162 research outputs found
Evaluation of a recombinant rift valley fever virus nucleocapsid protein as a vaccine and an immunodiagnostic reagent
The serodiagnosis of Rift Valley fever (RVF) relies on the use of inactivated whole virus based reagents
which present biosafety, financial and operational constraints. There are no vaccines for humans, the
availability of animal vaccines is limited and they have several drawbacks. The aim of this study was to
evaluate a bacterially expressed recombinant RVF virus (RVFV) nucleocapsid protein (recNP) as a safe
immunodiagnostic reagent, and an immunogen in a mouse and host animal model. Several enzyme-linked
immunosorbent assays (ELISAs) were developed in this study, enabling sensitive and specific detection
of antibodies and RVFV antigen in human and animal specimens. The recNP was combined with
different adjuvants and used to immunize mice and sheep subsequently challenged with a virulent wild
type RVFV strain. Depending on the recNP/adjuvant combination, protection against disease in mice
ranged between 17 and 100%, with sterilizing immunity elicited in some experimental groups, compared
to 100% morbidity/mortality and excessive viral replication in adjuvant and PBS control mice.
Immunization with recNP combined with Alhydrogel, an adjuvant that biases immunity towards Th2
humoral immunity, that yielded 100% protection, induced an earlier and stronger type I interferon
response in mice after challenge, compared to repression of the same gene in adjuvant and PBS control
mice. There was massive activation of pro-inflammatory responses and genes with pro-apoptotic effects
in the livers of control mice at the acute phase of infection, accompanied by high viral replication,
possibly contributing to the pathology of the liver. There was also evidence of activation and repression
of several genes involved in activation of B- and T-cell immunity in control mice, some indicating
possible immune evasion by the challenge virus. Immunization of sheep with the same recNP/adjuvant
combinations were, however, not able to decrease replication of challenge virus. The recNP based
ELISAs are an important addition to and improvement of the currently available serodiagnostic tests for
RVF. The mechanism by which recNP immunization protects mice from developing severe disease
during the acute phase of infection is now better understood, but the mechanism for earlier clearance of
the virus needs further investigation
Anti-Nucleocapsid Protein Immune Responses Counteract Pathogenic Effects of Rift Valley Fever Virus Infection in Mice
The known virulence factor of Rift Valley fever virus (RVFV), the NSs protein, counteracts the antiviral effects of the type I interferon response. In this study we evaluated the expression of several genes in the liver and spleen involved in innate and adaptive immunity of mice immunized with a RVFV recombinant nucleocapsid protein (recNP) combined with Alhydrogel adjuvant and control animals after challenge with wild type RVFV. Mice immunized with recNP elicited an earlier IFNΞ² response after challenge compared to non-immunized controls. In the acute phase of liver infection in non-immunized mice there was a massive upregulation of type I and II interferon, accompanied by high viral titers, and the up- and downregulation of several genes involved in the activation of B- and T-cells, indicating that both humoral and cellular immunity is modulated during RVFV infection. Various genes involved in pro-inflammatory responses and with pro-apoptotic effects were strongly upregulated and anti-apoptotic genes were downregulated in liver of non-immunized mice. Expression of many genes involved in B- and T-cell immunity were downregulated in spleen of non-immunized mice but normal in immunized mice. A strong bias towards apoptosis and inflammation in non-immunized mice at an acute stage of liver infection associated with suppression of several genes involved in activation of humoral and cellular immunity in spleen, suggests that RVFV evades the host immune response in more ways than only by inhibition of type I interferon, and that immunopathology of the liver plays a crucial role in RVF disease progression
Lack of endocrine disrupting effects in catfish (Clarias gariepinus) from a DDT sprayed area
The exposure and response of the catfish, Clarias gariepinus, was studied in male specimens collected in the vicinity of a DDT spraying programme to control malaria. Two sites were situated in the DDT sprayed areas and one site upstream from exposed areas, used as a reference site the collected specimens were analysed for DDT bioaccumulation and the extent of associated effects. The concentration of all DDT metabolites including p,pβ βand o,pβ βforms of DDT, DDE and DDD, were measured in the adipose tissue, whilst the effects were measured using a range of biomarkers. This included assessing the effectiveness of plasma calcium, magnesium, zinc and alkali-labile phosphates (ALPs) as indirect measures of vitellogenin (VTG). Gonad condition was determined by calculating the gonadosomatic index (GIS) for each individual and comparing it with the gonad mass that were adjusted with Analysis of Covariance (ANCOVA). The presence of intersex in gonads was identified and the overall body condition determined using the condition factor (CF). Overall, none of the biomarkers showed significant change in the presence of high levels of DDT nor lindane, dieldrin and endosulfan II. Subtle responses is the plasma concentrations of calcium, ALP and gonad condition were evident in the catfish where DDT concentrations were highest, whilst no effects related to intersex and body condition were evident. Overall this study highlighted the tolerance of C. gariepinus to DDT contamination, the practical implications of using biomarkers in developing countries, and the need for further research into developing biomarkers for much needed biomonitoring programmes in areas where malaria control programmes continue to use DDT.Water Research Commission (WRC) and the South African National Research Foundation (NRF).http://www.elsevier.com/locate/ecoen
Antibody responses to Marburg virus in Egyptian rousette bats and their role in protection against infection
Egyptian rousette bats (ERBs) are reservoir hosts for the Marburg virus (MARV).
