Prospective screening for sexually transmitted infections among US service members with Chlamydia trachomatis or Neisseria gonorrhoeae infection.

BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the most common bacterial causes of sexually transmitted infection (STI) in the United States (US). The purpose of this study was to determine the frequency of reinfection during a six-month study period and to evaluate the retesting interval for those infected with CT or NG. METHODS: We conducted a prospective, six-month follow-up study among US military personnel with new onset, laboratory-confirmed CT or NG, recruited from an STI clinic at a large military base from January 2018 to January 2020. Each participant was randomly assigned to one of four groups, which differed only by the timing of the first study-associated follow-up visit after CT or NG diagnosis. RESULTS: Of the 347 initially recruited into the study, 267 participants completed a follow-up visit prior to their scheduled, final visit 6 months after initial infection. The median age at enrollment was 22 years and 41.0% were female. There were 32 (12.0%) reinfections (30 CT and 2 NG) after treatment of an index diagnosis of CT or NG within the six-month study period. Six of the CT reinfections were only detected at the final visit. A review of medical records revealed additional CT and NG reinfections. The probability of detecting a reinfection did not vary significantly by timing of follow-up. CONCLUSIONS: The likelihood of detecting CT or NG reinfection did not differ according to time of follow up visit among study participants, thus supporting CDC guidance to retest three months post treatment. Efforts should continue to focus on STI prevention and risk reduction.

Knowledge and Attitudes Regarding Human Papillomavirus Among Active Duty Service Members at a Large Military Base.

OBJECTIVE: To assess gaps in human papillomavirus (HPV) knowledge and current attitudes toward HPV vaccination among active duty soldiers at Fort Bragg, NC, and to evaluate the impact of the instruction intervention on knowledge and attitudes regarding HPV vaccination. METHODS: A six-question assessment was administered to soldiers presenting for appointments through the Epidemiology and Disease Control (EDC) Clinic at Fort Bragg in January 2020. Questions included five multiple choice knowledge assessments and a Likert scale attitude question regarding HPV vaccination. The assessment was administered before and after a one-on-one educational intervention conducted by the EDC Clinic nursing staff. Pre- and post-assessments were matched using unique encounter numbers. RESULTS: A total of 139 matched pre- and post-education assessments were completed. Statistically significant changes in HPV knowledge were observed in test score and percent correct (P < .001). Additionally, for individuals reporting no prior HPV vaccination, attitudes toward receiving it increased from 4 (interquartile range 3-5) to 5 (4-5) following instructions (P < .001). This indicates a shift from moderately interested to very interested. CONCLUSIONS: Results among soldiers demonstrated a lack of knowledge regarding HPV infection, its long-term effects, and preventive measures available among this population of active duty members. Assessment results also illustrated education about HPV infection and vaccination positively impacts soldiers' knowledge and attitudes toward HPV vaccination.

EatWellNow: Formative Development of a Place-Based Behavioral "Nudge" Technology Intervention to Promote Healthier Food Purchases among Army Soldiers.

Approximately 17% of military service members are obese. Research involving army soldiers suggests a lack of awareness of healthy foods on post. Innovative approaches are needed to change interactions with the military food environment. Two complementary technological methods to raise awareness are geofencing (deliver banner ads with website links) and Bluetooth beacons (real-time geotargeted messages to mobile phones that enter a designated space). There is little published literature regarding the feasibility of this approach to promote healthy behaviors in retail food environments. Thus, we conducted a formative feasibility study of a military post to understand the development, interest in, and implementation of EatWellNow, a multi-layered interactive food environment approach using contextual messaging to improve food purchasing decisions within the military food environment. We measured success based on outcomes of a formative evaluation, including process, resources, management, and scientific assessment. We also report data on interest in the approach from a Fort Bragg community health assessment survey (n = 3281). Most respondents agreed that they were interested in receiving push notifications on their phone about healthy options on post (64.5%) and that receiving these messages would help them eat healthier (68.3%). EatWellNow was successfully developed through cross-sector collaboration and was well received in this military environment, suggesting feasibility in this setting. Future work should examine the impact of EatWellNow on military service food purchases and dietary behaviors.

