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1.
Am J Vet Res ; 85(5)2024 May 01.
Article in English | MEDLINE | ID: mdl-38422620

ABSTRACT

OBJECTIVE: To determine the efficacy of primary or booster intranasal vaccination of beef steers on clinical protection and pathogen detection following simultaneous challenge with bovine respiratory syncytial virus and bovine herpes virus 1. METHODS: 30 beef steers were randomly allocated to 3 different treatment groups starting at 2 months of age. Group A (n = 10) was administered a single dose of a parenteral modified-live vaccine and was moved to a separate pasture. Groups B (n = 10) and C (10) remained unvaccinated. At 6 months of age, all steers were weaned and transported. Subsequently, groups A and B received a single dose of an intranasal modified-live vaccine vaccine while group C remained unvaccinated. Group C was housed separately until challenge. Two days following vaccination, all steers were challenged with bovine respiratory syncytial virus and bovine herpes virus 1 and housed in a single pen. Clinical and antibody response outcomes and the presence of nasal pathogens were evaluated. RESULTS: The odds of clinical disease were lower in group A compared with group C on day 7 postchallenge; however, antibody responses and pathogen detection were not significantly different between groups before and following viral challenge. All calves remained negative for Histophilus somni and Mycoplasma bovis; however, significantly greater loads of Mannheimia haemolytica and Pasteurella multocida were detected on day 7 postchallenge compared with day -2 prechallenge. CLINICAL RELEVANCE: Intranasal booster vaccination of beef steers at 6 months of age reduced clinical disease early after viral challenge. Weaning, transport, and viral infection promoted increased detection rates of M haemolytica and P multocida regardless of vaccination status.


Subject(s)
Administration, Intranasal , Coinfection , Herpesvirus 1, Bovine , Immunization, Secondary , Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus, Bovine , Animals , Cattle , Herpesvirus 1, Bovine/immunology , Male , Administration, Intranasal/veterinary , Respiratory Syncytial Virus, Bovine/immunology , Immunization, Secondary/veterinary , Coinfection/veterinary , Coinfection/prevention & control , Coinfection/microbiology , Respiratory Syncytial Virus Infections/veterinary , Respiratory Syncytial Virus Infections/prevention & control , Infectious Bovine Rhinotracheitis/prevention & control , Infectious Bovine Rhinotracheitis/immunology , Cattle Diseases/prevention & control , Cattle Diseases/microbiology , Cattle Diseases/virology , Cattle Diseases/immunology , Viral Vaccines/immunology , Viral Vaccines/administration & dosage , Bacterial Shedding , Antibodies, Viral/blood , Herpesviridae Infections/veterinary , Herpesviridae Infections/prevention & control , Random Allocation , Vaccination/veterinary
2.
Viruses ; 16(1)2024 Jan 18.
Article in English | MEDLINE | ID: mdl-38257842

ABSTRACT

This study aimed to explore the current evidence on preventing blood-borne virus infections among people who inject drugs (PWID). We conducted a comprehensive search across three databases (PubMed, Embase, Cochrane Library) for relevant articles published in English between 2014 and 2023. We followed the Preferred Reporting Items for Systematic Reviews and Meta Analysis (PRISMA) guidelines, assessed the quality of the paper using the revised Cochrane Risk of Bias Tool (ROB 2), and conducted a meta-analysis using RevMan 5.3. Completing the harm reduction program (HRP) participation and receiving all three vaccine doses resulted in a 28% reduction in the risk of HBV infection (OR: 0.72, 95% CI: 0.37-1.42). Various interventions increased the willingness of PWIDs to undergo HCV treatment (OR: 5.91, 95% CI: 2.46-14.24) and promoted treatment adherence (OR: 15.04, 95% CI: 2.80-80.61). Taking PrEP, participating in HRP, and modifying risky behaviors were associated with a 33% reduction in the risk of HIV infection (OR: 0.67, 95% CI: 0.61-0.74). Conducting referrals, providing counseling, and implementing antiretroviral therapy resulted in a 44% reduction in the risk of viral transmission (OR: 0.56, 95% CI: 0.47-0.66). Co-infection may potentially compromise effectiveness, so it is important to consider drug resistance.


Subject(s)
Coinfection , Drug Users , HIV Infections , Hepatitis, Viral, Human , Humans , HIV Infections/drug therapy , HIV Infections/prevention & control , Coinfection/prevention & control , Databases, Factual
3.
JAMA ; 330(24): 2376-2387, 2023 12 26.
Article in English | MEDLINE | ID: mdl-37943548

