Aedes aegypti and Culex pipiens complex mosquitoes are prolific vectors of arboviruses that are a global threat to human and animal health. Increased globalization and ease of travel have facilitated ...the worldwide dissemination of these mosquitoes and the viruses they transmit. To assess disease risk, we determined the frequency of arboviruses in western Kenyan counties bordering an area of high arboviral activity. In addition to pathogenic viruses, insect-specific flaviviruses (ISFs), some of which are thought to impair the transmission of specific pathogenic arboviruses, were also evaluated. We trapped mosquitoes in the short and long rainy seasons in 2018 and 2019 at livestock markets and hospitals. Mosquitoes were screened for dengue, chikungunya and other human pathogenic arboviruses, ISFs, and their blood-meal sources as determined by high-resolution melting analysis of (RT-)PCR products. Of 6,848 mosquitoes collected, 89% were trapped during the long rainy season, with A. aegypti (59%) and Cx. pipiens sensu lato (40%) being the most abundant. Most blood-fed mosquitoes were Cx. pipiens s.l. with blood-meals from humans, chicken, and sparrow (Passer sp.). We did not detect dengue or chikungunya viruses. However, one Culex poicilipes female was positive for Sindbis virus, 30 pools of Ae. aegypti had cell fusing agent virus (CFAV; infection rate (IR) = 1.27%, 95% CI = 0.87%-1.78%); 11 pools of Ae. aegypti had Aedes flavivirus (AeFV; IR = 0.43%, 95% CI = 0.23%-0.74%); and seven pools of Cx. pipiens s.l. (IR = 0.23%, 95% CI = 0.1%-0.45%) and one pool of Culex annulioris had Culex flavivirus. Sindbis virus, which causes febrile illness in humans, can complicate the diagnosis and prognosis of patients with fever. The presence of Sindbis virus in a single mosquito from a population of mosquitoes with ISFs calls for further investigation into the role ISFs may play in blocking transmission of other arboviruses in this region.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Brazil detected community transmission of COVID-19 on March 13, 2020. In this study we identified which areas in the country were the most vulnerable for COVID-19, both in terms of the risk of ...arrival of cases, the risk of sustained transmission and their social vulnerability. Probabilistic models were used to calculate the probability of COVID-19 spread from São Paulo and Rio de Janeiro, the initial hotspots, using mobility data from the pre-epidemic period, while multivariate cluster analysis of socio-economic indices was done to identify areas with similar social vulnerability. The results consist of a series of maps of effective distance, outbreak probability, hospital capacity and social vulnerability. They show areas in the North and Northeast with high risk of COVID-19 outbreak that are also highly socially vulnerable. Later, these areas would be found the most severely affected. The maps produced were sent to health authorities to aid in their efforts to prioritize actions such as resource allocation to mitigate the effects of the pandemic. In the discussion, we address how predictions compared to the observed dynamics of the disease.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Fungal infections are underestimated threats that affect over 1 billion people, and Candida spp., Cryptococcus spp., and Aspergillus spp. are the 3 most fatal fungi. The treatment of these infections ...is performed with a limited arsenal of antifungal drugs, and the class of the azoles is the most used. Although these drugs present low toxicity for the host, there is an emergence of therapeutic failure due to azole resistance. Drug resistance normally develops in patients undergoing azole long-term therapy, when the fungus in contact with the drug can adapt and survive. Conversely, several reports have been showing that resistant isolates are also recovered from patients with no prior history of azole therapy, suggesting that other routes might be driving antifungal resistance. Intriguingly, antifungal resistance also happens in the environment since resistant strains have been isolated from plant materials, soil, decomposing matter, and compost, where important human fungal pathogens live. As the resistant fungi can be isolated from the environment, in places where agrochemicals are extensively used in agriculture and wood industry, the hypothesis that fungicides could be driving and selecting resistance mechanism in nature, before the contact of the fungus with the host, has gained more attention. The effects of fungicide exposure on fungal resistance have been extensively studied in Aspergillus fumigatus and less investigated in other human fungal pathogens. Here, we discuss not only classic and recent studies showing that environmental azole exposure selects cross-resistance to medical azoles in A. fumigatus, but also how this phenomenon affects Candida and Cryptococcus, other 2 important human fungal pathogens found in the environment. We also examine data showing that fungicide exposure can select relevant changes in the morphophysiology and virulence of those pathogens, suggesting that its effect goes beyond the cross-resistance.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
In sub-Saharan Africa, malaria is the common diagnosis for febrile illness and related clinical features, resulting in the under-diagnosis of other aetiologies, such as ...arboviruses and
Rickettsia
. While these may not be significant causes of mortality in malaria-endemic areas, they affect the daily life and performance of affected individuals. It is, therefore, important to have a clear picture of these other aetiologies to institute correct diagnoses at hospitals and improve patient outcomes.
