Treatment Of Acute Infections Research Articles

Higher diagnostic value of metagenomic next-generation sequencing in acute infection than chronic infection: a multicenter retrospective study.

The aim of this study is to compare the diagnostic value of metagenomic next-generation sequencing (mNGS) vs. conventional culture methods (CM) in chronic infection and acute infection. We retrospectively analyzed the bronchoalveolar lavage fluid (BALF) of 88 patients with acute infection and 105 patients with chronic infection admitted to three hospitals from 2017 to 2022. The results showed that the sensitivity and specificity of mNGS were higher than those of CM. The number of patients who changed the antibiotic treatment in the mNGS positive group was larger than that of patients in the mNGS negative group in both the acute infection group (60.5 vs. 28.0%, P = 0.0022) and chronic infection group (46.2 vs. 22.6%, P = 0.01112). High levels of temperature (OR: 2.02, 95% CI: 1.18-3.70, P: 0.015), C-reactive protein (CRP) (OR: 15, 95% CI: 2.74-280.69, P: 0.011), neutrophil count (OR: 3.09, 95% CI: 1.19-8.43, P: 0.023), and low levels of lymphocyte count (OR: 3.43, 95% CI:1.26-10.21, P: 0.020) may lead to positive mNGS results in the acute infection group while no significant factor was identified to predict positive results in the chronic infection group. mNGS could provide useful guidance on antibiotic strategies in infectious diseases and may be more valuable for the diagnosis and treatment of acute infection vs. chronic infection.

Chronic granulomatous disease in the United Arab Emirates: clinical and molecular characteristics in a single center.

Chronic granulomatous disease (CGD) is a genetic disorder caused by defective oxidative burst within phagocytes, manifesting as recurrent, severe infections as well as hyperinflammation. This is the first report from the United Arab Emirates (UAE) to describe the demographic, clinical, laboratory, radiological, and genetic characteristics of patients with CGD. This is a retrospective study that was conducted at Tawam Hospital in the UAE on patients with confirmed CGD between 2017 and 2022. A total of 14 patients were diagnosed with CGD, of whom 13 patients had autosomal recessive (AR) CGD due to NCF1 deficiency. Consanguinity was noted in all patients with AR CGD, whereas positive family history was identified in 50% of cases. The median age of onset of symptoms was 24 months, while the median age at diagnosis was 72 months. Lymphadenitis was the most common clinical feature identified in 71% of patients. Other common infectious manifestations included abscess formation (57%), pneumonia (50%), invasive aspergillosis (21%), oral thrush (14%), and sepsis (14%). Disseminated trichosporonosis was reported in one patient. Autoimmune and inflammatory manifestations included celiac disease in two patients, diabetes mellitus and asymptomatic colitis in one patient each. Genetic analysis was performed in all patients; NCF1 deficiency was diagnosed in 13 (93%) patients, with c.579G>A being the most prevalent pathogenic variant identified. The treatment modalities, as well as treatment of acute infections, treatment modalities included antimicrobial prophylaxis in 12 (86%) patients and hematopoietic stem cell transplant in six patients (42%). This is the first report from the UAE describing the clinical and molecular characteristics of patients with CGD. The homozygous variant c.579G>A causing NCF1 deficiency can be considered as a founder mutation for AR CGD in the UAE.

Antibiotic allergies: targeted approach in suspected β‑lactam allergy

Allergic reactions to antibiotics belong to hypersensitivity drug reactions and can trigger both immunoglobulinE-mediated symptoms and Tcell-mediated symptoms. Skin manifestations are the most common symptoms. Although reporting apenicillin allergy results in considerable restrictions in the treatment of acute infections, which may be associated with poor treatment outcomes, in most cases the label 'penicillin allergy' is not called into question or critically reviewed. However, in 85-90% of patients, 'penicillin allergy' constitutes amislabeling of anon-specific intolerance reaction that does not pose arisk to the patient when re-exposed to penicillins. Careful history taking, an evaluation of manifestations in the past, and easy-to-perform initial diagnostic steps are crucial in differentiating non-specific intolerance reactions from penicillin allergy sensu stricto. Thus, apenicillin de-labeling strategy allows for optimized antibiotic therapy in the event of afuture infection. Although allergic cross-reactivity between different β‑lactam antibiotics can occur, the risk for asevere cross-reactivity is dependent on chemical properties of the specific β‑lactam. Published cross-reactivity tables can help in risk stratification and choice of alternative β‑lactam agents.