ABSTRACT

Importance: Hepatitis D virus (HDV) infection occurs in association with hepatitis B virus (HBV) infection and affects approximately 12 million to 72 million people worldwide. HDV causes more rapid progression to cirrhosis and higher rates of hepatocellular carcinoma than HBV alone or hepatitis C virus. Observations: HDV requires HBV to enter hepatocytes and to assemble and secrete new virions. Acute HDV-HBV coinfection is followed by clearance of both viruses in approximately 95% of people, whereas HDV superinfection in an HBV-infected person results in chronic HDV-HBV infection in more than 90% of infected patients. Chronic hepatitis D causes more rapidly progressive liver disease than HBV alone. Approximately 30% to 70% of patients with chronic hepatitis D have cirrhosis at diagnosis and more than 50% die of liver disease within 10 years of diagnosis. However, recent studies suggested that progression is variable and that more than 50% of people may have an indolent course. Only approximately 20% to 50% of people infected by hepatitis D have been diagnosed due to lack of awareness and limited access to reliable diagnostic tests for the HDV antibody and HDV RNA. The HBV vaccine prevents HDV infection by preventing HBV infection, but no vaccines are available to protect those with established HBV infection against HDV. Interferon alfa inhibits HDV replication and reduces the incidence of liver-related events such as liver decompensation, hepatocellular carcinoma, liver transplant, or mortality from 8.5% per year to 3.3% per year. Adverse effects from interferon alfa such as fatigue, depression, and bone marrow suppression are common. HBV nucleos(t)ide analogues, such as entecavir or tenofovir, are ineffective against HDV. Phase 3 randomized clinical trials of bulevirtide, which blocks entry of HDV into hepatocytes, and lonafarnib, which interferes with HDV assembly, showed that compared with placebo or observation, these therapies attained virological and biochemical response in up to 56% of patients after 96 weeks of bulevirtide monotherapy and 19% after 48 weeks of lonafarnib, ritonavir, and pegylated interferon alfa treatment. Conclusions and Relevance: HDV infection affects approximately 12 million to 72 million people worldwide and is associated with more rapid progression to cirrhosis and liver failure and higher rates of hepatocellular carcinoma than infection with HBV alone. Bulevirtide was recently approved for HDV in Europe, whereas pegylated interferon alfa is the only treatment available in most countries.


Subject(s)
Coinfection , Hepatitis D, Chronic , Humans , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/prevention & control , Coinfection/epidemiology , Coinfection/prevention & control , Coinfection/virology , Hepatitis B/complications , Hepatitis B/drug therapy , Hepatitis B/epidemiology , Hepatitis B virus , Hepatitis D/complications , Hepatitis D/diagnosis , Hepatitis D/drug therapy , Hepatitis D, Chronic/complications , Hepatitis D, Chronic/diagnosis , Hepatitis D, Chronic/drug therapy , Hepatitis D, Chronic/epidemiology , Hepatitis Delta Virus/genetics , Interferon-alpha/adverse effects , Interferon-alpha/therapeutic use , Liver Cirrhosis/epidemiology , Liver Cirrhosis/etiology , Liver Cirrhosis/virology , Liver Neoplasms/epidemiology , Liver Neoplasms/etiology , Liver Neoplasms/prevention & control , Liver Neoplasms/virology , Polyethylene Glycols/adverse effects , Polyethylene Glycols/therapeutic use
4.
Mol Immunol ; 152: 86-96, 2022 12.
Article in English | MEDLINE | ID: mdl-36306645

ABSTRACT

Current seasonal influenza A virus (IAV) vaccines only protect against specific virus and require annual reconstitution to accommodate the viral mutations. A universal influenza vaccination that protects against all IAV strains is urgently needed. The influenza matrix protein 2 ectodomain (M2e) is a potential universal IAV vaccine candidate, but it has a low immunogenicity. ΔA146Ply was proved to be an effective protein adjuvant. Therefore, ΔA146Ply was used as an adjuvant of M2e in this study to evaluate its protective effect against IAV-related infection. Herein, a novel rM2e protein containing multiple M2e originated from different species of IAV was constructed and expressed in Escherichia coli (E. coli). Meanwhile, we also constructed and expressed the rM2e-ΔPly protein in E. coli. These proteins were administered intramuscularly to BALB/c mice. rM2e-ΔPly protein induces higher levels of humoral and cellular responses compared with their comprising protein mixture or rM2e alone. rM2e-ΔPly protein enhances the survival rate, reduces viral loads and inflammatory response in lung challenged with PR8. The serum induced by rM2e-ΔPly protein can protect against PR8 by passive immunity and cross-react with multiple M2e peptides derived from different IAV subtypes. After IAV and Streptococcus pneumoniae (S. pneumoniae) co-infection, rM2e-Ply protein can improve survival, lower viral and bacterial burdens, and diminish inflammatory response in the lungs. These results demonstrate that rM2e-ΔPly protein can significantly protect against influenza virus, IAV and S. pneumoniae co-infection, indicating that rM2e-ΔPly protein has the potential to become a universal influenza vaccine.


