- Email: [email protected]
Return of Haemophilus influenzae type b infections
CORRESPONDENCE
1
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Garner D, Weston V. Effectiveness of vaccination for Haemophilus influenzae type b. Lancet 2003; 361: 395–96. Eskola J, Ward J, Dagan R, Goldblatt D, Zepp F, Siegrist CA. Combined vaccination of Haemophilus influenzae type b conjugate and diphtheria-tetanus-pertussis containing acellular pertussis. Lancet 1999; 354: 2063–68.
Sir—We welcome David Garner and Vivienne Weston’s timely reminder1 that invasive Hib infection is returning. Between Dec 27, 2002, and Jan 12, 2003, we admitted three patients to our paediatric intensive-care unit with culture-positive invasive Hib disease. Two of the patients (aged 4 and 2 years) had received vaccine, and one (aged 6 weeks) was too young to have been vaccinated. The importance of raising awareness of this life-threatening infection is underlined by the fact that most medical and nursing staff who qualified in the past 5 years have never seen it before. Guidance about prophylaxis might need to be modified to include cover for families with children younger than 4 years (other than the index case), even if they are already vaccinated. *Patricia Fenton, Anton Mayer, Elisabeth Ridgway, R Lakshman, Fiona Shackley *Sheffield Children’s Hospital, Sheffield S10 2TH, UK (PF, AM, RL, FS); and Department of Microbiology, Royal Hallamshire Hospital, Sheffield, UK (ER) (e-mail: [email protected]) 1
Garner D, Weston V. Effectiveness of vaccination for Haemophilus influenzae type b. Lancet 2003; 361: 395–96.
Sir—Over the past decade, children in developed countries have received the benefit of highly effective conjugate vaccines that protect against many of the strains of bacteria that cause meningitis: Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis. As a result, bacterial meningitis has become rare in developed countries. By contrast, in developing countries, bacterial meningitis remains a major cause of mortality and morbidity: up to half of affected children die (an estimated 173 000 per year) and neurological sequelae occur in a quarter to half of survivors. The increasing problem of penicillin resistance among S pneumoniae is well recognised. Antibiotic resistance among H influenzae has been addressed in developed countries, first in the 1980s by the change to thirdgeneration cephalosporins as empiric therapy, and definitively in the 1990s by the widespread introduction of
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conjugate H influenzae type b vaccines. In developing countries, it has been assumed that H influenzae can be adequately treated with chloramphenicol. In a 1990 study, chloramphenicol-resistant H influenzae was found in only one of 11 developing countries.1 However, the efficacy of chloramphenicol can no longer be assumed. Recent studies have highlighted that chloramphenicolresistance among H influenzae is a bigger problem than previously recognised,2,3 and a review of published reports since 1990 shows that chloramphenicol resistance is widespread and increasing at an alarming rate (see webfigure: http://image.thelancet.com/03cor2148 webfigure.pdf). In Kenya, for example, chloramphenicol resistance increased from 8% in 1994 to 80% in 2000.3 Children with chloramphenicolresistant H influenzae meningitis have a very poor outcome where this antibiotic is used empirically.4 WHO suggests using a third-generation cephalosporin for empirical treatment of meningitis in areas where there is “significant drug resistance”, but this approach is too expensive for many countries. Moreover, data are not available on resistance rates in many areas due to the absence of microbiological facilities and trained personnel. Alternative economical approaches for the empirical treatment of bacterial meningitis in areas where antibiotic resistance is high or unknown might include the use of shorter (and therefore cheaper) courses of thirdgeneration cephalosporins, and the exploitation of the synergistic effect of aminoglycosides with  lactams against resistant H influenzae.5 These treatments need further assessment. However, affordable curative strategies will not overcome the other reasons children in developing countries have such a poor outcome from bacterial meningitis: particularly late presentation with established severe brain injury and failure to even reach medical facilities to receive treatment. As the development of cephalosporin resistance among S pneumoniae is showing, the use of increasingly complex and expensive antibiotics does not offer a long-term solution. Ensuring that most of the world’s children are provided with currently available vaccines that will prevent a large proportion of bacterial meningitis is now the only sensible option. This should be viewed with the highest priority, and a tangible measure of whether the world is
moving towards fulfilling the UN Convention of the Rights of the Child in the 21st century. Nigel Curtis, *Trevor Duke, David Fuller, Frank Shann *Departments of Paediatrics (NC, TD) and General Medicine (NC, DF), and Intensive Care Unit (FS), Royal Children’s Hospital, Melbourne, 3052 Victoria, Australia (e-mail: [email protected]) 1
2
3
4
5
Weinberg GA, Spitzer ED, Murray PR, et al. Antimicrobial susceptibility patterns of Haemophilus isolates from children in eleven developing nations. Bull World Health Organ 1990; 68: 179–84. Molyneux EM, Walsh AL, Forsyth H, et al. Dexamethasone treatment in childhood bacterial meningitis in Malawi: a randomised controlled trial. Lancet 2002; 360: 211–18. Mwangi I, Berkley J, Lowe B, Peshu N, Marsh K, Newton CR. Acute bacterial meningitis in children admitted to a rural Kenyan hospital: increasing antibiotic resistance and outcome. Pediatr Infect Dis J 2002; 21: 1042–48. Duke T, Michael A, Mokela D, Wal T, Reeder J. Chloramphenicol or ceftriaxone, or both, as treatment for meningitis in developing countries? Arch Dis Child (in press). Bingen E, Lambert-Zechovsky N, Aujard Y, et al. Early synergistic killing activity at concentrations attainable in CSF of amoxycillin or cefotaxime and aminoglycosides against Haemophilus influenzae. Infection 1998; 16: 121–25.
Bacterial meningitis in Angola Sir—Over the past 5 years (1998–2002), 5847 children (age 0–8 years) have been admitted with meningitis to the Paediatric Hospital of Luanda, Angola (290 beds, 50 admissions a day); 49·5% of these have died. Although in that period outbreaks of meningitis attributable to Neisseria meningitidis were reported in some Angolan provinces, in our hospital— located in the capital (4 million inhabitants)—we have been dealing with a high but steady prevalence, suggesting an endemic rather than an epidemic situation. However, because of local constraints, we were not able to have full microbiological knowledge of our patients, or a directed policy about antibiotics. But since July, 2002, a great improvement took place thanks to a link between our hospital and the National Health Institute of Lisbon, Portugal. A laboratory dedicated exclusively to meningitis was established, with provision of equipment for basic research and, when appropriate, transport of samples to Lisbon for inhibitory concentration studies.
THE LANCET • Vol 361 • May 3, 2003 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
1
2
Garner D, Weston V. Effectiveness of vaccination for Haemophilus influenzae type b. Lancet 2003; 361: 395–96. Eskola J, Ward J, Dagan R, Goldblatt D, Zepp F, Siegrist CA. Combined vaccination of Haemophilus influenzae type b conjugate and diphtheria-tetanus-pertussis containing acellular pertussis. Lancet 1999; 354: 2063–68.
Sir—We welcome David Garner and Vivienne Weston’s timely reminder1 that invasive Hib infection is returning. Between Dec 27, 2002, and Jan 12, 2003, we admitted three patients to our paediatric intensive-care unit with culture-positive invasive Hib disease. Two of the patients (aged 4 and 2 years) had received vaccine, and one (aged 6 weeks) was too young to have been vaccinated. The importance of raising awareness of this life-threatening infection is underlined by the fact that most medical and nursing staff who qualified in the past 5 years have never seen it before. Guidance about prophylaxis might need to be modified to include cover for families with children younger than 4 years (other than the index case), even if they are already vaccinated. *Patricia Fenton, Anton Mayer, Elisabeth Ridgway, R Lakshman, Fiona Shackley *Sheffield Children’s Hospital, Sheffield S10 2TH, UK (PF, AM, RL, FS); and Department of Microbiology, Royal Hallamshire Hospital, Sheffield, UK (ER) (e-mail: [email protected]) 1
Garner D, Weston V. Effectiveness of vaccination for Haemophilus influenzae type b. Lancet 2003; 361: 395–96.
Sir—Over the past decade, children in developed countries have received the benefit of highly effective conjugate vaccines that protect against many of the strains of bacteria that cause meningitis: Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis. As a result, bacterial meningitis has become rare in developed countries. By contrast, in developing countries, bacterial meningitis remains a major cause of mortality and morbidity: up to half of affected children die (an estimated 173 000 per year) and neurological sequelae occur in a quarter to half of survivors. The increasing problem of penicillin resistance among S pneumoniae is well recognised. Antibiotic resistance among H influenzae has been addressed in developed countries, first in the 1980s by the change to thirdgeneration cephalosporins as empiric therapy, and definitively in the 1990s by the widespread introduction of
1564
conjugate H influenzae type b vaccines. In developing countries, it has been assumed that H influenzae can be adequately treated with chloramphenicol. In a 1990 study, chloramphenicol-resistant H influenzae was found in only one of 11 developing countries.1 However, the efficacy of chloramphenicol can no longer be assumed. Recent studies have highlighted that chloramphenicolresistance among H influenzae is a bigger problem than previously recognised,2,3 and a review of published reports since 1990 shows that chloramphenicol resistance is widespread and increasing at an alarming rate (see webfigure: http://image.thelancet.com/03cor2148 webfigure.pdf). In Kenya, for example, chloramphenicol resistance increased from 8% in 1994 to 80% in 2000.3 Children with chloramphenicolresistant H influenzae meningitis have a very poor outcome where this antibiotic is used empirically.4 WHO suggests using a third-generation cephalosporin for empirical treatment of meningitis in areas where there is “significant drug resistance”, but this approach is too expensive for many countries. Moreover, data are not available on resistance rates in many areas due to the absence of microbiological facilities and trained personnel. Alternative economical approaches for the empirical treatment of bacterial meningitis in areas where antibiotic resistance is high or unknown might include the use of shorter (and therefore cheaper) courses of thirdgeneration cephalosporins, and the exploitation of the synergistic effect of aminoglycosides with  lactams against resistant H influenzae.5 These treatments need further assessment. However, affordable curative strategies will not overcome the other reasons children in developing countries have such a poor outcome from bacterial meningitis: particularly late presentation with established severe brain injury and failure to even reach medical facilities to receive treatment. As the development of cephalosporin resistance among S pneumoniae is showing, the use of increasingly complex and expensive antibiotics does not offer a long-term solution. Ensuring that most of the world’s children are provided with currently available vaccines that will prevent a large proportion of bacterial meningitis is now the only sensible option. This should be viewed with the highest priority, and a tangible measure of whether the world is
moving towards fulfilling the UN Convention of the Rights of the Child in the 21st century. Nigel Curtis, *Trevor Duke, David Fuller, Frank Shann *Departments of Paediatrics (NC, TD) and General Medicine (NC, DF), and Intensive Care Unit (FS), Royal Children’s Hospital, Melbourne, 3052 Victoria, Australia (e-mail: [email protected]) 1
2
3
4
5
Weinberg GA, Spitzer ED, Murray PR, et al. Antimicrobial susceptibility patterns of Haemophilus isolates from children in eleven developing nations. Bull World Health Organ 1990; 68: 179–84. Molyneux EM, Walsh AL, Forsyth H, et al. Dexamethasone treatment in childhood bacterial meningitis in Malawi: a randomised controlled trial. Lancet 2002; 360: 211–18. Mwangi I, Berkley J, Lowe B, Peshu N, Marsh K, Newton CR. Acute bacterial meningitis in children admitted to a rural Kenyan hospital: increasing antibiotic resistance and outcome. Pediatr Infect Dis J 2002; 21: 1042–48. Duke T, Michael A, Mokela D, Wal T, Reeder J. Chloramphenicol or ceftriaxone, or both, as treatment for meningitis in developing countries? Arch Dis Child (in press). Bingen E, Lambert-Zechovsky N, Aujard Y, et al. Early synergistic killing activity at concentrations attainable in CSF of amoxycillin or cefotaxime and aminoglycosides against Haemophilus influenzae. Infection 1998; 16: 121–25.
Bacterial meningitis in Angola Sir—Over the past 5 years (1998–2002), 5847 children (age 0–8 years) have been admitted with meningitis to the Paediatric Hospital of Luanda, Angola (290 beds, 50 admissions a day); 49·5% of these have died. Although in that period outbreaks of meningitis attributable to Neisseria meningitidis were reported in some Angolan provinces, in our hospital— located in the capital (4 million inhabitants)—we have been dealing with a high but steady prevalence, suggesting an endemic rather than an epidemic situation. However, because of local constraints, we were not able to have full microbiological knowledge of our patients, or a directed policy about antibiotics. But since July, 2002, a great improvement took place thanks to a link between our hospital and the National Health Institute of Lisbon, Portugal. A laboratory dedicated exclusively to meningitis was established, with provision of equipment for basic research and, when appropriate, transport of samples to Lisbon for inhibitory concentration studies.
THE LANCET • Vol 361 • May 3, 2003 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.