Neglected tropical diseases: diagnosis, clinical management, treatment and control

DOI: https://doi.org/10.4414/smw.2012.13727

Introduction

Diseases such as malaria, tuberculosis and HIV/AIDS are well known causes of major global mortality, morbidity and burden. Their negative impact on the social and economic development of the most severely affected countries has been emphasised [1–4]. Indeed, these “big three” are responsible for several million deaths every year and tens of millions of disability-adjusted life years (DALYs), which, in turn, exacerbates poverty [5–8]. Interestingly though, in two short assays pertaining to science, medicine and society, along with a comprehensive 25-year review of drug development efforts, published in leading journals a decade ago [9–11], malaria, tuberculosis and HIV/AIDS were still considered neglected diseases. In the meantime, funding for research and development of new tools has come to scale, and public-private partnerships and numerous initiatives have been put into place for the prevention, control and eventual elimination of the “big three”. Clearly, the creation of the Global Fund to Fight AIDS, Tuberculosis and Malaria, in 2002, considerably altered the funding landscape, and large-scale implementation of control interventions has saved millions of lives [7, 12–14].

However, a host of viral, bacterial, ectoparasitic, fungal, helminth and protozoal diseases that occur mainly in the tropics and subtropics remain truly neglected, and hence the phrase “neglected tropical diseases” [15–18] is applied to characterise these diseases. Reasons for this neglect are many-fold. Among others, important issues are the intimate connection of these diseases with poverty, geographical isolation, stigmatisation, paucity of data regarding local and global burden estimates, insufficient political and financial resources for their control, lack of lobbies for the most vulnerable population groups who are most severely affected by these diseases, and fragmented funding mechanisms [16, 19–22].

In the present review, we provide an overview of the neglected tropical diseases from a global perspective. We first address the question why and when this “brand-name” was coined, including implications for advocacy, policy, public health and research. Second, we put forth a comprehensive list of neglected tropical diseases, their causative agents and geographical distribution and highlight their importance for tourists, returning travellers, long-term expatriates and migrants in Switzerland. Given the large and growing size of the list, we then focus on the most important neglected tropical diseases, and characterise them in terms of the at-risk population, number of infections, mortality rates and global burden estimates. Knowledge gaps are identified and briefly discussed. The centre-piece of our review pertains to the diagnosis, clinical management and treatment of neglected tropical diseases. Emphasis is placed on helminth and protozoal infections and we focus on the situation in Switzerland within the global perspective. Hence, throughout our review, we highlight issues that are of particular relevance for the general practitioners, clinicians and reference laboratory personnel in Switzerland. We believe that issues discussed are central also for other countries in Europe, North America and elsewhere.

Neglected tropical diseases

Origin of a ‘brand-name’

A search on PubMed, performed on 19 September 2012, using the term “neglected tropical diseases”, revealed 730 hits. This search brought to bear that the first articles, editorials and personal viewpoints using the term “neglected diseases” in the title appeared in 2001/2002. For example, an interesting case study from India discussed the need for establishing local research and development capacity for neglected infectious and tropical diseases, emphasising medicines [23]. The lack of funds for research and development and the obviously limited interest of the industry to invest in diseases of poverty made this term necessary for researchers as well as public and private investors. In the same vein, a systematic review covering a 25-year period (1975–2000) revealed that virtually no new chemical entities were specifically developed for neglected diseases [10]. Hence, the need for efficacious, safe, easy-to-use and affordable drugs was discussed at a conference organised by Médecins Sans Frontières in early 2002 [9]. The pivotal role of public-private partnerships to stimulate discovery, development and deployment of new drugs for neglected diseases was stressed. This resulted, in 2003, in the creation of the Geneva-based Drugs for Neglected Diseases initiative (DNDi; http://www.dndi.org) [10, 11, 24]. Of note, the paucity of accurate, robust and rapid diagnostics for one of the “big three” motivated the Bill & Melinda Gates Foundation (BMGF) to put forward a 5-year start-up grant, which helped to set up, also in 2003 and again based in Geneva, the Foundation for Innovative New Diagnostics (FIND; http://www.finddiagnostics.org/). FIND has gradually expanded its portfolio of activities with a growing emphasis on developing and validating novel diagnostics not only for tuberculosis, but also the other two of the “big three”, as well as truly neglected diseases, such as human African trypanosomiasis, leishmaniasis and Chagas disease [25, 26].

