Africa is the second densely populated continent after Asia with a population of 1.88 billion in 2022, based on the latest United Nations estimates. Africa’s population is equivalent to 16.72% of the total world population[1]. Africa has a high rate of consanguineous mating with rates exceeding 60% in some areas of North and Sub-Saharan Africa [2]. Based on prevalence drawn from epidemiological studies, it was previously estimated that 988,000 persons in Africa may have underlying Inborn Errors of Immunity (IEI), which encompass more than 500 different diseases [3][4]. Despite steady improvement, IEIs remain underdiagnosed in the African continent with less than 6,000 patients having received a diagnosis [5]. Four main reasons could explain the lack of diagnosis of IEI: 1) lack of awareness at all levels of care, with the added lack of immunology expertise, poor networking and limited registries; 2) distraction by more urgent/confounding healthcare problems such as HIV and malaria; 3) heterogenicity and varied presentation given the range of endemic diseases in Africa and genetic polymorphisms in African population; and 4) lack of resources including diagnostic facilities. The African Society of Immunodeficiency (ASID) was established in 2008 to improve networking and spread awareness on IEI in Africa. In 2014, ASID delivered the first of many A-projects which are low-cost training days delivered in an African country by African immunology specialists to improve awareness on diagnosis and treatment of IEI, encourage local national and African continental ASID registry, as well as national patient groups. To date, A-projects of different levels and specialty have been delivered in 15 countries.
Barbouche et al. [6] investigated the prevalence of IEI in northern African countries by collecting data from IEI referral clinics in Morocco, Egypt and Tunisia and found that combined immunodeficiency (CID) was the most prevalent IEI reported from Egypt and Tunisia (41% and 27%; respectively) while syndromic immunodeficiency was the most common IEI in Morocco (34%) [6]. This is different from IEIs prevailing in European countries where B cell defects predominate. High rates of consanguinity, in parts of Africa, might underlie these differences in IEI patterns. An additional fact contributing to such differences could be the underdiagnosis of less severe IEIs of the B-cells. Results of a questionnaire-based survey sent to immunologists in different African countries on prevalence, category of IEI in their countries were presented in the 2018 European Society of Immunodeficiency biennial meeting in Lisbon, Portugal: 37 responded from 16 African countries with the most prevalent IEI being severe combined immune deficiency (SCID) (21.2%) followed by antibody deficiency (20.7%) which may be due to an increased incidence of autosomal recessive diseases [5]. However, this survey showed a different pattern of IEI between different African regions as shown in Fig. 1. While SCID was the most frequent IEI diagnosed in North Africa, antibody deficiency was most frequent IEI in South Africa followed by complement defects. On other parts of Africa, CID was the most frequently diagnosed IEI. Moreover, within Africa, specific ethnic populations were recognized to have a higher incidence of certain types of IEI diseases caused by founder mutations, such as adenosine deaminase deficient SCID in the Somali population [7], mutations of the RFXANK gene in North Africa [8][9][10][11] and of IL12RB in Tunisia [12]. A better understanding of clinical criteria and evolution of these diseases is mandatory.
Unfortunately, with delayed diagnosis, the overall mortality rate for patients with IEI among Africans is high, ranging from 25–34.5% [13] [14]. To support early diagnosis of IEI with Mendelian Susceptibility to Mycobacterial Disease (MSMD), the team in South Africa investigated whether severe, persistent, unusual or recurrent (SPUR) definitions of TB can be used as a surrogate marker for MSMD for considering IEI [14]. Using the SPUR criteria among a group of 22 patients with TB, a pathogenic mutation in one of MSMD genes, was identified in 36% of patients using NGS [15][16]. Thus endemic diseases pose a major challenge in identifying IEIs within the African setting. The challenges and discrepancies in African IEI diagnosis mentioned above would be improved in the presence of Africa suited IEI diagnosis and management guidelines. These could be disseminated through the ASID website, A-project training program and more widely. Thus there is an urgent need for establishment of diagnostic criteria for PID in Africa in alignment with international guidance and adapting these guidelines to the available facilities in African countries to ensure prompt diagnosis and treatment.