PLoS Negl Trop Dis Research Articles

Stumbles on the path to dengue control

Dengue control is in trouble. Since the severe form of dengue infection was described more than 50 years ago, this disease has spread to every corner of the tropics. 1 Hammon WM Rudnick A Sather GE Rogers KD Morse LJ New hemorrhagic fevers of children in the Philippines and Thailand. Trans Assoc Am Physicians. 1960; 73: 140-155 PubMed Google Scholar , 2 Brady OJ Gething PW Bhatt S et al. Refining the global spatial limits of dengue virus transmission by evidence-based consensus. PLoS Negl Trop Dis. 2012; 6: e1760 Crossref PubMed Scopus (977) Google Scholar , 3 Bhatt S Gething PW Brady OJ et al. The global distribution and burden of dengue. Nature. 2013; 496: 504-507 Crossref PubMed Scopus (5450) Google Scholar In 2010, 4 billion people were at risk of infection with any of the four dengue viruses (DENV1–4), more than 390 million individuals were infected, and 96 million had overt disease. 3 Bhatt S Gething PW Brady OJ et al. The global distribution and burden of dengue. Nature. 2013; 496: 504-507 Crossref PubMed Scopus (5450) Google Scholar During a dengue infection, a small subset of individuals with circulating infection-enhancing dengue antibodies are at risk of an abrupt onset of acute vascular permeability accompanied by abnormalities in haemostasis, potentially leading to shock, severe bleeding, and death. 4 Halstead SB Dengue. Lancet. 2007; 370: 1644-1652 Summary Full Text Full Text PDF PubMed Scopus (1153) Google Scholar This severe outcome typically occurs at the time of defervescence after several days of the symptoms of classic dengue fever. Additionally, dengue infections can have unfavourable outcomes in elderly individuals who have pre-existing chronic disorders. These clinical courses create a cruel diagnostic dilemma for physicians and have led to many efforts to identify clinical signs and symptoms premonitory of severe dengue. 5 Leo YS Gan VC Ng EL et al. Utility of warning signs in guiding admission and predicting severe disease in adult dengue. BMC Infect Dis. 2013; 13: 498 Crossref PubMed Scopus (53) Google Scholar Meanwhile, despite the availability of many powerful insecticides, mosquito abatement efforts directed at the control or eradication of the dengue vector Aedes aegypti have conspicuously and universally failed. 6 Gubler DJ Epidemic dengue/dengue hemorrhagic fever as a public health, social and economic problem in the 21st century. Trends Microbiol. 2002; 10: 100-103 Summary Full Text Full Text PDF PubMed Scopus (1129) Google Scholar Efficacy and safety of celgosivir in patients with dengue fever (CELADEN): a phase 1b, randomised, double-blind, placebo-controlled, proof-of-concept trialAlthough generally safe and well tolerated, celgosivir does not seem to reduce viral load or fever burden in patients with dengue. Full-Text PDF

Molecular evolution of Zika virus during its emergence in the 20th century

Zika virus (ZIKV) is a mosquito-borne flavivirus first isolated in Uganda in 1947. Although entomological and virologic surveillance have reported ZIKV enzootic activity in diverse countries of Africa and Asia, few human cases were reported until 2007, when a Zika fever epidemic took place in Micronesia. In the context of West Africa, the WHO Collaborating Centre for Arboviruses and Hemorrhagic Fever at Institut Pasteur of Dakar (http://www.pasteur.fr/recherche/banques/ CRORA/) reports the periodic circulation of ZIKV since 1968. Despite several reports on ZIKV, the genetic relationships among viral strains from West Africa remain poorly understood. To evaluate the viral spread and its molecular epidemiology, we investigated 37 ZIKV isolates collected from 1968 to 2002 in six localities in Senegal and Cote d’Ivoire. In addition, we included strains from six other countries. Our results suggested that these two countries in West Africa experienced at least two independent introductions of ZIKV during the 20 century, and that apparently these viral lineages were not restricted by mosquito vector species. Moreover, we present evidence that ZIKV has possibly undergone recombination in nature and that a loss of the N154 glycosylation site in the envelope protein was a possible adaptive response to the Aedes dalzieli vector. Citation: Faye O, Freire CCM, Iamarino A, Faye O, de Oliveira JVC, et al. (2014) Molecular Evolution of Zika Virus during Its Emergence in the 20 Century. PLoS Negl Trop Dis 8(1): e2636. doi:10.1371/journal.pntd.0002636 Editor: Brian Bird, Centers for Disease Control and Prevention, United States of America Received March 4, 2013; Accepted November 27, 2013; Published January 9, 2014 Copyright: 2014 Faye et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was made possible by the Institute Pasteur of Dakar in Senegal, FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, Brazil) projects #00/04205-6 (VGDN program), #08/17013-6 and #10/19341-4. CCMF has a CAPES studentship, AI (project #12/04818-5) and JVCdO received FAPESP scholarships and PMAZ holds a CNPq-PQ grant. Funding was also provided by NIH grant R01-AI069145. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: asall@pasteur.sn . These authors contributed equally to this work.

