#Analysis of #Diagnostic #Findings From the European Mobile #Laboratory in Guéckédou, #Guinea, March 2014 Through March 2015 (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Analysis of Diagnostic Findings From the European Mobile Laboratory in Guéckédou, Guinea, March 2014 Through March 2015

Romy Kerber1,2,4,a, Ralf Krumkamp1,4,a, Boubacar Diallo9, Anna Jaeger1,4, Martin Rudolf1,2,4, Simone Lanini2,13, Joseph Akoi Bore2,10, Fara Raymond Koundouno2,10, Beate Becker-Ziaja1,2,4, Erna Fleischmann2,4,5, Kilian Stoecker2,4,5, Silvia Meschi2,13, Stéphane Mély2,14,15, Edmund N. C. Newman2,17, Fabrizio Carletti2,13, Jasmine Portmann2,19, Misa Korva2,22, Svenja Wolff2,4,6, Peter Molkenthin2,4,5, Zoltan Kis2,23, Anne Kelterbaum2,4,6, Anne Bocquin2,14,15, Thomas Strecker2,4,6, Alexandra Fizet2,14,16, Concetta Castilletti2,13, Gordian Schudt2,4,6, Lisa Ottowell2,17, Andreas Kurth2,7, Barry Atkinson2,17, Marlis Badusche1,2,4, Angela Cannas2,13, Elisa Pallasch1,2,4, Andrew Bosworth2,17, Constanze Yue2,7, Bernadett Pályi2,23, Heinz Ellerbrok2,7, Claudia Kohl2,7, Lisa Oestereich1,2,4, Christopher H. Logue2,17, Anja Lüdtke2,3,4, Martin Richter2,7, Didier Ngabo2,17, Benny Borremans2,24, Dirk Becker2,4,6, Sophie Gryseels2,24, Saïd Abdellati2,25, Tine Vermoesen2,25, Eeva Kuisma2,17, Annette Kraus2,28, Britta Liedigk1,2,4, Piet Maes2,26, Ruth Thom2,17, Sophie Duraffour2,26, Sandra Diederich2,4,8, Julia Hinzmann2,7, Babak Afrough2,17, Johanna Repits2,29, Marc Mertens2,4,8, Inês Vitoriano2,17, Amadou Bah2,20, Andreas Sachse2,7, Jan Peter Boettcher2,7, Stephanie Wurr1,2,4, Sabrina Bockholt1,2,4, Andreas Nitsche2,7, Tatjana Avšič Županc2,22, Marc Strasser2,19, Giuseppe Ippolito2,13, Stephan Becker2,4,6, Herve Raoul2,15, Miles W. Carroll2,17,18, Hilde De Clerck27, Michel Van Herp27, Armand Sprecher27, Lamine Koivogui11, N’Faly Magassouba12, Sakoba Keïta10, Patrick Drury21, Cèline Gurry21, Pierre Formenty21, Jürgen May1,4, Martin Gabriel1,2,4,b, Roman Wölfel2,4,5,b, Stephan Günther1,2,4,b and Antonino Di Caro2,13,b

Author Affiliations: 1Bernhard Nocht Institute for Tropical Medicine; 2European Mobile Laboratory Consortium; 3Heinrich Pette Institute–Leibniz Institute for Experimental Virology, Hamburg; 4German Center for Infection Research, Hamburg–Munich–Marburg–Riems; 5Bundeswehr Institute of Microbiology, Munich; 6Institute of Virology, Philipps University Marburg; 7Robert Koch Institute, Berlin; 8Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald, Insel Riems, Germany; 9World Health Organization; 10Ministry of Health Guinea; 11Institut National de Santé Publique; 12Université Gamal Abdel Nasser de Conakry, Laboratoire des Fièvres Hémorragiques en Guinée, Guinea; 13National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, Italy; 14National Reference Center for Viral Hemorrhagic Fevers; 15Laboratoire P4 Inserm-Jean Mérieux; 16Unité de Biologie des Infections Virales Emergentes, Institut Pasteur, Lyon, France; 17Public Health England, Porton Down; 18South General Hospital, University of Southampton, United Kingdom; 19Spiez Laboratory, Federal Office for Civil Protection; 20Swiss Tropical and Public Health Institute, Basel; 21World Health Organization, Geneva, Switzerland; 22Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Slovenia; 23National Biosafety Laboratory, National Center for Epidemiology, Budapest, Hungary; 24Evolutionary Ecology Group, Department of Biology, University of Antwerp; 25Institute of Tropical Medicine, Antwerp; 26Department of Microbiology and Immunology, Rega Institute, KU Leuven; 27Médecins Sans Frontières, Brussels, Belgium; 28Public Health Agency of Sweden, Solna; 29Janssen-Cilag, Stockholm, Sweden

