Prevention Of Influenza Research Articles

Genotoxic effect of Tamiflu and Adamine on DNA content in male albino mice

BackgroundTamiflu (Oseltamivir) and Adamine (Amantadine HCl) are antiviral drugs which are used for prevention and treatment for influenza. The present study was carried out to evaluate the effect of Tamiflu and Adamine on DNA content of hepatocytes of adult male albino mice.ResultsThe results of comet assay showed that treatment with Tamiflu and Adamine significantly increased (P < 0.005) the mean of DNA damage in hepatocytes of the treated mice in time dependent manner compared to control one. However qRT-PCR analysis showed the mRNA expression of BAX in mice liver of all treated groups with Adamine was significantly increased (P < 0.05) after ten days of treatment while the same gene was significantly decreased in Tamiflu treated group after ten days compared to control one, While the treatment of mice with both drugs simultaneously showed a significant increase (P < 0.05) in expression of BCL-2 gene and a decrease in expression of BAX gene after fifteen days of treatment.ConclusionTamiflu and Adamine had produced deleterious impacts on DNA content of hepatocytes of treated mice. Whereas, the results of treatments with Adamine indicated pathogenic impacts more than that induced by Tamiflu.

Drug repurposing of rimantadine for treatment of cancer.

Repurposing of approved drugs allows strong savings in time and investment. Rimantadine is an FDA-approved drug for prevention and treatment of influenza A infection. Patent US2021330605 describes the use of rimantadine, an adamantane derivative, for the treatment of melanoma, breast cancerand head and neck squamous cell carcinoma. Rimantadine inhibited proliferation of cell lines of melanoma, breast cancer, and head and neck squamous cell carcinoma, increased the survival of mice injected with cancer cell linesand restores the expression of MHC class I. Rimantadine has the potential to be used successfully in the treatment of head and neck squamous cell carcinoma.

Recommendations for Prevention and Control of Influenza in Children, 2023-2024.

This statement updates the recommendations of the American Academy of Pediatrics for the routine use of influenza vaccine and antiviral medications in the prevention and treatment of influenza in children during the 2023-2024 influenza season. A detailed review of the evidence supporting these recommendations is published in the accompanying technical report (www.pediatrics.org/cgi/doi/10.1542/peds.2023-063773). The American Academy of Pediatrics recommends annual influenza vaccination of all children without medical contraindications starting at 6 months of age. Children are at risk for hospitalization and death from influenza. Influenza vaccination is an important strategy for protecting children and the broader community, as well as reducing the overall burden of respiratory illnesses when other viruses are cocirculating. Any licensed influenza vaccine appropriate for age and health status can be administered, ideally as soon as possible in the season, without preference for one product or formulation over another. Antiviral treatment of influenza is recommended for children with suspected (eg, influenza-like illness [fever with either cough or sore throat]) or confirmed influenza who are hospitalized, have severe or progressive disease, or have underlying conditions that increase their risk of complications of influenza, regardless of duration of illness. Antiviral treatment should be initiated as soon as possible. Antiviral treatment may be considered in the outpatient setting for symptomatic children with suspected or confirmed influenza disease who are not at high risk for influenza complications, if treatment can be initiated within 48 hours of illness onset. Antiviral treatment may also be considered for children with suspected or confirmed influenza disease whose siblings or household contacts either are younger than 6 months or have a high-risk condition that predisposes them to complications of influenza. Antiviral chemoprophylaxis is recommended for the prevention of influenza virus infection as an adjunct to vaccination in certain individuals, especially exposed children who are at high risk for influenza complications but have not yet been immunized or those who are not expected to mount an effective immune response.

Recommendations for Prevention and Control of Influenza in Children, 2023-2024.

This technical report accompanies the recommendations of the American Academy of Pediatrics for the routine use of influenza vaccine and antiviral medications in the prevention and treatment of influenza in children during the 2023-2024 season. The rationale for the American Academy of Pediatrics recommendation for annual influenza vaccination of all children without medical contraindications starting at 6 months of age is provided. Influenza vaccination is an important strategy for protecting children and the broader community against influenza. This technical report summarizes recent influenza seasons, morbidity and mortality in children, vaccine effectiveness, and vaccination coverage, and provides detailed guidance on vaccine storage, administration, and implementation. The report also provides a brief background on inactivated and live-attenuated influenza vaccines, available vaccines this season, vaccination during pregnancy and breastfeeding, diagnostic testing for influenza, and antiviral medications for treatment and chemoprophylaxis. Strategies to promote vaccine uptake are emphasized.

Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices — United States, 2023–24 Influenza Season

Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices — United States, 2023–24 Influenza Season

Protocol for establishing a model for integrated influenza surveillance in Tamil Nadu, India.

The potential for influenza viruses to cause public health emergencies is great. The World Health Organisation (WHO) in 2005 concluded that the world was unprepared to respond to an influenza pandemic. Available surveillance guidelines for pandemic influenza lack the specificity that would enable many countries to establish operational surveillance plans. A well-designed epidemiological and virological surveillance is required to strengthen a country's capacity for seasonal, novel, and pandemic influenza detection and prevention. Here, we describe the protocol to establish a novel mechanism for influenza and SARS-CoV-2 surveillance in the four identified districts of Tamil Nadu, India. This project will be carried out as an implementation research. Each district will identify one medical college and two primary health centres (PHCs) as sentinel sites for collecting severe acute respiratory infections (SARI) and influenza like illness (ILI) related information, respectively. For virological testing, 15 ILI and 10 SARI cases will be sampled and tested for influenza A, influenza B, and SARS-CoV-2 every week. Situation analysis using the WHO situation analysis tool will be done to identify the gaps and needs in the existing surveillance systems. Training for staff involved in disease surveillance will be given periodically. To enhance the reporting of ILI/SARI for sentinel surveillance, trained project staff will collect information from all ILI/SARI patients attending the sentinel sites using pre-tested tools. Using time, place, and person analysis, alerts for abnormal increases in cases will be generated and communicated to health authorities to initiate response activities. Advanced epidemiological analysis will be used to model influenza trends over time. Integrating virological and epidemiological surveillance data with advanced analysis and timely communication can enhance local preparedness for public health emergencies. Good quality surveillance data will facilitate an understanding outbreak severity and disease seasonality. Real-time data will help provide early warning signals for prevention and control of influenza and COVID-19 outbreaks. The implementation strategies found to be effective in this project can be scaled up to other parts of the country for replication and integration.

Epidemiological characteristics and analysis of related infection risk factors for influenza in Anhui Province from 2013 to 2021

Objective: Analysis of the characteristics of influenza epidemic in Anhui Province and quantification of the impact of different factors on influenza occurrence, providing scientific basis for better influenza prevention and control. Methods: Descriptive analysis and factor analysis were conducted on influenza-like illness (ILI) cases and RT-PCR results in Anhui Province from 2013 to 2021 using data from China's Influenza Monitoring Information System. Results: The percentage of influenza-like illness (ILI%) of sentinel hospitals in Anhui Province from April 1, 2013 to March 31, 2021 was 3.80% (1 209 142/31 779 987), showing an overall increasing trend, with a relatively high proportion in 2017-2018 at 4.30% (191 148/4 448 211). The proportion of ILI cases in infants and young children aged 0-4 years was a relatively high at 54.14% (654 676/1 209 142), and the highest ILI% was observed in Fuyang City, Anhui Province (6.25%, 236 863/3 788 863). Laboratory monitoring results showed that the positive rate of ILI cases in sentinel hospitals in 8 influenza monitoring years was 16.38% (34 868/212 912), showing an increasing trend year by year, with a relatively proportion in 2017-2018 at 26.19% (6 936/26 488). The detection rate of school-age children aged 5-14 years was a relativelyhigh at 28.81% (13 869/48 144), and the positive rate was a relatively high in Wuhu City among the 16 cities, reaching 22.01% (2 693/122 237). Influenza activity showed a single peak in winter-spring and alternating double peaks in winter-spring and summer, with different subtypes alternating, and A (H3N2) was the dominant subtype in summer. The results of a multiple logistic regression model showed that the positive rate was higher in 2017-2018, among children aged 5-14 years, in winter, and in southern Anhui. Conclusions: Influenza epidemic in Anhui Province has a clear seasonal pattern, and the ILI% and detection rate have shown an upward trend from 2013 to 2021. Therefore, it is suggested to ensure vaccine supply before the winter-spring influenza season arrives, and to strengthen vaccine uptake and health education to avoid the risk of infection during the peak period of influenza.

