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New circulation of genotype V of Crimean-Congo haemorrhagic fever virus in humans from Spain

PLoS Neglected Tropical Diseases News - 22 February 2021 - 2:00pm

by Lia Monsalve Arteaga, Juan Luis Muñoz Bellido, Ana Isabel Negredo, Jorge García Criado, Maria Carmen Vieira Lista, Jesús Ángel Sánchez Serrano, María Belén Vicente Santiago, Amparo López Bernús, Fernando de Ory Manchón, María Paz Sánchez Seco, Nuria Leralta, Montserrat Alonso Sardón, Antonio Muro, Moncef Belhassen-García

Background

Crimean-Congo haemorrhagic fever (CCHF) is a widespread tick-borne viral disease caused by the Crimean-Congo haemorrhagic fever virus (CCHFV). CCHFV has been implicated in severe viral haemorrhagic fever outbreaks. During the summer of 2016, the first two cases with genotype III (Africa 3) were reported in Spain. The first aim of our study was to determine the presence of CCHFV among patients with febrile illness during the spring and summer periods in 2017 and 2018. Finally, we perform a phylogenetic analysis to determine the genotype of the virus.

Methodology

We prospectively evaluated patients older than 18 years who came to the emergency unit at the University Salamanca Hospital (HUS) with fever. Specific IgM and IgG antibodies against CCHFV by ELISA and one immunofluorescence assay against two different proteins (nucleoprotein and glycoprotein C) was done. Moreover, molecular detection by Real Time PCR was performed in all collected samples. A phylogenetic analysis was carried out to genetically characterize CCHFV detected in this study.

Principal findings

A total of 133 patients were selected. The mean age was 67.63 years and 60.9% were male. One-third of the patients presented an acute undifferentiated febrile illness. Three patients had anti-CCHFV IgG antibodies, suggesting a previous infection. One patient was found confirmed anti-CCHFV IgM antibodies and positive RT-PCR was detected. Phylogenetic analysis indicated that the virus corresponds to the European genotype V. This patient came to the emergency unit at HUS in August 2018 presenting an acute febrile syndrome with thrombopenia and liver impairment.

Conclusions

We describe a new circulation of European genotype V CCHFV in Spain. Moreover, this study suggests that CCHFV is an identifiable cause of febrile illness of unknown origin in Spain. Thus, CCHF could be suspected in patients with fever, liver damage, and/or haemorrhagic disorders, particularly in people with risk activities who present in the spring or summer.

2-aminobenzimidazoles for leishmaniasis: From initial hit discovery to in vivo profiling

PLoS Neglected Tropical Diseases News - 22 February 2021 - 2:00pm

by Rafael Augusto Alves Ferreira, Celso de Oliveira Rezende Junior, Pablo David Grigol Martinez, Paul John Koovits, Bruna Miranda Soares, Leonardo L. G. Ferreira, Simone Michelan-Duarte, Rafael Consolin Chelucci, Adriano D. Andricopulo, Mariana K. Galuppo, Silvia R. B. Uliana, An Matheeussen, Guy Caljon, Louis Maes, Simon Campbell, Jadel M. Kratz, Charles E. Mowbray, Luiz Carlos Dias

Leishmaniasis is a major infectious disease with hundreds of thousands of new cases and over 20,000 deaths each year. The current drugs to treat this life-threatening infection have several drawbacks such as toxicity and long treatment regimens. A library of 1.8 million compounds, from which the hits reported here are publicly available, was screened against Leishmania infantum as part of an optimization program; a compound was found with a 2-aminobenzimidazole functionality presenting moderate potency, low metabolic stability and high lipophilicity. Several rounds of synthesis were performed to incorporate chemical groups capable of reducing lipophilicity and clearance, leading to the identification of compounds that are active against different parasite strains and have improved in vitro properties. As a result of this optimization program, a group of compounds was further tested in anticipation of in vivo evaluation. In vivo tests were carried out with compounds 29 (L. infantum IC50: 4.1 μM) and 39 (L. infantum IC50: 0.5 μM) in an acute L. infantum VL mouse model, which showed problems of poor exposure and lack of efficacy, despite the good in vitro potency.

NLRP6-associated host microbiota composition impacts in the intestinal barrier to systemic dissemination of <i>Brucella abortus</i>

PLoS Neglected Tropical Diseases News - 22 February 2021 - 2:00pm

by Marcella Rungue, Victor Melo, David Martins, Priscila C. Campos, Gabriela Leles, Izabela Galvão, Viviani Mendes, Mariana Aganetti, Ágatha Pedersen, Natan R. G. Assis, Raiany Santos, Geovanni D. Cassali, Ana Lúcia B. Godard, Flaviano S. Martins, Sergio C. Oliveira, Angélica T. Vieira