Subject(s)
Coinfection , Influenza A virus , Influenza Vaccines , Influenza, Human , Orthomyxoviridae Infections , Orthomyxoviridae , Mice , Animals , Humans , Streptococcus pneumoniae , Coinfection/prevention & control , Escherichia coli , Antibodies, Viral , Vaccination/methods , Viral Matrix Proteins , Immunization , Orthomyxoviridae Infections/prevention & control , Mice, Inbred BALB C , Adjuvants, Immunologic
5.
Microbiol Spectr ; 10(2): e0257421, 2022 04 27.
Article in English | MEDLINE | ID: mdl-35315711

ABSTRACT

G2 porcine epidemic diarrhea virus (G2 PEDV) and highly pathogenic porcine reproductive and respiratory syndrome virus 2 (HP-PRRSV2) are two of the most prevalent swine pathogens in China's swine herds, and their coinfection occurs commonly. Several PED and PRRS vaccines have been utilized in China for decades, and systemic homologous neutralizing antibodies (shnAbs) in serum are frequently used to evaluate the protective efficacy of PED and PRRS vaccines. To develop a vaccine candidate against G2 PEDV and HP-PRRSV2 coinfection, in this study, we generated a chimeric virus (rJSTZ1712-12-S) expressing S protein of G2 PEDV using an avirulent HP-PRRSV2 rJSTZ1712-12 infectious clone as the viral vector. The rJSTZ1712-12-S strain has similar replication efficacies as the parental rJSTZ1712-12 virus. In addition, animal inoculation indicated that rJSTZ1712-12-S is not pathogenic to piglets and can induce shnAbs against both G2 PEDV and HP-PRRSV2 isolates after prime-boost immunization. However, passive transfer study in neonatal piglets deprived of sow colostrum showed that rJSTZ1712-12-S-induced shnAbs may only decrease PEDV and PRRSV viremia but cannot confer sufficient protection against dual challenge of high virulent G2 PEDV XJ1904-34 strain and HP-PRRSV2 XJ17-5 isolate. Overall, this study provides the first evidence that shnAbs confer insufficient protection against PEDV and PRRSV coinfection and are inadequate for the evaluation of protective efficacy of PED and PRRS bivalent vaccine (especially for the PED vaccine). IMPORTANCE Porcine epidemic diarrhea virus (PEDV) and porcine reproductive and respiratory syndrome virus (PRRSV) coinfection occurs commonly and can synergistically reduce feed intake and pig growth. Vaccination is an effective strategy utilized for PED and PRRS control, and systemic homologous neutralizing antibodies (shnAbs) in serum are commonly used for protective efficacy evaluation of PED and PRRS vaccines. Currently, no commercial vaccine is available against PEDV and PRRSV coinfection. This study generated a chimeric vaccine candidate against the coinfection of prevalent PEDV and PRRSV in China. The chimeric strain can induce satisfied shnAbs against both PEDV and PRRSV after prime-boost inoculation in pigs. But the shnAbs cannot confer sufficient protection against PEDV and PRRSV coinfection in neonatal piglets. To the best of our knowledge, these findings provide the first evidence that shnAbs confer insufficient protection against PEDV and PRRSV coinfection and are inadequate for evaluating PED and PRRS bivalent vaccine protective efficacy.


Subject(s)
Coinfection , Porcine Reproductive and Respiratory Syndrome , Porcine epidemic diarrhea virus , Porcine respiratory and reproductive syndrome virus , Viral Vaccines , Animals , Antibodies, Neutralizing , Antibodies, Viral , Coinfection/prevention & control , Coinfection/veterinary , Female , Porcine Reproductive and Respiratory Syndrome/prevention & control , Porcine respiratory and reproductive syndrome virus/genetics , Swine , Vaccines, Combined
6.
Sci Rep ; 12(1): 2639, 2022 02 16.
Article in English | MEDLINE | ID: mdl-35173209

ABSTRACT

In this paper, we have considered a deterministic mathematical model to analyze effective interventions for meningitis and pneumonia coinfection as well as to make a rational recommendation to public healthy, policy or decision makers and programs implementers. We have introduced the epidemiology of infectious diseases, the epidemiology of meningitis, the epidemiology of pneumonia, and the epidemiology of infection of meningitis and pneumonia. The positivity and boundedness of the sated model was shown. Our model elucidate that, the disease free equilibrium points of each model are locally asymptotically stable if the corresponding reproduction numbers are less than one and globally asymptotically stable if the corresponding reproduction numbers are greater than one. Additionally, we have analyzed the existence and uniqueness of the endemic equilibrium point of each sub models, local stability and global stability of the endemic equilibrium points for each model. By using standard values of parameters we have obtained from different studies, we found that the effective reproduction numbers of meningitis [Formula: see text] and effective reproduction numbers of pneumonia [Formula: see text] that lead us to the effective reproduction number of the meningitis and pneumonia co-infected model is [Formula: see text]. Applying sensitivity analysis, we identified the most influential parameters that can change the behavior of the solution of the meningitis pneumonia coinfection dynamical system are [Formula: see text] and [Formula: see text]. Biologically, decrease in [Formula: see text] and increasing in [Formula: see text] is a possible intervention strategy to reduce the infectious from communities. Finally, our numerical simulation has shown that vaccination against those diseases, reducing contact with infectious persons and treatment have the great effect on reduction of these silent killer diseases from the communities.


