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Summary: Background: Due to challenges in measuring changes in malaria at low transmission, serology is increasingly being used to complement clinical and parasitological surveillance. Longitudinal studies have shown that serological markers, such as Etramp5.Ag1, can reflect spatio-temporal differences in malaria transmission. However, these markers have yet to be used as endpoints in intervention trials. Methods: Based on data from a 2017 cluster randomised trial conducted in Zambezi Region, Namibia, evaluating the effectiveness of reactive focal mass drug administration (rfMDA) and reactive vector control (RAVC), this study conducted a secondary analysis comparing antibody responses between intervention arms as trial endpoints. Antibody responses were measured on a multiplex immunoassay, using a panel of eight serological markers of Plasmodium falciparum infection - Etramp5.Ag1, GEXP18, HSP40.Ag1, Rh2.2030, EBA175, PfMSP119, PfAMA1, and PfGLURP.R2. Findings: Reductions in sero-prevalence to antigens Etramp.Ag1, PfMSP119, Rh2.2030, and PfAMA1 were observed in study arms combining rfMDA and RAVC, but only effects for Etramp5.Ag1 were statistically significant. Etramp5.Ag1 sero-prevalence was significantly lower in all intervention arms. Compared to the reference arms, adjusted prevalence ratio (aPR) for Etramp5.Ag1 was 0.78 (95%CI 0.65 – 0.91, p = 0.0007) in the rfMDA arms and 0.79 (95%CI 0.67 – 0.92, p = 0.001) in the RAVC arms. For the combined rfMDA plus RAVC intervention, aPR was 0.59 (95%CI 0.46 – 0.76, p < 0.0001). Significant reductions were also observed based on continuous antibody responses. Sero-prevalence as an endpoint was found to achieve higher study power (99.9% power to detect a 50% reduction in prevalence) compared to quantitative polymerase chain reaction (qPCR) prevalence (72.9% power to detect a 50% reduction in prevalence). Interpretation: While the observed relative reduction in qPCR prevalence in the study was greater than serology, the use of serological endpoints to evaluate trial outcomes measured effect size with improved precision and study power. Serology has clear application in cluster randomised trials, particularly in settings where measuring clinical incidence or infection is less reliable due to seasonal fluctuations, limitations in health care seeking, or incomplete testing and reporting. Funding: This study was supported by Novartis Foundation (A122666), the Bill & Melinda Gates Foundation (OPP1160129), and the Horchow Family Fund (5,300,375,400).

Background: In low-endemic malaria settings, screening and treatment near index cases (reactive case detection, RACD) is practiced for surveillance and response; however, other approaches may be more effective. Methods: We conducted a cluster-randomised controlled two-by-two factorial design trial to evaluate the impact of reactive focal mass drug administration, rfMDA, and reactive focal vector control, RAVC, in the low-endemic setting of Zambezi, Namibia. Fifty-six clusters were randomised to: RACD or rfMDA, and RAVC or no RAVC (RACD: rapid diagnostic testing and treatment with artemether-lumefantrine (AL); rfMDA: presumptive treatment with AL; RAVC: indoor residual spraying using pirimiphos-methyl), with interventions administered within 500 meters of index cases. To evaluate the effectiveness of interventions targeting the parasite reservoir in humans (rfMDA vs RACD), in mosquitos (RAVC vs no RAVC), and in both humans and mosquitoes (rfMDA+RAVC vs RACD only), a modified intention-to-treat analysis was used to compare cumulative incidence of locally acquired malaria cases and cross-sectional prevalence of infection with parasites. Trial registration: ClinicalTrials.gov NCT02610400. Findings: From Jan-Nov 2017, 55 clusters had index cases triggering 342 interventions that covered 8 948 individuals. Incidence per 1 000 person-years for rfMDA, RAVC, and rfMDA+RAVC clusters vs control was: 30·8 vs 38·3 (adjusted incidence rate ratio (aIRR) 0·54 [95% CI 0·14-0·94, p=0·03]), 30·2 vs 38·9 (aIRR 0·51 [0·12-0·90, p=0·01]), and 25·0 vs 41·4 (aIRR 0·28 [0·10-0·84, p=0·02]), respectively. Compared to control, prevalence of infection (%) for rfMDA, RAVC, and rfMDA+RAVC vs control was 3·2 vs 3·8 (adjusted prevalence ratio (aPR) 0·58 [95% CI 0·18-0·98, p=0·04]), 2·9 vs 4·1 (aPR 0·34 [0·11-0·57, p

GTP-binding proteins (G proteins) are heteromers composed of α, β and γ subunits. The expression of some G protein subunits is altered both by affective disorders and by antidepressant treatments. Here we have studied three G protein α subunit mRNAs in the hippocampus and frontoparietal cortex of rats treated with lithium for 14 days or with repeated electroconvulsive shock (five shocks over 10 days). After electroconvulsive shock, the three mRNAs changed differentially in the hippocampus. Specifically, Gsα mRNA was decreased in CA3 and CA1, whilst Goα mRNA was increased in dentate gyrus and Gi2α mRNA was reduced in dentate gyrus and CA3. Lithium carbonate treatment produced a modest, uniform increase in the three mRNAs in dentate gyrus and CA3, and a selective elevation of Goα mRNA in CA1. Neither treatment altered the G protein mRNAs in the cortex nor cyclophilin mRNA in any region. These data extend the evidence that altered G protein expression is a part of the biochemical response to antidepressant treatments. Differences in the molecular and anatomical pattern of the alterations induced by electroconvulsive shock compared to lithium may contribute to their different therapeutic profiles.