Background We assessed the impact of exposure to Plasmodium falciparum on parasite kinetics, clinical symptoms, and functional immunity after controlled human malaria infection (CHMI) in 2 cohorts with different levels of previous malarial exposure. Methods Nine adult males with high (sero-high) and 10 with low (sero-low) previous exposure received 3200 P. falciparum sporozoites (PfSPZ) of PfSPZ Challenge by direct venous inoculation and were followed for 35 days for parasitemia by thick blood smear (TBS) and quantitative polymerase chain reaction. Endpoints were time to parasitemia, adverse events, and immune responses. Results Ten of 10 (100%) volunteers in the sero-low and 7 of 9 (77.8%) in the sero-high group developed parasitemia detected by TBS in the first 28 days (P = .125). The median time to parasitemia was significantly shorter in the sero-low group than the sero-high group (9 days [interquartile range {IQR} 7.5–11.0] vs 11.0 days [IQR 7.5–18.0], respectively; log-rank test, P = .005). Antibody recognition of sporozoites was significantly higher in the sero-high (median, 17.93 [IQR 12.95–24] arbitrary units [AU]) than the sero-low volunteers (median, 10.54 [IQR, 8.36–12.12] AU) (P = .006). Growth inhibitory activity was significantly higher in the sero-high (median, 21.8% [IQR, 8.15%–29.65%]) than in the sero-low group (median, 8.3% [IQR, 5.6%–10.23%]) (P = .025). Conclusions CHMI was safe and well tolerated in this population. Individuals with serological evidence of higher malaria exposure were able to better control infection and had higher parasite growth inhibitory activity. Clinical Trials Registration NCT03496454.

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BackgroundClinical trials require high levels of participation and low drop-out rates to be successful. However, collecting blood samples from individuals recruited into clinical trials can be challenging when there is reticence about blood-taking. In addition to concerns regarding the feasibility of medical research, fears of ‘blood-stealing’ and ‘blood-selling’ have ethical implications related to cultural sensitivity and informed consent. This study explores anxieties around blood-taking during a malaria treatment trial in the Gambia.MethodsThis case study is based on ethnographic research in one theoretically selected village due to the high reticence to screening for the clinical trial ‘Primaquine's gametocytocidal efficacy in malaria asymptomatic carriers treated with dihydroartemisinin-piperaquine’ carried out in the Gambia between 2013 and 2014. Data collection tools included in-depth interviews, participant observation, informal conversations and group discussions.ResultsIn total only 176 of 411 habitants (42%) in the village accepted having a bloodspot taken to screen for malaria. Although trial recruitment was initially high in the village, some families refused screening when rumours started spreading that the trial team was taking too much blood. Concerns about ‘loss of blood’ were equated to loss of strength and lack of good food to replenish bodily forces. Families in the study village were concerned about the weakness of their body while they had to harvest their crops at the time of recruitment for the trial.ConclusionA common recommendation to prevent and avoid rumours against public health interventions and trials is the provision of full and consistent information during the consent procedure, which is assumed to lead to more accurate knowledge of the purpose of the intervention and increased trial participation. However, even when information provision is continuous, the emergence of rumours can be related to times of uncertainty and perceptions of vulnerability, which are often a reflection of structural inequalities and diverging value orientations between communities and public health institutions.

