Viral hepatitis and human immunodeficiency virus coinfections in Asia

Hepatitis B virus(HBV), hepatitis C virus(HCV),and human immunodeficiency virus(HIV) affect many people in Asian countries, although there are geographic differences. Both HBV and HIV(HBV/HIV) and HCV/HIV co-infections are highly prevalent in Asia. Hetero- and homosexual, injection drug use, and geographic area are strong predictors of HBV, HCV, and HIV serostatus. In HBV endemic regions, the prevalence and genotype distribution of HBV/HIV coinfection is almost comparable with that in the general population. In Japan, where HBV has low endemicity, the prevalence of HBV/HIV co-infection is approximately 10-fold higher than that in the general population, and HBV Ae is the most common subgenotype among HIV infected individuals. Highly active antiretroviral therapy(HAART) is an effective treatment for HIV/Acquired Immune Deficiency Syndrome. Lamivudine, a component of HAART, is an effective treatment for HBV, HIV, and HBV/HIV co-infection; however, cost, emerging drug resistance, antiretroviral-associated liver toxicity and liver-related morbidity due to HCV progression are particular concerns. HCV/HIV co-infection may accelerate the clinical progression of both HCV and HIV. The high prevalence of HBV/HIV and HCV/HIV co-infections in Asia underscores the need to improve prevention and control measures, as fewer evidencebased prevention strategies are available(compared with Western countries). In this review, the most recent publications on the prevalence of HBV/HIV and HCV/HIV co-infections and related issues, such as therapy and problems in Asia, are updated and summarized.

Prevalence of bacteria, fungi, and virus coinfections with SARS-CoV-2 Omicron variant among patients with severe COVID-19 in Guangzhou, China, winter 2022

The status of coinfection during the national outbreak of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron BA.5.2 or BF.7 in China in the winter of 2022,which is suspected to contribute substantially to the overloaded severe cases,needs to be investigated.We analyzed the coinfection status of 385 severe patients infected with the Omicron variant in Guangzhou using metagenomic sequencing.We found that 317(82.3%)patients were coinfected with at least one additional pathogen(s),including bacteria(58.7%),fungi(27.1%)and viruses(73.5%).Pseudomonas aeruginosa(P.aeruginosa)(24.2%),Staphylococcus aureus(S.aureus)(14.0%),andKlebsiella pneumoniae(K.pneumonia)(13.4%)ranked as the top three coinfected bacteria.Aspergillus fumigatus(A.fumigatus)(39.5%),Pneumocystis jirovecii(P.jirovecii)(24.4%)andCanidia albicans(C.albicans)(22.1%)were the top three coinfected fungi.Epstein-Barr virus(EBV)(63.1%),Human herpesvirus 7(HHV-7)(34.8%),and Herpes simplex virus 1(HSV-1)(32.6%)were the top three coinfected viruses.Of note,the detection of multiple coinfections of potential pathogenic bacteria,fungi,and viruses,despite lacking consistent patterns,highlighted a complicated synergistic contribution to disease severity.Our study presents the most comprehensive spectrum of bacterial,fungal,and viral coinfections in Omicron-associated severe coronavirus disease 2019(COVID-19),implying that the coinfection of conditional pathogens might synergistically deteriorate the Omicron infection outcomes.

Tuberculosis-diabetes comorbidities: Mechanistic insights for clinical considerations and treatment challenges

Tuberculosis(TB)remains a leading cause of death among infectious diseases,particularly in poor countries.Viral infections,multidrug-resistant and ex-tensively drug-resistant TB strains,as well as the coexistence of chronic illnesses such as diabetes mellitus(DM)greatly aggravate TB morbidity and mortality.DM[particularly type 2 DM(T2DM)]and TB have converged making their control even more challenging.Two contemporary global epidemics,TB-DM behaves like a syndemic,a synergistic confluence of two highly prevalent diseases.T2DM is a risk factor for developing more severe forms of multi-drug resistant-TB and TB recurrence after preventive treatment.Since a bidirectional relationship exists between TB and DM,it is necessary to concurrently treat both,and promote recommendations for the joint management of both diseases.There are also some drug-drug interactions resulting in adverse treatment outcomes in TB-DM patients including treatment failure,and reinfection.In addition,autophagy may play a role in these comorbidities.Therefore,the TB-DM comorbidities present several health challenges,requiring a focus on multidisciplinary collaboration and integrated strategies,to effectively deal with this double burden.To effectively manage the comorbidity,further screening in affected countries,more suitable drugs,and better treatment strategies are required.