Correspondence: S. Günther, Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Strasse 74, 20359 Hamburg, Germany (guenther@bni.uni-hamburg.de).

a R. K. and R. K. contributed equally to this work.

b M. G., R. W., S. G., and A. D. C. are co–senior authors and contributed equally to this work.

 

Abstract

Background. 

A unit of the European Mobile Laboratory (EMLab) consortium was deployed to the Ebola virus disease (EVD) treatment unit in Guéckédou, Guinea, from March 2014 through March 2015.

Methods. 

The unit diagnosed EVD and malaria, using the RealStar Filovirus Screen reverse transcription-polymerase chain reaction (RT-PCR) kit and a malaria rapid diagnostic test, respectively.

Results. 

The cleaned EMLab database comprised 4719 samples from 2741 cases of suspected EVD from Guinea. EVD was diagnosed in 1231 of 2178 hospitalized patients (57%) and in 281 of 563 who died in the community (50%). Children aged <15 years had the highest proportion of Ebola virus–malaria parasite coinfections. The case-fatality ratio was high in patients aged <5 years (80%) and those aged >74 years (90%) and low in patients aged 10–19 years (40%). On admission, RT-PCR analysis of blood specimens from patients who died in the hospital yielded a lower median cycle threshold (Ct) than analysis of blood specimens from survivors (18.1 vs 23.2). Individuals who died in the community had a median Ct of 21.5 for throat swabs. Multivariate logistic regression on 1047 data sets revealed that low Ct values, ages of <5 and ≥45 years, and, among children aged 5–14 years, malaria parasite coinfection were independent determinants of a poor EVD outcome.

Conclusions. 

Virus load, age, and malaria parasite coinfection play a role in the outcome of EVD.

Key words: Filovirus – Ebola virus disease – malaria – Guinea – epidemic – mobile laboratory

© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, contact journals.permissions@oup.com.

Keywords: Research; Abstracts; Ebola; Malaria; Guinea.

——

#Skin #scarification with #Plasmodium falciparum peptide #vaccine using synthetic TLR agonists as adjuvants elicits malaria sporozoite neutralizing immunity (Sci Rep., abstract)

[Source: Scientific Reports, full page: (LINK). Abstract, edited.]

Article | OPEN

Skin scarification with Plasmodium falciparum peptide vaccine using synthetic TLR agonists as adjuvants elicits malaria sporozoite neutralizing immunity

Robert A. Mitchell, Rita Altszuler, Ute Frevert & Elizabeth H. Nardin

Scientific Reports 6, Article number: 32575 (2016) / doi:10.1038/srep32575

Received: 16 February 2016 – Accepted: 10 August 2016 –  Published online: 14 September 2016

 

Abstract

Malaria eradication will require a combination of vector control, chemotherapy and an easily administered vaccine. Sterile immunity can be elicited in humans by immunization with sporozoites, the infective stage injected by bite of the mosquito vector, however, whole parasite vaccines present formidable logistical challenges for production, storage and administration. The “gold standard” for infectious disease eradiation, the Smallpox Eradication Programme, utilized mass immunization using the skin scarification (SS) route. SS may more closely mimic the natural route of malaria infection initiated by sporozoites injected by mosquito bite which elicits both neutralizing antibodies and protective cell mediated immunity. We investigated the potential of SS immunization using a malaria repeat peptide containing a protective B cell epitope of Plasmodium falciparum, the most lethal human species, and delivery vehicles containing TLR agonists as adjuvants. In a murine model, SS immunization with peptide in combination with TLR-7/8 and -9 agonists elicited high levels of systemic sporozoite neutralizing antibody, Th1- type CD4+ T cells and resistance to challenge by bites of infected mosquitoes. SS provides the potential to elicit humoral immunity to target Plasmodium at multiple stages of its complex life cycle.

