Food and Drug Administration Approval of Artesunate for Severe Malaria: Enough to Achieve Best Practice?

Intravenous artesunate has been the global standard of care for severe malaria for over 2 decades. Yet, until recently, artesunate has only been available to patients through an expanded-access protocol from the Centers for Disease Control and Prevention. In May 2020, the Food and Drug Administration approved artesunate, allowing US hospitals to stock the drug and ensuring prompt treatment for this life-threatening infection. However, because of artesunate's high cost and the infrequency of severe malaria in the United States, hospitals may be reluctant to stock the drug. As US health systems weigh the decision to stock artesunate, we propose a hospital tier framework to inform this decision and support clinicians caring for patients who present with severe malaria.

Transplantation and immigration: Comparing infectious complications and outcomes between foreign-born and US-born kidney transplant recipients in Minnesota.

BACKGROUND: Foreign-born kidney transplant recipients (FBKTRs) are at increased risk for reactivation of latent infections that may impact outcomes. We aimed to compare the etiology of infections and outcomes between FBKTR and United States KTRs (USKTR). METHODS: We performed a retrospective study of patients who underwent kidney transplantation between January 1, 2014 and December 31, 2018 at two transplant centers in Minnesota. Frequency and etiology of infections as well as outcomes (graft function, rejection, and patient survival) at 1-year post-transplant between FBKTR and USKTR were compared. RESULTS: Of the 573 transplant recipients, 124 (21.6%) were foreign-born and 449 (78.4%) US-born. At least one infection occurred in 411 (71.7%) patients (38.2% bacterial, 55% viral, 9.4% fungal). Viral infections were more frequent in FBKTR, particularly BK viremia (38.7% vs. 21.2%, p < .001). No statistical differences were found for bacterial or fungal infections; no parasitic infections were identified in either group. No geographically-restricted infections were noted aside from a single case of Madura foot in a FBKTR. Rejection episodes were more common in USKTR (p = .037), but stable/improving graft function (p = .976) and mortality (p = .451) at 1-year posttransplantation were similar in both groups. After adjusting for covariates, previous transplantation was associated with a higher number of infections (IRR 1.35, 95% confidence intervals 1.05-1.73, p = .020). CONCLUSION: Although viral infections were more frequent in FBKTR, overall frequency and etiology of most infections and outcomes were similar between FBKTR and USKTR suggesting that comprehensive transplant care is providing timely prevention, diagnosis, and treatment of latent infections in FBKTR.

Ancylostoma ceylanicum Hookworm in Myanmar Refugees, Thailand, 2012-2015.

During 2012-2015, US-bound refugees living in Myanmar-Thailand border camps (n = 1,839) were surveyed for hookworm infection and treatment response by using quantitative PCR. Samples were collected at 3 time points: after each of 2 treatments with albendazole and after resettlement in the United States. Baseline prevalence of Necator americanus hookworm was 25.4%, Ancylostoma duodenale 0%, and Ancylostoma ceylanicum (a zoonosis) 5.4%. Compared with N. americanus prevalence, A. ceylanicum hookworm prevalence peaked in younger age groups, and blood eosinophil concentrations during A. ceylanicum infection were higher than those for N. americanus infection. Female sex was associated with a lower risk for either hookworm infection. Cure rates after 1 dose of albendazole were greater for A. ceylanicum (93.3%) than N. americanus (65.9%) hookworm (p<0.001). Lower N. americanus hookworm cure rates were unrelated to ß-tubulin single-nucleotide polymorphisms at codons 200 or 167. A. ceylanicum hookworm infection might be more common in humans than previously recognized.

Trends in Pricing and Generic Competition Within the Oral Antibiotic Drug Market in the United States.

BACKGROUND: In recent years, the price of many older generic drugs, including numerous antibiotics, has increased substantially. We sought to analyze recent price changes and extent of generic competition within a cohort of commonly prescribed off-patent oral antibiotics. METHODS: We extracted oral antibiotics recommended for common outpatient conditions in the Infectious Diseases Society of America Practice Guidelines. We determined all US Food and Drug Administration-approved manufacturers for each formulation and strength in 2013 and 2016 and the yearly national average drug acquisition cost (NADAC) price between 2013 and 2016. Wilcoxon signed rank test was used to compare changes in drug prices and number of manufacturers from 2013 to 2016. Spearman correlation coefficient was used to assess the association between drug prices and number of manufacturers. RESULTS: Twenty-two antibiotics (81 formulations and strengths) were analyzed. There was no change in the median NADAC price or the number of manufacturers between 2013 and 2016. However, 11 (14%) formulations increased in price by 90% or more, and 13 (16%) had 2 or fewer manufacturers during all 4 years. Antibiotic prices were negatively associated with the number of available manufacturers. CONCLUSIONS: While prices and the number of manufacturers for common oral antibiotics were overall stable between 2013 and 2016, reduced manufacturer competition was associated with increased prices. A subset of antibiotics exhibited substantial price increases, and most, but not all, had limited manufacturer competition. Policy solutions are needed to ensure availability of low-cost, essential generic antibiotics.

