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Early identification of acute kidney injury in Russell’s viper (<i>Daboia russelii</i>) envenoming using renal biomarkers

PLoS Neglected Tropical Diseases News - 1 July 2019 - 9:00pm

by Indira Ratnayake, Fahim Mohamed, Nicholas A. Buckley, Indika B. Gawarammana, Dhammika M. Dissanayake, Umesh Chathuranga, Mahesh Munasinghe, Kalana Maduwage, Shaluka Jayamanne, Zoltan H. Endre, Geoffrey K. Isbister

Background

Acute kidney injury (AKI) is a major complication of snake envenoming, but early diagnosis remains problematic. We aimed to investigate the time course of novel renal biomarkers in AKI following Russell’s viper (Daboia russelii) bites.

Methodology/Principal findings

We recruited a cohort of patients with definite Russell’s viper envenoming and collected serial blood and urine samples on admission (<4h post-bite), 4-8h, 8-16h, 16-24h, 1 month and 3 months post-bite. AKI stage (1–3) was defined using the Acute Kidney Injury Network criteria. AKI stages (1–3) were defined by the Acute Kidney Injury Network (AKIN) criteria. There were 65 Russell’s viper envenomings and 49 developed AKI: 24 AKIN stage 1, 13 stage 2 and 12 stage 3. There was a significant correlation between venom concentrations and AKI stage (p = 0.007), and between AKI stage and six peak biomarker concentrations. Although most biomarker concentrations were elevated within 8h, no biomarker performed well in diagnosing AKI <4h post-bite. Three biomarkers were superior to serum creatinine (sCr) in predicting AKI (stage 2/3) 4-8h post-bite: serum cystatin C (sCysC) with an area under the receiver operating curve (AUC-ROC), 0.78 (95%CI:0.64–0.93), urine neutrophil gelatinase-associated lipocalin (uNGAL), 0.74 (95%CI:0.59–0.87) and urine clusterin (uClu), 0.81 (95%CI:0.69–0.93). No biomarker was better than sCr after 8h. Six other urine biomarkers urine albumin, urine beta2-microglobulin, urine kidney injury molecule-1, urine cystatin C, urine trefoil factor-3 and urine osteopontin either had minimal elevation, and/or minimal prediction for AKI stage 2/3 (AUC-ROC<0.7).

Conclusions/Significance

AKI was common and sometimes severe following Russell’s viper bites. Three biomarkers uClu, uNGAL and sCysC, appeared to become abnormal in AKI earlier than sCr, and may be useful in early identification of envenoming.

Model-based assessment of public health impact and cost-effectiveness of dengue vaccination following screening for prior exposure

PLoS Neglected Tropical Diseases News - 1 July 2019 - 9:00pm

by Guido España, Yutong Yao, Kathryn B. Anderson, Meagan C. Fitzpatrick, David L. Smith, Amy C. Morrison, Annelies Wilder-Smith, Thomas W. Scott, T. Alex Perkins

The tetravalent dengue vaccine CYD-TDV (Dengvaxia) is the first licensed vaccine against dengue, but recent findings indicate an elevated risk of severe disease among vaccinees without prior dengue virus (DENV) exposure. The World Health Organization currently recommends CYD-TDV only for individuals with serological confirmation of past DENV exposure. Our objective was to evaluate the potential health impact and cost-effectiveness of vaccination following serological screening. To do so, we used an agent-based model to simulate DENV transmission with and without vaccination over a 10-year timeframe. Across a range of values for the proportion of vaccinees with prior DENV exposure, we projected the proportion of symptomatic and hospitalized cases averted as a function of the sensitivity and specificity of serological screening. Scenarios about the cost-effectiveness of screening and vaccination were chosen to be representative of Brazil and the Philippines. We found that public health impact depended primarily on sensitivity in high-transmission settings and on specificity in low-transmission settings. Cost-effectiveness could be achievable from the perspective of a public payer provided that sensitivity and the value of a disability-adjusted life-year were both high, but only in high-transmission settings. Requirements for reducing relative risk and achieving cost-effectiveness from an individual perspective were more restricted, due to the fact that those who test negative pay for screening but receive no benefit. Our results predict that cost-effectiveness could be achieved only in high-transmission areas of dengue-endemic countries with a relatively high per capita GDP, such as Panamá (13,680 USD), Brazil (8,649 USD), México (8,201 USD), or Thailand (5,807 USD). In conclusion, vaccination with CYD-TDV following serological screening could have a positive impact in some high-transmission settings, provided that screening is highly specific (to minimize individual harm), at least moderately sensitive (to maximize population benefit), and sufficiently inexpensive (depending on the setting).

