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51.
  • Lindahl Rajala, Elisabeth, et al. (författare)
  • Detection and characterization of Brucella spp. in bovine milk in small-scale urban and peri-urban farming in Tajikistan
  • 2017
  • Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 11:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Brucellosis is one of the most common zoonoses globally, and Central Asia remains a Brucella hotspot. The World Health Organization classifies brucellosis as a neglected zoonotic disease that is rarely in the spotlight for research and mainly affects poor, marginalized people. Urban and peri-urban farming is a common practice in many low-income countries, and it increases the incomes of families that are often restrained by limited economic resources. However, there is a concern that the growing number of people and livestock living close together in these areas will increase the transmission of zoonotic pathogens such as Brucella. This study investigates the presence of Brucella DNA in bovine milk in the urban and peri-urban area of Dushanbe, Tajikistan. Brucella DNA was detected in 10.3% of 564 cow milk samples by IS711-based real-time PCR. This finding is concerning because consumption of unpasteurized dairy products is common in the region. Furthermore, Brucella DNA was detected in the milk of all seropositive cows, but 8.3% of the seronegative cows also showed the presence of Brucella DNA. In addition, sequence analysis of the rpoB gene suggests that one cow was infected with B. abortus and another cow was most likely infected with B. melitensis. The discrepancies between the serology and real-time PCR results highlight the need to further investigate whether there is a need for implementing complementary diagnostic strategies to detect false serological negative individuals in Brucella surveillance, control, and eradication programmes. Furthermore, vaccination of cattle with S19 in addition to vaccination of small ruminants with Rev 1 might be needed in order to control Brucella infections in the livestock population but further research focusing on the isolation of Brucella is required to obtain a comprehensive understanding of the Brucella spp. circulating among the livestock in this region.
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52.
  • Liyanage, Prasad, et al. (författare)
  • The impact of COVID-19 lockdown on dengue transmission in Sri Lanka : A natural experiment for understanding the influence of human mobility
  • 2021
  • Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science. - 1935-2727 .- 1935-2735. ; 15:6
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Dengue is one of the major public health problems in Sri Lanka. Its outbreak pattern depends on a multitude of drivers, including human mobility. Here we evaluate the impact of COVID-19 related mobility restriction (lockdown) on the risk of dengue in Sri Lanka.METHODOLOGY: Two-stage hierarchical models were fitted using an interrupted time-series design based on the notified dengue cases, January 2015 to July 2020. In the first stage model, the district level impact was estimated using quasi-Poisson regression models while accounting for temporal trends. Estimates were pooled at zonal and national levels in the second stage model using meta-analysis. The influence of the extended period of school closure on dengue in children in the western province was compared to adults.FINDINGS: Statistically significant and homogeneous reduction of dengue risk was observed at all levels during the lockdown. Overall an 88% reduction in risk (RR 0.12; 95% CI from 0.08 to 0.17) was observed at the national level. The highest impact was observed among children aged less than 19 years showing a 92% reduction (RR 0.8; 95% CI from 0.03 to 0.25). We observed higher impact in the dry zone having 91% reduction (RR 0.09; 95% CI from 0.05 to 0.15) compared to wet zone showing 83% reduction (RR 0.17; 95% CI from 0.09 to 0.30). There was no indication that the overall health-seeking behaviour for dengue had a substantial influence on these estimates.SIGNIFICANCE: This study offers a broad understanding of the change in risk of dengue during the COVID-19 pandemic and associated mobility restrictions in Sri Lanka. The analysis using the mobility restrictions as a natural experiment suggests mobility patterns to be a very important driver of dengue transmission.
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53.
