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Spatio-Temporal Distribution of Aedes aegypti (Diptera: Culicidae) Mitochondrial Lineages in Cities with Distinct Dengue Incidence Rates Suggests Complex Population Dynamics of the Dengue Vector in Colombia
by Jeiczon Jaimes-Dueñez, Sair Arboleda, Omar Triana-Chávez, Andrés Gómez-PalacioBackground
Aedes aegypti is the primary vector of the four serotypes of dengue virus (DENV1-4), Chikungunya and yellow fever virus to humans. Previous population genetic studies have revealed a particular genetic structure among the vector populations in the Americas that suggests differences in the ability to transmit DENV. In Colombia, despite its high epidemiologic importance, the genetic population structure and the phylogeographic depiction of Ae. aegypti, as well as its relationship with the epidemiologic landscapes in cities with heterogeneous incidence levels, remains unknown. We conducted a spatiotemporal analysis with the aim of determining the genetic structure and phylogeography of Colombian populations of Ae. aegypti among cities with different eco-epidemiologic characteristics with regard to DENV.Methods/Findings
Mitochondrial cytochrome oxidase C subunit 1 (COI) - NADH dehydrogenase subunit 4 (ND4) genes were sequenced and analyzed from 341 adult mosquitoes collected during 2012 and 2013 in the Colombian cities of Bello, Riohacha and Villavicencio, which exhibit low, medium and high levels of incidence of DENV, respectively. The results demonstrated a low genetic differentiation over time and a high genetic structure between the cities due to changes in the frequency of two highly supported genetic groups. The phylogeographic analyses indicated that one group (associated with West African populations) was found in all the cities throughout the sampling while the second group (associated with East African populations) was found in all the samples from Bello and in only one sampling from Riohacha. Environmental factors such as the use of chemical insecticides showed a significant correlation with decreasing genetic diversity, indicating that environmental factors affect the population structure of Ae. aegypti across time and space in these cities.Conclusions
Our results suggest that two Ae. aegypti lineages are present in Colombia; one that is widespread and related to a West African conspecific, and a second that may have been recently introduced and is related to an East African conspecific. The first lineage can be found in cities showing a high incidence of dengue fever and the use of chemical insecticides, whereas the second is present in cities showing a low incidence of dengue fever where the use of chemical insecticides is not constant. This study helps to improve our knowledge of the population structure of Ae. aegypti involved in the diversity of dengue fever epidemiology in Colombia.
A Recombinant Vesicular Stomatitis Virus-Based Lassa Fever Vaccine Protects Guinea Pigs and Macaques against Challenge with Geographically and Genetically Distinct Lassa Viruses
by David Safronetz, Chad Mire, Kyle Rosenke, Friederike Feldmann, Elaine Haddock, Thomas Geisbert, Heinz FeldmannBackground
Lassa virus (LASV) is endemic in several West African countries and is the etiological agent of Lassa fever. Despite the high annual incidence and significant morbidity and mortality rates, currently there are no approved vaccines to prevent infection or disease in humans. Genetically, LASV demonstrates a high degree of diversity that correlates with geographic distribution. The genetic heterogeneity observed between geographically distinct viruses raises concerns over the potential efficacy of a “universal” LASV vaccine. To date, several experimental LASV vaccines have been developed; however, few have been evaluated against challenge with various genetically unique Lassa virus isolates in relevant animal models.Methodologies/principle findings
Here we demonstrate that a single, prophylactic immunization with a recombinant vesicular stomatitis virus (VSV) expressing the glycoproteins of LASV strain Josiah from Sierra Leone protects strain 13 guinea pigs from infection / disease following challenge with LASV isolates originating from Liberia, Mali and Nigeria. Similarly, the VSV-based LASV vaccine yields complete protection against a lethal challenge with the Liberian LASV isolate in the gold-standard macaque model of Lassa fever.Conclusions/significance
Our results demonstrate the VSV-based LASV vaccine is capable of preventing morbidity and mortality associated with non-homologous LASV challenge in two animal models of Lassa fever. Additionally, this work highlights the need for the further development of disease models for geographical distinct LASV strains, particularly those from Nigeria, in order to comprehensively evaluate potential vaccines and therapies against this prominent agent of viral hemorrhagic fever.