Economic performance and cost-effectiveness of using a DEC-salt social enterprise for eliminating the major neglected tropical disease, lymphatic filariasis

PLoS Neglected Tropical Diseases News - 1 July 2019 - 9:00pm

by Swarnali Sharma, Morgan E. Smith, James Reimer, David B. O’Brien, Jean M. Brissau, Marie C. Donahue, Clarence E. Carter, Edwin Michael

Background

Salt fortified with the drug, diethylcarbamazine (DEC), and introduced into a competitive market has the potential to overcome the obstacles associated with tablet-based Lymphatic Filariasis (LF) elimination programs. Questions remain, however, regarding the economic viability, production capacity, and effectiveness of this strategy as a sustainable means to bring about LF elimination in resource poor settings.

Methodology and principal findings

We evaluated the performance and effectiveness of a novel social enterprise-based approach developed and tested in Léogâne, Haiti, as a strategy to sustainably and cost-efficiently distribute DEC-medicated salt into a competitive market at quantities sufficient to bring about the elimination of LF. We undertook a cost-revenue analysis to evaluate the production capability and financial feasibility of the developed DEC salt social enterprise, and a modeling study centered on applying a dynamic mathematical model localized to reflect local LF transmission dynamics to evaluate the cost-effectiveness of using this intervention versus standard annual Mass Drug Administration (MDA) for eliminating LF in Léogâne. We show that the salt enterprise because of its mixed product business strategy may have already reached the production capacity for delivering sufficient quantities of edible DEC-medicated salt to bring about LF transmission in the Léogâne study setting. Due to increasing revenues obtained from the sale of DEC salt over time, expansion of its delivery in the population, and greater cumulative impact on the survival of worms leading to shorter timelines to extinction, this strategy could also represent a significantly more cost-effective option than annual DEC tablet-based MDA for accomplishing LF elimination.

Significance

A social enterprise approach can offer an innovative market-based strategy by which edible salt fortified with DEC could be distributed to communities both on a financially sustainable basis and at sufficient quantity to eliminate LF. Deployment of similarly fashioned intervention strategies would improve current efforts to successfully accomplish the goal of LF elimination, particularly in difficult-to-control settings.

The E3 ligase TRIM56 is a host restriction factor of Zika virus and depends on its RNA-binding activity but not miRNA regulation, for antiviral function

PLoS Neglected Tropical Diseases News - 28 June 2019 - 9:00pm

by Darong Yang, Nan L. Li, Dahai Wei, Baoming Liu, Fang Guo, Husni Elbahesh, Yunzhi Zhang, Zhi Zhou, Guo-Yun Chen, Kui Li

Infection by Zika virus (ZIKV) is linked to microcephaly and other neurological disorders, posing a significant health threat. Innate immunity is the first line of defense against invading pathogens, but relatively little is understood regarding host intrinsic mechanisms that guard against ZIKV. Here, we show that host tripartite motif-containing protein 56 (TRIM56) poses a barrier to ZIKV infection in cells of neural, epithelial and fibroblast origins. Overexpression of TRIM56, but not an E3 ligase-dead mutant or one lacking a short C-terminal portion, inhibited ZIKV RNA replication. Conversely, depletion of TRIM56 increased viral RNA levels. Although the C-terminal region of TRIM56 bears sequence homology to NHL repeat of TRIM-NHL proteins that regulate miRNA activity, knockout of Dicer, which abolishes production of miRNAs, had no demonstrable effect on ZIKV restriction imposed by TRIM56. Rather, we found that TRIM56 is an RNA-binding protein that associates with ZIKV RNA in infected cells. Moreover, a recombinant TRIM56 fragment comprising the C-terminal 392 residues captured ZIKV RNA in cell-free reactions, indicative of direct interaction. Remarkably, deletion of a short C-terminal tail portion abrogated the TRIM56-ZIKV RNA interaction, concomitant with a loss in antiviral activity. Altogether, our study reveals TRIM56 is an RNA binding protein that acts as a ZIKV restriction factor and provides new insights into the antiviral mechanism by which this E3 ligase tackles flavivirus infections.

Elucidating diversity in the class composition of the minicircle hypervariable region of <i>Trypanosoma cruzi</i>: New perspectives on typing and kDNA inheritance

PLoS Neglected Tropical Diseases News - 27 June 2019 - 9:00pm

by Fanny Rusman, Nicolás Tomasini, Noelia Floridia Yapur, Andrea F. Puebla, Paula G. Ragone, Patricio Diosque

Background

Trypanosoma cruzi, the protozoan causative of Chagas disease, is classified into six main Discrete Typing Units (DTUs): TcI-TcVI. This parasite has around 105 copies of the minicircle hypervariable region (mHVR) in their kinetoplastic DNA (kDNA). The genetic diversity of the mHVR is virtually unknown. However, cross-hybridization assays using mHVRs showed hybridization only between isolates belonging to the same genetic group. Nowadays there is no methodologic approach with a good sensibility, specificity and reproducibility for direct typing on biological samples. Due to its high copy number and apparently high diversity, mHVR becomes a good target for typing.

