Indoleamine-2,3-dioxygenase inhibition improves immunity and is safe for concurrent use with cART during Mtb/SIV coinfection.

Chronic immune activation promotes tuberculosis (TB) reactivation in the macaque Mycobacterium tuberculosis (M. tuberculosis)/SIV coinfection model. Initiating combinatorial antiretroviral therapy (cART) early lowers the risk of TB reactivation, but immune activation persists. Studies of host-directed therapeutics (HDTs) that mitigate immune activation are, therefore, required. Indoleamine 2,3, dioxygenase (IDO), a potent immunosuppressor, is one of the most abundantly induced proteins in NHP and human TB granulomas. Inhibition of IDO improves immune responses in the lung, leading to better control of TB, including adjunctive to TB chemotherapy. The IDO inhibitor D-1 methyl tryptophan (D1MT) is, therefore, a bona fide TB HDT candidate. Since HDTs against TB are likely to be deployed in an HIV coinfection setting, we studied the effect of IDO inhibition in M. tuberculosis/SIV coinfection, adjunctive to cART. D1MT is safe in this setting, does not interfere with viral suppression, and improves the quality of CD4+ and CD8+ T cell responses, including reconstitution, activation and M. tuberculosis-specific cytokine production, and access of CD8+ T cells to the lung granulomas; it reduces granuloma size and necrosis, type I IFN expression, and the recruitment of inflammatory IDO+ interstitial macrophages (IMs). Thus, trials evaluating the potential of IDO inhibition as HDT in the setting of cART in M. tuberculosis/HIV coinfected individuals are warranted.

Prevalence and molecular analysis of some important viruses in honey bee colonies in Türkiye: the status of multiple infections.

In this study, seven bee viruses of significant importance for bee health in Türkiye were investigated using one-step RT-PCR. For this purpose, larvae from 1183 hives and adult bees from 1196 hives were sampled from 400 apiaries in 40 provinces. The prevalence of viral infections in hives was as follows: acute bee paralysis virus (ABPV), 6.4%; black queen cell virus (BQCV), 77%; chronic bee paralysis virus (CBPV), 3.2%; deformed wing virus (DWV), 63.8%; Israel acute bee paralysis virus (IAPV), 7%; Kashmir bee virus (KBV), 2.7%; sacbrood virus (SBV), 49.7%. Moreover, 50 different combinations of viral infections were identified in the hives. While dual infections (36.1%) were the most common in hives, triple infections with BQCV, DWV, and SBV were found to have the highest prevalence (22.1%). At least one viral infection was detected in all of the apiaries tested. Phylogenetic analysis showed that the isolates from this study generally exhibited the highest similarity to previously reported Turkish isolates. When similarity ratios and the locations and types of amino acid mutations were analyzed, it was observed that the isolates from our study exhibited high similarity to isolates from various countries, including China, the United Kingdom, Syria, and Germany.

Bacilli load in PTB- intestinal helminths co-infected and PTB non -infected patients at selected public health facilities in Jimma zone, Oromia, Ethiopia: comparative cross-sectional study.

BACKGROUND: Tuberculosis (TB) and intestinal helminths are diseases that pose a dual burden on public health in low-income countries. Previous studies have shown that helminths can affect the shedding of bacteria or the bacterial load in the sputum of active TB patients. However, there is limited information on bacterial load in TB patients with helminth infections. OBJECTIVE: This study aimed to compare bacterial load in helminths-infected and non-infected pulmonary tuberculosis patients at selected public health facilities in Jimma zone, Oromia, Ethiopia. METHODS: The study was conducted in Jimma Zone, Oromia, Ethiopia. A facility-based comparative cross-sectional study was employed from August 01, 2020, to January 2021. A total of 124 (55 intestinal helminths-infected and 69 non-infected) newly diagnosed smear-positive pulmonary tuberculosis (PTB) patients were included in the study. A convenience sampling technique was employed to recruit study participants, and a semi-structured questionnaire was used to collect data regarding socio-demographic characteristics and possible risk factors for intestinal helminths co-infection. Stool examination was performed using both wet mount and Kato Katz technique. Additionally, weight and height measurements, sputum, and blood samples were taken to determine body mass index, bacilli load, and diabetic mellitus, respectively. Data were entered into Epi-Data software version 3.1 and analyzed using Statistical Packages for Social Sciences (SPSS) Version 25. A statistically significant difference was defined as a P-value of less than 0.05. RESULTS: Intestinal helminths reduced bacilli load 3 times more than intestinal helminths non-infected PTB (AOR = 3.44; 95% CI; 1.52, 7.79; P = 0.003) However, diabetes mellitus, HIV, drinking alcohol and cigarette smoking were not associated with bacilli load. The rate of co-infection TB with intestinal helminths was 44%. The three most prevalent parasites detected were Trichuris trichiura 29 (66%), hookworm 19 (43%), and Ascaris lumbricoides 11(25%)). Among co-infected patients about 36 (81.8%) had a single parasite infection, and 19 (43.2%) had multiple infections. A body mass index < 18.5 (AOR = 3.26; 95% CI; 1.25, 8.56;P = 0.016) and untrimmed fingernail status (AOR = 3.63; 95%CI;1.32,9.93;P = 0.012) were significantly associated with PTB- intestinal helminth -co-infection. CONCLUSION: Helminth infection was associated with a lower bacilli load compared to helmenths non-infected PTB. The rate of co-infection TB with intestinal helminths was 44%. Trichuris trichiura was the most prevalent helminth. Untrimmed fingernail and a body mass index were associated with PTB-intestinal helminth co-infection.

