RSS news feeds

Maternal <i>Leishmania infantum</i> infection status has significant impact on leishmaniasis in offspring

PLoS Neglected Tropical Diseases News - 13 February 2019 - 10:00pm

by Angela J. Toepp, Carolyne Bennett, Benjamin Scott, Reid Senesac, Jacob J. Oleson, Christine A. Petersen

Visceral Leishmaniasis is a deadly disease caused by Leishmania infantum, endemic in more than 98 countries across the globe. Although the most common means of transmission is via a sand fly vector, there is growing evidence that vertical transmission may be critical for maintaining L. infantum infection within the reservoir, canine, population. Vertical transmission is also an important cause of infant morbidity and mortality particularly in sub-Saharan Africa. While vertical transmission of visceralizing species of Leishmania has been reported around the globe, risk factors associated with this unique means of Leishmania transmission have not been identified therefore interventions regarding this means of transmission have been virtually non-existent. Furthermore, the basic reproductive number, (R0), or number of new L. infantum infections that one infected mother or dam can cause has not been established for vertical transmission, also hampering the ability to assess the impact of this means of transmission within reservoir of human hosts. Canine Leishmaniosis (CanL) is enzootic within a U.S. hunting dog population. CanL is transmitted within this population via transplacental transmission with no reported vector transmission, despite many repeated attempts to find infected sand flies associated with these dogs and kennels. This population with predominantly, if not solely, vertical transmission of L. infantum was used to evaluate the critical risk factors for vertical transmission of Leishmania and establish the R0 of vertical L. infantum infection. Evaluation of 124 animals born to eighteen dams diagnostically positive for infection with L. infantum showed that there was a 13.84x greater chance of being positive for L. infantum within their lifetime if the mother was also positive within her lifetime (RR: 13.84, 95% CI: 3.54–54.20, p-value: <0.0001). The basic reproductive number for vertically transmitted L. infantum within this cohort was 4.12. These results underscore that there is a high risk of L. infantum infection to transmit from mother to offspring. Targeted public health interventions and control efforts that address vertical transmission of L. infantum are necessary in endemic countries to eliminate visceral leishmaniasis.

Potential for sylvatic and urban <i>Aedes</i> mosquitoes from Senegal to transmit the new emerging dengue serotypes 1, 3 and 4 in West Africa

PLoS Neglected Tropical Diseases News - 13 February 2019 - 10:00pm

by Alioune Gaye, Eryu Wang, Nikos Vasilakis, Hilda Guzman, Diawo Diallo, Cheikh Talla, Yamar Ba, Ibrahima Dia, Scott C. Weaver, Mawlouth Diallo

Dengue fever (DEN) is the most common arboviral disease in the world and dengue virus (DENV) causes 390 million annual infections around the world, of which 240 million are inapparent and 96 million are symptomatic. During the past decade a changing epidemiological pattern has been observed in Africa, with DEN outbreaks reported in all regions. In Senegal, all DENV serotypes have been reported. These important changes in the epidemiological profile of DEN are occurring in a context where there is no qualified vaccine against DEN. Further there is significant gap of knowledge on the vector bionomics and transmission dynamics in the African region to effectively prevent and control epidemics. Except for DENV-2, few studies have been performed with serotypes 1, 3, and 4, so this study was undertaken to fill out this gap. We assessed the vector competence of Aedes (Diceromyia) furcifer, Ae. (Diceromyia) taylori, Ae. (Stegomyia) luteocephalus, sylvatic and urban Ae. (Stegomyia) aegypti populations from Senegal for DENV-1, DENV-3 and DENV-4 using experimental oral infection. Whole bodies and wings/legs were tested for DENV presence by cell culture assays and saliva samples were tested by real time RT-PCR to estimate infection, disseminated infection and transmission rates. Our results revealed a low capacity of sylvatic and urban Aedes mosquitoes from Senegal to transmit DENV-1, DENV-3 and DENV-4 and an impact of infection on their mortality. The highest potential transmission rate was 20% despite the high susceptibility and disseminated infection rates up to 93.7% for the 3 Ae. aegypti populations tested, and 84.6% for the sylvatic vectors Ae. furcifer, Ae. taylori and Ae. luteocephalus.

Feasibility of feeding <i>Aedes aegypti</i> mosquitoes on dengue virus-infected human volunteers for vector competence studies in Iquitos, Peru

PLoS Neglected Tropical Diseases News - 12 February 2019 - 10:00pm

by Kanya C. Long, Juan Sulca, Isabel Bazan, Helvio Astete, Hugo L. Jaba, Crystyan Siles, Claudine Kocher, Stalin Vilcarromero, Julia Schwarz, Karin S. Escobedo-Vargas, Fanny Castro-Llanos, Leslye Angulo, Guadalupe Flores, Cesar Ramal-Asayag, Eric S. Halsey, Robert D. Hontz, Valerie A. Paz-Soldan, Thomas W. Scott, Louis Lambrechts, Amy C. Morrison

Background

Transmission of dengue virus (DENV) from humans to mosquitoes represents a critical component of dengue epidemiology. Examinations of this process have generally been hampered by a lack of methods that adequately represent natural acquisition of DENV by mosquitoes from humans. In this study, we assessed artificial and natural blood feeding methods based on rates of DENV infection and dissemination within mosquitoes for use in a field-based epidemiological cohort study in Iquitos, Peru.