Methodology/Principal findings

Around 22 million reads, obtained by amplicon sequencing of the mHVR, were analyzed for nine strains belonging to six T. cruzi DTUs. The number and diversity of mHVR clusters was variable among DTUs and even within a DTU. However, strains of the same DTU shared more mHVR clusters than strains of different DTUs and clustered together. In addition, hybrid DTUs (TcV and TcVI) shared similar percentages (1.9–3.4%) of mHVR clusters with their parentals (TcII and TcIII). Conversely, just 0.2% of clusters were shared between TcII and TcIII suggesting biparental inheritance of the kDNA in hybrids. Sequencing at low depth (20,000–40,000 reads) also revealed 95% of the mHVR clusters for each of the analyzed strains. Finally, the method revealed good correlation in cluster identity and abundance between different replications of the experiment (r = 0.999).

Conclusions/Significance

Our work sheds light on the sequence diversity of mHVRs at intra and inter-DTU level. The mHVR amplicon sequencing workflow described here is a reproducible technique, that allows multiplexed analysis of hundreds of strains and results promissory for direct typing on biological samples in a future. In addition, such approach may help to gain knowledge on the mechanisms of the minicircle evolution and phylogenetic relationships among strains.

The Shan people’s health beliefs, knowledge and perceptions of dengue in Eastern Shan Special Region IV, Myanmar

PLoS Neglected Tropical Diseases News - 27 June 2019 - 9:00pm

by Jian-Wei Xu, Hui Liu, Zadan Ai, Yan Yu, Bian Yu

Sustainable dengue intervention requires the participation of communities. Therefore, understanding the health beliefs, knowledge and perceptions of dengue among the local people can help to design locally appropriate strategies for effective interventions. A combination of qualitative semi-structured in-depth interviews (SDIs) and quantitative household questionnaire surveys (HHSs) was used to investigate the beliefs, knowledge and perceptions of dengue among the Shan people in Eastern Shan Special Region IV (ESSR4), Myanmar. The SDI was administered to 18 key informants, and the HHS was administered to 259 respondents. Only 14.7% (95% CI: 10.6–19.6%) of the HHS respondents could confirm that mosquitoes transmit dengue; 14.3% (95% CI: 10.3–19.1%) knew that piebald or Aedes mosquitoes transmit dengue; and 24.3% (95% CI: 19.2–30.0%) believed that dengue-transmitting mosquitoes mainly lived in small ponds. Merely ten (0.4%) of the 259 respondents of the HHS thought that dengue-transmitting mosquitoes bite in the day time. The people in the villages where there were outbreaks of dengue had more knowledge about dengue. This study demonstrates that the health beliefs of the Shan people were closely associated with their lifestyles, social and natural environments. To stay healthy, the Shan people clean their houses and surroundings regularly. However, their knowledge about dengue was not adequate for effective dengue control because it was mostly learned from previous dengue experiences and in a context that lacks systematic health education. Thus, in this setting, with a weak public health structure, more international support should be provided to promote the knowledge of the Shan people about dengue and to increase their sensitive awareness to dengue, which might be beneficial for social mobilization and community participation during future dengue prevention.

Risk of disability among adult leprosy cases and determinants of delay in diagnosis in five states of India: A case-control study

PLoS Neglected Tropical Diseases News - 27 June 2019 - 9:00pm

by Govindarajulu Srinivas, Thirumugam Muthuvel, Vivek Lal, Kanagasabapathy Vaikundanathan, Eva-Maria Schwienhorst-Stich, Christa Kasang

Introduction

A high proportion of grade 2 disability (visible deformity) is indicative of delay in detection of leprosy and leprosy is one of the major causes of preventable disability. We conducted this study to determine the risk factors associated with disability (G2D and G1D) among adult new leprosy cases and to measure their strength of association.

Methods

A multi-centric case-control study was undertaken in five states of India i.e. Andhra Pradesh, Delhi, Gujarat, Maharashtra and West Bengal). Among new adult patients, cases were defined as those with disability (G2D and G1D) at the time of diagnosis and controls were defined as those without any disability (G0D). Delays were quantified based on patient recall across a timeline. Patient delay defined as the time period between first noticed symptom by the patient and the first visit to any health care provider (HCP); HCP delay defined as the time period between patient’s first visit to any HCP and the confirmation of diagnosis of leprosy; and total delay defined as the sum of both patient and HCP delays.

