Prophylaxis.

Post Exposure Prophylaxis After Needle Prick


In modern medical practice especially with the pandemic of HIV the incidences of medical personnel receiving accidental pricks with needle containing blood from an HIV positive is on a rise.
Though the causes are the awareness of this mode of transmission and increased amount of reporting (as reporting became mandatory), it is an alarming realization.

OCCUPATIONAL EXPOSURE


Occupational exposure refers to the exposure to potential blood-borne infections (HIV, HBV and HCV) that occurs during performance of job duties.
“Exposure” is any event which may place a health care person at risk of blood-borne infection and this can be in the form of:
  • a percutaneous injury (e.g. needle-stick or cut with a sharp instrument).
  • contact with the mucous membranes of the eye or mouth.
  • contact with non-intact skin (particularly when the exposed skin is chapped, abraded, or afflicted with dermatitis).
  • contact with intact skin when the duration of contact is prolonged (e.g. several minutes or more) with blood or other potentially infectious body fluids.
Professionals highly prone for exposure include:
  • Interns and medical students.
  • Nursing staff and students.
  • Physicians.
  • Surgeons.
  • Emergency care providers.
  • Dentists.
  • Labour and delivery room personnel.
  • Laboratory technicians.
  • Health facility cleaning staff and clinical waste handlers.
POST EXPOSURE PROPHYLAXIS (PEP)
Refers to the comprehensive management given to minimize the risk of infection following potential exposure to blood-borne pathogens (HIV, HBV, HCV).

This includes
  • Counseling.
  • Risk assessment.
  • Relevant laboratory investigations based on informed consent of the source and exposed person.
  • First aid .
  • Depending on the risk assessment, the provision of short term (4 weeks) of antiretroviral drugs, with follow up and support.

HIV


Confidentiality has to be maintained in all steps following exposure.
The guidelines published by “National Aids Control Organization” India gives a simple step by step approach to handle occupational needle stick injury.
These steps are to be followed after prick with a needle contaminated with the blood of an HIV patient:

Step1:

  • Remove gloves, if appropriate
  • Manage exposure site Wash wound and surrounding skin with water and soap
  • Do not scrub,Do not use antiseptics or skin washes (bleach, chlorine, alcohol, betadine).
  • Irrigate exposed eye Immediately with water or normal saline
  • Rinse the Mouth thoroughly, using water or saline and spit again
  • Refer to Physician

Dos and don'ts

Do not panic
Wash the exposed site thoroughly with running water
Do not put the pricked finger in mouth
Irrigate with water or saline if eyes or mouth have been exposed
Do not squeeze the wound to bleed it
Wash the skin with soap and water
Do not use bleach, chlorine, alcohol, betadine, iodine or other antiseptics/detergents on the wound

Step 2:Decide for prophylactic treatment

  • Establish eligibility for PEP(Ideally within 2 hours but certainly within 72 hours)
  • Assess exposed individual
  • Assess exposure source
  • Assess type of exposure
  • Determine risk of transmission
  • Determine eligibility for PEP
PEP must be initiated as soon as possible, preferably within 2 hours
The first dose of PEP should be administered within the first 72 hours of exposure and the risk evaluated as soon as possible. If the risk is insignificant, PEP could be discontinued.
In animal studies, initiating PEP within 12, 24 or 36 hours of exposure was more effective than initiating PEP 48 hours or 72 hours following exposure.

Exposed individual


Rapid HIV testing should be done before starting PEP.
Initiation of PEP, where indicated, should not be delayed while waiting for the results of HIV testing of the source of exposure. Informed consent should be obtained before testing of the source and the exposed as per national HIV testing guidelines.
PEP needs to be started as soon as possible after the exposure and within 72 hours.

Type of exposure and the potential for disease transmission

Three categories of exposure can be described based on the amount of blood/fluid involved and the entry port. These categories are intended to help in assessing the severity of the exposure but may not cover all possibilities.

MILD EXPOSURE :

Mucous membrane/non intact skin with small volumes of blood.
E.g. : a superficial wound (erosion of the epidermis) with a plain or low calibre needle, or contact with the eyes or mucous membranes, subcutaneous injections following small-bore needles

MODERATE EXPOSURE:

mucous membrane/non intact skin with large volumes OR Percutaneous superficial exposure with solid needle E.g. : a cut or needle stick injury penetrating gloves

SEVERE EXPOSURE :


Percutaneous with large volume. Eg.: An accident with a high calibre needle (>18 G) visibly contaminated with blood.
Eg: a deep wound (hemorrhagic wound and/or very painful); transmission of a significant volume of blood; an accident with material that has previously been used intravenously or intra-arterially.