Subject(s)
Basic Reproduction Number , Coinfection/epidemiology , Computer Simulation , Meningitis/epidemiology , Models, Theoretical , Pneumonia/epidemiology , Coinfection/prevention & control , Humans , Meningitis/prevention & control , Pneumonia/prevention & control , Public Health
7.
Viruses ; 14(1)2022 01 14.
Article in English | MEDLINE | ID: mdl-35062354

ABSTRACT

The susceptibility to respiratory syncytial virus (RSV) infection in early life has been associated with a deficient T-helper cell type 1 (Th1) response. Conversely, healthy adults generally do not exhibit severe illness from RSV infection. In the current study, we investigated whether Th1 cytokine IFN-γ is essential for protection against RSV and RSV-associated comorbidities in adult mice. We found that, distinct from influenza virus, prior RSV infection does not induce significant IFN-γ production and susceptibility to secondary Streptococcus pneumoniae infection in adult wild-type (WT) mice. In ovalbumin (OVA)-induced asthmatic mice, RSV super-infection increases airway neutrophil recruitment and inflammatory lung damage but has no significant effect on OVA-induced eosinophilia. Compared with WT controls, RSV infection of asthmatic Ifng-/- mice results in increased airway eosinophil accumulation. However, a comparable increase in eosinophilia was detected in house dust mite (HDM)-induced asthmatic Ifng-/- mice in the absence of RSV infection. Furthermore, neither WT nor Ifng-/- mice exhibit apparent eosinophil infiltration during RSV infection alone. Together, these findings indicate that, despite its critical role in limiting eosinophilic inflammation during asthma, IFN-γ is not essential for protection against RSV-induced exacerbation of asthmatic inflammation in adult mice.


Subject(s)
Asthma/pathology , Inflammation/immunology , Interferon-gamma/immunology , Lung/immunology , Lung/pathology , Respiratory Syncytial Virus Infections/immunology , Animals , Asthma/chemically induced , Asthma/immunology , Bronchoalveolar Lavage Fluid , Coinfection/immunology , Coinfection/microbiology , Coinfection/prevention & control , Comorbidity , Female , Inflammation/prevention & control , Interferon-gamma/genetics , Lung/microbiology , Lung/virology , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Ovalbumin/administration & dosage , Respiratory Syncytial Virus Infections/prevention & control , Th1 Cells , Th2 Cells
8.
J Virol ; 96(5): e0179121, 2022 03 09.
Article in English | MEDLINE | ID: mdl-34936487

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and seasonal influenza viruses are cocirculating in the human population. However, only a few cases of viral coinfection with these two viruses have been documented in humans with some people having severe disease and others mild disease. To examine this phenomenon, ferrets were coinfected with SARS-CoV-2 and human seasonal influenza A viruses (IAVs; H1N1 or H3N2) and were compared to animals that received each virus alone. Ferrets were either immunologically naive to both viruses or vaccinated with the 2019 to 2020 split-inactivated influenza virus vaccine. Coinfected naive ferrets lost significantly more body weight than ferrets infected with each virus alone and had more severe inflammation in both the nose and lungs compared to that of ferrets that were single infected with each virus. Coinfected, naive animals had predominantly higher IAV titers than SARS-CoV-2 titers, and IAVs were efficiently transmitted by direct contact to the cohoused ferrets. Comparatively, SARS-CoV-2 failed to transmit to the ferrets that cohoused with coinfected ferrets by direct contact. Moreover, vaccination significantly reduced IAV titers and shortened the viral shedding but did not completely block direct contact transmission of the influenza virus. Notably, vaccination significantly ameliorated influenza-associated disease by protecting vaccinated animals from severe morbidity after IAV single infection or IAV and SARS-CoV-2 coinfection, suggesting that seasonal influenza virus vaccination is pivotal to prevent severe disease induced by IAV and SARS-CoV-2 coinfection during the COVID-19 pandemic. IMPORTANCE Influenza A viruses cause severe morbidity and mortality during each influenza virus season. The emergence of SARS-CoV-2 infection in the human population offers the opportunity to potential coinfections of both viruses. The development of useful animal models to assess the pathogenesis, transmission, and viral evolution of these viruses as they coinfect a host is of critical importance for the development of vaccines and therapeutics. The ability to prevent the most severe effects of viral coinfections can be studied using effect coinfection ferret models described in this report.


Subject(s)
Antibodies, Viral/blood , COVID-19/prevention & control , Coinfection/prevention & control , Influenza Vaccines/immunology , Orthomyxoviridae Infections/prevention & control , Animals , COVID-19/immunology , Female , Ferrets/immunology , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H3N2 Subtype/genetics , Influenza A Virus, H3N2 Subtype/immunology , Orthomyxoviridae Infections/immunology , Vaccination , Virus Shedding
9.
Front Immunol ; 12: 797117, 2021.
Article in English | MEDLINE | ID: mdl-34858440

ABSTRACT

Since its emergence in 2019 SARS-CoV-2 has proven to have a higher level of morbidity and mortality compared to the other prevailing coronaviruses. Although initially most African countries were spared from the devastating effect of SARS-CoV-2, at present almost every country has been affected. Although no association has been established between being HIV-1-infected and being more vulnerable to contracting COVID-19, HIV-1-infected individuals have a greater risk of developing severe COVID-19 and of COVID-19 related mortality. The rapid development of the various types of COVID-19 vaccines has gone a long way in mitigating the devastating effects of the virus and has controlled its spread. However, global vaccine deployment has been uneven particularly in Africa. The emergence of SARS-CoV-2 variants, such as Beta and Delta, which seem to show some subtle resistance to the existing vaccines, suggests COVID-19 will still be a high-risk infection for years. In this review we report on the current impact of COVID-19 on HIV-1-infected individuals from an immunological perspective and attempt to make a case for prioritising COVID-19 vaccination for those living with HIV-1 in Sub-Saharan Africa (SSA) countries like Malawi as one way of minimising the impact of COVID-19 in these countries.


