Progress And Challenges In Africa At The Time Of Molecular Haematology

Authors

  • Lucio Luzzatto University of Florence Firenze, Italy Author

DOI:

https://doi.org/10.60787/njhaem-7-1-2-69

Keywords:

Traditional haematology, molecular haematology, haemoglobinopathy, haematological malignancy, Nigeria, Africa

Abstract

The study of blood diseases has been traditionally at the border between clinical medicine and laboratory science. Many of us have been attracted to haematology by this combination: by the very fact that from examining a patient and looking at the blood picture it is often possible to make a diagnosis. As for understanding the nature of any disease, there are several layers: but since the middle of the last century, when the phrase ‘molecular disease’ was coined to aptly describe the basis of sickle cell anaemia,1 it became clear that in understanding the causes and the pathogenetic mechanisms of any disease the ultimate layer must be molecular.

From the middle of the last century African pioneers of haematology have been prominent: without detracting from others, let me mention Alex Boyo in Nigeria,2 Felix Konotey-Ahulu in Ghana,3 Edward Kasili in Kenya,4 Aloysius Nhonoli in Tanzania,5 Charles Olweny in Uganda6: as I have been fortunate to know each one of them in person. As clinical and epidemiological studies were being conducted, the pattern of blood disorders in sub-Saharan Africa (SSA) gradually emerged, and it had several important features. First, as could be expected, an African patient with megaloblastic anaemia, or one with thrombocytopenic purpura, or one with Hodgkin disease, or one with any other specific blood disease was not much different from a patient with the same disease in any other part of the world. Second, in contrast to clinical similarity, the prevalence of many blood conditions was very different: first and foremost, anaemia was and still is rampant,7 due to a variety of infectious and nutritional causes, and it is of great clinical importance particularly in children and in pregnancy.8 Third, whereas in USA and in Europe haemoglobinopathies are officially ‘rare diseases’, in many countries in SSA the prevalence of sickle cell disease (SCD) at birth is from 1 to 2%: with millions of people affected, it is a major public health problem. Fourth, a unique haematologic malignancy, Burkitt’s lymphoma, was discovered in Africa.9 Last, in SSA, and especially in West Africa, endemic malaria, in addition to being a major cause of mortality in children, is always in the background: during my first couple of years at UCH in Ibadan, when I regarded myself as being still very much in training, I learnt that when a patient had a fever the question was not whether he or she had malaria: rather, whether it was just malaria or also something else on top.

Downloads

Download data is not yet available.

Author Biography

  • Lucio Luzzatto, University of Florence Firenze, Italy

    Formerly at the Dept. of Haematology, University of Ibadan and University College Hospital, Ibadan, Nigeria (1964-1974); formerly at the Dept. of Haematology, Muhimbili University of Health and Allied Sciences, Dar-es-Salaam, Tanzania (2015-2022)

References

Pauling L, Itano HA, et al. Sickle cell anemia a molecular disease. Science. 1949 Nov 25;110(2865):543-8.

Boyo AE, Hendrickse RG. New fast abnormal hemoglobin in newborn Nigerians. Nature. 1959 Sep 26;184(Suppl 13):997-8.

Konotey-Ahulu FI. Sicklaemic human hygrometers. Lancet. 1965 May 8;1(7393):1003-4.

Kasili EG, Taylor JR. Leukaemia in Kenya. East Afr Med J. 1970 Sep;47(9):461-8.

Nhonoli AM, Kujwalile JM, Kigoni EP, Masawe AE. Correlation of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and sickle cell trait (Hb-AS). Trop Geogr Med. 1978 Mar;30(1):99-101.

Olweny CL, Ziegler JL, Berard CW, Templeton AC. Adult Hodgkin's disease in Uganda. Cancer. 1971 Jun;27(6):1295-301.

Stevens GA, Paciorek CJ, Flores-Urrutia MC, Borghi E, Namaste S, Wirth JP, Suchdev PS, Ezzati M, Rohner F, Flaxman SR, Rogers LM. National, regional, and global estimates of anaemia by severity in women and children for 2000-19: a pooled analysis of population-representative data. Lancet Glob Health. 2022 May;10(5):e627-e639.

Ojo OA. The pattern of anaemia in Western Nigeria. J Trop Med Hyg. 1965 Feb;68:32-6. PMID: 14261879.

Burkitt D. A "tumour safari" in East and Central Africa. Br J Cancer. 1962 Sep;16(3):379-86.

