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Clinical and molecular epidemiology of Crimean-Congo hemorrhagic fever in Oman

25 April 2019 - 9:00pm

by Seif S. Al-Abri, Roger Hewson, Hanan Al-Kindi, Idris Al-Abaidani, Amina Al-Jardani, Amal Al-Maani, Samira Almahrouqi, Barry Atkinson, Adil Al-Wahaibi, Bader Al-Rawahi, Shyam Bawikar, Nicholas J. Beeching

Background

Crimean-Congo hemorrhagic fever (CCHF) is a serious disease with a high fatality rate reported in many countries. The first case of CCHF in Oman was detected in 1995 and serosurveys have suggested widespread infection of humans and livestock throughout the country.

Methodology

Cases of CCHF reported to the Ministry of Health (MoH) of Oman between 1995 and 2017 were retrospectively reviewed. Diagnosis was confirmed by serology and/or molecular tests in Oman. Stored RNA from recent cases was studied by sequencing the complete open reading frame (ORF) of the viral S segment at Public Health England, enabling phylogenetic comparisons to be made with other S segments of strains obtained from the region.

Findings

Of 88 cases of CCHF, 4 were sporadic in 1995 and 1996, then none were detected until 2011. From 2011–2017, incidence has steadily increased and 19 (23.8%) of 80 cases clustered around Eid Al Adha. The median (range) age was 33 (15–68) years and 79 (90%) were male. The major risk for infection was contact with animals and/or butchering in 73/88 (83%) and only one case was related to tick bites alone. Severe cases were over-represented: 64 (72.7%) had a platelet count < 50 x 109/L and 32 (36.4%) died. There was no intrafamilial spread or healthcare-associated infection. The viral S segments from 11 patients presenting in 2013 and 2014 were all grouped in Asia 1 (IV) lineage.

Conclusions

CCHF is well-established throughout Oman, with a single strain of virus present for at least 20 years. Most patients are men involved in animal husbandry and butchery. The high mortality suggests that there is substantial under-diagnosis of milder cases. Preventive measures have been introduced to reduce risks of transmission to animal handlers and butchers and to maintain safety in healthcare settings.

Host immune responses induced by specific <i>Mycobacterium leprae</i> antigens in an overnight whole-blood assay correlate with the diagnosis of paucibacillary leprosy patients in China

24 April 2019 - 9:00pm

by Xiaohua Chen, Yuan-Gang You, You-Hua Yuan, Lian C. Yuan, Yan Wen

Background

Leprosy, caused by Mycobacterium leprae, affects over 200,000 people annually worldwide and remains endemic in the ethnically diverse, mountainous and underdeveloped southwestern provinces of China. Delayed diagnosis of leprosy persists in China, thus, additional knowledge to support early diagnosis, especially early diagnosis of paucibacillary (PB) patients, based on the host immune responses induced by specific M. leprae antigens is needed. The current study aimed to investigate leprosy patients and controls in Southwest China by comparing supernatants after stimulation with specific M. leprae antigens in an overnight whole-blood assay (WBA) to determine whether host markers induced by specific M. leprae antigens improve the diagnosis or discrimination of PB patients with leprosy.

Methodology/Principal findings

Leprosy patients [13 multibacillary (MB) patients and 7 PB patients] and nonleprosy controls [21 healthy household contacts (HHCs), 20 endemic controls (ECs) and 19 tuberculosis (TB) patients] were enrolled in this study. The supernatant levels of ten host markers stimulated by specific M. leprae antigens were evaluated by overnight WBA and multiplex Luminex assays. The diagnostic value in PB patients and ECs and the discriminatory value between PB patients and HHCs or TB patients were evaluated by receiver operator characteristics (ROC) analysis. ML2044-stimulated CXCL8/IL-8 achieved the highest sensitivity of 100%, with a specificity of 73.68%, for PB diagnosis. Compared to single markers, a 3-marker combination model that included ML2044-induced CXCL8/IL-8, CCL4/MIP-1 beta, and IL-6 improved the diagnostic specificity to 94.7% for PB patients. ML2044-stimulated IL-4 and CXCL8/IL-8 achieved the highest sensitivity (85.71% and 100%) and the highest specificity (95.24% and 84.21%) for discriminating PB patients from HHCs and TB patients, respectively.

Conclusions

Our findings suggest that the host markers induced by specific M. leprae antigens in an overnight WBA increase diagnostic and discriminatory value in PB patients with leprosy, with a particularly strong association with interleukin 8.