Brucella abortus is a Gram-negative bacterium responsible for a worldwide zoonotic infection—Brucellosis, which has been associated with high morbidity rate in humans and severe economic losses in infected livestock. The natural route of infection is through oral and nasal mucosa but the invasion process through host gut mucosa is yet to be understood. Studies have examined the role of NLRP6 (NOD-like receptor family pyrin domain-containing-6 protein) in gut homeostasis and defense against pathogens. Here, we investigated the impact of gut microbiota and NLRP6 in a murine model of Ba oral infection. Nlrp6-/- and wild-type (WT) mice were infected by oral gavage with Ba and tissues samples were collected at different time points. Our results suggest that Ba oral infection leads to significant alterations in gut microbiota. Moreover, Nlrp6-/- mice were more resistant to infection, with decreased CFU in the liver and reduction in gut permeability when compared to the control group. Fecal microbiota transplantation from WT and Nlrp6-/- into germ-free mice reflected the gut permeability phenotype from the donors. Additionally, depletion of gut microbiota by broad-spectrum-antibiotic treatment prevented Ba replication in WT while favoring bacterial growth in Nlrp6-/-. Finally, we observed higher eosinophils in the gut and leukocytes in the blood of infected Nlrp6-/- compared to WT-infected mice, which might be associated to the Nlrp6-/- resistance phenotype. Altogether, these results indicated that gut microbiota composition is the major factor involved in the initial stages of pathogen host replication and partially also by the resistance phenotype observed in Nlrp6 -/- mice regulating host inflammation against Ba infection.

Human infection with Seoul orthohantavirus in Korea, 2019

PLoS Neglected Tropical Diseases News - 22 February 2021 - 2:00pm

by Changmin Kang, Jin Il Kim, Jungmin Lee, Seongman Bae, Min Jae Kim, Ki-Joon Song, Jin-Won Song, Sung-Han Kim, Man-Seong Park

Of various rodent-borne hantaviruses, Seoul orthohantavirus (SEOV) causes haemorrhagic fever with renal syndrome (HFRS), as does Hantaan orthohantavirus (HTNV). Given global-scale of cases of human infection with SEOV, it is of great clinical importance to distinguish SEOV from other HFRS-causing hantaviruses. In May 2019, a middle-aged patient who had lived in a suburban area of Chungcheong Province, Republic of Korea and enjoyed outdoor activities was transferred to Asan Medical Center in Seoul, Republic of Korea with HFRS; his symptoms included high fever and generalized myalgia. The rapid diagnostic test performed immediately after his transfer detected HTNV-specific antibodies, and the patient was treated accordingly. However, two consecutive IFAs performed at ten-day intervals showed no HTNV-specific immunoglobulin (Ig) G. During continuous supportive care, next-generation sequencing successfully identified viral genomic sequences in the patient’s serum, which were SEOV and not HTNV. Phylogenetic analysis grouped the L, M, and S genes of this SEOV strain together with those of rat- or human-isolated Korean strains reported previously. Given global outbreaks and public health threats of zonotic hantaviruses, a causative pathogen of hantavirus HFRS should be identified correctly at the time of diagnosis and by point-of-care testing.

Indigenous knowledge of Rift Valley Fever among Somali nomadic pastoralists and its implications on public health delivery approaches in Ijara sub-County, North Eastern Kenya

PLoS Neglected Tropical Diseases News - 22 February 2021 - 2:00pm

by Geoffrey Otieno Muga, Washington Onyango-Ouma, Rosemary Sang, Hippolyte Affognon

Rift Valley Fever (RVF) is a zoonotic disease whose outbreak results in heavy economic and public health burdens. In East Africa, RVF is mainly experienced in arid and semi-arid areas predominantly inhabited by the pastoralists. These areas experience sudden, dramatic epidemics of the disease at intervals of approximately 10 years, associated with widespread flooding and the resultant swarms of mosquitoes. Pastoralists’ indigenous knowledge and experience of RVF is critical for public health interventions targeting prevention and control of RVF. The study adopted a descriptive cross-sectional design combining both quantitative and qualitative methods of data collection. A total of 204 respondents participated in questionnaire survey and 15 key informants and 4 focus group discussions were interviewed and conducted respectively. In addition, secondary data mainly journal publications, books, policy documents and research reports from conferences and government departments were reviewed. Findings indicated that the Somali pastoralists possess immense knowledge of RVF including signs and symptoms, risk factors, and risk pathways associated with RVF. Ninety eight percent (98%) of respondents identified signs and symptoms such as bloody nose, diarrhea, foul smell and discharge of blood from the orifices which are consistent with RVF. Heavy rains and floods (85%) and sudden emergence of mosquito swarms (91%) were also cited as the major RVF risk factors while mosquito bites (85%), drinking raw milk and blood (78%) and contact with animal fluids during mobility, slaughter and obstetric procedures (77%) were mentioned as the RVF entry risk pathways. Despite this immense knowledge, the study found that the pastoralists did not translate the knowledge into safer health practices because of the deep-seated socio-cultural practices associated with pastoralist production system and religious beliefs. On top of these practices, food preparation and consumption practices such as drinking raw blood and milk and animal ritual sacrifices continue to account for most of the mortality and morbidity cases experienced in humans and animals during RVF outbreaks. This article concludes that pastoralists’ indigenous knowledge on RVF has implications on public health delivery approaches. Since the pastoralists’ knowledge on RVF was definitive, integrating the community into early warning systems through training on reporting mechanisms and empowering the nomads to use their mobile phone devices to report observable changes in their livestock and environment could prove very effective in providing information for timely mobilization of public health responses. Public health advocacy based on targeted and contextually appropriate health messaging and disseminated through popular communication channels in the community such as the religious leaders and local radio stations would also be needed to reverse the drivers of RVF occurrence in the study area.