Subject(s)
COVID-19/mortality , COVID-19/prevention & control , Coinfection/prevention & control , HIV Infections/mortality , Mass Vaccination/methods , Africa South of the Sahara , CD4-Positive T-Lymphocytes/immunology , HIV Seropositivity , Health Priorities , Humans , SARS-CoV-2/genetics , SARS-CoV-2/immunology
10.
Int J Clin Pract ; 75(12): e14997, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34714574

ABSTRACT

BACKGROUND: Respiratory failure and death are the leading causes of severe Coronavirus disease 2019 (COVID-19). Hyper-inflammation and cytokine storm cause lung damage. This study aimed to compare the low-dose and high-dose effects of tocilizumab, an IL-6 receptor antagonist. METHOD: Patients with severe pneumonia and hyper-inflammation signs because of COVID-19 were included in this retrospective study. Patients receiving tocilizumab <200 mg intravenously were classified as the low-dose group, and receiving ≥200 mg as the high-dose group, and those not treated with tocilizumab as the control group. Demographic and clinical data of patients who died and survived in both low-high dose and control patients were compared. According to symptom day and radiological infiltration, patients with tocilizumab were also evaluated in two groups as early and late periods at tocilizumab administration time. RESULTS: A total of 160 patients were included in the study; 70 were treated with a low dose and 50 with high-dose tocilizumab. Forty patients were in the control group. Age, comorbidity and clinical features were similar in the control, low-dose tocilizumab and high-dose tocilizumab groups. The mortality rate (12.9%, 30.0%, 37.5, P = .008) was less in the low-dose tocilizumab group. The secondary infection rate was higher in the high-dose group than in the low-dose tocilizumab and control groups (44.0%, 10.0%, 10.0%, P < .001). Distinguishing between those patients who died and survived, age (OR: 1.1589, P < .001), higher APACHE II scores (OR: 1.225, P = .001) and needs for non-invasive mechanical ventilation (OR: 14.469, P < .001) were the most critical risk factors. Low-dose tocilizumab was associated with a lower mortality rate (OR: 0.244, P = .012). CONCLUSION: The use of tocilizumab at a low dose is associated with lower secondary infections and mortality.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19 Drug Treatment , Coinfection , Coinfection/prevention & control , Humans , Retrospective Studies , Treatment Outcome
11.
PLoS Negl Trop Dis ; 15(10): e0009912, 2021 10.
Article in English | MEDLINE | ID: mdl-34714824

ABSTRACT

Malaria, a disease caused by Plasmodium parasites, remains a major threat to public health globally. It is the most common disease in patients with sleeping sickness, another parasitic illness, caused by Trypanosoma brucei. We have previously shown that a T. brucei infection impairs a secondary P. berghei liver infection and decreases malaria severity in mice. However, whether this effect requires an active trypanosome infection remained unknown. Here, we show that Plasmodium liver infection can also be inhibited by the serum of a mouse previously infected by T. brucei and by total protein lysates of this kinetoplastid. Biochemical characterisation showed that the anti-Plasmodium activity of the total T. brucei lysates depends on its protein fraction, but is independent of the abundant variant surface glycoprotein. Finally, we found that the protein(s) responsible for the inhibition of Plasmodium infection is/are present within a fraction of ~350 proteins that are excreted to the bloodstream of the host. We conclude that the defence mechanism developed by trypanosomes against Plasmodium relies on protein excretion. This study opens the door to the identification of novel antiplasmodial intervention strategies.


Subject(s)
Coinfection/prevention & control , Liver/parasitology , Malaria/parasitology , Plasmodium/physiology , Protozoan Proteins/blood , Trypanosoma brucei brucei/metabolism , Trypanosomiasis, African/parasitology , Animals , Coinfection/parasitology , Humans , Male , Mice , Mice, Inbred C57BL , Plasmodium/genetics , Protozoan Proteins/genetics , Trypanosoma brucei brucei/genetics , Trypanosomiasis, African/blood
12.
Pediatr Infect Dis J ; 40(9S): S69-S78, 2021 Sep 01.
Article in English | MEDLINE | ID: mdl-34448746

