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1.
Front Cell Infect Microbiol ; 11: 637570, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33777847

RESUMEN

The human whipworm Trichuris trichiura infects 289 million people worldwide, resulting in substantial morbidity. Whipworm infections are difficult to treat due to low cure rates and high reinfection rates. Interactions between whipworm and its host's intestinal microbiome present a potential novel target for infection control or prevention but are very complicated and are identified using inconsistent methodology and sample types across the literature, limiting their potential usefulness. Here, we used a combined 16S rRNA gene OTU analysis approach (QIIME2) for samples from humans and mice infected with whipworm (T. trichiura and T. muris, respectively) to identify for the first time, bacterial taxa that were consistently associated with whipworm infection spanning host species and infection status using four independent comparisons (baseline infected vs uninfected and before vs after deworming for both humans and mice). Using these four comparisons, we identified significant positive associations for seven taxa including Escherichia, which has been identified to induce whipworm egg hatching, and Bacteroides, which has previously been identified as a major component of the whipworm internal microbiome. We additionally identified significant negative associations for five taxa including four members of the order Clostridiales, two from the family Lachnospiraceae, including Blautia which was previously identified as positively associated with whipworm in independent human and mouse studies. Using this approach, bacterial taxa of interest for future association and mechanistic studies were identified, and several were validated by RT-qPCR. We demonstrate the applicability of a mouse animal model for comparison to human whipworm infections with respect to whipworm-induced intestinal microbiome disruption and subsequent restoration following deworming. Overall, the novel cross-species analysis approach utilized here provides a valuable research tool for studies of the interaction between whipworm infection and the host intestinal microbiome.

2.
Parasitol Res ; 120(2): 535-545, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33415393

RESUMEN

Paragonimiasis is a foodborne trematode infection that affects 23 million people, mainly in Asia. Lung fluke infections lead frequently to chronic cough with fever and hemoptysis, and are often confused with lung cancer or tuberculosis. Paragonimiasis can be efficiently treated with praziquantel, but diagnosis is often delayed, and patients are frequently treated for other conditions. To improve diagnosis, we selected five Paragonimus kellicotti proteins based on transcriptional abundance, recognition by patient sera, and conservation among trematodes and expressed them as His-fusion proteins in Escherichia coli. Sequences for these proteins have 76-99% identity with amino acid sequences for orthologs in the genomes of Paragonimus westermani, Paragonimus heterotremus, and Paragonimus miyazakii. Immunohistology studies showed that antibodies raised to four recombinant proteins bound to the tegument of adult P. kellicotti worms, at the parasite host interface. Only a known egg antigen was absent from the tegument but present in developing and mature eggs. We evaluated the diagnostic potential of these antigens by Western blot with sera from patients with paragonimiasis (from MO and the Philippines), fascioliasis, and schistosomiasis, and with sera from healthy North American controls. Two recombinant proteins (a cysteine protease and a myoglobin) showed the highest sensitivity and specificity as diagnostic antigens, and they detected antibodies in sera from paragonimiasis patients with early or mature infections. In contrast, antibodies to egg yolk ferritin appeared to be specific marker for patients with adult fluke infections that produce eggs. Our study has identified and localized antigens that are promising for serodiagnosis of human paragonimiasis.

3.
J Clin Pharmacol ; 2020 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-33205449

RESUMEN

The non-vitamin K antagonist oral anticoagulant, rivaroxaban, is used in several thromboembolic disorders. Rivaroxaban is eliminated via both metabolic degradation and renal elimination as unchanged drug. Therefore, renal and hepatic impairment may reduce rivaroxaban clearance, and medications inhibiting these clearance pathways could lead to drug-drug interactions. This physiologically-based pharmacokinetic (PBPK) study investigated the pharmacokinetic behavior of rivaroxaban in clinical situations where drug clearance is impaired. A PBPK model was developed using mass balance and bioavailability data from adults and qualified using clinically observed data. Renal and hepatic impairment were simulated by adjusting disease-specific parameters and concomitant drug use was simulated by varying enzyme activity in virtual populations (n = 1000) and compared with pharmacokinetic predictions in virtual healthy populations and clinical observations. Rivaroxaban doses of 10 mg or 20 mg were used. Mild-to-moderate renal impairment had a minor effect on area under the concentration-time curve (AUC) and maximum plasma concentration (Cmax ) of rivaroxaban, whereas severe renal impairment caused a more pronounced increase in these parameters versus normal renal function. AUC and Cmax increased with severity of hepatic impairment. These effects were smaller in the simulations compared with clinical observations. AUC and Cmax increased with the strength of cytochrome P450 3A4 and P-glycoprotein inhibitors in simulations and clinical observations. This PBPK model can be useful for estimating the effects of impaired drug clearance on rivaroxaban pharmacokinetics. Identifying other factors that affect the pharmacokinetics of rivaroxaban could facilitate the development of models that approximate real-world pharmacokinetics more accurately. This article is protected by copyright. All rights reserved.

