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Direct cost of dengue hospitalization in Zhongshan, China: Associations with demographics, virus types and hospital accreditation

PLoS Neglected Tropical Diseases News - 3 August 2017 - 9:00pm

by Jing Hua Zhang, Juan Yuan, Tao Wang


Zhongshan City of Guangdong Province (China) is a key provincial and national level area for dengue fever prevention and control. The aim of this study is to analyze how the direct hospitalization costs and the length of stay of dengue hospitalization cases vary according to associated factors such as the demographics, virus types and hospital accreditation.


This study is based on retrospective census data from the Chinese National Disease Surveillance Reporting System. Totally, the hospital administrative data of 1432 confirmed dengue inpatients during 2013–2014 was obtained. A quantile regression model was applied to analyze how the direct cost of Dengue hospitalization varies with the patient demographics and hospital accreditation across the data distribution. The Length of Stay (LOS) was also examined.

Main findings

The average direct hospitalization cost of a dengue case in this study is US$ 499.64 during 2013, which corresponded to about 3.71% of the gross domestic product per capita in Zhongshan that year. The mean of the Length of Stay (LOS) is 7.2 days. The multivariate quantile regression results suggest that, after controlling potential compounding variables, the median hospitalization costs of male dengue patients were significantly higher than female ones by about US$ 18.23 (p<0.1). The hospitalization cost difference between the pediatric and the adult patients is estimated to be about US$ 75.25 at the median (p<0.01), but it increases sharply among the top 25 percentiles and reaches US$ 329 at the 90th percentile (p<0.01). The difference between the senior (older than 64 years old) and the adult patients increases steadily across percentiles, especially sharply among the top quartiles too. The LOS of the city-level hospitals is significantly shorter than that in the township-level hospitals by one day at the median (p<0.05), but no significant differences in their hospitalization costs.


The direct hospitalization costs of dengue cases vary widely according to the associated demographics factors, virus types and hospital accreditations. The findings in this study provide information for adopting hospitalization strategy, cost containment and patient allocation in dengue prevention and control. Also the results can be used as the cost-effective reference for future dengue vaccine adoption strategy in China.

Increasing airline travel may facilitate co-circulation of multiple dengue virus serotypes in Asia

PLoS Neglected Tropical Diseases News - 3 August 2017 - 9:00pm

by Huaiyu Tian, Zhe Sun, Nuno Rodrigues Faria, Jing Yang, Bernard Cazelles, Shanqian Huang, Bo Xu, Qiqi Yang, Oliver G. Pybus, Bing Xu

The incidence of dengue has grown dramatically in recent decades worldwide, especially in Southeast Asia and the Americas with substantial transmission in 2014–2015. Yet the mechanisms underlying the spatio-temporal circulation of dengue virus (DENV) serotypes at large geographical scales remain elusive. Here we investigate the co-circulation in Asia of DENV serotypes 1–3 from 1956 to 2015, using a statistical framework that jointly estimates migration history and quantifies potential predictors of viral spatial diffusion, including socio-economic, air transportation and maritime mobility data. We find that the spread of DENV-1, -2 and -3 lineages in Asia is significantly associated with air traffic. Our analyses suggest the network centrality of air traffic hubs such as Thailand and India contribute to seeding dengue epidemics, whilst China, Cambodia, Indonesia, and Singapore may establish viral diffusion links with multiple countries in Asia. Phylogeographic reconstructions help to explain how growing air transportation networks could influence the dynamics of DENV circulation.

Evolution and spread of Venezuelan equine encephalitis complex alphavirus in the Americas

PLoS Neglected Tropical Diseases News - 3 August 2017 - 9:00pm

by Naomi L. Forrester, Joel O. Wertheim, Vivian G. Dugan, Albert J. Auguste, David Lin, A. Paige Adams, Rubing Chen, Rodion Gorchakov, Grace Leal, Jose G. Estrada-Franco, Jyotsna Pandya, Rebecca A. Halpin, Kumar Hari, Ravi Jain, Timothy B. Stockwell, Suman R. Das, David E. Wentworth, Martin D. Smith, Sergei L. Kosakovsky Pond, Scott C. Weaver

