March 2007 | Back to Table of Contents

Clinical and Health Affairs

Hearing Hoofbeats, Thinking Zebras

Five Diseases Common Among Refugees that Minnesota Physicians Need to Know About

By William M. Stauffer, M.D., M.S.P.H., and Meghan Rothenberger, M.D.

Abstract
Minnesota accepts more refugees per capita than any other state. For that reason, primary care physicians throughout the state are likely to encounter refugees in their practices. This article describes 5 infectious diseases that are common among refugees and what physicians need to know about them in order to effectively screen and treat patients who are newcomers to this country. The diseases discussed are strongyloides, schistosomiasis, malaria, hepatitis B, and tuberculosis.

As he turned off and detached the ventilator, the resident felt his shoulders slump with the exhaustion and unspoken burden of having just lost a patient. The room, usually filled with the rhythmic sound of mechanical breaths and the incessant beeping of the cardiac monitor, was now silent. After what seemed like hours, the stillness was shattered by the anguished cry of the oldest daughter, a teenager. Looking up, the resident saw the younger children standing wide-eyed, sullen, but silent. Then the 2-year-old, who stood staring at his mother, began to cry, joining the grief-ridden solo of his older sister. It was not his father’s death that dismayed him but his mother, who stood, face in hands, head bobbing with muffled sobs, tears falling through her fingers.

This man, who died so helplessly in the intensive care unit, lived a courageous life unknown to most of those caring for him. He, in fact, carried with him a small piece of evidence of this life—a bit of lead in his left leg, the result of an injury sustained while working secretly in the service of the CIA for the United States military during the Vietnam conflict. As he lay in his hospital bed, did he relive the terror of the hand-to-hand combat in the green blur of the rainforest? The torture and starvation that followed in the prison camps? The joy of his eventual escape? Was he filled with solace during his last waking moments, with the belief that he had delivered his family to the safety of this foreign place, Minnesota?

Having watched this case unfold, the resident momentarily reflected on this ironic moment. This man who had survived untold horrors and toils beyond imagination had just succumbed to a silent killer too small to be seen. This microscopic killer had lain dormant in him for the last 20 years. Tragically, it was the actions of a well-intentioned physician who ended its period of silence. It had all begun 2 weeks earlier when the man became winded as he gardened at a community plot. Perhaps he wondered why no one had ever told him he had “asthma.” Perhaps he remembered the bitter taste of that first dose of prednisone that sat on his tongue a moment too long.

Although Minnesota is not one of the nation’s leaders when it comes to immigration, we accept more refugees per capita than any other state. In fact, last year, Minnesota trailed only California in absolute numbers of newly arriving refugees. Although all categories of newcomers (immigrants, refugees, and migrants) pose challenges to the health care system, refugees tend to have more acute health issues on arrival, particularly in regards to infectious diseases, given their living conditions prior to departure. It is important to note that before they immigrate refugees are generally excluded from their host countries’ national health programs, including parasite and malaria control and treatment. Therefore, refugees have special needs on arrival to the United States, which, if not addressed, may persist and cause future illness and even death. Although the Centers for Disease Control and Prevention are currently modifying and strengthening guidelines for both predeparture and postarrival presumptive treatment and medical screening, local health care professionals must be aware of the diseases most commonly encountered in refugee populations.

Given the increasing number of refugees who call Minnesota home, physicians should know a patient’s country of origin and travel history and be aware of diseases common to those parts of the world that might share symptoms with illnesses more commonly seen in this country. The potential for misdiagnosis is too great. At best, provider ignorance pays a disservice to patients. At worst, it leads to increased morbidity and mortality. This may occur unintentionally, through lack of appropriate care (for example, neglecting to screen for hepatocellular carcinoma in hepatitis B–infected individuals) or, sadly, through inadvertent iatrogenic actions (such as in the case cited, in which a patient infected with strongyloides was placed on immunosuppressant therapy).

This article briefly addresses 5 infections commonly found in refugees with which all Minnesota health care providers should be familiar. However, this is only an introduction, and there are many other disorders with which clinicians need to familiarize themselves. After all, the “global has become local.”

