OPPORTUNITIES FOR RHEUMATOLOGY RESEARCH IN AFRICA
PRIORITIES FOR AFRICA • RESEARCH • EDUCATION, TRAINING AND SERVICE DELIVERY • BOTH
CONSTRAINTS IMPOSED BY LACK OF DATA • •
• • •
POPULATION STATISTICS – availability and accuracy MORBIDITY DATA – lack of registries and information on disability grants or disability pensions MORTALITY DATA – availability and accuracy HEALTH INSURANCE DATABASES – Lack of ICD 10 coding and accuracy of diagnosis WORK ABSENTEEISM RECORDS – some data from INDUSTRY eg mines hospitals, rest inacurate
DISEASE SPECIFIC LIMITATIONS • Translation and validation of questionnaires (symptoms and disability) • Criteria for diagnosis – may miss mild disease • Lack of single diagnostic test • Need for assessment by experienced clinician • Travel to health care facility for assessment
DISEASE SPECIFIC LIMITATIONS • Need for invasive tests i.e. blood tests • Radiographs for diagnosis • Lower prevalence of many rheumatic diseases and need for larger sample size • Co-existent diseases with high prevalence of musculoskeletal symptoms – eg HIV
BURDEN OF DISEASE • More data available in past 25 years than in the century before • Growth in methodological skills within Africa (especially for) HIV studies • Establishment of pool of research centres in Africa
RHEUMATIC CLINICAL CASES UNIQUE TO, OR MODIFIED IN AFRICA
MSELENI JOINT DISEASE • Form of endemic dysplasia affecting local community in Northern Kwa ZuluNatal for over 30 years • Similar to Kashin Beck disease in Russia and Handigodu disease in India – but aetiology not worked out • Currently about 10,000 people estimated to be affected
EMERGING RHEUMATIC DISEASES IN AFRICA?
RHEUMATOID ARTHRITIS
• RA first recognised as a distinct clinical entity by Landre Beauvais in 1800 • RA first reported in African blacks in Malawi by Goodall in 1956 • First SA study of 23 patients by Anderson in 1970
EPIDEMIOLOGY PREVALENCE POPULATION
AUTHOR
0.12
Rural Tswana
Beighton et al 1975
0.90
Urban Africans
Solomon et al 1975
2
0.68
Rural Xhosa
Meyers et al 1977
3
0.30
Rural Sotho
Moolenberg et al 1985
4
0
Rural Venda
Brighton et al 1989
1
SLE • Prevalence of SLE – 3 to 4 fold increase in American blacks in the 15 to 64 year age group in New York (1973 ) and San Francisco (1974) • Incidence of SLE – 3 fold increase in Blacks in Baltimore (USA)(1985)
SLE IN AFRICAN BLACKS COUNTRY
YEAR
STUDY PERIOD (YEARS)
SA (Cape Town)
1973
11
8
SA (Durban)
1977
7
17
Nigeria
1980
4
3
Uganda
1980
11
21
Zimbabwe
1986
6
31
NUMBER
OBSERVATIONS IN AFRICA • GOUT – initially rare - with largest study of 19 patients over 5 years. Now common.) RA and SLE previously rare – are they emerging diseases in Africa?
GOUT IN AFRICAN BLACKS • Rare in African Blacks in 60’s and 70’s • Survey of 1985 people from 3 population groups in SA • No cases of gout in Blacks but the prevalence of 1.3% for men and 0.3 % for women – similar to European studies
GOUT IN AFRICAN BLACKS ADMISSIONS OR DURATION (YEARS)
COUNTRY
YEAR
Congo
1991
61
Togo
1992
71
SA (Durban)
1994
SA (Jhbg)
1998
5 years
NUMBER
107 90
RHEUMATIC DISEASES IN YAOUNDE, CAMEROON Singwe-Ngandeu M, Meli J, Ntshiba H et al East Afr Med J 2007 • • • • • • • • • • •
12,494 medical outpatients over 1 year 536(9.4%) patients with rheumatic diseases F:M 62.3: 37.7 Mean age 52.7 (+/- 5.3 years) Degenerative diseases of spine 196 Peripheral OA 110 Regional MSK disorders 83 Infections 50 Chronic inflammation and CTDx 44 Crystalline arthritis 32 Miscell 21
36.5% 20.5% 15.5% 9.3% 8.2% 5.9% 4.1%
Epidemiological and clinical features of knee Osteoarthritis Ndongo S, Ka MM, Leye A et al Dakar Med 2003; 48: 171 – 175 ( French) • • • • • •
