key: cord-0835966-91df9u93
authors: Abdul Aziz, Jeza Muhamad; Abdullah, Saman Kaka; Al-Ahdal, Tareq; Gubari, Mohammed I.M.; Rashid, Muhammad Jabar; Tahir, Kosar Shirwan; Khdhir Rasul, Rebwar Hassan; Hamarashid, Zardasht Muhammad; Huy, Nguyen Tien
title: Diagnostic bias during the COVID-19. A rare case report of salmonella typhi
date: 2022-01-26
journal: Ann Med Surg (Lond)
DOI: 10.1016/j.amsu.2022.103282
sha: 7964ddf6805a4ce8b76ef3103255b9ccb20e2ecf
doc_id: 835966
cord_uid: 91df9u93

INTRODUCTION: In poor countries, due to the limited resources, mostly they prescribe medications without proper diagnosis. The aim of this report is to show diagnostic bias of COVID-19 case. CASE PRESENTATION: A 17-year-old male patient was presented to the Hospital with a fever up to 39 °C associated with rigor, sweating, generalized body pain, myalgia, fatigue, loss of appetite, headache, and multiple joint pain with no swelling and redness. The vital signs were steady on physical examination, except temperature which was 39 °C. The chest was clear, and the pulse rate was 90 beats per minute. The heart rate relative bradycardia and lungs were normal. Both a PCR test for COVID-19, and a viral assay ELISA were negative. After further investigations, the culture findings revealed the strong development of Gram-negative coccobacilli (Salmonella serotype Typhi) bacteria under the microscope, which was confirmed by using VITEK 2 to identify it. and treated with ciprofloxacin tab, two times per day for five days and amikacin ampule 500 mg IV every 24 hours for 10 days. DISCUSSION: Fever is a well-known sign of COVID-19 infection which has been observed in 83%–98% of patients with COVID19. As a result, it may be difficult to tell the difference between COVID-19 and other febrile infections, causing delays in diagnosis and treatment and may blind the physician from considering other febrile illnesses. CONCLUSION: Physicians should construct more comprehensive differential diagnoses for people who experience fever, headache, or myalgia symptoms that are linked to a pandemic. COVID-19.

Diagnostic bias, COVID-19, Salmonella typhi, Fever, case report 23

Salmonella enterica subspecies enterica serovar Typhi causes typhoid fever (Salmonella Typhi). 25

In low-resource settings, typhoid fever is a systemic infection that is a primary cause of death 26 and illness (1) . Waterborne, foodborne, or significant person-to-person contact are all ways for 27 the disease to spread (2). Classically, typhoid fever is associated with prolonged fever with a step 28 ladder pattern, gastrointestinal symptoms (like nausea, vomiting, diarrhea, or constipation), 29 headache, fatigue, malaise, loss of appetite, and cough (3). 30

A novel coronavirus (SARS-CoV-2) is currently causing a severe pandemic of disease (termed 31 COVID-19) worldwide, causing a global pandemic (4). The majority of people infected with 32 SARS-CoV-2 are asymptomatic or complain of pneumonia-like symptoms consisting of fever, 33 cough, shortness of breath, and viral symptoms like myalgia, fatigue, and headache (5). Also, the 34 clinical spectrum of COVID-19 ranged from asymptomatic, mild, to moderate-severe, which 35 might lead to death (6). 36

Fever, lack of appetite, nausea, headache, constipation, and sometimes diarrhea are symptoms of 37 extensively drug-resistant typhoid fever, which are frequently non-specific and difficult to 38 identify from other febrile disorders, including COVID-19 (7). At the time of the COVID-19 39 pandemic, limited study had been done on typhoid fever diagnosis. 40

Medication is frequently provided in low-resource countries without a proper diagnosis in such 41 cases. Apart from the nonspecific symptoms of typhoid, they are similar to those of other 42 diseases such as malaria, dengue fever, and COVID19 (8) . 43 that can cause systemic disease and inflammation should be maintained (9). The aim of this 45 report is to describe a diagnostic bias COVID-19, after which proper diagnosis was established 46 as having typhoid fever. This report was written and used the SCARE criteria for case reports as 47 a guideline (10). 48 49

A 17-year-old male patient presented to the hospital with a five-day fever 39 °C. That was 51 episodic, mostly at night, and associated with rigor, sweating, generalized body pain, myalgia, 52 fatigue, loss of appetite, headache, and multiple joint pain with no swelling and redness. The 53 patient had no skin rash, redness, or swelling, did not have a pet or domestic animal at home. He 54 also had mild central abdominal pain, colicky in nature, associated with mild, non-bloody 55 diarrhea four times a day, with no bloody vomiting. He also had a mild dry cough that began one 56

week after the onset of his symptoms, but he had no shortness of breath, was not smoking or 57 drinking alcohol, and lived in a rural area, so his medical history did not indicate that he had a 58 major disease. He had not had any previous abdominal surgery or trauma. Then he was 59 approached with pyrexia of unknown origin.

