Correspondence
1 For more on WHOs IMAI initiative see http://apps. who.int/bookorders/anglais/ detart1.jsp?sesslan=1%20 &codlan=1&codcol= 15&codcch=830
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For more on global estimates of disease burden see http://www. who.int/healthinfo/global_ burden_disease/en/index.html
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The Lancet Infectious Diseases. For sepsis, the drugs don’t work. Lancet Infect Dis 2012; 12: 89. Bion J, Taylor N, Petros AJ, Silvestri L, van Saene HKF. Selective digestive decontamination and antibiotic resistance. Lancet Infect Dis 2012; 12: 181. Silvestri L, van Saene HKF, de la Cal MA, et al. Surviving sepsis campaign needed consensus to exclude selective decontamination of the digestive tract. Crit Care Med 2008; 36: 2716–17. de Smet AM, Kluytmans JA, Blok HE, et al. Selective digestive tract decontamination and selective oropharyngeal decontamination and antibiotic resistance in patients in intensive-care units: an open-label, clustered group-randomised, crossover study. Lancet Infect Dis 2011; 11: 372–80. Petros AJ, Taylor N, van Saene HKF, Silvestri L. Gut overgrowth harms the critically ill. Intensive Care Med 2011; 37: 1560–62. Conraads VM, Jorens PG, De Clerk LS, et al. Selective intestinal decontamination in advanced chronic heart failure: a pilot trial. Eur J Heart Fail 2004; 6: 483–91.
Your Editorial1 emphasises the substantial burden of sepsis worldwide and the disappointing absence of specific drugs to treat it. Development of such new treatments is crucial; however, most of the estimated 15–19 million cases of sepsis globally are in low-income and middle-income countries,2 which are home to more than 80% of the world’s population. Because of the scarcity of many basic necessities that are needed for the provision of medical care in many low-resource settings, novel treatments for sepsis are unlikely to become available to much of the world for many years. For example, many sub-Saharan African hospitals cannot provide supplemental oxygen because this therapy or the necessary delivery equipment are often unavailable.3 In view of the importance of early and appropriate treatment of sepsis, two basic strategies are needed in lowresource settings: development and implementation of standardised, evidence-based approaches to sepsis care, which are pertinent to these settings; and improvement in the capacity of essential health systems to reliably provide the most fundamental treatments of sepsis and its complications—namely, oxygen, antimicrobials, and fluids.
WHO’s Integrated Management of Adolescent and Adult Illness (IMAI) initiative has championed the first strategy by developing consensusbased treatment guidelines that are specific to low-resource settings. These guidelines have been piloted in various countries, including Uganda, Ethiopia, and Malawi. Research is strikingly scarce on the epidemiology, management, and outcomes of sepsis in low-resource settings. This research is important for informing the evidence base for further guideline development and implementation. The unanticipated increase in mortality noted in the treatment group of the Fluid Expansion as Supportive Therapy (FEAST) trial4 of fluid boluses in African children with severe infection underscores the necessity of assessment of interventions in the at-risk population, and the potential dangers of extrapolation of tenets of sepsis management that are established in high-resource settings. The second strategy requires acknowledgment of the burden of sepsis at the country level and a willingness to apply scarce resources judiciously. Akin to the development of surgical, trauma, and obstetric capacity, a compelling argument about cost-effectiveness exists to the development of essential health systems that can rapidly recognise and treat sepsis and other severe illnesses.5 Quality clinical research and prudent augmentation of essential health-care capacity in low-resource settings deserve an increased priority if we are to reduce the colossal burden of sepsis worldwide. STJ and EW have served on a WHO working group on sepsis in low-resource settings and contributed to the development of IMAI treatment guidelines for severe illness. STJ is an editor of the IMAI District Clinician Manual: hospital care for adolescents and adults. JRO has served on the Pulmonary Guideline Review Panel for the WHO IMAI District Clinician Manual.
Shevin T Jacob, Justin R Ortiz, *Eoin West
[email protected]
International Respiratory and Severe Illness Center, University of Washington, Seattle, WA 98104, USA 1
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The Lancet Infectious Diseases. For sepsis, the drugs don’t work. Lancet Infect Dis 2012; 12: 89. Adhikari NK, Fowler RA, Bhagwanjee S, Rubenfeld GD. Critical care and the global burden of critical illness in adults. Lancet 2010; 376: 1339–46. Belle J, Cohen H, Shindo N, et al. Influenza preparedness in low-resource settings: a look at oxygen delivery in 12 African countries. J Infect Dev Ctries 2010; 4: 419–24. Maitland K, Kiguli S, Opoka RO, et al. Mortality after fluid bolus in African children with severe infection. N Engl J Med 2011; 364: 2483–95. Riviello ED, Letchford S, Achieng L, Newton MW. Critical care in resource-poor settings: lessons learned and future directions. Crit Care Med 2011; 39: 860–67.
Virus suppression, eradication, or tolerance to treatment in patients with chronic hepatitis B In their Review, Robert Gish and colleagues1 provided an overview of the mechanisms of antiviral drug resistance of chronic hepatitis B and drew attention to the importance of selecting a first-line treatment, such as entecavir or tenofovir, with a high threshold for resistance. The Review will be very helpful for understanding and choosing the correct treatment. Although success rates for treatment of chronic hepatitis B have been improving during the recent decades, the confirmed treatment strategy seems to only focus on the permutation and combination of antiviral drugs. Moreover, most patients with chronic hepatitis B require long-term and even lifetime treatment. Because of high costs and insufficient healthcare resources, many patients do not receive proper antiviral treatment, especially in developing countries with the highest burden of chronic hepatitis B. Are there likely to be more potent treatments for the management of chronic hepatitis B in the future? First, how can we achieve persistent suppression of hepatitis B virus www.thelancet.com/infection Vol 12 October 2012