50 patients seen over 6 months 33 females and 17 males Mean age 62 years 9 range 45 to 81) FH of inflammatory joint disease 72% Physical stress on the knees in 60% Obesity common - 43 patients
MUSCULOSKELETAL CONDITIONS IN CHILDREN TWO TOGOLESE HOSPITALS Mijiwaya M, Oniankitan O, Attoh-Mensah K et al Rheumatology 1999; 38: 1010 – 1013 434 of 29620 children examined
Bone and joint infections
No 187
% 43
Limb deformities
106
24
Ostochondrosis
60
14
Vaso-occlusive crisis ((Haemoglobinopathies)
29
7
VALIDITY AND INTERNAL CONSISTENCY OF A HAUSA VERSION OF THE IBADAN KNEE / HIP OSTEOARTHRTIS OUTCOME MEASURE Odole AC, Akinpelu AO. Health Qual Life Outcomes 2008;6:86 A study of 67 patients with osteoarthritis showed that the Hausa version of the IKHOAM met the criteria for validity and internal consistency and may be used in the Hausa speaking parts of Nigeria and West Africa YORUBA version – above authors Afr J Med Sci 2006;35: 349-357 164 OA patients
REPORTS FROM NIGERIA Adebajo AO • Joints hypermobility in 8 (43%) of 204 individuals age 6 - 66 years • Healthy population 7% ANF 30.3% ACL • ANF 2X more common with TB/Malaria • Assoc between IgG ACL and TB • OA and soft tissue lesions commonest problems seen in urban and rural clinics in West Africa
REPORTS FROM NIGERIA Adebajo AO • • • •
RA in 1/2000 rural population (1992) RF 3 / 55 (5.5%) persons tested HLA DR4 1 / 55 ( 2%) Caucasians 30% Nigerian RA vs UK – younger at onset, FH uncommon, few extra-articular features and erosions, RF less often positive (1991)
COPCORD Studies Shanghai
Brazil
Vietnam
Australian Aborigines
Number
6584
3038
2119
84
Rheumatic Symptoms
13.3 %
30.9 %
14.5 %
33%
RA
0.28 %
0.46 %
0.28 %
Nil
GOUT
0.22 %
0.64 %
3.8 %
OA
4.1 %
4.1 %
5.5 %
4.1 %
Fibromyalgia
2.56 %
SLE
0..9 %
COPCORD Studies • Western studies – rheumatic disorders are among most prevalent chronic illnesses and one of the leading causes of disability • COPCORD STUDIES – Asia ( China, Indonesia, India, Vietnam), Kuwait, Central and South America and current studies in Egypt • Findings from COPCORD studies: – Rheumatic complaints in 24% of rural and 32% of urban population and 70% had to stop work because of rheumatic complaints (Indonesia) – Lower prevalence of RA
IL-1 RECEPTOR ANTAGONIST POLYMORPHISMS ARE ASSOCIATED WITH DISEASE SEVERITY IN BLACK SOUTH AFRICANS WITH RA Lubbe S, Tikly M, van Der Merwe L, Hodgkinson B, Ramsay M. Joint Bone Spine 2008; 75:422-425 A study of 141 RA patients and 101 controls provided evidence of a possible role for polymorphisms of the IL-1 gene in disease severity in RA, and particularly IL1RN*2 as a marker of erosive joint damage in Black South Africans with RA.
SOcIAL ASPECTS OF LIVING WITH RHEUMATOID ARTHRITIS: A QUALITATIVE DESCRIPTIVE STUDY IN SOWETO, SOUTH AFRICA – A LOW RESOURCE CONTEXT Schneider M, Manabile E, Tikly M Health Qual Life Outcomes 2008; 6: 54 A qualitative case study design showed study of 60 patients showed that the experiences of living with RA in a low resource context are similar to a mid to high resource context but are exacerbated by poverty and lack of basic services. Pain and social exclusion are some of the key experiences of women with RA living in Soweto.
JOINT REPLACEMENT REGISTRY IN MALAWI: ESTABLISHMENT OF A NATIONAL JOINT REGISTRY Lubega N, Mkandawire NC, Sibande GC, Norrish AR, Harrison WJ. J Bone Joint Surg Br 2009; 91: 341-3 The authors reported their registry of 73 THR performed on in 58 patients by 4 surgeons in 4 hospitals – 35 has AVN and 22 had OA.