Pre-existing Thyroid Autoimmunity and Risk of Papillary Thyroid Cancer: A Nested Case-Control Study of US Active-Duty Personnel.

PURPOSE: Thyroid autoimmunity has been associated with differentiated thyroid cancer although multiple potential biases might have influenced the results of previous studies. METHODS: We conducted a case-control study nested within the cohort of US active-duty personnel 1996-2014 to assess the association between thyroid autoimmunity, defined by serology, and thyroid cancer diagnosis. The primary exposure was thyroid peroxidase (TPO) antibody status 7-10 years before the thyroid cancer index date. We also assessed whether diagnosis of thyroid autoimmunity mediated any associations identified and if thyroid cancer features differed by autoimmunity status. RESULTS: Among 451 incident cases of papillary thyroid cancer and matched controls (median age 36 years, 61.4% men), TPO antibody positivity (v negative) 7-10 years prediagnosis was associated with thyroid cancer (odds ratio [OR] 1.90 [95% CI, 1.33 to 2.70]). Exploratory analyses suggested an increasing risk of thyroid cancer with higher TPO antibody titer (TPO antibody 550-1,399 IU/mL: OR 2.95 [95% CI, 1.37 to 6.36]; and ≥ 1,400 IU/mL: OR 3.91 [95% CI, 1.66 to 9.24]). Positive TPO antibody status remained associated with thyroid cancer after those with diagnosed autoimmunity were excluded, and the association was not mediated by diagnosis of thyroid autoimmunity. Among the cases with diagnosed autoimmunity, 58% thyroid cancers were ≤ 10 mm diameter. CONCLUSION: Longstanding prior thyroid autoimmunity up to 10 years before thyroid cancer diagnosis was associated with papillary thyroid cancer risk. The results could not be fully explained by diagnosis of thyroid autoimmunity although when autoimmunity had been identified, thyroid cancers were diagnosed at a very early stage.

Differentiating between smokers and nonsmokers using serum cotinine.

Aim: Our goal is to evaluate implications of cotinine cut points in subgroups of smokers and nonsmokers. Materials & methods: Data were assessed from 13,357 adult participants and collected over a period of 6 years by the National Health and Nutrition Examination Survey (2009-2014). Receiver operating characteristic curve analysis was used to identify optimal cut points. Rao-Scott χ2 tests measured associations between group characteristics. Results: The optimal serum cotinine cut point adult cigarette smokers was 3.63 ng/ml (sensitivity of 96.7%; specificity of 93.0%). This cut point differed by gender as well as race/ethnicity. Conclusion: There are notable differences in subgroup cut points compared with previous research. Use of gender or race/ethnicity specific cut points is more appropriate when feasible and may help clinician recommendations.

A Systems Evaluation of Occupational Injuries and Illness in the US Army.

OBJECTIVE: Workers' compensation (WC) processes do not lead to maximal return-to-work or cost savings. The aim of this study is to assess barriers and facilitators to reporting and managing injuries and illnesses among civilian employees in the US Army. METHODS: We triangulated a review of policy and practice documents, stakeholder interviews, a descriptive analysis of WC data, and a literature review to inform recommendations of best practices for improving return-to-work and lowering WC costs. RESULTS: Federal WC costs are trending downward for civilian employees in the US Army; however, the approaches are not uniform or optimized, especially at the installation level. CONCLUSIONS: This mixed methods evaluation of the Department of Defense WC elucidates areas for improvement and potential best practices within the Federal WC system.

Gender differences in the associations of body mass index, physical fitness and tobacco use with lower extremity musculoskeletal injuries among new US Army soldiers.

