Elevated levels of endothelial molecules ICAM-1, VEGF-A and VEGFR2 in microscopic asymptomatic malaria

Background In malaria, clinical disease has been associated with increased levels of endothelial activation due to the sequestration of infected erythrocytes. However, levels and impact of endothelial activation and pro-angiogenic molecules such as vascular endothelial growth factor (VEGF)-A and its receptor VEGFR2 in asymptomatic malaria have not been well characterized. Methods Blood samples were obtained from community children for malaria diagnosis using microscopy and PCR. A multiplex immunoassay was used to determine the levels of Intracellular adhesion molecule (ICAM)-1, VEGF-A, and VEGFR2 in the plasma of children with microscopic or submicroscopic asymptomatic parasitaemia and compared with levels in uninfected controls. Results Levels of ICAM-1, VEGF-A and VEGFR2 were significantly increased in children with microscopic asymptomatic parasitaemia compared with uninfected controls. Also, levels of VEGF-A were found to be inversely associated with age. Additionally, a receiver operating characteristic analysis revealed that plasma levels of ICAM-1 (AUC =0.72), showed a moderate potential in discriminating between children with microscopic malaria from uninfected controls when compared to VEGF-A (AUC =0.67) and VEGFR2 (AUC =0.69). Conclusion These data imply that endothelial activation and pro-angiogenic growth factors could be one of the early host responders during microscopic asymptomatic malaria, and may play a significant role in disease pathogenesis.

Suitability of IgG responses to multiple Plasmodium falciparum antigens as markers of transmission intensity and pattern

Detection of antibody reactivity to appropriate, specific parasite antigens may constitute a sensitive and cost-effective alternative to current tools to monitor malaria transmission across different endemicity settings. This study aimed to determine the suitability of IgG responses to a number of P. falciparum antigens as markers of transmission intensity and pattern. Antibody responses to multiple malaria antigens were determined in 905 participants aged 1–12 years from three districts with low (Keta), medium (Hohoe) and high (Krachi) transmission intensity in the Volta region of Ghana. Blood film microscopy slides and dry blood spots (DBS) were obtained for parasitaemia detection and antibody measurement, respectively. Sera were eluted from DBS and levels of IgG specific for 10 malaria antigens determined by a multiplex assay. Results were compared within and among the districts. Total IgG responses to MSPDBL1, MSPDBLLeucine, MSP2-FC27, RAMA, and PfRh2a and PfRh2b were higher in Krachi than in Hohoe and Keta. Seroprevalence of IgG specific for MSPDBLLeucine, RON4, and PfRh2b were also highest in Krachi. Responses to RALP-1, PfRh2a and PfRh2b were associated with patent but asymptomatic parasitaemia in Keta, while responses to MSPDBL1, MSPDBLLeucine, MSP2-FC27, RAMA, Rh2-2030, and PfRh2b were associated with parasite carriage in Hohoe, but not in Krachi. Using ROC analysis, only PfRh2b was found to predict patent, but asymptomatic, parasitaemia in Keta and Hohoe. Antibody breadth correlated positively with age (r = 0.29, p<0.0001) and parasitaemia (β = 3.91; CI = 1.53 to 6.29), and medium to high transmission (p<0.0001). Our findings suggest differences in malaria-specific antibody responses across the three transmission zones and that PfRh2b has potential as a marker of malaria transmission intensity and pattern. This could have implications for malaria control programs and vaccine trials.

Prevalence of asymptomatic malaria parasitaemia following mass testing and treatment in Pakro sub-district of Ghana