Keywords: Research; Abstracts; Plasmodium Falciparum; Malaria; Vaccines.

——

Severe #flooding and #malaria #transmission in the Western #Ugandan highlands: Implications for disease control in an era of global #climatechange (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Severe flooding and malaria transmission in the Western Ugandan highlands: Implications for disease control in an era of global climate change

Ross Boyce1,*, Raquel Reyes2, Michael Matte3, Moses Ntaro3, Edgar Mulogo3, Joshua P. Metlay4, Lawrence Band5 and Mark J. Siedner6

Author Affiliations: 1Division of Infectious Diseases, University of North Carolina at Chapel Hill, 130 Mason Farm Road, Chapel Hill, 27599, USA; 2Division of General Medicine & Clinical Epidemiology, University of North Carolina at Chapel Hill, 5039 Old Clinic Building, CB 7110, Chapel Hill, 27599, USA; 3Department of Community Health, Mbarara University of Science & Technology, P.O. Box 1410, Mbarara, Uganda; 4Division of General Internal Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston 02114, USA; 5Department of Geography, University of North Carolina at Chapel Hill, Carolina Hall CB 3220, Chapel Hill, 27599, USA; 6Department of Medicine, Harvard Medical School and, Massachusetts General Hospital, 125 Nashua Street, Suite 722, Boston 02114, USA

*Corresponding author: Ross M. Boyce MD, MSc, Division of Infectious Diseases, University of North Carolina at Chapel Hill, 130 Mason Farm Road, Chapel Hill, NC USA 27599, Phone: 919.966.2537, Fax: 919.966.6714, ross.boyce@unchealth.unc.edu

 

Abstract

Background. 

There are several mechanisms by which global climate change may impact malaria transmission. We sought to assess how the increased frequency of extreme precipitation events associated with global climate change will impact malaria transmission in highland areas of East Africa

Methods. 

We used a differences-in-differences, quasi-experimental design to examine spatial variability in the incidence rate of laboratory-confirmed malaria cases and malaria-related hospitalizations comparing villages at (1) high vs. low elevations, (2) with and without rivers, and (3) upstream vs. downstream before and after severe flooding that occurred in the Kasese District of Western Uganda in May 2013.

Results. 

During the study period 7,596 diagnostic test were performed and 1,285 patients were admitted with a diagnosis of malaria. We observed that extreme flooding resulted in an increase of approximately 30% in the risk of an individual having a positive malaria diagnostic test in the post-flood period in villages bordering a flood-affected river compared with villages farther from a river with a larger relative impact on upstream vs. downstream villages (adjusted rate ratio 1.91 vs. 1.33).

Conclusions. 

Extreme precipitation such as the flooding described here may pose significant challenges to malaria control programs, and will demand timely responses to mitigate deleterious impacts on human health.

10.1093/infdis/jiw368

© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Keywords: Research; Abstracts; Malaria; Extreme Weather; Floods; Climate Change; Uganda.

——

#Plasmodium #Parasitemia Associated With Increased #Survival in #Ebola Virus–Infected #Patients (Clin Infect Dis., abstract)

[Source: Clinical Infectious Diseases, full page: (LINK). Abstract, edited.]

Plasmodium Parasitemia Associated With Increased Survival in Ebola Virus–Infected Patients

Kyle Rosenke1,a, Jennifer Adjemian2,3,a, Vincent J. Munster1,a, Andrea Marzi1, Darryl Falzarano1,b, Clayton O. Onyango4, Melvin Ochieng5, Bonventure Juma4, Robert J. Fischer1, Joseph B. Prescott1, David Safronetz1,c, Victor Omballa5, Collins Owuor5, Thomas Hoenen1,d, Allison Groseth1,d, Cynthia Martellaro1, Neeltje van Doremalen1, Galina Zemtsova6, Joshua Self6, Trenton Bushmaker1, Kristin McNally1, Thomas Rowe6, Shannon L. Emery6, Friederike Feldmann7, Brandi N. Williamson1, Sonja M. Best1, Tolbert G. Nyenswah8, Allen Grolla9, James E. Strong9, Gary Kobinger9, Fatorma K. Bolay10, Kathryn C. Zoon11, Jorgen Stassijns12, Ruggero Giuliani12, Martin de Smet12, Stuart T. Nichol6, Barry Fields4, Armand Sprecher12, Moses Massaquoi8, Heinz Feldmann1, and Emmie de Wit1

