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Household costs of hospitalized dengue illness in semi-rural Thailand

PLoS Neglected Tropical Diseases News - 22 September 2017 - 9:00pm

by Yesim Tozan, Pitcha Ratanawong, Maquines Odhiambo Sewe, Annelies Wilder-Smith, Pattamaporn Kittayapong

Background

Dengue-related illness is a leading cause of hospitalization and death in Thailand and other Southeast Asian countries, imposing a major economic burden on households, health systems, and governments. This study aims to assess the economic impact of hospitalized dengue cases on households in Chachoengsao province in eastern Thailand.

Methods

We conducted a prospective cost-of-illness study of hospitalized pediatric and adult dengue patients at three public hospitals. We examined all hospitalized dengue cases regardless of disease severity. Patients or their legal guardians were interviewed using a standard questionnaire to determine household-level medical and non-medical expenditures and income losses during the illness episode.

Results

Between March and September 2015, we recruited a total of 224 hospitalized patients (<5 years, 4%; 5–14 years, 20%, 15–24 years, 36%, 25–34 years, 15%; 35–44 years, 10%; 45+ years, 12%), who were clinically diagnosed with dengue. The total cost of a hospitalized dengue case was higher for adult patients than pediatric patients, and was US$153.6 and US$166.3 for pediatric DF and DHF patients, respectively, and US$171.2 and US$226.1 for adult DF and DHF patients, respectively. The financial burden on households increased with the severity of dengue illness.

Conclusions

Although 74% of the households reported that the patient received free medical care, hospitalized dengue illness cost approximately 19–23% of the monthly household income. These results indicated that dengue imposed a substantial financial burden on households in Thailand where a great majority of the population was covered by the Universal Coverage Scheme for health care.

Recombinant vaccines of a CD4<sup>+</sup> T-cell epitope promote efficient control of <i>Paracoccidioides brasiliensis</i> burden by restraining primary organ infection

PLoS Neglected Tropical Diseases News - 22 September 2017 - 9:00pm

by Rodrigo Assunção Holanda, Julián Esteban Muñoz, Lucas Santos Dias, Leandro Buffoni Roque Silva, Julliana Ribeiro Alves Santos, Sthefany Pagliari, Érica Leandro Marciano Vieira, Tatiane Alves Paixão, Carlos Pelleschi Taborda, Daniel Assis Santos, Oscar Bruña-Romero

Paracoccidioidomycosis (PCM) is an infectious disease endemic to South America, caused by the thermally dimorphic fungi Paracoccidioides. Currently, there is no effective human vaccine that can be used in prophylactic or therapeutic regimes. We tested the hypothesis that the immunogenicity of the immunodominant CD4+ T-cell epitope (P10) of Paracoccidioides brasiliensis gp43 antigen might be significantly enhanced by using a hepatitis B virus-derived particle (VLP) as an antigen carrier. This chimera was administered to mice as a (His)6-purified protein (rPbT) or a replication-deficient human type 5 adenoviral vector (rAdPbT) in an immunoprophylaxis assay. The highly virulent Pb18 yeast strain was used to challenge our vaccine candidates. Fungal challenge evoked robust P10-specific memory CD4+ T cells secreting protective Th-1 cytokines in most groups of immunized mice. Furthermore, the highest level of fungal burden control was achieved when rAdPbT was inoculated in a homologous prime-boost regimen, with 10-fold less CFU recovering than in non-vaccinated mice. Systemic Pb18 spreading was only prevented when rAdPbT was previously inoculated. In summary, we present here VLP/P10 formulations as vaccine candidates against PCM, some of which have demonstrated for the first time their ability to prevent progression of this pernicious fungal disease, which represents a significant social burden in developing countries.

Molecular genomic characterization of tick- and human-derived severe fever with thrombocytopenia syndrome virus isolates from South Korea

PLoS Neglected Tropical Diseases News - 22 September 2017 - 9:00pm

by Seok-Min Yun, Su-Jin Park, Sun-Whan Park, WooYoung Choi, Hye Won Jeong, Young-Ki Choi, Won-Ja Lee

Background

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease caused by the SFTS virus (SFTSV) from Bunyaviridae that is endemic in East Asia. However, the genetic and evolutionary characteristics shared between tick- and human-derived Korean SFTSV strains are still limited.

