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Sickle cell disease (SCD) is a single gene blood disorder characterised by frequent episodes of pain, chronic anaemic, acute chest syndrome, severe disease complications and lifelong debilitating multi-system organ damage. Genetic testing and screening programs for SCD and the sickle cell trait (SCT) are valuable for early diagnosis and management of children living with SCD, and in the identification of carriers of SCT. People with SCT are for the most part asymptomatic and mainly identified as through genetic testing or when they have a child with SCD. This qualitative study explored perceptions towards genetic testing for SCD and SCT in Cameroon, Ghana, and Tanzania. The results show a general preference for newborn screening for SCD over prenatal and premarital/preconception testing, primarily due to its simpler decision-making process and lower risk for stigmatization. Premarital testing for SCT was perceived to be of low public health value, as couples are unlikely to alter their marriage plans despite being aware of their risk of having a child with SCD. Adolescents were identified as a more suitable population for SCT testing. In the case of prenatal testing, major concerns were centred on cultural, religious, and personal values on pregnancy termination. The study revealed a gender dimension to SCD/SCT testing. Participants mentionned that women bear a heightened burden of decision making in SCD/SCT testing, face a higher risk of rejection by potential in-laws/partners if the carriers of SCT, as well as the possibility of  divorce if they have a child with SCD. The study highlights the complex cultural, ethical, religious and social dynamics surrounding genetic testing for SCD and emphasises the need for public education on SCD and the necessity of incorporating genetic and psychosocial counselling into SCD/SCT testing programs., (© 2024. The Author(s).)

Background: Red blood cell (RBC) polymorphisms are common in malaria endemic regions and are known to protect against severe forms of the disease. Therefore, it is important to screen for these polymorphisms in drugs or vaccines efficacy trials. This study was undertaken to evaluate associations between clinical malaria and RBC polymorphisms to assess biological interactions that may be necessary for consideration when designing clinical trials., Method: In a cross-sectional study of 341 febrile children less than five years of age, associations between clinical malaria and common RBC polymorphisms including the sickle cell gene and G6PD deficiency was evaluated between November 2008 and June 2009 in the middle belt of Ghana, Kintampo. G6PD deficiency was determined by quantitative methods whiles haemoglobin variants were determined by haemoglobin titan gel electrophoresis. Blood smears were stained with Giemsa and parasite densities were determined microscopically., Results: The prevalence of clinical malarial among the enrolled children was 31.9%. The frequency of G6PD deficiency was 19.0% and that for the haemoglobin variants were 74.7%, 14.7%, 9.1%, 0.9% respectively for HbAA, HbAC, HbAS and HbSS. In Multivariate regression analysis, children with the HbAS genotype had 79% lower risk of malaria infection compared to those with the HbAA genotypes (OR = 0.21, 95% CI: 0.06-0.73, p = 0.01). HbAC genotype was not significantly associated with malaria infection relative to the HbAA genotype (OR = 0.70, 95% CI: 0.35-1.42, p = 0.33). G6PD deficient subgroup had a marginally increased risk of malaria infection compared to the G6PD normal subgroup (OR = 1.76, 95% CI: 0.98-3.16, p = 0.06)., Conclusion: These results confirm previous findings showing a protective effect of sickle cell trait on clinical malaria infection. However, G6PD deficiency was associated with a marginal increase in susceptibility to clinical malaria compared to children without G6PD deficiency.

Background: Previous studies on the association of malaria and stunted growth delivered inconsistent results. These conflicting results may be due to different levels of confounding and to considerable difficulties in elucidating a causal relationship. Randomized experiments are impractical and previous observational studies have not fully controlled for potential confounding including nutritional deficiencies, breastfeeding habits, other infectious diseases and socioeconomic status., Methods: This study aims to estimate the causal effect between malaria episodes and stunted growth by applying a combination of Mendelian randomization, using the sickle cell trait, and matching. We demonstrate the method on a cohort of children in the Ashanti Region, Ghana., Results: We found that the risk of stunting increases by 0.32 (P-value: 0.004, 95% CI: 0.09, 1.0) for every malaria episode. The risk estimate based on Mendelian randomization substantially differs from the multiple regression estimate of 0.02 (P-value: 0.02, 95% CI: 0.003, 0.03). In addition, based on the sensitivity analysis, our results were reasonably insensitive to unmeasured confounders., Conclusions: The method applied in this study indicates a causal relationship between malaria and stunting in young children in an area of high endemicity and demonstrates the usefulness of the sickle cell trait as an instrument for the analysis of conditions that might be causally related to malaria.