ASSESSING THE HIV STATUS OF THE SOURCE OF EXPOSURE

The risk of disease transmission depends on the viral load in the contaminated blood. Even in HIV patients, the viral load will be variable and will be more during acute exacerbations. Unfortunately the viral load can be significantly higher during the acute viremia phase of the window period, where the patient is HIV negative but has a high potential for disease transmission.

Source HIV Status Definition of risk in source

HIV negative --Source is not HIV infected
but consider HBV and HCV
Low risk --HIV positive but clinically asymptomatic
High risk --HIV positive and clinically symptomatic
Unknown --Status of the patient is unknown, and neither the patient nor his/her blood is available for testing (e.g. injury during medical waste management the source patient might be unknown). The risk assessment will be based only upon the exposure (HIV prevalence in the locality can be considered)

Eligibility for PEP

The necessity to continue PEP as well as eligibility can be established depending on the presence of HIV in the exposed even before exposure, as well as the HIV status of the source.
In case the victim is HIV positive beforehand, anti-retroviral therapy should be started instead of PEP with counseling and information on prevention of transmission.

Step 3:Informed consent

  • Counsel for PEP
  • Provide information on HIV and PEP
  • Obtain consent for PEP
  • Offer special leave from work
  • Exposed persons (clients) should receive appropriate information about what PEP is about and
     the risk and benefits of PEP in order to provide informed consent.
  •  It should be clear that PEP is not mandatory.
Exposed person has to be informed in detail about:

-The risk of acquiring HIV infection from the specific exposure
-what is known about PEP efficacy?
-PEP is provided to prevent potential transmission of the HIV virus.
-PEP is not 100% effective and should be given within 72 hours.

The risk of getting HIV infection from a person known to be HIV positive is estimated to be
- Sharps injury: 3 in 1000 exposures (0.3%)
- Mucous membrane splash: 1 in 1000 exposures (0.1%)

the risk in increased with large exposure eg needle stick  from hollow bore needles with visible blood, from artery or vein and from source patients with high viral load (usually very sick persons with OIs)

Balance risk and benefits of PEP: PEP may prevent HIV transmission; but there is risk of side effects which can be severe in some patients so that the PEP has to be abandoned.
The effectiveness of PEP is not 100 % - reduction in infection risk is reported to be more than 80 percent.
A negative test result does not exclude HIV infection.
In districts or some population groups with a high HIV prevalence, a higher proportion of HIV-infected individuals are found in the window period.
In these situations, a negative result has even less value for decision-making on PEP.
The exposed individual should be assessed for pre-existing HIV infection
PEP intended for people who are HIV negative at the time of their potential exposure to HIV.
Exposed individuals who are known or discovered to be HIV positive should not receive PEP.
They should be offered counseling and information on prevention of transmission and referred to clinical and laboratory assessment to determine eligibility for antiretroviral therapy (ART)

Step 4:Provide prophylactic medicine

Prescribe PEP
Assess source
patient’s ARV status
Check for pregnancy if exposed female HCP
Explain side effects of ARVs
Explain post exposure Measures against HBV and HBC

THERE ARE TWO TYPES OF PEP REGIMENS:
Basic regimen: 2-drug combination
Expanded regimen: 3-drug combination

Status of source HIV+ and asymptomatic

-mild :- Consider 2-drug PEP
-moderate :- Start 2-drug PEP
-severe :- Start 3-drug PEP

Status of source HIV+ and symptomatic

-Mild :-Start 2- drug PEP
-Moderate :-Start 3-drug PEP
-Severe :-Start 3-drug PEP

HIV status unknown

-Mild :- Usually no PEP or consider 2-drug PEP
-Moderate :- Usually no PEP or consider 2-drug PEP
-Severe :- Usually no PEP or consider 2-drug PEP

Medication 2-drug regimen
Zidovudine (AZT) 300 mg twice a day 300 mg twice a day
Stavudine (d4T) 30 mg twice a day 30 mg twice a day

Medication 3-drug regimen
Zidovudine (AZT) 300 mg twice a day 300 mg twice a day
Stavudine (d4T) 30 mg twice a day 30 mg twice a day
Lamivudine (3TC) 150 mg twice a day 150 mg twice a day

Step 5:Check for other blood borne diseases.