The arginine sensing and transport binding sites are distinct in the human pathogen <i>Leishmania</i>

24 April 2019 - 9:00pm

by Harsh Pawar, Madhu Puri, Renana Fischer Weinberger, Rentala Madhubala, Dan Zilberstein

The intracellular protozoan parasite Leishmania donovani causes human visceral leishmaniasis. Intracellular L. donovani that proliferate inside macrophage phagolysosomes compete with the host for arginine, creating a situation that endangers parasite survival. Parasites have a sensor that upon arginine deficiency activates an Arginine Deprivation Response (ADR). L. donovani transport arginine via a high-affinity transporter (LdAAP3) that is rapidly up-regulated by ADR in intracellular amastigotes. To date, the sensor and its ligand have not been identified. Here, we show that the conserved amidino group at the distal cap of the arginine side chain is the ligand that activates ADR, in both promastigotes and intracellular amastigotes, and that arginine sensing and transport binding sites are distinct in L. donovani. Finally, upon addition of arginine and analogues to deprived cells, the amidino ligand activates rapid degradation of LdAAP3. This study provides the first identification of an intra-molecular ligand of a sensor that acts during infection.

(De)glutamylation and cell death in <i>Leishmania</i> parasites

24 April 2019 - 9:00pm

by Louise Basmaciyan, Derrick R. Robinson, Nadine Azas, Magali Casanova

Trypanosomatids are flagellated protozoan parasites that are very unusual in terms of cytoskeleton organization but also in terms of cell death. Most of the Trypanosomatid cytoskeleton consists of microtubules, forming different substructures including a subpellicular corset. Oddly, the actin network appears structurally and functionally different from other eukaryotic actins. And Trypanosomatids have an apoptotic phenotype under cell death conditions, but the pathways involved are devoid of key mammal proteins such as caspases or death receptors, and the triggers involved in apoptotic induction remain unknown. In this article, we have studied the role of the post-translational modifications, deglutamylation and polyglutamylation, in Leishmania. We have shown that Leishmania apoptosis was linked to polyglutamylation and hypothesized that the cell survival process autophagy was linked to deglutamylation. A balance seems to be established between polyglutamylation and deglutamylation, with imbalance inducing microtubule or other protein modifications characterizing either cell death if polyglutamylation was prioritized, or the cell survival process of autophagy if deglutamylation was prioritized. This emphasizes the role of post-translational modifications in cell biology, inducing cell death or cell survival of infectious agents.

Systematic sampling of adults as a sensitive means of detecting persistence of lymphatic filariasis following mass drug administration in Sri Lanka

22 April 2019 - 9:00pm

by Ramakrishna U. Rao, Sandhya D. Samarasekera, Kumara C. Nagodavithana, Manjula W. Punchihewa, Udaya S. B. Ranasinghe, Gary J. Weil

Background

Sri Lanka’s Anti-Filariasis Campaign conducted 5 annual rounds of mass drug administration (MDA) with diethylcarbamazine (DEC) plus albendazole to eliminate lymphatic filariasis (LF) in all endemic districts between 2002 and 2006. Post-MDA surveillance has consistently documented Wuchereria bancrofti microfilaremia (Mf) rates below 1% in all sentinel and spot check sites since that time, and all implementation units easily satisfied WHO’s target for school-based transmission assessment surveys (school-TAS) in 2013. However, more detailed studies have identified foci of persistent infection in the large coastal evaluation unit (EU) (population about 0.6 million) in Galle district. Therefore, the purpose of this study was to assess the sensitivity and feasibility of community-based TAS in adults (adult-TAS) and to compare results obtained by adult-TAS with prior school-TAS and molecular xenomonitoring (MX, molecular detection of filarial DNA in systematically sampled mosquitoes) results in this known problem area.

Methodology and principal findings

Two cluster surveys were performed in independent samples of 30 evaluation areas (EAs) in the coastal Galle EU in 2015. Each survey tested approximately 1,800 adults for circulating filarial antigenemia (CFA) with the Alere Filariasis Test Strip. The CFA prevalence for all persons tested (N = 3,612) was 1.8% (CI 1.4–2.2), and this was significantly higher than the CFA rate of 0.4% obtained by school-TAS in 2013. CFA prevalences in the two samples were similar [1.5% (CI 1.0–2.2), and 2.0% (CI 1.4–2.7)]. Antigenemia prevalence in sampled EUs was highly variable (range 0–11%), and it exceeded 5% in 6 EAs. The 30 EAs sampled in one of our adult-TAS surveys had recently been assessed for persistent filariasis by molecular xenomonitoring (MX). CFA prevalence in adults and filarial DNA prevalence in mosquitoes in these EAs were significantly correlated (r = 0.43; P = 0.02).

Conclusions

Community based adult-TAS provided a reproducible measure of persistent W. bancrofti infection in a large evaluation unit in Sri Lanka that has low-level persistence of LF following multiple rounds of MDA. In addition, adult-TAS and MX results illustrate the focality of persistent LF in this setting. Adult-TAS may be more sensitive than school-TAS for this purpose. Adult-TAS and MX are potential options for post-MDA and post-validation surveillance programs to identify problem areas that require mop-up activities. Adult-TAS should also be useful for remapping areas with uncertain LF endemicity for possible inclusion in national LF elimination programs.