Methodology/Principal findings

In this study we identify, for the first time, the genome sequence of a tick (Haemaphysalis longicornis)-derived Korean SFTSV strain (designated as KAGWT) and compare this virus with recent human SFTSV isolates to identify the genetic variations and relationships among SFTSV strains. The genome of the KAGWT strain is consistent with the described genome of other members of the genus Phlebovirus with 6,368 nucleotides (nt), 3,378 nt, and 1,746 nt in the Large (L), Medium (M) and Small (S) segments, respectively. Compared with other completely sequenced human-derived Korean SFTSV strains, the KAGWT strain had highest sequence identities at the nucleotide and deduced amino acid level in each segment with the KAGWH3 strain which was isolated from SFTS patient within the same region, although there is one unique amino acid substitution in the Gn protein (A66S). Phylogenetic analyses of complete genome sequences revealed that at least four different genotypes of SFTSV are co-circulating in South Korea, and that the tick- and human-derived Korean SFTSV strains (genotype B) are closely related to one another. Although we could not detect reassortant, which are commonly observed in segmented viruses, further large-scale surveillance and detailed genomic analysis studies are needed to better understand the molecular epidemiology, genetic diversity, and evolution of SFTSV.

Conclusions/Significance

Full-length sequence analysis revealed a clear association between the genetic origins of tick- and human-derived SFTSV strains. While the most prevalent Korean SFTSV is genotype B, at least four different genotypes of SFTSV strains are co-circulating in South Korea. These findings provide information regarding the molecular epidemiology, genetic diversity, and evolution of SFTSV in East Asia.

Low antibody prevalence against <i>Bacillus cereus</i> biovar <i>anthracis</i> in Taï National Park, Côte d'Ivoire, indicates high rate of lethal infections in wildlife

PLoS Neglected Tropical Diseases News - 21 September 2017 - 9:00pm

by Fee Zimmermann, Susanne M. Köhler, Kathrin Nowak, Susann Dupke, Anne Barduhn, Ariane Düx, Alexander Lang, Hélène M. De Nys, Jan F. Gogarten, Roland Grunow, Emmanuel Couacy-Hymann, Roman M. Wittig, Silke R. Klee, Fabian H. Leendertz

Bacillus cereus biovar anthracis (Bcbva) is a member of the B. cereus group which carries both B. anthracis virulence plasmids, causes anthrax-like disease in various wildlife species and was described in several sub-Saharan African rainforests. Long-term monitoring of carcasses in Taï National Park, Côte d’Ivoire, revealed continuous wildlife mortality due to Bcbva in a broad range of mammalian species. While non-lethal anthrax infections in wildlife have been described for B. anthracis, nothing is known about the odds of survival following an anthrax infection caused by Bcbva. To address this gap, we present the results of a serological study of anthrax in five wildlife species known to succumb to Bcbva in this ecosystem. Specific antibodies were only detected in two out of 15 wild red colobus monkeys (Procolobus badius) and one out of 10 black-and-white colobus monkeys (Colobus polykomos), but in none of 16 sooty mangabeys (Cercocebus atys), 9 chimpanzees (Pan troglodytes verus) and 9 Maxwell’s duikers (Cephalophus maxwellii). The combination of high mortality and low antibody detection rates indicates high virulence of this disease across these different mammalian species.

Evaluation of the pharmacokinetic-pharmacodynamic relationship of praziquantel in the <i>Schistosoma mansoni</i> mouse model

PLoS Neglected Tropical Diseases News - 21 September 2017 - 9:00pm

by Nada Abla, Jennifer Keiser, Mireille Vargas, Natalie Reimers, Helmut Haas, Thomas Spangenberg

After more than 40 years of use, Praziquantel (PZQ) still remains the drug of choice for the treatment of intestinal and urogenital schistosomiasis. Its anti-parasitic activity resides primarily in the (R)-enantiomer. Hitherto neither the molecular target nor the pharmacokinetic-pharmacodynamic relationship have been fully elucidated. Here we investigated the efficacy and pharmacokinetics of PZQ in the Schistosoma mansoni mouse model to determine the key factors that drive its efficacy. Dose-response studies with racemic PZQ with or without addition of an irreversible pan-cytochrome P450 (CYP) inhibitor, 1-aminobenzotriazole (ABT), were performed. In addition, efficacy of PZQ in the presence of the CYP inducer, dexamethasone (DEX), was determined. Plasma samples were obtained by tail vein bleeding at 4 time points. The (R)-PZQ levels were determined using a LC-MS/MS method. Non-compartmental pharmacokinetic analysis was performed using PKsolver. In addition, experiments using an enhanced in vitro assay were conducted. We found that the use of ABT increased (R)-PZQ plasma exposures in the systemic circulation by ~10 to 20 fold but the latter were not predictive of efficacy. The use of DEX decreased plasma exposures of (R)-PZQ in the systemic circulation by ~10 fold without reducing efficacy. We extrapolated the (R)-PZQ concentrations in mouse portal vein / mesenteric veins from the systemic exposures and found that a free exposure of (R)-PZQ of ~ 20 μM*h in the portal vein was needed to obtain a worm burden reduction >60%. It is suggested that the high (R)-PZQ concentrations available before the hepatic first pass metabolism drive the efficacy against S. mansoni adult worms residing in the mesenteric veins. It is then possible that the current dosing regimen of 40 mg/kg in preventive chemotherapy programs may provide suboptimal concentrations in low-weight patients such as children, due to smaller total amounts of drug administered, and may consequently result in lower cure rates.

