For many years, most of the information and research in the field of allergy came from developed countries in both the northern and southern hemispheres. In contrast, knowledge about allergies and asthma in low and middle income countries in the tropical areas is relatively low; nonetheless, more insights on the burden, triggers, and management of these have increased over the last decades.

The Tropics is a very dynamic region surrounding the Equator with a vast biodiversity and climatic variability, ranging from warm to hot and moist year-round. Tropical rainforests have their rainfall equally distributed throughout the year. In addition, climate change could have a big impact on the region, having an influence not only on the climate of the Tropics by itself but also on its biodiversity. The northern limit of the Tropics is the Tropic of Cancer, whereas the limit in the southern hemisphere is the Tropic of Capricorn (23 ° 26’ 16” north and 23 ° 26′ 16″ south, respectively). The Tropics is also called the tropical zone or the Torrid Zone due to very hot usually dry temperatures. All twelve months have mean temperatures above 18 °C (64 °F). In the Tropics the sun’s rays are hitting the planet exactly perpendicular to its surface. The Tropics has clear distinguishable features from the other climatic and biomatic regions of the Earth, the middle latitudes, and the Polar Regions on either side of the equatorial zone. Therefore, different environmental factors, such as infections (e.g., parasitic infections), type and duration of allergen exposure, and disease expression can be found in patients from the tropical zones as compared to those from the other parts of the globe. In general, allergic diseases and asthma are underdiagnosed and undertreated, and since most of the tropical countries are non-affluent, many patients with allergies and asthma do not have access to appropriate diagnosis, care, and medications, or else they can hardly afford the cost of medications. Whereas the burden of allergic diseases and associated diseases has increased, the number of healthcare professionals trained in the diagnosis and treatment of allergy are very few in proportion. As a result, a large number of patients are undiagnosed or undertreated. While many developing countries have few or no allergy-trained physicians to treat millions of allergy and asthma sufferers, even in developed countries, many highly sophisticated areas have a shortage of allergists [240].

Africa

The International Study of Asthma and Allergy in Childhood (ISAAC) series provided new information concerning the prevalence of asthma, allergic rhinitis, and eczema in tropical countries. In Africa and as a part of the ISAAC Phase I study, only six African countries were involved (Algeria, Tunisia, Morocco, Kenya, South Africa, and Ethiopia), three of them located in the Tropics (Kenya, Ethiopia, and South Africa). Phase III, conducted 5–6 years later, enrolled 22 centers in 16 countries including the majority of the centers involved in Phase I and new centers in Morocco, Tunisia, Democratic Republic of Congo, Togo, Sudan, Cameroon, Gabon, Reunion Island, and South Africa (6 out of 16 belong to the tropical zone). There were considerable variations between the various centers in Africa on the prevalence of the main symptoms of the three conditions: wheeze (4.0–21.5 %), allergic rhinoconjunctivitis (7.2–27.3 %) and eczema (4.7–23.0 %). There was also a large variation between countries and between centers within the same country. Several centers, including Cape Town (20.3 %), Polokwane (18.0 %), Reunion Island (21.5 %), Brazzaville (19.9 %), Nairobi (18.0 %), Urban Ivory Coast (19.3 %) and Conakry (18.6 %), showed a relatively high asthma symptom prevalence, similar to those in Western Europe. There were also a number of centers showing high symptom prevalence for allergic rhinoconjunctivitis (Cape Town, Reunion Island, Brazzaville, Eldoret [Kenya], Urban Ivory Coast, Conakry, Casablanca, Wilays of Algiers, and Sousse) and eczema (Brazzaville, Eldoret, Addis Ababa, Urban Ivory Coast, Conakry, Marrakech, and Casablanca). In Africa, 13 countries located in the tropical area took part of the ISAAC Phase III Survey [241].

There is evidence that asthma is increasing in prevalence and severity in Africa. The ISAAC study has shown that there is also an increase in the prevalence of allergic rhinitis and eczema. Despite the fact that previous studies have suggested that the prevalence of atopy in West Africa is low, more recently it has been shown that allergic sensitization to house dust mite and other allergens such as cockroach are risk factors associated with asthma in Ghana [242]. As in other parts of the world the upward trend in allergic diseases has been associated with an increase in urbanization; the increased urbanization and change in lifestyles in the Tropics are possible among the factors associated with the increase in the prevalence of allergy and asthma. In the urban population in Ethiopia, Dermatophagoides pteronyssinus skin sensitization was a risk factor related to wheeze and was stronger than in the rural areas. D.pteronyssinus sensitization was common in rural areas but was not a risk factor for wheezing, possibly due to the high prevalence of parasitic infections in these areas. This study suggests that an increased prevalence of parasite infection may prevent the development of asthma in sensitized atopic individuals [243].

