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The new england journal of medicine Effectiveness of Antimalarial Drugs
to the editor: In his review article (April 14 issue),
by eliminating an effective treatment and increas- Baird1 states that prescribing “chloroquine . . . ing the chance of the development of resistance toin any setting, except one in which its effective- sulfadoxine–pyrimethamine.2ness has recently been demonstrated, should be We believe that chloroquine continues to have a considered irresponsible.” As physicians who have useful role in regions where falciparum malaria isworked in rural Zambia, where malaria is endem- endemic and resources are severely limited, even inic, we have witnessed the effect of falciparum ma- the face of significant resistance.
laria on children and are sensitive to Baird’s con- Stephen J. Gerrish, M.D.
cerns. However, adults rarely become severely ill. Kara CounsellingWe think that chloroquine remains an inexpen- Lusaka, Zambiasive, rapid-acting drug with few side effects and gerrish@zamnet.zmthat it is effective in most patients.
However, recent policy changes removed chlo- Costa Rica Straat roquine from our formulary on short notice and 2408 MH Alphen aan den Rijn, the Netherlands
without an effective and timely alternative. When 1. Baird JK. Effectiveness of antimalarial drugs. N Engl J Med 2005;
artemether-based drugs were supplied, the cost, 352:1565-77.
Pitmang SL, Thatcher TD, Madaki JK, Egah DZ, Fischer PR.
which was 20 to 50 times that of chloroquine, pre- Comparison of sulfadoxine-pyrimethamine with and without chlo-
vented its full implementation or use in patients for roquine for uncomplicated malaria in Nigeria. Am J Trop Med Hyg
whom it was clearly indicated. In addition, the re- 2005;72:263-6.
moval of chloroquine made its use in combination
with sulfadoxine–pyrimethamine impossible, there- to the editor: The adapted map in Figure 1 and its
legend in Baird’s article are misleading and appearto suggest that the southernmost African coun- THIS WEEK’S LETTERS
tries — South Africa, Swaziland, Lesotho, Botswa-na, and Namibia — have no malaria. Although Effectiveness of Antimalarial Drugs
these countries have some of the lowest rates of Respiratory Syncytial Virus Infection in Elderly
malaria in southern Africa (overall rate, <0.1 person at risk per square kilometer), malaria remains amajor cause of disease, death, and poverty there.
Treatment of Mild Asthma
Despite the presence of malaria-free districts, 10 Hyponatremia in Marathon Runners
percent of the people in South Africa and 66 per-cent of those in Namibia reside in regions with Inflammation, Atherosclerosis, and Coronary
malaria that have stable or unstable (epidemic- Artery Disease
prone) transmission of malaria.1 The resistance of Physician as Serial Killer
Plasmodium falciparum (the main plasmodium par-asite) to chloroquine is widespread, resistance to Medical Mystery: Bradycardia — The Answer
sulfadoxine–pyrimethamine is becoming increas- Natalizumab and Progressive Multifocal
ingly common, and multidrug resistance has been Leukoencephalopathy
reported.2-4 In these countries with unstable ma-laria transmission, all age groups are at risk for Downloaded from at HHS LIBRARIES CONSORTIUM on August 1, 2005 . Copyright 2005 Massachusetts Medical Society. All rights reserved. malaria, whereas in the southern African countries Andrew Herxheimer, F.R.C.P.
with stable malaria transmission (Angola, Como- United Kingdom Cochrane Center
ros, Madagascar, Malawi, Mozambique, Tanzania, Oxford OX2 7LG, United Kingdom
and Zambia), children younger than five years of 1. Overbosch D, Schilthuis H, Bienzle U, et al. Atovaquone-progua-
age and pregnant women are at the greatest risk nil versus mefloquine for malaria prophylaxis in nonimmune trav-
for malaria.
elers: results from a randomized, double-blind study. Clin Infect Dis2001;33:1015-21.
