Multivalent HIV Vaccine Induces Early and Potent Antibody Response

NEW YORK (Reuters Health) - A multivalent HIV vaccine that consists of envelope protein (gp120 Env) and either DNA or NYVAC vectors during priming leads to early and potent IgG-binding antibody responses, according to results from the HIV Vaccine Trials Network (HVTN).
"If the ongoing vaccine efficacy studies show significant levels of protection against acquisition of HIV, future vaccine studies may be designed to induce rapid appearance of antibody responses as shown in our study," Dr. Giuseppe Pantaleo from the Swiss Vaccine Research Institute, Lausanne University Hospital, told Reuters Health by email.
Dr. Pantaleo and colleagues in the HVTN 096 trial tested their hypothesis that coadministration of vaccines containing Env protein during priming in a heterologous prime and boost regimen would induce early generation of an antibody response against the conserved regions of the V1/V2 loop of Env, thereby extending the period of protection seen in an earlier trial (RV144).
Specifically, they compared vaccine regimens comprising coadministration during priming of either a DNA or NYVAC vector and gp120 Env protein versus DNA or NYVAC vector alone followed by a NYVAC vector and gp120 protein boost.

The trial enrolled 96 individuals at low risk of HIV infection. Twenty participants were randomly allocated to each of four treatment groups and four participants were assigned to each placebo group.
Vaccines containing the NYVAC vector triggered more-frequent severe reactogenicity and more adverse events than did vaccines containing the DNA vector, the researchers report in The Lancet HIV, online October 7.
Co-administration of gp120 Env protein during priming resulted in earlier peak neutralizing antibody responses, compared with regimens lacking gp120 Env protein at prime.
Gp120 Env protein co-administration during priming also yielded a significantly higher overall neutralizing antibody response (as measured by AUC), compared with groups that did not receive gp120 Env protein co-administration at prime.
For all groups, antibody responses and magnitudes of response decreased between two weeks and 12 months after the month-six vaccination, and there were no differences in the aggregate vaccine-matched response magnitudes between groups at 12 months after the month-six vaccination.
Priming with a DNA vector co-administered with gp120 Env protein generated the most rapid, potent and durable binding antibody response among the four vaccine regimens tested.
"DNA-based vaccines may represent an interesting strategy in combination with protein components to induce potent antibody responses," Dr. Pantaleo said. "This vaccine regimen may be instrumental for the development of vaccines against other difficult targets."
Dr. Barbara K. Felber of the National Cancer Institute, in Frederick, Maryland, who co-authored an accompanying editorial, told Reuters Health by email, "This study shows that inclusion of protein in the priming vaccination resulted in high humoral immune responses in humans. This changes the paradigm of using protein only in the booster phase of vaccinations."

"Interestingly, this study confirms what we found in the macaque model and this is another important finding and validates the effort for non-human macaque studies," she said. "This study also shows that inclusion of protein in the prime improves the rapid development of immune responses using different vaccine platforms (DNA, NYVAC). Thus, this demonstrates a more general application of improving the priming vaccination."
"We need to be innovative and explore novel ways to improve vaccine efficacy for HIV and likely other vaccines," Dr. Felber said.
Dr. Felber and co-author Dr. George N. Pavlakis are co-inventors of U.S. government-owned patents for DNA vaccine technology and DNA immunotherapy.
SOURCE: https://bit.ly/2oP0cJ3 and https://bit.ly/2N0WgNm
Lancet HIV 2019.