4.
Cells ; 9(9)2020 09 08.
Artículo en Inglés | MEDLINE | ID: mdl-32911832

RESUMEN

Endocytosis plays a particular role in the proteolytic activation of highly pathogenic henipaviruses Hendra (HeV) and Nipah virus (NiV) fusion (F) protein precursors. These proteins require endocytic uptake from the cell surface to be cleaved by cellular proteases within the endosomal compartment, followed by recycling to the plasma membrane for incorporation into budding virions or mediation of cell-cell fusion. This internalization largely depends on a tyrosine-based consensus motif for endocytosis present in the cytoplasmic tail of HeV and NiV F. Given the large number of tyrosine residues present in the F protein cytoplasmic domain of Cedar virus (CedV), a closely related but low pathogenic henipavirus, we aimed to investigate whether CedV F protein undergoes signal-mediated endocytosis from the cell surface controlled by tyrosine-based motifs present in its cytoplasmic tail and whether endocytosis is relevant for its biological activity. Therefore, tyrosine-based signals were mutated, and mutations were assessed for their effect on F cell surface expression, endocytosis, and biological activity. A membrane-proximal YXXΦ motif and a C-terminal di-tyrosine motif are of particular importance for cell surface expression and endocytosis rate. Furthermore, our data strongly indicate the pivotal role of endocytosis for the biological activity of the CedV F protein.

5.
Transbound Emerg Dis ; 2020 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-32915496

RESUMEN

In 2008, an outbreak of Reston ebolavirus (RESTV) in pigs in the Philippines expanded our understanding of the host range of ebolaviruses. Subsequent experimental infections with the human-pathogenic species Zaire ebolavirus (EBOV) confirmed that pigs are susceptible to African species of ebolaviruses. Pig keeping has become an increasingly important livelihood strategy throughout parts of sub-Saharan Africa, driven by increasing demand for pork. The growth in pig keeping is particularly rapid in Uganda, which has the highest per capita pork consumption in East Africa and a history of sporadic human outbreaks of Ebola virus disease (EVD). Using a systematic sampling protocol, we collected sera from 658 pigs presented for slaughter in Uganda between December 2015 and October 2016. Forty-six pigs (7%) were seropositive based on ELISA tests at two different institutions. Seropositive pigs had antibodies that bound to Sudan NP (n = 27), Zaire NP (Kikwit; n = 8) or both NPs (n = 11). Sera from 4 of the ELISA-positive pigs reacted in Western blot (EBOV NP = 1; RESTV NP = 2; both NPs = 2), and one sample had full neutralizing antibody against Sudan ebolavirus (SUDV) in virus neutralization tests. Pigs sampled in June 2016 were significantly more likely to be seropositive than pigs sampled in October 2016 (p = .03). Seropositive pigs were sourced from all regions except Western region. These observed temporal and spatial variations are suggestive of multiple introductions of ebolaviruses into the pig population in Uganda. This is the first report of exposure of pigs in Uganda to ebolaviruses and the first to employ systematic abattoir sampling for ebolavirus surveillance during a non-outbreak period. Future studies will be necessary to further define the role pigs play (if any) in ebolavirus maintenance and transmission so that potential risks can be mitigated.