Venezuelan equine encephalitis (VEE) complex alphaviruses are important re-emerging arboviruses that cause life-threatening disease in equids during epizootics as well as spillover human infections. We conducted a comprehensive analysis of VEE complex alphaviruses by sequencing the genomes of 94 strains and performing phylogenetic analyses of 130 isolates using complete open reading frames for the nonstructural and structural polyproteins. Our analyses confirmed purifying selection as a major mechanism influencing the evolution of these viruses as well as a confounding factor in molecular clock dating of ancestors. Times to most recent common ancestors (tMRCAs) could be robustly estimated only for the more recently diverged subtypes; the tMRCA of the ID/IAB/IC/II and IE clades of VEE virus (VEEV) were estimated at ca. 149–973 years ago. Evolution of the IE subtype has been characterized by a significant evolutionary shift from the rest of the VEEV complex, with an increase in structural protein substitutions that are unique to this group, possibly reflecting adaptation to its unique enzootic mosquito vector Culex (Melanoconion) taeniopus. Our inferred tree topologies suggest that VEEV is maintained primarily in situ, with only occasional spread to neighboring countries, probably reflecting the limited mobility of rodent hosts and mosquito vectors.

Chromoblastomycosis in India: Review of 169 cases

PLoS Neglected Tropical Diseases News - 3 August 2017 - 9:00pm

by Reshu Agarwal, Gagandeep Singh, Arnab Ghosh, Kaushal Kumar Verma, Mragnayani Pandey, Immaculata Xess

Chromoblastomycosis (CBM) is a chronic, progressive, cutaneous and subcutaneous fungal infection following the traumatic implantation of certain dematiaceous fungi. The disease has worldwide prevalence with predominant cases reported from humid tropical and subtropical regions of America, Asia, and Africa. Diagnosis is often delayed or misdirected either due to poor degree of clinical suspicions or clinical simulation of dermatological conditions. The infection is not uncommon in India and several case reports from the sub-Himalayan belt and western and eastern coasts of India have been published; however, very few have reviewed the cases. We reviewed 169 cases published in English literature from India during 1957 through May 2016, including 2 recent cases from our institute. A tremendous increase in the number of reported cases was noticed since 2012, since which, more than 50% of the cases had been published. A majority of the patients (74.1%) were involved in various agricultural activities directly or indirectly. The mean age at presentation was 43.3 years ± 16.0, with male to female ratio of 4.2:1. The duration of disease at the time of presentation varied from 20 days to 35 years. Any history of trauma was recalled only in 33.8% of the studied cases. The lower extremity was the most common site afflicted, followed by the upper extremity. The culture was positive in 80.3% of the cases with Fonsecaea pedrosoi, isolated as the most common fungal pathogen, followed by Cladophialophora carrionii. Although all the commercially available antifungals were prescribed in these cases, itraconazole and terbinafine were the most commonly used, either alone or in combination with other drugs/physical methods, with variable degrees of outcome. Combinations of different treatment modalities (chemotherapy and physical methods) yielded a cure rate of 86.3%. CBM is refractory to treatment and no single antifungal agent or regimen has demonstrated satisfactory results. Increased awareness with early clinical suspicion of the disease and adequate therapy are necessary to improve the outcome. However, depending upon the causative agent, disease severity, and the choice of antifungals, variable outcomes can be observed.

The global burden of disease study 2013: What does it mean for the NTDs?

PLoS Neglected Tropical Diseases News - 3 August 2017 - 9:00pm

by Jennifer R. Herricks, Peter J. Hotez, Valentine Wanga, Luc E. Coffeng, Juanita A. Haagsma, María-Gloria Basáñez, Geoffrey Buckle, Christine M. Budke, Hélène Carabin, Eric M. Fèvre, Thomas Fürst, Yara A. Halasa, Charles H. King, Michele E. Murdoch, Kapa D. Ramaiah, Donald S. Shepard, Wilma A. Stolk, Eduardo A. Undurraga, Jeffrey D. Stanaway, Mohsen Naghavi, Christopher J. L. Murray

Heterologous expression of the antimyotoxic protein DM64 in <i>Pichia pastoris</i>

PLoS Neglected Tropical Diseases News - 31 July 2017 - 9:00pm

by Saulo Martins Vieira, Surza Lucia Gonçalves da Rocha, Ana Gisele da Costa Neves-Ferreira, Rodrigo Volcan Almeida, Jonas Perales