Reuters Health Information © 2019

Emerging Significance of Vitamin D in Managing Dengue Fever

Growing evidence has underlined the critical contribution of vitamin D in regulating proinflammatory responses and protecting many infectious pathogens as well as viruses. Host nutritional status or micronutrient supplementation is a stronger predictor of immunity. Pertaining to Dengue Virus (DENV) infection, its adjuvant therapy could lower the likelihood of progressing from severe forms of disease or will reduce disease severity in patients. This article showcases the evidence-based significant role of Vitamin D in the management of dengue fever (DF).
At present, there are no antiviral drugs available to fight DENV. If dengue is not treated right, the progression to severe dengue is potentially fatal; it depends on multiple factors involving the virus and the host. Thus, drugs that are developed against DENV should not only have antiviral activity but should also be able to control the host inflammatory response involving cytokines to prevent subsequent vascular leakage, a characteristic of severe dengue. Newer studies are highlighting Vitamin D as a potentially useful compound that affects the disease process of dengue by altering immune responses.
A study estimated that globally, about 1 billion people are vitamin D deficient i.e. 25-hydroxy vitamin D (25-OHD) less than 50 nmol/L or vitamin D insufficient i.e. 25-OHD less than 75 nmol/L. Contrary to the assumption that vitamin D deficiency will never be a concern among Indians, a high prevalence of vitamin D deficiency was reported throughout the country in all age groups.
Relationship between 25-OH D Deficiency and a Variety of Chronic Diseases
Multiple studies have shown the various effects of vitamin D on the biological processes regulating calcium and phosphorus metabolism, effects on cell proliferation, differentiation, apoptosis, immune regulation, genome stability, and neurogenesis. Table. 1 reflects the clinical evidence and correlation of various chronic disorders with vitamin D deficiency.
Table. 1 Role of Vitamin D in chronic disorders and observed clinical evidence

Discussing the Potential Link of Vitamin D in Dengue Fever
As vitamin D showed a clinically significant role in managing various chronic infections, there are many observed clinical benefits of Vitamin D in treating dengue fever. Vitamin D3 is a potentially useful antiviral compound and is known to affect the disease process of dengue by changing the immune responses. Beneficial roles of vitamin D at the molecular levels are mentioned below:

• It leads to the monocyte differentiation and T-cell activation by binding to vitamin D receptors and activating vitamin D-responsive genes in the body.
• Inhibits the cytotoxic T cell responses as well as T-helper 1 cell.
• Enhances responses of IL-10 and Th2 cytokine.

Figure. 1 illustrates the potential link between vitamin D and miR (microRNA) directing DENV-induced inflammatory response and antiviral activity.

Figure 1: Potential link among vitamin D and miR controlling dengue virus-induced inflammatory response and antiviral activity. Adapted from Arboleda et al. 1. DENV replication products and proteins are recognized by several Pattern recognition receptors (PRRs) whose signaling pathways promote the pro-inflammatory response. 2. Vitamin D activity activates transcription of miRs and other target genes that play a critical role in the control of inflammation-related signaling pathways and antiviral activity.
Insights into Vitamin D and Dengue Infection
There are various mechanisms that link DENV infections and Vitamin D. Here is the brief explanation showcasing the antiviral effect and immune response of Vitamin D in Dengue;
DENV cell exposure to 1,25-(OH)2D3:
The effect of vitamin D therapy on DENV cell exposure showed that 1,25(OH)2D3 resulted in a significant reduction of DENV-infected cells, a variable modulation of toll-like receptor 2 (TLR2) and TLR4, and reduced levels of secreted pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β after infection.
Monocyte-derived macrophages differentiation:

• Monocyte-derived macrophages (MDM) that differentiate in the presence of 1,25(OH)2D3 are less susceptible to DENV infection and express lower levels of mannose receptor restricting binding of DENV to target cells.
• A study conducted by Giraldo et al. to determine the effect of oral vitamin D supplementation on DENV susceptibility and pro-inflammatory cytokine production in MDMs concluded that a supplement of 4000IU/day of vitamin D represents an adequate dose to control dengue progression and DENV replication.

VDR-induced regulation of miRs via VDRE:
Some miRs (let-7a) pri-miR has multiple VDR/RXR binding sites that could potentially be regulated by vitamin D. miR let-7a belongs to a highly conserved family of miRs that contain other miRs which were previously reported in various studies to inhibit DENV replicative activity, such as let-7c. Beyond the members of the let-7 family, other miRs were also linked with the suppression of DENV infection and the inflammatory responses against the virus.
Clinical Response in Patients with Dengue to Oral Calcium + Vitamin D
Calcium is a vital constituent for clotting of platelet and regulating the immune response. With the oral intake of calcium plus Vitamin D3, free Ca2+ gets restored more rapidly by experiencing an early clinical improvement and the reduction of thrombocytopenia.
Sanchez V et al. reported a case study of 5 patients that determined the decrease in duration of signs and symptoms of dengue fever with the administration of oral calcium and Vitamin D3 as shown in Fig. 2 .