Methodology/Principal findings

Our study was implemented, stepwise, between 2011 and 2015. Participants who were 5 years and older with 5 or fewer days of fever were enrolled from ongoing clinic- and neighborhood-based studies on dengue in Iquitos. Wild type, laboratory-reared Aedes aegypti were fed directly on febrile individuals or on blood collected from participants that was either untreated or treated with EDTA. Mosquitoes were tested after approximately 14 days of extrinsic incubation for DENV infection and dissemination. A total of 58 participants, with viremias ranging from 1.3 × 102 to 2.9 × 106 focus-forming units per mL of serum, participated in one or more feeding methods. DENV infection and dissemination rates were not significantly different following direct and indirect-EDTA feeding; however, they were significantly lower for mosquitoes that fed indirectly on blood with no additive. Relative to direct feeding, infection rates showed greater variation following indirect-EDTA than indirect-no additive feeding. Dissemination rates were correlated across all feeding methods. No differences were detected in DENV infection or dissemination rates in mosquitoes fed directly on participants with different dengue illness severity.

Conclusions/Significance

Our study demonstrates the feasibility of using direct and indirect feeding methods for field-based studies on vector competence. Direct mosquito feeding is preferable in terms of logistical ease, biosecurity, and reliability.

Vector competence of biting midges and mosquitoes for Shuni virus

PLoS Neglected Tropical Diseases News - 12 February 2019 - 10:00pm

by Tim W. R. Möhlmann, Judith Oymans, Paul J. Wichgers Schreur, Constantianus J. M. Koenraadt, Jeroen Kortekaas, Chantal B. F. Vogels

Background

Shuni virus (SHUV) is an orthobunyavirus that belongs to the Simbu serogroup. SHUV was isolated from diverse species of domesticated animals and wildlife, and is associated with neurological disease, abortions, and congenital malformations. Recently, SHUV caused outbreaks among ruminants in Israel, representing the first incursions outside the African continent. The isolation of SHUV from a febrile child in Nigeria and seroprevalence among veterinarians in South Africa suggests that the virus may have zoonotic potential as well. The high pathogenicity, extremely broad tropism, potential transmission via both biting midges and mosquitoes, and zoonotic features of SHUV require further investigation. This is important to accurately determine the risk for animal and human health, and to facilitate preparations for potential epidemics. To gain first insight into the potential involvement of biting midges and mosquitoes in SHUV transmission we have investigated the ability of SHUV to infect two species of laboratory-colonised biting midges and two species of mosquitoes.

Methodology/Principal findings

Culicoides nubeculosus, C. sonorensis, Culex pipiens pipiens, and Aedes aegypti were orally exposed to SHUV by providing an infectious blood meal. Biting midges showed high infection rates of approximately 40%-60%, whereas infection rates of mosquitoes were only 0–2%. Moreover, successful dissemination in both species of biting midges and no evidence for transmission by orally exposed mosquitoes was found.

Conclusions/Significance

The results of this study suggest that different species of Culicoides midges are efficient in SHUV transmission, while the involvement of mosquitoes has not been supported.

Genetic evidence of <i>Coxiella burnetii</i> infection in acute febrile illnesses in Iran

PLoS Neglected Tropical Diseases News - 11 February 2019 - 10:00pm

by Saber Esmaeili, Ashraf Mohabati Mobarez, Mohammad Khalili, Ehsan Mostafavi, Pardis Moradnejad

Mounting evidence suggests that Q-fever is more prevalent in Iran than originally believed. However, in most parts of the country, clinicians do not pay enough attention to Q fever in their differential diagnosis. The aim of this study was to investigate the prevalence of Coxiella burnetii in suspected cases of acute Q fever in north-western Iran using molecular techniques. Febrile patients were enrolled in the study and investigated for C. burnetii infection. Sera samples were tested using real-time PCR for detection of IS1111 gene, and positive samples were confirmed with nested PCR. Nine patients (4.2%) out of 216 suspected cases were positive for C. burnetii. Weakness and fatigue, headache, and lethargy were the most prevalent clinical symptoms in acute Q fever patients. According to the results of this study and other reports of human cases in Iran, the diagnosis system of Q fever in Iran should be urgently revamped.