Author Affiliations: 1Laboratory of Virology, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana; 2Epidemiology Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda; 3Commissioned Corps, US Public Health Service, Rockville, Maryland; 4Center for Global Health, Division of Global Health Protection, Centers for Disease Control and Prevention; 5Kenya Medical Research Institute, Center for Global Health Research, Nairobi; 6Centers for Disease Control and Prevention, Atlanta, Georgia; 7Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratories, National Institutes of Health, Hamilton, Montana; 8Ministry of Health and Social Welfare/Incident Management System, Monrovia, Liberia; 9Special Pathogens Program, Public Health Agency of Canada, Winnipeg, Manitoba; 10Liberian Institute for Biomedical Research, Charlesville; 11Cytokine Biology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; 12Médecins Sans Frontières, Operational Center, Brussels, Belgium

Correspondence: E. de Wit, Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, 903 S 4th St, Hamilton, MT 59840 (emmie.dewit@nih.gov).

a K. R., J. A., and V. J. M. contributed equally to this work.

b Present affiliations: Vaccine and Infectious Disease Organization–International Vaccine Center, University of Saskatchewan, Saskatoon, Canada.

c Public Health Agency of Canada, Winnipeg, Manitoba.

d Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.

 

Abstract

Background. 

The ongoing Ebola outbreak in West Africa has resulted in 28 646 suspected, probable, and confirmed Ebola virus infections. Nevertheless, malaria remains a large public health burden in the region affected by the outbreak. A joint Centers for Disease Control and Prevention/National Institutes of Health diagnostic laboratory was established in Monrovia, Liberia, in August 2014, to provide laboratory diagnostics for Ebola virus.

Methods. 

All blood samples from suspected Ebola virus–infected patients admitted to the Médecins Sans Frontières ELWA3 Ebola treatment unit in Monrovia were tested by quantitative real-time polymerase chain reaction for the presence of Ebola virus and Plasmodium species RNA. Clinical outcome in laboratory-confirmed Ebola virus–infected patients was analyzed as a function of age, sex, Ebola viremia, and Plasmodium species parasitemia.

Results. 

The case fatality rate of 1182 patients with laboratory-confirmed Ebola virus infections was 52%. The probability of surviving decreased with increasing age and decreased with increasing Ebola viral load. Ebola virus–infected patients were 20% more likely to survive when Plasmodium species parasitemia was detected, even after controlling for Ebola viral load and age; those with the highest levels of parasitemia had a survival rate of 83%. This effect was independent of treatment with antimalarials, as this was provided to all patients. Moreover, treatment with antimalarials did not affect survival in the Ebola virus mouse model.

Conclusions. 

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.

Key words: coinfection – ebolavirus – plasmodium – survival

Received April 5, 2016. Accepted June 28, 2016.

Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Keywords: Research; Abstracts; Ebola; Malaria.

—–

Comparison of #artesunate–mefloquine and #artemether–lumefantrine fixed-dose combinations for #treatment of uncomplicated P. falciparum #malaria in #children younger than 5 yrs in sub-Saharan #Africa: … (Lancet ID., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Articles

Comparison of artesunate–mefloquine and artemether–lumefantrine fixed-dose combinations for treatment of uncomplicated Plasmodium falciparum malaria in children younger than 5 years in sub-Saharan Africa: a randomised, multicentre, phase 4 trial

Sodiomon B Sirima, MD, Bernhards Ogutu, MD, John P A Lusingu, MD, Ali Mtoro, MD, Zakayo Mrango, MD, Alphonse Ouedraogo, MD, Jean Baptiste Yaro, MD, Kevin Omondi Onyango, MBChB, Samwel Gesase, MD, Ernest Mnkande, MD, James Samwel Ngocho, MD, Isabelle Ackermann, MSc, François Aubin, MD, Joelle Vanraes, PharmD, Nathalie Strub, MD, Gwenaelle Carn, MS

Published Online: 15 July 2016 / Open Access / DOI: http://dx.doi.org/10.1016/S1473-3099(16)30020-2 / Open access funded by Department of Health UK

User License:  Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0)

© 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND license. Published by Elsevier Ltd.

