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Project

Salmonella Paratyphi A: The emergence of a neglected pathogen in Asia

Introduction

Salmonella
The Gram-negative bacteria Salmonella causes a variety of clinical syndromes in humans, ranging from a mild gastro-enteritis to a life-threatening blood stream infection. Most widely known are the serovars Salmonella Typhi and Salmonella Paratyphi A that cause typhoid and paratyphoid fever respectively (also known combined as ‘enteric fever’). In contrast with other, non –typhoidal, Salmonella serovars (like Salmonella Typhimurium and Salmonella Enteritidis), Salmonella Typhi and Salmonella Paratyphi are restricted to humans.
As a consequence of improvements in sanitation and hygiene in the 20th century, enteric fever became a rare entity in developed countries. But in low resource settings, it still causes a major disease burden that disproportionally affects the poor. Through international travel it also increasingly affects travellers returning from endemic countries.

Emergence of Salmonella Paratyphi A
Historically, the majority of enteric fever cases were caused by Salmonella Typhi. However, the number of Salmonella Paratyphi A infections has been increasing steadily since the turn of the century. It is estimated that 6 million cases of paratyphoid fever occur annually. This increase has been most apparent in Asia, where it now accounts for 14% (Indonesia) to 64% (southeast China) of the enteric fever cases. A tremendous increase in number of paratyphoid fever cases has also been observed in Cambodia. Until the year 2013 the disease was rare, but at the Sihanouk Hospital Centre of HOPE in Phnom Penh, it now accounts for 90% of the enteric fever cases. In travellers, Salmonella Paratyphi A represented 30.9% of imported cases of enteric fever in the European Union in 2011.
There has been no clear explanation for this emergence of Salmonella Paratyphi A. Several hypotheses exist and include a change in virulence/immunity, changes in environmental factors, an increase in the number of chronic carriers and the introduction of typhoid vaccines.

Research gaps
In contrast to Salmonella Typhi, Salmonella Paratyphi A has received little attention from the international research community resulting in huge knowledge gaps. First, it is has not been established whether the clinical syndrome caused by Salmonella Paratyphi A is distinguishable from that caused by Salmonella Typhi. It has been assumed for a long time that Salmonella Paratyphi A has a milder course, but in the largest comparative study to date it was shown that both serovars cause a clinical indistinguishable syndrome. Also in travellers the clinical syndrome seems to be similar to Salmonella Typhi. More studies are needed to confirm or reject these new findings.
Second, the detection of Salmonella Paratyphi A in blood and stool samples remains very challenging. Blood culture is often used as the diagnostic reference method but this method shows poor sensitivity, is technically demanding and it takes several days before results are available. The low sensitivity is in part due to the very low bacterial concentrations of Salmonella Paratyphi A in blood (0.5 colony forming units (CFU)/mL), a problem further aggravated by self-treatment with antibiotics prior to sample collection. Other, more rapid, diagnostic tests based on antibody detection have shown a low sensitivity and specificity, especially in endemic regions. Recently developed rapid tests based on antigen detection seem more promising, but their performance has never been formally evaluated.
Last, only few antibiotics are left effective against Salmonella and resistance against these antibiotics is increasing. Worrying is that fact that Salmonella Paratyphi A seems to have a greater propensity for developing drug resistance than Salmonella Typhi.
Research questions
To bridge existing knowledge gaps concerning this emerging pathogen as well as to guide effective public health interventions, a transdisciplinary research approach is needed. Studies of this PhD will therefore vary in focus and include microbiology, infectiology and public health approaches and will address the following research questions:
1. Is there a single clone of Salmonella Paratyphi A responsible for the recent and successful spread in Asia and specifically Cambodia?
2. What are the risk factors for acquisition of Salmonella Paratyphi A in Cambodia?
3. What is the role of chronic carriers in the transmission of Salmonella Paratyphi A in Cambodia?
4. Do Salmonella Paratyphi A and Salmonella Typhi cause indistinguishable clinical syndromes in Cambodia?
5. What is the value of antigen based rapid diagnostic tests in the diagnosis of Salmonella Paratyphi A in Asia?

Most studies will be conducted in Cambodia, as Salmonella Paratyphi A is an emerging pathogen there and because the Institute of Tropical Medicine in Antwerp has a longstanding collaboration with the Sihanouk Hospital Centre of HOPE in Phnom Penh, Cambodia.
Datum:22 jan 2015  →  11 jan 2019
Trefwoorden:B780-tropische-geneeskunde
Project type:PhD project