Piloting delivery of PfSPZ vaccines for malaria through a cryogenic vaccine cold chain to travel and military medicine clinics.

BACKGROUND: PfSPZ vaccines comprising Plasmodium falciparum (Pf) sporozoites (SPZ) have demonstrated > 90% protection against variant Pf malaria infections for at least 12 weeks; they are the only vaccines with the level of efficacy necessary to protect travellers. PfSPZ are eukaryotic cells stabilized by cryopreservation and distributed using a cryogenic (below -150 °C) cold chain. The Ebola vaccine and mRNA vaccines against SARS-CoV-2 pioneered uptake of vaccines requiring non-standard ultra-low temperature cold chains. The cryogenic cold chain using liquid nitrogen (LN2) vapour phase (LNVP) cryoshippers, is simpler, more efficient than -80, -20 or 2-8 °C cold chains, and does not use electricity. This study was conducted to evaluate implementation and integration of a cryogenically distributed vaccine at travel and military immunization clinics. METHODS: We conducted sequential 28-day studies evaluating vaccine shipping, storage, maintenance and accession at two US military and two civilian travel health/immunization clinics. In each clinic, personnel were trained in equipment use, procurement and handling of LN2, temperature monitoring and inventory record keeping by in-person or video instruction. RESULTS: Sites required 2-4 h/person for two persons to assimilate and develop the expertise to manage vaccine storage and LNVP operations. LN2 for recharging cryoshippers was delivered every 1-2 weeks. Vaccine ordering, receipt, storage and inventory control was conducted effectively. Simulated single dose vaccine cryovial retrieval and thawing were performed successfully in different travel clinic settings. Continuous temperature monitoring at each site was maintained with only one short excursion above -150 °C (-145 °C) through shipping, use and reverse logistics. Staff, during and at study conclusion, provided feedback that has been incorporated into our models for cold chain logistics. CONCLUSIONS: These studies demonstrated that the training in delivery, storage, administration and integration of PfSPZ vaccines can be successfully managed in different immunization clinic settings for travellers and military personnel.

Factors Associated With Viral Suppression and Drug Resistance in Children and Adolescents Living With HIV in Care and Treatment Programs in Southern Tanzania.

BACKGROUND: Achieving viral suppression (VS) for persons living with HIV is key to reaching epidemic control. We assessed the prevalence of VS and the frequency of HIV drug resistance mutations (HIVDRM) among children and adolescents living with HIV (CALHIV) in the Southern Highland zone of Tanzania. METHODS: From 2019 to 2021, we enrolled CALHIV aged 1-19 years on ART for >6 months in a cross-sectional study. Participants had viral load (VL) testing; those with VL ≥ 1000 copies/mL underwent HIVDRM testing. VS (<1000 copies/mL) prevalence estimates were calculated and robust Poisson regression was used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for associations with potential predictors of VS. RESULTS: Of 707 participants, 595 had VS (PR: 0.84, 95% CI: 0.81-0.87). Use of an integrase strand transfer inhibitor-containing regimen (aPR 1.15, 95% CI: 0.99-1.34), age 5-9 years (aPR 1.16, 95% CI: 1.07-1.26), and seeking care at a referral center (aPR 1.12, 95% CI: 1.04-1.21) were associated with VS. Factors inversely associated with VS included having one (aPR 0.82, 95% CI: 0.72-0.92) or two or more (aPR 0.79, 95% CI: 0.66-0.94) referrals for adherence counselling, and self-reporting missing one to two (aPR 0.88, 95% CI: 0.78-0.99) or three or more (aPR 0.77, 95% CI: 0.63-0.92) doses of ART in the past month. Of 74 participants with PRRT and INT sequencing done, 60 (81.1%) had HIVDRMs at the following frequencies: 71.6%, 67.6%, 1.4%, and 4.1% for major NNRTI, NRTI, PI, and INSTI respectively. CONCLUSIONS: Higher rates of VS were observed in this cohort, and HIVDRMs were common in those without VS. This evidence supports ART optimization using dolutegravir-based regimens. However, better strategies to improve adherence are needed.

Evaluating Intersite Consistency Across 11 Geographically Distinct Pediatric Clerkship Training Sites: Providing Assurance That Educational Comparability Is Possible.