Effect of a sanitation intervention on soil-transmitted helminth prevalence and concentration in household soil: A cluster-randomized controlled trial and risk factor analysis

PLoS Neglected Tropical Diseases News - 11 February 2019 - 10:00pm

by Lauren Steinbaum, John Mboya, Ryan Mahoney, Sammy M. Njenga, Clair Null, Amy J. Pickering

Improved sanitation has been associated with a reduced prevalence of soil-transmitted helminth (STH) infection and has been hypothesized to prevent fecal contamination from spreading throughout the household environment. We evaluated the effect of providing households with a pit latrine with a plastic slab and drophole cover, child feces management tools, and associated behavioral messaging on reducing STH eggs in household soil. We collected soil samples from 2107 households (898 control and 1209 improved sanitation intervention households) that were enrolled in the WASH Benefits cluster randomized controlled trial in rural Kenya and performed a post-intervention analysis after two years of intervention exposure. Following a pre-specified analysis plan, we combined all households that received the sanitation intervention into one group for comparison to control households. The prevalence of STH eggs in soil was 18.9% in control households and 17.0% in intervention households. The unadjusted prevalence ratio of total STH eggs in the intervention groups compared to the control group was 0.94 (95% CI: 0.78–1.13). The geometric mean concentration was 0.05 eggs/g dry soil in control households and intervention households. Unadjusted and adjusted models gave similar results. We found use of a shared latrine, presence of a roof over the sampling area, and the number of dogs owned at baseline was associated with an increased prevalence of STH eggs in soil; the presence of a latrine that was at least 2 years old and a latrine with a covered drophole was associated with a reduction in the prevalence of STH eggs in soil. Soil moisture content was also associated with an increased prevalence of STH eggs in soil. Our results indicate that an intervention designed to increase access to improved latrines and child feces management tools may not be enough to impact environmental occurrence of STH in endemic areas where latrine coverage is already high.

The safety and efficacy of miltefosine in the long-term treatment of post-kala-azar dermal leishmaniasis in South Asia – A review and meta-analysis

PLoS Neglected Tropical Diseases News - 11 February 2019 - 10:00pm

by Joyce Pijpers, Margriet L. den Boer, Dirk R. Essink, Koert Ritmeijer

Background

Miltefosine (MF) is the only oral drug available for treatment of visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL). Although the drug is effective and well tolerated in treatment of VL, the efficacy and safety of MF for longer treatment durations (>28 days) in PKDL remains unclear. This study provides an overview of the current knowledge about safety and efficacy of long treatment courses with MF in PKDL, as a strategy in the VL elimination in South Asia.

Methodology/Principal findings

Literature was searched systematically for articles investigating MF treatment in PKDL. A meta-analysis included eight studies (total 324 PKDL patients) to estimate the efficacy of MF in longer treatment regimens (range 6–16 weeks). We found a per-protocol (PP) initial cure rate of 95.2% (95%CI 89.6–100.8) and a PP definite cure rate of 90% (95%CI 81.6–96.3). Descriptive analysis showed that 20% of patients experienced adverse events, which mostly had an onset in the first week of treatment and were likely to get more severe after four weeks of treatment. Gastrointestinal (GI) side effects such as vomiting, nausea, diarrhoea, and abdominal pain were most common.

Conclusions/Significance

Longer treatment regimens with MF are effective in PKDL patients in India, however with the caveat that the efficacy has recently been observed to decline. GI side effects are frequent, although mostly mild or moderate. However, on the basis of limited data, we cannot conclude that longer MF treatment regimens are safe. Moreover, VL and PKDL pharmacovigilance studies indicate a risk for serious adverse events, questioning the safety of MF. The provision of safer treatment regimens for PKDL patients are therefore recommended. Until these regimens are identified, it should be considered to halt the use of MF monotherapy for PKDL in order to preserve the drug’s efficacy.

Acceptability of <i>Aedes aegypti</i> blood feeding on dengue virus-infected human volunteers for vector competence studies in Iquitos, Peru

PLoS Neglected Tropical Diseases News - 11 February 2019 - 10:00pm

by Amy C. Morrison, Julia Schwarz, Kanya C. Long, Jhonny Cordova, Jennifer E. Rios, W. Lorena Quiroz, S. Alfonso Vizcarra, Robert D. Hontz, Thomas W. Scott, Louis Lambrechts, Valerie A. Paz Soldan

