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Heterogeneity of dengue transmission in an endemic area of Colombia

PLoS Neglected Tropical Diseases News - 14 September 2020 - 9:00pm

by María Isabel Estupiñán Cárdenas, Víctor Mauricio Herrera, María Consuelo Miranda Montoya, Anyela Lozano Parra, Zuly Milena Zaraza Moncayo, Janeth Patricia Flórez García, Isabel Rodríguez Barraquer, Luis Ángel Villar Centeno

Population based serological surveys are the gold-standard to quantify dengue (DENV) transmission. The purpose of this study was to estimate the age-specific seroprevalence and the force of infection of DENV in an endemic area of Colombia. Between July and October 2014, we conducted a household based cross-sectional survey among 1.037 individuals aged 2 to 40 years living in 40 randomly selected locations in urban Piedecuesta, Santander, Colombia. In addition, we also enrolled 246 indviduals living in rural “veredas”. Participants were asked to answer a questionnaire that included demographic, socioeconomic and environmental questions and to provide a 5 ml blood sample. Sera were tested using the IgG indirect ELISA (Panbio) kit to determine past DENV infection. The overall DENV seroprevalence was 70% (95% CI = 67%-71%), but was significantly higher in urban (81%, 95% CI = 78%-83%) as compared to rural (21%, 95% CI = 17%-27%) locations. Age was a major predictor of seropositivity, consistent with endemic circulation of the virus. Using catalytic models we estimated that on average, 12% (95%CI = 11%-13%) of susceptible individuals living in the city are infected by DENV each year. Beyond age, the only predictor of seropositivity in urban locations was prior history of dengue diagnosed by a physician (aPR 1.15, 95% CI = 0.98–1.35). Among participants living in rural settings, those that reported traveling outside of their vereda were more likely to be seropositive (aPR 3.60, 95%CI = 1.54–8.42) as well as those who were born outside of Santander department (aPR = 2.77, 95%CI = 1.20–6.37). These results are consistent with long term endemic circulation of DENV in Piedecuesta, with large heterogeneities between urban and rural areas located just a few kilometers apart. Design of DENV control interventions, including vaccination, will need to consider this fine scale spatial heterogeneity.

Dynamics of serological responses to defined recombinant proteins during <i>Schistosoma mansoni</i> infection in mice before and after the treatment with praziquantel

PLoS Neglected Tropical Diseases News - 11 September 2020 - 9:00pm

by Eman Sayed Mohammed, Risa Nakamura, Yombo DJ Kalenda, Sharmina Deloer, Taeko Moriyasu, Mio Tanaka, Yoshito Fujii, Satoshi Kaneko, Kenji Hirayama, Ahmed I. Ibrahim, Mahmoud A. El-Seify, Asmaa M. Metwally, Shinjiro Hamano

To eliminate schistosomiasis, appropriate diagnostic tests are required to monitor its prevalence and transmission, especially in the settings with low endemicity resulting from the consecutive mass drug administration. Antibodies that react with either crude soluble schistosome egg antigens or soluble worm antigen preparations have been used to monitor infection in low-prevalence regions. However, these detection methods cannot discriminate current and past infections and are cross-reactive with other parasites because both antigens contain numerous proteins and glycans from schistosomes, and standard preparations need maintenance of the life cycle of the schistosome. To evaluate the potential utility of nine recombinant Schistosoma mansoni proteins as single defined antigens for serological diagnosis, we monitored the kinetics of antibodies to each antigen during S. mansoni infection in mice before and after the treatment with praziquantel. C57BL/6 mice were infected with 50 cercariae. The levels of immunoglobulin G (IgG) raised against five recombinant antigens (RP26, sm31, sm32, GST, and LAP1) significantly increased as early as 2–4 weeks after infection and rapidly declined by 2 weeks after the treatment, whereas those raised against crude S. mansoni egg antigens or other antigens remained elevated long after the treatment. The IgG1 raised against RP26, sm31, and serpin decreased after the treatment with praziquantel, whereas the IgE raised against serpin declined strikingly after the treatment. This study clarifies the dynamics of the serological responses to recombinant S. mansoni proteins during infection and after the treatment with praziquantel and identifies several candidate antigens with potential utility in the monitoring and surveillance of schistosomiasis toward the elimination of schistosomiasis.