Antibiotikaallergien – gezieltes Vorgehen bei vermeintlicher β‑Laktam-Allergie

Allergic reactions to antibiotics belong to hypersensitivity drug reactions and can trigger both immunoglobulinE-mediated symptoms and Tcell-mediated symptoms. Skin manifestations are the most common symptoms. Although reporting apenicillin allergy results in considerable restrictions in the treatment of acute infections, which may be associated with poor treatment outcomes, in most cases the label 'penicillin allergy' is not called into question or critically reviewed. However, in 85-90% of patients, 'penicillin allergy' constitutes amislabeling of anon-specific intolerance reaction that does not pose arisk to the patient when re-exposed to penicillins. Careful history taking, an evaluation of manifestations in the past, and easy-to-perform initial diagnostic steps are crucial in differentiating non-specific intolerance reactions from penicillin allergy sensu stricto. Thus, apenicillin de-labeling strategy allows for optimized antibiotic therapy in the event of afuture infection. Although allergic cross-reactivity between different β‑lactam antibiotics can occur, the risk for asevere cross-reactivity is dependent on chemical properties of the specific β‑lactam. Published cross-reactivity tables can help in risk stratification and choice of alternative β‑lactam agents.

Concept of HBV and HCV as a risk factor and prevention of viral hepatitis-related hepatocellular carcinoma

Abstract Hepatocellular carcinoma (HCC) represents one of the most common cancers worldwide, and it is a very important reason for cancer-related death. Infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) is considered the major leading cause of HCC. The pathophysiology of HB and HC viral-related HCC includes chronic inflammation, deorganization of cell signaling pathways, and oxidative stress. Contrary to HCV, HBV is oncogenic by itself, due to its integration into the DNA of cell. Six months of ultrasound monitoring is recommended for high-risk patients. Using antiviral drugs to manage viral hepatitis decreases the risk of evolution and reoccurrence of HCC. Also, effective preventive measures are very important in decreasing the risk of HCC. The prevention involves primary prevention which is based on HBV vaccination, treatment of acute infection, and eliminating the route of transmission, while secondary prevention is based on using antiviral drugs against HBV and HCV infection to prevent the progress of disease into carcinoma. However, tertiary prevention involves treating the carcinoma to prevent the reoccurrence of the cancer.

Complications of the surgical treatment of fractures of the tibial plateau: prevalence, causes, and management

Open reduction and internal fixation is the gold standard treatment for tibial plateau fractures. However, the procedure is not free of complications such as knee stiffness, acute infection, chronic infection (osteomyelitis), malunion, non-union, and post-traumatic osteoarthritis.The treatment options for knee stiffness are mobilisation under anaesthesia (MUA) when the duration is less than 3 months, arthroscopic release when the duration is between 3 and 6 months, and open release for refractory cases or cases lasting more than 6 months. Early arthroscopic release can be associated with MUA.Regarding treatment of acute infection, if the fracture has healed, the hardware can be removed, and lavage and debridement can be performed along with antibiotic therapy. If the fracture has not healed, the hardware is retained, and lavage, debridement, and antibiotic therapy are performed (sometimes more than once until the fracture heals). Fracture stability is important not only for healing but also for resolving the infection.In cases of osteomyelitis, treatment should be performed in stages: aggressive debridement of devitalised tissue and bone, antibiotic spacing and temporary external fixation until the infection is resolved (first stage), followed by definitive surgery with grafting or soft tissue coverage depending on the bone defect (second stage).Intra-articular or extra-articular osteotomy is a good option to correct malunion in young, active patients without significant joint damage. When malunion is associated with extensive joint involvement or the initial cartilage damage has resulted in knee osteoarthritis, the surgical option is total knee arthroplasty.

Clinical Evidence on the Use of Chinese Herbal Medicine for Acute Infectious Diseases: An Overview of Systematic Reviews.