Defining the need for public health control of scabies in Solomon Islands

PLoS Neglected Tropical Diseases News - 22 February 2021 - 2:00pm

by Susanna J. Lake, Daniel Engelman, Oliver Sokana, Titus Nasi, Dickson Boara, Anneke C. Grobler, Millicent H. Osti, Ross Andrews, Michael Marks, Margot J. Whitfeld, Lucia Romani, John M. Kaldor, Andrew C. Steer

Pacific Island countries have a high burden of scabies and impetigo. Understanding of the epidemiology of these diseases is needed to target public health interventions such as mass drug administration (MDA). The aim of this study is to determine the prevalence of scabies and impetigo in Solomon Islands as well as the relationship between them and their distribution. We conducted a prevalence study in 20 villages in Western Province in Solomon Islands. All residents of the village were eligible to participate. Nurses conducted clinical assessments including history features and skin examination. Diagnosis of scabies was made using the 2020 International Alliance for the Control of Scabies diagnostic criteria. Assessments were completed on 5239 participants across 20 villages. Overall scabies prevalence was 15.0% (95%CI 11.8–19.1). There was considerable variation by village with a range of 3.3% to 42.6%. There was a higher prevalence of scabies in males (16.7%) than females (13.5%, adjusted relative risk 1.2, 95%CI 1.1–1.4). Children aged under two years had the highest prevalence (27%). Overall impetigo prevalence was 5.6% (95%CI 4.2–7.3), ranging from 1.4% to 19% by village. The population attributable risk of impetigo associated with scabies was 16.1% (95% CI 9.8–22.4). The prevalence of scabies in our study is comparable to previous studies in Solomon Islands, highlighting a persistent high burden of disease in the country, and the need for public health strategies for disease control.

Immune response dynamics and <i>Lutzomyia longipalpis</i> exposure characterize a biosignature of visceral leishmaniasis susceptibility in a canine cohort

PLoS Neglected Tropical Diseases News - 22 February 2021 - 2:00pm

by Manuela da Silva Solcà, Maiara Reis Arruda, Bruna Martins Macedo Leite, Tiago Feitosa Mota, Miriam Flores Rebouças, Matheus Silva de Jesus, Leila Denise Alves Ferreira Amorim, Valéria Matos Borges, Jesus Valenzuela, Shaden Kamhawi, Patrícia Sampaio Tavares Veras, Deborah Bittencourt Mothé Fraga, Claudia Ida Brodskyn

Background

Reports have shown correlations between the immune response to vector saliva and Leishmaniasis outcome. We followed dogs in an endemic area for two years characterizing resistance or susceptibility to canine visceral leishmaniasis (CVL) according to Leishmania infantum diagnosis and clinical development criteria. Then, we aimed to identify a biosignature based on parasite load, serum biological mediators’ interactions, and vector exposure intensity associated with CVL resistance and susceptibility.

Methodology/Principal findings

A prospective two-year study was conducted in an area endemic for CVL. Dogs were evaluated at 6-month intervals to determine infection, clinical manifestations, immune profile, and sandfly exposure. CVL resistance or susceptibility was determined upon the conclusion of the study. After two years, 78% of the dogs were infected with L. infantum (53% susceptible and 47% resistant to CVL). Susceptible dogs presented higher splenic parasite load as well as persistence of the parasite during the follow-up, compared to resistant ones. Susceptible dogs also displayed a higher number of correlations among the investigated biological mediators, before and after infection diagnosis. At baseline, anti-saliva antibodies, indicative of exposure to the vector, were detected in 62% of the dogs, reaching 100% in one year. Higher sandfly exposure increased the risk of susceptibility to CVL by 1.6 times (CI: 1.11–2.41). We identified a discriminatory biosignature between the resistant and susceptible dogs assessing splenic parasite load, interaction of biological mediators, PGE2 serum levels and intensity of exposure to sandfly. All these parameters were elevated in susceptible dogs compared to resistant animals.

Conclusions/Significance

The biosignature identified in our study reinforces the idea that CVL is a complex multifactorial disease that is affected by a set of factors which are correlated and, for a better understanding of CVL, should not be evaluated in an isolated way.

