Open Access Open Badges Research article

Transmission patterns of smallpox: systematic review of natural outbreaks in Europe and North America since World War II

Vibha Bhatnagar12*, Michael A Stoto3, Sally C Morton4, Rob Boer45 and Samuel A Bozzette14

Author Affiliations

1 Health Services Research and Development, Veterans Affairs San Diego Healthcare System, San Diego, California, USA

2 Department of Family and Preventive Medicine, University of California San Diego, San Diego, California, USA

3 The RAND Center for Domestic and International Health Security, Arlington, Virginia, USA

4 The RAND Center for Domestic and International Health Security, Santa Monica, California, USA

5 Department of Public Health, Erasmus MC, University Medical Center Rotterdam, The Netherlands

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BMC Public Health 2006, 6:126  doi:10.1186/1471-2458-6-126

Published: 5 May 2006



Because smallpox (variola major) may be used as a biological weapon, we reviewed outbreaks in post-World War II Europe and North America in order to understand smallpox transmission patterns.


A systematic review was used to identify papers from the National Library of Medicine, Embase, Biosis, Cochrane Library, Defense Technical Information Center, WorldCat, and reference lists of included publications. Two authors reviewed selected papers for smallpox outbreaks.


51 relevant outbreaks were identified from 1,389 publications. The median for the effective first generation reproduction rate (initial R) was 2 (range 0–38). The majority outbreaks were small (less than 5 cases) and contained within one generation. Outbreaks with few hospitalized patients had low initial R values (median of 1) and were prolonged if not initially recognized (median of 3 generations); outbreaks with mostly hospitalized patients had higher initial R values (median 12) and were shorter (median of 3 generations). Index cases with an atypical presentation of smallpox were less likely to have been diagnosed with smallpox; outbreaks in which the index case was not correctly diagnosed were larger (median of 27.5 cases) and longer (median of 3 generations) compared to outbreaks in which the index case was correctly diagnosed (median of 3 cases and 1 generation).


Patterns of spread during Smallpox outbreaks varied with circumstances, but early detection and implementation of control measures is a most important influence on the magnitude of outbreaks. The majority of outbreaks studied in Europe and North America were controlled within a few generations if detected early.