A highly expressed intestinal cysteine protease of <i>Ancylostoma ceylanicum</i> protects vaccinated hamsters from hookworm infection

22 April 2019 - 9:00pm

by Jason B. Noon, Erich M. Schwarz, Gary R. Ostroff, Raffi V. Aroian

Background

Human hookworms (Necator americanus, Ancylostoma duodenale, and Ancylostoma ceylanicum) are intestinal blood-feeding parasites that infect ~500 million people worldwide and are among the leading causes of iron-deficiency anemia in the developing world. Drugs are useful against hookworm infections, but hookworms rapidly reinfect people, and the parasites can develop drug resistance. Therefore, having a hookworm vaccine would be of tremendous benefit.

Methodology/Principal findings

We investigated the vaccine efficacy in outbred Syrian hamsters of three A. ceylanicum hookworm antigen candidates from two classes of proteins previously identified as promising vaccine candidates. These include two intestinally-enriched, putatively secreted cathepsin B cysteine proteases (AceyCP1, AceyCPL) and one small Kunitz-type protease inhibitor (AceySKPI3). Recombinant proteins were produced in Pichia pastoris, and adsorbed to Alhydrogel. Recombinant AceyCPL (rAceyCPL)/Alhydrogel and rAceySKPI3/Alhydrogel induced high serum immunoglobulin G (IgG) titers in 8/8 vaccinates, but were not protective. rAceyCP1/Alhydrogel induced intermediate serum IgG titers in ~60% of vaccinates in two different trials. rAceyCP1 serum IgG responders had highly significantly decreased hookworm burdens, fecal egg counts and clinical pathology compared to Alhydrogel controls and nonresponders. Protection was highly correlated with rAceyCP1 serum IgG titer. Antisera from rAceyCP1 serum IgG responders, but not nonresponders or rAceyCPL/Alhydrogel vaccinates, significantly reduced adult A. ceylanicum motility in vitro. Furthermore, rAceyCP1 serum IgG responders had canonical Th2-specific recall responses (IL4, IL5, IL13) in splenocytes stimulated ex vivo.

Conclusions/Significance

These findings indicate that rAceyCP1 is a promising vaccine candidate and validates a genomic/transcriptomic approach to human hookworm vaccine discovery.

Prevalence, intensity and associated risk factors of soil transmitted helminth infections: A comparison between Negritos (indigenous) in inland jungle and those in resettlement at town peripheries

22 April 2019 - 9:00pm

by Azdayanti Muslim, Sakinah Mohd Sofian, Syahrul Azlin Shaari, Boon-Peng Hoh, Yvonne Ai-Lian Lim

Background

Formerly known as the Malaysian hunter gatherers, the Negrito Orang Asli (OA) were heavily dependent on the forest for sustenance and early studies indicated high prevalence of intestinal parasitism. Initiation of a redevelopment program in the 1970s aimed to demarginalize the OA was expected to reduce soil transmitted helminth (STH) infections. Gradually, the OA were relocated to new resettlement areas at the peripheries. The aim of this study was to compare STH infections between Negritos who are still living in the inland jungle with those living in resettlements.

Methodology/Principal findings

A total of 416 Negrito participants were grouped into two categories of communities based on location; Inland Jungle Villages (IJV); and Resettlement Plan Scheme (RPS). Iodine wet mount, formalin-ether sedimentation, modified Trichrome and modified Ziehl-Neelsen staining and Kato-Katz methods were performed on stool samples. A questionnaire was used to collect information regarding demographic, socioeconomic, environmental and hygiene behaviors. Prevalence of STH was significantly higher in IJV (91.3%) versus RPS (83.1%) (P = 0.02). However, the percentage of individuals with severe intensity of Trichuris trichiura infections was significantly higher in the RPS (17.2%) compared to IJV (6.5%) (P = 0.01). Severe Ascaris lumbricoides infection was observed at 20.0% amongst RPS Negritos and 15.0% amongst IJV (P = 0.41). Whilst for hookworm infection, both prevalence and individuals with moderate to severe infections were higher in the IJV (26.2%, 41.0%) versus RPS (18.7%, 24.0%) (P values = 0.08, 0.09), accordingly. The prevalence other intestinal parasitic infections (e.g. Entamoeba sp., Blastocystis and flukes) was also higher in IJV versus RPS. Apart from poor hygienic behaviors as significant risk factors in both communities, low socio-economic status was highly associated with STH infections in RPS (P<0.001) but not significantly associated in IJV.

Conclusions

The findings showed that ex situ development plan by RPS has not profoundly contributed to the STH reduction among the OA. Conversely, burden rate of T. trichiura infections increased due to their extreme poverty and poor hygienic behaviors. Here, we are suggesting biannual mass albendazole intervention (triple dose regimens in RPS, but a single dose in IJV) and community empowerment to both communities. For a long-term and better uptake, these strategies must be done together with the community input and participation, respecting their traditional customs and accompanied by recruitment of more OA people in the health-care taskforce.

