Trial estimates single typhoid vaccine dose highly effective in African children

News brief

One dose of the conjugate typhoid vaccine has an estimated efficacy of 78.3% in children ages 9 months to 12 years and remained strong over 4 years of follow-up, concludes a phase 3 randomized controlled trial conducted in Africa and published in The Lancet.

Typhoid is a life-threatening bacterial infection spread by consuming contaminated food or drinks. Malawi rolled out the vaccine for children younger than 15 years in May 2023.

A team led by the Malawi-Liverpool-Wellcome Program and the University of Maryland recruited 28,130 healthy children in Malawi, randomly assigning half to receive one dose of the Vi polysaccharide conjugated to tetanus toxoid vaccine (Vi-TT) and half to a meningococcal (MenA) control vaccine from February to September 2018.

Effectiveness waned 1.3% per year

At a median follow-up of 4.3 years, the rate of blood culture–confirmed typhoid fever was 24 39.7 cases per 100,000 person-years in the Vi-TT group, compared with 110 (182.7) in the MenA group.

In the intention-to-treat population, vaccine effectiveness (VE) of Vi-TT was 78.3% (95% confidence interval [CI], 66.3% to 86.1%), with 163 vaccinations needed to prevent one case. By age-group, VEs were 70.6% (95% CI, 6.4% to 93.0%) for children ages 9 months to 2 years; 79.6% (95% CI, 45.8% to 93.9%) for those ages 2 to 4; and 79.3% (95% CI, 63.5% to 89.0%) for those ages 5 to 12. VE waned 1.3% each year.

In a University of Maryland news release, Mark Gladwin, MD, university vice president for medical affairs, said, "The research could not come at a more critical time when Malawi and other African countries are struggling with climate change, extreme weather events and increased urbanization patterns, which are likely to contribute to increases in enteric diseases, including typhoid."

In a commentary, Birkneh Tilahun Tadesse, MD, PhD, and colleagues at the International Vaccine Institute in South Korea, said, "Coordinated interventions involving the vaccination of children and adults with safe and effective typhoid vaccines and improvements in water, sanitation, and hygiene (WASH) practices could have a pivotal role in supporting elimination efforts."

UK tightens restrictions on fluoroquinolone use

News brief

Chris Dall, MA

Ciprofloxacin — Thirteen of Clubs / Flickr cc

UK health regulators have announced new restrictions on the use of fluoroquinolone antibiotics.

In a press release earlier this week, the UK's Medicines and Healthcare products Regulatory Agency (MHRA) said that fluoroquinolone antibiotics given systematically must only be administered when no other appropriate antibiotics are available for use. That includes situations where other recommended antibiotics have failed, are ineffective because of resistance, or are unsafe to use in individual patients.

Concerns about fluoroquinolones have grown in recent years in the United Kingdom and other countries, including the United States, because of reports and subsequent data showing increased risk of serious adverse reactions, including tendonitis or tendon rupture, muscle pain and weakness, joint pain, peripheral neuropathy, and central nervous system effects. The US Food and Drug Administration has issued several black box warnings for fluoroquinolones in response to those risks.

Mental health concerns

Previous MHRA regulations stated that fluoroquinolones should not be used for mild to moderate or self-limiting infections, or for non-bacterial infections. The MHRA says the new regulations are in response to Yellow Card reports from patients who have experienced long-term adverse reactions to fluoroquinolones.

They also follow a September 2023 drug safety update from MHRA that warned clinicians prescribing fluoroquinolones to be alert to the risk of psychiatric reactions, including suicidal thoughts.

"We have listened to the experience of patients regarding long-lasting and potentially irreversible adverse reactions following use of fluoroquinolone antibiotics, in some cases prescribed for mild-to-moderate infections," MHRA Chief Safety Officer Allison Cave said. "We recognise fully the importance of limiting the use of these medicines."