As part of a study to investigate drivers of dengue virus (DENV) transmission dynamics, this qualitative study explored whether DENV-infected residents of Iquitos, Peru, considered it acceptable (1) to participate in direct mosquito feeding experiments (lab-reared Aedes aegypti mosquitoes fed directly on human volunteers) and (2) to provide blood meals indirectly (Ae. aegypti fed on blood drawn from participants by venipuncture). Twelve focus group discussions (FGDs; 94 participants: 82 females and 12 males) were conducted in January 2014 to explore six themes: (1) concerns and preferences regarding direct mosquito feeds and blood draws, (2) comprehension of and misconceptions about study procedures, (3) motivating factors for participation, (4) acceptability of children’s participation, (5) willingness to provide multiple samples over several days, and (6) preference for direct feedings in homes versus the study laboratory. Results of FGDs, including one with 5 of 53 past direct mosquito feed participants, indicated that mosquito feeding procedures are acceptable to Iquitos residents when they are provided with information and a few key messages are properly reinforced. FGD participants’ concerns focused primarily on safety issues rather than discomfort associated with mosquito bites. A video explaining the study dramatically increased comprehension of the study procedures. The majority of participants expressed a preference for mosquito feeding over venipuncture. Adults supported child participation if the children themselves assented. For most participants, home feedings were preferred over those in a laboratory. A major impetus for participation was the idea that results would contribute to an improved understanding of DENV transmission in Iquitos. Findings from our study will support future large-scale studies that employ direct mosquito feeding, a low-risk, non-invasive procedure that is experimentally superior to artificial mosquito feeding methods.

Detection of Zika virus in mouse mammary gland and breast milk

PLoS Neglected Tropical Diseases News - 11 February 2019 - 10:00pm

by Jose Angel Regla-Nava, Karla M. Viramontes, Teodora Vozdolska, Anh-Thy Huynh, Tom Villani, Graeme Gardner, Michael Johnson, Pamela J. Ferro, Sujan Shresta, Kenneth Kim

Clinical reports of Zika Virus (ZIKV) RNA detection in breast milk have been described, but evidence conflicts as to whether this RNA represents infectious virus. We infected post-parturient AG129 murine dams deficient in type I and II interferon receptors with ZIKV. ZIKV RNA was detected in pup stomach milk clots (SMC) as early as 1 day post maternal infection (dpi) and persisted as late as 7 dpi. In mammary tissues, ZIKV replication was demonstrated by immunohistochemistry in multiple cell types including cells morphologically consistent with myoepithelial cells. No mastitis was seen histopathologically. In the SMC and tissues of the nursing pups, no infectious virus was detected via focus forming assay. However, serial passages of fresh milk supernatant yielded infectious virus, and immunohistochemistry showed ZIKV replication protein associated with degraded cells in SMC. These results suggest that breast milk may contain infectious ZIKV. However, breast milk transmission (BMT) does not occur in this mouse strain that is highly sensitive to ZIKV infection. These results suggest a low risk for breast milk transmission of ZIKV, and provide a platform for investigating ZIKV entry into milk and mechanisms which may prevent or permit BMT.

Comparing the performance of urine and copro-antigen detection in evaluating <i>Opisthorchis viverrini</i> infection in communities with different transmission levels in Northeast Thailand

PLoS Neglected Tropical Diseases News - 8 February 2019 - 10:00pm

by Chanika Worasith, Chompunoot Wangboon, Kunyarat Duenngai, Nadda Kiatsopit, Kulthida Kopolrat, Anchalee Techasen, Jiraporn Sithithaworn, Narong Khuntikeo, Watcharin Loilome, Nisana Namwat, Puangrat Yongvanit, Elizabeth J. Carlton, Paiboon Sithithaworn

To combat and eventually eliminate the transmission of the liver fluke Opisthorchis viverrini, an accurate and practical diagnostic test is required. A recently established urine antigen detection test using monoclonal antibody-based enzyme-immunosorbent assay (mAb-ELISA) has shown promise due to its high diagnostic accuracy and the use of urine in place of fecal samples. To further test the utility of this urine assay, we performed a cross sectional study of 1,043 people in 3 opisthorchiasis endemic communities in northeast Thailand by applying urine antigen detection together with copro-antigen detection methods. The quantitative formalin-ethyl acetate concentration technique (FECT) was concurrently performed as a reference method. The prevalence of O. viverrini determined by urine antigen detection correlated well with that by copro-antigen detection and both methods showed 10–15% higher prevalence than FECT. Within the fecal negative cases by FECT, 29% and 43% were positive by urine and copro-antigen detection, respectively. The prevalence and intensity profiles determined by antigen detection and FECT showed similar patterns of increasing trends of infection with age. The concentration of antigen measured in urine showed a positive relationship with the concentration of copro-antigen, both of which were positively correlated with fecal egg counts. The data observed in this study indicate that urine antigen detection had high diagnostic accuracy and was in concordance with copro-antigen detection. Due to the ease and noninvasiveness of sample collection, the urine assay has high potential for clinical diagnosis as well as population screening in the program for the control and elimination of opisthorchiasis.