The spatial epidemiology of leprosy in Kenya: A retrospective study

22 April 2019 - 9:00pm

by Fatihiyya Wangara, Hillary Kipruto, Oscar Ngesa, James Kayima, Enos Masini, Joseph Sitienei, Faith Ngari

Background

Leprosy elimination defined as a registered prevalence rate of less than 1 case per 10,000 persons was achieved in Kenya at the national level in 1989. However, there are still pockets of leprosy in some counties where late diagnosis and consequent physical disability persist. The epidemiology of leprosy in Kenya for the period 2012 through to 2015 was defined using spatial methods.

Methods

This was a retrospective ecological correlational study that utilized leprosy case based data extracted from the National Leprosy Control Program database. Geographic information system and demographic data were obtained from Kenya National Bureau of Statistics (KNBS). Chi square tests were carried out to check for association between sociodemographic factors and disease indicators. Two Spatial Poisson Conditional Autoregressive (CAR) models were fitted in WinBUGS 1.4 software. The first model included all leprosy cases (new, retreatment, transfers from another health facility) and the second one included only new leprosy cases. These models were used to estimate leprosy relative risks per county as compared to the whole country i.e. the risk of presenting with leprosy given the geographical location.

Principal findings

Children aged less than 15 years accounted for 7.5% of all leprosy cases indicating active leprosy transmission in Kenya. The risk of leprosy notification increased by about 5% for every 1 year increase in age, whereas a 1% increase in the proportion of MB cases increased the chances of new leprosy case notification by 4%. When compared to the whole country, counties with the highest risk of leprosy include Kwale (relative risk of 15), Kilifi (RR;8.9) and Homabay (RR;4.1), whereas Turkana had the lowest relative risk of 0.005.

Conclusion

Leprosy incidence exhibits geographical variation and there is need to institute tailored local control measures in these areas to reduce the burden of disability.

Spatio-temporal dynamics of dengue in Brazil: Seasonal travelling waves and determinants of regional synchrony

22 April 2019 - 9:00pm

by Mikhail Churakov, Christian J. Villabona-Arenas, Moritz U. G. Kraemer, Henrik Salje, Simon Cauchemez

Dengue continues to be the most important vector-borne viral disease globally and in Brazil, where more than 1.4 million cases and over 500 deaths were reported in 2016. Mosquito control programmes and other interventions have not stopped the alarming trend of increasingly large epidemics in the past few years. Here, we analyzed monthly dengue cases reported in Brazil between 2001 and 2016 to better characterise the key drivers of dengue epidemics. Spatio-temporal analysis revealed recurring travelling waves of disease occurrence. Using wavelet methods, we characterised the average seasonal pattern of dengue in Brazil, which starts in the western states of Acre and Rondônia, then travels eastward to the coast before reaching the northeast of the country. Only two states in the north of Brazil (Roraima and Amapá) did not follow the countrywide pattern and had inconsistent timing of dengue epidemics throughout the study period. We also explored epidemic synchrony and timing of annual dengue cycles in Brazilian regions. Using gravity style models combined with climate factors, we showed that both human mobility and vector ecology contribute to spatial patterns of dengue occurrence. This study offers a characterization of the spatial dynamics of dengue in Brazil and its drivers, which could inform intervention strategies against dengue and other arboviruses.

Loss of cytoplasmic incompatibility in <i>Wolbachia</i>-infected <i>Aedes aegypti</i> under field conditions

19 April 2019 - 9:00pm

by Perran A. Ross, Scott A. Ritchie, Jason K. Axford, Ary A. Hoffmann

Wolbachia bacteria are now being introduced into Aedes aegypti mosquito populations for dengue control. When Wolbachia infections are at a high frequency, they influence the local transmission of dengue by direct virus blocking as well as deleterious effects on vector mosquito populations. However, the effectiveness of this strategy could be influenced by environmental temperatures that decrease Wolbachia density, thereby reducing the ability of Wolbachia to invade and persist in the population and block viruses. We reared wMel-infected Ae. aegypti larvae in the field during the wet season in Cairns, North Queensland. Containers placed in the shade produced mosquitoes with a high Wolbachia density and little impact on cytoplasmic incompatibility. However, in 50% shade where temperatures reached 39°C during the day, wMel-infected males partially lost their ability to induce cytoplasmic incompatibility and females had greatly reduced egg hatch when crossed to infected males. In a second experiment under somewhat hotter conditions (>40°C in 50% shade), field-reared wMel-infected females had their egg hatch reduced to 25% when crossed to field-reared wMel-infected males. Wolbachia density was reduced in 50% shade for both sexes in both experiments, with some mosquitoes cleared of their Wolbachia infections entirely. To investigate the critical temperature range for the loss of Wolbachia infections, we held Ae. aegypti eggs in thermocyclers for one week at a range of cyclical temperatures. Adult wMel density declined when eggs were held at 26–36°C or above with complete loss at 30–40°C, while the density of wAlbB remained high until temperatures were lethal. These findings suggest that high temperature effects on Wolbachia are potentially substantial when breeding containers are exposed to partial sunlight but not shade. Heat stress could reduce the ability of Wolbachia infections to invade mosquito populations in some locations and may compromise the ability of Wolbachia to block virus transmission in the field. Temperature effects may also have an ecological impact on mosquito populations given that a proportion of the population becomes self-incompatible.