The first published paper with the full term “neglected tropical diseases” in the title was a piece put forward by Molyneux, Hotez & Fenwick, in November 2005 in PLoS Medicine [15], closely followed by another landmark paper in the same journal written by Hotez and colleagues [16]. The authors discussed a strategy of regular, large-scale administration of drugs for morbidity control due to neglected tropical diseases, and outlined how this drug-based intervention could be integrated within the control of the “big three”. An accompanying expert commentary critically examined the strengths and limitations of the proposed strategy [27]. A subsequent review by Hotez and colleagues entitled “Neglected tropical diseases”, published in the New England Journal of Medicine clearly demonstrated that the term “neglected tropical diseases” had become mainstream [28].

Of note, in October 2007, the Public Library of Sciences published the inaugural issue of a new open-access journal, PLoS Neglected Tropical Diseases [29]. As of late September 2012, more than 1,600 original research papers, editorials, expert opinions, viewpoints and other magazine-type articles have been published. In Swiss Medical Weekly, thus far, only a single article has been published when entering the search term “neglected tropical diseases” [30].

What is meant by neglected tropical diseases?

Neglected tropical diseases refer to a group of mainly chronic, debilitating and often stigmatising diseases that primarily affect the poorest of the poor living in remote rural and deprived urban settings of tropical and subtropical countries [16, 18, 21, 31–33]. Typical features of the neglected tropical diseases are their intricate interrelationships with poverty and social-ecological systems [21, 34, 35]. These diseases are associated with negative effects on the course and outcome of pregnancy, delayed physical and intellectual development during childhood and reduced working productivity in older age [28, 36].

Evolving scope of the neglected tropical diseases

The two seminal papers published in 2005 and 2006 provided a list of 15 neglected tropical diseases, 13 of which were deemed of particular importance in terms of annual mortality rates and global burden [15, 16]. This list of 15 diseases formed the initial scope of PLoS Neglected Tropical Diseases. Included were nine helminth infections (cysticercosis/taeniasis, drancunculiasis [guinea worm], food-borne trematodiasis, lymphatic filariasis, onchocerciasis, schistosomiasis and the three main soil-transmitted helminthiases [ascariasis, hookworm infection and trichuriasis]), three protozoal infections (Chagas disease, human African trypanosomiasis and leishmaniasis) and three bacterial infections (Buruli ulcer, leprosy and trachoma).

Interestingly, at the time, the World Health Organization (WHO) featured some additional diseases on their list of neglected tropical diseases, namely cholera/epidemic diarrhoeal disease, dengue/dengue haemorrhagic fever and endemic treponematoses (e.g., yaws, pinta and syphilis) [18, 37]. Meanwhile, the list of neglected tropical diseases has been further expanded and currently comprises over 40 diseases, which is reflected in the escalating scope of PLoS Neglected Tropical Diseases [38]. Table 1 provides a comprehensive overview of these 40+ neglected tropical diseases, stratified into helminth, protozoal, bacterial, fungal, viral and ectoparasitic infections. For each disease, the causative agent(s) and the current endemic areas are summarised. Moreover, the presence, management and relative importance of these diseases for tourists, long-term travellers and migrants in Switzerland is given, based on a combination of national statistics, case reports, the authors’ collective expertise and experience and useful input from two anonymous referees.

