Profiling the Plasmodium falciparum Erythrocyte Membrane Protein 1-Specific Immununoglobulin G Response Among Ghanaian Children With Hemoglobin S and C.

Members of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family are important targets for protective immunity. Abnormal display of PfEMP1 on the surfaces of infected erythrocytes (IEs) and reduced cytoadhesion have been demonstrated in hemoglobin (Hb) AS and HbAC, inherited blood disorders associated with protection against severe P. falciparum malaria. We found that Ghanaian children with HbAS had lower levels of immunoglobulin G against several PfEMP1 variants and that this reactivity increased more slowly with age than in their HbAA counterparts. Moreover, children with HbAS have lower total parasite biomass than those with HbAA at comparable peripheral parasitemias, suggesting impaired cytoadhesion of HbAS IEs in vivo and likely explaining the slower acquisition of PfEMP1-specific immunoglobulin G in this group. In contrast, the function of acquired antibodies was comparable among Hb groups and appears to be intact and sufficient to control parasitemia via opsonization and phagocytosis of IEs.

Plasmodium falciparum infection and naturally acquired immunity to malaria antigens among Ghanaian children in northern Ghana.

Background: The surge in malaria cases and deaths in recent years, particularly in Africa, despite the widespread implementation of malaria-control measures could be due to inefficiencies in malaria control and prevention measures in malaria-endemic communities. In this context, this study provides the malaria situation report among children in three Municipalities in Northern Ghana, where Seasonal Malaria Chemotherapy (SMC) is implemented by Ghana Health Service (GHS). Methods: A cross-sectional household survey was carried out to assess the malaria knowledge, attitudes, and practices (KAP) and malaria prevalence in 394 households in 13 rural communities in the Kumbugu, Nanton and Tolon Municipalities, Northern Region, Ghana. This was followed by screening for P. falciparum infection with anti-HRP2 RDT and PCR among children 1-17 years in the households. Plasma levels of IgG specific for crude P. falciparum antigen (3D7) and four recombinant malaria antigens (CSP, GLURP, MSP3, and Pfs230) were assessed by ELISA. The malaria and parasitaemia data were converted into frequency and subgroup proportions and disaggregated by study sites and demographic information of the participants. The ELISA data was converted to arbitrary units (AU) and similarly compared across study sites and demographic information. Results: The P. falciparum infection rate and frequency of malaria were high in the study areas with significant age-dependent and inter-community differences, which were reflected by differences in plasma levels of P. falciparum-specific IgG. Over 60% of households reported the use of bed nets and indoor insecticide sprays/coils, and 14% mentioned bush clearing around homes (14%) as malaria preventive measures. Community health centres were the preferred place for households (88%) to seek malaria treatment but over-the-counter drug stores were the major source (66%) of their antimalarials. Overall, malaria preventive and treatment practices were sub-optimal. Conclusions: P. falciparum infection and malaria are still high in the studied communities, indicating that preventive and control measures against the disease in the region remain inadequate. Efforts to ensure high SMC compliance and to improve preventative and treatment practices thus seem cost-beneficial "low-hanging fruits" in the fight against malaria in the Northern Region of Ghana.

Establishing and Maintaining In Vitro Cultures of Asexual Blood Stages of Plasmodium falciparum.

In vitro culture of asexual blood stages of Plasmodium falciparum is essential to study the parasite biology, and several aspects need to be addressed to successfully cultivate the parasites, including the requirements for red blood cells and specific nutrients. Since Trager and Jensen established the technique in 1976, some modifications have been introduced to improve the growth rate and yield. In brief, the method is based on the use of human red blood cells suspended in RPMI-1640 culture medium supplemented with a source of lipids and maintained at 37 °C in a low-oxygen atmosphere. In this protocol, a description of thawing, culturing, and cryopreservation of asexual blood stages of P. falciparum is presented.

PfEMP1-Specific Immunoglobulin G Reactivity Among Beninese Pregnant Women With Sickle Cell Trait.

BACKGROUND: Sickle cell trait (HbAS) protects against severe Plasmodium falciparum malaria but not against placental malaria (PM). In this study, P falciparum erythrocyte membrane protein (PfEMP1)-specific antibodies were measured in HbAA and HbAS Beninese pregnant women as a proxy of exposure to specific PfEMP1 variants. METHODS: Plasma samples collected at delivery from 338 HbAA and 63 HbAS women were used to measure immunoglobulin (Ig)G levels to 6 recombinant PfEMP1 proteins and 3 corresponding native proteins expressed on the infected erythrocyte (IE) surface. Immunoglobulin G-mediated inhibition of VAR2CSA+ IEs adhesion to chondroitin sulfate A (CSA) was also tested. RESULTS: Levels of PfEMP1-specific IgG were similar in the 2 groups, except for native IT4VAR09 on IEs, where IgG levels were significantly higher in HbAS women. Adjusted odds ratios for women with positive IgG to HB3VAR06 and PFD1235w suggest a lower risk of infection with these virulent variants among HbAS individuals. The percentage of IEs binding to CSA did not differ between HbAA and HbAS women, but it correlated positively with levels of anti-VAR2CSA and parity. Women with PM had lower levels of anti-VAR2CSA-specific IgG and lower IgG-mediated inhibition of IE adhesion to CSA. CONCLUSIONS: The findings support similar malaria exposure in HbAA and HbAS women and a lack of HbAS-dependent protection against placental infection among pregnant women.

WaSH CQI: Applying continuous quality improvement methods to water service delivery in four districts of rural northern Ghana.

Continuous, safely managed water is critical to health and development, but rural service delivery faces complex challenges in low- and middle-income countries (LMICs). We report the first application of continuous quality improvement (CQI) methods to improve the microbial quality of household water for consumption (HWC) and the functionality of water sources in four rural districts of northern Ghana. We further report on the impacts of interventions developed through these methods. A local CQI team was formed and trained in CQI methods. Baseline data were collected and analyzed to identify determinants of service delivery problems and microbial safety. The CQI team randomized communities, developed an improvement package, iteratively piloted it in intervention communities, and used uptake survey data to refine the package. The final improvement package comprised safe water storage containers, refresher training for community WaSH committees and replacement of missing maintenance tools. This package significantly reduced contamination of HWC (p<0.01), and significant reduction in contamination persisted two years after implementation. Repair times in both intervention and control arms decreased relative to baseline (p<0.05), but differences between intervention and control arms were not significant at endline. Further work is needed to build on the gains in household water quality observed in this work, sustain and scale these improvements, and explore applications of CQI to other aspects of water supply and sanitation.