Methods
Blood samples were collected from patients with fever and other clinical features associated with febrile illness at selected hospitals in the malaria-endemic counties of Busia, Bungoma, and Kakamega, and screened for Crimean-Congo haemorrhagic fever, Sindbis, dengue and chikungunya viruses,
Rickettsia africae
, and
Plasmodium
spp. using high-throughput real-time PCR techniques. A logistic regression was performed on the results to explore the effect of demographic and socio-economic independent variables on malaria infection.
Results
A total of 336 blood samples collected from hospital patients between January 2018 and February 2019 were screened, of which 17.6% (59/336) were positive for
Plasmodium falciparum
and 1.5% (5/336) for
Plasmodium malariae.
Two patients had dual
P. falciparum
/
P. malariae
infections. The most common clinical features reported by the patients who tested positive for malaria were fever and headache. None of the patients were positive for the arboviruses of interest or
R
.
africae
. Patients living in Busia (OR 5.2; 95% CI 2.46–11.79;
p
< 0.001) and Bungoma counties (OR 2.7; 95% CI 1.27–6.16;
p
= 0.013) had higher odds of being infected with malaria, compared to those living in Kakamega County.
Conclusions
The reported malaria prevalence is in line with previous studies. The absence of arboviral and
R. africae
cases in this study may have been due to the limited number of samples screened, low-level circulation of arboviruses during inter-epidemic periods, and/or the use of PCR alone as a detection method. Other sero-surveys confirming their circulation in the area indicate that further investigations are warranted.
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•Doxycycline (Dox) was tested on S. mansoni-induced granulomatous inflammation.•Dox increased cytokines production, macrophages and neutrophils recruitment.•Dox increased the number and size of lung ...granulomatous.•Dox inhibited MMP-1 and MMP-2 activity and potentiated lung fibrosis.•Dox aggravated elastin depletion and lung damage in S. mansoni-infected mice.
Although doxycycline exhibits immunomodulatory properties, its effects on pulmonary infection by Schistosoma mansoni remain overlooked. Thus, we investigated the impact of this drug on lung granulomatous inflammation and microstructural remodeling in a murine model of schistosomiasis. Swiss mice were randomized in four groups: (i) uninfected, (ii) infected with S. mansoni and untreated, (iii) infected treated with praziquantel (Pzq; 200 mg/kg), and (iv) infected treated with Dox (50 mg/kg). Pz was administered in a single dose, and Dox for 60 days. S. mansoni induced marked granulomatous lung inflammation, which was associated to cytokines upregulation (IL-2, IL-4, IL-10, IFN-γ, TNF-α, and TGF-β), neutrophils and macrophages recruitment, alveolar collapse, lung fibrosis, and extensive depletion of elastic fibers. These parameters were attenuated by Pzq and aggravated by Dox. Exudative/productive granulomas were predominant in untreated and Dox-treated animals, while fibrotic granulomas were more frequent in Pzq-treated mice. The number and size of granulomas in Dox-treated animals was higher than untreated and Pzq-treated mice. Dox treatment inhibited the increase in MMP-1 and MMP-2 activity but upregulated myeloperoxidase and N-acetylglucosaminidase activity compared to untreated and Pzq-treated animals. Dox and Pzq exerted no effect on elastin depletion and upregulation of elastase activity. Together, our findings indicated that Dox aggravated granulomatous inflammation, accelerating lung microstructural remodeling by downregulating MMP-1 and MMP-2 activity without impair neutrophils and macrophages recruitment or elastase activity. Thus, Dox potentiates inflammatory damage associated with lung fibrosis, elastin depletion and massive alveolar collapse, profoundly subverting lung structure in S. mansoni-infected mice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This study used a murine model of Chagas disease to investigate the isolated and combined impact of Trypanosoma cruzi infection