In contrast, children from Kenya living in rural areas had a lower percentage of body fat, smaller and fewer skin test responses to allergens, a higher prevalence of IgE antibodies to Ascaris, and 10-fold higher total IgE compared to urban children in Kenya. In the urban area of Kenya, there was a strong correlation between exercise-induced bronchospasm (EIB) and atopy determined both by IgE antibodies and positive skin prick tests. By contrast, in the rural area, none of the 13 children with EIB were skin-test positive (vs 13/109 of children without EIB) [244].

Besides the above information regarding the upward trend in the prevalence of asthma and allergies in Africa as reported in the ISAAC study, another study has confirmed not only the increased prevalence of asthma but also increased allergen sensitization. Two surveys conducted using the same methodology 10 years apart (1993 and 2003) among schoolchildren aged 9–16 years attending urban rich (UR), urban poor (UP), and rural (R) schools were performed in Ghana. The prevalence of both exercise-induced asthma (EIA) and sensitization approximately doubled over the ten-year period among Ghanaian children and adolescents irrespective of location, with both asthma and atopy being more common among the UR than the UP and R children [245]. Moreover, students from affluent schools had higher levels of IgE to mites compared to those non-affluent and suburban/rural students from Ghana [246].

In a survey conducted in Kigali (the capital of Rwanda) and in Huye District (a rural area located in southern Rwanda), airflow obstruction was found in 256 participants (14 %). Of that number, 163 (8.9 %) subjects were asthmatics and 82 (4.5 %) had chronic obstructive pulmonary disease (COPD). 584 subjects (26.5 %) had positive skin-prick tests, and house dust mite and grass pollen mix were the main allergen sources found. The major risk factors for asthma were allergy, female gender, and living in Kigali [247].

All of this information confirms that asthma and allergic sensitization are becoming more prevalent in many African countries and that this upward trend is mainly related to sensitization to house dust mite, tobacco smoking, and living in urban affluent westernized locations. The high prevalence of severe asthma found in Africa in the ISAAC study (Fig. 4) suggests that limitations in getting access to care, as well as the availability and affordability of medications, can contribute to severe forms associated with non-treated patients, as defined by the World Health Organization (WHO). A better socio-economic situation could help to treat those non-treated patients and decrease the severity of asthma and allergy [248, 249].

Fig. 4 Blue triangles identify locations where prevalence was reduced by at least 1 standard error (SE) per year. Green squares identify locations where there was little change in prevalence (i.e., change of less than 1 SE per year). Red triangles identify locations where prevalence increased by at least 1 SE per year. Reused with permission from Elsevier [141] Full size image

The tropical environmental factors which may cause allergy include food items, animals, birds as well as the house dust mites and stinging insects (bees and wasps) that are present, to varying degrees in all continents. Plant derived allergen sources span trees, grasses, and weeds which can be unique to local environments. There is also sensitization to airborne mold spores. Tropical dietary habits are influenced by the availability of edible grains, plants, fruits and even insects. These are potential sources of allergen sensitization and due to their habitat specificity are likely to display regional peculiarities. This discussion of allergen sensitization in tropical Africa is limited to the observations that have been made in Zimbabwe, a Subtropical African country. Examples from some neighboring countries are incorporated [141].

The ISAAC was limited to a handful of centers in tropical Africa [141, 243]. In the limited number of centers, the study reported prevalence rates of wheezing, allergic rhino-conjunctivitis or eczema to range between 4 % and 27 % amongst 12–14 year olds in 22 centers selected from 16 African countries. These findings debunked the commonly held perception that allergies are infrequent in Africa. Whereas the presence of wheezing, rhinitis, conjunctivitis and dermatitis points towards allergen sources as potential triggers, there remains a dearth of studies that identify triggering specific allergen sources. There have been limited attempts to correlate allergen sources with clinical disease manifestations. In Zimbabwe the predominant allergen sources are house dust mites (D. pteronyssinus and D. farinae), grass pollen, animal hair and molds [250–252] (Fig. 5).

