Imported Infections in Rural Mid-West United States - A Report from a Tertiary Care Center

Abstract

Background

There is lack of specific data on imported infections in the mid-west United States (U.S.).

Methods

Retrospective data on demographic and geographic data of imported infections seen by the infectious diseases clinics and consultation service from 2001–2018 was collected.

Results

Of the 64 infections, tuberculosis(TB) was most common [20(31.3%); pulmonary(11,55%), lymphadenopathy(8,40%), gastrointestinal(4,20%), disseminated(2,10%), and 1(5%) each of genitourinary and vertebral spine infection, 4 Human immune-deficiency virus infection and 1 echinococcosis)] followed by malaria(11,17.2%). Other infections: Cysticercosis [7,10.9%], giardiasis (4,6.3%), 3 each (4.7%) Human T-lymphotrophic Virus infection and schistosomiasis, 2 each (3.1%) leprosy, strongyloidiasis, and typhoid fever, one each (1.6%) of ascariasis, brucellosis, Chagas disease, Chikungunya virus, hepatitis A virus, echinococcosis, Japanese encephalitis virus, loiasis, paratyphoid fever, Q fever, and unspecified parasitosis. Geographic origins: Africa(26,40.6%), Asia(16,25%), Central America(11,17.2%), Europe(2,3.1%), Oceania(2,3.1%), South America(2,3.1%), and Unknown(5). More cases were seen after 2015.

Conclusions

With increasing tourism, it is important to educate rural mid-west healthcare professionals on travel medicine. The current COVID-19 pandemic illustrates the importance of this type of education and data accumulation now and in the future.

Introduction

As of 2015, foreign born individuals constituted approximately 4% of the population in Missouri.¹ Among these individuals, 39.5% were from Asia, 31.1% from Latin America, 16.2% from Europe, 2.3% from North America and 0.9% from Oceania.¹ Despite a significant number of foreign-born individuals in Missouri and 33,864,417 year-to-date international arrivals to the United States (U.S.) as of June 2017, the variety and number of imported infections acquired by Midwest travelers and immigrants is not well-known.² As a consequence of inadequate data supporting the occurrence of imported infectious diseases in the region, Midwest physicians, particularly in rural settings, may not consider foreign, imported infections as the cause of illness among patients who were also travelers or immigrants.³ We conducted a retrospective review of imported diseases seen at a referral center for the rural mid-west.

Methods

A sub-list (Table 1) was abstracted from the GeoSentinel diagnosis list of the International Society for Travel Medicine (ISTM) and the Centers for Disease Control and Prevention(CDC). This includes infections that were acquired outside of the continental U.S. that would raise concern for health care providers and public health officials in Missouri based on our prior experiences. Common infections such as influenza were excluded. GeoSentinel sites are specialized travel medicine clinics that conduct continuous clinician-based sentinel surveillance for travel-related illnesses in cooperation with the International Society for Travel Medicine and the Centers for Disease Control.^4–6 Using this abstracted sub-list, we first performed a retrospective chart review of all cases aged ≥18 years and had a diagnosis of an imported infection listed within our focused list of imported diseases seen within the Division of Infectious Diseases at the University of Missouri Hospital and Clinics from 2001–2014. Demographic, clinical, laboratory, and imaging data were gathered. These data were presented as a poster in the 2014 IDWeek (San Francisco, CA).⁷ But, as we suspected that the number of cases were an underestimation, we continued to gather data for 2015–2018. We performed descriptive analysis using Microsoft ® Excel 2019. Data presented as number(N)/percentages, mean/standard deviation or median/range. Travelers were classified as visiting family/relatives(VFR), business, mission/relief work, immigrants, refugees, schooling and vacationers.

Table 1.