and benznidazole (BZ) therapy on liver structure and function. Male ...C57BL/6 mice were challenged with T. cruzi and BZ for 15 days. Serum levels of cytokines and hepatic enzymes, liver oxidative stress, morphology, collagen, and glycogen content were monitored. Separately, T. cruzi infection and BZ treatment resulted in a pro-oxidant status and hepatic reactive damage. Concurrently, both T. cruzi infection and BZ treatment induced upregulation of antioxidant enzymes and pathological reorganization of the liver parenchyma and stroma. T. cruzi infection increased serum levels of Th1 cytokines, which were reduced by BZ in both infected and non-infected animals. BZ also induced functional organ damage, increasing serum levels of liver enzymes. When combined, T. cruzi infection and BZ therapy elicited intense hepatic reactive damage that was not compensated by antioxidant enzymatic reaction, subsequently culminating in more severe morphofunctional hepatic injury. Taken together, these findings indicate that during specific treatment of Chagas disease, hepatic pathology may be a result of an interaction between BZ metabolism and specific mechanisms activated during the natural course of T. cruzi infection, rather than an isolated toxic effect of BZ on liver structure and function.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
African swine fever (ASF) is believed to have evolved in eastern and southern Africa in a sylvatic cycle between common warthogs (Phacochoerus africanus) and argasid ticks of the Ornithodoros moubata ...complex that live in their burrows. The involvement of warthogs and possibly other wild suids in the maintenance of ASF virus means that the infection cannot be eradicated from Africa, but only prevented and controlled in domestic pig populations. Historically, outbreaks of ASF in domestic pigs in Africa were almost invariably linked to the presence of warthogs, but subsequent investigations of the disease in pigs revealed the presence of another cycle involving domestic pigs and ticks, with a third cycle becoming apparent when the disease expanded into West Africa where the sylvatic cycle is not present. The increase in ASF outbreaks that has accompanied the exponential growth of the African pig population over the last three decades has heralded a shift in the epidemiology of ASF in Africa, and the growing importance of the pig husbandry and trade in the maintenance and spread of ASF. This review, which focuses on the ASF situation between 1989 and 2017, suggests a minor role for wild suids compared with the domestic cycle, driven by socio‐economic factors that determine the ability of producers to implement the control measures needed for better management of ASF in Africa.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
Tick-borne pathogens (TBPs) are of global importance, especially in sub-Saharan Africa where they represent a major constraint to livestock production. Their association with ...human disease is also increasingly recognized, signalling their zoonotic importance. It is therefore crucial to investigate TBPs prevalence in livestock populations and the factors associated with their presence. We set out to identify TBPs present in cattle and to determine associated risk factors in western Kenya, where smallholder livestock production is important for subsistence and market-driven income.
Results
Tick-borne pathogen infections in blood samples collected from cattle at livestock markets and slaughterhouses between May 2017 and January 2019 were identified by high-resolution melting analysis and sequencing of PCR products of genus-specific primers. Of the 422 cattle sampled, 30.1% (127/422) were infected with at least one TBP, while 8.8% (37/422) had dual infections.
Anaplasma
spp. (19.7%) were the most prevalent, followed by
Theileria
(12.3%),
Ehrlichia
(6.6%), and
Babesia
(0.2%) spp. Sequence analysis of the TBPs revealed them to be
Anaplasma platys
-like organisms (13.5%),
Theileria velifera
(7.4%),
Anaplasma marginale
(4.9%),
Theileria mutans
(3.1%),
Theileria parva
(1.6%), and
Babesia bigemina
(0.2%).