A multicenter non-randomized, uncontrolled single arm trial for evaluation of the efficacy and the safety of the treatment with favipiravir for patients with severe fever with thrombocytopenia syndrome

PLoS Neglected Tropical Diseases News - 22 February 2021 - 2:00pm

by Koichiro Suemori, Masayuki Saijo, Atsushi Yamanaka, Daisuke Himeji, Masafumi Kawamura, Takashi Haku, Michihiro Hidaka, Chinatsu Kamikokuryo, Yasuyuki Kakihana, Taichi Azuma, Katsuto Takenaka, Toru Takahashi, Akitsugu Furumoto, Toshiyuki Ishimaru, Masayuki Ishida, Masahiko Kaneko, Norimitsu Kadowaki, Kenichi Ikeda, Shigetoshi Sakabe, Tomohiro Taniguchi, Hiroki Ohge, Takeshi Kurosu, Tomoki Yoshikawa, Masayuki Shimojima, Masaki Yasukawa

Severe fever with thrombocytopenia syndrome (SFTS) is a bunyavirus infection with high mortality. Favipiravir has shown effectiveness in preventing and treating SFTS virus (SFTSV) infection in animal models. A multicenter non-randomized, uncontrolled single arm trial was conducted to collect data on the safety and the effectiveness of favipiravir in treatment of SFTS patients. All participants received favipiravir orally (first-day loading dose of 1800 mg twice a day followed by 800 mg twice a day for 7–14 days in total). SFTSV RT-PCR and biochemistry tests were performed at designated time points. Outcomes were 28-day mortality, clinical improvement, viral load evolution, and adverse events (AEs). Twenty-six patients were enrolled, of whom 23 were analyzed. Four of these 23 patients died of multi-organ failure within one week (28-day mortality rate: 17.3%). Oral favipiravir was well tolerated in the surviving patients. AEs (abnormal hepatic function and insomnia) occurred in about 20% of the patients. Clinical symptoms improved in all patients who survived from a median of day 2 to day10. SFTSV RNA levels in the patients who died were significantly higher than those in the survivors (p = 0.0029). No viral genomes were detectable in the surviving patients a median of 8 days after favipiravir administration. The 28-day mortality rate in this study was lower than those of the previous studies in Japan. The high frequency of hepatic dysfunction as an AE was observed. However, it was unclear whether this was merely a side effect of favipiravir, because liver disorders are commonly seen in SFTS patients. The results of this trial support the effectiveness of favipiravir for patients with SFTS.

Health beliefs and health seeking behavior towards lymphatic filariasis morbidity management and disability prevention services in Luangwa District, Zambia: Community and provider perspectives

PLoS Neglected Tropical Diseases News - 22 February 2021 - 2:00pm

by Patricia Maritim, Adam Silumbwe, Joseph Mumba Zulu, George Sichone, Charles Michelo

Background

Morbidity management and disability prevention (MMDP) services are essential for the management of chronic stages of lymphatic filariasis (LF) infection. However, there is limited information on health beliefs and health seeking behavior towards MMDP services for LF in endemic regions of Zambia. This study sought to document health beliefs and health seeking behavior towards MMDP services for LF in Luangwa District, Zambia.

Methods

This was an exploratory qualitative study conducted with community members including LF patients, community health workers and healthcare providers. Data was collected through a series of four focus group discussions stratified by sex and 26 in-depth interviews. Data was analyzed by thematic analysis using NVivo software.

Results

The perceived causes of the chronic manifestations of LF included; contact with animal feces, use of traditional herbal aphrodisiacs (mutoto), witchcraft and sexual contact with women who were menstruating or had miscarried. LF patients opted to visit traditional healers before going to health facilities. Hydrocele patients were afraid of hydrocelectomies as they were thought to cause infertility or death. Very few community members were able to identify any home and facility-based care strategies for LF patients. Health system and cultural barriers to seeking healthcare included; long distances to the health facilities, lack of awareness of existing MMDP services, perceived costs of accessing MMDP services, gender and social norms, and fear of stigmatization.

Conclusion

Health seeking behavior for LF in the district is mainly driven by negative beliefs about the causes of the disease and lack of awareness of available MMDP services and homecare strategies. Lymphatic filariasis programs should promote strategies that seek to empower patients and community members with the required information to access and use the MMDP services at the health facilities, as well as adhere to self-care practices in their households.

The lymphatic system as a potential mechanism of spread of melioidosis following ingestion of <i>Burkholderia pseudomallei</i>

PLoS Neglected Tropical Diseases News - 22 February 2021 - 2:00pm

by Michelle Nelson, Alejandro Nunez, Sarah A. Ngugi, Timothy P. Atkins

Burkholderia pseudomallei is the causative agent of melioidosis, which is a Gram negative, facultative intracellular bacterium. Disease is prevalent in SE Asia and in northern Australia, as well as in other tropical and subtropical regions. Recently, there is an increasing awareness of the importance of bacterial ingestion as a potential route of infection, particularly in cases of unexplained origin of the disease. The marmoset is a New World Monkey (NWM) species that is being developed as an alternative NHP model to complement the more traditionally used Old World Monkeys (OWM). Models have been developed for the traditional routes of disease acquisition, subcutaneous and inhalational. This manuscript details the development and characterisation of an ingestion model of melioidosis. Dose-ranging study assessed the lethality of B. pseudomallei and disease progression was assessed by euthanizing animals at predetermined time points, 12, 36, 48 and 54 hours post-challenge. Challenge doses of greater than 6.2 x 106 cfu resulted in an acute, lethal, febrile disease. Following challenge the lung was the first organ, outside of the gastrointestinal tract, to become colonised. Enteritis (duodenitis, ileitis and/or jejunitis) was observed in sections of the small intestine from animals that succumbed to disease. However, the most severe pathological features were observed in the mesenteric lymph nodes from these animals. These findings are consistent with lymphatic draining as route of dissemination.

