Advertisement

Socio-epidemiological Aspects of Respiratory Allergic Diseases in Southern Africa

      Abstract

      The prevalence of respiratory allergic diseases has been increasing in Southern Africa both in urban and in rural environments. Various factors may contribute toward this situation, namely, exposure to aeroallergens, such as grass pollens and house dust mites. However, other irritant environmental triggers, such as exposure to tobacco smoke and certain indoor and outdoor fumes, may also play a relevant part. Furthermore, certain parasitic and mycobacterial infections may act as allergic disease risk modifiers, although such an influence should be confirmed. Finally, certain cultural and socioeconomic factors may also influence accessibility to healthcare and adherence to treatment of these diseases.

      Keywords

      This article was originally published online on 13 January 2012
      The United Nations region of Southern Africa comprises South Africa, Namibia, Botswana, Lesotho, and Swaziland. However, the broader geographic region of Southern Africa also includes countries such as Angola, Zambia, Malawi, Zimbabwe, and Mozambique. This region is known to be affected by poverty and malnutrition and plagued by acquired immunodeficiency syndrome and tuberculosis (TB). However, allergies are far more prevalent than TB or acquired immunodeficiency syndrome, affecting 25 to 30% of the population and result in significant morbidity, employment absenteeism, loss of quality of life, and in some instances, fatal outcomes. Allergies pose a huge cost to the health sector, affecting all ages, from the poorest to the richest, across the geographical spectrum of Southern Africa.
      Southern Africa is home to the Khoisan tribes of Namibia and Botswana, numerous African Bantu tribes, whites, Indians, and immigrants from all over the world. Superimposed on the vast ethnic genetic and cultural diversity of its peoples is a wide variety of climatic conditions (or biomes), a rich diversity of flora and fauna, and the rapid migration and urbanization of its peoples. It is against the backdrop of this change from the old to the new lifestyle that we have observed a dramatic increase in the prevalence of allergies in the region. Southern Africa may therefore be one of the most informative parts of the world to study the factors that have contributed to the increased expression of the allergic phenotype worldwide.

      Prevalence Rates of Respiratory Allergic Diseases

      It is generally accepted that rural Africans who live in the grasslands or deserts of Southern Africa in traditional accommodation with traditional dietary practices rarely, if ever, suffer from allergic disease. Asthma, for example, is so rare among certain peoples of Southern Africa, that until recently there was no term to describe the condition in the local indigenous idiom. Diseases such as eczema, food allergy, and allergic rhinitis are still rare in rural Africans. They were not even mentioned in a health survey of the Bushmen in the Kalahari published in The Lancet in 1989 by O'Keefe and Lavender [

      O'Keefe D, Lavender S: The plight of modern bushman. Lancet. 1989, 255-257. ii

      ]. However, there is evidence that the prevalence of allergic diseases is increasing in Southern Africa.

      Asthma

      One of the earliest asthma studies was a questionnaire-based study of the prevalence of asthma performed in 1975, in a small Rhodesian (currently, Zimbabwean) town, involving almost 10,000 subjects aged 5 years and older. The overall prevalence of asthma was 1.40%, ranging between 1.20% in those under 20 years of age and 1.57% in adults [
      • Cookson J.B.
      • Makoni G.
      Prevalence of asthma in Rhodesian Africans.
      ]. Similar results were obtained in another study that analyzed the prevalence of childhood asthma in Southern Africa, in 1977 [
      • van Niekerk C.H.
      • Weinberg E.G.
      • Shore S.C.
      • Heese H.D.
      Prevalence of childhood asthma in Africa.
      ]. These studies suggested that the prevalence of asthma in an African urban environment was low.
      About 20 years later, in 1995, a study carried out in Cape Town, South Africa, used a questionnaire focusing on wheeze and asthma, which was completed by parents of 1955 children, followed by 620 personal interviews repeating the questions [
      • Ehrlich R.I.
      • Du Toit D.
      • Jordaan E.
      • Volmink J.A.
      • Weinberg E.G.
      • Zwarenstein M.
      Prevalence and reliability of asthma symptoms in primary school children in Cape Town.
      ]. The prevalence of recent wheeze (previous 12 months) was 26.8% and that of self-reported asthma was 10.8%. Similarly, high prevalence values for wheeze were also found in a study carried out in one of the most polluted areas of South Africa, in Durban, KwaZulu-Natal [
      • Nriagu J.
      • Robins T.
      • Gary L.
      • Liggans G.
      • Davila R.
      • et al.
      Prevalence of asthma and respiratory symptoms in south-central Durban, South Africa.
      ]. About 10% of the children and 12% of adults reported doctor-diagnosed asthma, although the self-reported prevalence rates were higher for wheezing (37-40%) and for attacks of shortness of breath with wheeze (16-28%). These findings suggest that the hygiene hypothesis protecting the development of atopic diseases, such as allergic asthma, was not readily applicable to Southern Africa where asthma is increasing even in the poor areas of low saturation and income.
      In a study aiming to assess the 12-month prevalence of wheeze and severe wheeze along with their potential risk factors within a 60-km radius from the Polokwane city center, Limpopo Province in South Africa, the 12-month prevalence rates of wheeze and severe wheeze were 11.2 and 5.7%, respectively [
      • Wichmann J.
      • Wolvaardt J.E.
      • Maritz C.
      • Voyi K.V.
      Household conditions, eczema symptoms and rhinitis symptoms: relationship with wheeze and severe wheeze in children living in the Polokwane area, South Africa.
      ]. In Thokoza, Gauteng, a total of four hundred seventy-five 9- and 10-year-old children performed the free-running asthma screening test, and an overall prevalence rate of bronchial hyperreactivity (BHR) of 7.26% was detected [
      • Mashalane M.B.
      • Stewart A.
      • Feldman C.
      • Becker P.
      • de Charmoy S.
      Prevalence of exercise-induced bronchospasm in Thokoza schoolchildren.
      ].
      In Mozambique, the International Study of Asthma and Allergies in Childhood (ISAAC) study was carried out in 1614 adolescents aged 13 to 14 years in schools located in urban, suburban, and semirural areas of Maputo [
      • Mavale-Manuel S.
      • Joaquim O.
      • Nunes E.
      • Pedro A.
      • Bandeira S.
      • et al.
      Prevalence of asthma-like symptoms by ISAAC video questionnaire in Mozambican schoolchildren.
      ,
      • Mavale-Manuel S.
      • Joaquim O.
      • Macome C.
      • Almeida L.
      • Nunes E.
      • et al.
      Asthma and allergies in schoolchildren in Maputo.
      ]. The prevalence of current asthma was shown to vary between 11.9% (based on video) and 13.3% (based on the written questionnaire).
      An important South African study aimed to document the current prevalence of BHR by comparing traditional rural Xhosa children, recently urbanized Xhosa children, and established city white children and to consider factors that may account for the observed increase in all these groups [
      • Steinman H.
      • Dawson H.
      • Kawalski M.
      • Toerien A.
      • Potter P.C.
      Bronchial hyperresponsiveness and atopy in urban, peri-urban and rural South African children.
      ]. The sample included 1457 schoolchildren aged 10 to 14 years from the rural Transkei, from a recently urbanized peri-urban area, and from urban Cape Town areas. Four hundred eighty of these children had histamine challenges, and 492 were skin prick tested for atopy. Bronchial histamine challenge showed that 17% of rural and 34.4% of recently urbanized Xhosa children had increased BHR, which is a marked increase from the 0.03 and 3.17% prevalence of increased BHR that had previously been found using the exercise challenge. The prevalence of increased BHR in white urban children was 33%.
      Comparing data from Phase I or Phase II versus Phase III ISAAC study, allowing comparison of data between 1995 and 2002, focusing on self-reported symptoms in 13- to 14-year-old adolescents (5178 in 1995 and 5037 in 2002) in the Cape Town area, [
      • Zar H.J.
      • Ehrlich R.I.
      • Workman L.
      • Weinberg E.G.
      The changing prevalence of asthma, allergic rhinitis and atopic eczema in African adolescents from 1995 to 2002.
      ] found that the 12-month prevalence of wheezing (16 vs 20.3% for 1995 and 2002, respectively), exercise-induced wheeze (21.5 vs 32.5%), nocturnal cough (23.6 vs 36.6%), sleep disturbance due to wheeze (9.6 vs 16%), or severe wheeze (5.1 vs 7.8%) had increased significantly. A rise in asthma symptoms was confirmed by the video questionnaire responses, in which the 12-month prevalence of wheezing (6.5 vs 11.2%), exercise-induced wheeze (11.5 vs 13.9%), nocturnal wheeze (3.9 vs 5.3%), nocturnal cough (11.6 vs 19.2%), or severe wheeze (5 vs 7%) had also increased significantly. Overall, there is evidence to confirm that the prevalence of asthma and asthma-related phenotypes (eg, BHR; wheezing) has been increasing in Southern Africa, not only in rural but also in urban settings, [
      • Green R.J.
      Paediatric asthma in Southern Africa.
      ] which also is not consistent with the hygiene hypothesis.