Snakebite envenomation is a neglected condition that constitutes a public health problem in tropical and subtropical countries, including Brazil. Interestingly, some animals are resistant to snake envenomation due to the presence of inhibitory glycoproteins in their serum that target toxic venom components. DM64 is an acidic glycoprotein isolated from Didelphis aurita (opossum) serum that has been characterized as an inhibitor of the myotoxicity induced by bothropic toxins bearing phospholipase A2 (PLA2) structures. This antitoxic protein can serve as an excellent starting template for the design of novel therapeutics against snakebite envenomation, particularly venom-induced local tissue damage. Therefore, the aim of this work was to produce a recombinant DM64 (rDM64) in the methylotrophic yeast Pichia pastoris and to compare its biological properties with those of native DM64. Yeast fermentation in the presence of Pefabloc, a serine protease inhibitor, stimulated cell growth (~1.5-fold), increased the rDM64 production yield approximately 10-fold and significantly reduced the susceptibility of rDM64 to proteolytic degradation. P. pastoris fermentation products were identified by mass spectrometry and Western blotting. The heterologous protein was efficiently purified from the culture medium by affinity chromatography (with immobilized PLA2 myotoxin) and/or an ion exchange column. Although both native and recombinant DM64 exhibit different glycosylation patterns, they show very similar electrophoretic mobilities after PNGase F treatment. rDM64 formed a noncovalent complex with myotoxin II (Lys49-PLA2) from Bothrops asper and displayed biological activity that was similar to that of native DM64, inhibiting the cytotoxicity of myotoxin II by 92% at a 1:1 molar ratio.

Control of chronic <i>Strongyloides stercoralis</i> infection in an endemic community may be possible by pharmacological means alone: Results of a three-year cohort study

PLoS Neglected Tropical Diseases News - 31 July 2017 - 9:00pm

by Russell Hays, Adrian Esterman, Robyn McDermott


To assess the effect of treatment with ivermectin on the prevalence of S. stercoralis infection in an Australian Aboriginal population over a three year period, and to assess the validity of using a lower ELISA cut-off in diagnosis.


A three-year cohort study of 259 adult Australian Aboriginals living in a remote community in northern Australia. S stercoralis infection was diagnosed using commercial ELISA testing, and employed a lower threshold for treatment than that recommended. Follow up was conducted at 6 months and 3 years following ivermectin treatment.


Treatment with ivermectin was highly effective and resulted in a sustained fall in the prevalence of infection in the study group (Initial prevalence 35.3%, 3 year prevalence 5.8%, McNemar’s chi2 = 56.5, p<0.001). Results of treatment suggested use of a lower ELISA threshold for treatment was valid in this setting. Follow up identified a small group of subjects with persistently positive ELISA serology despite repeated treatment.


Control of S. stercoralis infection in this cohort appears to be feasible using pharmacological treatment alone.

Genome-wide diversity and differentiation in New World populations of the human malaria parasite <i>Plasmodium vivax</i>

PLoS Neglected Tropical Diseases News - 31 July 2017 - 9:00pm

by Thais C. de Oliveira, Priscila T. Rodrigues, Maria José Menezes, Raquel M. Gonçalves-Lopes, Melissa S. Bastos, Nathália F. Lima, Susana Barbosa, Alexandra L. Gerber, Guilherme Loss de Morais, Luisa Berná, Jody Phelan, Carlos Robello, Ana Tereza R. de Vasconcelos, João Marcelo P. Alves, Marcelo U. Ferreira


The Americas were the last continent colonized by humans carrying malaria parasites. Plasmodium falciparum from the New World shows very little genetic diversity and greater linkage disequilibrium, compared with its African counterparts, and is clearly subdivided into local, highly divergent populations. However, limited available data have revealed extensive genetic diversity in American populations of another major human malaria parasite, P. vivax.


We used an improved sample preparation strategy and next-generation sequencing to characterize 9 high-quality P. vivax genome sequences from northwestern Brazil. These new data were compared with publicly available sequences from recently sampled clinical P. vivax isolates from Brazil (BRA, total n = 11 sequences), Peru (PER, n = 23), Colombia (COL, n = 31), and Mexico (MEX, n = 19).

Principal findings/Conclusions

We found that New World populations of P. vivax are as diverse (nucleotide diversity π between 5.2 × 10−4 and 6.2 × 10−4) as P. vivax populations from Southeast Asia, where malaria transmission is substantially more intense. They display several non-synonymous nucleotide substitutions (some of them previously undescribed) in genes known or suspected to be involved in antimalarial drug resistance, such as dhfr, dhps, mdr1, mrp1, and mrp-2, but not in the chloroquine resistance transporter ortholog (crt-o) gene. Moreover, P. vivax in the Americas is much less geographically substructured than local P. falciparum populations, with relatively little between-population genome-wide differentiation (pairwise FST values ranging between 0.025 and 0.092). Finally, P. vivax populations show a rapid decline in linkage disequilibrium with increasing distance between pairs of polymorphic sites, consistent with very frequent outcrossing. We hypothesize that the high diversity of present-day P. vivax lineages in the Americas originated from successive migratory waves and subsequent admixture between parasite lineages from geographically diverse sites. Further genome-wide analyses are required to test the demographic scenario suggested by our data.