Global burden of neglected tropical diseases

Table 2 summarises the main parasitic neglected tropical diseases (helminth and protozoal infections) in terms of the at-risk population, number of infections, annual mortality rates and global burden of disease estimates. For comparison, the “big three” are also listed in table 2. Some authors have argued that the collective global burden due to the 13 most important neglected tropical diseases exceeds that of malaria and tuberculosis and is close to that of HIV/AIDS [16], which spurred advocacy for the integrated control of neglected tropical diseases [17, 39, 40]. Indeed, according to data presented by Hotez and colleagues, which is largely derived from technical reports of WHO and the annex table 3 of the world health report 2004, the collective global burden of the initial set of 13 neglected tropical diseases amounts to 56.6 million DALYs, which is higher than that due to malaria (46.5 million DALYs) and tuberculosis (34.7 million DALYs). However, it must be noted that there are considerable uncertainties regarding global burden estimates, and the neglected tropical diseases proved particularly challenging for estimating global burden estimates [18, 41–43]. For example, two different WHO sources reveal a more than 300-fold difference regarding the estimated global burden due to hookworm infection. While the lower estimate is as little as 59,000 DALYs [44], the upper estimate is 22.1 million DALYs [45] with the difference mainly explained by whether or not anaemia is partially accounted for by hookworm infections. It is hoped that current efforts to re-estimate the global burden of more than 175 diseases, injuries and risk factors will fill current gaps and resolve discrepancies [46].

Diagnosis

While the primary indices of an infection are mostly the presentation of clinical signs and symptoms, outcomes due to an infection with neglected tropical diseases are often unspecific, if signs and symptoms are present at all. Yet, an accurate and early diagnosis is important for adequate patient management and treatment [47–49]. The lack of rapid, accurate, simple-to-use, point-of-care tests for many of the neglected tropical diseases is an important feature for their general neglect and the under-appreciation of their disease burden [50, 51].

The diagnosis of neglected tropical diseases, and particularly the detection of the endoparasitic infections emphasised here, is primarily based on well established and widely used laboratory techniques, such as the examination of blood, stool and urine samples under a microscope. As shown in table 3, the mainstay to detect intestinal helminths and protozoan infections is the visualisation of helminth eggs or larvae and protozoan cysts or trophozoites, respectively, in stool smears [50, 52–54]. Lymphatic filariasis, acute or congenital Chagas disease and human African trypanosomiasis are diagnosed through the microscopic identification of microfilariae or trypomastigotes in blood and other body fluids [55–60]. Leishmaniasis is confirmed by the isolation and visualisation of the amastigote parasite stage from tissue [61–63]. Noteworthy, the reliable identification of parasitic infections requires in-depth training for specimen preparation, and expertise and experience for subsequent microscopic examination. While microscopy of parasites is considered as highly specific, its sensitivity depends on the intensity of infection, which is a function of the number of parasitic elements in a sample [49, 64, 65].

For the diagnosis of chronic Chagas disease, echinococcosis, toxocariasis and trichinellosis, the direct documentation of the infecting parasite is difficult and immuno-assays as well as physical imaging techniques or trichinelloscopy, respectively, are applied [54, 60, 66–68].

Immunodiagnosis is applicable for most of the neglected tropical diseases, but may lack sensitivity and/or specificity. While some serological tests show excellent performance (i.e., for the diagnosis of Chagas disease and visceral leishmaniasis), or are particularly useful when parasite loads are low or for patients from non-endemic countries (i.e., for the diagnosis of schistosomiasis and strongyloidiasis), others are highly error-prone. For example, antibodies produced against one helminth species are known to cross-react with antigens from other helminths [66, 69]. Moreover, antibodies produced against infectious agents do not give any indication of the severity of infection [70], and are often detectable for several months or years after an infection has cleared, and hence do not allow to distinguish between current and past infections [71–74]. In European clinics specialised for returning travellers and migrants, immunodiagnosis applied in combination with physical imaging or microscopy, and particularly in consideration of disease history and clinical outcome, is a valuable tool for the assessment of neglected tropical diseases. The commercial availability of standardised test kits is still the exception rather than the norm. Indeed, often high-valuable in-house antigen preparations and tests are in use, but efforts are underway to develop rapid diagnostic tests that can be used at the point-of-care in developing countries [51].