6.
PLoS Negl Trop Dis ; 14(6): e0008231, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32544158

RESUMEN

BACKGROUND: Nucleic acid amplification tests (NAATs) are increasingly being used as diagnostic tools for soil-transmitted helminths (STHs; Ascaris lumbricoides, Trichuris trichiura, Necator americanus, Ancylostoma duodenale and A. ceylanicum), Strongyloides stercoralis and Schistosoma in human stool. Currently, there is a large diversity of NAATs being applied, but an external quality assessment scheme (EQAS) for these diagnostics is lacking. An EQAS involves a blinded process where test results reported by a laboratory are compared to those reported by reference or expert laboratories, allowing for an objective assessment of the diagnostic performance of a laboratory. In the current study, we piloted an international EQAS for these helminths (i) to investigate the feasibility of designing and delivering an EQAS; (ii) to assess the diagnostic performance of laboratories; and (iii) to gain insights into the different NAAT protocols used. METHODS AND PRINCIPAL FINDINGS: A panel of twelve stool samples and eight DNA samples was validated by six expert laboratories for the presence of six helminths (Ascaris, Trichuris, N. americanus, Ancylostoma, Strongyloides and Schistosoma). Subsequently this panel was sent to 15 globally dispersed laboratories. We found a high degree of diversity among the different DNA extraction and NAAT protocols. Although most laboratories performed well, we could clearly identify the laboratories that were poorly performing. CONCLUSIONS/SIGNIFICANCE: We showed the technical feasibility of an international EQAS for the NAAT of STHs, Strongyloides and Schistosoma. In addition, we documented that there are clear benefits for participating laboratories, as they can confirm and/or improve the diagnostic performance of their NAATs. Further research should aim to identify factors that explain poor performance of NAATs.


Asunto(s)
Helmintiasis/diagnóstico , Ensayos de Aptitud de Laboratorios/organización & administración , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificación de Ácido Nucleico/métodos , Adolescente , Animales , Niño , Heces/parasitología , Femenino , Helmintos/clasificación , Helmintos/genética , Helmintos/aislamiento & purificación , Humanos , Masculino , Técnicas de Diagnóstico Molecular/normas , Técnicas de Amplificación de Ácido Nucleico/normas , Proyectos Piloto
7.
Plant Cell ; 32(5): 1703-1726, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32111666

RESUMEN

Studies on Glucose-6-phosphate (G6P)/phosphate translocator isoforms GPT1 and GPT2 reported the viability of Arabidopsis (Arabidopsis thaliana) gpt2 mutants, whereas heterozygous gpt1 mutants exhibited a variety of defects during fertilization/seed set, indicating that GPT1 is essential for this process. Among other functions, GPT1 was shown to be important for pollen and embryo-sac development. Because our previous work on the irreversible part of the oxidative pentose phosphate pathway (OPPP) revealed comparable effects, we investigated whether GPT1 may dually localize to plastids and peroxisomes. In reporter fusions, GPT2 localized to plastids, but GPT1 also localized to the endoplasmic reticulum (ER) and around peroxisomes. GPT1 contacted two oxidoreductases and also peroxins that mediate import of peroxisomal membrane proteins from the ER, hinting at dual localization. Reconstitution in yeast (Saccharomyces cerevisiae) proteoliposomes revealed that GPT1 preferentially exchanges G6P for ribulose-5-phosphate (Ru5P). Complementation analyses of heterozygous +/gpt1 plants demonstrated that GPT2 is unable to compensate for GPT1 in plastids, whereas GPT1 without the transit peptide (enforcing ER/peroxisomal localization) increased gpt1 transmission significantly. Because OPPP activity in peroxisomes is essential for fertilization, and immunoblot analyses hinted at the presence of unprocessed GPT1-specific bands, our findings suggest that GPT1 is indispensable in both plastids and peroxisomes. Together with its G6P-Ru5P exchange preference, GPT1 appears to play a role distinct from that of GPT2 due to dual targeting.

8.
Emerg Infect Dis ; 26(4): 760-763, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32186496

RESUMEN

Ebola virus (EBOV) is a highly pathogenic zoonotic virus for which the reservoir host has not been identified. To study the role of dogs as potential hosts, we screened 300 serum samples from dogs in Sierra Leone and found EBOV neutralizing antibodies in 12, suggesting their susceptibility to natural infection.

9.
Transbound Emerg Dis ; 67(2): 724-732, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31627257

RESUMEN

The genus Ebolavirus comprises several virus species with zoonotic potential and varying pathogenicity for humans. Ebolaviruses are considered to circulate in wildlife with occasional spillover events into the human population which then often leads to severe disease outbreaks. Several studies indicate a significant role of bats as reservoir hosts in the ebolavirus ecology. However, pigs from the Philippines have been found to be naturally infected with Reston virus (RESTV), an ebolavirus that is thought to only cause asymptomatic infections in humans. The recent report of ebolavirus-specific antibodies in pigs from Sierra Leone further supports natural infection of pigs with ebolaviruses. However, susceptibility of pigs to highly pathogenic Ebola virus (EBOV) was only shown under experimental settings and evidence for natural infection of pigs with EBOV is currently lacking. Between October and December 2017, we collected 308 serum samples from pigs in Guinea, West Africa, and tested for the presence of ebolavirus-specific antibodies with different serological assays. Besides reactivity to EBOV nucleoproteins in ELISA and Western blot for 19 (6.2%) and 13 (4.2%) samples, respectively, four sera recognized Sudan virus (SUDV) NP in Western blot. Furthermore, four samples specifically detected EBOV or SUDV glycoprotein (GP) in an indirect immunofluorescence assay under native conditions. Virus neutralization assay based on EBOV (Mayinga isolate) revealed five weakly neutralizing sera. The finding of (cross-) reactive and weakly neutralizing antibodies suggests the exposure of pigs from Guinea to ebolaviruses or ebola-like viruses with their pathogenicity as well as their zoonotic potential remaining unknown. Future studies should investigate whether pigs can act as an amplifying host for ebolaviruses and whether there is a risk for spillover events.


