Clinical and Epidemiological Characteristics of Imported Infectious Diseases in Spanish Travelers

Pilar Zamarrón Fuertes MD, Ana Pérez‐Ayala MD, José A. Pérez Molina PhD, MD, Francesca F. Norman MBBS, BmedSci, Begoña Monge‐Maíllo MD, Miriam Navarro MD, Rogelio López‐Vélez MD, DTM&H, PhD
DOI: 303-309 First published online: 1 September 2010


Introduction Spain could be a potential area in Europe for the development and spread of emerging diseases from the tropics due to its geoclimatic characteristics, but there is little information on infectious diseases imported by travelers. The aim of this article was to analyze clinical–epidemiological characteristics of infectious diseases imported by Spanish travelers from the tropics.

Methods A retrospective descriptive study of 2,982 travelers seeking medical advice who return ill from the tropics was conducted. Demographic data, details of travel (destination, type, and duration), preventive measures, clinical syndromes, and diagnoses were analyzed.

Results Nearly half (46.5%) the travelers had traveled to sub‐Saharan Africa; 46.5% reported a stay exceeding 1 month (and almost a quarter more than 6 months). Following pre‐travel advice, 69.1% received at least one vaccine and 35.5% took malarial chemoprophylaxis with variations according to geographical area of travel. In all, 58.8% of this took chemoprophylaxis correctly. Most common syndromes were fever 1,028 (34.5%), diarrhea 872 (29.3%), and cutaneous syndrome 684 (22.9%). Most frequent diagnoses were traveler's diarrhea (17.2%), malaria (17%), and intestinal parasites (10.4%). The three main syndromes in travelers to the Caribbean–Central America, Indian subcontinent–Southeast Asia, and other areas were diarrhea, fever, and cutaneous syndrome (p < 0.05); in sub‐Saharan Africa were fever, cutaneous syndrome, and diarrhea (p < 0.05); and in South America were cutaneous syndrome, diarrhea, and fever (p < 0.05). Travelers to sub‐Saharan Africa showed a higher frequency of malaria, rickettsiosis, filariasis, and schistosomiasis (p < 0.05); those to South America showed cutaneous larva migrants, other ectoparasitosis, and cutaneous/mucocutaneous leishmaniasis; and those to the Indian subcontinent–Southeast Asia showed intestinal parasitosis, arboviriasis, and enteric fever (p < 0.05).

Conclusions Increased international travel is a key factor for the development and spread of emerging pathogens. Information on these diseases is essential to establish early warning mechanisms and action plans. Spain represents a unique setting for this.

From 1950 to 2007, international tourist arrivals grew from 25 million to 903 million. While in 1950 the top 15 destinations accounted for 98% of all international tourist arrivals, in 2007 this proportion fell to 57%, reflecting the emergence of new destinations, many of them in developing countries. 1

Travel‐associated infections represent one of the leading causes of morbidity, with an estimated mortality of 2% to 3% in this group. The risk of acquiring an infectious disease during travel varies and is influenced, among other factors, by destination, type and duration of travel, exposure activities, and use of preventive measures such as vaccines or chemoprophylaxis. Overall, febrile syndrome is more common in travelers returning from sub‐Saharan Africa and Southeast Asia, acute diarrhea in those returning from Asia, and skin problems in those visiting sub‐Saharan Africa and the Indian subcontinent–Southeast Asia. 2,3

During 2007 Spain received 59.2 million of international tourist arrivals and approximately 700,000 immigrants, and this country has remained a bridge for movements between Europe and Africa. 4 Moreover, of the 11 million journeys abroad by Spanish travelers in that year, more than 10% were to the tropics and subtropics. 5 If the magnitude of these figures are considered in the context of presence of local vectors such as Anopheles atroparvus or Aedes albopictus, the proximity to Africa and the current climate changes, Spain may become a crucible where these factors could merge and contribute to the emergence of tropical diseases as occurred in the recent outbreak of Chikungunya in Italy. 6,7 Immigrants and international transfers will only be a risk if a specific vector would establish itself in Spain, or if a disease for which human‐to‐human transmission is possible.

Although there are some data in the medical literature on the potential risk for Spanish travelers, 8,9 there is little information on imported infectious disease in this group. These data represent a large sample of ill‐returned travelers from the tropics, thus completing the spectrum of imported diseases into Europe. This provides a reference for likely diagnosis analyzed according to destination among ill travelers seeking medical care. It is very important for physicians who need to know the epidemiology and clinical manifestations of tropical diseases.