INTRODUCTION: We compared core pediatric clerkship student assessments across 11 geographically distinct learning environments following a major curriculum change. We sought to determine if intersite consistency existed, which can be used as a marker of program evaluation success. METHODS: We evaluated students' overall pediatric clerkship performance along with individual assessments that target our clerkship learning objectives. Using the data of graduating classes from 2015 to 2019 (N = 859), we conducted an analysis of covariance and multivariate logistic regression analysis to investigate whether the performance varied across training sites. RESULTS: Of the students, 833 (97%) were included in the study. The majority of the training sites did not show statistically significant differences from each other. After controlling for the Medical College Admission Test total score and the average pre-clerkship National Board of Medical Examiners final exam score, the clerkship site only explained a 3% additional variance of the clerkship final grade. CONCLUSIONS: Over the ensuing 5-year period after a curriculum overhaul to an 18-month, integrated module pre-clerkship curriculum, we found that student pediatric clerkship performance in clinical knowledge and skills did not differ significantly across 11 varied geographic teaching sites when controlling for students' pre-clerkship achievement. Specialty-specific curriculum resources, faculty development tools, and assessment of learning objectives may provide a framework for maintaining intersite consistency when faced with an expanding network of teaching facilities and faculty.

The Burden of Arboviral Infections in the Military Health System 2012-2019.

Arboviral infections, including dengue (DNV), chikungunya (CHIKV), and Zika (ZIKV), impact both travelers and native populations of endemic regions. We sought to assess the disease burden of arboviral infections in the Military Health System, the validity of arboviral diagnostic codes, and the role of pretravel counseling on insect avoidance precautions. We searched for diagnostic codes consistent with arboviral infection and grouped them into DNV, CHIKV, ZIKV, Japanese encephalitis virus (JEV), and Other. Demographic data were evaluated. A subset of charts in each category were reviewed for diagnostic validity and travel characteristics. In all, 10,547 unique subjects carried 17,135 arboviral diagnostic codes, including 1,606 subjects (15.2%) coded for DNV, 230 (2.2%) for ZIKV, 65 (0.6%) for CHIKV, and 4,317 (40.9%) for JEV. A chart review was performed on 807 outpatient charts, yielding outpatient diagnostic code positive predictive values of 60.5% (DNV), 15.3% (ZIKV), and 64.5% (CHIKV); there were no valid cases of JEV. Dengue represented the greatest burden of arboviral infections with 2.2 cases per 100,000 military healthcare enrollees over the 2012-2019 fiscal years. More than 80% of subjects with arboviral infection did not have documented pretravel counseling. Arboviral infections represent a significant disease burden in young travelers to endemic regions. After adjustment for diagnostic validity, DNV represented the greatest burden. Diagnostic codes for ZIKV and JEV overestimate the burden of these diseases. Low rates of pretravel visits represent an opportunity for increased emphasis on insect exposure precautions.

Strongyloides stercoralis in the US Military Health System.

Background: Strongyloides stercoralis is an intestinal nematode most commonly found in subtropical and tropical locations. Military service members are believed to be at increased risk of exposure due to their unique occupational exposures in endemic regions. Methods: Burden, clinical course, and risk factors associated with all Strongyloides infections within the US Military Health System from fiscal years 2012 to 2019 were assessed by manual chart review of records with International Classification of Diseases, Ninth Revision/Tenth Revision codes for Strongyloides infection. Infection risk in demographic subgroups based on region of birth, military occupation, and age was quantified with univariate analysis and multivariate logistic regression. Results: We reviewed 243 charts based on diagnosis coding, yielding 210 confirmed diagnoses (86.4%). Immigrant patients born in Latin America/Caribbean, sub-Saharan Africa, and East Asia/Pacific regions had statistically significant increased risk ratios of infection at 34.4, 32.0, and 22.4, respectively, when compared to patients born in Europe and North America. In univariate analysis, active duty members in the healthcare occupational category had a statistically significant increased risk ratio of infection at 2.31 compared to those outside this occupation. Multivariate logistic regression analysis demonstrated that occupational categories of healthcare, admininstrative/support, warfighter/combat specialist, and engineering/repair/maintenance occupations, being an immigrant patient, and age ≥65 were all associated with statistically significant increased odds ratios for infection. Conclusions: In the Military Health System, occupational exposures, region of birth, and age serve as risk factors for Strongyloides infection. Because infections may be chronic, the impact of targeted screening programs to complement routine medical care should be considered.

