Low Use of Standard-of-Care Antiparasitic Drugs and Increased Estimated Outpatient Payments for Treating Schistosomiasis in the United States, 2013-19.

Drug utilization and payment estimates for standard-of-care treatment of schistosomiasis have not been reported previously in the United States. This study estimates the utilization of praziquantel (standard-of-care drug) among patients with schistosomiasis and outpatient payments among those who were treated with praziquantel, and investigates the factors associated with praziquantel use from 2013-19 using IBM's MarketScan® Commercial Claims and Encounters database. Claims data showed that only 21% of patients with schistosomiasis diagnoses were treated with praziquantel. The mean total drug payments per patient treated with praziquantel increased from $110 in 2013-14 to $612 in 2015-18 (P < 0.01), and use decreased. These factors, including residing in a rural area, having a documented Schistosoma haematobium infection, or having a first schistosomiasis diagnosis in 2015-16, were associated with a decreased likelihood of patients receiving standard-of-care treatment. Policy solutions to exorbitant drug pricing, and better awareness and education among healthcare providers about schistosomiasis-especially those practicing in rural areas with high immigrant populations-are needed.

Characteristics and Price Increases Among Sole-Source, Off-Patent Drugs in the United States, 2008 to 2018.

Importance: Some sole-source, off-patent drugs in the United States have undergone substantial price hikes in recent years. Despite increased attention by lawmakers, there are limited data to guide policy. Objectives: To describe key attributes of sole-source, off-patent, off-exclusivity drugs; to characterize the prevalence of price increases; and to identify attributes associated with price increases. Design, Setting, and Participants: In this cross-sectional study, 300 sole-source, off-patent, off-exclusivity drug products met inclusion criteria and were selected for analysis from January 1, 2008, to December 31, 2018. Attributes were identified from multiple sources, and yearly wholesale acquisition cost prices were determined from First Databank. Main Outcomes and Measures: The association of drug attributes with the following 2 price change thresholds was measured after adjusting for inflation: 25% or more price increase in a calendar year (wholesale acquisition cost) and 50% or more price increase in a calendar year. The rate of annual price increase over time was also measured. Results: Of the 300 drug products and 2242 observations analyzed, the overall inflation-adjusted mean increase in drug prices was 8.8% (95% CI, 7.8%-9.8%) per year. Ninety-five drugs (31.7%) increased by 25% or more during any calendar year, and 66 drugs (22.0%) increased by 50% or more during any calendar year. An initial price of less than $2 per unit (adjusted odds ratio [aOR], 2.36; 95% CI, 1.69-3.29), antineoplastic and immunomodulatory class (aOR, 2.72; 95% CI, 1.31-5.65), dermatologic class (aOR, 2.95; 95% CI, 1.80-4.84), oral route (aOR, 2.01; 95% CI, 1.45-2.79), and US Food and Drug Administration (FDA) approval before 1990 (aOR, 1.52; 95% CI, 1.14-2.03) were attributes of drugs that were more likely to be associated with a 25% or more price increase in a calendar year after adjusting for by initial price. Similarly, an initial price of less than $2 per unit (aOR, 2.68; 95% CI, 1.76-4.09), antineoplastic and immunomodulatory class (aOR, 3.07; 95% CI, 1.54-6.12), oral route of administration (aOR, 1.70; 95% CI, 1.11-2.60), and FDA approval before 1990 (aOR, 2.02; 95% CI, 1.40-2.94) were attributes of drugs that were more likely to be associated with a 50% or more price increase in a calendar year after adjusting for by initial price. Price increases of 25% or more were most common in 2014, and price increases of 50% or more were most common in 2013. Conclusions and Relevance: Price increases among sole-source, off-patent drugs are common, and policy interest in this practice is warranted. These findings should inform state drug pricing legislation.

Barriers to malaria prevention among immigrant travelers in the United States who visit friends and relatives in sub-Saharan Africa: A cross-sectional, multi-setting survey of knowledge, attitudes, and practices.