Genomic analysis of the diversity, antimicrobial resistance and virulence potential of clinical <i>Campylobacter jejuni</i> and <i>Campylobacter coli</i> strains from Chile

PLoS Neglected Tropical Diseases News - 19 February 2021 - 2:00pm

by Veronica Bravo, Assaf Katz, Lorena Porte, Thomas Weitzel, Carmen Varela, Narjol Gonzalez-Escalona, Carlos J. Blondel

Campylobacter jejuni and Campylobacter coli are the leading cause of human gastroenteritis in the industrialized world and an emerging threat in developing countries. The incidence of campylobacteriosis in South America is greatly underestimated, mostly due to the lack of adequate diagnostic methods. Accordingly, there is limited genomic and epidemiological data from this region. In the present study, we performed a genome-wide analysis of the genetic diversity, virulence, and antimicrobial resistance of the largest collection of clinical C. jejuni and C. coli strains from Chile available to date (n = 81), collected in 2017–2019 in Santiago, Chile. This culture collection accounts for more than one third of the available genome sequences from South American clinical strains. cgMLST analysis identified high genetic diversity as well as 13 novel STs and alleles in both C. jejuni and C. coli. Pangenome and virulome analyses showed a differential distribution of virulence factors, including both plasmid and chromosomally encoded T6SSs and T4SSs. Resistome analysis predicted widespread resistance to fluoroquinolones, but low rates of erythromycin resistance. This study provides valuable genomic and epidemiological data and highlights the need for further genomic epidemiology studies in Chile and other South American countries to better understand molecular epidemiology and antimicrobial resistance of this emerging intestinal pathogen.

A prospective study to evaluate the accuracy of rapid diagnostic tests for diagnosis of human leptospirosis: Result from THAI-LEPTO AKI study

PLoS Neglected Tropical Diseases News - 19 February 2021 - 2:00pm

by Janejira Dinhuzen, Umaporn Limothai, Sasipha Tachaboon, Panadda Krairojananan, Bangon Laosatiankit, Sakarin Boonprasong, Nuttha Lumlertgul, Sadudee Peerapornratana, Nattachai Srisawat

Background

Rapid diagnostic tests (RDTs) have become widely used in low-resource settings for leptospirosis diagnostic. This study aims to evaluate the diagnostic performance of the five commercially available RDTs to detect human IgM against Leptospira spp. in Thai population.

Methodology/Principal findings

Ninety-nine serum samples from Leptospirosis suspicious patients were tested with five RDTs, including Medical Science Public Health, Leptocheck-WB, SD bioline, TRUSTline, and J.Mitra. The case definition was based on MAT, qPCR, and culture results. Diagnostic accuracy was determined based on the first day of enrollment in an overall analysis and stratified according to days post-onset of fever. The five RDTs had overall sensitivity ranging from 1.8% to 75% and specificity ranging from 52.3% to 97.7%. Leptocheck-WB had high sensitivity of 75.0%. The sensitivity of five RDTs increased on days 4–6 post-onset of fever, while the specificity of all tests remained relatively stable at different days post-onset of fever.

Conclusions/Significance

The tested RDTs showed low sensitivity. Therefore, based on the present study, five commercially available RDTs might not be an appropriate test for acute leptospirosis screening in the Thai population.

The intersection of land use and human behavior as risk factors for zoonotic pathogen exposure in Laikipia County, Kenya

PLoS Neglected Tropical Diseases News - 19 February 2021 - 2:00pm

by Joseph Kamau, Elizabeth Ashby, Lindsey Shields, Jennifer Yu, Suzan Murray, Megan Vodzak, Allan Ole Kwallah, Peris Ambala, Dawn Zimmerman

A majority of emerging infectious diseases (EIDs) are zoonotic, mainly caused through spillover events linked to human-animal interactions. We conducted a survey-based human behavioral study in Laikipia County, Kenya, which is characterized by a dynamic human-wildlife-livestock interface. Questionnaires that assessed human-animal interactions, sanitation, and illnesses experienced within the past year were distributed to 327 participants among five communities in Laikipia. This study aimed to 1) describe variation in reported high-risk behaviors by community type and 2) assess the relationship between specific behaviors and self-reported illnesses. Behavioral trends were assessed in R via Fisher’s exact tests. A generalized linear mixed model with Lasso penalization (GLMMLasso) was used to assess correlations between behaviors and participants’ self-reported illness within the past year, with reported behaviors as independent variables and reported priority symptoms as the outcome. Reported behaviors varied significantly among the study communities. Participants from one community (Pastoralist-1) were significantly more likely to report eating a sick animal in the past year (p< 0.001), collecting an animal found dead to sell in the past year (p<0.0001), and not having a designated location for human waste (p<0.0001) when compared to participants from other communities. The GLMMLasso revealed that reports of an ill person in the household in the past year was significantly associated with self-reported illness. Sixty-eight percent of participants reported that bushmeat is available within the communities. Our study demonstrates community-level variation in behaviors that may influence zoonotic pathogen exposure. We further recommend development of targeted studies that explore behavioral variations among land use systems in animal production contexts.