BACKGROUND: Musculoskeletal (MSK) injuries are a leading cause of morbidity among US Army soldiers, especially among women and the newly enlisted. While extremes of body mass index (BMI), low physical fitness and tobacco use have been identified as risk factors, no prior studies have determined the combined effects of these risk factors or tested for gender differences in the associations. METHODS: We conducted a retrospective cohort study utilising the Stanford Military Data Repository to study all enlisted soldier accessions to the US Army between January 2011 and January 2014, with follow-up through December 2014 (n=238 772). We used discrete-time logistic regression to test for associations between demographic, socioeconomic and health behaviour-related predictors and incident lower extremity injuries. We included interaction terms to test for gender differences. RESULTS: Among men, there were greater adjusted odds of injury among underweight (OR 1.27), overweight (OR 1.14) and obese soldiers (OR 1.54) (all p<0.001) relative to normal-weight soldiers. No statistically significant differences in the odds of injury on the basis of BMI were observed for female soldiers. Physical fitness was a significantly stronger predictor of injury for female as compared with male soldiers, while the association between tobacco use and injury was stronger for men (OR 1.47) than for women (OR 1.30) (p<0.001 for both). CONCLUSION: This is the largest known study to simultaneously assess important, modifiable musculoskeletal injury risk factors and to test for gender differences in these associations. These findings provide critical gender-related nuances for clinicians and leaders seeking to reduce the risk of these problems.

Epidemiologic Evidence and Possible Mechanisms for the Association Between Cigarette Smoking and Injuries. Part 2: Is the Relationship Between Smoking and Injuries Causal?

Part 1 of this series reviewed the epidemiologic evidence for the association between cigarette smoking and injuries and possible biological and psychosocial mechanisms to account for this relationship. In the present article, nine criteria are explored to determine if smoking is a direct cause of injuries (i.e., a causal relationship). There is substantial evidence that individuals who smoked in the past have a higher subsequent risk of injury. A recent meta-analysis found that smokers in the military were 1.31 times more likely to be injured than nonsmokers and Servicemembers with low, medium, and high levels of smoking had 1.27, 1.37, and 1.71 times, respectively, the risk of injury compared with nonsmokers. The association between smoking and injuries has been reported in at least 18 US military studies and in 14 civilian studies in seven countries. The biological plausibility of the association was discussed extensively in part 1 of this series. A possible alternative explanation with sufficient data was that smokers may be risk takers and it is the risk-taking behavior that increases injury risk (not smoking per se). Once an individual no longer smokes, a decrease in injury risk has been reported for at least bone health and wound healing. The effects of smoking do not appear to be specific to one type of injury, possibly because of the numerous compounds in tobacco smoke that could affect tissues and physiological processes, with evidence provided for bones, tendons, and healing processes. The association was consistent with other knowledge, with some evidence provided from other types of medical problems and trends in smoking and injury-related mortality. In summary, the association between smoking and injuries appears to meet many of the criteria for a causal relationship.

Epidemiological Evidence and Possible Mechanisms for the Association Between Cigarette Smoking and Injuries (Part 1).

Surveys indicated that 24% of military personnel are current cigarette smokers. Smoking is well known to increase the risk of cancers, cardiovascular and respiratory diseases, reproductive problems, and other medical maladies, but one of the little known effects of smoking is that on injuries. There is considerable evidence from a variety of sources that (1) smoking increases overall injury risk, (2) the greater the amount of smoking, the higher is the injury risk, and (3) smoking is an independent injury risk factor. Smoking not only affects the overall injury risk but also impairs healing processes following fractures (e.g., longer healing times, more nonunions, more complications), ligament injury (e.g., lower subjective function scores, greater joint laxity, lower subsequent physical activity, more infections), and wounding (e.g., delayed healing, more complications, less satisfying cosmetic results). Smoking may elicit effects on fractures through low bone mineral density (BMD), lower dietary intake of calcium and vitamin D, altered calcium metabolism, and effects on osteogenesis and sex hormones. Effects on wound healing may be mediated through altered neutrophils and monocytes functions resulting in reduced ability to fight infections and remove damaged tissue, reduced gene expression of cytokines important for tissue healing, and altered fibroblast function leading to lower density and amount of new tissue formation. Limited data suggest smoking cessation has favorable effects on various aspects of bone health over periods of 1 to 30 years. Favorable effects on neutrophil and monocyte functions may occur as early as 4 weeks, but fibroblast function and collagen metabolism (important for wound remodeling) appear to take considerably longer and may be dependent on the amount of prior smoking. Part 2 of this series will use this information to explore the possibility of a causal relationship between smoking and injuries.