Using Hospital Discharge Database to Characterize Chagas Disease Evolution in Spain: There Is a Need for a Systematic Approach towards Disease Detection and Control
by Zaida Herrador, Eva Rivas, Alin Gherasim, Diana Gomez-Barroso, Jezabel García, Agustín Benito, Pilar AparicioAfter the United States, Spain comes second in the list of countries receiving migrants from Latin America, and, therefore, it is the European country with the highest expected number of infected patients of Chagas disease. We have studied the National Health System’s Hospital Discharge Records Database (CMBD) in order to describe the disease evolution from 1997 to 2011 in Spain. We performed a retrospective descriptive study using CMBD information on hospitalizations including Chagas disease. Data was divided in two periods with similar length in time: 1997-2004 and 2005-2011. Hospitalization rates were calculated and clinical characteristics were described. We used multivariable logistic regression to calculate adjusted odds-ratio (aOR) for the association between various conditions and being hospitalized with organ affectation. A total of 1729 hospitalization records were identified. Hospitalization rates for the two periods were 18 and 242.8/100000 population, respectively. The median age was 35 years (range 0-87), 74% were female and the 16-45 age-group was mostly represented (69.8%). Overall, 23.4% hospitalizations included the diagnosis of Chagas disease with organ complications. Being male [aOR: 1.3 (1.00-1.77)], aged 45 and 64 years [aOR: 2.59 (1.42-4.71)], and a median hospitalization cost above 3,065 euro [aOR: 2.03 (3.73-7.86)] were associated with hospitalizations with organ affectation. Since 2005, the number of detected infections increased in Spain. The predominant patients’ profile (asymptomatic women at fertile age) and the conditions associated with organ affectation underlines the need for increased efforts towards the early detection of T cruzi.
by Larissa M. Bandeira, Silvia N. O. Uehara, Marcel A. Asato, Gabriela S. Aguena, Cristiane M. Maedo, Nikolas H. Benites, Marco A. M. Puga, Grazielli R. Rezende, Carolina M. Finotti, Gabriela A. Cesar, Tayana S. O. Tanaka, Vivianne O. L. Castro, Koko Otsuki, Ana C. P. Vicente, Carlos E. Fernandes, Ana R. C. Motta-CastroBackground
Human T-lymphotropic virus type 1 (HTLV-1) has worldwide distribution and is considered endemic in many world regions, including southwestern Japan and Brazil. Japanese immigrants and their descendants have a high risk of acquiring this infection due to intense population exchange between Brazil and Japan.Objective
This cross-sectional study aimed to estimate the prevalence of HTLV, analyze the main risk factors associated with this infection, identify the main circulating types and subtypes of HTLV in Japanese immigrants and descendants living in Campo Grande-MS (Middle-West Brazil), as well as analyze the phylogenetic relationship among isolates of HTLV.Study Design
A total of 219 individuals were interviewed and submitted to blood collection. All collected blood samples were submitted for detection of anti-HTLV-1/2 using the immunoassay ELISA and confirmed by immunoblot method. The proviral DNA of the 14 samples HTLV- 1 positive were genotyped by nucleotide sequencing.Results
The overall prevalence of HTLV-1 was 6.8% (IC 95%: 3,5-10,2). Descriptive analysis of behavioral risk factors showed statistical association between HTLV-1 and age greater than or equal to 45 years. The proviral DNA of HTLV-1 was detected in all HTLV-1 positive samples. Of these, 14 were sequenced and classified as Cosmopolitan subtype, and 50% (7/14) belonged to subgroup A (transcontinental) and 50% (7/14) to the subgroup B (Japanese).Conclusion
The high prevalence of HTLV-1 found evidence of the importance of early diagnosis and counseling of individuals infected with HTLV-1 for the control and prevention of the spread of this infection among Japanese immigrants and their descendants in Central Brazil.
