Economic impact of malaria-related hospitalizations in the United States, 2000-2014.

BACKGROUND: Despite its elimination in the early 1950s, about 1700 cases of malaria are reported in the US every year. Few studies have quantified the direct and indirect costs of imported malaria in the US. METHODS: Disparities in the mean and total hospital days, hospital charges, and hospital costs for malaria-related hospitalizations in the US by demographic, clinical, species, financial, geographic, and institutional characteristics were examined using the 2000-2014 Nationwide Inpatient Sample (NIS). Trends and potential predictors for length of stay and hospital charges and costs were identified using negative binomial regression and linear regression, respectively. RESULTS: From 2000 to 2014, 22,029 malaria cases resulted in 95,948 hospital days for malaria-related hospitalizations, $176,391,466 in total hospital costs, and $555,435,849 in total charges. Mean charges increased significantly over the study period. Males, Blacks, and patients aged 25-44years accounted for the highest direct and indirect costs. Older age and having severe malaria was associated with a longer length of stay. Older age, severe malaria, HIV infection, and longer lengths of stay were associated with higher charges and costs. CONCLUSIONS: Malaria resulted in substantial direct and indirect costs in the US. Primary and secondary prevention measures should be prioritized among high-risk groups to reduce the economic burden.

Risk factors for severe malaria among hospitalized patients in the United States, 2000-2014.

BACKGROUND: Factors associated with the development of severe malaria have not been well described for cases occurring in the United States (US). METHODS: Severe malaria hospitalizations data from the 2000-2014 Nationwide Inpatient Sample were analyzed. Frequencies were reported by demographic, clinical, species, financial, geographic, and institutional characteristics, and trends and disparities were identified. Logistic regression models were used to identify potential predictors for severe disease among those with malaria. RESULTS: From 2000 to 2014, there were an estimated 4823 severe malaria cases, representing 21.9% of all malaria-related hospitalizations, including 182 severe malaria deaths. Severe malaria was most common among inpatients who were male, Black, aged 45-64 years, and hospitalized in the South Atlantic division of the US. Older age was associated with higher odds of severe malaria, cerebral malaria, ARDS, severe anemia, and renal failure. Males had higher odds of developing renal failure and jaundice, while females had higher odds of developing severe anemia. HIV infection was associated with increased odds of severe malaria, severe anemia, and renal failure. CONCLUSION: Primary and secondary prevention measures, such as pre-travel consultations, chemoprophylaxis, and early diagnosis and treatment, should be emphasized and improved among high-risk prospective travelers to malaria endemic countries.

Malaria-Related Hospitalizations in the United States, 2000-2014.

Few data are available on the burden of malaria hospitalization in the United States. Study of malaria using hospital-based data can better define the impact of malaria and help inform prevention efforts. U.S. malaria cases identified from hospitalization discharge records in the 2000-2014 Nationwide Inpatient Sample were examined. Frequencies and population rates were reported by demographics, infecting species, clinical, financial, institutional, geographic, and seasonal characteristics, and disparities were identified. Time trends in malaria cases were assessed using negative binomial regression. From 2000 to 2014, there were an estimated 22,029 malaria-related hospitalizations (4.88 per 1 million population) in the United States, including 182 in-hospital deaths and 4,823 severe malaria cases. The rate of malaria-related hospitalizations did not change significantly over the study period. The largest number of malaria-related hospitalizations occurred in August. Malaria-related hospitalizations occurred disproportionately among patients who were male, black, or 25-44 years of age. Plasmodium falciparum accounted for the majority of malaria-related hospitalizations. On average, malaria patients were hospitalized for 4.36 days with charges of $25,789. Patients with a malaria diagnosis were more often hospitalized in the Middle Atlantic and South Atlantic census divisions, urban teaching, private not-for-profit, and large-bed-size hospitals. Malaria imposes a substantial disease burden in the United States. Enhanced primary and secondary prevention measures, including strategies to increase the use of pretravel consultations and prompt diagnosis and treatment are needed.

Melanoma-related mortality and productivity losses in the USA, 1990-2008.