The immune dynamics and responses to MARV infection in ERBs are poorly understood, and
limited information exists on the role of antibodies in protection of ERBs against MARV infection.
Here, we determine the duration of maternal immunity to MARV in juvenile ERBs, and evaluate the
duration of the antibody response to MARV in bats naturally or experimentally infected with the virus.
We further explore whether antibodies in previously naturally exposed bats is fully protective against
experimental reinfection with MARV. Maternal immunity was lost in juvenile ERBs by 5 months of
age. Antibodies to MARV remained detectable in 67% of experimentally infected bats approximately
4 months post inoculation (p.i.), while antibodies to MARV remained present in 84% of naturally
exposed bats at least 11 months after capture. Reinfection of seropositive ERBs with MARV produced
an anamnestic response from day 5 p.i. Although PCR-defined viremia was present in 73.3% of
reinfected ERBs, replicating virus was recovered from the serum of only one bat on day 3 p.i. The
negative PCR results in the salivary glands, intestines, bladders and reproductive tracts of reinfected
bats, and the apparent absence of MARV in the majority of swabs collected from these bats suggest
that reinfection may only play a minor role in the transmission and maintenance of MARV amongst
ERBs in nature.The National Institute for Communicable Diseases, the National Research Foundation of South Africa (86228), the Poliomyelitis Research Foundation (13/54), and the University of Pretoria (postgraduate bursary).http://www.mdpi.com/journal/virusesam2018Medical VirologyMicrobiology and Plant Patholog
Rift Valley fever virus exposure amongst farmers, farm workers, and veterinary professionals in central South Africa
Rift Valley fever (RVF) is a re-emerging arboviral disease of public health and veterinary
importance in Africa and the Arabian Peninsula. Major RVF epidemics were documented in South
Africa in 1950β1951, 1974β1975, and 2010β2011. The number of individuals infected during these
outbreaks has, however, not been accurately estimated. A total of 823 people in close occupational
contact with livestock were interviewed and sampled over a six-month period in 2015β2016 within
a 40,000 km2 study area encompassing parts of the Free State and Northern Cape provinces that
were affected during the 2010β2011 outbreak. Seroprevalence of RVF virus (RVFV) was 9.1% (95%
Confidence Interval (CI95%): 7.2β11.5%) in people working or residing on livestock or game farms
and 8.0% in veterinary professionals. The highest seroprevalence (SP = 15.4%; CI95%: 11.4β20.3%)
was detected in older age groups ( 40 years old) that had experienced more than one known
large epidemic compared to the younger participants (SP = 4.3%; CI95%: 2.6β7.3%). The highest
seroprevalence was in addition found in people who injected animals, collected blood samples (Odds
ratio (OR) = 2.3; CI95%: 1.0β5.3), slaughtered animals (OR = 3.9; CI95%: 1.2β12.9) and consumed
meat from an animal found dead (OR = 3.1; CI95%: 1.5β6.6), or worked on farms with dams for
water storage (OR = 2.7; CI95%: 1.0β6.9). We estimated the number of historical RVFV infections of
farm staff in the study area to be most likely 3849 and 95% credible interval between 2635 and 5374
based on seroprevalence of 9.1% and national census data. We conclude that human RVF cases were
highly underdiagnosed and heterogeneously distributed. Improving precautions during injection,
sample collection, slaughtering, and meat processing for consumption, and using personal protective
equipment during outbreaks, could lower the risk of RVFV infection.U.S. Department of Defense, Defense Threat Reduction Agencyhttps://www.mdpi.com/journal/virusespm2020Animal and Wildlife Science
Vector competence of Eucampsipoda africana (Diptera: Nycteribiidae) for Marburg virus transmission in Rousettus aegyptiacus (Chiroptera: Pteropodidae)
This study aimed to determine the vector competence of bat-associated nycteribiid flies
(Eucamsipoda africana) for Marburg virus (MARV) in the Egyptian Rousette Bat (ERB), Rousettus
aegyptiacus. In flies fed on subcutaneously infected ERBs and tested from 3 to 43 days post infection
(dpi), MARV was detected only in those that took blood during the peak of viremia, 5β7 dpi.
