Trends and Risk Factors for Leishmaniasis among Reproductive Aged Women in the United States

1. Introduction

Leishmaniasis, classified as a neglected tropical disease (NTD) by the World Health Organization (WHO), is estimated to affect between 700,000 and 1 million people worldwide per year.1 Caused by infection with a protozoan parasite of the Leishmania species and transmitted via the bite of an infected female phlebotomine sandfly; leishmaniasis is typically categorized into three main clinical subtypes: (1) visceral, (2) cutaneous and (3) mucocutaneous.1 Globally, leishmaniasis is commonly found in parts of the tropics and subtropics of Asia, the Middle East, southern Europe, Mexico, Central America and South America.2 The disease tends to be more widespread among those living in poverty-stricken areas where malnutrition, poor housing and inadequate sanitation are pervasive; leishmaniasis has also been found to be associated with population displacement, urbanization, environmental changes and compromised immunity.3,4

Generally regarded as a disease of travelers in the United States (US), epidemiological data on leishmaniasis in humans within US is limited.2 According to the Centers for Disease Control and Prevention (CDC), the occurrence of leishmaniasis in the US is rare, with most cases occurring among immigrants, military personnel and travelers returning from leishmaniasis endemic areas.2 In recent years, a few studies have reported leishmaniasis as endemic to the US due to autochthonous infections, with the majority of cases reported in the state of Texas.5,6 Factors such as immigration, socioeconomic and environmental conditions, ease of travel, and the proximity of Texas to the southern US border (which is shared with Mexico) are suspected to be associated with the cases observed.6,7 Data from these studies suggest that leishmaniasis may be acquired more frequently in the US than previously suspected and is likely under-reported due to a lack of awareness and unmandated reporting at the state and federal levels.5 Therefore, gaining a better understanding of the disease patterns and risk factors for leishmaniasis in the US may help increase awareness among public health officials and health care providers.

Cutaneous leishmaniasis, the most common form affecting humans, typically causes skin lesions on exposed areas of the body and may result in life-long scars, disability or stigma.1 The majority of US cases identified have been cutaneous2 and recent data suggest that approximately 68% of US endemic cases of cutaneous leishmaniasis occurred among women.5 Females of any age can acquire the disease; however, leishmaniasis infection during pregnancy (particularly visceral), has been shown to be debilitating and associated with congenital transmission and fetal death.8-11 There is also concern that pregnant women may be more susceptible to infection due to the changes in cellular immunity that occur during pregnancy.10 Given that epidemiological data is limited in this area, we sought to add to the literature on national rates of leishmaniasis in the US. Thus, the aim of this study was to examine trends and risk factors associated with a leishmaniasis diagnosis among women of reproductive age in the US.

2. Methods

For this cross-sectional, population-based study, we utilized data collected by the Agency for Healthcare Research and Quality’s (AHRQ) Nationwide Inpatient Sample (NIS), a component of the Healthcare Cost and Utilization Project (HCUP).12 NIS is a publicly available healthcare database containing information regarding inpatient hospitalizations throughout the US. It contains a 20% systematic random sample of discharges from all HCUP-participating US community hospitals, excluding long-term acute care and rehabilitation hospitals.12 As of 2017, the NIS has data from more than 7 million inpatient stays each year and approximates more than 35 million hospitalizations when weighted. Clinical and non-clinical data from each hospital stay are available in the NIS, including patient sociodemographics, discharge status, expected payment source, and hospital characteristics (including size, type and location).12 The NIS database, as well as documentation and additional information are publicly available on the HCUP website13 The Institutional Review Board of Baylor College of Medicine designated this study exempt, as publicly available, de-identified data was utilized in the research.

3. Results

3.2. Trends in the Rates of Leishmaniasis

Figure 1 illustrates the trends in the rates of leishmaniasis per million hospitalizations of women of reproductive age over the 16-year study period. Peak incidences of the disease were seen in 2006, 2010, and 2016 with nadirs in 2005, 2009, and 2017. Joinpoint regression analysis demonstrated that the overall rate of leishmaniasis remained relatively stable over the study period, with no statistically significant change in average annual rates (AAPC: -0.6, 95% CI: -6.9, 6.1).