 

Summary

Background

WHO recommends combinations of an artemisinin derivative plus an antimalarial drug of longer half-life as treatment options for uncomplicated Plasmodium falciparum infection. In Africa, artemether–lumefantrine is the most widely used artemisinin-based combination therapy, whereas artesunate–mefloquine is used infrequently because of a perceived poor tolerance to mefloquine. WHO recommends reconsideration of the use of artesunate–mefloquine in Africa. We compared the efficacy and safety of fixed-dose artesunate–mefloquine with that of artemether–lumefantrine for treatment of children younger than 5 years with uncomplicated P falciparum malaria.

Methods

We did this multicentre, phase 4, open-label, non-inferiority trial in Burkina Faso, Kenya, and Tanzania. Children aged 6–59 months with uncomplicated malaria were randomly assigned (1:1), via a computer-generated randomisation list, to receive 3 days’ treatment with either one or two artesunate–mefloquine tablets (25 mg artesunate and 55 mg mefloquine) once a day or one or two artemether–lumefantrine tablets (20 mg artemether and 120 mg lumefantrine) twice a day. Parasitological assessments were done independently by two microscopists who were blinded to treatment allocation. The primary outcome was the PCR-corrected rate of adequate clinical and parasitological response (ACPR) at day 63 in the per-protocol population. Non-inferiority was shown if the lower limit of the 95% CI for the difference between groups was greater than −5%. Early vomiting was monitored and neuropsychiatric status assessed regularly during follow-up. This study is registered with ISRCTN, number ISRCTN17472707, and the Pan African Clinical Trials Registry, number PACTR201202000278282.

Findings

945 children were enrolled and randomised, 473 to artesunate–mefloquine and 472 to artemether–lumefantrine. The per-protocol population consisted of 407 children in each group. The PCR-corrected ACPR rate at day 63 was 90·9% (370 patients) in the artesunate–mefloquine group and 89·7% (365 patients) in the artemether–lumefantrine group (treatment difference 1·23%, 95% CI −2·84% to 5·29%). At 72 h after the start of treatment, no child had detectable parasitaemia and less than 6% had fever, with a similar number in each group (21 in the artesunate–mefloquine group vs 24 in the artemether–lumefantrine group). The safety profiles of artesunate–mefloquine and artemether–lumefantrine were similar, with low rates of early vomiting (71 [15·3%] of 463 patients in the artesunate–mefloquine group vs 79 [16·8%] of 471 patients in the artemether–lumefantrine group in any of the three dosing days), few neurological adverse events (ten [2·1%] of 468 vs five [1·1%] of 465), and no detectable psychiatric adverse events.

Interpretation

Artesunate–mefloquine is effective and safe, and an important treatment option, for children younger than 5 years with uncomplicated P falciparum malaria in Africa.

Funding

Agence Française de Développement, France; Department for International Development, UK; Dutch Ministry of Foreign Affairs, Netherlands; European and Developing Countries Clinical Trials Partnership; Fondation Arpe, Switzerland; Médecins Sans Frontières; Swiss Agency for Development and Cooperation, Switzerland.

Keywords: Research; Abstracts; Malaria; Artemisin.

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#Safety and #immunogenicity of #RTS,S/AS01 #malaria #vaccine in #infants and #children with #WHO stage 1 or 2 #HIV disease: a randomised, double-blind, controlled trial (Lancet ID., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Articles

Safety and immunogenicity of RTS,S/AS01 malaria vaccine in infants and children with WHO stage 1 or 2 HIV disease: a randomised, double-blind, controlled trial

Dr Lucas Otieno, MD, Martina Oneko, MD, Walter Otieno, PhD, Joseph Abuodha, MBChB, Emmanuel Owino, MSc, Chris Odero, PGD PH, Yolanda Guerra Mendoza, MD, Ben Andagalu, MSc, Norbert Awino, MSc, Karen Ivinson, BSc, Dirk Heerwegh, PhD, Nekoye Otsyula, MSc, Maria Oziemkowska, MPH, Effua Abigail Usuf, PhD, Allan Otieno, MD, Kephas Otieno, MPH, Didier Leboulleux, MD, Amanda Leach, MRCPCH, Janet Oyieko, MD, Laurence Slutsker, MD, Marc Lievens, MSc, Jessica Cowden, MD, Didier Lapierre, MD, Simon Kariuki, PhD, Bernhards Ogutu, PhD, Johan Vekemans, PhD, Mary J Hamel, MD

Published Online: 06 July 2016 / DOI: http://dx.doi.org/10.1016/S1473-3099(16)30161-X

© 2016 Elsevier Ltd. All rights reserved.