  • Lundin, Johan, et al. (författare)
  • Diagnosis of soil-transmitted helminth infections with digital mobile microscopy and artificial intelligence in a resource-limited setting
  • 2024
  • Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 18:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Infections caused by soil-transmitted helminths (STHs) are the most prevalent neglected tropical diseases and result in a major disease burden in low- and middle-income countries, especially in school-aged children. Improved diagnostic methods, especially for light intensity infections, are needed for efficient, control and elimination of STHs as a public health problem, as well as STH management. Image-based artificial intelligence (AI) has shown promise for STH detection in digitized stool samples. However, the diagnostic accuracy of AI-based analysis of entire microscope slides, so called whole-slide images (WSI), has previously not been evaluated on a sample-level in primary healthcare settings in STH endemic countries.Methodology/Principal findings: Stool samples (n = 1,335) were collected during 2020 from children attending primary schools in Kwale County, Kenya, prepared according to the Kato-Katz method at a local primary healthcare laboratory and digitized with a portable whole-slide microscopy scanner and uploaded via mobile networks to a cloud environment. The digital samples of adequate quality (n = 1,180) were split into a training (n = 388) and test set (n = 792) and a deep-learning system (DLS) developed for detection of STHs. The DLS findings were compared with expert manual microscopy and additional visual assessment of the digital samples in slides with discordant results between the methods. Manual microscopy detected 15 (1.9%) Ascaris lumbricoides, 172 (21.7%) Tricuris trichiura and 140 (17.7%) hookworm (Ancylostoma duodenale or Necator americanus) infections in the test set. Importantly, more than 90% of all STH positive cases represented light intensity infections. With manual microscopy as the reference standard, the sensitivity of the DLS as the index test for detection of A. lumbricoides, T. trichiura and hookworm was 80%, 92% and 76%, respectively. The corresponding specificity was 98%, 90% and 95%. Notably, in 79 samples (10%) classified as negative by manual microscopy for a specific species, STH eggs were detected by the DLS and confirmed correct by visual inspection of the digital samples.Conclusions/Significance: Analysis of digitally scanned stool samples with the DLS provided high diagnostic accuracy for detection of STHs. Importantly, a substantial number of light intensity infections were missed by manual microscopy but detected by the DLS. Thus, analysis of WSIs with image-based AI may provide a future tool for improved detection of STHs in a primary healthcare setting, which in turn could facilitate monitoring and evaluation of control programs.
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54.
  • Lundström, Jan O, et al. (författare)
  • Sindbis virus polyarthritis outbreak signalled by virus prevalence in the mosquito vectors
  • 2019
  • Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 13:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Polyarthritis and rash caused by Sindbis virus (SINV), was first recognised in northern Europe about 50 years ago and is known as Ockelbo disease in Sweden and Pogosta disease in Finland. This mosquito-borne virus occurs mainly in tropical and sub-tropical countries, and in northern Europe it is suggested to cause regularly reoccurring outbreaks. Here a seven-year cycle of SINV outbreaks has been referred to in scientific papers, although the hypothesis is based solely on reported human cases. In the search for a more objective outbreak signal, we evaluated mosquito abundance and SINV prevalence in vector mosquitoes from an endemic area in central Sweden. Vector mosquitoes collected in the River Dalalven floodplains during the years before, during, and after the hypothesised 2002 outbreak year were assayed for virus on cell culture. Obtained isolates were partially sequenced, and the nucleotide sequences analysed using Bayesian maximum clade credibility and median joining network analysis. Only one SINV strain was recovered in 2001, and 4 strains in 2003, while 15 strains were recovered in 2002 with significantly increased infection rates in both the enzootic and the bridge-vectors. In 2002, the Maximum Likelihood Estimated infection rates were 10.0/1000 in the enzootic vectors Culex torrentium/pipiens, and 0.62/1000 in the bridge-vector Aedes cinereus, compared to 4.9/1000 and 0.0/1000 in 2001 and 0.0/1000 and 0.32/1000 in 2003 Sequence analysis showed that all isolates belonged to the SINV genotype I (SINV-I). The genetic analysis revealed local maintenance of four SINV-I clades in the River Dalalven floodplains over the years. Our findings suggest that increased SINV-I prevalence in vector mosquitoes constitutes the most valuable outbreak marker for further scrutinising the hypothesized seven-year cycle of SINV-I outbreaks and the mechanisms behind.
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55.