Evaluating the role of interleukin-2 and interleukin-12 in pediatric patients with concurrent Mycoplasma pneumoniae and Epstein-Barr virus infections

BACKGROUND Mycoplasma pneumoniae(MP)frequently causes respiratory infections in children,whereas Epstein-Barr virus(EBV)typically presents subclinical manifestations in immunocompetent pediatric populations.The incidence of MP and EBV coinfections is often overlooked clinically,with the contributory role of EBV in pulmonary infections alongside MP remaining unclear.AIM To evaluate the serum concentrations of interleukin-2(IL-2)and interleukin-12(IL-12)in pediatric patients with MP pneumonia co-infected with EBV and assess their prognostic implications.METHODS We retrospectively analyzed clinical data from patients diagnosed with MP and EBV co-infection,isolated MP infection,and a control group of healthy children,spanning from January 1,2018 to December 31,2021.Serum IL-2 and IL-12 levels were quantified using enzyme-linked immunosorbent assay.Logistic regression was employed to identify factors influencing poor prognosis,while receiver operating characteristic(ROC)curves evaluated the prognostic utility of serum IL-2 and IL-12 levels in co-infected patients.RESULTS The co-infection group exhibited elevated serum IL-2 and C-reactive protein(CRP)levels compared to both the MP-only and control groups,with a reverse trend observed for IL-12(P<0.05).In the poor prognosis cohort,elevated CRP and IL-2 levels,alongside prolonged fever duration,contrasted with reduced IL-12 levels(P<0.05).Logistic regression identified elevated IL-2 as an independent risk factor and high IL-12 as a protective factor for adverse outcomes(P<0.05).ROC analysis indicated that the area under the curves for IL-2,IL-12,and their combination in predicting poor prognosis were 0.815,0.895,and 0.915,respectively.CONCLUSION Elevated serum IL-2 and diminished IL-12 levels in pediatric patients with MP and EBV co-infection correlate with poorer prognosis,with combined IL-2 and IL-12 levels offering enhanced predictive accuracy.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Coinfection with Malaria in Selected States in Nigeria

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Plasmodium species are the causative agents of coronavirus disease 2019 (COVID-19) and malaria respectively with similar clinical presentations. The objective of this study is to determine the burden of co-infection of SARS-CoV-2 and malaria in the general population. Five (5 mLs) of blood samples were collected for SARS-CoV-2 and malaria parasite test. The malaria test was performed using a commercially available one-step malaria antigen Plasmodium falciparum histidine-rich protein 2 (Pf HRP-II) rapid test kit. The results of the study showed that the participants that were coinfected with SARS-CoV-2 IgG and malaria were 13 (2.5%) in Lagos, 1114 (39.1%) in Delta and 49 (2.3%) in Sokoto States. The prevalence of coinfection of SARS-CoV-2 and malaria in urban areas in Lagos, Delta and Sokoto States were 7 (2.2%), 1373 (48.1%), and 5 (0.2%) respectively. In rural areas, the prevalence of coinfection of SARS-CoV-2 and malaria in Lagos, Delta and Sokoto States were 6 (0.3%), 365 (12.8%), and 44 (2.1%) respectively in this study. This suggests that participants in the urban areas were more prone to co-infections than the rural areas in Lagos and Delta states, while it was otherwise in Sokoto State. In conclusion, the co-infection of SARS-CoV-2 and malaria was very high in Delta State compared to the other States. It is important for clinics to screen for both diseases when patients present with symptoms of malaria. This is because the infections have similar symptoms and the public is quick to assume malaria infection without diagnosing for COVID-19 and vice versa.