Prevalence and genetic diversity of <i>Burkholderia pseudomallei</i> isolates in the environment near a patient’s residence in Northeast Thailand

19 April 2019 - 9:00pm

by Rathanin Seng, Natnaree Saiprom, Rungnapa Phunpang, Christine Joy Baltazar, Sarika Boontawee, Thanatchanan Thodthasri, Wirayut Silakun, Narisara Chantratita

Background

Burkholderia pseudomallei is the causative agent of melioidosis, a severe infectious disease in tropical regions. It is necessary to understand the risk of acquiring this infection from the environment.

Methodology /Principal Findings

The prevalence, concentration and genetic diversity of B. pseudomallei isolates collected from two sites in Buriram, Northeast Thailand were investigated. Forty-four environmental samples (18 from soil, 14 from rice rhizosphere, and 12 from water) were collected; of those 44 samples, 19 were collected from near a patient’s residence and 25 from suspected exposure sites and compared with 10 clinical isolates of the patient. Quantitative culture was performed, and B. pseudomallei was identified using the latex agglutination test and matrix-laser absorption ionisation mass spectrometry. Genotyping was performed in 162 colonies from clinical (N = 10) and environmental samples (N = 152) using pulse-field gel electrophoresis (PFGE) followed by multi-locus sequence typing (MLST) of the clinical strain. B. pseudomallei was detected in 11 of the 44 environmental samples (1 from soil, 4 from rice rhizosphere, and 6 from water). The bacterial count in the positive soil sample was 115 CFU/g. The mean concentrations ± SDs of B. pseudomallei in the positive water and rhizosphere samples were 5.1 ± 5.5 CFU/ml and 80 ± 49 CFU/g, respectively. Six water samples with positive results were collected from a pond and water sources for drinking and daily use. All colonies isolated from the patient shared the same PFGE type (PT) indicating monoclonal infection of ST99. Although the 152 colonies from environmental isolates exhibited 25 PTs, none were identical to the patient’s isolates. PT5 and PT7 were most common genotype among the environmental samples.

Conclusions/Significance

Diverse genotypes of B. pseudomallei were prevalent in the environment. However, the patient may have been infected with a low-density genotype. Intervention strategies for preventing B. pseudomallei infection are required.

Genetic landscape and macro-evolution of co-circulating Coxsackieviruses A and Vaccine-derived Polioviruses in the Democratic Republic of Congo, 2008-2013

19 April 2019 - 9:00pm

by Serge Alain Sadeuh-Mba, Hugo Kavunga-Membo, Marie-Line Joffret, Riziki Yogolelo, Marie Claire Endegue-Zanga, Maël Bessaud, Richard Njouom, Jean-Jacques Muyembe-Tamfu, Francis Delpeyroux

Enteroviruses (EVs) are among the most common viruses infecting humans worldwide but only a few Non-Polio Enterovirus (NPEV) isolates have been characterized in the Democratic Republic of Congo (DR Congo). Moreover, circulating vaccine-derived polioviruses (PVs) [cVDPVs] isolated during multiple outbreaks in DR Congo from 2004 to 2018 have been characterized so far only by the sequences of their VP1 capsid coding gene. This study was carried to i) investigate the circulation and genetic diversity of NPEV and polio vaccine isolates recovered from healthy children and Acute Flaccid Paralysis (AFP) patients, ii) evaluate the occurrence of genetic recombination among EVs belonging to the Enterovirus C species (including PVs) and iii) identify the virological factors favoring multiple emergences of cVDPVs in DR Congo. The biological material considered in this study included i) a collection of 91 Sabin-like PVs, 54 cVDPVs and 150 NPEVs isolated from AFP patients between 2008 and 2012 in DR Congo and iii) a collection of 330 stool specimens collected from healthy children in 2013 in the Kasai Oriental and Maniema provinces of DR Congo. Studied virus isolates were sequenced in four distinct sub-genomic regions 5’-UTR, VP1, 2CATPase and 3Dpol. Resulting sequences were compared through comparative phylogenetic analyses. Virus isolation showed that 19.1% (63/330) healthy children were infected by EVs including 17.9% (59/330) of NPEVs and 1.2% (4/330) of type 3 Sabin-like PVs. Only one EV-C type, EV-C99 was identified among the NPEV collection from AFP patients whereas 27.5% of the 69 NPEV isolates typed in healthy children belonged to the EV-C species: CV-A13 (13/69), A20 (5/69) and A17 (1/69). Interestingly, 50 of the 54 cVDPVs featured recombinant genomes containing exogenous sequences in at least one of the targeted non-structural regions of their genomes: 5’UTR, 2CATPase and 3Dpol. Some of these non-vaccine sequences of the recombinant cVDPVs were strikingly related to homologous sequences from co-circulating CV-A17 and A20 in the 2CATPase region as well as to those from co-circulating CV-A13, A17 and A20 in the 3Dpol region. This study provided the first evidence uncovering CV-A20 strains as major recombination partners of PVs. High quality AFP surveillance, sensitive environmental surveillance and efficient vaccination activities remain essential to ensure timely detection and efficient response to recombinant cVDPVs outbreaks in DR Congo. Such needs are valid for any epidemiological setting where high frequency and genetic diversity of Coxsackieviruses A13, A17 and A20 provide a conducive viral ecosystem for the emergence of virulent recombinant cVDPVs.

