International Journal of Advanced Medical and Health Research

: 2019  |  Volume : 6  |  Issue : 2  |  Page : 37--38

Typhoid fever: Is the past the future of the present?

Tamilarasu Kadhiravan 
 Department of Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India

Correspondence Address:
Tamilarasu Kadhiravan
Department of Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Dhanvantri Nagar, Puducherry - 605 006

How to cite this article:
Kadhiravan T. Typhoid fever: Is the past the future of the present?.Int J Adv Med Health Res 2019;6:37-38

How to cite this URL:
Kadhiravan T. Typhoid fever: Is the past the future of the present?. Int J Adv Med Health Res [serial online] 2019 [cited 2021 Jul 27 ];6:37-38
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Typhoid fever is an enduring classic among infectious diseases so much so that the first chapter in Sir William Osler's magnum opus “The Principles and Practice of Medicine” was on typhoid fever.[1] More than a century later, unfortunately, typhoid fever continues to be an important cause of acute febrile illness in the tropics, which largely includes developing nations such as India, Pakistan, Nepal, Bangladesh, and Vietnam.[2] Notwithstanding the fact that age-standardized incidence rates of typhoid and paratyphoid fevers had declined by about 55% between 1999 and 2017, typhoid and paratyphoid fevers caused an estimated 14.3 million cases and 136,000 deaths globally in 2017.[3]

In the preantibiotic era, typhoid fever was a fatal illness with an associated mortality in excess of 20%.[4] However, with the discovery of the clinical effectiveness of chloromycetin (chloramphenicol) in 1948, typhoid fever became an eminently treatable illness.[5] The success story did not last long. Within 2 years, resistance to chloramphenicol was reported.[6] Since 1989, several outbreaks of multidrug-resistant (MDR) typhoid fever caused by Salmonella Typhi, defined as resistance to chloramphenicol, ampicillin, and co-trimoxazole, were reported in endemic countries.[7] Fortunately, around the same time, ciprofloxacin became available for clinical use. Fluoroquinolones such as ciprofloxacin and ofloxacin were highly effective for the treatment of MDR-typhoid fever, making them the treatment-of-choice.[8] However, indiscriminate use of fluoroquinolones unwittingly resulted in the emergence of S. Typhi strains with decreased susceptibility to fluoroquinolones, soon to be followed by the emergence of overtly resistant S. Typhi.[9] Currently, most isolates of S. Typhi circulating in endemic countries are nonsusceptible to ciprofloxacin.[10] Reasonable choices to treat such strains are limited – only ceftriaxone and azithromycin.

Then, our worst fears came true. An outbreak of ceftriaxone-resistant typhoid fever, called extensively drug-resistant (XDR) typhoid fever, was reported in November 2016 from the Sindh Province of Pakistan.[11] Till date, more than 10,000 XDR-typhoid fever cases have been reported in Pakistan.[12] Most of the cases were among children aged <10 years. These XDR isolates harbor a blaCTX-M-15 extended-spectrum β-lactamase (ESBL) gene that mediates resistance to ceftriaxone.[11] In addition, these isolates are resistant to ciprofloxacin, conferred by a combination of gyrA mutation and acquisition of a qnrS gene. The blaCTX-M-15 and qnrS genes are carried on an IncY plasmid specific to the XDR isolates. It is believed that this plasmid originated first among Escherichia coli and was later acquired by S. Typhi.[11] Only carbapenems such as meropenem and macrolides such as azithromycin are effective in treating XDR-typhoid fever. Published data indicate that XDR-typhoid fever is associated with a higher rate of complications.[13] To make things worse, within months of this outbreak, travel-associated XDR-typhoid fever cases were reported from the United Kingdom, United States, Denmark, and Canada. Subsequently, the US Centers for Disease Control and Prevention has issued a Level 1 (Watch–practice usual precautions) travel alert.[14]

Infections caused by ESBL-producing S. Typhi and S. Paratyphi isolates have been reported earlier from other settings in Bangladesh, Nepal, Philippines, Iraq, Kuwait, Guatemala, Democratic Republic of the Congo, India, and Sri Lanka. Earliest of them was in the year 2000.[15] These infections remained isolated sporadic instances and never evolved into outbreaks, unlike the current XDR-typhoid isolates from Pakistan. Epidemiologic investigation of the XDR-typhoid outbreak suggests that contamination of drinking water with sewage water is the probable source of infection.[16] In response to this outbreak, health authorities in Pakistan have embarked on a mass vaccination campaign with the typhoid conjugate vaccine, in addition to water purification and sanitation activities.[17]

In this context, it is worthwhile to note that the public health burden of typhoid fever in Vietnam markedly decreased over the period of 1994–2004, attributable to improvements in standard of living, access to safe drinking water and sanitation, and mass vaccination of school-going children aged 3–10 years.[18] It remains to be seen how the current outbreak in Pakistan unfolds and whether the public health interventions manage to contain and halt XDR-typhoid fever in its tracks. One thing becomes clear. In the bug versus drug game, bugs will always have the last laugh. If we are really serious about conquering this historical malady, sustained improvement in sanitation and hygiene is essential. In the meanwhile, large scale deployment of effective vaccines could help us buy some time. From a clinician's perspective, judicious use of antibiotics in clinical practice is the primary way to prevent emergence and spread of antimicrobial resistance in typhoid fever. With the emergence of XDR-typhoid fever, the decisive moment in the history of typhoid control has arrived. If the global community fails to act at least now, the foreseeable future of the present is nothing but the past, when typhoid fever reigned supreme.


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