Protozoa, like fungi are relatively closely related to humans, and because of this and probably also the fact that most severe protozoal disease is suffered by those in developing countries, there are relatively few treatments for many protozoal diseases. Although it is rare to see severe protozoal disease in most developed countries, on a global scale they are responsible for significant morbidity and mortality (Chabé et al. 2017). Helminths are worms, which rarely reproduce in humans but are transmitted through the environment and are often asymptomatic in the human host (Grencis 2015).
The most common protozoal disease is malaria, which in humans is caused by either Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae or Plasmodium knowlesi. Because plasmodia are carried and transmitted by a mosquito which is not endemic to most of Europe, primary transmission does not occur here, malaria almost always being an imported disease. Most severe infection is associated with Plasmodium falciparum. Because the treatments are complex, and resistance patterns vary widely, it is necessary to consult the current guidelines whenever a case of malaria is encountered (Phillips et al. 2017).
The most important intervention for the control of malaria is not treatment with drugs but efforts to reduce the incidence of the mosquito that carries the Plasmodium protozoa, such as the removal of still water pools, or to separate them from humans, particularly at times when they are most likely to bite, for example, by using bed nets. Visitors to malaria-endemic countries are advised to take antimalarial prophylaxis, but this is not always an option for the indigenous residents.
7.1 Choosing an Antimicrobial
It is important when treating infections that the most appropriate antimicrobial is used. Choosing an antimicrobial regimen is complex and involves clinical experience and interpreting test results, but at the same time being careful not to overuse drugs that might ultimately result in resistance and reduced effectiveness in the future. There are four questions that a clinician needs to ask in this respect (Leibovici et al. 1999):
Based on the prescriber’s knowledge and the results of tests, is this the right drug for the known or likely infection?
Is the balance of likely benefit against harm appropriate in this case?
Given the cost of the drug, is its use appropriate?
Is there an equally good option which would be less likely to promote resistant organisms?
Recent guidance from NICE in the United Kingdom (National Institute for Health and Care Excellence 2015) states that when prescribing antimicrobials the prescriber should follow any local or national guidance on:
Prescribing the shortest effective course.
At the most appropriate dose.
Using the best route of administration.
Unlike any other treatments though, the antimicrobial prescriber has an additional consideration, which is the likelihood of antimicrobial resistance developing at either the individual or population levels.
In some cases treatment can be delayed until test results are known (remembering that false-negative results, or contamination resulting in a false-positive may occur); but in others such as febrile neutropenia, this is not possible and empirical therapy may be needed while awaiting test results.
There are a variety of tests that are used in informing antimicrobial use, but they all aim to help the clinician find the best drug for the infecting organism. Depending upon the results, each drug-microorganism combination can be put into one of three categories (Rodloff et al. 2008):
Susceptible—The bacterium is inhibited in vitro by a concentration of the drug that is associated with a high likelihood of therapeutic success.
Intermediately resistant —The bacterium is inhibited in vitro by a concentration of the drug that is associated with an uncertain therapeutic effect.
Resistant—The bacterium is inhibited in vitro by a concentration of the drug that is associated with a high likelihood of therapeutic failure.
These are usually calculated using breakpoints and the drug-bacterium minimum inhibitory concentration. A breakpoint is a specified concentration of an antimicrobial which is used to define susceptibility or resistance of a bacteria to it. The susceptibility of a particular organism is based on this and the minimum inhibitory concentration or MIC of the specific organism, which is the lowest (or minimum) concentration of the antimicrobial which inhibits the growth of the organism. If the MIC is equal to or less than the breakpoint that defines susceptibility, the bacteria is categorised as being susceptible to that antibiotic; if it is more, it is either resistant or intermediately resistant (British Society for Antimicrobial Chemotherapy 2018).
For example, the current breakpoint between susceptibility and resistance for vancomycin for the treatment of Staphylococcus aureus is defined by the minimum concentration of the drug that will stop the bacterium from growing, currently set at a level of 2 mg/L. If it is less than or equal to this, it is sensitive; if above this, it is resistant. This is based on the minimum concentration that inhibits growth; it is not necessarily the same as the concentration that kills the bacterium (the minimum bactericidal concentration). For practical reasons, most tests are based on inhibition rather than killing the bacteria. There is no intermediate category between these two outcomes as vancomycin is a toxic drug and higher doses cannot usually be given to account for this. This is in contrast to drugs such as penicillin, where higher doses can usually be safely given.
The most common tests used are those using phenotypic traits (these are things that are measureable or observable); for example, microscopy, culture and sensitivity (MC&S), but genotypic tests looking for specific microbial genes and molecular tests are increasingly being used. These have the benefit of not requiring the laboratory to be able to grow the organism, as it does for tests such as MC&S. Such techniques include polymerase chain reaction (PCR), high-throughput genome sequencing and matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry (MALDI-TOF MS).
When interpreting any test result, one must be aware of the possibilities of false-positive, or in this case the more likely scenario of false-negative results, where the test fails to identify an infecting organism. While there are many reasons why this may occur, an important consideration is that laboratory conditions do not replicate those found in the human body, and in particular the attempt to culture individual species does not reflect the polymicrobial nature of the body where multiple species and subspecies interact.