Potasman I, Juven Y, Weller B, Schwartz E. Does mefloquine prophylaxis affect electroencephalographic patterns? Am J Med 2002; National Institute of Allergy and Infectious Diseases Schlagenhauf P, Tschopp A, Johnson R, et al. Tolerability of Southern Africa Malaria Control Web site. (Accessed July 7, malaria chemoprophylaxis in non-immune travellers to sub-Saharan Africa: multicentre, randomised, double blind, four arm study. BMJ Williams CH, Fredlund VG. Resistant malaria in KwaZulu-Natal.
Croft AM, Herxheimer A. Adverse effects of the antimalaria Roper C, Pearce R, Bredenkamp B, et al. Antifolate antimalarial drug, mefloquine: due to primary liver damage with secondary thy- resistance in southeast Africa: a population-based analysis. Lancet roid involvement? BMC Public Health 2002;2:6. (Also available at Schwab U, Alloueche A, Doherty JF. Multidrug-resistant malaria from South Africa. Clin Infect Dis 2005;40:493.
dr. baird replies: Gerrish and De Koning express
their views about the withdrawal of chloroquine
to the editor: Baird states that “mefloquine given
before alternatives become available. The advo- as prophylaxis is as well tolerated as other anti- cated abandonment of chloroquine speaks to themalarial drugs.” Recent trials do not support this difference between “most” patients with a satisfac-view, however. Three randomized, controlled tri- tory therapeutic response and “all” such patients.
als of mefloquine prophylaxis in nonmilitary travel- Needless suffering occurs in that range of differ-ers reported an excess of adverse neuropsychiatric ence between them, be it narrow or wide. The au-effects in the mefloquine groups.1-3 Schlagenhauf thorities responsible for the decision either toand colleagues noted that mefloquine and chloro- continue or to withdraw chloroquine bear the re-quine–chloroguanide were associated with simi- sponsibility for either of those actions, as well aslar rates of adverse events and that both regimens for the provision of alternative therapies.
showed a trend toward a greater frequency of se- Smego points to the low risk of malaria across vere adverse events than did regimens of doxycy- the southern frontier of regions where malariacline or atovaquone–chloroguanide (12 percent had is endemic on the African continent. The map wasadverse events with chloroquine–chloroguanide based on similar maps published by the Worldand 11 percent with mefloquine, vs. 7 percent with Health Organization (WHO), as noted in the legend;atovaquone–chloroguanide and 6 percent with dox- these maps illustrate the locations of appreciableycycline; P=0.14); the frequency of mild-to-mod- risk. The WHO officers who constructed the orig-erate adverse effects showed a similar pattern (P= inal maps undoubtedly applied a threshold of the 0.05, for the comparison of all four treatments).3 risk of infection, but one I do not know. The risk of Early trials of mefloquine in prisoners and sol- malaria occurs almost anywhere between the po- diers suggested good tolerability, but the results lar circles (as outbreaks near North American cit-cannot be generalized to civilian travelers who have ies demonstrate). If the risk mentioned by Smegovery different lifestyles and higher rates of concur- crosses the threshold for the mapping of substan-rent medication use and coexisting illnesses.4 With tial risk, I hope his letter and this reply will contrib-safer drugs now available, we believe mefloquine ute to the improved accuracy of maps in the future.
should no longer be used as first-line prophylaxis The recent studies cited by Croft et al. were dis- cussed in my review. We have differences of in- Ashley M. Croft, D.T.M.&H., F.F.P.H.M.
