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Identifying wildlife reservoirs of neglected taeniid tapeworms: Non-invasive diagnosis of endemic <i>Taenia serialis</i> infection in a wild primate population

PLoS Neglected Tropical Diseases News - 13 July 2017 - 9:00pm

by India Schneider-Crease, Randi H. Griffin, Megan A. Gomery, Pierre Dorny, John C. Noh, Sukwan Handali, Holly M. Chastain, Patricia P. Wilkins, Charles L. Nunn, Noah Snyder-Mackler, Jacinta C. Beehner, Thore J. Bergman

Despite the global distribution and public health consequences of Taenia tapeworms, the life cycles of taeniids infecting wildlife hosts remain largely undescribed. The larval stage of Taenia serialis commonly parasitizes rodents and lagomorphs, but has been reported in a wide range of hosts that includes geladas (Theropithecus gelada), primates endemic to Ethiopia. Geladas exhibit protuberant larval cysts indicative of advanced T. serialis infection that are associated with high mortality. However, non-protuberant larvae can develop in deep tissue or the abdominal cavity, leading to underestimates of prevalence based solely on observable cysts. We adapted a non-invasive monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA) to detect circulating Taenia spp. antigen in dried gelada urine. Analysis revealed that this assay was highly accurate in detecting Taenia antigen, with 98.4% specificity, 98.5% sensitivity, and an area under the curve of 0.99. We used this assay to investigate the prevalence of T. serialis infection in a wild gelada population, finding that infection is substantially more widespread than the occurrence of visible T. serialis cysts (16.4% tested positive at least once, while only 6% of the same population exhibited cysts). We examined whether age or sex predicted T. serialis infection as indicated by external cysts and antigen presence. Contrary to the female-bias observed in many Taenia-host systems, we found no significant sex bias in either cyst presence or antigen presence. Age, on the other hand, predicted cyst presence (older individuals were more likely to show cysts) but not antigen presence. We interpret this finding to indicate that T. serialis may infect individuals early in life but only result in visible disease later in life. This is the first application of an antigen ELISA to the study of larval Taenia infection in wildlife, opening the doors to the identification and description of infection dynamics in reservoir populations.

Phenotypic, chemical and functional characterization of cyclic nucleotide phosphodiesterase 4 (PDE4) as a potential anthelmintic drug target

PLoS Neglected Tropical Diseases News - 13 July 2017 - 9:00pm

by Thavy Long, Liliana Rojo-Arreola, Da Shi, Nelly El-Sakkary, Kurt Jarnagin, Fernando Rock, Maliwan Meewan, Alberto A. Rascón Jr., Lin Lin, Katherine A. Cunningham, George A. Lemieux, Larissa Podust, Ruben Abagyan, Kaveh Ashrafi, James H. McKerrow, Conor R. Caffrey

Background

Reliance on just one drug to treat the prevalent tropical disease, schistosomiasis, spurs the search for new drugs and drug targets. Inhibitors of human cyclic nucleotide phosphodiesterases (huPDEs), including PDE4, are under development as novel drugs to treat a range of chronic indications including asthma, chronic obstructive pulmonary disease and Alzheimer’s disease. One class of huPDE4 inhibitors that have yielded marketed drugs is the benzoxaboroles (Anacor Pharmaceuticals).

Methodology/Principal findings

A phenotypic screen involving Schistosoma mansoni and 1,085 benzoxaboroles identified a subset of huPDE4 inhibitors that induced parasite hypermotility and degeneration. To uncover the putative schistosome PDE4 target, we characterized four PDE4 sequences (SmPDE4A-D) in the parasite’s genome and transcriptome, and cloned and recombinantly expressed the catalytic domain of SmPDE4A. Among a set of benzoxaboroles and catechol inhibitors that differentially inhibit huPDE4, a relationship between the inhibition of SmPDE4A, and parasite hypermotility and degeneration, was measured. To validate SmPDE4A as the benzoxaborole molecular target, we first generated Caenorhabditis elegans lines that express a cDNA for smpde4a on a pde4(ce268) mutant (hypermotile) background: the smpde4a transgene restored mutant worm motility to that of the wild type. We then show that benzoxaborole inhibitors of SmPDE4A that induce hypermotility in the schistosome also elicit a hypermotile response in the C. elegans lines that express the smpde4a transgene, thereby confirming SmPDE4A as the relevant target.

Conclusions/Significance

The orthogonal chemical, biological and genetic strategies employed identify SmPDE4A’s contribution to parasite motility and degeneration, and its potential as a drug target. Transgenic C. elegans is highlighted as a potential screening tool to optimize small molecule chemistries to flatworm molecular drug targets.

Visceral leishmaniasis in an environmentally protected area in southeastern Brazil: Epidemiological and laboratory cross-sectional investigation of phlebotomine fauna, wild hosts and canine cases

PLoS Neglected Tropical Diseases News - 13 July 2017 - 9:00pm

by Maria Rita Donalisio, Laís Moraes Paiz, Vanessa Gusmon da Silva, Virgínia Bodelão Richini-Pereira, Andrea Paula Bruno von Zuben, Claudio Luiz Castagna, Gabriela Motoie, Roberto Mitsuyoshi Hiramoto, José Eduardo Tolezano

Background

Leishmaniasis is a rapidly expanding zoonosis that shows increasing urbanization. Concern exists regarding the role of wildlife in visceral leishmaniasis (VL) transmission, due to frequent natural or anthropogenic environmental changes that facilitate contact between wildlife, humans and their pets. The municipality of Campinas, in southeastern Brazil, initially recorded VL in 2009, when the first autochthonous case was confirmed in a dog living in an upscale residential condominium, located inside an environmentally protected area (EPA). Since then, disease transmission remains restricted to dogs inhabiting two geographically contiguous condominiums within the EPA.