The development and use of molecular tools such as polymerase chain reaction (PCR) tests for the diagnosis of neglected tropical diseases is the focus of multiple research groups, but the commercial availability of DNA amplification kits is rare. Moreover, the isolation of parasite DNA from stool or tissue is challenging, cumbersome and quite often not fruitful at all [72]. Nevertheless, progress has been made with molecular high-throughput multiplexing. For example, multiplex real-time PCR assays have been developed and are increasingly being utilised in a specialised laboratory in Leiden, the Netherlands for differential diagnosis of helminths and intestinal protozoan infections [75–77]. Hence, according to some authors, multi-parasitic screenings based on molecular assays might one day replace microscopy and immunodiagnosis, at least in specialised laboratories in the industrialised world [78]. An advantage of microscopy though, is that it is an untargeted approach, and hence well trained laboratory technicians might detect an infection that would have been missed by a more targeted molecular approach [50].

As discussed in the next section under the example of clinical management of strongyloidiasis, to avoid false negative results due to the lack of sensitivity of any single diagnostic technique, examination of multiple specimens obtained over consecutive days and the combination of different methods is recommended [74, 79, 80]. The development of advanced and standardised sensitive diagnostic approaches that are practicable and affordable not only in well equipped laboratories of the North, but also in developing country settings is of prime importance to identify and tackle neglected tropical diseases [81].

Clinical management

General considerations

The signs and symptoms of the various neglected tropical diseases are perhaps as diverse as the different infectious agents involved in their pathogenesis. The spectrum of possible clinical presentations ranges from asymptomatic infection to fulminant life-threatening or to chronic debilitating conditions. As virtually all organs can be affected, a high suspicion index and knowledge about the different groups of tropical pathogens can assist clinicians for an early recognition and timely diagnosis of these infections in returning travellers, long-term expatriates, migrants and patients from endemic areas, based on knowledge of the respective geographical epidemiology. Clinical signs and patient complaints are often indistinctive, thus seldom allowing a specific diagnosis based on history and clinical examination alone without knowledge of epidemiology and further diagnostic work-up.

Table 4 comprises common clinical presentations of selected parasitic neglected tropical diseases. Despite many similarities, some infections exhibit unique features clinicians should know about, as they may be encountered in the tropics as well as in temperate regions (e.g., in Switzerland and elsewhere in Europe). Due to space restrictions in this review, only two neglected tropical diseases are presented in greater detail: (i) strongyloidiasis (a helminth infection that might be fatal in immunocompromised patients) and (ii) leptospirosis (a bacterial infection that might cause outbreaks and is emerging in Europe). For a third example – Chagas disease (caused by a protozoon infection that is emerging in Switzerland due to the growing number of Latin American migrants) – the reader is referred to a recent excellent review by Jackson and Chappuis [82].

Strongyloidiasis

While the three main soil-transmitted helminth species (i.e., Ascaris lumbricoides, Trichuris trichiura and hookworm) are easily diagnosed and cause mainly chronic, often asymptomatic infections that usually respond well to empiric treatment with albendazole or mebendazole, particular attention has to be paid to the diagnosis and clinical management of Strongyloides stercoralis (threadworm). Figure 1 shows the life cycle of S. stercoralis. In contrast to the common soil-transmitted helminths [54, 83], S. stercoralis is able to replicate within the intestines of infected individuals for long time periods (autoinfection) [54, 84]. The larvae hatch in the gut and are able to penetrate the intestinal mucosa, from where they may spread to all organs [85]. As these tissue-invasive larvae carry bacteria on the surface, their migration can lead to systemic infections with septicaemia, leading to a high fatality rate (hyperinfection syndrome). Such dissemination may occur even decades after the first contact, so that the absence of recent travel to endemic areas is never sufficient to exclude strongyloidiasis as a potential differential diagnosis in symptomatic patients. Asymptomatic strongyloidiasis must be ruled out in patients requiring immunosuppressive treatment who may have experienced exposure, as this parasite may flare up as a life-threatening infection. Symptoms may be absent or unspecific in healthy individuals, but can rapidly evolve in immunosuppressed hosts [86].