Results

A total of 1400 new leprosy patients (700 G2D/G1D and 700 G0D) across five states were interviewed. Among G2D/G1D, the median patient delay was 8 months compared with 4 months among G0D. The median HCP delay was 2 months for G2D/G1D and 1 month for G0D. The median total delay was 14 months for G2D/G1D and 6.2 months for G0D; observed median difference between groups was statistically significant (p<0.001). When patient delay was more than 3 months, odds of G2D/G1D at diagnosis were 1.6 times higher compared to when patient delay was less than 3 months. When the HCP delay was more than one month, the odds of G2D/G1D were 1.4 times higher compared to when the HCP delay was less than one month. When the patient had multi-bacillary type leprosy the odds of G2D/G1D at the time of diagnosis was nine times higher compared to pauci-bacillary type leprosy.

Conclusion

Patient delay is the major reason for risk of disability (G2D/G1D) among adult leprosy patients. A patient delay of more than 3 months from the notice of first symptom is a significant indicator for the disabilities among adult leprosy patients. Early case detection campaigns like active surveys in endemic spots should be done periodically as this can reduce delays and promote early diagnosis. Additionally, the program should lay greater emphasis on raising community awareness regarding the disease. Also, health care provider delay of more than 1 month have been significant risk factors for disability among adult leprosy cases. Hence, periodical capacitation of all HCPs including private practitioners would significantly contribute to reduce diagnostic delay and promote timely referral and early detection.

“It’s just a fever”: Gender based barriers to care-seeking for visceral leishmaniasis in highly endemic districts of India: A qualitative study

PLoS Neglected Tropical Diseases News - 27 June 2019 - 9:00pm

by Beulah Jayakumar, Nirmala Murthy, Kingsuk Misra, Sakib Burza

Introduction

Diagnosis and treatment for visceral leishmaniasis (VL) is considered to be delayed amongst poor, rural women in highly endemic districts of Bihar and Jharkhand. The objective of this study was to assess and understand barriers to VL diagnosis and treatment for women in endemic districts with a high burden of VL.

Methods

The study used a stratified and purposive sample of 33 female patients with VL, 11 health staff, 11 local (unqualified) health providers and 12 groups of community elders drawn from ten districts in Bihar and four in Jharkhand with high burdens of VL. The study was conducted within an exploratory and inductive framework, using semi-structured in-depth interviews and discussions.

Results

Women accessing treatment more quickly tended to move faster from treating their symptoms on their own to seeking care from local providers. Perception among female patients of the illness being not serious (owing to initially non-specific and mild symptoms), lack of money, prioritisation of household chores over their need to seek care and the absence of a male guardian to accompany them in seeking care at facilities worked together to drive these choices. Most patients and their families did not suspect VL as the cause for their non-specific symptoms, but when VL was suspected, treatment shopping ended. Lack of prioritization of women’s health issues appears to be a pervasive underlying factor. Public health facilities were not an early treatment choice for the majority, but where it was, the diagnosis of VL was often not considered when presenting with under 2 weeks of symptoms, nor were appropriate follow-up plans instituted.

Conclusion

The insidious presentation of VL and the low prioritisation of women’s health need to be jointly addressed through messages that emphasise the importance of early diagnosis and treatment of disease, which is low-cost in time and money when managed in public health facilities. Clear messages that project prioritising women’s care-seeking over household work as a smart choice and the need for rallying male support are needed. Additionally, efforts to reduce missed opportunities through early case suspicion and engaging private providers to better counsel women with suspected VL could close critical gaps in the continuum of care.

One hypervirulent clone, sequence type 283, accounts for a large proportion of invasive <i>Streptococcus agalactiae</i> isolated from humans and diseased tilapia in Southeast Asia

PLoS Neglected Tropical Diseases News - 27 June 2019 - 9:00pm

by Timothy Barkham, Ruth N. Zadoks, Mohammad Noor Amal Azmai, Stephen Baker, Vu Thi Ngoc Bich, Victoria Chalker, Man Ling Chau, David Dance, Rama Narayana Deepak, H. Rogier van Doorn, Ramona A. Gutierrez, Mark A. Holmes, Lan Nguyen Phu Huong, Tse Hsien Koh, Elisabete Martins, Kurosh Mehershahi, Paul Newton, Lee Ching Ng, Nguyen Ngoc Phuoc, Ornuma Sangwichian, Pongpun Sawatwong, Uraiwan Surin, Thean Yen Tan, Wen Ying Tang, Nguyen Vu Thuy, Paul Turner, Manivanh Vongsouvath, Defeng Zhang, Toni Whistler, Swaine L. Chen

Background

In 2015, Singapore had the first and only reported foodborne outbreak of invasive disease caused by the group B Streptococcus (GBS; Streptococcus agalactiae). Disease, predominantly septic arthritis and meningitis, was associated with sequence type (ST)283, acquired from eating raw farmed freshwater fish. Although GBS sepsis is well-described in neonates and older adults with co-morbidities, this outbreak affected non-pregnant and younger adults with fewer co-morbidities, suggesting greater virulence. Before 2015 ST283 had only been reported from twenty humans in Hong Kong and two in France, and from one fish in Thailand. We hypothesised that ST283 was causing region-wide infection in Southeast Asia.

