Evidence of arbovirus co-infection in suspected febrile malaria and typhoid patients in Nigeria

Introduction: Clinical symptoms of malaria and typhoid infections are virtually indistinguishable from those initially seen in many arbovirus infections. Here we describe arbovirus co-infection detected in 310 sera samples collected from febrile, clinically suspected malaria/typhoid patients in Borno State, Nigeria. Methodology: Tested initially for Plasmodium falciparum by microscopy and for Salmonella Typhi by Widal test, samples were subsequently tested for chikungunya (CHIKV), yellow fever (YFV), dengue (DENV) and West Nile viruses (WNV) by plaque reduction neutralization test. Results: While 92% of patients tested positive for malaria, typhoid, an arbovirus infection, or a combination of one or more of these types of infections, less than 1% of the patients tested positive for malaria alone and only 3.9% tested positive for typhoid alone. Approximately half of the patients tested positive for infection with a single arbovirus (48%) regardless of the presence or absence of malaria or typhoid. Of those who showed 90% to 95% virus neutralization, 67.7% had neutralizing antibodies against DENV, 50% against CHIKV, 25% against WNV and 8.7% against YFV. Eight per cent tested negative against all six pathogens, suggesting that other arboviruses not tested for in this study may also be circulating in Nigeria. Conclusions: The results suggest that misdiagnosis of arbovirus co-infections as malaria infections, combined with a lack of virus surveillance and underreporting of arbovirus infections, increases the potential for undetected and uncontrolled spread of important vector-borne arboviruses becoming serious underlying public health concerns in Nigeria.

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Evaluation of the Diagnosis of Typhoid Fever Using the Widal Test and the Anti Salmonella typhi IgM Test

Medical Laboratory Technology Journal ◽

10.31964/mltj.v6i2.327 ◽

2020 ◽

Vol 6 (2) ◽

pp. 128

Author(s):

Wahdah Norsiah ◽

Neni Oktiyani

Keyword(s):

Typhoid Fever ◽

Clinical Symptoms ◽

Sampling Technique ◽

Salmonella Typhi ◽

Definitive Diagnosis ◽

Community Survey ◽

Test Results ◽

Widal Test ◽

Initial Examination ◽

Long Time

Typhoid fever is a systemic infectious disease caused by Salmonella enteric serotype typhi. Laboratory tests are essential because the clinical symptoms of typhoid fever are not specific. The definitive diagnosis of typhoid fever make by culture isolation of Salmonella typhi, but this test is expensive and takes a long time. Other supporting tests that can do quickly are the Widal and Salmonella typhi IgM tests. This study aimed to determine the suitability between the results of the Widal test and the results of the anti-Salmonella typhi IgM test. This type of research is an observational analytic study determining the sample based on the accidental sampling technique. The number of samples taken was 42 samples. The results showed that the Widal Test in typhoid patients was 76% positive and 24% negative. Based on the anti-Salmonella typhi IgM test results in typhoid patients, 38% were positive, and 62% were negative. The study concluded a fragile agreement between the Widal test results and the results of the anti-Salmonella typhi IgM test. It recommended that the Widal test carried out for the initial examination and a quick community survey. The Tubex test highly recommends for diagnosis.

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Evaluation of the Diagnosis of Typhoid Fever Using the Widal Test and the Anti Salmonella typhi IgM Test

Medical Laboratory Technology Journal ◽

10.31964/mltj.v0i0.327 ◽

2020 ◽

Vol 6 (2) ◽

pp. 128

Author(s):

Wahdah Norsiah ◽

Neni Oktiyani

Keyword(s):

Typhoid Fever ◽

Clinical Symptoms ◽

Sampling Technique ◽

Salmonella Typhi ◽

Definitive Diagnosis ◽

Community Survey ◽

Test Results ◽

Widal Test ◽

Initial Examination ◽

Long Time

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Seroprevalence and correlates of SARS-CoV-2 neutralizing antibodies from a population-based study in Bonn, Germany

Nature Communications ◽

10.1038/s41467-021-22351-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

N. Ahmad Aziz ◽

Victor M. Corman ◽

Antje K. C. Echterhoff ◽

Marcel A. Müller ◽

Anja Richter ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Response Rate ◽

