Microbiological, clinical and molecular findings of non-typhoidal Salmonella bloodstream infections associated with malaria, Oriental Province, Democratic Republic of the Congo

Dadi Falay, Laura Maria Francisca Kuijpers, Marie-France Phoba, Hilde De Boeck, Octavie Lunguya, Emmanuel Vakaniaki, Sophie Bertrand, Wesley Mattheus, Pieter-Jan Ceyssens, Raymond Vanhoof, Hugo Devlieger, Chris Van Geet, Erik Verheyen, Dauly Ngbonda, Jan Jacobs, Dadi Falay, Laura Maria Francisca Kuijpers, Marie-France Phoba, Hilde De Boeck, Octavie Lunguya, Emmanuel Vakaniaki, Sophie Bertrand, Wesley Mattheus, Pieter-Jan Ceyssens, Raymond Vanhoof, Hugo Devlieger, Chris Van Geet, Erik Verheyen, Dauly Ngbonda, Jan Jacobs

Abstract

Background: In sub-Saharan Africa, non-typhoidal Salmonella (NTS) can cause bloodstream infections, referred to as invasive non-typhoidal Salmonella disease (iNTS disease); it can occur in outbreaks and is often preceded by malaria. Data from Central Africa is limited.

Methods: Clinical, microbiological and molecular findings of NTS recovered in a blood culture surveillance project (2009-2014) were analyzed.

Results: In March-July 2012 there was an epidemic increase in malaria infections in the Oriental Province of the Democratic Republic of the Congo (DRC). In one referral hospital, overall hospital admissions in June 2012 were 2.6 times higher as compared to the same period in the years before and after (336 versus an average of 128 respectively); numbers of malaria cases and blood transfusions were nearly three- and five-fold higher respectively (317 versus 112 and 250 versus 55). Case fatality rates (in-hospital deaths versus all admissions) peaked at 14.6 %. Salmonella Typhimurium and Salmonella Enteritidis together accounted for 88.9 % of pathogens isolated from blood cultures collected during an outreach visit to the affected districts in June 2012. Children infected with Salmonella Enteritidis (33 patient files available) tended to be co-infected with Plasmodium falciparum more often than children infected with Salmonella Typhimurium (40 patients files available) (81.8 % versus 62.5 %). Through the microbiological surveillance project (May 2009-May 2014) 113 unique NTS isolates were collected (28.5 % (113/396) of pathogens); most (95.3 %) were recovered from children < 15 years. Salmonella Typhimurium (n = 54) and Salmonella Enteritidis (n = 56) accounted for 47.8 % and of 49.6 % NTS isolates respectively. Multilocus variable-number tandem-repeat analysis (MLVA) revealed more heterogeneity for Salmonella Typhimurium than for Salmonella Enteritidis. Most (82/96, 85.4 %) NTS isolates that were available for antibiotic susceptibility testing were multidrug resistant. All isolates were susceptible to ceftriaxone and azithromycin.

Conclusion: During the peak of an epidemic increase in malaria in the DRC in 2012, a high proportion of multidrug resistant Salmonella Typhimurium and Salmonella Enteritidis were isolated from blood cultures. Overall, the two serovars showed subtle differences in clinical presentation and genetic diversity.

Keywords: Antibiotic; Bloodstream infections; Children; Democratic Republic of the Congo; Malaria; Molecular typing; Salmonella; Symptoms.

Figures

Fig. 1
Fig. 1
Map of DRC with the three places recently affected by a microbiologically documented (epidemic) increase in Salmonella infections (i) Kisantu [15]; (ii) Bwamanda [16]; (iii) districts of Bas-Uélé and Haut-Uélé (present report). © Institute of Tropical Medicine, Antwerp
Fig. 2
Fig. 2
The four health zones affected by the iNTS disease outbreak in 2012: Wamba and Isiro (Haut-Uélé) and Pawa and Poko (Bas-Uélé). © Institute of Tropical Medicine, Antwerp
Fig. 3
Fig. 3
Hospital admissions, malaria cases, blood transfusions and case-fatality rates (2011–2013) for a Pawa Health Zone Referral Hospital; b Wamba Health Zone Referral Hospital; c Poko Health Zone Referral Hospital; d Isiro Health Zone Referral Hospital. HGR = General Referal Hospital
Fig. 4
Fig. 4
Rainfall in the Oriental Province, DRC (2011–2013). Peak months of the outbreak were April 2012 to June 2012