      Rhinitis

      Fewer studies have analyzed the prevalence of allergic rhinitis in Southern Africa. The Mozambican ISAAC study that included 27 schools in urban, suburban, and semirural areas around Maputo showed that the prevalence of rhinoconjunctivitis was 23% in teenagers and 8.8% in 6- to 7-year-old children. In symptomatic adolescents, 41.3% had rhinoconjunctivitis, whereas only 18.1% of children had this condition. Hay fever was commoner in the semi-urban area [
      • Mavale-Manuel S.
      • Joaquim O.
      • Macome C.
      • Almeida L.
      • Nunes E.
      • et al.
      Asthma and allergies in schoolchildren in Maputo.
      ]. These values suggest that the prevalence of allergic rhinitis in Southern Africa is not much lower than that observed in industrialized countries, which is not expected from the hygiene hypothesis. The ISAAC Phase III versus Phase I comparison study, using surveys carried out 7 years apart in 13- to 14-year-old adolescents, in randomly selected schools in Cape Town showed that the 12-month prevalence of symptoms of allergic rhinitis (30.4 vs 38.5%) and rhinoconjunctivitis (17.6 vs 24.3%) had increased significantly between the 2 time points [
      • Zar H.J.
      • Ehrlich R.I.
      • Workman L.
      • Weinberg E.G.
      The changing prevalence of asthma, allergic rhinitis and atopic eczema in African adolescents from 1995 to 2002.
      ].

      Triggers and Risk Factors for Respiratory Diseases

      Atopy and Sensitization to Aeroallergens

      The main aeroallergens in Southern Africa are house dust mites (HDMs), cockroach, and pollens. Ordman [
      • Ordman D.
      The climate group of respiratory allergy patients in South Africa; their sensitivity to house dust and desensitization with extracts of the allergenically potent coastal house dust.
      ,
      • Ordman D.
      Respiratory allergy in the coastal areas of South Africa; the climate factors in relation to house-dust sensitivity.
      ] first showed that mite levels were consistently higher along humid coastal areas and usually lower in areas of high altitude, in South Africa. Further studies including Soweto, Johannesburg, [
      • Davis G.
      • Luyt D.
      • Prescott R.
      • Potter P.C.
      House dust mites in Soweto.
      ] Durban, [
      • Manjra A.I.
      • Berman D.
      • Toerien A.
      • Weinberg E.G.
      • Potter P.C.
      The effects of a single appilcation of an acaricide (Acarosan) and a detergent (Metsan) on Der p 1 levels on carpets and mattresses of asthmatic children.
      ] and Cape Town [
      • Jooma O.F.
      • Weinberg E.G.
      • Berman D.
      • Manjra A.I.
      • Potter P.C.
      Accumulation of housedust mite (Der p 1) levels on mattress covers.
      ,
      • Potter P.C.
      • Berman D.
      • Toerien A.
      • Malherbe D.
      • Weinberg E.G.
      Clinical significance of aero-allergen identification in the Western Cape.
      ] confirmed the presence of high levels of HDMs in coastal and inland cities. In Cape Town, in vivo skin tests in 209 children with known allergic disease were positive to Dermatophagoides pteronyssinus (Der p) in 73% of cases.
      The levels of the HDM allergen Der p 1 were studied over a 4-season period during 1994 to 1995 by sampling mattresses and carpets in the main bedrooms of 30 randomly selected suburban homes and analyzing the levels of mite aeroallergens in the Edenvale area in South Africa [
      • Cadman A.
      • Prescott R.
      • Potter P.C.
      Year-round housedust mite levels on the Highveld.
      ]. All homes tested positive for Der p 1. Similar results were obtained in Zimbabwe, showing that IgE-mediated allergies were common in Zimbabwe and that HDM and grass pollens represented the most prevalent allergen sources [
      • Westritschnig K.
      • Sibanda E.
      • Thomas W.
      • Auer H.
      • Aspöck H.
      • et al.
      Analysis of the sensitization profile towards allergens in central Africa.
      ]. In South Africa, dust mites have been found in both humid areas and in areas of low humidity, such as Johannesburg [
      • Potter P.C.
      • Davis G.
      • Manjra A.
      • Luyt D.
      House dust mite allergy in Southern Africa--historical perspective and current status.
      ].
      Both HDM and cockroach were shown to be the main sensitizers in asthmatic patients living in the coastal town of Durban, South Africa [
      • Fraser B.N.
      Cockroaches in relation to bronchial asthma in the Durban area.
      ]. Similar results in terms of HDM sensitization were found in asthmatic children in the Cape Peninsula, [
      • van Niekerk C.H.
      • Shore S.C.
      • Weinberg E.G.
      The house-dust mite and childhood asthma in the Cape Peninsula.
      ] in Zambia, [
      • Buchanan D.J.
      • Jones I.G.
      Mites and house dust mite allergy in bronchial asthma in Northern Zambia.
      ] and in Zimbabwe [
      • Kambarami R.A.
      • Marechera F.
      • Sibanda E.N.
      • Chitiyo M.E.
      Aero-allergen sensitisation patterns amongst atopic Zimbabwean children.
      ].
      In a prospective analysis of 455 black asthmatic children (277 boys) attending the Johannesburg-based Baragwanath Hospital asthma clinic, [
      • Luyt D.K.
      • Davis G.
      • Dance M.
      • Simmank K.
      • Patel D.
      Clinical characteristics of black asthmatic children.
      ] associated atopic conditions were present in 75.5% of patients and a family background in 22.2%. Other respiratory diagnoses were commonly made, particularly TB, which was diagnosed in 7.4%. Importantly, the commonest allergens were HDM and grass pollens. A study carried out in the Free State, South Africa, in 50 consecutive patients with allergic rhinitis attending the ear, nose, and throat clinic at Universitas Hospital showed that 46% were sensitized to mites and cockroaches [
      • Seedat R.Y.
      • Claassen J.
      • Claassen A.J.
      • Joubert G.
      Mite and cockroach sensitisation in patients with allergic rhinitis in the Free State.
      ].
      Pollen allergy was first documented in Southern Africa by Potts between 1919 and 1921 [
      • Potts G.
      The pepper tree (Schinus molle) in its relationship to epidemic hayfever: interim report.
      ,
      • Potts G.
      The potency of pepper tree pollen as a cause of hayfever.
      • Potts G.
      The pepper tree (Schinus molle L.) as a cause of hayfever in South Africa.
      ]. Ordman, for example, studied the distribution of aeroallergens in various areas of Southern Africa and concluded that grass pollens and the fungus Cladosporium were the most frequent inhalants in former Southern Rhodesia (now Zimbabwe), the Cape Province, Namibia, and Natal (now Kwazulu-Natal) [
      • Ordman D.
      Cypress pollinosis in South Africa. A study of seasonal hayfever and allergic conjunctivitis occurring in the winter/spring period.
      ,
      • Ordman D.
      Pollinosis in South Africa.
      ,
      • Ordman D.
      Cereal grain dusts as a cause of respiratory allergy in South Africa.
      ,
      • Ordman D.
      Seasonal respiratory allergy and the associated pollens in South Africa.
      ,
      • Ordman D.
      Seasonal respiratory allergy in Windhoek: the pollen and fungus factors.
      • Ordman D.
      Seasonal respiratory allergy in Bulawayo, Rhodesia: the pollen and fungus factors.
      ]. Allergic rhinitis is predominantly caused by grass pollens, namely, Pooideae and Chloridoideae, Bermuda grass (Cynodon dactylon) [
      • Ordman D.
      Respiratory allergy in the coastal areas of South Africa; the significance of climate.
      ,
      • Orren A.
      • Dowdle E.B.
      Studies on Bermuda grass pollen allergens.
      ]. More than 95% of grass-allergic individuals in Gauteng and 80% of grass allergic subjects in the Cape Province have IgE antibodies to Bermuda grass [
      • Potter P.C.
      Identifying the allergenic grasses of Southern Africa.
      ]. In addition, southern African grass pollens, kikuyu grass (Pennisetum clandestinum), [
      • Potter P.C.
      • Mather S.
      • Lockey P.
      • Ainslie G.
      • Cadman A.
      IgE specific immune responses to an African grass (Kikuyu, Pennisetum clandestinum).
      ] buffalo grass (Stenotaphrum secundatum), and Boer love grass (Eragrostis curvula), [
      • Prescott R.A.
      • Potter P.C.
      Allergenicity and cross-reactivity of buffalo grass (Stenotaphrum secundatum).
      ] have also been identified as highly allergenic grass pollens in South Africa [
      • Potter P.C.
      Allergy in Southern Africa.
      ,
      • Potter P.C.
      • Cadman A.
      Pollen allergy in South Africa.
      ].
      An important clinical feature of grass allergy in Southern Africa is that grass pollen allergic symptoms occur up to 10 months per year, due to a long pollination season. Grass pollens are important in Zimbabwe [
      • Westritschnig K.
      • Sibanda E.
      • Thomas W.
      • Auer H.
      • Aspöck H.
      • et al.
      Analysis of the sensitization profile towards allergens in central Africa.
      ].
      Of the tree allergens, the predominant trees inducing allergy in Southern Africa are oak (Quercus) and plane (Platanus acerifolia) trees. The Acacia genus, including the "doringboom" tree, seems to be weakly allergenic. Whereas the prosopis tree (mesquite) found in Namibia is highly allergenic (Christo Buys, personal communication).