The invasive giant African snail <i>Lissachatina fulica</i> as natural intermediate host of <i>Aelurostrongylus abstrusus</i>, <i>Angiostrongylus vasorum</i>, <i>Troglostrongylus brevior</i>, and <i>Crenosoma vulpis</i> in Colombia

19 April 2019 - 9:00pm

by Felipe Penagos-Tabares, Malin K. Lange, Juan Vélez, Jörg Hirzmann, Jesed Gutiérrez-Arboleda, Anja Taubert, Carlos Hermosilla, Jenny J. Chaparro Gutiérrez

Background

Several metastrongyloid lungworms are unreported pathogens in Colombia. Angiostrongylus vasorum and Crenosoma vulpis target the cardiopulmonary system of domestic and wild canids. Aelurostrongylus abstrusus and Troglostrongylus brevior infect felids and considering that six wild felid species exist in Colombia, knowledge of feline lungworm infections is important for their conservation. The zoonotic metastrongyloids Angiostrongylus costaricensis and Angiostrongylus cantonensis can cause severe gastrointestinal and neurological diseases. Angiostrongylus costaricensis has been reported in Colombia, while Ang. cantonensis is present in neighbouring countries. Research on the epidemiology of metastrongyloids in Colombia and South America more broadly requires evaluating the role that gastropods play as intermediate hosts in their life cycles. This study assessed the prevalence of metastrongyloid larvae in populations of the invasive giant African snail, Lissachatina fulica, in Colombia.

Methodology/Principal findings

A total of 609 Lissachantina fulica were collected from 6 Colombian municipalities. The snails were then cryo-euthanized, artificially digested and the sediments examined microscopically for the presence of metastrongyloid larvae. Based on morphological characteristics 53.3% (56/107) of the snails from Puerto Leguízamo (Department of Putumayo) were infected with Ael. abstrusus larvae, 8.4% (9/107) with Ang. vasorum larvae, 6.5% (7/107) with T. brevior larvae and 5.6% (6/107) with C. vulpis larvae, being the region with highest prevalences of the four species. Snails from Andes (Department of Antioquia) and Tulúa (Department of Valle del Cauca) were positive for Ang. vasorum larvae with a prevalence of 4.6 (11/238) and 6.3% (4/64), respectively. Species identifications were confirmed by PCR and sequencing.

Conclusions/Significance

This epidemiological survey reports for first time the presence of Ael. abstrusus, T. brevior, C. vulpis and Ang. vasorum in L. fulica in a number of regions of Colombia.

Inhibition of <i>Tityus serrulatus</i> venom hyaluronidase affects venom biodistribution

19 April 2019 - 9:00pm

by Bárbara Bruna Ribeiro de Oliveira-Mendes, Sued Eustáquio Mendes Miranda, Douglas Ferreira Sales-Medina, Bárbara de Freitas Magalhães, Yan Kalapothakis, Renan Pedra de Souza, Valbert Nascimento Cardoso, André Luís Branco de Barros, Clara Guerra-Duarte, Evanguedes Kalapothakis, Carolina Campolina Rebello Horta

Background

The hyaluronidase enzyme is generally known as a spreading factor in animal venoms. Although its activity has been demonstrated in several organisms, a deeper knowledge about hyaluronidase and the venom spreading process from the bite/sting site until its elimination from the victim's body is still in need. Herein, we further pursued the goal of demonstrating the effects of inhibition of T. serrulatus venom (TsV) hyaluronidase on venom biodistribution.