Fig 2. Clinical case study conducted by Sanchez V et al. to determine decrease symptomology in DENV with Vitamin D.
Comparison of Vitamin D Levels in Patients with Dengue Hemorrhagic Fever (DHF) and Dengue Fever (DF)
Mahmud MR et al. conducted a study to compare the level of vitamin D in patients of DHF and DF.

• Study subjects: A total of 50 patients diagnosed with DF and fulfilling the inclusion criteria were enrolled in the study. The patients were divided into two groups having 25 participants each; one group had DF while the other DHF.
• Method: Vitamin D was assessed in host nutritional status by the chemiluminescence method. To compare the proportion of patients in each study group, Pearson’s Chi-square was applied. Relative Risk was determined along with a 95% confidence interval.
• Results: The results showed that the mean vitamin D levels in DF patients were higher (21.5 ± 13.6 ng/ml) as compared to DHF (12.4 ± 5.6 ng/ml). Independent sample test reflects that the difference was statistically significant (p=0.003), as shown in Table 2.

 Table 2. Comparison of Vitamin D levels of the patients
Adapted from Mahmud MR et al. *independent sample t-test; # chi-square test

• The study concluded that Vitamin D has a significant role in the management of DF, and low levels of vitamin D could be associated with DHF.

Conclusion

• Adequately circulating 25-hydroxy (25-OH) vitamin D concentrations are required to be maintained for the functioning of the metabolic, immune, reproductive, muscular, skeletal, respiratory and cutaneous systems of men and women of all ages.
• Vitamin D has shown a significant role in managing Dengue fever with its antiviral and pro-inflammatory response.
• Additionally, Vitamin D led to a decrease in the duration of signs and symptoms of dengue fever and in preventing DHF.

References
1.           Arboleda JF, Urcuqui-Inchima S. Vitamin D-Regulated MicroRNAs: Are They Protective Factors against Dengue Virus Infection? Adv Virol. 2016;2016.
2.           Mahmud MR, Zaman S, Naseem N, Iqbal N, Tanveer N, Khalid MA, et al. Comparison of Vitamin D Levels in Patients with Dengue Haemorrhagic Fever and Dengue Fever. J Rawalpindi Med Coll [Internet]. 2018;22(2):92–5. Available from: http://www.journalrmc.com/index.php/JRMC/article/view/870
3.           Jadhav NJ, Gokhale S, Seervi M, Patil PS, Alagarasu K. Immunomodulatory effect of 1, 25 dihydroxy vitamin D3 on the expression of RNA sensing pattern recognition receptor genes and cytokine response in dengue virus infected U937-DC-SIGN cells and THP-1 macrophages. Int Immunopharmacol [Internet]. 2018;62(July):237–43. Available from: https://doi.org/10.1016/j.intimp.2018.07.019
4.           Tiwari P, Sharma N. Role of Vitamin D in Various Illnesses: A Review. J Pharm Care Heal Syst. 2017;04(03).
5.          Pilz S, Tomaschitz A, Drechsler C, Dekker JM, März W. Vitamin D deficiency and myocardial diseases. Mol Nutr Food Res. 2010;54(8):1103–13.
6.          Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, Staehelin HB, Bazemore MG, Zee RY, Wong JB. Effect of vitamin D on falls: a meta-analysis. Jama. 2004 Apr 28;291(16):1999-2006.
7.          Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: Results of a randomized trial (American Journal of Clinical Nutrition (2007) 85, (1586-1591)). Am J Clin Nutr. 2008;87(3):794.
8.         Heaney RP. Vitamin D in health and disease. Clin J Am Soc Nephrol. 2008;3(5):1535–41.
9.          Scragg R, Sowers M, Bell C. Serum 25-hydroxyvitamin D, diabetes, and Ethnicity in the Third National Health and Nutr ition Examination. Diabetes Care. 2004;27(12).
10.         Giraldo DM, Cardona A, Urcuqui-Inchima S. High-dose of vitamin D supplement is associated with reduced susceptibility of monocyte-derived macrophages to dengue virus infection and pro-inflammatory cytokine production: An exploratory study. Clin Chim Acta [Internet]. 2018;478(October 2017):140–51. Available from: https://doi.org/10.1016/j.cca.2017.12.044
11.         Sánchez-Valdéz E, Delgado-Aradillas M, Torres-Martínez JA, Torres-Benítez JM. Clinical Response in Patients with Dengue Fever to Oral Calcium Plus Vitamin D Administration: Study of 5 Cases. Proc West Pharmacol Soc. 2009;52(January 2009):14–7.
12.         Arboleda Alzate JF, Rodenhuis-Zybert IA, Hernández JC, Smit JM, Urcuqui-Inchima S. Human macrophages differentiated in the presence of vitamin D3restrict dengue virus infection and innate responses by downregulating mannose receptor expression. PLoS Negl Trop Dis. 2017;11(10):1–18.
 SAIN.VITD.19.12.1437