Predicting spatial spread of rabies in skunk populations using surveillance data reported by the public

PLoS Neglected Tropical Diseases News - 31 July 2017 - 9:00pm

by Kim M. Pepin, Amy J. Davis, Daniel G. Streicker, Justin W. Fischer, Kurt C. VerCauteren, Amy T. Gilbert


Prevention and control of wildlife disease invasions relies on the ability to predict spatio-temporal dynamics and understand the role of factors driving spread rates, such as seasonality and transmission distance. Passive disease surveillance (i.e., case reports by public) is a common method of monitoring emergence of wildlife diseases, but can be challenging to interpret due to spatial biases and limitations in data quantity and quality.

Methodology/Principal findings

We obtained passive rabies surveillance data from dead striped skunks (Mephitis mephitis) in an epizootic in northern Colorado, USA. We developed a dynamic patch-occupancy model which predicts spatio-temporal spreading while accounting for heterogeneous sampling. We estimated the distance travelled per transmission event, direction of invasion, rate of spatial spread, and effects of infection density and season. We also estimated mean transmission distance and rates of spatial spread using a phylogeographic approach on a subsample of viral sequences from the same epizootic. Both the occupancy and phylogeographic approaches predicted similar rates of spatio-temporal spread. Estimated mean transmission distances were 2.3 km (95% Highest Posterior Density (HPD95): 0.02, 11.9; phylogeographic) and 3.9 km (95% credible intervals (CI95): 1.4, 11.3; occupancy). Estimated rates of spatial spread in km/year were: 29.8 (HPD95: 20.8, 39.8; phylogeographic, branch velocity, homogenous model), 22.6 (HPD95: 15.3, 29.7; phylogeographic, diffusion rate, homogenous model) and 21.1 (CI95: 16.7, 25.5; occupancy). Initial colonization probability was twice as high in spring relative to fall.


Skunk-to-skunk transmission was primarily local (< 4 km) suggesting that if interventions were needed, they could be applied at the wave front. Slower viral invasions of skunk rabies in western USA compared to a similar epizootic in raccoons in the eastern USA implies host species or landscape factors underlie the dynamics of rabies invasions. Our framework provides a straightforward method for estimating rates of spatial spread of wildlife diseases.

Knowledge, attitudes and practices towards yaws and yaws-like skin disease in Ghana

PLoS Neglected Tropical Diseases News - 31 July 2017 - 9:00pm

by Michael Marks, Cynthia Kwakye-Maclean, Rachel Doherty, Paul Adwere, Abdul Aziz Abdulai, Fredrick Duah, Sally-Ann Ohene, Oriol Mitja, Blanche Oguti, Anthony W. Solomon, David C. W. Mabey, Yaw Adu-Sarkodie, Kingsley Asiedu, Mercy M. Ackumey


Yaws is endemic in Ghana. The World Health Organization (WHO) has launched a new global eradication campaign based on total community mass treatment with azithromycin. Achieving high coverage of mass treatment will be fundamental to the success of this new strategy; coverage is dependent, in part, on appropriate community mobilisation. An understanding of community knowledge, attitudes and practices related to yaws in Ghana and other endemic countries will be vital in designing effective community engagement strategies.


A verbally administered questionnaire was administered to residents in 3 districts in the Eastern region of Ghana where a randomised trial on the treatment of yaws was being conducted. The questionnaire combined both quantitative and qualitative questions covering perceptions of the cause and mechanisms of transmission of yaws-like lesions, the providers from which individuals would seek healthcare for yaws-like lesions, and what factors were important in reaching decisions on where to seek care. Chi-square tests and logistic regression were used to assess relationships between reported knowledge, attitudes and practices, and demographic variables. Thematic analysis of qualitative data was used to identify common themes.


A total of 1,162 individuals participated. The majority of individuals (n = 895, 77%) reported that “germs” were the cause of yaws lesions. Overall 13% (n = 161) of respondents believed that the disease was caused by supernatural forces. Participants frequently mentioned lack of personal hygiene, irregular and inefficient bathing, and washing with dirty water as fundamental to both the cause and the prevention of yaws. A majority of individuals reported that they would want to take an antibiotic to prevent the development of yaws if they were asymptomatic (n = 689, 61.2%), but a substantial minority reported they would not want to do so. A majority of individuals (n = 839, 72.7%) reported that if they had a yaws-like skin lesion they would seek care from a doctor or nurse. Both direct and indirect costs of treatment were reported as key factors affecting where participants reported they would seek care.


