| 31. |
- Horstick, Olaf, et al.
(författare)
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Reviewing dengue : still a neglected tropical disease?
- 2015
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Ingår i: PLoS Neglected Tropical Diseases. - : Public library science. - 1935-2727 .- 1935-2735. ; 9:4
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Forskningsöversikt (refereegranskat)abstract
- Dengue is currently listed as a "neglected tropical disease" (NTD). But is dengue still an NTD or not? Classifying dengue as an NTD may carry advantages, but is it justified? This review considers the criteria for the definition of an NTD, the current diverse lists of NTDs by different stakeholders, and the commonalities and differences of dengue with other NTDs. We also review the current research gaps and research activities and the adequacy of funding for dengue research and development (R&D) (2003-2013). NTD definitions have been developed to a higher precision since the early 2000s, with the following main features: NTDs are characterised as a) poverty related, b) endemic to the tropics and subtropics, c) lacking public health attention, d) having poor research funding and shortcomings in R&D, e) usually associated with high morbidity but low mortality, and f) often having no specific treatment available. Dengue meets most of these criteria, but not all. Although dengue predominantly affects resource-limited countries, it does not necessarily only target the poor and marginalised in those countries. Dengue increasingly attracts public health attention, and in some affected countries it is now a high profile disease. Research funding for dengue has increased exponentially in the past two decades, in particular in the area of dengue vaccine development. However, despite advances in dengue research, dengue epidemics are increasing in frequency and magnitude, and dengue is expanding to new areas. Specific treatment and a highly effective vaccine remain elusive. Major research gaps exist in the area of integrated surveillance and vector control. Hence, although dengue differs from many of the NTDs, it still meets important criteria commonly used for NTDs. The current need for increased R& D spending, shared by dengue and other NTDs, is perhaps the key reason why dengue should continue to be considered an NTD.
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| 32. |
- Höög, Johanna L, 1979, et al.
(författare)
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3D Architecture of the Trypanosoma brucei Flagella Connector, a Mobile Transmembrane Junction : Electron Tomography of the Flagella Connector
- 2016
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Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Cellular junctions are crucial for the formation of multicellular organisms, where they anchor cells to each other and/or supportive tissue and enable cell-to-cell communication. Some unicellular organisms, such as the parasitic protist Trypanosoma brucei, also have complex cellular junctions. The flagella connector (FC) is a three-layered transmembrane junction that moves with the growing tip of a new flagellum and attaches it to the side of the old flagellum. The FC moves via an unknown molecular mechanism, independent of new flagellum growth. Here we describe the detailed 3D architecture of the FC suggesting explanations for how it functions and its mechanism of motility. Methodology/Principal Findings We have used a combination of electron tomography and cryo-electron tomography to reveal the 3D architecture of the FC. Cryo-electron tomography revealed layers of repetitive filamentous electron densities between the two flagella in the interstitial zone. Though the FC does not change in length and width during the growth of the new flagellum, the interstitial zone thickness decreases as the FC matures. This investigation also shows interactions between the FC layers and the axonemes of the new and old flagellum, sufficiently strong to displace the axoneme in the old flagellum. We describe a novel filament, the flagella connector fibre, found between the FC and the axoneme in the old flagellum. Conclusions/Significance The FC is similar to other cellular junctions in that filamentous proteins bridge the extracellular space and are anchored to underlying cytoskeletal structures; however, it is built between different portions of the same cell and is unique because of its intrinsic motility. The detailed description of its structure will be an important tool to use in attributing structure / function relationships as its molecular components are discovered in the future. The FC is involved in the inheritance of cell shape, which is important for the life cycle of this human parasite.
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| 33. |
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| 34. |
- Jakobsen, Frida, et al.
(författare)
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Urban livestock-keeping and dengue in urban and peri-urban Hanoi, Vietnam.
