If the eschar can be identified, it is quite diagnostic of scrub typhus, but this can be unreliable on dark skin, and moreover, the site of eschar which is usually where the mite bites is often located in covered areas. Unless it is actively searched for, the eschar can easily be missed. History of mite bite is often absent since the bite does not inflict pain and the mites are almost too small to be seen by the naked eye. Usually, scrub typhus is often labelled as PUO in remote endemic areas, since blood culture is often negative, yet it can be treated effectively with chloramphenicol. Where doubt exists, the diagnosis may be confirmed by a laboratory test such as serology. Again, this is often unavailable in most endemic areas, since the serological test involved is not included in the routine screening tests for PUO, especially in Burma (Myanmar).The choice of laboratory test is not straightforward, and all currently available tests have their limitations. The cheapest and most easily available serological test is the Weil-Felix test, but this is notoriously unreliable. The gold standard is indirect immunofluorescence, but the main limitation of this method is the availability of fluorescent microscopes, which are not often available in resource-poor settings where scrub typhus is endemic. Indirect immunoperoxidase, a modification of the standard IFA method, can be used with a light microscope, and the results of these tests are comparable to those from IFA.
The initial in vitro studies appeared to indicate a major role for ester hydrolysis but, with accumulation of clinical data over time, the preponderance of evidence indicated that Hofmann elimination at physiological pH is the major degradation pathway vindicating the premise for the design of atracurium to undergo an organ-independent metabolism.Hofmann elimination is a temperature- and pH-dependent process, and therefore atracuriums rate of degradation in vivo is highly influenced by body pH and temperature: An increase in body pH favors the elimination process, whereas a decrease in temperature slows down the process. Otherwise, the breakdown process is unaffected by the level of plasma esterase activity, obesity, age, or by the status of renal or hepatic function. On the other hand, excretion of the metabolite, laudanosine, and, to a small extent, atracurium itself is dependent on hepatic and renal functions that tend to be less efficient in the elderly population. The pharmaceutical presentation is a mixture of all ten possible stereoisomers. Although there are four stereocentres, which could give 16 structures, there is a plane of symmetry running through the centre of the diester bridge, and so 6 meso structures (structures that can be superimposed by having the opposite configuration then 180° rotation) are formed. This reduces the number from sixteen to ten. There are three cis-cis isomers (an enantiomeric pair and a meso structure), four cis-trans isomers (two enantiomeric pairs), and three trans-trans isomers (an enantiomeric pair and a meso structure).