Pulmonary Diseases in Refugees and Migrants in Europe

Ohm’s law (I = V/R) not only applies to electrical currents, but describes very well the forces of human migration (I) following gradients (V) despite obstacles (R). Poverty, war, climate change, and sometimes missing or inadequate healthcare provision are driving people to leave their homes and to move to places that provide a prospect of better living conditions, security, or simply a chance to survive a potentially life-threatening disease. Approximately 22.5 million people worldwide were forced to leave their country due to persecution, conflict, or violence in the year 2016 [1]. Following political instability and civil war in countries like Syria, Afghanistan, or Iraq, or as a consequence of poverty in countries of the Balkan region or many African countries, large numbers of refugees have been seeking asylum in high-income European countries in recent years. Despite severe hardships during travel, risking their lives during passage across the Northern African desert, the Mediterranean Sea, as well as other obstacles, large numbers of people have applied for asylum in what could be considered the largest wave of migration to Europe since the end of World War II [2]. 1.26 million people applied for asylum in the countries of the European Union in the year 2015, and another 1.20 million asylum seekers were registered in 2016 [3]. Of those, almost 700,000 were Syrian refugees. More than 80% of the first-time asylum seekers in countries of the European Union in 2016 were < 35 years of age, and 63,300 asylum applications were from unaccompanied minors [3]. The number of asylum applications for individual countries is shown in Figure 1.

Most asylum seekers, refugees, and migrants come from countries where certain infectious diseases are more prevalent, while in Western Europe the same infectious diseases might be rare or nonexistent. Taking into account this large number of refugees and migrants over recent years, European physicians and pulmonologists will have to consider a wider range of conditions when dealing with such patients, including diseases encountered in their countries of origin (Table 1). Screening for tuberculosis has been widely implemented to identify active cases in refugees [4]. However, tuberculosis in migrants and refugees has extensively been described elsewhere [5, 6] and is beyond the scope of this review. The aim of this review was to provide an overview of pulmonary diseases that might be encountered in refugees and migrants to high-income European countries. Due to the number and diversity of infectious organisms that have the potential to cause pulmonary disease, we will only focus on a few of these organisms which are either more common or more likely to pose problems in clinical practice.

Migrants are especially vulnerable to the acquisition of drug-resistant organisms and facilitating their subsequent spread [7]. Studies of refugees arriving in high-income countries have noted a high prevalence of drug-resistant tuberculosis [8], infections with antibiotic-resistant Enterobacteriaceae [9, 10], and colonization with antibiotic-resistant bacteria [11]. Refugees seem to be particularly at risk in part due to the elevated levels of antimicrobial resistance in their countries of origin and enhanced acquisition due to failing infrastructure and insanitary conditions [12]. Although refugees appear to be a high-risk group, whether routine preemptive isolation and screening should be recommended and would be worthwhile is not as yet resolved [13]. The risk of colonization with drug-resistant organisms should be assessed in all patients admitted to healthcare facilities taking into account areas visited, patient history, and other risk factors such as previous hospitalization. Although colonization and infections due to multidrug-resistant organisms represent an issue of the highest importance, most healthcare facilities in high-income European countries should ideally have protocols in place for patient screening and infection prevention. These would enable healthcare workers to rapidly identify and manage patients with colonization/infections caused by multidrug-resistant organisms.

A rarer bacterial infection is melioidosis caused by Burkholderia pseudomallei. It is prevalent in tropical and subtropical regions, most commonly Northern Australia and Southeast Asia [14], although cases in Africa [15] and the Americas have been reported [16]. Melioidosis principally affects those in direct contact with muddy water and soil and is predominantly acquired through inhalation, ingestion, or inoculation [17]. Older immunosuppressed adults, particularly those with diabetes mellitus or alcoholism, are particularly at risk of infection [18]. In temperate regions, infections are typically imported by migrants and travelers [19]. Incubation periods may be as short as 1–3 weeks [20], but latent infections with recrudescence many years later are recognized [21]. Patients characteristically present with pneumonia, genitourinary and cutaneous presentations being less common [18]. Notably, many patients become septicemic [17]. The diagnosis is typically confirmed by the culture of B. pseudomallei from clinical samples including blood, respiratory tract secretions, and abscess pus. Serology and molecular methods are also used [22]. Localized disease may be treated with doxycycline; however, severe disease requires intravenous treatment with ceftazidime or meropenem for several weeks followed by oral consolidation with co-trimoxazole and doxycycline for up to 20 weeks [23]. Currently, there is no vaccine in clinical use; prevention is best achieved by avoiding contact with contaminated water or soil, particularly by wearing shoes [19].