  • Ma'ayeh, Showgy Y., et al. (författare)
  • Characterization of the Giardia intestinalis secretome during interaction with human intestinal epithelial cells : The impact on host cells
  • 2017
  • Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 11:12
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Giardia intestinalis is a non-invasive protozoan parasite that causes giardiasis in humans, the most common form of parasite-induced diarrhea. Disease mechanisms are not completely defined and very few virulence factors are known.METHODOLOGY:To identify putative virulence factors and elucidate mechanistic pathways leading to disease, we have used proteomics to identify the major excretory-secretory products (ESPs) when Giardia trophozoites of WB and GS isolates (assemblages A and B, respectively) interact with intestinal epithelial cells (IECs) in vitro.FINDINGS:The main parts of the IEC and parasite secretomes are constitutively released proteins, the majority of which are associated with metabolism but several proteins are released in response to their interaction (87 and 41 WB and GS proteins, respectively, 76 and 45 human proteins in response to the respective isolates). In parasitized IECs, the secretome profile indicated effects on the cell actin cytoskeleton and the induction of immune responses whereas that of Giardia showed anti-oxidation, proteolysis (protease-associated) and induction of encystation responses. The Giardia secretome also contained immunodominant and glycosylated proteins as well as new candidate virulence factors and assemblage-specific differences were identified. A minor part of Giardia ESPs had signal peptides (29% for both isolates) and extracellular vesicles were detected in the ESPs fractions, suggesting alternative secretory pathways. Microscopic analyses showed ESPs binding to IECs and partial internalization. Parasite ESPs reduced ERK1/2 and P38 phosphorylation and NF-κB nuclear translocation. Giardia ESPs altered gene expression in IECs, with a transcriptional profile indicating recruitment of immune cells via chemokines, disturbances in glucose homeostasis, cholesterol and lipid metabolism, cell cycle and induction of apoptosis.CONCLUSIONS:This is the first study identifying Giardia ESPs and evaluating their effects on IECs. It highlights the importance of host and parasite ESPs during interactions and reveals the intricate cellular responses that can explain disease mechanisms and attenuated inflammatory responses during giardiasis.
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56.
  • Macleod, Colin, et al. (författare)
  • Eyelash Epilation in the Absence of Trichiasis : Results of a Population-Based Prevalence Survey in the Western Division of Fiji
  • 2017
  • Ingår i: PLoS Neglected Tropical Diseases. - : PUBLIC LIBRARY SCIENCE. - 1935-2727 .- 1935-2735. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The WHO definition of trachomatous trichiasis (TT) is "at least one eyelash touching the globe, or evidence of recent epilation of in-turned eyelashes ", reflecting the fact that epilation is used as a self-management tool for TT. In Fiji's Western Division, a high TT prevalence (8.7% in those aged >= 15 years) was reported in a 2012 survey, yet a 2013 survey found no TT and Fijian ophthalmologists rarely see TT cases. Local anecdote suggests that eyelash epilation is a common behaviour, even in the absence of trichiasis. Epilators may have been identified as TT cases in previous surveys. Methods We used a preliminary focus group to design an interview questionnaire, and subsequently conducted a population-based prevalence survey to estimate the prevalence of epilation in the absence of trichiasis, and factors associated with this behaviour, in the Western Division of Fiji. Results We sampled 695 individuals aged >= 15 years from a total of 457 households in 23 villages. 125 participants (18%) reported epilating their eyelashes at least once within the past year. Photographs were obtained of the eyes of 121/125 (97%) individuals who epilated, and subsequent analysis by an experienced trachoma grader found no cases of trachomatous conjunctival scarring or trichiasis. The age-and sex-adjusted prevalence of epilation in those aged >= 15 years was 8.6% ( 95% Cl 5.7-11.3%). iTaukei ethnicity, female gender, and a higher frequency of drinking kava root were independently associated with epilation. Conclusion Epilation occurs in this population in the absence of trichiasis, with sufficient frequency to have markedly inflated previous estimates of local TT prevalence. Individuals with epilated eyelashes should be confirmed as having epilated in-turned eyelashes in an eye with scarring of the conjunctiva before being counted as cases of TT.
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57.