Dengue infection modulates locomotion and host seeking in <i>Aedes aegypti</i>

PLoS Neglected Tropical Diseases News - 10 September 2020 - 9:00pm

by Anaïs K. Tallon, Marcelo G. Lorenzo, Luciano A. Moreira, Luis E. Martinez Villegas, Sharon Rose Hill, Rickard Ignell

Pathogens may manipulate their human and mosquito hosts to enhance disease transmission. Dengue, caused by four viral serotypes, is the fastest-growing transmissible disease globally resulting in 50–100 million infections annually. Transmission of the disease relies on the interaction between humans and the vector Aedes aegypti and is largely dependent on the odor-mediated host seeking of female mosquitoes. In this study, we use activity monitors to demonstrate that dengue virus-1 affects the locomotion and odor-mediated behavior of Ae. aegypti, reflecting the progression of infection within the mosquito. Mosquitoes 4–6 days post-infection increase locomotion, but do not alter their odor-driven host-seeking response. In contrast, females 14–16 days post-infection are less active, yet more sensitive to human odors as assessed by behavioral and electrophysiological assays. Such an increase in physiological and behavioral sensitivity is reflected by the antennal-specific increase in abundance of neural signaling transcripts in 14 days post-infection females, as determined by transcriptome analysis. This suggests that the sensitivity of the mosquito peripheral olfactory system is altered by the dengue virus by enhancing the overall neural responsiveness of the antenna, rather than the selective regulation of chemosensory-related genes. Our study reveals that dengue virus-1 enhances vector-related behaviors in the early stages post-infection that aid in avoiding predation and increasing spatial exploration. On the other hand, at the later stages of infection, the virus enhances the host-seeking capacity of the vector, thereby increasing the risk of virus transmission. A potential mechanism is discussed.

A bug’s life: Delving into the challenges of helminth microbiome studies

PLoS Neglected Tropical Diseases News - 10 September 2020 - 9:00pm

by Fabio Formenti, Alba Cortés, Paul J. Brindley, Cinzia Cantacessi, Gabriel Rinaldi

<i>Fasciola hepatica</i> Extracellular Vesicles isolated from excretory-secretory products using a gravity flow method modulate dendritic cell phenotype and activity

PLoS Neglected Tropical Diseases News - 8 September 2020 - 9:00pm

by Anna Murphy, Krystyna Cwiklinski, Richard Lalor, Barry O’Connell, Mark W. Robinson, Jared Gerlach, Lokesh Joshi, Michelle Kilcoyne, John P. Dalton, Sandra M. O’Neill

Parasite-released extracellular vesicles (EVs) deliver signals to the host immune system that are critical to maintaining the long-term relationship between parasite and host. In the present study, total EVs (FhEVs) released in vitro by adults of the helminth parasite Fasciola hepatica were isolated using a recently described gravity flow method that protects their structural integrity. The FhEVs molecular cargo was defined using proteomic analysis and their surface topology characterised by glycan microarrays. The proteomic analysis identified 618 proteins, 121 of which contained putative N-linked glycosylation sites while 132 proteins contained putative O-linked glycosylation sites. Glycan arrays revealed surface-exposed glycans with a high affinity for mannose-binding lectins indicating the predominance of oligo mannose-rich glycoproteins, as well as other glycans with a high affinity for complex-type N-glycans. When added to bone-marrow derived dendritic cells isolated FhEV induced a novel phenotype that was categorised by the secretion of low levels of TNF, enhanced expression of cell surface markers (CD80, CD86, CD40, OX40L, and SIGNR1) and elevation of intracellular markers (SOCS1 and SOCS3). When FhEV-stimulated BMDCs were introduced into OT-II mice by adoptive transfer, IL-2 secretion from skin draining lymph nodes (sdLN) and spleen cells was inhibited in response to both specific and non-specific antigen stimulation. Immunisation of mice with a suspension of FhEV did not elicit significant immune responses; however, in the presence of alum, FhEVs induced a mixed Th1/Th2 immune response with high antigen specific antibody titres. Thus, we have demonstrated that FhEVs induce a unique phentotype in DC capable of suppressing IL-2 secretion from T-cells. Our studies add to the growing immuno-proteomic database that will be an important source for the discovery of future parasite vaccines and immunotherapeutic biologicals.

