Tag: typhoid

Environmental Monitoring Offers Low-cost Tool for Typhoid Fever Surveillance

Detection of the viruses that infect the typhoid fever bacterium in sewage indicates disease burden

Researchers can accurately track where typhoid fever cases are highest by monitoring environmental samples for viruses called bacteriophages that specifically infect the bacterium that causes typhoid fever. Senjuti Saha of the Child Health Research Foundation in Bangladesh and colleagues report these findings in a new study published February 15 in the open access journal PLOS Neglected Tropical Diseases.

Typhoid fever is a common infection in many low- and middle-income countries and causes an estimated 135 000 deaths and 14 million infections globally each year. The World Health Organization has prequalified two typhoid vaccines, but for policymakers to plan effective vaccination strategies, they need accurate, high-resolution estimates of where the burden is highest.

Traditionally, people have cultured the bacterium that causes typhoid fever from blood samples to determine where the infection is most common, but in the new paper, researchers tried a more cost-effective surveillance approach. They tested environmental water samples from sewage and other locations to detect bacteriophages specific to the water-borne pathogen that causes typhoid fever, Salmonella Typhi.

The team tested 303 water samples from two locations in Bangladesh: the urban capital city, Dhaka, and a rural district, Mirzapur. They found that bacteriophages specific for Salmonella Typhi were present in 31% of environmental samples in Dhaka, compared to just 3% of samples from Mirzapur. This corresponds to results from more than 8,400 blood cultures, in which 5% of cultures from Dhaka and 0.05% from Mirzapur tested positive.

The new results suggest that detecting bacteriophages specific for Salmonella Typhi may be a rapid environmental surveillance method that could help decision makers understand the presence of typhoid fever in the community. The researchers propose that environment monitoring of bacteriophage could be a simple, cost-effective and scalable tool to assist policy decisions on typhoid control.

The authors add: “Looking for bacteriophages in wastewater is a low-cost method for identifying typhoid hotspots without doing expensive blood cultures on thousands of people.”

Single Dose Typhoid Conjugate Vaccine (TCV) Provides Lasting Efficacy in Children

Healthy children in Malawi participating in study to test efficacy of typhoid conjugate vaccine. Credit: TyVAC/Madalitso Mvula

A single dose of the typhoid conjugate vaccine, Typbar TCV®, provides lasting efficacy in preventing typhoid fever in children ages 9 months to 12 years old, according to a new phase 3 clinical study published in The Lancet.

The study conducted by researchers at University of Maryland School of Medicine’s (UMSOM) Center for Vaccine Development and Global Health (CVD) and led by in-country partners at the Malawi-Liverpool Wellcome Trust (MLW) Clinical Research Programme.

The research team enrolled more than 28 000 healthy children in Malawi and randomly assigned about half the group to receive the TCV and the other half to receive a meningococcal capsular group A conjugate (MenA) control vaccine. During the more than four years of follow-up, 24 children in the TCV group and 110 in the MenA group developed typhoid fever, which was confirmed via blood culture. That resulted in an efficacy of 78.3% in the TCV group, with one case of typhoid prevented for every 163 children vaccinated. TCV was effective in all age groups and over the study period – which ended in 2022 – vaccine efficacy remained strong, decreasing by only 1.3% per year.

Typhoid fever causes more than 9 million illnesses and at least 110,000 deaths worldwide every year, mostly in sub-Saharan Africa and southeast Asia. It is a contagious bacterial infection that occurs from consuming contaminated food or beverages. Symptoms include nausea, fever, and abdominal pain that, if left untreated, can be deadly.

“These findings have significant implications for identification of the contribution of TCVs in the control and potential elimination of typhoid fever in endemic settings,” wrote the authors of a commentary published in The Lancet alongside the study.

In May 2023, the Malawi government launched a national rollout of the TCV in children under 15 years. Going forward, all children in Malawi will receive TCV at 9 months of age as part of the routine immunisation schedule.

“The newly published study supports the long-lasting impacts of a single shot of TCV, even in the youngest children, and offers hope of preventing typhoid in the most vulnerable children,” said Kathleen Neuzil, MD, MPH, CVD Director, the Myron M. Levine, MD, DTPH, Professor in Vaccinology at UMSOM and coauthor of the current study.  “We could not have had a better partner in this endeavor than MLW, whose long-standing excellence in typhoid research and strong surveillance infrastructure made this study possible.”

“The CVD’s outstanding record of generating data to accelerate public health decisions continues with this landmark study,” said UMSOM Dean Mark T. Gladwin, MD, Vice President for Medical Affairs, University of Maryland, Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor. “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 urbanisation patterns, which are likely to contribute to increases in enteric diseases, including typhoid.”

Source: University of Maryland

S. Typhi is Developing Antibiotic Resistance

Bacteria causing Typhoid fever are becoming increasingly resistant to the macrolide and quinone antibiotic classes, according to a study published in The Lancet Microbe. The largest genome analysis of Salmonella enterica serovar Typhi also reveals that resistant strains, mostly from South Asia, have spread to other countries nearly 200 times since 1990.

Typhoid fever is a global public health concern, causing 11 million infections and more than 100 000 deaths per year. While it is most prevalent in South Asia, making 70% of global cases, it also has significant impacts in sub-Saharan Africa, Southeast Asia, and Oceania, highlighting the need for a global response.