The Prevalence and Clinical Manifestations of Co-Infection in Pediatric Infectious Mononucleosis: A Single-Centered, Retrospective Study

Background: Recent studies indicate that the incidence of infectious mononucleosis (IM) has increased in China. Furthermore, it has been shown that children diagnosed with IM are prone to acquiring other pathogens. However, there is limited research on the prevalence of these co-infections in children with IM. Thus, we conducted this study to determine the prevalence of coinfections and common pathogens, as well as to compare clinical manifestations in children with and without coinfections. Methods: This retrospective observational study was conducted at the Department of Pediatrics Zhongnan Hospital of Wuhan University, Wuhan, China, with data from January 2018 to January 2023. Data, including demographics, symptoms, lab results, and complications, were collected from the hospital&#8217;s electronic database and analyzed. The statistical analysis included descriptive statistics, independent samples t-tests and Mann-Whitney tests to compare the means of continuous variables. Statistical significance was determined by p-values less than 0.05. Results: The study involved 216 participants diagnosed with IM, predominantly males (61.6%) aged 0 - 4 years (50.9%). Coinfection was detected in 39.8% of children, with multiple pathogens present in 33.72% of these cases. Among coinfection cases, 40% occurred in children under 5 years old, and females made up 54.2% of these cases. Mycoplasma pneumoniae (MP) was the most prevalent pathogen, accounting for 18.1% of cases. Influenza B (IFB) and Influenza A (IFA) viruses were found in 16.7% and 13.9% of participants, respectively, indicating a notable occurrence of respiratory pathogen coinfections. Male gender, fever, tonsillopharyngitis, lower HGB levels, higher ESR, CRP, and AST levels were correlated with coinfections. Conclusion: In summary, the study revealed a high prevalence of coinfections among children diagnosed with IM, particularly involving Mycoplasma pneumoniae and influenza viruses. These coinfections were notably common in children under 5 years old and were more frequent among females. Clinical manifestations such as fever and tonsillopharyngitis, along with specific laboratory findings including lower hemoglobin levels, elevated ESR, CRP and AST levels, were found to be correlated with coinfections.

Challenges of the Global COVID-19 Pandemic and Invasive Fungal Pathogens in SARS-COV-2 Associations: A Dangerous Relationship

Background: COVID-19 is a rapidly transmissible pneumonia-like illness caused by SARS-CoV-2 that out broke in China in 2019 and is currently circulating worldwide. In the current context of the SARS-CoV-2 pandemic, complications are observed in clinical settings for the treatment of severe COVID-19 disease in nosocomial settings, due to cases of fungal co-infections. Objective: To carry out a review on fungal infections associated with respiratory infections caused by COVID-19 (Sars-Cov-2) and their aggravation. Methodology: The purpose of this study is to inform the reader about the characteristics of SARS-CoV-2 and the main fungal species that are affecting patients undergoing treatment for severe COVID-19, provoking discussion of the importance of the proposed topic, in relation to co-infections by different fungal microorganisms. Result: 80 scientific studies were selected, resulting from patients with COVID-19 and most commonly observed in patients with a history of comorbidities such as diabetes mellitus, hypertension, kidney disease, severe liver disease, oncological diseases, obesity and with severe COVID-19. These data do not represent the total number of records of the disease in the world, but cases reported by researchers in their series, showing the overlapping of fungal co-infection through the compromised immune status due to the use of therapeutic drugs, dysregulation of the microbiota, age of patients and the severity itself of the severe inflammation caused by COVID-19. Conclusion: The immunosuppression caused by the infection of COVID-19 concomitant with its therapy through corticosteroid therapy and comorbidities of the patients made fungal infections more susceptible, and these interfere in the evolution of the case and in the treatment of COVID-19, being relevant to distinguish secondary infections to therapy and the best possible reconstitution of the clinical picture.

