9 research outputs found
Clinical and microbiological characterisation of invasive enteric pathogens in a South African population: the interaction with HIV
A Thesis Submitted to the School of Public Health,
Faculty of Health Sciences,
University of the Witwatersrand,
in fulfilment of the requirements for the degree of Doctor of Philosophy
Johannesburg, South Africa 2016.Introduction
Human immunodeficiency virus (HIV) has been associated with invasive enteric infections in
HIV-infected patients, since it was first described in the 1980s. In South Africa, HIV remains
an important health challenge, despite the introduction of antiretroviral therapy (ART) in
2003. In association with this, is an ongoing problem of invasive enteric infections, including
those due to Shigella and Salmonella, including Salmonella enterica serovar Typhi
(Salmonella Typhi). There are few South African data available as to the incidence of
invasive disease due to these pathogens and how these data may contrast with the
presentation and outcome in HIV-uninfected patients. The associated risk factors for
mortality due to invasive enteric pathogens and whether there has been a response with ART
as an intervention also needs further elucidation.
Aims
This work was undertaken to better describe the burden of invasive enteric infections
(Shigella, nontyphoidal Salmonella and Salmonella Typhi) in association with HIV, define
risk factors for mortality and establish whether the introduction of ART has impacted on
disease burdens due to these pathogens.
Methods
Laboratory-based surveillance for enteric pathogens was initiated in 2003. Basic
demographic details (age and gender) were collected on all patients where possible. In 25
hospital sites in all nine provinces, additional clinical information was collected by trained
surveillance officers, including HIV status, data reflecting severity of illness, other immune
suppressive conditions, antimicrobial and antiretroviral usage and outcome (survival versus
death). Laboratories were requested to transport all isolates to the Centre for Enteric Diseases
(CED) at the National Institute for Communicable Diseases of the National Health
Laboratory Service (NHLS) in Johannesburg for further characterisation, including
serotyping, antimicrobial susceptibility testing and molecular typing where relevant (whether
isolates could respectively be classified as Salmonella Typhimurium ST313 and Salmonella
Typhi H58). Additional cases were sought through audits of the Central Data Warehouse
(CDW) of the NHLS.
Annual incidence rates were calculated according to published estimates of population by age
group by the Actuarial Society of South Africa for the Department of Statistics of the South
African government. Analyses were specifically directed at invasive shigellosis, Salmonella
meningitis, typhoid fever in South Africa and nontyphoidal salmonellosis in Gauteng
Province, South Africa. Data were recorded in an Access database and analysed using chisquared
test to establish differences between HIV-infected and uninfected individuals and
univariate and multivariate analysis to compare risk factors for mortality. Data in the number
of patients accessing ART were derived through audits of the CDW, by using the numbers of
patients on whom viral loads were done annually as a proxy.
Results
Between 2003 and 2013, a total of 10111 invasive enteric isolates were received by CED. For
patients for whom sex was recorded, 3283/6244 (52.6%) of patients presenting with invasive
enteric infections were male; invasive disease was predominantly observed in children less
than five years of age (1605/6131; 26.2%) and those who were aged between 25 and 54 years
(3186/6131; 52.0%), with the exception of typhoid fever where the major burden was in
patients aged 5 to 14 years (302/855; 35.3%).
KH Keddy 81-11384 PhD
iv
More HIV-infected adult women were observed with invasive shigellosis (P=0.002) and with
typhoid fever compared with adult men (P=0.009). Adults aged ≥ 15 years were more likely
to die than children aged < 15 years (invasive shigellosis, odds ratio [OR]=3.2, 95%
confidence interval [CI]=1.6 – 6.6, P=0.001; Salmonella meningitis, OR=3.7, 95% CI=1.7 –
8.1, P=0.001; typhoid fever, OR=3.7, 95% CI=1.1 – 14.9, P=0.03; invasive nontyphoidal
salmonellosis, OR=2.0, 95% CI=1.6 – 2.5, P<0.001).