Tuberculosis-associated mortality and risk factors for HIV-infected population in Ethiopia: a systematic review and meta-analysis.

Background: Despite the effectiveness of antiretroviral therapy in reducing mortality from opportunistic infections among people living with HIV (PLHIV), tuberculosis (TB) continues to be a significant cause of death, accounting for over one-third of all deaths in this population. In Ethiopia, there is a lack of comprehensive and aggregated data on the national level for TB-associated mortality during co-infection with HIV. Therefore, this systematic review and meta-analysis aimed to estimate TB-associated mortality and identify risk factors for PLHIV in Ethiopia. Methods: We conducted an extensive systematic review of the literature using the Preferred Reporting of Systematic Review and Meta-Analysis (PRISMA) guidelines. More than seven international electronic databases were used to extract 1,196 published articles from Scopus, PubMed, MEDLINE, Web of Science, HINARY, Google Scholar, African Journal Online, and manual searching. The pooled mortality proportion of active TB was estimated using a weighted inverse variance random-effects meta-regression using STATA version-17. The heterogeneity of the articles was evaluated using Cochran's Q test and I 2 statistic test. Subgroup analysis, sensitivity analysis, and Egger's regression were conducted to investigate publication bias. This systematic review is registered in Prospero with specific No. CRD42024509131. Results: Overall, 22 individual studies were included in the final meta-analysis reports. During the review, a total of 9,856 cases of TB and HIV co-infection were screened and 1,296 deaths were reported. In the final meta-analysis, the pooled TB-associated mortality for PLHIV in Ethiopia was found to be 16.2% (95% CI: 13.0-19.2, I 2 = 92.9%, p = 0.001). The subgroup analysis revealed that the Amhara region had a higher proportion of TB-associated mortality, which was reported to be 21.1% (95% CI: 18.1-28.0, I 2 = 84.4%, p = 0.001), compared to studies conducted in Harari and Addis Ababa regions, which had the proportions of 10% (95% CI: 6-13.1%, I 2 = 83.38%, p = 0.001) and 8% (95% CI: 1.1-15, I 2 = 87.6%, p = 0.001), respectively. During the random-effects meta-regression, factors associated with co-infection of mortality in TB and HIV were identified, including WHO clinical stages III & IV (OR = 3.01, 95% CI: 1.9-4.7), missed co-trimoxazole preventive therapy (CPT) (OR = 1.89, 95% CI: 1.05-3.4), and missed isoniazid preventive therapy (IPT) (OR = 1.8, 95% CI: 1.46-2.3). Conclusion: In Ethiopia, the mortality rate among individuals co-infected with TB/HIV is notably high, with nearly one-fifth (16%) of individuals succumbing during co-infection; this rate is considered to be higher compared to other African countries. Risk factors for death during co-infection were identified; the included studies examined advanced WHO clinical stages IV and III, hemoglobin levels (≤10 mg/dL), missed isoniazid preventive therapy (IPT), and missed cotrimoxazole preventive therapy (CPT) as predictors. To reduce premature deaths, healthcare providers must prioritize active TB screening, ensure timely diagnosis, and provide nutritional counseling in each consecutive visit. Systematic review registration: Trial registration number in Prospero =CRD42024509131 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=509131.

Dengue and leptospirosis coinfection: a case series.