Background Global efforts to scale-up malaria control interventions are gaining steam. These include the use of Long-Lasting Insecticide Nets, Indoor Residual Spraying, Intermittent Preventive Treatment and Test, Treat and Track. Despite these, the drive for malaria elimination is far from being realistic in endemic communities in Africa. This is partly due to the fact that asymptomatic parasite carriage, not specifically targeted by most interventions, remains the bedrock that fuels transmission. This has led to mass testing, treatment and tracking (MTTT) as an alternative strategy to target asymptomatic individuals. We report the impact of MTTT on the prevalence of asymptomatic malaria parasitaemia over a one-year period in Ghana, hypothesizing that implementing MTTT could reduce the rate of asymptomatic parasitaemia. Methods A population of about 5000 individuals in seven communities in the Pakro sub-district of Ghana participated in this study. A register was developed for each community following a census. MTTT engaged trained community-based health volunteers who conducted house-to-house testing using RDTs every 4 months and treated positive cases with Artemisinin–based Combination Therapy. Between interventions, community-based management of malaria was implemented for symptomatic cases. Results MTTT Coverage was 98.8% in July 2017 and 79.3% in July 2018. Of those tested, asymptomatic infection with malaria parasites reduced from 36.3% (1795/4941) in July 2017 to 32.9% (1303/3966) in July 2018 (p = 0.001). Prevalence of asymptomatic parasitaemia among children under 15 years declined from 52.6% (1043/1984) in July 2017 to 47.5% (820/1728) in July 2018 (p = 0.002). Implementing MTTT significantly reduced asymptomatic parasitaemia by 24% from July 2017 to July 2018 after adjusting for age, ITN use and axillary temperature (OR = 0.76, CI = 0.67, 0.85 p ≤ 0.001). Conclusion This study has demonstrated that implementing MTTT is feasible and could reduce the prevalence of asymptomatic malaria parasitaemia in children under 15 years of age. Furthermore, the use of community-based health volunteers could ensure high coverage at lower cost of implementation. Trial registration NCT04167566, Date 14/11/2019. Retrospective registration.

Prevalence of asymptomatic malaria parasitaemia following mass testing and treatment in Pakro sub-district of Ghana

Background: Global efforts to scale-up malaria control interventions are gaining steam. These include the use of Long-Lasting Insecticide Nets, Indoor Residual Spraying, Intermittent Preventive Treatment and Test, Treat and Track. Despite these, the drive for malaria elimination is far from being realistic in endemic communities in Africa. This is partly due to the fact that asymptomatic parasite carriage, not specifically targeted by most interventions, remains the bedrock that fuels transmission. This has led to mass testing, treatment and tracking (MTTT) as an alternative strategy to target asymptomatic individuals. We report the impact of MTTT on the prevalence of asymptomatic malaria parasitaemia over a one-year period in Ghana, hypothesizing that implementing MTTT could reduce the rate of asymptomatic parasitaemia. Methods: A population of about 5,000 individuals in seven communities in the Pakro sub-district of Ghana participated in this study. A register was developed for each community following a census. MTTT engaged trained community-based health volunteers who conducted house-to-house testing using RDTs every four months and treated positive cases with Artemisinin–based Combination Therapy. Between interventions, community-based management of malaria was implemented for symptomatic cases. Results: MTTT Coverage was 98.8% in July 2017 and 79.3% in July 2018. Of those tested, asymptomatic infection with malaria parasites reduced from 36.3% (1,795/4941) in July 2017 to 32.9% (1,303/3966) in July 2018 (p=0.001). Prevalence of asymptomatic parasitaemia among children under 15 years declined from 52.6% (1,043/1984) in July 2017 to 47.5% (820/1,728) in July 2018 (p=0.002). Implementing MTTT significantly reduced asymptomatic parasitaemia by 24% from July 2017 to July 2018 after adjusting for age, ITN use and axillary temperature (OR=0.76, CI=0.67, 0.85 p≤0.001). Conclusion: This study has demonstrated that implementing MTTT is feasible and could reduce the prevalence of asymptomatic malaria parasitaemia in children under 15 years of age. Furthermore, the use of community-based health volunteers could ensure high coverage at lower cost of implementation. Trial registration: NCT04167566, Date 14/11/2019 Retrospective registration.