Neutralization Test ◽

Population Based ◽

Immunofluorescence Assay ◽

Test Results ◽

Community Based ◽

Population Based Study ◽

Temporal Course ◽

Confirmatory Tests

AbstractTo estimate the seroprevalence and temporal course of SARS-CoV-2 neutralizing antibodies, we embedded a multi-tiered seroprevalence survey within an ongoing community-based cohort study in Bonn, Germany. We first assessed anti-SARS-CoV-2 immunoglobulin G levels with an immunoassay, followed by confirmatory testing of borderline and positive test results with a recombinant spike-based immunofluorescence assay and a plaque reduction neutralization test (PRNT). Those with a borderline or positive immunoassay result were retested after 4 to 5 months. At baseline, 4771 persons participated (88% response rate). Between April 24th and June 30th, 2020, seroprevalence was 0.97% (95% CI: 0.72−1.30) by immunoassay and 0.36% (95% CI: 0.21−0.61) when considering only those with two additional positive confirmatory tests. Importantly, about 20% of PRNT+ individuals lost their neutralizing antibodies within five months. Here, we show that neutralizing antibodies are detectable in only one third of those with a positive immunoassay result, and wane relatively quickly.

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Relying on Widal test alone could lead to over diagnosis of typhoid fever: Findings from a records review of febrile patients at Damphu Hospital, Bhutan, 2011-2012

Bhutan Health Journal ◽

10.47811/bhj.57 ◽

2018 ◽

Vol 4 (1) ◽

pp. 50-54

Author(s):

Tej Nath Nepal ◽

Tshering Dorji ◽

Tsheten Tsheten ◽

Karma Tenzin ◽

Dorji Pelzom ◽

...

Keyword(s):

Typhoid Fever ◽

Scrub Typhus ◽

Correct Diagnosis ◽

High Sensitivity ◽

Salmonella Typhi ◽

Clinical Judgement ◽

Test Results ◽

Widal Test ◽

Duration Of Illness ◽

The Right

Introduction: The Widal test is widely used in hospitals in Bhutan for diagnosis of typhoid fever. The right test with high sensitivity and specificity supplements clinical judgement and contributes to correct diagnosis of disease. This study focuses on the contribution of the Widal test in the diagnosis of typhoid fever. Methods: Data was collected from records of patients who presented to Damphu hospital from March 2011 to June 2012 with clinical suspicion of typhoid fever. Blood samples were collected from patients and tested at Damphu Hospital, Tsirang and the Royal Centre for Disease Control, Thimphu. Seventy records were used for the study. Results: There was no growth of Salmonella typhi on blood cultures from patients who had tested positive in the Widal test. There were 20 (28.57%) samples which tested positive for scrub typhus; among these Widal test was positive in 10 (50%) samples. Thirty four out of 36 (94.44%) patients had duration of illness less than seven days and among them 26 (74.47%) had positive Widal test results. Conclusion: None of the samples that tested positive by Widal test gave a definite diagnosis of typhoid fever with blood culture. Clinical judgement may be more challenging because patients with other febrile illnesses like Scrub typhus also have positive Widal test result. We conclude that it is best not to rely on the Widal test alone for the diagnosis of typhoid fever and this test should be replaced by more accurate ones.

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Low serum neutralizing anti-SARS-CoV-2 S antibody levels in mildly affected COVID-19 convalescent patients revealed by two different detection methods

Cellular and Molecular Immunology ◽

10.1038/s41423-020-00573-9 ◽

2020 ◽

Cited By ~ 1

Author(s):

Berislav Bošnjak ◽

Saskia Catherina Stein ◽

Stefanie Willenzon ◽

Anne Katrin Cordes ◽

Wolfram Puppe ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Clinical Symptoms ◽

Neutralization Test ◽

Antibody Therapy ◽

Neutralization Assay ◽

Detection Methods ◽

Angiotensin Converting Enzyme 2 ◽

Iga Antibodies ◽

Vesicular Stomatitis ◽

Antibody Levels

Abstract Neutralizing antibodies targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry into cells via surface-expressed angiotensin-converting enzyme 2 (ACE2). We used a surrogate virus neutralization test (sVNT) and SARS-CoV-2 S protein-pseudotyped vesicular stomatitis virus (VSV) vector-based neutralization assay (pVNT) to assess the degree to which serum antibodies from coronavirus disease 2019 (COVID-19) convalescent patients interfere with the binding of SARS-CoV-2 S to ACE2. Both tests revealed neutralizing anti-SARS-CoV-2 S antibodies in the sera of ~90% of mildly and 100% of severely affected COVID-19 convalescent patients. Importantly, sVNT and pVNT results correlated strongly with each other and to the levels of anti-SARS-CoV-2 S1 IgG and IgA antibodies. Moreover, levels of neutralizing antibodies correlated with the duration and severity of clinical symptoms but not with patient age. Compared to pVNT, sVNT is less sophisticated and does not require any biosafety labs. Since this assay is also much faster and cheaper, sVNT will not only be important for evaluating the prevalence of neutralizing antibodies in a population but also for identifying promising plasma donors for successful passive antibody therapy.