The aim of this study was to analyze the clinical and epidemiological characteristics of infectious diseases imported by Spanish travelers to the tropics.

Materials and Methods

A retrospective and descriptive study of travelers returning from the tropics and attended at the Tropical Medicine Unit, Infectious Diseases Department of Hospital Ramón y Cajal in Madrid (Spain) during the period January 1989 to November 2006 was conducted. We excluded immigrant travelers (VFRs—Visiting Friends and Relatives) because these represent a population of travelers with very different characteristics.

The following variables were recorded: gender, age, time from return to consultation, travel characteristics (geographical area, duration, and type of travel), and prophylactic measures.

We evaluated clinical syndromes at consultation and final diagnoses made. Main diagnoses were analyzed based on the geographical area of travel and on the presenting clinical syndrome.

Geographical area of travel was divided into five areas: sub‐Saharan Africa, Central America–Caribbean, South America, Indian subcontinent–Southeast Asia, and other (North Africa, West Asia, East Asia, and Pacific islands).

Travel duration (three groups were defined) was categorized as: short term (≤30 days), medium term (>30 and <180 days), and long term (≥180 days).

Type of travel (four types were defined) was as follows: organized tours in the usual tourist routes (type A); tours outside the usual tourist routes (eg, as backpackers and hunters; type B); professional travel of short duration or repeated travel (eg, business travel and airline crews; type C); and professional travel in close contact with local environment (eg, aid workers, missionaries, and expatriates; type D).

Preventive measures were as follows: specific vaccinations for the trip (inside period of validity); correct/ adequate antimalarial chemoprophylaxis; and drug compliance and duration considered if appropriate dosing and duration of prophylaxis.

Five presenting clinical syndromes were analyzed: fever (body temperature ≥37.7°C); diarrheal syndrome, classified as acute diarrhea (≥3 loose stools in 24 h) or prolonged diarrhea (>2 weeks duration); eosinophilic syndrome (absolute number of eosinophils in peripheral blood ≥500/µl); cutaneous syndrome (presence of skin lesions, such as rash, pruritus, or ulcers); and respiratory syndrome (presence of dyspnea, pleuritic pain, hemoptysis, or coughing).

Final diagnosis was based on positive standard microbiological studies and other tests as indicated according to clinical manifestations. In those cases where a specific pathogen was not identified, diagnosis was established based on epidemiological/clinical data and response to empiric treatment. A single diagnosis may produce different clinical syndromes, and patients may present with several diagnoses, so the total number of syndromes and symptoms may exceed 100%. To simplify the analysis, the most common diagnoses were assigned to one of the following 20 diagnostic groups: malaria, traveler's diarrhea, filariasis, intestinal protozoa, intestinal helminthes, schistosomiasis, hepatic amebic abscess, acute viral hepatitis, mononucleosis‐like syndrome, HIV/sexually transmitted infections, dengue, other arboviruses, enteric fever, bacterial respiratory infection, rickettsiosis, latent tuberculosis infection, cutaneous larva migrans, other ectoparasitoses, cutaneous‐mucocutaneous leishmaniasis, and superficial mycoses. Infrequent diagnoses (those with a frequency of <10 cases) were also recorded.

Continuous variables were expressed as the mean and standard deviation when normally distributed, as the median and interquartile range (IQR) if distribution was skewed, and discrete variables as percentages. The Student's independent samples t‐test was used to compare continuous variables and the Mann–Whitney U‐test for continuous variables without a normal distribution. The association between categorical variables was evaluated using a chi‐squared test (when samples were of sufficient size) or with a Fisher's exact test. Magnitude of the effect was expressed as a 95% confidence interval. A p value of <0.005 was considered statistically significant.


A total of 2,993 travelers were included in the study; 11 of them were excluded because destination did not correspond with the areas included in the study. The total number of travelers analyzed was 2,982.

In total, 47.8% were women; median age was 35 years (IQR 28 to 40). Median time elapsed from return to consultation was 30 days (IQR 13 to 90).

Geographical areas of travel and number of travelers to each area are shown in Figure 1.

Figure 1

Geographical area of travel and number of travelers to each area.