Destination based errors in chloroquine malaria chemoprophylaxis vary based on provider specialty and credentials.

BACKGROUND: The Deployment and Travel Medicine Knowledge, Attitudes, Practices, and Outcomes Study (KAPOS) evaluates health outcomes and provider practices associated with travel and deployments within the US Military Health System. We analyzed prescribing errors for chloroquine malaria chemoprophylaxis between travel medicine specialists and non-specialists over a five-year period. METHODS: A sample of 291 chloroquine prescriptions were reviewed to determine if malaria chemoprophylaxis was appropriate for destination of travel based on both transmission and chloroquine resistance risk. We included non-active-duty beneficiaries of all ages seeking care at military treatment facilities. RESULTS: 10.3% (n = 30) of patients were prescribed chloroquine inappropriately. Non-travel medicine specialists prescribed chloroquine inappropriately more frequently than travel medicine specialists with 16.5% vs 2.3% error, respectively. Physicians were less likely to erroneously prescribe chloroquine as compared to non-physicians with 6.4% vs 22.2% error, respectively. 93.3% of prescribing errors were due to chloroquine-resistance presence at the travel destination. Africa was the most common destination of erroneous prescriptions, creating significant risk for travelers. CONCLUSIONS: While chloroquine is infrequently prescribed, this analysis demonstrates travel medicine proficiency is associated with reduced errors, highlighting the need to supply travel medicine education and decision support tools to non-specialists, to safeguard patients who seek pre-travel medical care.

Costs and Prescribing Patterns of Anthelmintics in the United States Military: A Retrospective Analysis.

BACKGROUND: Recent price increases in medications used to treat helminth infections have had demonstrated impacts on Medicaid and immigrant patient populations. Helminth infections are common within the US military; however, anthelmintic prescribing patterns and costs have not yet been investigated in this patient population. METHODS: We conducted a retrospective analysis of pharmaceutical data from the Military Health System Data Repository between fiscal years 2012 and 2019. Prescription information, including costs and demographics, were abstracted for all anthelmintic medications as well as associated helminth diagnostic codes within 30 days of the prescription dispensing date. RESULTS: On average, there were 10 871 anthelmintic medications prescribed per year, for a total of 86 697 during the study period. Ivermectin and albendazole were each prescribed >34 000 times. There were 15 498 mebendazole prescriptions and 1327 praziquantel prescriptions. The total cost of all anthelmintic prescriptions was $16 018 381. Annual costs for anthelmintic medications increased 16-fold during the study period, up to nearly $5 000 000 in fiscal year 2019, primarily driven by price increases in albendazole and mebendazole. Albendazole prescriptions accounted for $12 282 891 of total costs (76.7%), though only 39.1% of total prescriptions. The most common diagnosis associated with albendazole and mebendazole prescriptions was enterobiasis. CONCLUSIONS: Price increases in anthelmintic medications have significantly impacted the costs borne by the US government for treating parasitic infections. There are a substantial number of anthelmintic prescriptions in the US military health care system annually, suggesting a higher number of helminth infections than previously thought.

Military and Civilian Sector Practice Patterns for Short-Term Travelers' Diarrhea Self-Treatment in Adults.

The Deployment and Travel Medicine Knowledge, Attitude, Practice and Outcomes Study investigates the various clinician and traveler contributions to medical outcomes within the U.S. Military Health System. Travelers' diarrhea is among the most common travel-related illnesses, making travelers' diarrhea self-treatment (TDST) important for traveler health. A cohort of 80,214 adult travelers receiving malaria chemoprophylaxis for less than 6 weeks of travel were identified within the U.S. Department of Defense Military Health System Data Repository. Associated prescriptions for TDST medications within 2 weeks of chemoprophylaxis prescriptions were identified. Prescription patterns were compared by service member versus beneficiary status and site of care, military facility versus civilian facility. At military facilities, medical provider demographics were analyzed by clinical specialty and categorized as travel medicine specialists versus nonspecialists. Overall, there was low prescribing of TDST, particularly among civilian providers and military nonspecialists, despite guidelines recommending self-treatment of moderate to severe travelers' diarrhea. This practice gap was largest among service member travelers, but also existed for beneficiaries. Compared with nonspecialists, military travel medicine specialists were more likely to prescribe a combination of an antibiotic and antimotility agent to beneficiaries, more likely to provide any form of TDST to service members, and more likely to prescribe azithromycin than quinolones when using antibiotics. Our study suggests that enhancing provider knowledge and use of travelers' diarrhea treatment recommendations combined with improved access to formal travel medicine services may be important to increase the quality of care.