References

    1. Gordon MA, Graham SM, Walsh AL, Wilson L, Phiri A, Molyneux E, et al. Epidemics of invasive Salmonella enterica serovar enteritidis and S-enterica serovar typhimurium infection associated with multidrug resistance among adults and children in Malawi. Clin Infect Dis. 2008;46(7):963–9. doi: 10.1086/529146.
    1. Feasey NA, Dougan G, Kingsley RA, Heyderman RS, Gordon MA. Invasive non-typhoidal salmonella disease: an emerging and neglected tropical disease in Africa. Lancet. 2012;379(9835):2489–99. doi: 10.1016/S0140-6736(11)61752-2.
    1. Graham SM, English M. Non-typhoidal salmonellae: a management challenge for children with community-acquired invasive disease in tropical African countries. Lancet. 2009;373(9659):267–9. doi: 10.1016/S0140-6736(09)60073-8.
    1. Morpeth SC, Ramadhani HO, Crump JA. Invasive non-typhi salmonella disease in Africa. Clin Infect Dis. 2009;49(4):606–11. doi: 10.1086/603553.
    1. MacLennan CA. Out of Africa. Links between invasive nontyphoidal salmonella disease, typhoid fever, and malaria. Clin Infect Dis. 2014;58(5):648–50. doi: 10.1093/cid/cit803.
    1. Lunguya O, Lejon V, Phoba MF, Bertrand S, Vanhoof R, Glupczynski Y, et al. Antimicrobial resistance in invasive Non-typhoid salmonella from the Democratic Republic of the Congo: emergence of decreased fluoroquinolone susceptibility and extended-spectrum beta lactamases. PLoS Negl Trop Dis. 2013;7(3):e2103. doi: 10.1371/journal.pntd.0002103.
    1. Biggs HM, Lester R, Nadjm B, Mtove G, Todd JE, Kinabo GD, et al. Invasive salmonella infections in areas of high and Low malaria transmission intensity in Tanzania. Clin Infect Dis. 2014;58(5):638–47. doi: 10.1093/cid/cit798.
    1. Kleinschmidt I, Schwabe C, Benavente L, Torrez M, Ridl FC, Segura JL, et al. Marked increase in child survival after four years of intensive malaria control. Am J Trop Med Hyg. 2009;80(6):882–8.
    1. Mabey DCW, Brown A, Greenwood BM. Plasmodium-falciparum malaria and salmonella infections in gambian children. J Infect Dis. 1987;155(6):1319–21. doi: 10.1093/infdis/155.6.1319.
    1. Gordon MA, Banda HT, Gondwe M, Gordon SB, Boeree MJ, Walsh AL, et al. Non-typhoidal salmonella bacteraemia among HIV-infected Malawian adults: high mortality and frequent recrudescence. AIDS. 2002;16(12):1633–41. doi: 10.1097/00002030-200208160-00009.
    1. Mtove G, Amos B, von Seidlein L, Hendriksen I, Mwambuli A, Kimera J, et al. Invasive salmonellosis among children admitted to a rural tanzanian hospital and a comparison with previous studies. PLoS One. 2010;5(2):e9244. doi: 10.1371/journal.pone.0009244.
    1. Kariuki S, Revathi G, Kariuki N, Kiiru J, Mwituria J, Hart CA. Characterisation of community acquired non-typhoidal Salmonella from bacteraemia and diarrhoeal infections in children admitted to hospital in Nairobi, Kenya. BMC Microbiol. 2006;6:101. doi: 10.1186/1471-2180-6-101.
    1. Dione MM, Ikumapayi UN, Saha D, Mohammed NI, Geerts S, Ieven M, et al. Clonal differences between non-typhoidal salmonella (NTS) recovered from children and animals living in close contact in the Gambia. PLoS Negl Trop Dis. 2011;5:5. doi: 10.1371/journal.pntd.0001148.
    1. Mandomando I, Macete E, Sigauque B, Morais L, Quinto L, Sacarlal J, et al. Invasive non-typhoidal Salmonella in Mozambican children. Trop Med Int Health. 2009;14(12):1467–74. doi: 10.1111/j.1365-3156.2009.02399.x.