Strongyloides
Strongyloides stercoralis is an intestinal nematode similar to hookworm. Because of its ability to replicate inside its host, it may persist asymptomatically in its human host for more than 60 years after initial infection. When an individual who is harboring strongyloides is immunosuppressed because he or she is taking corticosteroids, amplification of the autoinfective life cycle occurs, leading to hyperinfection and disseminated disease. This life-threatening condition is often associated with gram-negative sepsis thought to be caused by the attachment of enteric bacteria to stronglyoides larvae as they migrate though host tissue.

During its normal life cycle, the organism migrates through the lungs and may cause wheezing that’s often misdiagnosed as asthma or COPD. Patients are then treated with corticosteroids that may disseminate the disease. Also, disseminated disease may occur in patients who are chronically infected and are started on immunosuppressant therapy for an unrelated condition.

Although disseminated stongyloidiasis was once considered rare, Ashley Newberry, M.D., a former internal medicine resident at Hennepin County Medical Center, reported 9 cases of strongyloides dissemination/hyperinfection in the Twin Cities during the last decade.¹ All patients suffered serious illness, and 4 did not survive. One subsequent case that occurred in the Twin Cities also proved to be fatal. In all cases, the patients had been in Minnesota on average more than 5 years before disease onset. All were placed on cortisteroids by well-intentioned clinicians intending to treat reactive airway disease or other steroid-responsive disorders.

Despite the occurrence of these cases and their being highlighted in teaching rounds and at conferences, David Boulware, M.D., an infectious diseases fellow at the University of Minnesota, and Brett Handel-Paterson, M.D., a pediatrics-internal medicine resident at the University of Minnesota, discovered after reviewing more than 150 cases of strongyloides at a local hospital in which 2 patients had died from disseminated disease that practicing physicians in Minnesota are not equipped to prevent, diagnose, or treat this common infection. Boulware and colleagues subsequently surveyed residents asking them to diagnose a hypothetical patient and found that fewer than 10% of University of Minnesota residents could identify that the patient was at risk for strongyloides; the majority advocated steroid use in the hypothetical patient. Boulware and his team compared the residents’ knowledge with that of physicians in 5 other residencies, 2 in the United States and 3 in other countries with endemic strongyloides, and found that U.S. residents consistently did poorly in identifying patients at risk for the disease while most residents in Brazil, Singapore, and Thailand knew the risks well and managed patients appropriately.²

Because disseminated disease usually presents as gram-negative sepsis, most cases are misdiagnosed and go unrecognized. If clinicians were more aware of this condition, the number of reported cases would likely be far greater. This point was emphasized by Lim et al., who found 10 cases of disseminated strongyloides in Toronto over a 7-month period at a facility in which clinicians were aware of the disease.³ Several seroprevalence studies in refugee populations have demonstrated high rates of infection, suggesting that many refugees are at risk for disseminated disease. Among Sudanese refugees (“the Lost Boys”), 44% showed serologic evidence of infection.⁴ Another recent study conducted in Australia found that 11% of arriving East African and 42% of Cambodian refugees were infected.⁵ Yet another study found that 24% of Laotian refugees were infected 12 years after migration to Australia.⁶ Therefore, it is imperative for Minnesota clinicians to be aware of this infection and take steps to prevent iatrogenic-induced disease. When planning to immunosuppress a patient who is at risk of strongyloides (which includes most immigrants), prevention of disease dissemination must be considered. Any patient who was not previously tested or treated should undergo serologic testing for strongyloides prior to starting immunosuppressive therapy. When time does not allow for testing, empiric treatment for strongyloides is an acceptable alternative.