Melanoma remains among the deadliest cancers in the USA, ranking presently as the leading cause of death from skin disease in this country. The present analysis presents national statistics on the health burden (mortality) and productivity losses attributable to this cancer over a 19-year period. Melanoma-related deaths and mortality rates from 1990 through 2008 were identified and calculated using multiple-cause-of-death data and data from the 2000 US Census. Productivity losses were estimated using previously published methods that accounted for life expectancy, labor force participation, productivity growth, and the imputed values of caregiving and housekeeping activities. A total of 155,571 melanoma-related deaths occurred during 1990-2008, resulting in 1,811,701 years of potential life lost. Age-adjusted mortality rates stratified by sex and race/ethnicity revealed differences: whites had the highest rate (3.55 per 100 000 population; 95% confidence interval 3.54, 3.57) and male individuals were 2.21 times more likely than female individuals to succumb to the disease. Cumulatively, the numbers of death for blacks, Hispanics, Asian/Pacific Islanders, and American Indians/Alaskan Natives exceeded 6000 deaths. The total productivity losses attributable to melanoma-related mortality during the sampled period were ∼$66.9 billion. The burden and economic consequences of melanoma-related deaths in the USA are not inconsequential. Understanding the mortality trends and productivity losses attributed to this skin cancer is important for evaluating the feasibility and trade-offs of public health and behavioral counseling interventions that focus on promoting skin cancer prevention.

Human echinococcosis mortality in the United States, 1990-2007.

BACKGROUND: Despite the endemic nature of Echinococcus granulosus and Echinococcus multilocularis infection in regions of the United States (US), there is a lack of data on echinococcosis-related mortality. To measure echinococcosis-associated mortality in the US and assess possible racial/ethnic disparities, we reviewed national-death certificate data for an 18-year period. METHODOLOGY/PRINCIPAL FINDINGS: Echinococcosis-associated deaths from 1990 through 2007 were identified from multiple-cause-coded death records and were combined with US census data to calculate mortality rates. A total of 41 echinococcosis-associated deaths occurred over the 18-year study period. Mortality rates were highest in males, Native Americans, Asians/Pacific Islanders, Hispanics and persons 75 years of age and older. Almost a quarter of fatal echinococcosis-related cases occurred in residents of California. Foreign-born persons accounted for the majority of echinococcosis-related deaths; however, both of the fatalities in Native Americans and almost half of the deaths in whites were among US-born individuals. CONCLUSIONS/SIGNIFICANCE: Although uncommon, echinococcosis-related deaths occur in the US. Clinicians should be aware of the diagnosis, particularly in foreign-born patients from Echinococcus endemic areas, and should consider tropical infectious disease consultation early.

Congenital cytomegalovirus mortality in the United States, 1990-2006.

BACKGROUND: Congenital cytomegalovirus (CMV) infection is the most common intrauterine infection in the United States disproportionately affecting minority races and those of lower socio-economic class. Despite its importance there is little information on the burden of congenital CMV-related mortality in the US. To measure congenital CMV-associated mortality in the US and assess possible racial/ethnic disparities, we reviewed national death certificate data for a 17-year period. METHODS: Congenital CMV-associated deaths from 1990 through 2006 were identified from multiple-cause-coded death records and were combined with US census data to calculate mortality rates. RESULTS: A total of 777 congenital CMV-associated deaths occurred over the 17-year study period resulting in 56,355 years of age-adjusted years of potential life lost. 71.7% (557) of congenital CMV-associated deaths occurred in infants (age less than 1 year). Age-adjusted mortality rates stratified by race/ethnicity revealed mortality disparities. Age-adjusted rate ratios were calculated for each racial/ethnic group using whites as the reference. Native Americans and African Americans were 2.34 (95% CI, 2.11-2.59) and 1.89 (95% CI, 1.70-2.11) times respectively, more likely to die from congenital CMV than whites. Asians and Hispanics were 0.54 (95% CI, 0.44-0.66) and 0.96 (95% CI, 0.83-1.10) times respectively, less likely to die from congenital CMV than whites. CONCLUSIONS/SIGNIFICANCE: Congenital CMV infection causes appreciable mortality in the US exacting a particular burden among African Americans and Native Americans. Enhanced surveillance and increased screening are necessary to better understand the epidemiology of congenital CMV infection in addition to acceleration of vaccine development efforts.

A heterotrimeric death domain complex in Toll signaling.

Signaling from the transmembrane receptor Toll to Rel-related transcription factors regulates dorsoventral patterning of the Drosophila embryo, as well as larval and adult immunity. To identify additional pathway components, we have used double-stranded RNA interference to investigate Drosophila counterparts of genes that regulate the mammalian Rel family member NF-kappaB. Experiments in cultured cells reveal that the fly orthologue of the adaptor protein MyD88 is essential for signal transduction from Toll to a second adaptor protein, Tube. By using coimmunoprecipitation studies, we find a heterotrimeric association of the death domains of MyD88, Tube, and the protein kinase Pelle. Site-directed mutational analyses of interaction sites defined by crystallographic studies demonstrate that Tube recruits MyD88 and Pelle into the heterotrimer by two distinct binding surfaces on the Tube death domain. Furthermore, functional assays confirm that the formation of this heterotrimer is critical for signal transduction by the Toll pathway.