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Use of Animal Models in Studying Roles of Antibodies and Their Secretion Cells in Dengue Vaccine Development

Viruses ◽

10.3390/v12111261 ◽

2020 ◽

Vol 12 (11) ◽

pp. 1261

Author(s):

Kulkanya Chokephaibulkit ◽

Yu-Wen Chien ◽

Sazaly AbuBakar ◽

Kovit Pattanapanyasat ◽

Guey Chuen Perng

Keyword(s):

Animal Models ◽

Neutralizing Antibodies ◽

Vaccine Development ◽

Clinical Symptoms ◽

Therapeutic Modality ◽

Dengue Vaccine ◽

Efficacy Evaluation ◽

Vector Borne ◽

Memory Immune Response ◽

Cardinal Feature

The cardinal feature of adaptive immunity is its ability to form memory responses that can be rapidly recalled to contain pathogens upon reencountering. Conferring a robust memory immune response to an infection is a key feature for a successful vaccination program. The plasmablasts are cells that not only can secret non-neutralizing antibodies but also can secrete the specific antibodies essential to neutralize and inactivate the invading pathogens. Dengue has been recognized as one of the most important vector-borne human viral diseases globally. Currently, supportive care with vigilant monitoring is the standard practice since there is as yet no approved therapeutic modality to treat dengue. Even though the approved vaccine has become available, its low efficacy with the potential to cause harm is the major hurdle to promote the widespread usage of the vaccine. Despite the decades of research on dengue, the major challenge in dengue vaccine development is the absence of suitable experimental animal models that reflect the pathological features and clinical symptoms, as seen in humans. Dengue is transmitted by the bite of mosquitoes carrying infectious dengue virus (DENV), which has four distinct serotypes. Recently, cases resulting from unconventional transmission routes, such as blood transfusion, organs as well as stem cells and bone marrow transplantations, and mother-to-infant vertical transmission, have been reported, suggesting an alternate route of DENV transmission exists in nature. This review discusses issues and challenges needing to be resolved to develop an effective dengue vaccine. Development of a robust and reliable dengue animal model that can reflect not only dynamic human clinical symptoms but also can answer around why preexisting neutralizing antibodies do not confer protection upon re-infection and immune protection marker for dengue vaccine efficacy evaluation.

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Novel surrogate virus neutralization test reveals low serum neutralizing anti-SARS-CoV-2-S antibodies levels in mildly affected COVID-19 convalescents

10.1101/2020.07.12.20151407 ◽

2020 ◽

Author(s):

Berislav Bošnjak ◽

Saskia Catherina Stein ◽

Stefanie Willenzon ◽

Anne Katrin Cordes ◽

Wolfram Puppe ◽

...

Keyword(s):

Vesicular Stomatitis Virus ◽

Neutralizing Antibodies ◽

Clinical Symptoms ◽

Neutralization Test ◽

Antibody Therapy ◽

Neutralization Assay ◽

Receptor Binding Domain ◽

Angiotensin Converting Enzyme 2 ◽

Iga Antibodies ◽

Vesicular Stomatitis

Neutralizing antibodies targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry into cells using surface-expressed angiotensin-converting enzyme 2 (ACE2). We developed a surrogate neutralization test (sVNT) to assess at what degree serum antibodies interfere with the binding of SARS-CoV-2-S-RBD to ACE2. The sVNT revealed neutralizing anti-SARS-CoV-2-S antibodies in the sera of 90% of mildly and 100% of severely affected coronavirus-disease-2019 (COVID-19) convalescent patients. Importantly, sVNT results correlated strongly to the results from pseudotyped-vesicular stomatitis virus-vector-based neutralization assay and to levels of anti-SARS-CoV-2-S1 IgG and IgA antibodies. Moreover, levels of neutralizing antibodies also correlated to duration and severity of clinical symptoms, but not patient age or gender. These findings together with the sVNT will not only be important for evaluating the prevalence of neutralizing antibodies in a population but also for identifying promising plasma donors for successful passive antibody therapy.