Day care surgery

Day case surgery is the admission of selected patients to hospital for a planned surgical procedure, returning home on the same day. They represent about 70% of all surgery.

Surgical day cases have been identified as the number one high-impact change to improve productivity; healthcare guidelines advise for a target of “treating day surgery (rather than inpatient surgery) as the norm for elective surgery”.

The advantages of day case surgery are:

• Shorter inpatient stays
• Lower infection rates
• Reduced waiting lists
• Cheaper than surgery requiring an overnight stay

Preparing for Day Case

A patient undergoing a day case procedure should be advised not to eat and drink for the 6 hours prior to the surgery (when involving a general anaesthetic). Many surgeons will allow a patient to drink small volumes of water up to 2 hours before a general anaesthetic and local guidelines should be adhered to.

Medications should be reviewed to ensure that they will not interfere with the planned surgery and guidance is sometimes necessary from the operating surgeon.

In general, most medications may be continued up to the day of the operation, including the day of the procedure. However, special care should be taken over certain classes of medication, such as anti-coagulants (+/- anti-platelets) in operations where bleeding is a risk.

Types of Day Case Surgery

For a surgical procedure to be considered for day case surgery, it must meet the following criteria:

• Minimal blood loss expected
• Short operating time (<1 hour="" li="">
• No expected intra-operative or post-operative complications
• No requirement for specialist aftercare

  Selection of the Patient

  Much of the success of day-case surgery is down to care in patient selection. In the UK, most hospitals follow local guidelines to aid in this – these generally include absolute and relative contraindications based on co-morbidities.
  
  The selection of a patient for day surgery should be based upon social and medical factors:
• Social factors – a patient must understand the planned procedure, consent appropriately, and understand the following post-operative care
  • The patient should also have sufficient provisions to have a responsible adult escort them home and provide support for the first 24 hours of post-operative care.
• Medical factors – a patient’s health must be suitable for a day case procedure, remembering that some stable chronic diseases (e.g. DM or asthma) can often be better managed as a day procedure to minimise any disruption to their daily routine.

Diabetes is REVERSIBLE

If you have a diagnosis of type 2 diabetes or if you have been told you are at high risk or if you have significant abdominal obesity,  
Here are 11 ways to start reversing the effects immediately:

1. Avoid or reduuce ALL refined carbohydrates. That means no / little pasta, rice or bread (even wholegrain bread will spike your insulin)
2. Avoid ALL added sugar. If your body is already in a state where you cannot process carbohydrates and sugars properly, you are going to have to take steps to fully eliminate all sugars, at least in the short term.
3. Avoid ALL sweet drinks. It is best to stick to water, tea, coffee.
4. Do not be scared of good quality, healthy, natural fat – avocados, olives, almonds etc. Don’t worry about this causing you to put on weight. A study published in 2003 showed that people who supplemented their diet with almonds lost more weight than those who supplemented with so-called “healthy, complex carbs”
5. Do not waste your energy counting calories. Concentrate on the quality of the food that you are eating and the calorie control will take care of itself.
6. FEED YOUR GUT BUGS, not just yourself. There are trillions of bugs that live in your gut – their health is critical in determining your health. Many studies show links between the state of your gut bugs (your microbiota) and type 2 diabetes. Start improving the health of your gut immediately by eating five servings of different coloured vegetables each day. The non digestible fibre in vegetables is the preferred food for your gut bacteria and when your gut bugs are happy, you will be happy. The wider the variety of colours, the more phytonutrients you will be getting.
7. Do my 30 minutes  workout once a day. This could be before breakfast, lunch or dinner – whatever works for you.
8. If you like to snack, keep some high fat healthy snacks with you, such as olives, nuts or hummus. When you snack on refined carbohydrates such as biscuits, you go on a blood sugar rollercoaster that results in you feeling hungry shortly after. Fats, on the other hand, will keep you fuller for longer.
9. Include high quality protein and fat with EVERY single meal. This helps to stabilise your blood sugars and promotes satiety and fullness, making it less likely that you will want to reach for dessert after your meal.
10. Eat your meals sitting down at a table. Eating on the sofa while watching TV encourages a mindless form of eating – this can lead you to eat higher quantities than you otherwise would. If you sit at a table and concentrate on what you’re eating, you are more likely to enjoy your food, feel satisfied at the end of your meal and eat less.
11. Consider a form of regular fasting (more to come in a later blog), such as intermittent fasting or time-restricted feeding (TRF). TRF means eating your calories during a specific window of the day, and choosing not to eat food for the rest. It’s a great way to reduce insulin levels in your body and help undo the effects of chronically elevated levels.

Screening Test for Pre-eclampsia in different Trimesters.

Women are generally health-conscious during pregnancy. But no matter how cautious a woman can be, adverse situations may still arise and one of these is the development of pre-eclampsia.       

Pre-eclampsia is a complication of pregnancy marked by high blood pressure and the presence of protein in the urine (proteinuria). The cause of pre-eclampsia remains unknown but studies have shown that it affects blood flow in the placenta, which can lead to pregnancy-induced hypertension and fetal complications such as intrauterine growth restriction and prematurity. Left untreated, it may progress into more severe conditions like eclampsia, wherein the mother develops seizures, and on one extreme, may, unfortunately, lead to death. Various reports show that 5-8 percent of pregnancies are affected by pre-eclampsia worldwide, with 76,000 maternal and 500,000 fetal deaths yearly. In the Philippines, eclampsia was the leading cause of maternal death (19.6 percent) based on local statistics (PSA, 2015).     

Although the blood pressure of pregnant women tends to decrease in the first trimester, early screening to predict pre-eclampsia can be performed at this time. By the second trimester, symptoms of pre-eclampsia may begin to appear. Undiagnosed and untreated, pre-eclampsia may lead to early delivery during the third trimester.

Thus, when it comes to pre-eclampsia, timing is of the essence. The earlier women at high risk for pre-eclampsia are identified, the better the outcome for both Mommy and baby.       

To date, the most sensitive first-trimester test for pre-eclampsia is PLGF 1-2-3. It is the 2nd generation PLGF assay, and when it is used in combination with a comprehensive first-trimester screening program that includes maternal medical history and mean arterial blood pressure, women at high risk for pre-eclampsia can be identified long before symptoms appear. The PLGF 1-2-3 assay can also be used in the second and third trimester of pregnancy for effective reassessment, monitoring, or diagnosis.    

Pre-eclampsia screening for 1st trimester – screening test for pre-eclampsia for patients  in their 1st trimester of pregnancy

          o PLGF 1-2-3 (placental growth factor)  

          o PAPP-A (pregnancy-associated plasma protein A)        

          o Risk assessment for pre-eclampsia     
Pre-eclampsia screening for 2nd and 3rd trimester – screening for risk of pre-eclampsia for patients in their 2nd/3rd trimester of pregnancy  

•   PLGF 1-2-3    
•   Risk assessment for pre-eclampsia

Interpretation of Hepatitis B Serologic Test Results(CDC)

Hepatitis B serologic testing involves measurement of several hepatitis B virus (HBV)-specific antigens and antibodies. Different serologic “markers” or combinations of markers are used to identify different phases of HBV infection and to determine whether a patient has acute or chronic HBV infection, is immune to HBV as a result of prior infection or vaccination, or is susceptible to infection.

Adapted from: A Comprehensive Immunization Strategy to EliminateTransmission of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices.

Part I: Immunization of Infants, Children, and Adolescents. MMWR 2005;54(No. RR-16).