      Risk Factors

      Most studies addressing the issues of risk factors in respiratory allergic diseases in Southern Africa have focused on bronchial asthma. In a study based on a random sample of 742 students aged 13 to 14 years attending various schools at Polokwane, in the Province of Limpopo, South Africa, persistent cough [odds ratio (OR) = 4.01], exposure to smoke at the household level (OR = 2.39), and lack of access to flush toilet at the household level (OR = 1.89) were key predictors of asthma in children [
      • Nriagu J.
      • Robins T.
      • Gary L.
      • Liggans G.
      • Davila R.
      • et al.
      Prevalence of asthma and respiratory symptoms in south-central Durban, South Africa.
      ]. In another comparative study [
      • Steinman H.
      • Dawson H.
      • Kawalski M.
      • Toerien A.
      • Potter P.C.
      Bronchial hyperresponsiveness and atopy in urban, peri-urban and rural South African children.
      ] of adolescents included 1457 students aged 10 to 14 years from the rural Transkei, from a recently urbanized peri-urban area, and from urban Cape Town areas, passive cigarette smoking was not identified as a risk factor for increased BHR or atopy. Wood smoke in the indoor environment did not play a role in the rural Xhosa children's BHR. Finally, Ascaris infection did not seem to play any modifying role in the development of increased BHR in the rural or urban children [
      • van Niekerk C.H.
      • Weinberg E.G.
      • Shore S.C.
      • Heese H.D.
      Prevalence of childhood asthma in Africa.
      ].
      A cross-sectional survey of 213 households in the communities of Merewent (97% Indians) and Austerville (98% coloreds), in Durban, South Africa, showed that the factors in the community that were associated with asthma, wheeze, and shortness of breath with wheeze among the adult population included cigarette smoking, use of insecticides (coils and pump spray), and home ownership. In contrast, an association between asthma among children and household risk factors, such as dampness, carpet, pets, or use of pesticides, was not apparent in the community [
      • Maluleke K.R.
      • Worku Z.
      Environmental determinants of asthma among school children aged 13-14 in and around Polokwane, Limpopo Province, South Africa.
      ]. Thus, there are differences in the findings of different studies relating to risk factors.
      Environmental tobacco smoke exposure is also associated with decreased BHR in children [
      • Ehrlich R.
      • Jordaan E.
      • Du Toit D.
      • Potter P.
      • Volmink J.
      • Zwarenstein M.
      • Weinberg E.
      Household smoking and bronchial hyperresponsiveness in children with asthma.
      ]. This study involved 249 asthmatic children aged 7 to 11 years identified in a community survey in Cape Town. Children with asthma whose mothers smoked had a lower frequency of BHR than asthmatic children of nonsmoking mothers. BHR was also less common among children sharing a house with 4 or more smokers versus fewer or none. In contrast, FEV1 was lower among children whose mothers currently smoked.
      In a questionnaire completed by parents of 1955 children aged 7 to 9 years, from which 368 cases and 294 controls were selected on the basis of reported asthma diagnosis or symptoms, [
      • Ehrlich R.I.
      • Du Toit D.
      • Jordaan E.
      • Zwarenstein M.
      • Potter P.
      • Volmink J.A.
      • Weinberg E.
      Risk factors for childhood asthma and wheezing. Importance of maternal and household smoking.
      ] an exposure-response relationship between the urinary cotinine to creatinine ratio and asthma/wheeze was observed, confirming that household smoking is an important risk factor in asthma/wheeze among young schoolchildren. In addition, this study also suggested that maternal smoking in pregnancy and current household exposure may be independent contributors to this effect. The study in Polokwane [
      • Wichmann J.
      • Wolvaardt J.E.
      • Maritz C.
      • Voyi K.V.
      Household conditions, eczema symptoms and rhinitis symptoms: relationship with wheeze and severe wheeze in children living in the Polokwane area, South Africa.
      ] showed that exposure to environmental tobacco smoke at home increased the likelihood of wheeze by 77%.
      In adolescents and adults and from a stratified national sample of households, [
      • Ehrlich R.I.
      • White N.
      • Norman R.
      • Laubscher R.
      • Steyn K.
      • Lombard C.
      • Bradshaw D.
      Wheeze, asthma diagnosis and medication use: a national adult survey in a developing country.
      ] of a total of 5671 men and 8155 women, smoking was associated with wheeze but not with asthma diagnosis. In Thokoza (Gauteng), the use of gas and electricity as domestic fuels was the strongest risk factor associated with exercise-induced bronchospasm [
      • Mashalane M.B.
      • Stewart A.
      • Feldman C.
      • Becker P.
      • de Charmoy S.
      Prevalence of exercise-induced bronchospasm in Thokoza schoolchildren.
      ].
      A case-control study focused on anthropometric measurements, asthma, and atopy in 773 Xhosa children with exercise-induced bronchoconstriction (EIB) [
      • Calvert J.
      • Burney P.
      Effect of body mass on exercise-induced bronchospasm and atopy in African children.
      ]. The authors measured specific IgE to 5 common aeroallergens, performed skin prick tests (11 aeroallergens), and determined body mass index measured as a standard deviation score (BMISDS). Results showed that increasing BMISDS was associated with an increased risk of EIB after controlling for atopy and income (OR = 1.74). In addition, an increasing BMISDS was also associated with increasing IgE and corresponding positive skin tests (P = 0.0001; OR = 37.9). Thus, this study suggested that in Southern African children, fatness also increases the risk of EIB. A relationship between obesity and wheeze may also be observed in young women [
      • Ehrlich R.I.
      • White N.
      • Norman R.
      • Laubscher R.
      • Steyn K.
      • Lombard C.
      • Bradshaw D.
      Wheeze, asthma diagnosis and medication use: a national adult survey in a developing country.
      ].
      Studies have also been conducted on the possible protection of breastfeeding on the development of allergic diseases in the region [
      • Obihara C.C.
      • Marais B.J.
      • Gie R.P.
      • Potter P.
      • Bateman E.D.
      • et al.
      The association of prolonged breastfeeding and allergic disease in poor urban children.
      ]. Data were collected from a 15% random sample of households from 2 poor suburbs of Cape Town, in which parents completed a validated ISAAC questionnaire on allergic diseases for children aged 6 to 14 years. Other questions included breastfeeding duration, maternal smoking, and parental allergy. Results were adjusted for possible confounders and for possible clustering within the household. Of the 861 children included in the study, allergic diseases, in general, and hay fever, in particular, were significantly less frequent in those with prolonged (≥ 6 months) breastfeeding. There was a significant linear inverse association between prolonged breastfeeding duration and allergic disease in children without allergic parents but not in children with an allergy in the family.