Resistance profiles for the investigational neuraminidase inhibitor AV5080 in influenza A and B viruses

Neuraminidase inhibitors (NAIs) are recommended for influenza treatment and prevention worldwide. The most widely prescribed NAI is oral oseltamivir, while inhaled zanamivir is less commonly used. Using phenotypic neuraminidase (NA) enzymatic assays and molecular modeling approaches, we examined the ability of the investigational orally-dosed NAI AV5080 to inhibit viruses of the influenza A(H1N1)pdm09, A(H3N2), A(H5N1), and A(H7N9) subtypes and the influenza B/Victoria- and B/Yamagata-lineages containing NA substitutions conferring oseltamivir or zanamivir resistance including: NA-R292K, NA-E119G/V, NA-H274Y, NA-I122L/N, and NA-R150K. Broadly, AV5080 showed enhanced in vitro efficacy when compared with oseltamivir and/or zanamivir. Reduced AV5080 inhibition was determined for influenza A viruses with NA-E119G and NA-R292K, and for B/Victoria-lineage viruses with NA-I122N/L and B/Yamagata-lineage virus with NA-R150K. Molecular modeling suggested loss of the short hydrogen bond to the carboxyl group of AV5080 affected inhibition of NA-R292K viruses, whereas loss of the salt bridge with the guanidine group of AV5080 affected inhibition of NA-E119G. The resistance profiles and predicted binding modes of AV5080 and zanamivir are most similar, but dissimilar to those of oseltamivir, in part because of a guanidine moiety compensatory binding effect. Overall, our data suggests that AV5080 is a promising orally-dosed NAI that exhibited similar or superior in vitro efficacy against viruses with reduced or highly reduced inhibition phenotypes with respect to currently approved NAIs.

Influenza H7N9 Virus Hemagglutinin with T169A Mutation Possesses Enhanced Thermostability and Provides Effective Immune Protection against Lethal H7N9 Virus Challenge in Chickens.

H7N9 avian influenza virus (AIV) has caused huge losses in the poultry industry and impacted human public health security, and still poses a potential threat. Currently, immune prevention and control of avian influenza relies on traditional inactivated vaccines; however, they have some limitations and genetically engineered avian influenza subunit vaccines may be potential candidate vaccines. In this study, a T169A mutation in the HA protein derived from H7N9 AIV A/Chicken/Guangdong/16876 (H7N9-16876) was generated using the baculovirus expression system (BVES). The results showed that the mutant (HAm) had significantly increased thermostability compared with the wild-type HA protein (HA-WT). Importantly, immunizing chickens with HAm combined with ISA 71VG elicited higher cross-reactive hemagglutination inhibition (HI) antibody responses and cytokine (IFN-γ and IL-4) secretion. After a lethal challenge with heterologous H7N9 AIV, the vaccine conferred chickens with 100% (10/10) clinical protection and effectively inhibited viral shedding, with 90% (9/10) of the chickens showing no virus shedding. The thermostability of HAm may represent an advantage in practical vaccine manufacture and application. In general, the HAm generated in this study represents a promising subunit vaccine candidate for the prevention and control of H7N9 avian influenza.

Arbidol: The current demand, strategies, and antiviral mechanisms.

High morbidity and mortality of influenza virus infection have made it become one of the most lethal diseases threatening public health; the lack of drugs with strong antiviral activity against virus strains exacerbates the problem. Two independent researchers searched relevant studies using Embase, PubMed, Web of Science, Google Scholar, and MEDLINE databases from its inception to December 2022. Based on the different antiviral mechanisms, current antiviral strategies can be mainly classified into virus-targeting approaches such as neuraminidase inhibitors, matrix protein 2 ion channel inhibitors, polymerase acidic protein inhibitors and other host-targeting antivirals. However, highly viral gene mutation has underscored the necessity of novel antiviral drug development. Arbidol (ARB) is a Russian-made indole-derivative small molecule licensed in Russia and China for the prevention and treatment of influenza and other respiratory viral infections. ARB also has inhibitory effects on many other viruses such as severe acute respiratory syndrome coronavirus 2, Coxsackie virus, respiratory syncytial virus, Hantaan virus, herpes simplex virus, and hepatitis B and C viruses. ARB is a promising drug which can not only exert activity against virus at different steps of virus replication cycle, but also directly target on hosts before infection to prevent virus invasion. ARB is a broad-spectrum antiviral drug that inhibits several viruses in vivo and in vitro, with high safety profile and low resistance; the antiviral mechanisms of ARB deserve to be further explored and more high-quality clinical studies are required to establish the efficacy and safety of ARB.

