The latest medical research on Infectious Disease

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about infectious disease gathered by our medical AI research bot.

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Secondary antibody deficiency is associated with development of infection in kidney transplantation: results of a multicenter study.

Transplant Infectious Disease

We performed a multicenter study to assess the association between secondary antibody deficiency (IgG hypogammaglobulinemia combined with low levels of specific antibodies) and development of infection in kidney transplantation.

Multivariate logistic regression.

At day 7, IgG hypogammaglobulinemia (IgG levels < 700 mg/dL) combined with low IgG anti-CMV antibody titers (defined as levels < 10000 units) was present in 12% of kidney recipients. IgG hypogammaglobulinemia combined with low IgG anti-PPS antibody titers (defined as levels < 10 mg/dL) at one month after kidney transplantation were recorded in 16% of patients. At day 7 the combination of IgG hypogammaglobulinemia and low anti-CMV titers was independently associated with development of CMV disease (odds ratio [OR], 6.95; 95% confidence interval, 1.17-41.31; p=0.033). At day 30 after transplantation, the combination of IgG < 700 mg/dL and IgG anti-PPS < 10 mg/dL, was independently associated with recurrent bacterial infection (OR, 5.942; 95% CI, 1.943-18.172; p=0.002).

In a prospective multicenter study, early immunologic monitoring of secondary antibody deficiency proved useful for the identification of kidney recipients who developed severe infection.

Significant decline in heavily treatment experienced persons with HIV with limited antiretroviral treatment options in the US, 2000-2017.

AIDS

Historically, a high burden of resistance to antiretroviral therapy (ART) in heavily treatment experienced (HTE) persons with HIV (PWH) resulted in limited treatment options (LTO). We evaluated the prevalence, risk factors, and virologic control of HTE PWH with LTO throughout the modern ART era.

We computed the annual prevalence of HTE PWH with LTO defined as having ≤2 available classes with ≤2 active drugs per class based on genotypic data and cumulative antiretroviral resistance. We used multivariable Cox proportional hazards models to examine risk of LTO by 3-year study entry periods adjusting for demographic and clinical characteristics.

Among 27,133 ART-experienced PWH, 916 were classified as having LTO. The prevalence of PWH with LTO was 5.2-7.5% in 2000-2006, decreased to 1.8% in 2007, and remained < 1% after 2012. Persons entering the study in 2009-2011 had an 80% lower risk of LTO compared with those entering in 2006-2008 (adjusted hazard ratio 0.20; 95% CI: 0.09-0.42). We found a significant increase in undetectable HIV viral loads among PWH ever classified as having LTO from < 30% in 2001 to >80% in 2011, comparable to persons who never had LTO.

Results of this large multicenter study show a dramatic decline in the prevalence of PWH with LTO to < 1% with the availability of more potent drugs and a marked increase in virologic suppression in the current ART era.

Antiretroviral therapy reduces but does not normalize immune and vascular inflammatory markers in adults with chronic HIV infection in Kenya.

AIDS

Markers of monocyte/macrophage activation and vascular inflammation are associated with HIV-related cardiovascular diseases (CVD) and mortality. We compared these markers among African people living with HIV (PLWH) and HIV-negative adults, and examined risk factors associated with elevated biomarkers (>75% percentile) in PLWH on antiretroviral therapy (ART).

We measured serum concentrations of a gut integrity biomarker (I-FABP), monocyte/macrophage activation biomarkers (soluble CD14 and CD163), and vascular inflammation biomarkers (soluble/circulating intercellular[sICAM-1] and vascular[sVCAM-1] cell adhesion molecules-1). We assessed the relationship of these inflammatory parameters with HIV, using logistic regression adjusting for traditional CVD risk factors.

Among the 541 participants, median age was 43 years and half were female. Among 275 PLWH, median CD4+T-cell count and duration of ART use was 509 cells/mm and 8 years respectively. PLWH had significantly higher prevalence of elevated inflammatory biomarkers compared to HIV-negative individuals even after adjustment for traditional CVD risk factors. Compared to subjects without HIV, the prevalence of elevated biomarkers was highest among persons with detectable viral load and CD4+T-cell counts≤200 cells/mm. In a sub-analysis among PLWH, nadir CD4+T-cell count≤200 cells/mm was associated with elevated sCD14; dyslipidemia with elevated sCD14, sICAM-1, and sVCAM-1; and overweight/obesity with reduced sCD14. Longer ART exposure (>4 years) was associated with reduced sVCAM-1 and sICAM-1.

HIV and not traditional CVD risk factors is a primary contributor of monocyte/macrophage activation and inflammation despite ART. Anti-inflammatory therapies in addition to ART may be necessary to reduce these immune dysregulations and improve health outcomes of African PLWH.

Detectable HIV RNA in late pregnancy associated with low tenofovir hair levels at time of delivery among women living with HIV in the United States.

AIDS

We evaluated peripartum tenofovir (TFV) exposure via hair measures among women living with HIV (WLHIV) in the United States.