Ehrlichia ruminantium
,
Rickettsia
spp., and arboviruses were not detected. Exotic breeds of cattle were more likely to be infected with
A. marginale
compared to local breeds (OR: 7.99, 95% CI: 3.04–22.02,
p
< 0.001). Presence of ticks was a significant predictor for
Anaplasma
spp. (OR: 2.18, 95% CI: 1.32–3.69,
p
= 0.003) and
Ehrlichia
spp. (OR: 2.79, 95% CI: 1.22–7.23,
p
= 0.022) infection. Cattle sampled at slaughterhouses were more likely to be positive for
Anaplasma
spp. (OR: 1.64, 95% CI: 1.01–2.70,
p
= 0.048) and
A. marginale
(OR: 3.84, 95% CI: 1.43–12.21,
p
= 0.012), compared to those sampled at livestock markets.
Conclusion
This study reports TBP prevalence and associated risk factors in western Kenya, factors which are key to informing surveillance and control measures.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Although suramin (Sur) is suggested as a potential drug candidate in the management of Chagas disease, this issue has not been objectively tested. In this study, we examined the applicability of ...concomitant treatment with benznidazole (Bz) and suramin in mice infected with a virulent strain of Trypanosoma cruzi. Eighty 12-week-old male C57BL/6 mice were equally randomized in eight groups: (i) noninfected mice (negative control) and mice infected with T. cruzi Y strain receiving (ii) no treatment (positive control), (iii) Bz, 100 mg/kg of body weight per day, (iv) Sur, 20 mg/kg/day, and (v to viii) Sur, 20 mg/kg/day, combined with Bz, 100, 50, 25, or 5 mg/kg/day. Bz was administered by gavage, and Sur was administered intraperitoneally. Sur dramatically increased the parasitemia, cardiac content of parasite DNA, inflammation, oxidative tissue damage, and mortality. In response to high parasitic load in cardiac tissue, Sur stimulated the immune system in a manner typical of the acute phase of Chagas disease, increasing tissue levels of gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) and inducing a preferential IgG2a anti-T. cruzi serum pattern. When Sur and Bz were combined, the infection severity was attenuated, showing a dose-dependent Bz response. Sur therapy had a more harmful effect on the host than on the parasite and reduced the efficacy of Bz against T. cruzi infection. Considering that Sur drastically reinforced the infection evolution, potentiating the inflammatory process and the severity of cardiac lesions, the in vivo findings contradicted the in vitro anti-T. cruzi potential described for this drug.
The high-latitude regions of the Northern Hemisphere are a nexus for the interaction between land surface physical properties and their exchange of carbon and energy with the atmosphere. At these ...latitudes, two carbon pools of planetary significance – those of the permanently frozen soils (permafrost), and of the great expanse of boreal forest – are vulnerable to destabilization in the face of currently observed climatic warming, the speed and intensity of which are expected to increase with time. Improved projections of future Arctic and boreal ecosystem transformation require improved land surface models that integrate processes specific to these cold biomes. To this end, this study lays out relevant new parameterizations in the ORCHIDEE-MICT land surface model. These describe the interactions between soil carbon, soil temperature and hydrology, and their resulting feedbacks on water and CO2 fluxes, in addition to a recently developed fire module. Outputs from ORCHIDEE-MICT, when forced by two climate input datasets, are extensively evaluated against (i) temperature gradients between the atmosphere and deep soils, (ii) the hydrological components comprising the water balance of the largest high-latitude basins, and (iii) CO2 flux and carbon stock observations. The model performance is good with respect to empirical data, despite a simulated excessive plant water stress and a positive land surface temperature bias. In addition, acute model sensitivity to the choice of input forcing data suggests that the calibration of model parameters is strongly forcing-dependent. Overall, we suggest that this new model design is at the forefront of current efforts to reliably estimate future perturbations to the high-latitude terrestrial environment.
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