  • Matiko, Mirende Kichuki, et al. (författare)
  • Serological evidence of inter-epizootic/interepidemic circulation of Rift Valley fever virus in domestic cattle in Kyela and Morogoro, Tanzania
  • 2018
  • Ingår i: PLoS Neglected Tropical Diseases. - San Francisco : Public Library of Science. - 1935-2727 .- 1935-2735. ; 12:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Tanzania is among the Rift Valley fever (RVF) epizootic/endemic countries in sub Saharan Africa, where RVF disease outbreaks occur within a range of 3 to 17-year intervals. Detection of Rift Valley fever virus (RVFV) antibodies in animals in regions with no previous history of outbreaks raises the question of whether the disease is overlooked due to lack-of effective surveillance systems, or if there are strains of RVFV with low pathogenicity. Furthermore, which vertebrate hosts are involved in the inter-epidemic and inter-epizootic maintenance of RVFV? In our study region, the Kyela and Morogoro districts in Tanzania, no previous RVF outbreaks have been reported.Methodology: The study was conducted from June 2014 to October 2015 in the Kyela and Morogoro districts, Tanzania. Samples (n = 356) were retrieved from both the local breed of zebu cattle (Bos indicus) and Bos indicus/Bos Taurus cross breed. RVFV antibodies were analyzed by two enzyme-linked immunosorbent assay (ELISA) approaches. Initially, samples were analyzed by a RVFV multi-species competition ELISA (cELISA), which detected both RVFV IgG and IgM antibodies. All serum samples that were positive with the cELISA method were specifically analysed for the presence of RVFV IgM antibodies to trace recent infection. A plaque reduction neutralization assay (PRNT80) was performed to determine presence of RVFV neutralizing antibodies in all cELISA positive samples.Findings: Overall RVFV seroprevalence rate in cattle by cELISA in both districts was 29.2% (104 of 356) with seroprevalence rates of 33% (47/147) in the Kyela district and 27% (57/209) in the Morogoro district. In total, 8.4% (30/356) of all cattle sampled had RVFV IgM antibodies, indicating current disease transmission. When segregated by districts, the IgM antibody seroprevalence was 2.0% (3/147) and 12.9% (27/209) in Kyela and Morogoro districts respectively. When the 104 cELISA positive samples were analyzed by PRNT80 to confirm that RVFV-specific antibodies were present, the majority (89%, 93/104) had RVFV neutralising antibodies.Conclusion: The results provided evidence of widespread prevalence of RVFV antibody among cattle during an inter-epizootic/inter-epidemic period in Tanzania in regions with no previous history of outbreaks. There is a need for further investigations of RVFV maintenance and transmission in vertebrates and vectors during the long inter-epizootic/inter-epidemic periods.
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58.
  • Mero, Sointu, et al. (författare)
  • Prevalence of diarrhoeal pathogens among children under five years of age with and without diarrhoea in Guinea-Bissau
  • 2021
  • Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 15:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Childhood diarrhoea, a major cause of morbidity and mortality in low-income regions, remains scarcely studied in many countries, such as Guinea-Bissau. Stool sample drying enables later qPCR analyses of pathogens without concern about electricity shortages. Methods Dried stool samples of children under five years treated at the Bandim Health Centre in Bissau, Guinea-Bissau were screened by qPCR for nine enteric bacteria, five viruses, and four parasites. The findings of children having and not having diarrhoea were compared in age groups 0-11 and 12-59 months. Results Of the 429 children- 228 with and 201 without diarrhoea- 96.9% and 93.5% had bacterial, 62.7% and 44.3% viral, and 52.6% and 48.3% parasitic pathogen findings, respectively. Enteroaggregarive Escherichia coli (EAEC; 60.5% versus 66.7%), enteropathogenic E. coli (EPEC; 61.4% versus 62.7%), Campylobacter (53.2% versus 51.8%), and enterotoxigenic E. coli (ETEC; 54.4% versus 44.3%) were the most common bacterial pathogens. Diarrhoea was associated with enteroinvasive E. coli (EIEC)/Shigella (63.3%), astrovirus (75.0%), norovirus GII (72.6%) and Cryptosporidium (71.2%). The only pathogen associated with severe diarrhoea was EIEC/Shigella (p<0.001). EAEC was found more frequent among the infants, and EIEC/Shigella, Giardia duodenalis and Dientamoeba fragilis among the older children. Conclusions Stool pathogens proved common among all the children regardless of them having diarrhoea or not. Author summary Diarrhoeal diseases rank second as cause of childhood mortality and morbidity in low-income countries, yet prospective cohort studies in children with and without diarrhea covering the large variety of diarrhoeal pathogens are limited. While some studies have been conducted among Guinea-Bissauan children, many of them were from the 1990s, when the coverage of the various pathogens was less extensive and the diagnostic methods less sensitive than the modern qPCR methods. We conducted an observational study with a large cohort and covered concomitantly the various bacterial, viral and parasitic agents, and analyzed their associations with the presence/absence of diarrhoeal symptoms and age groups. Importantly, the assay performed well with dried stool samples and, therefore, appears applicable for epidemiological studies in resource-poor regions. A pathogen finding was recorded for almost all (98%) children: bacteria in 97%, viruses in 59% and parasites in 51%. Ongoing diarrhoea was associated with findings of enteroninvasive Escherichia coli/Shigella, astrovirus, norovirus GII and Cryptosporidium. Differences were seen between age groups, infants and young children. The only pathogen associated with severe diarrhoea was enteroninvasive Escherichia coli/Shigella.