Background: Acute infectious diseases constitute the most prevalent public health emergency (PHE) in China. Chinese herbal medicine (CHM) has long been used in the treatment of acute infections, but the overall evidence of its benefit and harm has not been comprehensively and systematically evaluated. Methods: We searched CBM, CNKI, Wanfang, PubMed, Cochrane Library, embase and preprint platforms to retrieve systematic reviews (SRs) on CHM for acute infectious. Participants with COVID-19, SARS, H1N1, tuberculosis, bacillary dysentery, mumps, herpangina, hand-foot-and-mouth disease (HFMD), and other acute infectious diseases were included. Interventional group consisting of patients treated with CHM combined with Western medicine or CHM alone. The AMSTAR 2 tool was used to assess the methodological quality of the retrieved studies. Information on interventions, control measures and outcomes of the included studies was extracted, and meta-analyses were qualitatively synthesized. Results: A total of 51 SRs and meta-analyses were eligible for this overview, including 19 for COVID-19, 11 for hand-foot-and-mouth disease, 8 for severe acute respiratory syndrome (SARS), 4 for tuberculosis, 3 for mumps, 2 for bacillary dysentery, 2 for H1N1 influenza and 2 for herpangina. Six systematic reviews were of high quality, all of which were on the use of CHM for COVID-19; 24 were of moderate quality; 10 were of low quality; and 11 were of very low quality. CHM appeared to have potential benefits in improving clinical symptoms and signs for most infections with an acceptable safety profile, and the clinical evidence of the benefits of CHM for acute respiratory infections such as COVID-19, SARS and H1N1 seems more sufficient than that for other acute infections. Conclusion: Overall, CHM, both decoction and Chinese patent medicine, used alone or in combination with conventional medicine may offer potential benefits to relieving symptoms of people with acute respiratory infections. Full reporting of disease typing, staging, and severity, and intervention details is further required for a better evidence translation to the responses for PHE. Future CHM research should focus mainly on the specific aspects of respiratory infections such as its single use for mild infections, and the adjunct administration for sever infections, and individual CHM prescriptions for well-selected outcomes should be prioritized.

P19 IV antimicrobial duration in practice

BackgroundTackling antimicrobial resistance by reducing unnecessary or inappropriate prescribing is a key priority.ObjectivesTo review current clinical practice at Guy's and St Thomas’ Hospital around duration of IV antimicrobial therapy framed with Start Smart Then Focus national guidelines.MethodsNewly started inpatient prescriptions for IV antimicrobials over three consecutive Mondays were reviewed. Prescriptions not for treatment of acute infections were excluded, as were patients admitted to critical care, obstetrics/gynaecology and paediatric wards. Each patient's record was reviewed at Day 0, 3 and 5. Data were analysed using IBM® SPSS Statistics version 27.ResultsIn total, 80 patients with 89 antibiotic prescriptions (71 = β-lactam, 5 = aminoglycoside, 2 = glycopeptide, 1 = ciprofloxacin, 9 = metronidazole, 1 = linezolid) were included. Median age was 66 (IQR 53–75). Documented indications were for suspected or proven infection of urinary tract (15%), respiratory tract (25%), skin/soft tissue (14%), sepsis (1.25%), intra-abdominal (15%), bacteraemia (7.5%), bone and joint infections (2.5%) or other (20%). Median initial NEWS2 on Day 0 was 3 (IQR 1–4), WCC 11.45 (IQR 8.27–14.15) and CRP 121 (IQR 47–208). Median length of stay was 7.5 days. Median duration of IV antimicrobial was 4 (IQR 2–6) days. By D3, 3 patients had died and 16 had been discharged. Of 61 remaining inpatients on D3, 4 had their antimicrobials switched, 14 had been switched to PO antimicrobials, 43 were continued on IV antibiotics. By D5, 17 further patients had been discharged, 44 remained inpatients. Twenty-two had stopped antimicrobials with 22 continuing IV therapy. A number of patients could have been switched from IV to oral therapy by current guidance but were not (D3 x = 11, D5 n = 8). Higher median D0 CRP was seen in those who continued on IV therapy on D3 (139 versus 79 mg/dL) as was higher D3 WCC (13.9 versus 11.9 × 109/L). There was no significant relationship between a NEWS2 score ≥3 and IV to PO switch at D3 or D5. Thirty-two patients had input from the Infection team within 7 days of first prescription. Fifteen patients (21%) received IV antibiotics for more than 7 days, and 14/15 had Infection team input. Three patients were discharged with OPAT.ConclusionsMedian duration of IV therapy for suspected/proven infections in our centre is less than 5 days and only 28% of patients were still receiving IV antibiotics by D5. A number of missed opportunities for earlier switch to oral therapy were identified. The potential for earlier safe discontinuation of IV therapy using patient-specific measures should be explored. A minority of patients received IV therapy for >7 days, and this was almost universally associated with specialist Infection involvement in complex infections with a view to optimizing patient management and antimicrobial stewardship.