Meta-analysis of Cigarette Smoking and Musculoskeletal Injuries in Military Training.

PURPOSE: Tobacco use is common among military personnel, as is musculoskeletal injury during training. In a review of the literature on musculoskeletal injuries, there was mixed evidence on the role of smoking as a risk factor. The purpose of this study is to review and analyze the literature on the impact of cigarette smoking on lower-extremity overuse injuries in military training. METHODS: We performed a literature search on articles published through October 2016. Search terms focused on lower-extremity overuse musculoskeletal injuries and cigarette smoking in military populations. We conducted a meta-analysis overall and by sex, including smoking intensity. RESULTS: We identified 129 potential studies and selected 18 based on quality. The overall rate ratio for smoking was 1.31, 1.31 for men, and 1.23 for women. Overall and for each sex, rate ratios were significantly greater than 1.0 for each intensity level of smoking. CONCLUSIONS: Smoking is a moderate risk factor for musculoskeletal injury and may account for a meaningful proportion of injuries among men and women due to the high prevalence of smoking and injury in this population. Although enlistees are not allowed to smoke during basic training, their risk of injury remains high, indicating that smokers may remain at increased risk for medium- to long-term duration.

Epidemiology of Exercise- and Sports-Related Injuries in a Population of Young, Physically Active Adults: A Survey of Military Servicemembers.

BACKGROUND: Numerous studies document the health benefits of a physically active lifestyle, but relatively few document the hazards of physical activity. Because of the requirement for physical fitness to complete their mission, the United States military services have a vested interest in understanding the benefits and risks of physical activity including exercise and sports. One of these risks is injury. Rates and proportion of injuries caused by exercise- and sports-related (ESR) activities have not been reported previously across the services. PURPOSE: The purposes of this population survey were to (1) document the rates and proportion of all injuries caused by ESR activities among military personnel, (2) compare rates across the military services, and (3) describe the causes and types of ESR injuries as well as associated days of limited activity. STUDY DESIGN: Descriptive epidemiology study. METHODS: The Defense Manpower Data Center administered the web-based 2008 Status of Forces Survey of Active Duty Service Members to a random sample of active-duty personnel. In all, 10,692 servicemembers completed the survey, which included questions about injuries from any cause and from exercise and sports during the previous year. Responses were weighted to produce population estimates for injury rates (any injury and ESR injury). Percentage distributions were used to describe activities, injury types, days of limited activity, and contributing factors for ESR injuries. RESULTS: There were 49% of servicemembers who sustained an injury from any cause in the previous year; 25% had an ESR injury. Thus, 52% of all injuries were ESR injuries. ESR injury rates ranged from 20% for the Navy to 33% for the Marine Corps. Running accounted for 45% of ESR injuries. Forty percent of ESR injuries were sprains and strains. As an indicator of injury severity, 35% of ESR injuries required more than 2 weeks of limited activity. CONCLUSION: This study quantified the overall incidence of injuries and the large proportion that are caused by exercise and sports among military personnel, a population of healthy, physically active adults. Prevention strategies should focus on running, weight training, basketball, and football. Recommendations include adherence to evidence-based practices to reduce the occurrence of ESR injuries.

Effects of personal and occupational stress on injuries in a young, physically active population: a survey of military personnel.

