RSS news feeds

Error message

  • Warning: date_timezone_set() expects parameter 1 to be DateTime, boolean given in format_date() (line 2041 of /home/bizmesol/public_html/prod/drupal-7/includes/common.inc).
  • Warning: date_format() expects parameter 1 to be DateTime, boolean given in format_date() (line 2051 of /home/bizmesol/public_html/prod/drupal-7/includes/common.inc).

Shortening of Zika virus CD-loop reduces neurovirulence while preserving antigenicity

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

by Kenneth Dinnon, Emily Gallichotte, Ethan Fritch, Vineet Menachery, Ralph Baric

Zika virus (ZIKV) is a mosquito-borne positive sense RNA virus. Recently, ZIKV emerged into the Western hemisphere as a human health threat, with severe disease associated with developmental and neurological complications. The structural envelope protein of ZIKV and other neurotropic flaviviruses contains an extended CD-loop relative to non-neurotropic flaviviruses, and has been shown to augment ZIKV stability and pathogenesis. Here we show that shortening the CD-loop in ZIKV attenuates the virus in mice, by reducing the ability to invade and replicate in the central nervous system. The CD-loop mutation was genetically stable following infection in mice, though secondary site mutations arise adjacent to the CD-loop. Importantly, while shortening of the CD-loop attenuates the virus, the CD-loop mutant maintains antigenicity in immunocompetent mice, eliciting an antibody response that similarly neutralizes both the mutant and wildtype ZIKV. These findings suggest that the extended CD-loop in ZIKV is a determinant of neurotropism and may be a target in live-attenuated vaccine design, for not only ZIKV, but for other neurotropic flaviviruses.

Evaluation of a novel West Nile virus transmission control strategy that targets <i>Culex tarsalis</i> with endectocide-containing blood meals

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

by Chilinh Nguyen, Meg Gray, Timothy A. Burton, Soleil L. Foy, John R. Foster, Alex Lazr Gendernalik, Claudia Rückert, Haoues Alout, Michael C. Young, Broox Boze, Gregory D. Ebel, Brady Clapsaddle, Brian D. Foy

Control of arbovirus transmission remains focused on vector control through application of insecticides directly to the environment. However, these insecticide applications are often reactive interventions that can be poorly-targeted, inadequate for localized control during outbreaks, and opposed due to environmental and toxicity concerns. In this study, we developed endectocide-treated feed as a systemic endectocide for birds to target blood feeding Culex tarsalis, the primary West Nile virus (WNV) bridge vector in the western United States, and conducted preliminary tests on the effects of deploying this feed in the field. In lab tests, ivermectin (IVM) was the most effective endectocide tested against Cx. tarsalis and WNV-infection did not influence mosquito mortality from IVM. Chickens and wild Eurasian collared doves exhibited no signs of toxicity when fed solely on bird feed treated with concentrations up to 200 mg IVM/kg of diet, and significantly more Cx. tarsalis that blood fed on these birds died (greater than 80% mortality) compared to controls (less than 25% mortality). Mosquito mortality following blood feeding correlated with IVM serum concentrations at the time of blood feeding, which dropped rapidly after the withdrawal of treated feed. Preliminary field testing over one WNV season in Fort Collins, Colorado demonstrated that nearly all birds captured around treated bird feeders had detectable levels of IVM in their blood. However, entomological data showed that WNV transmission was non-significantly reduced around treated bird feeders. With further development, deployment of ivermectin-treated bird feed might be an effective, localized WNV transmission control tool.

Development of a screening eye clinic for Ebola virus disease survivors: Lessons learned and rapid implementation at ELWA Hospital in Monrovia, Liberia 2015

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

by Jessica G. Shantha, Brent R. Hayek, Ian Crozier, Catherine Gargu, Robert Dolo, Jerry Brown, John Fankhauser, Steven Yeh

Background

In the wake of the West African Ebola virus disease (EVD) outbreak of 2014–2016, thousands of EVD survivors began to manifest a constellation of systemic and ophthalmic sequelae. Besides systemic arthralgias, myalgias, and abdominal pain, patients were developing uveitis, a spectrum of inflammatory eye disease leading to eye pain, redness, and vision loss. To investigate this emerging eye disease, resources and equipment were needed to promptly evaluate this sight-threatening condition, particularly given our identification of Ebola virus in the ocular fluid of an EVD survivor during disease convalescence.