ABSTRACT

BACKGROUND: HIV-1 infection predisposes to an increased burden of pneumonia caused by community-acquired and opportunistic pathogens. METHODS: Within the context of the Pneumonia Etiology Research for Child Health case-control study of under 5 pneumonia, we investigated the etiology of World Health Organization-defined severe/very severe pneumonia requiring hospitalization in South African HIV-infected children. Nasopharyngeal-oropharyngeal swabs and blood, collected from cases and age- and season-matched HIV-infected controls attending outpatient antiretroviral therapy (ART) clinics, were analyzed using molecular diagnostic methods. Cases were also investigated for tuberculosis. Etiologic fractions among cases with radiologically confirmed pneumonia were derived using Bayesian analytic techniques. RESULTS: Of 115 HIV-infected cases, 89 (77.4%) had radiologically confirmed pneumonia. Severe immunosuppression (adjusted odds ratio, 32.60; 95% confidence interval, 7.25-146.64) was significantly associated with radiologically confirmed pneumonia. Cotrimoxazole prophylaxis (46.4% vs. 77.4%) and ART (28.2% vs. 83.1%) coverage were significantly lower in cases compared with ART-clinic controls. An etiologic agent was identified in 99.0% of the radiologically confirmed cases. The 'top 4' pathogens associated with radiologically confirmed pneumonia were Pneumocystis jirovecii [23.0%; 95% credible interval (CrI), 12.4%-31.5%], Staphylococcus aureus (10.6%; 95% CrI, 2.2%-20.2%), pneumococcus (9.5%; 95% CrI, 2.2%-18.0%) and respiratory syncytial virus (9.3%; 95% CrI, 2.2%-14.6%). Bacteremia (6.7%) and in-hospital death (10.1%) were frequent among those with radiologically confirmed disease. CONCLUSIONS: Pneumocystis jirovecii, S. aureus, pneumococcus and respiratory syncytial virus contribute a considerable burden of radiologically confirmed pneumonia in South African HIV-infected children under 5 years. Expediting access to ART and cotrimoxazole prophylaxis would decrease the burden of pneumonia in these children.


Subject(s)
AIDS-Related Opportunistic Infections/etiology , Anti-Retroviral Agents/therapeutic use , Coinfection/etiology , HIV-1 , Pneumonia/etiology , AIDS-Related Opportunistic Infections/diagnosis , AIDS-Related Opportunistic Infections/epidemiology , AIDS-Related Opportunistic Infections/prevention & control , Bayes Theorem , Case-Control Studies , Child Health , Child, Preschool , Coinfection/diagnosis , Coinfection/epidemiology , Coinfection/prevention & control , Developing Countries , Female , Hospitalization , Humans , Infant , Logistic Models , Male , Patient Acuity , Pneumonia/diagnosis , Pneumonia/epidemiology , Pneumonia/prevention & control , Risk Factors , South Africa/epidemiology
13.
Viruses ; 13(5)2021 05 13.
Article in English | MEDLINE | ID: mdl-34068217

ABSTRACT

Patients after LT due to combined HBV/HDV infection are considered to be high-risk patients for recurrence of hepatitis B and D. To date, life-long prophylaxis with hepatitis B immunoglobulin (HBIG) and replication control with nucleos(t)ide analogs (NA) remains standard. We examined the course of 36 patients that underwent liver transplantation from 1989 to 2020 for combined HBV/HDV-associated end-stage liver disease in this retrospective study. Seventeen patients eventually discontinued HBIG therapy for various reasons. Their graft function, histopathological findings from routine liver biopsies and overall survival were compared with those that received an unaltered NA-based standard regimen combined with HBIG. The median follow-up was 204 and 227 months, respectively. The recurrence of HBV was 25% and did not differ between the groups of standard reinfection prophylaxis NA/HBIG (21.1%) and HBIG discontinuation (29.4%); (p = 0.56). No significant differences were found regarding the clinical course or histopathological aspects of liver tissue damage (inflammation, fibrosis, steatosis) between these two groups. Overall, and adjusted survival did not differ between the groups. Discontinuation of HBIG in stable patients after LT for combined HBV/HDV did not lead to impaired overall survival or higher recurrence rate of HBV/HDV infection in this long-term follow-up. Therefore, the recommendation of the duration of HBG administration must be questioned. The earliest time of discontinuation remains unclear.


Subject(s)
Coinfection/prevention & control , Hepatitis B virus/immunology , Hepatitis B/prevention & control , Hepatitis D/prevention & control , Hepatitis Delta Virus/immunology , Immunization, Passive , Liver Transplantation/adverse effects , Biomarkers , Coinfection/epidemiology , Female , Hepatitis B/epidemiology , Hepatitis D/epidemiology , Humans , Immunohistochemistry , Liver Transplantation/statistics & numerical data , Male , Postoperative Period , Prognosis , Recurrence
16.
PLoS Pathog ; 17(5): e1009555, 2021 05.
Article in English | MEDLINE | ID: mdl-34015063

ABSTRACT

Although a growing number of studies suggest interactions between Schistosoma parasites and viral infections, the effects of schistosome infections on the host response to viruses have not been evaluated comprehensively. In this systematic review, we investigated how schistosomes impact incidence, virulence, and prevention of viral infections in humans and animals. We also evaluated immune effects of schistosomes in those coinfected with viruses. We screened 4,730 studies and included 103. Schistosomes may increase susceptibility to some viruses, including HIV and Kaposi's sarcoma-associated herpesvirus, and virulence of hepatitis B and C viruses. In contrast, schistosome infection may be protective in chronic HIV, Human T-cell Lymphotropic Virus-Type 1, and respiratory viruses, though further research is needed. Schistosome infections were consistently reported to impair immune responses to hepatitis B and possibly measles vaccines. Understanding the interplay between schistosomes and viruses has ramifications for anti-viral vaccination strategies and global control of viral infections.