This is the first study that has explored community knowledge, attitudes and practices in relation to yaws in any endemic population. The belief that ‘germs’ are in some way related to disease through a variety of transmission routes including both contact and dirty water are similar to those reported for other skin diseases in Ghana. The prominent role of private healthcare providers is an important finding of this study and suggests engagement with this sector will be important in yaws eradication efforts. Strategies to address the substantial minority of individuals who reported they would not take treatment for yaws if they were currently asymptomatic will be needed to ensure the success of yaws eradication efforts. The data collected will be of value to the Ghana Health Service and also to WHO and other partners, who are currently developing community mobilisation tools to support yaws eradication efforts worldwide.

Prevalence of <i>Toxocara</i> species infection in the U.S.: Results from the National Health and Nutrition Examination Survey, 2011-2014

PLoS Neglected Tropical Diseases News - 31 July 2017 - 9:00pm

by Aaron Farmer, Thomas Beltran, Young Sammy Choi

Toxocariasis is one of the most common neglected infections of poverty in the U.S. with a reported National Health and Nutrition Examination Survey (NHANES) III (1988–1994) seroprevalence of 13.9% based on enzyme immunoassay testing. We reviewed NHANES data from 2011–2014 to assess current levels. Sera collected from NHANES 2011–2014 participants six years and older were tested for exposure using rTc-CTL-1 antigen, a more sensitive and specific recombinant antigen for IgG antibodies for Toxocara spp. These results were subdivided into children (age 6–17) and adults (age ≥ 18) and then compared between various sociodemographic characteristics. Given prior associations of Toxocara exposure with atopic disease and lead exposure, we also reviewed laboratory values including complete blood counts and blood and urine lead levels. Data from 13,509 individuals with Toxocara antibody results were examined including 3337 children (15.2%) and 10172 adults (84.8%). Overall seroprevalence was 5.1%. In adults increased antibody positivity occurred with non-White ethnicity, male gender, less than college-level education and lower income. Among children, increased antibody positivity was solely related to a lack of health insurance. Additionally, seropositivity was associated with increased blood lead and eosinophil levels in adults and both blood and urine lead levels in children. Relative to NHANES III (1988–1994), current data suggest an overall decrease in Toxocara spp. seroprevalence from 13.9% to 5.1%, however this may be artificially lowered due to difference in testing methods used. Persistent disparities appear to be associated with at-risk populations such as minority ethnicity and low socioeconomic status.

Mixed Th1 and Th2 <i>Mycobacterium tuberculosis</i>-specific CD4 T cell responses in patients with active pulmonary tuberculosis from Tanzania

PLoS Neglected Tropical Diseases News - 31 July 2017 - 9:00pm

by Patrizia Amelio, Damien Portevin, Klaus Reither, Francis Mhimbira, Maxmillian Mpina, Anneth Tumbo, Beatrice Nickel, Hanspeter Marti, Stefanie Knopp, Song Ding, Adam Penn-Nicholson, Fatoumatta Darboe, Khalid Ohmiti, Thomas J. Scriba, Giuseppe Pantaleo, Claudia Daubenberger, Matthieu Perreau

Mycobacterium tuberculosis (Mtb) and helminth infections elicit antagonistic immune effector functions and are co-endemic in several regions of the world. We therefore hypothesized that helminth infection may influence Mtb-specific T-cell immune responses. We evaluated the cytokine profile of Mtb-specific T cells in 72 individuals with pulmonary TB disease recruited from two Sub-Saharan regions with high and moderate helminth burden i.e. 55 from Tanzania (TZ) and 17 from South Africa (SA), respectively. We showed that Mtb-specific CD4 T-cell functional profile of TB patients from Tanzania are primarily composed of polyfunctional Th1 and Th2 cells, associated with increased expression of Gata-3 and reduced expression of T-bet in memory CD4 T cells. In contrast, the cytokine profile of Mtb-specific CD4 T cells of TB patients from SA was dominated by single IFN-γ and dual IFN-γ/TNF-α and associated with TB-induced systemic inflammation and elevated serum levels of type I IFNs. Of note, the proportion of patients with Mtb-specific CD8 T cells was significantly reduced in Mtb/helminth co-infected patients from TZ. It is likely that the underlying helminth infection and possibly genetic and other unknown environmental factors may have caused the induction of mixed Th1/Th2 Mtb-specific CD4 T cell responses in patients from TZ. Taken together, these results indicate that the generation of Mtb-specific CD4 and CD8 T cell responses may be substantially influenced by environmental factors in vivo. These observations may have major impact in the identification of immune biomarkers of disease status and correlates of protection.