Prevalence of Coinfection Malaria-Covid-19 at the International Hospital Center of Kinshasa during the 3rd Wave of the Pandemic

Background: Since 2019, Covid-19 pandemic has afflicted the world and countries of Africa. Despite the limited resources, these countries already disturbed by multiple diseases that have not yet been controlled such as malaria, must face this pandemic whose success in the management depends on the early detection of the disease. The objective of this study was to determine the prevalence of Malaria-Covid-19 coinfection in our environment. Methods: This was a retrospective analysis of patients’ data with Covid-19 infection from May to July 2021 at the International Hospital center of Kinshasa “CHIK”. We collected data and analysis was performed on the sociodemographic parameters, the notion of anticovid-19 vaccination as well as the duration of the symptomatology before the consultation, the clinical manifestations and the laboratory data available while including the data of the thick drop. Results: A total of 84 patients were registered with an average age of 35.23 ± 12.74 years. The male sex was predominant (82.1%). The Indian community was the most affected (44.2%). The average of days elapsed before the consultation of 3.63 days. The anti-Covid-19 vaccination rate was 20.3%. The prevalence of Malaria-Covid-19 coinfection was 29.76%. In coinfected patients, fever and cough were more reported (64%). Regarding biological and inflammatory parameters, 31.8% of coinfected patients had a platelet count less than 150,000 elements/mm3 compared to 11.6% in non-Co-infected (p = 0.046). Conclusion: The Malaria-Covid-19 comorbidity prevalence is high in Malaria endemic country like Democratic Republic of Congo (DRC). It is necessary to make better distinction, to detect early the comorbidity in order to better guide care and not be limited to treating malaria, letting the Covid-19 evolve.

Coexisting cytomegalovirus colitis in an immunocompetent patient with Clostridioides difficile colitis:A case report

BACKGROUND Clostridioides difficile(C.difficile)colitis is one of the most common infections in hospitalized patients,characterized by fever and diarrhea.It usually improves after appropriate antibiotic treatment;if not,comorbidities should be considered.Cytomegalovirus(CMV)colitis is a possible co-existing diagnosis in patients with C.difficile infection with poor treatment response.However,compared with immunocompromised patients,CMV colitis in immunocompetent patients is not well studied.CASE SUMMARY We present an unusual case of co-existing CMV colitis in an immunocompetent patient with C.difficile infection.An 80-year-old female patient was referred to the infectious disease department due to diarrhea,abdominal discomfort,and fever for 1 wk during her hospitalization for surgery.C.difficile toxin B polymerase chain reaction on stool samples was positive.After C.difficile infection was diagnosed,oral vancomycin treatment was administered.Her symptoms including diarrhea,fever and abdominal discomfort improved for ten days.Unfortunately,the symptoms worsened again with bloody diarrhea and fever.Therefore,a sigmoidoscopy was performed for evaluation,showing a longitudinal ulcer on the sigmoid colon.Endoscopic biopsy confirmed CMV colitis,and the clinical symptoms improved after using ganciclovir.CONCLUSION Co-existing CMV colitis should be considered in patients with aggravated C.difficile infection on appropriate treatment,even in immunocompetent hosts.

Mortality and Morbidity among COVID-19-Associated Mucormycosis Patients in Iran: A Prospective Cohort Study

Background: The key contribution of this paper is from investigating the mortality and morbidity rates and related factors associated with COVID-19-associated-mucormycosis among Iranian patients. The existing literature is scarce on this topic, particularly in the context of Iran. The present study investigates mortality and morbidity among 62 confirmed COVID-19-associated-mucormycosis Iranian patients in relation to their demographic characteristics, laboratory test results, predisposing factors, and COVID-related factors. Material and Methods: In this prospective cohort study, the patients were identified in the fifth wave of the disease, between 1st August and 15th October 2021, with data collected at baseline with a three-week follow-up. This was a multicenter investigation with patients admitted to two clinics in Iran. 62 participants were admitted, with the key criteria of them being COVID-19-associated-mucormycosis patients. 53 out of 60 patients underwent corticosteroid therapy and debridement surgery. Intravenous remdesivir (200 mg/ kg/day at day 1, 100 mg/kg/day in following days for up to 5 days) and corticosteroids were administered for 53 out 54 patients. Oxygen therapy was only needed for 30% (n = 19) of the patients. Results: A 40% mortality rate was observed within the three-week follow-up, with deaths concentrated among those with controlled diabetes mellitus (61%) and long-term diabetes mellitus patients (an average of eight versus four years). Higher mortality was also observed in patients with higher leucocytes and those with rhino-orbital-cerebral (59%), followed by nasal (55.6%) mucormycosis. Among survivors, 32% were reinfected, and 56% suffered from loss of vision. Conclusion: The study concludes that mucormycosis is associated with a higher mortality rate among COVID-19 patients with diabetes mellitus, particularly corticosteroid recipients. Thus, urgent attention to this coinfection is warranted in Iran.