Redefining enteroaggregative <i>Escherichia coli</i> (EAEC): Genomic characterization of epidemiological EAEC strains

PLoS Neglected Tropical Diseases News - 8 September 2020 - 9:00pm

by Nadia Boisen, Mark T. Østerlund, Katrine G. Joensen, Araceli E. Santiago, Inacio Mandomando, Alejandro Cravioto, Marie A. Chattaway, Laura A. Gonyar, Søren Overballe-Petersen, O. Colin Stine, David A. Rasko, Flemming Scheutz, James P. Nataro

Although enteroaggregative E. coli (EAEC) has been implicated as a common cause of diarrhea in multiple settings, neither its essential genomic nature nor its role as an enteric pathogen are fully understood. The current definition of this pathotype requires demonstration of cellular adherence; a working molecular definition encompasses E. coli which do not harbor the heat-stable or heat-labile toxins of enterotoxigenic E. coli (ETEC) and harbor the genes aaiC, aggR, and/or aatA. In an effort to improve the definition of this pathotype, we report the most definitive characterization of the pan-genome of EAEC to date, applying comparative genomics and functional characterization on a collection of 97 EAEC strains isolated in the course of a multicenter case-control diarrhea study (Global Enteric Multi-Center Study, GEMS). Genomic analysis revealed that the EAEC strains mapped to all phylogenomic groups of E. coli. Circa 70% of strains harbored one of the five described AAF variants; there were no additional AAF variants identified, and strains that lacked an identifiable AAF generally did not have an otherwise complete AggR regulon. An exception was strains that harbored an ETEC colonization factor (CF) CS22, like AAF a member of the chaperone-usher family of adhesins, but not phylogenetically related to the AAF family. Of all genes scored, sepA yielded the strongest association with diarrhea (P = 0.002) followed by the increased serum survival gene, iss (p = 0.026), and the outer membrane protease gene ompT (p = 0.046). Notably, the EAEC genomes harbored several genes characteristically associated with other E. coli pathotypes. Our data suggest that a molecular definition of EAEC could comprise E. coli strains harboring AggR and a complete AAF(I-V) or CS22 gene cluster. Further, it is possible that strains meeting this definition could be both enteric bacteria and urinary/systemic pathogens.

A smartphone microscopic method for simultaneous detection of (oo)cysts of <i>Cryptosporidium</i> and <i>Giardia</i>

PLoS Neglected Tropical Diseases News - 8 September 2020 - 9:00pm

by Retina Shrestha, Rojina Duwal, Sajeev Wagle, Samiksha Pokhrel, Basant Giri, Bhanu Bhakta Neupane

Background

Food and water-borne illness caused by ingestion of (oo)cysts of Cryptosporidium and Giardia is one of the major health problems globally. Several methods are available to detect Giardia cyst and Cryptosporidium oocyst in food and water. Most of the available methods require a good laboratory facility and well-trained manpower and are therefore costly. There is a need of affordable and reliable method that can be easily implemented in resource limited settings.

Methodology/Principle findings

We developed a smartphone based microscopic assay method to screen (oo)cysts of Cryptosporidium and Giardia contamination of vegetable and water samples. The method consisting of a ball lens of 1 mm diameter, white LED as illumination source and Lugols's iodine staining provided magnification and contrast capable of distinguishing (oo)cysts of Cryptosporidium and Giardia. The analytical performance of the method was tested by spike recovery experiments. The spike recovery experiments performed on cabbage, carrot, cucumber, radish, tomatoes, and water resulted in 26.8±10.3, 40.1±8.5, 44.4±7.3, 47.6±11.3, 49.2 ±10.9, and 30.2±7.9% recovery for Cryptosporidium, respectively and 10.2±4.0, 14.1±7.3, 24.2±12.1, 23.2±13.7, 17.1±13.9, and 37.6±2.4% recovery for Giardia, respectively. The spike recovery results are comparable with data obtained using commercial brightfield and fluorescence microscope methods. Finally, we tested the smartphone microscope system for detecting (oo)cysts on 7 types of vegetable (n = 196) and river water (n = 18) samples. Forty-two percent vegetable and thirty-nine percent water samples were found to be contaminated with Cryptosporidium oocyst. Similarly, thirty-one percent vegetable and thirty-three percent water samples were contaminated with Giardia cyst.

Conclusions

The newly developed smartphone microscopic method showed comparable performance to commercial microscopic methods. The new method can be a low-cost and easy to implement alternative method for simultaneous detection of (oo)cysts in vegetable and water samples in resource limited settings.

An agonist of the CXCR4 receptor accelerates the recovery from the peripheral neuroparalysis induced by Taipan snake envenomation

PLoS Neglected Tropical Diseases News - 8 September 2020 - 9:00pm

by Marco Stazi, Giorgia D’Este, Andrea Mattarei, Samuele Negro, Florigio Lista, Michela Rigoni, Aram Megighian, Cesare Montecucco