HIV-infected patients had a significantly higher risk of mortality compared with HIVuninfected
patients (invasive shigellosis, OR=4.1, 95% CI=1.5 – 11.8, P=0.008; Salmonella
meningitis OR=5.3, 95% CI=1.4-20.0, P=0.013; typhoid fever, OR=11.3, 95% CI=3.0 – 42.4,
P<0.001; invasive nontyphoidal salmonellosis OR=2.5, 95% CI=1.7 – 3.5, P<0.001). In all
patients, severity of illness was the most significant factor contributing to mortality (invasive
shigellosis, OR=22.9, 95% CI=2.7 – 194.2, P=0.004; Salmonella meningitis OR=21.6, 95%
CI=3.5 – 133.3, P=0.01; typhoid fever, OR=10.8, 95% CI=2.9 – 39.5, P<0.001; invasive
nontyphoidal salmonellosis OR=5.4, 95% CI=3.6 – 8.1, P<0.001). Between 2003 and 2013,
ART was significantly associated with decreasing incidence rates of invasive nontyphoidal
salmonellosis in adults aged 25 - 49 years (R=-0.92; P<0.001), but not in children (R=-0.50;
P=0.14).
Conclusion
Decreasing incidence rates of invasive nontyphoidal salmonellosis and shigellosis suggest
that ART is having an impact on opportunistic enteric disease in HIV. Further work is
necessary however, to fully understand the associations between age, sex and invasive enteric
pathogens. Specifically, this work would include typhoid fever, Shigella transmission from
child to adult carer, development of invasive enteric infections in HIV-exposed children and
whether the decreasing incidence rates can be sustained. Moving forward, an understanding
of invasive enteric infections in the HIV-uninfected patient may assist in targeting severity of
illness as a risk factor for mortality.MT201
Laboratory-acquired infections of Salmonella enterica serotype Typhi in South Africa: phenotypic and genotypic analysis of isolates
BACKGROUND: Workers in clinical microbiology laboratories are exposed to a variety of pathogenic microorganisms. Salmonella species is among the most commonly reported bacterial causes of laboratory-acquired infections. We report on three cases of laboratory-acquired Salmonella enterica serotype Typhi (Salmonella Typhi) infection which occurred over the period 2012 to 2016 in South Africa. METHODS: Laboratory investigation included phenotypic and genotypic characterization of isolates. Phenotypic analysis included standard microbiological identification techniques, serotyping and antimicrobial susceptibility testing. Genotypic analysis included the molecular subtyping methodologies of pulsed-field gel electrophoresis analysis, multilocus sequence typing and whole-genome sequencing (WGS); with WGS data analysis including phylogenetic analysis based upon comparison of single nucleotide polymorphism profiles of isolates. RESULTS: All cases of laboratory-acquired infection were most likely the result of lapses in good laboratory practice and laboratory safety. The following critical issues were highlighted. There was misdiagnosis and misreporting of Salmonella Typhi as nontyphoidal Salmonella by a diagnostic laboratory, with associated public health implications. We highlight issues concerning the importance of accurate fluoroquinolone susceptibility testing and interpretation of results according to updated guidelines. We describe potential shortcomings of a single disk susceptibility screening test for fluoroquinolone susceptibility and suggest that confirmatory minimum inhibitory concentration testing should always be performed in cases of invasive Salmonella infections. These antimicrobial susceptibility testing issues resulted in inappropriate ciprofloxacin therapy which may have been responsible for failure in clearance of pathogen from patients. Salmonella Typhi capsular polysaccharide vaccine was not protective in one case, possibly secondarily to a faulty vaccine. CONCLUSIONS: Molecular subtyping of isolates proved effective to investigate the genetic relatedness of isolates. Molecular subtyping data interpreted together with epidemiological data allowed us to pinpoint the most likely sources for our cases of laboratory-acquired infection
Detection of Campylobacter species in stool specimens from patients with symptoms of acute flaccid paralysis in South Africa
Investigation of Salmonella Enteritidis outbreaks in South Africa using multi-locus variable-number tandem-repeats analysis, 2013-2015
Origin of blood cultures and <i>Salmonella</i> Typhi isolates in DR Congo.
<p>Number of <i>Salmonella</i> Typhi grown/number of blood cultures received at INRB. •: Places where <i>Salmonella</i> Typhi positive cultures were obtained.</p
Number of blood cultures, clinically significant organisms and <i>Salmonella</i> Typhi in function of age.
<p>CSO: Clinically significant organisms [<i>Salmonella,</i> other <i>Enterobacteriaceae (Klebsiella spp., Enterobacter spp</i>., <i>Citrobacter spp., Escherichia coli), Staphylococcus aureus, Candida sp., Streptococcus spp</i>.].</p><p>ND: not determined.</p