Incentives for Bushmeat Consumption and Importation among West African Immigrants, Minnesota, USA.

The knowledge, attitudes, and practices surrounding bushmeat consumption and importation in the United States are not well described. Focus groups of West African persons living in Minnesota, USA, found that perceived risks are low and unlikely to deter consumers. Incentives for importation and consumption were multifactorial in this community.

High-cost generic drugs--implications for patients and policymakers.

Some older generic drugs have become very expensive, owing to factors including drug shortages, supply disruptions, and consolidations in the generic-drug industry. But generics manufacturers that legally obtain a market monopoly can also unilaterally raise prices.

Increasing Hepatitis B Vaccine Prevalence Among Refugee Children Arriving in the United States, 2006-2012.

OBJECTIVES: To determine whether the addition of hepatitis B virus (HBV) vaccine to national immunization programs improved vaccination rates among refugee children, a marginalized population with limited access to care. METHODS: The sample included 2291 refugees younger than 19 years who completed HBV screening after arrival in the United States. Children were categorized by having been born before or after the addition of the 3-dose HBV vaccine to their birth country's national immunization program. The outcome was serological evidence of immunization. RESULTS: The odds of serological evidence of HBV immunization were higher for children born after the addition of HBV vaccine to their birth country's national immunization program (adjusted odds ratio = 2.54; 95% confidence interval = 2.04, 3.15). CONCLUSIONS: National HBV vaccination programs have contributed to the increase in HBV vaccination coverage observed among US-bound refugee children. PUBLIC HEALTH IMPLICATIONS: Ongoing public health surveillance is needed to ensure that vaccine rates are sustained among diverse, conflict-affected, displaced populations.

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.

Albendazole therapy and enteric parasites in United States-bound refugees.

BACKGROUND: Beginning on May 1, 1999, the Centers for Disease Control and Prevention (CDC) recommended presumptive treatment of refugees for intestinal parasites with a single dose of albendazole (600 mg), administered overseas before departure for the United States. METHODS: We conducted a retrospective cohort study involving 26,956 African and Southeast Asian refugees who were screened by means of microscopical examination of stool specimens for intestinal parasites on resettlement in Minnesota between 1993 and 2007. Adjusted prevalence ratios for intestinal nematodes, schistosoma species, giardia, and entamoeba were calculated among refugees who migrated before versus those who migrated after the CDC recommendation of presumptive predeparture albendazole treatment. RESULTS: Among 4370 untreated refugees, 20.8% had at least one stool nematode, most commonly hookworm (in 9.2%). Among 22,586 albendazole-treated refugees, only 4.7% had one or more nematodes, most commonly trichuris (in 3.9%). After adjustment for sex, age, and region, albendazole-treated refugees were less likely than untreated refugees to have any nematodes (prevalence ratio, 0.19), ascaris (prevalence ratio, 0.06), hookworm (prevalence ratio, 0.07), or trichuris (prevalence ratio, 0.27) but were not less likely to have giardia or entamoeba. Schistosoma ova were identified exclusively among African refugees and were less prevalent among those treated with albendazole (prevalence ratio, 0.60). After implementation of the albendazole protocol, the most common pathogens among 17,011 African refugees were giardia (in 5.7%), trichuris (in 5.0%), and schistosoma (in 1.8%); among 5575 Southeast Asian refugees, only giardia remained highly prevalent (present in 17.2%). No serious adverse events associated with albendazole use were reported. CONCLUSIONS: Presumptive albendazole therapy administered overseas before departure for the United States was associated with a decrease in the prevalence of intestinal nematodes among newly arrived African and Southeast Asian refugees.

Travel-associated disease among US residents visiting US GeoSentinel clinics after return from international travel.

