection may therefore give rise to multiple episodes of malaria, in the absence of a new mosquito bite. These relapses can occur weeks, months or even years after the initial infection. The dormant liver forms of the parasite cannot be treated with most other antimalarial treatments.

Another issue is that the only medicine currently available to stop the relapse is primaquine, a medicine approved in the 1950s, which must be given for 14 days. Given this length of treatment course, many people do not comply with the full course, which results in reduced effectiveness.

The aim of the DETECTIVE study was to look at the effectiveness of treatment in preventing relapse over six months with a 1-day course of tafenoquine, a 14-day course of primaquine, or placebo, with all patients also receiving a 3-day course of chloroquine, a medicine that is used to treat the initial infection. What are the main findings?

Response: The DETECTIVE study met its primary endpoint. A significantly greater proportion of patients in the tafenoquine group did not have relapses compared to patients in the placebo group. A similar result was observed for the patients in the primaquine group compared to the placebo group. When considering the compliance issue of primaquine in the real-world setting, we saw that more than 95% of patients in the primaquine group took their treatment as instructed in the setting of a clinical study. From a safety perspective, adverse events from the study were consistent with the known safety profile of tafenoquine. What should readers take away from your report?

Response: The positive results of the DETECTIVE study demonstrate the efficacy and safety of tafenoquine in an unprecedented single-dose for relapsing malaria.  These data supported the approval of the medicine by the US Food and Drug Administration and Australia Therapeutic Goods Administration in 2018 marking it as the first new medicine for the radical cure of P. vivax malaria in more than 60 years. Having the data published in the NEJM will help other P. vivax malaria endemic countries as they strive towards malaria elimination. What recommendations do you have for future research as a result of this work?

Response: The DETECTIVE study was conducted in adult patients with P. vivax malaria and a significant part of the global burden of the disease is in children. GSK and MMV are therefore studying the use of tafenoquine in paediatric patients aged 6 months to 16 years (TEACH study).  In addition, since vivax malaria in Indonesia is frequently resistant to chloroquine, we are conducting another study that is looking at tafenoquine plus dihydroartemisinin–piperaquine as the blood schizonticide (INSPECTOR study) in patients with P. vivax malaria in Indonesia.

Disclosures: The DETECTIVE study was supported by GSK and MMV.


Single-Dose Tafenoquine to Prevent Relapse of Plasmodium vivax Malaria
Marcus V.G. Lacerda, M.D., Alejandro Llanos-Cuentas, M.D., Srivicha Krudsood, M.D., Chanthap Lon, M.D., David L. Saunders, M.D., Rezika Mohammed, M.D., Daniel Yilma, M.D., Dhelio Batista Pereira, M.D., Fe E.J. Espino, M.D., Reginaldo Z. Mia, M.D., Raul Chuquiyauri, M.D., Fernando Val, Ph.D., et al.

January 17, 2019
N Engl J Med 2019; 380:215-228
DOI: 10.1056/NEJMoa1710775


The information on is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.


Does Preloading With a Nicotine Patch Help Smokers Quit? Interview with:
“Day 1 of nicotine patch, just stuffed my face with lunch at work and do NOT even want a cigarette” by David Bruce Jr. is licensed under CC BY 2.0Paul Aveyard
Professor of Behavioural Medicine
Nuffield Department of Primary Care Health Sciences
University of Oxford
Radcliffe Primary Care Building
Radcliffe Observatory Quarter
Oxford What is the background for this study? What are the main findings? 

Response: Tobacco addiction occurs because of repeated pairings of the act and sensation of smoking with binding of nicotine in the midbrain leading to release of dopamine in the nucleus accumbens. These repeated pairings create associative learning and, when brain nicotine concentrations fall, this produces a compulsion to keep using tobacco. In theory, blocking the actions of nicotine released while smoking ought to reverse this learning. One way to do this is to use a nicotine patch which provides a steady state high concentration of nicotine that desensitises the nicotinic receptors in the midbrain, making them unresponsive to nicotine from a smoked cigarette. This is the theory behind nicotine preloading.

The clinical trial evidence that preloading works is equivocal, with some trials suggesting a very large therapeutic effect and others no benefit at all. In the light of both the promise and the uncertainty, we aimed to complete the largest trial to date of nicotine preloading to examine its effectiveness, safety, and tolerability.

Continue reading

New SHINGRIX Vaccine Induces Stronger Immune Protection Against Shingles in Elderly Interview with:

Herpes Zoster or Shingles of chest Wikipedia

Herpes Zoster or Shingles of chest

Anthony. L. Cunningham, MD
The Westmead Institute for Medical Research
Westmead, NSW
University of Sydney, Sydney, What is the background for this study? What are the main findings?

Response: This study examines the reasons why the HZ subunit vaccine candidate (HZ/su vaccine) consisting of a single viral protein, varicella-zoster glycoprotein E, and and adjuvant (immunostimulant) combination AS01B is so effective as a vaccine to prevent shingles (>90%), especially in those over the age of 70 years and 80 years, as published in recent trials i.e. it combats the declining immunity in the aging which usually restricts vaccine efficacy to under 60% in these age groups.  Continue reading