      Modifiers of Expression of Allergic Diseases in Southern Africa

      The most important modifiers of disease expression in Southern Africa may include helminthic, mycobacterial, and viral infections.

      Parasitic Infection

      Infection with certain parasites (eg, schistosomiasis and Ascaris roundworm infestation) is extremely common in Southern Africa, where it is endemic in certain areas. Parasites stimulate IgE production and may interfere with mechanisms of allergen-specific IgE production or end organ sensitivity to allergens.
      Recent investigations showed that infection with Ascaris may occur concurrently with allergy in adolescents [
      • Levin M.E.
      • Le Souëf P.N.
      • Motala C.
      Total IgE in urban black South African teenagers: the influence of atopy and helminth infection.
      ]. Total IgE levels were markedly skewed toward the left and were not distributed in a Gaussian or a log-normal distribution in black Xhosa high school children in Cape Town. Skin prick tests were positive for aeroallergens in 32.3% of subjects and 34% of the individuals had elevated Ascaris-specific IgE levels. As expected, total serum IgE levels were higher in atopic than in nonatopic subjects and correlated with the number of positive skin prick tests, self-reported asthma, and bronchial hyperresponsiveness. In addition, total serum IgE levels correlated with the levels of Ascaris-specific IgE.
      A previous study in which 17% of the nonallergic controls and 51% of the allergic asthmatics had a clinically detectable immunogenic response to the parasite, the inhalation of Ascaris antigen induced asthmatic reactions in 7 of 8 patients who had positive skin prick tests to Ascaris but not in the negative controls [
      • Joubert J.R.
      • de Klerk H.C.
      • Malan C.
      Ascaris lumbricoides and allergic asthma: a new perspective.
      ]. Thus, this study suggested that infection with Ascaris may indeed be associated with IgE-mediated asthma-like reactions. Ascaris-specific IgE responses may be a risk factor for atopic disease in children exposed to mild Ascaris infection [
      • Obihara C.C.
      • Beyers N.
      • Gie R.P.
      • Hoekstra M.O.
      • Fincham J.E.
      • et al.
      Respiratory atopic disease, Ascaris-immunoglobulin E and tuberculin testing in urban South African children.
      ]. This study included 359 randomly selected children aged 6 to 14 years from a poor urban suburb. Ascaris-specific IgE levels were elevated in 48% of children, and Ascaris eggs were found in 15%. Children with elevated Ascaris-specific IgE levels had significantly increased risk of positive SPT to aeroallergens, particularly HDM, atopic asthma (ever and recent), atopic rhinitis (ever and recent), and increased atopy-related bronchial hyperresponsiveness.
      Curiously, in a cross-sectional prevalence study, with a nested case-control component, carried out in urban and rural South African children, Ascaris infection was associated with an increased risk of EIB (OR = 1.62; 95% confidence interval, 1.23-2.11; P = 0.001), independently of total and specific IgE levels, suggesting that mechanisms other than those that are mediated by IgE may be operative in the affected patients [
      • Calvert J.
      • Burney P.
      Ascaris, atopy, and exercise-induced bronchoconstriction in rural and urban South African children.
      ].
      In contrast, the study carried out in South African 10- to 14-year-old children from Transkei, from different ethnical and sociological backgrounds (traditional rural Xhosa children, recently urbanized Xhosa children and established city white children), failed to show any modifying role of Ascaris infection in the development of increased BHR in the rural or urban children [
      • Mavale-Manuel S.
      • Joaquim O.
      • Macome C.
      • Almeida L.
      • Nunes E.
      • et al.
      Asthma and allergies in schoolchildren in Maputo.
      ].
      A previous study from the Western Cape, South Africa, showed that Cape Coloureds and Africans tended to have elevated serum IgE concentrations; however, Cape Coloureds and Africans had high prevalence values of helminthic infestation and a relatively low prevalence of allergic symptoms.
      Finally, serum IgE levels were examined in 237 infants aged 2 weeks to 12 months in a remote rural area of Namibia [
      • Heese H.D.
      • du Plessis J.M.
      • Dempster W.S.
      • McKenzie D.
      • Super M.
      • Lerch W.H.
      Serum-IgE levels in rural Namibian infants.
      ]. Median values were higher than those reported from Western countries. Investigations did not suggest that parasitic infestations or atopy were of significant importance for the determination of total serum IgE levels.

      Mycobacterial and Viral Infections

      In the study involving a stratified national probability sample of households involving adolescents (> 14 years) and adults (5671 men and 8155 women), a history of TB was an independent predictor of both recent wheeze and asthma diagnosis [
      • Ehrlich R.I.
      • White N.
      • Norman R.
      • Laubscher R.
      • Steyn K.
      • Lombard C.
      • Bradshaw D.
      Wheeze, asthma diagnosis and medication use: a national adult survey in a developing country.
      ]. This study therefore suggested that, in this population, previous TB may predispose to wheeze or asthma. However, it was stressed that heterogeneity of the categories wheeze and asthma diagnosis, which may overlap with posttuberculous airways obstruction, may have been confounding factors.
      The study by Obihara et al [
      • Obihara C.C.
      • Beyers N.
      • Gie R.P.
      • Hoekstra M.O.
      • Fincham J.E.
      • et al.
      Respiratory atopic disease, Ascaris-immunoglobulin E and tuberculin testing in urban South African children.
      ] showed that in children with negative tuberculin test (< 10 mm), elevated Ascaris-specific IgE levels were associated with a significantly increased risk of atopic symptoms, whereas in those with a positive tuberculin test (≥ 10 mm) this association was not present. This suggests that infection with mycobacteria may be protective against the Ascaris-associated increased risk of atopic allergic disease. Whether a similarly protective effect of mycobacterial infection upon development of atopic symptoms in children not infected with Ascaris also takes place, still has to be ascertained.
      Human immunodeficiency virus (HIV) infection has very high prevalence values in Southern African countries. Although it is controversial, chronic HIV infection may affect some of the immunological mechanisms related to allergic inflammation, namely, IgE production and other mechanisms. A recent study included 50 HIV-infected children, aged 3 months to 12 years, all of whom were on antiretroviral therapy and 50 HIV-negative healthy controls [
      • Masekela R.
      • Moodley T.
      • Mahlaba N.
      • Wittenberg D.F.
      • Becker P.
      • Kitchin O.
      • Green R.J.
      Atopy in HIV-infected children in Pretoria.
      ]. The authors failed to find a difference in the frequency of atopy between the groups but the prevalence of asthma was higher than historical data from South African ISAAC studies. It was concluded that there was no association between HIV disease stage and presence of atopy and that bronchial asthma in these children was nonallergic.