Methodology/Principal findings

We performed a literature review, whole genome sequencing on 145 GBS isolates collected from six Southeast Asian countries, and phylogenetic analysis on 7,468 GBS sequences including 227 variants of ST283 from humans and animals. Although almost absent outside Asia, ST283 was found in all invasive Asian collections analysed, from 1995 to 2017. It accounted for 29/38 (76%) human isolates in Lao PDR, 102/139 (73%) in Thailand, 4/13 (31%) in Vietnam, and 167/739 (23%) in Singapore. ST283 and its variants were found in 62/62 (100%) tilapia from 14 outbreak sites in Malaysia and Vietnam, in seven fish species in Singapore markets, and a diseased frog in China.

Conclusions

GBS ST283 is widespread in Southeast Asia, where it accounts for a large proportion of bacteraemic GBS, and causes disease and economic loss in aquaculture. If human ST283 is fishborne, as in the Singapore outbreak, then GBS sepsis in Thailand and Lao PDR is predominantly a foodborne disease. However, whether transmission is from aquaculture to humans, or vice versa, or involves an unidentified reservoir remains unknown. Creation of cross-border collaborations in human and animal health are needed to complete the epidemiological picture.

Prioritizing surveillance of Nipah virus in India

PLoS Neglected Tropical Diseases News - 27 June 2019 - 9:00pm

by Raina K. Plowright, Daniel J. Becker, Daniel E. Crowley, Alex D. Washburne, Tao Huang, P. O. Nameer, Emily S. Gurley, Barbara A. Han

The 2018 outbreak of Nipah virus in Kerala, India, highlights the need for global surveillance of henipaviruses in bats, which are the reservoir hosts for this and other viruses. Nipah virus, an emerging paramyxovirus in the genus Henipavirus, causes severe disease and stuttering chains of transmission in humans and is considered a potential pandemic threat. In May 2018, an outbreak of Nipah virus began in Kerala, > 1800 km from the sites of previous outbreaks in eastern India in 2001 and 2007. Twenty-three people were infected and 21 people died (16 deaths and 18 cases were laboratory confirmed). Initial surveillance focused on insectivorous bats (Megaderma spasma), whereas follow-up surveys within Kerala found evidence of Nipah virus in fruit bats (Pteropus medius). P. medius is the confirmed host in Bangladesh and is now a confirmed host in India. However, other bat species may also serve as reservoir hosts of henipaviruses. To inform surveillance of Nipah virus in bats, we reviewed and analyzed the published records of Nipah virus surveillance globally. We applied a trait-based machine learning approach to a subset of species that occur in Asia, Australia, and Oceana. In addition to seven species in Kerala that were previously identified as Nipah virus seropositive, we identified at least four bat species that, on the basis of trait similarity with known Nipah virus-seropositive species, have a relatively high likelihood of exposure to Nipah or Nipah-like viruses in India. These machine-learning approaches provide the first step in the sequence of studies required to assess the risk of Nipah virus spillover in India. Nipah virus surveillance not only within Kerala but also elsewhere in India would benefit from a research pipeline that included surveys of known and predicted reservoirs for serological evidence of past infection with Nipah virus (or cross reacting henipaviruses). Serosurveys should then be followed by longitudinal spatial and temporal studies to detect shedding and isolate virus from species with evidence of infection. Ecological studies will then be required to understand the dynamics governing prevalence and shedding in bats and the contacts that could pose a risk to public health.

The European Medicines Agency’s scientific opinion on oral fexinidazole for human African trypanosomiasis

PLoS Neglected Tropical Diseases News - 27 June 2019 - 9:00pm

by Eric Pelfrene, Martin Harvey Allchurch, Nsengi Ntamabyaliro, Victoria Nambasa, Fátima V. Ventura, Nithyanandan Nagercoil, Marco Cavaleri

Failure of the dog culling strategy in controlling human visceral leishmaniasis in Brazil: A screening coverage issue?

