We described a widespread measles outbreak involving 18,431 laboratory-confirmed measles case-patients, the largest outbreak since 1992 when more than 22,000 clinically diagnosed case-patients were reported 
. Due to challenges with submission and collation of clinical notifications, laboratory confirmation was conducted throughout the course of the outbreak, even though this is not a WHO recommendation 
. As our analysis was restricted to laboratory-confirmed case-patients it represents a minimum estimate of the total number of persons infected. Children aged <1 year were the most affected age group especially those <9 months. Even though the nationwide periodic vaccination campaign was conducted late in the outbreak course (13 months after the first case-patients were reported), we estimate that over 1,300 laboratory-confirmed case-patients were prevented.
Similar to the measles outbreak from 2003 through 2005, the 2009 to 2011 outbreak began in Gauteng Province 
. Possible reasons for this include the fact that Gauteng Province has a high density population and experiences relatively high rates immigration from other areas and countries 
. The numbers of reported case-patients differed between provinces. Variation in reported case-numbers by geographic area may be affected by differential access to care between urban and rural areas, as well as differences in laboratory specimen taking practices and underreporting in some areas.
A high proportion of cases (24%) were aged <9 months, those not eligible to receive the first dose of measles vaccine from routine immunisation in South Africa. Our data indicate that there is a substantial immunity gap in this group, possibly due to waning maternal antibodies in the setting when immunity is from vaccination not natural infection, 
compounded by HIV exposure 
. Disease in this age group is of concern as they are at high risk for severe and complicated measles. By 6 months of age, HIV-1 infected infants have lower antibody levels that are unlikely to affect immune response to measles vaccine 
. Lepage et
demonstrated a higher seroconversion rates in HIV-infected children vaccinated at 6 months 
. In South Africa, a supplemental dose of measles vaccine at six months of age currently is recommended for infants at high risk especially HIV-infected, HIV-exposed [Unpublished: Integrated management of childhood illness, IMCI, South Africa 2010, HIV infection in children, Module S1. Draft version] and infants admitted to hospitals 
; however implementation of this recommendation is variable.
Although the highest cumulative incidence was in those aged <5 years, 48% were reported in those aged ≥5 years. This suggests that a significant immunity gap existed in this age group, likely due to the accumulation of susceptible individuals over several years. An additional booster dose at school entry, which is currently not part of the routine schedule in South Africa, would be of value. Recent outbreaks in Europe have shown a higher proportion (64%) of cases were among patients aged ≥5 years 
; however, in France the highest incidence was observed in those aged <1 year 
In 2010, South Africa conducted a non-selective nationwide vaccination campaign that showed an impact, even though it was conducted late in the outbreak course. A reduction in incidence of laboratory-confirmed measles case-patients was observed in all age groups following the nationwide vaccination campaign with a shift in the age distribution of cases away from the targeted age group similar to what has been described in other African settings 
. However, cases continued to be reported within this age group indicating that despite the vaccination campaign an immunity gap continued to exist in this group. More cases could have been averted if the campaign was carried out earlier. It is known that outbreak-response vaccination may fail to contain spread if not conducted promptly, within a short space of time to a wide age range or if the coverage is not adequately high enough 
. The campaign could not be brought forward due to challenges in procuring adequate volumes of registered vaccines and effectively organizing a campaign of such magnitude within a short space of time. Even given these limitations, it does appear that the campaign did have an impact in reducing the total number of measles case-patients and possibly also shortened the duration of the outbreak.
A single outbreak strain was detected, which is reflective of an outbreak with a low vaccine coverage setting. This particular strain of B3 has not circulated in South Africa previously. Genotype B3 viruses have been identified as circulating endemically in West and Central Africa 
. It is thus likely that this strain of genotype B3 was imported into South Africa from this region. During 2009 to 2010 other African countries also experienced measles outbreaks; these were predominantly caused by strains of genotype B3 
Our study had several limitations. First, data presented here relate only to laboratory-confirmed measles case-patients tested at the NICD-NHLS and do not include case-patients where no specimens were taken or from specimens that were tested only at the private laboratories. Second, we may have underestimated the number of cases as testing efficiencies may be greater in better resourced provinces and not all patients will seek medical advice. In addition clinicians may be more likely to test children. Third, we could not comment on the clinical presentation and/or severity of cases, vaccination status and mortality data as these information is rarely submitted to the laboratory. Fourth, our estimates of vaccination coverage were based on administrative data, which depend on the validity of the numerators or denominators and therefore can only provide a relatively imprecise estimation of the vaccination coverage. Reported coverage figures of >100% in some areas are likely a result of use of denominators extrapolated from the 2001 census. Unfortunately no post campaign surveys were conducted. Lastly, we may have underestimated the impact of the vaccination campaign as cases prevented during the campaign period were excluded from the analysis as it is expected to see the impact from as early as 72 hrs to the first 2 weeks of campaign. In addition, unvaccinated persons may have benefited from the indirect effect of vaccination in the target age group and the two provinces with the highest numbers of cases were excluded from the analysis. In addition the campaign in Gauteng could have reduced case numbers in neighbouring provinces 
. Numbers of reported cases were decreasing in some provinces at the time the campaign was conducted, thus some of the reductions could have been due to the epidemic burning out. We did however; attempt to adjust for this by controlling for trends in the age groups not targeted for vaccination. The contribution of seasonal forces to the outbreak is unclear although peaks in incidence in the outbreak were observed in Autumn and Spring, the peak seasonal periods prior to widespread introduction of measles vaccine in South Africa was also experienced during Spring and Autumn each year 
. Apart from reduced testing in the Western Cape Provinces there were no documented changes in reporting efficiency following the campaign.
In conclusion, this nationwide outbreak, affecting a wide age range, highlights that South Africa remains vulnerable to large measles outbreaks. Efforts to maintain high routine measles vaccination coverage should be emphasized. These can be strengthened by conducting biannual analysis of the potential risk of measles outbreaks with action plans to improve routine vaccination coverage if below 90%. Specific interventions such as immunisation awareness days can also be held to reach unvaccinated children and/or those who did not develop protective immune responses; thus lessening the number of susceptible individuals. Furthermore, efforts to conform to the recommendations for a measles vaccine dose at six months for infants at high risk should be strengthened. In addition, a booster dose at school entry should be considered. Our findings indicate that mass measles vaccination campaigns conducted during the course of an outbreak may reduce total case numbers affected in countries where there is a potential for a large outbreak to occur. However, the decision to conduct a campaign should be based on a comprehensive risk-benefit assessment including assessment of the potential for epidemic spread and the costs of the intervention.