Antimicrobial resistance in bacterial infections in urban and rural Tanzania
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Infectious diseases cause one in every six deaths worldwide. Antimicrobial drugs have helped dramatically in curing patients suffering from bacterial infections. However, emerging antimicrobial resistance in bacteria threatens to undermine the management of bacterial infections. Developing countries have greater burden of infectious diseases. A number of factors, which may promote antimicrobial resistance such as availability of antimicrobials without prescription, use of counterfeit or substandard antimicrobial drugs, suboptimal hygiene, immunosuppression due to malnutrition or HIV, may be more frequent in developing countries. At the same time, consequences of antimicrobial resistance may be felt harder in resource-poor settings, since second-line antimicrobial drugs for resistant bacteria may be unavailable or unaffordable. There are many unresolved questions regarding antimicrobial resistance in general, including regarding its impact on patient outcome. In Sub-Saharan, some studies on antimicrobial resistance have been done, but, by and large, the issue has received far too little attention. We set out to improve available antimicrobial susceptibility data in Tanzania. We implemented a free-of-charge computerized software (WHONET) for resistance surveillance in the University Teaching Hospital in Dar es Salaam. This exercise showed that resistance surveillance is feasible in the setting and provided useful data on antimicrobial resistance. The surveillance data indicated high rates of resistance to common antibiotics in Gram-negative bacteria. We performed a prospective, observational cohort study of bloodstream infections in 1828 admissions of children with fever or suspected serious infection at the hospital. We performed blood culture, malaria testing and HIV testing and collected clinical data from the study subjects. The study showed that a disturbingly high proportion of Gram-negative bacteria produced extended-spectrum beta-lactamases (ESBL), with prevalent genotypes being TEM-63, SHV-12 and CTX-M 15. The ESBL-producing bacteria had a high rate of resistance to almost all other available drugs, except for ciprofloxacin, and bloodstream infection caused by these multiresistant bacteria were associated with extremely high case-fatality rates. The study showed that inappropriate treatment due to antimicrobial resistance, as well as malnutrition and HIV-infection, were risk factors for death in children admitted with bloodstream infections. We investigated an outbreak of pediatric / neonatal meningitis at Haydom Lutheran Hospital, finding that Salmonella serovar Enteritidis, resistant to ampicillin and susceptible to gentamicin, was the cause of the outbreak. Although the numbers were small, the case-fatality rate for meningitis caused by these organisms was 100% (5/5). Antimicrobial resistance varies greatly from one geographical area to another. Thus, data obtained at major hospitals in urban centers may not be representative for the whole country. We analyzed the antimicrobial susceptibilities of isolates of uropathogenic bacterial obtained from the urine of pregnant women in a rural area in Northern Tanzania. This study indicated that there is less antimicrobial resistance in E. coli isolates from this rural area than in isolates from the commercial capital, Dar es Salaam. In formulating guidelines for antimicrobial use this possible rural-urban difference should be taken into account. For some of the bacteria carrying resistance traits for multiple antimicrobials, there are actually no good alternative drugs available. Based on the findings of these studies, we recommend sober, rational use of antimicrobial drugs, restrictions on sale and use of antimicrobials, and attention to hygiene.
Paper I: BMC Public Health 4(45), Blomberg, Bjørn; Mwakagile, D. S. M.; Urassa, W. K.; Maselle, S. Y.; Mashurano, M.; Digranes, A.; Harthug, S. & Nina Langeland, Surveillance of antimicrobial resistance at a tertiary hospital in Tanzania. Copyright 2004 Blomberg et al; licensee BioMed Central Ltd. Reproduced with permission. Published version. The published version is also available at: http://dx.doi.org/10.1186/1471-2458-4-45Paper II: BMC Infectious Diseases 7(43), Blomberg, Bjørn; Manji, K. P.; Urassa, W. K.; Tamim, B. S.; Mwakagile, D. S. M.; Jureen, R.; Msangi, V.; Tellevik, M. G.; Holberg-Petersen, M.; Harthug, S.; Maselle, S. Y. & Nina Langeland, Antimicrobial resistance predicts death in Tanzanian children with bloodstream infections: a prospective cohort study. Copyright 2007 Blomberg et al; licensee BioMed Central Ltd. Reproduced with permission. Submitted version. The published version is available at: http://dx.doi.org/10.1186/1471-2334-7-43Paper III: Journal of Clinical Microbiology 43(2), Blomberg, Bjørn; Jureen, R. M.; Manji, K. P.; Tamim, B. S.; Mwakagile, D. S. M.; Urassa, W. K.; Fataki, M.; Msangi, V.; Tellevik, M. G.; Maselle, S. Y. & Nina Langeland, High rate of fatal cases of pediatric septicemia caused by gram-negative bacteria with extended-spectrum betalactamases in Dar es Salaam, Tanzania, pp. 745-749. Copyright 2005 American Society for Microbiology. Reproduced with permission. Published version. The published version is also available at: http://dx.doi.org/10.1128/JCM.43.2.745-749.2005Paper IV: BMC Infectious Diseases 4(35), Vaagland, Hogne; Blomberg, B.; Krüger, C.; Naman, N.; Jureen, R. & Nina Langeland, Nosocomial outbreak of neonatal Salmonella enterica serotype Enteritidis meningitis in a rural hospital in northern Tanzania. Copyright 2004 Vaagland et al; licensee BioMed Central Ltd. Reproduced with permission. Published version. The published version is also available at: http://dx.doi.org/10.1186/1471-2334-4-35Paper V: Scandinavian Journal of Infectious Diseases 37(4), Blomberg, Bjørn; Olsen, B. E.; Hinderaker, S. G.; Langeland, N.; Gasheka, P.; Jureen, R.; Kvåle, G. & Tore Midtvedt, Antimicrobial resistance in urinary bacterial isolates from pregnant women in rural Tanzania: implications for public health, pp. 262-268. Copyright 2005 Taylor & Francis. Reproduced with permission. Published version. The published version is also available at: http://dx.doi.org/10.1080/00365540410021045