 

Summary

Background

Malaria remains a major global public health concern, especially in sub-Saharan Africa. The RTS,S/AS01 malaria candidate vaccine was reviewed by the European Medicines Agency and received a positive scientific opinion; WHO subsequently recommended pilot implementation in sub-Saharan African countries. Because malaria and HIV overlap geographically, HIV-infected children should be considered for RTS,S/AS01 vaccination. We therefore aimed to assess the safety of RTS,S/AS01 in HIV-infected children at two sites in western Kenya.

Methods

We did a randomised, double-blind, controlled trial at the clinical trial sites of the Kenya Medical Research Institute (KEMRI)–Walter Reed Army Institute of research in Kisumu and the KEMRI/US Centers for Disease Control and Prevention in Siaya. Eligible participants were infants and children aged from 6 weeks to 17 months with WHO stage 1 or 2 HIV disease (documented positive by DNA PCR), whether or not they were receiving antiretroviral therapy (ART). We randomly assigned participants (1:1) to receive three doses of either RTS,S/AS01 or rabies vaccine (both 0·5 mL per dose by intramuscular injection), given once per month at 0, 1, and 2 months. We did the treatment allocation using a web-based central randomisation system stratified by age (6 weeks–4 months, 5–17 months), and by baseline CD4% (<10, 10–14, 15–19, and ≥20). Data were obtained in an observer-blind manner, and the vaccine recipient, their parent or carer, the funder, and investigators responsible for the assessment of endpoints were all masked to treatment allocation (only staff responsible for the preparation and administration of the vaccines were aware of the assignment and these individuals played no other role in the study). We provided ART, even if the participants were not receiving ART before the study, and daily co-trimoxazole for prevention of opportunistic infections. The primary outcome was the occurrence of serious adverse events until 14 months after dose 1 of the vaccine, assessed in the intention-to-treat population. This trial was registered at ClinicalTrials.gov, number NCT01148459.

Findings

Between July 30, 2010, and May 24, 2013, we enrolled 200 children to our study and randomly assigned 99 to receive RTS,S/AS01 and 101 to receive rabies vaccine. 177 (89%) of the 200 children enrolled completed 14 months of follow-up. Serious adverse events were noted in 41 (41·4%, 95% CI 31·6–51·8) of 99 RTS,S/AS01 recipients and 37 (36·6%, 27·3–46·8) of 101 rabies-vaccine recipients (relative risk 1·1, 95% CI 0·8–1·6). 20 (20·2%, 95% CI 12·8–29·5) of 99 RTS,S/AS01 recipients and 12 (11·9%, 6·3–19·8) of 101 rabies-vaccine recipients had at least one serious adverse event within 30 days after vaccination, mainly pneumonia, febrile convulsions, and salmonella sepsis. Five (5·1%, 95% CI 1·7–11·4) of 99 RTS,S/AS01 recipients and four (4·0%, 1·1–9·8) of 101 rabies-vaccine recipients died, but no deaths were deemed related to vaccination. Mortality was associated with five cases of pneumonia (1% RTS,S/AS01 recipients vs 3% rabies-vaccine recipients), five cases of gastroenteritis (3% RTS,S/AS01 recipients vs 2% rabies-vaccine recipients), five cases of malnutrition (2% RTS,S/AS01 recipients vs 3% rabies-vaccine recipients), one case of sepsis (1% rabies-vaccine recipients), one case of Haemophilus influenza meningitis (1% rabies-vaccine recipients), and one case of tuberculosis (1% RTS,S/AS01 recipients).

Interpretation

RTS, S/AS01 was well tolerated when given to children with WHO clinical stage 1 or 2 HIV disease along with high antiretroviral and co-trimoxazole use. Children with HIV disease could be included in future RTS,S/AS01 vaccination programmes.

Funding

GlaxoSmithKline Biologicals SA and PATH Malaria Vaccine Initiative.

Keywords: Research; Abstracts; Malaria; Vaccines; HIV.

