(This article is a slightly shortened version of an article published in the International Journal of Pediatric Hematology/ Oncology, 1995. The list of references was omitted, can be obtained from the editors)

There are many influences on the disease patterns seen in South Africa, which lies outside the African malarial belt but has received migrants from the rest of Africa and from Europe over centuries, as well as being the seat of sociopolitical upheaval. Mortality rates reflect both First and Third World patterns. Red cell polymorphisms, common in other parts of Africa, are seen only in the migrant population. The founder effect is thought to account for a higher prevalence of diseases such as Fanconi's anemia and porphyria among Afrikaners. Only two-thirds of the expected number of malignancies are registered each year, with a pattern more akin to Western countries than to the rest of Africa. Differences are noted between black and white patients with respect to disease incidence, remission rates, and disease-free survival, the reasons for which are being sought. Malignant diseases are a low-priority pediatric problem in the developing world. In South Africa, facilities are available, including those of bone marrow transplantation, for state-of-the-art treatment, but socioeconomic problems do not always allow their full utilization by all sections of the population. This should change in a post-apartheid South Africa, and it will become easier to determine whether observed differences are genetic or environmental.

The practice of pediatric hematology and oncology in South Africa is at once exciting and challenging, but frustrating and fraught with ethical dilemmas. South Africa is part of the African continent, but not within the malaria belt. Economic and political upheaval has resulted in southward migration from the rest of Africa, and since the 17th century migrants of European extraction have been settling in South Africa, resulting in a melting pot of genes, traditions, and lifestyles. Sociopolitical events in South Africa have further complicated this picture.

While the infant mortality rates for South African whites in 1985 were comparable to those of developed countries (11 of 1000 male births and 7 of 1000 female births), the infant mortality rates of blacks (73 of 1000 male births) were 10 times higher. In 1988, in the more affluent white population, accidental deaths (51%) were the main causes of deaths for the age group 5 to 14 years, while cancer constituted the second most important cause of death (14%). In black, colored, and Asian children, the main causes of death for this age group were trauma and infectious and respiratory diseases with cancer being very low on the list. These disparities have a bearing on the provision of medical services and the allocation of health budgets.

Pediatric hematology: genetic and environmental influences

Malnutrition is still rife in South Africa, and nutritional anemias are frequently encountered, often in association with infection. The red cell polmorphisms, such as sickle-cell trait, thalassemia, and glucose-6-phosphate-dehydro-genase deficiency, proposed by Haldane to confer a selective advantage in regions where malaria is endemic, are not seen in the indigenous population. In recent years, migration from the tropical and subtropical countries to the north of South Africa has resulted in sickle-cell disease being seen in South Africa. There are large Greek-Cypriot and Asian communities in South Africa with a high prevalence of the ß-thalassemia gene in both communities. Lack of awareness of the significance of the heterozygous state has resulted in underutilization of antenatal diagnosis in these communities.

Random genetic drift in the form of the founder effect is thought to account for a higher prevalence of Fanconi's anemia in the South African Afrikaner population. Rosendorff et al. showed that Afrikaans-speaking heterozygotes occur with a minimum prevalence of approximately 1 in 80, compared with a minimum frequency of 1 in 300 in New York State. The Afrikaans community started with a small number of "founders" when the Dutch East India Company established a refreshment station at the Cape in 1652. Such a founder effect was also postulated to account for the extremely high prevalence of porphyria variegata among Afrikaners. Fanconi's anemia has rarely been reported in black children in the United States or Africa. A prevalence of homozygotes of 1: 476,000 in indigenous Bantu-speaking Negroid peoples in South Africa suggests that this disorder is not as rare in the black population as previous reports have suggested.

The incidence of inherited bleeding disorders derived from the registry of South African Haemophilia Foundation suggests a much lower incidence among the black population, with an incidence among whites equal to that in Western countries. The reason for this is not clear. It is still debated whether this is a true decreased incidence or whether this reflects a lack of clinical awareness and social acceptability with patients seeking the services of a traditional healer before turning to scientific medicine. As opposed to the findings of Kasili that mild and moderately sever forms of the disease predominate in other parts of Africa, the more severe form of the disease is more prevalent in South Africa.

Hemophiliacs have been treated in South Africa with locally produced blood products from volunteer donors, except for a 15-month period in 1982 to 1984 when, owing to a shortage of locally produced material, an imported factor VIII concentrate was used. The timing could not have been worse. Of the patients who received the imported factor VIII concentrate, 85% were seropositive for human immunodeficiency virus (HIV) while 3% of the patients who received only locally produced products were seropositive. Apart from the hemopheliacs, in the pediatric age group we are seeing an alarming increase in vertically transmitted HIV infection with attendant hematological consequences.

Pediatric oncology

A national children's cancer registry was initiated by the South African Children's Cancer Study Group (SACCSG) in 1987. The number of new cases registered annually until 1991 has varied between 564 and 632. This represents an incidence of between 7.0 and 7.6 per 100,000 children younger than 15 years of age. This would suggest that despite having good infrastructures for a developing country only two thirds of the expected number of malignancies are diagnosed.