- 2019
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Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 13:11
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Tidskriftsartikel (refereegranskat)abstract
- Urban livestock provides an important source of food and income, but it may increase the risks for disease transmission. Vectors, such as mosquitoes, might increase and thereby cause an enhanced transmission of infectious diseases, such as dengue fever; considered the most important mosquito-borne viral disease globally. This cross-sectional study evaluated the awareness of dengue fever and investigated how the presence of dengue vectors is affected by the keeping of livestock in urban households in the city of Hanoi, Vietnam. From February to March 2018, during the season of lowest occurrence of dengue in Hanoi, 140 households were interviewed, of which 69 kept livestock. A general trend was observed; respondents living in the Dan Phuong district, a peri-urban district, had better knowledge and practice regarding dengue as compared to the urban Ha Dong district. In total, 3899 mosquitoes were collected and identified, of which 52 (1.33%) were Aedes species. A significant difference between the two districts was observed, with more households in Ha Dong having Aedes spp. mosquitoes (p = 0.02) and a higher incidence of dengue fever (p = 0.001). There was no significant association between livestock-rearing and the presence of Aedes spp. mosquitoes (p = 0.955), or between livestock-rearing and the incidence of dengue fever (p = 0.08). In conclusion, this study could not find any indication that households keeping livestock were at higher risk of dengue virus infections in Hanoi during the season of lowest occurrence of dengue, but clearly indicated the need of more information provided to urban inhabitants, particularly on personal protection.
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| 35. |
- Jidling, Carl, et al.
(författare)
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Screening for Chagas disease from the electrocardiogram using a deep neural network
- 2023
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Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 17:7
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Tidskriftsartikel (refereegranskat)abstract
- Chagas disease (ChD) is a neglected tropical disease, and the diagnosis relies on blood testing of patients from endemic areas. However, there is no clear recommendation on how to select patients for testing in endemic regions. Since most cases of Chronic ChD are asymptomatic, the diagnostic rates are low, preventing patients from receiving adequate treatment.The Electrocardiogram (ECG) is a widely available, low-cost exam, often available in primary care settings. We present an Artificial intelligence (AI) model for automatically detecting ChD from the ECG. AI algorithms have allowed the detection of hidden conditions on the ECG and, to the best of our knowledge, this is the first study that does it for ChD. We utilize large cohorts of patients from the relevant population of all-comers in affected regions in Brazil to develop a model for ChD detection that is then validated on datasets with ground truth labels obtained directly from the patients’ serological status.Our findings demonstrate a promising AI-ECG-based model for discriminating patients with chronic Chagas cardiomyopathy (CCC). The capacity of detecting ChD patients without CCC is still limited. But we believe this can be improved with the addition of epidemiological questions, and that such models can become useful tools for pre-selecting patients for further testing.
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| 36. |
- Jin, Jing, et al.
(författare)
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An attenuated replication-competent chikungunya virus with a fluorescently tagged envelope
- 2018
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Ingår i: PLoS Neglected Tropical Diseases. - : PUBLIC LIBRARY SCIENCE. - 1935-2727 .- 1935-2735. ; 12:7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chikungunya virus (CHIKV) is the most common alphavirus infecting humans worldwide, causing acute and chronically debilitating arthralgia at a great economic expense.Methodology/Principal findings: To facilitate our study of CHIKV, we generated a mCherry tagged replication-competent chimeric virus, CHIKV 37997-mCherry. Single particle cryoEM demonstrated icosahedral organization of the chimeric virus and the display of mCherry proteins on virus surface. CHIKV 37997-mCherry is attenuated in both IFN alpha R knockout and wild-type mice. Strong antiCHIKV and anti-mCherry antibody responses were induced in CHIKV 37997-mCherry infected mice.Conclusions/Significance: Our work suggests that chimeric alphaviruses displaying foreign antigen can serve as vaccines against both aphaviruses and other pathogens and diseases.
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| 37. |
- Kairu-Wanyoike, Salome, et al.
(författare)
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Positive association between Brucella spp. seroprevalences in livestock and humans from a cross-sectional study in Garissa and Tana River Counties, Kenya.