The Level of CD4⁺T Cell Count among Reproductive Age Women Coinfected with Human Immune Virus, Hepatitis Surface Antigen and Herpes Simplex Virus in Kogi State, Nigeria

Background: There are pockets of evidence to show the existence of co-infections of viral particles in humans. Aim: The study aimed at evaluating the CD4+ T cell count among women of reproductive age co-infected with human immune virus, hepatitis surface antigen and herpes simplex virusin Kogi state, Nigeria. Methodology: 342 females of reproductive age within the ages of 15 - 49 years participated in this study. They were recruited from various local government areas of three Senatorial districts of Kogi state. Blood samples were collected from participants and analyzed for HSV1/HSV2, HIV, HBsAg and CD4 using different scientific methods and procedures. Results: There was no significant differences in mean CD4+ T cell counts between subjects who tested positive and those who tested negative for only HSV1 (p = 0.61), HSV2 (p = 0.95), HIV (p = 0.48) and co-infection for HSV1, HSV2, HIV (0.68). In contrast, mean CD4+ T cell count was significantly higher in those who tested positive compared with those who tested negative for HBsAg alone (p = 0.03) and those co-infected with HSV1, HSV2, HBsAg (p = 0.01). Analysis of variance (ANOVA) indicated no significant differences in CD4+ T cell counts among the different classes of infections. Conclusion: This study shows no decline in the count of CD4+ T cell on the co-infections of HSV1, HSV2 and HIV, but higher significant difference in those co-infected with HSV1, HSV2 and HBsAg was recorded among the women of child bearing age in Kogi state.

Early initiation of antiretroviral treatment: Challenges in the Middle East and North Africa

New World Health Organization guidelines recommend the initiation of antiretroviral treatment(ART) for asymptomatic patients with CD4+ T-cell counts of ≤ 500 cells/mm3. Substantial reduction of human immunodeficiency virus(HIV) transmission is addressed as a major public health outcome of this new approach. Middle East and North Africa(MENA), known as the area of controversies in terms of availability of comprehensive data, has shown concentrated epidemics among most of it's at risk population groups. Serious challenges impede the applicability of new guidelines in the MENA Region. Insufficient resources restrict ART coverage to less than 14%, while only one fourth of the countries had reportable data on patients' CD4 counts at the time of diagnosis. Clinical guidelines need to be significantly modified to reach practical utility, and surveillance systems have not yet been developed in many countries of MENA. Based on available evidence in several countries people who inject drugs and men who have sex with men are increasingly vulnerable to HIV and viral hepatitis, while their sexual partners- either female sex workers or women in monogamous relationships with high-risk men- are potential bridging populations that are not appropriately addressed by regional programs. Research to monitor the response to ART among the mentioned groups are seriously lacking, while drug resistant HIV strains and limited information on adherence patterns to treatment regimens require urgent recognition by health policymakers. Commitment to defined goals in the fight against HIV, development of innovative methods to improve registration and reporting systems, monitoring and evaluation of current programs followed by costeffective modifications are proposed as effective steps to be acknowledged by National AIDS Programs of the countries of MENA Region.

Hepatitis B virus and hepatitis C virus dual infection

Hepatitis B virus(HBV)and hepatitis C virus(HCV)share common mode of transmission and both are able to induce a chronic infection.Dual HBV/HCV chronic coinfection is a fairly frequent occurrence,especially in high endemic areas and among individuals at high risk of parenterally transmitted infections.The intracellular interplay between HBV and HCV has not yet been sufficiently clarified,also due to the lack of a proper in vitro cellular model.Longitudinal evaluation of serum HBV DNA and HCV RNA amounts has revealed that complex virological profiles may be present in coinfected patients.Dual HBV/HCV infection has been associated to a severe course of the liver disease and to a high risk of developing hepatocellular carcinoma.Despite the clinical importance,solid evidence and clear guidelines for treatment of this special population are still lacking.This review summarizes the available data on the virological and clinical features as well as the therapeutic options of the dual HBV/HCV infection,and highlights the aspects that need to be better clarified.