terpretation. Croft et al. express the view that mef-loquine should no longer be used as first-line British Forces Germany Health Service41179 Mönchengladbach, Germany prophylaxis on the basis of what I consider statisti- cally insignificant (P= 0.14) differences in the risk of severe adverse events between this and otherantimalarial drugs. On the less important issue of London UniversityLondon SE5 8AF, United Kingdom mild-to-moderate adverse events, mefloquine and Downloaded from at HHS LIBRARIES CONSORTIUM on August 1, 2005 . Copyright 2005 Massachusetts Medical Society. All rights reserved. The new england journal of medicine chloroquine–chloroguanide (a drug combination very early and limited clinical trials in special popu-used successfully by travelers for several decades lations may mislead readers; mefloquine has beenbut now abandoned because of poor protective ef- widely used by the traveling public for more thanficacy) are similar. On the basis of adverse-event a decade. The responsibility for the decision toprofiles, mefloquine clearly is associated with a sta- recommend mefloquine as first-line or as alterna-tistically significant higher risk of neuropsychiatric tive prophylaxis rests with the national authoritiessymptoms than other antimalarial drugs, as I ex- weighing factors of safety, efficacy, cost, and otherplained in my review. For most travelers who are determinants of effectiveness in the context of theconsidered good candidates for mefloquine pro- populations they serve.
phylaxis, including pregnant women and young J. Kevin Baird, Ph.D.
children, the regimen carries distinct advantagesin terms of cost, convenience, proven efficacy, and U.S. Naval Medical Research Unit No. 2, Jakarta, Indonesia demonstrated safety. The suggestion that the safety FPO AP 96520 USAand adverse-event profiles of mefloquine hinge on Respiratory Syncytial Virus Infection in Elderly Adults
to the editor: Falsey et al. (April 28 issue), in their
to the editor: Falsey and colleagues probably un-
report on respiratory syncytial virus (RSV) infec- derestimate the burden of influenza-related mor-tion in elderly and high-risk adults,1 claim that “the tality among elderly patients. Influenza-related hos-symptoms and signs of RSV infection and those pitalization often results from secondary bacterialof influenza were not substantially different” and infection that occurs after the virus is cleared, ham-also that the demographic and clinical character- pering confirmation of the presence of the virusistics of the patients with influenza and of those by viral isolation, polymerase-chain-reaction analy-with RSV infection were similar. If the clinical man- sis, or serologic studies on admission. Studies ofifestations of the two diseases were the same, and excess mortality,1,2 which sidestep the difficultiesif the populations that were affected could not be of case ascertainment, set the current mortality bur-distinguished, how do the authors explain the strik- den associated with influenza in the elderly at threeing differences between the patients with influen- times that of RSV infection.
za and those with RSV infection in the rate of office This point pales, however, beside the fascinat- visits (42 percent vs. 17 percent, respectively) and ing data presented by Falsey et al. on the benefits ofuse of antibiotics (33 percent vs. 9 percent)? influenza vaccine. Vaccine coverage among elderly Most clinicians make treatment decisions on hospitalized patients with confirmed influenza was the basis of a combination of science, experience, 68 percent, as compared with 75 percent amongand intuition. I suspect that there was some differ- those with RSV infection, indicating that the effi-ence that was either not captured or not quantified cacy of vaccination in preventing influenza-relat-that influenced both patients’ decisions to see a phy- ed hospitalizations was only 29 percent (95 per-sician and physicians’ decisions to prescribe an cent confidence interval, 2 to 48 percent). A singleantibiotic.
clinical trial of influenza vaccination in the elderlyshowed that the efficacy of the vaccine against mild influenza was 57 percent.3 Cohort studies without laboratory confirmation show an astonishing ben- Newtown Square, PA efit in terms of mortality from all causes in the el-derly, but such studies are prone to self-selection Falsey AR, Hennessey PA, Formica MA, Cox C, Walsh EE. Respi- ratory syncytial virus infections in elderly and high-risk adults.
Falsey et al. may come closest to the truth for severe Downloaded from at HHS LIBRARIES CONSORTIUM on August 1, 2005 . Copyright 2005 Massachusetts Medical Society. All rights reserved.


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Recent Declines in ß-Lactam and MLSB Resistances Among S. pneumoniae and Age-Related Effects: Report from the SENTRY Antimicrobial Surveillance Program (North America, 1997 - 2002) RN JONES, DM JOHNSON, HS SADER, TR FRITSCHE The JONES Group/JMI Laboratories, North Liberty, IA A M E N D E D A B S T R A C T M A T E R I A L S A C D S ( C o n t i n u e d ) Background: The

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