The duration of travel in order of frequency was: short term in 1,594 (53.4%), long term in 710 (23.8%), and medium term in 678 (22.7%) cases.

The type of travel in order of frequency was: type A in 979 (32.8%), type B in 511 (17.1%), type C in 508 (17%), and type D in 984 (33%) cases.

The age of the traveler, duration, and type of travel depending on the geographic area visited are shown in Table 1.

View this table:
Table 1

Age of traveler, duration, and type of travel depending on the geographic area visited

Sub‐Saharan Africa, n = 1,387 (%)Caribbean–Central America, n = 575 (%)South America, n = 464 (%)Indian subcontinent–Southeast Asia, n = 418 (%)Others, n = 138 (%)Total, n = 2,982 (%)
Mean age36.132.934.933.536.535.06
Duration of travel*
 Short term616 (44.4)343 (59.7)255 (55)270 (64.6)110 (79.7)1,594 (53.5)
 Medium term323 (23.3)124 (21.6)115 (24.8)101 (24.2)15 (10.9)678 (22.7)
 Long term448 (32.3)108 (18.8)94 (20.3)47 (11.2)13 (9.4)710 (23.8)
Type of travel
 Type A602 (43.4)176 (30.6)135 (29.1)61 (14.6)10 (7.2)979 (32.8)
 Type B208 (15)62 (10.8)85 (18.3)142 (34)14 (10.1)511 (17.1)
 Type C321 (23.1)248 (43.1)153 (33)169 (40.4)88 (63.8)508 (17)
 Type D256 (18.5)89 (15.5)91 (19.6)46 (11)26 (18.8)984 (33)
  • *Duration of travel: short term (≤30 days); medium term (>30 and <180 days); long term (≥180 days).

  • Type of travel: type A (tours organized in the usual tourist routes); type B (tours outside the usual tourist routes, such as backpackers and hunters); type C (professional travel of short duration and repeated travel, such as business travel and airline crews); type D (professional travel in close contact with local population or environment, such as aid workers, missionaries, and expatriates).

In total, 2,062 had received a travel‐related vaccine (69.1%), and the median number of vaccines received was two (IQR: 1 to 4). In order of frequency, vaccines received were: yellow fever (79.1%), typhoid fever (55.9%), tetanus–diphtheria (44%), hepatitis B (40.6%), and hepatitis A (31.8%). Complete information was available regarding malarial chemoprophylaxis in 2,568 (86.08%) cases. In total, 1,059 (35.5%) had taken malarial chemoprophylaxis, with variations according to geographical area of travel: prophylaxis was used by 54.4% of travelers to sub‐Saharan Africa, 33.5% to Central Asia Southeast, 19.4% to South America, 11.5% to the Caribbean–Central America, and 5.1% to other destinations (p < 0.05). Of these 1,059, 623 (58.8%) took chemoprophylaxis correctly. This proportion varied depending on the drug used: 57 of 71 (80.3%) taking atovaquone–proguanil did so correctly, 274 of 409 (67%) taking mefloquine, 23 of 43 (53.5%) taking doxycycline, 193 of 379 (50.9%) taking chloroquine–proguanil, and 85 of 176 (48.3%) taking chloroquine; χ2 = 43.3 (p < 0.001).

More than 75% of the cases had one of the following five presenting syndromes: 1,028 (34.5%) febrile syndrome, 872 (29.3%) diarrheal syndrome, 684 (22.9%) cutaneous syndrome, 253 (8.5%) eosinophilic syndrome, and 223 (7.5%) respiratory syndrome. The remaining 25% had other syndromes which have not been analyzed in this study, such as cardiovascular syndrome or osteoarticular syndrome.

The major presenting clinical syndromes depending on the geographic area of travel are shown in Table 2.

View this table:
Table 2

The major clinical syndromes of consultation* depending on the geographic area of travel

SyndromesTotal, n (%)Sub‐Saharan Africa, n = 1,387 (%)Caribbean–Central America, n = 575 (%)South America, n = 464 (%)Indian subcontinent–Southeast Asia, n = 418 (%)Others, n = 138 (%)p
Febrile syndrome1,028 (34.5)532 (38.4)180 (31.3)112 (24.1)165 (39.5)39 (28.3)<0.05
Diarrheal syndrome872 (29.3)261 (18.8)230 (40)135 (29.1)179 (42.8)67 (48.6)<0.05
Cutaneous syndrome684 (22.9)300 (21.6)129 (22.4)148 (31.9)90 (21.5)17 (12.3)<0.05
Eosinophilic syndrome253 (8.5)147 (10.6)36 (6.3)32 (6.9)29 (6.9)9 (6.5)0.045
Respiratory syndrome223 (7.5)113 (8.1)44 (7.7)20 (4.3)41 (9.8)5 (3.6)0.008
  • *>75% of cases had one of these five syndromes.