Shoo A, Swai P, Kindole C, Ngailo E, Godfrey E, Massawe E, et al. Severe congenital neutropenia with elastase, neutrophil expressed (ELANE) gene mutation in a Tanzanian child. Br J Haematol. 2022 Mar;196(5):1271-1274.

Myburgh JK, Szydlo RM, Bain BJ. The accuracy of haemoglobin A2 measurements in the presence and absence of haemoglobin S. EJHaem. 2023 Apr 17;4(2):437-44.

Christopher H, Burns A, Josephat E, Makani J, Schuh A, Nkya S. Using DNA testing for the precise, definite, and low-cost diagnosis of sickle cell disease and other Haemoglobinopathies: findings from Tanzania. BMC Genomics. 2021 Dec 16;22(1):902.

Bunn HF. The triumph of good over evil: protection by the sickle gene against malaria. Blood. 2013 Jan 3;121(1):20-5.

Luzzatto L, Nwachuku-Jarrett ES, Reddy S. Increased sickling of parasitised erythrocytes as mechanism of resistance against malaria in the sickle-cell trait. Lancet. 1970 Feb 14;1(7642):319-21.

Ayi K, Turrini F, Piga A, Arese P. Enhanced phagocytosis of ring-parasitized mutant erythrocytes: a common mechanism that may explain protection against falciparum malaria in sickle trait and beta-thalassemia trait. Blood. 2004 Nov 15;104(10):3364-71.

Luzzatto L. Sickle cell anaemia and malaria. Mediterr J Hematol Infect Dis. 2012;4(1):e2012065. doi: 10.4084/MJHID.2012.065.

Elguero E, Délicat-Loembet LM, Rougeron V, Arnathau C, Roche B, Becquart P, et al. Malaria continues to select for sickle cell trait in Central Africa. Proc Natl Acad Sci U S A. 2015 Jun 2;112(22):7051-4.

Pagnier J, Mears JG, Dunda-Belkhodja O, Schaefer-Rego KE, Beldjord C, Nagel RL, Labie D. Evidence for the multicentric origin of the sickle cell hemoglobin gene in Africa. Proc Natl Acad Sci U S A. 1984 Mar;81(6):1771-3.

Shriner D, Rotimi CN. Whole-Genome-Sequence-Based Haplotypes Reveal Single Origin of the Sickle Allele during the Holocene Wet Phase. Am J Hum Genet. 2018 Apr 5;102(4):547-556.

Piel FB, Rees DC, DeBaun MR, Nnodu O, Ranque B, Thompson AA, et alWare RE, Abboud MR, Abraham A, Ambrose EE, Andemariam B, Colah R, Colombatti R, Conran N, Costa FF, Cronin RM, de Montalembert M, Elion J, Esrick E, Greenway AL, Idris IM, Issom DZ, Jain D, Jordan LC, Kaplan ZS, King AA, Lloyd-Puryear M, Oppong SA, Sharma A, Sung L, Tshilolo L, Wilkie DJ, Ohene-Frempong K. Defining global strategies to improve

outcomes in sickle cell disease: a Lancet Haematology Commission. Lancet Haematol. 2023 Aug;10(8):e633-e686.

Onovo AA, Adeyemi A, Onime D, Kalnoky M, Kagniniwa B, Dessie M, et al. Estimation of HIV prevalence and burden in Nigeria: a Bayesian predictive modelling study. EClinicalMedicine. 2023 Jul 20;62:102098.

Bensinger TA, Gillette PN. Hemolysis in sickle cell disease. Arch Intern Med. 1974 Apr;133(4):624-31.

Kato GJ, Steinberg MH, Gladwin MT. Intravascular hemolysis and the pathophysiology of sickle cell disease. J Clin Invest. 2017 Mar 1;127(3):750-760.

Conran N, Belcher JD. Inflammation in sickle cell disease. Clin Hemorheol Microcirc. 2018;68(2-3):263-299.

Bunn, H.F. and Forget, B.G. In: Hemoglobin: Molecular, Genetic, and Clinical Aspects. USA: WB Saunders; 1986.

Luzzatto L, Makani J. Hydroxyurea - An Essential Medicine for Sickle Cell Disease in Africa. N Engl J Med. 2019 Jan 10;380(2):187-189.

Mtatiro SN, Singh T, Rooks H, Mgaya J, Mariki H, Soka D, et al. Genome wide association study of fetal hemoglobin in sickle cell anemia in Tanzania. PLoS One. 2014 Nov 5;9(11):e111464.

