<i>Plasmodium</i>Parasitemia Associated With Increased Survival in Ebola Virus–Infected Patients

Rosenke, Kyle; Adjemian, Jennifer; Munster, Vincent J.; Marzi, Andrea; Falzarano, Darryl; Onyango, Clayton; Ochieng, Melvin; Juma, Bonventure; Fischer, Robert J.; Prescott, Joseph; Safronetz, David; Omballa, Victor; Owuor, Collins; Hoenen, Thomas; Groseth, Allison; Martellaro, Cynthia; Doremalen, Neeltje van; Zemtsova, Galina E.; Self, Joshua S.; Bushmaker, Trenton; McNally, Kristin L.; Rowe, Thomas; Emery, Shannon; Feldmann, Friederike; Williamson, Brandi N.; Best, Sonja M.; Nyenswah, Tolbert; Grolla, Allen; Strong, James E.; Kobinger, Gary P.; Bolay, Fatorma K.; Zoon, Kathryn C.; Stassijns, Jorgen; Giuliani, Ruggero; Smet, Martin De; Nichol, Stuart T.; Fields, Barry S.; Sprecher, Armand; Massaquoi, Moses; Feldmann, Heinz; Wit, Emmie de

doi:10.1093/cid/ciw452

Cited by 46 publications

(46 citation statements)

References 23 publications

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“…A diagnosis of Plasmodium parasitemia did not impact the risk of mortality or presence of fever in a subpopulation of children who had testing performed, which differs from a recent report in which a diagnosis of malaria reduced the risk of EVD mortality [32]. …”

Section: Discussioncontrasting

confidence: 85%

Characteristics and Outcomes of Pediatric Patients With Ebola Virus Disease Admitted to Treatment Units in Liberia and Sierra Leone: A Retrospective Cohort Study

Smit

Michelow

Glavis-Bloom

et al. 2016

CLINID

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Section: Discussioncontrasting

confidence: 85%

Characteristics and Outcomes of Pediatric Patients With Ebola Virus Disease Admitted to Treatment Units in Liberia and Sierra Leone: A Retrospective Cohort Study

Smit

Michelow

Glavis-Bloom

et al. 2016

CLINID

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“…Asymptomatic malaria causes significant co-morbidity through anemia [52]; however, it remains to be established if this risk on its own is sufficiently severe to justify the administration of a full treatment course. Moreover, the recent observation that the malaria parasite burden correlates positively with survival from Ebola infection will complicate this further [53]. Median parasite burdens may be lower in asymptomatic populations [54], but their range overlaps with the range found in uncomplicated symptomatic malaria patients (Kamija Phiri et al, submitted; the median baseline was 1240 parasites/ml and the range was 80–55,400/ml in asymptomatic subjects).…”

Section: Compounds Ideally Need To Target More Than One Plasmodium LImentioning

confidence: 99%

New developments in anti-malarial target candidate and product profiles

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Duparc

Gutteridge

et al. 2017

Malar J

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A decade of discovery and development of new anti-malarial medicines has led to a renewed focus on malaria elimination and eradication. Changes in the way new anti-malarial drugs are discovered and developed have led to a dramatic increase in the number and diversity of new molecules presently in pre-clinical and early clinical development. The twin challenges faced can be summarized by multi-drug resistant malaria from the Greater Mekong Sub-region, and the need to provide simplified medicines. This review lists changes in anti-malarial target candidate and target product profiles over the last 4 years. As well as new medicines to treat disease and prevent transmission, there has been increased focus on the longer term goal of finding new medicines for chemoprotection, potentially with long-acting molecules, or parenteral formulations. Other gaps in the malaria armamentarium, such as drugs to treat severe malaria and endectocides (that kill mosquitoes which feed on people who have taken the drug), are defined here. Ultimately the elimination of malaria requires medicines that are safe and well-tolerated to be used in vulnerable populations: in pregnancy, especially the first trimester, and in those suffering from malnutrition or co-infection with other pathogens. These updates reflect the maturing of an understanding of the key challenges in producing the next generation of medicines to control, eliminate and ultimately eradicate malaria.