BACKGROUND: US residents make 60 million international trips annually. Family practice providers need to be aware of travel-associated diseases affecting this growing mobile population. OBJECTIVE: To describe demographics, travel characteristics and clinical diagnoses of US residents who present ill after international travel. METHODS: Descriptive analysis of travel-associated morbidity and mortality among US travellers seeking care at 1 of the 22 US practices and clinics participating in the GeoSentinel Global Surveillance Network from January 2000 to December 2012. RESULTS: Of the 9624 ill US travellers included in the analysis, 3656 (38%) were tourist travellers, 2379 (25%) missionary/volunteer/research/aid workers (MVRA), 1580 (16%) travellers visiting friends and relatives (VFRs), 1394 (15%) business travellers and 593 (6%) student travellers. Median (interquartile range) travel duration was 20 days (10-60 days). Pre-travel advice was sought by 45%. Hospitalization was required by 7%. Compared with other groups of travellers, ill MVRA travellers returned from longer trips (median duration 61 days), while VFR travellers disproportionately required higher rates of inpatient care (24%) and less frequently had received pre-travel medical advice (20%). Illnesses of the gastrointestinal tract were the most common (58%), followed by systemic febrile illnesses (18%) and dermatologic disorders (17%). Three deaths were reported. Diagnoses varied according to the purpose of travel and region of exposure. CONCLUSIONS: Returning ill US international travellers present with a broad spectrum of travel-associated diseases. Destination and reason for travel may help primary health care providers to generate an accurate differential diagnosis for the most common disorders and for those that may be life-threatening.

Costs of malaria treatment in the United States.

We estimated inpatient and outpatient payments for malaria treatment in the USA. The mean cost per hospitalized patient was significantly higher than for non-hospitalized patients (e.g. $27 642 vs $1177 among patients with private insurance). Patients with severe malaria payed two to four times more than those hospitalized with uncomplicated malaria.

Cost-effectiveness of treatment strategies for populations from strongyloidiasis high-risk areas globally who will initiate corticosteroid treatment in the United States.

BACKGROUND: The risk of developing strongyloidiasis hyperinfection syndrome appears to be elevated among individuals who initiate corticosteroid treatment. Presumptive treatment or treatment after screening for populations from Strongyloides stercoralis-endemic areas has been suggested before initiating corticosteroids. However, potential clinical and economic impacts of preventative strategies have not been evaluated. METHODS: Using a decision tree model for a hypothetical cohort of 1000 individuals from S. stercoralis-endemic areas globally initiating corticosteroid treatment, we evaluated clinical and economic impacts of two interventions, 'Screen and Treat' (i.e. screening and ivermectin treatment after a positive test), and 'Presumptively Treat,' compared to current practice (i.e. 'No Intervention'). We evaluated the cost-effectiveness (net cost per death averted) of each strategy using broad ranges of pre-intervention prevalence and hospitalization rates for chronic strongyloidiasis patients initiating corticosteroid treatment. RESULTS: For the baseline parameter estimates, 'Presumptively Treat' was cost-effective (i.e. clinically superior with cost per death averted less than a threshold of $10.6 million per life) compared to 'No Intervention' ($532 000 per death averted) or 'Screen and Treat' ($39 000 per death averted). The two parameters contributing the most uncertainty to the analysis were the hospitalization rate for individuals with chronic strongyloidiasis who initiate corticosteroids (baseline 0.166%) and prevalence of chronic strongyloidiasis (baseline 17.3%) according to a series of one-way sensitivity analyses. For hospitalization rates greater than 0.022%, 'Presumptively Treat' would remain cost-effective. Similarly, 'Presumptively Treat' remained preferred at prevalence rates of 4% or above; 'Screen and Treat' was preferred for prevalence between 2% and 4%, and 'No Intervention' was preferred for prevalence less than 2%. CONCLUSIONS: The findings support decision-making for interventions for populations from S. stercoralis endemic areas before initiating corticosteroid treatment. Although some input parameters are highly uncertain and prevalence varies across endemic countries, 'Presumptively Treat' would likely be preferred across a range for many populations given plausible parameters.

Understanding COVID-19 Health Disparities With Birth Country and Language Data.

INTRODUCTION: Understanding of COVID-19-related disparities in the U.S. is largely informed by traditional race/ethnicity categories that mask important social group differences. This analysis utilizes granular information on patients' country of birth and preferred language from a large health system to provide more nuanced insights into health disparities. METHODS: Data from patients seeking care from a large Midwestern health system between January 1, 2019 and July 31, 2021 and COVID-19-related events occurring from March 18, 2020 to July 31, 2021 were used to describe COVID-19 disparities. Statistics were performed between January 1, 2022 and March 15, 2023. Age-adjusted generalized linear models estimated RR across race/ethnicity, country of birth grouping, preferred language, and multiple stratified groups. RESULTS: The majority of the 1,114,895 patients were born in western advanced economies (58.6%). Those who were Hispanic/Latino, were born in Latin America and the Caribbean, and preferred Spanish language had highest RRs of infection and hospitalization. Black-identifying patients born in sub-Saharan African countries had a higher risk of infection than their western advanced economies counterparts. Subanalyses revealed elevated hospitalization and death risk for White-identifying patients from Eastern Europe and Central Asia and Asian-identifying patients from Southeast Asia and the Pacific. All non-English languages had a higher risk of all COVID-19 outcomes, most notably Hmong and languages from Burma/Myanmar. CONCLUSIONS: Stratifications by country of birth grouping and preferred language identified culturally distinct groups whose vulnerability to COVID-19 would have otherwise been masked by traditional racial/ethnic labels. Routine collection of these data is critical for identifying social groups at high risk and for informing linguistically and culturally relevant interventions.