Prevalence and Correlates of Viral Load Suppression and Human Immunodeficiency Virus (HIV) Drug Resistance Among Children and Adolescents in South Rift Valley and Kisumu, Kenya.

BACKGROUND: Children and adolescents living with HIV (CALHIV) face unique challenges, including poorer treatment outcomes, risk for drug-resistance mutations (HIVDRMs), and limited drug formulations. We estimated viral suppression (VS) prevalence and evaluated predictors of VS and HIVDRMs in Kenya. METHODS: From 2018-2020, CALHIV 1-19 years on antiretroviral therapy (ART) >6 months were enrolled in this cross-sectional study. Participants underwent viral load (VL) testing; those with VL ≥1000 copies/mL had HIVDRM testing. Sociodemographic questionnaires and medical record abstraction were completed. VS prevalence (VL <1000 copies/mL) was estimated; robust Poisson regression models were used to estimate prevalence ratios (PRs) and 95% CIs for associations between potential predictors of VS. RESULTS: Nine hundred and sixty-nine participants were enrolled. VS prevalence was .80 (95% CI: .78-.83). Being on ART >24 months (adjusted PR [aPR]: 1.22; 95% CI: 1.06-1.41), an integrase strand transfer inhibitor-containing regimen (1.13; 1.02-1.26), and attending a level 3 health facility (1.23; 1.11-1.36) were associated with VS. Missing ≥3 doses of ART in the past month (aPR: .73; 95% CI: .58-.92), having a viremic mother with HIV (.72; .53-.98), and having 3-7 (.90; .83-.97), 8-13 (.89; .82-.97), or ≥14 (.84; .77-.92) compared with <2 adherence counseling referrals were inversely associated with VS. A high proportion (n = 119, 81.5%) of unsuppressed participants had evidence of any major HIVDRM. CONCLUSIONS: HIV treatment programs should target interventions for pediatric patients at risk for treatment failure-namely, those with a caregiver with failed VS and those struggling with adherence.

The pregnancy factor: the prevalence of depression among women living with HIV enrolled in the African Cohort Study (AFRICOS) by pregnancy status.

Among Sub-Saharan African women living with HIV (WLWH), pregnancy creates unique stressors that may cause depression. We describe the prevalence of depression among WLWH enrolled in the African Cohort Study (AFRICOS) by pregnancy status and describe factors associated with depression. WLWH < 45 years of age underwent six-monthly visits with depression diagnosed using the Center for Epidemiological Studies-Depression scale. Visits were categorized as "pregnant;" "postpartum" (the first visit made after the last pregnancy visit), and "non-pregnant." The prevalence of depression was calculated for each visit type and compared using prevalence odds ratios (POR) with 95% confidence intervals (CI). Logistic regression with generalized estimating equations was used to evaluate sociodemographic factors associated with depression. From January 2013 to March 1, 2020, 1333 WLWH were enrolled, and 214 had pregnancies during follow-up. As compared to the prevalence of depression during "non-pregnant" visits (9.1%), depression was less common at "pregnant" (6.3%; POR = 0.68 [CI: 0.42, 1.09]) and "postpartum" (3.4%; POR = 0.36 [CI: 0.17, 0.76]) visits. When controlling for other factors, the visit category was not independently associated with depression. Visit number, study site, employment status, and food security were independently associated with decreased odds of depression. We observed a lower prevalence of depression during pregnancy and the postpartum period than has been previously described among WLWH during similar time points. We observed protective factors against depression which highlight the impact that holistic and consistent health care at HIV-centered clinics may have on the well-being of WLWH in AFRICOS.