- 2019
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Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 13:10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Brucella spp. is a zoonotic bacterial agent of high public health and socio-economic importance. It infects many species of animals including wildlife, and people may get exposed through direct contact with an infected animal or consumption of raw or undercooked animal products. A linked livestock-human cross-sectional study to determine seroprevalences and risk factors of brucellosis in livestock and humans was designed. Estimates were made for intra-cluster correlation coefficients (ICCs) for these observations at the household and village levels.METHODOLOGY: The study was implemented in Garissa (specifically Ijara and Sangailu areas) and Tana River (Bura and Hola) counties. A household was the unit of analysis and the sample size was derived using the standard procedures. Serum samples were obtained from selected livestock and people from randomly selected households. Humans were sampled in both counties, while livestock could be sampled only in Tana River County. Samples obtained were screened for anti-Brucella IgG antibodies using ELISA kits. Data were analyzed using generalized linear mixed effects logistic regression models with the household (herd) and village being used as random effects.RESULTS: The overall Brucella spp. seroprevalences were 3.47% (95% confidence interval [CI]: 2.72-4.36%) and 35.81% (95% CI: 32.87-38.84) in livestock and humans, respectively. In livestock, older animals and those sampled in Hola had significantly higher seroprevalences than younger ones or those sampled in Bura. Herd and village random effects were significant and ICC estimates associated with these variables were 0.40 (95% CI: 0.22-0.60) and 0.24 (95% CI: 0.08-0.52), respectively. In humans, Brucella spp. seroprevalence was significantly higher in older people, males, and people who lived in pastoral areas than younger ones, females or those who lived in irrigated or riverine areas. People from households that had at least one seropositive animal were 3.35 (95% CI: 1.51-7.41) times more likely to be seropositive compared to those that did not. Human exposures significantly clustered at the household level; the ICC estimate obtained was 0.21 (95% CI: 0.06-0.52).CONCLUSION: The presence of a Brucella spp.-seropositive animal in a household significantly increased the odds of Brucella spp. seropositivity in humans in that household. Exposure to Brucella spp. of both livestock and humans clustered significantly at the household level. This suggests that risk-based surveillance measures, guided by locations of primary cases reported, either in humans or livestock, can be used to detect Brucella spp. infections in livestock or humans, respectively.
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| 38. |
- Kamuyu, Gathoni, et al.
(författare)
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Exposure to Multiple Parasites Is Associated with the Prevalence of Active Convulsive Epilepsy in Sub-Saharan Africa
- 2014
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Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 8:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epilepsy is common in developing countries, and it is often associated with parasitic infections. We investigated the relationship between exposure to parasitic infections, particularly multiple infections and active convulsive epilepsy (ACE), in five sites across sub-Saharan Africa. Methods and Findings: A case-control design that matched on age and location was used. Blood samples were collected from 986 prevalent cases and 1,313 age-matched community controls and tested for presence of antibodies to Onchocerca volvulus, Toxocara canis, Toxoplasma gondii, Plasmodium falciparum, Taenia solium and HIV. Exposure (seropositivity) to Onchocerca volvulus (OR = 1.98; 95% CI: 1.52-2.58, p<0.001), Toxocara canis (OR = 1.52; 95% CI: 1.23-1.87, p<0.001), Toxoplasma gondii (OR = 1.28; 95% CI: 1.04-1.56, p=0.018) and higher antibody levels (top tertile) to Toxocara canis (OR = 1.70; 95% CI: 1.30-2.24, p<0.001) were associated with an increased prevalence of ACE. Exposure to multiple infections was common (73.8% of cases and 65.5% of controls had been exposed to two or more infections), and for T. gondii and O. volvulus co-infection, their combined effect on the prevalence of ACE, as determined by the relative excess risk due to interaction (RERI), was more than additive (T. gondii and O. volvulus, RERI = 1.19). The prevalence of T. solium antibodies was low (2.8% of cases and 2.2% of controls) and was not associated with ACE in the study areas. Conclusion: This study investigates how the degree of exposure to parasites and multiple parasitic infections are associated with ACE and may explain conflicting results obtained when only seropositivity is considered. The findings from this study should be further validated.
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| 39. |
- Kesik-Brodacka, Malgorzata, et al.