Methodology/Principal findings

A collaborative effort involving ophthalmologists, infectious disease specialists, eye care nurses, and physician leadership at Eternal Love Winning Africa (ELWA) Hospital in Liberia led to the development of a unique screening eye clinic for EVD survivors to screen, treat, and refer patients for more definitive care. Medications, resources, and equipment were procured from a variety of sources including discount websites, donations, purchasing with humanitarian discounts, and limited retail to develop a screening eye clinic and rapidly perform detailed ophthalmologic exams. Findings were documented in 96 EVD survivors to inform public health officials and eye care providers of the emerging disease process. Personal protective equipment was tailored to the environment and implications of EBOV persistence within intraocular fluid.

Conclusions/Significance

A screening eye clinic was feasible and effective for the rapid screening, care, and referral of EVD survivors with uveitis and retinal disease. Patients were screened promptly for an initial assessment of the disease process, which has informed other efforts within West Africa related to immediate patient care needs and our collective understanding of EVD sequelae. Further attention is needed to understand the pathogensis and treatment of ophthalmic sequelae given recent EVD outbreaks in West Africa and ongoing outbreak within Democratic Republic of Congo.

Host and parasite responses in human diffuse cutaneous leishmaniasis caused by <i>L</i>. <i>amazonensis</i>

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

by Stephen M. Christensen, Ashton T. Belew, Najib M. El-Sayed, Wagner L. Tafuri, Fernando T. Silveira, David M. Mosser

Diffuse cutaneous leishmaniasis (DCL) is a rare form of leishmaniasis where parasites grow uncontrolled in diffuse lesions across the skin. Meta-transcriptomic analysis of biopsies from DCL patients infected with Leishmania amazonensis demonstrated an infiltration of atypical B cells producing a surprising preponderance of the IgG4 isotype. DCL lesions contained minimal CD8+ T cell transcripts and no evidence of persistent TH2 responses. Whereas localized disease exhibited activated (so-called M1) macrophage presence, transcripts in DCL suggested a regulatory macrophage (R-Mϕ) phenotype with higher levels of ABCB5, DCSTAMP, SPP1, SLAMF9, PPARG, MMPs, and TM4SF19. The high levels of parasite transcripts in DCL and the remarkable uniformity among patients afforded a unique opportunity to study parasite gene expression in this disease. Patterns of parasite gene expression in DCL more closely resembled in vitro parasite growth in resting macrophages, in the absence of T cells. In contrast, parasite gene expression in LCL revealed 336 parasite genes that were differently upregulated, relative to DCL and in vitro macrophage growth, and these transcripts may represent transcripts that are produced by the parasite in response to host immune pressure.

Genomic, epidemiological and digital surveillance of Chikungunya virus in the Brazilian Amazon

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

by Felipe Gomes Naveca, Ingra Claro, Marta Giovanetti, Jaqueline Goes de Jesus, Joilson Xavier, Felipe Campos de Melo Iani, Valdinete Alves do Nascimento, Victor Costa de Souza, Paola Paz Silveira, José Lourenço, Mauricio Santillana, Moritz U. G. Kraemer, Josh Quick, Sarah C. Hill, Julien Thézé, Rodrigo Dias de Oliveira Carvalho, Vasco Azevedo, Flavia Cristina da Silva Salles, Márcio Roberto Teixeira Nunes, Poliana da Silva Lemos, Darlan da Silva Candido, Glauco de Carvalho Pereira, Marluce Aparecida Assunção Oliveira, Cátia Alexandra Ribeiro Meneses, Rodrigo Melo Maito, Claudeth Rocha Santa Brígida Cunha, Daniela Palha de Sousa Campos, Marcia da Costa Castilho, Thalita Caroline da Silva Siqueira, Tiza Matos Terra, Carlos F. Campelo de Albuquerque, Laura Nogueira da Cruz, André Luis de Abreu, Divino Valerio Martins, Daniele Silva de Moraes Vanlume Simoes, Renato Santana de Aguiar, Sérgio Luiz Bessa Luz, Nicholas Loman, Oliver G. Pybus, Ester C. Sabino, Osnei Okumoto, Luiz Carlos Junior Alcantara, Nuno Rodrigues Faria

Background

Since its first detection in the Caribbean in late 2013, chikungunya virus (CHIKV) has affected 51 countries in the Americas. The CHIKV epidemic in the Americas was caused by the CHIKV-Asian genotype. In August 2014, local transmission of the CHIKV-Asian genotype was detected in the Brazilian Amazon region. However, a distinct lineage, the CHIKV-East-Central-South-America (ECSA)-genotype, was detected nearly simultaneously in Feira de Santana, Bahia state, northeast Brazil. The genomic diversity and the dynamics of CHIKV in the Brazilian Amazon region remains poorly understood despite its importance to better understand the epidemiological spread and public health impact of CHIKV in the country.