Helminth infections in the US military: from strongyloidiasis to schistosomiasis.

BACKGROUND: Helminth infections caused by parasitic worms, including nematodes (roundworms), cestodes (tapeworms) and trematodes (flukes), can cause chronic symptoms and serious clinical outcomes if left untreated. The US military frequently conducts activities in helminth-endemic regions, particularly Africa, the Middle East and Southeast Asia. However, the military does not currently screen for these infections, and to date, no comprehensive surveillance studies have been completed to assess the frequency of helminth diagnoses in the military personnel and their families. METHODS: To determine the burden of helminth infections in the US Military Health System (MHS), we conducted a retrospective analysis of International Classification of Diseases (ICD)-9/10 diagnosis codes from all medical encounters in the MHS Data Repository (MDR) from fiscal years (FY) 2012 to 2018. Chart reviews were conducted to assign ICD diagnoses as incorrect, suspected, probable or confirmed based on the laboratory results and symptoms. RESULTS: Abstraction of MHS data revealed over 50 000 helminth diagnoses between FY 2012 and FY 2018. Of these, 38 445 of diagnoses were amongst unique subjects. After chart review, we found there were 34 425 validated helminth infections diagnosed amongst the unique subjects of US military personnel, retirees and dependents. Nearly 4000 of these cases represented infections other than enterobiasis. There were 351 validated strongyloidiasis diagnoses, 317 schistosomiasis diagnoses and 191 diagnoses of cysticercosis during the study period. Incidence of intestinal nematode infection diagnoses showed an upward trend, whilst the incidence of cestode infection diagnoses decreased. CONCLUSIONS: The results of this study demonstrate that helminth infections capable of causing severe morbidity are often diagnosed in the US military. As helminth infections are often asymptomatic or go undiagnosed, the true burden of helminth infections in US military personnel and dependents may be higher than observed here. Prospective studies of US military personnel deployed to helminth-endemic areas may be indicated to determine if post-deployment screening and/or empirical treatment are warranted.

Sixteen Weeks Later: Expanding the Risk Period for Multisystem Inflammatory Syndrome in Children.

Multisystem inflammatory syndrome in children (MIS-C) has been observed in temporal association with coronavirus disease 2019 (COVID-19), typically within 2 to 6 weeks of illness or exposure. We present a case of MIS-C occurring 16 weeks after initial COVID-19 illness to highlight the prolonged period of risk for developing MIS-C.

Attaining 95-95-95 through Implementation Science: 15 Years of Insights and Best Practices from the Walter Reed Army Institute of Research's Implementation of the U.S. President's Emergency Plan for AIDS Relief.

The Walter Reed Army Institute of Research (WRAIR) supports more than 350,000 people on lifesaving HIV treatment in Kenya, Nigeria, Tanzania, and Uganda through funding from the U.S. President's Emergency Plan for AIDS Relief (PEPFAR). Here, we review and synthesize the range of impacts WRAIR's implementation science portfolio has had on PEPFAR service delivery for military and civilian populations since 2003. We also explore how investments in implementation science create institutional synergies within the U.S. Department of Defense, contributing to broad global health engagements and improving health outcomes for populations served. Finally, we discuss WRAIR's contributions to PEPFAR priorities through use of data to drive and improve programming in real time in the era of HIV epidemic control and public health messaging that includes prevention, the 95-95-95 goals, and comorbidities.

The Impact of Military Pediatrics: Assessing Clinical, Leadership, Academic, and Operational Experience Among Pediatric-trained Graduates From the Uniformed Services University of the Health Sciences (USU).