Certain similarities and differences are seen by comparison with other African and developing countries. The excess of lymphoma over leukemia, noted in Northern and equatorial Africa, is not seen, and patients with Burkitt's lymphoma, even among black patients, most commonly exhibit the endemic (American) rather than the African type. Fewer brain tumors are registered, which may reflect lack of diagnosis in both population groups, but also reflects the fact that many children with brain tumors are not referred to the pediatric oncologist, remaining with neurosurgeons without being registered. Ewing' s sarcoma is rarely seen in black patients. Among black patients a higher incidence of Wilms' tumor is seen and fewer cases of neuroblastoma when compared to their white counterparts. The possibility exists that neuroblastoma and leukemia may not be diagnosed because myelosuppression in patients caused by the disease process results in presentation with septicanemia and bleeding with the underlying cause being overlooked. Doctors treating children with malignancies in the rest of Africa make the point that the most common malignancies seen are those that disfigure, namely the swollen jaw of Burkitt's lymphoma, the diseased, protruding eye of retinoblastoma, and the large abdominal tumor of nephroblastoma.

With increasing westernization of the African black society, we are seeing an increase in childhood ALL and the emergence of a peak age incidence in black children in the 3 to 4-year old age group, the absence of which has been a feature of reports from developing countries. Remission rates and disease-free survival for black children with ALL were significantly lower than for white children. This poorer prognosis has variably been attributed to nutritional and socioeconomic factors, availability of medical care, and possibly impaired tolerance to chemotherapeutic drugs. Yet no differences in response to treatment and survival have been noted between black and white patients with ANLL. This raised the possibility that ALL in developing countries may differ at a biologic level.

With the flow cytometer, comparative analysis of CD10 expression was performed on children with ALL with a common/pre-B phenotype treated in Johannesburg. A pattern of segregation was found between boys and girls and between black and white children. Black boys, who are the worst prognostic group had the lowest CD10 density, whereas white girls, known to constitute the best prognostic group, had significantly higher CD10 antigen density than the other groups. While these rankings according to race and sex could be coincidental and unrelated to prognosis, it is tempting to suggest that they are not. If they are related, this study reinforces the notion that CD10, a neutral endopeptidase, is directly concerned with prognosis and that the adverse prognosis seen in black children reflects biologic rather than sociologic differences. The patient cohort is being followed to see whether the association with prognosis is confirmed.

Facilities and obstacles to their utilization

Pediatric oncology is a registerable subspecialty in South Africa. All seven medical schools in South Africa have pediatric hematology/oncology units, which fulfill the criteria for recognition by the International Society of Pediatric Oncology (SIOP). Facilities for bone marrow transplantation are available at two of the centers, namely Johannesburg and Cape Town. Irrespective of socioeconomic status, First World state-of-the-art treatment is available to every child with a blood disorder or malignancy once the child reaches the academic center. Despite this, not all sections of the population benefit from or avail themselves of the available facilities. Traditional healers and medicines are utilized by a significant proportion of the population. Access to primary health care is often not easy and medical staff in rural areas may know little about the clinical signs of cancer and blood disorders. It is not uncommon for the diagnosis in a child of one of the more common medical problems, such as tuberculosis, to result in a delay in appropriate referral and treatment of malignancy. The level of education of rural parents is poor and family income is low. In many instances, the child comes from a single-parent family and before diagnosis may have been staying with an elderly caregiver while the parent is employed in the urban area.

While no one is denied therapy because of cost at a referral center, minimal support is available in the community to cover costs of transport to the hospital or for assistance once the child is at home. For many parents, attendance at hospital with a child results in the loss of a day's salary. For families living on the breadline, these costs are not inconsiderable. For many black children, treatment often involves prolonged hospitalization because of the practical problems of commuting. On discharge many of the black patients return to a home with overcrowding, lack of sanitation, no electricity, and no telephone. Problems of communication are encountered not only because of language differences but also because of differing cultural concepts of disease and death. Black parental understanding of the illness and aims of treatment is poor. Despite intensive attempts at education, the need for ongoing therapy in the cancer patient is often no appreciated, resulting in children not being brought back for therapy after remission is achieved and poor compliance with chemotherapy. All these factors contribute to the alter presentation of the black child with advances disease and contribute to the generally poorer prognosis seen in this population group.

Discussion

In South Africa we have patients from First and Third World environments, with First World facilities available for treatment. Increasing costs and a shortage of nurses are endangering the maintenance of standards. The possibility exists that in a post-apartheid society funding will be reduced for an expensive subspecialty affecting a small number of the population, despite the fact that the majority of patients are cured. Practical issues and budget cuts may necessitate exploration of intensified protocols up front, with shorter duration of total therapy. Given the desperate backgrounds of the patients, the inpatient facilities must be increased as it is not feasible for many of the patients to receive outpatient treatment. Effective means of communication and education must be developed to ensure optimal compliance with drug regimens. Community based facilities must be improved as it is a waste of resources to induce remission then lose children to follow-up.

As the disparities between the population groups with regard to socioeconomic, nutritional, and health services disappear in a post-apartheid South Africa, it will become clearer to what extent environmental and genetic factors play a role in disease patterns and response to therapy. Attempts are being made to explore further biological differences, which may hold the key to the etiology of the various disorders or their therapy.

Therapy for hematologic and oncologic disorders in the countries beyond South Africa's borders is minimal, and we are frequently asked for assistance. Not only is medical expertise limited but often drugs required even for basic supportive care are lacking. Given the funding, South Africa is well placed to collaborate with countries in Africa. The first continental meeting of the International Society of Pediatric Oncology in Africa was held in South Africa in April 1994. It is hoped that how developed countries can assist in improving the care of oncology patients in Africa will be explored. The problems are shared by many countries with populations that are as heterogeneous in terms of language, culture, religion, and education. The challenge to the pediatric hematologist/ oncologist in South Africa is to maintain standards and to extend the available services to all patients in such a way that they are accessible, affordable, and acceptable to all.