Detailed Laboratory evaluation for blood borne infections
  • Provide HIV pretest counseling
  • Check Immunization status for hepatitis B
  • Offer HIV, HBV, HBC test
  • Draw blood to include CBC, liver function tests, pregnancy test, if applicable
  • Provide HIV post-test counseling

Step 6:

Follow up and monitor adherence
  • Record-keeping
  • Follow up visits for clinical assessment at 2 weeks and hepatitis B vaccination if needed
  • HIV test at 3 and 6 months
The provision of information regarding PEP should be confidential including information about :
-HIV testing,
-PEP provision and
-The reasons for seeking PEP.
Informed the consent should be taken for HIV testing as well as for giving PEP and needs to be done according to national counseling and testing guidelines.
In special situations where the individual has limited/no capacity to consent (eg. children, or unconscious or mentally ill adults), a proxy may be able to provide consent. eg: parents/guardian/caretaker.

Post Exposure Prophylaxis HBV


Though hepatitis-B is a highly infectious disease, it can be prevented by vaccination. Those who are not vaccinated can be aided with immunoglobulin along with post exposure vaccination.
Center For Disease Control America has given a detailed description on HBV prophylaxis. the general information is quoted down:

Management of Exposures to HBV

For percutaneous or mucosal exposures to blood, several factors must be considered when making a decision to provide prophylaxis, including the HBsAg status of the source and the hepatitis B vaccination and vaccine-response status of the exposed person. Such exposures usually involve persons for whom hepatitis B vaccination is recommended. Any blood or body fluid exposure to an unvaccinated person should lead to initiation of the hepatitis B vaccine series.

The hepatitis B vaccination status and the vaccine-response status (if known) of the exposed person should be reviewed. A summary of prophylaxis recommendations for percutaneous or mucosal exposure to blood according to the HBsAg status of the exposure source and the vaccination and vaccine-response status of the exposed person is included in this report

When HBIG is indicated, it should be administered as soon as possible after exposure (preferably within 24 hours). The effectiveness of HBIG when administered >7 days after exposure is unknown. When hepatitis B vaccine is indicated, it should also be administered as soon as possible (preferably within 24 hours) and can be administered simultaneously with HBIG at a separate site (vaccine should always be administered in the deltoid muscle).

For exposed persons who are in the process of being vaccinated but have not completed the vaccination series, vaccination should be completed as scheduled, and HBIG should be added as indicated (Table 3). Persons exposed to HBsAg-positive blood or body fluids who are known not to have responded to a primary vaccine series should receive a single dose of HBIG and reinitiate the hepatitis B vaccine series with the first dose of the hepatitis B vaccine as soon as possible after exposure. Alternatively, they should receive two doses of HBIG, one dose as soon as possible after exposure, and the second dose 1 month later. The option of administering one dose of HBIG and reinitiating the vaccine series is preferred for nonresponders who did not complete a second 3-dose vaccine series. For persons who previously completed a second vaccine series but failed to respond, two doses of HBIG are preferred.

Efficiency

For perinatal exposure to an HBsAg-, HBeAg-positive mother, a regimen combining HBIG and initiation of the hepatitis B vaccine series at birth is 85%--95% effective in preventing HBV infection (44,45). Regimens involving either multiple doses of HBIG alone or the hepatitis B vaccine series alone are 70%--75% effective in preventing HBV infection (46). In the occupational setting, multiple doses of HBIG initiated within 1 week following percutaneous exposure to HBsAg-positive blood provides an estimated 75% protection from HBV infection (47--49). Although the postexposure efficacy of the combination of HBIG and the hepatitis B vaccine series has not been evaluated in the occupational setting, the increased efficacy of this regimen observed in the perinatal setting, compared with HBIG alone, is presumed to apply to the occupational setting as well. In addition, because persons requiring PEP in the occupational setting are generally at continued risk for HBV exposure, they should receive the hepatitis B vaccine series

Post Exposure Prophylaxis HCV

Post exposure management of HCV is in its early phase of development. Scientists have hardly cultured it, hence fool proof method for experimentation is still awaited .But fortunately in about 25% of cases there can be spontaneous cure of the disease by the innate immunity of the person.
The present status of HCV prophylaxis can be briefed as Data upon which to base a recommendation for therapy of acute infection are insufficient because
a) No data exist regarding the effect of treating patients with acute infection who have no evidence of disease,
b) Treatment started early in the course of chronic infection might be just as effective and would eliminate the need to treat persons who will spontaneously resolve their infection,
c) The appropriate regimen is unknown.