Asunto(s)
Anticuerpos Antivirales/sangre , Brotes de Enfermedades/veterinaria , Reservorios de Enfermedades/veterinaria , Ebolavirus/inmunología , Fiebre Hemorrágica Ebola/veterinaria , Inmunoglobulina G/sangre , Enfermedades de los Porcinos/epidemiología , Animales , Anticuerpos Neutralizantes/sangre , Reacciones Cruzadas , Ebolavirus/aislamiento & purificación , Ensayo de Inmunoadsorción Enzimática/veterinaria , Granjas , Femenino , Guinea/epidemiología , Fiebre Hemorrágica Ebola/epidemiología , Fiebre Hemorrágica Ebola/virología , Humanos , Masculino , Nucleoproteínas/inmunología , Sus scrofa , Porcinos , Enfermedades de los Porcinos/virología
10.
J Exp Bot ; 71(3): 823-836, 2020 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-31641750

RESUMEN

Recent work revealed that PGD2, an Arabidopsis 6-phosphogluconate dehydrogenase (6-PGD) catalysing the third step of the oxidative pentose-phosphate pathway (OPPP) in peroxisomes, is essential during fertilization. Earlier studies on the second step, catalysed by PGL3, a dually targeted Arabidopsis 6-phosphogluconolactonase (6-PGL), reported the importance of OPPP reactions in plastids but their irrelevance in peroxisomes. Assuming redundancy of 6-PGL activity in peroxisomes, we examined the sequences of other higher plant enzymes. In tomato, there exist two 6-PGL isoforms with the strong PTS1 motif SKL. However, their analysis revealed problems regarding peroxisomal targeting: reporter-PGL detection in peroxisomes required construct modification, which was also applied to the Arabidopsis isoforms. The relative contribution of PGL3 versus PGL5 during fertilization was assessed by mutant crosses. Reduced transmission ratios were found for pgl3-1 (T-DNA-eliminated PTS1) and also for knock-out allele pgl5-2. The prominent role of PGL3 showed as compromised growth of pgl3-1 seedlings on sucrose and higher activity of mutant PGL3-1 versus PGL5 using purified recombinant proteins. Evidence for PTS1-independent uptake was found for PGL3-1 and other Arabidopsis PGL isoforms, indicating that peroxisome import may be supported by a piggybacking mechanism. Thus, multiple redundancy at the level of the second OPPP step in peroxisomes explains the occurrence of pgl3-1 mutant plants.

11.
Clin Infect Dis ; 71(4): 933-943, 2020 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-31536624

RESUMEN

BACKGROUND: Improved treatment for onchocerciasis is needed to accelerate onchocerciasis elimination in Africa. Aiming to better exploit registered drugs, this study was undertaken to determine whether annual or semiannual treatment with ivermectin (IVM; 200 µg/kg) plus albendazole (ALB; 800 mg single dose) is superior to IVM alone. METHODS: This trial was performed in Ghana and included 272 participants with microfilariae (MF), who were randomly assigned to 4 treatment arms: (1) IVM annually at 0, 12, and 24 months; (2) IVM semiannually at 0, 6, 12, 18, and 24 months; (3) IVM+ALB annually; or (4) IVM+ALB semiannually. Microfiladermia was determined pretreatment and at 6, 18, and 36 months. The primary outcome was the proportion of fertile and viable female worms in onchocercomata excised at 36 months. RESULTS: Posttreatment nodule histology showed that 15/135 (11.1%), 22/155 (14.2%), 35/154 (22.7%), and 20/125 (16.0%) living female worms had normal embryogenesis in the IVM annual, IVM semiannual, IVM+ALB annual, and IVM+ALB semiannual groups, respectively (P = .1229). Proportions of dead worms also did not differ between the 4 groups (P = .9198). Proportions of patients without MF at 36 months (1 year after the last treatment) were 35/56 (63%) after annual IVM, 42/59 (71%) after semiannual IVM, 39/64 (61%) after annual IVM+ALB, and 43/53 (81%) after semiannual IVM+ALB. CONCLUSIONS: The combination treatment of IVM plus ALB was no better than IVM alone for sterilizing, killing adult worms, or achieving sustained MF clearance. However, semiannual treatment was superior to annual treatment for achieving sustained clearance of Onchocerca volvulus MF from the skin (P = .024). CLINICAL TRIALS REGISTRATION: ISRCTN50035143.