Methodology/Principal findings

We conducted a cross-sectional study of the VL focus to investigate Leishmania spp. infection in domestic dogs, wild mammals and sand flies using molecular tools and recommended serological techniques. Canine seroprevalences of 1.5% and 1.2% were observed in 2013 and 2015, respectively. Six insect species, confirmed or suspected vectors or potential transmitters of Leishmania, were identified. Two specimens of the main L. (L.) infantum vector in Brazil, Lutzomyia longipalpis, were captured in the EPA. Natural infection by L. (L.) infantum was recorded in one Expapillata firmatoi specimen and two Pintomyia monticola. Natural infection by L. (L.) infantum and Leishmania subgenus Viannia was also detected in two white-eared opossums (Didelphis albiventris), a known reservoir of VL. Geographical coordinates of each sampling of infected animals were plotted on a map of the EPA, demonstrating proximity between these animals, human residences, including the dogs positive for VL, and forest areas.

Conclusions/Significance

The EPA, which is inhabited by humans, has an active VL focus. The risk of establishing and maintaining disease transmission foci in similar scenarios, i.e. wild areas that undergo environmental modifications, is evident. Moreover, different epidemiological profiles of VL must be included to elaborate prevention and control measures that consider the particularities of each transmission area.

Insights into the sand fly saliva: Blood-feeding and immune interactions between sand flies, hosts, and <i>Leishmania</i>

PLoS Neglected Tropical Diseases News - 13 July 2017 - 9:00pm

by Tereza Lestinova, Iva Rohousova, Michal Sima, Camila I. de Oliveira, Petr Volf

Background

Leishmaniases are parasitic diseases present worldwide that are transmitted to the vertebrate host by the bite of an infected sand fly during a blood feeding. Phlebotomine sand flies inoculate into the mammalian host Leishmania parasites embedded in promastigote secretory gel (PSG) with saliva, which is composed of a diverse group of molecules with pharmacological and immunomodulatory properties.

Methods and findings

In this review, we focus on 3 main aspects of sand fly salivary molecules: (1) structure and composition of salivary glands, including the properties of salivary molecules related to hemostasis and blood feeding, (2) immunomodulatory properties of salivary molecules and the diverse impacts of these molecules on leishmaniasis, ranging from disease exacerbation to vaccine development, and (3) use of salivary molecules for field applications, including monitoring host exposure to sand flies and the risk of Leishmania transmission. Studies showed interesting differences between salivary proteins of Phlebotomus and Lutzomyia species, however, no data were ever published on salivary proteins of Sergentomyia species.

Conclusions

In the last 15 years, numerous studies have characterized sand fly salivary proteins and, in parallel, have addressed the impact of such molecules on the biology of the host–sand fly–parasite interaction. The results obtained shall pave the way for the development of field-application tools that could contribute to the management of leishmaniasis in endemic areas.

Central and peripheral nervous system involvement caused by Zika and chikungunya coinfection

PLoS Neglected Tropical Diseases News - 13 July 2017 - 9:00pm

by Carlos A. A. Brito, Fernanda Azevedo, Marli T. Cordeiro, Ernesto T. A. Marques Jr., Rafael F. O. Franca

Modeling the risk of transmission of schistosomiasis in Akure North Local Government Area of Ondo State, Nigeria using satellite derived environmental data

PLoS Neglected Tropical Diseases News - 12 July 2017 - 9:00pm

by Oluwaremilekun G. Ajakaye, Oluwatola I. Adedeji, Paul O. Ajayi

Schistosomiasis is a parasitic disease and its distribution, in space and time, can be influenced by environmental factors such as rivers, elevation, slope, land surface temperature, land use/cover and rainfall. The aim of this study is to identify the areas with suitable conditions for schistosomiasis transmission on the basis of physical and environmental factors derived from satellite imagery and spatial analysis for Akure North Local Government Area (LGA) of Ondo State. Nigeria. This was done through methodology multicriteria evaluation (MCE) using Saaty’s analytical hierarchy process (AHP). AHP is a multi-criteria decision method that uses hierarchical structures to represent a problem and makes decisions based on priority scales. In this research AHP was used to obtain the mapping weight or importance of each individual schistosomiasis risk factor. For the purpose of identifying areas of schistosomiasis risk, this study focused on temperature, drainage, elevation, rainfall, slope and land use/land cover as the factors controlling schistosomiasis incidence in the study area. It is by reclassifying and overlaying these factors that areas vulnerable to schistosomiasis were identified. The weighted overlay analysis was done after each factor was given the appropriate weight derived through the analytical hierarchical process. The prevalence of urinary schistosomiasis in the study area was also determined by parasitological analysis of urine samples collected through random sampling. The results showed varying risk of schistosomiasis with a larger portion of the area (82%) falling under the high and very high risk category. The study also showed that one community (Oba Ile) had the lowest risk of schistosomiasis while the risk increased in the four remaining communities (Iju, Igoba, Ita Ogbolu and Ogbese). The predictions made by the model correlated strongly with observations from field study. The high risk zones corresponded to known endemic communities. This study revealed that environmental factors can be used in identifying and predicting the transmission of schistosomiasis as well as effective monitoring of disease risk in newly established rural and agricultural communities.