Proteogenomic analysis of the total and surface-exposed proteomes of <i>Plasmodium vivax</i> salivary gland sporozoites

PLoS Neglected Tropical Diseases News - 31 July 2017 - 9:00pm

by Kristian E. Swearingen, Scott E. Lindner, Erika L. Flannery, Ashley M. Vaughan, Robert D. Morrison, Rapatbhorn Patrapuvich, Cristian Koepfli, Ivo Muller, Aaron Jex, Robert L. Moritz, Stefan H. I. Kappe, Jetsumon Sattabongkot, Sebastian A. Mikolajczak

Plasmodium falciparum and Plasmodium vivax cause the majority of human malaria cases. Research efforts predominantly focus on P. falciparum because of the clinical severity of infection and associated mortality rates. However, P. vivax malaria affects more people in a wider global range. Furthermore, unlike P. falciparum, P. vivax can persist in the liver as dormant hypnozoites that can be activated weeks to years after primary infection, causing relapse of symptomatic blood stages. This feature makes P. vivax unique and difficult to eliminate with the standard tools of vector control and treatment of symptomatic blood stage infection with antimalarial drugs. Infection by Plasmodium is initiated by the mosquito-transmitted sporozoite stage, a highly motile invasive cell that targets hepatocytes in the liver. The most advanced malaria vaccine for P. falciparum (RTS,S, a subunit vaccine containing of a portion of the major sporozoite surface protein) conferred limited protection in Phase III trials, falling short of WHO-established vaccine efficacy goals. However, blocking the sporozoite stage of infection in P. vivax, before the establishment of the chronic liver infection, might be an effective malaria vaccine strategy to reduce the occurrence of relapsing blood stages. It is also thought that a multivalent vaccine comprising multiple sporozoite surface antigens will provide better protection, but a comprehensive analysis of proteins in P. vivax sporozoites is not available. To inform sporozoite-based vaccine development, we employed mass spectrometry-based proteomics to identify nearly 2,000 proteins present in P. vivax salivary gland sporozoites. Analysis of protein post-translational modifications revealed extensive phosphorylation of glideosome proteins as well as regulators of transcription and translation. Additionally, the sporozoite surface proteins CSP and TRAP, which were recently discovered to be glycosylated in P. falciparum salivary gland sporozoites, were also observed to be similarly modified in P. vivax sporozoites. Quantitative comparison of the P. vivax and P. falciparum salivary gland sporozoite proteomes revealed a high degree of similarity in protein expression levels, including among invasion-related proteins. Nevertheless, orthologs with significantly different expression levels between the two species could be identified, as well as highly abundant, species-specific proteins with no known orthologs. Finally, we employed chemical labeling of live sporozoites to isolate and identify 36 proteins that are putatively surface-exposed on P. vivax salivary gland sporozoites. In addition to identifying conserved sporozoite surface proteins identified by similar analyses of other Plasmodium species, our analysis identified several as-yet uncharacterized proteins, including a putative 6-Cys protein with no known ortholog in P. falciparum.

Risk factors for inadequate antibody response to primary rabies vaccination in dogs under one year of age

PLoS Neglected Tropical Diseases News - 31 July 2017 - 9:00pm

by Ryan M. Wallace, Anna Pees, Jesse B. Blanton, Susan M. Moore

Ensuring the adequacy of response to rabies vaccination in dogs is important, particularly in the context of pet travel. Few studies have examined the factors associated with dogs’ failure to achieve an adequate antibody titer after vaccination (0.5 IU/ml). This study evaluated rabies antibody titers in dogs after primary vaccination. Dogs under one year of age whose serum was submitted to a reference laboratory for routine diagnostics, and which had no prior documented history of vaccination were enrolled (n = 8,011). Geometric mean titers (GMT) were calculated and univariate analysis was performed to assess factors associated with failure to achieve 0.5 IU/mL. Dogs vaccinated at >16 weeks of age had a significantly higher GMT compared to dogs vaccinated at a younger age (1.64 IU/ml, 1.57–1.72, ANOVA p < 0.01). There was no statistical difference in GMT between dogs vaccinated <12 weeks and dogs vaccinated 12–16 weeks (1.22 IU/ml and 1.21 IU/ml). The majority of dogs failed to reach an adequate titer within the first 3 days of primary vaccination; failure rates were also high if the interval from vaccination to titer check was greater than 90 days. Over 90% of dogs that failed primary vaccination were able to achieve adequate titers after booster vaccination. The ideal timing for blood draw is 8–30 days after primary vaccination. In the event of a failure, most dogs will achieve an adequate serologic response upon a repeat titer (in the absence of booster vaccination). Booster vaccination after failure provided the highest probability of an acceptable titer.