BackgroundAsymptomatic low-density gametocyte carriers represent the majority of malaria-infected individuals. However, the impact of recommended treatment with single low dose of primaquine and an artemisinin-based combination therapy to reduce transmission in this group is unknown.MethodsThis was a four-arm, open label, randomized controlled trial comparing the effect of dihydroartemisinin-piperaquine (DHAP) alone or combined with single dose of primaquine (PQ) at 0.20 mg/kg, 0.40 mg/kg, or 0.75 mg/kg on Plasmodium falciparum gametocytaemia, infectiousness to mosquitoes and hemoglobin change in asymptomatic, malaria-infected, glucose-6-phosphate dehydrogenase (G6PD) normal individuals. Randomization was done using a computer-generated sequence of uneven block sizes with codes concealed in sequentially numbered opaque envelopes. The primary endpoint was the prevalence of P. falciparum gametocytemia at day 7 of follow-up determined by quantitative nucleic acid sequence based assay and analysis was by intention to treat. The trial has been concluded (registration number: NCT01838902; https://clinicaltrials.gov/ct2/show/NCT01838902).ResultsA total of 694 asymptomatic, malaria-infected individuals were enrolled. Gametocyte prevalence at day 7 was 37.0% (54/146; 95% CI 29.2–45.4), 19.0% (27/142; 95% CI 12.9–26.4), 17.2% (25/145; 95% CI 11.0–23.5) and 10.6% (15/141; 95% CI 6.1–16.9) in the DHAP alone, 0.20 mg/kg, 0.40 mg/kg, and 0.75 mg/kg PQ arms, respectively. The main adverse events reported include headache (130/471, 27.6%), cough (73/471, 15.5%), history of fever (61/471, 13.0%) and abdominal pain (57/471, 12.1%). There were five serious adverse events however, none was related to the interventions.InterpretationA single course of PQ significantly reduces gametocyte carriage in malaria-infected asymptomatic, G6PD-normal individuals without increasing the risk of clinical anemia. The limited number of successful mosquito infections suggests that post-treatment transmission potential in this asymptomatic population is low.

Background Current knowledge on the burden of, and interactions between malaria and helminth co-infections, as well as the impact of the dual infections on anaemia, remains inconclusive. We have conducted a systematic review with meta-analysis to update current knowledge as a first step towards developing and deploying coordinated approaches to the control and, ultimately, elimination of malaria-helminth co-infections among children living in endemic countries. Methodology/Principal findings We searched Medline, Embase, Global Health and Web of Science from each database inception until 16 March 2020, for peer-reviewed articles reporting malaria-helminth co-infections in children living in a LMIC. No language restriction was applied. Following removal of duplicates, two reviewers independently screened the studies for eligibility. We used the summary odds ratio (OR) and 95% confidence intervals (CI) as a measure of association (random-effects model). We also performed Chi-square heterogeneity test based on Cochrane’s Q and evaluated the severity of heterogeneity using I2 statistics. The included studies were examined for publication bias using a funnel plot and statistical significance was assessed using Egger’s test (bias if p<0.1). Fifty-five of the 3,507 citations screened were eligible, 28 of which had sufficient data for meta-analysis. The 28 studies enrolled 22, 114 children in 13 countries across sub-Saharan Africa, Southeast Asia and South America. Overall, the pooled estimates showed a prevalence of Plasmodium-helminth co-infections of 17.7% (95% CI 12.7–23.2%). Summary estimates from 14 studies showed a lower odds of P. falciparum infection in children co-infected with Schistosoma spp (OR: 0.65; 95%CI: 0.37–1.16). Similar lower odds of P. falciparum infection were observed from the summary estimates of 24 studies in children co-infected with soil transmitted helminths (STH) (OR: 0.42; 95%CI: 0.28–0.64). When adjusted for age, gender, socio-economic status, nutritional status and geographic location of the children, the risk of P. falciparum infection in children co-infected with STH was higher compared with children who did not have STH infection (OR = 1.3; 95% CI 1.03–1.65). A subset of 16 studies showed that the odds of anaemia were higher in children co-infected with Plasmodium and STH than in children with Plasmodium infection alone (OR = 1.20; 95% CI: 0.59–2.45), and were almost equal in children co-infected with Plasmodium-Schistosoma spp or Plasmodium infection alone (OR = 0.97, 95% CI: 0.30–3.14). Conclusions/Significance The current review suggests that prevalence of malaria-helminth co-infection is high in children living in endemic countries. The nature of the interactions between malaria and helminth infection and the impact of the co-infection on anaemia remain inconclusive and may be modulated by the immune responses of the affected children.