In Vivo Evaluation of ECP Peptide Analogues for the Treatment of Acinetobacter baumannii Infection.

Antimicrobial peptides (AMPs) are alternative therapeutics to traditional antibiotics against bacterial resistance. Our previous work identified an antimicrobial region at the N-terminus of the eosinophil cationic protein (ECP). Following structure-based analysis, a 30mer peptide (ECPep-L) was designed that combines antimicrobial action against Gram-negative species with lipopolysaccharides (LPS) binding and endotoxin-neutralization activities. Next, analogues that contain non-natural amino acids were designed to increase serum stability. Here, two analogues were selected for in vivo assays: the all-D version (ECPep-D) and the Arg to Orn version that incorporates a D-amino acid at position 2 (ECPep-2D-Orn). The peptide analogues retained high LPS-binding and anti-endotoxin activities. The peptides efficacy was tested in a murine acute infection model of Acinetobacter baumannii. Results highlighted a survival rate above 70% following a 3-day supervision with a single administration of ECPep-D. Moreover, in both ECPep-D and ECPep-2D-Orn peptide-treated groups, clinical symptoms improved significantly and the tissue infection was reduced to equivalent levels to mice treated with colistin, used as a last resort in the clinics. Moreover, treatment drastically reduced serum levels of TNF-α inflammation marker within the first 8 h. The present results support ECP-derived peptides as alternative candidates for the treatment of acute infections caused by Gram-negative bacteria.

675. Crimean-Congo Hemorrhagic Fever Beyond Ribavirin: A Systematic Review

BackgroundThe Crimean-Congo Hemorrhagic Fever (CCHF) is a tick-borne virus infection that has been reported in about 30 countries worldwide. Clinical presentation is divided into three phases: pre-hemorrhagic, hemorrhagic, and convalescence. Ribavirin is standard of care treatment for acute infection and prophylaxis. However, the use of other treatments beyond ribavirin is largely unknown.MethodsWe conducted a systematic review using MOOSE protocol. The inclusion and exclusion criteria are seen in the Prisma diagram. For Bias Analysis we use a Robin-1 tool. Literature review algorithm ResultsWe gathered a total of 10 studies, which included 4 therapeutic plasma exchange (TPE), 2 corticosteroids, 2 IVIG, and 1 with convalescent plasma (CP).TPE in one study showed decreased mortality rate and increased efficacy in patients with severe CCHF. While the other study reported pulmonary embolism related to the use of TPE. Nevertheless, the patients had good outcome in the end. Two case reports used TPE plus ribavirin and supportive measures. Both were discharged home and recovered without sequela. Corticosteroids were found to be beneficial in one study were the case fatality rate was lower with the addition of corticosteroids to ribavirin in severely ill patients (p=0.0014). In a case series of six patients, who received the combination in early stages of the disease had good clinical outcomes with improved survival. IVIG was shown to increase platelet counts in two studies. In the first study, platelet count increased above 150,000/mL in 8.5 +/- 2.5 days. While in the other study the normalization of platelets was seen in 4 - 4.8 days, with no significant difference (P = 0.49). In addition, there was a decrease in the duration of symptoms but there was no statistically significant difference in mortality rates (P = 0.171). CP treatment showed a survival rate of 86% in treated patients. CP was more useful in high-risk patients, defined as having a viral load of 108 copies/mL or more. The main limitations of the studies were the sample size and heterogenicity among the outcomes of the studies. ConclusionTPE, CP, IVIG, and corticosteroids were effective in improving the clinical outcomes of the patients. The use of these treatments beyond ribavirin should be explored in future studies. Disclosures All Authors: No reported disclosures

Phenothiazines as dual inhibitors of SARS-CoV-2 main protease and COVID-19 inflammation