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“…Such heterologous or off-target effects of vaccines to enhance immunity in an antigen-nonspecific manner have been observed with some childhood vaccinations, and the presence of malaria has recently been reported to be associated with an improved outcome in patients with EVD, 10 a finding that suggests possible cross-reactive immunity. 11,12 To determine whether this finding is possibly a result of trained immunity 13 or a chance finding (as stated in the Methods section, P values of <0.05 but not <0.01 should be interpreted cautiously), future studies are needed.…”

Section: Discussionmentioning

confidence: 86%

Phase 2 Placebo-Controlled Trial of Two Vaccines to Prevent Ebola in Liberia

et al. 2017

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BACKGROUND The safety and efficacy of vaccines to prevent Ebola virus disease (EVD) were unknown when the incidence of EVD was peaking in Liberia. METHODS We initiated a randomized, placebo-controlled, phase 3 trial of the chimpanzee adenovirus 3 vaccine (ChAd3-EBO-Z) and the recombinant vesicular stomatitis virus vaccine (rVSVΔG-ZEBOV-GP) in Liberia. A phase 2 subtrial was embedded to evaluate safety and immunogenicity. Because the incidence of EVD declined in Liberia, the phase 2 component was expanded and the phase 3 component was eliminated. RESULTS A total of 1500 adults underwent randomization and were followed for 12 months. The median age of the participants was 30 years; 36.6% of the participants were women. During the week after the administration of vaccine or placebo, adverse events occurred significantly more often with the active vaccines than with placebo; these events included injection-site reactions (in 28.5% of the patients in the ChAd3-EBO-Z group and 30.9% of those in the rVSVΔG-ZEBOV-GP group, as compared with 6.8% of those in the placebo group), headache (in 25.1% and 31.9%, vs. 16.9%), muscle pain (in 22.3% and 26.9%, vs. 13.3%), feverishness (in 23.9% and 30.5%, vs. 9.0%), and fatigue (in 14.0% and 15.4%, vs. 8.8%) (P<0.001 for all comparisons); these differences were not seen at 1 month. Serious adverse events within 12 months after injection were seen in 40 participants (8.0%) in the ChAd3-EBO-Z group, in 47 (9.4%) in the rVSVΔG-ZEBOV-GP group, and in 59 (11.8%) in the placebo group. By 1 month, an antibody response developed in 70.8% of the participants in the ChAd3-EBO-Z group and in 83.7% of those in the rVSVΔG-ZEBOV-GP group, as compared with 2.8% of those in the placebo group (P<0.001 for both comparisons). At 12 months, antibody responses in participants in the ChAd3-EBO-Z group (63.5%) and in those in the rVSVΔG-ZEBOV-GP group (79.5%) remained significantly greater than in those in the placebo group (6.8%, P<0.001 for both comparisons). CONCLUSIONS A randomized, placebo-controlled phase 2 trial of two vaccines that was rapidly initiated and completed in Liberia showed the capability of conducting rigorous research during an outbreak. By 1 month after vaccination, the vaccines had elicited immune responses that were largely maintained through 12 months. (Funded by the National Institutes of Allergy and Infectious Diseases and the Liberian Ministry of Health; PREVAIL I ClinicalTrials.gov number, NCT02344407.)

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PlasmodiumParasitemia Associated With Increased Survival in Ebola Virus–Infected Patients

Abstract: Plasmodium species parasitemia is associated with an increase in the probability of surviving Ebola virus infection. More research is needed to understand the molecular mechanism underlying this remarkable phenomenon and translate it into treatment options for Ebola virus infection.

Cited by 46 publications

References 23 publications

Characteristics and Outcomes of Pediatric Patients With Ebola Virus Disease Admitted to Treatment Units in Liberia and Sierra Leone: A Retrospective Cohort Study

Characteristics and Outcomes of Pediatric Patients With Ebola Virus Disease Admitted to Treatment Units in Liberia and Sierra Leone: A Retrospective Cohort Study

New developments in anti-malarial target candidate and product profiles

Phase 2 Placebo-Controlled Trial of Two Vaccines to Prevent Ebola in Liberia

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