Influenza A, B, and C viruses cause predominately pulmonary infections in humans, with influenza A and B responsible for seasonal outbreaks that afflict up to 15% of the world’s population annually [24]. Migrants do not specifically represent a risk of spreading influenza to receiving countries [25]. Nonetheless, migrants are more susceptible to influenza in part due to lower levels of vaccine coverage [26, 27]. Infection may be transmitted by droplet, aerosol, or contact [28]. The respiratory features of influenza range from asymptomatic infection to severe pneumonia [29]. Those patients who are hospitalized with proven or suspected infection should be treated with neuraminidase inhibitors such as oseltamivir or zanamivir [30]. Prevention measures include hand sanitization, vaccination, and possibly face masks [31].

The Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia in 2012 [32]. It is thought that most cases occur on the Arabian Peninsula and/or are epidemiologically linked to this region [33]. Dromedary camels are thought to be the natural host for MERS-CoV, which may be transmitted to humans by close contact with the animals [34]. Human-to-human transmission has occurred mainly in healthcare settings; thus, control measures should focus on rapid case identification and strict infection control practices to prevent onward transmission [35]. The average incubation period is 5 days (range 2–13 days) [36], and any patient with fever and pneumonia or acute respiratory distress syndrome with onset within 14 days of travel to an endemic area should be considered a patient under investigation for MERS-CoV [37]. The clinical spectrum of disease ranges in severity from asymptomatic infection to severe pneumonia requiring mechanical ventilation [32]. Patients particularly at risk of severe disease include those with chronic kidney disease requiring hemodialysis, those with diabetes mellitus, or those aged > 50 years [38]. MERS-CoV cases are confirmed by detection of viral RNA in clinical samples or by demonstration of seroconversion [39]. Treatment is primarily supportive, with virus-directed therapies currently deemed investigational [40].

An estimated 36.7 million people are living with HIV worldwide, with > 70% of them residing in low- and middle-income countries [41]. HIV infection can be associated with a number of infectious and noninfectious pulmonary complications (Table 2). This section does not aim to describe them in detail, but rather to provide an overview of conditions that pulmonologists should be aware of when treating HIV-infected patients. Also, it is beyond the scope of this paper to describe the relationship between HIV and tuberculosis, which cause substantial morbidity and mortality particularly in low-income settings. It is widely known that HIV infection is associated with an increased risk of tuberculosis, with people living with HIV accounting for 10% of the new tuberculosis cases reported in 2016 [42]. Other opportunistic infections associated particularly with advanced HIV infection are Pneumocystis jirovecii pneumonia, disseminated histoplasmosis, and recurrent bacterial pneumonias [43].

With antiretroviral therapy scale-up and co-trimoxazole prophylaxis, there has been a decline in pulmonary infections and an increased survival of people living with HIV [44, 45]. This is turn has led to an increased importance of chronic and noninfectious lung diseases. Noninfectious pulmonary conditions encountered in people living with HIV can be categorized into three main groups: interstitial lung diseases (ILDs), pulmonary vascular diseases, and malignancies.

Certain ILDs are more frequently encountered in people living with HIV. Before the widespread use of antiretroviral therapy, lymphocytic interstitial pneumonia in children and nonspecific interstitial pneumonia were more common, whereas now the spectrum of ILDs has changed towards cryptogenic organizing pneumonia, sarcoidosis, and hypersensitivity pneumonitis [46].

HIV-related pulmonary arterial hypertension (PAH) is included in group I of the updated classification of pulmonary hypertension [47]. It is estimated that the prevalence of PAH related to HIV is much higher than that in the general population [48]. According to a systematic review, the prevalence of PAH among HIV-infected individuals presenting with cardiovascular symptoms from Africa is as high as 14% [49], but the number of studies included was very small. Schistosomiasis (see below), which is independently associated with PAH [47, 50], and other concurrent chronic lung diseases could also contribute to an increased burden of PAH in low-income settings [51]. The true prevalence of HIV-related PAH is however difficult to ascertain due to differences in methods used for establishing the diagnosis. Transthoracic echocardiography tends to overestimate the prevalence and cannot accurately evaluate pulmonary vascular pressures [46]. Patients with HIV-related PAH are likely to benefit from the same therapies as non-HIV patients [50]. However, physicians should note that there are drug interactions between phosphodiesterase type V inhibitors such as sildenafil and protease inhibitors [52].

