Cover photo: The Hôpital de la SIM Galmi surgical team ready to operate on another case of typhoid. The team operates on about 200 children with typhoid intestinal perforation (TIP) each year. Credit: Hopital de la SIM Galmi.
Typhoid, if not treated early or with the correct antibiotics, can become life-threatening due to serious late complications such as typhoid intestinal perforation (TIP). TIP typically occurs two weeks after initial symptoms and results in holes, or perforations, in the intestines. Patients with TIP, which is common in children in typhoid-endemic regions, require immediate surgery and experience high morbidity and mortality rates from the condition. TIP remains a leading cause of pediatric and adult non-traumatic emergency abdominal surgery in Niger.
Drug resistance is making typhoid harder to treat and more dangerous. The number of typhoid cases that are resistant to fluoroquinolones and beta-lactam antibiotics, two classes of drugs used to treat the disease, is growing. As a result, serious complications like TIP are becoming more common. A recent peer-reviewed study focuses on one patient in Niger who developed TIP and damage to his gallbladder caused by typhoid, which was confirmed during surgery.
Dr. Katherine Shafer, Dr. Yakoubou Sanoussi, and Dr. Laura Hobbs, three authors of the study, joined us to discuss what the findings tell us about typhoid, drug resistance, and typhoid prevention.
Can you share some background on the study and what made this case stand out?
TIP most commonly occurs in the distal ileum, located at the end of the small intestine, and not usually in the gallbladder. Each year, the Hôpital de la SIM Galmi in Niger treats a small number of patients (three in 2024) who have intraoperative findings of typhoid affecting both the intestines with perforations and the gallbladder with necrosis or perforation. This 11-year-old boy in rural Niger presented with free fluid in his pelvis. Based on his clinical history and living in a typhoid-endemic region, the ultrasound finding was concerning due to leakage of fluid from a typhoid intestinal perforation (TIP). He was taken to the operating room for surgery, and he had multiple TIPs and damage to his gallbladder (gallbladder necrosis) caused by typhoid bacteria. What made this case stand out was that his blood culture later showed a bloodstream infection with a drug-resistant type of E. coli called extended-spectrum beta-lactamase (ESBL)-producing E. coli.
Notably, this is the first reported case of ESBL E. coli bacteremia occurring alongside TIP and gallbladder necrosis in a pediatric patient. The fact that these three complications occurred together highlights the difficulty of treating typhoid, especially in health care settings with limited access to supplies and medication. The standard inpatient antibiotic choice for a patient with suspected TIP is ceftriaxone and metronidazole, but ESBL E. coli is not sensitive to this antibiotic regimen and the preferred antibiotic, meropenem, took several days to acquire due to limited availability in the region and the high cost. Drug resistance is making it harder to find and obtain the right antibiotics to treat typhoid and the bacteremia that can also result from other bacteria, increasing the risk of dangerous complications like TIP and gallbladder necrosis.
This case is especially concerning because it occurred in a patient with no major medical or surgical history, indicating that people in the community are at risk for infections that don’t respond to common antibiotics. In many typhoid-endemic regions, health care providers lack diagnostics for typhoid, so similar cases may be underreported.
How does drug resistance contribute to typhoid complications like TIP?
The rise in drug-resistant strains of Salmonella Typhi has contributed to an increase in severe typhoid complications like TIP. Even when surgery for TIP is successful, antibiotic resistance can complicate recovery, especially in the setting of a bloodstream infection and sepsis. Carbapenems, often the only treatment option against resistant bacteria, are scarce and expensive in rural hospitals.
In this case, the presence of ESBL-producing E. coli introduced another layer of complexity. Doctors had to figure out whether the typhoid treatment wasn’t working, or if there was a new infection. The E. coli bacteria were resistant to many common antibiotics, including those usually used to treat typhoid, like fluoroquinolones and ceftriaxone. That meant the usual medicines weren’t strong enough to fight the infection.
Although meropenem was the preferred treatment for ESBL E. coli, it was initially unavailable in Galmi, the rural village where this patient was treated. The hospital staff eventually obtained the drug from a neighboring country and were only able to initiate it on day 13 of the patient’s hospital stay. This delay highlights the serious challenges in treating TIP in low-resource areas. Meropenem is not only hard to find in rural hospitals, it’s also very expensive, making it unaffordable for many families. Waiting nearly two weeks for the right antibiotic gave the infection time to worsen, increasing the risk of complications and making recovery much harder.
What challenges do health care providers in resource-limited settings face when treating cases like this one?
This case underscores that even with timely and appropriate surgical intervention for presumed TIP—with or without gallbladder necrosis—not knowing the particular bacteria involved and if the available antibiotics are effective against it can lead to worsening postoperative complications and possibly death. Before we had blood culture capabilities through the study, we did not know drug resistance patterns in the region. It was difficult to know how to treat patients who continued to deteriorate, sometimes to the point of death—despite good surgical intervention and source control—without knowing what antibiotics were or were not working.
Because of the partnership with the University of Maryland and the Epicentre laboratory in Maradi for blood cultures, this past year was the first time Hôpital de la SIM Galmi was able to know there was even ESBL E. coli in our region and that S. typhi had a high resistance pattern to ciprofloxacin. This was important, as we made a major change in the antibiotics we now use to treat early non-perforated and post-operative perforated typhoid patients.
Blood cultures are rarely available in endemic regions, and even when they are, it can sometimes take several days for results. Cost barriers further complicate care. Even when effective antibiotics are available, there may be deaths if the right drugs aren’t accessible in time or if patients’ families cannot afford these expensive drugs.
What can we do to prevent typhoid—and the severe complications that accompany it—in endemic settings?
Vaccination with typhoid conjugate vaccine (TCV) is a critical first step in preventing disease. Equally important are improvements in access to clean water and sanitation, as well as the promotion of handwashing and safe food practices.
Additionally, expanding access to diagnostic testing and surveillance enables earlier detection and more targeted treatment, while responsible antibiotic use is essential to slow the spread of drug-resistant strains. Finally, strengthening health systems to support early detection and surgical care is vital to manage typhoid complications like TIP and improve patient outcomes.
As surgeons, the problem with typhoid in our region is that patients who need surgery the most have often been to several other health centers first, whether because of delays in access to care due to family finances or lack of typhoid diagnostics at other rural clinics where they were seen first. This leads to delays in providing the proper antibiotics that match the resistance patterns in the region.
Even putting in the maximum effort to provide the best surgical care, we see a high rate of morbidity and mortality in our region’s health centers. Prevention is key, and we are very excited about the planned introduction of TCV in Niger.
These three girls, and their mothers in front of them, all had emergency surgery for TIP at Hôpital de la SIM Galmi. They live in the same village about 15 minutes from the hospital. Credit: Alina Farcas.