Cave urged patients on fluoroquinolones to read the patient information leaflet and seek immediate medical advice if they experience side effects involving symptoms relating to tendons, joints, muscles, nerves, or mental health at any point during treatment.

High rate of Watch antibiotic use reported in 4 African countries

News brief

Chris Dall, MA

A study conducted in four African countries found relatively high use of antibiotics that have a greater potential for promoting resistance, particularly among febrile patients, researchers reported yesterday in Antimicrobial Resistance and Infection Control.

The study, led by researchers with Germany's Robert Koch Institute, examined hospital-based surveillance data from the African Network for Improved Diagnostics, Epidemiology, and Management of Common Infectious Agents (ANDEMIA), which collects data from 12 urban and rural health facilities in Ivory Coast, Burkina Faso, Democratic Republic of the Congo, and South Africa. The study enrolled patients with acute respiratory tract infection (RTI), acute gastrointestinal infection, and acute febrile disease of unknown cause (AFDUC), with researchers focusing on self-reported antibiotic use in the 10 days prior to enrollment. Reported antibiotics were grouped by the World Health Organization's (WHO's) AWaRe (Access, Watch, and Reserve) classification system.

A nuanced perspective on the clinical presentation of the patient, the country-context, accessibility, and affordability of care and treatment needs to be considered when planning and implementing strategies to reduce inappropriate Watch group antibiotic use.

Among 19,700 ANDEMIA patients enrolled from February 2018 through May 2022, 7,258 (36.8%) reported antibiotic use. Slightly more than half (57.5%) of enrolled patients with reported antibiotic use were children under 5, and 45.9% were female. Of the 9,965 antibiotics reported, 5,299 (54.7%) were from the Access group and 4,330 (44.7%) were from the Watch group, which have been associated with selection for multidrug resistance. The most commonly reported antibiotic was the Watch antibiotic ceftriaxone (31.7%). No Reserve antibiotic use was reported.

Watch antibiotic use ranged from 17.4% among RTI patients in Ivory Coast urban facilities to 73.7% among AFDUC patients in Burkina Faso urban facilities, and climbed from 40.7% prior to the COVID-19 pandemic to 50.6% during the pandemic.

Availability, access may be issues

The study authors note the WHO's proposed 2023 target calls for at least 60% of national antibiotic consumption to come from the Access group. But they also caution that the results, while concerning, need to be considered within the context of limited antibiotic availability and access in the four countries.

"A nuanced perspective on the clinical presentation of the patient, the country-context, accessibility, and affordability of care and treatment needs to be considered when planning and implementing strategies to reduce inappropriate Watch group antibiotic use," they concluded.

CWD strikes deer farm in another Wisconsin county

News brief

Lisa Schnirring

The Wisconsin Department of Agriculture, Trade, and Consumer Protection (DATCP) yesterday announced that chronic wasting disease (CWD) has been detected at another deer farm, this time in Sheboygan County in the far eastern part of the state.

Wisconsin buck in snow — Ken Mattison/Flickr cc

Although CWD has been detected in wild deer from Sheboygan County before, the latest detection is the first to be reported in one of the county's deer farms. The DATCP said the detection involved a 5-year-old buck, and the result was confirmed by the US Department of Agriculture National Veterinary Services Laboratory in Ames, Iowa.

The farm is in quarantine while officials from the DATCP and the US Department of Agriculture conduct an epidemiological investigation.

Wisconsin has 243 registered deer premises, which includes 65 hunting ranches. Since 2001, deer at 44 farms have tested positive for CWD, according to DATCP data as of September 2023. The first CWD detection in wild deer from Sheboygan County occurred in 2019.

CWD is a fatal prion disease, similar to bovine spongiform encephalopathy ("mad cow disease"), affecting deer, elk, and other cervids. The disease spreads among animals through direct contact and from exposure to contaminated saliva, blood, feces, or urine. It isn't known to affect humans, but health officials have urged people to avoid eating meat from infected animals and to take precautions when field dressing, butchering, or disposing of potentially infected animals.