Envenomation by snakes is a major neglected human disease. Hospitalization and use of animal-derived antivenom are the primary therapeutic supports currently available. There is consensus that additional, not expensive, treatments that can be delivered even long after the snake bite are needed. We recently showed that the drug dubbed NUCC-390 shortens the time of recovery from the neuroparalysis caused by traumatic or toxic degeneration of peripheral motor neurons. These syndromes are characterized by the activation of a pro-regenerative molecular axis, consisting of the CXCR4 receptor expressed at the damaged site in neuronal axons and by the release of its ligand CXCL12α, produced by surrounding Schwann cells. This intercellular signaling axis promotes axonal growth and functional recovery from paralysis. NUCC-390 is an agonist of CXCR4 acting similarly to CXCL12α. Here, we have tested its efficacy in a murine model of neuroparalytic envenoming by a Papuan Taipan (Oxyuranus scutellatus) where a degeneration of the motor axon terminals caused by the presynaptic PLA2 toxin Taipoxin, contained in the venom, occurs. Using imaging of the neuromuscular junction and electrophysiological analysis, we found that NUCC-390 administration after injection of either the purified neuroparalytic Taipoxin or the whole Taipan venom, significantly accelerates the recovery from paralysis. These results indicate that NUCC-390, which is non-toxic in mice, should be considered for trials in humans to test its efficacy in accelerating the recovery from the peripheral neuroparalysis induced by Taipans. NUCC-390 should be tested as well in the envenomation by other snakes that cause neuroparalytic syndromes in humans. NUCC-390 could become an additional treatment, common to many snake envenomings, that can be delivered after the bite to reduce death by respiratory deficits and to shorten and improve functional recovery.

Genetic evidence for the role of non-human primates as reservoir hosts for human schistosomiasis

PLoS Neglected Tropical Diseases News - 8 September 2020 - 9:00pm

by Tadesse Kebede, Nicolas Bech, Jean-François Allienne, Rey Olivier, Berhanu Erko, Jerome Boissier

Background

Schistosomiasis is a chronic parasitic disease, that affects over 207 million people and causes over 200,000 deaths annually, mainly in sub-Saharan Africa. Although many health measures have been carried out to limit parasite transmission, significant numbers of non-human primates such as Chlorocebus aethiops (Ch. aethiops) (vervet) and Papio anubis (baboon) are infected with S. mansoni, notably in Ethiopia, where they are expected to have potentially significant implications for transmission and control efforts.

Objective

The objective of this study was to assess and compare the genetic diversity and population structure of S. mansoni isolates from human and non-human primates free-ranging in close proximity to villages in selected endemic areas of Ethiopia.

Methods

A cross-sectional study was conducted in three transmission sites: Bochesa, Kime and Fincha. A total of 2,356 S. mansoni miracidia were directly isolated from fecal specimens of 104 hosts (i.e. 60 human hosts and 44 non-human primates). We performed DNA extraction and PCR amplification using fourteen microsatellite loci.

Results

At population scale we showed strong genetic structure between the three sample sites. At the definitive host scale, we observed that host factors can shape the genetic composition of parasite infra-populations. First, in male patients, we observed a positive link between parasite genetic diversity and the age of the patients. Second, we observed a difference in genetic diversity which was high in human males, medium in human females and low in non-human primates (NHPs). Finally, whatever the transmission site no genetic structure was observed between human and non-human primates, however, there appears to be little barriers, if any, host specificity of the S. mansoni populations with cross-host infections.

Conclusion

Occurrence of infection of a single host with multiple S. mansoni strains and inter- and intra-host genetic variations was observed. Substantial genetic diversity and gene flow across the S. mansoni population occurred at each site and non-human primates likely play a role in local transmission and maintenance of infection. Therefore, public health and wildlife professionals should work together to improve disease control and elimination strategies.

Zika virus transmission by Brazilian <i>Aedes aegypti</i> and <i>Aedes albopictus</i> is virus dose and temperature-dependent

PLoS Neglected Tropical Diseases News - 8 September 2020 - 9:00pm

by Thais Chouin-Carneiro, Mariana Rocha David, Fernanda de Bruycker Nogueira, Flavia Barreto dos Santos, Ricardo Lourenço-de-Oliveira

Background

Zika virus (ZIKV) emerged in the Pacific Ocean and subsequently caused a dramatic Pan‐American epidemic after its first appearance in the Northeast region of Brazil in 2015. The virus is transmitted by Aedes mosquitoes. We evaluated the role of temperature and infectious doses of ZIKV in vector competence of Brazilian populations of Ae. aegypti and Ae. albopictus.