Estimating the prevalence and intensity of <i>Schistosoma mansoni</i> infection among rural communities in Western Tanzania: The influence of sampling strategy and statistical approach

PLoS Neglected Tropical Diseases News - 21 September 2017 - 9:00pm

by Jared S. Bakuza, Matthew J. Denwood, Gamba Nkwengulila, Barbara K. Mable

Background

Schistosoma mansoni is a parasite of major public health importance in developing countries, where it causes a neglected tropical disease known as intestinal schistosomiasis. However, the distribution of the parasite within many endemic regions is currently unknown, which hinders effective control. The purpose of this study was to characterize the prevalence and intensity of infection of S. mansoni in a remote area of western Tanzania.

Methodology/Principal findings

Stool samples were collected from 192 children and 147 adults residing in Gombe National Park and four nearby villages. Children were actively sampled in local schools, and adults were sampled passively by voluntary presentation at the local health clinics. The two datasets were therefore analysed separately. Faecal worm egg count (FWEC) data were analysed using negative binomial and zero-inflated negative binomial (ZINB) models with explanatory variables of site, sex, and age. The ZINB models indicated that a substantial proportion of the observed zero FWEC reflected a failure to detect eggs in truly infected individuals, meaning that the estimated true prevalence was much higher than the apparent prevalence as calculated based on the simple proportion of non-zero FWEC. For the passively sampled data from adults, the data were consistent with close to 100% true prevalence of infection. Both the prevalence and intensity of infection differed significantly between sites, but there were no significant associations with sex or age.

Conclusions/Significance

Overall, our data suggest a more widespread distribution of S. mansoni in this part of Tanzania than was previously thought. The apparent prevalence estimates substantially under-estimated the true prevalence as determined by the ZINB models, and the two types of sampling strategies also resulted in differing conclusions regarding prevalence of infection. We therefore recommend that future surveillance programmes designed to assess risk factors should use active sampling whenever possible, in order to avoid the self-selection bias associated with passive sampling.

Platelet dysfunction contributes to bleeding complications in patients with probable leptospirosis

PLoS Neglected Tropical Diseases News - 21 September 2017 - 9:00pm

by Rahajeng N. Tunjungputri, Muhammad Hussein Gasem, Willemijn van der Does, Pandu H. Sasongko, Bambang Isbandrio, Rolf T. Urbanus, Philip G. de Groot, Andre van der Ven, Quirijn de Mast

Background

Severe leptospirosis is frequently complicated by a hemorrhagic diathesis, of which the pathogenesis is still largely unknown. Thrombocytopenia is common, but often not to the degree that spontaneous bleeding is expected. We hypothesized that the hemorrhagic complications are not only related to thrombocytopenia, but also to platelet dysfunction, and that increased binding of von Willebrand factor (VWF) to platelets is involved in both platelet dysfunction and increased platelet clearance.

Methodology/Principal findings

A prospective study was carried out in Semarang, Indonesia, enrolling 33 hospitalized patients with probable leptospirosis, of whom 15 developed clinical bleeding, and 25 healthy controls. Platelet activation and reactivity were determined using flow cytometry by measuring the expression of P-selectin and activation of the αIIbβ3 integrin by the binding of fibrinogen in unstimulated samples and after ex vivo stimulation by the platelet agonists adenosine-diphosphate (ADP) and thrombin-receptor activating peptide (TRAP). Platelet-VWF binding, before and after VWF stimulation by ristocetin, as well as plasma levels of VWF, active VWF, the VWF-inactivating enzyme ADAMTS13, thrombin-antithrombin complexes (TAT) and P-selectin were also measured. Bleeding complications were graded using the WHO bleeding scale. Our study revealed that platelet activation, with a secondary platelet dysfunction, is a feature of patients with probable leptospirosis, especially in those with bleeding manifestations. There was a significant inverse correlation of bleeding score with TRAP-stimulated P-selectin and platelet-fibrinogen binding (R = -0.72, P = 0.003 and R = -0.66, P = 0.01, respectively) but not with platelet count. Patients with bleeding also had a significantly higher platelet-VWF binding. Platelet counts were inversely correlated with platelet-VWF binding (R = -0.74; P = 0.0009. There were no correlations between platelet-VWF binding and the degree of platelet dysfunction, suggesting that increased platelet-VWF binding does not directly interfere with the platelet αIIbβ3 signaling pathway in patients with probable leptospirosis.