Fig. 5 Inhalant allergen sensitization pattern in children and adolescents in Zimbabwe. The vertical scale represents a percentage of some 987 sensitized patients. Source: Elopy N Sibanda Full size image

House dust mites

House dust mite sensitization is ubiquitous, occurring worldwide in both temperate and tropical environments. House dust mites are the predominant sources of inhaled allergens in Zimbabwe. Dust mite sensitivity is associated with asthma and rhinitis. Approximately half (52 %) of all the patients with asthma or allergic rhinitis and conjunctivitis are sensitized to house dust mites. While house dust mite sensitization is ubiquitous, there are significant differences between specific house dust mite component molecules that elicit allergic diseases in this tropical country compared to temperate climate, with Austria used as an example. In Zimbabwe, the major allergenic molecules are the Der p 1 (80 %), Der p2 (45 %), Der p 7 (35 %), Der p10 (55 %). This allergenic molecule pattern differs from the observations in Austria, where there was no (0 %) sensitization to Der p 7. Similarly Group 10 tropomyosins are comparatively high (55 %) in Zimbabwe compared to the Austrian population (10 %). Higher prevalence of Group 10 tropomyosin sensitivity has also been reported from tropical Japan (80 %). Tropomyosins that are structurally similar to Der p10 are found in crustaceans (crab, lobster, and shrimp) and insects (cockroaches). The presence of crustaceans and insects is influenced by climate and geography. Significant differences in the IgE-binding frequency of Der p 11 (the mite paromyosin) have also been observed between temperate (Austria 12 %, France 5 %, Italy 7 % and Sweden 11 %) and tropical (Zimbabwe) countries. In Zimbabwe, the IgE binding frequency of Der p 11 was much higher (36 %) and was associated with atopic dermatitis [253].

A careful analysis of specific allergenic molecules reveals geographical variations in the prevalence of sensitization and allergic reactivity to specific molecules (Table 5). Different house dust mite molecules can cause similar respiratory symptoms in different climatic environments. There are implications on the diagnosis and management of allergic conditions. The use of house dust mite extracts in skin prick tests and/or in serological diagnostic techniques only provides a general guide to the sensitization patterns. Component resolved molecular detection techniques are required to identify specific sensitivity patterns and regional specificities and ultimately to tailor specific immunotherapy interventions.

Table 5 Comparison of sensitization to house dust mite molecules between a tropical and temperate country. Source: Elopy N Sibanda Full size table

Cockroaches

Sensitization to cockroach allergens is common. Cockroach allergy is a recognized cofactor in both asthma and rhinitis and increases the severity of both. Asthma severity is greater in cockroach sensitive subjects and is associated with other atopic conditions such as dermatitis. Patterns of sensitization to cockroach allergens were noted to be variable in two neighboring tropical countries (South Africa and Zimbabwe). Patients who live in cities that are located at higher altitudes (Harare, Zimbabwe and Pretoria, South Africa) have predominant Blatella germanica sensitization, whereas patients from coastal Cape Town and Durban (both in South Africa) have a mix of B. germanica, Periplaneta americana and B. orientalis [254]. The results show that sensitization patterns can vary within the same climatic zones and are influenced by factors such as proximity to the sea or altitude. However the relative effect of sensitization to one or the other types of cockroaches in this region has not been investigated.

Pollen

The predominant grass pollen source is Bermuda grass (Cynodon dactylon) which belongs to the Poaceae family of grasses in Bermuda and Southern Africa. This is a typically tropical grass whose optimum growth occurs at temperatures between 24 and 37 °C and is most abundant at latitudes between 30 °N and 31.4 ° + 7.5 °S. In view of its value in soil erosion control, this grass variety was widely planted alongside roads and school fields across Zimbabwe and has become widely abundant. Bermuda grass is implicated in seasonal exacerbations of allergic rhinitis, asthma and allergic conjunctivitis.

Maize pollen (Zea mais) another Type 1 grass is a common source of respiratory allergens in Zimbabwe. Like Bermuda grass, maize belongs to the Poaceae family of grasses and is an important cereal crops. It is widely cultivated in tropical climates and is responsible for respiratory and to a lesser extent food allergy.

Food allergy

Food allergen sources that are prevalent in Zimbabwe reflect the dietary habits of the people. The full repertoire of these is limited by the availability of both skin prick testing extracts and locally relevant test panels. The reported results reflect a concordance of both skin prick testing and serological assays of IgE mediated reactivity. The predominant food allergen sources are potato (24 %), peanut (21 %), rice (15 %), carrot (14 %), soya (13 %), hazelnut (13 %) and wheat (11 %) (Fig. 6). These allergen sources have been relatively recently introduced and became popular components of the diet of the indigenous Zimbabwean population in the last 50 years. A closer evaluation of peanut sensitization was conducted in view of world reports of their association with anaphylaxis and mortality.