Prevalence of asymptomatic malaria parasitaemia following mass testing and treatment in Pakro sub-district of Ghana

Background: Global efforts to scale-up malaria control interventions are gaining steam. These include the use of Long-Lasting Insecticide Nets, Indoor Residual Spraying, Intermittent Preventive Treatment and Test, Treat and Track. Despite these, the drive for malaria elimination is far from being realistic in endemic communities in Africa. This is partly due to the fact that asymptomatic parasite carriage, not specifically targeted by most interventions, remains the bedrock that fuels transmission. This has led to mass testing, treatment and tracking (MTTT) as an alternative strategy to target asymptomatic individuals. We report the impact of MTTT on the prevalence of asymptomatic malaria parasitaemia over a one-year period in Ghana, hypothesizing that implementing MTTT could reduce the rate of asymptomatic parasitaemia. Methods: A population of about 5,000 individuals in seven communities in the Pakro sub-district of Ghana participated in this study. A register was developed for each community following a census. MTTT engaged trained community-based health volunteers who conducted house-to-house testing using RDTs every four months and treated positive cases with Artemisinin–based Combination Therapy. Between interventions, community-based management of malaria was implemented for symptomatic cases. Results: MTTT Coverage was 98.8% in July 2017 and 79.3% in July 2018. Of those tested, asymptomatic infection with malaria parasites reduced from 36.3% (1,795/4941) in July 2017 to 32.9% (1,303/3966) in July 2018 (p=0.001). Prevalence of asymptomatic parasitaemia among children under 15 years declined from 52.6% (1,043/1984) in July 2017 to 47.5% (820/1,728) in July 2018 (p=0.002). Implementing MTTT significantly reduced asymptomatic parasitaemia by 24% from July 2017 to July 2018 after adjusting for age, ITN use and axillary temperature (OR=0.76, CI=0.67, 0.85 p≤0.001). Conclusion: This study has demonstrated that implementing MTTT is feasible and could reduce the prevalence of asymptomatic malaria parasitaemia in children under 15 years of age. Furthermore, the use of community-based health volunteers could ensure high coverage at lower cost of implementation.

Prevalence of asymptomatic malaria parasitaemia following mass testing and treatment in Pakro sub-district of Ghana

Background: Global efforts to scale-up malaria control interventions are gaining steam. These include the use of Long-Lasting Insecticide Nets, Intermittent Preventive Treatment and Test, Treat and Track (T3) using ACTs. Intermittent preventive treatment of children (IPTc) in Ghana has demonstrated a parasite load reduction of 90%. However, unanswered questions include – whether mass treatment of population sub-groups such as IPTc could be scaled-up to whole populations as in mass testing, treatment and tracking (MTTT)? What is needed to implement MTTT at scale? Can MTTT reduce asymptomatic parasitaemia levels in children under 15? And whether MTTT of populations complemented by community-based management of malaria (CBMm) using volunteers could be an effective strategy for malaria control at a lower cost. Methods: A population of 5,000 asymptomatic individuals in seven communities in the Pakro sub-district of Ghana participated in this study. A register was developed for each community following a census. MTTT engaged trained community-based health volunteers (CBHVs) who conducted house-to-house testing using RDTs every four months and treated positive cases with ACTs. Between interventions, CBMm was done on symptomatic cases. Results: MTTT Coverage was 98.8% in July 2017 and 79.3% in July 2018. Of those tested, asymptomatic infection with malaria parasites reduced from 1,795 (36.3%) in July 2017 to 1,303 (32.9%) in July 2018. Implementing MTTT significantly averted asymptomatic parasitaemia by 24% from July 2017 to July 2018 after adjusting for age, ITN use and temperature (OR=0.76, CI=0.67, 0.85 p ≤ 0.001). In comparison, treatment of symptomatic patients at the Health Centre reduced parasitaemia by 9% over the same period which was however, not statistically significant (OR=0.91, CI=0.67, 1.38 p = 0.672). A total of 223 (5.1%) cases were averted in children under 15 years (X² = 9.7, p < 0.002). An important observation was a decrease in hospital attendance, which negatively affected the internally generated funds (IGF) scheme of the participating health facilities. Conclusion: This study has demonstrated that implementing MTTT was feasible and could reduce prevalence of malaria asymptomatic parasitaemia in children under 15 years of age. Furthermore, the use of CBHVs could ensure high coverage at lower cost.