Correction: Diagnosis of Bacterial Bloodstream Infections: A 16S Metagenomics Approach

PLoS Neglected Tropical Diseases News - 28 July 2017 - 9:00pm

by Saskia Decuypere, Conor J. Meehan, Sandra Van Puyvelde, Tessa De Block, Jessica Maltha, Lompo Palpouguini, Marc Tahita, Halidou Tinto, Jan Jacobs, Stijn Deborggraeve

Correction: Use of Oral Cholera Vaccine and Knowledge, Attitudes, and Practices Regarding Safe Water, Sanitation and Hygiene in a Long-Standing Refugee Camp, Thailand, 2012-2014

PLoS Neglected Tropical Diseases News - 28 July 2017 - 9:00pm

by Heather M. Scobie, Christina R. Phares, Kathleen A. Wannemuehler, Edith Nyangoma, Eboni M. Taylor, Anna Fulton, Nuttapong Wongjindanon, Naw Rody Aung, Philippe Travers, Kashmira Date

Double impact: natural molluscicide for schistosomiasis vector control also impedes development of <i>Schistosoma mansoni</i> cercariae into adult parasites

PLoS Neglected Tropical Diseases News - 28 July 2017 - 9:00pm

by Ronaldo de Carvalho Augusto, Guillaume Tetreau, Philippe Chan, Marie-Laure Walet-Balieu, Clélia Christina Mello-Silva, Claudia Portes Santos, Christoph Grunau


Schistosomiasis has been reported in 78 endemic countries and affects 240 million people worldwide. The digenetic parasite Schistosoma mansoni needs fresh water to compete its life cycle. There, it is susceptible to soluble compounds that can affect directly and/or indirectly the parasite’s biology. The cercariae stage is one of the key points in which the parasite is vulnerable to different soluble compounds that can significantly alter the parasite’s life cycle. Molluscicides are recommended by the World Health Organization for the control of schistosomiasis transmission and Euphorbia milii latex is effective against snails intermediate hosts.

Methodology/Principal findings

We used parasitological tools and electron microscopy to verify the effects of cercariae exposure to natural molluscicide (Euphorbia milii latex) on morphology, physiology and fitness of adult parasite worms. In order to generate insights into key metabolic pathways that lead to the observed phenotypes we used comparative transcriptomics and proteomics.


We describe here the effect of latex on the adult is not due to direct toxicity but it triggers an early change in developmental trajectory and perturbs cell memory, mobility, energy metabolism and other key pathways. We conclude that latex has not only an effect on the vector but applies also long lasting schistosomastatic action. We believe that these results are of interest not only to parasitologists since it shows that natural compounds, presumably without side effects, can have an impact that occurred unexpectedly on developmental processes in the parasite. Such collateral damage is in this case positive, since it impacts the true target of the treatment campaign. This type of treatment could also provide a rational for the control of other pests. Our results will contribute to enforce the use of E. milii latex in Brazil and other endemic countries as cheap alternative or complement to mass drug treatment with Praziquantel, the only available drug to cure the patients (without preventing re-infection).

Extensive sonographic ulnar nerve enlargement above the medial epicondyle is a characteristic sign in Hansen’s neuropathy

PLoS Neglected Tropical Diseases News - 28 July 2017 - 9:00pm

by Lokesh Bathala, Venkataramana N. Krishnam, Hari Kishan Kumar, Vivekananda Neladimmanahally, Umashankar Nagaraju, Himanshu M. Kumar, Johan A. Telleman, Leo H. Visser


Earlier studies have shown sonographic enlargement of the ulnar nerve in patients with Hansen’s neuropathy. The present study was performed to determine whether sonography or electrophysiological studies can detect the specific site of ulnar nerve pathology in leprosy.


Eighteen patients (thirty arms) with Hansen’s disease and an ulnar neuropathy of whom 66% had borderline tuberculoid (BT), 27% lepromatous leprosy (LL) and 7% mid-borderline (BB) leprosy were included in the study. Cross-sectional area (CSA) of ulnar nerve was measured every two centimeters from wrist to medial epicondyle and from there to axilla. All patients underwent standard motor and sensory nerve conduction studies of the ulnar nerve. Thirty age and sex matched controls underwent similar ulnar nerve CSA measurements and conduction studies.