INTRODUCTION: This article uses alumni survey data from the Uniformed Services University of the Health Sciences (USU) F. Edward Hébert School of Medicine to assess the professional impact of pediatric-trained USU graduates over the course of their careers. We specifically report on the clinical and leadership roles held, career accomplishments, and operational involvement among military pediatricians. MATERIALS AND METHODS: This study analyzed survey data that were collected from alumni of USU. We used descriptive statistics to report the career achievements and operational experiences among USU graduates who completed training in pediatrics. This study was deemed exempt by the USU Institutional Review Board. RESULTS: The survey response rate was 49.5% among 2,400 eligible respondents. Out of 1,189 alumni respondents, 110 (9.3%) trained in pediatrics. Among the pediatric-trained USU graduates, 98.2% spent some time as a full-time clinician, 73.6% served as chief of a clinical service, 42.7% held the role of department chair/chief or the equivalent, and 26.3% filled leadership positions in deployed settings. Forty percent of USU-trained military pediatricians deployed to combat areas at least once, and 35.5% participated in at least one peacetime humanitarian mission. CONCLUSIONS: Our findings contribute to the unique story of military pediatricians who graduated from USU. These uniformed pediatricians participate actively in all realms of military medicine and have demonstrated their versatility through participation in a wide variety of vital functions. Their contributions include the provision of clinical care for both military children and active duty service members, serving in varied leadership positions, engaging in health professions education and other academic pursuits, and participating in operational assignments. Future studies could aim to more fully address the diverse contributions of military pediatricians to the overall mission by including more specific data about career experiences from all uniformed pediatricians.

Deployment and Travel Medicine Knowledge, Attitudes, Practices, and Outcomes Study (KAPOS): Malaria Chemoprophylaxis Prescription Patterns in the Military Health System.

The Deployment and Travel Medicine Knowledge, Attitudes, Practices, and Outcomes Study (KAPOS) examines the integrated relationship between provider and patient inputs and health outcomes associated with travel and deployments. This study describes malaria chemoprophylaxis prescribing patterns by medical providers within the U.S. Department of Defense's Military Health System and its network of civilian healthcare providers during a 5-year period. Chemoprophylaxis varied by practice setting, beneficiary status, and providers' travel medicine expertise. Whereas both civilian and military facilities prescribe an increasing proportion of atovaquone-proguanil, doxycycline remains the most prevalent antimalarial at military facility based practices. Civilian providers dispense higher rates of mefloquine than their military counterparts. Within military treatment facilities, travel medicine specialists vary their prescribing pattern based on service member versus beneficiary status of the patient, both in regards to primary prophylaxis, and use of presumptive anti-relapse therapy (PQ-PART). By contrast, nonspecialists appear to carry over practice patterns developed under force health protection (FHP) policy for service members, into the care of beneficiaries, particularly in high rates of prescribing doxycycline and PQ-PART compared with both military travel medicine specialists and civilian comparators. Force health protection policy plays an important role in standardizing and improving the quality of care for deployed service members, but this may not be the perfect solution outside of the deployment context. Solutions that broaden both utilization of decision support tools and travel medicine specialty care are necessary.

Deployment Infectious Disease Threats: IDCRP Initiatives and Vision Forward.

BACKGROUND: Infectious diseases pose a significant threat to health and readiness of military personnel deployed globally during wartime and peacekeeping activities. Surveillance and improvement in mitigation through research of infectious disease threats remain an integral part of Force Health Protection. Herein, we review research efforts of the Infectious Disease Clinical Research Program related to deployment and travel-related infections. METHODS: The objectives of the Deployment and Travel-Related Infections Research Area are to (1) provide epidemiologic and clinical data, including pathogen-specific estimates of disease incidence among deployed troops, (2) execute clinical trials and effectiveness studies to improve recommendations regarding prevention and treatment of infections during deployment, and (3) evaluate the knowledge and practice patterns of health care providers engaged in deployment/travel medicine and the impact on outcomes. The centerpiece protocol of the research area is the Deployment and Travel-Related Infectious Disease Risk Assessment, Outcomes, and Prevention Strategies cohort study (TravMil), which was initiated in 2010 and collects data on a broad range of deployment-related infections. RESULTS: To date, 4,154 deployed military personnel and traveling Department of Defense (DoD) beneficiaries have been enrolled in TravMil. Surveillance data collected through the TravMil study provide assessment of deployment and travel-related infectious disease threats, and the effectiveness of mitigation strategies. The incidence of travelers' diarrhea, influenza-like illness, and undifferentiated febrile illness is 20.48%, 9.34%, and 6.16%, respectively. The cohort study also provides necessary infrastructure to execute clinical trials. The TrEAT TD clinical trial evaluated the effectiveness of single-dose antibiotic therapy for travelers' diarrhea in the deployed setting. When compared to levofloxacin, azithromycin was not inferior; however, inferiority was not demonstrated with use of single dose of rifaximin. The trial findings supported the development of a deployment-related health guideline for the management of acute diarrheal disease. A clinical trial evaluating the effectiveness of rifaximin for prevention for travelers' diarrhea (Prevent TD) is underway. CONCLUSIONS: The research area has proven its ability to conduct impactful research, including the development of field-expedient diagnostics, the largest DoD multi-site travelers' diarrhea randomized control trial in peacetime and combat settings, and informed Force Health Protection guidance. The research area continues to provide surveillance data to military commands via an established collaborative network of military treatment facilities, DoD laboratories (both within and outside the continental United States), foreign militaries, and academia. The conduct of clinical and translational research in a deployment setting presents significant challenges, most notably in recruitment/enrollment and compliance with study-related procedures during deployment.