Focused list of imported infectious diseases

Focused Sub-List of GeoSentinel Diagnoses
Respiratory	Diarrheal/Gastrointestinal
1. Pulmonary Anthrax	1. Amebiasis
2. Tropical Pulmonary eosinophilia	2. Cholera
3. Mycobacterium tuberculosis – Pulmonary, Extrapulmonary	3. Cryptosporidiosis
Febrile Illness	4. Cyclosporiasis
1. Bartonella bacilliformis	5. Giardiasis
2. Bartonella henselae	6. Isosporiasis
3. Acute brucellosis	7. Ascariasis
4. Chronic brucellosis	8. Clonorchiasis
5. Chagas disease	9. Echinococcosis
6. Dengue	10. Fascioliasis
7. Ebola Virus	11. Helminth
8. Acute hemorrhagic fever	12. Hepatitis A, E
9. Acute HIV infection	13. Hook worm
10. Lassa fever	14. Schistosomiasis (recurrent)
11.Leptospira	15. Strongyloidiasis
12. Malaria	16. Tapeworm (D. latum, H. nana, T. saginata, T. solium)
13. Measles	Neurologic
14. Melioidosis	1. Japanese encephalitis
15. Q fever	2. CNS Tuberculosis
16. Rickettsioses (akari, felis, prowazeki, rickettsii, tsutsugamushi)	3. Neurocysticercosis
17. Salmonellosis, S. typhi	Tissue Parasite
18. Yellow fever	1. Filariasis (Wuchereriasis, Loiasis, Onchocerciasis)
19. Bubonic and pneumonic plague	2. Visceral leishmaniasis
Genitourinary	3. Strongyloides hyperinfection syndrome
1. Schistosomiasis	4. Trichinellosis
Dermatologic	5. African Trypanosomiasis (T. gambiense, T.rhodesiense)
1. Cutaneous larva migrans	6. Visceral larva migrans
2. Cutaneous leishmaniasis
3. Mucocutaneous leishmaniasis
4. Leprosy
5. Myiasis
6. Rabies
7. Tungiasis
8. Yaws

Results

In total, 64 cases (57.8% male, mean age 38.54 ± 13.14 years) of imported infections were seen between 2001 and 2018. We identified relatively more cases during the shorter 2015–18 study period (18 cases) than the longer previous study period (46 cases from 2001–2014).

Symptoms at presentation: In 55(85.94%) cases, the most common symptoms were fever(14.9%), chills(8.9%), abdominal pain(7.2%), diarrhea(7.2%), and headache(5.9%). The rest(each <5%) were cough, myalgia, nausea, vomiting, masses/swellings, night sweats, weakness, seizures, dermatologic symptoms, vision changes, decreased appetite, malaise, dizziness, infection diagnosis during blood donation, dyspnea, back pain, bloating, chest pain, fatigue, hematochezia, anemia, weight loss, urinary frequency, eye pain, hematuria, insomnia, dysuria, flatulence, decreased urination, and cramping.

Diagnoses associated with travel destinations: Tuberculosis (TB) was the most common infection seen in 20 patients (31.3%) with one or more of the following manifestations: pulmonary TB(11, 55%), lymphadenopathy (8, 40%), gastrointestinal TB (4, 20%), disseminated TB (2, 10%), and vertebral/spine TB (1, 5%). There were no specific geographical trends for TB acquisition: 6 each from Africa and Asia, 3 from Central America, 2 from Oceania, and 1 from Europe. Four patients with TB also had HIV and another had concomitant echinococcosis. Excluding TB, the remaining cases were diverse in diagnosis and geographic area of acquisition (Table 2). Of all cases of imported infections including TB, Africa was the most frequently documented geographic origin of infection, followed by Asia then Central America.

Table 2.

geographic origin of disease acquisition for infections other than tuberculosis.