      Sociocultural Factors

      Until fairly recently, children in many African countries lived mainly in rural areas and were not exposed to the effects of a Western lifestyle. Early studies in a limited number of African countries, including South Africa, showed a very low rural prevalence of childhood asthma, especially where children lived according to a traditional lifestyle. These studies also showed that asthma was not uncommon in urbanized African children. There has been a massive migration over the past 20 years from those in rural communities to the large periurban squatter areas. The prevalence of current asthma has been on the increase not only in peri-urban and urban but also even in rural areas. This may be due, at least in part, to exposure of rural children to agricultural pesticides and irritants as well as of an increasing tendency to adopt a more Westernized lifestyle, such as the use of beds with mattresses, pillows, and blankets even in the rural areas [
      • Weinberg E.G.
      Urbanization and childhood asthma: an African perspective.
      ].
      The first study to address urban-rural differences in the prevalence of allergic diseases was an epidemiological study undertaken in 1979 to determine the prevalence of asthma in young urban and rural black (Xhosa) children [
      • Van Niekerk C.H.
      • Weinberg E.G.
      • Shore S.C.
      • Heese H.V.
      • Van Schalkwyk J.
      Prevalence of asthma: a comparative study of urban and rural Xhosa children.
      ]. One thousand three hundred seventy-five children were studied, 694 from a Cape Town African township and 671 from a rural area in Transkei. Whereas 22 children were found to be asthmatic in the city area, only 1 from the country was diagnosed as asthmatic, giving a prevalence figure for asthma of 3.17% in the urban group and 0.14% for the rural group.
      Twenty years later, the study carried out by Steinman et al, [
      • Steinman H.
      • Dawson H.
      • Kawalski M.
      • Toerien A.
      • Potter P.C.
      Bronchial hyperresponsiveness and atopy in urban, peri-urban and rural South African children.
      ] of BHR and atopy in Xhosa and white children cross a gradient of environments from rural, peri-urban, to urban environments found an increase in BHR and specific IgE responsiveness when rural children adopted a more Western life style that was similar to the prevalence found in children who were born in a Cape Town suburb.
      In Mozambique, using the ISAAC protocol applied to 2630 students aged 13 to 14 years, and in 2383 schoolchildren aged 6 to 7 years, exercise-induced wheeze, nocturnal cough, and ever asthma were reported more frequently in children of the suburban area than in the urban or semirural environments [
      • Mavale-Manuel S.
      • Joaquim O.
      • Macome C.
      • Almeida L.
      • Nunes E.
      • et al.
      Asthma and allergies in schoolchildren in Maputo.
      ]. However, another study by the same group, carried out in Maputo and involving 100 asthmatic children and 99 nonasthmatic children aged between 18 months and 8 years (mean age of around 3 years for both groups), showed that having been born or living in inner Maputo were independent and significant risk factors for bronchial asthma [
      • Mavale-Manuel S.
      • Alexandre F.
      • Duarte N.
      • Albuquerque O.
      • Scheinmann P.
      • Poisson-Salomon A.S.
      • de Blic J.
      Risk factors for asthma among children in Maputo (Mozambique).
      ]. Curiously, another South African study suggested that urban-rural differences in the prevalence of atopy may be partly due to differences in dietary components in the 2 areas [
      • Poyser M.A.
      • Nelson H.
      • Ehrlich R.I.
      • Bateman E.D.
      • Parnell S.
      • Puterman A.
      • Weinberg E.
      Socioeconomic deprivation and asthma prevalence and severity in young adolescents.
      ].
      In general, the least socioeconomically deprived pupils report a higher prevalence of asthma symptoms "ever" and "in the last 12 months."[
      • Poyser M.A.
      • Nelson H.
      • Ehrlich R.I.
      • Bateman E.D.
      • Parnell S.
      • Puterman A.
      • Weinberg E.
      Socioeconomic deprivation and asthma prevalence and severity in young adolescents.
      ] In contrast, the most socioeconomically deprived pupils reported higher occurrence of asthma symptoms monthly or more frequently in the previous 12 months. In addition, a subgroup of pupils from low-income areas commuting to better-off schools showed the highest symptom prevalence. This study therefore suggests that an increase in the incidence of asthma in this population may be driven by factors associated with improved social circumstances, whereas severity is determined by factors associated with poverty [
      • Poyser M.A.
      • Nelson H.
      • Ehrlich R.I.
      • Bateman E.D.
      • Parnell S.
      • Puterman A.
      • Weinberg E.
      Socioeconomic deprivation and asthma prevalence and severity in young adolescents.
      ].
      Education problems are a special type of socioeconomic issues. Education levels in African populations tend to be low, which may lead to poor patient adherence to treatment based upon wrong perceptions of allergic disease. It is extremely to overcome language and cultural difficulties. In this regard, a South African study carried out in 1955 parents of pupils from 16 schools in Cape Town showed that current treatment and, to a lesser degree, recognition of asthma by parents were more common among children of higher socioeconomic status [
      • Ehrlich R.I.
      • Jordaan E.
      • du Toit D.
      • Volmink J.A.
      • Weinberg E.
      • Zwarenstein M.
      Underrecognition and undertreatment of asthma in Cape Town primary school children.
      ]. Another study, performed at clinics, hospitals, or respondents' homes in a rural setting, showed that fear and ignorance surrounding asthma were common, strengthening the need for a greater level of patient education in the rural areas [
      • Green R.J.
      • Greenblatt M.M.
      • Plit M.
      • Jones S.
      • Adam B.
      Asthma management and perceptions in rural South Africa.
      ].
      In the study from Maputo (Mozambique), knowledge about asthma was poor [
      • Mavale-Manuel S.
      • Duarte N.
      • Alexandre F.
      • Albuquerque O.
      • Scheinmann P.
      • Poisson-Salomon A.S.
      • de Blic J.
      Knowledge, attitudes, and behavior of the parents of asthmatic children in Maputo.
      ]: 11% of the adults thought that asthma was contagious and transmitted from person to person, and 4% thought that it was transmitted by contaminated food. A large proportion of the parents thought that asthma could be cured by medical treatment in 7% of cases and by alternative treatment in 43% of cases. The precipitating factors were well identified by the adults, but they had an inaccurate perception of the symptoms of an asthma attack. Finally, the actions of the various classes of drugs used were poorly understood.
      A study aimed to obtain information useful to asthma care in a relatively poor, high asthma prevalence population involved 72 parents of children with asthma or recurrent wheezing [
      • Jones S.L.
      • Weinberg M.
      • Ehrlich R.I.
      • Roberts K.
      Knowledge, attitudes, and practices of parents of asthmatic children in Cape Town.
      ]. There was a reasonable level of understanding of the causes of asthma, although variable acceptance of the diagnosis. Willingness to undertake home management of acute episodes and environmental control measures was high. However, reported treatment was characterized by reliance on syrups, use of home remedies, resistance to inhaled therapy, and relatively low compliance with prescribed treatment. Thus, this study showed that there is an urgent need to improve the quality of asthma care communication and general knowledge of the situation in patients and relatives [
      • Green R.
      • Davis G.
      • Price D.
      Perceptions, impact and management of asthma in South Africa: a patient questionnaire study.
      ]. In fact, these factors strongly affect implementation of therapy and adherence to prescribed asthma treatments. This was further explored in a study that aimed to analyze the impact on quality of life of asthma on South African asthmatics [
      • Jones S.L.
      • Weinberg M.
      • Ehrlich R.I.
      • Roberts K.
      Knowledge, attitudes, and practices of parents of asthmatic children in Cape Town.
      ]. Symptom analysis of asthmatic patients showed that 21.4% of respondents were coughing on most days, 25.6% were wheezing on most days, and 22.8% were experiencing nighttime symptoms on most days. Symptoms were exacerbated by exercise in 56.9%, whereas nocturnal wakening due to asthma occurred in 36.9% more than 4 times per week. Only 35.1% of respondents had not missed school or work in the preceding year. In the study by Ehrlich et al [
      • Ehrlich R.I.
      • Du Toit D.
      • Jordaan E.
      • Volmink J.A.
      • Weinberg E.G.
      • Zwarenstein M.
      Prevalence and reliability of asthma symptoms in primary school children in Cape Town.
      ] in 1995, of children with more than 12 recent attacks of wheeze, only 60% were reported as asthmatic and only 55% were receiving regular treatment, confirming that underdiagnosis and under-treatment of asthma were still important problems in the region. The extent and progress with this problem can be further gauged from a retrospective study that aimed to investigate the incidence of fatal and near-fatal asthma between 1980 and 1997 in Cape Town [
      • Zar H.J.
      • Stickells D.
      • Toerien A.
      • Wilson D.
      • Klein M.
      • Bateman E.D.
      Changes in fatal and near-fatal asthma in an urban area of South Africa from 1980-1997.
      ]. There were 1506 reported deaths (mean age, 56 years) from asthma, 39 and 3% occurred in people younger than 55 and 15 years, respectively. The average annual asthma mortality rate (8.1 ± 1.9 per 100,000 population) was highest among people of mixed race (10.1 ± 2.0), followed by blacks (6.8 ± 3.1) and whites (5.0 ± 1.9, P < 0.001). Asthma mortality declined by 0.28 deaths per 100,000 population per year; rates decreased in all ethnic groups. Most deaths (72.3%) were outside a health facility, and a significantly higher number of deaths occurred on weekends. Pediatric asthma intensive care unit admissions also declined by 1.81 children per year, but the annual number of adults admitted to intensive care unit for asthma did not change. These results indicate that the incidence of fatal and near-fatal asthma in this area has declined over the period, and this may reflect generally improved asthma management. However, the relatively high asthma mortality rate in people of mixed race and the predominance of deaths outside health facilities and on weekends suggest problems with access to care.
      Fewer studies have addressed the issue of patient adherence to treatment for allergic rhinitis. This was one of the objectives of a questionnaire-based study about allergic rhinitis that was applied to 1181 patients in South Africa [
      • Green R.J.
      • Davis G.
      • Price D.
      Concerns of patients with allergic rhinitis: the Allergic Rhinitis Care Programme in South Africa.
      ]. This study showed that nasal symptoms affected sleep in 76.6% of sufferers, and in at least a third, this was every night. The quality of life was poor in 85.2% of patients, due to uncontrolled symptoms. About 37% of patients did not take rhinitis medication or did not take it as frequently as recommended, and various perceived concerns regarding having and being treated for allergic rhinitis were identified, suggesting multiple reasons for nonadherence.