Geographic strain differentiation of <i>Schistosoma japonicum</i> in the Philippines using microsatellite markers

PLoS Neglected Tropical Diseases News - 10 July 2017 - 9:00pm

by Kharleezelle J. Moendeg, Jose Ma. M. Angeles, Ryo Nakao, Lydia R. Leonardo, Ian Kendrich C. Fontanilla, Yasuyuki Goto, Masashi Kirinoki, Elena A. Villacorte, Pilarita T. Rivera, Noboru Inoue, Yuichi Chigusa, Shin-ichiro Kawazu

Background

Microsatellites have been found to be useful in determining genetic diversities of various medically-important parasites which can be used as basis for an effective disease management and control program. In Asia and Africa, the identification of different geographical strains of Schistosoma japonicum, S. haematobium and S. mansoni as determined through microsatellites could pave the way for a better understanding of the transmission epidemiology of the parasite. Thus, the present study aims to apply microsatellite markers in analyzing the populations of S. japonicum from different endemic areas in the Philippines for possible strain differentiation.

Methodology/ Principal findings

Experimental mice were infected using the cercariae of S. japonicum collected from infected Oncomelania hupensis quadrasi snails in seven endemic municipalities. Adult worms were harvested from infected mice after 45 days of infection and their DNA analyzed against ten previously characterized microsatellite loci. High genetic diversity was observed in areas with high endemicity. The degree of genetic differentiation of the parasite population between endemic areas varies. Geographical separation was considered as one of the factors accounting for the observed difference between populations. Two subgroups have been observed in one of the study sites, suggesting that co-infection with several genotypes of the parasite might be present in the population. Clustering analysis showed no particular spatial structuring between parasite populations from different endemic areas. This result could possibly suggest varying degrees of effects of the ongoing control programs and the existing gene flow in the populations, which might be attributed to migration and active movement of infected hosts from one endemic area to another.

Conclusions/ Significance

Based on the results of the study, it is reasonable to conclude that genetic diversity could be one possible criterion to assess the infection status in highly endemic areas. Genetic surveillance using microsatellites is therefore important to predict the ongoing gene flow and degree of genetic diversity, which indirectly reflects the success of the control program in schistosomiasis-endemic areas.

Poor efficacy of preemptive amoxicillin clavulanate for preventing secondary infection from <i>Bothrops</i> snakebites in the Brazilian Amazon: A randomized controlled clinical trial

PLoS Neglected Tropical Diseases News - 10 July 2017 - 9:00pm

by Jacqueline A. G. Sachett, Iran Mendonça da Silva, Eliane Campos Alves, Sâmella S. Oliveira, Vanderson S. Sampaio, Fábio Francesconi do Vale, Gustavo Adolfo Sierra Romero, Marcelo Cordeiro dos Santos, Hedylamar Oliveira Marques, Mônica Colombini, Ana Maria Moura da Silva, Fan Hui Wen, Marcus V. G. Lacerda, Wuelton M. Monteiro, Luiz C. L. Ferreira

Background

Secondary bacterial infections from snakebites contribute to the high complication rates that can lead to permanent function loss and disabilities. Although common in endemic areas, routine empirical prophylactic use of antibiotics aiming to prevent secondary infection lacks a clearly defined policy. The aim of this work was to estimate the efficacy of amoxicillin clavulanate for reducing the secondary infection incidence in patients bitten by Bothrops snakes, and, secondarily, identify risk factors for secondary infections from snakebites in the Western Brazilian Amazon.

Methods and findings

This was an open-label, two-arm individually randomized superiority trial to prevent secondary infection from Bothrops snakebites. The antibiotic chosen for this clinical trial was oral amoxicillin clavulanate per seven days compared to no intervention. A total of 345 patients were assessed for eligibility in the study period. From this total, 187 accomplished the inclusion criteria and were randomized, 93 in the interventional group and 94 in the untreated control group. All randomized participants completed the 7 days follow-up period. Enzyme immunoassay confirmed Bothrops envenoming diagnosis in all participants. Primary outcome was defined as secondary infection (abscess and/or cellulitis) until day 7 after admission. Secondary infection incidence until 7 days after admission was 35.5% in the intervention group and 44.1% in the control group [RR = 0.80 (95%CI = 0.56 to 1.15; p = 0.235)]. Survival analysis demonstrated that the time from patient admission to the onset of secondary infection was not different between amoxicillin clavulanate treated and control group (Log-rank = 2.23; p = 0.789).Secondary infections incidence in 7 days of follow-up was independently associated to fibrinogen >400 mg/dL [AOR = 4.78 (95%CI = 2.17 to 10.55; p<0.001)], alanine transaminase >44 IU/L [AOR = 2.52 (95%CI = 1.06 to 5.98; p = 0.037)], C-reactive protein >6.5 mg/L [AOR = 2.98 (95%CI = 1.40 to 6.35; p = 0.005)], moderate pain [AOR = 24.30 (95%CI = 4.69 to 125.84; p<0.001)] and moderate snakebites [AOR = 2.43 (95%CI = 1.07 to 5.50; p = 0.034)].