The aim of this study was to document risk factors for any injury and sports- and exercise-related injuries, including personal and occupational stress among active duty service members (SMs) in the Air Force, Army, Marine Corps, and Navy. A total of 10,692 SMs completed the April 2008 Status of Forces Survey of Active Duty Members. The survey asked about demographics, personal stress and occupational stress, injuries from any cause, and participation in sports- and exercise- related activities in the past year. The survey used a complex sampling procedure to create a representative sample of SMs. Logistic regression was used to examine the associations of injury outcomes with potential risk factors. 49% of SMs sought medical care for an injury in the past year and 25% sustained a sports- and exercise-related activities injury. Odds of injury were higher for the Army and Marine Corps than for the Air Force or Navy. This survey showed that higher personal and occupational stress was associated with higher risks of injury. SMs who experienced higher levels of personal or occupational stress reported higher risks of injuries. The effects of stress reduction programs on injury risks should be evaluated in military and other young physically active populations.

Effect of pre-accession physical fitness on training injuries among US Army recruits.

OBJECTIVE: To evaluate the association of pre-accession physical fitness, as measured by a five-minute step test, with incidence of overuse injuries and outpatient healthcare utilization among male United States (US) Army recruits. PARTICIPANTS: US Army male trainees who met weight standards and took a pre-accession fitness test. METHODS: In this prospective cohort study, incidence and outpatient healthcare visits for overuse injuries during the first 90 days of military service were compared between recruits who failed the pre-accession step test with those who passed. RESULTS: The hazard rate ratio for injury among recruits who failed the fitness test compared to those who passed the test was 1.31 (95% C.I = 1.20-1.44). Among the subset of recruits with at least one medical encounter for an overuse injury, the utilization rate ratio for subjects who failed the fitness test versus those who passed was 1.15 (95% C.I = 1.09-1.22). Other factors associated with increased risk of injury or healthcare utilization include age, body mass index, and smoking history. CONCLUSIONS: Risk of injury and utilization were associated with fitness test results. These findings may have implications for military accession and training policy as well as for other physically demanding training programs such as police, fire fighters and athletes.

Step test performance and risk of stress fractures among female army trainees.

BACKGROUND: Stress fractures and other musculoskeletal injuries are major sources of morbidity among female military trainees. Several risk factors have been postulated, particularly pre-existing fitness, usually assessed with post-entry run time for ≥ 1.0 mile. PURPOSE: Physical fitness is not formally evaluated prior to Army entry. If a valid and simple test that identified women at increased risk of stress fracture were available and could be applied prior to entry, it would facilitate cost-benefit studies of deferral or interventions. These analyses were undertaken to determine if a 5-minute step test conducted before entry identified women at increased risk. METHODS: A prospective study was conducted of weight-qualified women entering the Army in 2005-2006, with analyses completed in 2011. At the pre-entry examination, information was collected on age, BMI, smoking, race, and activity level. Everyone took the step test. All outpatient medical encounters were captured, and stress fractures and other musculoskeletal injuries identified. Women with stress fractures and those with other musculoskeletal injuries were evaluated separately. RESULTS: 1568 women were included in the study; 109 developed stress fractures and 803 other musculoskeletal injury. Women who failed the step test had a 76% higher stress fracture incidence and a 35% higher incidence of other musculoskeletal injuries. There was effect modification between age and test failure for stress fracture. CONCLUSIONS: A step test that can be administered before military entry identifies women with increased incidence of stress fracture and other musculoskeletal injury. This test could be used pre-entry to defer or target high-risk recruits for tailored fitness training before or after military entrance.

The in-service examination score as a predictor of success on the American Board of Preventive Medicine certification examination.

BACKGROUND: To date, there has been no study correlating the American College of Preventive Medicine (ACPM) in-service exam (ISE) with the American Board of Preventive Medicine (ABPM) certification exam. PURPOSE: To validate the ACPM ISE as a predictor of success on the ABPM certification exam. METHODS: ISE and ABPM certification exam scores were standardized by year using z-scores. The correlation between practicum year ISE scores and certification exam scores for military preventive medicine residencies in the National Capital and Washington State areas (core component only) was analyzed. A multivariable linear regression model included adjustments for age, gender, Master of Public Health grade point average (GPA), prior specialty board certification, and board deferral ≥1 year after graduation. Data were collected in 2010 and analyzed in 2011. RESULTS: Performance on the ISE was correlated with performance on the ABPM certification core exam (r=0.61, p<0.001). Performance on the ISE was still significant after adjusting for relevant demographic and educational variables (p<0.001). Other significant covariates included GPA (p=0.001) and board deferral (p=0.04) in the linear regression model. CONCLUSIONS: Performance on the ISE is moderately correlated with performance on the board certification core exam, and this correlation remained significant after adjustment in the linear regression model. These results serve to validate the ISE as a means for program directors to identify residents at academic risk and as encouragement for residents to take the certification exam as soon as possible after graduation.