Conclusion/Significance

Platelet dysfunction is common in probable leptospirosis patients with manifest bleeding. Increased VWF-platelet binding may contribute to the activation and clearance of platelets.

A scoring model for predicting prognosis of patients with severe fever with thrombocytopenia syndrome

PLoS Neglected Tropical Diseases News - 21 September 2017 - 9:00pm

by Bei Jia, Xiaomin Yan, Yuxin Chen, Guiyang Wang, Yong Liu, Biyun Xu, Peixin Song, Yang Li, Yali Xiong, Weihua Wu, Yingying Hao, Juan Xia, Zhaoping Zhang, Rui Huang, Chao Wu

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging epidemic infectious disease caused by the SFTS bunyavirus (SFTSV) with an estimated high case-fatality rate of 12.7% to 32.6%. Currently, the disease has been reported in mainland China, Japan, Korea, and the United States. At present, there is no specific antiviral therapy for SFTSV infection. Considering the higher mortality rate and rapid clinical progress of SFTS, supporting the appropriate treatment in time to SFTS patients is critical. Therefore, it is very important for clinicians to predict these SFTS cases who are more likely to have a poor prognosis or even more likely to decease. In the present study, we established a simple and feasible model for assessing the severity and predicting the prognosis of SFTS patients with high sensitivity and specificity. This model may aid the physicians to immediately initiate prompt treatment to block the rapid development of the illness and reduce the fatality of SFTS patients.

Updated estimation of the impact of a Japanese encephalitis immunization program with live, attenuated SA 14-14-2 vaccine in Nepal

PLoS Neglected Tropical Diseases News - 21 September 2017 - 9:00pm

by Shyam Raj Upreti, Nicole P. Lindsey, Rajendra Bohara, Ganga Ram Choudhary, Sushil Shakya, Mukunda Gautam, Jagat Narain Giri, Marc Fischer, Susan L. Hills

Background

Japanese encephalitis (JE) is a mosquito-borne disease that is associated with considerable morbidity and mortality in many Asian countries. The objective of this study was to describe the impact of the JE immunization program using SA 14-14-2 JE vaccine implemented in Nepal during 2006 through 2011. A previous assessment after the initial program implementation phase described a significantly lower post-campaign JE incidence compared to expected incidence; however, the previous evaluation had limited post-campaign data for some districts.

Methodology/Principal findings

JE and acute encephalitis syndrome (AES) data gathered through Nepal’s routine surveillance system from 2004 through 2014 were analyzed to assess the impact of the JE immunization program implemented in 31 districts. Expected incidence rates were determined by calculating the incidence of cases per 100,000 person-years in each district before the vaccination campaigns. This rate was applied to the relevant population after the vaccination campaigns, which provided the expected number of cases had the campaign not occurred. The observed incidence rate was the number of reported cases per 100,000 person-years post-campaign. Expected and observed JE and AES cases and incidence rates were compared. The post-campaign JE incidence rate of 0.7 cases per 100,000 was 78% (95% CI 76%–79%) lower than expected had no campaign occurred and an estimated 3,011 (95% CI 2,941–3,057) JE cases were prevented. The post-vaccination AES incidence of 5.5 cases per 100,000 was 59% (58%–60%) lower than the expected and an estimated 9,497 (95% CI 9,268–9,584) AES cases were prevented.

Conclusions/Significance

This analysis strengthens previous findings of the substantial impact of Nepal’s JE immunization program using SA 14-14-2 JE vaccine.

<i>“Koko et les lunettes magiques”</i>: An educational entertainment tool to prevent parasitic worms and diarrheal diseases in Côte d’Ivoire

PLoS Neglected Tropical Diseases News - 21 September 2017 - 9:00pm

by Clémence Essé, Véronique A. Koffi, Abel Kouamé, Kouassi Dongo, Richard B. Yapi, Honorine M. Moro, Christiane A. Kouakou, Marta S. Palmeirim, Bassirou Bonfoh, Eliézer K. N’Goran, Jürg Utzinger, Giovanna Raso

Background

Integrated control programs, emphasizing preventive chemotherapy along with health education, can reduce the incidence of soil-transmitted helminthiasis and schistosomiasis. The aim of this study was to develop an educational animated cartoon to improve school children’s awareness regarding soil-transmitted helminthiasis, diarrheal diseases, and related hygiene practices in Côte d’Ivoire. The key messages included in the cartoon were identified through prior formative research to specifically address local knowledge gaps.