Methodology/Principal findings

Two Ae. aegypti (Rio de Janeiro and Natal) and two Ae. albopictus (Rio de Janeiro and Manaus) populations were orally challenged with five viral doses (102 to 106 PFU / ml) of a ZIKV strain (Asian genotype) isolated in Northeastern Brazil, and incubated for 14 and 21 days in temperatures mimicking the spring-summer (28°C) and winter-autumn (22°C) mean values in Brazil. Detection of viral particles in the body, head and saliva samples was done by plaque assays in cell culture for determining the infection, dissemination and transmission rates, respectively. Compared with 28°C, at 22°C, transmission rates were significantly lower for both Ae. aegypti populations, and Ae. albopictus were not able to transmit the virus. Ae. albopictus showed low transmission rates even when challenged with the highest viral dose, while both Ae. aegypti populations presented higher of infection, dissemination and transmission rates than Ae. albopictus. Ae. aegypti showed higher transmission efficiency when taking virus doses of 105 and 106 PFU/mL following incubation at 28°C; both Ae. aegypti and Ae. albopictus were unable to transmit ZIKV with virus doses of 102 and 103 PFU/mL, regardless the incubation temperature.

Conclusions/Significance

The ingested viral dose and incubation temperature were significant predictors of the proportion of mosquito’s biting becoming infectious. Ae. aegypti and Ae. albopictus have the ability to transmit ZIKV when incubated at 28°C. However Brazilian populations of Ae. aegypti exhibit a much higher transmission potential for ZIKV than Ae. albopictus regardless the combination of infection dose and incubation temperature.

Biodistribution of degradable polyanhydride particles in <i>Aedes aegypti</i> tissues

PLoS Neglected Tropical Diseases News - 8 September 2020 - 9:00pm

by Edmund J. Norris, Adam S. Mullis, Yashdeep Phanse, Balaji Narasimhan, Joel R. Coats, Lyric C. Bartholomay

Insecticide resistance poses a significant threat to the control of arthropods that transmit disease agents. Nanoparticle carriers offer exciting opportunities to expand the armamentarium of insecticides available for public health and other pests. Most chemical insecticides are delivered by contact or feeding, and from there must penetrate various biological membranes to reach target organs and kill the pest organism. Nanoparticles have been shown to improve bioactive compound navigation of such barriers in vertebrates, but have not been well-explored in arthropods. In this study, we explored the potential of polyanhydride micro- and nanoparticles (250 nm– 3 μm), labeled with rhodamine B to associate with and/or transit across insect biological barriers, including the cuticle, epithelium, midgut and ovaries, in female Ae. aeygpti mosquitoes. Mosquitoes were exposed using conditions to mimic surface contact with a residual spray or paint, topical exposure to mimic contact with aerosolized insecticide, or per os in a sugar meal. In surface contact experiments, microparticles were sometimes observed in association with the exterior of the insect cuticle. Nanoparticles were more uniformly distributed across exterior tissues and present at higher concentrations. Furthermore, by surface contact, topical exposure, or per os, particles were detected in internal organs. In every experiment, amphiphilic polyanhydride nanoparticles associated with internal tissues to a higher degree than hydrophobic nanoparticles. In vitro, nanoparticles associated with Aedes aegypti Aag2 cells within two hours of exposure, and particles were evident in the cytoplasm. Further studies demonstrated that particle uptake is dependent on caveolae-mediated endocytosis. The propensity of these nanoparticles to cross biological barriers including the cuticle, to localize in target tissue sites of interest, and to reach the cytoplasm of cells, provides great promise for targeted delivery of insecticidal candidates that cannot otherwise reach these cellular and subcellular locations.

Knowledge, attitudes, practices of/towards COVID 19 preventive measures and symptoms: A cross-sectional study during the exponential rise of the outbreak in Cameroon

PLoS Neglected Tropical Diseases News - 4 September 2020 - 9:00pm

by Ngwewondo Adela, Lucia Nkengazong, Lum Abienwi Ambe, Jean Thierry Ebogo, Fabrice Medou Mba, Hamadama Oumarou Goni, Nyemb Nyunai, Marie Chantal Ngonde, Jean-Louis Essame Oyono

Severe Acute Respiratory Syndrome Coronavirus 2 (COVID 19) has plagued the world with about 7,8 million confirmed cases and over 430,000 deaths as of June 13th, 2020. The knowledge, attitude, and practices (KAP) people hold towards this new disease could play a major role in the way they accept measures put in place to curb its spread and their willingness to seek and adhere to care. We sought to understand if: a) demographic variables of Cameroonian residents could influence KAP and symptomatology, and b) KAP could influence the risk of having COVID19.A cross-sectional KAP/symptomatology online survey was conducted between April 20 to May 20. All analyses were performed using SPSS version 23. Of all respondents (1006), 53.1% were female, 26.6% were students, 26.9% interacted face to face and 62.8% were residents in Yaoundé with a median age of 33. The overall high score was 84.19% for knowledge, 69% for attitude, and 60.8% for practice towards COVID 19. Age > 20 years was associated with a high knowledge of COVID 19. Women had lower practice scores compared to men (OR = 0.72; 95%CI 0.56–0.92). 41 respondents had ≥3 symptoms and only 9 (22.95%) of them had called 1510 (emergency number). There was no significant difference between KAP and symptomatology. The presence of ≥ 3 symptoms in 4% of respondents (with 56% of them having co-morbidities) supports the current trend in the number of confirmed cases (8681) in Cameroon. The continuous increase in the number of cases and the overall good KAP warrants further investigation to assess the effectiveness of the measures put in place to curb the spread of the disease. Sensitization is paramount to preclude negative health-seeking behaviors and encourage positive preventive and therapeutic practices, for fear of an increase in mortality.