Etiology and severity of diarrheal diseases in infants at the semiarid region of Brazil: A case-control study

PLoS Neglected Tropical Diseases News - 8 February 2019 - 10:00pm

by Aldo A. M. Lima, Domingos B. Oliveira, Josiane S. Quetz, Alexandre Havt, Mara M. G. Prata, Ila F. N. Lima, Alberto M. Soares, José Q. Filho, Noélia L. Lima, Pedro H. Q. S. Medeiros, Ana K. S. Santos, Herlice N. Veras, Rafhaella N. D. G. Gondim, Rafaela C. Pankov, Mariana D. Bona, Francisco A. P. Rodrigues, Renato A. Moreira, Ana C. O. M. Moreira, Marcelo Bertolini, Luciana R. Bertolini, Vicente J. F. Freitas, Eric R. Houpt, Richard L. Guerrant

Background

Diarrheal diseases are an important cause of morbidity and mortality among children in developing countries. We aimed to study the etiology and severity of diarrhea in children living in the low-income semiarid region of Brazil.

Methodology

This is a cross-sectional, age-matched case-control study of diarrhea in children aged 2–36 months from six cities in Brazil’s semiarid region. Clinical, epidemiological, and anthropometric data were matched with fecal samples collected for the identification of enteropathogens.

Results

We enrolled 1,200 children, 596 cases and 604 controls. By univariate analysis, eight enteropathogens were associated with diarrhea: Norovirus GII (OR 5.08, 95% CI 2.10, 12.30), Adenovirus (OR 3.79, 95% CI 1.41, 10.23), typical enteropathogenic Escherichia coli (tEPEC), (OR 3.28, 95% CI 1.39, 7.73), enterotoxigenic E. coli (ETEC LT and ST producing toxins), (OR 2.58, 95% CI 0.99, 6.69), rotavirus (OR 1.91, 95% CI 1.20, 3.02), shiga toxin-producing E. coli (STEC; OR 1.77, 95% CI 1.16, 2.69), enteroaggregative E. coli (EAEC), (OR 1.45, 95% CI 1.16, 1.83) and Giardia spp. (OR 1.39, 95% CI 1.05, 1.84). By logistic regression of all enteropathogens, the best predictors of diarrhea were norovirus, adenovirus, rotavirus, STEC, Giardia spp. and EAEC. A high diarrhea severity score was associated with EAEC.

Conclusions

Six enteropathogens: Norovirus, Adenovirus, Rotavirus, STEC, Giardia spp., and EAEC were associated with diarrhea in children from Brazil’s semiarid region. EAEC was associated with increased diarrhea severity.

Evaluation of a class of isatinoids identified from a high-throughput screen of human kinase inhibitors as anti-Sleeping Sickness agents

PLoS Neglected Tropical Diseases News - 8 February 2019 - 10:00pm

by Dana M. Klug, Rosario Diaz-Gonzalez, Guiomar Pérez-Moreno, Gloria Ceballos-Pérez, Raquel García-Hernández, Veronica Gomez-Pérez, Luis Miguel Ruiz-Pérez, Domingo I. Rojas-Barros, Francisco Gamarro, Dolores González-Pacanowska, María S. Martínez-Martínez, Pilar Manzano, Lori Ferrins, Conor R. Caffrey, Miguel Navarro, Michael P. Pollastri

New treatments are needed for neglected tropical diseases (NTDs) such as Human African trypanosomiasis (HAT), Chagas disease, and schistosomiasis. Through a whole organism high-throughput screening campaign, we previously identified 797 human kinase inhibitors that grouped into 59 structural clusters and showed activity against T. brucei, the causative agent of HAT. We herein report the results of further investigation of one of these clusters consisting of substituted isatin derivatives, focusing on establishing structure-activity and -property relationship scope. We also describe their in vitro absorption, distribution, metabolism, and excretion (ADME) properties. For one isatin, NEU-4391, which offered the best activity-property profile, pharmacokinetic parameters were measured in mice.

Serological evidence of infection with dengue and Zika viruses in horses on French Pacific Islands

PLoS Neglected Tropical Diseases News - 7 February 2019 - 10:00pm

by Cécile Beck, Isabelle Leparc-Goffart, Denise Desoutter, Estelle Debergé, Hervé Bichet, Steeve Lowenski, Marine Dumarest, Gaelle Gonzalez, Camille Migné, Jessica Vanhomwegen, Stéphan Zientara, Benoit Durand, Sylvie Lecollinet