Methods and principal findings

We used technetium-99m radiolabeled Tityus serrulatus venom (99mTc-TsV) to evaluate the venom distribution kinetics in mice. To understand the hyaluronidase’s role in the venom’s biodistribution, 99mTc-TsV was immunoneutralized with specific anti-T.serrulatus hyaluronidase serum. Venom biodistribution was monitored by scintigraphic images of treated animals and by measuring radioactivity levels in tissues as heart, liver, lungs, spleen, thyroid, and kidneys. In general, results revealed that hyaluronidase inhibition delays venom components distribution, when compared to the non-neutralized 99mTc-TsV control group. Scintigraphic images showed that the majority of the immunoneutralized venom is retained at the injection site, whereas non-treated venom is quickly biodistributed throughout the animal’s body. At the first 30 min, concentration peaks are observed in the heart, liver, lungs, spleen, and thyroid, which gradually decreases over time. On the other hand, immunoneutralized 99mTc-TsV takes 240 min to reach high concentrations in the organs. A higher concentration of immunoneutralized 99mTc-TsV was observed in the kidneys in comparison with the non-treated venom. Further, in situ neutralization of 99mTc-TsV by anti-T.serrulatus hyaluronidase serum at zero, ten, and 30 min post venom injection showed that late inhibition of hyaluronidase can still affect venom biodistribution. In this assay, immunoneutralized 99mTc-TsV was accumulated in the bloodstream until 120 or 240 min after TsV injection, depending on anti-hyaluronidase administration time. Altogether, our data show that immunoneutralization of hyaluronidase prevents venom spreading from the injection site.

Conclusions

By comparing TsV biodistribution in the absence or presence of anti-hyaluronidase serum, the results obtained in the present work show that hyaluronidase has a key role not only in the venom spreading from the inoculation point to the bloodstream, but also in venom biodistribution from the bloodstream to target organs. Our findings demonstrate that hyaluronidase is indeed an important spreading factor of TsV and its inhibition can be used as a novel first-aid strategy in envenoming.

Epidemiological trend of chikungunya outbreak in Pakistan: 2016–2018

18 April 2019 - 9:00pm

by Nazish Badar, Muhammad Salman, Jamil Ansari, Aamer Ikram, Javaria Qazi, Muhammad Masroor Alam

Combating infectious disease epidemics through China’s Belt and Road Initiative

18 April 2019 - 9:00pm

by Jin Chen, Robert Bergquist, Xiao-Nong Zhou, Jing-Bo Xue, Men-Bao Qian

Zika viruses of African and Asian lineages cause fetal harm in a mouse model of vertical transmission

17 April 2019 - 9:00pm

by Anna S. Jaeger, Reyes A. Murrieta, Lea R. Goren, Chelsea M. Crooks, Ryan V. Moriarty, Andrea M. Weiler, Sierra Rybarczyk, Matthew R. Semler, Christopher Huffman, Andres Mejia, Heather A. Simmons, Michael Fritsch, Jorge E. Osorio, Jens C. Eickhoff, Shelby L. O’Connor, Gregory D. Ebel, Thomas C. Friedrich, Matthew T. Aliota

Congenital Zika virus (ZIKV) infection was first linked to birth defects during the American outbreak in 2015/2016. It has been proposed that mutations unique to the Asian/American-genotype explain, at least in part, the ability of Asian/American ZIKV to cause congenital Zika syndrome (CZS). Recent studies identified mutations in ZIKV infecting humans that arose coincident with the outbreak in French Polynesia and were stably maintained during subsequent spread to the Americas. Here we show that African ZIKV can infect and harm fetuses and that the S139N substitution that has been associated with the American outbreak is not essential for fetal harm. Our findings, in a vertical transmission mouse model, suggest that ZIKV will remain a threat to pregnant women for the foreseeable future, including in Africa, Southeast Asia, and the Americas. Additional research is needed to better understand the risks associated with ZIKV infection during pregnancy, both in areas where the virus is newly endemic and where it has been circulating for decades.

Human collectin-11 (<i>COLEC11</i>) and its synergic genetic interaction with <i>MASP2</i> are associated with the pathophysiology of Chagas Disease

17 April 2019 - 9:00pm

by Thaisa Lucas Sandri, Fabiana Antunes Andrade, Kárita Cláudia Freitas Lidani, Elias Einig, Angelica Beate Winter Boldt, Benjamin Mordmüller, Meral Esen, Iara J. de Messias Reason

Chagas Disease (CD) is an anthropozoonosis caused by Trypanosoma cruzi. With complex pathophysiology and variable clinical presentation, CD outcome can be influenced by parasite persistence and the host immune response. Complement activation is one of the primary defense mechanisms against pathogens, which can be initiated via pathogen recognition by pattern recognition molecules (PRMs). Collectin-11 is a multifunctional soluble PRM lectin, widely distributed throughout the body, with important participation in host defense, homeostasis, and embryogenesis. In complex with mannose-binding lectin-associated serine proteases (MASPs), collectin-11 may initiate the activation of complement, playing a role against pathogens, including T. cruzi. In this study, collectin-11 plasma levels and COLEC11 variants in exon 7 were assessed in a Brazilian cohort of 251 patients with chronic CD and 108 healthy controls. Gene-gene interactions between COLEC11 and MASP2 variants were analyzed. Collectin-11 levels were significantly decreased in CD patients compared to controls (p<0.0001). The allele rs7567833G, the genotypes rs7567833AG and rs7567833GG, and the COLEC11*GGC haplotype were related to T. cruzi infection and clinical progression towards symptomatic CD. COLEC11 and MASP2*CD risk genotypes were associated with cardiomyopathy (p = 0.014; OR 9.3, 95% CI 1.2–74) and with the cardiodigestive form of CD (p = 0.005; OR 15.2, 95% CI 1.7–137), suggesting that both loci act synergistically in immune modulation of the disease. The decreased levels of collectin-11 in CD patients may be associated with the disease process. The COLEC11 variant rs7567833G and also the COLEC11 and MASP2*CD risk genotype interaction were associated with the pathophysiology of CD.

