Salmonella blood stream infections in a tertiary care setting in Ghana

Invasive salmonellosis remains a global public health problem. Global estimates in 2000 showed that typhoid fever accounted for 21, 000 000 illnesses and 216, 000 deaths, whilst 5, 412 744 illnesses were attributable to paratyphoid fever [1]. The epidemiology of invasive salmonellosis varies worldwide. In Europe, non-typhoidal Salmonella (NTS) mainly Salmonella Enteritidis predominate but are rarely associated with systemic disease other than diarrhoea except for severely immunocompromised patients) [2]. In South East Asia, the predominant organism is Salmonella Typhi [1],[3], whilst in Africa NTS predominates [1],[4]-[8]. The disease is common in developing countries and concomitant with poor public health and low socio economic indices [9],[3]. Thus the bulk of the disease burden is seen in South East Asia, Africa and Latin America [3]. Its’ epidemiology is also affected by seasonal variations [2],[10]. In India peak incidence of Salmonella Typhi occurs between April-June (dry season) followed by July-September (monsoon season). In Africa the epidemiology of invasive salmonellosis has been linked with malaria infections [4],[8],[11],[12].

In Ghana, there is paucity of epidemiological data on invasive salmonellosis with a few studies suggesting high disease burden in children. A recent report found invasive non-typhoidal salmonellosis in 10% of hospitalized children [5], whilst another study documented a prevalence of 57% in infant bactereamia [4].

Salmonella species are increasingly evolving antimicrobial resistance to several commonly used antimicrobial agents. This phenomenon which started with a report of chloramphenicol resistant Salmonella Typhi from India in 1972 [13] has increased to the extent that multi-drug resistant strains are now circulating globally [14]. This is the result of indiscriminate use of antibiotics in areas of high transmission or endemicity [14]. The problem of MDR Salmonella increases the challenge in the management of the disease in endemic regions by increasing morbidity and mortality as well as cost of treatment.

Surveillance data worldwide remains limited (2), and is more so exemplified by the lack of data from Africa especially in eastern, central and western Africa (1). Such data is relevant in decision making by public health officials for disease prevention and control programmes (1). In Ghana the situation is no different. In this study, we have documented the epidemiology of invasive salmonellosis in a tertiary hospital setting in Ghana. Our primary outcomes were to report the prevalence, circulating serotypes, antimicrobial resistance patterns, seasonal variations in disease incidence and some predisposing factors for this infection.

When poor public health prevails in low socio-economic settings, it is natural to speculate that it will have an impact on the health status of the people. This may manifest itself as an increase in the incidence of diseases, including Salmonella infections. Over the last decade, several studies have demonstrated the clinical significance of salmonellae causing infections in hospitals. Despite this rise, there are very few reports from West Africa, and Ghana in particular, on the occurrence of Salmonella infections.

To our knowledge this is the first study conducted in Ghana across children and adult populations to document the prevalence, circulating serotypes, antimicrobial resistance patterns, and seasonal variations in disease incidence, as well as predisposing factors for blood stream infections with salmonellae. Our study reveals an overall low prevalence (6.5%) of Salmonella bactereamia among patients in KBTH from January 2010 through December 2013. Approximately 64% (n = 115/181) of the isolates were non-typhoidal Salmonella. Our finding of salmonellae in KBTH is lower compared with that documented elsewhere in Ghana (50%) [18], but higher than those reported in other salmonellae-affected institutions in India (0.69%) [10], and Tanzania (4.7%) [8]. The Korle-bu Teaching Hospital from which these isolates were recovered serves as a referral centre for primary and secondary health care facilities mostly from the Southern sector of Ghana. Thus most of these patients are likely to have been treated with prior antibiotics which is likely to reduce the culture yields.

