Skip to main content

Military Health System

Letter to the Editor: G6PD Deficiency in the Tafenoquine Era

Image of Female Anopheles funestus mosquito that had landed on a human skin surface and was in the process of obtaining its blood meal. This image shows a female Anopheles funestus mosquito that had landed on a human skin surface and was in the process of obtaining its blood meal. A. funestus is a known vector for the parasitic disease malaria.
CDC/James Gathany

Recommended Content:

Medical Surveillance Monthly Report

In the Dec. 2019 issue of the MSMR, Lee and Poitras reported a 2.2% prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency among active duty U.S. service members between 2004 and 2018.1 Their study utilized Health Level 7-formatted chemistry data archived in the Composite Health Care System (CHCS), but it did not stratify by quantitative or qualitative testing.

When tafenoquine was approved by the U.S. Food and Drug Administration in 2018 for chemoprophylaxis and radical cure of Plasmodium vivax,2 the distinction between quantitative and qualitative testing became clinically significant. Formerly, primaquine was the only approved medication to treat hypnozoites, the dormant form of the parasite in the liver stage of malaria. Its use required a “normal” G6PD activity level, the threshold of which on qualitative tests was usually established at 30%–40%. Tafenoquine, with its longer half-life of 14 days (compared to 6 hours for primaquine), provides a far simpler dosing regimen for malaria chemoprophylaxis and radical cure, but it may precipitate hemolytic anemia at higher levels of G6PD activity. Consequently, the U.S. Centers for Disease Control and Prevention recommends a quantitative G6PD assessment before tafenoquine prescription2 to ensure activity exceeding 70%.3,4

An X-linked genetic disorder, G6PD deficiency in males is usually severe (enzyme activity < 30%), meaning that a “deficient” result on qualitative testing contraindicates the use of both primaquine and tafenoquine. The same is true for females who are homozygous or double heterozygous for mutant alleles—both of which are rare. However, single heterozygous females usually have milder deficiency (enzyme activity 30%–80%),3 meaning they would have a “normal” result on qualitative testing and could safely take primaquine but potentially not tafenoquine.

Univeral G6PD deficiency screening is required across the U.S. Armed Forces, but current policy does not mandate quantitative testing.5 Since tafenoquine may improve medication adherence and thus become a preferable antimalarial option, it is important to understand how many service members have only been qualitatively tested. In the U.S. Air Force, 167,945 active duty members had at least 1 G6PD test performed and recorded in the CHCS between 1 Jan. 2015 and 31 Dec. 2019. Of these, only 4,325 (2.6%), including 1,602 females, had a normal qualitative test with no quantitative result. This low percentage should continue to decrease since quantitative testing is standard protocol for all new recruits at U.S. Air Force basic military training as well as new officer accessions at the U.S. Air Force Academy and Officer Training School (email communication, Maj Dianne Frankel and Lt Col Kevin Baldovich, Dec. 2019 and Jan. 2020, respectively).

While the article by Lee and Poitras provides valuable information, G6PD deficiency surveillance in the tafenoquine era should incorporate quantitative values. These values should also be documented in service members’ deployment readiness records. For example, the Aeromedical Services Information Management System, the U.S. Air Force’s readiness platform, defines G6PD status as either “normal” or “deficient”—essentially as a qualitative test, even if a quantitative enzyme activity level is available in the electronic health record. This may lead to improper prescription of tafenoquine to airmen, particularly females, who are coded as having “normal” G6PD activity levels but whose levels are in fact intermediate.

Author affiliations: Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD (Maj Sayers; Lt Col Webber); Public Health and Preventive Medicine Department, U.S. Air Force School of Aerospace Medicine, Wright-Patterson Air Force Base, OH (Lt Col Webber).

Disclaimer: The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Air Force, the Department of Defense, or the U.S. Government.

