Low density parasitaemia, red blood cell polymorphisms and Plasmodium falciparumspecific immune responses in a low endemic area in northern Tanzania

Shekalaghe, Seif; Alifrangis, Michael; Mwanziva, Charles; Enevold, Anders; Mwakalinga, Steve; Mkali, Humphrey; Kavishe, Reginald A.; Manjurano, Alphaxard; Sauerwein, Robert W.; Drakeley, Chris; Bousema, Teun

doi:10.1186/1471-2334-9-69

Cited by 46 publications

(50 citation statements)

References 41 publications

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“…However, these data are entirely consistent with a recent report from a low transmission region in Tanzania in which a submicroscopic parasite infection detected by DNA analysis was associated with significantly higher malaria antibody levels than those in control populations that were parasite-free (17). Whether these findings in regions of low transmission reflect repeated submicroscopic infection, relatively long survival of parasite DNA in the circulation, or both is not yet clear.…”

Section: Discussionsupporting

confidence: 86%

Interaction of malaria with a common form of severe thalassemia in an Asian population

O’Donnell

Premawardhena

Arambepola

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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In many Asian populations, the commonest form of severe thalassemia results from the coinheritance of HbE and ␤ thalassemia. The management of this disease is particularly difficult because of its extreme clinical diversity; although some genetic and adaptive factors have been identified as phenotypic modifiers, the reasons remain unclear. Because the role of the environment in the course of severe thalassemia has been neglected completely and because malaria due to both Plasmodium falciparum and Plasmodium vivax has been prevalent in Sri Lanka, we carried out a pilot study of patients with HbE ␤ thalassemia that showed high frequencies of antibodies to both parasite species and that 28.6% of the children had DNA-based evidence of current infection with P. vivax. Malarial antibodies then were assessed in patients with HbE ␤ thalassemia compared with those in age-matched controls. There was a significant increase in the frequency of antibodies in the thalassemic patients, particularly against P. vivax and in young children. There was also a higher frequency in those who had been splenectomized compared with those with intact spleens, although in the latter it was still higher than that in the controls. The thalassemic patients showed significant correlations between malaria antibody status and phenotype. Patients with HbE ␤ thalassemia may be more prone to malaria, particularly P. vivax, which is reflected in their clinical severity. Because P. vivax malaria is widespread in Asia, further studies of its interaction with HbE ␤ thalassemia and related diseases are required urgently as a part of ongoing thalassemia control programs. I n excess of 300,000 babies have been estimated recently to be born each year with a serious inherited hemoglobin disorder (1). In sub-Saharan Africa, the main diseases of this type result from HbS or ␣ thalassemia. Throughout the Mediterranean region and the Middle East, ␣ and ␤ thalassemia predominate, although the sickle-cell gene occurs in the oasis populations of Saudi Arabia and extends to some of the tribal groups in India, where ␤ thalassemia also occurs at a high frequency (2). In the eastern parts of the Indian subcontinent, Bangladesh, Myanmar, Thailand, and in other parts of Southeast Asia, HbE is by far the most common hemoglobin variant (2), although both ␣ and ␤ thalassemia also occur at variable frequencies. Because HbE is synthesized at a reduced rate, it behaves phenotypically like a mild form of ␤ thalassemia (3). Because of its extremely high frequency, reaching a 70% carrier rate in some populations, it often is found in the compound heterozygous state with ␤ thalassemia, a condition called HbE ␤ thalassemia. This is the most common severe form of thalassemia in many Asian countries; in Thailand, for example, there are estimated to be Ϸ100,000 patients with this disease, and in Bangladesh, there are estimated to be twice this number (4, 5).One of the extraordinary features of HbE ␤ thalassemia, and one that makes its control and management extremely difficult, is it...

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Section: Discussionsupporting

confidence: 86%

Interaction of malaria with a common form of severe thalassemia in an Asian population

O’Donnell

Premawardhena

Arambepola

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…This study provides evidence for reductions in Hb concentrations after a single dose of PQ, at least in the context of coadministration with SPϩAS. Because the prevalence of the G6PD AϪ genotype was low in the current study population (ϳ4%) (36), because hemolysis in individuals with Africanvariant G6PD deficiency is generally milder than that in individuals with the Mediterranean variant (6), and because we excluded all children with moderate anemia, we did not expect any clinically relevant hemolysis in the current study. In contrast to our expectations, we observed considerable and statistically significant reductions in Hb concentrations, and Ͼ5% of the children became moderately anemic after the intervention with SPϩASϩPQ.…”