Seroconversion did not occur in control bats in contact with MARV-infected bats infested with bat
flies up to 43 days post exposure. In flies inoculated intra-coelomically with MARV and tested on
days 0β29 post inoculation, only those assayed on day 0 and day 7 after inoculation were positive
by q-RT-PCR, but the virus concentration was consistent with that of the inoculum. Bats remained
MARV-seronegative up to 38 days after infestation and exposure to inoculated flies. The first filial
generation pupae and flies collected at different times during the experiments were all negative by
q-RT-PCR. Of 1693 nycteribiid flies collected from a wild ERB colony in Mahune Cave, South Africa
where the enzootic transmission of MARV occurs, only one (0.06%) tested positive for the presence
of MARV RNA. Our findings seem to demonstrate that bat flies do not play a significant role in the
transmission and enzootic maintenance of MARV. However, ERBs eat nycteribiid flies; thus, the
mechanical transmission of the virus through the exposure of damaged mucous membranes and/or
skin to flies engorged with contaminated blood cannot be ruled out.http://www.mdpi.com/journal/virusespm2022Medical Virolog
The use of the urogenital papillae of male feral African sharptooth catfish (Clarias gariepinus) as indicator of exposure to estrogenic chemicals in two polluted dams in an urban nature reserve, Gauteng, South Africa
The African sharptooth catfish (Clarias gariepinus) is indigenous to South Africa where it is commonly found in calm waters such as lakes, streams,
rivers, swamps and floodplains. The males of this gonochoristic species can be readily distinguished from females via a distinct elongated urogenital
papilla with a pointed tip, located just behind the anus. This structure is an androgen controlled secondary sexual characteristic and could potentially
be affected by chemicals displaying endocrine disrupting properties during development. Results of previous studies on effects on papillae of different
fish species indicated that these structures could be useful as bio-indicators of exposure due to alterations in the structures. This study investigated
the occurrence of abnormal morphology in urogenital papillae compared to the macroscopic and microscopic structure of the gonads of presumed
male or intersex catfish sampled from the Rietvlei and Marais dams in an urban nature reserve, due to exposure to endocrine disrupting chemicals
(EDCs). Macroscopic observation of the UGP, gonad examination after laparotomy and histology were done. Gonadosomatic index (GSI) and
Urogenital papilla length index (UGPLI) were determined for all fish collected. Mesenteric fat analyzed for selected alkylphenols and organochlorines
showed high levels of especially nonylphenol indicating long term exposure to these chemicals due to bio-accumulation. The GSI indicated that fish
with intersex gonads were probably feminized males. It was concluded that use of the UGP alone, without macroscopic and microscopic analyses of
the gonads, could not effectively indicate exposure to EDCs.Water Research Commission (WRC) of South Africahttp://www.elsevier.com/locate/ecoenvhb201
Detection and genome characterization of Middelburg virus strains isolated from CSF and whole blood samples of humans with neurological manifestations in South Africa
BACKGROUND : The Old world Alphavirus, Middelburg virus (MIDV), is not well known and although a few cases associated with animal illness have previously been described from Southern Africa, there has been no investigation into the association of the virus with human illness. The current study aimed to investigate possible association of MIDV infection with febrile or neurological manifestations in hospitalized or symptomatic patients from Gauteng, South Africa. METHODS : This study is a descriptive retrospective and prospective laboratory based study. Archived cerebrospinal fluid (CSF) samples submitted to the National Health Laboratory Service (NHLS), Tshwane Academic division for viral investigation from public sector hospitals in Gauteng as well as EDTA (ethylenediaminetetraacetic acid) whole blood samples from ad hoc cases of veterinary students, presenting with neurological and febrile illness, were selected and screened for the presence of alphaviruses using real-time reverse transcription(rtRT) PCR. Virus isolations from rtRT-PCR positive samples were conducted in Vero cell culture and used to obtain full genome sequences. Basic descriptive statistical analysis was conducted using Epi Info. RESULTS : MIDV was detected by rtRT-PCR in 3/187 retrospective CSF specimens obtained from the NHLS from hospitalised patients in the Tshwane region of Gauteng and 1/2 EDTA samples submitted in the same year (2017) from ad hoc query arbovirus cases from veterinary students from the Faculty of Veterinary Science University of Pretoria. Full genome sequences were obtained for virus isolates from two cases; one from an EDTA whole blood sample (ad hoc case) and another from a CSF sample (NHLS sample). Two of the four Middelburg virus positive cases, for which clinical information was available, had other comorbidities or infections at the time of infection. CONCLUSION : Detection of MIDV in CSF of patients with neurological manifestations suggests that the virus should be investigated as a human pathogen with the potential of causing or contributing to neurological signs in children and adults.The G7 Global Health Fund program, the National Research Foundation, Poliomyelitis Research Foundation and the German Federal Ministry of Education and Research.https://journals.plos.org/plosntdsdm2022Paraclinical Science
Rift Valley fever virus seroprevalence among humans, Northern KwaZulu-Natal Province, South Africa, 2018-2019
We detected Rift Valley fever virus (RVFV) IgM and IgG
in human serum samples collected during 2018β2019
in northern KwaZulu-Natal Province, South Africa. Our
results show recent RVFV circulation and likely RVFV
endemicity in this tropical coastal plain region of South
Africa in the absence of apparent clinical disease.The Division of Global Migration and Quarantine, National Center for Emerging and Zoonotic Infectious Diseases, US Centers for Disease Control and Prevention Division .http://www.cdc.gov/eidam2022Medical Virolog
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