Human exposure to zoonotic malaria vectors in village, farm and forest habitats in Sabah, Malaysian Borneo

PLoS Neglected Tropical Diseases News - 4 September 2020 - 9:00pm

by Rebecca Brown, Tock H. Chua, Kimberly Fornace, Chris Drakeley, Indra Vythilingam, Heather M. Ferguson

The zoonotic malaria parasite, Plasmodium knowlesi, is now a substantial public health problem in Malaysian Borneo. Current understanding of P. knowlesi vector bionomics and ecology in Sabah comes from a few studies near the epicentre of human cases in one district, Kudat. These have incriminated Anopheles balabacensis as the primary vector, and suggest that human exposure to vector biting is peri-domestic as well as in forest environments. To address the limited understanding of vector ecology and human exposure risk outside of Kudat, we performed wider scale surveillance across four districts in Sabah with confirmed transmission to investigate spatial heterogeneity in vector abundance, diversity and infection rate. Entomological surveillance was carried out six months after a cross-sectional survey of P. knowlesi prevalence in humans throughout the study area; providing an opportunity to investigate associations between entomological indicators and infection. Human-landing catches were performed in peri-domestic, farm and forest sites in 11 villages (3–4 per district) and paired with estimates of human P. knowlesi exposure based on sero-prevalence. Anopheles balabacensis was present in all districts but only 6/11 villages. The mean density of An. balabacensis was relatively low, but significantly higher in farm (0.094/night) and forest (0.082/night) than peri-domestic areas (0.007/night). Only one An. balabacensis (n = 32) was infected with P. knowlesi. Plasmodium knowlesi sero-positivity in people was not associated with An. balabacensis density at the village-level however post hoc analyses indicated the study had limited power to detect a statistical association due low vector density. Wider scale sampling revealed substantial heterogeneity in vector density and distribution between villages and districts. Vector-habitat associations predicted from this larger-scale surveillance differed from those inferred from smaller-scale studies in Kudat; highlighting the importance of local ecological context. Findings highlight potential trade-offs between maximizing temporal versus spatial breadth when designing entomological surveillance; and provide baseline entomological and epidemiological data to inform future studies of entomological risk factors for human P. knowlesi infection.

A complement component C1q-mediated mechanism of antibody-dependent enhancement of Ebola virus infection

PLoS Neglected Tropical Diseases News - 4 September 2020 - 9:00pm

by Wakako Furuyama, Asuka Nanbo, Junki Maruyama, Andrea Marzi, Ayato Takada

Besides the common Fc receptor (FcR)-mediated mechanism of antibody-dependent enhancement (ADE), Ebola virus (EBOV) is known to utilize the complement component C1q for ADE of infection. This mechanism is FcR-independent and mediated by cross-linking of virus-antibody-C1q complexes to cell surface C1q receptors, leading to enhanced viral entry into cells. Using confocal microscopy, we found that virus-like particles (VLPs) consisting of EBOV glycoprotein, nucleoprotein, and matrix protein attached to the surface of human kidney 293 cells more efficiently in the presence of an ADE monoclonal antibody and C1q than with the antibody or C1q alone, and that there was no significant difference in the efficiency of VLP uptake into endosomes between the C1q-mediated ADE and non-ADE entry. Accordingly, both ADE and non-ADE infection were similarly decreased by inhibitors of the signaling pathways known to be required for endocytosis. These results suggest that C1q-mediated ADE of EBOV infection is simply caused by increased attachment of virus particles to the cell surface, which is distinct from the mechanism of FcR-mediated ADE requiring intracellular signaling to promote phagocytosis/macropinocytosis.

