Back to Top Skip to main content Skip to sub-navigation

Letter to the Editor: G6PD Deficiency in the Tafenoquine Era

CDC/James Gathany 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
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.

Recommended Content:

Medical Surveillance Monthly Report

In the December 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 January 2015 and 31 December 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, December 2019 and January 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–September 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 December 2018.

In reply:

We appreciate the response by Drs. Sayers and Webber to our article published in the December 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...

Long-Acting Reversible Contraceptive Use, Active Component Service Women, U.S. Armed Forces, 2016–2020

Article
7/1/2021
Lt. Col. Paula Neemann, 15th Healthcare Operations Squadron clinical medicine flight commander, demonstrates several birth options, such as an intrauterine device, at the 15th MDG's contraceptive clinic at Joint Base Pearl Harbor-Hickam, Hawaii, May 6, 2021. The contraceptive clinic opened June 7 to service beneficiaries and provide same-day procedures without a referral. (U.S. Air Force photo by 2nd Lt. Benjamin Aronson)

Long-Acting Reversible Contraceptive Use, Active Component Service Women, U.S. Armed Forces, 2016–2020

Recommended Content:

Medical Surveillance Monthly Report

Oral Cavity and Pharynx Cancers, Active Component, U.S. Armed Forces, 2007–2019

Article
7/1/2021
Moist snuff, chewing tobacco is placed between cheek and gum. All varieties of smokeless tobacco can cause harmful effects on the oral cavity.

Oral Cavity and Pharynx Cancers, Active Component, U.S. Armed Forces, 2007–2019

Recommended Content:

Medical Surveillance Monthly Report

The Evolution of Military Health Surveillance Reporting: A Historical Review

Article
7/1/2021
The inaugural issue of the Medical Surveillance Monthly Report

The Evolution of Military Health Surveillance Reporting: A Historical Review

Recommended Content:

Medical Surveillance Monthly Report

Brief Report: Medical Encounters for Snakebite Envenomation, Active and Reserve Components, U.S. Armed Forces, 2016–2020

Article
6/1/2021
Masters of camouflage, the Sidewinder Rattlesnakes are out and about aboard Marine Corps Logistics Base Barstow, California, May 11. Watch where you put your hands and feet, and observe children and pets at all times, as this is the natural habitat for these venomous snakes and a bite can cause serious medical problems. Notice the sharp arrow-shaped head with pronounced jaws, and the raised eye sockets, as well as the telltale rattles. Keep in mind, however, that rattles can be broken or lost, so you may or may not hear a rattle before they strike to protect themselves.

Brief Report: Medical Encounters for Snakebite Envenomation, Active and Reserve Components, U.S. Armed Forces, 2016–2020

Recommended Content:

Medical Surveillance Monthly Report

The Cost of Lower Extremity Fractures Among Active Duty U.S. Army Soldiers, 2017

Article
6/1/2021
X-ray image of a fractured tibia.

Recommended Content:

Medical Surveillance Monthly Report

Early Identification of SARS-CoV-2 Emergence in the Department of Defense via Retrospective Analysis of 2019–2020 Upper Respiratory Illness Samples

Article
6/1/2021
Army Maj. Raymond Nagley, S-3 officer assigned to the 50th Regional Support Group (RSG), receives a nasal swab to screen for COVID-19 at Fort Hood, Texas, on Feb. 5, 2021, from Spc. Yoali Muniz, a lab tech assigned to the 7406th Troop Medical Clinic, based in Columbia, Missouri. The 50th RSG, a Florida Guard unit based in Homestead, Florida, is preparing for deployment to Poland. (U.S. Army Guard photo by Sgt. 1st Class Shane Klestinski)

Early Identification of SARS-CoV-2 Emergence in the Department of Defense via Retrospective Analysis of 2019–2020 Upper Respiratory Illness Samples

Recommended Content:

Medical Surveillance Monthly Report

Department of Defense Mid-Season Vaccine Effectiveness Estimates for the 2019– 2020 Influenza Season

Article
6/1/2021
201019-N-PC065-1062 NORFOLK (Oct. 19, 2020) Hospital Corpsman 2nd Class Sashee Robinson, assigned to amphibious transport dock ship USS Arlington (LPD 24), administers an influenza vaccine to Machinery Repairman 2nd Class Hannah Swearingen in medical aboard the Arlington. Influenza vaccines are an annual medical readiness requirement throughout the Department of Defense. (U.S. Navy photo by Mass Communication Specialist 2nd Class John Bellino/Released)

Department of Defense Mid-Season Vaccine Effectiveness Estimates for the 2019– 2020 Influenza Season

Recommended Content:

Medical Surveillance Monthly Report

Morbidity Burdens Attributable to Various Illnesses and Injuries, Deployed Active and Reserve Component Service Members, U.S. Armed Forces, 2020

Article
5/1/2021
Navy Lt. James E. Lamb, left, and Sgt. Ryan Eskandary exercise aboard USS Pearl Harbor, May 6. Lamb is a Minneapolis native and serves as a firepower control team leader. Eskandary hails from St. Paul, Minn., and serves as a forward observer. Both serve with the 11th Marine Expeditionary Unit’s command element. The unit embarked USS Makin Island, USS New Orleans and USS Pearl Harbor in San Diego, Nov. 14, beginning a seven-month deployment to the Western Pacific, Horn of Africa and Middle East regions. (U.S. Navy photo by Cpl. Tommy Huynh, Arabian Sea/Released)