HIV-related pulmonary malignancies can be classified as AIDS-defining of non-AIDS-defining. The former group includes Kaposi sarcoma and non-Hodgkin lymphoma. Pulmonary Kaposi sarcoma presents in patients with advanced HIV and usually has concomitant mucocutaneous involvement which can be helpful in establishing the diagnosis. During bronchoscopy, Kaposi sarcoma lesions appear as red or purple-colored; however, if located distally, they are not always visualized. Histologically, Kaposi sarcoma has characteristic spindle cells and high vascularization [46]. Treatment consists of antiretroviral therapy, which can lead to regression, or if this is not effective, additional chemotherapy and/or radiotherapy.

Primary lung cancer is 2.5 times more common in people living with HIV than in the general population [53] and carries a worse prognosis, possibly because patients tend to present with more advanced disease [54, 55].

HIV has also been shown to increase the risk of other pulmonary disorders, such as chronic obstructive pulmonary disease (COPD) [56] or bronchiectasis [57].

Histoplasmosis. Infection caused by Histoplasma capsulatum var. capsulatum is found worldwide, particularly in North, Central, and South America [58], but also in Southeast Asia and Africa [59]. In Africa it coexists with H. capsulatum var. duboisii [60]. The infection is rare in Europe and most cases are imported [59]. It is a dimorphic fungus that can lead to pulmonary infection after inhalation of microscopic fungal spores. At risk are people visiting caves infested by bats or people who are exposed during construction renovations, but it has al so the ability to cause outbreaks [61]. Most infections are asymptomatic, but some individuals develop flu-like symptoms. Only a few, especially immunocompromised patients can develop severe disease and progressive pulmonary or disseminated infection. Acute respiratory symptoms with diffuse infiltrates on chest imaging are common presentations, but acute localized infiltrates, mediastinal lymphadenopathy, chronic cavitary pulmonary histoplasmosis, mediastinal syndromes (e.g., mediastinitis, fibrosis), broncholithiasis, or pulmonary nodules can also occur [58]. The diagnosis should be based on a combination of at least two diagnostic methods including histology, culture, antigen test, serology, or polymerase chain reaction [62]. The treatment depends on disease severity. Patients with mild to moderate pulmonary histoplasmosis and < 4 weeks of symptoms do not benefit from antifungal treatment. In patients with symptoms > 4 weeks, treatment with itraconazole 200–400 mg for 6–12 weeks is recommended [63]. The treatment duration is extended to 18–24 months in patients with chronic cavitary histoplasmosis. A lipid formulation of amphotericin B (3.0–5.0 mg/kg daily intravenously for 1–2 weeks) is recommended in patients with moderate to severe acute pulmonary histoplasmosis or in patients with progressive disseminated histoplasmosis, which can be switched to oral itraconazole after clinical improvement. Itraconazole prophylaxis with 200 mg daily is recommended in HIV-positive patients with a CD4 cell count < 150 cells/mm³ in high endemic regions [63].

Paracoccidioidomycosis. Paracoccidioidomycosis is endemic in certain parts of South America, especially in Brazil [64]. Outdoor activities such as agriculture are risk factors for infection. Most infections are asymptomatic. Symptomatic disease can occur as an acute/subacute (juvenile) form, which usually presents with enlarged lymph nodes, hepatosplenomegaly, and/or cutaneous/mucosal lesions, but rarely with pulmonary manifestations. In contrast, the chronic (adult) form often presents with severe pulmonary involvement, but other organs such as the central nervous system, bones, or the adrenal glands can also be involved. Severe infections are usually seen in immunocompromised patients. The radiological signs are apical pleural-pulmonary lesions and enlarged hilar lymph nodes. The diagnosis can be made after identification of yeast forms in tissue samples or by culturing. Patients with mild to moderate disease are usually treated with itraconazole 200 mg daily for an average duration of 12 months [64]. Co-trimoxazole is recommended as an alternative treatment. Amphotericin B can be used for severe disease.