Continent	Imported infection	Region (Number of cases)
Africa	Malaria (5 P. falciparum, 3 unknown spp.)	Angola (1), Burundi (1), East Africa (1),Ghana (1) Ivory Coast (2), Malawi (1)
	Giardiasis	East Africa (1), Gambia(1) Unspecified (1)
	Neurocysticercosis	Congo(1)
		Nigeria(1)
	Schistosomiasis	Eritrea(1)
		Ethiopia(1)
	Leprosy	Burundi (1)
	Loiasis	Gabon (1)
	Paratyphoid fever	Sierra Leone (1)
	Typhoid fever	Ghana(1)
	Unspecified gastrointestinal parasitosis	West Africa(1)
Asia	Malaria (1 P. vivax, 1 unknown spp.)	India (1), Unknown (1)
	Strongyloidiasis	Cambodia (1), Malaysia (1)
	Hepatitis A Virus	Bangladesh (1)
	Japanese Encephalitis	Thailand (1)
	Leprosy	Sri Lanka (1)
	Q fever	Iraq (1)
	Typhoid fever	Nepal(1)
Central America	Neurocysticercosis	Mexico (3)
	Human T lymphocytic virus infection	Jamaica(1), Mexico (1)
	Ascariasis	Costa Rica
	Brucellosis	Mexico
	Chagas disease	El Salvador
South America	Chikungunya virus	Trinidad(1)
	Giardiasis	Ecuador(1)
Europe	Schistosomiasis	Unknown (1)
Unknown	Chickungunya virus	Unknown (1)
	Human T lymphocytic virus infection	Unknown (1)
	Malaria (P. vivax)	Unknown (1)
	Neurocysticercosis	Unknown (1)

Diagnoses associated with reasons for travel: The reasons for travel among those whose destinations were outside the U.S. included visiting family or relatives (VFR), business, and mission/relief work. Travelers from elsewhere to the U.S. included immigrants, refugees, students studying within the United States, and vacationers. Reason for travel was documented in 51 of 64 cases of imported infection. Diagnoses and associated reasons for travel are represented as a sunburst diagram (Figure 1). Most cases of imported infections were in those immigrants to the U.S., followed by VFR. TB was the single most common infection among immigrants (70.6%), refugees (57.1%), and students (33.3%). Malaria was the most common diagnosis in those traveling for VFR(37.5%) and giardiasis was the most common diagnosis in those traveling for mission/relief purposes, there was no specific disease that was common for business travel. All vacationers to the U.S. were diagnosed with malaria. In 13 patients, reasons for travel were not known.

Figure 1.

Sunburst diagram for reasons (%) for travel and corresponding number/s of imported infections

Travel period and time to medical attention: Duration of travel was not documented among immigrants and refugees to the U.S. and those who came to the U.S. for schooling. It was 203 days for business (N=1/6), 7 days (median, N=4/4, range 8–750 days) for mission/relief, 50 ± 17.3 days for VFR (N = 3/8) and 23 days (median, N=3/3, range 22–150 days) for vacation. Time to first medical attention following return from travel destinations was 1080 days (median, N=12/17, range 14 – 4015 days) for immigrants, 1460 days (median, N= 7/7, range 240 – 4680 days) for refugees, 730 days (median, N = 3/6, range 7–1440 days) for schooling and 51 days (median, N=4/8, range 30 – 720 days) for VFR travelers returning to the U.S.. This data was not documented for those who travelled for mission/relief and vacation. Among those diagnosed with TB, 8 immigrants presented at a median of 1080 days, whereas refugees presented with 1991.25±1865.34 days.

Discussion

According to the United Nations World Tourism Organization 2016 Report, international tourism has increased by approximately 4% annually since 2009, totaling 1.2 billion international tourist arrivals in 2016. The largest increases were seen in Africa, Asia, and Pacific regions, portending potential for transmission of imported infections.⁸ The CDC reported that approximately 22–64% of travelers to developing countries experience health problems and up to 8% of travelers eventually seek healthcare attention.^6,8 At least a portion of the 8% of travelers do so in the rural mid-west. Similar to travelers and immigrants in coastal and urban U.S. settings, rural mid-west travelers and immigrants are also at risk of acquiring imported infections.