Schistosomaisis (Bilharzia)
The geographic origin of newly arriving refugees has shifted away from Europe and Asia toward sub-Saharan Africa. In fact, the proportion of newly arriving refugees whose country of origin was in Africa has climbed from 9% in 1998 to 39% in 2005.⁷ This change has brought a corresponding shift in disease epidemiology. Schistosomiasis, a parasitic disease rarely seen in Minnesota 10 years ago, has emerged as a very common cause of symptomatology in the sub-Saharan refugee population. Ironically, African patients often know more about this disease than the health care providers caring for them, although those providers will usually recognize it by its British name, “bilharzia.” There are 3 species of schistosomiasis that commonly affect humans; but in Minnesota, we chiefly see 2 species in refugees from sub-Saharan Africa: S. hematobium and S. mansoni. Studies in the United States have shown that 46% of Sudanese and more than 80% of Bantu Somali refugees have serologic evidence of infection.^4,8 Another study demonstrated that 15% of East African refugees arriving in Australia had chronic infection with a schistosomiasis
parasite.⁵

Schistosomiasis hematobium has a predilection for the venous plexus of the urinary bladder and commonly presents with either terminal hematuria (which may be icroscopic) or asymptomatic eosinophilia (defined as an absolute eosinophil count over 400 eosinophils/µL). The hematuria may be accompanied by dysuria and increased frequency of urination. Chronic infection may lead to urologic complications such as renal colic, obstructive uropathy, hydronephrosis, renal failure, and squamous-cell bladder carcinoma. In addition to genitourinary symptoms, the pathogenic ova that are swept into the blood system from the venous plexus can settle in virtually any area of the body leading to a multitude of symptoms. One such area of predilection is the central nervous system, which may result in acute myelitis. In some endemic regions of the world (ie, Nigeria and Ghana), the prevalence rate of S. hematobium can exceed 90%.^9,10 In fact, some cultures believe it is a sign of maturity when a child develops hematuria.¹¹ Unfortunately, clinicians in Minnesota often neglect to consider this diagnosis in patients presenting with asymptomatic hematuria. This may lead to expensive, invasive, and unnecessary testing.¹² Any sub-Saharan African refugee presenting with hematuria or other urologic disease especially when accompanied by eosinophilia should be screened for schistosomiasis.

Schistosomiasis mansoni has a predilection for the inferior mesenteric venous plexus. It usually presents as asymptomatic eosinophilia; however, it may present with portal hypertension, hepatomegaly, splenomegaly, hepatic cirrhosis with associated disorders (ie, varices), pulmonary hypertension, colonic polyposis, colicky hypogastric pain, melena, and either or alternatively diarrhea or constipation. When a patient from sub-Saharan Africa presents with any of these signs or associated symptoms, particularly if they are associated with eosinophilia, schistosomiasis should be considered.

Malaria
Malaria, particularly that caused by Plasmodium falciparum, is another under-recognized disease that has become more common in Minnesota with the increase of refugees from sub-Saharan Africa. This is not surprising, given that in some areas of Africa, referred to as holoendemic areas, malaria prevalence may exceed 75% at any given time. In those areas, young children are most likely to die from malaria. In fact, in sub-Saharan Africa, a child dies every 30 seconds from malaria, causing approximately 3,000 deaths per day, or the equivalent of the number of lives that would be lost if 10 jumbo jets crashed each day.¹³ Persons who survive early childhood malarial infections gain partial immunity. As opposed to a traveler with P. falciparum, who will usually present within weeks of exposure, individuals who have partial immunity may have the parasite circulating in their system for months after leaving an endemic area and show few, if any, symptoms of disease. Studies have demonstrated that between 9% and 60% of Liberian refugees arriving in Minnesota from 4 countries of asylum in western Africa have malaria 4 weeks after arrival.^14,15 A Canadian study demonstrated that 3 months after arrival, 18% of refugees originating in Tanzania had ongoing malarial infection.¹⁶ Unfortunately, misdiagnosis and improper treatment is the rule, rather than the exception, with this disease. It has been shown that when a patient presents with malaria in a location where it is not endemic, the diagnosis is initially missed 60% of the time.¹⁷ Furthermore, the patient is evaluated by an average of 3 health professionals before diagnosis, which occurs, on average, 7.6 days after initial presentation for P. falciparum.¹⁷ Newman et al. of the Centers for Disease Control and Prevention found that of the deaths caused by malaria in the United States during the last several decades, an estimated 80% were preventable; a significant proportion of these deaths resulted from delay or error in diagnosis and treatment.¹⁸

It is important for clinicians to realize that malaria may present with only subtle symptoms in newly arrived immigrants. Patients may not have a fever but instead present with such common symptoms as diarrhea, headaches, and, in children, failure to thrive. Clinicians need to gain greater awareness and understanding of this disease and must consider it in ill refugees, especially those they are seeing within 1 year of their migration.