A Regulatory Structure for Working with Genetically Modified Mosquitoes: Lessons from Mexico

A Regulatory Structure for Working with Genetically Modified Mosquitoes: Lessons from Mexico

Global Burden of Toxocariasis: A Common Neglected Infection of Poverty

Toxocariasis is a zoonosis of global importance, yet our understanding of the burden of human disease is limited by insufficient clinical awareness, absence of standardized diagnostic criteria and lack of coordinated epidemiological surveillance (Macpherson in Int J Parasitol 43(12–13):999–1008, 2013; Smith et al. in Trends Parasitol 25(4):182–188, 2009; Rubinsky-Elefant et al. in Ann Trop Med Parasitol 104(1):3–23, 2010). Human infection results from zoonotic transmission of the nematode Toxocara canis, and to a lesser extent T. cati, whose definitive hosts are dogs and cats, respectively (Despommier in Clin Microbiol Rev 16(2):265–272, 2003). Toxocara canis and T. cati are distributed worldwide, and seroprevalence studies have shown that toxocariasis is especially prevalent among socioeconomically disadvantaged children in both developing and developed nations (Smith et al. in Trends Parasitol 25(4):182–188, 2009; Hotez in PLoS Negl Trop Dis 3(3):e400, 2009). Infection in humans occurs after accidental ingestion of embryonated eggs containing Toxocara larvae present in contaminated soil or food (Despommier in Clin Microbiol Rev 16(2):265–272, 2003), or by ingestion of encapsulated larvae in raw tissues of paratenic hosts, such as cows, sheep and chickens (Akao and Ohta in Parasitol Int 56(2):87–93, 2007). Clinical manifestations range from asymptomatic infection to severe organ injury, and treatment varies according to symptoms and location of the larvae (Macpherson in Int J Parasitol 43(12–13):999–1008, 2013). Improved understanding of the global health impact of toxocariasis would assist control of this common neglected infection.

Pathogenesis of Chagas Cardiomyopathy: Role of Inflammation and Oxidative Stress

Described by the Brazilian scientist Carlos Chagas more than a century ago, Chagas disease (ChD) currently affects 8 to 10 million persons and causes more than 10 000 deaths each year.[1][1] Originally confined to Latin American countries, ChD had been considered an exotic disease and received less

Control of River Blindness

Annual mass treatment with ivermectin to prevent the parasitic disease onchocerciasis, also called river blindness, has led to cost-effective health improvements in sub-Saharan Africa (Coffeng LE. PLoS Negl Trop Dis. 2013;7[1]:e2032).

Parasitic Infections in Solid Organ Transplantation

Parasitic Infections in Solid Organ Transplantation

Subcutaneous Infection with Non-mouse Adapted Dengue Virus D2Y98P Strain Induces Systemic Vascular Leakage in AG129 Mice

Dengue (DEN) is a mosquito-borne viral disease which has become an increasing economic and health burden for the tropical and subtropical world. Plasma leakage is the most life threatening condition of DEN and may lead to hypovolaemic shock if not properly managed. We recently reported a unique dengue virus strain (D2Y98P) which upon intraperitoneal (IP) administration to immunocompromised mice led to systemic viral dissemination, intestine damage, liver dysfunction, and increased vascular permeability, hallmarks of severe DEN in patients (Tan et al, PLoS Negl Trop Dis 2010;4:e672). Here we report the clinical manifestations and features observed in mice subcutaneously (SC) infected with D2Y98P, which is a route of administration closer to natural infection. Similar to the IP route, increased vascular permeability, intestine damage, liver dysfunction, transient lymphopenia (but no thrombocytopenia) were observed in the SC infected mice. Furthermore, the SC route of infection was found more potent than the IP route whereby higher viral titers and earlier time-of-death rates were measured. In addition, various staining approaches revealed structurally intact blood vessels in the moribund animals despite pronounced systemic vascular leakage, as reported in dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) patients. Interestingly, measurement of soluble mediators involved in vascular permeability indicated that vascular leakage may occur at an early stage of the disease, as proposed in DEN patients. We believe that this novel mouse model of DEN-associated vascular leakage will contribute to a better understanding of DEN pathogenesis and represents a relevant platform for testing novel therapeutic treatments and interventions.