Fig. 6 Allergen-specific IgE reactivity in patients presenting to the Asthma Allergy and Immune Dysfunction Clinic in Harare. Source: Elopy N Sibanda Full size image

A unique observation is that despite high levels of sensitization to both potatoes and peanuts there are no reported cases of severe peanut induced reactions or anaphylaxis. Peanut sensitization was demonstrated using skin prick extracts and confirmed by allergen specific IgE detected using the ImmunoCAP technique. Allergen specific IgE antibodies were also confirmed using a Western blotting technique. All the extracts and serological reagents used were from commercial sources and were the same that identified sensitization in patients with severe reactions and anaphylaxis in temperate countries. Further testing using resolved allergen molecular components confirmed sensitization to rAra h 2, rAra h 1, rAra h 3, nAra h 6 and rAra h 9. The levels of IgE antibodies to Ara h 1 Ara h 2 were sometimes greater than 15 kU A /L. These allergens and this level of sensitization is often associated with severe reactions and anaphylaxis in temperate countries, but not in Zimbabwe, suggesting unexplained peanut tolerance. Similar tolerance has been reported from Nigeria [255]. The authors speculate that it is the method of peanut preparation and the timing of its introduction to the diet that produces tolerance as opposed to allergy. There may well be other explanations.

The Americas

The tropical area in the Americas extends from Mexico in the Northern hemisphere to a line that crosses Paraguay and the South of Brazil. Most of the Latin American countries are part of the Tropics except Argentina, Chile, and Uruguay. The Tropics also includes the southern half of Mexico, Central America, and the Caribbean. The tropical South America sub-region comprising 10 countries (Colombia, French Guiana, Suriname, Guyana, Venezuela, Ecuador, Peru, Bolivia, Paraguay, and Brazil) represents the greatest concentration of tropical rainforest in the world. The Amazonian tropical rainforest is considered to be the world’s richest ecosystem in terms of biodiversity. The rainforest in South America is approximately 885 million hectares in the Amazon Basin and another 85 million hectares in the Orinoco and Paraná watershed complex. The total land area of tropical South America is 1,387 million hectares. The temperature in a rainforest rarely is higher than 93 °F (34 °C) or drops below 68 °F (20 °C), and the average humidity ranges between 77–88 %. The rainfall is often more than 100 in. a year. Terrestrial biodiversity (degree of variation of life) tends to be the highest at low latitudes near the Equator. The tropics in Mexico, Central and South America are extremely rich in terms of genetic variation, species variation, or ecosystem variation. For instance, Mexico is home to 10–12 % of the world's biodiversity and is one of the 17 M diverse countries as well as other 7 Latin American countries (Brazil, Bolivia, Colombia, Costa Rica, Ecuador, Perú, and Venezuela).

The ISAAC Study in Latin America has shown that the prevalence of lifetime asthma ranged from 1.2–33.1 %, whereas current wheezing was from 3.9 to 30.8 %. An important proportion of centers (55 %) reported a prevalence of asthma symptoms over 15 %. There was no significant correlation between prevalence of asthma symptoms and the latitude, altitude, or tropical setting. It is suggested that ecological interactions, probably typical for each locality, may be the main determinants for the large variability of asthma prevalence in Latin America [256].

Regarding allergic rhinitis, 93,851 children (6–7 years old) from 35 centers in 14 Latin American countries, and 165,917 adolescents (13–14 years old) from 56 centers in 17 Latin American countries, were enrolled. The mean prevalence rate of current rhinoconjunctivitis was 12.7 % in the region while the highest prevalence was found in Caracas (Venezuela) – 21.2 % of the schoolchildren. The mean prevalence rate of current rhinoconjunctivitis was 18.5 % and ranged from 7.1 % in Cuernavaca (México) to 45.1 % in Asunción (Paraguay) for the adolescents. In general the prevalence of rhinitis-related symptoms was higher among the Spanish speaking centers. As it happens for asthma, a great variability in the prevalence was also found for allergic rhinitis including differences observed even in centers from the same country [257].

The prevalence of eczema in tropical Latin America is also very high compared to other regions and countries that participated in the global survey. The mean prevalence of current flexural eczema in schoolchildren was 11.3 %, ranging from 3.2 % in Ciudad Victoria (México) to 25.0 % in Barranquilla (Colombia). For adolescents, the prevalence varied from 3.4 % in Santo André (Brazil) to 30.2 % in Barranquilla (mean prevalence, 10.6 %) [258].

