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Gatifloxacin – Very Effective For Typhoid Treatment

Nepalese researchers identify cost-effective treatment for drug-resistant typhoid. Researchers has shown that a new and affordable drug, Gatifloxacin, may be more effective at treating typhoid fever than the drug currently recommended by the World Health Organisation. Enteric fever, of which typhoid fever is the most common form, is a major disease affecting the developing world, where sanitary conditions remain poor. The best global estimates are of at least 22 million cases of typhoid fever each year with 200,000 deaths.

Drug resistance is becoming a major problem and treatment is becoming increasingly difficult, leading to patients taking longer to recover, suffering more complications and continuing to spread the disease to their family and to their community.

Clinical investigators based at Patan Hospital Lalitpur in Kathmandu, Nepal, and the Oxford University Clinical Research Unit in Vietnam have completed a study to see if they can improve the treatment for patients with typhoid fever. Kathmandu has been termed the typhoid fever capital of the world as a result of this disease remaining so common.

"Typhoid fever is a major problem in Nepal and in the developing world and drug-resistant strains are making it even more difficult to tackle," says Dr Buddha Basnyat, senior investigator on the study. "The currently recommended treatment, Cefixime, is relatively expensive and must be administered for a longer duration than is ideal. Clearly there is an urgent need for a treatment that is cost-effective and easy to administer."

The results of the study show that a cost-effective new fluoroquinolone drug, Gatifloxacin, may be a better treatment for enteric fever than Cefixime, which is currently recommended by the World Health Organisation.

In addition, Salmonella enterica Typhi and Salmonella enterica serovar Paratyhpi A, the two most common bacteria to cause enteric fever, do not show resistance to Gatifloxacin, unlike for other fluoroquinolones.

"We have shown that Gatifloxacin may be better than an established drug used by many doctors around the world," says Dr Basnyat. "There is currently no resistance to the drug, and at just over US1 dollar for a seven day treatment course is relatively inexpensive."

"This is an important study with major implications for treating disease widespread in the developing world," says Professor Jeremy Farrar from the Oxford University Clinical Research Unit in Vietnam. "It also shows the major contribution that clinical investigators in Nepal, with the experience and knowledge gained from access to thousands of patients, can help make to improving treatment for our patients and to global health."

Source-EurekalertJAY/M

New DNA Sequencing Technology Help Improve Diagnosis, Treatment Of Typhoid

A first of its kind study on next-generation DNA sequencing technologies has revealed new genetic signatures that may enable researchers to track and tackle typhoid, a disease that kills 600,000 people each year. The results of this study will help to improve diagnosis, tracking of disease spread and could help to design new strategies for vaccination. It is the first study of multiple samples of any bacterial pathogen at this level of detail and has thus set a new standard for analysing the evolution and spread of a disease-causing bacterium. It has also revealed previously hidden genetic signatures of the evolution of individual lineages of Salmonella Typhi.

The researchers developed methods that are being used to type outbreaks, allowing researchers to identify individual organisms that are spreading in the population: using Google Earth, the outbreaks can be easily visualized. The team hope that these mapping data can be used to target vaccination campaigns more successfully with the aim of eradicating typhoid fever.

Typhi is found only in humans and the genomes of all isolates are superficially extremely similar, hampering attempts to track infections or to type more prevalent variants. The detail of the new study transforms the ability of researchers to tackle Typhi.

"Modern genomic methods can be used to develop answers to diseases that have plagued humans for many years. Genomes are a legacy of an organism's existence, indicating the paths it has taken and the route it is on," explained Professor Gordon Dougan from the Wellcome Trust Sanger Institute and senior author on the study.

He added: "We believe that concerted vaccination programmes, combined with epidemiological studies aiming to track down and treat carriers, could be used to eradicate typhoid as a disease."

"A key to survival of Salmonella Typhi is its ability to lie dormant in carriers, who show no symptoms but remain able to infect others. Our new tools will assist us in tracing the source of typhoid outbreaks, potentially even to infected carriers, allowing those individuals to be treated to prevent further spread of the disease," said Kathryn Holt, a PhD student at the Wellcome Trust Sanger Institute and first author on the study.

She added: "Using the genomic biology of this study, we can now type Typhi, identify the strain that is causing infection, identify carriers and direct vaccination programmes most efficiently. It is a remarkable step forward."

The researchers examined 19 isolates of Typhi from ten countries, using new sequencing methods that meant they could capture the rare signals of genetic variation in this stubborn genome. They produced more than 1.7 billion letters of genetic sequence and found evidence of fewer than 2000 mutation events, suggesting very little evolution since the emergence of Typhi at least 15,000 years ago.