COVID-19, caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2), currently has no treatment for acute infection. The main protease (Mpro) of SARS-CoV-2 is an essential enzyme for viral replication and an attractive target for disease intervention. The phenothiazine moiety has demonstrated drug versatility for biological systems, including inhibition of butyrylcholinesterase, a property important in the cholinesterase anti-inflammatory cascade. Nineteen phenothiazine drugs were investigated using in silico modelling techniques to predict binding energies and inhibition constants (Ki values) with SARS-CoV-2 Mpro. Because most side-effects of phenothiazines are due to interactions with various neurotransmitter receptors and transporters, phenothiazines with few such interactions were also investigated. All compounds were found to bind to the active site of SARS-CoV-2 Mpro and showed Ki values ranging from 1.30 to 52.4 µM in a rigid active site. Nine phenothiazines showed inhibition constants <10 µM. The compounds with limited interactions with neurotransmitter receptors and transporters showed micromolar (µM) Ki values. Docking results were compared with remdesivir and showed similar interactions with key residues Glu-166 and Gln-189 in the active site. This work has identified several phenothiazines with limited neurotransmitter receptor and transporter interactions and that may provide the dual action of inhibiting SARS-CoV-2 Mpro to prevent viral replication and promote the release of anti-inflammatory cytokines to curb viral-induced inflammation. These compounds are promising candidates for further investigation against SARS-CoV-2.

Geographic Variability and Pathogen-Specific Considerations in the Diagnosis and Management of Chronic Granulomatous Disease.

Chronic granulomatous disease (CGD) is a rare but serious primary immunodeficiency with varying prevalence and rates of X-linked and autosomal recessive disease worldwide. Functional defects in the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex predispose patients to a relatively narrow spectrum of bacterial and fungal infections that are sometimes fastidious and often difficult to identify. When evaluating and treating patients with CGD, it is important to consider their native country of birth, climate, and living situation, which may predispose them to types of infections that are atypical to your routine practice. In addition to recurrent and often severe infections, patients with CGD and X-linked female carriers are also susceptible to developing many non-infectious complications including tissue granuloma formation and autoimmunity. The DHR-123 oxidation assay is the gold standard for making the diagnosis and it along with genetic testing can help predict the severity and prognosis in patients with CGD. Disease management focuses on prophylaxis with antibacterial, antifungal, and immunomodulatory medications, prompt identification and treatment of acute infections, and prevention of secondary granulomatous complications. While hematopoietic stem-cell transplantation is the only widely available curative treatment for patients with CGD, recent advances in gene therapy may provide a safer, more direct alternative.

Treatment of acute infection around prosthesis with vacuum sealing drainage and sensitive antibiotics

To investigate the therapeutic effects of vacuum sealing drainage (VSD) combined with antibiotics in treating acute periprosthetic joint infection (PJI). From March 2012 to December 2018, there were 11 patients with acute PJI underwent debridement, VSD, antibiotics and retention of implant, including 7 males and 4 females, with an average age of 72.5 years old (ranged, 58 to 88 years old). There were 8 hips and 3 knees. Three patients had sinus tract. There were 2 patients with negative culture result and 9 patients with positive culture result, including 5 cases of methicillin sensitive staphylococcus aureus, 2 cases of methicillin-resistant staphylococcus aureus (MRSA), 2 cases of staphylococcus epidermidis. The mean follow up duration was 28 months (ranged from 8 to 52 months). One case of infection around hip prosthesis failed to be debrided. The time of debridement and replacement of the calcar joint was 84 days. Debridement was successful in 10 cases. At the latest follow up, Harris score of patients with successful debridement of hip periprosthetic infection ranged from 74 to 93, with an average score of 84.1;Knee Society scores of patients with periprosthetic infection were 84, 84, 89. For acute infection around the prosthesis within 1 month after knee replacement and 6 weeks after hip replacement, and for bleeding around the prosthesis with acute infection caused by anticoagulant drugs, satisfactory results can be obtained by debridement, VSD and sensitive antibiotics.

Infection associated relapses in children with nephrotic syndrome: A short-term outcome study.

Children with nephrotic syndrome (NS) encounter multiple episodes of relapses associated/triggered by an episode of infection. The primary objective of this study was to find the proportion of infection associated relapses that resolve on the treatment of acute infection over an observation period of two weeks in children with NS. This prospective observational study enrolled 45 children with steroid-sensitive NS presenting with an infection associated relapse during the study period (February 2015 to February 2016). Baseline information and examination findings of all children were recorded. Biochemical and other investigations were performed according to the site of infection for all patients and were treated appropriately. None of the patients received daily 2 mg/kg of prednisolone during the observation period. All children were followed for two weeks for resolution of relapse and subsequently every month for another three months. The 45 patients (median age 66 months) enrolled in the study had 64 episodes of infections, of which upper respiratory tract infections (45%) were the commonest, followed by peritonitis (18.5%) and diarrhea in 12%. Twenty-seven (60%) patients achieved remission on symptomatic treatment of infection with/without the use of stress doses of prednisolone. Most (77.8%) patients who achieved remission without the use of daily 2 mg/kg of prednisolone did so within the 1st week and a majority of patients were still in remission at three months follow-up. We conclude that most infection associated relapses can be managed with treatment of underlying infection alone and use of stress doses of steroids for inducing remission without increasing the prednisolone doses to 2 mg/kg/d and thus reducing the cumulative steroid doses.

