Date of Award
Open Access Thesis
Master of Public Health (MPH)
School of Public Health
Yap Boum II
Introduction: Malaria transmission in Uganda is remarkably heterogeneous, and declines in prevalence have not been uniform. Previous surveys in southwestern Uganda have shown declines in parasite prevalence from 2004 to 2010. As malaria transmission continues to decline in southwestern Uganda, aggressive strategies, such as the addition of primaquine (PQ) to artemisinin-combination therapies (ACTs), are being considered in low transmission settings. Despite the potential benefit of PQ in reducing transmission, concerns over its safety and efficacy have hampered its deployment. In particular, those with glucose-6-phosphate dehydrogenase (G6PD) deficiency are at a higher risk of hemolytic toxicity.
Methods: To better assess how primaquine may impact upon southwestern Uganda, we conducted a cross sectional survey among 631 children under five years of age sampled from districts previously characterized as low (Mbarara), intermediate (Bushenyi), and high (Isingiro) transmission intensities. Blood samples were collected via capillary fingerprick to determine the current status of malaria control and the prevalence of G6PD deficiency. Parasite prevalence was determined using (1) a combined Plasmodium HRP-2/LDH rapid diagnostic test (RDT) (SD Bioline Malaria Ag P.f/Pan) and (2) light microscopy. G6PD deficiency was evaluated by: (1) quantitative G6PD deficiency by spectrophotometric assay (Trinity Biotech®), (2) qualitative G6PD deficiency assay by rapid diagnostic test (CareStart™ G6PD RDT), and (3) DNA was isolated to conduct PCR-RFLP analysis to detect the G6PD A- 202A/376G allele.
Results: Prevalence of parasitemia was higher by RDT compared to microscopy (6.2% (95% CI: 4.3-8.1) vs. 3.2% (95% CI: 1.8-4.5)). By district, parasitemia prevalence was 1.2% (3/242) in Mbarara, 3.2% (5/157) in Bushenyi, and 5.2% (12/232) in Isingiro. All 20 microscopy positive cases were detected by RDT. Of the 19 cases detected only by RDT, 7 (36.8%) reported having been treated for malaria within the past month. Notably, of the 20 microscopy positive children, 50% (10/20) were infected with P. falciparum, 40% (8/20) with P. malariae, and the remaining 2 children were P. vivax and P. ovale mono-infections. Knowledge, attitudes, and practice regarding malaria prevention were also assessed, revealing a high proportion of households reporting bednet use (91.6%), but only a small fraction of households participating in indoor residual spraying (0.8%). The prevalence of mild G6PD deficiency (defined as 10-60% of normal activity) was 13.8% (95% CI: 11.1-16.5) as compared to 8.6% (95% CI: 6.4-10.8) by RDT. No participants in our study exhibited severe G6PD deficiency (<10% enzyme activity). Of the 577/631 children considered normal by RDT, 37 were mildly deficient by quantitative assay. Of the 54 children found to be G6PD deficient by RDT, 4 were quantitatively normal. Performance characteristics of the CareStart™ G6PD RDT as compared with the Trinity Biotech® assay revealed low/moderate sensitivity and high specificity (57.5% and 99.3%, respectively). The currently recommended qualitative G6PD assay, the fluorescent spot test (FST), defines deficiency as 10% to 30% of normal G6PD activity. When compared to FST, the sensitivity of CareStart™ G6PD RDT increased to 94.7%, while specificity slightly decreased (94.1%). We found a lack of correlation between genotypic and phenotypic assays. The sensitivity and specificity of the quantitative enzymatic assay to detect the G202A mutation was 29.8% and 87.8%.
Conclusion: Our preliminary findings indicate continued strides toward malaria control over the past 10 years in southwestern Uganda. Most notably, our survey reveals a striking shift in species prevalence in this region of Uganda, with nearly 50% of asymptomatic children infected with non-falciparum species. Furthermore, our results strongly suggest the need for better qualitative screening methods evaluating both the phenotype and genotype of G6PD deficiency.
Roh, Michelle, "Prevalence Of Malaria And Glucose-6-Phosphate Dehydrogenase Deficiency In Malaria-Endemic Southwestern Uganda: Implications For Primaquine Use" (2015). Public Health Theses. 1248.