Effects of steroid therapy in patients with severe fever with Thrombocytopenia syndrome: A multicenter clinical cohort study

PLoS Neglected Tropical Diseases News - 19 February 2021 - 2:00pm

by Sook In Jung, Ye Eun Kim, Na Ra Yun, Choon-Mee Kim, Dong-Min Kim, Mi Ah Han, Uh Jin Kim, Seong Eun Kim, Jieun Kim, Seong Yeol Ryu, Hyun ah Kim, Jian Hur, Young Keun Kim, Hye Won Jeong, Jung Yeon Heo, Dong Sik Jung, Hyungdon Lee, Kyungmin Huh, Yee Gyung Kwak, Sujin Lee, Seungjin Lim, Sun Hee Lee, Sun Hee Park, Joon-Sup Yeom, Shin-Woo Kim, In-Gyu Bae, Juhyung Lee, Eu Suk Kim, Jun-Won Seo

Background

Severe fever with thrombocytopenia syndrome (SFTS) is an acute, febrile, and potentially fatal tick-borne disease caused by the SFTS Phlebovirus. Here, we evaluated the effects of steroid therapy in Korean patients with SFTS.

Methods

A retrospective study was performed in a multicenter SFTS clinical cohort from 13 Korean university hospitals between 2013 and 2017. We performed survival analysis using propensity score matching of 142 patients with SFTS diagnosed by genetic or antibody tests.

Results

Overall fatality rate was 23.2%, with 39.7% among 58 patients who underwent steroid therapy. Complications were observed in 37/58 (63.8%) and 25/83 (30.1%) patients in the steroid and non-steroid groups, respectively (P < .001). Survival analysis after propensity score matching showed a significant difference in mean 30-day survival time between the non-steroid and steroid groups in patients with a mild condition [Acute Physiology and Chronic Health Evaluation II (APACHE II) score <14; 29.2 (95% CI 27.70–30.73] vs. 24.9 (95% CI 21.21–28.53], P = .022]. Survival times for the early steroid (≤5 days from the start of therapy after symptom onset), late steroid (>5 days), and non-steroid groups, were 18.4, 22.4, and 27.3 days, respectively (P = .005).

Conclusions

After steroid therapy, an increase in complications was observed among patients with SFTS. Steroid therapy should be used with caution, considering the possible negative effects of steroid therapy within 5 days of symptom onset or in patients with mild disease (APACHE II score <14).

Analysis of D-A locus of tRNA-linked short tandem repeats reveals transmission of <i>Entamoeba histolytica</i> and <i>E</i>. <i>dispar</i> among students in the Thai-Myanmar border region of northwest Thailand

PLoS Neglected Tropical Diseases News - 18 February 2021 - 2:00pm

by Urassaya Pattanawong, Chaturong Putaporntip, Azumi Kakino, Naoko Yoshida, Seiki Kobayashi, Surasuk Yanmanee, Somchai Jongwutiwes, Hiroshi Tachibana

Intestinal parasitic infections, including those caused by Entamoeba species, are a persistent problem in rural areas of Thailand. The aims of this study were to identify pathogenic Entamoeba species and to analyze their genotypic diversity. Stool samples were collected from 1,233 students of three schools located in the Thai-Myanmar border region of Tak Province, Thailand. The prevalence of Entamoeba infection was measured by polymerase chain reaction (PCR) using species-specific primers. Thirty-one (2.5%) positive cases were detected for E. histolytica, 55 (4.5%) for E. dispar, and 271 (22.0%) for E. coli. Positive samples for E. histolytica and E. dispar were exclusively obtained from a few school classes, whereas E. coli was detected in all grades. No infections caused by E. moshkovskii, E. nuttalli, E. chattoni, and E. polecki were detected in the students studied. The D-A locus of tRNA-linked short tandem repeats was analyzed in samples of E. histolytica (n = 13) and E. dispar (n = 47) to investigate their diversity and potential modes of transmission. Five genotypes of E. histolytica and 13 genotypes of E. dispar were identified. Sequences of the D-A were divergent, but several unique genotypes were significantly prevalent in limited classes, indicating that intra-classroom transmission has occurred. As it was unlikely that infection would have been limited within school classes if the mode of transmission of E. histolytica and E. dispar had been through the intake of contaminated drinking water or food, these results suggest a direct or indirect person-to-person transmission mode within school classes. Positive rates for three Entamoeba species were 2-fold higher in students who had siblings in the schools than in those without siblings, suggesting that transmission occurred even at home due to heavy contacts among siblings.