Conclusions/Significance

Preemptive amoxicillin clavulanate was not effective for preventing secondary infections from Bothrops snakebites. Laboratorial markers, such as high fibrinogen, alanine transaminase and C-reactive protein levels, and severity clinical grading of snakebites, may help to accurately diagnose secondary infections.

Trial registration

Brazilian Clinical Trials Registry (ReBec): RBR-3h33wy; UTN Number: U1111-1169-1005.

Cardio-haemodynamic assessment and venous lactate in severe dengue: Relationship with recurrent shock and respiratory distress

PLoS Neglected Tropical Diseases News - 10 July 2017 - 9:00pm

by Sophie Yacoub, Trieu Huynh Trung, Phung Khanh Lam, Vuong Huynh Ngoc Thien, Duong Ha Thi Hai, Tu Qui Phan, Oanh Pham Kieu Nguyet, Nguyen Than Ha Quyen, Cameron Paul Simmons, Christopher Broyd, Gavin Robert Screaton, Bridget Wills

Background

Dengue can cause plasma leakage that may lead to dengue shock syndrome (DSS). In approximately 30% of DSS cases, recurrent episodes of shock occur. These patients have a higher risk of fluid overload, respiratory distress and poor outcomes. We investigated the association of echocardiographically-derived cardiac function and intravascular volume parameters plus lactate levels, with the outcomes of recurrent shock and respiratory distress in severe dengue.

Methods/Principle findings

We performed a prospective observational study in Paediatric and adult ICU, at the Hospital for Tropical Diseases (HTD), Ho Chi Minh City, Vietnam. Patients with dengue were enrolled within 12 hours of admission to paediatric or adult ICU. A haemodynamic assessment and portable echocardiograms were carried out daily for 5 days from enrolment and all interventions recorded.102 patients were enrolled; 22 patients did not develop DSS, 48 had a single episode of shock and 32 had recurrent shock. Patients with recurrent shock had a higher enrolment pulse than those with 1 episode or no shock (median: 114 vs. 100 vs. 100 b/min, P = 0.002), significantly lower Stroke Volume Index (SVI), (median: 21.6 vs. 22.8 vs. 26.8mls/m2, P<0.001) and higher lactate levels (4.2 vs. 2.9 vs. 2.2 mmol/l, P = 0.001). Higher SVI and worse left ventricular function (higher Left Myocardial Performance Index) on study days 3–5 was associated with the secondary endpoint of respiratory distress. There was an association between the total IV fluid administered during the ICU admission and respiratory distress (OR: 1.03, 95% CI 1.01–1.06, P = 0.001). Admission lactate levels predicted patients who subsequently developed recurrent shock (P = 0.004), and correlated positively with the total IV fluid volume received (rho: 0.323, P = 0.001) and also with admission ALT (rho: 0.764, P<0.001) and AST (rho: 0.773, P<0.001).

Conclusions/Significance

Echo-derived intravascular volume assessment and venous lactate levels can help identify dengue patients at high risk of recurrent shock and respiratory distress in ICU. These findings may serve to, not only assist in the management of DSS patients, but also these haemodynamic endpoints could be used in future dengue fluid intervention trials.

A novel, species-specific, real-time PCR assay for the detection of the emerging zoonotic parasite <i>Ancylostoma ceylanicum</i> in human stool

PLoS Neglected Tropical Diseases News - 10 July 2017 - 9:00pm

by Marina Papaiakovou, Nils Pilotte, Jessica R. Grant, Rebecca J. Traub, Stacey Llewellyn, James S. McCarthy, Alejandro J. Krolewiecki, Rubén Cimino, Rojelio Mejia, Steven A. Williams

Background

Molecular-based surveys have indicated that Ancylostoma ceylanicum, a zoonotic hookworm, is likely the second most prevalent hookworm species infecting humans in Asia. Most current PCR-based diagnostic options for the detection of Ancylostoma species target the Internal Transcribed Spacer (ITS) regions of the ribosomal gene cluster. These regions possess a considerable degree of conservation among the species of this genus and this conservation can lead to the misidentification of infecting species or require additional labor for accurate species-level determination. We have developed a novel, real-time PCR-based assay for the sensitive and species-specific detection of A. ceylanicum that targets a non-coding, highly repetitive genomic DNA element. Comparative testing of this PCR assay with an assay that targets ITS sequences was conducted on field-collected samples from Argentina and Timor-Leste to provide further evidence of the sensitivity and species-specificity of this assay.

Methods/Principal findings

A previously described platform for the design of primers/probe targeting non-coding highly repetitive regions was used for the development of this novel assay. The assay’s limits of detection (sensitivity) and cross-reactivity with other soil-transmitted helminth species (specificity) were assessed with real-time PCR experiments. The assay was successfully used to identify infections caused by A. ceylanicum that were previously only identified to the genus level as Ancylostoma spp. when analyzed using other published primer-probe pairings. Further proof of sensitive, species-specific detection was provided using a published, semi-nested restriction fragment length polymorphism-PCR assay that differentiates between Ancylostoma species.