    1. Phoba MF, Lunguya O, Mayimon DV, di Mputu PL, Bertrand S, Vanhoof R, Verhaegen J, Van Geet C, Muyembe JJ, Jacobs J. Multidrug-resistant salmonella enterica, Democratic Republic of the Congo. Emerg Infect Dis. 2012;18(10):1692–4. doi: 10.3201/eid1810.120525.
    1. Phoba MF, De Boeck H, Ifeka BB, Dawili J, Lunguya O, Vanhoof R, et al. Epidemic increase in Salmonella bloodstream infection in children, Bwamanda, the Democratic Republic of Congo. Eur J Clin Microbiol Infect Dis. 2014;33(1):79–87. doi: 10.1007/s10096-013-1931-8.
    1. MSF . MSF launches massive malaria response across three provinces. 2012.
    1. Gouvernement de la Province Orientale . Plan quinquennal de croissance et de l’emploi 2011–2015. 2011.
    1. World Health Organization (WHO) World malaria report 2013. 2013.
    1. UNICEF . UNICEF humanitarian action update: Democratic Republic of the Congo. 2012.
    1. United Nations Office for the Coordination of Humanitarian Affairs (OCHA) Humanitarian action in the Democratic Republic of the Congo (DRC) weekly bulletin 10 February 2012. 2012.
    1. Lunguya O, Phoba MF, Mundeke SA, Bonebe E, Mukadi P, Muyembe JJ, et al. The diagnosis of typhoid fever in the Democratic Republic of the Congo. Trans R Soc Trop Med Hyg. 2012;106(6):348–55. doi: 10.1016/j.trstmh.2012.03.006.
    1. Kalonji LM, Post A, Phoba MF, Falay D, Ngbonda D, Muyembe JJ, et al. Invasive Salmonella Infections at Multiple Surveillance Sites in the Democratic Republic of the Congo, 2011–2014. Clin Infect Dis. 2015;61(Supplement 4):S346–53. doi: 10.1093/cid/civ713.
    1. Grimont PA, Weill FX. Antigenic formulae of the Salmonella serovars. 9 2007.
    1. World Health Organization (WHO) Background document: the diagnosis, treatment and prevention of typhoid fever. 2003.
    1. Griggs DJ, Gensberg K, Piddock LJV. Mutations in gyrA gene of quinolone-resistant Salmonella serotypes isolated from humans and animals. Antimicrob Agents Chemother. 1996;40(4):1009–13.
    1. Cavaco LM, Aarestrup FM. Evaluation of Quinolones for Use in Detection of Determinants of Acquired Quinolone Resistance, Including the New Transmissible Resistance Mechanisms qnrA, qnrB, qnrS, and aac(6 ’)Ib-cr, in Escherichia coli and Salmonella enterica and Determinations of Wild-Type Distributions. J Clin Microbiol. 2009;47(9):2751–8. doi: 10.1128/JCM.00456-09.
    1. Hopkins KL, Peters TM, de Pinna E, Wain J. Standardisation of multilocus variable-number tandem-repeat analysis (MLVA) for subtyping of Salmonella enterica serovar Enteritidis. Eurosurveillance. 2011;16(32):2–12.
    1. Bertrand S, De Bex GDL, Wildemauwe C, Lunguya O, Phoba MF, Ley B, et al. Multi Locus Variable-Number Tandem Repeat (MLVA) Typing Tools Improved the Surveillance of Salmonella Enteritidis: A 6 Years Retrospective Study. PLoS One. 2015;10:2.
    1. Danoff-Burg J. Measuring Biological Diversity. 2003.
    1. World Health Organization (WHO) Manual of Basic Techniques for a Health Laboratory. 1980.
    1. Ministère de la Santé RDC . Bonnes pratiques transfusionnelles. 2005.
    1. World Health Organization (WHO) Pocket book of Hospital care for children. Guidelines for the management of common childhood illnesses. 2013.
    1. Global Information and Early Warning System . Food and Agriculture Organization of the United Nations. Interpolated Estimated Dekadal Rainfall. Democratic Republic of the Congo. 2015.