Early immune suppression leads to uncontrolled mite proliferation and potent host inflammatory responses in a porcine model of crusted versus ordinary scabies

PLoS Neglected Tropical Diseases News - 4 September 2020 - 9:00pm

by Sajad A. Bhat, Shelley F. Walton, Tomer Ventura, Xiaosong Liu, James S. McCarthy, Stewart T. G. Burgess, Kate E. Mounsey

Scabies is a neglected tropical disease of global significance. Our understanding of host-parasite interactions has been limited, particularly in crusted scabies (CS), a severe clinical manifestation involving hyper-infestation of Sarcoptes scabiei mites. Susceptibility to CS may be associated with immunosuppressive conditions but CS has also been seen in cases with no identifiable risk factor or immune deficit. Due to ethical and logistical difficulties with undertaking research on clinical patients with CS, we adopted a porcine model which parallels human clinical manifestations. Transcriptomic analysis using microarrays was used to explore scabies pathogenesis, and to identify early events differentiating pigs with ordinary (OS) and crusted scabies. Pigs with OS (n = 4), CS (n = 4) and non-infested controls (n = 4) were compared at pre-infestation, weeks 1, 2, 4 and 8 post-infestation. In CS relative to OS, there were numerous differentially expressed genes including pro-inflammatory cytokines (IL17A, IL8, IL19, IL20 and OSM) and chemokines involved in immune cell activation and recruitment (CCL20, CCL27 and CXCL6). The influence of genes associated with immune regulation (CD274/PD-L1 and IL27), immune signalling (TLR2, TLR8) and antigen presentation (RFX5, HLA-5 and HLA-DOB) were highlighted in the early host response to CS. We observed similarities with gene expression profiles associated with psoriasis and atopic dermatitis and confirmed previous observations of Th2/17 pronounced responses in CS. This is the first comprehensive study describing transcriptional changes associated with the development of CS and significantly, the distinction between OS and CS. This provides a basis for clinical follow-up studies, potentially identifying new control strategies for this severely debilitating disease.

Introduction of <i>Mycobacterium ulcerans</i> disease in the Bankim Health District of Cameroon follows damming of the Mapé River

PLoS Neglected Tropical Diseases News - 4 September 2020 - 9:00pm

by Koen Vandelannoote, Gerd Pluschke, Miriam Bolz, Martin W. Bratschi, Sarah Kerber, Timothy P. Stinear, Bouke C. de Jong

Buruli ulcer (BU) is an emerging ulcerative skin disease caused by infection with Mycobacterium ulcerans. Efforts to control its spread have been hampered by our limited understanding of M. ulcerans reservoirs and transmission, and the factors leading to the emergence of BU disease in a particular region. In this report we investigate an anecdotal link between damming the Mapé River in Cameroon and the emergence of BU in the Health Districts bordering Lake Bankim, the impoundment created by the Mapé dam. We used bacterial population genomics and molecular dating to find compelling support for a 2000 M. ulcerans introduction event that followed about 10 years after the filling of the newly created impoundment in 1988. We compared the genomic reconstructions with high-resolution satellite imagery to investigate what major environmental alterations might have driven the emergence of the new focus.

The viewpoint by White and colleagues critiquing the evaluation of the safety and efficacy of mass chemotherapy for <i>Taenia solium</i> taeniasis is unsubstantiated

PLoS Neglected Tropical Diseases News - 3 September 2020 - 9:00pm

by Michelle M. Haby, Leopoldo A. Sosa Leon, Ana Luciañez, Ruben Santiago Nicholls, Ludovic Reveiz, Meritxell Donadeu

Spatial spillover analysis of a cluster-randomized trial against dengue vectors in Trujillo, Venezuela

PLoS Neglected Tropical Diseases News - 3 September 2020 - 9:00pm

by Neal Alexander, Audrey Lenhart, Karim Anaya-Izquierdo

Background

The ability of cluster-randomized trials to capture mass or indirect effects is one reason for their increasing use to test interventions against vector-borne diseases such as malaria and dengue. For the same reason, however, the independence of clusters may be compromised if the distances between clusters is too small to ensure independence. In other words they may be subject to spillover effects.

Methods

We distinguish two types of spatial spillover effect: between-cluster dependence in outcomes, or spillover dependence; and modification of the intervention effect according to distance to the intervention arm, or spillover indirect effect. We estimate these effects in trial of insecticide-treated materials against the dengue mosquito vector, Aedes aegypti, in Venezuela, the endpoint being the Breteau index. We use a novel random effects Poisson spatial regression model. Spillover dependence is incorporated via an orthogonalized intrinsic conditional autoregression (ICAR) model. Spillover indirect effects are incorporated via the number of locations within a certain radius, set at 200m, that are in the intervention arm.