Subject(s)
Antiviral Agents/pharmacology , Coinfection/prevention & control , Immunity/immunology , Schistosoma/immunology , Schistosomiasis/complications , Virus Diseases/prevention & control , Viruses/immunology , Animals , Coinfection/etiology , Coinfection/pathology , Humans , Schistosomiasis/parasitology , Virus Diseases/etiology , Virus Diseases/pathology
17.
Virology ; 559: 100-110, 2021 07.
Article in English | MEDLINE | ID: mdl-33865073

ABSTRACT

While T cell immunity is an important component of the immune response to Zika virus (ZIKV) infection generally, the efficacy of these responses during pregnancy remains unknown. Here, we tested the capacity of CD8 lymphocytes to protect from secondary challenge in four macaques, two of which were depleted of CD8+ cells prior to rechallenge with a heterologous ZIKV isolate. The initial challenge during pregnancy produced transcriptional signatures suggesting complex patterns of immune modulation as well as neutralizing antibodies that persisted until rechallenge, which all animals efficiently controlled, demonstrating that the primary infection conferred adequate protection. The secondary challenge promoted activation of innate and adaptive immune cells, possibly suggesting a brief period of infection prior to clearance. These data confirm that ZIKV infection during pregnancy induces sufficient immunity to protect from a secondary challenge and suggest that this protection is not dependent on CD8 T cells.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Coinfection/immunology , Coinfection/prevention & control , Zika Virus Infection/immunology , Zika Virus/genetics , Zika Virus/immunology , Animals , Antibodies, Neutralizing/blood , Chlorocebus aethiops , Female , Gene Expression Profiling , Kinetics , Macaca , Pregnancy , Vero Cells , Zika Virus Infection/virology
18.
Microbes Infect ; 23(8): 104813, 2021.
Article in English | MEDLINE | ID: mdl-33798714

ABSTRACT

Respiratory tract coinfections, specifically involving influenza A virus (IAV) and Streptococcus pneumoniae (S. pneumoniae), remain a major health problem worldwide. Secondary bacterial pneumonia is a common complication and an important cause of mortality related to seasonal and pandemic influenza infections. Vaccination is a basic control strategy against influenza and S. pneumoniae. The fusion protein DnaJ-ΔA146Ply is a vaccine candidate which can induce immune responses against pneumococcal infections via mucosal and subcutaneous immunization in mice. In the present study, we established a co-infection model using mouse-adapted laboratory strains of IAV (PR8) and S. pneumoniae (19F) in mice intranasally and subcutaneously immunized with DnaJ-ΔA146Ply. Our results showed that vaccinated mice suffered decreased weight loss compared with control mice. The survival rates were higher in intranasally and subcutaneously immunized mice than in control mice. In addition, the bacterial loads in nasal washes and lung homogenates were lower in vaccinated mice than in control mice. Furthermore, lung damage was alleviated in vaccinated mice compared with control mice, with less broken alveoli and less proinflammatory cytokine production. Taken together, these results indicate that vaccination with DnaJ-ΔA146Ply shows protective potential against influenza and S. pneumoniae co-infection in mice.


Subject(s)
Coinfection , Influenza A virus , Influenza Vaccines , Influenza, Human , Pneumococcal Infections , Animals , Coinfection/prevention & control , Humans , Immunization , Mice , Streptococcus pneumoniae , Vaccination
19.
J Med Virol ; 93(7): 4411-4419, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33792956

ABSTRACT

In late December 2019, an outbreak of a novel coronavirus which caused coronavirus disease 2019 (COVID-19) was initiated. Acute kidney injury (AKI) was associated with higher severity and mortality of COVID-19. We aimed to evaluate the effects of comorbidities and medications in addition to determining the association between AKI, antibiotics against coinfections (AAC) and outcomes of patients. We conducted a retrospective study on adult patients hospitalized with COVID-19 in a tertiary center. Our primary outcomes were the incidence rate of AKI based on comorbidities and medications. The secondary outcome was to determine mortality, intensive care unit (ICU) admission, and prolonged hospitalization by AKI and AAC. Univariable and multivariable logistic regression method was used to explore predictive effects of AKI and AAC on outcomes. Out of 854 included participants, 118 patients developed AKI in whom, 57 used AAC and 61 did not. Hypertension and diabetes were the most common comorbidities in patients developed AKI. AAC, lopinavir/ritonavir, ribavirin, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, and corticosteroids had significant higher rate of administration in patients developed AKI. AAC were associated with higher deaths (odds ratio [OR] = 5.13; 95% confidence interval (CI): 3-8.78) and ICU admission (OR = 5.87; 95%CI: 2.81-12.27), while AKI had higher OR for prolonged hospitalization (3.37; 95%CI: 1.76-6.45). Both AKI and AAC are associated with poor prognosis of COVID-19. Defining strict criteria regarding indications and types of antibiotics would help overcoming concomitant infections and minimizing related adverse events.