Concerning final diagnoses, the most relevant in order of decreasing frequency were: 384 intestinal parasitoses (Giardia intestinalis 127, Entamoeba histolytica 67, Taenia saginata 28, Ascaris lumbricoides 15), 285 malaria (Plasmodium falciparum alone or mixed 166 and non‐P. falciparum malaria 119), 102 other ectoparasites (Sarcoptes scabiei 50, Tunga penetrans 30, myasis 24, Pediculus sp. 4), and 50 filariases (Loa loa 26, Onchocerca volvulus 17, Mansonella perstans 13, Dirofilaria sp. 1, and Wuchereria bancrofti 1).

Main diagnostic groups according to the presenting clinical syndrome are shown in Table 3. The most frequent etiologic diagnoses responsible for the different clinical syndromes are listed below: febrile syndrome—P. falciparum malaria (single and mixed infections) 153 (14.9%), traveler's diarrhea 256 (24.9%), non‐P. falciparum malaria 111 (10.8%), rickettsiosis 41 (4%), and dengue 40 (3.9%); diarrheal syndrome—diarrhea of unknown etiology 652 (74.8%), G. intestinalis 83 (9.5%), bacterial diarrhea 73 (8.5%) (Shigella sp. 28, Salmonella sp. 20, Campylobacter sp. 8), E. histolytica 48 (5.5%), and malaria 34 (3.9%); cutaneous syndrome—cutaneous larva migrans 69 (10.1%), scabies 49 (7.2%), superficial fungal infection 40 (5.8%), dengue fever 39 (5.7%), and spotted fever 32 (4.7%); eosinophilic syndrome—schistosomiasis 33 (13%) (Schistosoma haematobium 17), L. loa 21 (8.3%), O. volvulus 14 (5.5%), M. perstans 11 (4.3%), and cutaneous larva migrans 8 (3.2%); bacterial respiratory infection 32 (14.3%) (Mycoplasma pneumoniae 17, Chlamydia pneumoniae 5, Legionella pneumophila 5, Bordetella sp. 1, pneumonia with response to antibiotics 4); malaria 20 (9%); intestinal helminthiasis 13 (5.8%); and schistosomiasis 10 (4.5%). Uncommon diagnoses were tuberculosis (6), gnathostomiasis (5), toxoplasmosis (4), brucellosis (3), cystic echinococcosis (2), toxocariasis (2), leprosy (1), and visceral leishmaniasis (1).

View this table:
Table 3

The main diagnostic groups according to the presenting clinical syndrome

Febrile syndrome, n = 1,028
 Traveler's diarrhea of unknown etiology25624.9
 Bacterial respiratory infection343.3
Diarrheal syndrome, n = 872
 Traveler's diarrhea of unknown etiology65274.8
 Intestinal parasites19322.1
 Bacterial diarrhea738.4
 Enteric fever91
Cutaneous syndrome, n = 684
 Other ectoparasitosis9614
 Cutaneous larva migrans6910.1
 Superficial mycosis405.8
Eosinophilic syndrome, n = 253
 Intestinal helminthiasis135.1
 Other ectoparasitosis114.3
 Cutaneous larva migrans83.2
Respiratory syndrome, n = 223
 Traveler's diarrhea of unknown etiology4620.6
 Bacterial respiratory infection3214.3
 Intestinal helminthiasis135.8

Main diagnostic groups according to the geographical area of travel are shown in Table 4. When analyzing clinical syndromes of consultation and diagnostic groups by geographical area of travel, we found that in travelers to Caribbean–Central America, Indian subcontinent–Southeast Asia, and other areas, the three major presenting clinical syndromes, in order of frequency, were diarrheal syndrome, febrile syndrome, and cutaneous syndrome (p < 0.05). In travelers to sub‐Saharan Africa the main syndromes were febrile syndrome, cutaneous syndrome, and diarrheal syndrome (p < 0.05). In travelers to South America the most frequent syndromes were cutaneous syndrome, diarrheal, and febrile syndrome (p < 0.05).