PLoS Neglected Tropical Diseases News - 26 June 2019 - 9:00pm

by Lucas Christian de Sousa-Paula, Lidiane Gomes da Silva, Kamila Gaudêncio da Silva Sales, Filipe Dantas-Torres

In the present study, we assessed the annual screening coverage (i.e., the percentage of dogs that are screened for anti-Leishmania antibodies annually) in the municipality of Sobral, Ceará state, Brazil. Data on the number of dogs screened during 2008−2017 (except 2010) were obtained from the Centre for Zoonoses Control of Sobral. The annual screening coverage during 2012−2017 was calculated. Data on human visceral leishmaniasis (VL) cases during 2008−2017 were compiled from the National Disease Notification System. Correlation analyses were performed to assess the correlation between canine and human data. During 2008−2017, 73,964 dogs (range, 0 to 13,980 dogs/year) were serologically screened and 2,833 (3.8%) were positive. The annual screening coverage during 2012−2017 ranged from 11.1% to 45.7%. There were no significant correlations between the number of dogs culled and the number of human VL cases, canine positivity and human VL incidence, number of dogs culled and human VL incidence, or between canine positivity and number of human VL cases. An inconsistent and relatively low annual screening coverage was found in the study area, with no dog being screened in 2010 due to the lack of serological tests. Our results highlight that many dogs potentially infected with Leishmania infantum have been virtually overlooked by public health workers in the study area, perhaps with a negative, yet underestimated, impact on the control of canine and human VL. Hence, the failure of the dog culling strategy in controlling human VL in Brazil may be due to the low screening coverage and low percentage of culled dogs, rather than the absence of associations between canine and human infections.

Performance of recombinant chimeric proteins in the serological diagnosis of <i>Trypanosoma cruzi</i> infection in dogs

PLoS Neglected Tropical Diseases News - 26 June 2019 - 9:00pm

by Leonardo M. Leony, Natália E. M. Freitas, Rodrigo P. Del-Rei, Claudia M. Carneiro, Alexandre B. Reis, Ana Maria Jansen, Samanta C. C. Xavier, Yara M. Gomes, Edmilson D. Silva, Mitermayer G. Reis, Deborah B. M. Fraga, Paola A. F. Celedon, Nilson I. T. Zanchin, Filipe Dantas-Torres, Fred L. N. Santos

Background

Dogs are considered sentinels in areas of Trypanosoma cruzi transmission risk to humans. ELISA is generally the method of choice for diagnosing T. cruzi exposure in dogs, but its performance substantially depends on the antigenic matrix employed. In previous studies, our group has developed four chimeric antigens (IBMP-8.1, 8.2, 8.3, and 8.4) and evaluated their potential for diagnosing T. cruzi exposure in humans. For human sera, these chimeric antigens presented superior diagnostic performances as compared to commercial tests available in Brazil, Spain, and Argentina. Therefore, in this study we have evaluated the potential of these antigenic proteins for detection of anti-T. cruzi IgG antibodies in dog sera.

Methodology/Principal findings

The IBMP-ELISA assays were optimized by checkerboard titration. Subsequently, the diagnostic potential was validated through analysis of ROC curves and the performance of the tests was determined using double entry tables. Cross-reactivity was also evaluated for babesiosis, ehrlichiosis, dirofilariosis, anaplasmosis, and visceral leishmaniosis. Best performance was shown by IBMP-8.3 and IBMP-8.4, although all four antigens demonstrated a high diagnostic performance with 46 positive and 149 negative samples tested. IBMP-8.3 demonstrated 100% sensitivity, followed by IBMP-8.4 (96.7–100%), IBMP-8.2 (73.3–87.5%), and IBMP-8.1 (50–100%). The highest specificities were achieved with IBMP-8.2 (100%) and IBMP-8.4 (100%), followed by IBMP-8.3 (96.7–97.5%) and IBMP 8.1 (89.1–100%).

Conclusions/Significance

The use of chimeric antigenic matrices in immunoassays for anti-T. cruzi IgG antibody detection in sera of infected dogs was shown to be a promising tool for veterinary diagnosis and epidemiological studies. The chimeric antigens used in this work allowed also to overcome the common hurdles related to serodiagnosis of T. cruzi infection, especially regarding variation of efficiency parameters according to different strains and cross-reactivity with other infectious diseases.

Sampling strategies for monitoring and evaluation of morbidity targets for soil-transmitted helminths

PLoS Neglected Tropical Diseases News - 26 June 2019 - 9:00pm

by Federica Giardina, Luc E. Coffeng, Sam H. Farrell, Carolin Vegvari, Marleen Werkman, James E. Truscott, Roy M. Anderson, Sake J. de Vlas

Background

The current World Health Organization (WHO) target for the three major soil-transmitted helminth (STH) infections is to reduce prevalence of moderate-to-heavy infections to below 1% by 2020. In terms of monitoring and evaluation (M&E), the current WHO guidelines for control of STHs recommend evaluation of infection levels in school-age children (SAC) after five to six years of preventive chemotherapy (PC), using the standard Kato-Katz faecal smear. Here, we assess the predictive performance of various sampling designs for the evaluation of the morbidity target.