Hepatitis B
An estimated 350 million persons worldwide have chronic hepatitis B, and it is estimated that at least 1 million persons a year will die from complications, including liver cancer and cirrhosis.^19,20 Prevalence of chronic hepatitis B in refugees varies with country of origin but ranges from approximately 1% up to approximately 20% (average, 9% in 2005) in groups arriving in Minnesota.²¹ The risk of hepatocellular carcinoma (HCC) in a chronic carrier is 12- to 300-times higher than that in the general population, and it has been estimated that the annual incidence is 0.5% per person.^19,20

Proper management of chronic hepatitis, including screening for HCC and treatment, should be of paramount importance in these patients. As early as 1985, it was shown in Native American populations that screening could decrease mortality from HCC, which is almost universally fatal if diagnosed after symptoms occur.²² All clinicians should know the hepatitis B status of their patients and should refer appropriately for treatment. In addition, primary care clinicians must offer HCC screening. A reasonable screening regimen is an alpha-feto protein test at least every 6 months and an ultrasound of the right upper quadrant at least every year. Ultimately, hepatitis B is prevented by vaccination, and more equitable and global distribution of the vaccine could virtually eliminate infection, disease, and associated complications.

Tuberculosis
According to the World Health Organization, an estimated one-third of the world’s population is chronically infected with tuberculosis (TB). The bacterium that causes it, Mycobacterium tuberculosis, leads to more deaths than any other single infectious agent. Among all refugees relocating to Minnesota in 2005, 40% had a positive tuberculin skin test; positive tests were noted among 51% of refugees from sub-Saharan Africa, 30% of those from Europe, and 24% of those from Asia.²¹ With approximately 80% of cases occurring among persons born outside the United States, the incidence of TB peaked in Minnesota in 2001 with 239 cases. It has declined slightly to 199 cases reported in 2005.²³ Extra-pulmonary disease is more common among immigrants, occurring in more than 50% of cases.²³ For unexplained reasons, migration seems to trigger active disease as the majority of immigrants with latent TB will see their disease reactivate within 5 years of migration, and more than 50% will have it happen within the first 2 years.

It is imperative for health care providers to know the TB status of their patients, either by tuberculin skin test or gamma-interferon testing, and to offer therapy to those with latent tuberculosis infections. Further, clinicians need to suspect TB when a patient at risk (most immigrants) present with any symptoms of the disease. Classic symptoms include weight loss, night sweats, and fevers accompanied by chronic respiratory symptoms. Other common extra-pulmonary sites of TB infection include the lymph nodes (ie, neck, mediastinum), spine (Pott’s disease), pericardium, urinary system, central nervous system (ie, meningitis, tuberculoma), and gastrointestinal tract. Because TB may occur in virtually any area of the body, it should be considered among any patient at risk for the disease who presents with unexplained symptoms. Examples of unusual cases of extra-pulmonary infection that have occurred in Minnesota include tuberculosis otitis media; laryngeal TB; endometrial TB; and parotid gland, chest wall, and cutaneous TB. Early consideration, appropriate diagnostic evaluation, and treatment are imperative to protect public health and prevent advanced illness and death in patients.

Conclusion
Minnesota is a community of immigrants. In fact, an estimated 99% of Americans are either immigrants or descendents of immigrants. Refugees arriving in our state contribute to its cultural fabric and economic success. The health care community has an obligation to provide them the same kind of high-quality care that other Minnesotans receive. To do that and reduce disparities between the health of newcomers and long-term residents, clinicians must learn to provide culturally competent care and understand which infectious diseases are common among various populations and test patients for them. Providers who are ignorant of these diseases may do a disservice to their patients not only by failing to detect or prevent serious illness but by inadvertently causing harm with inappropriate therapy. MM

William Stauffer is an assistant professor in the department of medicine’s division of infectious diseases and international medicine at the University of Minnesota and a member of the staff at HealthPartners’ Travel Medicine Clinic. Meghan Rothenberger is a third-year internal medicine resident at the University of Minnesota.

References
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