The misdiagnosis continues: an allegory of COVID-19, enteric fever, and a couple of outdated tests

Abstract

Dear Editor, The coronavirus disease-2019 (COVID-19) pandemic started in late 2019 as the first case was reported in China, and being the neighboring country, it reached Pakistan in early 2020 (https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC7240311/). Since the start of the pandemic, multiple waves of COVID-19 have affected Pakistan severely, with the death toll reaching around 30 000 (https://www.google. com/search?q=coid + 19 +Death + in + pakistan&oq=coid + 19 +Death + in + pakistan&aqs=chrome.69i57j0i22i30l6j69i60. 30843j0j7&sourceid=chrome&ie=UTF-8). The death toll was higher than our expectations, as a rapid increase in COVID-19 cases wreaked havoc on an already overburdened country’s health system. As a South Asian country, Pakistan was already suffering from an epidemic of typhoid fever with increasing antibiotic resistance. Emergence of COVID-19 in Pakistan diverted the attention of the government and the general population, leading to the negligence towards typhoid fever resulting in shifting of all the available resources towards COVID-19. The first case of extensive drug-resistant typhoid was reported in 2016, and there were 5274 cases till 2018 (https://www. who.int/emergencies/disease-outbreak-news/item/27-december2018-typhoid-pakistan-en). This number has increased tremendously, reaching up to 14 360 in 2021. The bacterium Salmonella typhi causes extensive drug-resistant typhoid fever. It is resistant to at least five antibiotic classes used for treating typhoid. Multiple reasons contribute to the endemic, including lack of proper water sanitation, a poor hygienic environment, irrational use of antimicrobials leading to resistance, and the carelessness of the government as well as the general population (https://www.cidrap.umn.edu/news-perspective/2021/02/cdcissues-health-advisory-extensively-drug-resistant-typhoid). Typhoid manifests in the form of high-grade fever, headache, malaise, abdominal pain, and rash. Typhidot and Widal tests are the most commonly used tests for the diagnosis of typhoid in Pakistan, but they are considered obsolete in the rest of the world. This leads to the misdiagnosis of typhoid. The typhidot test has only 26.7% sensitivity, 61.5% specificity, 7.4% positive predictive value, and 87.9% negative predictive value (https://www.ncbi.nlm. nih.gov/pmc/articles/PMC4476358/#ref4). The Widal test has a sensitivity of 81.5%, a specificity of 18.3%, a positive predictive value of 10.1%, and a negative predictive value of 89.7%. The stool antigen test has a sensitivity of 31.3, a specificity of 91.5, a positive predictive value of 29%, and a negative predictive value of 91.5% (https://www.ncbi.nlm. nih.gov/pmc/articles/PMC6551910/#:~:text=Widal%20test% 20recorded%2081.5%25%20sensitivity,and%2091.5%25% 20negative%20predictive%20value). On the contrary, developed countries use blood and bone marrow cultures to test for and make an effective diagnosis of typhoid fever. Comparisons of these tests are shown in Figure 1. As some of the symptoms of typhoid and COVID-19 are similar and also with the usage of outdated testing methods, false-positive results of widal and typhidot tests lead to the misdiagnosis of COVID-19 as typhoid fever. In these types of scenarios, the treatment given to the patient includes antibiotics, which are ineffective against COVID-19. It causes a delay in the treatment of COVID-19, ultimately leading to complications like acute respiratory failure, pneumonia, acute respiratory distress syndrome, etc.. It is important to use modern techniques such as blood culture and bone culture for the diagnosis of typhoid and PCR to effectively diagnose COVID-19. As these tests are expensive and not easily available, the government should provide subsidies for them and make them accessible to the general public. These steps will help not only in avoiding the misdiagnosis of COVID-19 and typhoid, but also in the early diagnosis of other infections. Furthermore, if the person presents with complaints of high-grade fever, headache, abdominal pain, arthralgia, and myalgia, there should be a high degree of suspicion of COVID-19 along with typhoid in endemic areas like Pakistan. Hence, before starting any treatment, definitive tests should be used to make an effective diagnosis. aMayo Hospital, Anarkali, Lahore, Punjab and bJinnah Sindh Medical University, Karachi, Pakistan