Methodology/Principal findings

We report a large CHIKV outbreak (5,928 notified cases between August 2014 and August 2018) in Boa vista municipality, capital city of Roraima’s state, located in the Brazilian Amazon region. We generated 20 novel CHIKV-ECSA genomes from the Brazilian Amazon region using MinION portable genome sequencing. Phylogenetic analyses revealed that despite an early introduction of the Asian genotype in 2015 in Roraima, the large CHIKV outbreak in 2017 in Boa Vista was caused by an ECSA-lineage most likely introduced from northeastern Brazil. Epidemiological analyses suggest a basic reproductive number of R0 of 1.66, which translates in an estimated 39 (95% CI: 36 to 45) % of Roraima’s population infected with CHIKV-ECSA. Finally, we find a strong association between Google search activity and the local laboratory-confirmed CHIKV cases in Roraima.

Conclusions/Significance

This study highlights the potential of combining traditional surveillance with portable genome sequencing technologies and digital epidemiology to inform public health surveillance in the Amazon region. Our data reveal a large CHIKV-ECSA outbreak in Boa Vista, limited potential for future CHIKV outbreaks, and indicate a replacement of the Asian genotype by the ECSA genotype in the Amazon region.

Diel periodicity and visual cues guide oviposition behavior in <i>Phlebotomus papatasi</i>, vector of old-world cutaneous leishmaniasis

PLoS Neglected Tropical Diseases News - 5 March 2019 - 10:00pm

by Tatsiana Shymanovich, Lindsey Faw, Nima Hajhashemi, Jimmie Teague, Coby Schal, Loganathan Ponnusamy, Charles S. Apperson, Eduardo Hatano, Gideon Wasserberg

Background

Phlebotomine sand flies are vectors of human leishmaniases, important neglected tropical diseases. In this study, we investigated diel patterns of oviposition behavior, effects of visual cues on oviposition-site selection, and whether these affect the attraction of gravid Phlebotomus papatasi (Scopoli), the vector of old-world cutaneous leishmaniasis, to olfactory cues from oviposition sites.

Methodology/principal findings

To evaluate these questions, we conducted a series of experiments using attraction and oviposition assays within free-flight test chambers containing gravid females entrained under a 14:10 hrs light:dark photoperiod. By replacing sticky-screens or moist filter papers every three hours, we showed that oviposition site search occurs mainly in the latest part of the night whereas peak oviposition occurs during the early part of the night. Behavioral responses to olfactory oviposition cues are regulated by time-of-day and can be disrupted by transient exposure to a constant darkness photoperiod. Gravid females, but not any other stage, age, or sex, were attracted to dark, round oviposition jars, possibly resembling rodent burrow openings. This visual attraction disappeared in the absence of an illumination source. Egg deposition rate was not affected by jar color. Olfactory cues had the strongest effect when the visual cues were minimal.

Conclusion and significance

Our study showed, for the first time, that visual cues in the form of oviposition-site color, lighting level, and photoperiod are important in guiding the oviposition behavior of phlebotomine sand flies. Furthermore, such visual cues could modify the flies’ sensitivity to olfactory oviposition cues. Our results suggest that chemosensory and visual cues are complementary, with visual cues used to orient gravid females towards oviposition sites, possibly at long- to medium-ranges during crepuscular periods, while olfactory cues are used to approach the burrow in darkness and assess its suitability at close-range. Implications to sand fly control are discussed.

Quantitative polymerase chain reaction in paucibacillary leprosy diagnosis: A follow-up study

PLoS Neglected Tropical Diseases News - 5 March 2019 - 10:00pm

by Raquel R. Barbieri, Fernanda S. N. Manta, Suelen J. M. Moreira, Anna M. Sales, José A. C. Nery, Lilian P. R. Nascimento, Mariana A. Hacker, Antônio G. Pacheco, Alice M. Machado, Euzenir M. Sarno, Milton O. Moraes

Objective

The diagnosis of paucibacillary (PB) leprosy cases remains a challenge because of the absence of a confirmatory laboratory method. While quantitative polymerase chain reaction (qPCR) has been shown to provide reliable sensitivity and specificity in PB diagnoses, a thorough investigation of its efficacy in clinical practice has not yet been published. The present study evaluated patients with suspected leprosy skin lesions by using qPCR to identify PB individuals in the Leprosy Outpatient clinic at the Oswaldo Cruz Foundation in Rio de Janeiro, Brazil.

Methods

One hundred seventy-two suspected PB cases were included in the study. The patients were evaluated by a dermatologist at three different times. The clinical dermato-neurological examination and collected samples were performed on the first visit. On the second visit, the results of the histopathological analysis and PCR assay (DNA-based Mycobacterium leprae qPCR-targeting 16S gene) results were analyzed, and a decision regarding multi-drug therapy was made. A year later, the patients were re-examined, and the consensus diagnosis was established.