Methodology

In a first step, preliminary research was conducted to assess the knowledge, attitudes, practices, and beliefs of school-aged children regarding parasitic worm infections and hygiene, to identify key health messages to be included in an animated cartoon. Second, an animated cartoon was produced, which included the drafting of the script and story board, and the production of the cartoon’s initial version. Finally, the animated cartoon was pilot tested in eight selected schools and further fine-tuned.

Principal findings

According to the questionnaire results, children believed that the consumption of sweet food, eating without washing their hands, sitting on the floor, and eating spoiled food were the main causes of parasitic worm infections. Abdominal pain, diarrhea, lack of appetite, failure to grow, and general fatigue were mentioned as symptoms of parasitic worm infections. Most of the children knew that they should go to the hospital for treatment if they experienced symptoms of parasitic worm diseases. The animated cartoon titled “Koko et les lunettes magiques” was produced by Afrika Toon, in collaboration with a scientific team composed of epidemiologists, civil engineers, and social scientists, and the local school children and teachers. Pilot testing of the animated cartoon revealed that, in the short term, children grasped and kept key messages. Most of the children who were shown the cartoon reported to like it.

Conclusion/Significances

Acceptance of the animated cartoon was high among children and teachers alike. The messaging was tailored to improve knowledge and practices for prevention of helminthiases and diarrheal diseases through prior identification of knowledge gaps. Integration of such education tools into the school curriculum, along with deworming campaigns, might improve sustainability of control and elimination efforts against helminthiases and diarrheal diseases.

Differential virulence between Asian and African lineages of Zika virus

PLoS Neglected Tropical Diseases News - 21 September 2017 - 9:00pm

by Yannick Simonin, Debby van Riel, Philippe Van de Perre, Barry Rockx, Sara Salinas

Mucosal leishmaniasis mimicking T-cell lymphoma in a patient receiving monoclonal antibody against TNFα

PLoS Neglected Tropical Diseases News - 21 September 2017 - 9:00pm

by Antonio Carlos Nicodemo, Daniel Fernandes Duailibi, Diego Feriani, Maria Irma Seixas Duarte, Valdir Sabbaga Amato

The clinical and microbiological characteristics of enteric fever in Cambodia, 2008-2015

PLoS Neglected Tropical Diseases News - 20 September 2017 - 9:00pm

by Laura M. F. Kuijpers, Thong Phe, Chhun H. Veng, Kruy Lim, Sovann Ieng, Chun Kham, Nizar Fawal, Laetitia Fabre, Simon Le Hello, Erika Vlieghe, François-Xavier Weill, Jan Jacobs, Willy E. Peetermans

Background

Enteric fever remains a major public health problem in low resource settings and antibiotic resistance is increasing. In Asia, an increasing proportion of infections is caused by Salmonella enterica serovar Paratyphi A, which for a long time was assumed to cause a milder clinical syndrome compared to Salmonella enterica serovar Typhi.

Methodology

A retrospective chart review study was conducted of 254 unique cases of blood culture confirmed enteric fever who presented at a referral adult hospital in Phnom Penh, Cambodia between 2008 and 2015. Demographic, clinical and laboratory data were collected from clinical charts and antibiotic susceptibility testing was performed. Whole genome sequence analysis was performed on a subset of 121 isolates.

Results

One-hundred-and-ninety unique patients were diagnosed with Salmonella Paratyphi A and 64 with Salmonella Typhi. In the period 2008–2012, Salmonella Paratyphi A comprised 25.5% of 47 enteric fever cases compared to 86.0% of 207 cases during 2013–2015. Presenting symptoms were identical for both serovars but higher median leukocyte counts (6.8 x 109/L vs. 6.3 x 109/L; p = 0.035) and C-reactive protein (CRP) values (47.0 mg/L vs. 36 mg/L; p = 0.034) were observed for Salmonella Typhi infections. All but one of the Salmonella Typhi isolates belonged to haplotype H58 associated with multidrug resistance (MDR) (i.e. resistance to ampicillin, chloramphenicol and co-trimoxazole).;42.9% actually displayed MDR compared to none of the Salmonella Paratyphi A isolates. Decreased ciprofloxacin susceptibility (DCS) was observed in 96.9% (62/64) of Salmonella Typhi isolates versus 11.5% (21/183) of Salmonella Paratyphi A isolates (all but one from 2015). All isolates were susceptible to azithromycin and ceftriaxone.

Conclusions

In Phnom Penh, Cambodia, Salmonella Paratyphi A now causes the majority of enteric fever cases and decreased susceptibility against ciprofloxacin is increasing. Overall, Salmonella Typhi was significantly more associated with MDR and DCS compared to Salmonella Paratyphi A.