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Detection of Viruses and Virus-Neutralizing Antibodies Using Synthetic Erythrocytes: Toward a Tuneable Tool for Virus Surveillance

ACS Sensors ◽

10.1021/acssensors.0c01830 ◽

2021 ◽

Vol 6 (1) ◽

pp. 83-90

Author(s):

Ana Sánchez-Cano ◽

Cristina Andrés ◽

José R. Herance ◽

Tomás Pumarola ◽

Andrés Antón ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Virus Surveillance

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Five Commercial Immunoassays for SARS-CoV-2 Antibody Determination and Their Comparison and Correlation with the Virus Neutralization Test

Diagnostics ◽

10.3390/diagnostics11040593 ◽

2021 ◽

Vol 11 (4) ◽

pp. 593

Author(s):

Václav Šimánek ◽

Ladislav Pecen ◽

Zuzana Krátká ◽

Tomáš Fürst ◽

Hana Řezáčková ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Neutralization Test ◽

Young Patients ◽

Virus Neutralization Test ◽

Virus Neutralization ◽

Age Dependent ◽

Previous Contact ◽

Dependent Elderly ◽

Protein Assays ◽

Antibody Determination

There is an ongoing debate as to whether SARS-CoV-2 antibodies can be found in patients who have recovered from COVID-19 disease. Currently, there is no consensus on whether the antibodies, if present, are protective. Our regular measurements of SARS-CoV-2 antibodies, starting in July 2020, have provided us with the opportunity of becoming acquainted with the five different immunoassays. A total of 149 patients were enrolled in our study. We measured the samples using each immunoassay, then performing a virus neutralization test and comparing the results of SARS-CoV-2 antibodies with this test. We observed that the production of neutralizing antibodies is age-dependent. Elderly patients have a higher proportion of high neutralizing titers than young patients. Based on our results, and in combination with the literature findings, we can conclude that the serological SARS-CoV-2 antibody measurement is a helpful tool in the fight against COVID-19. The assays can provide information about the patient’s previous contact with the virus. Anti-spike protein assays correlate well with the virus neutralization test and can be used in the screening of potential convalescent plasma donors.

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Development of SARS-CoV-2 Specific IgG and Virus-Neutralizing Antibodies after Infection with Variants of Concern or Vaccination

Vaccines ◽

10.3390/vaccines9070700 ◽

2021 ◽

Vol 9 (7) ◽

pp. 700

Author(s):

Franziska Neumann ◽

Ruben Rose ◽

Janine Römpke ◽

Olaf Grobe ◽

Thomas Lorentz ◽

...

Keyword(s):

Immune Response ◽

Receptor Binding ◽

Neutralizing Antibodies ◽

Neutralization Test ◽

Vaccine Dose ◽

High Avidity ◽

Receptor Binding Domain ◽

Robust Immune Response ◽

Specific Igg ◽

Nucleoprotein N

The humoral immunity after SARS-CoV-2 infection or vaccination was examined. Convalescent sera after infection with variants of concern (VOCs: B.1.1.7, n = 10; B.1.351, n = 1) and sera from 100 vaccinees (Pfizer/BioNTech, BNT162b2, n = 33; Moderna, mRNA-1273, n = 11; AstraZeneca, ChAdOx1 nCoV-19/AZD1222, n = 56) were tested for the presence of immunoglobulin G (IgG) directed against the viral spike (S)-protein, its receptor-binding domain (RBD), the nucleoprotein (N) and for virus-neutralizing antibodies (VNA). For the latter, surrogate assays (sVNT) and a Vero-cell based neutralization test (cVNT) were used. Maturity of IgG was determined by measuring the avidity in an immunoblot (IB). Past VOC infection resulted in a broad reactivity of anti-S IgG (100%), anti-RBD IgG (100%), and anti-N IgG (91%), while latter were absent in 99% of vaccinees. Starting approximately two weeks after the first vaccine dose, anti-S IgG (75–100%) and particularly anti-RBD IgG (98–100%) were detectable. After the second dose, their titers increased and were higher than in the convalescents. The sVNT showed evidence of VNA in 91% of convalescents and in 80–100%/100% after first/second vaccine dose, respectively. After the second dose, an increase in VNA titer and IgGs of high avidity were demonstrated by cVNT and IB, respectively. Re-vaccination contributes to a more robust immune response.

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