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WHO guidelines for antimicrobial treatment in children admitted to hospital in an area of intense Plasmodium falciparum transmission: prospective study

BMJ 2010; 340 doi: https://doi.org/10.1136/bmj.c1350 (Published 30 March 2010) Cite this as: BMJ 2010;340:c1350
  1. Behzad Nadjm, clinical lecturer1,
  2. Ben Amos, laboratory manager2,
  3. George Mtove, clinical research scientist3,
  4. Jan Ostermann, associate professor of health economics4,
  5. Semkini Chonya, data manager5,
  6. Hannah Wangai, research nurse5,
  7. Juma Kimera, research laboratory assistant2,
  8. Walii Msuya, research clinical officer2,
  9. Frank Mtei, data manager5,
  10. Denise Dekker, microbiologist5,
  11. Rajabu Malahiyo, hospital superintendant2,
  12. Raimos Olomi, professor of paediatrics5,
  13. John A Crump, associate professor of clinical microbiology6,
  14. Christopher J M Whitty, professor of international health1,
  15. Hugh Reyburn, clinical senior lecturer1
  1. 1London School of Hygiene and Tropical Medicine, London WCIE 7HT
  2. 2Teule Hospital, Muheza, Tanga, Tanzania
  3. 3National Institute for Medical Research, Amani Centre, Tanga
  4. 4Centre for Health Policy, Duke University, Box 90392, Durham, NC 27705, USA
  5. 5Joint Malaria Programme, Box 2228, Kilimanjaro Christian Medical Centre, Moshi, Tanzania
  6. 6Division of Infectious Diseases and International Health, Box 102359, Duke University Medical Center, Durham, NC 27710, USA
  1. Correspondence to: H Reyburn Hugh.reyburn{at}lshtm.ac.uk
  • Accepted 25 January 2010

Abstract

Objectives To assess the performance of WHO’s “Guidelines for care at the first-referral level in developing countries” in an area of intense malaria transmission and identify bacterial infections in children with and without malaria.

Design Prospective study.

Setting District hospital in Muheza, northeast Tanzania.

Participants Children aged 2 months to 13 years admitted to hospital for febrile illness.

Main outcome measures Sensitivity and specificity of WHO guidelines in diagnosing invasive bacterial disease; susceptibility of isolated organisms to recommended antimicrobials.

Results Over one year, 3639 children were enrolled and 184 (5.1%) died; 2195 (60.3%) were blood slide positive for Plasmodium falciparum, 341 (9.4%) had invasive bacterial disease, and 142 (3.9%) were seropositive for HIV. The prevalence of invasive bacterial disease was lower in slide positive children (100/2195, 4.6%) than in slide negative children (241/1444, 16.7%). Non-typhi Salmonella was the most frequently isolated organism (52/100 (52%) of organisms in slide positive children and 108/241 (45%) in slide negative children). Mortality among children with invasive bacterial disease was significantly higher (58/341, 17%) than in children without invasive bacterial disease (126/3298, 3.8%) (P<0.001), and this was true regardless of the presence of P falciparum parasitaemia. The sensitivity and specificity of WHO criteria in identifying invasive bacterial disease in slide positive children were 60.0% (95% confidence interval 58.0% to 62.1%) and 53.5% (51.4% to 55.6%), compared with 70.5% (68.2% to 72.9%) and 48.1% (45.6% to 50.7%) in slide negative children. In children with WHO criteria for invasive bacterial disease, only 99/211(47%) of isolated organisms were susceptible to the first recommended antimicrobial agent.

Conclusions In an area exposed to high transmission of malaria, current WHO guidelines failed to identify almost a third of children with invasive bacterial disease, and more than half of the organisms isolated were not susceptible to currently recommended antimicrobials. Improved diagnosis and treatment of invasive bacterial disease are needed to reduce childhood mortality.

Footnotes

  • We thank the staff and patients of Teule Hospital for their cooperation during the study. Aikande Shoo, Halima Mohammed, Charles Mgaya, Selina Wycliffe, Emmanuel Swai, Edward Mtili, Christina Kemi, Stella Emmanuel, Rosalia Marwa, and Simphorosa Silaye were involved in clinical and laboratory data collection. Anne B Morrissey and Susan C Morpeth provided advice and support for microbiology.

  • Contributors: BN was responsible for all the clinical data collection, contributed to the data analysis, and wrote the manuscript with HR. BA, DD, and JK were responsible for the laboratory analysis, drafted sections of the methods and provided critical review of the manuscript. GM was responsible for clinical data collection and contributed to the writing of the manuscript. JO was responsible for the statistical analysis and provided critical review of the manuscript. KC and FM were responsible for managing the data and provided critical review of the manuscript. HM, WM, and RM were responsible for clinical data collection and provided critical review of the manuscript. RO, JAC, and CJMW contributed to funding applications, study design, and critical review of the manuscript. HR was responsible for the study design, obtained core funding, co-wrote the manuscript, and contributed to the analysis; he is the guarantor.

  • Funding: Core funding for the study was provided by European Commission (Europaid) grant code SANTE/2004/078-607. BN was supported by grants from the Berkeley Fellowship, Sir Halley Stewart Trust, and Pfizer Pharmaceuticals. Pfizer Pharmaceuticals provided equipment and consumables for microbiology. Abbott Pharmaceuticals provided reagents for HIV testing. Netspear (www.netspear.org) funded the E-tests, which were performed at the KEMRI/Wellcome Trust Centre for Geographic Medicine (Coast), Kilifi, Kenya. None of the funders had a role in the design, analysis, or interpretation of results.

  • Competing interests: None declared.

  • Ethical approval: The study was approved by the ethics committees of the National Institute for Medical Research, Tanzania, and the London School of Hygiene and Tropical Medicine. Written informed consent was obtained from the caregiver of each child in the study, and pre-test counselling was provided before HIV testing.

  • Data sharing: Technical appendix, statistical code, and dataset are available from the corresponding author (hugh.reyburn{at}lshtm.ac.uk). Specific consent for data sharing was not obtained prospectively from study participants but may be granted by the Tanzanian national ethical review board.

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