Glucose-6-phosphate dehydrogenase deficiency in Nigerian children.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy and in Sub-Saharan Africa, is a significant cause of infection- and drug-induced hemolysis and neonatal jaundice. Our goals were to determine the prevalence of G6PD deficiency among Nigerian children of different ethnic backgrounds and to identify predictors of G6PD deficiency by analyzing vital signs and hematocrit and by asking screening questions about symptoms of hemolysis. We studied 1,122 children (561 males and 561 females) aged 1 month to 15 years. The mean age was 7.4 ± 3.2 years. Children of Yoruba ethnicity made up the largest group (77.5%) followed by those Igbo descent (10.6%) and those of Igede (10.2%) and Tiv (1.8%) ethnicity. G6PD status was determined using the fluorescent spot method. We found that the overall prevalence of G6PD deficiency was 15.3% (24.1% in males, 6.6% in females). Yoruba children had a higher prevalence (16.9%) than Igede (10.5%), Igbo (10.1%) and Tiv (5.0%) children. The odds of G6PD deficiency were 0.38 times as high in Igbo children compared to Yoruba children (p=0.0500). The odds for Igede and Tiv children were not significantly different from Yoruba children (p=0.7528 and 0.9789 respectively). Mean oxygen saturation, heart rate and hematocrit were not significantly different in G6PD deficient and G6PD sufficient children. The odds of being G6PD deficient were 2.1 times higher in children with scleral icterus than those without (p=0.0351). In conclusion, we determined the prevalence of G6PD deficiency in Nigerian sub-populations. The odds of G6PD deficiency were decreased in Igbo children compared to Yoruba children. There was no association between vital parameters or hematocrit and G6PD deficiency. We found that a history of scleral icterus may increase the odds of G6PD deficiency, but we did not exclude other common causes of icterus such as sickle cell disease or malarial infection

Mean oxygen saturation, heart rate and hematocrit in G6PD deficient and G6PD sufficient children.

<p>The Satterthwaite <i>t-</i> test was used to compare G6PD deficient to G6PD sufficient. The p-values for oxygen saturation, heart rate and hematocrit were 0.2812, 0.3837, and 0.3515 respectively.</p

Screening questions about symptoms of hemolysis.

<p>Screening questions about symptoms of hemolysis.</p

Relationship between G6PD deficiency and gender, age, ethnic group, hematocrit, oxygen saturation, heart rate, tea-colored urine and scleral icterus.

*<p>RE is the random effect of family.</p><p>Note: The backward elimination results are not shown in this table.</p><p>The odds of being G6PD deficient were 3.6 times higher in males than in females (p<0.0001). The odds of being G6PD deficient were 0.38 times as high in Igbo children compared to Yoruba children (p = 0.0500). The odds for Igede and Tiv children were not significantly different from Yoruba children (p = 0.7528 and 0.9789 respectively). The odds of being G6PD deficient were 2.1 times higher in children with scleral icterus than those without (p = 0.0351). The magnitude of the scleral icterus effect appeared to be lower if these children also reported tea-colored urine, but the number of children reporting both conditions (N = 10) is too small to be certain.</p

Data obtained from sampled population.

<p>Data obtained from sampled population.</p

Result notification forms.

<p>Result notification forms.</p

Population characteristics.

<p>Population characteristics.</p

Rates of scleral icterus and tea-colored urine among G6PD deficient children of different ages.

†<p>Total number of G6PD deficient children within age group.</p

Hydroxyurea to lower transcranial Doppler velocities and prevent primary stroke: the Uganda NOHARM sickle cell anemia cohort

In summary, the NOHARM trial provides additional evidence for the safety and efficacy of short-term hydroxyurea treatment for SCA in sub-Saharan Africa within a clinical trial setting. Data from both the blinded treatment phase and the open-label treatment phase demonstrate clinical and hematological benefits of hydroxyurea in a malarial endemic region, including evidence of reduced TCD velocities and primary stroke prevention. Additional TCD screening programs and clinical trials are urgently needed in sub-Saharan Africa to document the feasibility and benefits of hydroxyurea treatment for children with conditional or even abnormal TCD velocities, given the challenges of providing chronic blood transfusions. To help prevent primary stroke in this high-risk population, future studies should also focus on optimal dosing strategies and monitoring regimens, in an effort to determine the overall feasibility and safety of introducing hydroxyurea therapy for SCA widely across sub-Saharan Africa

Novel Use of Hydroxyurea in an African Region With Malaria: Protocol for a Randomized Controlled Clinical Trial. JMIR Res Protoc.

Background:Sickle cell anemia (SCA), one of most prevalent monogenic diseases worldwide, is caused by a glutamic acid to valine substitution on the beta globin protein of hemoglobin, which leads to hemolytic anemia. Hydroxyurea, the only disease-modifying therapy approved by the Food and Drug Administration for SCA, has proven to be a viable therapeutic option for SCA patients in resource-rich settings, given clinical improvements experienced while taking the medication and its once-daily oral dosing. Significant studies have demonstrated its safety and clinical efficacy among children and adults in developed countries. In Sub-Saharan Africa, however, the risk of malaria, hematologic toxicities, and safety of hydroxyurea in children with SCA living in malaria-endemic areas are unknown. Objectives:Study objectives include determining the incidence of malaria in SCA patients taking hydroxyurea versus placebo; establishing the frequency of hematologic toxicities and adverse events (AEs) in children with SCA treated with hydroxyurea versus placebo; and defining the relationships between hydroxyurea treatment and fetal hemoglobin, soluble intracellular adhesion molecule-1, and nitric oxide levels, and between levels of these factors and risk of subsequent malaria. Methods:Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM, NCT01976416) is a prospective, randomized, placebo-controlled, double-blinded phase III trial to compare risk of malaria with oral hydroxyurea versus placebo. Children will be recruited from the Mulago Hospital Sickle Cell Clinic in Kampala, Uganda. Results:Two hundred Ugandan children aged between 1.00 and 3.99 years with confirmed SCA will be randomized into treatment groups by order of entry in the study, based on a predetermined blinded randomization list. The primary outcome of the trial is malaria incidence in the 2 study groups, defined as episodes of clinical malaria occurring over the 1-year randomized study treatment period. Conclusion:NOHARM will be the first prospective randomized, placebo-controlled clinical trial investigating the use of hydroxyurea for children with SCA in a malaria-endemic region within Africa. The results of this trial have the potential to significantly advance understanding of how to safely and effectively use hydroxyurea in children with SCA in malaria-endemic areas