BACKGROUND: Both dengue and Leptospira infections are endemic to tropical and subtropical regions, with their prevalence increasing in recent decades. Coinfection with these pathogens presents significant diagnostic challenges for clinicians due to overlapping clinical manifestations and laboratory findings. This case report aims to elucidate two clinical scenarios where the coinfection of dengue and leptospirosis complicates the disease course, creating a diagnostic conundrum. CASE PRESENTATION: We present the clinical scenarios of two Bangladeshi males, aged 25 and 35 years, who were admitted to our hospital with acute febrile illness. The first patient exhibited hepatic and renal involvement, while the second presented with symptoms initially suggestive of meningoencephalitis. Both cases were initially managed under the presumption of dengue infection based on positive serology. However, further evaluation revealed coinfection with Leptospira, complicating the disease course. Both patients received appropriate treatment for dengue and antibacterial therapy for leptospirosis, ultimately resulting in their recovery. CONCLUSION: These case scenarios underscore the critical importance for clinicians in regions where dengue and Leptospira are endemic to consider both diseases when evaluating patients presenting with acute febrile illness.

Humans seropositive for Trypanosoma cruzi co-infected with intestinal helminths have higher infectiousness, parasitaemia and Th2-type response in the Argentine Chaco.

BACKGROUND: The Gran Chaco ecoregion is a well-known hotspot of several neglected tropical diseases (NTDs) including Chagas disease, soil-transmitted helminthiasis and multiparasitic infections. Interspecific interactions between parasite species can modify host susceptibility, pathogenesis and transmissibility through immunomodulation. Our objective was to test the association between human co-infection with intestinal parasites and host parasitaemia, infectiousness to the vector and immunological profiles in Trypanosoma cruzi-seropositive individuals residing in an endemic region of the Argentine Chaco. METHODS: We conducted a cross-sectional serological survey for T. cruzi infection along with an intestinal parasite survey in two adjacent rural villages. Each participant was tested for T. cruzi and Strongyloides stercoralis infection by serodiagnosis, and by coprological tests for intestinal parasite detection. Trypanosoma cruzi bloodstream parasite load was determined by quantitative PCR (qPCR), host infectiousness by artificial xenodiagnosis and serum human cytokine levels by flow cytometry. RESULTS: The seroprevalence for T. cruzi was 16.1% and for S. stercoralis 11.5% (n = 87). We found 25.3% of patients with Enterobius vermicularis. The most frequent protozoan parasites were Blastocystis spp. (39.1%), Giardia lamblia (6.9%) and Cryptosporidium spp. (3.4%). Multiparasitism occurred in 36.8% of the examined patients. Co-infection ranged from 6.9% to 8.1% for T. cruzi-seropositive humans simultaneously infected with at least one protozoan or helminth species, respectively. The relative odds of being positive by qPCR or xenodiagnosis (i.e. infectious) of 28 T. cruzi-seropositive patients was eight times higher in people co-infected with at least one helminth species than in patients with no such co-infection. Trypanosoma cruzi parasite load and host infectiousness were positively associated with helminth co-infection in a multiple regression analysis. Interferon-gamma (IFN-γ) response, measured in relation to interleukin (IL)-4 among humans infected with T. cruzi only, was 1.5-fold higher than for T. cruzi-seropositive patients co-infected with helminths. The median concentration of IL-4 was significantly higher in T. cruzi-seropositive patients with a positive qPCR test than in qPCR-negative patients. CONCLUSIONS: Our results show a high level of multiparasitism and suggest that co-infection with intestinal helminths increased T. cruzi parasitaemia and upregulated the Th2-type response in the study patients.

Cystatin F Depletion in Mycobacterium tuberculosis-Infected Macrophages Improves Cathepsin C/Granzyme B-Driven Cytotoxic Effects on HIV-Infected Cells during Coinfection.

Cystatin F (CstF) is a protease inhibitor of cysteine cathepsins, including those involved in activating the perforin/granzyme cytotoxic pathways. It is targeted at the endolysosomal pathway but can also be secreted to the extracellular milieu or endocytosed by bystander cells. CstF was shown to be significantly increased in tuberculous pleurisy, and during HIV coinfection, pleural fluids display high viral loads. In human macrophages, our previous results revealed a strong upregulation of CstF in phagocytes activated by interferon γ or after infection with Mycobacterium tuberculosis (Mtb). CstF manipulation using RNA silencing led to increased proteolytic activity of lysosomal cathepsins, improving Mtb intracellular killing. In the present work, we investigate the impact of CstF depletion in macrophages during the coinfection of Mtb-infected phagocytes with lymphocytes infected with HIV. The results indicate that decreasing the CstF released by phagocytes increases the major pro-granzyme convertase cathepsin C of cytotoxic immune cells from peripheral blood-derived lymphocytes. Consequently, an observed augmentation of the granzyme B cytolytic activity leads to a significant reduction in viral replication in HIV-infected CD4+ T-lymphocytes. Ultimately, this knowledge can be crucial for developing new therapeutic approaches to control both pathogens based on manipulating CstF.