Correction: A Colour Opponent Model That Explains Tsetse Fly Attraction to Visual Baits and Can Be Used to Investigate More Efficacious Bait Materials
by Roger D. Santer
Release of Lungworm Larvae from Snails in the Environment: Potential for Alternative Transmission Pathways
by Alessio Giannelli, Vito Colella, Francesca Abramo, Rafael Antonio do Nascimento Ramos, Luigi Falsone, Emanuele Brianti, Antonio Varcasia, Filipe Dantas-Torres, Martin Knaus, Mark T. Fox, Domenico OtrantoBackground
Gastropod-borne parasites may cause debilitating clinical conditions in animals and humans following the consumption of infected intermediate or paratenic hosts. However, the ingestion of fresh vegetables contaminated by snail mucus and/or water has also been proposed as a source of the infection for some zoonotic metastrongyloids (e.g., Angiostrongylus cantonensis). In the meantime, the feline lungworms Aelurostrongylus abstrusus and Troglostrongylus brevior are increasingly spreading among cat populations, along with their gastropod intermediate hosts. The aim of this study was to assess the potential of alternative transmission pathways for A. abstrusus and T. brevior L3 via the mucus of infected Helix aspersa snails and the water where gastropods died. In addition, the histological examination of snail specimens provided information on the larval localization and inflammatory reactions in the intermediate host.Methodology/Principal Findings
Twenty-four specimens of H. aspersa received ~500 L1 of A. abstrusus and T. brevior, and were assigned to six study groups. Snails were subjected to different mechanical and chemical stimuli throughout 20 days in order to elicit the production of mucus. At the end of the study, gastropods were submerged in tap water and the sediment was observed for lungworm larvae for three consecutive days. Finally, snails were artificially digested and recovered larvae were counted and morphologically and molecularly identified. The anatomical localization of A. abstrusus and T. brevior larvae within snail tissues was investigated by histology. L3 were detected in the snail mucus (i.e., 37 A. abstrusus and 19 T. brevior) and in the sediment of submerged specimens (172 A. abstrusus and 39 T. brevior). Following the artificial digestion of H. aspersa snails, a mean number of 127.8 A. abstrusus and 60.3 T. brevior larvae were recovered. The number of snail sections positive for A. abstrusus was higher than those for T. brevior.Conclusions
Results of this study indicate that A. abstrusus and T. brevior infective L3 are shed in the mucus of H. aspersa or in water where infected gastropods had died submerged. Both elimination pathways may represent alternative route(s) of environmental contamination and source of the infection for these nematodes under field conditions and may significantly affect the epidemiology of feline lungworms. Considering that snails may act as intermediate hosts for other metastrongyloid species, the environmental contamination by mucus-released larvae is discussed in a broader context.
Social Pathways for Ebola Virus Disease in Rural Sierra Leone, and Some Implications for Containment
by Paul Richards, Joseph Amara, Mariane C. Ferme, Prince Kamara, Esther Mokuwa, Amara Idara Sheriff, Roland Suluku, Maarten VoorsThe current outbreak of Ebola Virus Disease in Upper West Africa is the largest ever recorded. Molecular evidence suggests spread has been almost exclusively through human-to-human contact. Social factors are thus clearly important to understand the epidemic and ways in which it might be stopped, but these factors have so far been little analyzed. The present paper focuses on Sierra Leone, and provides cross sectional data on the least understood part of the epidemic—the largely undocumented spread of Ebola in rural areas. Various forms of social networking in rural communities and their relevance for understanding pathways of transmission are described. Particular attention is paid to the relationship between marriage, funerals and land tenure. Funerals are known to be a high-risk factor for infection. It is suggested that more than a shift in awareness of risks will be needed to change local patterns of behavior, especially in regard to funerals, since these are central to the consolidation of community ties. A concluding discussion relates the information presented to plans for halting the disease. Local consultation and access are seen as major challenges to be addressed.