He did not eat Kurdish cheese, which is made from 60 unpasteurized milk. None of his family members developed the same condition, but history 61 revealed that he drank tap water and ate food on the local street during the 12 days before the 62 onset of fever. physician outside the hospital suspected a mild case of COVID-19 and treated for 63 five days based on the COVID-19 standard care. 64

The vital signs were stable during the physical examination, except temperature which was 67 39°C.The pulse rate and blood pressure were 118bpm, 120/80 mmHg, respectively. SpO2 was 68 97%. The chest was clear, and the pulse rate was 90 beats per minute. The heart rate relative 69 bradycardia and lungs were normal. He had poor skin turgor and appeared to be dehydrated. A 70 part mild splenic enlargement and there was no palpable enlargement of the liver. 71

The following tests were done to differential diagnosis of fever; a PCR test for COVID-19, and a 73 viral assay ELISA (Biotek) for detecting antibody IgM anti-SARS-CoV-2 was also done, the 74 results for both tests were negative. ESR (erythrocyte sedimentation rate) to rule out 75 rheumatological disease, vasculitis and malignancy, which was 17, serological test for Brucella 76 was done by using Brucella agglutination titer, which was negative (<25 IU/mL). CBC to 77 exclude hematological disease, which was normal, CRP, and D-Dimer were 43.94 mg⁄L and 0.29 78 µg/ml, respectively. Echocardiography had been done to exclude cardiac vegetation for IE 79 (Infective Endocarditis), it showed no vegetation and was normal. Procalcitonin for evidence of 80 bacterial infection, which was high at 0.319, abdominal ultrasound, which showed mild 81 splenomegaly size (14 cm on long axis), urinary bladder wall at 8 mm (cystitis), and HRCT of 82 the chest was normal. Blood was sent for bacterial culture and patient treated by paracetamol and 83 ceftriaxone and the patient return home, after seven days the patient came back and the culture 84 findings revealed the strong development of Gram-negative coccobacilli (Salmonella serotype 85 Typhi) bacteria under the microscope, which was confirmed by using VITEK 2 to identify it. 86

The VITEK 2 AST-N325 card was used to detect antimicrobial drug susceptibilities according to 87 the Clinical Laboratory Standards Institute's criteria. (bioMérieux). Salmonella enterica Typhi cefoxitin, and ceftriaxone. But Susceptible to ertapenem, meropenem, amikacin, 90 gentamicin, tigecycline, ceftazidime, ciprofloxacin, and piperacillin. 91

Based on the results of the culture and antibiotic sensitivity tests, he was treated for 10 days, and 92 the patient's follow-up convalescent COVID-19 antibody remained negative. After 10 days, the 93 patient was fully recovered with no symptoms. 94

The patient outside hospital suspected a mild COVID-19 and treated with clexane vial one time 96 per day and ceftriaxone vial 1gm twice per day for five days but fever, sweating, myalgia, and 97 headache continued. After diagnosis, the previous treatment was stopped and treated with 98 ciprofloxacin tab 500 mg, two times per day for five days and amikacin ampule 500 mg IV every 99 24 hours for 10 days. The patient recovered clinically after 10 days on amikacin antibiotics. 100

In low-and middle-income countries, typhoid fever is a public health hazard., killing around 102 200,000 deaths per year (11). Salmonella Typhi is spread by contaminated water, undercooked 103 foods, and infected patients, and is more common in regions with overpopulation, social disorder, 104 and inadequate sanitation (12). The present case is infected by contaminated food and water. 105

Access to efficient antibiotic medication at the right time is critical for avoiding consequences 106 including intestinal perforation and death. As a result, the worrying emergence of antibiotic 107 resistance in Salmonella Typhi is anticipated to impair clinical outcomes (13). In Pakistan and 108 other low-and middle-income countries, extensively drug-resistant (XDR) typhoid fever is a 109 severe public health problem., particularly during the COVID-19 epidemic, when excessive 110 chloramphenicol were the first-line therapies for typhoid. Multidrug-resistant (MDR) S. Typhi 112 strains have been commonly documented since fluoroquinolones (ciprofloxacin, gemifloxacin, 113 levofloxacin, and moxifloxacin) became the favored therapy in areas where MDR infections are 114 prevalent. When alternative treatments are not available, ceftriaxone, a third-generation 115 cephalosporin, and azithromycin, a macrolide, are drugs used nowadays to treat typhoid fever. 116