Kirkham JK, Estepp JH, Weiss MJ, Rashkin SR. Genetic Variation and Sickle Cell Disease Severity: A Systematic Review and Meta-Analysis. JAMA Netw Open. 2023 Oct 2;6(10):e2337484.

Urio F, Nkya S, Rooks H, Mgaya JA, Masamu U, Zozimus Sangeda R, et al. F cell numbers are associated with an X-linked genetic polymorphism and correlate with haematological parameters in patients with sickle cell disease. Br J Haematol. 2020 Dec;191(5):888-896. doi: 10.1111/bjh.17102. Epub 2020 Oct 19.

Vermylen C, Cornu G, Ferster A, Sariban E. Bone marrow transplantation for sickle cell anemia. J Pediatr. 1994 Feb;124(2):329-30.

Bazuaye N, Nwogoh B, Ikponmwen D, Irowa O, Okugbo S, Isa I, et al. First successful allogeneic hematopoietic stem cell transplantation for a sickle cell disease patient in a low resource country (Nigeria): a case report. Ann Transplant. 2014 May 5;19:210-3.

Krishnamurti L. Hematopoietic cell transplantation for sickle cell disease: updates and future directions. Hematology Am Soc Hematol Educ Program. 2021 Dec 10;2021(1):181-189.

Ribeil JA, Hacein-Bey-Abina S, Payen E, Magnani A, Semeraro M, Magrin E, et al. Gene Therapy in a Patient with Sickle Cell Disease. N Engl J Med. 2017 Mar 2;376(9):848-855.

Frangoul H, Altshuler D, Cappellini MD, Chen YS, Domm J, Eustace BK, et al. CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia. N Engl J Med. 2021 Jan 21;384(3):252-260.

Magrin E, Semeraro M, Hebert N, Joseph L, Magnani A, Chalumeau A, et al. Long-term outcomes of lentiviral gene therapy for the β-hemoglobinopathies: the HGB-205 trial. Nat Med. 2022 Jan;28(1):81-88.

Jones RJ, DeBaun MR. Leukemia after gene therapy for sickle cell disease: insertional mutagenesis, busulfan, both, or neither. Blood. 2021 Sep 16;138(11):942-947.

Ahmed IO, Ochogwu LO, Owojuyigbe TO, Akinola NO, Durosinmi MA. Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia with e1a3 BCR-ABL1 transcript in a Nigerian with sickle cell anemia: a case report. J Med Case Rep. 2021 Oct 8;15(1):504.

Moshi G, Sheehan VA, Makani J. Africa must participate in finding a gene therapy cure for sickle-cell disease. Nat Med. 2022 Dec;28(12):2451-2452.

Breda L, Papp TE, Triebwasser MP, Yadegari A, Fedorky MT, Tanaka N, et al. In vivo hematopoietic stem cell modification by mRNA delivery. Science. 2023 Jul 28;381(6656):436-443.

Lawrence MB, Springer TA. Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell. 1991 May 31;65(5):859-73.

Matsui NM, Borsig L, Rosen SD, Yaghmai M, Varki A, Embury SH. P-selectin mediates the adhesion of sickle erythrocytes to the endothelium. Blood. 2001 Sep 15;98(6):1955-62.

Ataga KI, Kutlar A, Kanter J, Liles D, Cancado R, Friedrisch J, et al. Crizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease. N Engl J Med. 2017 Feb 2;376(5):429-439.

Metcalf B, Chuang C, Dufu K, Patel MP, Silva-Garcia A, Johnson C, et al. Discovery of GBT440, an Orally Bioavailable R-State Stabilizer of Sickle Cell Hemoglobin. ACS Med Chem Lett. 2017 Jan 23;8(3):321-326.

Vichinsky E, Hoppe CC, Ataga KI, Ware RE, Nduba V, El-Beshlawy A, et al. A Phase 3 Randomized Trial of Voxelotor in Sickle Cell Disease. N Engl J Med. 2019 Aug 8;381(6):509-519.

van Dijk MJ, Rab MAE, van Oirschot BA, Bos J, Derichs C, Rijneveld AW, et al. One-year safety and efficacy of mitapivat in sickle cell disease: follow-up results of a phase 2, open-label study. Blood Adv. 2023 Dec 26;7(24):7539-7550.

Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV, et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N Engl J Med. 1995 May 18;332(20):1317-22.

Tshilolo L, Tomlinson G, Williams TN, Santos B, Olupot-Olupot P, Lane A, et al. Hydroxyurea for Children with Sickle Cell Anemia in Sub-Saharan Africa. N Engl J Med. 2019 Jan 10;380(2):121-131.