Conclusions/Significance

Due to the close proximity of people and domestic/wild animals in many regions of the world, the potential for zoonotic infections is substantial. Sensitive tools enabling the screening for different soil-transmitted helminth infections are essential to the success of mass deworming efforts and facilitate the appropriate interpretation of data. This study describes a novel, species-specific, real-time PCR-based assay for the detection of A. ceylanicum that will help to address the need for such tools in integrated STH deworming programs.

Trial registration

ClinicalTrials.gov ACTRN12614000680662

Improper wound treatment and delay of rabies post-exposure prophylaxis of animal bite victims in China: Prevalence and determinants

PLoS Neglected Tropical Diseases News - 10 July 2017 - 9:00pm

by Qiaoyan Liu, Xiaojun Wang, Bing Liu, Yanhong Gong, Naomie Mkandawire, Wenzhen Li, Wenning Fu, Liqing Li, Yong Gan, Jun Shi, Bin Shi, Junan Liu, Shiyi Cao, Zuxun Lu

Background

Rabies is invariably a fatal disease. Appropriate wound treatment and prompt rabies post-exposure prophylaxis (PEP) are of great importance to rabies prevention. The objective of this study was to investigate the prevalence and influencing factors of improper wound treatment and delay of rabies PEP after an animal bite in Wuhan, China.

Methodology

This cross-sectional study was conducted among animal bite victims visiting rabies prevention clinics (RPCs). We selected respondents by a multistage sampling technique. A face-to-face interview was conducted to investigate whether the wound was treated properly and the time disparity between injury and attendance to the RPCs. Determinants of improper wound treatment and delay of rabies PEP were identified by a stepwise multivariate logistic regression analysis.

Principal findings

In total, 1,015 animal bite victims (564 women and 451 men) responded to the questionnaire, and the response rate was 93.98%. Overall, 81.2% of animal bite victims treated their wounds improperly after suspected rabies exposure, and 35.3% of animal bite victims delayed the initiation of PEP. Males (OR = 1.871, 95% CI: 1.318–2.656), residents without college education (OR = 1.698, 95% CI: 1.203–2.396), participants liking to play with animals (OR = 1.554, 95% CI: 1.089–2.216), and people who knew the fatality of rabies (OR = 1.577, 95% CI: 1.096–2.270), were more likely to treat wounds improperly after an animal bite. Patients aged 15–44 years (OR = 2.324, 95% CI: 1.457–3.707), who were bitten or scratched by a domestic animal (OR = 1.696, 95% CI: 1.103–2.608) and people who knew the incubation period of rabies (OR = 1.844, 95% CI: 1.279–2.659) were inclined to delay the initiation of PEP.

Conclusions

Our investigation shows that improper wound treatment and delayed PEP is common among animal bite victims, although RPCs is in close proximity and PEP is affordable. The lack of knowledge and poor awareness might be the main reason for improper PEP. Educational programs and awareness raising campaigns should be a priority to prevent rabies, especially targeting males, the less educated and those aged 15–44 years.

Congenital toxoplasmosis in Austria: Prenatal screening for prevention is cost-saving

PLoS Neglected Tropical Diseases News - 10 July 2017 - 9:00pm

by Andrea-Romana Prusa, David C. Kasper, Larry Sawers, Evelyn Walter, Michael Hayde, Eileen Stillwaggon

Background

Primary infection of Toxoplasma gondii during pregnancy can be transmitted to the unborn child and may have serious consequences, including retinochoroiditis, hydrocephaly, cerebral calcifications, encephalitis, splenomegaly, hearing loss, blindness, and death. Austria, a country with moderate seroprevalence, instituted mandatory prenatal screening for toxoplasma infection to minimize the effects of congenital transmission. This work compares the societal costs of congenital toxoplasmosis under the Austrian national prenatal screening program with the societal costs that would have occurred in a No-Screening scenario.

Methodology/Principal findings

We retrospectively investigated data from the Austrian Toxoplasmosis Register for birth cohorts from 1992 to 2008, including pediatric long-term follow-up until May 2013. We constructed a decision-analytic model to compare lifetime societal costs of prenatal screening with lifetime societal costs estimated in a No-Screening scenario. We included costs of treatment, lifetime care, accommodation of injuries, loss of life, and lost earnings that would have occurred in a No-Screening scenario and compared them with the actual costs of screening, treatment, lifetime care, accommodation, loss of life, and lost earnings. We replicated that analysis excluding loss of life and lost earnings to estimate the budgetary impact alone.Our model calculated total lifetime costs of €103 per birth under prenatal screening as carried out in Austria, saving €323 per birth compared with No-Screening. Without screening and treatment, lifetime societal costs for all affected children would have been €35 million per year; the implementation costs of the Austrian program are less than €2 million per year. Calculating only the budgetary impact, the national program was still cost-saving by more than €15 million per year and saved €258 million in 17 years.

Conclusions/Significance

Cost savings under a national program of prenatal screening for toxoplasma infection and treatment are outstanding. Our results are of relevance for health care providers by supplying economic data based on a unique national dataset including long-term follow-up of affected infants.

