Download presentation
Presentation is loading. Please wait.
Published byNaomi Walters Modified over 6 years ago
1
Alpha+ thalassaemia and the severity of Plasmodium falciparum infection in microcytic children from the Kumasi metropolis of Ghana Clement Opoku-Okrah1,2; Caroline Smith2; Mike Gordge2; Martin Parry2 Claire Robertson2; Tsiri Abgenyega1; Emmanuel Nakua1 Kwame Nkrumah University of Science and Technology, Ghana1 University of Westminster, Biosciences, London, UK2 KNUST
2
Malaria More than 90% of global morbidity and mortality of malaria is suffered by Africa Mostly affect children less than 5 years old. (Mockenhaupt et al., 2004)
3
Malaria Situation in Ghana
Malaria is hyper-endemic Over 900,000 cases of suspected malaria involving children <5years are reported each year Malaria accounts for 22% of under-five mortality (Roll back malaria, Ghana, 2005).
4
Protective effects of inherited red cell disorders
It is well recognised that protection against malaria is provided by a variety of inherited red cell disorders G6PD deficiency Southeast Asian ovalocytosis Duffy antigen negative status Structural haemoglobinopathies Thalassaemia
5
Alpha+-thalassaemia In people of African descent the -α3.7 deletional α+- thalassaemia is predominant In the Northern and Ashanti regions of Ghana, prevalence of α+-thalassaemia, is estimated at 26-33% (Mockenhaupt et al., 2001; 2004a) The disease is often mistaken for iron deficiency anaemia and treated inappropriately Evidence suggests that a+-thalassaemia ameliorates the severity of malaria, but does not reduce initial infection rates
6
OBJECTIVES Determine prevalence of malaria parasitaemia among children attending outpatient clinic in Kumasi, Ghana Determine the prevalence of α+-thalassaemia among those children with malaria infection Determine whether the presence of an + thalassaemia genotype influences the density of malaria parasitaemia
7
Screened Subjects (n=1672) Mps-ve and Mps +ve, confounders (n=940)
Enrolled Subjects Mps +ve and non- confounders (n=732) Screened Subjects (n=1672) Mps+ve (904); Mps +ve (n=904) Mps –ve (n=768) Mps-ve and Mps +ve, confounders (n=940) Hb AS (n=123) Mps-ve (79) Mps +ve (44) HbAC (n=147) Mps –ve (68) Mps +ve (79) G6PD deficiency n=102) Mps –ve (40) Mps +ve (62) No Mps (n=768). Some already included in Hb AS, Hb AC and G6PD deficiency Mean Hb RBC MCV MCH GMPD Normal Genotype (αα/αα) (n=358) Alpha+ thalassaemia (n=175) Homozygous (-α/-α) (n=49) Heterozygous (-α/αα) (n=126) PCR Microcytic (MCV 76 fL) Hypochromic (MCH 25 pg) (n= 238) Normocytic (MCV > 76 fL) Normochromic (MCH > 25 pg) (n=114) Microcytic (MCV 76 fL) Normochromic (MCH > 25 pg) (n= 351) Normocytic (MCV > 76 fL) Hypochromic (MCH 25 pg) (n= 29) No Amplification (n=56). Study Population
8
Parasitological Studies
Ring form of Plasmodium falciparum Parasitological Studies Thick and thin blood films were stained with 10% Giemsa and read for malaria parasites Parasitaemia was graded as: Low (1-999/μL) Moderate ( /μL) High ( /μL). Severe malaria was defined as Mean Parasite Density (MPD) ≥100,000/μL Gametocyte
9
PCR for –α3.7 deletion W W M H W N L Primer sequence
2000bp 1800bp Name 5’-3’ Sequence GenBank ID: Nucleotide α2/3.7-F CCCCTCGCCAAGTCCACCC HUMHB A4: 3.7/20.5-R AAAGCACTCTAGGGTCCAGCG HUMHB A4: α2-R AGACCAGGAAGGGCCGGTG HUMHB A4: Ethidium bromide-stained gels showing results from multiplex PCR for the 3.7 thalassaemia. Sizes of the amplified fragments are given in base pair (bp). Lane L is the 100 bp DNA; M is -a/-a homozygote (2000 bp); H is -a/aa heterozygote (1800 bp and 2000 bp); W is αα/ααWildtype (1800 bp);N is negative (Chong et al., 2000)
10
RESULTS The frequency of P. falciparum malaria in the studied population was 54.1% Frequencies for α+-thalassaemia genotypes were: heterozygous (-α/αα) % homozygous (-α/-α) % total carriage rate (α/αα & -α/-α) 29.3%
11
Results (2) Among microcytic patients, mean parasite density was lower in the presence of a+-thalassaemia genotype, compared with normal genotype Severe malaria (defined as parasite density ≥100,000/μL) was less prevalent in microcytic patients with a+- thalassaemia genotype than in those with normal genotype
12
P<0.001 Parasite density/μL
Homozygous(-α/-α) Heterozygous (-α/αα) Normal genotype(αα/αα)
13
Percentage of patients
The effect of alpha+ thalassaemia genotypes on Plasmodium falciparum(n=533), Error bars:95% confidence interval (p<0.001)
14
CONCLUSIONS There is a prevalence of 29.3% a+-thalassaemia among malaria-infected children in this population Microcytic hypochromic anaemia should not, therefore be assumed to be due to iron deficiency The presence of an a+-thalassaemia genotype (both -α/αα and α/-α) reduces the severity of P. falciparum parasitaemia, compared to normal genotype. The mechanism of this protection is still not clear
15
THANK YOU
Similar presentations
© 2024 SlidePlayer.com. Inc.
All rights reserved.