Trypanosomiasis-Induced Megacolon Illustrates How Myenteric Neurons Modulate the Risk for Colon Cancer in Rats and Humans
by Vinicius Kannen, Enio C. de Oliveira, Bruno Zene Motta, Annuar Jose Chaguri, Mariângela Ottoboni Brunaldi, Sérgio B. GarciaBackground
Trypanosomiasis induces a remarkable myenteric neuronal degeneration leading to megacolon. Very little is known about the risk for colon cancer in chagasic megacolon patients. To clarify whether chagasic megacolon impacts on colon carcinogenesis, we investigated the risk for colon cancer in Trypanosoma cruzi (T. cruzi) infected patients and rats.Methods
Colon samples from T. cruzi-infected and uninfected patients and rats were histopathologically investigated with colon cancer biomarkers. An experimental model for chemical myenteric denervation was also performed to verify the myenteric neuronal effects on colon carcinogenesis. All experiments complied the guidelines and approval of ethical institutional review boards.Results
No colon tumors were found in chagasic megacolon samples. A significant myenteric neuronal denervation was observed. Epithelial cell proliferation and hyperplasia were found increased in chagasic megacolon. Analyzing the argyrophilic nucleolar organiser regions within the cryptal bottom revealed reduced risk for colon cancer in Chagas’ megacolon patients. T. cruzi-infected rats showed a significant myenteric neuronal denervation and decreased numbers of colon preneoplastic lesions. In chemical myenteric denervated rats preneoplastic lesions were reduced from the 2nd wk onward, which ensued having the colon myenteric denervation significantly induced.Conclusion/Significance
Our data suggest that the trypanosomiasis-related myenteric neuronal degeneration protects the colon tissue from carcinogenic events. Current findings highlight potential mechanisms in tropical diseases and cancer research.
Neglected Tropical Diseases among the Association of Southeast Asian Nations (ASEAN): Overview and Update
by Peter J. Hotez, Maria Elena Bottazzi, Ulrich Strych, Li-Yen Chang, Yvonne A. L. Lim, Maureen M. Goodenow, Sazaly AbuBakarThe ten member states of the Association of Southeast Asian Nations (ASEAN) constitute an economic powerhouse, yet these countries also harbor a mostly hidden burden of poverty and neglected tropical diseases (NTDs). Almost 200 million people live in extreme poverty in ASEAN countries, mostly in the low or lower middle-income countries of Indonesia, the Philippines, Myanmar, Viet Nam, and Cambodia, and many of them are affected by at least one NTD. However, NTDs are prevalent even among upper middle-income ASEAN countries such as Malaysia and Thailand, especially among the indigenous populations. The three major intestinal helminth infections are the most common NTDs; each helminthiasis is associated with approximately 100 million infections in the region. In addition, more than 10 million people suffer from either liver or intestinal fluke infections, as well as schistosomiasis and lymphatic filariasis (LF). Intestinal protozoan infections are widespread, while leishmaniasis has emerged in Thailand, and zoonotic malaria (Plasmodium knowlesi infection) causes severe morbidity in Malaysia. Melioidosis has emerged as an important bacterial NTD, as have selected rickettsial infections, and leptospirosis. Leprosy, yaws, and trachoma are still endemic in focal areas. Almost 70 million cases of dengue fever occur annually in ASEAN countries, such that this arboviral infection is now one of the most common and economically important NTDs in the region. A number of other arboviral and zoonotic viral infections have also emerged, including Japanese encephalitis; tick-borne viral infections; Nipah virus, a zoonosis present in fruit bats; and enterovirus 71 infection. There are urgent needs to expand surveillance activities in ASEAN countries, as well as to ensure mass drug administration is provided to populations at risk for intestinal helminth and fluke infections, LF, trachoma, and yaws. An ASEAN Network for Drugs, Diagnostics, Vaccines, and Traditional Medicines Innovation provides a policy framework for the development of new control and elimination tools. Together with prominent research institutions and universities, the World Health Organization (WHO), and its regional offices, these organizations could implement important public health improvements through NTD control and elimination in the coming decade.