Observational cohort study METHODS:: Hair samples were collected at or shortly after childbirth among mothers enrolled in the Surveillance Monitoring for ART Toxicities Study of the Pediatric HIV/AIDS Cohort Study (PHACS) between 6/2014-7/2016. Among mothers receiving tenofovir-disoproxil-fumarate (TDF)-based regimens during pregnancy, TFV hair concentrations were analyzed using liquid chromatography/tandem mass spectrometry. Weight-normalized TFV concentrations were log10 transformed. Multivariable linear regression assessed correlates of TFV concentrations.

Overall, 121 mothers on TDF-based ART during pregnancy had hair specimens tested for TFV concentrations and were included in the analysis. Median age at delivery was 31 years (IQR 26-36); 71% self-identified as non-Hispanic black, and 10% had unsuppressed viral loads (VL) in late pregnancy (HIV-RNA ≥400 copies/mL). Median time from birth to hair collection was 3 days (IQR 1-14) and median TFV hair concentration was 0.02 ng/mg (IQR 0.01-0.04). In multivariable models, an unsuppressed VL in late pregnancy was associated with 80% lower adjusted mean peripartum TFV concentrations than pregnancies with viral suppression (95% CI: -90% to -59%, p < 0.001). Use of TDF only in the first trimester and attaining high school graduation were also associated with lower TFV hair concentrations.

Unsuppressed VL during late pregnancy was strongly associated with lower maternal TFV hair concentrations at birth, though viremia was rare. Efforts to improve maternal virological outcomes and eliminate vertical HIV transmission could incorporate drug exposure monitoring using hair or other metrics.

Human distribution and spatial-temporal clustering analysis of human brucellosis in China from 2012 to 2016.

Infectious Diseases of Poverty

Brucellosis is a major public health issue in China, while its temporal and spatial distribution have not been studied in depth. This study aims to better understand the epidemiology of brucellosis in the mainland of China, by investigating the human, temporal and spatial distribution and clustering characteristics of the disease.

Human brucellosis data from the mainland of China between 2012 and 2016 were obtained from the China Information System for Disease Control and Prevention. The spatial autocorrelation analysis of ArcGIS10.6 and the spatial-temporal scanning analysis of SaTScan software were used to identify potential changes in the spatial and temporal distribution of human brucellosis in the mainland of China during the study period.

A total of 244 348 human brucellosis cases were reported during the study period of 2012-2016. The average incidence of human brucellosis was higher in the 40-65 age group. The temporal clustering analysis showed that the high incidence of brucellosis occurred between March and July. The spatial clustering analysis showed that the location of brucellosis clustering in the mainland of China remained relatively fixed, mainly concentrated in most parts of northern China. The results of the spatial-temporal clustering analysis showed that Heilongjiang represents a primary clustering area, and the Tibet, Shanxi and Hubei provinces represent three secondary clustering areas.

Human brucellosis remains a widespread challenge, particularly in northern China. The clustering analysis highlights potential high-risk human groups, time frames and areas, which may require special plans and resources to monitor and control the disease.

Risk factors for intra-abdominal fungal infection after simultaneous pancreas-kidney transplantation: a single-center retrospective experience.

Transplant Infectious Disease

Data on the risk factors and outcome of intra-abdominal fungal infections (IAFI) following simultaneous pancreas-kidney transplantation (PKT) are scarce.

A retrospective monocentric study was conducted on all patients who underwent simultaneous PKT from January 2007 to December 2016. Deep sites positive cultures for fungi during the first post-transplantion year were collected. Clinical, radiological, and microbiological data of proven and probable invasive fungal infections were analysed.

Among sixteen PKT patients, 15 were included. Seven patients (47%) developed an invasive fungal infection, exclusively IAFI (six proven, one probable). The proven IAFI included four peritonitis, one pancreatic necrosis with infected haematoma and one patient with positive preservation fluid only (PF). Candida albicans (n=4) was the most prevalent species (associated with Galactomyces candidus in one case), C. glabrata, C. dubliniensis and C. krusei were found in one case each. Three patients had either a positive direct examination and/or culture for renal or pancreatic PF and the culture of PF was positive for the same species that caused IAFI. IAFIs were significantly associated with pancreatic graft arterial thrombosis (5/7 vs. 0/8, p=0.007) and fungal contamination of PF (3/7 vs. 0/8, p=0.008). Among patients with IAFI, all required an early surgical revision post-transplantation [1-18 days] and six had early or delayed pancreatic graft removal. One patient died in the first post-transplant year.

IAFI is a common complication in PKT, associated with pancreatic graft thrombosis or fungal contamination of the graft PF, and can sometimes lead to pancreatic detransplantation.

The dihydroquinolizinone compound RG7834 inhibits the polyadenylase function of PAPD5/7 and accelerates the degradation of matured HBV surface protein mRNA.

Antimicrobial Agents and Chemotherapy

Hepatitis B virus (HBV) mRNA metabolism is dependent upon host proteins PAPD5 and PAPD7 (PAPD5/7). PAPD5/7 are cellular, non-canonical, poly(A) pol...

TP0591816, a Novel Macrocyclic Respiratory Syncytial Virus Fusion Inhibitor with Antiviral Activity against F Protein Mutants: Pharmacological Characterization.