Section: Discussionmentioning

confidence: 99%

“…The sample size for hemoglobin measurements was based on an estimated prevalence of G6PD AϪ individuals of 4% and of G6PD A individuals of 10% in the study area (36) and an expected proportion of 50% of the individuals with the G6PD AϪ genotype and 5% of the individuals with the G6PD B genotype experiencing hemolysis after treatment, defined as a reduction in Hb level of at least 20% compared to baseline values (37). Based on these assumptions, enrolling 500 individuals who were treated with SPϩASϩPQ would result in an estimated 20 individuals with the G6PD AϪ genotype, 50 with the G6PD A genotype, and 430 with the G6PD B wild-type genotype, giving sufficient power to detect the expected difference between the G6PD AϪ and G6PD B groups (Z ␣ ϭ 1.96; Z ␤ ϭ Ϫ0.84).…”

Section: Methodsmentioning

confidence: 99%

In Tanzania, Hemolysis after a Single Dose of Primaquine Coadministered with an Artemisinin Is Not Restricted to Glucose-6-Phosphate Dehydrogenase-Deficient (G6PD A−) Individuals

Shekalaghe

Braak

Daou

et al. 2010

Antimicrob Agents Chemother

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The current interest in malaria elimination has led to a renewed interest in drugs that can be used for mass administration to minimize malaria transmission. Primaquine (PQ) is the only generally available drug with a strong activity against mature Plasmodium falciparum gametocytes, the parasite stage responsible for transmission. Despite concerns about PQ-induced hemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals, a single dose of PQ may be safe and efficacious in clearing gametocytes that persist after conventional treatment. As part of a mass drug intervention, we determined the hemolytic effect of sulfadoxinepyrimethamine (SP) plus artesunate (AS) plus a single dose of primaquine (PQ; 0.75 mg/kg of body weight) in children aged 1 to 12 years. Children were randomized to receive SP؉AS؉PQ or placebo; those with a hemoglobin (Hb) level below 8 g/dl were excluded from receiving PQ and received SP؉AS. The Hb concentration was significantly reduced 7 days after SP؉AS؉PQ treatment but not after placebo or SP؉AS treatment. This reduction in Hb was most pronounced in G6PD-deficient (G6PD A؊) individuals (؊2.5 g/dl; 95% confidence interval [95% CI], ؊1.2 to ؊3.8 g/dl) but was also observed in heterozygotes (G6PD A) (؊1.6 g/dl; 95% CI, ؊0.9 to ؊2.2 g/dl) and individuals with the wild-type genotype (G6PD B) (؊0.5 g/dl; 95% CI, ؊0.4 to ؊0.6 g/dl). Moderate anemia (Hb level of <8 g/dl) was observed in 40% (6/15 individuals) of the G6PD A؊, 11.1% (3/27 individuals) of the G6PD A, and 4.5% (18/399 individuals) of the G6PD B individuals; one case of severe anemia (Hb level of <5 g/dl) was observed. PQ may cause moderate anemia when coadministered with artemisinins, and excluding individuals based on G6PD status alone may not be sufficient to prevent PQinduced hemolysis.

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“…Contrary to previous studies, we did not find evidence for a boosting of immune responses by submicroscopic parasite carriage. 43,44 We observed few submicroscopic infections in children 1-5 years of age ( N = 11), which will have affected our power to detect such an immune-boosting effect. These findings confirm previous indications that parasitization status can be an important consideration in longitudinal assessments of the protective role of immune responses.…”

Section: Discussionmentioning

confidence: 99%

Continuing Intense Malaria Transmission in Northern Uganda

Proietti¹,

Pettinato²,

Kanoi³

et al. 2011

The American Society of Tropical Medicine and Hygiene

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Abstract. Recent reports of reductions in malaria transmission in several African countries have resulted in optimism that malaria can be eliminated in parts of Africa where it is currently endemic. It is not known whether these trends are global or whether they are also present in areas where political instability has hindered effective malaria control. We determined malaria parasite carriage and age-dependent antibody responses to Plasmodium falciparum antigens in cross-sectional surveys in Apac, northern Uganda that was affected by political unrest. Under-five parasite prevalence was 55.8% (115/206) by microscopy and 71.9% (41/57) by polymerase chain reaction. Plasmodium ovale alone, or as a co-infection, was detected in 8.6% (12/139) and Plasmodium malariae in 4.3% (6/139) of the infections. Age seroprevalence curves gave no indication of recent changes in malaria transmission intensity. Malaria control remains a tremendous challenge in areas that have not benefited from large-scale interventions, illustrated here by the district of Apac.

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Low density parasitaemia, red blood cell polymorphisms and Plasmodium falciparumspecific immune responses in a low endemic area in northern Tanzania

Cited by 46 publications

References 41 publications

Interaction of malaria with a common form of severe thalassemia in an Asian population

Interaction of malaria with a common form of severe thalassemia in an Asian population

In Tanzania, Hemolysis after a Single Dose of Primaquine Coadministered with an Artemisinin Is Not Restricted to Glucose-6-Phosphate Dehydrogenase-Deficient (G6PD A−) Individuals

Continuing Intense Malaria Transmission in Northern Uganda

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