ABSTRACT
Blood group O is associated with protection against severe malaria and reduced size and stability of P. falciparum- host red blood cell (RBC) rosettes compared to non-O blood groups. Whether the non-O blood groups encoded by the specific ABO genotypes AO, BO, AA, BB and AB differ in their associations with severe malaria and rosetting is unknown. The A and B antigens are host RBC receptors for rosetting, hence we hypothesized that the higher levels of A and/or B antigen on RBCs from AA, BB and AB genotypes compared to AO/BO genotypes could lead to larger rosettes, increased microvascular obstruction and higher risk of malaria pathology. We used a case-control study of Kenyan children and in vitro adhesion assays to test the hypothesis that “double dose” non- O genotypes ( AA, BB, AB ) are associated with increased risk of severe malaria and larger rosettes than “single dose” heterozygotes ( AO, BO ). In the case-control study, compared to OO , the double dose genotypes consistently had higher odds ratios (OR) for severe malaria than single dose genotypes, with AB (OR 1.93) and AO (OR 1.27) showing most marked difference (P=0.02, Wald test). In vitro experiments with blood group A-preferring P. falciparum parasites showed that significantly larger rosettes were formed with AA and AB host RBCs compared to OO , whereas AO genotype rosettes were indistinguishable from OO . Overall, the data show that ABO genotype influences P. falciparum rosetting and support the hypothesis that double dose non- O genotypes confer a greater risk of severe malaria than AO/BO heterozygosity.
Subject(s)
MalariaABSTRACT
BACKGROUNDVirtual global health partnership initiatives (VGHPIs) evolved rapidly during the COVID-19 pandemic to ensure partnership continuity, however the current landscape for VGHPI use and preference is unknown. This study aimed to increase understanding of GH partners’ perspectives on VGHPIs.METHODSFrom 15 October to 30 November 2020, authors conducted an online, international survey using snowball sampling to document pandemic-related changes in partnership activities; preferences for VGHPIs; and perceived acceptability and barriers. Analysis stratified responses by country income classification and partnership type. RESULTSA total of 128 respondents described 219 partnerships. 152/219 (69%) partnerships were transnational, 157/219 (72%) were of >5 years duration, and 127/219 (60%) included bidirectional site visits. High-income country (HIC) partners sent significantly more learners to low- to middle-income country (LMIC) partner sites ( P< 0.01). Participants commented on pandemic-related disruptions affecting 217/219 (99%) partnerships; 195/217 (90%) were disruption to activities; 122/217 (56%) to communication; 73/217 (34%) to access to professional support; and 72/217 (33%) to funding. Respondents indicated that VGHPIs would be important to 206/219 (94%) of their partnerships moving forward. There were overall differences in resource availability, technological capacity, and VGHPI preferences between LMIC and HIC respondents, with a statistically significant difference in VGHPI acceptability (p<0.001). There was no significant difference between groups regarding VGHPIs’ perceived barriers. CONCLUSIONSThe pandemic disrupted essential partnership elements, compounding differences between LMIC and HIC partners in their resources and preferences for partnership activities. VGHPIs have the potential to bridge new and existing gaps and maximize gains, bi-directionality, and equity in partnerships during and after COVID-19.