Talaromycosis. Talaromyces marneffei, previously known as Penicillium marneffei, is a dimorphic fungus endemic to Southeast Asia that causes severe infections in immunocompromised patients, especially in patients with HIV/AIDS, and has a mortality of up to 30% [65]. The clinical symptoms range from mild forms presenting with skin lesions to moderate disease with multiple organ involvement and severe disease including respiratory failure. The radiological appearance is characterized by reticulonodular or alveolar infiltrations with or without consolidation, which can be localized or disseminated. The diagnosis can be made by culture of clinical samples (e.g., skin biopsy, blood culture). Antifungal treatment includes itraconazole and amphotericin B. Recently, a large study reported a better outcome for amphotericin B compared to itraconazole [66].

Cryptococcosis. Apart from central nervous system involvement, Cryptococcus neoformans and Cryptococcus gattii can also cause pulmonary cryptococcosis [67]. Immunocompetent patients often stay asymptomatic or develop mild pneumonitis. There is no specific radiological pattern, but it frequently presents as solitary nodules, lobar infiltrates, and/or hilar and mediastinal lymphadenopathy. Disease severity strongly depends on the patient’s immune status. The diagnosis is usually made by histology, fungal culture, and/or serum antigen test. Immunocompromised patients with pulmonary cryptococcosis should also be screened for central nervous system involvement by lumbar puncture with culture and antigen test of cerebrospinal fluid. Asymptomatic immunocompetent patients do not benefit from antifungal treatment. For focal pulmonary infiltrates, fluconazole 400 mg daily for 6–12 month is recommended. However, patients with HIV infection and diffuse pulmonary cryptococcosis should be treated similarly to those with central nervous system diseases, using amphotericin B and flucytosine for a minimum of 2 weeks during the induction phase, followed by consolidation and maintenance with fluconazole for at least 12 months [68]. Alternative treatment includes other azoles such as itraconazole, voriconazole, posaconazole, or isavuconazole [69].

P. jirovecii Pneumonia. P. jirovecii is an opportunistic pathogen causing severe infections in immunocompromised patients. Interestingly, the disease dynamics differs between HIV and non-HIV cases. While the latter is an acute disease developing within days with high mortality, the disease shows a much slower progression in HIV/AIDS patients [70]. Chest computed tomography usually shows symmetric ground glass opacities. Co-trimoxazole 15–20 mg/kg in four divided doses per day for 21 days is the treatment of choice. The dosage is calculated based on the trimethoprim component. In severe HIV-positive cases, adjunct corticosteroids are recommended. The role of corticosteroids in non-HIV patients remains unclear, with a recent meta-analysis showing no benefit [71], and they should not be prescribed routinely in patients with respiratory failure [72]. Alternative treatment regimens include pentamidine, primaquine + clindamycin, atovaquone, or dapsone + trimethoprim [68, 72].

Chronic Pulmonary Aspergillosis. Chronic pulmonary aspergillosis is found worldwide and is not restricted to the tropics. Pulmonary tuberculosis, which is more prevalent in low-income countries, is one of the most important risk factors for the development of chronic pulmonary aspergillosis [73, 74]. The clinical presentation can vary considerably from asymptomatic to life-threating hemoptysis [75]. The diagnosis is made by a combination of radiological, clinical, and mycological criteria [76]. Beside an Aspergillus IgG antibody test from serum, bronchoscopy should be performed in all patients, depending on a risk/benefit assessment to prove mycological evidence and to exclude alternative diagnoses [77]. Itraconazole (200 mg b.i.d.) or voriconazole (150–200 mg b.i.d.) for at least 6 months is the treatment of choice [76]. Surgery should be considered in patients with single aspergillomas. A multidisciplinary approach could improve the management and treatment outcome of these difficult-to-treat patients with chronic pulmonary aspergillosis [78].