In our study 19 different imported infectious diseases from a wide variety of geographical origins, were seen. Most illnesses were acquired from Africa, Asia, and Central America. Our data suggests that the likelihood of acquiring is probably not a function of volume, but rather, specific to travel destination and/or demographics.^9–11 A thorough review of the travel itinerary is important to recognize destination-specific differences in epidemiology, differential diagnosis and empiric therapy as recommended by others.^4,12

TB was the most common diagnosis among all (70.6% of immigrants, 57.14% of refugees, and 33.3% of those who came to the U.S. for schooling). They are mostly acquired from their native countries with a later re-activation or incidental discovery of latent disease while in Missouri. Malaria was most common among VFR travelers mostly due to the perceived belief that prophylaxis is unnecessary for destinations native to the traveler.¹³ They are more likely to stay in rural regions and are less likely to seek pre-travel health consultation or stay in urban hotels.^8,13 Giardiasis was most common among mission/relief travelers, reflecting rural destinations with poor water quality and inadequate preventative measures. Other infections with mission/relief travel were typhoid and Hepatitis A, both transmitted by fecal-oral route reflecting rural unhygienic conditions. Considering all diseases and their duration to presentation, the average time to presentation for both immigrants and refugees was approximately 48 months, whereas, it was only 24 months for those attending school in the U.S.. This is mostly from improved healthcare access through institutional student health programs.

The small number of cases seen for the study period (N=64 for 18 years) is an underestimation. We suspect that many cases were missed from lack of documentation, inability to extract or track/data from electronic records and also ignorance on imported diseases not prevalent in the rural mid-west U.S.. We saw more cases within the past 4 years than over the preceding 14 years, reflecting either an increase in international tourism and/or suggesting that a prospective study may accrue more data. In the future, we hope to create a database of imported infections to guide physicians regarding appropriate evaluation, diagnosis, and treatment. As international tourism steadily increases in all geographic locations, hospitals and clinics must be prepared to not only provide pre-travel prophylaxis, but also appropriately triage and manage travel-related diseases by making a timely diagnosis and treatment^14–16 The 2002–2003 severe acute respiratory syndrome coronavirus (SARS CoV) spread within few days to a few countries and the 2009 H1N1 influenza pandemic spread to 30 countries within six weeks, similarly, the ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus -2 (SARS-CoV-2) spread to >28 countries within six weeks affecting >40,000 people.^17–19 This is primarily related to the vast increase in international travel in past couple of decades, partly from expanding economy and wealth among populations and travelers.²⁰ Institutional data such as our study will promote these goals by providing regional epidemiological data, educating local health care providers, fostering the development of travel medicine clinics and potentially serve as hubs for identifying emerging infections at and from foreign destinations. Travel clinics in Missouri are located in their major cities. Below you will find the links to a few of these clinics in Columbia, Springfield, Kansas City and St. Louis. When travelling to destinations requiring Yellow fever vaccination, travelers will need to seek a travel clinic specifically authorized for providing this vaccination. Useful Links to Travel Clinics in Missouri: https://www.muhealth.org/locations/travel-clinic, https://www.mercy.net/practice/mercy-clinic-travelmedicine-whiteside/, https://www.passporthealthusa.com/locations/mo/kansas-city/, https://www.passporthealthusa.com/st-louis.

Obvious limitations of our study include the use of an abstracted sub-list, retrospective data with incomplete documentation regarding illness severity, travel duration/itinerary, timing of illness in relation to travel, pre-travel consultation, adherence to chemoprophylaxis, and individual exposures while abroad.⁸ But such limitations have also been observed by the International Society of Travel Medicine’s (ISTM), who has been tracking traveler imported diseases at the point of entry for past 2 decades.^21,22 Travel and immigration are believed to be infrequent in the rural mid-west U.S., but through our study we demonstrate that a wide variety of imported diseases were seen and treated.

Conclusions

A wide variety of imported infections were diagnosed and/or treated in a referral center for the rural mid-west U.S. from 2001–2018. Infections were related to travel destinations and the reasons for travel. Pre-travel education is important for rural mid-west travelers. Presenting symptoms were non-specific in nature. Education of mid-west physicians on travel medicine is important to enable early diagnosis and treatment of imported infections among returning travelers. The current COVID-19 pandemic illustrates the importance of this type of education and data accumulation now and in the future.