Intravital Imaging of a Massive Lymphocyte Response in the Cortical Dura of Mice after Peripheral Infection by Trypanosomes
by Jonathan A. Coles, Elmarie Myburgh, Ryan Ritchie, Alana Hamilton, Jean Rodgers, Jeremy C. Mottram, Michael P. Barrett, James M. BrewerPeripheral infection by Trypanosoma brucei, the protozoan responsible for sleeping sickness, activates lymphocytes, and, at later stages, causes meningoencephalitis. We have videoed the cortical meninges and superficial parenchyma of C56BL/6 reporter mice infected with T.b.brucei. By use of a two-photon microscope to image through the thinned skull, the integrity of the tissues was maintained. We observed a 47-fold increase in CD2+ T cells in the meninges by 12 days post infection (dpi). CD11c+ dendritic cells also increased, and extravascular trypanosomes, made visible either by expression of a fluorescent protein, or by intravenous injection of furamidine, appeared. The likelihood that invasion will spread from the meninges to the parenchyma will depend strongly on whether the trypanosomes are below the arachnoid membrane, or above it, in the dura. Making use of optical signals from the skull bone, blood vessels and dural cells, we conclude that up to 40 dpi, the extravascular trypanosomes were essentially confined to the dura, as were the great majority of the T cells. Inhibition of T cell activation by intraperitoneal injection of abatacept reduced the numbers of meningeal T cells at 12 dpi and their mean speed fell from 11.64 ± 0.34 μm/min (mean ± SEM) to 5.2 ± 1.2 μm/min (p = 0.007). The T cells occasionally made contact lasting tens of minutes with dendritic cells, indicative of antigen presentation. The population and motility of the trypanosomes tended to decline after about 30 dpi. We suggest that the lymphocyte infiltration of the meninges may later contribute to encephalitis, but have no evidence that the dural trypanosomes invade the parenchyma.
by Yi Hu, Rui Li, Yue Chen, Fenghua Gao, Qizhi Wang, Shiqing Zhang, Zhijie Zhang, Qingwu JiangBackground
The Chinese national surveillance system showed that the risk of Schistosoma japonicum infection fluctuated temporally. This dynamical change might indicate periodicity of the disease, and its understanding could significantly improve targeted interventions to reduce the burden of schistosomiasis. The goal of this study was to investigate how the schistosomiasis risk varied temporally and spatially in recent years.Methodology/Principal Findings
Parasitological data were obtained through repeated cross-sectional surveys that were carried out during 1997-2010 in Anhui Province, East China. A multivariate autoregressive model, combined with principal oscillation pattern (POP) analysis, was used to evaluate the spatio-temporal variation of schistosomiasis risk. Results showed that the temporal changes of schistosomiasis risk in the study area could be decomposed into two sustained damped oscillatory modes with estimated period of approximately 2.5 years. The POPs associated with these oscillatory components showed that the pattern near the Yangtze River varied markedly and that the disease risk appeared to evolve in a Southwest/Northeast orientation. The POP coefficients showed decreasing tendency until 2001, then increasing during 2002-2005 and decaying afterwards.Conclusion
The POP analysis characterized the variations of schistosomiasis risk over space and time and demonstrated that the disease mainly varied temporally along the Yangtze River. The schistosomiasis risk declined periodically with a temporal fluctuation. Whether it resulted from previous national control strategies on schistosomiasis needs further investigations.
by Natsuko Imai, Ilaria Dorigatti, Simon Cauchemez, Neil M. FergusonBackground
Estimates of dengue transmission intensity remain ambiguous. Since the majority of infections are asymptomatic, surveillance systems substantially underestimate true rates of infection. With advances in the development of novel control measures, obtaining robust estimates of average dengue transmission intensity is key for assessing both the burden of disease from dengue and the likely impact of interventions.Methodology/Principal Findings
The force of infection (λ) and corresponding basic reproduction numbers (R0) for dengue were estimated from non-serotype (IgG) and serotype-specific (PRNT) age-stratified seroprevalence surveys identified from the literature. The majority of R0 estimates ranged from 1–4. Assuming that two heterologous infections result in complete immunity produced up to two-fold higher estimates of R0 than when tertiary and quaternary infections were included. λ estimated from IgG data were comparable to the sum of serotype-specific forces of infection derived from PRNT data, particularly when inter-serotype interactions were allowed for.Conclusions/Significance
Our analysis highlights the highly heterogeneous nature of dengue transmission. How underlying assumptions about serotype interactions and immunity affect the relationship between the force of infection and R0 will have implications for control planning. While PRNT data provides the maximum information, our study shows that even the much cheaper ELISA-based assays would provide comparable baseline estimates of overall transmission intensity which will be an important consideration in resource-constrained settings.