The global procurement landscape of leishmaniasis medicines

PLoS Neglected Tropical Diseases News - 18 February 2021 - 2:00pm

by Hye Lynn Choi, Saurabh Jain, José A. Ruiz Postigo, Bettina Borisch, Daniel Argaw Dagne

Ensuring access to essential medicines for leishmaniasis control is challenging, as leishmaniasis is a very small and unattractive market for pharmaceutical industry. Furthermore, control programmes are severely underfunded. We conducted an analysis of global procurement of leishmaniasis medicines for the past 5 years in order to shed light on the current leishmaniasis market landscape and supply and demand dynamics. We estimated global demand of each leishmaniasis medicines, the amount of each medicine required to treat all reported cases, based on the number of cases reported to WHO and the first-line treatment regimen used in each country. Procurement data were obtained from procurement agencies, international organizations, WHO, national leishmaniasis programmes and manufacturers. Expert interviews were conducted to have a better understanding of how medicines were procured and used. The comparison of estimated need and procurement data indicated discrepancies in supply and demand at global level as well as in the most endemic countries. The extent of the gap in supply was up to 80% of the needs for one of the leishmaniasis medicines. Mismatch between supply and demand was much wider for cutaneous leishmaniasis than visceral leishmaniasis. This study presents a current picture of procurement patterns and imbalance in global supply and demand. Addressing improved access and supply barriers requires concerted and coordinated efforts at the global and national levels. Priority actions include setting up a procurement coordination mechanism among major procurers, partners and national programmes where forecasting and supply planning is jointly developed and communicated with manufacturers. In addition, continuous engagement of manufacturers and advocacy is critical to diversify the supplier base and ensure quality-assured and affordable generic medicines for leishmaniasis.

Host interactions of <i>Aedes albopictus</i>, an invasive vector of arboviruses, in Virginia, USA

PLoS Neglected Tropical Diseases News - 18 February 2021 - 2:00pm

by Eliza A. H. Little, Olivia T. Harriott, Karen I. Akaratovic, Jay P. Kiser, Charles F. Abadam, John J. Shepard, Goudarz Molaei

Background

As an invasive mosquito species in the United States, Aedes albopictus is a potential vector of arboviruses including dengue, chikungunya, and Zika, and may also be involved in occasional transmission of other arboviruses such as West Nile, Saint Louis encephalitis, eastern equine encephalitis, and La Crosse viruses. Aedes albopictus feeds on a wide variety of vertebrate hosts, wild and domestic, as well as humans.

Methodology/Principal findings

In order to investigate blood feeding patterns of Ae. albopictus, engorged specimens were collected from a variety of habitat types using the Centers for Disease Control and Prevention light traps, Biogents Sentinel 2 traps, and modified Reiter gravid traps in southeast Virginia. Sources of blood meals were determined by the analysis of mitochondrial cytochrome b gene sequences amplified in PCR assays. Our aims were to quantify degrees of Ae. albopictus interactions with vertebrate hosts as sources of blood meals, investigate arboviral infection status, assess the influence of key socioecological conditions on spatial variability in blood feeding, and investigate temporal differences in blood feeding by season. Analysis of 961 engorged specimens of Ae. albopictus sampled between 2017–2019 indicated that 96%, 4%, and less than 1% obtained blood meals from mammalian, reptilian, and avian hosts, respectively. Domestic cats were the most frequently identified (50.5%) hosts followed by Virginia opossums (17.1%), white-tailed deer (12.2%), and humans (7.3%), together representing 87.1% of all identified blood hosts. We found spatial patterns in blood feeding linked to socioecological conditions and seasonal shifts in Ae. albopictus blood feeding with implications for understanding human biting and disease risk. In Suffolk Virginia in areas of lower human development, the likelihood of human blood feeding increased as median household income increased and human blood feeding was more likely early in the season (May-June) compared to later (July-October). Screening of the head and thorax of engorged Ae. albopictus mosquitoes by cell culture and RT-PCR resulted in a single isolate of Potosi virus.

Conclusion and significance

Understanding mosquito-host interactions in nature is vital for evaluating vectorial capacity of mosquitoes. These interactions with competent reservoir hosts support transmission, maintenance, and amplification of zoonotic agents of human diseases. Results of our study in conjunction with abundance in urban/suburban settings, virus isolation from field-collected mosquitoes, and vector competence of Ae. albopictus, highlight the potential involvement of this species in the transmission of a number of arboviruses such as dengue, chikungunya, and Zika to humans. Limited interaction with avian hosts suggests that Ae. albopictus is unlikely to serve as a bridge vector of arboviruses such as West Nile and eastern equine encephalitis in the study region, but that possibility cannot be entirely ruled out.

A family-based intervention for prevention and self-management of disabilities due to leprosy, podoconiosis and lymphatic filariasis in Ethiopia: A proof of concept study

PLoS Neglected Tropical Diseases News - 18 February 2021 - 2:00pm

by Anna T. van‘t Noordende, Moges Wubie Aycheh, Tesfaye Tadesse, Tanny Hagens, Eva Haverkort, Alice P. Schippers