Characteristics of SARS-CoV-2 and Opisthorchis viverrini coinfections: insights into immune responses and clinical outcomes.

The effects of co-infections with SARS-CoV-2 and parasitic diseases have been little investigated in terms of immune response, disease dynamics, and clinical outcomes. This study aimed to explore the impact of co-infection with Opisthorchis viverrini and SARS-CoV-2 on the immune response concerning clinical symptoms and the severity of pulmonary abnormalities. A cross-sectional study was conducted, including healthy participants as controls, participants with opisthorchiasis, SARS-CoV-2 infection, and a co-infection group with both diseases. Characteristics of SARS-CoV-2 infection were assessed based on clinical parameters and severity of pulmonary abnormalities, whereas opisthorchiasis burden was evaluated by eggs-per-gram (EPG) counts. Immune responses were assessed by measuring levels of interferon-γ (IFN-γ), SARS-CoV-2 anti-spike receptor binding domain (RBD) IgG, and neutralizing antibody against SARS-CoV-2. In the co-infected group, clinical parameters and hospitalization rates were lower than in the SARS-CoV-2 group. Pulmonary abnormalities, such as bronchial fibrosis, were commonly observed in the SARS-CoV-2 group, leading to hospitalization in some cases. Participants with opisthorchiasis had higher IFN-γ levels than healthy individuals. IFN-γ levels were significantly lower in the co-infection group compared with the SARS-CoV-2 group (P = 0.002). There was a significant (P = 0.044) positive correlation between RBD-specific IgG and percent neutralization levels in the SARS-CoV-2 group. Levels of both were somewhat lower (not statistically significant) in the co-infection group. A negative correlation was observed between opisthorchiasis burden (EPG counts) and IFN-γ and RBD-specific IgG levels in the co-infected group. Following vaccination, the increase in IgG levels against the RBD protein was significantly lower in the co-infected group than in the SARS-CoV-2 group. These results suggest that O. viverrini infection suppresses immune responses and may lead to a reduction in severity in cases of SARS-CoV-2 co-infection.

Seroprevalence of HIV, HBV, and syphilis co-infections and associated factors among pregnant women attending antenatal care in Amhara regional state, northern Ethiopia: A hospital-based cross-sectional study.

BACKGROUND: Co-infections involving human immunodeficiency virus (HIV), hepatitis B virus (HBV), and syphilis pose significant public health problems during pregnancy. It can increase the risk of adverse outcomes for both the woman and the infant more than each infection alone does. However, the magnitude of these co-infections remains insufficiently documented. Hence, this study aimed to determine the seroprevalence of HIV, HBV, and syphilis co-infections and associated risk factors among pregnant women attending antenatal care in Amhara region referral hospitals in northern Ethiopia. METHODS: A hospital-based cross-sectional study was conducted in Amhara regional state referral hospitals from January 1 to February 30, 2024, among 606 pregnant women. Pregnant women were selected using a systematic random sampling technique. An interviewer-administered questionnaire and chart review were used to collect data. Data were analyzed in SPSSV26.0. Descriptive statistics were used to determine the magnitude of co-infections, and binary logistic regression was used to determine associated factors. Variables with a P-value < 0.05 were used to declare statistical significance. RESULT: Overall, 4.1% (95% CI: 2.7, 6.1) of pregnant women were co-infected. The prevalence of specific co-infections was 2% (95% CI: 1, 3.5) for HIV/HBV, 1.3% (95% CI: 0.6, 2.6) for HIV/syphilis, and 0.8% (95% CI: 0.3, 1.9) for HBV/syphilis. No cases of triple co-infection were observed. Women with a history of unsafe sex (AOR = 8.2, 95% CI: 1.5, 16.7) and incarceration (AOR = 9.3, 95% CI: 1.6, 20.8) were associated with HIV/syphilis co-infection. For HIV/HBV co-infection, contact with jaundice patients (AOR = 5.5, 95% CI: 1.3, 22.5) and women with a history of STIs (AOR = 4.6, 95% CI: 1.4, 14.9) was significantly associated. Women with STI history (AOR = 6.3, 95% CI: 1.2, 15.9) were also significantly associated with HBV/syphilis co-infection. CONCLUSION: Despite the government's elimination efforts, a relatively high prevalence of coinfections with the infections studied was found among pregnant women. Therefore, HIV, HBV, and syphilis testing and treatment packages should be strengthened by targeting pregnant women with a history of STIs, contact with patients with jaundice, a history of incarceration, and unsafe sex.