Self-reported physical activity and preaccession fitness testing in U.S. Army applicants.

The Assessment of Recruit Motivation and Strength (ARMS) study evaluated a physical fitness screening test for Army applicants before basic training. This report examines applicants' self-reported physical activity as a predictor of objective fitness measured by ARMS. In 2006, the ARMS study administered a fitness test and physical activity survey to Army applicants during their medical evaluation, using multiple logistic regression for comparison. Among both men and women, "qualified" and "exceeds-body-fat" subjects who met American College of Sports Medicine adult physical activity guidelines were more likely to pass the fitness test. Overall, subjects who met physical activity recommendations, watched less television, and played on sports teams had a higher odds of passing the ARMS test after adjustment for age, race, and smoking status. This study demonstrates that self-reported physical activity was associated with physical fitness and may be used to identify those at risk of failing a preaccession fitness test.

U.S. military recruits waived for pathological curvature of the spine: increased risk of discharge from service.

Selective accession waivers for medically disqualifying conditions like spinal curvature are one way the military meets its manpower needs. We evaluated retention patterns during the first 2 years of service of a cohort of military recruits with waivers for pathological curvature of the spine (spinal curvature). Recruits waived for spinal curvature (n = 417), who accessed from 1998 to 2005 were identified and matched with 3 qualified recruits. Kaplan-Meier survival analysis and Cox proportional hazards model were used to compare survival patterns and adjusted attrition hazard estimates. Waived recruits experienced significantly increased risk of "all cause" discharge (relative risk = 1.3; 95% confidence interval: 1.1, 1.5) and "existing prior to service" discharge (relative risk = 2.4; confidence interval: 1.6, 3.5). Despite the increased risk of discharge, current waiver criteria allowed a majority with spinal curvature to complete at least 2 years of service. Policy makers must consider risks and benefits before modifying the current accession standard for spinal curvature.

Incidence of adult onset schizophrenic disorders in the US military: patterns by sex, race and age.

BACKGROUND: There are limited data describing the epidemiology of adult-onset schizophrenic disorders in the United States. Although the military is not proportionately comparable in all demographic characteristics to the civilian population, it is drawn from all racial/ethnic subgroups, and members range in age from 17 to >60 years. We describe the incidence of hospitalization for new onset schizophrenic disorders among military members by sex, race, and age. METHODS: Using military inpatient data, we evaluated patterns of initial hospitalizations for schizophrenic disorders among military personnel for 2000-2009, focusing on sex, race, and age. No individual-level data were available. RESULTS: From 2000-2009, 1976 military personnel had a first schizophrenic disorder hospitalization, with an overall incidence rate of 0.14/1000 person-years. There were no consistent changes in rates over time. While overall incidence rates were similar for men and women (incidence rate ratio (IRR)=1.10), rates were higher among men than women below age 25; after 25-30 rates were higher among women. Incidence was higher among blacks and other racial groups, with IRR=2.0 and 1.3, respectively. CONCLUSION: Medical screening of military applicants prevents persons with overt or a reported history of psychosis, and most with serious behavior problems, from enlisting; therefore, first hospitalization is likely to reflect new illness. No pre-military socioeconomic data were available, however, essentially all study subjects were high school graduates; unmeasured differences in socioeconomic status were unlikely to explain the observed results. This report may provide lower bound estimates of the schizophrenic disorder incidence in the United States.

Body mass index, medical qualification status, and discharge during the first year of US Army service.