Repeatability and timing of tropical influenza epidemics

Much of the world experiences influenza in yearly recurring seasons, particularly in temperate areas. These patterns can be considered repeatable if they occur predictably and consistently at the same time of year. In tropical areas, including southeast Asia, timing of influenza epidemics is less consistent, leading to a lack of consensus regarding whether influenza is repeatable. This study aimed to assess repeatability of influenza in Vietnam, with repeatability defined as seasonality that occurs at a consistent time of year with low variation. We developed a mathematical model incorporating parameters to represent periods of increased transmission and then fitted the model to data collected from sentinel hospitals throughout Vietnam as well as four temperate locations. We fitted the model for individual (sub)types of influenza as well as all combined influenza throughout northern, central, and southern Vietnam. Repeatability was evaluated through the variance of the timings of peak transmission. Model fits from Vietnam show high variance (sd = 64–179 days) in peak transmission timing, with peaks occurring at irregular intervals and throughout different times of year. Fits from temperate locations showed regular, annual epidemics in winter months, with low variance in peak timings (sd = 32–57 days). This suggests that influenza patterns are not repeatable or seasonal in Vietnam. Influenza prevention in Vietnam therefore cannot rely on anticipation of regularly occurring outbreaks.

Isolation and identification of Eurasian avian-like H1N1 swine influenza virus and evaluation of their pathogenicity and immune protective effects in pigs

Swine influenza (SI) is a severe disease affecting pigs, with a huge economic impact on pig farmers. Currently, available SIV vaccines do not meet the requirements for Swine influenza prevention and control, indicating the need for vaccine development using predominant strains. Here, we isolated and identified the swine influenza virus in farms and slaughterhouses in nine provinces in China to determine the most prevalent strain. A total of 8383 samples were collected between 2013 and 2022, from which 87 swine influenza virus strains were isolated. Genome sequencing identified 62 strains of the H1N1 subtype, three strains of the H1N2 subtype, and 22 strains of the H3N2 subtype. The 521# strain virus possesses the viral ribonucleoprotein (vRNP) and matrix (M) genes from the pdm/09 lineage, the HA, NA from the original Eurasian avian-like (EA) H1N1 lineage, and the nonstructural (NS) gene from the triple-reassortant (TR) lineage. The 431# strain was also a TR, except its M-gene was derived from the original EA H1N1 lineage. The pathogenicity of two 431# strains and one typical 521# strain was evaluated in mice, and the 431# strain exhibited higher pathogenicity. Therefore, a new 521# strain was selected for vaccine production because it is the current circulating strain. The vaccine produced using the 521# strain and pre-evaluated adjuvants was effective against the homologous H05 strain, as evidenced by the normal body temperature of vaccinated pigs and low virus titer of nasal swabs. In contrast, infection with the H05 strain significantly increased the body temperature of unvaccinated pigs and increased the virus titer of nasal swabs. Notably, vaccination with the 521#-based vaccine conferred some level of protection against the heterologous B15 strain (H3N2 subtype), thus reducing the viral load in pigs.

Alarming case of avian influenza A (H5) in humans: call for urgent action in Ecuador

Alarming case of avian influenza A (H5) in humans: call for urgent action in Ecuador

The impact of adjuvanted and non-adjuvanted influenza vaccines on &lt;i&gt;in vitro&lt;/i&gt; lymphocyte immunophenotype