Comparison of a new multiplex real-time PCR with the Kato Katz thick smear and copro-antigen ELISA for the detection and differentiation of <i>Taenia</i> spp. in human stools

PLoS Neglected Tropical Diseases News - 7 July 2017 - 9:00pm

by Dinh Ng-Nguyen, Mark A. Stevenson, Pierre Dorny, Sarah Gabriël, Tinh Van Vo, Van-Anh Thi Nguyen, Trong Van Phan, Sze Fui Hii, Rebecca J. Traub

Background

Taenia solium, the cause of neurocysticercosis (NCC), has significant socioeconomic impacts on communities in developing countries. This disease, along with taeniasis is estimated to infect 2.5 to 5 million people globally. Control of T. solium NCC necessitates accurate diagnosis and treatment of T. solium taeniasis carriers. In areas where all three species of Taenia tapeworms (T. solium, Taenia saginata and Taenia asiatica) occur sympatrically, conventional microscope- and copro-antigen based diagnostic methods are unable to distinguish between these three Taenia species. Molecular diagnostic tools have been developed to overcome this limitation; however, conventional PCR-based techniques remain unsuitable for large-scale deployment in community-based surveys. Moreover, a real-time PCR (qPCR) for the discrimination of all three species of Taenia in human stool does not exist. This study describes the development and validation of a new triplex Taq-Man probe-based qPCR for the detection and discrimination of all three Taenia human tapeworms in human stools collected from communities in the Central Highlands of Vietnam. The diagnostic characteristics of the test are compared with conventional Kato Katz (KK) thick smear and copro-antigen ELISA (cAgELISA) method utilizing fecal samples from a community based cross-sectional study. Using this new multiplex real-time PCR we provide an estimate of the true prevalence of taeniasis in the source population for the community based cross-sectional study.

Methodology/Principal findings

Primers and TaqMan probes for the specific amplification of T. solium, T. saginata and T. asiatica were designed and successfully optimized to target the internal transcribed spacer I (ITS-1) gene of T. solium and the cytochrome oxidase subunit I (COX-1) gene of T. saginata and T. asiatica. The newly designed triplex qPCR (T3qPCR) was compared to KK and cAgELISA for the detection of Taenia eggs in stool samples collected from 342 individuals in Dak Lak province, Central Highlands of Vietnam. The overall apparent prevalence of taeniasis in Dak Lak province was 6.72% (95% confidence interval (CI) [3.94–9.50]) in which T. solium accounted for 1.17% (95% CI [0.37–3.17]), according to the T3qPCR. There was sympatric presence of T. solium, T. saginata and T. asiatica. The T3qPCR proved superior to KK and cAgELISA for the detection and differentiation of Taenia species in human feces. Diagnostic sensitivities of 0.94 (95% credible interval (CrI) [0.88–0.98]), 0.82 (95% CrI [0.58–0.95]) and 0.52 (95% CrI [0.07–0.94]), and diagnostic specificities of 0.98 (95% CrI [0.94–1.00]), 0.91 (95% CrI [0.85–0.96]) and 0.99 (95% CrI [0.96–1.00]) were estimated for the diagnosis of taeniasis for the T3qPCR, cAgELISA and KK thick smear in this study, respectively.

Conclusions

T3qPCR is not only superior to the KK thick smear and cAgELISA in terms of diagnostic sensitivity and specificity, but it also has the advantage of discriminating between species of Taenia eggs in stools. Application of this newly developed T3qPCR has identified the existence of all three human Taenia tapeworms in Dak Lak province and proves for the first time, the existence of T. asiatica in the Central Highlands and the south of Vietnam.

The sero-epidemiology of Rift Valley fever in people in the Lake Victoria Basin of western Kenya

PLoS Neglected Tropical Diseases News - 7 July 2017 - 9:00pm

by Elizabeth Anne Jessie Cook, Elysse Noel Grossi-Soyster, William Anson de Glanville, Lian Francesca Thomas, Samuel Kariuki, Barend Mark de Clare Bronsvoort, Claire Njeri Wamae, Angelle Desiree LaBeaud, Eric Maurice Fèvre

Rift Valley fever virus (RVFV) is a zoonotic arbovirus affecting livestock and people. This study was conducted in western Kenya where RVFV outbreaks have not previously been reported. The aims were to document the seroprevalence and risk factors for RVFV antibodies in a community-based sample from western Kenya and compare this with slaughterhouse workers in the same region who are considered a high-risk group for RVFV exposure. The study was conducted in western Kenya between July 2010 and November 2012. Individuals were recruited from randomly selected homesteads and a census of slaughterhouses. Structured questionnaire tools were used to collect information on demographic data, health, and risk factors for zoonotic disease exposure. Indirect ELISA on serum samples determined seropositivity to RVFV. Risk factor analysis for RVFV seropositivity was conducted using multi-level logistic regression. A total of 1861 individuals were sampled in 384 homesteads. The seroprevalence of RVFV in the community was 0.8% (95% CI 0.5–1.3). The variables significantly associated with RVFV seropositivity in the community were increasing age (OR 1.2; 95% CI 1.1–1.4, p<0.001), and slaughtering cattle at the homestead (OR 3.3; 95% CI 1.0–10.5, p = 0.047). A total of 553 slaughterhouse workers were sampled in 84 ruminant slaughterhouses. The seroprevalence of RVFV in slaughterhouse workers was 2.5% (95% CI 1.5–4.2). Being the slaughterman, the person who cuts the animal’s throat (OR 3.5; 95% CI 1.0–12.1, p = 0.047), was significantly associated with RVFV seropositivity. This study investigated and compared the epidemiology of RVFV between community members and slaughterhouse workers in western Kenya. The data demonstrate that slaughtering animals is a risk factor for RVFV seropositivity and that slaughterhouse workers are a high-risk group for RVFV seropositivity in this environment. These risk factors have been previously reported in other studies providing further evidence for RVFV circulation in western Kenya.