Antimicrobial Agents and Chemotherapy

Human respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in early childhood. However, no vaccines have yet be...

Is once-daily high-dose ceftriaxone plus ampicillin an alternative for Enterococcus faecalis infective endocarditis in OPAT?

Antimicrobial Agents and Chemotherapy

Ceftriaxone administered as once-daily high-dose short infusion combined with ampicillin has been proposed for the treatment Enterococcus faecalis infectious endocarditis in outpatient parenteral antibiotic therapy programs (OPAT). This combination requires synergistic activity, but the attainment of ceftriaxone synergic concentration (Cs) with the regimen proposed for OPAT has not been studied.

This Phase II pharmacokinetic study enrolled healthy adult volunteers, who underwent two sequential treatment phases. During Phase A volunteers received 2 g of ceftriaxone each 12 hours during 24 hours followed by 7-day washout. Then, the participants received Phase B, which consisted on 4 g single dose of ceftriaxone. Throughout both phases each volunteers underwent intensive pharmacokinetic (PK) sampling over 24 h. Ceftriaxone total and unbound concentrations were measured.

Twelve participants were enrolled and completed both phases. Mean ceftriaxone total and free concentration 24 hours after the administration of 2 g each 12 hours were 86.44±25.90 mg/L and 3.59±1.35 mg/L and after 4 g single dose 34.60±11.16 mg/L and 1.40±0.62 mg/L, respectively. Only 3 (25%) patients in phase A maintained unbound plasma concentrations superior to the suggested Cs=5 mg/L during 24 hours, and none (0%) in phase B. No grade 3-4 adverse events or laboratory abnormalities were observed.

Ceftriaxone optimal exposure combined with ampicillin to achieve maximal synergistic activity against E. faecalis required for the treatment of infective endocarditis remains unknown. Whereas, the administration of a single daily dose 4 g of ceftriaxone implies a reduction in the time of exposure to the proposed Cs.

Tuberculosis symptom screening for children and adolescents living with HIV in six high HIV/TB burden countries in Africa.

AIDS

The World Health Organization recommends that children and adolescents living with HIV (CALHIV) complete TB symptom screening at every clinical encounter, but evidence supporting this recommendation is limited. We evaluated the performance of the recommended TB symptom screening in six high burden TB/HIV countries.

We extracted data from electronic medical records of CALHIV receiving care from clinics in Botswana, Eswatini, Lesotho, Malawi, Tanzania, and Uganda from January 2014 to June 2017. We defined incident TB cases as those prescribed TB treatment within 30 days of TB diagnosis. We analyzed the most recent symptom screen preceding a TB diagnosis. In accordance with WHO guidelines, positive screens were defined as current fever, cough, poor weight gain, or recent TB contact. Odds of TB disease was modeled by screen result and age at which screening was conducted.

20,706 patients collectively had 316,740 clinic visits, of which 240,161 (75.8%) had documented TB symptom screens. There were 35,701 (14.9%) positive TB symptom screens, and 1212 incident TB diagnoses. Sensitivity and specificity of the TB symptom screen to diagnose TB were 61.2% (95% CI 58.4 to 64.0) and 88.8% (95% CI 88.7 to 88.9), respectively. Log odds of documented TB for positive or negative screens was statistically different only for screens conducted at ages 7 to 17.

While specificity was high, the sensitivity of the TB symptom screen to detect TB in CALHIV was low. More accurate screening approaches are needed to optimally identify TB disease in CALHIV.

Tenofovir alafenamide versus tenofovir disoproxil fumarate - an updated meta-analysis of 14,894 patients across 14 trials.

AIDS

Both TDF/FTC and TAF/FTC demonstrate excellent efficacy and safety overall, but concerns remain over specific changes in markers of bone and renal function. Lower plasma tenofovir concentrations are seen with tenofovir alafenamide (TAF) and in unboosted regimens. We assess TAF versus TDF safety with and without booster co-formulation.

A previous systematic review was updated with recent clinical trials. TAF versus TDF efficacy and safety were compared in boosted and unboosted subgroups. Efficacy was measured by viral suppression. Key safety endpoints included all adverse events (AEs), serious AEs, grade 3-4 AEs and AE discontinuation. Further specific renal and bone markers were also assessed.

14 clinical trials comparing TDF and TAF regimens were identified. A significant difference (p=0.0004) in efficacy was shown in the boosted subgroup in favour of TAF, but no difference was seen in the unboosted subgroup. There were no significant differences between TAF and TDF for any of the key safety endpoints analysed. No differences were seen for the bone markers analysed. No difference was found for renal tubular events. There was a difference in risk for discontinuation due to renal adverse events when boosted (p=0.03), but none when unboosted.

Across all main safety endpoints, no differences between TAF and TDF are seen. Boosted TDF regimens were associated with lesser comparative efficacy than boosted TAF and a higher risk of renal event discontinuation. However, modern antiretroviral regimens are more commonly unboosted. This study finds no difference in efficacy or safety in unboosted TAF versus TDF.