Typhoid troubles

May 28, 2023

Unnecessary prescription of antibiotics and dispatching antibiotics without a prescription is increasing the burden of drug-resistant typhoid

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nteric fever is caused by bacteria of the Salmonella Enterica species. Salmonella typhi cause typhoid fever, whereas Salmonella Paratyphi cause paratyphoid fever. Both infections present with similar features, such as step-ladder patterned high-grade fever, constipation or diarrhoea, chills, vomiting and body aches, etc.

Enteric fever should be suspected if the duration of the fever is more than three days or if the patient also has gastrointestinal symptoms. Salmonella Typhi live only in humans. Persons with typhoid fever carry the bacteria in their bloodstream and intestinal tract.

As of 2019 estimates, there are nine million cases of typhoid fever annually, resulting in about 110,000 deaths per year.

An ongoing outbreak of extensively drug-resistant (XDR) typhi that emerged in Pakistan in 2016 has caused more than 5,200 infections in the country as well as infections abroad. A majority of the cases have been in Sindh, including Karachi and Hyderabad.

The circulating strains of XDR Salmonella Typhi that emerged in Pakistan belong to the H58 haplotype, which is common in parts of Asia and Africa. These strains are resistant to at least five antibiotic classes recommended for treating typhoid fever – ampicillin, ceftriaxone, chloramphenicol, ciprofloxacin and trimethoprim-sulfamethoxazole, but susceptible to azithromycin and carbapenem antibiotics.

Initially, ceftriaxone injectable was commonly used as empirical therapy, but since ceftriaxone-resistant cases were reported in Hyderabad in November 2016, treatment of typhoid has become more challenging. This resistance was also reported by British and Pakistani scientists in 2018.

The World Health Organisation has also warned that the risk of acquiring XDR typhoid in Pakistan is high because of insufficient access to clean water, along with poor sanitation and hygiene.

Another potential challenge is the absence of standardised and fully equipped laboratories in rural areas, leading to ineffective treatment and drug resistance. Frequent and unnecessary prescription of antibiotics by healthcare professionals and dispatching antibiotics without prescription at the pharmacy is further increasing the magnitude of the disease burden. Despite available vaccines, the prevalence of vaccination has been limited in Pakistan due to cultural practices and a lack of public knowledge and understanding.

In addition to decreasing the disease burden in endemic countries and saving lives, widespread use of the typhoid conjugate vaccine in affected countries is expected to reduce the need for antibiotics for typhoid treatment and slow the increase in antibiotic resistance in Salmonella Typhi.

Diagnostic tests?

The diagnosis of enteric fever is made by blood culture. The organism can also be cultured from stool, urine, duodenal contents or bone marrow. In many cases, the diagnosis of enteric fever is made presumptively by doctors in patients with protracted fever without alternative explanation and empirical treatment is started. The blood culture takes 5-7 days to report bacterial organisms and sensitivity to the medicine.

The Widal test is of limited clinical utility and is not reliable. It is now obsolete and hence, not recommended.

How can this be prevented?

All travellers to endemic areas (South Asia, especially India, Pakistan, Bangladesh) are at potential risk of typhoid fever, although the risk is generally low in tourist and business centres where standards of accommodation, sanitation and food hygiene are high. A few preventive steps are helpful in preventing disease while planning travel to endemic areas.

Buy bottled water or bring local water to a rolling boil for one minute before use. Bottled carbonated water is safer than uncarbonated water. Use drinks without ice unless the ice is made from bottled or boiled water. Avoid popsicles and flavoured ice that may have been made with contaminated water. When the safety of drinking water is questionable, boil it, or if this is not possible, disinfect it with a reliable, slow-release disinfectant (usually available at pharmacies).

Make sure the food you eat is well-cooked. Avoid raw milk and products made from raw milk. Drink only pasteurised or boiled milk.

Avoid raw vegetables and fruits that cannot be peeled. Lettuce can remain contaminated even after it is washed.

Wash your hands with soap and water before eating.

How can we prevent the spread of disease?

Hygiene and proper sanitisation play a key role. Even when the symptoms go away, people may still be carrying typhoid bacteria, meaning they can spread it to others by shedding bacteria in their faeces. Although the available vaccine does protect against typhoid strains of Salmonella enterica, it does not protect against the brother infection, paratyphoid fever.

Those affected should make sure they complete the antibiotic regime as prescribed by the doctor even though the symptoms resolve early.

Role of immunisation?

Pakistan introduced Typhoid Conjugate Vaccine into its routine immunisation programme in Nov 2019. It is the first typhoid vaccine that can be given to children as young as six months of age and to adults up to 45 years or 65 years of age (depending on the vaccine) and confers long-term protection against it. It is an intramuscular injection usually prescribed as a single dose at nine months or in the second year of life.

In addition to decreasing the disease burden in endemic countries and saving lives, widespread use of the typhoid conjugate vaccine in affected countries is expected to reduce the need for antibiotics for typhoid treatment and slow the increase in antibiotic resistance in Salmonella Typhi.

Dr Naseem Amin Dhedhi [MBBS, FCPS, MRCGP(INT)], is a consultant in family medicine at Al-Khidmat Raazi Hospital, CBR Town, Islamabad

Dr Naureen Kazim [MBBS, DFM, MCPS] is a senior registrar at Department of Family Medicine at Ziauddin Medical University, Karachi

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