Dengue virus specific IgY provides protection following lethal dengue virus challenge and is neutralizing in the absence of inducing antibody dependent enhancement

PLoS Neglected Tropical Diseases News - 7 July 2017 - 9:00pm

by Ashley L. Fink, Katherine L. Williams, Eva Harris, Travis D. Alvine, Thomas Henderson, James Schiltz, Matthew L. Nilles, David S. Bradley

Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are severe disease manifestations that can occur following sequential infection with different dengue virus serotypes (DENV1-4). At present, there are no licensed therapies to treat DENV-induced disease. DHF and DSS are thought to be mediated by serotype cross-reactive antibodies that facilitate antibody-dependent enhancement (ADE) by binding to viral antigens and then Fcγ receptors (FcγR) on target myeloid cells. Using genetically engineered DENV-specific antibodies, it has been shown that the interaction between the Fc portion of serotype cross-reactive antibodies and FcγR is required to induce ADE. Additionally, it was demonstrated that these antibodies were as neutralizing as their non-modified variants, were incapable of inducing ADE, and were therapeutic following a lethal, antibody-enhanced infection. Therefore, we hypothesized that avian IgY, which do not interact with mammalian FcγR, would provide a novel therapy for DENV-induced disease. We demonstrate here that goose-derived anti-DENV2 IgY neutralized DENV2 and did not induce ADE in vitro. Anti-DENV2 IgY was also protective in vivo when administered 24 hours following a lethal DENV2 infection. We were also able to demonstrate via epitope mapping that both full-length and alternatively spliced anti-DENV2 IgY recognized different epitopes, including epitopes that have not been previously identified. These observations provide evidence for the potential therapeutic applications of goose-derived anti-DENV2 IgY.

The esperanza window trap reduces the human biting rate of <i>Simulium ochraceum</i> s.l. in formerly onchocerciasis endemic foci in Southern Mexico

PLoS Neglected Tropical Diseases News - 7 July 2017 - 9:00pm

by Mario A. Rodríguez-Pérez, Javier A. Garza-Hernández, Mario C. Salinas-Carmona, Ildefonso Fernández-Salas, Filiberto Reyes-Villanueva, Olga Real-Najarro, Eddie W. Cupp, Thomas R. Unnasch

Background

The Esperanza Window Trap (EWT) baited with CO2 and human sweat compounds is attractive to Simulium ochraceum s.l., the primary vector of Onchocerca volvulus in the historically largest endemic foci in México and Guatemala.

Methodology/Principal findings

The ability of the EWT to locally reduce numbers of questing S. ochraceum s.l. was evaluated in two formerly onchocerciasis endemic communities in Southern México. At each community, two EWTs were placed in or near a school or household and flies were collected sequentially for a total of 10 days. Black fly collections were then carried out for an additional 10 days in the absence of the EWTs. Flies were also collected outside the dwellings to control for variations in the local fly populations. When the EWTs were present, there was a significant reduction in the human biting rate at both the household and school locations at collection sites, with a greater effect observed in the schools.

Conclusions/Significance

These results indicate that the EWTs not only have potential as a black fly monitoring tool but may be used for reducing personal exposure to fly bites in Mesoamerica.

Ivermectin treatment of <i>Loa loa</i> hyper-microfilaraemic baboons (<i>Papio anubis</i>): Assessment of microfilarial loads, haematological and biochemical parameters and histopathological changes following treatment

PLoS Neglected Tropical Diseases News - 7 July 2017 - 9:00pm

by Samuel Wanji, Ebanga-Echi J. Eyong, Nicholas Tendongfor, Che J. Ngwa, Elive N. Esuka, Arnaud J. Kengne-Ouafo, Fabrice R. Datchoua-Poutcheu, Peter Enyong, Dalen Agnew, Rob R. Eversole, Adrian Hopkins, Charles D. Mackenzie

Background

Individuals with high intensity of Loa loa are at risk of developing serious adverse events (SAEs) post treatment with ivermectin. These SAEs have remained unclear and a programmatic impediment to the advancement of community directed treatment with ivermectin. The pathogenesis of these SAEs following ivermectin has never been investigated experimentally. The Loa/baboon (Papio anubis) model can be used to investigate the pathogenesis of Loa-associated encephalopathy following ivermectin treatment in humans.

Methods

12 baboons with microfilarial loads > 8,000mf/mL of blood were randomised into four groups: Group 1 (control group receiving no drug), Group 2 receiving ivermectin (IVM) alone, Group 3 receiving ivermectin plus aspirin (IVM + ASA), and Group 4 receiving ivermectin plus prednisone (IVM + PSE). Blood samples collected before treatment and at Day 5, 7 or 10 post treatment, were analysed for parasitological, hematological and biochemical parameters using standard techniques. Clinical monitoring of animals for side effects took place every 6 hours post treatment until autopsy. At autopsy free fluids and a large number of standard organs were collected, examined and tissues fixed in 10% buffered formalin and processed for standard haematoxylin-eosin staining and specific immunocytochemical staining.