BACKGROUND: Despite achievements in the reduction of malaria globally, imported malaria cases to the United States by returning international travelers continue to increase. Immigrants to the United States from sub-Saharan Africa (SSA) who then travel back to their homelands to visit friends and relatives (VFRs) experience a disproportionate burden of malaria illness. Various studies have explored barriers to malaria prevention among VFRs and non-VFRs-travelers to the same destinations with other purpose for travel-but few employed robust epidemiologic study designs or performed comparative analyses of these two groups. To better quantify the key barriers that VFRs face to implement effective malaria prevention measures, we conducted a comprehensive community-based, cross-sectional, survey to identify differences in malaria prevention knowledge, attitudes, and practices (KAP) among VFRs and others traveling to Africa and describe the differences between VFRs and other types of international travelers. METHODS AND FINDINGS: Three distinct populations of travelers with past or planned travel to malaria-endemic countries of SSA were surveyed: VFRs diagnosed with malaria as reported through a state health department; members of the general VFR population (community); and VFR and non-VFR travelers presenting to a travel health clinic, both before their pretravel consultation and again, after return from travel. A Community Advisory Board of African immigrants and prior qualitative research informed survey development and dissemination. Across the three groups, 489 travelers completed surveys: 351 VFRs and 138 non-VFRs. VFRs who reported taking antimalarials on their last trip rated their concern about malaria higher than those who did not. Having taken five or more trips to SSA was reported more commonly among VFRs diagnosed with malaria than community VFRs (44.0% versus 20.4%; p = 0.008). Among travel health clinic patients surveyed before and after travel, VFR travelers were less successful than non-VFRs in adhering to their planned use of antimalarials (82.2% versus 98.7%; p = 0.001) and employing mosquito bite avoidance techniques (e.g., using bed nets: 56.8% versus 81.8%; p = 0.009). VFRs who visited the travel health clinic were more likely than VFR respondents from the community to report taking an antimalarial (83.0% versus 61.9%; p = 0.009), or to report bite avoidance behaviors (e.g., staying indoors when mosquitoes were out: 80.9% versus 59.5%; p = 0.009). CONCLUSIONS: We observed heterogeneity in malaria prevention behaviors among VFRs and between VFR and non-VFR traveler populations. Although VFRs attending the travel health clinic appear to demonstrate better adherence to malaria prevention measures than VFR counterparts surveyed in the community, specialized pretravel care is not sufficient to ensure chemoprophylaxis use and bite avoidance behaviors among VFRs. Even when seeking specialized pretravel care, VFRs experience greater barriers to the use of malaria prevention than non-VFRs. Addressing access to health care and upstream barrier reduction strategies that make intended prevention more achievable, affordable, easier, and resonant among VFRs may improve malaria prevention intervention effectiveness.

Barriers to malaria prevention in US-based travellers visiting friends and relatives abroad: a qualitative study of West African immigrant travellers†.

BACKGROUND: Over half of malaria cases reported in the USA occur among people travelling to visit friends and relatives (VFRs), predominantly to West Africa. Few studies have queried VFR travellers directly on barriers to seeking pre-travel care. We aim to describe the knowledge, attitudes and practices of VFRs travelling to malaria-endemic countries from the USA. With these findings, we aim to design interventions to encourage preventive behaviours before and during travel. METHODS: Sixteen focus groups were held in two US metropolitan areas with West African immigrant populations: Minneapolis-St. Paul, MN, and New York City, NY. A total of 172 people from 13 African countries participated. Focus group discussions were audio-recorded and transcribed, and modified grounded theory analysis was performed. Participants reviewed themes to verify intent of statements. RESULTS: Participants described the high cost of provider visits and chemoprophylaxis, challenges in advocating for themselves in healthcare settings and concerns about offending or inconveniencing hosts as barriers to malaria prevention. Cultural barriers to accessing pre-travel care included competing priorities when trip planning, such as purchasing gifts for family, travel logistics and safety concerns. When participants sought pre-travel care, most consulted their primary care provider. Participants expressed low confidence in US providers' knowledge and training about malaria and other tropical diseases. CONCLUSION: Barriers to pre-travel care for VFR travellers are multifaceted and extend beyond their perception of disease risk. Only some barriers previously reported in anecdotal and qualitative literature were supported in our findings. Future interventions should be aimed at barriers identified by individual communities and involve primary and travel specialist healthcare providers. Additional work is needed to address systems-level barriers to accessing care and establishing community-based programs to support West African VFR traveller health.

