Today we'll be talking about a bacterial infection of the blood, that can quickly lead to death if it goes untreated. In the case of this 19 year old college student, quick recognition of the infection by the hospital team, allowed for life saving treatment to be delivered. Neil was brought to the By his concerned roommate, who found him lethargic and sweating profusely, lying in their shared dorm room. The roommate tells the attending physician that he thinks Neal has some kind of flu. For the past two days he'd been febrile and was complaining of a terrible headache and neck stiffness. This morning Neal vomitted twice. The roommate has been sleeping in a friends room. Firstly, because he didn't want to catch anything, but also because he says that Neil has been extremely sensitive to light and sound. And has wanted the room to be completely dark all through the day. The attending physician, notices that Neil appears to be very drowsy. But he's able to state today's date and seems to know that he's in the hospital. Several of his vital signs are out of the normal range. His blood pressure is low and he has an elevated heart rate and an elevated temperature. On physical examination, the physician notes a red, spotty rash on Neil's trunk and extremities, even though his skin tone makes it somewhat difficult to see. The rash doesn't go away when the physician pushes down on it. As she begins to remove Neil's socks, she is alarmed to see that the fourth and fifth toes on his left foot appear to be turning black. On examination, Neil also demonstrates signs of meningeal irritation, including difficulty putting his chin to his chest and extreme sensitivity to light. This collection of findings leads the physician to suspect that Neil is suffering from meningitis. And inflammation of the meninges surrounding the brain. As opposed to encephalitis, which is an infection of the brain perincama itself. Meningitis classically presents with fever, severe headaches, neck stiffness, vomiting, and lethargy. While encephalitis is much more likely to also involve diffuse or focal neurological deficits. Like behavior changes, disorientation or partial loss of voluntary movements. The accompanying skin rash on Neal's trunk and extremities leads the physician to suspect an infection of Neisseria meningitides. Although N meningitides isn't the only bacterial infection that can present in this way, she decides to start empiric antibiotic therapy and aggressive hydration with IV fluids to treat Neil's low blood pressure. She also orders a CBC, blood cultures, and performs a lumbar puncture to examine the cerebral fluid. Neil's blood work returns with a markedly elevated white blood cell count and a low platelet count. The cerebral spinal fluid, collected during the lumbar puncture, reveals many neutrophils, decrease glucose levels, and elevated CSF protein levels. This findings support the expected diagnosis of bacterial meningitis with meningococcemia. Gram stain of the CSF shows gram negative diplococci, with many neutrophils, further supporting the physician's suspicion that the causative microorganism is N meningitides. N meningitides typically enters it's human host when it manages to cross the nasopharyngeal mucosa. A physical barrier that usually protects the host from microbial invasion. The bacteria then colonize the respiratory epithelium and begin replicating inside epithelial cells, before passing into the blood stream. The host immune system recognizes a bacterial invasion, and the complement system is activated to try and eliminate the bacteria. Inflammatory cytokines are also released to deploy other immune defense pathways. But N meningitidis has evolved several survival mechanisms. Including a capsule that protects it from complement-mediated bacteriolysis and IgA proteases that prevent it from being tagged for phagocytosis. Once inside the bloodstream, N meningitidis exhibits neurotropism. The bacteria preferentially travel to the brain, where they've evolved to be able to cross the endothelium of the blood-brain barrier. Then, they can replicate in the cerebrospinal fluid. In some cases, like Neil's, infections with N meningitidis can go on to cause further complications. Once the bacteria had infected the bloodstream, they can multiply rapidly. And produce an endotoxin, or LPS, that triggers inflammation and clotting inside the small vessels. This leads to break down of the vessels and micro-hemorrhages, the cause of the petechial rash seen on Neal's trunk and extremities. The wide spread formation of clots in his blood vessels explain's Neil low platelet count. And the interruption of normal blood flow, causes ischemia to the limbs. Neal's black toes were a sign that his infection was progressing to a much more serious condition. The wide spread inflammation that results from disseminated meningococcal infection leads to a collection of physical findings, known as systemic inflammatory response syndrome or SIRS. SIRS is diagnosed when a patient suffers from two or more of the following. Abnormal body temperature, rapid heart rate and respiratory rate, and abnormal white blood cell count. When SIRS is caused by an infection, the condition is called sepsis. And it can rapidly progress to severe sepsis or septic shock in which widespread hypoperfusion of the body's organs leads to organ failure and death. Fortunately the rapid intervention in this case prevented any irreversible end organ damage. But the prolonged ischemia to Neal's toes meant that two of them had to be amputated. Because blood flow to these areas had been compromised, the intravenous antibiotics couldn't reach the tissues that needed them. So the two toes and the tissue around them had to be surgically debrided, once his infection was controlled and he was in stable condition. Days later, the CSF and blood cultures returned, providing final confirmation of infection with N meningitides. And antibiotic susceptibility studies guided the choice of IV antibiotics for the next seven days of Neil's treatment. Over the past century with advances in antibiotic therapy, and the availability of meningococcal vaccines, the mortality rate for this disease has dropped dramatically. In Neil's case, a good call on the part of his roommates and the rapid intervention of the medical team ended up saving his life.