However, isolated instances of S. Typhi resistant to ceftriaxone or azithromycin have lately been 117 documented (14). 118

In the present case, resistance to the first line and low response to the second line, also resistance 119 to the third line of ceftriaxone, which was used before proper diagnosis, therefore, the treatment 120 was a failure. Typhoid symptoms can range from acute to severe and appear between 0 to 36 days 121 following the disease's beginning (8) . Many typhoid patients have a generic febrile illness that is 122 not clinically identified as typhoid (15). Also, fever is a well-known sign of COVID-19 infection 123 which has been observed in 83%-98% of patients with COVID19. As a result, it may be difficult 124 to tell the difference between COVID-19 and other febrile infections, causing delays in diagnosis 125 and treatment and may blind the physician from considering other febrile illnesses (16). 126

Furthermore, the present case depends on the clinical finding of fever, headache and myalgia 127 previously diagnosed as However, the presence of microbial assays such as real-time polymerase chain reaction or 129 sequencing is the primary diagnostic technique for confirming COVID-19 infection (RT-PCR) 130 (17). But this tool has not always existed in the emergency departments, especially in low-income 131 settings, so this might lead to biased diagnosis and, in turn, false treatment. 132 headache, and myalgia, might be ignored, making diagnosis bias or the COVID-19 diagnostic 134 technique more challenging. Fever is one of the most common symptoms of COVID-19 infection. 135

Therefore, with the current epidemic, physicians must be more vigilant in recognizing other 136 infections that appear with a prolonged fever. Malignancy, viral disorders, and rheumatological 137 problems are among the differential diagnoses for chronic febrile sickness. A thorough medical 138 history, including work, travel, and animal contact, may lead to the diagnosis of previously 139 undiagnosed febrile diseases (16, 18). The current case history helped physicians to suspect 140

Typhoid fever. 141

A study in Brazil, they showed how the spread of the Zika virus during the pandemic, which is 142 similar clinically to COVID-19, aggravates the problem of misdiagnosing the condition and leads 143 to improper treatment (19). 144

Also, a study from Pakistan showed how during the COVID-19 pandemic, the mutual differential 145 diagnosis between COVID-19 and typhoid was challenging for physicians, due to the fact that they 146 were relying on clinical diagnosis in most cases, which makes the diagnosis challenging. Beyond 147 that, the diagnostic tools for typhoid fever in low-income settings, such as the Widal test and 148 Typhidot, have low sensitivity and specificity (7). 149

When symptoms are compatible with a current global pandemic virus, it is difficult to identify 150 the real underlying cause without adequate diagnosis testing, and it is critical to rule out 151 alternative possibilities (8, 20) . 152

Global Typhoid Fever Incidence: A Systematic Review and 2

COVID-19 and Salmonella Typhi 199 co-epidemics in Pakistan: A real problem

A 3-Year-Old With Fever and Abdominal Pain: Availability Bias 201 in the Time of COVID-19

Updating Consensus Surgical CAse REport (SCARE) Guidelines

The global burden of typhoid fever. Bulletin of the World Health 206 Organization

Distribution Based on Whole-Genome Sequence in a Chicken Slaughterhouse in Jiangsu, China. Frontiers 209 in veterinary science

Drug-Resistant <i>Salmonella enterica</i> Serovar Typhi Clone Harboring a Promiscuous Plasmid 212

Encoding Resistance to Fluoroquinolones and Third-Generation Cephalosporins

Laboratory Diagnosis, Antimicrobial Resistance, and Antimicrobial Management of Invasive Salmonella 15

The evolution of antimicrobial resistance in Salmonella Typhi. 217 Current opinion in gastroenterology

Murine typhus mistaken for COVID-19 in a young man

COVID-19 pneumonia: a 220 review of typical CT findings and differential diagnosis. Diagnostic and interventional imaging

Physicians should establish more complete differential diagnoses for individuals who have 156 symptoms of fever, headache and myalgia that correlate with pandemic COVID-19. 157

Written informed consent was obtained from the patient for publication of this case report and 159 accompanying images. A copy of the written consent is available for review by the Editor-in-160Chief of this journal on request. 161Source of funding: This study did not receive any specific grant from funding agencies in the 162 public, commercial, or not-for-profit sectors 163Conflict of interest: none to be declared. 164Authors Contributions: JAA, NTH participated in the design of the study, SKA, MJR, ZMH, 165 follow up the patient and wrote the manuscript. All authors carried out literature review, edited 166 and approved the final manuscript. 167

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