The results indicated that the Typhi genome is decaying - as it becomes more closely allied to us, its human host, it is losing genes that are superfluous to life in the human body. Specifically, genes that contain instructions for the proteins on the surface of the bacterium - those most often attacked by our immune system defences - vary much less than do the equivalent genes in most other bacteria, suggesting that Typhi has a strategy to circumvent the selective pressures of our immune system.

"Both the genome and the proteins that make up the surface of Typhi - the targets for vaccines - show amazingly little variation. We have been able to use novel technologies, developed for the analysis of human genome variation, to identify this variation: this would have been impossible a year ago. The technologies we have developed here could also be used in the battles against other disease-causing bacteria," said Professor Julian Parkhill, Head of Pathogen Genomics.

Source-ANIKAR

CDC Reports Year's First Typhoid Fever, Measles Cases

By Lee I-chia / Staff reporter

The Centers for Disease Control (CDC) yesterday reported this year's first locally acquired case of typhoid fever, a day after reporting the year's first locally acquired measles case.

The typhoid fever case is a woman in her 20s living in northern Taiwan who has not visited other countries recently, CDC Epidemic Intelligence Center Deputy Director Lee Chia-lin (李佳琳) said.

She began experiencing symptoms on Feb. 2 and a test result on Friday confirmed that she had contracted the disease, Lee said, adding that the woman is being treated in a hospital.

Photo: Chiu Chih-jou, Taipei Times

Forty-nine typhoid fever cases have been reported in Taiwan since 2019, with 18 local cases and 31 imported cases, she said.

The woman began vomiting and had diarrhea early this month, and after developing a fever while the diarrhea persisted, she was admitted to an emergency room on Tuesday last week, CDC physician Lin Yung-ching (林詠青) said.

Contact tracing showed that the woman had eaten raw oysters and fish at a harbor in northern Taiwan, which could be the source of her infection, Lin said, adding that transmission usually occurs through ingestion of food or water contaminated with Salmonella Typhi, or raw or undercooked seafood harvested from contaminated waters.

CDC Deputy Director-General Philip Lo (羅一鈞) said the center would not identify the seafood restaurant where she dined, as a link between it and the disease has not been confirmed.

The incubation period of typhoid fever is usually one to two weeks, but can range from three to 60 days, while the fatality rate, which can be up to 10 percent if untreated, can be lower than 1 percent if treated with antibiotics, Lin said.

People can still be contagious long after recovering from typhoid fever, so the woman would be required to undergo follow-up tests after recovery, he said.

Maintaining good food and hand hygiene, avoiding eating undercooked food and boiling water can help prevent infection, he said.

On Monday afternoon, the CDC said in a news release that this year's first local case of measles was reported in a man in his 30s living in northern Taiwan who had not traveled abroad recently.

After developing a fever on Monday last week, the man sought treatment the next day, but continued to have a fever, coughing and a sore throat after going home, the centers said.

He sought treatment again on Thursday last week after developing rashes, and was diagnosed with measles and kept in isolation in a hospital, it said.

A local health department is conducting contact tracing, and so far 199 close contacts have been identified and would be monitored until March 4, it said.

People who were at conveyor-belt sushi restaurant chain Kura Sushi's Zhubei Wenxing Branch (竹北文興店) in Hsinchu County between 2pm and 3:30pm on Feb. 11 should monitor their health until Thursday next week, and wear a mask and seek medical attention immediately if they develop a fever, rhinitis, inflamed eyes, rashes or other suspected symptoms of measles, the CDC said.

As measles is highly contagious, people who were at that restaurant at the time are at risk of infection and should monitor their health, Lo said.

The CDC yesterday also reported 711 hospitalizations for COVID-19 last week, the highest weekly number in six months, as well as 103,250 hospital visits for influenza-like illnesses, 40 serious flu complications and five flu-related deaths.

Flu during the Lunar New Year holiday was not as prevalent as predicted, but cases of flu-like illnesses and COVID-19 are expected to increase, Lo said.

Cases could reach another peak next week or the following week, as infection risk is likely to increase due to schools opening, lantern festival events, and an increase in international and domestic travel, he said.

In other news, as no mpox cases have been reported in Taiwan for 14 weeks, it can be considered eliminated in the country under WHO guidelines, he said.

However, as mpox can still be brought in by international travelers, Lo urged people at a higher risk of infection, especially the 27,214 people who received the first dose of vaccine, but did not get a second dose, to get vaccinated.

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