Figure 1

Life cycle of Strongyloides stercoralis. (Adapted from Olsen A, van Lieshout L, Marti H, Polderman T, Polman K, Steinmann P, et al. Strongyloidiasis – the most neglected of the neglected tropical diseases? Trans R Soc Trop Med Hyg. 2009;103:967–72 [85]. © Elsevier, 2009. Printed with permission).

The diagnosis of S. stercoralis is challenging, as microscopy of stool samples usually fails to detect the larvae (table 3). Hence, more laborious techniques have to be employed (e.g., agar plate culture and Baermann funnel technique), but the sensitivity of these methods is usually limited [80]. Multiple examinations and the combination of techniques enhance the diagnostic sensitivity [79, 80, 87, 88]. The direct demonstration of larvae in bronchoalveolar lavages, bronchial or duodenal aspirates or faecal specimens proves S. stercoralis infection, but lacks sensitivity in patients with low worm loads. Recent advantages in serology, the development of a faecal antigen-capture enzyme-linked immunosorbent assay (ELISA) for S. stercoralis and the ongoing validation of a PCR approach will help to further improve the diagnosis of strongyloidiasis [84, 88, 89].

Frequently affected organs are the gastrointestinal tract, the skin and the lungs, whereas the central nervous system (e.g., meningitis) is rarely affected (table 4). Possible symptoms and clinical observations are diarrhoea, abdominal bloating and tenderness, a skin rash, pruritus ani, wheezing on pulmonary auscultation and chronic cough. A distinctive, fast-moving cutaneous itchy eruption called “larva currens” is sometimes observed by the patient and peripheral blood eosinophilia is suggestive of parasitic infection, but not always present.

Disseminated infection should always be excluded in patients on immunosuppressive long-term treatment, especially organ transplant recipients (e.g., following renal transplantation), and in symptomatic individuals from endemic areas with a history of chronic alcohol abuse [90] or HTLV-1 co-infection, which is common in Japan, Jamaica, South America, sub-Saharan Africa and parts of Asia [91]. Corticosteroids appear to activate hormone receptors of S. stercoralis larvae and might mediate the development of a hyperinfection syndrome [92]. Hence, patients from endemic areas should be screened for asymptomatic strongyloidiasis before starting immunosuppressive medication. Due to the broad range of possible clinical presentations, the decision to treat a patient suspected of carrying S. stercoralis remains challenging. An indication for treatment is usually given if at least two of the following observational criteria are met: (i) pulmonary, abdominal and/or skin symptoms, (ii) elevated peripheral eosinophil count and (iii) positive serology [93]. However, all patients with a positive S. stercoralis serology prior to organ transplantation should be treated to avoid the development of a life-threatening hyperinfection syndrome. Recommended treatment options include albendazole and ivermectin, whereas the latter has become the drug of choice to treat strongyloidiasis [36, 92].