Recurrent Urinary Tract Infection in Women

The purpose of this review is to discuss the pathophysiology, diagnosis, treatment, and prevention of recurrent urinary tract infection (UTI) in the setting of antimicrobial stewardship. Although recurrent UTI was traditionally thought to occur by repeated ascension of uropathogenic colonizers, newer evidence suggests that a subset of bacteria becomes internalized within uroepithelial cells forming quiescent intracellular reservoirs. These quiescent reservoirs do not elicit an immune response and persist after treatment of acute infection. In time, epithelial turnover results in release of these bacteria potentially leading to recurrent infection. Given the rise in antimicrobial resistance, the concept of antimicrobial stewardship has been developed to promote appropriate use of antimicrobials, improve patient outcomes, decrease microbial resistance, and reduce the spread of infections caused by multidrug-resistant organisms. This has sparked interest in non-antimicrobial measures for UTI prevention. Although cranberry products and probiotics may prevent UTI, the data for their efficacy are limited. Current evidence supports vaginal estrogen use for UTI prevention in postmenopausal women. Daily or post-coital low-dose antimicrobial prophylaxis may also be beneficial, particularly for women who develop UTI despite non-antimicrobial measures. Nevertheless, studies demonstrating the efficacy of antimicrobial prophylaxis are > 10 years old when antibiotic resistance was less common. Prevention of recurrent UTI requires identifying and addressing risk factors for infection. Non-antimicrobial strategies should be recommended whenever possible given increasing antimicrobial resistance. However, more studies are needed to define the ideal populations that may benefit from current non-antimicrobial strategies and to identify other potential ways UTI may be prevented.

Clinical study on operation in treatment of acute infection after joint replacement surgery

Clinical study on operation in treatment of acute infection after joint replacement surgery

Body Mass Index and Risk of Infections Among Women in the Danish National Birth Cohort.

We investigated the possible association between body mass index (BMI; weight (kg)/height (m)(2)) and hospitalization or treatment for acute infection in a prospective cohort study. We linked 75,001 women enrolled in the Danish National Birth Cohort from 1996 to 2002, who had information on BMI and a broad range of confounders, to data on infectious diseases and use of antimicrobial agents from the National Patient Register and the Danish Prescription Register. Associations were tested using Cox proportional hazards models. During 12 years of follow-up, we observed a U-shaped association between baseline BMI and later hospitalization for 1) any infectious disease and 2) infections of the respiratory tract, whereas a dose-response relationship was seen for skin infections. The most pronounced associations were seen for acute upper respiratory infections at multiple and unspecified sites (underweight (BMI <18.5): hazard ratio (HR) = 4.26, 95% confidence interval (CI): 1.69, 10.7; obesity (BMI ≥30): HR = 3.64, 95% CI: 1.62, 8.18), erysipelas (obesity: HR = 5.19, 95% CI: 3.38, 7.95), and fungal infections (underweight: HR = 3.19, 95% CI: 1.53, 6.66). Slightly greater use of antimicrobials was observed among overweight (BMI 25-<30; HR = 1.08, 95% CI: 1.06, 1.10) and obese (HR = 1.21, 95% CI: 1.17, 1.24) women. Among Danish women, underweight and obesity were associated with increased risk of community-acquired infectious diseases, especially infections of the upper respiratory tract and skin.

Interferon Alpha Subtype-Specific Suppression of HIV-1 Infection In Vivo.