Association of the US President's Emergency Plan for AIDS Relief's Funding With Prevention of Mother-to-Child Transmission of HIV in Kenya.

Importance: From 2004 to 2014, the US President's Emergency Plan for AIDS Relief (PEPFAR) invested more than $248 000 000 in the prevention of mother-to-child transmission (PMTCT) of HIV in Kenya. Concurrently, child mortality in Kenya decreased by half. Objective: To identify the extent to which the decrease in child mortality in Kenya is associated with PEPFAR funding for PMTCT of HIV. Design, Setting, and Participants: This population-based survey study conducted in Kenya estimated the association between annual per capita PEPFAR funding for PMTCT (annual PCF) and cumulative per capita PEPFAR funding for PMTCT (cumulative PCF), extracted using 2004-2014 country operational reports as well as individual-level health outcomes, extracted from the 2003, 2008-2009, and 2014 Kenya Demographic and Health Surveys and the 2007 and 2012 Kenya AIDS Indicator Surveys. The study included children of female respondents to the 2003, 2008-2009, and 2014 Kenya Demographic and Health Surveys who were born 1 to 60 months (for neonatal mortality) or 12 to 60 months (for infant mortality) before the survey, as well as female respondents who had recently given birth and reported on HIV testing during antenatal care (ANC) during the 2007-2014 surveys. Results were adjusted for year, province, and survey respondent characteristics. Statistical analysis was performed from July 8, 2016, to December 10, 2018. Main Outcomes and Measures: Neonatal mortality was defined as death within the first month of life and infant mortality was defined as death within the first year of life. HIV testing during ANC was defined as receiving counseling on PMTCT, undergoing an HIV test, and receiving test results during ANC. Results: The analysis included 33 181 neonates (16 870 boys), 26 876 infants (13 679 boys), and 20 775 mothers (mean [SD] age, 28.0 [6.7] years). PEPFAR funding was not associated with neonatal mortality. A $0.33 increase in annual PCF, corresponding to the difference between the 75th and 25th (interquartile range) percentiles of funding, was significantly associated with a 16% (95% CI, 4%-27%) reduction in infant mortality after a 1-year lag. A 14% to 16% reduction persisted after 2- and 3-year lags, and comparable reductions were observed for unlagged and 1-year lagged cumulative PCF. An increase of 1 interquartile range in cumulative PCF was associated with a 7% (95% CI, 3%-11%) increase in HIV testing during ANC, which intensified with subsequent lags. Between 2004 and 2014, sustained funding levels of $0.33 annual PCF could have averted 118 039 to 273 924 infant deaths. Conclusions and Relevance: Evidence from publicly available data suggests that PEPFAR's PMTCT funding was associated with a reduction in infant mortality and an increase in HIV testing during ANC in Kenya. The full outcome of funding may not be realized until several years after allocation.

A Comparison of Pretravel Health Care, Travel-Related Exposures, and Illnesses among Pediatric and Adult U.S. Military Beneficiaries.

