Multidrug and extensively drug resistant typhoid fever

Multidrug resistant typhoid fever is an increasingly common health concern across the

Typhoid is an infectious disease. It is caused by infection of Salmonella typhi or paratyphi. Antibiotics are only effective treatments for the Typhoid. Inappropriate use of drugs to treat typhoid has caused development of strains that are resistant to commonly used antibiotics. Today we will discuss multidrug-resistant Typhoid.

What is resistance to antibiotics?

The bacteria which were susceptible to specific antibiotics previously become non susceptible to specific antibiotics. This phenomenon is called resistance to antibiotics.

Antibiotics were definitely the truck which caused benefits to humanity. In the last 1 century antibiotics have revolutionised the medical treatment for infectious diseases. But as the antibiotics are discovered by medical science there is a phenomenon of antibiotic resistance shown by the bacteria.

What is multidrug resistant typhoid?

Decades back Salmonella paratyphi and Salmonella typhi where it is susceptible to antibiotics like chloramphenicol. Over the period decades new strains have appeared and they are resistant to antibiotics that were previously used to treat Typhoid fever.

Multidrug resistance typhoid also called MDR typhoid is defined as resistance to at least three first line drugs to treat Typhoid fever. These three antibiotics include chloramphenicol, ampicillin, and cotrimoxazole. 

When did Drug resistance occur?

According to a review article published in 2020, chloramphenicol was the first effective treatment in 1948 for the treatment of the Typhoid fever. The resistance and low efficacy of chloramphenicol was first noted within two years of the start of effective treatment of typhoid. 

Because of drug resistance to chloramphenicol, Ampicillin and cotrimoxazole became the drug of choice for treatment of Typhoid fever in the 1960s.

Over the next two decades from 1960 to 1970 there were various reports suggesting low efficacy and resistance to ampicillin and cotrimoxazole.

Because of strains that were resistant to all the three drugs namely chloramphenicol, ampicillin and cotrimoxazole later on in 1990s fluoroquinolones became drugs of choice for treatment of typhoid fever.

Later on XDR typhoid that was resistant to fluoroquinolones were found increasingly. So clinicians use cephalosporins and azithromycin for the treatment of Typhoid fever.

Later on there were many reports of resistance to cephalosporins. In a strain that was resistant to chloramphenicol, ampicillin, cotrimoxazole, fluoroquinolones, and cephalosporins where is reported in Pakistan in 2016. It was named as xdr typhoid.

Which strain of Salmonella typhi is found to be resistant?

H58 strain of Salmonella typhi is found to be resistant to multiple drugs. H 58 strain of Salmonella typhi is the leading cause of typhoid across the world. It is the dominant strain of Salmonella typhi causing Typhoid fever.

What is the impact of drug resistant Typhoid fever?

Typhoid fever is a disease occurring in low and middle-income countries. Millions of cases of typhoid fever are found yearly. Globally Typhoid fever causes the death of lakhs of people.

As the new strains which are the resistance to commonly used antibiotics are inverting it has become difficult to treat the common illness.

Following are the impacts of drug resistance in typhoid.

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  • Because of drug resistance the complications of typhoid may occur.
  • Drug resistance may cause increased stay of patients in hospitals and prolong the treatment.
  • Resistance to commonly used antibiotics needs higher antibiotics and increases the cost of treatment.
  • Inadequate response to treatment can cause increased mortality because of the disease which was previously treatable.
  • Emergence of the new drug resistant strains may lead to an increased number of typhoid cases each year.
  • Increased total number of typhoid cases each year can strain the economics of families and entire nations.

How large is this problem of resistance in typhoid fever?

In a meta-analysis, the studies published from 1989 to 2018 were examined. In this meta analysis studies from across the world were considered. The data was finally analysed for mode of spread and detection of resistant typhoid. These studies all examined various outbreaks of typhoid fever that occurred in 20 years across the world.

It was found that 32% outbreaks had resistant typhoid to fluoroquinolones and 42% outbreaks were MDR typhoid.

So MDR TB and drug resistance in TB is a universal phenomenon.

What is the solution to MDR and XDR typhoid?

All the diseases in which treatments are not available or effective treatment are not available, the best solution is not getting sick. The strategies that are very helpful in preventing typhoid disease are as follows:

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  • Taking typhoid vaccine if you are staying in an endemic area or if you are going to visit an endemic area.
  • Good sanitation facilities accessible to the entire population.
  • Avoiding open defecation practices.
  • Consuming clean drinking water and access to clean drinking water to the entire population.
  • Consuming the food that was prepared with adequate care.
  • Washing hands with soap water after use of latrine.
  • Washing hands with soap water before consuming the food.
  • Screening the people who handle for the regularly like employees of the hotel.
  • Vaccinating the people who regularly handle the food and meat.
  • Judicious use of antibiotics.

How does typhoid develop resistance?

A systematic review of Salmonella typhi was published in 2018. It studied various mechanisms of the development of resistance in typhoid bacteria. 

Salmonella typhi bacteria mainly develops resistance by following mechanisms:

  • It can inactivate the antibiotics changing its chemical properties with its enzymes.
  • It can change the characteristic of the target site of antibiotics on bacteria. This leads to antibiotics becoming ineffective as they cannot act on the target site.
  • Another mechanism of resistance is typhoid can throw out antibiotics very rapidly from itself.

Many of these are acquired by the plasmids. These plasmids can transmit these properties to non-registered bacteria very effectively.


Sources
  1. Appiah, G. D., Chung, A., Bentsi-Enchill, A. D., Kim, S., Crump, J. A., Mogasale, V., Pellegrino, R., Slayton, R. B., & Mintz, E. D. (2020). Typhoid Outbreaks, 1989-2018: Implications for Prevention and Control. The American journal of tropical medicine and hygiene, 102(6), 1296–1305. https://pubmed.ncbi.nlm.nih.gov/32228795/
  2. Akram, J., Khan, A. S., Khan, H. A., Gilani, S. A., Akram, S. J., Ahmad, F. J., & Mehboob, R. (2020). Extensively drug-resistant (XDR) typhoid: evolution, prevention, and its management. BioMed Research International, 2020. https://www.hindawi.com/journals/bmri/2020/6432580/
  3. McAteer, J., Derado, G., Hughes, M., Bhatnagar, A., Medalla, F., Chatham-Stevens, K., Appiah, G. D., & Mintz, E. (2020). Typhoid Fever in the US Pediatric Population, 1999-2015: Opportunities for Improvement. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, ciaa914. Advance online publication. https://doi.org/10.1093/cid/ciaa914
  4. Typhoid fever, Mayo clinic staff https://www.mayoclinic.org/diseases-conditions/typhoid-fever/symptoms-causes/syc-20378661
  5. Britto, C. D., Wong, V. K., Dougan, G., & Pollard, A. J. (2018). A systematic review of antimicrobial resistance in Salmonella enterica serovar Typhi, the etiological agent of typhoid. PLoS neglected tropical diseases, 12(10), e0006779. https://doi.org/10.1371/journal.pntd.0006779



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