12.
Vet Microbiol ; 237: 108405, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31561922

RESUMEN

Nipah virus (NiV), a BSL-4 pathogen, belongs to the genus Henipavirus within the family Paramyxoviridae. To date, no effective vaccine is available. Although most of the current vaccine studies aim to induce a neutralizing antibody response, it has become evident that a promising vaccine should target both, humoral and cell-mediated immune response. Virus-like particles (VLPs) have been shown to activate both arms of the adaptive immune response. In our study, VLPs composed of the NiV surface glycoproteins G and F and the matrix protein of the closely related Hendra virus (HeV M) induced both, a neutralizing antibody response and an antigen-specific CD8 T cell response with proliferation, IFN-γ expression and Th1 cytokine secretion in C57BL/6 mice. In contrast, in BALB/c mice only a neutralizing antibody response was observed. All three viral proteins included in the VLPs were shown to harbor CD8 T cell epitopes; however, the combination of all three proteins enhanced the magnitude of the CD8 T cell response. To conclude, VLPs represent a promising vaccine candidate, as they induce humoral as well as CD8 T cell-mediated immune responses.


Asunto(s)
Antígenos Virales/inmunología , Linfocitos T CD8-positivos/fisiología , Proliferación Celular/fisiología , Henipavirus/inmunología , Proteínas Virales/inmunología , Animales , Anticuerpos Neutralizantes , Chlorocebus aethiops , Citocinas , Regulación de la Expresión Génica/inmunología , Células HEK293 , Humanos , Interferón gamma/genética , Interferón gamma/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Plásmidos , Bazo/citología , Células TH1 , Células Th2 , Células Vero , Proteínas Virales/genética
13.
Front Cell Neurosci ; 13: 225, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31178698

RESUMEN

Inner hair cell (IHC) Cav1.3 Ca2+ channels are multifunctional channels mediating Ca2+ influx for exocytosis at ribbon synapses, the generation of Ca2+ action potentials in pre-hearing IHCs and gene expression. IHCs of deaf systemic Cav1.3-deficient (Cav1.3-/-) mice stay immature because they fail to up-regulate voltage- and Ca2+-activated K+ (BK) channels but persistently express small conductance Ca2+-activated K+ (SK2) channels. In pre-hearing wildtype mice, cholinergic neurons from the superior olivary complex (SOC) exert efferent inhibition onto spontaneously active immature IHCs by activating their SK2 channels. Because Cav1.3 plays an important role for survival, health and function of SOC neurons, SK2 channel persistence and lack of BK channels in systemic Cav1.3-/- IHCs may result from malfunctioning neurons of the SOC. Here we analyze cochlea-specific Cav1.3 knockout mice with green fluorescent protein (GFP) switch reporter function, Pax2::cre;Cacna1d-eGFP flex/flex and Pax2::cre;Cacna1d-eGFP flex/-. Profound hearing loss, lack of BK channels and persistence of SK2 channels in Pax2::cre;Cacna1d-eGFP flex/- mice recapitulated the phenotype of systemic Cav1.3-/- mice, indicating that in wildtype mice, regulation of SK2 and BK channel expression is independent of Cav1.3 expression in SOC neurons. In addition, we noticed dose-dependent GFP toxicity leading to death of basal coil IHCs of Pax2::cre;Cacna1d-eGFP flex/flex mice, likely because of high GFP concentration and small repair capacity. This and the slower time course of Pax2-driven Cre recombinase in switching two rather than one Cacna1d-eGFPflex allele lead us to study Pax2::cre;Cacna1d-eGFP flex/- mice. Notably, control Cacna1d-eGFPflex/- IHCs showed a significant reduction in Cav1.3 channel cluster sizes and currents, suggesting that the intronic construct interfered with gene translation or splicing. These pitfalls are likely to be a frequent problem of many genetically modified mice with complex or multiple gene-targeting constructs or fluorescent proteins. Great caution and appropriate controls are therefore required.