Olupot-Olupot P, Tomlinson G, Williams TN, Tshilolo L, Santos B, Smart LR, et al. Hydroxyurea treatment is associated with lower malaria incidence in children with sickle cell anemia in sub-Saharan Africa. Blood. 2023 Mar 23;141(12):1402-1410.

Adeyemo TA, Diaku-Akinwunmi IN, Ojewunmi OO, Bolarinwa AB, Adekile AD. Barriers to the use of hydroxyurea in the management of sickle cell disease in Nigeria. Hemoglobin. 2019 May;43(3):188-192.

Costa E, Tibalinda P, Sterzi E, Leufkens HMG, Makani J, Kaale E, Luzzatto L. Making hydroxyurea affordable for sickle cell disease in Tanzania is essential (HASTE): How to meet major health needs at a reasonable cost. Am J Hematol. 2021 Jan;96(1):E2-E5.

Luzzatto L. Sickle cell disease strategies and priorities. Lancet Haematol. 2023 Oct;10(10):e794-e795.

Makani J, Cavazzana M, Gupta K, Nnodu O, Odame I, Tshilolo L, et al. Blood diseases in Africa: Redressing unjust disparities is an urgent unmet need. Am J Hematol. 2022 Dec;97(12):1505-1506.

Ugwu NI, Okoye AE, Ugwu CN, Iyare FE, Edegbe FO, Ugwu GC, et al. Distribution pattern and prevalence of haematological cancers among adults in Abakaliki, South-Eastern Nigeria. Niger Postgrad Med J. 2021 Oct-Dec;28(4):266-272.

Natukunda B, Omoding A, Bongomin F, Mubiru KR, Ddungu H, Sekaggya-Wiltshire C, Mayanja-Kizza H. One-Year Survival and Prognosticators of Adults With Acute Leukemia at the Uganda Cancer Institute. JCO Glob Oncol. 2023 Jul;9:e2200244.

Luzzatto L, Fasola F, Tshilolo L. Haematology in Africa. Br J Haematol. 2011 Sep;154(6):777-82.

Owojuyigbe TO, Durosinmi MA, Bolarinwa RAA, Salawu L, Akinola NO, Ademosun AA, Bosede OT. Distribution of BCR-ABL1 Transcript Variants in Nigerians with Chronic Myeloid Leukemia. Indian J Hematol Blood Transfus. 2020 Oct;36(4):646-651.

Nasser A, Hussein A, Chamba C, Yonazi M, Mushi R, Schuh A, Luzzatto L. Molecular response to imatinib in patients with chronic myeloid leukemia in Tanzania. Blood Adv. 2021 Mar 9;5(5):1403-1411.

Ferrata, A. (1934) Le Emopatie, Vallardi. Mawalla WF, Morrell L, Chirande L, Achola C, Mwamtemi H, Sandi G, et al. Treatment delays in children and young adults with lymphoma: a report from an East Africa lymphoma cohort study. Blood Adv. 2023 Sep 12;7(17):4962-4965.

Cowan AJ, Allen C, Barac A, Basaleem H, Bensenor I, Curado MP, et al. Global Burden of Multiple Myeloma: A Systematic Analysis for the Global Burden of Disease Study 2016. JAMA Oncol. 2018 Sep 1;4(9):1221-1227.

Landgren O, Katzmann JA, Hsing AW, Pfeiffer RM, Kyle RA, Yeboah ED, et al. Prevalence of monoclonal gammopathy of undetermined significance among men in Ghana. Mayo Clin Proc. 2007 Dec;82(12):1468-73.

Nwabuko OC, Igbigbi EE, Chukwuonye II, Nnoli MA. Multiple myeloma in Niger Delta, Nigeria: complications and the outcome of palliative interventions. Cancer Manag Res. 2017 May 22;9:189-196.

Novitzky N, Thomson J, Thomas V, du Toit C, Mohamed Z, McDonald A. Combined submyeloablative and myeloablative dose intense melphalan results in satisfactory responses with acceptable toxicity in patients with multiple myeloma. Biol Blood Marrow Transplant. 2010 Oct;16(10):1402-10.

Mallon B, Kaboré R, Couitchere L, Akonde FB, Lukamba R, Dackono TA, et al. The development of an international childhood cancer hospital register database in 13 African countries. A project of the French African Pediatric Oncology Group (GFAOP). Pediatr Blood Cancer. 2022 Mar;69(3):e29464.

Simone JV. History of the treatment of childhood ALL: a paradigm for cancer cure. Best Pract Res Clin Haematol. 2006;19(2):353-9.