Characterising the urinary acylcarnitine and amino acid profiles of HIV/TB co-infection, using LC-MS metabolomics.

INTRODUCTION: The human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection presents significant challenges due to the complex interplay between these diseases, leading to exacerbated metabolic disturbances. Understanding these metabolic profiles is crucial for improving diagnostic and therapeutic approaches. OBJECTIVE: This study aimed to characterise the urinary acylcarnitine and amino acid profiles, including 5-hydroxyindoleacetic acid (5-HIAA), in patients co-infected with HIV and TB using targeted liquid chromatography mass spectrometry (LC-MS) metabolomics. METHODS: Urine samples, categorised into HIV, TB, HIV/TB co-infected, and healthy controls, were analysed using HPLC-MS/MS. Statistical analyses included one-way ANOVA and a Kruskal-Wallis test to determine significant differences in the acylcarnitine and amino acid profiles between groups. RESULTS: The study revealed significant metabolic alterations, especially in TB and co-infected groups. Elevated levels of medium-chain acylcarnitines indicated increased fatty acid oxidation, commonly associated with cachexia in TB. Altered amino acid profiles suggested disruptions in protein and glucose metabolism, indicating a shift towards diabetes-like metabolic states. Notably, TB was identified as a primary driver of these changes, affecting protein turnover, and impacting energy metabolism in co-infected patients. CONCLUSION: The metabolic profiling of HIV/TB co-infection highlights the profound impact of TB on metabolic pathways, which may exacerbate the clinical complexities of co-infection. Understanding these metabolic disruptions can guide the development of targeted treatments and improve management strategies, ultimately enhancing the clinical outcomes for these patients. Further research is required to validate these findings and explore their implications in larger, diverse populations.

Prevalence of hepatitis B, hepatitis C, and tuberculosis among people living with HIV in Iran: a systematic review and meta-analysis.

BACKGROUND: Up to now several studies estimate the prevalence of HBV, HCV, and TB among people living with HIV (PLWH) in Iran; however, their results are inconsistent. This study aimed to estimate the overall prevalence of HBV, HVC, and TB among Iranian PLWH. METHODS: In this systematic review and meta-analysis six databases including Medline, Web of Science, Scopus, MagIran, Scientific Information Database (SID), and Barakat Knowledge network system were searched up to October 2023 with no language restriction. All studies estimated the prevalence of HBV, HCV, and TB among PLWH in Iran were included. The random-effects model was used to report the study estimates. Results were reported at a 95% confidence interval (CI). RESULTS: Out of 1050 retrieved references, 58 articles met the eligibility criteria. Overall among PLWH, HBV prevalence was 13.0% (95% CI: 11.0, 15.0), HCV prevalence was 54% (95% CI: 45.0, 64.0), and TB prevalence was 19% (95% CI: 13.0, 24.0). The results from multivariate meta-regression analysis showed no statistically significant association between HBV and TB prevalence with the year of study, quality of studies, age, gender, and persons who inject drugs (PWID). HCV prevalence was significantly associated with PWID. CONCLUSION: We found HBV, HCV, and TB infections are common among PLWH in Iran and required to be screened and treated with effective and timely services.

Occurrence and identification of lungworms in Iranian wild boars.

This study represents the first investigation into the occurrence and identification of Metastrongylus spp. in wild boars (Sus scrofa) in Iran, utilizing both molecular and morphological methods. Thirteen wild boars from Kerman Province were examined, with 92.3% found to be infected with at least one species of Metastrongylus. Mixed infections were observed in 38.46% of the animals. Morphological and molecular analyses confirmed the presence of M. pudendotectus and M. salmi, with prevalence rates of 76.9% and 53.9%, respectively. Histopathological examination revealed transverse and longitudinal sections of Metastrongylus parasites within the airways, causing partial to complete obstruction, interstitial pneumonia, and inflammatory responses. The study also highlights the public health significance of these parasites. The higher prevalence observed compared to earlier studies suggests changes in environmental conditions, host dynamics, or agricultural practices as possible factors, warranting further investigation. The findings underscore the need for comprehensive surveillance and control measures to mitigate the risk of zoonotic transmission, particularly in regions with significant wild and domestic swine populations. This study contributes to the understanding of Metastrongylus spp. distribution and their pathological impact, emphasizing the ecological importance of wild boars and the necessity for continued monitoring and research to prevent and control infections in both animal and human populations.