Subject(s)
Acute Kidney Injury/epidemiology , Antiviral Agents/therapeutic use , COVID-19 Drug Treatment , COVID-19/pathology , SARS-CoV-2/drug effects , Acute Kidney Injury/drug therapy , Acute Kidney Injury/virology , Adult , Angiotensin-Converting Enzyme Inhibitors , Azithromycin/therapeutic use , Coinfection/drug therapy , Coinfection/prevention & control , Critical Care/statistics & numerical data , Drug Combinations , Female , Hospital Mortality , Hospitalization/statistics & numerical data , Humans , Iran/epidemiology , Linezolid/therapeutic use , Lopinavir/therapeutic use , Male , Middle Aged , Retrospective Studies , Ribavirin/therapeutic use , Ritonavir/therapeutic use , Treatment Outcome , Vancomycin/therapeutic use
20.
Rev. cuba. med. trop ; 73(1): e376, tab, graf
Article in Spanish | LILACS, CUMED | ID: biblio-1280322

ABSTRACT

Introducción: La fascioliasis es causada por el trematodo Fasciola hepatica que afecta a animales herbívoros, omnívoros y al humano. Los niños de edad escolar son los más afectados y el órgano más dañado es el hígado. Este parásito requiere de reservorio y huésped intermediario para completar su ciclo biológico. Objetivo: Determinar la asociación de la fascioliasis con el estado nutricional y coinfección enteroparasitaria en niños. Métodos: La investigación se realizó entre septiembre de 2016 y abril de 2017 en el distrito de Santa María de Chicmo, región Apurímac. El estudio fue analítico de corte transversal. La población de niños de 6 a 16 años estuvo constituida por 2 172 individuos. El tamaño de muestra fue de 435 niños y se determinó mediante un muestreo simple al azar. Además, para que el muestreo fuera más eficiente se distribuyó el tamaño total de la muestra entre los estratos I.E. Primaria e I.E. Secundaria, para un resultado de 209 y 226 muestras, respectivamente. Sin embargo, se logró tomar 493 muestras coprológicas y serológicas repartidas proporcionalmente entre la totalidad de 23 instituciones educativas. Resultados: La prevalencia de fascioliasis fue de 5,3 por ciento (26/493; IC95 por ciento =3,2-7,4). Las instituciones educativas con mayor prevalencia fueron: Taramba con 17,2 por ciento (5/29; IC95 por ciento = 5,9-35,8), Libertadores de América con 16,1 por ciento (5/31; IC95 por ciento = 5,5-33,7), Mariano Melgar con 15 por ciento (3/20; IC95 por ciento = 3,2-37,9) y Nuestra Señora de Guadalupe con 10,8 por ciento (4/37; IC95 por ciento = 3-25,4). No se encontró asociación de fascioliasis con la valoración nutricional antropométrica ni con la coinfección enteroparasitaria en niños (p˃ 0,05). Conclusiones: La fascioliasis no estaría afectando el estado nutricional de los niños; asimismo, los signos clínicos, atribuidos a fascioliasis, corresponderían también a la alta presentación de parásitos entéricos(AU)


Introduction: Fascioliasis is caused by the trematode Fasciola hepatica and affects herbivorous and omnivorous animals as well as humans. Schoolchildren are the most affected group, and the organ most commonly targeted is the liver. This parasite requires an intermediate reservoir and host to complete its biological cycle. Objective: Determine the association of fascioliasis to nutritional status and enteroparasite coinfection in children. Methods: An analytical cross-sectional study was conducted from September 2016 to April 2017 in the district of Santa María de Chicmo, Apurímac Region. The child population aged 6-16 years was composed of 2 172 individuals. The sample size was 435 children, and it was determined by simple random sampling. Additionally, in order for the sampling to be more efficient, the total sample size was distributed between the strata Primary E.I. and Secondary E.I., for 209 and 226 samples, respectively. However, 493 coprological and serological samples were proportionally taken from the total 23 educational institutions. Results: Prevalence of fascioliasis was 5.3 percent (26/493; CI95 percent=3.2-7.4). The educational institutions with the highest prevalence were Taramba with 17.2 percent (5/29; CI95 percent= 5.9-35.8), Libertadores de América with 16.1 percent (5/31; CI95 percent= 5.5-33.7), Mariano Melgar with 15 percent (3/20; CI95 percent= 3.2-37.9) and Nuestra Señora de Guadalupe with 10.8 percent (4/37; CI95 percent= 3-25.4). No association was found between fascioliasis and nutritional anthropometric assessment or enteroparasite coinfection in children (p˃ 0.05). Conclusions: Fascioliasis was not found to affect the nutritional status of children. On the other hand, the clinical signs attributed to fascioliasis also correspond to the high presentation of enteric parasites(AU)


Subject(s)
Humans , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Fascioliasis/complications , Intestinal Diseases, Parasitic/etiology , Fascioliasis/diet therapy , Coinfection/prevention & control
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