Results

From the model with ICAR spatial dependence, and the degree of surroundedness, the intervention effect is estimated as 0.74—favouring the intervention—with a 95% credible interval of 0.34 to 1.69. The point estimates are stronger with increasing surroundedness within intervention locations.

Conclusion

In this trial there is some evidence of a spillover indirect effect of the intervention, with the Breteau index tending to be lower in locations which are more surrounded by locations in the intervention arm.

Assessing dehydration status in dengue patients using urine colourimetry and mobile phone technology

PLoS Neglected Tropical Diseases News - 3 September 2020 - 9:00pm

by Natalie Chew, Abdul Muhaimin Noor Azhar, Aida Bustam, Mohamad Shafiq Azanan, Crystal Wang, Lucy C. S. Lum

Background

Dengue is a systemic and dynamic disease with symptoms ranging from undifferentiated fever to dengue shock syndrome. Assessment of patients’ severity of dehydration is integral to appropriate care and management. Urine colour has been shown to have a high correlation with overall assessment of hydration status. This study tests the feasibility of measuring dehydration severity in dengue fever patients by comparing urine colour captured by mobile phone cameras to established laboratory parameters.

Methodology/Principal findings

Photos of urine samples were taken in a customized photo booth, then processed using Adobe Photoshop to index urine colour into the red, green, and blue (RGB) colour space and assigned a unique RGB value. The RGB values were then correlated with patients’ clinical and laboratory hydration indices using Pearson’s correlation and multiple linear regression. There were strong correlations between urine osmolality and the RGB of urine colour, with r = -0.701 (red), r = -0.741 (green), and r = -0.761 (blue) (all p-value <0.05). There were strong correlations between urine specific gravity and the RGB of urine colour, with r = -0.759 (red), r = -0.785 (green), and r = -0.820 (blue) (all p-value <0.05). The blue component had the highest correlations with urine specific gravity and urine osmolality. There were moderate correlations between RGB components and serum urea, at r = -0.338 (red), -0.329 (green), -0.360 (blue). In terms of urine biochemical parameters linked to dehydration, multiple linear regression studies showed that the green colourimetry code was predictive of urine osmolality (β coefficient -0.082, p-value <0.001) while the blue colourimetry code was predictive of urine specific gravity (β coefficient -2,946.255, p-value 0.007).

Conclusions/Significance

Urine colourimetry using mobile phones was highly correlated with the hydration status of dengue patients, making it a potentially useful hydration status tool.

Toward implementation of combined incompatible and sterile insect techniques for mosquito control: Optimized chilling conditions for handling <i>Aedes albopictus</i> male adults prior to release

PLoS Neglected Tropical Diseases News - 3 September 2020 - 9:00pm

by Dongjing Zhang, Zhiyong Xi, Yongjun Li, Xiaohua Wang, Hanano Yamada, Jieru Qiu, Yongkang Liang, Meichun Zhang, Yu Wu, Xiaoying Zheng

Combined incompatible and sterile insect technique (IIT-SIT) has been considered to be an effective and safe approach to control mosquito populations. Immobilization of male adults by chilling is a crucial process required for the packing, transportation and release of the mosquitoes during the implementation of IIT-SIT for mosquito control. In this study, effects of chilling on the Aedes albopictus males with triple Wolbachia infections (HC line), a powerful weapon to fight against the wild type Ae. albopictus population via IIT-SIT, were evaluated under both laboratory and field conditions. Irradiated HC (IHC) males were exposed to 1, 5 and 10°C for 1, 2, 3, 6 and 24 h. The survival rate of the post-chilled IHC males was then monitored. Longevity of post-chilled IHC males was compared to non-chilled males under laboratory and semi-field conditions. Mating competitiveness of IHC/HC males after exposure to 5 or 10°C for 0, 3 and 24 h was then evaluated. Effects of compaction and transportation under chilled conditions on the survival rate of IHC males were also monitored. The optimal chilling conditions for handling IHC males were temperatures between 5 and 10°C for a duration of less than 3 h with no negative impacts on survival rate, longevity and mating competitiveness when compared to non-chilled males. However, the overall quality of post-chilled IHC/HC males decreased when exposed to low temperatures for 24 h. Reduced survival was observed when IHC males were stored at 5°C under a compaction height of 8 cm. Transportation with chilling temperatures fluctuating from 8 to 12°C has no negative impact on the survival of IHC males. This study identified the optimal chilling temperature and duration for the handling and transportation of Ae. albopictus IHC male adults without any detrimental effect on their survival, longevity and mating competitiveness. Further studies are required to develop drone release systems specific for chilled mosquitoes to improve release efficiency, as well as to compare the population suppression efficiency between release of post-chilled and non-chilled males in the field.

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