Field-applicable simultaneous multiplex LAMP assay for screening HBV and HCV co-infection in a single tube.

BACKGROUND: Globally, around 7 to 20 million people are believed to be suffering from coinfection with both hepatitis B virus (HBV) and hepatitis C virus (HCV). The loop-mediated isothermal amplification (LAMP) approach, introduced by Notomi and colleagues, has undergone substantial advancements as an effective molecular tool that enables the simultaneous analysis of multiple samples in a single tube. METHODS: The present study examined the simultaneous detection of HBV and HCV in a single tube using melt curve analysis multiplex LAMP (mLAMP), which is based on the identification of unique melting peak temperatures. Selected regions for primer design including the S gene of HBV and the UTR gene of HCV. Primer optimization is initially performed through individual HBV and HCV LAMP analysis. Following the optimization process, the mLAMP assay was evaluated by optimizing the multiplex reaction mixture, determining the reaction time, and analyzing the limit of detection (LOD). The results are also analyzed using lateral flow dipsticks (LFD), which enable the visual detection of HBV and HCV by adding 20 pmol FITC-labeled LF primers into the reaction mixture prior the mLAMP. RESULTS: The LOD for the mLAMP assay was determined as 10 copies/µl, and no cross-reactivity with other microorganisms was detected. The detection results obtained from patient plasma were also visually demonstrated using LFD, and displayed significant concordance with those obtained from Real-Time Polymerase Chain Assay. The mLAMP assay revealed a diagnostic sensitivity of 95% for detecting the HBV, and LOD is 90% for HCV. The overall diagnostic sensitivity of the mLAMP assay for both viruses was 85%. The assay confirmed a specificity of 100%. CONCLUSION: The mLAMP assay displays significant promise for analyzing coinfected samples by simultaneously detecting the dual targets HBV and HCV within a set temperature of 62 °C, all within a time frame of 1 h. Additionally, when paired with disposable LFD, the mLAMP assay enables rapid visual detection of assay results in a matter of minutes. The result contributes to the mLAMP assay being highly suitable for coinfection screening, particularly in field conditions.

HPV specificity and multiple infections and association with cervical cytology in Chongqing, China: a cross-sectional study.

BACKGROUND: It is important to assess the relationship between specific HPV genotype or multiple infection and cervical cytology. The protection provided by the HPV vaccine is type-specific, and the epidemiology feature of coinfections needs to be investigated. The aim is to provide baseline information for developing HPV vaccination and management of HPV-positive populations in the region. METHODS: A total of 3649 HPV-positive women were collected from 25,572 women who underwent 15 HR-HPV genotypes and ThinPrep cytologic test (TCT) results. Logistic regression was used to determine the correlation between the risk of cytology abnormalities and specific HPV infection. We calculated odds ratios (ORs) to assess coinfection patterns for the common two-type HPV infections. chi-squared test was used to estimate the relationship between single or multiple HPV (divided into species groups) infection and cytology results. RESULTS: The results showed there was a positive correlation between HPV16 (OR = 4.742; 95% CI 3.063-7.342) and HPV33 (OR = 4.361; 95% CI 2.307-8.243) infection and HSIL positive. There was a positive correlation between HPV66 (OR = 2.445; 95% CI 1.579-3.787), HPV51 (OR = 1.651; 95% CI 1.086-2.510) and HPV58(OR = 1.661; 95% CI 1.166-2.366) infection and LSIL. Multiple HPV infections with α9 species (OR = 1.995; 95% CI 1.101-3.616) were associated with a higher risk of high-grade intraepithelial lesions (HSIL) compared with single HPV infection. There were positive correlations between HPV66 and HPV56 (α6) (OR = 3.321; 95% CI 2.329-4.735) and HPV39 and HPV68 (α7). (OR = 1.677; 95% CI 1.127-2.495). There were negative correlations between HPV52, 58, 16 and the other HPV gene subtypes. CONCLUSION: HPV33 may be equally managed with HPV16. The management of multiple infections with α9 may be strengthened. The 9-valent vaccine may provide better protection for the population in Chongqing currently. The development of future vaccines against HPV51 and HPV66 may be considered in this region.