BACKGROUND: The high prevalence of overweight and obesity in military recruits and in the US population as a whole necessitates understanding the health effects of body composition and associated morbidity. OBJECTIVE: In this study, we examined the effect of body mass index (BMI; in kg/m(2)) and medical status on premature discharge from the US Army in a large cohort of first-time-enlisted, active-duty soldiers. DESIGN: We determined the odds ratios (ORs) associated with BMI and medical status at enlistment by using a retrospective cohort of first-time, active-duty army recruits. RESULTS: ORs for BMI, calculated by using 24-24.9 as a reference, exhibited a U-shaped pattern. Soldiers with a BMI >34 had the highest ORs for all-cause (OR: 1.47; 95% CI: 1.32, 1.64) and medical (OR: 1.68; 95% CI: 1.46, 1.93) discharges. A BMI <17 was 1.35 times as likely (95% CI: 1.02, 1.80) to result in an all-cause discharge and 1.45 times as likely (95% CI: 1.01, 2.08) to result in a medical discharge. ORs for soldiers who required a medical reexamination did not vary when all-cause discharge (OR: 1.10; 95% CI: 1.06, 1.14) and medical discharge (OR: 1.10; 95% CI: 1.05, 1.15) were compared. The medical discharge OR for soldiers who required a medical waiver to enter the army (OR: 1.56; 95% CI: 1.48, 1.64) was higher than the OR for all-cause discharge (OR: 1.27; 95% CI: 1.22, 1.32). CONCLUSION: Enlistment BMI and medical qualification status play an important role in early discharge and may provide a valuable tool in the development of fitness, nutrition, and injury-prevention interventions in higher-risk groups.

Increased prevalence of the pfdhfr/phdhps quintuple mutant and rapid emergence of pfdhps resistance mutations at codons 581 and 613 in Kisumu, Kenya.

BACKGROUND: Anti-malarial drug resistance in Kenya prompted two drug policy changes within a decade: sulphadoxine-pyrimethamine (SP) replaced chloroquine (CQ) as the first-line anti-malarial in 1998 and artemether-lumefantrine (AL) replaced SP in 2004. Two cross-sectional studies were conducted to monitor changes in the prevalence of molecular markers of drug resistance over the period in which SP was used as the first-line anti-malarial. The baseline study was carried out from 1999-2000, shortly after implementation of SP, and the follow-up study occurred from 2003-2005, during the transition to AL. MATERIALS AND METHODS: Blood was collected from malaria smear-positive, symptomatic patients presenting to outpatient centers in Kisumu, Kenya, during the baseline and follow-up studies. Isolates were genotyped at codons associated with SP and CQ resistance. In vitro IC50 values for antifolates and quinolones were determined for isolates from the follow-up study. RESULTS: The prevalence of isolates containing the pfdhfr N51I/C59R/S108N/pfdhps A437G/K540E quintuple mutant associated with SP-resistance rose from 21% in the baseline study to 53% in the follow-up study (p < 0.001). Isolates containing the pfdhfr I164L mutation were absent from both studies. The pfdhps mutations A581G and A613S/T were absent from the baseline study but were present in 85% and 61%, respectively, of isolates from the follow-up study. At follow-up, parasites with mutations at five pfdhps codons, 436, 437, 540, 581, and 613, accounted for 39% of isolates. The CQ resistance-associated mutations pfcrt K76T and pfmdr1 N86Y rose from 82% to 97% (p = 0.001) and 44% to 76% (p < 0.001), respectively, from baseline to follow-up. CONCLUSIONS: During the period in which SP was the first-line anti-malarial in Kenya, highly SP-resistant parasites emerged, including isolates harboring pfdhps mutations not previously observed there. SP continues to be widely used in Kenya; however, given the highly resistant genotypes observed in this study, its use as a first-line anti-malarial should be discouraged, particularly for populations without acquired immunity to malaria. The increase in the pfcrt K76T prevalence, despite efforts to reduce CQ use, suggests that either these efforts are not adequate to alleviate CQ pressure in Kisumu, or that drug pressure is derived from another source, such as the second-line anti-malarial amodiaquine.