Atopy is very common among children and adults with asthma and/or allergic rhinitis. A study looking at the prevalence of sensitization to 6 different mites species (Dermatophagoides pteronyssinus, D. farinae, Blomia tropicalis, Chortoglyphus arcuatus, Lepidoglyphus destructor, and Aleuroglyphus ovatus) in 297 children and adults with asthma from 7 cities in 5 Latin American countries (most of them tropical cities – Bogotá, Caracas, Cartagena, São Paulo, and Mexico City) was performed. Sensitization to D. pteronyssinus varied from 60.7 % in Cartagena to 91.2 % in São Paulo; to D. farinae from 53.3 % in Córdoba to 97.2 % in Caracas; to A. ovatus from 26.6 % in Bogotá to 71.2 % in São Paulo; to B. tropicalis from 46.5 % in Mexico City to 93.7 % in São Paulo; to C. arcuatus from 33.3 % in Mexico City to 75 % in São Paulo; and to L. destructor from 30 % in Mexico City to 76.2 % in São Paulo. The studies carried out in São Paulo and Córdoba were confined to children and thus could be compared; there was a significantly higher prevalence of cutaneous sensitivity to mite allergens in the children of São Paulo (in the Tropics) than in those of Córdoba (p < 0.001 for all mite species). Cutaneous sensitivity to mite allergens is very common in young and adult asthmatics in Latin America, in areas both at sea level and at high altitudes [259].

More recently, it has been shown that 76 % of patients with respiratory allergy are sensitized to aeroallergens, especially mites in Caracas, a tropical city [260]. Moreover, anaphylactic reactions after the ingestion of mite-contaminated pankakes has been also described in Venezuela indicating that not only the inhalation of mite particles but also ingestion can elicit oral mite allergic reactions [261]. An online registry of anaphylaxis has been developed and 191 patients registered from Latin America and Portugal. Anaphylactic reaction to foods (36.1 %), drugs (27.7 %), and insect stings (26.2 %) were analyzed. The most common symptoms during an acute episode were cutaneous (94.2 %) as well as respiratory (78.5 %). Most patients were treated in emergency setting, yet only 34.6 % received injective epinephrine and 14.3 % had to be hospitalized. The management of anaphylaxis needs to be improved in the region [262].

Environmental features in the tropics in Latin America have to be taken in account regarding risk factors and potential pathogenic agents. Ascariasis infections are important health problems in low-income settings such as those located in the tropics where environmental conditions also promote the perennial co-exposure to high concentrations of domestic mite allergens. Experimental evidence of a high cross-reactivity between the allergenic extracts of these invertebrates, involving well-known allergens such as tropomyosin and glutathione transferasas has been described [263]. Ascaris lumbricoides induces a Th2 response and specific IgE synthesis in humans; in addition, Ascaris tropomyosin is cross-reactive to mite tropomyosin and can induce wheal and flare reaction in skin prick tests and histamine release from basophils. There is indirect evidence suggesting that the clinical impact of these findings may be important [263].

In a recent study performed in the north of Brazil, it was found that children of more educated mothers, living in improved environmental conditions, and with a low burden of infection were significantly more likely to have the responsive phenotype. The so-called responsive phenotype was significantly associated with an increased prevalence of atopy but not asthma. A better understanding of the underlying immune mechanisms of the hygiene hypothesis in urban Latin America is needed [264].

Early life sensitization to aeroallergens, presence of atopic dermatitis or allergic rhinitis, maternal smoking during pregnancy and children's environmental exposure to tobacco smoke, lower respiratory tract infections with respiratory syncytial virus and potentially with other viruses including rhinovirus and metapneumovirus, exposure to air pollutants, several perinatal factors other than maternal smoking, are among the factors associated with an increased risk for the development of chronic diseases like asthma and atopy [265].

Conclusions

Allergen sources predispose to allergic diseases in genetically predisposed individuals worldwide. This is true and expected for allergen sources that are geographically demarcated such as food items, tree and grass pollen. There are also significant differences with ubiquitous allergen sources such as house dust mites and cockroaches. The molecules responsible for allergy vary geographically. Tropomyosins contribute more to allergy in the tropics (Japan, Zimbabwe) than they do in the temperate regions. While the allergen sources may be the same, the allergen molecules differ, necessitating component resolved diagnosis and targeted treatment for house dust mite allergy. Cockroach allergy varies with altitude and proximity to the sea. The germanica species thrive in high altitude whereas the P. americana are in low altitude. The lesson to be learned is that while major allergen sources may be ubiquitous, local variations impact on accurate diagnosis, prevention and treatment of resultant allergic diseases.