Results

In 58% (100/172) of cases, a conclusive diagnosis via histopathological analysis was not possible; however, 30% (30/100) of these cases had a positive PCR. One hundred ten patients (110/172) attended the third visit. The analysis showed that while the sensitivity of the histopathological test was very low (35%), a qPCR alone was more effective for identifying leprosy, with 57% sensitivity.

Conclusion

The use of qPCR in suspected PB cases with an inconclusive histology improved the sensitivity of leprosy diagnoses.

The unique tropism of Mycobacterium leprae to the nasal epithelial cells can be explained by the mammalian cell entry protein 1A

PLoS Neglected Tropical Diseases News - 5 March 2019 - 10:00pm

by Viesta Beby Fadlitha, Fuki Yamamoto, Irfan Idris, Haslindah Dahlan, Naoya Sato, Vienza Beby Aftitah, Andini Febriyanda, Takao Fujimura, Hiroaki Takimoto

Leprosy is a chronic infection where the skin and peripheral nervous system is invaded by Mycobacterium leprae. The infection mechanism remains unknown in part because culture methods have not been established yet for M. leprae. Mce1A protein (442 aa) is coded by mce1A (1326 bp) of M. leprae. The Mce1A homolog in Mycobacterium tuberculosis is known to be associated with M. tuberculosis epithelial cell entry, and survival and multiplication within macrophages. Studies using recombinant proteins have indicated that Mce1A of M. leprae is also associated with epithelial cell entry. This study is aimed at identifying particular sequences within Mce1A associated with M. leprae epithelial cell entry. Recombinant proteins having N-terminus and C-terminus truncations of the Mce1A region of M. leprae were created in Escherichia coli. Entry activity of latex beads, coated with these truncated proteins (r-lep37 kDa and r-lep27 kDa), into HeLa cells was observed by electron microscopy. The entry activity was preserved even when 315 bp (105 aa) and 922 bp (308 aa) was truncated from the N-terminus and C-terminus, respectively. This 316–921 bp region was divided into three sub-regions: 316–531 bp (InvX), 532–753 bp (InvY), and 754–921 bp (InvZ). Each sub-region was cloned into an AIDA vector and expressed on the surface of E. coli. Entry of these E. coli into monolayer-cultured HeLa and RPMI2650 cells was observed by electron microscopy. Only E. coli harboring the InvX sub-region exhibited cell entry. InvX was further divided into 4 domains, InvXa—InvXd, containing sequences 1–24 aa, 25–46 aa, 47–57 aa, and 58–72 aa, respectively. Recombinant E. coli, expressing each of InvXa—InvXd on the surface, were treated with antibodies against these domains, then added to monolayer cultured RPMI cells. The effectiveness of these antibodies in preventing cell entry was studied by colony counting. Entry activity was suppressed by antibodies against InvXa, InvXb, and InvXd. This suggests that these three InvX domains of Mce1A are important for M. leprae invasion into nasal epithelial cells.

Comparison of Kato Katz, antibody-based ELISA and droplet digital PCR diagnosis of schistosomiasis japonica: Lessons learnt from a setting of low infection intensity

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

by Pengfei Cai, Kosala G. Weerakoon, Yi Mu, Remigio M. Olveda, Allen G. Ross, David U. Olveda, Donald P. McManus

Background

Zoonotic schistosomiasis in Asia, caused by Schistosoma japonicum, remains a major public health concern in China and the Philippines. The developing epidemiological and socio-economic picture of the disease in endemic areas necessitates the development of affordable and highly accurate field diagnostics as an important component in evaluating ongoing integrated control and elimination efforts.

Methods

Three diagnostic methods, namely Kato-Katz stool microscopy, ELISA and droplet digital (dd) PCR assays, were compared by detecting infection in a total of 412 participants from an area moderately endemic for schistosomiasis in the Philippines.

Results

This comprehensive comparison further defined the diagnostic performance and features for each assay. Compared with the ddPCR assay analysing DNA from faeces (F_ddPCR), which exhibited the highest sensitivity, the SjSAP4 + Sj23-LHD-ELISA had the best accuracy (67.72%) among all five ELISA assays assessed. Schistosomiasis prevalence determined by the SjSAP4 + Sj23-LHD-ELISA and ddPCRs was similar and was at least 2.5 times higher than obtained with the KK method. However, the agreement between these assays was low. In terms of cost and logistical convenience, the SjSAP4 + Sj23-LHD-ELISA represents a cost-effective assay with considerable diagnostic merits. In contrast, although the ddPCR assays exhibited a high level of diagnostic performance, the high cost and the need for specialized equipment presents a major obstacle in their application in screening campaigns.