Factors associated with mortality among laboratory-diagnosed drug-resistant tuberculosis patients on treatment, KwaZulu-Natal Province, 2017-2019.

Introduction: tuberculosis (TB) remains a leading cause of death in South Africa. KwaZulu-Natal (KZN) is one of the provinces with a high burden of TB/drug-resistant TB cases and deaths. We determined predictors for mortality among drug-resistant TB patients on treatment in KZN province. Methods: we conducted a retrospective cohort study using secondary data from the Electronic Drug-Resistant Tuberculosis Register. We used a modified Poisson regression model with robust standard errors to determine predictors for drug-resistant TB mortality. Results: of the 7,692 eligible patients, 1,234 (16.0%) died. Males predominated (707, 57.3%) and the median age was 36 years (Interquartlile Range: 29-45 years). The majority (978, 79.2%) were HIV-TB co-infected with 911 (93%) on antiretroviral treatment (ART). The predictors included HIV-TB co-infection without ART (aIRR 3.4; 95% CI: 2.3-5.1), unknown ART status (aIRR: 1.8; 95% CI: 1.4-2.3), aged ≥60 years (aIRR: 2.1; 95% CI: 1.6-2.7), previous drug-resistant TB (aIRR: 1.5; 95% CI: 1.2-1.8) and exposure to second-line drugs (aIRR: 1.7; 95% CI: 1.4-2.0). Other predictors were hospitalization during treatment initiation (aIRR 2.5; 95% CI 2.0-3.1), initiation in other treatment facilities (aIRR: 2.2; 95% CI: 1.6-2.9) and rifampicin-resistant (aIRR: 1.2; 95% CI: 1.1-1.4). Bedaquiline fumarate was a significant protective factor against death (aIRR: 0.5; 95% CI: 0.4-0.5). Conclusion: older age, HIV co-infection without ART, hospitalization for treatment initiation, exposure to second-line drugs and a previous episode of drug-resistant TB were predictors for DR-TB mortality. Early treatment initiation and provision of antiretroviral treatment for all co-infected patients may reduce DR-TB mortality in the Province.

[Chronic HBV and HDV infection]. / Chronische Hepatitis-B- und Hepatitis-D-Virusinfektion.

About 0,5% of the population in Germany has a chronic hepatitis B virus (HBV) infection. Untreated, chronic HBV infection can progress to liver cirrhosis and hepatocellular carcinoma (HCC). If diagnosed early, antiviral therapy can effectively prevent liver disease progression, but a cure is currently hardly achievable. About 5% of those chronically infected with HBV are also co-infected with the hepatitis D virus (HDV). HBV/HDV co-infection leads to liver cirrhosis in approximately 50% of patients within 5-10 years. Since 2020, the cell entry inhibitor bulevirtide is available as a specific therapy for HBV/HDV co-infection.

Distribution and diagnostic value of single and multiple high-risk HPV infections in detection of cervical intraepithelial neoplasia: A retrospective multicenter study in China.

The risk associated with single and multiple human papillomavirus (HPV) infections in cervical intraepithelial neoplasia (CIN) remains uncertain. This study aims to explore the distribution and diagnostic significance of the number of high-risk HPV (hr-HPV) infections in detecting CIN, addressing a crucial gap in our understanding. This comprehensive multicenter, retrospective study meticulously analyzed the distribution of single and multiple hr-HPV, the risk of CIN2+, the relationship with CIN, and the impact on the diagnostic performance of colposcopy using demographic information, clinical histories, and tissue samples. The composition of a single infection was predominantly HPV16, 52, 58, 18, and 51, while HPV16 and 33 were identified as the primary causes of CIN2+. The primary instances of dual infection were mainly observed in combinations such as HPV16/18, HPV16/52, and HPV16/58, while HPV16/33 was identified as the primary cause of CIN2+. The incidence of hr-HPV infections shows a dose-response relationship with the risk of CIN (p for trend <0.001). Compared to single hr-HPV, multiple hr-HPV infections were associated with increased risks of CIN1 (1.44, 95% confidence interval [CI]: 1.20-1.72), CIN2 (1.70, 95% CI: 1.38-2.09), and CIN3 (1.08, 95% CI: 0.86-1.37). The colposcopy-based specificity of single hr-HPV (93.4, 95% CI: 92.4-94.4) and multiple hr-HPV (92.9, 95% CI: 90.8-94.6) was significantly lower than negative (97.9, 95% CI: 97.0-98.5) in detecting high-grade squamous intraepithelial lesion or worse (HSIL+). However, the sensitivity of single hr-HPV (73.5, 95% CI: 70.8-76.0) and multiple hr-HPV (71.8, 95% CI: 67.0-76.2) was higher than negative (62.0, 95% CI: 51.0-71.9) in detecting HSIL+. We found that multiple hr-HPV infections increase the risk of developing CIN lesions compared to a single infection. Colposcopy for HSIL+ detection showed high sensitivity and low specificity for hr-HPV infection. Apart from HPV16, this study also found that HPV33 is a major pathogenic genotype.