by Hannah Brown, Ann H. Kelly, Almudena Marí Sáez, Elisabeth Fichet-Calvet, Rashid Ansumana, Jesse Bonwitt, N’Faly Magassouba, Foday Sahr, Matthias Borchert
by Katie Hampson, Laurent Coudeville, Tiziana Lembo, Maganga Sambo, Alexia Kieffer, Michaël Attlan, Jacques Barrat, Jesse D. Blanton, Deborah J. Briggs, Sarah Cleaveland, Peter Costa, Conrad M. Freuling, Elly Hiby, Lea Knopf, Fernando Leanes, François-Xavier Meslin, Artem Metlin, Mary Elizabeth Miranda, Thomas Müller, Louis H. Nel, Sergio Recuenco, Charles E. Rupprecht, Carolin Schumacher, Louise Taylor, Marco Antonio Natal Vigilato, Jakob Zinsstag, Jonathan Dushoff, on behalf of the Global Alliance for Rabies Control Partners for Rabies PreventionBackground
Rabies is a notoriously underreported and neglected disease of low-income countries. This study aims to estimate the public health and economic burden of rabies circulating in domestic dog populations, globally and on a country-by-country basis, allowing an objective assessment of how much this preventable disease costs endemic countries.Methodology/Principal Findings
We established relationships between rabies mortality and rabies prevention and control measures, which we incorporated into a model framework. We used data derived from extensive literature searches and questionnaires on disease incidence, control interventions and preventative measures within this framework to estimate the disease burden. The burden of rabies impacts on public health sector budgets, local communities and livestock economies, with the highest risk of rabies in the poorest regions of the world. This study estimates that globally canine rabies causes approximately 59,000 (95% Confidence Intervals: 25-159,000) human deaths, over 3.7 million (95% CIs: 1.6-10.4 million) disability-adjusted life years (DALYs) and 8.6 billion USD (95% CIs: 2.9-21.5 billion) economic losses annually. The largest component of the economic burden is due to premature death (55%), followed by direct costs of post-exposure prophylaxis (PEP, 20%) and lost income whilst seeking PEP (15.5%), with only limited costs to the veterinary sector due to dog vaccination (1.5%), and additional costs to communities from livestock losses (6%).Conclusions/Significance
This study demonstrates that investment in dog vaccination, the single most effective way of reducing the disease burden, has been inadequate and that the availability and affordability of PEP needs improving. Collaborative investments by medical and veterinary sectors could dramatically reduce the current large, and unnecessary, burden of rabies on affected communities. Improved surveillance is needed to reduce uncertainty in burden estimates and to monitor the impacts of control efforts.
by The PLOS Neglected Tropical Diseases Staff
Case Report: Actinomycetoma Caused by Nocardia aobensis from Lao PDR with Favourable Outcome after Short-Term Antibiotic Treatment
by Inthanomchanh Vongphoumy, David A. B. Dance, Sabine Dittrich, Julie Logan, Viengmon Davong, Sayaphet Rattanavong, Joerg BlessmannBackground
Mycetoma is a neglected, chronic, localized, progressively destructive, granulomatous infection caused either by fungi (eumycetoma) or by aerobic actinomycetes (actinomycetoma). It is characterized by a triad of painless subcutaneous mass, multiple sinuses and discharge containing grains. Mycetoma commonly affects young men aged between 20 and 40 years with low socioeconomic status, particularly farmers and herdsmen.Methodology / Principal Findings
A 30 year-old male farmer from an ethnic minority in Phin District, Savannakhet Province, Lao PDR (Laos) developed a painless swelling with multiple draining sinuses of his right foot over a period of approximately 3 years. X-ray of the right foot showed osteolysis of tarsals and metatarsals. Aerobic culture of sinus discharge yielded large numbers of Staphylococcus aureus and a slow growing Gram-positive rod. The organism was subsequently identified as Nocardia aobensis by 16S ribosomal RNA gene sequencing. The patient received antimicrobial treatment with amikacin and trimethoprim-sulfamethoxazole according to consensus treatment guidelines. Although slight improvement was noted the patient left the hospital after 14 days and did not take any more antibiotics. Over the following 22 weeks the swelling of his foot subsequently diminished together with healing of discharging sinuses.Conclusion
This is the first published case of Actinomycetoma caused by Nocardia aobensis and the second case of Actinomycetoma from Laos. A treatment course of only 14 days with amikacin and trimethoprim-sulfamethoxazole was apparently sufficient to cure the infection, although long-term treatment up to one year is currently recommended. Treatment trials or prospective descriptions of outcome for actinomycetoma should investigate treatment efficacy for the different members of Actinomycetales, particularly Nocardia spp., with short-term and long-term treatment courses.
