Extensively Drug Resistant Salmonella Enterica Serovar Typhi Misdiagnosis in Pakistan: A Matter of Serious Concern

Principal Investigator (PI):   Dr Rizwan Uppal

Author Names:  Rizwan Uppal, Umar Saeed, Sara Rizwan Uppal, Zahra Zahid Piracha, Azhar Rasheed, Zubair Aftab, Hafsah Zaheer

Corresponding Author & Co-PI:  Dr. Umar Saeed

In Pakistan, across several rural areas of Punjab, Sindh, Balochistan, and KPK, the Widal and TyphiDOT are still being used as diagnostic tests by less qualified clinical laboratories which results into misdiagnosis of the typhoid. The Widal and TyphiDOT tests should be discontinued as there is no use of these tests and merely wastage of time and resources for accurate diagnosis against XDR S. Typhi. The blood culture is gold standard test for typhoid diagnosis and it confirmed before starting antibiotics. In other words the gold standard method is more reliable for determining XDR S.

Abstract

There have been several outbreaks of antimicrobial resistant (AMR) strains of Salmonella enterica serovar Typhi that cause extensively drug resistant (XDR) typhoid fever in Pakistan. It has been observed that many clinicians use serological diagnostic tests such as Widal agglutination, and TyphiDOT that detects IgM and IgG antibodies against the outer membrane protein of S. Typhi. However, it has been confirmed by many scientists that these test maylead to misdiagnosis against XDR S. Typhi. Due to lack of implementation strategies health authorities are unable to hamper Widal or TyphiDOT tests which are still practiced in many rural and urban areas.

Introduction

In Pakistan, since 2016 there have been several outbreaks of antimicrobial resistant (AMR) strains of Salmonella enterica serovar Typhi (S.Typhi) belonging to the H58 haplotype, that cause extensively drug resistant (XDR) typhoid fever (1). Some of the H58 strains are resistant to chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole antibiotics (2). Fluoroquinolones and ceftriaxone have also shown resistance to S. Typhi (3). While, only azithromycin antibiotic have shown significant responses for treatment of XDR S. Typhi. The positive serological tests such as Widal agglutination, and TyphiDOT that detects IgM and IgG antibodies against the outer
membrane protein of S.Typhi are not recommended for diagnosis of typhoid fever (4,5). There has been excessive usage of azithromycin during COVID-19 pandemic which may turn into havoc if azithromycin resistance strain appeared in near future (6). Recently, several studies questioned the authenticity of rapid diagnostic testing kits in Pakistan.

 Specifically diagnosis of XDR typhoid fever caused by XDR S. Typhi, is the matter of serious concern (7,8). Pathogenic microorganisms are increasing day by day due to lack of appropriate knowledge and awareness among general populations (9-14). In Pakistan, across several rural areas of Punjab, Sindh, Balochistan, and KPK, the Widal and TyphiDOT are still being used as diagnostic tests by less qualified clinical laboratories which results into misdiagnosis of the typhoid. The Widal and TyphiDOT tests should be discontinued as there is no use of these tests and merely wastage of time and resources for accurate diagnosis against XDR S. Typhi. The blood culture is gold standard test for typhoid diagnosis and it confirmed before starting antibiotics. In other words the gold standard method is more reliable for determining XDR S. Typhi in subjects.

The Government of Pakistan public sector National Institute of Health has also directed to stop forth with from conducting Widal and TyphiDOT tests for diagnosis of typhoid fever (15,16). Among 241 patients positive for salmonella, TUBEX®TF was positive in 42.64% of subjects, however Widal was positive among 36.76% of the patients, with low sensitivity and specificity (17). Several non-government organizations of Pakistan should also put join efforts to implement water purification and sanitation activities, at both urban and rural community levels for health safety. Several awareness campaigns on safe hygiene and sanitation practices should be initiated in schools, colleges and universities. The government should ensure safe mass vaccination campaign (using Vi-polysaccharide typhoid vaccine or the typhoid conjugate vaccine) by creating national XDR S. Typhi taskforce to combat prevalence of multidrug resistant S. Typhi in Pakistan. 

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