14.
J Vis Exp ; (148)2019 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-31205309

RESUMEN

Sequencing in remote locations and resource-poor settings presents unique challenges. Nanopore sequencing can be successfully used under such conditions, and was deployed to West Africa during the recent Ebola virus epidemic, highlighting this possibility. In addition to its practical advantages (low cost, ease of equipment transport and use), this technology also provides fundamental advantages over second-generation sequencing approaches, particularly the very long read length, ability to directly sequence RNA, and real-time availability of data. Raw read accuracy is lower than with other sequencing platforms, which represents the main limitation of this technology; however, this can be partially mitigated by the high read depth generated. Here, we present a field-compatible protocol for sequencing of the mRNAs encoding for Niemann-Pick C1, which is the cellular receptor for ebolaviruses. This protocol encompasses extraction of RNA from animal blood samples, followed by RT-PCR for target enrichment, barcoding, library preparation, and the sequencing run itself, and can be easily adapted for use with other DNA or RNA targets.


Asunto(s)
Secuenciación de Nanoporos , ARN Mensajero/sangre , Análisis de Secuencia de ARN/métodos , Animales , Ebolavirus/genética , Biblioteca de Genes , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Nanoporos , ARN Mensajero/química
15.
Vector Borne Zoonotic Dis ; 19(7): 455-465, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30985268

RESUMEN

Nipah virus (NiV) and Hendra virus (HeV) are closely related members within the genus Henipavirus, family Paramyxoviridae, for which fruit bats serve as the reservoir. The initial emergence of NiV infections in pigs and humans in Malaysia, and HeV infections in horses and humans in Australia, posed severe impacts on human and animal health, and continues threatening lives of humans and livestock within Southeast Asia and Australia. Recently, henipavirus-specific antibodies have also been detected in fruit bats in a number of sub-Saharan African countries and in Brazil, thereby considerably increasing the known geographic distribution of henipaviruses. Africa is progressively being recognized as a new high prevalence zone for henipaviruses, as deduced from serological and molecular evidence of past infections in Madagascar, Ghana, Republic of Congo, Gulf of Guinea, Zambia, Tanzania, Cameroon, and Nigeria lately. Serological data suggest henipavirus spillover from bats to livestock and human populations in Africa without reported clinical disease in any of these species. All virus isolation attempts have been abortive, highlighting the need for further investigations. The genome of the Ghanaian bat henipavirus designated Ghana virus (GhV), which was detected in a pteropid Eidolon helvum bat, is the only African henipavirus that has been completely sequenced limiting our current knowledge on the genetic diversity and pathogenesis of African henipaviruses. In this review, we summarize the available data on the circulation of henipaviruses in Africa, discuss potential sources for virus spillover, and highlight existing research gaps.


Asunto(s)
Quirópteros/virología , Infecciones por Henipavirus/epidemiología , Henipavirus , África/epidemiología , Animales , Anticuerpos Antivirales , Infecciones por Henipavirus/veterinaria , Infecciones por Henipavirus/virología , Humanos , Ganado/virología , Estudios Seroepidemiológicos , Zoonosis/virología
16.
PLoS Negl Trop Dis ; 13(3): e0007192, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30849120

RESUMEN

BACKGROUND: Mapping of lymphatic filariasis (LF) caused by Wuchereria bancrofti largely relies on the detection of circulating antigen using ICT cards. Several studies have recently shown that this test can be cross-reactive with sera of subjects heavily infected with Loa loa and thus mapping results in loiasis endemic areas may be inaccurate. METHODOLOGY/PRINCIPAL FINDINGS: In order to develop an LF mapping strategy for areas with high loiasis prevalence, we collected day blood samples from 5,001 subjects residing in 50 villages that make up 6 health districts throughout Cameroon. Antigen testing using Filarial Test Strip (FTS, a novel platform that uses the same reagents as ICT) revealed an overall positivity rate of 1.1% and L. loa microfilaria (Mf) rates of up to 46%. Among the subjects with 0 to 8,000 Mf/ml in day blood, only 0.4% were FTS positive, while 22.2% of subjects with >8,000 Mf/ml were FTS positive. A Mf density of >8,200 Mf/ml was determined as the cut point at which positive FTS results should be excluded from the analysis. No FTS positive samples were also positive for W. bancrofti antibodies as measured by two different point of care tests that use the Wb123 antigen not found in L. loa. Night blood examination of the FTS positive subjects showed a high prevalence of L. loa Mf with densities up to 12,710 Mf/ml. No W. bancrofti Mf were identified, as confirmed by qPCR. Our results show that high loads of L. loa Mf in day blood are a reliable indicator of FTS positivity, and Wb123 rapid test proved to be relatively specific. CONCLUSIONS/SIGNIFICANCE: Our study provides a simple day blood-based algorithm for LF mapping in loiasis areas. The results indicate that many districts that were formerly classified as endemic for LF in Cameroon are non-endemic and do not require mass drug administration for elimination of LF.