Insensitivity to the Spatial Repellent Action of Transfluthrin in Aedes aegypti: A Heritable Trait Associated with Decreased Insecticide Susceptibility
by Joseph M. Wagman, Nicole L. Achee, John P. GriecoBackground
New vector control paradigms expanding the use of spatial repellents are promising, but there are many gaps in our knowledge about how repellents work and how their long-term use might affect vector populations over time. Reported here are findings from a series of in vitro studies that investigated the plasticity and heritability of spatial repellent (SR) behaviors in Aedes aegypti exposed to airborne transfluthrin, including results that indicate a possible link between repellent insensitivity and insecticide resistance.Methodology/principal findings
A dual-choice chamber system was used to observe directional flight behaviors in Aedes aegypti mosquitoes exposed to passively emanating transfluthrin vapors (1.35 mg/m3). Individual SR responder and SR non-responder mosquitoes were identified, collected and maintained separately according to their observed phenotype. Subsequent testing included re-evaluation of behavioral responses in some mosquito cohorts as well as testing the progeny of selectively bred responder and non-responder mosquito strains through nine generations. At baseline (F0 generation), transfluthrin actively repelled mosquitoes in the assay system. F0 mosquitoes repelled upon initial exposure to transfluthrin vapors were no more likely to be repelled again by subsequent exposure 24h later, but repelled mosquitoes allowed to rest for 48h were subsequently repelled at a higher proportion than was observed at baseline. Selective breeding of SR responders for nine generations did not change the proportion of mosquitoes repelled in any generation. However, selective breeding of SR non-responders did produce, after four generations, a strain of mosquitoes that was insensitive to the SR activity of transfluthrin. Compared to the SR responder strain, the SR insensitive strain also demonstrated decreased susceptibility to transfluthrin toxicity in CDC bottle bioassays and a higher frequency of the V1016Ikdr mutation.Conclusions/significance
SR responses to volatile transfluthrin are complex behaviors with multiple determinants in Ae. aegypti. Results indicate a role for neurotoxic irritation of mosquitoes by sub-lethal doses of airborne chemical as a mechanism by which transfluthrin can produce SR behaviors in mosquitoes. Accordingly, how prolonged exposure to sub-lethal doses of volatile pyrethroids might impact insecticide resistance in natural vector populations, and how already resistant populations might respond to a given repellent in the field, are important considerations that warrant further monitoring and study. Results also highlight the critical need to develop new repellent active ingredients with novel mechanisms of action.
by Mugenyi Albert, Nicola A Wardrop, Peter M Atkinson, Steve J Torr, Susan C WelburnTsetse flies transmit trypanosomes, the causative agent of human and animal African trypanosomiasis. The tsetse vector is extensively distributed across sub-Saharan Africa. Trypanosomiasis maintenance is determined by the interrelationship of three elements: vertebrate host, parasite and the vector responsible for transmission. Mapping the distribution and abundance of tsetse flies assists in predicting trypanosomiasis distributions and developing rational strategies for disease and vector control. Given scarce resources to carry out regular full scale field tsetse surveys to up-date existing tsetse maps, there is a need to devise inexpensive means for regularly obtaining dependable area-wide tsetse data to guide control activities. In this study we used spatial epidemiological modelling techniques (logistic regression) involving 5000 field-based tsetse-data (G. f. fuscipes) points over an area of 40,000 km2, with satellite-derived environmental surrogates composed of precipitation, temperature, land cover, normalised difference vegetation index (NDVI) and elevation at the sub-national level. We used these extensive tsetse data to analyse the relationships between presence of tsetse (G. f. fuscipes) and environmental variables. The strength of the results was enhanced through the application of a spatial autologistic regression model (SARM). Using the SARM we showed that the probability of tsetse presence increased with proportion of forest cover and riverine vegetation. The key outputs are a predictive tsetse distribution map for the Lake Victoria basin of Uganda and an improved understanding of the association between tsetse presence and environmental variables. The predicted spatial distribution of tsetse in the Lake Victoria basin of Uganda will provide significant new information to assist with the spatial targeting of tsetse and trypanosomiasis control.