A key issue for persons with leprosy-, lymphatic filariasis- and podoconiosis-related disabilities is the life-long need to practice self-management routines. This is difficult to sustain without regular encouragement and support of others. Family-based support may be a sustainable and feasible strategy to practice self-management routines. This proof of concept study aimed to develop and pilot a family-based intervention to support prevention and self-management of leprosy, lymphatic filariasis and podoconiosis-related disabilities in Ethiopia. We used a quasi-experimental pre/post intervention study design with a mixed methods approach. The study population included persons affected by leprosy, lymphatic filariasis and podoconiosis and their family members. All persons affected had visible impairments due to their condition. We collected physical impairment outcomes, data on activity limitations, stigma and family quality of life using the SALSA scale (range 0–80), the SARI stigma scale (range 0–63) and the Beach Centre Family Quality of Life scale (range 0–125) and conducted in-depth interviews and focus group discussions. Quantitative data were analysed using paired t-tests, unequal variances t-tests, linear regression and binary logistic regression. Qualitative data were coded using open, inductive coding and content analysis. The family-based intervention consisted of self-management of disabilities, awareness raising and socio-economic empowerment. The intervention was delivered over several monthly group meetings over the course of several months. A total of 275 (100%) persons affected attended at least one session with a family member, and 215 (78%) attended at least three sessions. There was no significant improvement in eye and hand problems after the intervention. However, foot and leg impairments, number of acute attacks, lymphedema and shoe wearing all significantly improved at follow-up. In addition, family quality of life significantly improved from 67.4 at baseline to 89.9 at follow-up for family members and from 76.9 to 84.1 for persons affected (p<0.001). Stigma levels significantly decreased from 24.0 at baseline to 16.7 at follow-up (p<0.001). Activity levels improved, but not significantly. This proof of concept study showed that the family-based intervention had a positive effect on impairments and self-management of disabilities, family quality of life and stigma. We recommend a large-scale efficacy trial, using a randomised controlled trial and validated measurement tools, to determine its effectiveness and long-term sustainability.

Biogeographical venom variation in the Indian spectacled cobra (<i>Naja naja</i>) underscores the pressing need for pan-India efficacious snakebite therapy

PLoS Neglected Tropical Diseases News - 18 February 2021 - 2:00pm

by R. R. Senji Laxme, Saurabh Attarde, Suyog Khochare, Vivek Suranse, Gerard Martin, Nicholas R. Casewell, Romulus Whitaker, Kartik Sunagar

Background

Snake venom composition is dictated by various ecological and environmental factors, and can exhibit dramatic variation across geographically disparate populations of the same species. This molecular diversity can undermine the efficacy of snakebite treatments, as antivenoms produced against venom from one population may fail to neutralise others. India is the world’s snakebite hotspot, with 58,000 fatalities and 140,000 morbidities occurring annually. Spectacled cobra (Naja naja) and Russell’s viper (Daboia russelii) are known to cause the majority of these envenomations, in part due to their near country-wide distributions. However, the impact of differing ecologies and environment on their venom compositions has not been comprehensively studied.

Methods

Here, we used a multi-disciplinary approach consisting of venom proteomics, biochemical and pharmacological analyses, and in vivo research to comparatively analyse N. naja venoms across a broad region (>6000 km; seven populations) covering India’s six distinct biogeographical zones.

Findings

By generating the most comprehensive pan-Indian proteomic and toxicity profiles to date, we unveil considerable differences in the composition, pharmacological effects and potencies of geographically-distinct venoms from this species and, through the use of immunological assays and preclinical experiments, demonstrate alarming repercussions on antivenom therapy. We find that commercially-available antivenom fails to effectively neutralise envenomations by the pan-Indian populations of N. naja, including a complete lack of neutralisation against the desert Naja population.

Conclusion

Our findings highlight the significant influence of ecology and environment on snake venom composition and potency, and stress the pressing need to innovate pan-India effective antivenoms to safeguard the lives, limbs and livelihoods of the country’s 200,000 annual snakebite victims.

Surveillance of <i>Trypanosoma cruzi</i> infection in Triatomine vectors, feral dogs and cats, and wild animals in and around El Paso county, Texas, and New Mexico

PLoS Neglected Tropical Diseases News - 18 February 2021 - 2:00pm

by Felipe Rodriguez, Brenda S. Luna, Olivia Calderon, Claudia Manriquez-Roman, Karsten Amezcua-Winter, Jonathan Cedillo, Rebeca Garcia-Vazquez, Itzel A. Tejeda, Alvaro Romero, Kenneth Waldrup, Douglas M. Watts, Camilo Khatchikian, Rosa A. Maldonado

The causative agent of Chagas disease, Trypanosoma cruzi, is transmitted by triatomine vectors. The insect is endemic in the Americas, including the United States, where epidemiological studies are limited, particularly in the Southwestern region. Here, we have determined the prevalence of T. cruzi in triatomines, and feral cats and dogs, and wild animals, the infecting parasite genotypes and the mammalian host bloodmeal sources of the triatomines at four different geographical sites in the U.S.-Mexico border, including El Paso County, Texas, and nearby cities in New Mexico. Using qualitative polymerase chain reaction to detect T. cruzi infections, we found 66.4% (n = 225) of triatomines, 45.3% (n = 95) of feral dogs, 39.2% (n = 24) of feral cats, and 71.4% (n = 7) of wild animals positive for T. cruzi. Over 95% of T. cruzi genotypes or discrete typing units (DTUs) identified were TcI and some TcIV. Furthermore, Triatoma rubida was the triatomine species most frequently (98.2%) collected in all samples analyzed. These findings suggest a high prevalence of T. cruzi infections among triatomines, and feral and wild animals in the studied sites. Therefore, our results underscore the urgent need for implementation of a systematic epidemiological surveillance program for T. cruzi infections in insect vectors, and feral and wild animals, and Chagas disease in the human population in the southwestern region of the United States.

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