Entamoeba histolytica is a protozoan with a worldwide distribution, although it is by far more prevalent the tropics. An estimated 104 million cases of E. histolytica infection occurred in 2010 [79]. Infection occurs by ingestion of contaminated food or water and can be asymptomatic or can lead to dysentery or less frequently to extraintestinal disease in < 1% of cases [80]. Pleuropulmonary infection is the second most common extraintestinal localization [81] and occurs usually by extension from a liver abscess. It can take the form of pneumonia, lung abscess, pleural effusion. and empyema or bronchohepatic fistula [82]. The clinical symptoms consist of fever, cough, and pleuritic chest pain and, if a bronchohepatic fistula develops, expectoration of “anchovy-sauce” pus [83]. Right-sided atelectasis and pleural effusions are the most common presentations [84], while elevation of the right diaphragm can be observed due to a hepatic abscess [83]. E. histolytica-specific antibody assays, antigen detection, or species-specific polymerase chain reaction are the most useful diagnostic tools for extraintestinal amebiasis [80]. The treatment consists of nitroimidazole followed by paromomycin or alternatively diloxanide furoate to eradicate intestinal carriage [80]. Disappearance of the lesions at imaging takes much longer than the relatively fast clinical recovery; this should not be considered as treatment failure.

Cystic echinococcosis (CE) is a neglected zoonotic disease caused by the larval stage of the cestode (tapeworm) Echinococcus granulosus. An estimated 188,000 new cases of CE occurred in 2010 globally [85]. CE has a worldwide distribution, but is more prevalent in regions of the Eastern Mediterranean, Northern Africa, Southern and Eastern Europe, southern South America, Central Asia, and parts of China. Its incidence can exceed 50 per 100,000 person-years in areas of high endemicity, with a prevalence of 5–10% in humans [86]. In high-income countries, CE is mostly an imported disease; however, it is endemic in some regions of Southeastern Europe [87].

Adult worms inhabit the small intestine of carnivores (canines, felids); eggs are passed with the feces and ingested by the intermediate hosts (sheep, cattle, horses, etc.). In the intermediate host, the larval stages develop into (hydatid) cysts and produce protoscolices which in turn develop into adult worms if ingested by the definitive host [88]. Humans can accidentally acquire the infection by ingesting parasite eggs (contaminated food, contact with dogs). In humans, cysts most commonly develop in the liver (70%) or lungs (20%), but can also occur in any other organ [89]. The risk factors for acquiring CE are having a rural lifestyle, where there are high populations of free-roaming or stray dogs, poor-quality abattoirs, and animal home slaughtering practices [87, 90]. The prevalence of CE increases with age and women are more frequently affected [91].

The incubation period can be highly variable, and cysts can be asymptomatic for years in the absence of complications. Symptoms are related to compression or rupture and are extremely variable according to the cyst localization. Lung hydatid cysts can be an incidental finding at chest X-rays. The presenting signs and symptoms of pulmonary cysts can be nonspecific, such as chronic cough, hemoptysis, dyspnea, and pleuritic chest pain. In case of rupture, the cyst content may be expectorated into the bronchial tree or discharged into the pleural space, with accompanying anaphylactic manifestations. Most of the time, less abrupt ruptures lead to bacterial superinfection and lung abscess [89].

The diagnosis is usually established using imaging studies (X-ray, computed tomography, ultrasound, etc.) and by detecting specific anti-Echinococcus antibodies in serum. The sensitivity for serology in pulmonary CE is 60–84%, with IgG-ELISA being more sensitive than other methods [92]. The treatment of pulmonary CE is complex, depending on the presentation, and should be conducted in centers with experience. The only radical treatment is careful surgical removal of the entire cyst. Watchful observation can be offered for small asymptomatic cysts. Medical treatment alone (albendazole) can be considered for small, uncomplicated pulmonary cysts, but the cure rate is rather low (< 50%). Antihelminthic therapy should be avoided preoperatively for larger cysts since there is a small risk of leakage/rupture, which would lead to an emergency intervention. Percutaneous aspiration procedures are contraindicated for lung cysts [93].