Impact of Enhanced Health Interventions for United States-Bound Refugees: Evaluating Best Practices in Migration Health.

With an unprecedented number of displaced persons worldwide, strategies for improving the health of migrating populations are critical. United States-bound refugees undergo a required overseas medical examination to identify inadmissible conditions (e.g., tuberculosis) 2-6 months before resettlement, but it is limited in scope and may miss important, preventable infectious, chronic, or nutritional causes of morbidity. We sought to evaluate the feasibility and health impact of diagnosis and management of such conditions before travel. We offered voluntary testing for intestinal parasites, anemia, and hepatitis B virus infection, to U.S.-bound refugees from three Thailand-Burma border camps. Treatment and preventive measures (e.g., anemia and parasite treatment, vaccination) were initiated before resettlement. United States refugee health partners received overseas results and provided post-arrival medical examination findings. During July 9, 2012 to November 29, 2013, 2,004 refugees aged 0.5-89 years enrolled. Among 463 participants screened for seven intestinal parasites overseas and after arrival, helminthic infections decreased from 67% to 12%. Among 118 with positive Strongyloides-specific antibody responses, the median fluorescent intensity decreased by an average of 81% after treatment. The prevalence of moderate-to-severe anemia (hemoglobin < 10 g/dL) was halved from 14% at baseline to 7% at departure (McNemar P = 0.001). All 191 (10%) hepatitis B-infected participants received counseling and evaluation; uninfected participants were offered vaccination. This evaluation demonstrates that targeted screening, treatment, and prevention services can be conducted during the migration process to improve the health of refugees before resettlement. With more than 250 million migrants globally, this model may offer insights into healthier migration strategies.

Economic Analysis of the Impact of Overseas and Domestic Treatment and Screening Options for Intestinal Helminth Infection among US-Bound Refugees from Asia.

BACKGROUND: Many U.S.-bound refugees travel from countries where intestinal parasites (hookworm, Trichuris trichuria, Ascaris lumbricoides, and Strongyloides stercoralis) are endemic. These infections are rare in the United States and may be underdiagnosed or misdiagnosed, leading to potentially serious consequences. This evaluation examined the costs and benefits of combinations of overseas presumptive treatment of parasitic diseases vs. domestic screening/treating vs. no program. METHODS: An economic decision tree model terminating in Markov processes was developed to estimate the cost and health impacts of four interventions on an annual cohort of 27,700 U.S.-bound Asian refugees: 1) "No Program," 2) U.S. "Domestic Screening and Treatment," 3) "Overseas Albendazole and Ivermectin" presumptive treatment, and 4) "Overseas Albendazole and Domestic Screening for Strongyloides". Markov transition state models were used to estimate long-term effects of parasitic infections. Health outcome measures (four parasites) included outpatient cases, hospitalizations, deaths, life years, and quality-adjusted life years (QALYs). RESULTS: The "No Program" option is the least expensive ($165,923 per cohort) and least effective option (145 outpatient cases, 4.0 hospitalizations, and 0.67 deaths discounted over a 60-year period for a one-year cohort). The "Overseas Albendazole and Ivermectin" option ($418,824) is less expensive than "Domestic Screening and Treatment" ($3,832,572) or "Overseas Albendazole and Domestic Screening for Strongyloides" ($2,182,483). According to the model outcomes, the most effective treatment option is "Overseas Albendazole and Ivermectin," which reduces outpatient cases, deaths and hospitalization by around 80% at an estimated net cost of $458,718 per death averted, or $2,219/$24,036 per QALY/life year gained relative to "No Program". DISCUSSION: Overseas presumptive treatment for U.S.-bound refugees is a cost-effective intervention that is less expensive and at least as effective as domestic screening and treatment programs. The addition of ivermectin to albendazole reduces the prevalence of chronic strongyloidiasis and the probability of rare, but potentially fatal, disseminated strongyloidiasis.

Health Profiles of Newly Arrived Refugee Children in the United States, 2006-2012.