Asunto(s)
Filariasis Linfática/epidemiología , Enfermedades Endémicas , Loiasis/epidemiología , Topografía Médica , Wuchereria bancrofti/aislamiento & purificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Animales , Anticuerpos Antiprotozoarios/sangre , Antígenos de Protozoos/análisis , Camerún/epidemiología , Niño , Estudios Transversales , Pruebas Diagnósticas de Rutina/métodos , Femenino , Humanos , Inmunoensayo/métodos , Masculino , Persona de Mediana Edad , Prevalencia , Reacción en Cadena en Tiempo Real de la Polimerasa , Población Rural , Adulto Joven
17.
Transbound Emerg Dis ; 66(2): 921-928, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30576076

RESUMEN

Hendra virus (HeV) and Nipah virus (NiV), belonging to the genus Henipavirus, are among the most pathogenic of viruses in humans. Old World fruit bats (family Pteropodidae) are the natural reservoir hosts. Molecular and serological studies found evidence of henipavirus infection in fruit bats from several African countries. However, little is known about the potential for spillover into domestic animals in East Africa, particularly pigs, which served as amplifying hosts during the first outbreak of NiV in Malaysia and Singapore. We collected sera from 661 pigs presented for slaughter in Uganda between December 2015 and October 2016. Using HeV G and NiV G indirect ELISAs, 14 pigs (2%) were seroreactive in at least one ELISA. Seroprevalence increased to 5.4% in October 2016, when pigs were 9.5 times more likely to be seroreactive than pigs sampled in December 2015 (p = 0.04). Eight of the 14 ELISA-positive samples reacted with HeV N antigen in Western blot. None of the sera neutralized HeV or NiV in plaque reduction neutralization tests. Although we did not detect neutralizing antibodies, our results suggest that pigs in Uganda are exposed to henipaviruses or henipa-like viruses. Pigs in this study were sourced from many farms throughout Uganda, suggesting multiple (albeit rare) introductions of henipaviruses into the pig population. We postulate that given the widespread distribution of Old World fruit bats in Africa, spillover of henipaviruses from fruit bats to pigs in Uganda could result in exposure of pigs at multiple locations. A higher risk of a spillover event at the end of the dry season might be explained by higher densities of bats and contact with pigs at this time of the year, exacerbated by nutritional stress in bat populations and their reproductive cycle. Future studies should prioritize determining the risk of spillover of henipaviruses from pigs to people, so that potential risks can be mitigated.


Asunto(s)
Virus Hendra/aislamiento & purificación , Infecciones por Henipavirus/veterinaria , Virus Nipah/aislamiento & purificación , Enfermedades de los Porcinos/epidemiología , Animales , Ensayo de Inmunoadsorción Enzimática , Femenino , Infecciones por Henipavirus/epidemiología , Infecciones por Henipavirus/virología , Masculino , Prevalencia , Factores de Riesgo , Estudios Seroepidemiológicos , Sus scrofa , Porcinos , Enfermedades de los Porcinos/virología , Uganda/epidemiología
18.
Emerg Infect Dis ; 24(8): 1551-1554, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-30016245

RESUMEN

We examined human stool samples from Liberia for soil-transmitted helminth ova by Kato-Katz smear and by quantitative PCR. Twenty-five samples were positive for Trichuris trichiura by smear but negative by quantitative PCR. Reexamination of samples showed that they contained Capillaria eggs that resemble T. trichiura in Kato-Katz smears.