Results

Mf counts dropped significantly (p<0.05) in all animals following ivermectin treatment with reductions as high as (89.9%) recorded; while no significant drop was observed in the control animals. Apart from haemoglobin (Hb) levels which recorded a significant (p = 0.028) drop post treatment, all other haematological and biochemical parameters did not show any significant changes (p>0.05). All animals became withdrawn 48 hours after IVM administration. All treated animals recorded clinical manifestations including rashes, itching, diarrhoea, conjunctival haemorrhages, lymph node enlargement, pinkish ears, swollen face and restlessness; one animal died 5 hours after IVM administration. Macroscopic changes in post-mortem tissues observed comprised haemorrhages in the brain, lungs, heart, which seen in all groups given ivermectin but not in the untreated animals. Microscopically, the major cellular changes seen, which were present in all the ivermectin treated animals included microfilariae in varying degrees of degeneration in small vessels. These were frequently associated with fibrin deposition, endothelial changes including damage to the integrity of the blood vessel and the presence of extravascular erythrocytes (haemorrhages). There was an increased presence of eosinophils and other chronic inflammatory types in certain tissues and organs, often in large numbers and associated with microfilarial destruction. Highly vascularized organs like the brain, heart, lungs and kidneys were observed to have more microfilariae in tissue sections. The number of mf seen in the brain and kidneys of animals administered IVM alone tripled that of control animals. Co-administration of IVM + PSE caused a greater increase in mf in the brain and kidneys while the reverse was noticed with the co-administration of IVM + ASA.

Conclusions

The treatment of Loa hyper-microfilaraemic individuals with ivermectin produces a clinical spectrum that parallels that seen in Loa hyper-microfilaraemic humans treated with ivermectin. The utilization of this experimental model can contribute to the improved management of the adverse responses in humans.

Impact of the Three Gorges project on ecological environment changes and snail distribution in Dongting Lake area

PLoS Neglected Tropical Diseases News - 6 July 2017 - 9:00pm

by Feiyue Li, Shujuan Ma, Yiyi Li, Hongzhuan Tan, Xunya Hou, Guanghui Ren, Kaiping Cai

Background

The Three Gorges Dam (TGD) is a remarkable, far-reaching project in China. This study was conducted to assess the impact of TGD on changes in the ecological environment, snail distribution and schistosomiasis transmission in Dongting Lake area.

Methods

Hydrological data were collected from 12 monitoring sites in Hunan section of Yangtze River before and after TGD was established. Data on snail distribution and human schistosomiasis infection were also collected. Correlation analyses were performed to detect the significance of snail distribution to changes in ecological environmental factors and human schistosomiasis infection.

Findings

A series of ecological environmental factors have changed in Dongting Lake area following the operation of TGD. Volume of annual runoff discharged into Dongting Lake declined by 20.85%. Annual sediment volume discharged into the lake and the mean lake sedimentation rate decreased by 73.9% and 32.2%, respectively. From 2003 to 2015, occurrence rate of frames with living snails and mean density of living snails decreased overall by 82.43% and 94.35%, respectively, with annual decrements being 13.49% and 21.29%. Moreover, human infection rate of schistosomiasis had decreased from 3.38% in 2003 to 0.44% in 2015, with a reduction of 86.98%. Correlation analyses showed that mean density of living snails was significantly associated with water level (r = 0.588, p<0.001), as well as the mean elevation range of the bottomland (r = 0.374, p = 0.025) and infection rate of schistosomiasis (r = 0.865, p<0.001).

Conclusion

Ecological environmental changes caused by the TGD were associated with distribution of snails, and might further affect the transmission and prevalence of schistosomiasis. Risk of schistosomiasis transmission still exists in Dongting Lake area and long-term monitoring is required.

The socio-economic burden of snakebite in Sri Lanka

PLoS Neglected Tropical Diseases News - 6 July 2017 - 9:00pm

by Anuradhani Kasturiratne, Arunasalam Pathmeswaran, A. Rajitha Wickremasinghe, Shaluka F. Jayamanne, Andrew Dawson, Geoff K. Isbister, Hithanadura Janaka de Silva, David G. Lalloo

Background

Snakebite is a major problem affecting the rural poor in many of the poorest countries in the tropics. However, the scale of the socio-economic burden has rarely been studied. We undertook a comprehensive assessment of the burden in Sri Lanka.

Methods

Data from a representative nation-wide community based household survey were used to estimate the number of bites and deaths nationally, and household and out of pocket costs were derived from household questionnaires. Health system costs were obtained from hospital cost accounting systems and estimates of antivenom usage. DALYs lost to snakebite were estimated using standard approaches using disability weights for poisoning.

Findings

79% of victims suffered economic loss following a snakebite with a median out of pocket expenditure of $11.82 (IQR 2–28.57) and a median estimated loss of income of $28.57 and $33.21 for those in employment or self-employment, respectively. Family members also lost income to help care for patients. Estimated health system costs for Sri Lanka were $ 10,260,652 annually. The annual estimated total number of DALYS was 11,101 to 15,076 per year for envenoming following snakebite.

Interpretation

Snakebite places a considerable economic burden on the households of victims in Sri Lanka, despite a health system which is accessible and free at the point of care. The disability burden is also considerable, similar to that of meningitis or dengue, although the relatively low case fatality rate and limited physical sequelae following bites by Sri Lankan snakes means that this burden may be less than in countries on the African continent.

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