OBJECTIVES: We conducted a large-scale study of newly arrived refugee children in the United States with data from 2006 to 2012 domestic medical examinations in 4 sites: Colorado; Minnesota; Philadelphia, Pennsylvania; and Washington State. METHODS: Blood lead level, anemia, hepatitis B virus (HBV) infection, tuberculosis infection or disease, and Strongyloides seropositivity data were available for 8148 refugee children (aged < 19 years) from Bhutan, Burma, Democratic Republic of Congo, Ethiopia, Iraq, and Somalia. RESULTS: We identified distinct health profiles for each country of origin, as well as for Burmese children who arrived in the United States from Thailand compared with Burmese children who arrived from Malaysia. Hepatitis B was more prevalent among male children than female children and among children aged 5 years and older. The odds of HBV, tuberculosis, and Strongyloides decreased over the study period. CONCLUSIONS: Medical screening remains an important part of health care for newly arrived refugee children in the United States, and disease risk varies by population.

Seroprevalence of antibodies against Taenia solium cysticerci among refugees resettled in United States.

Neurocysticercosis (NCC) is a disease caused by central nervous system infection by the larval stage of the pork tapeworm, Taenia solium. In developing countries, NCC is a leading cause of adult-onset epilepsy. Case reports of NCC are increasing among refugees resettled to the United States and other nations, but the underlying prevalence among refugee groups is unknown. We tested stored serum samples from the Centers for Disease Control and Prevention Migrant Serum Bank for antibodies against T. solium cysts by using the enzyme-linked immunoelectrotransfer blot. Seroprevalence was high among all 4 populations tested: refugees from Burma (23.2%), Lao People's Democratic Republic (18.3%), Bhutan (22.8%), and Burundi (25.8%). Clinicians caring for refugee populations should suspect NCC in patients with seizure, chronic headache, or unexplained neurologic manifestations. Improved understanding of the prevalence of epilepsy and other associated diseases among refugees could guide recommendations for their evaluation and treatment before, during, and after resettlement.

Initial refugee health assessments. New recommendations for Minnesota.

Historically, the purpose of medical screening of new refugees has been to identify acute conditions such as infections that can be effectively addressed with short-term therapy. More recently, screening of refugees who are new to Minnesota has included identifying conditions that require ongoing care. But regular screening for chronic conditions only makes sense when follow-up care can be provided. To address this issue, the Minnesota Department of Health's Refugee Health Program, in conjunction with outside experts, reviewed its guidelines for medical screening of new refugees and revised its recommendations. In addition to recommending screening for infections and other acute conditions, the new guidelines call for screening for chronic conditions and repeat testing for diseases or conditions of long latency. The guidelines take into account the ability of the screening clinic to provide ongoing care or assure the patient's transition to primary care.

Maltreatment of Strongyloides infection: case series and worldwide physicians-in-training survey.

BACKGROUND: Strongyloidiasis infects hundreds of millions of people worldwide and is an important cause of mortality from intestinal helminth infection in developed countries. The persistence of infection, increasing international travel, lack of familiarity by health care providers, and potential for iatrogenic hyperinfection all make strongyloidiasis an important emerging infection. METHODS: Two studies were performed. A retrospective chart review of Strongyloides stercoralis cases identified through microbiology laboratory records from 1993-2002 was conducted. Subsequently, 363 resident physicians in 15 training programs worldwide were queried with a case scenario of strongyloidiasis, presenting an immigrant with wheezing and eosinophilia. The evaluation focused on resident recognition and diagnostic recommendations. RESULTS: In 151 strongyloidiasis cases, stool ova and parasite sensitivity is poor (51%), and eosinophilia (>5% or >400 cells/microL) commonly present (84%). Diagnosis averaged 56 months (intra-quartile range: 4-72 months) after immigration. Presenting complaints were nonspecific, although 10% presented with wheezing. Hyperinfection occurred in 5 patients prescribed corticosteroids, with 2 deaths. Treatment errors occurred more often among providers unfamiliar with immigrant health (relative risk of error: 8.4; 95% confidence interval, 3.4-21.0; P <.001). When presented with a hypothetical case scenario, US physicians-in-training had poor recognition (9%) of the need for parasite screening and frequently advocated empiric corticosteroids (23%). International trainees had superior recognition at 56% (P <.001). Among US trainees, 41% were unable to choose any parasite causing pulmonary symptoms. CONCLUSIONS: Strongyloidiasis is present in US patients. Diagnostic consideration should occur with appropriate exposure, nonspecific symptoms including wheezing, or eosinophilia (>5% relative or >400 eosinophils/microL). US residents' helminth knowledge is limited and places immigrants in iatrogenic danger. Information about Strongyloides should be included in US training and continuing medical education programs.

