Volume 15, Number 7—July 2009
Peer Reviewed Report Available Online Only
Meeting on Establishment of Consortium to Study Invasive Salmonelloses in Sub-Saharan Africa
Estimates of typhoid fever in Africa have been based exclusively on placebo group incidence rates during vaccine trials in the Arab Republic of Egypt and the Republic of South Africa (1–4); population-based data on infections caused by Salmonella enterica serotype Typhi have not been available. In the Gambia, Mabey et al. described a series of 5,466 febrile patients hospitalized during 1979–1984 from whom blood cultures were taken (5). Of the 246 blood cultures from which bacteria were isolated, 45 (18%) were positive for Salmonella serotype Typhi and 71 (28%) were positive for non-Typhi serotypes of S. enterica. The importance of S. enterica non-Typhi serotypes in febrile illness also has been demonstrated in other studies (6–9), including a population-based study (9). In that study, of 1,094 children with bacteremia admitted to the hospital during 1998–2002 in Kilifi, Kenya, 166 (15%) had S. enterica non-Typhi serotypes and 1 had Salmonella Typhi; S. enterica non-Typhi serotypes were the second most frequently isolated bacterial species.
The few published data do not clarify whether Salmonella Typhi causes as much disease and death in sub-Saharan Africa as in Asia. This uncertainty is an impediment to public health decisions about the deployment of modern typhoid vaccines, which are inexpensive, safe, and effective. Bacteremia from other salmonellae are increasingly recognized to cause considerable illness in sub-Saharan Africa; this finding contrasts with reports from industrialized countries, where S. enterica non-Typhi serotypes are associated mainly with noninvasive illness, such as gastroenteritis (10). The relative importance of invasive Salmonella infections in sub-Saharan Africa is likely to increase as the other major causes of bacteremia, Streptococcus pneumoniae and Haemophilus influenzae type b (Hib), are increasingly targeted for control through vaccination, and malaria, hitherto the main cause of febrile illness in the region, steadily decreases in some areas.
On January 24, 2009, the International Vaccine Institute (located in Seoul, Republic of Korea) and the Kenya Medical Research Institute (Kilifi, Kenya) cohosted a meeting to review published and unpublished data on invasive disease caused by Salmonella Typhi and S. enterica non-Typhi serotypes in sub-Saharan Africa. The meeting was supported by the Swedish International Cooperation and Development Agency and held in conjunction with the Seventh International Conference on Typhoid Fever and Other Invasive Salmonelloses in Kilifi, Kenya. Twenty-eight investigators from 14 research sites in sub-Saharan Africa and 5 international institutions presented data on invasive bacterial diseases that focused on salmonelloses and discussed the way forward for defining invasive Salmonella in sub-Saharan Africa.
Characteristics of 11 fever surveillance sites were compared (Table). Most sites identified both Salmonella Typhi and S. enterica non-Typhi serotypes as causes of invasive infections. Salmonella Typhi seemed to be affecting older children and young adults, whereas invasive S. enterica non-Typhi serotypes were more common in infants, toddlers, and HIV-infected adults. The ratio of Salmonella Typhi to invasive S. enterica non-Typhi serotypes varied greatly across sites. In infants, the incidence of S. enterica non-Typhi serotypes was similar to the incidences of S. pneumoniae and Hib in some sites. Predominant S. enterica non-Typhi serotypes differed by site: Salmonella serotypes Typhimurium and Enteritidis accounted for a large proportion of the S. enterica non-Typhi serotypes identified, but Salmonella serotypes Dublin, Hvittingfoss, Heidelberg, Isangi, and Stanleyville also were reported as noteworthy causes of infection with S. enterica non-Typhi serotypes. Antimicrobial drug resistance patterns of S. enterica non-Typhi serotypes were heterogeneous by site; however, the levels were high enough to warrant concern. The lack of rapid diagnostic tests for S. enterica non-Typhi serotypes infection was also a concern because poor diagnostics contribute to the inaccurate reporting of disease, and treating febrile illnesses only with antimalarial medication is widely practiced, particularly in malaria-endemic areas. Culture confirmation is considered the accepted standard but is not always performed because it is expensive and requires considerable infrastructure and expertise and, considering its sensitivity, is likely to grossly underestimate the actual prevalence of disease.
Variability in findings across sites can be explained partly by differences in setting (e.g., urban/rural, hospital-based/population-based), criteria for enrollment, age groups included, and laboratory methods. The use of standard protocols across sites would make combining data for analysis and comparing and contrasting results possible. The Diseases of the Most Impoverished Program conducted by the International Vaccine Institute in Asia produced comparative data on typhoid and paratyphoid fever infections through implementation of common epidemiologic and laboratory methods across multiple sites (11). An array of evidence was generated on the need to control typhoid fever through the program's multidisciplinary approach, which also included policy, economic, and sociobehavioral studies and vaccine demonstration projects. A similar approach may be emulated in sub-Saharan Africa for the studies on invasive salmonelloses.
Meeting participants concluded that existing epidemiologic information about invasive salmonelloses in sub-Saharan Africa remains fragmentary and hindered by heterogeneous study methods. Participants agreed on an urgent need to collect better data on invasive Salmonella infections in these areas. Collection of standardized, multicountry, multidisciplinary data on the prevalence of, risk factors for, and costs of these infections is essential for developing consensus at the regional, national, and international levels in establishing appropriate control measures. The optimal study approach is to use existing fever surveillance sites and to standardize epidemiologic and laboratory procedures across sites. In addition, at sites where the prevalence of disease associated with Salmonella Typhi is known and considerable, vaccine demonstration projects should be conducted to control the disease. The framework for a multicenter proposal was discussed, and the group agreed on the creation of an African salmonelloses initiative for research and advocacy. This consortium will undertake much-needed standardized multicountry studies to yield evidence about typhoid and other invasive salmonelloses and the effectiveness of typhoid vaccines in sub-Saharan Africa, which ultimately can lead to deployment of preventive interventions, including vaccination, against invasive Salmonella infections.