View this table:
Table 4

Main diagnostic groups according to the geographical area of travel

DiagnosisSub‐Saharan Africa, n = 1,387 (%)Caribbean–Central America, n = 575 (%)South America, n = 464 (%)Indian subcontinent–Southeast Asia, n = 418 (%)Others, n = 138 (%)Totalp
Traveler's diarrhea of unknown etiology239(17.2)170(29.6)97(20.9)120(28.7)54(39.1)680(22.8)<0.05
Intestinal parasites144(10.4)86(15)68(14.7)70(16.7)16(11.6)384(12.9)<0.05
Other ectoparasites45(3)17(3)31(7)7(2)2(1)102(3.4)<0.05
Bacterial diarrhea22(1.6)18(3.1)15(3.2)23(5.5)7(5.1)85(2.9)<0.05
Cutaneous larva migrans22(2)15(3)22(5)10(2)069(2.3)0.001
Superficial mycosis34(2)10(2)15(3)6(1)4(3)69(2.3)0.364
Bacterial respiratory infection15(1)9(2)4(0.9)9(2.2)3(2.2)40(1.3)0.338
Acute viral hepatitis14(1)5(0.9)6(1.3)6(1.4)2(1.4)33(1.1)0.891
Enteric fever2(0.1)6(1)2(0.4)9(2.2)1(0.7)20(0.7)<0.05
MNL virus8(1)3(0.5)2(0.4)2(0.5)1(0.7)16(0.5)0.992
Cutaneous‐mucocutaneous leishmaniasis03(0.5)4(0.9)1(0.2)08(0.3)0.020
  • Other ectoparasites includes Sarcoptes scabiei, Tunga penetrans, Miasis, and Pediculus sp.

  • LTI = latent tuberculosis infection; HIV/STI = human immunodeficiency virus/sexually transmitted infections; AHA = amebic liver abscess; MNL virus = mononucleosis‐like virus.

Frequencies of diagnoses per 100 travelers according to geographical area of travel are shown in Figure 2. Comparing the geographical areas, travelers to sub‐Saharan Africa had a greater incidence of malaria, rickettsiosis, filariasis, and schistosomiasis (p < 0.05). Travelers to South America showed a higher frequency of ectoparasitoses, cutaneous larva migrans, and cutaneous/mucocutaneous leishmaniasis (p < 0.05). Travelers to Southeast Asia–Indian subcontinent suffered from intestinal parasites, enteric fever, and arboviriasis more frequently (p < 0.05). Travelers to other areas had a higher frequency of traveler's diarrhea (p < 0.005).

Figure 2

Frequencies of diagnoses per 100 travelers depending on the geographical area of travel.For a better understanding, decimals of percentages are rounded up and only statistically significant data have been represented.*Traveler's diarrhea with non‐filiated etiology.Other ectoparasites includes Sarcoptes scabiei, Tunga penetrans, Miasis, and Pediculus sp.C‐MC leishmaniasis = cutaneous‐mucocutaneous leishmaniasis.


This retrospective study of nearly 3,000 patients represents the largest series of infectious diseases imported by travelers described in Spain. The study center is located in a tertiary referral hospital where patients from Madrid usually come with more complex pathology, as the diagnosis and treatment of minor illnesses are usually performed in primary care centers and more acute diseases are seen by emergency services. As the travelers are referred to a specialist center may be do not reflect conditions in returning travelers per se. Nearly half (46.5%) of the travelers had travelled to sub‐Saharan Africa, and 46.5% reported a stay exceeding 1 month (and almost a quarter more than 6 months). The average time from return to presentation was 30 days and these characteristics may be associated with an increased complexity of disease processes. These aspects should be taken into account when considering the results as they may explain the increased proportion of typical tropical diseases (including filariasis) and diseases with longer incubation periods at the expense of other more global infections with shorter incubation periods (such as traveler's diarrhea).