      Racial Differences

      One of the earliest reports on childhood asthma in Southern Africa was published in 1969 and analyzed asthma hospital admissions of black, Indian, and white children in Durban, South Africa, during a 5-year period (1963-1967) [
      • Wesley A.G.
      • Clyde J.H.
      • Wallace H.L.
      Asthma in Durban children of three racial groups.
      ]. There were only 9 admissions for asthma among black children (admission rate of 0.02 percent of all hospitalizations), which was much lower than that of white children (0.79 percent) during the same period, suggesting that there could be race-linked socioeconomic and cultural differences associated with asthma admissions to hospital.
      In Cape Town, South Africa, the prevalence of EIB was compared between 698 white and 494 colored schoolchildren [
      • Terblanche E.
      • Stewart R.I.
      The prevalence of exercise-induced bronchoconstriction in Cape Town schoolchildren.
      ]. The prevalence of EIB was significantly higher among white (5.87%) than colored children (4.05%).
      More respiratory tract infections occur in colored patients, and they are more exposed to their own and secondary cigarette smoke [
      • Joubert J.R.
      • Brink S.
      • Hentzen G.M.
      Allergic asthma in different population groups in the Western Cape. Causative and complicating factors.
      ]. Curiously, sensitization to pets and grass pollens was more common among whites, whereas allergy to Aspergillus fumigatus and Ascaris lumbricoides was found more frequently among colored patients. Although both white and colored patients had problems with regular prophylactic control of their symptoms with inhaled beta2-agonists, this was greater in the colored group (60%) than the white group (27%).
      In a prospective study, a questionnaire was applied to white asthmatic children in Johannesburg to compare these with a similar population of black asthmatic children resident in Soweto, from whom data had been previously obtained [
      • Green R.
      • Luyt D.
      Clinical characteristics of childhood asthmatics in Johannesburg.
      ]. Although there were many common clinical points, some differences were apparent. For instance, cold weather was a much more frequent trigger of cough and wheeze in Soweto than in Johannesburg (64.6 vs 10.5%). In addition, environmental dust was described as trigger of symptoms a lot more frequently in Soweto than in Johannesburg (38.6% of children vs 13.1%). In addition, although fungal extracts tested were different, mould sensitivity was less common in black children from Soweto than in white children from Johannesburg. Although genetic factors may have explained part of the results, the poorer living conditions in Soweto may explain the differences observed. In a study carried out in 1991, in Zimbabwe, children of different race but with similar socioeconomic background demonstrated that the prevalence of bronchial hyperresponsiveness was similar between black and white children of a similar social status [
      • Keeley D.J.
      • Neill P.
      • Gallivan S.
      Comparison of the prevalence of reversible airways obstruction in rural and urban Zimbabwean children.
      ].
      A very important study aimed to determine whether death rates from asthma have been rising in South Africa calculated asthma mortality rates among colored and white South Africans from official figures for the years 1962 to 1988 [
      • Ehrlich R.I.
      • Bourne D.E.
      Asthma deaths among coloured and white South Africans: 1962 to 1988.
      ]. Sharp increases in the 1960s were noted in both groups. However, since the early 1970s, death rates in whites have generally shown a downward trend. In contrast, rates in colored patients remained generally high and were consistently higher than those in white patients across different age ranges. Again, the intergroup differences detected seem to be due to greater exposure to environmental triggers or to well-known inequalities in medical care between white and colored patients rather than to genetic differences between these 2 racial groups.
      Although socioeconomic, cultural, and health facility accessibility differences may explain most of the interracial differences observed by some studies in some features of expression of respiratory allergic disease, a genetic basis may not be fully excluded. In this regard, a curious study used an amplification refractory mutation system-polymerase chain reaction to analyze the prevalence of 3 mutations in the beta chain of the high-affinity IgE receptor (Fcepsilon RI-beta): I181L, V183L, and E237G in a sample of black and white asthmatic and control subjects in South Africa [
      • Green S.L.
      • Gaillard M.C.
      • Song E.
      • Dewar J.B.
      • Halkas A.
      Polymorphisms of the beta chain of the high-affinity immunoglobulin E receptor (Fcepsilon RI-beta) in South African black and white asthmatic and nonasthmatic individuals.
      ]. One of the main objectives was to determine whether the discrepancy in the prevalence of atopy in these groups could be attributed to these variants. A significant difference in the frequency of I181L between white asthmatics (28%) and white control subjects (3%) was detected, and also between black control subjects (16%) and white control subjects. Furthermore, there was a significant difference in the frequency of E237G between black asthmatics (20%) and white asthmatics (12%), and also between control subjects (20%) and white control subjects (5%). E237G was significantly more prevalent in blacks (20%) than in whites (8.5%). This study concluded that I181L might predispose to atopy in the white population but not in the black population. In addition, the significantly higher prevalence of E237G in blacks than in whites might explain why blacks tend to have more severe asthma than whites.
      This review has shown that systematic studies of allergies and asthma have confirmed that the prevalence of respiratory allergic diseases has been increasing in Southern Africa both in urban and in rural environments. Various factors may contribute toward this situation, in particular, recent changes in exposure to certain aeroallergens or other irritant environmental triggers due to migration and adoption of a Western life style. Certain cultural and socioeconomic factors may also influence accessibility to healthcare and adherence to treatment of these diseases. Furthermore, importance of communication with patients with allergic diseases in their own indigenous African language has recently been studied and emphasized by Levin [
      • Levin M.E.
      Different use of medical terminology and culture specific models of disease affecting communication between Xhosa-speaking patients and English-speaking doctors at a South African teaching hospital.
      ,
      • Levin M.E.
      • Moloiwa R.
      • Motala C.
      Associations between asthma and bronchial hyper responsiveness with allergy and atopy phenotypes in urban black South African teenagers.
      ] and must be taken into consideration both in assessing the prevalence of disease in the region and in formulation of treatment plans in the future.
      Thus, studies from Southern Africa in the context of westernization, parasite infestation and TB have provided new insights into many of the factors believed to influence the expression of allergic diseases, such as asthma and rhinitis, some of which are not consistent with the hygiene hypothesis, which more fully explains the development of allergens in more affluent countries.