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59.
  • Mero, Sointu, et al. (författare)
  • Seasonal variation of diarrhoeal pathogens among Guinea-Bissauan children under five years of age
  • 2023
  • Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 17:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Diarrhoea remains a major cause of childhood morbidity and mortality in low-income countries (LICs). The frequency of diarrhoeal episodes may vary by season, yet few prospective cohort studies have examined seasonal variation among various diarrhoeal pathogens using multiplex qPCR to analyse bacterial, viral and parasitic pathogens.Methods: We combined our recent qPCR data of diarrhoeal pathogens (nine bacterial, five viral and four parasitic) among Guinea-Bissauan children under five years old with individual background data, dividing by season. The associations of season (dry winter and rainy summer) and the various pathogens were explored among infants (0-11 months) and young children (12-59 months) and those with and without diarrhoea.Results: Many bacterial pathogens, especially EAEC, ETEC and Campylobacter, and parasitic Cryptosporidium, prevailed in the rainy season, whereas many viruses, particularly the adenovirus, astrovirus and rotavirus proved common in the dry season. Noroviruses were found constantly throughout the year. Seasonal variation was observed in both age groups.Conclusion: In childhood diarrhoea in a West African LIC, seasonal variation appears to favour EAEC, ETEC, and Cryptosporidium in the rainy and viral pathogens in the dry season.
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60.
  • Moreno, Hector, et al. (författare)
  • A novel circulating tamiami mammarenavirus shows potential for zoonotic spillover
  • 2020
  • Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science. - 1935-2727 .- 1935-2735. ; 14:12
  • Tidskriftsartikel (refereegranskat)abstract
    • A detailed understanding of the mechanisms underlying the capacity of a virus to break the species barrier is crucial for pathogen surveillance and control. New World (NW) mammarenaviruses constitute a diverse group of rodent-borne pathogens that includes several causative agents of severe viral hemorrhagic fever in humans. The ability of the NW mammarenaviral attachment glycoprotein (GP) to utilize human transferrin receptor 1 (hTfR1) as a primary entry receptor plays a key role in dictating zoonotic potential. The recent isolation of Tacaribe and lymphocytic choriominingitis mammarenaviruses from host-seeking ticks provided evidence for the presence of mammarenaviruses in arthropods, which are established vectors for numerous other viral pathogens. Here, using next generation sequencing to search for other mammarenaviruses in ticks, we identified a novel replication-competent strain of the NW mammarenavirus Tamiami (TAMV-FL), which we found capable of utilizing hTfR1 to enter mammalian cells. During isolation through serial passaging in mammalian immunocompetent cells, the quasispecies of TAMV-FL acquired and enriched mutations leading to the amino acid changes N151K and D156N, within GP. Cell entry studies revealed that both substitutions, N151K and D156N, increased dependence of the virus on hTfR1 and binding to heparan sulfate proteoglycans. Moreover, we show that the substituted residues likely map to the sterically constrained trimeric axis of GP, and facilitate viral fusion at a lower pH, resulting in viral egress from later endosomal compartments. In summary, we identify and characterize a naturally occurring TAMV strain (TAMV-FL) within ticks that is able to utilize hTfR1. The TAMV-FL significantly diverged from previous TAMV isolates, demonstrating that TAMV quasispecies exhibit striking genetic plasticity that may facilitate zoonotic spillover and rapid adaptation to new hosts.
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