Investigators participating in the meeting were Katrin Kösters, Albert Schweitzer Hospital, Lambaréné, Gabon; Jürgen May, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany; Robert F. Breiman, US Centers for Disease Control and Prevention, Nairobi, Kenya; John A. Crump, Duke University–Kilimanjaro Christian Medical Centre Collaboration, Moshi, Tanzania; John Clemens, Michael Favorov, Florian Marks, and R. Leon Ochiai, International Vaccine Institute, Seoul, Republic of Korea; Kamala Thriemer, International Vaccine Institute, Pemba, Tanzania; Lorenz von Seidlein, International Vaccine Institute, Zanzibar, Tanzania; Sam Kariuki, Kenya Medical Research Institute, Nairobi, Kenya; Kevin Marsh and Susan C. Morpeth, Kenya; Medical Research Institute–Wellcome Research Program, Kilifi, Kenya; Yaw Adu-Sarkodie, Kwame Nkrumah University of Science and Technology School of Medical Sciences, Kumasi, Republic of Ghana; Denise Dekker, London School of Hygiene and Tropical Medicine, Korogwe, Tanzania; Hugh Reyburn, London School of Hygiene and Tropical Medicine, Moshi, Tanzania; Robert Heyderman, Malawi–Liverpool–Wellcome Trust Clinical Research Program, Blantyre, Malawi; Usman Nurudeen Ikumpayi, Medical Research Council Laboratories, Basse, The Gambia; Stephen Obaro, Michigan State University, East Lansing, Michigan, USA; George Mtove, National Institute of Medical Research, Amani, Tanzania; Saidi M Ali and Shaali Ame, Public Health Laboratory–Ivo de Carneiro, Pemba, Tanzania; Gordon Dougan, Sanger Institute, Cambridge, UK; John Wain, Health Protection Agency, London, UK; Karen H. Keddy, National Institute for Communicable Diseases, Johannesburg, Republic of South Africa; Ben Amos, Teule Hospital, Muheza, Tanzania; Myron M. Levine, Center for Vaccine Development, Bamako, Mali; and William Mwengee, World Health Organization, Dar es Salaam, Tanzania.
Dr Clemens is Director General of the International Vaccine Institute. In addition to field evaluations of vaccines, his research interests include innovative methods approaches to evaluating vaccines in developing countries and to generating evidence needed for policy decisions about vaccine introduction in developing countries.
- Klugman KP, Gilbertson IT, Koornhof HJ, Robbins JB, Schneerson R, Schulz D, Protective activity of Vi capsular polysaccharide vaccine against typhoid fever. [PubMed DOI]. Lancet. 1987;2:1165–9.
- Klugman KP, Koornhof HJ, Robbins JB, Le Cam NN. Immunogenicity, efficacy and serological correlate of protection of Salmonella Typhi Vi capsular polysaccharide vaccine three years after immunization. [PubMed DOI]. Vaccine. 1996;14:435–8.
- Wahdan MH, Serie C, Cerisier Y, Sallam S, Germanier R. A controlled field trial of live Salmonella Typhi strain Ty 21a oral vaccine against typhoid: three-year results. J Infect Dis. 1982;145:292–5.
- Wahdan MH, Serie C, Germanier R, Lackany A, Cerisier Y, Guerin N, A controlled field trial of liver oral typhoid vaccine Ty21a. Bull World Health Organ. 1980;58:469–74.
- Mabey DC, Brown A, Greenwood BM. Plasmodium falciparum malaria and Salmonella infections in Gambian children. J Infect Dis. 1987;155:1319–21.
- Sigauque B, Roca A, Mandomando I, Morais L, Quintó L, Sacarlal J, Community-acquired bacteremia among children admitted to a rural hospital in Mozambique. [PubMed DOI]. Pediatr Infect Dis J. 2009;28:108–13.
- Gordon MA, Graham SM, Walsh AL, Wilson L, Phiri A, Molyneux E, Epidemics of invasive Salmonella enterica serovar enteritidis and S. enterica serovar typhimurium infection associated with multidrug resistance among adults and children in Malawi. [PubMed DOI]. Clin Infect Dis. 2008;46:963–9.
- Brent AJ, Oundo JO, Mwangi I, Ochola L, Lowe B, Berkley JA. Salmonella bacteremia in Kenyan children. [PubMed DOI]. Pediatr Infect Dis J. 2006;25:230–6.
- Berkley JA, Lowe BS, Mwangi I, Williams T, Bauni E, Mwarumba S, Bacteremia among children admitted to a rural hospital in Kenya. [PubMed DOI]. N Engl J Med. 2005;352:39–47.
- Hohmann EL. Nontyphoidal salmonellosis. [PubMed DOI]. Clin Infect Dis. 2001;32:263–9.
- Ochiai RL, Acosta CJ, Agtini M, Bhattacharya SK, Bhutta ZA, Do CG, The use of typhoid vaccines in Asia: the DOMI experience. [PubMed DOI]. Clin Infect Dis. 2007;45(Suppl 1):S34–8.
Suggested citation for this article: LeDuc JW, Anderson K, Bloom ME, Carrion R Jr, Feldmann H, Fitch JP, et al. Potential impact of a 2-person security rule on BioSafety Level 4 laboratory workers [online report]. Emerg Infect Dis [serial on the Internet]. 2009 Jul [date cited]. Available from http://wwwnc.cdc.gov/eid/article/15/7/09-0416
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