Back to Top Skip to main content

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...

Update: Heat Illness, Active Component, U.S. Armed Forces, 2019

Article
4/1/2020
Service members from Joint Task Force-Bravo participate in Chapel Hike 75. In spite of the heat, sun and exhaustion, service members were enthusiastically hiking the road mountain to provide food for the local community. (U.S. Army photo by Martin Chahin)

Recommended Content:

Medical Surveillance Monthly Report

Commentary: The Warrior Heat- and Exertion-Related Event Collaborative and the Fort Benning Heat Center

Article
4/1/2020
A U.S. Navy Basic Underwater Demolition/SEAL student moves through the weaver during an obstacle course session in the first phase of training. (U.S. Navy photo by Mass Communication Specialist 2nd Class Kyle D. Gahlau/Released)

Recommended Content:

Medical Surveillance Monthly Report

Update: Exertional Rhabdomyolysis, Active Component, U.S. Armed Forces, 2015–2019

Article
4/1/2020
Midshipmen from the U.S Naval Academy Class of 2016 conduct a log carrying exercise. (U.S. Navy photo by Mass Communication Specialist 2nd Class Todd Frantom)

Update: Exertional Rhabdomyolysis, Active Component, U.S. Armed Forces, 2015–2019

Recommended Content:

Medical Surveillance Monthly Report

Update: Exertional Hyponatremia, Active Component, U.S. Armed Forces, 2004–2019

Article
4/1/2020
Builder 3rd Class, assigned to Mobile Construction Battalion (NMCB) 1, detachment Guam, drinks water while reconstructing a roof for a home that was damaged during Typhoon Mangkhut. U.S. Navy photo by Mass Communication Specialist 2nd Class Kelsey J. Hockenberger)

Recommended Content:

Medical Surveillance Monthly Report

Update: Sexually Transmitted Infections, Active Component, U.S. Armed Forces, 2011-2019

Article
3/1/2020
Photomicrograph of a Gram-stained specimen demonstrating the presence of Gram-negative, intracellular diplococci, which is a finding indicative of the possible presence of Neisseria gonorrhoeae bacteria. Credit: CDC/Bill Schwartz

Recommended Content:

Medical Surveillance Monthly Report

Incidence of Sexually Transmitted Infections Before and After Insertion of an Intrauterine Device or Contraceptive Implant, Active Component Service Women, U.S. Armed Forces, 2014–2019

Article
3/1/2020
A copper intrauterine device.

Recommended Content:

Medical Surveillance Monthly Report

Blood Lead Level Surveillance Among Pediatric Beneficiaries in the Military Health System, 2010–2017

Article
3/1/2020
U.S. Air Force Staff Sgt. Katie Duff, a medical technician with the 193rd Special Operations Wing's Medical Group, pricks the finger of brave 23-month old Kahia Inman, while his mother Malia Duvauchelle holds him during a free health screening. (U.S. Air Force photo by Tech. Sgt. Culeen Shaffer)

Recommended Content:

Medical Surveillance Monthly Report

Diabetes Mellitus and Gestational Diabetes, Active and Reserve Component Service Members and Dependents, 2008–2018

Article
2/1/2020
Master Sgt. Tara Taylor performs a glucose checks wile a young girl consoles her mother. (U.S. Air National Guard photo by Staff Sgt. Bethany Rizor)

Recommended Content:

Medical Surveillance Monthly Report

Increased Risk for Stress Fractures and Delayed Healing with NSAID Receipt, U.S. Armed Forces, 2014–2018

Article
2/1/2020
Credit: iStock

Recommended Content:

Medical Surveillance Monthly Report

Images in Health Surveillance: Skin Rashes in Children due to Infectious Causes

Article
2/1/2020
A maculopapular rash, a hallmark symptom of measles, on an infant’s face. Credit: CDC/Jim Goodson, M.P.H.

Recommended Content:

Medical Surveillance Monthly Report

Brief Report: Diagnoses of Scarlet Fever in Military Health System (MHS) Beneficiaries Under 17 Years of Age Across the MHS and in England, 2013–2018

Article
2/1/2020
A maculopapular rash, a hallmark symptom of measles, on an infant’s face. Credit: CDC/Jim Goodson, M.P.H.

Recommended Content:

Medical Surveillance Monthly Report

Update: Malaria, U.S. Armed Forces, 2019

Article
2/1/2020
An Anopheles gambiae mosquito in the process of obtaining a blood meal. Credit: CDC/James D. Gathany

Recommended Content:

Medical Surveillance Monthly Report

Respiratory Pathogen Surveillance Trends and Influenza Vaccine Effectiveness Estimates for the 2018–2019 Season Among Department of Defense Beneficiaries

Article
1/6/2020
Navy Seaman Kenny Liu prepares a needle with a flu vaccination aboard the USS Gerald R. Ford in Newport News, Va., Oct. 22, 2019. The ship’s crew received flu vaccines.

Recommended Content:

Medical Surveillance Monthly Report

Carbon Monoxide Poisoning, Active and Reserve Component Service Members and Non-Service Member Beneficiaries of the Military Health System, U.S. Armed Forces, July 2009–June 2019

Article
1/6/2020
Combustion fumes from a car exhaust pipe. (iStock photo).

Recommended Content:

Medical Surveillance Monthly Report

Incidence and Prevalence of Idiopathic Corneal Ectasias, Active Component, 2001–2018

Article
1/6/2020
Keratoconus. Credit: © 2019 American Academy of Ophthalmology.

Recommended Content:

Medical Surveillance Monthly Report
<< < 1 2 3 4 5  ... > >> 
Showing results 46 - 60 Page 4 of 13

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.