Geographic shifts in <i>Aedes aegypti</i> habitat suitability in Ecuador using larval surveillance data and ecological niche modeling: Implications of climate change for public health vector control

17 April 2019 - 9:00pm

by Catherine A. Lippi, Anna M. Stewart-Ibarra, M. E. Franklin Bajaña Loor, Jose E. Dueñas Zambrano, Nelson A. Espinoza Lopez, Jason K. Blackburn, Sadie J. Ryan

Arboviral disease transmission by Aedes mosquitoes poses a major challenge to public health systems in Ecuador, where constraints on health services and resource allocation call for spatially informed management decisions. Employing a unique dataset of larval occurrence records provided by the Ecuadorian Ministry of Health, we used ecological niche models (ENMs) to estimate the current geographic distribution of Aedes aegypti in Ecuador, using mosquito presence as a proxy for risk of disease transmission. ENMs built with the Genetic Algorithm for Rule-Set Production (GARP) algorithm and a suite of environmental variables were assessed for agreement and accuracy. The top model of larval mosquito presence was projected to the year 2050 under various combinations of greenhouse gas emissions scenarios and models of climate change. Under current climatic conditions, larval mosquitoes were not predicted in areas of high elevation in Ecuador, such as the Andes mountain range, as well as the eastern portion of the Amazon basin. However, all models projected to scenarios of future climate change demonstrated potential shifts in mosquito distribution, wherein range contractions were seen throughout most of eastern Ecuador, and areas of transitional elevation became suitable for mosquito presence. Encroachment of Ae. aegypti into mountainous terrain was estimated to affect up to 4,215 km2 under the most extreme scenario of climate change, an area which would put over 12,000 people currently living in transitional areas at risk. This distributional shift into communities at higher elevations indicates an area of concern for public health agencies, as targeted interventions may be needed to protect vulnerable populations with limited prior exposure to mosquito-borne diseases. Ultimately, the results of this study serve as a tool for informing public health policy and mosquito abatement strategies in Ecuador.

Competence of non-human primates to transmit <i>Leishmania infantum</i> to the invertebrate vector <i>Lutzomyia longipalpis</i>

17 April 2019 - 9:00pm

by Ayisa Rodrigues de Oliveira, Guilherme Rafael Gomide Pinheiro, Herlandes P. Tinoco, Maria Elvira Loyola, Carlyle Mendes Coelho, Edelberto Santos Dias, Érika Michalsky Monteiro, Fabiana de Oliveira Lara e Silva, Angela Tinoco Pessanha, Andreza Geisiane Maia Souza, Nathália Cristina Lima Pereira, Nelder F. Gontijo, Ricardo T. Fujiwara, Tatiane Alves da Paixão, Renato Lima Santos

Leishmaniasis is a zoonotic disease of worldwide relevance. Visceral leishmaniasis is endemic in Brazil, where it is caused by Leishmania infantum with Lutzomyia longipalpis being the most important invertebrate vector. Non-human primates are susceptible to L. infantum infection. However, little is known about the role of these species as reservoirs. The aim of this study was to evaluate the transmissibility potential of visceral leishmaniasis by non-human primates through xenodiagnosis using the phlebotomine Lu. longipalpis as well as to identify phlebotomine species prevalent in the area where the primates were kept in captivity, and assess infection by Leishmania in captured phlebotomine specimens. Fifty two non-human primates kept in captivity in an endemic area for leishmaniasis were subjected to xenodiagnosis. All primates were serologically tested for detection of anti-Leishmania antibodies. Additionally, an anti-Lu. longipalpis saliva ELISA was performed. Sand flies fed on all animals were tested by qPCR to identify and quantify L. infantum promastigotes. Eight of the 52 non-human primates were positive by xenodiagnosis, including three Pan troglodytes, three Leontopithecus rosalia, one Sapajus apella, and one Miopithecus talapoin, with estimated numbers of promastigotes ranging from 5.67 to 1,181.93 per μg of DNA. Positive animals had higher levels of IgG anti-Lu. longipalpis saliva when compared to negative animals, prior to xenodiagnosis. Captive non-human primates are capable of infecting Lu. longipalpis with L. infantum. Our findings also demonstrate the relevance of non-human primates as sentinels to zoonotic diseases. Several phlebotomine species, including Lu. longipalpis, have been identified in the area where the primates were maintained, but only one pool of Lutzomyia lenti was infected with L. infantum. This study has implications for public health strategies and conservation medicine.

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