Estimation of Plasmodium falciparum Transmission Intensity in Lilongwe, Malawi, by Microscopy, Rapid Diagnostic Testing, and Nucleic Acid Detection

Estimates of malaria transmission intensity (MTI) typically rely upon microscopy or rapid diagnostic testing (RDT). However, these methods are less sensitive than nucleic acid amplification techniques and may underestimate parasite prevalence. We compared microscopy, RDT, and polymerase chain reaction (PCR) for the diagnosis of Plasmodium falciparum parasitemia as part of an MTI study of 800 children and adults conducted in Lilongwe, Malawi. PCR detected more cases of parasitemia than microscopy or RDT. Age less than 5 years predicted parasitemia detected by PCR alone (adjusted odds ratio = 1.61, 95% confidence interval = 1.09–2.38, Wald P = 0.02). In addition, we identified one P. falciparum parasite with a false-negative RDT result due to a suspected deletion of the histidine-rich protein 2 (hrp2) gene and used a novel, ultrasensitive PCR assay to detect low-level parasitemia missed by traditional PCR. Molecular methods should be considered for use in future transmission studies as a supplement to RDT or microscopy

Understanding the Transmission Intensity of Plasmodium Falciparum in Lilongwe, Malawi

The GlaxoSmithKline RTS,S vaccine has been undergoing Phase III trials to evaluate efficacy for protection from malaria, a disease infecting between 300-600 million people every year. As RTS,S is a transmission blocking vaccine, transmission intensity may be important in vaccine efficacy. Therefore, all trial sites conducted a concordant Malaria Transmission Intensity (MTI) study, from 2011-2013, to look at the prevalence of malaria by microscopy within the trial site. Malaria parasitemia prevalence is often used as a surrogate of transmission intensity. Unfortunately, it is known that microscopy can miss many, if not most, of malaria parasitemia in a population. Nucleic acid detection methods are more sensitive than microscopy, often detecting parasitemia counts below the detection limit of microscopy (called “submicroscopic” parasitemia). We use a real-time Polymerase Chain Reaction (RT-PCR) assay for pfldh on dried blood spots from 800 patient blood samples collected during the 2013 MTI study in Lilongwe, Malawi to determine the difference in prevalence of parasitemia between testing methods. We found that the addition of RT-PCR nearly tripled the number of participants with malaria detected (5.6% by microscopy vs. 14.3% composite microscopy or RT-PCR.). We then analyzed the malaria prevalence of submicroscopic parasitemia within specific demographic groups to identify risk factors associated with greater rates of parasitemia. This data suggests that transmission intensity within Lilongwe was greater than previously expected, which may have impacted vaccine efficacy, and that differences in transmission intensity may have differed significantly between demographics groups. Future studies should research the impact this has on vaccine effectiveness and how this can be utilized when redesigning the vaccine so that future versions can be more effective in reducing infections.Bachelor of Scienc

Partnership for Research on Ebola VACcination (PREVAC): protocol of a randomized, double-blind, placebo-controlled phase 2 clinical trial evaluating three vaccine strategies against Ebola in healthy volunteers in four West African countries

International audienceAbstract Introduction The Ebola virus disease (EVD) outbreak in 2014–2016 in West Africa was the largest on record and provided an opportunity for large clinical trials and accelerated efforts to develop an effective and safe preventative vaccine. Multiple questions regarding the safety, immunogenicity, and efficacy of EVD vaccines remain unanswered. To address these gaps in the evidence base, the Partnership for Research on Ebola Vaccines (PREVAC) trial was designed. This paper describes the design, methods, and baseline results of the PREVAC trial and discusses challenges that led to different protocol amendments. Methods This is a randomized, double-blind, placebo-controlled phase 2 clinical trial of three vaccine strategies against the Ebola virus in healthy volunteers 1 year of age and above. The three vaccine strategies being studied are the rVSVΔG-ZEBOV-GP vaccine, with and without a booster dose at 56 days, and the Ad26.ZEBOV,MVA-FN-Filo vaccine regimen with Ad26.ZEBOV given as the first dose and the MVA-FN-Filo vaccination given 56 days later. There have been 4 versions of the protocol with those enrolled in Version 4.0 comprising the primary analysis cohort. The primary endpoint is based on the antibody titer against the Ebola virus surface glycoprotein measured 12 months following the final injection. Results From April 2017 to December 2018, a total of 5002 volunteers were screened and 4789 enrolled. Participants were enrolled at 6 sites in four countries (Guinea, Liberia, Sierra Leone, and Mali). Of the 4789 participants, 2560 (53%) were adults and 2229 (47%) were children. Those < 18 years of age included 549 (12%) aged 1 to 4 years, 750 (16%) 5 to 11 years, and 930 (19%) aged 12–17 years. At baseline, the median (25th, 75th percentile) antibody titer to Ebola virus glycoprotein for 1090 participants was 72 (50, 116) EU/mL. Discussion The PREVAC trial is evaluating—placebo-controlled—two promising Ebola candidate vaccines in advanced stages of development. The results will address unanswered questions related to short- and long-term safety and immunogenicity for three vaccine strategies in adults and children. Trial registration ClinicalTrials.gov NCT02876328 . Registered on 23 August 2016

Contemporary assessment and pharmacotherapy of Tourette syndrome

To develop a guide to clinical assessment and pharmacotherapy for children and adults with Tourette syndrome (TS), we reviewed published literature over the past 25 years to identify original articles and reviews on the assessment and pharmacological treatment of Tourette syndrome, attention—deficit/hyperactivity disorder (ADHD) and obsessive—compulsive disorder (OCD). The literature search also included a survey of reviews published in book chapters. The assessment section was compiled from several reviews. Pharmacological treatments were classified into those with strong empirical support (as evidenced by two positive placebo-controlled studies for tics, OCD, or ADHD in TS samples); modest empirical support (one positive placebo-controlled study), or minimal support (open-label data only). We conclude that accurate diagnosis, including identification of comorbid conditions, is an essential step toward appropriate treatment for patients with TS. In many patients with TS, symptom management requires pharmacotherapy for tics or coexisting conditions. The evidence supporting efficacy and safety for medications used in patients with TS varies. But this evidence offers the best guide to clinical practice