Plasmodium vivax Populations Are More Genetically Diverse and Less Structured than Sympatric Plasmodium falciparum Populations
by Charlie Jennison, Alicia Arnott, Natacha Tessier, Livingstone Tavul, Cristian Koepfli, Ingrid Felger, Peter M. Siba, John C. Reeder, Melanie Bahlo, Ivo Mueller, Alyssa E. BarryIntroduction
The human malaria parasite, Plasmodium vivax, is proving more difficult to control and eliminate than Plasmodium falciparum in areas of co-transmission. Comparisons of the genetic structure of sympatric parasite populations may provide insight into the mechanisms underlying the resilience of P. vivax and can help guide malaria control programs.Methodology/Principle findings
P. vivax isolates representing the parasite populations of four areas on the north coast of Papua New Guinea (PNG) were genotyped using microsatellite markers and compared with previously published microsatellite data from sympatric P. falciparum isolates. The genetic diversity of P. vivax (He = 0.83–0.85) was higher than that of P. falciparum (He = 0.64–0.77) in all four populations. Moderate levels of genetic differentiation were found between P. falciparum populations, even over relatively short distances (less than 50 km), with 21–28% private alleles and clear geospatial genetic clustering. Conversely, very low population differentiation was found between P. vivax catchments, with less than 5% private alleles and no genetic clustering observed. In addition, the effective population size of P. vivax (30353; 13043–69142) was larger than that of P. falciparum (18871; 8109–42986).Conclusions/Significance
Despite comparably high prevalence, P. vivax had higher diversity and a panmictic population structure compared to sympatric P. falciparum populations, which were fragmented into subpopulations. The results suggest that in comparison to P. falciparum, P. vivax has had a long-term large effective population size, consistent with more intense and stable transmission, and limited impact of past control and elimination efforts. This underlines suggestions that more intensive and sustained interventions will be needed to control and eventually eliminate P. vivax. This research clearly demonstrates how population genetic analyses can reveal deeper insight into transmission patterns than traditional surveillance methods.
Overexpression of Cytoplasmic TcSIR2RP1 and Mitochondrial TcSIR2RP3 Impacts on Trypanosoma cruzi Growth and Cell Invasion
by Carla Ritagliati, Victoria L. Alonso, Romina Manarin, Pamela Cribb, Esteban C. SerraBackground
Trypanosoma cruzi is a protozoan pathogen responsible for Chagas disease. Current therapies are inadequate because of their severe host toxicity and numerous side effects. The identification of new biotargets is essential for the development of more efficient therapeutic alternatives. Inhibition of sirtuins from Trypanosoma brucei and Leishmania ssp. showed promising results, indicating that these enzymes may be considered as targets for drug discovery in parasite infection. Here, we report the first characterization of the two sirtuins present in T. cruzi.Methodology
Dm28c epimastigotes that inducibly overexpress TcSIR2RP1 and TcSIR2RP3 were constructed and used to determine their localizations and functions. These transfected lines were tested regarding their acetylation levels, proliferation and metacyclogenesis rate, viability when treated with sirtuin inhibitors and in vitro infectivity.Conclusion
TcSIR2RP1 and TcSIR2RP3 are cytosolic and mitochondrial proteins respectively. Our data suggest that sirtuin activity is important for the proliferation of T. cruzi replicative forms, for the host cell-parasite interplay, and for differentiation among life-cycle stages; but each one performs different roles in most of these processes. Our results increase the knowledge on the localization and function of these enzymes, and the overexpressing T. cruzi strains we obtained can be useful tools for experimental screening of trypanosomatid sirtuin inhibitors.