Incidence of hepatocellular carcinoma in patients with chronic liver disease due to hepatitis B or C and coinfected with the human immunodeficiency virus:a retrospective cohort study

AIM To assess the incidence of hepatocellular carcinoma(HCC) in chronic liver disease due to hepatitis B virus(HBV) or hepatitis C virus(HCV) coinfected with human immunodeficiency virus(HIV).METHODS A retrospective cohort study was performed, including patients with chronic liver disease due to HBV or HCV, with and without HIV coinfection. Patients were selected in the largest tertiary public hospital complex in southern Brazil between January 2007 and June 2014. We assessed demographic and clinical data, including lifestyle habits such as illicit drug use or alcohol abuse, in addition to frequency and reasons for hospital admissions via medical records review.RESULTS Of 804 patients were included(399 with HIV coinfection and 405 monoinfected with HBV or HCV). Coinfected patients were younger(36.7 ± 10 vs 46.3 ± 12.5, P < 0.001). Liver cirrhosis was observed in 31.3% of HIV-negative patients and in 16.5% of coinfected(P < 0.001). HCC was diagnosed in 36 patients(10 HIV coinfected and 26 monoinfected). The incidence density of HCC in coinfected and monoinfected patients was 0.25 and 0.72 cases per 100 patient-years(95%CI: 0.12-0.46 vs 0.47-1.05)(long-rank P = 0.002), respectively. The ratio for the HCC incidence rate was 2.98 for HIV-negative. However, when adjusting for age or when only cirrhotic are analyzed, the absence of HIV lost statistical significance for the development of HCC. CONCLUSION In this study, the presence of HIV coinfection in chronic liver disease due to HBV or HCV showed no relation to the increase of HCC incidence.

A high frequency of GBV-C/HGV coinfection in hepatitis C patients in Germany

AIM To detect infection rate of GBV-C/HGV inhepatitis C patients,to determine the methodsof higher sensitivity and the primers of higherefficiency for GBV-C/HGV RNA detection and tostudy the dominant subtype and mutation ofGBV-C/HGV.METHODS Quantitative RT-PCR for detectionpf HCV RNA concentration in serum samples,RT-nested PCR with two sets of primers fordetection of GBV-C RNA,RT-PCR ELISA with twosets of primers for detection of HGV RNA,nucleotide sequence and putative amino acidsequence analysis.RESULTS The positive rates of GBV-C RNA atthe 5’-NCR and NS3 region in 211 serums amplesfrom the patients with HCV infection were 31.8%and 22.8% respectively.The positive rates ofHGV RNA at the 5’-NCR and NS5 region in thesame samples were 47.9% and 31.8%respectively.The total positive rate of GBV-C/HGV RNA was as high as 55.5%.HCV copynumbers in the patients without GBV-C/ HGVcoinfection were statistically higher than that inthe patients with GBV-C/ HGV coinfection(P【0.01).Frequent mutation of nucleotideresidue was present in the amplificationproducts.Frameshift mutation was found in twosamples with GBV-C NS3 region nucleotidesequences.All nucleotide sequences fromamplification products showed higher homologyto HGV genome than to GBV-C genome even though part of the sequences were amplifiedwith GBV-C primers.CONCLUSION A high frequency of GBV-C/ HGV coinfection existed in the hepatitis C patients. RT-PCR ELISA was more sensitive than RT-nested PCR for detection of GBV-C/ HGV RNA. The primers derived from the 5 -NCR was more efficient than those derived from the NS3 and NS5 regions. A reverse relationship was found to exist between HCV RNA concentration and GBV-C/ HGV infection frequency. HGV was the dominant subtype of the virus in the local area. The major mutations of GBV-C/ HGV genomes were random mutation of nucleotide residue.