We evaluated differences in pretravel care, exposures, and illnesses among pediatric and adult travelers, using a prospective, observational cohort. Eighty-one pediatric travelers were matched 1:1 with adult military dependents by travel region, destination's malaria risk, and travel duration. Pediatric travelers were more likely to have coverage for hepatitis A and B (90% versus 67% of adults; 85% versus 44%), visit friends and relatives (36% versus 16%), report mosquito bites (69% versus 44%), and have close contact with wild or domesticated animals (40% versus 20%) than adults (P < 0.05). Subjects < 10 years of age were less likely to be prescribed antibiotics (28% versus 95%; RR = 0.63; 95% CI: 0.46-0.85) and antidiarrheals (9% versus 100%; RR = 0.10; 95% CI: 0.03-0.29) for travelers' diarrhea (TD) self-treatment than adults. Travel medicine providers should emphasize strategies for vector avoidance, prevention of animal bites and scratches, and TD self-treatment in pediatric pretravel consultations.

Noninfectious Comorbidity in the African Cohort Study.

BACKGROUND: Noninfectious comorbid diseases (NCDs) contribute to morbidity and mortality in human immunodeficiency virus (HIV)-infected populations in resource-rich countries. With antiretroviral therapy (ART) scale-up in Africa, understanding burden NCD informs public health strategy. METHODS: At enrollment, participants at 11 HIV clinics in Kenya, Uganda, Tanzania, and Nigeria underwent medical history, physical, laboratory, and neuropsychological assessments to identify elevated blood pressure, hypercholesterolemia, dysglycemia, renal insufficiency, and cognitive impairment. Poisson regression models estimated adjusted relative risks (ARRs) and 95% confidence intervals (CIs) for the number of NCDs associated with factors of interest. Logistic regression was used to evaluate each NCD separately among HIV-infected participants. RESULTS: Among 2720 participants with complete NCD data, 2159 (79.4%) were HIV-infected. Of those, 1426 (66.0%) were taking ART and 813 (37.7%) had at least 1 NCD. HIV infection was associated with more NCDs, especially with ART (ARR, 1.42; 95% CI, 1.22-1.66). In addition to age, body mass index, and program site, ART usage was associated with more NCDs (ARR, 1.50; 95% CI, 1.27-1.78 for virologically suppressed and ARR, 1.38; 95% CI, 1.13-1.68 for viremic) among HIV-infected participants. In participants taking ART, CD4 nadir below 200 cells/mm3 was associated with more NCDs (ARR, 1.43; 95% CI, 1.06-1.93). ART use was independently associated with hypercholesterolemia and dysglycemia. Program site was significantly associated with all comorbidities except renal insufficiency. CONCLUSIONS: HIV infection was a risk for NCDs, which were common in HIV-infected participants, geographically variable, and largely consistent with metabolic complications of first-line ART.

Persistent Low-level Viremia Predicts Subsequent Virologic Failure: Is It Time to Change the Third 90?

BACKGROUND: World Health Organization (WHO) guidelines identify human immunodeficiency virus (HIV) viral load <1000 copies/mL as the goal of antiretroviral therapy (ART). However, the clinical implications of viremia below this threshold are unclear in the African context. We examined factors associated with persistent low-level viremia (pLLV) and quantified the risk of subsequent virologic. METHODS: The African Cohort Study enrolled HIV-infected adults at clinics in Uganda, Kenya, Tanzania, and Nigeria, with assessments every 6 months. We evaluated participants prescribed ART for at least 6 months without virologic failure for pLLV. We used multinomial logistic regression to evaluate associations between prespecified factors of interest and 3 levels of pLLV (<200, 200-499, and 500-999 copies/mL). We used Anderson-Gill extended Cox proportional hazards to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for viremia category associations with time to failure. RESULTS: We included 1511 participants with 4382 person-years of follow-up. PLLV <200 copies/mL was observed at 20% of visits while 2% of visits had pLLV 200-499 and 500-999 copies/mL each, with substantial variation by site. Protease inhibitor-containing ART was associated with increased risk of pLLV. Compared to undetectable viral load, pLLV ≥200 copies/mL doubled the risk of developing virologic failure (pLLV 200-499: HR, 1.81 [95% CI, 1.08-3.02]); pLLV 500-999: HR, 2.36 [95% CI, 1.52-3.67]). CONCLUSIONS: Participants with pLLV ≥200 copies/mL were at increased risk of subsequent virologic failure. Optimized HIV care in this setting should target viral suppression <200 copies/mL.