Paper: Prevalence of asthma: a comparative study of urban and rural Xhosa children
Christo van Niekerk, EG Weinberg, SC Shore, H de V Heese, and DJ Van Schalkwyk
Clinical & Experimental Allergy 1979; 9 (4)
Several studies have been undertaken to determine the prevalence of asthma in childhood, and a wide variety has been reported in different population groups. . . . In African and other non-industrialised countries, childhood asthma appears to be rare, with a reported prevalence varying between 0.007 and 1.96%. Analysis of these reports suggests that asthma is rare in rural communities at all ages. However, in urbanised areas, asthma is said to be common. . . .
In order to ascertain whether asthma was as rare a disorder in the black children of our city as we suspected from our clinical experience, a study of urban and rural Xhosa children was undertaken to determine the prevalence of asthma in these two groups. . . . One thousand three hundred and seventy five children were studied, 694 from a Cape Town African township and 671 from a rural area in Transkei. . . . The exercise challenge test was selected as the most reliable single test for identifying children with asthma. . . .
A diagnosis of asthma was made in twenty-two of the urban children (Guguletu) and in one child from the rural area (Transkei). The prevalence among Guguletu children was 3.17% and for children from the Tsolo district, 0.14%.
Epidemiological research depends strongly on the presence of natural variation, but until the 1970s there was relatively little evidence of wide variation between groups in the occurrence of asthma. In the 1960s, John Morrison Smith in Birmingham, UK noted that there was relatively little asthma among migrant children who were born in the West Indies, but the 1958 national birth cohort showed very little evidence of variation by social factors. This picture changed markedly in the 1970s with Christo van Niekerk et al.’s study and three others showing marked variation in asthma between urban and rural populations in low-income countries.1–3 This strong signal remains one of the clearest clues to the origins of the disease.
All four studies made individual and important contributions. Ross Anderson’s study in particular made important observations in relation to indoor air pollution. I have selected van Niekerk’s study from these four for a number of reasons. First, because it used an objective measure of airway responsiveness in a population-based survey; second, because it has been imitated by others in sub-Saharan Africa;4–6 and finally, more personally, because as a medical student I was doing a survey of tuberculosis at around that time in the same rural location and the study caught my imagination then and strengthened my interest in both respiratory disease and epidemiology.
At the time of the study, asthma was already a serious clinical problem among children in urban areas of the Western Cape, including among the poor townships, whose population came in large part from the rural areas of the Transkei. In contrast, doctors practising in the rural areas, from which these populations were largely drawn, rarely if ever saw the condition. The first question was whether this could reflect a true difference in prevalence and the study was set up to test this.
The design of the study was straightforward. It was to take all children aged 6–9 years old living in a random sample of houses in one of the urban townships in the Western Cape, Gugulethu and compare the prevalence of exercise-induced broncho-constriction among these children with that of children of the same age living in a rural area defined as being within 9 kilometres of St Lucy’s Hospital in the Transkei. All the children had to have been resident for at least 4 years. The exercise challenge was 6 minutes maximum running with a post-exercise pulse rate of at least 170 beats/minute. A positive test was defined as a fall in either PEFR or FEV1 of at least 15%. The results were unequivocal. Of 672 children tested in the urban area, 22 (3.2%) were positive; of 670 children in the rural area only one (0.1%) was positive.