New Caledonia and French Polynesia are areas in which arboviruses circulate extensively. A large serological survey among horses from New Caledonia and French Polynesia was carried out to investigate the seroprevalence of flaviviruses in the horse population. Here, 293 equine sera samples were screened for flaviviruses using a competitive enzyme-linked immunosorbent assay (cELISA). The positive sera were then confirmed using a flavivirus-specific microsphere immunoassay (MIA) and seroneutralization tests. This serosurvey showed that 16.6% (27/163) and 30.8% (40/130) of horses were positive for cELISA tests in New Caledonia and French Polynesia, respectively, but the MIA technique, targeting only flaviviruses causing neuro-invasive infections in humans and horses (i.e. West Nile virus [WNV], Japanese encephalitis virus [JEV] and tick-borne encephalitis virus [TBEV]), showed negative results for more than 85% (57/67) of the cELISA-positive animals. Seroneutralization tests with the main flaviviruses circulating in the South Pacific revealed that 6.1% (10/163; confidence interval [95% CI] 3.0%-11.0%) of sera in New Caledonia and 7.7% (10/130; 95% CI 3.8%-13.7%) in French Polynesia were positive for dengue virus serotype 1 (DENV1) and 4.3% (7/163; 95% CI 1.7%-8.6%) in New Caledonia and 15.4% (20/130, 95% CI 9.7%-22.8%) in French Polynesia were found positive for Zika virus (ZIKV). Seroprevalence of the JEV and WNV flaviviruses on the 293 samples from both island groups were comparatively much lower (less than 2%). This seroprevalence study in the horse population shows that horses can be infected with dengue and Zika viruses and that these infections lead to seroconversions in horses. The consequences of these infections in horses and their role in ZIKV and DENV epidemiological cycles are two issues that deserve further investigation.

Inward rectifier potassium (Kir) channels mediate salivary gland function and blood feeding in the lone star tick, <i>Amblyomma americanum</i>

PLoS Neglected Tropical Diseases News - 7 February 2019 - 10:00pm

by Zhilin Li, Kevin R. Macaluso, Lane D. Foil, Daniel R. Swale

Background

Tick feeding causes extreme morbidity and mortality to humans through transmission of pathogens and causes severe economic losses to the agricultural industry by reducing livestock yield. Salivary gland secretions are essential for tick feeding and thus, reducing or preventing saliva secretions into the vertebrate host is likely to reduce feeding and hinder pathogen life cycles. Unfortunately, the membrane physiology of tick salivary glands is underexplored and this gap in knowledge limits the development of novel therapeutics for inducing cessation of tick feeding.

Methodology

We studied the influence of inward rectifier potassium (Kir) channel subtypes to the functional capacity of the isolated tick salivary gland through the use of a modified Ramsay assay. The secreted saliva was subsequently used for quantification of the elemental composition of the secreted saliva after the glands were exposed to K+ channel modulators as a measure of osmoregulatory capacity. Lastly, changes to blood feeding behavior and mortality were measured with the use of a membrane feeding system.

Principal findings

In this study, we characterized the fundamental role of Kir channel subtypes in tick salivary gland function and provide evidence that pharmacological inhibition of these ion channels reduces the secretory activity of the salivary gland of Amblyomma americanum. The reduced secretory capacity of the salivary gland was directly correlated with a dramatic reduction of blood ingestion during feeding. Further, exposure to small-molecule modulators of Kir channel subtypes induced mortality to ticks that is likely resultant from an altered osmoregulatory capacity.

Conclusions

Our data contribute to understanding of tick salivary gland function and could guide future campaigns aiming to develop chemical or reverse vaccinology technologies to reduce the worldwide burden of tick feeding and tick-vectored pathogens.

Knowledge, attitudes and practices with regard to schistosomiasis prevention and control: Two cross-sectional household surveys before and after a Community Dialogue intervention in Nampula province, Mozambique

PLoS Neglected Tropical Diseases News - 7 February 2019 - 10:00pm

by Christian Rassi, Sandrine Martin, Kirstie Graham, Monica Anna de Cola, Celine Christiansen-Jucht, Lauren E. Smith, Ercílio Jive, Anna E. Phillips, James N. Newell, Marilia Massangaie

Background

The Community Dialogue Approach is a promising social and behaviour change intervention, which has shown potential for improving health seeking behaviour. To test if this approach can strengthen prevention and control of schistosomiasis at community level, Malaria Consortium implemented a Community Dialogue intervention in four districts of Nampula province, Mozambique, between August 2014 and September 2015.

Methodology/Principal findings

Cross-sectional household surveys were conducted before (N = 791) and after (N = 792) implementation of the intervention to assess its impact on knowledge, attitudes and practices at population level. At both baseline and endline, awareness of schistosomiasis was high at over 90%. After the intervention, respondents were almost twice as likely to correctly name a risk behaviour associated with schistosomiasis (baseline: 18.02%; endline: 30.11%; adjusted odds ratio: 1.91; 95% confidence interval: 1.14–2.58). Increases were also seen in the proportion of people who knew that schistosomiasis can be spread by infected persons and who could name at least one correct transmission route (baseline: 25.74%; endline: 32.20%; adjusted odds ratio: 1.36; 95% confidence interval: 1.01–1.84), those who knew that there is a drug that treats the disease (baseline: 29.20%, endline: 47.55%; adjusted odds ratio: 2.19; 95% confidence interval: 1.67–2.87) and those who stated that they actively protect themselves from the disease and cited an effective behaviour (baseline: 40.09%, endline: 59.30%; adjusted odds ratio: 2.14; 95% confidence interval: 1.40–3.28). The intervention did not appear to lead to a reduction in misconceptions. In particular, the belief that the disease is sexually transmitted continued to be widespread.