References

  1. Lee J, Poitras BT. Prevalence of glucose-6-phosphate dehydrogenase deficiency, U.S. Armed Forces, May 2004–Sept. 2018. MSMR. 2019;26(12):14–17.
  2. Haston JC, Hwang J, Tan KR. Guidance for using tafenoquine for prevention and antirelapse therapy for malaria—United States, 2019. MMWR Morb Mortal Wkly Rep. 2019;68(46):1062–1068.
  3. Commons RJ, McCarthy JS, Price RN. Tafenoquine for the radical cure and prevention of malaria: the importance of testing for G6PD deficiency. Med J Aust. 2020;212(4):152–153.e1.
  4. Price RN, Commons RJ, Battle KE, Thriemer K, Mendis K. Plasmodium vivax in the era of the shrinking P. falciparum map. Trends Parasitol. 2020;36(6):560–570.
  5. Defense Health Agency, Department of Defense. Procedural Instruction 6025.14. Active Duty Service Members (ADSM) Erythrocyte Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency and Sickle Cell Trait (SCT) Screening. 6 Dec. 2018.

In reply:

We appreciate the response by Drs. Sayers and Webber to our article published in the Dec. 2019 issue of the MSMR on the prevalence of G6PD deficiency among active duty service members. We are in agreement that quantitative as well as qualitative testing for the genetic condition is imperative to prevent the potentially harmful side effects from the use of the 8-aminoquinoline (8-AQ) class of antimalarial drugs (tafenoquine and primaquine) for malaria chemoprophylaxis and radical cure. We applaud the Air Force for the implementation of quantitative screening of G6PD deficiency among new recruits.

Our article highlights the need for leadership awareness of G6PD deficiency diagnoses to reduce the possibility of adverse events from the use of the 8-AQ class of antimalarial drugs. The inclusion of quantitative G6PD testing is an important tool to further identify at-risk service members.

Respectfully,

MAJ Jangwoo Lee, PhD; Beth Poitras, MPH

You also may be interested in...

Disparities in COVID-19 Vaccine Initiation and Completion Among Active Component Service Members and Health Care Personnel, 11 December 2020–12 March 2021

Article
4/1/2021
Capt. Shamira Conerly, 149th Medical Group, gives Staff Sgt. Timmy Sanders, 149th Maintenance Squadron, his first dose of COVID-19 vaccine

Recommended Content:

Medical Surveillance Monthly Report

Update: Exertional Hyponatremia, Active Component, U.S. Armed Forces, 2005–2020

Article
4/1/2021

Recommended Content:

Medical Surveillance Monthly Report

A Retrospective Cohort Study of Blood Lead Levels Among Special Operations Forces Soldiers Exposed to Lead at a Firing Range in Germany

Article
3/1/2021
A soldier fires a pistol during small arms training

Recommended Content:

Medical Surveillance Monthly Report

Update: Sexually Transmitted Infections, Active Component, U.S. Armed Forces, 2012–2020

Article
3/1/2021
Magnified photomicrograph of a Gram-stained urethral discharge specimen

Update: Sexually Transmitted Infections, Active Component, U.S. Armed Forces, 2012–2020

Recommended Content:

Medical Surveillance Monthly Report

Influenza Surveillance Trends and Influenza Vaccine Effectiveness Among Department of Defense Beneficiaries During the 2019–2020 Influenza Season

Article
3/1/2021
Captured in 2011, this transmission electron microscopic (TEM) image depicts some of the ultrastructural details displayed by H3N2 influenza virions, responsible for causing illness in Indiana and Pennsylvania in 2011. See PHIL 13469, for the diagrammatic representation of how this Swine Flu stain came to be, through the “reassortment” of two different Influenza viruses.  Credit: CDC/ Dr. Michael Shaw; Doug Jordan, M.A.