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Figure 1

Trends in the rates of leishmaniasis per million hospitalizations of women of reproductive age, United States, 2002-2017 Notes on figure legend: The X-axis represents the year of discharge and the Y-axis represents prevalence of leishmaniasis per million hospitalizations of women of reproductive age. Lines represent the trend estimated by joinpoint regression. Value represents the average annual percent change (AAPC), point estimate (95% confidence interval)

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4. Discussion

Despite the peaks and troughs in leishmaniasis rates over the 16-year period covered in our study, our findings suggest that the overall prevalence of leishmaniasis among hospitalized women of reproductive age in the US has remained relatively low. Consistent with data reported by the CDC2 and prior research,5,6,16-18 our data suggest that the greatest proportion of leishmaniasis cases were in the Southern region of the US, but also geographically prevalent across the US. Additional research, including qualitative, observational, and case studies, are needed to provide an in-depth understanding of the factors contributing to the rate trends and geographic distribution of leishmaniasis in recent decades in the US. Nevertheless, at minimum, findings from this study are in support of the argument5 for mandatory reporting at the state and federal level.

The finding that Hispanic women were twice as likely to be diagnosed with leishmaniasis compared to White women is unclear. Considering that the clinical manifestations of leishmaniasis may not occur until weeks or months after exposure,2 one potential reason for this observation may be related to the large number immigrating into the US from countries where leishmaniasis is more common. Data suggest that from 1980 to 2017, the Central American immigration population in the US grew approximately tenfold,19 and Hispanic immigrants represented the second largest racial/ethnic group arriving in recent years.20 Aside from immigration or recent travels, it is also possible that many Hispanics currently live and/or work in areas of the US where there is an increased risk for exposure due to the presence of Leishmania sandflies. Even so, additional research is needed to better elucidate the reasons for this finding.

Our data also suggest that women with Medicaid were less likely to be diagnosed with leishmaniasis. It is probable that women with Medicaid have socioeconomic constraints which inhibit or limit their ability to travel to leishmaniasis endemic areas. Another possible explanation for this finding is that Medicaid recipients in this study may have utilized preventive health services and/or outpatient medical care, which allows for earlier diagnosis and treatment of leishmaniasis, if acquired, prior to hospitalization. In contrast, we also found that women of reproductive age diagnosed with leishmaniasis were more likely to die prior to discharge, compared to those routinely discharged. One reason for this observation may be due to the severity of disease at presentation or misdiagnosis of leishmaniasis, coupled with inappropriate treatment. For example, visceral leishmaniasis can be fatal if not treated.1 Additional research is needed to further validate and better understand the factors contributing to the observed findings.

Despite its strengths—including the large sample size, use of standardized nationally-representative dataset and analysis over a 16-year period—this study has some limitations. First, the generalizability of our results may be limited. Given that individuals admitted to the hospital tend to be sicker and have more comorbid medical conditions than the general populace, our findings may not be fully representative of all women of reproductive age in the US with leishmaniasis, but rather those with access to care. Second, as a limitation of the NIS dataset, we were not able to account for other potential confounders such as educational level, travel history, social history, military status or immigrant status. Third, while we recognize that cutaneous is the more common form/subtype among humans, and that the subtypes (cutaneous, mucocutaneous and visceral leishmaniasis) have vastly different clinical presentations and consequences, we were not able to distinguish between the clinical subtypes in our analyses. Thus, given the rarity of the disease in the US, limitations of the dataset and nature of ICD-9-CM and ICD-10-CM codes, estimates from this study are representative of all leishmaniasis diagnoses among hospitalized women during this study period. Further, considering the under-detection and under-reporting of human leishmaniasis in the US, the estimates presented in this study may not reflect the true prevalence of leishmaniasis among women of reproductive age over the 16-year period.

5. Conclusion and Global Health Implications

In summary, our study underscores the need for further research about neglected tropical diseases in the US. Due to potential underreporting, it is likely that the prevalence of endemic human leishmaniasis in the US is higher than reported in this and prior research. Appropriate educational, public health and policy initiatives aimed at increasing clinical awareness and timely diagnosis/treatment of the disease may serve as a first step in improved identification and tracking of human leishmaniasis in the US.