Pyrethroid resistance alters the blood-feeding behavior in Puerto Rican <i>Aedes aegypti</i> mosquitoes exposed to treated fabric

PLoS Neglected Tropical Diseases News - 20 September 2017 - 9:00pm

by Natasha M. Agramonte, Jeffrey R. Bloomquist, Ulrich R. Bernier

Emerging insecticide resistance is a major issue for vector control. It decreases the effectiveness of insecticides, thereby requiring greater quantities for comparable control with a net increase in risk of disease resurgence, product cost, and damage risk to the ecosystem. Pyrethroid resistance has been documented in Puerto Rican populations of Aedes aegypti (L.) mosquitoes. In this study, topical toxicity of five insecticides (permethrin, etofenprox, deltamethrin, DDT, transfluthrin) was determined for susceptible (Orlando—ORL) and resistant (Puerto Rico—PR) strains of Ae. aegypti. Resistance ratios were calculated using LD50 values, and high resistance ratios for permethrin (112) and etofenprox (228) were observed for the Puerto Rico strain. Behavioral differences in blood-feeding activity for pyrethroid-resistant and pyrethroid-susceptible strains of Ae. aegypti when exposed to pyrethroid-treated cloth were also explored. Strains were exposed for 15 min to a range of concentrations of pyrethroid-treated uniform fabric in a cage that contained 60 female Ae. aegypti mosquitoes. Interestingly, the resistance ratios for blood-feeding were similar for permethrin (61) and etofenprox (70), but were lower than their respective resistance ratios for topical toxicity, suggesting that knockdown resistance was the primary mechanism of resistance in the blood feeding assays. Results showed a rightward shift in the dose-response curves for blood-feeding that indicated higher concentrations of pyrethroids were necessary to deter blood-feeding behavior in the pyrethroid-resistant Puerto Rican strain of Ae. aegypti.

Metabolomics analyses identify platelet activating factors and heme breakdown products as Lassa fever biomarkers

PLoS Neglected Tropical Diseases News - 18 September 2017 - 9:00pm

by Trevor V. Gale, Timothy M. Horton, Donald S. Grant, Robert F. Garry

Lassa fever afflicts tens of thousands of people in West Africa annually. The rapid progression of patients from febrile illness to fulminant syndrome and death provides incentive for development of clinical prognostic markers that can guide case management. The small molecule profile of serum from febrile patients triaged to the Viral Hemorrhagic Fever Ward at Kenema Government Hospital in Sierra Leone was assessed using untargeted Ultra High Performance Liquid Chromatography Mass Spectrometry. Physiological dysregulation resulting from Lassa virus (LASV) infection occurs at the small molecule level. Effects of LASV infection on pathways mediating blood coagulation, and lipid, amino acid, nucleic acid metabolism are manifest in changes in the levels of numerous metabolites in the circulation. Several compounds, including platelet activating factor (PAF), PAF-like molecules and products of heme breakdown emerged as candidates that may prove useful in diagnostic assays to inform better care of Lassa fever patients.

Detecting and confirming residual hotspots of lymphatic filariasis transmission in American Samoa 8 years after stopping mass drug administration

PLoS Neglected Tropical Diseases News - 18 September 2017 - 9:00pm

by Colleen L. Lau, Sarah Sheridan, Stephanie Ryan, Maureen Roineau, Athena Andreosso, Saipale Fuimaono, Joseph Tufa, Patricia M. Graves

The Global Programme to Eliminate Lymphatic Filariasis (LF) aims to eliminate the disease as a public health problem by 2020 by conducting mass drug administration (MDA) and controlling morbidity. Once elimination targets have been reached, surveillance is critical for ensuring that programmatic gains are sustained, and challenges include timely identification of residual areas of transmission. WHO guidelines encourage cost-efficient surveillance, such as integration with other population-based surveys. In American Samoa, where LF is caused by Wucheraria bancrofti, and Aedes polynesiensis is the main vector, the LF elimination program has made significant progress. Seven rounds of MDA (albendazole and diethycarbamazine) were completed from 2000 to 2006, and Transmission Assessment Surveys were passed in 2010/2011 and 2015. However, a seroprevalence study using an adult serum bank collected in 2010 detected two potential residual foci of transmission, with Og4C3 antigen (Ag) prevalence of 30.8% and 15.6%. We conducted a follow up study in 2014 to verify if transmission was truly occurring by comparing seroprevalence between residents of suspected hotspots and residents of other villages. In adults from non-hotspot villages (N = 602), seroprevalence of Ag (ICT or Og4C3), Bm14 antibody (Ab) and Wb123 Ab were 1.2% (95% CI 0.6–2.6%), 9.6% (95% CI 7.5%-12.3%), and 10.5% (95% CI 7.6–14.3%), respectively. Comparatively, adult residents of Fagali’i (N = 38) had significantly higher seroprevalence of Ag (26.9%, 95% CI 17.3–39.4%), Bm14 Ab (43.4%, 95% CI 32.4–55.0%), and Wb123 Ab 55.2% (95% CI 39.6–69.8%). Adult residents of Ili’ili/Vaitogi/Futiga (N = 113) also had higher prevalence of Ag and Ab, but differences were not statistically significant. The presence of transmission was demonstrated by 1.1% Ag prevalence (95% CI 0.2% to 3.1%) in 283 children aged 7–13 years who lived in one of the suspected hotspots; and microfilaraemia in four individuals, all of whom lived in the suspected hotspots, including a 9 year old child. Our results provide field evidence that integrating LF surveillance with other surveys is effective and feasible for identifying potential hotspots, and conducting surveillance at worksites provides an efficient method of sampling large populations of adults.