Asunto(s)
Ascariasis/diagnóstico , Capillaria/aislamiento & purificación , Infecciones por Enoplida/diagnóstico , Esquistosomiasis mansoni/diagnóstico , Tricuriasis/diagnóstico , Trichuris/aislamiento & purificación , Adolescente , Adulto , Animales , Ascariasis/epidemiología , Ascariasis/parasitología , Ascaris lumbricoides/anatomía & histología , Ascaris lumbricoides/clasificación , Ascaris lumbricoides/genética , Ascaris lumbricoides/aislamiento & purificación , Capillaria/anatomía & histología , Capillaria/clasificación , Capillaria/genética , Niño , Diagnóstico Diferencial , Infecciones por Enoplida/epidemiología , Infecciones por Enoplida/parasitología , Heces/parasitología , Femenino , Humanos , Liberia/epidemiología , Masculino , Persona de Mediana Edad , Recuento de Huevos de Parásitos , Reacción en Cadena en Tiempo Real de la Polimerasa , Schistosoma mansoni/anatomía & histología , Schistosoma mansoni/clasificación , Schistosoma mansoni/genética , Schistosoma mansoni/aislamiento & purificación , Esquistosomiasis mansoni/epidemiología , Esquistosomiasis mansoni/parasitología , Tricuriasis/epidemiología , Tricuriasis/parasitología , Trichuris/anatomía & histología , Trichuris/clasificación , Trichuris/genética
19.
J Infect Dis ; 218(suppl_5): S305-S311, 2018 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-29982580

RESUMEN

Many human ebolavirus outbreaks have been linked to contact with wildlife including nonhuman primates and bats, which are assumed to serve as host species. However, it is largely unknown to what extent other animal species, particularly livestock, are involved in the transmission cycle or act as additional hosts for filoviruses. Pigs were identified as a susceptible host for Reston virus with subsequent transmission to humans reported in the Philippines. To date, there is no evidence of natural Ebola virus (EBOV) infection in pigs, although pigs were shown to be susceptible to EBOV infection under experimental settings. To investigate the potential role of pigs in the ecology of EBOV, we analyzed 400 porcine serum samples from Sierra Leone for the presence of ebolavirus-specific antibodies. Three samples reacted with ebolavirus nucleoproteins but had no neutralizing antibodies. Our results (1) suggest the circulation of ebolaviruses in swine in Sierra Leone that are antigenically related but not identical to EBOV and (2) could represent undiscovered ebolaviruses with unknown pathogenic and/or zoonotic potential.


Asunto(s)
Ebolavirus/genética , Fiebre Hemorrágica Ebola/virología , Porcinos/virología , Animales , Animales Salvajes/sangre , Animales Salvajes/inmunología , Animales Salvajes/virología , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Ebolavirus/inmunología , Femenino , Fiebre Hemorrágica Ebola/sangre , Fiebre Hemorrágica Ebola/inmunología , Humanos , Masculino , Nucleoproteínas/inmunología , Filipinas , Suero/inmunología , Suero/virología , Sierra Leona
20.
PLoS One ; 13(4): e0194385, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29708971

RESUMEN

Hendra virus (HeV) and Nipah virus (NiV) belong to the genus Henipavirus in the family Paramyxoviridae. Henipavirus infections were first reported in the 1990's causing severe and often fatal outbreaks in domestic animals and humans in Southeast Asia and Australia. NiV infections were observed in humans in Bangladesh, India and in the first outbreak in Malaysia, where pigs were also infected. HeV infections occurred in horses in the North-Eastern regions of Australia, with singular transmission events to humans. Bats of the genus Pteropus have been identified as the reservoir hosts for henipaviruses. Molecular and serological indications for the presence of henipa-like viruses in African fruit bats, pigs and humans have been published recently. In our study, truncated forms of HeV and NiV attachment (G) proteins as well as the full-length NiV nucleocapsid (N) protein were expressed using different expression systems. Based on these recombinant proteins, Enzyme-linked Immunosorbent Assays (ELISA) were developed for the detection of HeV or NiV specific antibodies in porcine serum samples. We used the NiV N ELISA for initial serum screening considering the general reactivity against henipaviruses. The G protein based ELISAs enabled the differentiation between HeV and NiV infections, since as expected, the sera displayed higher reactivity with the respective homologous antigens. In the future, these assays will present valuable tools for serosurveillance of swine and possibly other livestock or wildlife species in affected areas. Such studies will help assessing the potential risk for human and animal health worldwide by elucidating the distribution of henipaviruses.


Asunto(s)
Anticuerpos Antivirales/sangre , Virus Hendra/metabolismo , Virus Nipah/metabolismo , Proteínas de la Nucleocápside/inmunología , Proteínas Virales/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Antivirales/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Infecciones por Henipavirus/inmunología , Infecciones por Henipavirus/patología , Infecciones por Henipavirus/veterinaria , Leishmania/metabolismo , Ratones , Ratones Endogámicos BALB C , Microscopía Fluorescente , Pruebas de Neutralización , Proteínas de la Nucleocápside/genética , Proteínas de la Nucleocápside/metabolismo , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/aislamiento & purificación , Porcinos , Proteínas Virales/genética , Proteínas Virales/metabolismo
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