Bangladesh is a typhoid-endemic country with a high burden of the disease. Yet, in the community, typhoid diagnosis is often made based on clinical symptoms rather than blood culture, the standard diagnostic test. Since the symptoms of typhoid fever are like many other illnesses, it likely leads to an underestimated burden. A modeling study estimated that for each blood-culture confirmed case of typhoid, there are at least three additional suspected cases who receive antibiotics without a confirmed diagnosis. These factors contribute to the overuse of antibiotics to treat typhoid, which increases the risk of the bacteria developing resistance to these medicines.
Drug resistance is driven largely by the misuse of antimicrobials, including antibiotics. As a result, these drugs become less effective, necessitating the use of more expensive, less available, and harder-to-administer treatments. Consequently, patients may experience longer, more severe, and complicated illnesses, leading to limited and costly treatment options for typhoid. This situation places additional pressure on a country’s public health system.
Resistance patterns
We conducted a study to examine drug-resistant typhoid trends in Bangladesh across two decades, comparing these trends with antibiotic consumption in the country. We analyzed more than 12,000 blood-culture-confirmed typhoid cases from the two largest pediatric hospitals and three branches of a private community clinic in Dhaka, Bangladesh. Our study found a decrease in resistance to older antibiotic options—amoxicillin, chloramphenicol, and cotrimoxazole. Strains resistant to these three drugs, called multidrug-resistant (MDR) typhoid, fell from 80% in 2002 to 17% in 2022. Since 2017, more than 80% of typhoid isolates have been susceptible to these older antibiotics.
We observed a high level of persistent resistance to ciprofloxacin, the primary treatment choice during mid-1980s to 1990s. By the mid-2010s, more than 90% of typhoid bacteria in South Asia exhibited resistance to ciprofloxacin. This prompted the use of newer third-generation antibiotics. However, evidence indicates that typhoid is increasingly developing resistance to those drugs as well.
While these newer drugs remain effective for treating typhoid in Bangladesh, our study observed low levels of resistance to third-generation antibiotics like ceftriaxone and emerging resistance to azithromycin, the primary treatment options, raising concerns about the diminishing availability of effective oral antibiotics to treat typhoid.
Innovative strategies to reduce drug resistance
Drug resistance is a global challenge requiring innovative strategies. Our study with typhoid suggests that overuse of the newer oral antibiotics likely contributed to emergence of the resistance. Given the substantial decline in resistance to the older first-line antibiotics that we observed, it is possible that these medicines could be reintroduced for typhoid treatment in Bangladesh, should the reports of MDR cases drop below 5 percent.
Such an innovative approach requires careful oversight to ensure that resistance to these antibiotics does not reappear quickly. We must maintain regular antibiotic resistance surveillance and continue detecting drug-resistant typhoid strains through susceptibility testing to guide treatment strategies. This should be supported by updating guidelines and policies to ensure appropriate antibiotic use and minimize resistance. Enhanced surveillance efforts can provide crucial data to monitor changes in disease burden and inform public health interventions.
Amid numerous competing priorities, policymakers in Bangladesh must consider the surveillance data on drug resistance and antibiotic consumption patterns. These data are crucial for making informed decisions about treatment guidelines while implementing an effective typhoid conjugate vaccine (TCV) program.
TCV to decrease drug-resistant typhoid
Vaccines are a key part of the strategy to reduce drug resistance. The introduction of TCV is projected to drastically reduce the number of typhoid cases including the drug-resistant ones, lower transmission rates, and decrease the need for antibiotics. A report from the WHO stated that accelerating the introduction of TCVs in high-burden countries like Bangladesh could prevent the use of 45 million doses of antibiotics each year.
Our study provides baseline data on drug-resistant typhoid, which can help monitor the impact of TCV introduction on typhoid burden and drug resistance trends as the government of Bangladesh works to introduce TCV.
Photo: Participants in a typhoid conjugate vaccine study in Bangladesh. Credit: icddr,b