Although not usually a cause of pulmonary disease, Strongyloides stercoralis is a widely distributed soil-transmitted helminth that can establish a lifelong infection if not treated [94]. The prevalence of infection in some regions of Africa and South America can exceed 50% [95]. In special circumstances such as prolonged corticosteroid treatment or organ transplantation, S. stercoralis can cause a hyperinfection syndrome that can lead to multiorgan failure by invasion of all organs, including the lungs (Fig. 2) [96]. Patients with severe strongyloidiasis can therefore develop acute respiratory distress syndrome and pulmonary hemorrhages, together with bacteremia due to intestinal translocation. Chest X-rays frequently show diffuse shadowing [97], and mortality can be as high as 60% [96]. Usually, as far as this syndrome is considered, the diagnosis is rather easy because worms can be found in all fluids and secretions (including sputum and bronchoalveolar lavage). In immunocompetent individuals, serology is the most sensitive diagnostic tool (compared to parasitological methods), but its performance is much more limited in immunosuppressed patients with malignant strongyloidiasis. The treatment of hyperinfection syndrome consists of daily administration of ivermectin until parasite clearance in the feces, often followed by maintenance therapy with monthly ivermectin. Physicians should be aware of this syndrome, since long-term corticosteroids are prescribed for a wide range of pulmonary conditions. Screening including serology should be performed in patients at risk of developing this syndrome, such as candidates for immunosuppressive treatment and organ transplant who have previously resided in endemic areas [96].

Gnathostomiasis, also called larva migrans profundus, is caused predominantly by the nematode (roundworm) Gnathostoma spinigerum. Regions of high endemicity are Japan and Southeast Asia, but its reporting in Central and South America has increased due to the consumption of ceviche (raw fish marinated in lime) [98]. Humans usually become infected with the larvae of Gnathostoma spp. through consumption of raw or inadequately cooked freshwater fish or other intermediate hosts such as snakes, frogs, and chickens. The Gnathostoma larvae are highly invasive and motile and therefore can produce a wide range of symptoms affecting virtually any organ. Migratory cutaneous swellings [99] and eosinophilic meningoencephalitis are the most common and dangerous presentations, but several pulmonary symptoms have been attributed to infection with Gnathostoma spp. as well [100, 101]. Patients can present with cough, pleuritic chest pain, hemoptysis, lobar consolidation or collapse, pleural effusions, and pneumo- or hydropneumothorax. Most patients present with eosinophilia and eosinophilic pleural effusions. The triad of eosinophilia, subcutaneous swellings, and unexplained eosinophilic pleural effusion with a history of appropriate exposure should raise the suspicion of gnathostomiasis. The diagnosis is made by isolation of the larvae from the lesions, but this is usually not possible for visceral disease. Various serological tests are available, and in Europe the immunoblot detecting specific 24-kDa antigenic bands is mostly used [99]. Albendazole 400 mg twice daily for 21 days is the treatment of choice for pulmonary disease. Ivermectin 200 µg/kg for 2 consecutive days is a valid alternative.

Tropical pulmonary eosinophilia (Weingarten syndrome) is caused by an immune hyperresponsiveness to microfilariae trapped in the lungs. Since Wuchereria bancrofti and Brugia malayi are the main etiologies, the syndrome has also been termed “tropical filarial pulmonary eosinophilia.” Rarely, a similar hyperresponsive pulmonary syndrome, originally described by Löffler, can be cause by S. stercoralis and Ascaris or Schistosoma spp. [102]. Tropical pulmonary eosinophilia is common on the Indian subcontinent and in Southeast Asia and less frequent in South America and Africa. Males are affected four to seven times more than females [103].

The symptoms can easily be mistaken for asthma, and initial misdiagnosis is very frequent in nonendemic settings [104]. Most commonly cough, breathlessness, wheezing, and chest pain are reported, and symptoms are mostly nocturnal. Fever, weight loss, and fatigue may accompany the respiratory complaints. Evolution towards patchy nonprogressive pulmonary fibrosis is described [103]. Striking eosinophilia of > 3,000/µL that can reach as high as 80,000/µL together with high serum IgE levels is characteristic of tropical pulmonary eosinophilia. Filarial-specific IgE and IgG are markedly raised. The serology for W. bancrofti is positive in 35% of cases. Paradoxically, search of microfilaria in blood (the usual parasitological method for filarial diagnosis) is always negative, since a few trapped parasites are sufficient to cause a strong immune reaction. Response to a specific treatment with diethylcarbamazine 5 mg/kg/day for 4 weeks can therefore support the diagnosis. Steroids can be beneficial in case of severe symptoms. One in 5 patients relapses within 5 years [103].