Ulnar nerve was clinically palpable in 19 of the 30 arms of patients. Motor and sensory nerve conduction studies of the ulnar nerve showed a reduced compound motor action potential and sensory nerve action potential amplitude in all patients. Motor Conduction Velocity (MCV) in patients were slower in comparison to controls, especially at the elbow and upper arm, but unable to exactly locate the site of the lesion. In comparison to controls the ulnar nerveCSA was larger in the whole arm in patients and quite specific the maximum enlargement was seen between nulnar sulcus and axilla, peaking at four centimeters above the sulcus.


A unique sonographic pattern of nerve enlargement is noted in patients with ulnar neuropathy due to Hansen’s disease, while this was not the case for the technique used until now, the electrodiagnostic testing. The enlargement starts at ulnar sulcus and is maximum four centimeters above the medial epicondyle and starts reducing further along the tract. This characteristic finding can help especially in diagnosing pure neuritic type of Hansen’s disease, in which skin lesions are absent, and alsoto differentiate leprosy from other neuropathies in which nerve enlargement can occur.

Amino acid metabolic signaling influences <i>Aedes aegypti</i> midgut microbiome variability

PLoS Neglected Tropical Diseases News - 28 July 2017 - 9:00pm

by Sarah M. Short, Emmanuel F. Mongodin, Hannah J. MacLeod, Octavio A. C. Talyuli, George Dimopoulos

The mosquito midgut microbiota has been shown to influence vector competence for multiple human pathogens. The microbiota is highly variable in the field, and the sources of this variability are not well understood, which limits our ability to understand or predict its effects on pathogen transmission. In this work, we report significant variation in female adult midgut bacterial load between strains of A. aegypti which vary in their susceptibility to dengue virus. Composition of the midgut microbiome was similar overall between the strains, with 81–92% of reads coming from the same five bacterial families, though we did detect differences in the presence of some bacterial families including Flavobacteriaceae and Entobacteriaceae. We conducted transcriptomic analysis on the two mosquito strains that showed the greatest difference in bacterial load, and found that they differ in transcript abundance of many genes implicated in amino acid metabolism, in particular the branched chain amino acid degradation pathway. We then silenced this pathway by targeting multiple genes using RNA interference, which resulted in strain-specific bacterial proliferation, thereby eliminating the difference in midgut bacterial load between the strains. This suggests that the branched chain amino acid (BCAA) degradation pathway controls midgut bacterial load, though the mechanism underlying this remains unclear. Overall, our results indicate that amino acid metabolism can act to influence the midgut microbiota. Moreover, they suggest that genetic or physiological variation in BCAA degradation pathway activity may in part explain midgut microbiota variation in the field.

<i>Leptospira interrogans</i> causes quantitative and morphological disturbances in adherens junctions and other biological groups of proteins in human endothelial cells

PLoS Neglected Tropical Diseases News - 27 July 2017 - 9:00pm

by Hiromi Sato, Jenifer Coburn

Pathogenic Leptospira transmits from animals to humans, causing the zoonotic life-threatening infection called leptospirosis. This infection is reported worldwide with higher risk in tropical regions. Symptoms of leptospirosis range from mild illness to severe illness such as liver damage, kidney failure, respiratory distress, meningitis, and fatal hemorrhagic disease. Invasive species of Leptospira rapidly disseminate to multiple tissues where this bacterium damages host endothelial cells, increasing vascular permeability. Despite the burden in humans and animals, the pathogenic mechanisms of Leptospira infection remain to be elucidated. The pathogenic leptospires adhere to endothelial cells and permeabilize endothelial barriers in vivo and in vitro. In this study, human endothelial cells were infected with the pathogenic L. interrogans serovar Copenhageni or the saprophyte L. biflexa serovar Patoc to investigate morphological changes and other distinctive phenotypes of host cell proteins by fluorescence microscopy. Among those analyzed, 17 proteins from five biological classes demonstrated distinctive phenotypes in morphology and/or signal intensity upon infection with Leptospira. The affected biological groups include: 1) extracellular matrix, 2) intercellular adhesion molecules and cell surface receptors, 3) intracellular proteins, 4) cell-cell junction proteins, and 5) a cytoskeletal protein. Infection with the pathogenic strain most profoundly disturbed the biological structures of adherens junctions (VE-cadherin and catenins) and actin filaments. Our data illuminate morphological disruptions and reduced signals of cell-cell junction proteins and filamentous actin in L. interrogans-infected endothelial cells. In addition, Leptospira infection, regardless of pathogenic status, influenced other host proteins belonging to multiple biological classes. Our data suggest that this zoonotic agent may damage endothelial cells via multiple cascades or pathways including endothelial barrier damage and inflammation, potentially leading to vascular hyperpermeability and severe illness in vivo. This work provides new insights into the pathophysiological mechanisms of Leptospira infection.