Hepatitis B reactivation in patients receiving direct-acting antiviral therapy or interferon-based therapy for hepatitis C:A systematic review and meta-analysis

AIM To assess the incidence of hepatitis B virus(HBV) reactivation in patients receiving direct-acting antiviral agent(DAA)-based therapy or interferon(IFN)-based therapy for hepatitis C and the effectiveness of preemptive antiHBV therapy for preventing HBV reactivation.METHODS The Pub Med, MEDLINE and EMBASE databases were searched, and 39 studies that reported HBV reactivation in HBV/hepatitis C virus coinfected patients receiving DAAbased therapy or IFN-based therapy were included. The primary outcome was the rate of HBV reactivation. The secondary outcomes included HBV reactivation-related hepatitis and the effectiveness of preemptive anti-HBV treatment with nucleos(t)ide analogues. The pooled effects were assessed using a random effects model. RESULTS The rate of HBV reactivation was 21.1% in hepatitis Bsurface antigen(HBs Ag)-positive patients receiving DAAbased therapy and 11.9% in those receiving IFN-based therapy. The incidence of hepatitis was lower in HBs Agpositive patients with undetectable HBV DNA compared to patients with detectable HBV DNA receiving DAA therapy(RR = 0.20, 95%CI: 0.06-0.64, P = 0.007). The pooled HBV reactivation rate in patients with previous HBV infection was 0.6% for those receiving DAA-based therapy and 0 for those receiving IFN-based therapy, and none of the patients experienced a hepatitis flare related to HBV reactivation. Preemptive anti-HBV treatment significantly reduced the potential risk of HBV reactivation in HBs Agpositive patients undergoing DAA-based therapy(RR = 0.31, 95%CI: 0.1-0.96, P = 0.042).CONCLUSION The rate of HBV reactivation and hepatitis flare occurrence is higher in HBs Ag-positive patients receiving DAA-based therapy than in those receiving IFN-based therapy, but these events occur less frequently in patients with previous HBV infection. Preemptive anti-HBV treatment is effective in preventing HBV reactivation.

Bacteriophage secondary infection

Phages are credited with having been first described in what we now, officially, are commemorating as the 100 th anniversary of their discovery. Those one-hundred years of phage history have not been lacking in excitement, controversy, and occasional convolution. One such complication is the concept of secondary infection, which can take on multiple forms with myriad consequences. The terms secondary infection and secondary adsorption, for example, can be used almost synonymously to describe virion interaction with already phage-infected bacteria, and which can result in what are described as superinfection exclusion or superinfection immunity. The phrase secondary infection also may be used equivalently to superinfection or coinfection, with each of these terms borrowed from medical microbiology, and can result in genetic exchange between phages, phage-on-phage parasitism, and various partial reductions in phage productivity that have been termed mutual exclusion, partial exclusion, or the depressor effect. Alternatively, and drawing from epidemiology, secondary infection has been used to describe phage population growth as that can occur during active phage therapy as well as upon phage contamination of industrial ferments. Here primary infections represent initial bacterial population exposure to phages while consequent phage replication can lead to additional, that is, secondary infections of what otherwise are not yet phage-infected bacteria. Here I explore the varying meanings and resultant ambiguity that has been associated with the term secondary infection. I suggest in particular that secondary infection, as distinctly different phenomena, can in multiple ways influence the success of phage-mediated biocontrol of bacteria, also known as, phage therapy.

Prevalence and virological profiles of hepatitis B infection in human immunodeficiency virus patients