Typhoid fever infections are treatable with antibiotics, but their effectiveness is threatened by the emergence of resistant S. Typhi strains. Thus far, little is known about the rise and spread of resistant S. Typhi has so far been limited, with most studies based on small samples, prompting researchers led by Stanford University to conduct a wider spread study.

The study researchers genetically sequenced 3489 S. Typhi isolates obtained from blood samples collected between 2014 and 2019 from people in Bangladesh, India, Nepal, and Pakistan with confirmed cases of typhoid fever. A collection of 4169 S. Typhi samples isolated from more than 70 countries between 1905 and 2018 was also sequenced and included in the analysis.

Resistance-conferring genes in the 7658 sequenced genomes were identified using genetic databases. Strains were classified as multidrug-resistant (MDR) if they contained genes giving resistance to classical front-line antibiotics ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole. The authors also traced the presence of genes conferring resistance to the crucially important macrolides and quinolones.

The analysis shows resistant S. Typhi strains have spread between countries at least 197 times since 1990. While these strains most often occurred within South Asia and from South Asia to Southeast Asia, East and Southern Africa, they have also been reported in the UK, USA, and Canada.

Since 2000, MDR S. Typhi has declined steadily in Bangladesh and India, and remained low in Nepal (less than 5% of Typhoid strains), though it has increased slightly in Pakistan. However, these are being replaced by strains resistant to other antibiotics.

For example, gene mutations giving resistance to quinolones have arisen and spread at least 94 times since 1990, with nearly all of these (97%) originating in South Asia. Quinolone-resistant strains accounted for more than 85% of S. Typhi in Bangladesh by the early 2000s, increasing to more than 95% in India, Pakistan, and Nepal by 2010.

Azithromycin resistance mutations have emerged at least seven times in the past 20 years. In Bangladesh, strains with these mutations emerged around 2013, and since then their population size has steadily increased. The findings add to recent evidence of the rapid rise and spread of S. Typhi strains resistant to third-generation cephalosporins, another class of antibiotics critically important for human health.

The speed at which highly-resistant strains of S. Typhi have emerged and spread in recent years is a real cause for concern, and highlights the need to urgently expand prevention measures, particularly in countries at greatest risk. At the same time, the fact resistant strains of S. Typhi have spread internationally so many times also underscores the need to view typhoid control, and antibiotic resistance more generally, as a global rather than local problem.”

Dr Jason Andrews, Study Lead Author Stanford University

The authors acknowledge some limitations to their study. S. Typhi sequences are underrepresented in several regions, particularly many countries in sub-Saharan Africa and Oceania, where typhoid is endemic. More sequences from these regions are needed to improve understanding of timing and patterns of spread.

Even in countries with better sampling, most isolates come from a small number of surveillance sites and may not be representative of the distribution of circulating strains. As S. Typhi genomes only cover a fraction of all typhoid fever cases, estimates of resistance-causing mutations and international spread are likely underestimated. These potential underestimate highlight the need to expand genomic surveillance to provide a more comprehensive window into the emergence, expansion, and spread of antibiotic-resistant organisms.

Source: EurekAlert!

Typhoid Vaccine Safe for Children in Sub-Saharan Africa

Source: Pixabay CC0

typhoid vaccine has proven to be safe and effective for children, which raises hope of fighting the disease in Sub-Saharan Africa, according to a new study conducted in Malawi.

There are more than 1.2 million typhoid cases and 18 703 deaths per year in the region, the researchers wrote. The World Health Organization (WHO) recommended the typhoid conjugate vaccine in 2018 for use in countries where the disease is endemic.

Clinical trials in Malawi showed that a single dose of typhoid conjugate vaccine (the only one licensed for children as young as six months) prevented typhoid in roughly 84% of 14 069 children aged 9 months to 12 years.

“It is a great result for Malawi and for Africa,” says study co-author Melita Gordon, professor of clinical infection, microbiology and immunology at the University of Liverpool and the Malawi-Liverpool-Wellcome Trust Clinical Research Programme.

“We were the only site chosen for the trial on the continent. The other sites were in Nepal and Bangladesh and the results were completely consistent across the three sites.”

Typhoid is endemic in Malawi, which records 400 to 500 cases per 100 000 every year, according to Queen Dube, chief of health services at Malawi’s Ministry of Health.

While typhoid is treatable, it can impair physical and cognitive development in children, affect school attendance and performance, limit productivity and reduce earning potential.

“The existing vaccine could not be used in very young children. In addition, the first line antibiotics have been found to be ineffective against multi-drug resistant strains,” Prof Gordon said. “With this vaccine, we can now expect a reduced typhoid burden.”

After 18 to 24 months of surveillance, the vaccine was found to be safe, with no serious adverse effects on children. It also worked equally well on pre-school aged children.

Prof Gordon explains that the study encountered challenges such as a few children moving out of the research sites within the study period, and COVID-19 forced them to suspend the study for two months.

“However, we eventually managed a good retention rate due to regular text messaging to parents and the hard work of health surveillance assistants in mobilisation activities,” she added.

The efficacy data of the typhoid conjugate vaccine is the first in Africa, according to Gordon, who hopes that other African countries will follow Malawi’s example in planning to roll out the vaccine.

Source: SciDev.Net