Vaccination is the most effective method of influenza prophylaxis resulting in reduced frequency and severity of complications. Currently, for the prevention of influenza, inactivated split and subunit vaccines as the safest and promoting formation of protective level of strain-specific virus neutralizing antibodies are used. It is known that not all inactivated vaccines are effective enough for select human groups. While nowadays the level of public health is low, there is a need to improve the effectiveness of vaccines that should activate all chains of the immune system. In order to enhance intensity of influenza virus strain-specific antibody production, adjuvant vaccines exerting other mechanisms to activate humoral and cellular immunity compared to non-adjuvant vaccines have been used. The aim of the study was to examine lymphocyte immunophenotype in 27 healthy donors treated with polymer-subunit (immunoadjuvant) and non-adjuvanted split and subunit influenza vaccines.&#x0D; Materials and methods. Peripheral blood lymphocyte subpopulations were studied in vitro by flow cytometer FC-500 Cytomics (Beckman Coulter, USA) using FITC- and PE-labeled monoclonal antibodies (mAbs).&#x0D; Results. All examined influenza vaccines activate the effectors of cellular immunity, increasing the number of NK-cells (CD16/56), NKT-lymphocytes (CD3/CD16/56), B-lymphocytes (CD45/CD20), activated (CD3/HLA-DR) and cytotoxic (CD8/HLA-DR) T-lymphocytes, as well as cells bearing early activation marker (CD45/CD25). Among them the immunoadjuvant vaccine showed the greatest potential to induce cellular response eliciting regulatory mechanisms that prevent hyperactivation, stimulating growth of NK (CD16/56), NKT-cells (CD3/CD16/56), B-lymphocytes (CD45/CD20), activated (CD3/HLA-DR) and cytotoxic (CD8/HLA-DR) T-lymphocytes, T-regulatory cells (Tregs, CD4/CD25/Foxp3).&#x0D; Conclusion. Vaccination against influenza besides the formation of specific antibodies render a transient, immunomodulating effect that is more noticeable after immunoadjuvant vaccine. It can be assumed that vaccination of people with dysfunctions of the immune system an additional prophylactic effect will be observed.

New Advances and Perspectives of Influenza Prevention: Current State of the Art

The modern world, swaddled in the benefits of civilization, has fostered the development of science and the introduction of products of technological progress. This has allowed serious individual health problems, including those associated with viral diseases, to become targets for prophylaxis, treatment, and even cure. Human immunodeficiency viruses, hepatitis viruses, coronaviruses, and influenza viruses are among the most disturbing infectious agents in the human experience. Influenza appears to be one of the oldest viruses known to man; these viruses were among the first to cause major epidemics and pandemics in human history, collectively causing up to 0.5 million deaths worldwide each year. The main problem in the fight against influenza viruses is that they mutate constantly, which leads to molecular changes in antigens, including outer membrane glycoproteins, which play a critical role in the creation of modern vaccines. Due to the constant microevolution of the virus, influenza vaccine formulas have to be reviewed and improved every year. Today, flu vaccines represent an eternal molecular race between a person and a virus, which neither entity seems likely to win.

Behavioral changes of preventive activities of influenza among children in satellite cities of a metropolitan area of Tokyo, Japan, by the COVID-19 pandemic

ObjectiveIn children in a metropolitan area of Tokyo, Japan, behavioral change and influenza infection associated with the frequency of nonpharmaceutical interventions (NPI) was assessed from the 2018–2019 season (Preseason) and the 2020–2021 season (coronavirus disease 2019 [COVID-19] season).MethodsWe conducted an exclusive survey among children attending preschool, elementary school, and junior high school in the Toda and Warabi regions, Japan, during the 2018–2019 (Preseason, distributed via mail) and 2020–2021 seasons (COVID-19 season, conducted online). The proportion of preventive activities (hand washing, face mask-wearing, and vaccination) was compared in the Preseason with that of the COVID-19 season. The multivariate logistic regression model was further applied to calculate the adjusted odds ratio (AOR) with 95% confidence intervals (CIs) for influenza infection associated with NPI frequency (hand washing and face mask wearing) in each Preseason and COVID-19 season.ResultsThe proportion of vaccinated children who carried out hand washing and face mask wearing was remarkably higher during the COVID-19 season (48.8%) than in the Preseason (18.2%). A significant influenza infection reduction was observed among children who washed hands and wore face masks simultaneously (AOR, 0.87; 95% CI, 0.76–0.99; P = 0.033).ConclusionsA strong interest and performance in the intensive measures for the prevention of influenza under the COVID-19 pandemic was demonstrated. Positive association was observed from a combination of NPI, hand washing, and face mask-wearing and influenza infection. This study’s findings could help in activities or preventive measures against influenza and other communicable diseases in children.