(författare)
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Immune response of rats vaccinated orally with various plant-expressed recombinant cysteine proteinase constructs when challenged with Fasciola hepatica metacercariae
- 2017
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Ingår i: PLoS Neglected Tropical Diseases. - : PUBLIC LIBRARY SCIENCE. - 1935-2727 .- 1935-2735. ; 11:3
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Tidskriftsartikel (refereegranskat)abstract
- Background Cysteine proteinases of Fasciola hepatica are important candidates for vaccine antigens because of their role in fluke biology and host-parasite relationships. In our previous experiments, we found that a recombinant cysteine proteinase cloned from adult F. hepatica ( CPFhW) can protect rats against liver fluke infections when it is administered intramuscularly or intranasally in the form of cDNA. We also observed considerable protection upon challenge following mucosal vaccination with inclusion bodies containing recombinant CPFhW produced in Escherichia coli. In this study, we explore oral vaccination, which may be the desired method of delivery and is potentially capable of preventing infections at the site of helminth entry. To provide antigen encapsulation and to protect the vaccine antigen from degradation in the intestinal tract, transgenic plant-based systems are used. Methodology Conclusions We obtained substantial protection after oral administration of the plant-produced hybrids of CPFhW and HBcAg. The highest level of protection (65.4%)was observed in animals immunised with transgenic plants expressing the mature CPFhW enzyme flanked by Gly-rich linkers and inserted into c/e1 epitope of truncated HBcAg. The immunised rats showed clear IgG1 and IgM responsesIn the present study, we aimed to evaluate the protective ability of mucosal vaccinations of 12-week- old rats with CPFhW produced in a transgenic-plant-based system. To avoid inducing tolerance and to maximise the immune response induced by oral immunisation, we used the hepatitis B virus (HBV) core protein ( HBcAg) as a carrier. Animals were immunised with two doses of the antigen and challenged with 25 or 30 metacercariae of F. hepatica. Conclusions We obtained substantial protection after oral administration of the plant-produced hybrids of CPFhW and HBcAg. The highest level of protection (65.4%) was observed in animals immunised with transgenic plants expressing the mature CPFhW enzyme flanked by Gly- rich linkers and inserted into c/e1 epitope of truncated HBcAg. The immunised rats showed clear IgG1 and IgM responses to CPFhW for 4 consecutive weeks after the challenge.
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| 40. |
- Khalil, Eltahir A G, et al.
(författare)
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Safety and efficacy of single dose versus multiple doses of AmBisome for treatment of visceral leishmaniasis in eastern Africa : a randomised trial.
- 2014
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Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 8:1, s. e2613-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Anti-leishmanial drug regimens that include a single dose AmBisome could be suitable for eastern African patients with symptomatic visceral leishmaniasis (VL) but the appropriate single dose is unknown.METHODOLOGY: A multi-centre, open-label, non-inferiority, randomized controlled trial with an adaptive design, was conducted to compare the efficacy and safety of a single dose and multiple doses of AmBisome for the treatment of VL in eastern Africa. The primary efficacy endpoint was definitive cure (DC) at 6 months. Symptomatic patients with parasitologically-confirmed, non-severe VL, received a single dose of AmBisome 7.5 mg/kg body weight or multiple doses, 7 times 3 mg/kg on days 1-5, 14, and 21. If interim analyses, evaluated 30 days after the start of treatment following 40 or 80 patients, showed the single dose gave significantly poorer parasite clearance than multiple doses at the 5% significance level, the single dose was increased by 2·5 mg/kg. In a sub-set of patients, parasite clearance was measured by quantitative reverse transcriptase (qRT) PCR.PRINCIPAL FINDINGS: The trial was terminated after the third interim analysis because of low efficacy of both regimens. Based on the intention-to-treat population, DC was 85% (95%CI 73-93%), 40% (95%CI 19-64%), and 58% (95%CI 41-73%) in patients treated with multiple doses (n = 63), and single doses of 7·5 (n = 21) or 10 mg/kg (n = 40), respectively. qRT-PCR suggested superior parasite clearance with multiple doses as early as day 3. Safety data accorded with the drug label.CONCLUSIONS: The tested AmBisome regimens would not be suitable for VL treatment across eastern Africa. An optimal single dose regimen was not identified.TRIALS REGISTRATION: www.clinicaltrials.govNCT00832208.
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