AIM: To determine the prevalence of hepatitis B virus (HBV) in adult human immunodeficiency virus (HIV) patients with CD4+ T-cell count less than 500/mm 3 and without antiretroviral therapy; to describe different HBV-HIV coinfection virological profiles; and to search for factors associated with HBs antigen (HBsAg) presence in these HIV positive patients.METHODS: During four months (June through September 2006), 491 patients were received in four HIV positive monitoring clinical centers in Abidjan. Inclusion criteria: HIV-1 or HIV-1 and 2 positive patients, age ≥ 18 years, CD4+ T-cell count < 500/mL and formal and signed consent of the patient. Realized blood tests included HIV serology, CD4+ T-cell count, quantitative HIV RNA load and HBV serological markers, such as HBsAg and HBc antibody (anti-HBcAb). We performed HBeAg, anti-HBe antibody (anti-HBeAb), anti-HBc IgM and quantitative HBV DNA load in HBsAg positive patients. Anti-HBsAb had been tested in HIV patients with HBsAg negative and anti-HBcAb-positive. HBV DNA was also tested in 188 anti-HBcAb positive patients with HBsAg negative status and without anti-HBsAb. Univariate analysis (Pearsonχ 2 test or Fischer exact test) and multivariate analysis (backward step-wise selection logistic regression) were performed as statistical analysis. RESULTS: Mean age of 491 patients was 36 ± 8.68 years and 73.3% were female. Type-1 HIV was found in 97% and dual-type HIV (type 1 plus type 2) in 3%. World Health Organization (WHO) clinical stage was 1, 2, 3 and 4 respectively in 61 (12.4%), 233 (47.5%), 172 (35%) and 25 patients (5.1%). Median CD4+ T-cell count was 341/mm 3 (interquartile range: 221-470). One hundred and twelve patients had less than 200 CD4+ T-cell/mm 3 . Plasma HIV-1 RNA load was elevated (≥ 5 log 10 copies/mL) in 221 patients (45%). HBsAg and anti-HBcAb prevalence was respectively 13.4% and 72.9%. Of the 66 HBsAg positive patients, 22 were inactive HBV carriers (33.3%), 21 had HBeAg positive hepatitis (31.8%) and 20 had HBeAg negative hepatitis (30.3%). HBeAg and anti-HBeAb were indeterminate in 3 of them. Occult B infection prevalence (HBsAg negative, anti-HBcAb positive, anti-HBsAb negative and detectable HBV DNA) was 21.3%. Three parameters were significantly associated with the presence of HBsAg: male [odds ratio (OR): 2.2;P = 0.005; 95% confidence interval (CI): 1.3-3.8]; WHO stage 4 (OR: 3.2;P = 0.01;95% CI: 1.3-7.9); and aspartate aminotransferase (AST) level higher than the standard (OR: 1.9;P = 0.04; 95% CI: 1.02-3.8). CONCLUSION: HBV infection prevalence is high in HIV-positive patients. HBeAg positive chronic hepatitis and occult HBV infection are more frequent in HIVpositive patients than in HIV negative ones. Parameters associated with HBsAg positivity were male gender, AIDS status and increased AST level.

Clinical significance of occult hepatitis B virus infection

Occult hepatitis B virus(HBV) infection(OBI) is defined as the presence of HBV DNA in the liver(with or without detectable HBV DNA in serum) for individuals testing HBV surface antigen negative.Until recently,the clinical effect of OBI was unclear on the progression of liver disease;on the development of hepatocellular carcinoma;and on the risk for reactivation or transmission of HBV infection.Several studies suggest a high prevalence of OBI among patients with cryptogenic chronic liver disease,but its role in the progression to cirrhosis remains unclear.Although OBI has been well documented in human immunodeficiency virus(HIV) -positive patients,especially among those coinfected with hepatitis C virus,further studies are needed to determine its current clinical impact in HIV setting.

Interaction between hepatitis B virus and SARS-CoV-2 infections

Coronavirus disease 2019(COVID-19)has become a global pandemic and garnered international attention.The causative pathogen of COVID-19 is severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),a novel,highly contagious coronavirus.Numerous studies have reported that liver injury is quite common in patients with COVID-19.Hepatitis B has a worldwide distribution as well as in China.At present,hepatitis B virus(HBV)remains a leading cause of cirrhosis,liver failure,and hepatocellular carcinoma.Because both viruses challenge liver physiology,it raises questions as to how coinfection with HBV and SARS-CoV-2 affect disease progression and mortality.Is there an increased risk of COVID-19 in patients with HBV infection?In this review,we summarize the current reports of SARS-CoV-2 and HBV coinfection and elaborate the interaction of the two diseases.The emphasis was placed on evaluating the impact of HBV infection on disease severity and clinical outcomes in patients with COVID-19 and discussing the potential mechanism behind this effect.