Methodology/Principal findings

Using two mathematical models for STH transmission and control, we simulate how the number of villages and SAC sampled affect the ability of survey results in sentinel villages to predict the achievement of the morbidity target in PC implementation units (e.g. district). As PC is stopped when the prevalence of infection in SAC in sentinel villages is less than 1%, we estimate the positive predictive value (PPV) of this indicator for meeting the morbidity target in the whole district. The PPV varies by species and PC strategy, and it is generally higher in areas with lower pre-control prevalence. Sampling a fixed number of SAC spread out over 10 instead of 5 sentinel villages may increase the PPV by up to 20 percentage points. If every SAC in a village is tested, a higher number of villages may increase the PPV by up to 80 percentage points. Increasing the proportion of SAC tested per village does not result in a relevant increase of PPV.

Conclusions/Significance

Although the WHO guidelines provide a combined strategy to control the three STH species, the efficacy of PC strategies clearly differs by species. There is added value in considering more villages within implementation units for M&E of morbidity targets, the extent varying by STH species. A better understanding of pre- and post-control local STH prevalence levels is essential for an adequate M&E strategy including the definition of morbidity targets at the appropriate geographical scale.

The effectiveness of inspections on reported mosquito larval habitats in households: A case-control study

PLoS Neglected Tropical Diseases News - 26 June 2019 - 9:00pm

by Joel Aik, Zhi Wei Neo, Jayanthi Rajarethinam, Kaiyun Chio, Wing Mun Lam, Lee-Ching Ng

Background

Dengue is an arboviral disease that imposes substantial health and economic burdens across the globe. Vector control remains a key strategy in settings where Dengvaxia (a dengue vaccine) has not been licenced due to safety concerns and where mass immunization programmes are not cost-effective. Though inspections are used as part of arboviral disease control programmes, evidence of their impact on the entomological activity in households is sparse.

Methodology/Principal findings

We analysed nationally representative household inspection data collected from Singapore over a 3-year period, to determine the effect of inspections on reported mosquito larval habitats in households. A case was a household with a positive report of a mosquito larval habitat in its most recent inspection in 2017. A control was a household that was reported free of mosquito larvae in its most recent inspection in 2017. Using multivariable logistic regression, we analysed 3,205 cases and 557,044 controls. Households averaging three inspections per annum were associated with reduced odds of mosquito larval habitat reports [Adjusted Odds Ratio (AOR): 0.49, 95% Confidence Interval (95% CI): 0.38 to 0.63]. The effect of inspections declined with decreasing inspection frequencies but remained protective at lower levels. Longer intervals (30 to 36 months) between the most recent two successive inspections were associated with increased odds of mosquito larval habitat reports (AOR: 1.28, 95% CI: 1.06 to 1.56) compared to those carried out less than 6 months apart. Mosquito larval habitat reports exhibited a dependence on spatial and household-level characteristics such as the location of the community district, housing type and housing floor level. We observed a four-fold increase in the odds of mosquito larval habitat reports in households with an immediate previous report of larval activity compared to those that did not have one (AOR: 4.52, 95% CI: 3.67 to 5.56).

Conclusions/Significance

Our study confirms the protective effect of inspections on reported mosquito larval habitat reporting in households. Spatial, temporal and household-level characteristics should be accounted for in prioritizing vector control resources. Alternative strategies may help address recurrent entomological activity in households.

TIM-1 serves as a receptor for Ebola virus in vivo, enhancing viremia and pathogenesis

PLoS Neglected Tropical Diseases News - 26 June 2019 - 9:00pm

by Bethany Brunton, Kai Rogers, Elisabeth K. Phillips, Rachel B. Brouillette, Ruayda Bouls, Noah S. Butler, Wendy Maury

Background

T cell immunoglobulin mucin domain-1 (TIM-1) is a phosphatidylserine (PS) receptor, mediating filovirus entry into cells through interactions with PS on virions. TIM-1 expression has been implicated in Ebola virus (EBOV) pathogenesis; however, it remains unclear whether this is due to TIM-1 serving as a filovirus receptor in vivo or, as others have suggested, TIM-1 induces a cytokine storm elicited by T cell/virion interactions. Here, we use a BSL2 model virus that expresses EBOV glycoprotein to demonstrate the importance of TIM-1 as a virus receptor late during in vivo infection.

Methodology/Principal findings

Infectious, GFP-expressing recombinant vesicular stomatitis virus encoding either full length EBOV glycoprotein (EBOV GP/rVSV) or mucin domain deleted EBOV glycoprotein (EBOV GPΔO/rVSV) was used to assess the role of TIM-1 during in vivo infection. GFP-expressing rVSV encoding its native glycoprotein G (G/rVSV) served as a control. TIM-1-sufficient or TIM-1-deficient BALB/c interferon α/β receptor-/- mice were challenged with these viruses. While G/rVSV caused profound morbidity and mortality in both mouse strains, TIM-1-deficient mice had significantly better survival than TIM-1-expressing mice following EBOV GP/rVSV or EBOV GPΔO/rVSV challenge. EBOV GP/rVSV or EBOV GPΔO/rVSV in spleen of infected animals was high and unaffected by expression of TIM-1. However, infectious virus in serum, liver, kidney and adrenal gland was reduced late in infection in the TIM-1-deficient mice, suggesting that virus entry via this receptor contributes to virus load. Consistent with higher virus loads, proinflammatory chemokines trended higher in organs from infected TIM-1-sufficient mice compared to the TIM-1-deficient mice, but proinflammatory cytokines were more modestly affected. To assess the role of T cells in EBOV GP/rVSV pathogenesis, T cells were depleted in TIM-1-sufficient and -deficient mice and the mice were challenged with virus. Depletion of T cells did not alter the pathogenic consequences of virus infection.