Leptospirosis

Leptospirosis is probably the most common zoonosis affecting humans worldwide, with the highest disease burden encountered in tropical and subtropical countries [94, 95]. Figure 2 depicts its life cycle. In brief, bacteria of the genus Leptospira are spirochetes, able to survive in the environment for long time periods of time, especially in warm and humid areas [95]. Pathogenic Leptospira spp. infect many different kinds of mammals (e.g., rodents, pigs and dogs), which excrete the bacteria in their urine. Human infection occurs either by direct contact with infected animals or indirectly through contact with urine-contaminated water or soil. As the spirochetes easily penetrate human skin, farmers using traditional methods of irrigating their fields are at an elevated risk of infection [96]. While recreational sources (e.g., adventure travellers and water-based sports activities) account for most leptospirosis cases and outbreaks in industrialised countries, close contact with infected animals and a contaminated environment remain the major source of infection in most tropical countries, particularly in social-ecological contexts characterised by traditional agriculture and crowded urban settings, where inadequate sanitation and poverty prevail [96, 97].

Figure 2

Life cycle of pathogenic Leptospira spp., the infectious agents of leptospirosis.

Outbreaks accounting for thousands of deaths worldwide underline the importance of leptospirosis as a re-emerging, yet severely neglected infectious disease. It is widely under-recognised due to difficult, poorly standardised diagnosis and often mild and unspecific clinical presentations. It is estimated that more than 500,000 severe cases occur annually around the world [98] with a recent trend towards a higher proportion of infections with severe pulmonary haemorrhages in endemic populations [99].

The typical combination of high fever, chills, calf myalgia, headache and an abrupt onset of disease in the early stage is seldom present, so that clinicians should include leptospirosis in their differential diagnosis in any unexplained febrile illness when risk factors for infection are present. In a second disease stage, multiple organ failure may occur. Hepatic dysfunction leading to jaundice and acute renal failure are relatively frequent, but as a result of haematogenous spread, every organ including the central nervous system (e.g., meningitis, meningoencephalitis) can be affected. Laboratory confirmation of leptospirosis, e.g. by microscopic agglutination test, is difficult and often time-consuming, expensive, relatively insensitive and not available in many diagnostic centres, especially in the developing world [100]. Rapid serological testing, e.g. by an ELISA detecting Leptospira-specific IgM antibodies, is easy to perform and recommended by the WHO in resource-constrained settings. The introduction of such assays represented a major step forward, as they are increasingly becoming available throughout the tropics and allow rapid confirmation of the diagnosis of suspected leptospirosis cases. The diagnostic accuracy of the IgM assay, however, has been reported to vary in different settings [101, 102]. If severe leptospirosis is suspected, patients should receive early antibiotic treatment with doxycycline, penicillin G or ampicillin, even if recent meta-analyses question the clinical benefit of such therapeutic regimens [103]. Supportive treatment in the case of organ failure (e.g., haemodialysis for acute renal failure) is essential, while uncertainty remains regarding the use of immunosuppressive medication [96].

Treatment

Table 5 summarises the most widely used drugs and treatment schemes for parasitic neglected tropical diseases. We distinguish between large-scale community-based drug interventions (an approach phrased “preventive chemotherapy” [36]) that have become the key strategy in resource-constrained settings of the developing world on one hand, and individual patient management as applied in Switzerland and other non-endemic settings on the other hand. For example, while in Switzerland mebendazole is used as 100 mg two times daily for three days in the treatment of common soil-transmitted helminthiases, a single dose of 500 mg is administered in preventive chemotherapy programmes in endemic settings. Given the ease of administration of the latter treatment scheme, as a result, non-medical personnel (e.g., school teachers) can deliver these drugs to large populations (e.g., all children in a school) as a public health measure [36]. A disadvantage, however, is that the efficacy of single doses is often lower than multiple dosing. For example, while overall cure rates of 63–89% have been reported for multiple doses of mebendazole against T. trichiura infection, the cure rate of single-dose mebendazole is considerably lower (36%) [104]. Nevertheless, in terms of parasite burden reduction (indirectly measured by egg reduction rates), single dosing usually results in high efficacy. Hence, preventive chemotherapy has been endorsed by WHO as the key strategy for morbidity control and tens of millions of people in developing countries are treated every year [28, 36, 105–108].