There was a significant (P = 0.0002) prevalence of NTS (4.1%) compared to TS (2.4%) over the study period. The predominance of NTS over TS could be explained in part by the preponderance of children in our study population (86.8%, n = 151/174). In 2002, the estimated prevalence of TS (27.6%) predominated over that of NTS (40.7%) in patients with bacterial bloodstream infections in rural hospitals in Ghana [18]. The figures were lower (NTS, 18.8%; TS, 31.3%) 7 years later in the same study, but still higher for TS contrary to the results described in this study. In our study most patients were children, while patients who had their diagnostic samples collected in the previous rural study were primarily adults with a reported interquartile range of 26 years. Using comparable methodology, our finding is much closer to the 59% NTS and 25% TS previously reported among bacteraemia children in this institution [19]. In a separate Ghanaian study that included 99 villages and 1,456 hospitalized children <15 years of age, the prevalence of TS, driven largely by S. Typhi, was 2.4% [20]. We cannot directly compare our figures with those observed in that study because they did not assess NTS; nevertheless, they seem to provide a similar qualitative picture, in that the incidence of typhoidal fever is low in children. Elsewhere in Africa, NTS has been shown to be a prominent cause of blood stream infections in children [7],[21]-[23]. The interrelationship between severe malaria, NTS, and HIV infection has been described [24]. However, a much more consistent association has been suggested between bactereamia due to NTS and severe malaria [24],[25]. In this study, we are unable to determine the proportion of patients with HIV. But given that children in Ghana are prone to develop malaria due to the endemicity of the disease in this region, our finding is perhaps be more explained by the association of malaria with NTS.

Our study shows that TS and NTS bactereamia increased with age and were highest in children below 5 years, but declined gradually after the age of five years. This is corroborated by other studies in Ghana [20]. The high prevalence of Salmonella bloodstream infections in children under five could be explained by the relative poor hygiene observed by children within this group. We also observed that children under 1 year were less likely to be infected with TS and were less often infected with MDR strains; this is at variance with another study in Ghana which showed that the frequency of TS was low in children <2 years [20].

Peak isolation of Salmonella bloodstream infections occurred between the periods of March and November. This period marks the rainy season in Ghana [26], a time when floods occur leading to contamination of water bodies and an increase in the risk of developing Salmonella infections. Similar associations have been found in India [10] and Malawi [23] where the increase in incidence of invasive Salmonella infections has been associated with the rainy season.

Overall resistance of NTS and TS to ampicillin, tetracycline and chloramphenicol was over 70%. Such high resistance rates of Ghanaian salmonellae for ampicillin, chloramphenicol and tetracycline have been recently described by Marks et al. [27]. There are other reports in Ghana where high resistance of salmonellae to these agents have been documented [5],[18],[20]. High resistance of salmonellae to antimicrobial agents have also been documented elsewhere in subsaharan Africa [23],[28],[27]. In this current study, resistance of NTS and TS to ciprofloxacin and cefotaxime (recommended agents for treatment in Ghana) [29] was very low compared to reports from India where high resistance of about 13% to ciprofloxacin have been documented [30]. The low resistance ciprofloxacin and cefotaxime in Ghana have been coroborrated by others [18],[20],[31]. The relatively recent introduction of these agents as treatment options for invasive Salmonellosis may have contributed to such low resistance. Morover, resistance to these agents on the African continent is not widespread but is said to be an emerging problem [27].

There are some potential limitations of this study that should be discussed briefly. Blood stream infections from Korle-Bu were identified as including TS and NTS which constituted 6.5% of blood culture positive isolates. Whereas this may reflect the relative incidence of organisms in a Ghanaian tertiary care setting biased by its referral policies, we were unable to determine if these were nosocomial incidents or community acquired infections because of insufficient data on inpatient and outpatient status. Another issue worth mentioning is the unavailability of data on nalidixic acid screening for the detection of reduced susceptibility of fluoroquinolone. To test for in vivo fluoroquinolone resistance, in vitro nalidixic acid is more appropriate. Quinolone-therapy will fail in spite of apparent ciprofloxacin sensitivity if first resistance mutations have occurred leading to in-vitro nalidixic acid resistance. Note also that by being retrospective, some patients had been stratified with predetermined definitions to which we were unable to fully assess clinical history for correlations that might contribute to the risk of TS or NTS infections. Patient clinical outcome data would have been very helpful in the contextual interpretation of the multi-drug resistant strain infections. Despite these shortcomings, our findings offer baseline information needed to create the awareness of salmonellae blood stream infections in Ghanaian hospitals, and also the need for surveillance and control.

In conclusion, we report a 6.5% prevalence of Salmonella bacteraemia at the Korle-Bu Teaching Hospital; with a preponderance of NTS over TS. Children under five bear the brunt of the disease. Resistance to ciprofloxacin and cefotaxime, the recommended antimicrobial agents for treatment remains low; although multi drug resistance to other agents is high. In Ghana where Salmonella infections are endemic, it is important to maintain surveillance of the disease to allow for appropriate and timely interventions when required.