      References

      1. O'Keefe D, Lavender S: The plight of modern bushman. Lancet. 1989, 255-257. ii

        • Cookson J.B.
        • Makoni G.
        Prevalence of asthma in Rhodesian Africans.
        Thorax. 1980; 35: 833-837
        • van Niekerk C.H.
        • Weinberg E.G.
        • Shore S.C.
        • Heese H.D.
        Prevalence of childhood asthma in Africa.
        Lancet. 1977; 1: 96-97
        • Ehrlich R.I.
        • Du Toit D.
        • Jordaan E.
        • Volmink J.A.
        • Weinberg E.G.
        • Zwarenstein M.
        Prevalence and reliability of asthma symptoms in primary school children in Cape Town.
        Int J Epidemiol. 1995; 24: 1138-1145
        • Nriagu J.
        • Robins T.
        • Gary L.
        • Liggans G.
        • Davila R.
        • et al.
        Prevalence of asthma and respiratory symptoms in south-central Durban, South Africa.
        Eur J Epidemiol. 1999; 15: 747-755
        • Wichmann J.
        • Wolvaardt J.E.
        • Maritz C.
        • Voyi K.V.
        Household conditions, eczema symptoms and rhinitis symptoms: relationship with wheeze and severe wheeze in children living in the Polokwane area, South Africa.
        Matern Child Health J. 2009; 13: 107-118
        • Mashalane M.B.
        • Stewart A.
        • Feldman C.
        • Becker P.
        • de Charmoy S.
        Prevalence of exercise-induced bronchospasm in Thokoza schoolchildren.
        S Afr Med J. 2006; 96: 67-70
        • Mavale-Manuel S.
        • Joaquim O.
        • Nunes E.
        • Pedro A.
        • Bandeira S.
        • et al.
        Prevalence of asthma-like symptoms by ISAAC video questionnaire in Mozambican schoolchildren.
        Monaldi Arch Chest Dis. 2006; 65: 189-195
        • Mavale-Manuel S.
        • Joaquim O.
        • Macome C.
        • Almeida L.
        • Nunes E.
        • et al.
        Asthma and allergies in schoolchildren in Maputo.
        Allergy. 2007; 62: 265-271
        • Steinman H.
        • Dawson H.
        • Kawalski M.
        • Toerien A.
        • Potter P.C.
        Bronchial hyperresponsiveness and atopy in urban, peri-urban and rural South African children.
        Paediatr Allergy Clin Immunol. 2003; 14: 383-393
        • Zar H.J.
        • Ehrlich R.I.
        • Workman L.
        • Weinberg E.G.
        The changing prevalence of asthma, allergic rhinitis and atopic eczema in African adolescents from 1995 to 2002.
        Pediatr Allergy Immunol. 2007; 18: 560-565
        • Green R.J.
        Paediatric asthma in Southern Africa.
        Open Allergy J. 2011; 4: 8-15
        • Ordman D.
        The climate group of respiratory allergy patients in South Africa; their sensitivity to house dust and desensitization with extracts of the allergenically potent coastal house dust.
        S Afr Med J. 1958; 32: 853-855
        • Ordman D.
        Respiratory allergy in the coastal areas of South Africa; the climate factors in relation to house-dust sensitivity.
        S Afr Med J. 1958; 32: 117-118
        • Davis G.
        • Luyt D.
        • Prescott R.
        • Potter P.C.
        House dust mites in Soweto.
        Curr Allergy Clin Immunol. 1994; 7: 16-17
        • Manjra A.I.
        • Berman D.
        • Toerien A.
        • Weinberg E.G.
        • Potter P.C.
        The effects of a single appilcation of an acaricide (Acarosan) and a detergent (Metsan) on Der p 1 levels on carpets and mattresses of asthmatic children.
        S Afr Med J. 1994; 84: 278-280
        • Jooma O.F.
        • Weinberg E.G.
        • Berman D.
        • Manjra A.I.
        • Potter P.C.
        Accumulation of housedust mite (Der p 1) levels on mattress covers.
        S Afr Med J. 1995; 85: 1002-1005
        • Potter P.C.
        • Berman D.
        • Toerien A.
        • Malherbe D.
        • Weinberg E.G.
        Clinical significance of aero-allergen identification in the Western Cape.
        S Afr Med J. 1991; 79: 80-84
        • Cadman A.
        • Prescott R.
        • Potter P.C.
        Year-round housedust mite levels on the Highveld.
        S Afr Med J. 1998; 88: 1580-1582
        • Westritschnig K.
        • Sibanda E.
        • Thomas W.
        • Auer H.
        • Aspöck H.
        • et al.
        Analysis of the sensitization profile towards allergens in central Africa.
        Clin Exp Allergy. 2003; 33: 22-27
        • Potter P.C.
        • Davis G.
        • Manjra A.
        • Luyt D.
        House dust mite allergy in Southern Africa--historical perspective and current status.
        Clin Exp Allergy. 1996; 26: 132-137
        • Fraser B.N.
        Cockroaches in relation to bronchial asthma in the Durban area.
        S Afr Med J. 1979; 55: 637-638
        • van Niekerk C.H.
        • Shore S.C.
        • Weinberg E.G.
        The house-dust mite and childhood asthma in the Cape Peninsula.
        S Afr Med J. 1977; 52: 74-75
        • Buchanan D.J.
        • Jones I.G.
        Mites and house dust mite allergy in bronchial asthma in Northern Zambia.
        Postgrad Med J. 1974; 50: 680-682
        • Kambarami R.A.
        • Marechera F.
        • Sibanda E.N.
        • Chitiyo M.E.
        Aero-allergen sensitisation patterns amongst atopic Zimbabwean children.
        Cent Afr J Med. 1999; 45: 144-147
        • Luyt D.K.
        • Davis G.
        • Dance M.
        • Simmank K.
        • Patel D.
        Clinical characteristics of black asthmatic children.
        S Afr Med J. 1995; 85: 999-1001
        • Seedat R.Y.
        • Claassen J.
        • Claassen A.J.
        • Joubert G.
        Mite and cockroach sensitisation in patients with allergic rhinitis in the Free State.
        S Afr Med J. 2010; 100: 160-163
        • Potts G.
        The pepper tree (Schinus molle) in its relationship to epidemic hayfever: interim report.
        S Afr J Sci. 1919; 15: 525-530
        • Potts G.
        The potency of pepper tree pollen as a cause of hayfever.
        S Afr J Sci. 1922; 18: 336-341
        • Potts G.
        The pepper tree (Schinus molle L.) as a cause of hayfever in South Africa.
        S Afr J Sci. 1922; 19: 146-195
        • Ordman D.
        Cypress pollinosis in South Africa. A study of seasonal hayfever and allergic conjunctivitis occurring in the winter/spring period.
        S Afr Med J. 1945; 19: 142-153
        • Ordman D.
        Pollinosis in South Africa.
        S Afr Med J. 1947; 21: 38-48
        • Ordman D.
        Cereal grain dusts as a cause of respiratory allergy in South Africa.
        S Afr Med J. 1958; 32: 784-788
        • Ordman D.
        Seasonal respiratory allergy and the associated pollens in South Africa.
        S Afr Med J. 1963; 37: 321-325
        • Ordman D.
        Seasonal respiratory allergy in Windhoek: the pollen and fungus factors.
        S Afr Med J. 1963; 44: 250-253
        • Ordman D.
        Seasonal respiratory allergy in Bulawayo, Rhodesia: the pollen and fungus factors.
        S Afr Med J. 1972; 46: 1898-1901
        • Ordman D.
        Respiratory allergy in the coastal areas of South Africa; the significance of climate.
        S Afr Med J. 1955; 29: 173-179
        • Orren A.
        • Dowdle E.B.
        Studies on Bermuda grass pollen allergens.
        S Afr Med J. 1977; 51: 586-591
        • Potter P.C.
        Identifying the allergenic grasses of Southern Africa.
        Curr Allergy Clin Immunol. 1994; 7: 2
        • Potter P.C.
        • Mather S.
        • Lockey P.
        • Ainslie G.
        • Cadman A.
        IgE specific immune responses to an African grass (Kikuyu, Pennisetum clandestinum).
        Clin Exp Allergy. 1993; 23: 581-586
        • Prescott R.A.
        • Potter P.C.
        Allergenicity and cross-reactivity of buffalo grass (Stenotaphrum secundatum).
        S Afr Med J. 2001; 91: 237-243
        • Potter P.C.
        Allergy in Southern Africa.
