Under ideal program conditions, MDR-TB cure rates can approach 70%. Mechanism of drug resistance
The TB bacterium has natural defenses against some drugs, and can acquire drug resistance through genetic mutations. The bacterium does not have the ability to transfer genes for resistance between organisms through plasmids (see horizontal transfer). Some mechanisms of drug resistance include:
Cell wall: The cell wall of M. tuberculosis (TB) contains complex lipid molecules which act as a barrier to stop drugs from entering the cell. Drug modifying & inactivating enzymes: The TB genome codes for enzymes (proteins) that inactivate drug molecules. These enzymes are usually phosphorylate, acetylate, or adenylate drug compounds. Drug efflux systems: The TB cell contains molecular systems that actively pump drug molecules out of the cell. Mutations: Spontaneous mutations in the TB genome can alter proteins which are the target of drugs, making the bacteria drug-resistant.One example is a mutation in the rpoB gene, which encodes the beta subunit of the bacteriums RNA polymerase. In non-resistant TB, rifampin binds the beta subunit of RNA polymerase and disrupt transcription elongation. Mutation in the rpoB gene changes the sequence of amino acids and eventual conformation of the beta subunit. In this case rifampin can no longer bind or prevent transcription, and the bacterium is resistant.Other mutations make the bacterium resistant to other drugs. For example, there are many mutations that confer resistance to isoniazid (INH), including in the genes katG, inhA, ahpC and others.
This results in the adult stage, where it feeds one last time and is able to sexually reproduce.The stage when ticks are most able to transmit this disease is the nymph stage. They are also the most dangerous in this stage since they are usually less than two millimeters in size and can stay virtually undetected until they are done feeding. Transmission
Queensland tick typhus is transmitted primarily by two types of tick: Ixodes holocyclus and Ixodes tasmani. After the initial attachment to a host, depending on the species and life stage of the tick, it takes anywhere from 10 minutes to 2 hours for it to begin to feed. Once a tick attaches, it can stay on a host for about 12 to 18 hours and then falls off when full. A tick must be attached for a long period of time to transmit bacteria. A tick that appears flat and small probably has not eaten yet. Pathogenesis
After transmission from the infected tick, the bacterium Rickettsia australias enters the body via the bloodstream. The first sign of disease is damage to the skins microcirculation, which results in a rash. From there, the damage continues further into vital organs and can ultimately result in sepsis with multi-organ failure if left untreated. Diagnosis
This disease can be challenging to diagnose because the initial signs are non-descript and relatively common. Analyzing recent travel history can be vital in the beginning stages of treatment.