Conclusions

Our studies provide evidence that at late times during EBOV GP/rVSV infection, TIM-1 increased virus load and associated mortality, consistent with an important role of this receptor in virus entry. This work suggests that inhibitors which block TIM-1/virus interaction may serve as effective antivirals, reducing virus load at late times during EBOV infection.

Accurate diagnosis of lesions suspected of being caused by <i>Taenia solium</i> in body organs of pigs with naturally acquired porcine cysticercosis

PLoS Neglected Tropical Diseases News - 25 June 2019 - 9:00pm

by Charles G. Gauci, Chrisostom Ayebazibwe, Zachary Nsadha, Chris Rutebarika, Ishab Poudel, Keshav Sah, Dinesh Kumar Singh, Andrew Stent, Angela Colston, Meritxell Donadeu, Marshall W. Lightowlers

The definitive method for diagnosis of porcine cysticercosis is the detection of cysticerci at necropsy. Cysts are typically located in the striated muscle and brain. Until recently Taenia solium cysticerci have not been definitively identified in other tissue locations, despite several comprehensive investigations having been undertaken which included investigation of body organs other than muscle and brain. Recently a study conducted in Zambia reported 27% infection with T. solium in the liver of pigs with naturally acquired porcine cysticercosis, as well as some T. solium infection in the lungs and spleen of some animals. We investigated the cause of lesions in sites other than the muscle or brain in a total of 157 pigs from T. solium endemic regions of Uganda and Nepal which were subjected to extensive investigations at necropsy. Lesions which had the potential to be caused by T. solium were characterised by macroscopic and microscopic examination, histology as well as DNA characterisation by PCR-RFLP and sequencing. Lesions were confirmed as being caused by Taenia hydatigena (both viable and non-viable), by T. asiatica and Echinococcus granulosus (in Nepal) and nematode infections. No T. solium-related lesions or cysticerci were identified in any tissue other than muscle and brain. It is recommended that future evaluations of porcine cysticercosis in aberrant tissue locations include DNA analyses that take appropriate care to avoid the possibility of contamination of tissue specimens with DNA from a different tissue location or a different animal. The use of appropriate control samples to confirm the absence of cross-sample contamination is also recommended.

Reviewing evidence of the clinical effectiveness of commercially available antivenoms in sub-Saharan Africa identifies the need for a multi-centre, multi-antivenom clinical trial

PLoS Neglected Tropical Diseases News - 24 June 2019 - 9:00pm

by Julien Potet, James Smith, Lachlan McIver

Background

Snakebite envenoming kills more than more than 20,000 people in Sub-Saharan Africa every year. Poorly regulated markets have been inundated with low-price, low-quality antivenoms. This review aimed to systematically collect and analyse the clinical data on all antivenom products now available in markets of sub-Saharan Africa.

Methodology/Principal findings

Our market analysis identified 12 polyspecific and 4 monospecific antivenom products in African markets. Our search strategy was first based on a systematic search of publication databases, followed by manual searches and discussions with experts. All types of data, including programmatic data, were eligible. All types of publications were eligible, including grey literature. Cohorts of less than 10 patients were excluded. 26 publications met the inclusion criteria. Many publications had to be excluded because clinical outcomes were not clearly linked to a specific product. Our narrative summaries present product-specific clinical data in terms of safety and effectiveness against the different species and envenoming syndromes. Three products (EchiTabPlus, EchiTabG, SAIMR-Echis-monovalent) were found to have been tested in robust clinical studies and found effective against envenoming caused by the West African carpet viper (Echis ocellatus). Four products (Inoserp-Panafricain, Fav-Afrique, SAIMR-Polyvalent, Antivipmyn-Africa) were found to have been evaluated only in observational single-arm studies, with varying results. For nine other products, there are either no data in the public domain, or only negative data suggesting a lack of effectiveness.

Conclusions/Significance

Clinical data vary among the different antivenom products currently in African markets. Some products are available commercially although they have been found to lack effectiveness. The World Health Organization should strengthen its capacity to assess antivenom products, support antivenom manufacturers, and assist African countries and international aid organizations in selecting appropriate quality antivenoms.

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