Conclusions/Significance

Given its overall positive impact on knowledge and behaviour at population level, Community Dialogue can play an important role in schistosomiasis prevention and control. The intervention could be further strengthened by better enabling communities to take suitable action and linking more closely with community governance structures and health system programmes.

Very severe tungiasis in Amerindians in the Amazon lowland of Colombia: A case series

PLoS Neglected Tropical Diseases News - 7 February 2019 - 10:00pm

by Hollman Miller, Jovana Ocampo, Alvaro Ayala, Julian Trujillo, Hermann Feldmeier

Background

Tungiasis is a parasitic skin disease caused by penetrating female sand fleas. By nature, tungiasis is a self-limiting infection. However, in endemic settings re-infection is the rule and parasite load gradually accumulates over time. Intensity of infection and degree of morbidity are closely related.

Methodology/principal findings

This case series describes the medical history, the clinical pathology, the socio-economic and the environmental characteristics of very severe tungiasis in five patients living in traditional Amerindian communities in the Amazon lowland of Colombia. Patients had between 400 and 1,300 penetrated sand fleas. The feet were predominantly affected, but clusters of embedded sand fleas also occurred at the ankles, the knees, the elbows, the hands, the fingers and around the anus. The patients were partially or totally immobile. Patients 1 and 3 were cachectic, patient 2 presented severe malnutrition. Patient 3 needed a blood transfusion due to severe anemia. All patients showed a characteristic pattern of pre-existing medical conditions and culture-dependent behavior facilitating continuous re-infection. In all cases intradomiciliary transmission was very likely.

Conclusion/significance

Although completely ignored in the literature, very severe tungiasis occurs in settings where patients do not have access to health care and are stricken in a web of pre-existing illness, poverty and neglect. If not treated, very severe tungiasis may end in a fatal disease course.

Protective immunity by an engineered DNA vaccine for Mayaro virus

PLoS Neglected Tropical Diseases News - 7 February 2019 - 10:00pm

by Hyeree Choi, Sagar B. Kudchodkar, Emma L. Reuschel, Kanika Asija, Piyush Borole, Michelle Ho, Krzysztof Wojtak, Charles Reed, Stephanie Ramos, Nathen E. Bopp, Patricia V. Aguilar, Scott C. Weaver, J. Joseph Kim, Laurent Humeau, Pablo Tebas, David B. Weiner, Kar Muthumani

Mayaro virus (MAYV) of the genus alphavirus is a mosquito-transmitted emerging infectious disease that causes an acute febrile illness, rash, headaches, and nausea that may turn into incapacitating, persistent arthralgias in some victims. Since its discovery in Trinidad in 1954, cases of MAYV infection have largely been confined there and to the northern countries of South America, but recently, MAYV cases have been reported in some island nations in the Caribbean Sea. Accompanying these reports is evidence that new vectors, including Aedes spp. mosquitos, recently implicated in the global spread of Zika and chikungunya viruses, are competent for MAYV transmission, which, if true, could facilitate the spread of MAYV beyond its current range. Despite its status as an emerging virus, there are no licensed vaccines to prevent MAYV infection nor therapeutics to treat it. Here, we describe the development and testing of a novel DNA vaccine, scMAYV-E, that encodes a synthetically-designed consensus MAYV envelope sequence. In vivo electroporation-enhanced immunization of mice with this vaccine induced potent humoral responses including neutralizing antibodies as well as robust T-cell responses to multiple epitopes in the MAYV envelope. Importantly, these scMAYV-E-induced immune responses protected susceptible mice from morbidity and mortality following a MAYV challenge.

Strategies to increase adoption of animal vaccines by smallholder farmers with focus on neglected diseases and marginalized populations

PLoS Neglected Tropical Diseases News - 7 February 2019 - 10:00pm

by Meritxell Donadeu, Nick Nwankpa, Bernadette Abela-Ridder, Baptiste Dungu

Background

Most smallholder farmers (SHFs) and marginalized populations (MPs) in Africa, Asia, and Latin America depend on livestock for their livelihoods. However, significant numbers of these animals do not achieve their potential, die due to disease, or transmit zoonotic diseases. Existing vaccines could prevent and control some of these diseases, but frequently the vaccines do not reach SHFs, especially MPs, making it necessary for specific vaccine adoption strategies.