Morbidity Burdens Attributable to Various Illnesses and Injuries, Deployed Active and Reserve Component Service Members, U.S. Armed Forces, 2020

Recommended Content:

Medical Surveillance Monthly Report

Surveillance snapshot: Illness and injury burdens, recruit trainees, U.S. Armed Forces, 2020

Article
5/1/2021
A U.S. Marine Corps drill instructor with Golf Company, 2nd Recruit Training Battalion, motivates a recruit during a Marine Corps Martial Arts Program (MCMAP) training session at Marine Corps Recruit Depot, San Diego, Aug. 2, 2021. The drill instructors ensured recruits conducted the techniques safely and effectively during the training session. (U.S. Marine Corps photo by Cpl. Zachary T. Beatty)

Recommended Content:

Medical Surveillance Monthly Report

Surveillance snapshot: Illness and injury burdens, reserve component, U.S. Armed Forces, 2020

Article
5/1/2021
U.S. Army Col. Kris Marshall, co-director of Exercise Agile Spirit 2021, salutes during a closing ceremony August 6, 2021 at Orpholo Training Area, Georgia. Agile Spirit 21 promotes regional stability and security, while increasing readiness, strengthening partner capabilities and fostering trust. Agile Spirit provides vital opportunities, not only for multiple U.S. services to work together, but also for integrated, total force training with U.S. Reserve and National Guard units and our partner nations’ militaries to ensure interoperability. (U.S. Army National Guard photo by Cpl. Rydell Tomas)

Surveillance snapshot: Illness and injury burdens, reserve component, U.S. Armed Forces, 2020

Recommended Content:

Medical Surveillance Monthly Report

Absolute and Relative Morbidity Burdens Attributable to Various Illnesses and Injuries, Non-service Member Beneficiaries of the Military Health System, 2020

Article
5/1/2021
MAYPORT, Fla. (Sept. 18, 2020) – Cmdr. Mary Gracia, a pediatric nurse practitioner at Naval Branch Health Clinic Mayport, checks five-year-old Gabriella’s ears. Gracia, a native of McAllen, Texas, says, “It's been an honor and a privilege to impart my expertise to the children of our active duty members who are graciously serving our country. These children, our future leaders, prayers lifted and bountiful blessings for each one. And to the children I've helped during overseas deployments, prayers continued.” (U.S. Navy photo by Jacob Sippel, Naval Hospital Jacksonville/Released).

Absolute and Relative Morbidity Burdens Attributable to Various Illnesses and Injuries, Non-service Member Beneficiaries of the Military Health System, 2020

Recommended Content:

Medical Surveillance Monthly Report

Medical Evacuations out of the U.S. Central Command, Active and Reserve Components, U.S. Armed Forces, 2020

Article
5/1/2021
U.S. Army Soldiers from the 115th Brigade Support Battalion, 1st Armored Brigade Combat Team, evacuate casualties onto waiting HH-60M MEDEVAC Blackhawk helicopters from Charlie Company, 6th Battalion, 101st Combat Aviation Brigade during Combined Resolve XV, Feb. 27, 2021, at Hohenfels Training Area. Combined Resolve XV is a Headquarters Department of the Army directed Multinational exercise designed to build 1st Armored Brigade Combat Team, 1st Cavalry Division’s readiness and enhance interoperability with allied forces and partner nations to fight and win against any adversary.(U.S. Army photo by Sgt. 1st Class Garrick W. Morgenweck)

Medical Evacuations out of the U.S. Central Command, Active and Reserve Components, U.S. Armed Forces, 2020

Recommended Content:

Medical Surveillance Monthly Report

Hospitalizations, Active Component, U.S. Armed Forces, 2020

Article
5/1/2021
Hospitalizations, Active Component, U.S. Armed Forces, 2020

Hospitalizations, Active Component, U.S. Armed Forces, 2020

Recommended Content:

Medical Surveillance Monthly Report

Absolute and Relative Morbidity Burdens Attributable to Various Illnesses and Injuries, Active Component, U.S. Armed Forces, 2020

Article
5/1/2021
U.S. Air Force Capt. Sean Wilson, a native of Winston-Salem, N.C., and a physical therapist with the 59th Orthopedic and Rehabilitation Squadron, teaches a patient some home exercises that he can perform on his own at the Craig Joint-Theater Hospital, Jan. 23, 2012. (U.S. Air Force photo by Spc.Cody Barber, Bagram Air Field, Afghanistan/Released)

Absolute and Relative Morbidity Burdens Attributable to Various Illnesses and Injuries, Active Component, U.S. Armed Forces, 2020

Recommended Content:

Medical Surveillance Monthly Report

Ambulatory Visits, Active Component, U.S. Armed Forces, 2020

Article
5/1/2021
Tech. Sgt. Kimberly Weaver, 606th Air Control Squadron noncommissioned officer in charge of medical readiness, measures an Airman’s blood pressure at Aviano Air Base, Italy, May 10, 2021. The primary job of an Independent Duty Medical Technician is to ensure the health and safety of Airmen and their families. (U.S. Air Force photo by Senior Airman Ericka A. Woolever)

Recommended Content:

Medical Surveillance Monthly Report
<< < 1 2 3 4 5  ... > >> 
Showing results 1 - 15 Page 1 of 14

DHA Address: 7700 Arlington Boulevard | Suite 5101 | Falls Church, VA | 22042-5101

Some documents are presented in Portable Document Format (PDF). A PDF reader is required for viewing. Download a PDF Reader or learn more about PDFs.