        Curr Allergy Clin Immunol. 2009; 22: 156-161
        • Potter P.C.
        • Cadman A.
        Pollen allergy in South Africa.
        Clin Exp Allergy. 1996; 26: 1347-1354
        • Maluleke K.R.
        • Worku Z.
        Environmental determinants of asthma among school children aged 13-14 in and around Polokwane, Limpopo Province, South Africa.
        Int J Environ Res Public Health. 2009; 6: 2354-2374
        • Ehrlich R.
        • Jordaan E.
        • Du Toit D.
        • Potter P.
        • Volmink J.
        • Zwarenstein M.
        • Weinberg E.
        Household smoking and bronchial hyperresponsiveness in children with asthma.
        J Asthma. 2001; 38: 239-251
        • Ehrlich R.I.
        • Du Toit D.
        • Jordaan E.
        • Zwarenstein M.
        • Potter P.
        • Volmink J.A.
        • Weinberg E.
        Risk factors for childhood asthma and wheezing. Importance of maternal and household smoking.
        Am J Respir Crit Care Med. 1996; 154: 681-688
        • Ehrlich R.I.
        • White N.
        • Norman R.
        • Laubscher R.
        • Steyn K.
        • Lombard C.
        • Bradshaw D.
        Wheeze, asthma diagnosis and medication use: a national adult survey in a developing country.
        Thorax. 2005; 60: 895-901
        • Calvert J.
        • Burney P.
        Effect of body mass on exercise-induced bronchospasm and atopy in African children.
        J Allergy Clin Immunol. 2005; 116: 773-779
        • Obihara C.C.
        • Marais B.J.
        • Gie R.P.
        • Potter P.
        • Bateman E.D.
        • et al.
        The association of prolonged breastfeeding and allergic disease in poor urban children.
        Eur Respir J. 2005; 25: 970-977
        • Levin M.E.
        • Le Souëf P.N.
        • Motala C.
        Total IgE in urban black South African teenagers: the influence of atopy and helminth infection.
        Pediatr Allergy Immunol. 2008; 19: 449-454
        • Joubert J.R.
        • de Klerk H.C.
        • Malan C.
        Ascaris lumbricoides and allergic asthma: a new perspective.
        S Afr Med J. 1979; 56: 599-602
        • Obihara C.C.
        • Beyers N.
        • Gie R.P.
        • Hoekstra M.O.
        • Fincham J.E.
        • et al.
        Respiratory atopic disease, Ascaris-immunoglobulin E and tuberculin testing in urban South African children.
        Clin Exp Allergy. 2006; 36: 640-648
        • Calvert J.
        • Burney P.
        Ascaris, atopy, and exercise-induced bronchoconstriction in rural and urban South African children.
        J Allergy Clin Immunol. 2010; 125: 100-105
        • Orren A.
        • Dowdle E.B.
        Effects of allergy, intestinal helminthic infestation and sex on serum IgE concentrations and immediate skin hypersensitivity in three ethnic groups.
        Int Arch Allergy Appl Immunol. 1975; 49: 814-830
        • Heese H.D.
        • du Plessis J.M.
        • Dempster W.S.
        • McKenzie D.
        • Super M.
        • Lerch W.H.
        Serum-IgE levels in rural Namibian infants.
        J Allergy Clin Immunol. 1984; 74: 514-523
        • Masekela R.
        • Moodley T.
        • Mahlaba N.
        • Wittenberg D.F.
        • Becker P.
        • Kitchin O.
        • Green R.J.
        Atopy in HIV-infected children in Pretoria.
        S Afr Med J. 2009; 99: 822-825
        • Weinberg E.G.
        Urbanization and childhood asthma: an African perspective.
        J Allergy Clin Immunol. 2000; 105: 224-231
        • Van Niekerk C.H.
        • Weinberg E.G.
        • Shore S.C.
        • Heese H.V.
        • Van Schalkwyk J.
        Prevalence of asthma: a comparative study of urban and rural Xhosa children.
        Clin Allergy. 1979; 9: 319-324
        • Mavale-Manuel S.
        • Alexandre F.
        • Duarte N.
        • Albuquerque O.
        • Scheinmann P.
        • Poisson-Salomon A.S.
        • de Blic J.
        Risk factors for asthma among children in Maputo (Mozambique).
        Allergy. 2004; 59: 388-393
        • Poyser M.A.
        • Nelson H.
        • Ehrlich R.I.
        • Bateman E.D.
        • Parnell S.
        • Puterman A.
        • Weinberg E.
        Socioeconomic deprivation and asthma prevalence and severity in young adolescents.
        Eur Respir J. 2002; 19: 892-898
        • Ehrlich R.I.
        • Jordaan E.
        • du Toit D.
        • Volmink J.A.
        • Weinberg E.
        • Zwarenstein M.
        Underrecognition and undertreatment of asthma in Cape Town primary school children.
        S Afr Med J. 1998; 88: 986-994
        • Green R.J.
        • Greenblatt M.M.
        • Plit M.
        • Jones S.
        • Adam B.
        Asthma management and perceptions in rural South Africa.
        Ann Allergy Asthma Immunol. 2001; 86: 343-347
        • Mavale-Manuel S.
        • Duarte N.
        • Alexandre F.
        • Albuquerque O.
        • Scheinmann P.
        • Poisson-Salomon A.S.
        • de Blic J.
        Knowledge, attitudes, and behavior of the parents of asthmatic children in Maputo.
        J Asthma. 2004; 41: 533-538
        • Jones S.L.
        • Weinberg M.
        • Ehrlich R.I.
        • Roberts K.
        Knowledge, attitudes, and practices of parents of asthmatic children in Cape Town.
        J Asthma. 2000; 37: 519-528
        • Green R.
        • Davis G.
        • Price D.
        Perceptions, impact and management of asthma in South Africa: a patient questionnaire study.
        Prim Care Respir J. 2008; 17: 212-216
        • Zar H.J.
        • Stickells D.
        • Toerien A.
        • Wilson D.
        • Klein M.
        • Bateman E.D.
        Changes in fatal and near-fatal asthma in an urban area of South Africa from 1980-1997.
        Eur Respir J. 2001; 18: 33-37
        • Green R.J.
        • Davis G.
        • Price D.
        Concerns of patients with allergic rhinitis: the Allergic Rhinitis Care Programme in South Africa.
        Prim Care Respir J. 2007; 16: 299-303
        • Wesley A.G.
        • Clyde J.H.
        • Wallace H.L.
        Asthma in Durban children of three racial groups.
        S Afr Med J. 1969; 43: 87-89
        • Terblanche E.
        • Stewart R.I.
        The prevalence of exercise-induced bronchoconstriction in Cape Town schoolchildren.
        S Afr Med J. 1990; 78: 744-747
        • Joubert J.R.
        • Brink S.
        • Hentzen G.M.
        Allergic asthma in different population groups in the Western Cape. Causative and complicating factors.
        S Afr Med J. 1988; 73: 150-154
        • Green R.
        • Luyt D.
        Clinical characteristics of childhood asthmatics in Johannesburg.
        S Afr Med J. 1997; 87: 878-882
        • Keeley D.J.
        • Neill P.
        • Gallivan S.
        Comparison of the prevalence of reversible airways obstruction in rural and urban Zimbabwean children.
        Thorax. 1991; 146: 549-553
        • Ehrlich R.I.
        • Bourne D.E.
        Asthma deaths among coloured and white South Africans: 1962 to 1988.
        Respir Med. 1994; 88: 195-202
        • Green S.L.
        • Gaillard M.C.
        • Song E.
        • Dewar J.B.
        • Halkas A.
        Polymorphisms of the beta chain of the high-affinity immunoglobulin E receptor (Fcepsilon RI-beta) in South African black and white asthmatic and nonasthmatic individuals.
        Am J Respir Crit Care Med. 1998; 158: 1487-1492
        • Levin M.E.
        Different use of medical terminology and culture specific models of disease affecting communication between Xhosa-speaking patients and English-speaking doctors at a South African teaching hospital.
        S Afr Med J. 2006; 96: 1080-1084
        • Levin M.E.
        • Moloiwa R.
        • Motala C.
        Associations between asthma and bronchial hyper responsiveness with allergy and atopy phenotypes in urban black South African teenagers.
        S Afr Med J. 2011; 101: 472-476