Objective: To explore the attitudes of Ghanaian women toward genetic testing for the sickle cell trait and to investigate key factors that promote or impede the decision to pursue knowledge of the carrier status., Methods: A survey, administered in person to Ghanaian women, collected demographic information and information on the participants' knowledge about their carrier status, their attitudes toward genetic testing, and their perceptions of the implications of being a carrier. The results for women who had previously undergone testing and those who had not were compared., Results: Of 124 participants, 75 had been tested for the sickle cell trait and 49 had not. Some 53% of the women who had been tested did not know their carrier status. Most women agreed that getting a prenatal genetic test was important. However, nontested women were more likely to lack the financial resources to undergo testing, to think that testing is futile because sickle cell disease is not curable, and to believe that the outcome of their child's health is determined by God., Conclusion: The women tended to have favorable attitudes toward genetic testing, but numerous barriers remained that precluded knowledge of their carrier status or the pursuit of this knowledge., (Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

The haemoglobin (Hb) variants HbS and HbC protect against severe malaria. Yet, the influence particularly of HbC on asymptomatic or mild Plasmodium infection is not well established. In a dry season cross-sectional survey among 2108 children aged 0.5-9 years in the Northern Region of Ghana, Plasmodium species and density, as well as Hb, were analysed with respect to Hb genotypes. HbAC occurred in 19.7% and HbAS in 7.4% (HbSC, 0.8%; HbCC, 0.8%; HbSS, 0.3%). Overall, 56% of the children had microscopically visible parasitaemia. By PCR, P. falciparum, P. malariae, and P. ovale were present in 74.5%, 9.7%, and 5.5%, respectively. Febrile parasitaemia was rare (2.8%) but anaemia (Hb<11g/dL) frequent (59.3%). Children with HbAA and HbAC showed virtually identical malariometric parameters. In contrast, children with HbAS had significantly less parasitaemia, lower parasite densities, and a higher proportion of submicroscopic P. falciparum infection. Remarkably, in children with HbCC, P. malariae infection occurred in 37.5% (adjusted odds ratio (aOR), 5.8; 95% CI, 1.8-18.8) and P. ovale in 18.8% (aOR, 3.61; 95% CI, 0.97-13.5). In this population with predominantly asymptomatic Plasmodium infection, HbAC shows no discernible effect on malaria-related parameters. Homozygous HbC, in contrast, confers an increased risk of P. malariae infection which conceivably may modulate falciparum malaria., (Copyright © 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.)

The high prevalence of hemoglobin S (HbS) in Africa and hemoglobin C (HbC) in parts of West Africa is caused by the strong protection against severe falciparum malaria during childhood. Much less is known about the effect of HbS and especially HbC on Plasmodium falciparum infection, uncomplicated malaria, and anemia. A total of 1070 children from the Ashanti Region, Ghana, were enrolled at the age of 3 months and visited monthly until 2 years of age. The effects of the beta-globin genotype on the age-dependent incidence of malaria, levels of parasitemia, and hemoglobin as well as physical development were analyzed by population-averaged models. Infants with HbAS were protected from uncomplicated malaria (P < .005) and anemia (P < .001), had lower age-adjusted parasite densities (P < .001), and higher age-adjusted hemoglobin levels compared with children with the HbAA genotype (P = .004). In contrast, HbAC carriers had lower hemoglobin levels (P < .033) and were not protected against malaria or anemia. Notably, infants with HbAS were also significantly protected against stunting compared with carriers of HbAA or HbAC. This indicates differing mechanisms of protection against malaria of HbAS and HbAC and might help to understand why HbC is restricted to distinct areas of West Africa.

Background: While the protective effects of sickle cell trait (HbAS) against severe malaria and the resulting survival advantage are well known, the impact on the physical development in young children remains unclear. This study was aimed to investigate the relationship between HbS carriage and stunting in children below two years of age in a cohort from the Ashanti Region, Ghana., Methods: 1,070 children were recruited at three months of age and followed-up for 21 months with anthropometric measurements performed every three months. Incidence rate ratios with 95% confidence intervals were calculated by Poisson regression to estimate the association of beta-globin genotypes with the number of malaria episodes. Odds ratios (OR) were calculated for the association between the occurrence of beta-globin genotypes and/or malaria episodes and stunting. The age-dependent between-group and within-group effects for the beta-globin genotypes were assessed by population-averaged models estimated by generalized estimation equation with autoregressive correlation structure., Results: Analyses showed a significantly lower age-dependent risk of stunting (OR 0.56; 95% CI 0.33-0.96) in carriers of the HbAS genotype (n = 102) in comparison to those with HbAA (n = 692). This effect was restricted to children who experienced malaria episodes during the observation period suggesting that the beneficial effect of the beta-globin HbS variant on the incidence of stunting is closely linked to its protection from mild malaria episodes., Conclusion: The lower risk of chronic malnutrition in early childhood, mediated by protection against mild malaria episodes, may contribute to the survival advantage of HbAS carriers in areas of high malaria transmission.