This lung fluke occurs in Southeast Asia and the Far East as well as in Central and Western Africa [105]. In America, its distribution is limited to Central America and the north of South America. Paragonimus westermani is the species that causes most infections in humans. Humans are only an exceptional host. They become infected by eating raw freshwater crabs and river crayfish which contain infectious metacercariae [106]. Excysted larvae bore through the intestinal wall and migrate to the lungs via the abdominal cavity and diaphragm, where they develop into adult worms. The worms form a cavity 1–4 cm in diameter. They may also migrate to ectopic sites where they cause eosinophilic abscess. Mild infections are asymptomatic. In the acute stage (invasion and migration of the larvae) there may be diarrhea, abdominal pain, urticaria, and eosinophilia. This is followed by fever, thoracic pain, cough, dyspnea, and malaise. The chronic illness can mimic, as is often misdiagnosed as, tuberculosis with cavitary lesions, presenting mostly with recurrent cough and hemoptysis [107] and/or pleural effusion. Incubation can occasionally be extremely long [108]. The diagnosis is made by detection of eggs in sputum with concentration methods (e.g., mix sputum + water + potassium hydroxide, then centrifuge and examine the sediment). Pleural effusions with high eosinophilia can be found [109]. If sputum is swallowed, eggs may also be found in the feces. ELISA testing has a sensitivity and specificity > 90%. Praziquantel 75 mg/day for 3 days or triclabendazole 10 mg/kg twice on a single day are both very effective treatments (> 95% cure rates) [110, 111].

Acute schistosomiasis, an immune-allergic reaction on Schistosoma larvae (schistosomulae) which may involve the lungs, is almost never seen in immune migrants and will not be developed here. Severe and long-lasting schistosomiasis can lead to PAH related to chronic granulomatous inflammation, followed by scarring fibrosis, around embolized eggs trapped in the pulmonary capillaries. This syndrome may be partly reversible with praziquantel treatment, except when the fibrotic changes are already established at diagnosis. Recently, Italian researchers have identified a new clinical entity related to chronic schistosomiasis, characterized by chronic pulmonary nodules, sometimes symptomatic but usually incidentally diagnosed by chest X-ray, and corresponding to deposition of schistosome eggs [112]. Slow spontaneous cure seems to be the rule, but is accelerated by the administration of praziquantel. It is recommended to consider this condition in the differential diagnosis of chronic pulmonary nodules in (African) migrants since invasive diagnostic procedures can be easily avoided or postponed.

An estimated 174 million people worldwide have COPD [113]. Increased smoking prevalence in migrants in response to migration-related stress as well as acculturation pressures in the respective host countries [114, 115] can lead to significantly increased airway disease. Smoking-related COPD is well recognized as a major cause of morbidity and mortality worldwide. However, nonsmoking-related COPD is a further entity not commonly encountered in industrialized countries, but prevalent in the context of prolonged biomass smoke exposure. Exposure to indoor smoke from biomass fuels is estimated to account for 35% of COPD cases in low- and middle-income countries [116]. It is now increasingly recognized as a distinct small airways disease with different inflammatory phenotype [117, 118] and significantly less established emphysema than seen in cigarette smoking-associated COPD. Upper zone predominant bronchial anthracofibrosis is one manifestation that is typically seen in elderly women from rural settings [119]. Water pipe (shisha) smoking, which is more prevalent in some population groups, is also associated with an increased risk of COPD, oral cancer, and lung cancer [120].

Environmental and occupational toxin exposures linked to ILDs may have affected some refugees prior to their departure. Prolonged unsafe industrial working practices can lead to unusual and serious disease presentations, sometimes in very young individuals [121-123]. The range of potential hazardous exposures is vast, and a detailed occupational history is paramount. Extensive lung scarring will in many cases be related to previous tuberculosis, often without records of previous effective treatment.

Respiratory infectious diseases that are uncommon in high-income European countries can be encountered in refugees and migrants originating from regions where these diseases occur sporadically or where they are endemic. Some of these infections are very rare and geographically limited to certain regions, while others, such as strongyloidiasis and echinococcosis, have a wide distribution. Analogous to tuberculosis, some of the organisms can lead to a long-lasting latent or subclinical infection which can progress, even decades after the initial infection, to severe disease in the setting of immunosuppression. Also, noncommunicable diseases can be more prevalent in refugees and can have unusual risk factors. When the diagnosis and treatment of migrant patients with respiratory signs and/or symptoms is challenging, they should be referred to centers of excellence in order to ensure a correct diagnosis and improved treatment outcome.

The study has no funding. The authors have no conflicts of interest to declare.