Principal findings

Several strategies that have the potential to increase the adoption of animal vaccines by SHFs and MPs have been identified depending on the type of vaccines involved. The strategies differed depending on whether the vaccines were aimed at diseases that cause economic losses, government-controlled diseases, or neglected diseases. The adoption of vaccines for neglected diseases presents a major challenge, because they are mostly for zoonotic diseases that produce few or no clinical signs in the animals, making it more difficult for the farmers to appreciate the value of the vaccines.Strategies can be aimed at increasing the availability of quality vaccines, so that they are produced in sufficient quantity, or aimed at increasing access and demand by SHFs and/or MPs. Some of the strategies to increase vaccine adoption might not provide a definite solution but might facilitate vaccine uptake by decreasing barriers. These strategies are varied and include technical considerations, policy components, involvement by the private sector (local and international), and innovation.

Conclusions

Several strategies with the potential to reduce livestock morbidity and mortality, or prevent zoonoses in SHFs communities and MPs through vaccination, require the involvement of donors and international organisations to stimulate and facilitate sustainable adoption. This is especially the case for neglected zoonotic diseases. Support for national and regional vaccine manufacturers is also required, especially for vaccines against diseases of interest only in the developing world and public goods.

Reprogramming of <i>Trypanosoma cruzi</i> metabolism triggered by parasite interaction with the host cell extracellular matrix

PLoS Neglected Tropical Diseases News - 6 February 2019 - 10:00pm

by Eliciane C. Mattos, Gisele Canuto, Nubia C. M. Varón, Rubens D. M. Magalhães, Thomas W. M. Crozier, Douglas J. Lamont, Marina F. M. Tavares, Walter Colli, Michael A. J. Ferguson, Maria Júlia M. Alves

Trypanosoma cruzi, the etiological agent of Chagas’ disease, affects 8 million people predominantly living in socioeconomic underdeveloped areas. T. cruzi trypomastigotes (Ty), the classical infective stage, interact with the extracellular matrix (ECM), an obligatory step before invasion of almost all mammalian cells in different tissues. Here we have characterized the proteome and phosphoproteome of T. cruzi trypomastigotes upon interaction with ECM (MTy) and the data are available via ProteomeXchange with identifier PXD010970. Proteins involved with metabolic processes (such as the glycolytic pathway), kinases, flagellum and microtubule related proteins, transport-associated proteins and RNA/DNA binding elements are highly represented in the pool of proteins modified by phosphorylation. Further, important metabolic switches triggered by this interaction with ECM were indicated by decreases in the phosphorylation of hexokinase, phosphofructokinase, fructose-2,6-bisphosphatase, phosphoglucomutase, phosphoglycerate kinase in MTy. Concomitantly, a decrease in the pyruvate and lactate and an increase of glucose and succinate contents were detected by GC-MS. These observations led us to focus on the changes in the glycolytic pathway upon binding of the parasite to the ECM. Inhibition of hexokinase, pyruvate kinase and lactate dehydrogenase activities in MTy were observed and this correlated with the phosphorylation levels of the respective enzymes. Putative kinases involved in protein phosphorylation altered upon parasite incubation with ECM were suggested by in silico analysis. Taken together, our results show that in addition to cytoskeletal changes and protease activation, a reprogramming of the trypomastigote metabolism is triggered by the interaction of the parasite with the ECM prior to cell invasion and differentiation into amastigotes, the multiplicative intracellular stage of T. cruzi in the vertebrate host.

The validity of diagnostic cut-offs for commercial and in-house scrub typhus IgM and IgG ELISAs: A review of the evidence

PLoS Neglected Tropical Diseases News - 4 February 2019 - 10:00pm

by Kartika Saraswati, Meghna Phanichkrivalkosil, Nicholas P. J. Day, Stuart D. Blacksell

Background

Scrub typhus is a neglected tropical disease that causes acute febrile illness. Diagnosis is made based upon serology, or detection of the causative agent–Orientia tsutsugamushi–using PCR or in vitro isolation. The enzyme-linked immunosorbent assay (ELISA) is an objective and reproducible means of detecting IgM or IgG antibodies. However, lack of standardization in ELISA methodology, as well as in the choice of reference test with which the ELISA is compared, calls into question the validity of cut-offs used in diagnostic accuracy studies and observational studies.

Methodology/Principal findings

A PubMed search and manual screening of reference lists identified 46 studies that used ELISA antibody cut-offs to diagnose scrub typhus patients, 22 of which were diagnostic accuracy studies. Overall, 22 studies (47.8%) provided little to no explanation as to how the ELISA cut-off was derived, and 7 studies (15.2%) did not even state the cut-off used. Variation was seen locally in reference standards used, in terms of both the diagnostic test and cut-off titer. Furthermore, with the exception of studies using ELISAs manufactured by InBios, there was no standardization of the selection of antigenic strains. As a result, no consensus was found for determining a cut-off, ELISA methodology, or for a single value diagnostic cut-off.

Conclusions/Significance

We have concluded that there is a lack of consensus in the determination of a cut-off. We recommend interpreting the results from these studies with caution. Further studies will need to be performed at each geographic location to determine region-specific cut-offs, taking into consideration background antibody levels to discriminate true disease from healthy individuals.

Pages