Prevalence of asymptomatic malaria parasitaemia following mass testing and treatment in Pakro sub-district of Ghana

Background: Global efforts to scale-up malaria control interventions are gaining steam. These include the use of Long-Lasting Insecticide Nets, Intermittent Preventive Treatment and Test, Treat and Track (T3) using ACTs. Intermittent preventive treatment of children (IPTc) in Ghana has demonstrated a parasite load reduction of 90%. However, unanswered questions include – whether mass treatment of population sub-groups such as IPTc could be scaled-up to whole populations as in mass testing, treatment and tracking (MTTT)? What is needed to implement MTTT at scale? Can MTTT reduce asymptomatic parasitaemia levels in children under 15? And whether MTTT of populations complemented by community-based management of malaria (CBMm) using volunteers could be an effective strategy for malaria control at a lower cost. Methods: A population of 5,000 asymptomatic individuals in seven communities in the Pakro sub-district of Ghana participated in this study. A register was developed for each community following a census. MTTT engaged trained community-based health volunteers (CBHVs) who conducted house-to-house testing using RDTs every four months and treated positive cases with ACTs. Between interventions, CBMm was done on symptomatic cases. Results: MTTT Coverage was 98.8% in July 2017 and 79.3% in July 2018. Of those tested, asymptomatic infection with malaria parasites reduced from 1,795 (36.3%) in July 2017 to 1,303 (32.9%) in July 2018. Implementing MTTT significantly averted asymptomatic parasitaemia by 24% from July 2017 to July 2018 after adjusting for age, ITN use and temperature (OR=0.76, CI=0.67, 0.85 p ≤ 0.001). In comparison, treatment of symptomatic patients at the Health Centre reduced parasitaemia by 9% over the same period which was however, not statistically significant (OR=0.91, CI=0.67, 1.38 p = 0.672). A total of 223 (5.1%) cases were averted in children under 15 years (X² = 9.7, p < 0.002). An important observation was a decrease in hospital attendance, which negatively affected the internally generated funds (IGF) scheme of the participating health facilities. Conclusion: This study has demonstrated that implementing MTTT was feasible and could reduce prevalence of malaria asymptomatic parasitaemia in children under 15 years of age. Furthermore, the use of CBHVs could ensure high coverage at lower cost.

OC 8453 SCALING-UP MASS TESTING AND TREATMENT EFFECTIVELY REDUCED MALARIA ASYMPTOMATIC PARASITAEMIA IN CHILDREN UNDER 15 YEARS OF AGE IN GHANA

BackgroundGlobal efforts to scale up malaria control interventions that work, are gaining momentum. These include the use of long-lasting insecticide nets, intermittent preventive treatment and test, treat and track using artemisinin-based combination therapies. Mass testing, treatment and tracking (MTTT) of the entire populations complemented by home-based management (HBM) using volunteers could be an effective approach at lower cost. MTTT of children in Ghana has demonstrated a parasite load reduction of 90%. However, unanswered questions include – Could this be scaled-up? What proportion of the community could be covered? What do we need? Can MTTT reduce asymptomatic parasitaemia levels in under-15 children?MethodsThe target population for this study was 5000 asymptomatic individuals in seven communities in the Pakro subdistrict in Ghana. A community register was developed following a census. Community volunteers conducted quarterly house-to-house testing (using RDTs) and treating positive cases with ACTs. Between interventions HBM was conducted.ResultsIn those tested, asymptomatic malaria parasitaemia reduced from 1795 (36.3%) in July 2017 to 942 (23.1%) in March 2018. In eight months, parasitaemia declined by 43.5% and 37.3% in children under 15 and under 5, respectively. Coverage was 98.8% in July 2017 and 81.4% in March 2018. One of the challenges that surfaced was the fact that decrease in hospital attendance had a negative effect on money generated by the health facility. The district and subdistrict services, though appreciating the work, indicated that the negative effect on the health system may be serious and that measures need to be taken to address alternative financing for the health system.ConclusionThis study has demonstrated that combining MTTT and home-based management of malaria could reduce prevalence in under-15 children and that using community volunteers could ensure effective coverage at lower cost. There is need to start looking at financing of the health system without malaria.