Biondi A, Conter V, Chandy M, Ewald P, Lucia de Martino Lee M, Radhakrishnan VS, et al. Precursor B-cell acute lymphoblastic leukaemia-a global view. Br J Haematol. 2022 Feb;196(3):530-547.

Essien EM, Folami AO, Luzzatto L. Haemophilia in Nigeria. Trop Geogr Med. 1970 Dec;22(4):403-8.

Oldenburg J, Pavlova A. Genetic risk factors for inhibitors to factors VIII and IX. Haemophilia. 2006 Dec;12 Suppl 6:15-22.

Oldenburg J, Mahlangu JN, Kim B, Schmitt C, Callaghan MU, Young G, et al. Emicizumab Prophylaxis in Hemophilia A with Inhibitors. N Engl J Med. 2017 Aug 31;377(9):809-818.

Mahlangu J, Oldenburg J, Paz-Priel I, Negrier C, Niggli M, Mancuso ME, et al. Emicizumab Prophylaxis in Patients Who Have Hemophilia A without Inhibitors. N Engl J Med. 2018 Aug 30;379(9):811-822.

Pierce GF, Adediran M, Diop S, Dunn AL, El Ekiaby M, Kaczmarek R, et al. Achieving access to haemophilia care in low-income and lower-middle-income countries: expanded Humanitarian Aid Program of the World Federation of Hemophilia after 5 years. Lancet Haematol. 2022 Sep;9(9):e689-e697.

Lambert C, Meité N, Kouassi GK, Dohoma AS, Bognini Akou SA, Sanogo I, Hermans C. Nonreplacement therapy for hemophilia in low-income countries: experience from a prospective study in Ivory Coast. Res Pract Thromb Haemost. 2022 Dec 28;7(1):100033.

Oni SB, Osunkoya BO, Luzzatto L. Paroxysmal nocturnal hemoglobinuria: evidence for monoclonal origin of abnormal red cells. Blood. 1970 Aug;36(2):145-52.

Takeda J, Miyata T, Kawagoe K, Iida Y, Endo Y, Fujita T, et al. Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria. Cell. 1993 May 21;73(4):703-11.

Luzzatto L, Bessler M, Rotoli B. Somatic mutations in paroxysmal nocturnal hemoglobinuria: a blessing in disguise? Cell. 1997 Jan 10;88(1):1-4.

Luzzatto L, Risitano AM. Advances in understanding the pathogenesis of acquired aplastic anaemia. Br J Haematol. 2018 Sep;182(6):758-776.

Young NS. Acquired aplastic anemia. Ann Intern Med. 2002 Apr 2;136(7):534-46.

Ally M, Magesa P, Luzzatto L. High frequency of acquired aplastic anemia in Tanzania. Am J Hematol. 2019 Apr;94(4):E86-E88.

Hillmen P, Young NS, Schubert J, Brodsky RA, Socié G, Muus P, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006 Sep 21;355(12):1233-43.

de Latour RP, Szer J, Weitz IC, Röth A, Höchsmann B, Panse J, et al. Pegcetacoplan versus eculizumab in patients with paroxysmal nocturnal haemoglobinuria (PEGASUS): 48-week follow-up of a randomised, open-label, phase 3, active-comparator, controlled trial. Lancet Haematol. 2022 Sep;9(9):e648-e659.

Jang JH, Wong L, Ko BS, Yoon SS, Li K, Baltcheva I, et al. Iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria: a 2-cohort open-label proof-of-concept study. Blood Adv. 2022 Aug 9;6(15):4450-4460.

Pujadas E, Feinberg AP. Regulated noise in the epigenetic landscape of development and disease. Cell. 2012 Mar 16;148(6):1123-31.

Liang A, Kong Y, Chen Z, Qiu Y, Wu Y, Zhu X, Li Z. Advancements and applications of single-cell multi-omics techniques in cancer research: Unveiling heterogeneity and paving the way for precision therapeutics. Biochem Biophys Rep. 2023 Nov 29;37:101589.

Luzzatto L. A Journey from Blood Cells to Genes and Back. Annu Rev Genomics Hum Genet. 2023 Aug 25;24:1-33.

Additional Files

Published

2024-02-28

Issue

Section

Articles

How to Cite

Luzzatto, L. (2024). Progress And Challenges In Africa At The Time Of Molecular Haematology. Nigerian Journal of Haematology, 7(1&2). https://doi.org/10.60787/njhaem-7-1-2-69

Most read articles by the same author(s)

1 2 3 4 > >>