People living with HIV co-infected with the Kaposi Sarcoma-associated Herpes Virus have a distinct HIV Tat profile and higher rates of antiretroviral virologic failure, more evident among those with Kaposi's sarcoma.

Kaposi sarcoma (KS) is a neoplasm of vascular origin that promotes angiogenesis and the growth of endothelial cells triggered by the Kaposi Sarcoma-associated Herpes Virus (KSHV). When associated with HIV, KSHV becomes more aggressive and rapidly evolves. The HIV-1 TAT protein can be essential in developing AIDS-associated KS by promoting angiogenesis and increasing KSHV replication. Therefore, we evaluated the genetic profile of the first exon of tat gene among groups of people living with HIV (PLHIV) with (case group, n = 36) or without KS, this later with (positive control group, n = 46) and without KSHV infection (negative control group, n = 24); all individuals under antiretroviral therapy. The genetic diversity, the DN/DS ratio, and the genetic entropy of the first exon of tat were higher in the case group, followed by the positive control group, which was higher than the negative control group. The number of tat codons under positive selection was seven in the case group, six in the positive control group, and one in the negative control group. The prevalence of HIV viral loads below the detection limit was equal in the case and positive control groups, which were lower than in the negative control group. The mean CD4+ T cell counts were higher in the negative control group, followed by the positive control group, and followed by the case group. These results emphasize the negative influence of KSHV in antiretroviral treatment, as well as the HIV-specific TAT profile among PLHIV who developed KS.

Mortality and associated factors among patients with TB-HIV co-infection in Ethiopia: a systematic review and meta-analysis.

BACKGROUND: Tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection is a major public health problem in Ethiopia. Patients with TB-HIV co-infection have significantly higher mortality rates compared to those with TB or HIV mono-infection. This systematic review and meta-analysis aim to summarize the evidence on mortality and associated factors among patients with TB-HIV co-infection in Ethiopia. METHODS: Comprehensive searches were conducted in multiple electronic databases (PubMed/MEDLINE, Embase, CINAHL, Web of Science) for observational studies published between January 2000 and present, reporting mortality rates among TB/HIV co-infected individuals. Two reviewers performed study selection, data extraction, and quality assessment independently. Random-effects meta-analysis was used to pool mortality estimates, and heterogeneity was assessed using I² statistics. Subgroup analyses and meta-regression were performed to explore potential sources of heterogeneity. RESULTS: 185 articles were retrieved with 20 studies included in the final analysis involving 8,113 participants. The pooled mortality prevalence was 16.65% (95% CI 12.57%-19.65%) with I2 : 95.98% & p-value < 0.00. Factors significantly associated with increased mortality included: older age above 44 years (HR: 1.82; 95% CI: 1.31-2.52), ambulatory(HR: 1.64; 95% CI: 1.23-2.18) and bedridden functional status(HR: 2.75; 95% CI: 2.01-3.75), extra-pulmonary Tuberculosis (ETB) (HR: 2.34; 95% CI: 1.76-3.10), advanced WHO stage III (HR: 1.76; 95% CI: 1.22-2.38) and WHO stage IV (HR: 2.17; 95% CI:1.41-3.34), opportunistic infections (HR: 1.75; 95% CI: 1.30-2.34), low CD4 count of < 50 cells/mm3 (HR: 3.37; 95% CI: 2.18-5.22) and lack of co-trimoxazole prophylaxis (HR: 2.15; 95% CI: 1.73-2.65). CONCLUSIONS: TB/HIV co-infected patients in Ethiopia experience unacceptably high mortality, driven by clinical markers of advanced immunosuppression. Early screening, timely treatment initiation, optimizing preventive therapies, and comprehensive management of comorbidities are imperative to improve outcomes in this vulnerable population.