Identification of Heterophilic Epitopes of H1N1 Influenza Virus Hemagglutinin

Our previous studies found that the H1-50 monoclonal antibody (mAb) of influenza A virus hemagglutinin (HA) cross-reacted with pancreatic tissue and islet β-cells, and further studies showed that H1-50 mAb binds to prohibitin (PHB) protein of islet β-cells. These suggest that there are heterophilic epitopes between influenza virus HA and pancreatic tissue, which may be involved in the pathogenesis of type 1 diabetes. To further investigate these heterophilic epitopes, we screened binding epitopes of H1-50 mAb using a phage 12-peptide library. DNA sequencing and comparative analysis were performed on specific positive phage clones, and the sequence of 12-peptide binding to H1-50 mAb was obtained. The binding epitopes of H1-50 mAb in influenza virus HA were determined by sequence analysis and experimental verification, and their distribution within the three-dimensional structure was assessed by PyMOL. The results showed that H1-50 mAb specifically binds to polypeptides (306-SLPFQNIHPITIGK-319) of influenza A virus HA, located in the stem of the HA protein. However, there is no specific binding sequence between H1-50 mAb and the PHB protein of islet β-cells in the primary structure, and we speculate that the binding of H1-50 mAb to islet β-cells may depend on the spatial conformation. The identification of the heterophilic epitopes of H1N1 influenza virus hemagglutinin provides a new perspective on type 1 diabetes that may be caused by influenza virus infection, which may contribute to the prevention and control of influenza.

Эффективность осельтамивира в профилактике и лечении гриппа у детей

Эффективность осельтамивира в профилактике и лечении гриппа у детей

Proteomics analysis of methionine enkephalin upregulated macrophages against infection by the influenza-A virus

Macrophages have a vital role in phagocytosis and antiviral effect against invading influenza viruses. Previously, we found that methionine enkephalin (MENK) inhibited influenza virus infection by upregulating the “antiviral state” of macrophages. To investigate the immunoregulatory mechanism of action of MENK on macrophages, we employed proteomic analysis to identify differentially expressed proteins (DEPs) between macrophages infected with the influenza-A virus and cells infected with the influenza-A virus after pretreatment with MENK. A total of 215 DEPs were identified: 164 proteins had upregulated expression and 51 proteins had downregulated expression. Proteomics analysis showed that DEPs were highly enriched in “cytokine-cytokine receptor interaction”, “phagosome”, and “complement and coagulation cascades pathway”. Proteomics analysis revealed that MENK could be an immune modulator or prophylactic for the prevention and treatment of influenza. MENK promoted the polarization of M1 macrophages, activated inflammatory responses, and enhanced phagocytosis and killing function by upregulating opsonizing receptors.

PHILIPPINE GUIDELINES ON PERIODIC HEALTH EXAMINATION: PEDIATRIC IMMUNIZATION

This Clinical Practice Guideline for the Periodic Health Examination (Pediatric Immunization) is an output from the joint undertaking of the Department of Health and National Institutes of Health-Institute of Clinical Epidemiology. This clinical practice guideline is a systematic synthesis of scientific evidence on immunization for the prevention of human papilloma virus (HPV) infection, influenza, typhoid fever, Japanese encephalitis, poliomyelitis, meningococcal infection, and Hepatitis A in the pediatric population. The CPG provides nine (9) recommendations on prioritized questions regarding the relevant vaccines for preventing these seven (7) diseases. Recommendations are based on the appraisal of the best available evidence on each of the eight identified clinical questions. The CPG is intended to be used by general practitioners and specialists in the primary care setting, policy makers, employers and administrators, allied health practitioners and even patients. The guideline development process followed the widely accepted Grading of Recommendations, Assessment, Development, and Evaluation or the GRADE approach including GRADE Adolopment, a systematic process of adapting evidence summaries and the GRADE Evidence to Decision (EtD) framework. , It includes 1) identification of critical questions and critical outcomes, 2) retrieval of current evidence, 3) assessment and synthesis of the evidence base for these critical questions, 4) formulation of draft recommendations, 5) convening of a multi­sectoral stakeholder panel to discuss values and preferences and assess the strength of the recommendations, and 6) planning for dissemination, implementation, impact evaluation and updating. The recommendations in this CPG shall hold and will be updated after 3 years or when new evidence arise.