Use of Point-of-Care Handheld Ultrasound for Splenomegaly in United States-Bound Refugees: A Novel Technology with Far-Reaching Implications.

Ultrasound (US) is an invaluable clinical tool. New point-of-care US technology holds great promise for hard-to-reach and mobile populations such as refugees. The implementation of US in unique and challenging settings has been hindered by cost, fragility of equipment, need for uninterrupted electricity, training, and difficulty in sharing data/image files impeding quality assurance. The recent development of more flexible, durable, high-quality, low-cost, handheld US technology has offered increased potential to address many of these barriers. We describe a pilot program using a new point-of-care US technology to identify and monitor splenomegaly in United States-bound Congolese refugees. This experience and model may hold lessons for planning and development of similar approaches in other hard-to-reach mobile populations.

Innovative Approaches to Improve COVID-19 Case Investigation and Contact Tracing Among Refugees, Immigrants, and Migrants: Lessons Learned from a Newly Established National Resource Center.

Effective COVID-19 case investigation and contact tracing (CICT) among refugee, immigrant, and migrant (RIM) communities requires innovative approaches to address linguistic, cultural and community specific preferences. The National Resource Center for Refugees, Immigrants, and Migrants (NRC-RIM) is a CDC-funded initiative to support state and local health departments with COVID-19 response among RIM communities, including CICT. This note from the field will describe NRC-RIM and initial outcomes and lessons learned, including the use of human-centered design to develop health messaging around COVID-19 CICT; training developed for case investigators, contact tracers, and other public health professionals working with RIM community members; and promising practices and other resources related to COVID-19 CICT among RIM communities that have been implemented by health departments, health systems, or community-based organizations.

Evaluation of Preferred Language and Timing of COVID-19 Vaccine Uptake and Disease Outcomes.

Importance: Beyond traditional race and ethnicity demographic characteristics, additional discrete data variables are needed for informed health interventions in the US. Objective: To examine whether COVID-19 vaccine uptake patterns and associated disease outcomes differ among language preference groups. Design, Setting, and Participants: A cohort study of 851 410 individuals aged 18 years or older in a large multispecialty health system in Minnesota and western Wisconsin was conducted between December 15, 2020, and March 31, 2022. Exposure: Self-identified language preference and limited English proficiency (LEP) as measured by interpreter need were used to create subgroups using US census categories and attention to capture languages known to represent refugee groups. Main Outcomes and Measures: The primary outcome was COVID-19 vaccination uptake rates and time to first vaccine. Secondary outcomes were rates of COVID-19-associated hospitalization and death. Results: Most of the 851 410 participants (women, 493 910 [58.0%]; median age, 29 [IQR, 35-64] years) were US-born English speakers; 7.5% were born in other countries, 4.0% had a language preference other than English (LPOE), and 3.0% indicated LEP as measured by interpreter need. Marked temporal clusters were observed for COVID-19 vaccination uptake, hospitalizations, and deaths associated with primary series vaccine eligibility, booster availability, and COVID-19 variants. Delayed first-dose vaccine was observed with LPOE (hazard ratio [HR], 0.83; 95% CI, 0.82-0.84) and interpreter need (HR, 0.81; 95% CI, 0.80-0.82) compared with those with English language preference and proficiency. Patients with LPOE were approximately twice as likely to be hospitalized (rate ratio [RR], 1.85; 95% CI, 1.63-2.08) or die (RR, 2.13; 95% CI, 1.65-2.69). Patients with LEP experienced even higher rates of hospitalization (RR, 1.98; 95% CI, 1.73-2.25) and COVID-19-associated death (RR, 2.32; 95% CI, 1.79-2.95). Outcomes varied for individual language preference groups. Conclusions and Relevance: In this study, delayed time to first-dose vaccine was associated with increased COVID-19 hospitalization and death rates for specific LPOE and LEP groups. The findings suggest that data collection of language preference and interpreter need provides actionable health intervention information. Standardized system-level data collection, including at a national level, may improve efficient identification of social groups with disproportionate health disparities and provide key information on improving health equity in the US.