Conclusion

The SjSAP4 + Sj23-LHD-ELISA represents a cost-effective tool for the diagnosis of schistosomiasis that could prove an important component in the monitoring of integrated control measures as elimination draws closer, whereas the ddPCR assays, in addition to their high sensitivity and specificity, are capable of quantifying infection intensity. However, the high cost of ddPCR hinders its wider application in screening programs, although it could be a valuable reference in the development and improvement of other diagnostic assays.

Correction: Modification and optimization of the FECPAK<sup>G2</sup> protocol for the detection and quantification of soil-transmitted helminth eggs in human stool

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

by Mio Ayana, Johnny Vlaminck, Piet Cools, Shaali Ame, Marco Albonico, Daniel Dana, Jennifer Keiser, Helen Manly, Leonardo F. Matoso, Zeleke Mekonnen, Antonio Montresor, Rodrigo Correa-Oliveira, Laura Rinaldi, Somphou Sayasone, Stephen J. Sowerby, Lensa Tesfaye, Jozef Vercruysse, Greg Mirams, Bruno Levecke

Virulence difference of five type I dengue viruses and the intrinsic molecular mechanism

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

by Chunling Zou, Chenxiao Huang, Jinyu Zhang, Qihan Wu, Xiaohua Ni, Jiufeng Sun, Jianfeng Dai

Dengue virus (DENV) is the most important vector-borne virus globally. The safe and effective vaccines are still under development and there are no antiviral drugs for DENV induced diseases. In this study, we obtained five DENV1 isolates (DENV1 A to E) from the outbreak of dengue fever in 2014 of Guangzhou, China, and analyzed their replication efficiency and virulence in vitro and in vivo. The results suggested that among the five DENV1 strains, DENV1 B has the highest replication efficiency in both human and mosquito cells in vitro, also causes the highest mortality to suckling mice. Further study suggested that nonstructural proteins from DENV1B have higher capacity to suppress host interferon signaling. In addition, the NS2B3 protease from DENV1B has higher enzymatic activity compared with that from DENV1 E. Finally, we identified that the 64th amino acid of NS2A and the 55th amino acid of NS2B were two virulence determining sites for DENV1. This study provided new evidences of the molecular mechanisms of DENV virulence.

Insecticide–impregnated dog collars reduce infantile clinical visceral leishmaniasis under operational conditions in NW Iran: A community–wide cluster randomised trial

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

by Orin Courtenay, Ahad Bazmani, Parviz Parvizi, Paul D. Ready, Mary M. Cameron

Objective

To assess the effectiveness of community-wide deployment of insecticide–impregnated collars for dogs- the reservoir of Leishmania infantum–to reduce infantile clinical visceral leishmaniasis (VL).

Methods

A pair matched–cluster randomised controlled trial involving 40 collared and 40 uncollared control villages (161 [95% C.L.s: 136, 187] children per cluster), was designed to detect a 55% reduction in 48 month confirmed VL case incidence. The intervention study was designed by the authors, but implemented by the Leishmaniasis Control Program in NW Iran, from 2002 to 2006.

Results

The collars provided 50% (95% C.I. 17·8%–70·0%) protection against infantile VL incidence (0·95/1000/yr compared to 1·75/1000/yr). Reductions in incidence were observed across 76% (22/29) of collared villages compared to pair–matched control villages, with 31 fewer cases by the end of the trial period. In 11 paired villages, no further cases were recorded post–intervention, whereas in 7 collared villages there were 9 new clinical cases relative to controls. Over the trial period, 6,835 collars were fitted at the beginning of the 4 month sand fly season, of which 6.9% (95% C.I. 6.25%, 7.56%) were lost but rapidly replaced. Collar coverage (percent dogs collared) per village varied between 66% and 100%, with a mean annual coverage of 87% (95% C.I. 84·2, 89·0%). The variation in post-intervention clinical VL incidence was not associated with collar coverage, dog population size, implementation logistics, dog owner compliance, or other demographic variables tested. Larger reductions and greater persistence in incident case numbers (indicative of transmission) were observed in villages with higher pre-existing VL case incidence.

Conclusion

Community–wide deployment of collars can provide a significant level of protection against infantile clinical VL, achieved in this study by the local VL Control Program, demonstrating attributes desirable of a sustainable public health program. The effectiveness is not dissimilar to the community-level protection provided against human and canine infection with L. infantum.

Pages