Gram positive laboratory algorithm

We are living in an exciting time in microbiology and clinical infectious diseases in which new methods are becoming more readily available and rapid to detect pathogens in clinical specimens. While PCR, 16S rDNA sequencing, microarrays and MALDI-TOF are becoming more readily available in more microbiology labs, as of "now", working through a gram positive lab algorithm is still necessary for boards and helpful in timely and skillful clinical practice.

The gram positive laboratory algorithm is like a map. We will run through this literally as a map...of KU SOM.

This is the KU SOM we will use as a reference. Obviously, most first year medical students walk the halls and think about gram positive bacteria.  

For your reference, here is a gram positive lab algorithm similar to that which you will find in First Aid and other board-prep and clinical micro references.

We will first run through this with a Prezi, linked here (need to unlock adobe flash in browser): Gram Positive Lab Algorithm

Finally, we will walk through it with an amateur video tour. While you are watching, think about where these gram positive bacteria live in a human host and which clinical diseases they may cause.

Gram Positive Lab Algorithm Video

Hepatitis B

Hepatitis B virus infection is transmitted via the "Bs" blood, birthing, bonking (sex) and this includes injection drug use (sharing needles/syringes), occupational needle stick, or much less commonly contact with open wounds of an infected person or sharing items with bodily fluids on them (razors, toothbrushes, etc).

When the virus enters the bloodstream it circulates and then primarily infects hepatocytes.

source: https://www.qiagen.com/us/shop/genes-and-pathways/pathway-details/?pwid=217

In the initial or immunotolerent phase there is limited immune response with minimal increase in liver transaminases (AST, ALT). The HBsAg shows up as early as week 4 and circulates during ACTIVE DISEASE. The HbeAg is next and indicates ability to infect others. Circulating HBV DNA will be high at this time and can be found with a nucleic acid amplification test as well. Around week 6 IgM anti-HBc and total anti-HBc start to rise. In immunocompetent adult hosts this phase is present during "incubation." If disease is acquired at birth this phase can last for decades - see chronic hepatitis below. Some individuals will then convert on their own to anti-HBe. The total anti-HBc peaks around week 20 and persists (which is how we know years later who at one time DID have the Hepatitis B virus).

In the immunoactive phase the HBV DNA declines and the immune system revs up leading to increased inflammation evident in rising liver transaminases. In the next phase (the third phase) if the individual did not already convert to anti-HBe they can after the immunoactive phase immune system surge. IgM to anti-HBc can go up here so it confuses whether or not THIS stage is brand-new infection (so often in clinical practice we don't use this particular Ab test). Most people during this third phase will have decline in HBV DNA as their immune system has attacked the virus, some will convert to HBsAg neg.

In the last phase (resolution) anti-HBs (aka HBsAb) develops (starts at variable times - as early as week 32 in few individuals) and we say they have "natural immunity." (i.e. their immune system developed immunity as a result of actual infection and not from a "man-made" vaccination).

To make it even more complicated, hepatitis B has a different pattern of Ab response when it behaves as a "chronic" infection (defined as surface Ag + > 6 months). Now you have the same pattern with initial HBsAg and Total + IgM anti-HBc but the surface Ag and HBeAg are present much longer (years) in an asymptomatic state (which may include normal liver transaminases). The IgM to anti-HBc still falls but the total core remains.

Seriously? Can this get any worse? Yes. Individuals with resolved hepatitis B viral infection who are: HBsAg negative, anti-HBs and anti-HBc positive and those with chronic active hepatitis B infection who are HBsAg positive but with negative circulating HBV DNA who get immunosuppressive therapies can REACTIVATE their hepatitis to an acute pattern which can progress to fulminant hepatitis and death. We should look for hepatitis B infection in these patients and they should be on a hepatitis B antiviral treatment before/while they are immunosuppressed.

Hepatitis B infection can be prevented with vaccination. As the first opportunity for infection of a newborn is at birth, this is when the vaccine is first recommended. The vaccine only gives you a positive surface antibody never a positive core. Think of this as to get to the CORE of immunity you have to have the actual virus.

UpToDate has some case examples if you find yourself still obsessed with Hepatitis B. Good luck!