    1. Bronzan RN, Taylor TE, Mwenechanya J, Tembo M, Kayira K, Bwanaisa L, et al. Bacteremia in Malawian children with severe malaria: prevalence, etiology, HIV coinfection, and outcome. J Infect Dis. 2007;195(6):895–904. doi: 10.1086/511437.
    1. Sigauque B, Roca A, Mandomando I, Morais L, Quinto L, Sacarlal J, et al. Community-acquired bacteremia among children admitted to a rural hospital in Mozambique. Pediatr Infect Dis J. 2009;28(2):108–13. doi: 10.1097/INF.0b013e318187a87d.
    1. Enwere G, Biney E, Cheung Y, Zaman SMA, Okoko B, Oluwalana C, et al. Epidemiologic and clinical characteristics of community-acquired invasive bacterial infections in children aged 2–29 months in the Gambia. Pediatr Infect Dis J. 2006;25(8):700–5. doi: 10.1097/01.inf.0000226839.30925.a5.
    1. Feasey NA, Archer BN, Heyderman RS, Sooka A, Dennis B, Gordon MA, et al. Typhoid fever and invasive nontyphoid salmonellosis, Malawi and south Africa. Emerg Infect Dis. 2010;16(9):1448–51. doi: 10.3201/eid1609.100125.
    1. Brent AJ, Oundo JO, Mwangi I, Ochola L, Lowe B, Berkley JA. Salmonella bacteremia in Kenyan children. Pediatr Infect Dis J. 2006;25(3):230–6. doi: 10.1097/01.inf.0000202066.02212.ff.
    1. Church J, Maitland K. Invasive bacterial co-infection in African children with Plasmodium falciparum malaria: a systematic review. BMC Med. 2014;12:31. doi: 10.1186/1741-7015-12-31.
    1. Takem EN, Roca A, Cunnington A. The association between malaria and non-typhoid Salmonella bacteraemia in children in sub-Saharan Africa: a literature review. Malar J. 2014;13:400. doi: 10.1186/1475-2875-13-400.
    1. Walsh AL, Molyneux EM, Kabudula M, Phiri AJ, Molyneux ME, Graham SM. Bacteraemia following blood transfusion in Malawian children: predominance of Salmonella. Trans R Soc Trop Med Hyg. 2002;96(3):276–7. doi: 10.1016/S0035-9203(02)90098-2.
    1. Cunnington AJ, de Souza JB, Walther M, Riley EM. Malaria impairs resistance to Salmonella through heme- and heme oxygenase-dependent dysfunctional granulocyte mobilization. Nat Med. 2012;18(1):120–7. doi: 10.1038/nm.2601.
    1. Roux CM, Butler BP, Chau JY, Paixao TA, Cheung KW, Santos RL, et al. Both hemolytic anemia and malaria parasite-specific factors increase susceptibility to nontyphoidal salmonella enterica serovar typhimurium infection in mice. Infect Immun. 2010;78(4):1520–7. doi: 10.1128/IAI.00887-09.
    1. Cunnington AJ, Njie M, Correa S, Takem EN, Riley EM, Walther M. Prolonged neutrophil dysfunction after plasmodium falciparum malaria is related to hemolysis and heme oxygenase-1 induction. J Immunol. 2012;189(11):5336–46. doi: 10.4049/jimmunol.1201028.
    1. Malaria Atlas Project . The spatial distribution of Plasmodium falciparum malaria stratified by endemicity class map in 2010 in Democratic Republic of the Congo. 2010.
    1. World Health Organization (WHO) Sickle-cell disease: A strategy for the WHO African region. 2010.
    1. Ley B, Le Hello S, Lunguya O, Lejon V, Muyembe JJ, Weill FX, et al. Invasive salmonella enterica serotype typhimurium infections, democratic Republic of the Congo, 2007–2011. Emerg Infect Dis. 2014;20(4):701–4. doi: 10.3201/eid2004.131488.
    1. Kingsley RA, Msefula CL, Thomson NR, Kariuki S, Holt KE, Gordon MA, et al. Epidemic multiple drug resistant Salmonella Typhimurium causing invasive disease in sub-Saharan Africa have a distinct genotype. Genome Res. 2009;19(12):2279–87. doi: 10.1101/gr.091017.109.

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