——

#Efficacy of #topical #mosquito #repellent (#picaridin) plus long-lasting insecticidal nets versus long-lasting insecticidal nets alone for control of #malaria: a cluster randomised controlled trial (Lancet ID, abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Articles

Efficacy of topical mosquito repellent (picaridin) plus long-lasting insecticidal nets versus long-lasting insecticidal nets alone for control of malaria: a cluster randomised controlled trial

Vincent Sluydts, PhD, Lies Durnez, PhD, Somony Heng, MD, Charlotte Gryseels, MSc, Lydie Canier, MSc, Saorin Kim, BSc, Karel Van Roey, MSc, Karen Kerkhof, MSc, Nimol Khim, PhD, Sokny Mao, MSc, Sambunny Uk, MSc, Siv Sovannaroth, MD, Prof Koen Peeters Grietens, PhD, Tho Sochantha, MD, Didier Menard, PhD, Prof Marc Coosemans, PhD

Published Online: 29 June 2016 / Open Access / Article has an altmetric score of 1 / DOI: http://dx.doi.org/10.1016/S1473-3099(16)30148-7  / Open access funded by Bill & Melinda Gates Foundation

© 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.

 

Summary

Background

Although effective topical repellents provide personal protection against malaria, whether mass use of topical repellents in addition to long-lasting insecticidal nets can contribute to a further decline of malaria is not known, particularly in areas where outdoor transmission occurs. We aimed to assess the epidemiological efficacy of a highly effective topical repellent in addition to long-lasting insecticidal nets in reducing malaria prevalence in this setting.

Methods

A cluster randomised controlled trial was done in the 117 most endemic villages in Ratanakiri province, Cambodia, to assess the efficacy of topical repellents in addition to long-lasting insecticidal nets in controlling malaria in a low-endemic setting. We did a pre-trial assessment of village accessibility and excluded four villages because of their inaccessibility during the rainy season. Another 25 villages were grouped because of their proximity to each other, resulting in 98 study clusters (comprising either a single village or multiple neighbouring villages). Clusters were randomly assigned (1:1) to either a control (long-lasting insecticidal nets) or intervention (long-lasting insecticidal nets plus topical repellent) study group after a restricted randomisation. All clusters received one long-lasting insecticidal net per individual, whereas those in the intervention group also received safe and effective topical repellents (picaridin KBR3023, SC Johnson, Racine, WI, USA), along with instruction and promotion of its daily use. Cross-sectional surveys of 65 randomly selected individuals per cluster were done at the beginning and end of the malaria transmission season in 2012 and 2013. The primary outcome was Plasmodium species-specific prevalence in participants obtained by real-time PCR, assessed in the intention-to-treat population. Complete safety analysis data will be published seperately; any ad-hoc adverse events are reported here. This trial is registered with ClinicalTrials.gov, number NCT01663831.

Findings

Of the 98 clusters that villages were split into, 49 were assigned to the control group and 49 were assigned to the intervention group. Despite having a successful distribution system, the daily use of repellents was suboptimum. No post-intervention differences in PCR plasmodium prevalence were observed between study groups in 2012 (4·91% in the control group vs 4·86% in the intervention group; adjusted odds ratio [aOR] 1·01 [95% CI 0·60–1·70]; p=0·975) or in 2013 (2·96% in the control group vs 3·85% in the intervention group; aOR 1·31 [0·81–2·11]; p=0·266). Similar results were obtained according to Plasmodium species (1·33% of participants in the intervention group vs 1·10% in the intervention group were infected with Plasmodium falciparum; aOR 0·83 [0·44–1·56]; p=0·561; and 1·85% in the control group vs 2·67% in the intervention group were infected with Plasmodium vivax; aOR 1·51 [0·88–2·57]; p=0·133). 41 adverse event notifications from nine villages were received, of which 33 were classified as adverse reactions (11 of these 33 were cases of repellent abuse through oral ingestion, either accidental or not). All participants with adverse reactions fully recovered and 17 were advised to permanently stop using the repellent.

Interpretation

Mass distribution of highly effective topical repellents in resource-sufficient conditions did not contribute to a further decline in malaria endemicity in a pre-elimination setting in the Greater Mekong subregion. Daily compliance and appropriate use of the repellents remains the main obstacle.

Funding

Bill & Melinda Gates Foundation.

Keywords: Research; Abstracts; Malaria; Insecticides.

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