Postexposure Management for HCV

In several studies, researchers have attempted to assess the effectiveness of IG following possible exposure to non-A, non-B hepatitis. These studies have been difficult to interpret because they lack uniformity in diagnostic criteria and study design, and, in all but one study, the first dose of IG was administered before potential exposure (48,85,86). In an experiment designed to model HCV transmission by needlestick exposure in the health-care setting, high anti-HCV titer IG administered to chimpanzees 1 hour after exposure to HCV-positive blood did not prevent transmission of infection (87). In 1994, the Advisory Committee on Immunization Practices (ACIP) reviewed available data regarding the prevention of HCV infection with IG and concluded that using IG as PEP for hepatitis C was not supported.

    based on the following facts:
  • No protective antibody response has been identified following HCV infection.
  • Previous studies of IG use to prevent posttransfusion non-A, non-B hepatitis might not be relevant in making recommendations regarding PEP for hepatitis C.
  • Experimental studies in chimpanzees with IG containing anti-HCV failed to prevent transmission of infection after exposure.

No clinical trials have been conducted to assess postexposure use of antiviral agents (e.g., interferon with or without ribavirin) to prevent HCV infection, and antivirals are not FDA-approved for this indication. Available data suggest that an established infection might need to be present before interferon can be an effective treatment. Kinetic studies suggest that the effect of interferon on chronic HCV infection occurs in two phases. During the first phase, interferon blocks the production or release of virus from infected cells. In the second phase, virus is eradicated from the infected cells (89); in this later phase, higher pretreatment alanine aminotransferase (ALT) levels correlate with an increasing decline in infected cells, and the rapidity of the decline correlates with viral clearance. In contrast, the effect of antiretrovirals when used for PEP after exposure to HIV is based on inhibition of HIV DNA synthesis early in the retroviral replicative cycle.

In the absence of PEP for HCV, recommendations for postexposure management are intended to achieve early identification of chronic disease and, if present, referral for evaluation of treatment options. However, a theoretical argument is that intervention with antivirals when HCV RNA first becomes detectable might prevent the development of chronic infection. Data from studies conducted outside the United States suggest that a short course of interferon started early in the course of acute hepatitis C is associated with a higher rate of resolved infection than that achieved when therapy is begun after chronic hepatitis C has been well established (90--92). These studies used various treatment regimens and included persons with acute disease whose peak ALT levels were 500--1,000 IU/L at the time therapy was initiated (2.6--4 months after exposure).

No studies have evaluated the treatment of acute infection in persons with no evidence of liver disease (i.e., HCV RNA-positive 6 months duration with normal ALT levels); among patients with chronic HCV infection, the efficacy of antivirals has been demonstrated only among patients who also had evidence of chronic liver disease (i.e., abnormal ALT levels). In addition, treatment started early in the course of chronic HCV infection (i.e., 6 months after onset of infection) might be as effective as treatment started during acute infection (13). Because 15%--25% of patients with acute HCV infection spontaneously resolve their infection (93), treatment of these patients during the acute phase could expose them unnecessarily to the discomfort and side effects of antiviral therapy.

http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5011a1.htm



Pre Exposure Prophylaxis


Pre-exposure prophylaxis (PrEP) is any medical or public health procedure used before exposure to the disease causing agent, its purpose is to prevent, rather than treat or cure a disease.