Evaluation of malaria screening in newly arrived refugees to the United States by microscopy and rapid antigen capture enzyme assay.

Before an empiric malaria treatment program, >60% of Liberian refugees had malaria on arrival to Minnesota. We compared microscopy with rapid antigen testing for detecting asymptomatic parasitemia. Nine of 103 (8.7%) had malaria by polymerase chain reaction (blood smear and rapid testing had a sensitivity of 22%). The empiric treatment program has decreased the rate of imported asymptomatic malaria. Blood film and rapid antigen testing are poor screening tests.

Biliary liver flukes (Opisthorchiasis and Clonorchiasis) in immigrants in the United States: often subtle and diagnosed years after arrival.

BACKGROUND: Biliary liver flukes are extremely common parasites in some regions of the world where consumption of raw fresh-water fish is a cultural practice. Clonorchis sinensis and Opisthorchis spp. are the major biliary liver flukes associated with human disease. Some of these parasites are highly associated with cholangiocarcinoma. It was noted that several cases presenting at our center had been in the US for prolonged periods. This prompted us to retrospectively review cases of liver fluke infection diagnosed at our facility. METHODS: All cases of biliary liver fluke infection over a 6-year period were retrospectively investigated at a clinic serving international patients, to determine the prevalence and risk factors for infection in a nonendemic area. Cases were identified through review of stool ova and parasite (O&P) records maintained at Regions Hospital/HealthPartners microbiology laboratory. All O&P samples positive for Opisthorchis spp. or Clonorchis sinensis were included in the review. RESULTS: Seventeen cases were identified during the study period. Our center performed approximately 1,800 stool O&P examinations per year on approximately 1,100 individuals per year during the study period. Biliary liver flukes were uncommon, accounting for 1.3% of individuals infected with organisms considered to be potentially pathogenic. Infections were predominantly found in migrants from Laos, Cambodia and Thailand. Cases were also identified in migrants from the former Soviet Union and South America. It is of note that 25% of patients were detected after 5 years of residence in the US. Often, the only clinical clue to infection was a mild absolute eosinophilia (500 to 1000 microL). CONCLUSIONS: Although biliary liver fluke is an infrequent cause of infection in immigrants to the US, because of the potential long-term consequences of chronic infection, educational information highlighting routes of infection and the fact that asymptomatic infection is common and may eventually lead to cancer should be aimed at high-risk community members and those who have been visiting friends and relatives in endemic areas.

Screening of international immigrants, refugees, and adoptees.

Frequently clinicians are faced with screening and providing preventive care to immigrants, refugees, and international adoptees. Evidence-based medicine on which to base screening protocols for these populations is lacking. It is important to review all health and vaccination records of the patient. In addition to acute symptoms, one should inquire about the symptoms of diseases prevalent in the country of origin or transit (e.g., hematuria). Many unexpected pathologic conditions may be detected by a thorough physical examination. If a reliable immunization record is presented, one need not repeat the vaccines or check titers. Remaining vaccines should be administered according to ACIP guidelines, except for certain populations (e.g., adoptees). Routine laboratory screening tests should include CBC with differential, stool for ova and parasites, urinalysis, general chemistry profile, serology for hepatitis B, and tests for HIV and syphilis. A tuberculin skin test should be performed on all immigrants, and a chest radiograph should be obtained for any patient with symptoms or a positive PPD. Lead level, hepatitis C, and TSH should be obtained for all children and most adoptees. In addition, special screening tests (e.g., for malaria, hepatitis C, and STIs) may be indicated in high-risk populations. A more organized screening system that emphasizes evidence-based and population-specific screening protocols and better communication between international, federal, state, and local levels is needed in the United States.