ARTHROPLASTY FOLLOWING AVN OF HIPS IN SICKLERS Alonge TO, Shokumbi WA J Natl Med Association 2004; 96: 678 - 681 • Study from Univ of Ibadan reported successful cementless bipolar arthroplasty of 6 hips in 5 patients with Sickle cell anemia and AVN
MITOCHONDRIAL DEPOLARISATION AND OXIDATIVE STRESS IN RHEUMATOID ARTHRTIS PATIENTS Moodley D, Mody G, Patel N, Chutergoon AA Clin Biochem 2008;41: 1396-1401 A study of 50 RA patients and controls showed significantly elevated levels of cytotoxicity and lipid peroxidation in peripheral lymphocytes suggesting a possible role for mitochondrial membrane alterations in the pathogenesis of RA
ANKYLOSING SPONDYLITIS IN TOGO Lopez- Larrea C, Mijiyawa M et al Arthritis Rheum 2002; 46: 2968 - 71 • As in 8 / 9065 patients ( < 0.1%) • B*14 in 62.5% of AS and 2% of controls • Commonest subtype was B*1403 Controls – virtually absent • B27 positive in 1 patient
OBSERVATIONS IN AFRICA • GOUT – initially rare - with largest study of 19 patients over 5 years. Now common. • Low prevalence of nodal OA (African and Jamaican blacks) • Low prevalence of Hip OA (African blacks, Asian Indians and Chinese in Beijing and Hong Kong) • Spondyloarthropathies rare – probably related to low prevalence of HLA B27 (<1%) • RA and SLE previously rare – are they emerging diseases in Africa? • PMR / Temporal arteritis rarely reported. Takayasu’s arteritis seen.
SPECTRUM OF HIV ASSOCIATED RHEUMATIC DISORDERS • • • •
ARTHRALGIA PAINFUL ARTICULAR SYNDROME HIV ARTHROPATHY SPONDYLOARTHROPATHY (SpA) Reactive arthritis Psoriatic arthritis Undifferentiated SpA
• AVASCULAR NECROSIS OF BONE • SEPTIC ARTHRITIS
SPECTRUM OF ARTICULAR MANIFESTATIONS WITH HIV INFECTION IN AFRICA HIV ASSOCIATED ARTHRITIS
OTHER
COUNTRY NUMBER
SPA
SEPTIC ARTHRITIS
Zambia
289
222
-
66
1
Zimbabwe
64
27
-
34
1
Rwanda
26
10
9
4
3
Congo
39
2
2
32
3
South Africa
78
15
7
49
7
RECOMMENDATIONS FOR THE CONDUCT OF STUDIES • Identify regions where studies need to be conducted ( international focus) while encouraging other local studies • Identify PRINCIPAL INVESTIGATOR (rheumatologist or experienced clinician) • ILAR / WHO /EULAR – to identify key panel of experts to assist and support project at all stages • HIV / AIDS projects have resulted in a considerable amount of local expertise and infrastructure. This can be utilised to extend research to musculoskeletal diseases at relatively little cost.
STAKEHOLDERS IN COMMUNITY BASED STUDIES • COMMUNITY – community leaders, local headmen, community at large and targeted groups • GOVERNMENT AGENCIES – National, regional and local • PROJECT TEAM – field workers, health workers, professional consultants • REGULATORY APPROVAL – Ethics committees • FUNDING AGENCIES
Source of Funding • Government agents – National, Provincial, Regional • Private donors • Pharmaceutical industry • Research / University sources • International collaboration • International agencies
RECOMMENDATIONS FOR FUNDING • Local sources of funding – Universities, government agencies and government • Local philantropic trusts and organisations • Pharmaceutical companies in lieu of contract research • Identify countries where there are already government to government agreements • Identify Universities which have MOU with partner institutions – jointly source funds from global donors • Local businessmen and businesswomen • Support by the WHO / ILAR as strategic focus
The Way Forward • Identify project leader • Identify population • Moral support • Scientific support • Start up capital • Collaborative Study
AFRICA CENTRE • University of Kwa Zulu – Natal associated project supported by Wellcome Foundation – over 20m pounds • Mini Framingham type study of population of 78,000 rural and peri-urban people already followed for 5 years (initial primary focus on HIV infection) • HIV prevalence of about 30%
Responsibilities to the Communities • Support for health care services for identified patients • Discuss results of surveys • Impact of outcome of surveys
SUMMARY I • Research should be both a national as well as a health priority for countries in Africa • The documentation and publication of case reports and especially case series unique to, or modified in Africa, are important • Hospital based surveys can be informative and also helpful in generating hypotheses • However, cross-sectional, longitudinal and community based surveys (such as the COPCORD Studies) are especialy needed in Africa
SUMMARY II • There are various constraints to research in Africa including, human resource shortage, lack of data, disease specific limitations and funding problems • These various constraints however, can be overcome • Basic research such as molecular genetics, experimental biology and translational medicine is capable of being performed in some academic research centres in Africa • Randomised controlled studies of various pharmacological and non pharmacological interventions in Africa and Africans are essential
CONCLUSION AFRICA HAS MUCH TO CONTRIBUTE TO WORLD WIDE RHEUMATOLOGICAL RESEARCH
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