A DNA vaccine for Crimean-Congo hemorrhagic fever protects against disease and death in two lethal mouse models

PLoS Neglected Tropical Diseases News - 18 September 2017 - 9:00pm

by Aura R. Garrison, Charles J. Shoemaker, Joseph W. Golden, Collin J. Fitzpatrick, John J. Suschak, Michelle J. Richards, Catherine V. Badger, Carolyn M. Six, Jacqueline D. Martin, Drew Hannaman, Marko Zivcec, Eric Bergeron, Jeffrey W. Koehler, Connie S. Schmaljohn

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus capable of causing a severe hemorrhagic fever disease in humans. There are currently no licensed vaccines to prevent CCHFV-associated disease. We developed a DNA vaccine expressing the M-segment glycoprotein precursor gene of CCHFV and assessed its immunogenicity and protective efficacy in two lethal mouse models of disease: type I interferon receptor knockout (IFNAR-/-) mice; and a novel transiently immune suppressed (IS) mouse model. Vaccination of mice by muscle electroporation of the M-segment DNA vaccine elicited strong antigen-specific humoral immune responses with neutralizing titers after three vaccinations in both IFNAR-/- and IS mouse models. To compare the protective efficacy of the vaccine in the two models, groups of vaccinated mice (7–10 per group) were intraperitoneally (IP) challenged with a lethal dose of CCHFV strain IbAr 10200. Weight loss was markedly reduced in CCHFV DNA-vaccinated mice as compared to controls. Furthermore, whereas all vector-control vaccinated mice succumbed to disease by day 5, the DNA vaccine protected >60% of the animals from lethal disease. Mice from both models developed comparable levels of antibodies, but the IS mice had a more balanced Th1/Th2 response to vaccination. There were no statistical differences in the protective efficacies of the vaccine in the two models. Our results provide the first comparison of these two mouse models for assessing a vaccine against CCHFV and offer supportive data indicating that a DNA vaccine expressing the glycoprotein genes of CCHFV elicits protective immunity against CCHFV.

Eco-epidemiological analysis of rickettsial seropositivity in rural areas of Colombia: A multilevel approach

PLoS Neglected Tropical Diseases News - 18 September 2017 - 9:00pm

by Juan C. Quintero V., Luis E. Paternina T., Alexander Uribe Y., Carlos Muskus, Marylin Hidalgo., Juliana Gil., Astrid Vanessa Cienfuegos G., Lisardo Osorio Q., Carlos Rojas A.

Rickettsiosis is a re-emergent infectious disease without epidemiological surveillance in Colombia. This disease is generally undiagnosed and several deadly outbreaks have been reported in the country in the last decade. The aim of this study is to analyze the eco-epidemiological aspects of rickettsial seropositivity in rural areas of Colombia where outbreaks of the disease were previously reported. A cross-sectional study, which included 597 people living in 246 households from nine hamlets in two municipalities of Colombia, was conducted from November 2015 to January 2016. The survey was conducted to collect sociodemographic and household characteristics (exposure) data. Blood samples were collected to determine the rickettsial seropositivity in humans, horses and dogs (IFA, cut-off = 1/128). In addition, infections by rickettsiae were detected in ticks from humans and animals by real-time PCR targeting gltA and ompA genes. Data was analyzed by weighted multilevel clog-log regression model using three levels (person, household and hamlets) and rickettsial seropositivity in humans was the main outcome. Overall prevalence of rickettsial seropositivity in humans was 25.62% (95%CI 22.11–29.12). Age in years (PR = 1.01 95%CI 1.01–1.02) and male sex (PR = 1.65 95%CI 1.43–1.90) were risk markers for rickettsial seropositivity. Working outdoors (PR = 1.20 95%CI 1.02–1.41), deforestation and forest fragmentation for agriculture use (PR = 1.75 95%CI 1.51–2.02), opossum in peridomiciliary area (PR = 1.56 95%CI 1.37–1.79) and a high proportion of seropositive domestic animals in the home (PR20-40% vs <20% = 2.28 95%CI 1.59–3.23 and PR>40% vs <20% = 3.14 95%CI 2.43–4.04) were associated with rickettsial seropositivity in humans. This study showed the presence of Rickettsia antibodies in human populations and domestic animals. In addition, different species of rickettsiae were detected in ticks collected from humans and animals. Our results highlighted the role of domestic animals as sentinels of rickettsial infection to identify areas at risk of transmission, and the importance of preventive measures aimed at curtailing deforestation and the fragmentation of forests as a way of reducing the risk of transmission of emergent and re-emergent pathogens.