Correction: Collaborative Teaching and Learning: A Model for Building Capacity and Partnerships to Address NTDs

Several authors were not included in the author byline. Please see the correct list of authors, affiliations, and citation here: Mary Elizabeth Wilson1*, Felipe Fregni2, Maria Amelia de S.M.Veras3, Jason Dyett4, Amie Shei5, Guilherme Sousa Ribeiro6, John David7, Marcia C. Castro1, Aluisio Cotrim Segurado8, Albert Icksang Ko9, Mitermayer G. Reis10 1 Department of Global Health and Population, Harvard School of Public Health, Boston, Massachusetts, United States of America, 2 Harvard Medical School; Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Boston, Massachusetts, United States of America, 3 Department of Social Medicine, School of Medical Sciences, Santa Casa do Sao Paulo, Sao Paulo, Brazil, 4 Brazil Office, David Rockefeller Center for Latin American Studies at Harvard, Sao Paulo, Brazil, 5 Harvard University Ph.D. Program in Health Policy, Cambridge, Massachusetts, United States of America, 6 Instituto de Saude Coletva, Universidade Federal da Bahia and Fundacao Oswaldo Cruz, Salvador, Bahia, Brazil, 7 Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, United States of America, 8 Department of Infectious Diseases, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil 9 Yale School of Public Health, Epidemiology of Microbial Disease Division, New Haven, Connecticut, United States of America, 10 Fundacao Oswaldo Cruz, Salvador, Bahia, Brazil; Escola Bahiana de Medicina e Saude Publica and Faculdade de Medicina da Bahia, Federal University of Bahia, Salvador, Bahia, Brazil Wilson ME, Fregni F, Veras MASM, Dyett J, Shei A (2011) Collaborative Teaching and Learning: A Model for Building Capacity and Partnerships to Address NTDs. PLoS Negl Trop Dis 5(3): e939. doi:10.1371/journal.pntd.0000939

Elimination of neglected diseases in Latin America and the Caribbean: A mapping of selected diseases

In Latin America and the Caribbean, around 195 million people live in poverty, a situation that increases the burden of some infectious diseases. Neglected diseases, in particular, are often restricted to poor, marginalized sections of the population. Tools exist to combat these diseases, making it imperative to work towards their elimination. In 2009, the Pan American Health Organization (PAHO) received a mandate to support the countries in the Region in eliminating neglected diseases and other poverty-related infections. The objective of this study is to analyze the presence of selected diseases using geoprocessing techniques. Five diseases with information available at the first sub-national level (states) were mapped, showing the presence of the disease (‘‘hotspots’’) and overlap of diseases (‘‘major hotspots’’). In the 45 countries/territories (approximately 570 states) of the Region, there is: lymphatic filariasis in four countries (29 states), onchocerciasis in six countries (25 states), schistosomiasis in four countries (39 states), trachoma in three countries (29 states), and human rabies transmitted by dogs in ten countries (20 states). Of the 108 states with one or more of the selected diseases, 36 states present the diseases in overlapping areas (‘‘major hotspots’’). Additional information about soil-transmitted helminths was included. The analysis suggests a majority of the selected diseases are not widespread and can be considered part of an unfinished agenda with elimination as a goal. Integrated plans and a comprehensive approach, ensuring access to existing diagnostic and treatment methods, and establishing a multi-sectoral agenda that addresses social determinants, including access to adequate water and sanitation, are required. Future studies can include additional diseases, socio-economic and environmental variables. Citation: Schneider MC, Aguilera XP, Barbosa da Silva Junior J, Ault SK, Najera P, et al. (2011) Elimination of Neglected Diseases in Latin America and the Caribbean: A Mapping of Selected Diseases. PLoS Negl Trop Dis 5(2): e964. doi:10.1371/journal.pntd.0000964 Editor: Simon Brooker, London School of Hygiene & Tropical Medicine, United Kingdom Received June 22, 2010; Accepted January 12, 2011; Published February 15, 2011 Copyright: 2011 Schneider et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was completed with resources from the Pan American Health Organization. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: schneidc@paho.org

Reframing Critical Needs in Vector Biology and Management of Vector-Borne Disease

Reframing Critical Needs in Vector Biology and Management of Vector-Borne Disease

From Tucson to Genomics and Transgenics: The Vector Biology Network and the Emergence of Modern Vector Biology

From Tucson to Genomics and Transgenics: The Vector Biology Network and the Emergence of Modern Vector Biology

Reports on the Prevalence of Clinical Conditions Are More Convincing When Supported by Objective Evidence

Reports on the Prevalence of Clinical Conditions Are More Convincing When Supported by Objective Evidence