It is interesting to note that the neglected tropical diseases are often classified on the basis of available control tools, hence separating between “tool-deficient” (costly and difficult to manage) and “tool-ready diseases” (safe and highly efficacious drugs available for large-scale administration by personnel outside the health sector) [36]. While the helminth diseases summarised in tables 1 and 2 would fall into the category of “tool-ready diseases”, for T. brucei rhodesiense, currently available drugs cause serious adverse events in a considerable proportion of all treated patients [58, 109].

Prevention and integrated control

While the unit of intervention to address the neglected tropical diseases in the developing world is often at the population level (e.g., many of the helminth infections), some diseases require enhanced patient management (e.g., Buruli ulcer and human African trypanosomiasis). Clearly, the advent of safe, efficacious and cheap drugs that can be administered by non-health personnel spurred the way for preventive chemotherapy [36]. It should be noted, however, that this strategy has several shortcomings. For example, it is difficult to reach some of the most vulnerable population groups. Moreover, compliance is an issue, particularly when interventions must be repeated once or twice a year for an unknown period of time. Indeed, a growing number of people might feel healthy, and hence might not appreciate the need for repeated treatment. Growing drug pressure must be carefully monitored in terms of potential resistance development. Importantly, rapid reinfection occurs, as preventive chemotherapy does not address the root behavioural, ecological and socio-economic causes [18, 110]. These issues call for preventive measures, such as improved access to clean water, sanitation and hygiene have to been emphasised [18, 111, 112]. Whenever resources allow, integrated control approaches should be pursued (i.e., implementation of a set of interventions that are readily tailored to an endemic setting and adapted over time). This will require a deep understanding of the demographic, health and social-ecological systems contexts [18].

In Switzerland and other industrialised countries, the focus is on the individual patient, in line with a growing emphasis on personalised health care. However, preventive measures (e.g., raising awareness among travellers about common risk factors and mitigation strategies for neglected tropical diseases in endemic countries) [113, 114] are as important as adequate patient management of the returning traveller and migrants.

Conclusions

Starting with an initial set of 13–15 diseases, there are now over 40 helminth, protozoal, bacterial, viral, fungal and ectoparasitic infections covered under the brand-name of the neglected tropical diseases. Important gaps in our understanding of the epidemiology and control of many of the neglected tropical diseases remain, which calls for additional funding, so that innovative research will eventually lead to new validated tools and strategies that can be applied in the field. Although rarely seen in industrialised countries, specific signs and symptoms should prompt physicians to rule out neglected tropical diseases, particularly among travellers, expatriates and migrants with a history of geographical and behavioural exposure to disease-endemic areas. Importantly, many of those infections are easily and effectively treated with short oral drug regimens (e.g., soil-transmitted helminthiasis, including strongyloidiasis). Other neglected tropical disease may cause extensive and more costly investigations (e.g., leishmaniasis, leprosy). In many cases, additional advice from, or referral to specialists in tropical medicine is recommended for more detailed laboratory and clinical work up. Due to the growing importance of neglected tropical diseases in Switzerland and elsewhere in Europe, partially driven by enhanced international travel, trade and migration, efforts should be made by scientific societies and networks (e.g., Network for Education in International Health, tropEd in short) to train and inform general practitioners on the prevention, diagnosis, treatment and management of neglected tropical diseases, including proper referral when need be.

Acknowledgements: We thank Professor André Perruchoud very much indeed for the kind invitation to prepare this review pertaining to neglected tropical diseases for Swiss Medical Weekly and are grateful to the entire editorial team for the patience to have our final product delivered. We thank Dr. Hanspeter Marti, Dr. Peter Steinmann and Ms. Yvette Endriss from the Swiss Tropical and Public Health Institute and Dr. Laura Rinaldi and Ms. Paola Pepe from the University of Naples for pictures and hand-drawings for the two life cycles.

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