Influenza Surveillance Trends and Influenza Vaccine Effectiveness Among Department of Defense Beneficiaries During the 2019–2020 Influenza Season

Recommended Content:

Medical Surveillance Monthly Report

Influenza Outbreak During Exercise Talisman Sabre, Queensland, Australia, July 2019

Article
3/1/2021
Flight Lt. Michael Campion, an aviation medical officer from No. 3 Aeromedical Evacuation Squadron prepares a medical patient leaving Exercise Talisman Sabre to be transferred to a C-27J Spartan aircraft July 18, 2019 at Rockhampton Airport. No. 3 Aeromedical Evacuation Squadron is providing medical support to troops participating in Talisman Sabre 2019, a bilateral combined Australian and United States exercise designed to train respective military services in planning and conducting Combined and Joint Task Force operations, and improve the combat readiness and interoperability between Australian and US forces. (U.S. Army photo by Sgt. 1st Class John Etheridge)

Influenza Outbreak During Exercise Talisman Sabre, Queensland, Australia, July 2019

Recommended Content:

Medical Surveillance Monthly Report

Surveillance for Vector-borne Diseases Among Active and Reserve Component Service Members, U.S. Armed Forces, 2016–2020

Article
2/1/2021
Dorsal view of a female lone star tick

Recommended Content:

Medical Surveillance Monthly Report

Historical Perspective: The Evolution of Post-exposure Prophylaxis for Vivax Malaria Since the Korean War

Article
2/1/2021
An Aedes aegypti mosquito

Recommended Content:

Medical Surveillance Monthly Report

Update: Malaria, U.S. Armed Forces, 2020

Article
2/1/2021
Preventive medicine specialists check an insect trap

Recommended Content:

Medical Surveillance Monthly Report

Attrition Rates and Incidence of Mental Health Disorders in an Attention-Deficit/Hyperactivity Disorder (ADHD) Cohort, Active Component, U.S. Armed Forces, 2014–2018

Article
1/1/2021
Capt. Michelle Tsai, the behavioral health officer for the 4th Brigade, 2nd Infantry Division, reviews medical information in her office at the Joint Readiness Training Center June 17. Tsai, an Alexandria, Va., native, is here with the Raider Brigade in support of training operations for the unit's upcoming deployment to Iraq. (Photo by Pfc. Luke Rollins)

Recommended Content:

Medical Surveillance Monthly Report

The Prevalence of Attention-Deficit/Hyperactivity Disorder (ADHD) and ADHD Medication Treatment in Active Component Service Members, U.S. Armed Forces, 2014–2018

Article
1/1/2021
New Recruits are screened after arriving at Depot

Recommended Content:

Medical Surveillance Monthly Report

Exertional Rhabdomyolysis and Sickle Cell Trait Status in the U.S. Air Force, Jan. 2009–Dec. 2018

Article
1/1/2021
Master Sgt. Daniel Bedford prepares to pump up a gold medal lift in the bench press during the United States Powerlifting Association 2020 Texas State Bench Press Championship

Exertional Rhabdomyolysis and Sickle Cell Trait Status in the U.S. Air Force, Jan. 2009–Dec. 2018

Recommended Content:

Medical Surveillance Monthly Report

Cases of Coronavirus Disease 2019 and Comorbidities Among Military Health System Beneficiaries, 1 Jan. 2020 through 30 Sept. 2020

Article
12/1/2020
A U.S. Army nurse paratrooper provides patient care in support of preventative efforts against COVID-19

Recommended Content:

Medical Surveillance Monthly Report

Air Evacuation of Service Members for COVID-19 in U.S. Central Command and U.S. European Command From 11 March 2020 Through 30 September 2020

Article
12/1/2020
3D graphical representation of a generic Influenza virion’s ultrastructure

Recommended Content:

Medical Surveillance Monthly Report

SARS-CoV-2 and Influenza Coinfection in a Deployed Military Setting—Two Case Reports

Article
12/1/2020
Illustration reveals ultrastructural morphology exhibited by coronaviruses

Recommended Content:

Medical Surveillance Monthly Report
<< < ... 6 7 8 9 10  ... > >> 
Showing results 76 - 90 Page 6 of 13
Refine your search
Last Updated: October 24, 2022
Follow us on Instagram Follow us on LinkedIn Follow us on Facebook Follow us on Twitter Follow us on YouTube Sign up on GovDelivery