HIV

Recent research results shows promise for a new HIV prevention strategy called pre-exposure prophylaxis or PrEP. PrEP involves HIV-negative people at risk for HIV using antiretroviral medications (ARVs) to reduce the risk of HIV infection. The iPrEx trial results were released in November, 2010 and showed that in gay men, transgender women and other men who have sex with men, daily TDF/FTC (tenofovir disoproxyl fumarate plus emtricitabine also known as Truvada) reduced the risk of HIV by 44 percent. Additional studies are ongoing in other populations.
www.avac.org

More than 7,000 people continue to become infected around the world every day (approximately 2.7 million per year, With an effective vaccine years away, there is mounting evidence that antiretroviral agents may be able to play an important role in reducing the risk for transmission. Researchers believe that an HIV drug approved by the U.S. Food and Drug Administration (FDA)―tenofovir disoproxil fumarate (tenofovir, brand name Viread) used alone or in combination with emtricitabine (together, known by the brand name Truvada)―taken daily as an oral preventive drug, is among the most important new prevention approaches being investigated today. The approach is called pre-exposure prophylaxis, or PrEP.
www.cdc.gov

HBV

Hepatitis B vaccine is a vaccine developed for the prevention of hepatitis B virus infection. The vaccine contains one of the viral envelope proteins, hepatitis B surface antigen (HBsAg). It is produced by yeast cells, into which the genetic code for HBsAg has been inserted.[1] A course of three (3) vaccine injections are given with the second injection at least one month after the first dose and the third injection given six months after the first dose.[2] Afterward an immune system antibody to HBsAg is established in the bloodstream. The antibody is known as anti-HBsAg. This antibody and immune system memory then provide immunity to hepatitis B infection.[3] The first vaccine became available in 1981.
Presently recombinant DNA vaccines are available, which means they are produced by inserting the gene for HBV into common baker's yeast where it is grown, harvested, and purified. HBV infection cannot occur from receiving hepatitis B vaccine.

Vaccine Recommendations

The hepatitis B vaccine is recommended specifically for all infants and children by the Centers for Disease Control and the American Academy of Pediatrics. The CDC also recommends that adults in high-risk groups be vaccinated.
The following list is a general guide for vaccination, but since every person is at some risk for infection, these guidelines should be individualized for each situation.
  • All infants at birth and all children up to 18 years.
  • Health care professionals and emergency personnel.
  • Sexually active teens and adults
  • Men who have sex with men.
  • Sex partners or close family/household members living with an infected person.
  • Families considering adoption, either domestic or international.
  • Travelers to countries where hepatitis B is common (Asia, Africa, South America, the Pacific Islands, Eastern Europe, and the Middle East).
  • Patients with kidney disease or undergoing dialysis.
  • Residents and staff of correctional facilities and group homes.
  • Any person who may fall into a high risk group due to occupation or lifestyle choices.

Vaccine Schedule

The vaccine is readily available at your doctor's office or local health clinic. Three doses are generally required to complete the hepatitis B vaccine series, although there is an accelerated two-dose series for adolescents.
  • First Injection - At any given time
  • Second Injection - At least one month after the first dose
  • Third Injection - Six months after the first dose
www.hepb.org

HCV

Currently, there is no hepatitis C vaccine for three basic reasons:
  • HCV has different genotypes. These genotypes are basically genetic variations of a theme. They're hepatitis C viruses, but they have enough genetic difference to be classified in distinct genotypes. Since hepatitis C has at least six genotypes, several different vaccines would be needed to protect against each genotype.

    Maybe it's helpful to compare genotypes with members of a family. A family is made up of many different people, each with their own personality and looks, but all are still members of a family. It's very similar with the hepatitis virus. There are different genotypes, but they are all hepatitis C viruses.
  • HCV mutates very easily. This means that some of its genetic code can change a little bit when it replicates itself. The result is a virus that keeps its genotype, but is different enough to confuse a vaccine.
  • There is no effective small animal model or cell culture system. This makes vaccine development very challenging because researchers can't see how the virus really works in a natural environment. Really, scientists don't truly understand the whole life-cycle of the hepatitis C virus because infecting liver cells (called hepatocytes) is very difficult.

    This may be changing. Researchers from the University of California, San Diego School of Medicine announced in July 2008 that they have developed a culture system that can model infection with the hepatitis C virus. This is great news for HCV vaccine development.

http://hepatitis.about.com/od/prevention/a/HCVvaccine.htm

Several promising approaches have been used to develop an HCV vaccine. generated a novel T-cell vaccine based on adenovirus vectors from rare serotypes expressing HCV NS proteins, that is safe and highly immunogenic in patients with chronic HCV infection
www.natap.org