Rapid, actionable diagnosis of urban epidemic leptospirosis using a pathogenic <i>Leptospira lipL32</i>-based real-time PCR assay

PLoS Neglected Tropical Diseases News - 15 September 2017 - 9:00pm

by Irina N. Riediger, Robyn A. Stoddard, Guilherme S. Ribeiro, Sueli M. Nakatani, Suzana D. R. Moreira, Irene Skraba, Alexander W. Biondo, Mitermayer G. Reis, Alex R. Hoffmaster, Joseph M. Vinetz, Albert I. Ko, Elsio A. Wunder Jr

Background

With a conservatively estimated 1 million cases of leptospirosis worldwide and a 5–10% fatality rate, the rapid diagnosis of leptospirosis leading to effective clinical and public health decision making is of high importance, and yet remains a challenge.

Methodology

Based on parallel, population-based studies in two leptospirosis-endemic regions in Brazil, a real-time PCR assay which detects lipL32, a gene specifically present in pathogenic Leptospira, was assessed for the diagnostic effectiveness and accuracy. Patients identified by active hospital-based surveillance in Salvador and Curitiba during large urban leptospirosis epidemics were tested. Real-time PCR reactions were performed with DNA-extracted samples obtained from 127 confirmed and 23 unconfirmed cases suspected of leptospirosis, 122 patients with an acute febrile illness other than leptospirosis, and 60 healthy blood donors.

Principal findings

The PCR assay had a limit of detection of 280 Leptospira genomic equivalents/mL. Sensitivity for confirmed cases was 61% for whole blood and 29% for serum samples. Sensitivity was higher (86%) for samples collected within the first 6 days after onset of illness compared to those collected after 7 days (34%). The real-time PCR assay was able to detect leptospiral DNA in blood from 56% of serological non-confirmed cases. The overall specificity of the assay was 99%.

Conclusions

These findings indicate that real-time PCR may be a reliable tool for early diagnosis of leptospirosis, which is decisive for clinical management of severe and life-threatening cases and for public health decision making.

Improved reliability of serological tools for the diagnosis of West Nile fever in horses within Europe

PLoS Neglected Tropical Diseases News - 15 September 2017 - 9:00pm

by Cécile Beck, Steeve Lowenski, Benoit Durand, Céline Bahuon, Stéphan Zientara, Sylvie Lecollinet

West Nile Fever is a zoonotic disease caused by a mosquito-borne flavivirus, WNV. By its clinical sensitivity to the disease, the horse is a useful sentinel of infection. Because of the virus’ low-level, short-term viraemia in horses, the primary tools used to diagnose WNV are serological tests. Inter-laboratory proficiency tests (ILPTs) were held in 2010 and 2013 to evaluate WNV serological diagnostic tools suited for the European network of National Reference Laboratories (NRLs) for equine diseases. These ILPTs were designed to evaluate the laboratories’ and methods’ performances in detecting WNV infection in horses through serology. The detection of WNV immunoglobulin G (IgG) antibodies by ELISA is widely used in Europe, with 17 NRLs in 2010 and 20 NRLs in 2013 using IgG WNV assays. Thanks to the development of new commercial IgM capture kits, WNV IgM capture ELISAs were rapidly implemented in NRLs between 2010 (4 NRLs) and 2013 (13 NRLs). The use of kits allowed the quick standardisation of WNV IgG and IgM detection assays in NRLs with more than 95% (20/21) and 100% (13/13) of satisfactory results respectively in 2013. Conversely, virus neutralisation tests (VNTs) were implemented in 33% (7/21) of NRLs in 2013 and their low sensitivity was evidenced in 29% (2/7) of NRLs during this ILPT. A comparison of serological diagnostic methods highlighted the higher sensitivity of IgG ELISAs compared to WNV VNTs. They also revealed that the low specificity of IgG ELISA kits meant that it could detect animals infected with other flaviviruses. In contrast VNT and IgM ELISA assays were highly specific and did not detect antibodies against related flaviviruses. These results argue in favour of the need for and development of new, specific serological diagnostic assays that could be easily transferred to partner laboratories.

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