This study was not the first to use exercise challenge for the more objective assessment of airway pathology in epidemiological studies. Michael Burr had already started a series of studies using exercise-induced broncho-constriction in population-based studies in South Wales, a technique he subsequently extended to international studies that were to be the precursors of the International Study of Asthma and Allergies in Childhood (ISAAC). Although the ISAAC studies did not in the end use this method, others picked it up, including further studies in Africa.4–6 Although Anderson had used the technique he had not given the results much prominence.1
By the time that this research was done there was already a well-developed hypothesis linking the presence of parasites to the lack of asthma and, by implication, to atopic disease in general. This hypothesis has evolved over time and has become more sophisticated. At that time, the idea was that polyclonal expansion of IgE induced by parasites would block antibody responses by occupying IgE receptors. Subsequently there emerged a further hypothesis that parasites might block the inflammatory response by stimulating IL-10. The detailed answer to the question of what role parasites play in this story is still to be found, but the idea that differences in parasite load were going to explain the urban–rural differences in Africa was clearly seen to be unpromising from this study 35 years ago. In a separate paper, van Niekerk reported that 97% of the urban children in this study had evidence of helminths in their stools (68% had ascaris), whereas this was true for only 10% of the rural children (2.6% had ascaris).7
A major omission from this study was a detailed assessment of allergy, although at around the same time Terry and Josephine Merrett and John Cookson were investigating this issue in what is now Zimbabwe.8 Their finding that both total and specific levels of IgE were high rather than low in rural areas was a further clue that has been largely ignored. This finding was later confirmed in Kenya9 and in the Transkei,6 together with the finding that the relation between skin tests and specific IgE was very much weaker in the rural population, a finding that was in turn associated with body weight6 and diet.10 One aspect of this result that should be particularly surprising is that it is the custom in the rural areas of the Cape for women to re-lay the floor of their hut with cow dung in the weeks before the birth of a child. However, this intense exposure to the microbiome of the farmyard does not lead, as has been hypothesized in Europe, to a failure to produce specific antibodies to aeroallergens. The African findings strongly suggest the need for some revision of the current version of the hygiene hypothesis.
It is disappointing that the work that was started by a number of investigators in the 1970s has not been followed up more vigorously. It is important in part because of the local importance of emerging chronic diseases in low- and middle-income countries, but also because of what additional information it provides for building and discarding hypotheses related to conditions that affect both rich and poor. The failure to follow up these striking results more energetically has probably delayed our understanding of a common disease by several decades.
1 Anderson HR. The epidemiological and allergic features of asthma in the New Guinea highlands. Clin Allergy 1974; 4: 171–83.Find this resource:
2 Godfrey RC. Asthma and IgE levels in rural and urban communities of the Gambia. Clin Allergy 1975; 5: 201–7.Find this resource:
3 Waite DA, Eyles EF, Tonkin SL, O’Donnell TV. Asthma prevalence in Tokelauan children in two environments. Clin Allergy 1980; 10: 71–5.Find this resource:
4 Keeley DJ, Neill P, Gallivan S. Comparison of the prevalence of reversible airways obstruction in rural and urban Zimbabwean children. Thorax 1991; 46 (8): 549–53.Find this resource:
5 Ng’ang’a L, Odhiambo JA, Mungai MW, Gicheha CM, Nderitu P, Maingi B et al. Prevalence of exercise induced bronchospasm in Kenyan school children: An urban-rural comparison. Thorax 1998; 53: 919–26.Find this resource:
6 Calvert J, Burney P. Effect of body mass on exercise-induced bronchospasm and atopy in African children. J Allergy Clin Immunol 2005; 116: 773–9.Find this resource:
7 van Niekerk CH, Weinberg EG, Shore SC, de Heese H. Intestinal parasitic infestation in urban and rural Xhosa children. A comparative study. South African Med J 1979; 55 (19): 756–7.Find this resource:
8 Merrett T, Merrett J, Cookson J. Allergy and parasites; the measurement of total and specific IgE levels in urban and rural communities in Rhodesia. Clin Allergy 1976; 6: 131–4.Find this resource:
9 Perzanowski MS, Ng’ang’a LW, Carter MC, Odhiambo J, Ngari P, Vaughan JW et al. Atopy, asthma, and antibodies to ascaris among rural and urban children in Kenya. J Pediatr 2002; 140: 582–8.Find this resource:
10 Hooper R, Calvert J, Thompson RL, Deetlefs ME, Burney P. Urban/rural differences in diet and atopy in South Africa. Allergy 2008; 63 (4): 425–31.Find this resource: