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evaluation of such strategies and why we welcome Metin Gülmezoglu and João Paulo Souza’s response. Braunholtz and colleagues commend our openness. We encourage others who use our model to make the parameter estimates used and the reasoning behind these choices publicly available when presenting findings. A dedicated webpage has been constructed on which to publish such material. In addition to its primary function, our model provides a framework for exploring the policy implications of uncertainty in incidence and case fatality rates, achievable coverage of community interventions, and plausible increases in health-facility delivery. Given the unquestioned importance of reducing maternal mortality, but differing opinions as to how, open and rational debate is not just welcome but urgently required. We declare that we have no conflicts of interest.
*Christina Pagel, Anthony Costello, Martin Utley
[email protected] University College London, London WC1H 0BT, UK 1
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Khan KS, Wojdyla D, Say L, Gülmezoglu AM, Van Look PFA. WHO analysis of causes of maternal death: a systematic review. Lancet 2006; 267: 1066–74 Seale AC, Mwaniki M, Newton CRJC, Berkley JA. Maternal and early onset neonatal bacterial sepsis: burden and strategies for prevention in sub-Saharan Africa. Lancet Infect. Dis. 2009; 9: 428–38 Dolea C, Stein C. Global burden of maternal sepsis in the year 2000. Geneva: World Health Organization, 2003. http://www.who.int/ healthinfo/statistics/bod_maternalsepsis.pdf (accessed March 20, 2009).
Empowering women to control post-partum haemorrhage The study by Christina Pagel and colleagues1 on the community-based provision of drugs to reduce maternal mortality adds to a growing and compelling body of evidence2 that, in regions where home births are prevalent, empowering women to use
misoprostol to control post-partum haemorrhage at home is a viable and effective way to reduce maternal mortality. The International Federation of Gynaecology and Obstetrics (FIGO), the International Confederation of Midwives (ICM),3 and, in a 2007 report, WHO4 have endorsed use of misoprostol at the community level. However, WHO has now reversed its earlier position. Its most recent statement declares: “WHO does not recommend distribution of misoprostol to community-level health workers or women and their families for routine or emergency use.”5 We find the reasons given (minor inconsistencies in clinical trials, increased risk of shivering or fever, and “an unresolved concern of a possible increase in the risk of maternal mortality”) contrived and unsubstantiated. These risks pale in comparison to the very real danger of post-partum haemorrhage after home births where skilled attention is inaccessible. Pagel and colleagues estimate that tens of thousands of maternal deaths could be averted in sub-Saharan Africa alone by widespread community use of misoprostol. The women at greatest risk from the scourge of post-partum haemorrhage have no direct voice, but we, the undersigned, call on senior members of WHO to (a) re-evaluate the place of misoprostol in the Essential Medicines List, and (b) reissue their recommendation on the use of misoprostol during home births, bringing it in line with the current evidence base.
For the website dedicated to the publication of model-based findings see http://www.ucl.ac. uk/operational-research/ downloads/Maternal_mortality
We declare that we have no conflicts of interest.
*Malcolm Potts, Ndola Prata, Hazem El Refaey, Harsah Sanghvi, Phil Darney, Veronica Ades, Sadiqua N Jafarey, Emmanuel Rwamushaija, Nuriye Hodoglugil, Cassimo Bique, Rudofo Gomez, Jean Paul Rokotovao, Abdul Quaiyum, Joseph Karanja, Edgar Kuchingale
The printed journal includes an image merely for illustration
[email protected]
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misoprostol use in Nepal and Indonesia. Estimates for the efficacy of both oxytocin and misoprostol in preventing haemorrhage were taken from a meta-analysis (fewer deaths are consequently predicted due to the link between haemorrhage and death). Ronsmans and Huang also suggest that we overestimate deaths from postpartum haemorrhage and sepsis. But the data they cite1 concerns all Africa and not sub-Saharan Africa, where incidence and case-fatality rates are probably higher (see page 8 of our webappendix). Further, Seale and colleagues2 have argued that maternal sepsis in sub-Saharan Africa is grossly underestimated. Yusuf Ahmed and colleagues correctly point out that many maternal deaths in sub-Saharan Africa are from infectious diseases other than genital tract infections—eg, malaria, tuberculosis, or other HIV-related disorders; these diseases are indeed a considerable burden on maternal health. We would like to clarify that our estimates relating to infection pertain only to puerperal sepsis, defined by WHO as “infection of the genital tract” in the 42 days after birth.3 Our estimates for both the incidence and case fatality of puerperal sepsis are derived from WHO estimates for sub-Saharan Africa (see pages 10–11 of our webappendix), and not from estimates of puerperal infection, which would include malaria and other infectious diseases.3 Thus the estimated effect of oral antibiotics in preventing deaths from puerperal sepsis does not assume any effect on other infectious diseases. As discussed briefly in the conclusion of our paper, the mathematical model could be adapted to consider maternal deaths from other causes; the limiting factor is the availability of evidence to use in estimating plausible values of the model parameters. We agree with Braunholtz and colleagues that legitimate questions remain about the feasibility of sustainable community interventions; this is precisely why we advocated the careful
Correspondence
University of California, Berkeley, CA 94720, USA (MP, NP); Chelsea and Westminster Hospital, London, UK (HER); Johns Hopkins University, Baltimore, MD, USA (HS); University of California, San Francisco, CA, USA (PD, VA); Ziauddin University, Karachi, Pakistan (SNJ); Venture Strategies Innovations, Dar es Salaam, Tanzania (ER); Venture Strategies Innovations, Berkeley, CA, USA (NH); Jose Macamo Hospital, Maputo, Mozambique (CB); Ipas, Chapel Hill, NC, USA (RG); Befelatanana Maternity Center, Antananarivo, Madagascar (JPR); International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh (AQ); University of Nairobi, Nairobi, Kenya (JK); and Ministry of Health, Lilongwe, Malawi (EK) 1
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Pagel C, Lewycka S, Colbourn T, et al. Estimation of potential effects of improved communitybased drug provision, to augment healthfacility strengthening, on maternal mortality due to post-partum haemorrhage and sepsis in sub-Saharan Africa: an equity-effectiveness model. Lancet 2009; 374: 1441–48. Prata N, Gessessew A, Abraha AK, Holston M, Potts M. Prevention of postpartum hemorrhage: options for home births in rural Ethiopia. Afr J Reprod Health 2009; 13: 87–95. International Confederation of Midwives (ICM) / International Federation of Gynaecology and Obstetrics (FIGO). Prevention and treatment of post-partum haemorrhage: new advances for low resource settings: joint statement. http://www. pphprevention.org/files/FIGO-ICM_ Statement_November2006_Final.pdf (accessed Jan 13, 2010). WHO. WHO recommendations for the prevention of postpartum haemorrhage. http://whqlibdoc.who.int/hq/2007/WHO_ MPS_07.06_eng.pdf (accessed Jan 13, 2010). WHO. WHO Statement regarding the use of misoprostol for postpartum haemorrhage prevention and treatment. http://whqlibdoc. who.int/hq/2009/WHO_RHR_09.22_eng.pdf (accessed Jan 13, 2010).
Preventable deaths in sickle-cell anaemia in African children Science Photo Library
Thomas Williams and colleagues (Oct 17, p 1364)1 provide the strongest evidence to date on the risk of bacteraemia in sub-Saharan African children with sickle-cell anaemia. That Streptococcus pneumoniae was the leading cause of bacteraemia in such children in Kenya comes as no surprise given that this has already been shown in the general population of children in the same region.2 Data on the use of penicillin prophylaxis or prior immunisation with pneumococcal 460
polysaccharide vaccine in children with sickle-cell anaemia in the population study would have been helpful in further defining the magnitude of this problem. Given the prevailing data on the burden of pneumococcal disease in the general population of children in the subregion,2 priority should be given to immunising children with sicklecell anaemia as a minimum, while the relative importance of other prevalent encapsulated bacterial pathogens in the subregion are explored. The leading cause of childhood bacteraemia in Malawi is non-typhi salmonella, not S pneumoniae,3 and virtually all the reports of bacteraemia in sickle-cell anaemia from Nigeria, the most populated country in sub-Saharan Africa and home to the largest population of children with sickle-cell anaemia, did not identify S pneumoniae as a significant pathogen.4 Although these studies may have had methodological flaws, the published results continue to promote complacency in developing structured prophylactic management of these children.5 The role of Neisseria meningitidis and Salmonella typhi, agents for which licensed vaccines already exist, deserve attention and development of vaccines against nontyphi salmonellae should be explored. Stemming the death toll from sicklecell anaemia should be a priority within the Millennium Development Goals for reduction of childhood morality in the subregion. I declare that I have no conflicts of interest.
Stephen Obaro
[email protected] Division of Pediatric Infectious Disease, Michigan State University, East Lansing, MI 48824, USA 1
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Williams TN, Uyoga S, Macharia A, et al. Bacteraemia in Kenyan children with sickle-cell anaemia: a retrospective cohort and case-control study. Lancet 2009; 374: 1364–70. Berkley JA, Lowe BS, Mwangi I, et al. Bacteremia among children admitted to a rural hospital in Kenya. N Engl J Med 2005; 352: 39–47.
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O’Brien KL, Wolfson LJ, Watt JP, et al, for the Hib and Pneumococcal Global Burden of Disease Study Team. Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. Lancet 2009; 374: 893–902. Walsh AL, Phiri AJ, Graham SM, Molyneux EM, Molyneux ME. Bacteremia in febrile Malawian children: clinical and microbiologic features. Pediatr Infect Dis J 2000; 19: 312–18. Obaro S. Pneumococcal infections and sickle cell disease in Africa: does absence of evidence imply evidence of absence? Arch Dis Child 2009; 94: 713–16.
Thomas Williams and colleagues1 present important new evidence on the epidemiology of bacteraemias in children with sickle-cell anaemia in Kenya. Recently, a group of reports2–4—also from east and central Africa—have raised concern that the landscape of bacterial drug resistance may be changing in this part of the world. The emergence of extended-spectrum β-lactamaseproducing gram-negative bacteria (ESBLs; specifically among Escherichia coli, Klebsiella pneumoniae, and non-typhoidal salmonella strains) in hospital inpatients and in the community is a most unwelcome change for the worse in the landscape of drug resistance in Africa. ESBLs compromise the cephalosporin classes of antibiotics which have become a vital part of curative programmes in east Africa. Further, the expression of these enzymes is associated with the presence of resistance to other antibiotic classes.5 Since E coli, K pneumoniae, and nontyphoidal salmonella were commonly isolated in the study presented by Williams and colleagues, we request them to report on the prevalence of drug resistance patterns consistent with the presence of ESBL-producing strains. In general, it would be welcome if reports on the epidemiology of bacterial infection in sub-Saharan Africa could routinely comment on drug resistance profiles, including resistance patterns that are compatible with the presence of ESBL-producing organisms, since they have very important implications on the choice of antibiotic therapy for www.thelancet.com Vol 375 February 6, 2010