There was a higher rate of vaccination in this series (69.1%) when compared with the results of another study of Spanish travelers to destinations at risk in the tropics (55.5%), 9 and this could be explained by the higher number of travelers to sub‐Saharan Africa in the current study (countries which often require yellow fever vaccination). In fact, 79% of the travelers included in the study had been vaccinated against the disease. The high rate of hepatitis B vaccination (40.6%) may also be explained by the large number of travelers who had visited the tropics on repeated occasions (43.1%), and expatriates and aid workers (18.5%) in whom vaccination against hepatitis B is usually indicated. However, less than one third (31.8%) of travelers had been vaccinated against hepatitis A, probably because, until recently, Spain was considered an endemic country and vaccination was not routinely recommended for travelers aged more than 35 years (the average age of travelers in this series was 35 years).

The overall percentage of patients who took antimalarial chemoprophylaxis (42.1%) was similar to other studies, 10 but lower among those returning from sub‐Saharan Africa (56.2%) compared with healthy Spanish travelers (64.6%) to the same geographical area. The fact that mainly unwell returning travelers were seen at the unit could explain this observation. 9 The best reported correct use was in those who received atovaquone–proguanil, probably due to its better tolerability, even in prolonged treatments. 11

The most frequent presenting clinical syndromes in this series were febrile syndrome (34.5%), diarrheal syndrome (29.3%), cutaneous syndrome (29.3%) eosinophilic syndrome (8.5%), and respiratory syndrome (7.5%). The frequency of diagnoses varied depending on the geographical area of travel with malaria, filariasis, schistosomiasis, and rickettsiosis being the most frequent in sub‐Saharan Africa, arboviriasis and enteric fever the most frequent in the Indian subcontinent–Southeast Asia, and cutaneous/mucocutaneous leishmaniasis in South America. When analyzing presenting clinical syndromes by geographical area of travel, as in other published series, febrile syndrome was more common in travelers from sub‐Saharan Africa and diarrheal syndrome in travelers from Indian subcontinent–Southeast Asia and Caribbean–Central America as found in other published series. However, unlike other series done in specialist units, where diarrheal syndrome represents the most frequent reason for consultation in patients from South America, in our series, in this group the most frequent clinical syndrome was cutaneous syndrome. 3,10,12–14

In other general series of travelers to all destinations, febrile syndrome is always one of the three most common (up to 22%), and the most frequent causes are traveler's diarrhea, malaria, and arboviruses. In travelers from sub‐Saharan Africa, as in this series, febrile syndrome is the most frequent and malaria is the main cause (27%–34%). 14–18 Rickettsiosis is a major cause of febrile syndrome in travelers to Southern Africa. 3

In most of the published series, diarrheal syndrome is the most frequent (up to 55%), with bacterial infections of unknown etiology as the leading cause (20%), but in this series there were more of the latter (34.7%), because enteropathogenic Escherichia coli was not specifically identified. E. coli is the major cause of traveler's diarrhea according to the literature, and in this series Shigella sp., Salmonella sp., Campylobacter sp., and G intestinalis were the most frequently isolated bacterial agents and parasites which are the next most frequent causes of traveler's diarrhea in published studies. 10,12,19–23

As in this series, cutaneous syndrome is usually the third or fourth cause for consultation (20%), and the most frequent causes were cutaneous larva migrans, other ectoparasites and bacterial infections, and arboviruses as the main causes of rash. 3,12,13,24–30

Eosinophilic syndrome is the most common hematologic disease (up to 8%) in travelers and is associated more frequently with travel to sub‐Saharan Africa, the most frequent cause being schistosomiasis, and more rarely other pathogens. 31–34 In this series, filarial infections predominated primarily in long‐term travelers to West Africa, where such diseases are endemic. 35

Respiratory syndrome was diagnosed with a similar frequency to cutaneous syndrome, with viral infections being the most common cause. For lower respiratory tract infections of bacterial origin, L. pneumophila, M. pneumoniae, and C. pneumoniae were the most frequent pathogens identified as shown by others. 36,37

In conclusion, these results are similar to other international series, excepting the higher rates in vaccination, probably explained by the special features of this series, as we have commented previously. It is important to take into account other factors as type and duration of travel, which will be deeply analyzed in another study.

Increase in international travel is one of the leading factors for the development and spread of emerging pathogens. Imported tropical infectious diseases in Spain represent a burden for the medical system and can be of potential public health risk for people in the country. Adequate information on imported infectious diseases is of importance.

Declaration of interests

The authors state they have no conflicts of interest to declare.


The clinical research team acknowledges the support provided by the Red de Investigación de Centros de Enfermedades Tropicales (RICET). RED: RD06/0021/ 0020.


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