Although all 12 subtypes of human interferon alpha (IFN-α) bind the same receptor, recent results have demonstrated that they elicit unique host responses and display distinct efficacies in the control of different viral infections. The IFN-α2 subtype is currently in HIV-1 clinical trials, but it has not consistently reduced viral loads in HIV-1 patients and is not the most effective subtype against HIV-1 in vitro We now demonstrate in humanized mice that, when delivered at the same high clinical dose, the human IFN-α14 subtype has very potent anti-HIV-1 activity whereas IFN-α2 does not. In both postexposure prophylaxis and treatment of acute infections, IFN-α14, but not IFN-α2, significantly suppressed HIV-1 replication and proviral loads. Furthermore, HIV-1-induced immune hyperactivation, which is a prognosticator of disease progression, was reduced by IFN-α14 but not IFN-α2. Whereas ineffective IFN-α2 therapy was associated with CD8(+) T cell activation, successful IFN-α14 therapy was associated with increased intrinsic and innate immunity, including significantly higher induction of tetherin and MX2, increased APOBEC3G signature mutations in HIV-1 proviral DNA, and higher frequencies of TRAIL(+) NK cells. These results identify IFN-α14 as a potent new therapeutic that operates via mechanisms distinct from those of antiretroviral drugs. The ability of IFN-α14 to reduce both viremia and proviral loads in vivo suggests that it has strong potential as a component of a cure strategy for HIV-1 infections. The broad implication of these results is that the antiviral efficacy of each individual IFN-α subtype should be evaluated against the specific virus being treated. The naturally occurring antiviral protein IFN-α2 is used to treat hepatitis viruses but has proven rather ineffective against HIV in comparison to triple therapy with the antiretroviral (ARV) drugs. Although ARVs suppress the replication of HIV, they fail to completely clear infections. Since IFN-α acts by different mechanism than ARVs and has been shown to reduce HIV proviral loads, clinical trials are under way to test whether IFN-α2 combined with ARVs might eradicate HIV-1 infections. IFN-α is actually a family of 12 distinct proteins, and each IFN-α subtype has different efficacies toward different viruses. Here, we use mice that contain a human immune system, so they can be infected with HIV. With this model, we demonstrate that while IFN-α2 is only weakly effective against HIV, IFN-α14 is extremely potent. This discovery identifies IFN-α14 as a more powerful IFN-α subtype for use in combination therapy trials aimed toward an HIV cure.

Chronic Neutropenia in Childhood: Experience From a Single Center.

Chronic neutropenia (CN) is defined as neutropenia that persists for >3 months; it is caused by a heterogeneous group of diseases in children. The aim of the present study was to evaluate the significance and clinical manifestations of CN in children at a single children's hospital. Between October 2004 and April 2014, CN patient data were evaluated retrospectively. Thirty-one patients were assessed in this study. Thirteen of them (41.9%) were younger than 12 months of age at initial diagnosis. There was no difference in the absolute number of neutrophils at diagnosis between the children aged younger than 12 months and those aged 12 months and older at CN onset. Twenty-two of the patients (70.9%) were diagnosed during treatment for acute infections. A total of 11 patients (35.5%) were hospitalized because of recurrent infections. Most of the recurrent infections occurred in the lungs (81.8%). Congenital neutropenia (CoN) was identified in 14 patients (45.1%). Eight of 14 patients (57.1%) required granulocyte-colony stimulating factor treatment, and none of them experienced adverse effects from this treatment. Fifteen patients (48.3%) were diagnosed with idiopathic neutropenia. Comparison between the idiopathic and CoN groups revealed no differences in age, the absolute number of neutrophils, or the presence of infection at diagnosis; however, differences were detected in sex and the rate of spontaneous recovery from neutropenia. Ten of the patients (32.2%) experienced spontaneous recovery from neutropenia during a follow-up period of 7 to 52 months. In current study, we found a higher CoN ratio in the CN patients compared with previous reports, which may be due to the high rate of consanguineous marriages in our country. However, the finding of CN requires several laboratory investigations, prolonged follow-up, and advanced molecular analysis, and its etiology can remain idiopathic.

The feasibility of eliminating podoconiosis.

Podoconiosis is an inflammatory disease caused by prolonged contact with irritant minerals in soil. Major symptoms include swelling of the lower limb (lymphoedema) and acute pain. The disease has major social and economic consequences through stigma and loss of productivity. In the last five years there has been good progress in podoconiosis research and control. Addressing poverty at household level and infrastructure development such as roads, water and urbanization can all help to reduce podoconiosis incidence. Specific control methods include the use of footwear, regular foot hygiene and floor coverings. Secondary and tertiary prevention are based on the management of the lymphoedema-related morbidity and include foot hygiene, foot care, wound care, compression, exercises, elevation of the legs and treatment of acute infections. Certain endemic countries are taking the initiative to include podoconiosis in their national plans for the control of neglected tropical diseases and to scale up interventions against the disease. Advocacy is needed for provision of shoes as a health intervention. We suggest case definitions and elimination targets as a starting point for elimination of the disease.