Measles Outbreak in South Africa: Epidemiology of Laboratory-Confirmed Measles Cases and Assessment of Intervention, 2009–2011

Background

Since 1995, measles vaccination at nine and 18 months has been routine in South Africa; however, coverage seldom reached >95%. We describe the epidemiology of laboratory-confirmed measles case-patients and assess the impact of the nationwide mass vaccination campaign during the 2009 to 2011 measles outbreak in South Africa.

Methods

Serum specimens collected from patients with suspected-measles were tested for measles-specific IgM antibodies using an enzyme-linked immunosorbent assay and genotypes of a subset were determined. To estimate the impact of the nationwide mass vaccination campaign, we compared incidence in the seven months pre- (1 September 2009–11 April 2010) and seven months post-vaccination campaign (24 May 2010–31 December 2010) periods in seven provinces of South Africa.

Results

A total of 18,431 laboratory-confirmed measles case-patients were reported from all nine provinces of South Africa (cumulative incidence 37 per 100,000 population). The highest cumulative incidence per 100,000 population was in children aged <1 year (603), distributed as follows: <6 months (302/100,000), 6 to 8 months (1083/100,000) and 9 to 11 months (724/100,000). Forty eight percent of case-patients were ≥5 years (cumulative incidence 54/100,000). Cumulative incidence decreased with increasing age to 2/100,000 in persons ≥40 years. A single strain of measles virus (genotype B3) circulated throughout the outbreak. Prior to the vaccination campaign, cumulative incidence in the targeted vs. non-targeted age group was 5.9-fold higher, decreasing to 1.7 fold following the campaign (P<0.001) and an estimated 1,380 laboratory-confirmed measles case-patients were prevented.

Conclusion

We observed a reduction in measles incidence following the nationwide mass vaccination campaign even though it was conducted approximately one year after the outbreak started. A booster dose at school entry may be of value given the high incidence in persons >5 years.     

Knowledge,Attitudes, and Practices regarding Diarrhea and Cholera following an Oral Cholera Vaccination Campaign in the Solomon Islands

BackgroundIn response to a 2011 cholera outbreak in Papua New Guinea, the Government of the Solomon Islands initiated a cholera prevention program which included cholera disease prevention and treatment messaging, community meetings, and a pre-emptive cholera vaccination campaign targeting 11,000 children aged 1–15 years in selected communities in Choiseul and Western Provinces.ConclusionsThis pre-emptive OCV campaign in a cholera-naïve community provided a unique opportunity to assess household-level knowledge, attitudes, and practices regarding diarrhea, cholera, and water, sanitation, and hygiene (WASH). Our findings suggest that education provided during the vaccination campaign may have reinforced earlier mass messaging about cholera and diarrheal disease in vaccinated communities.     

Documenting Freedom From Disease and Re-Establishing a Free Status After a Breakdown Rabies

Rabies reappeared in Finland in the spring of 1988 after a 29-year absence. This time rabies occurred in sylvatic form and the major species involved was the raccoon dog. During the outbreak 1988–89 66 animals were diagnosed rabid. Vaccination of cats, cattle and horses was strongly recommended and vaccination of dogs was compulsory in the outbreak area. A field trial was started on oral immunisation of raccoon dogs and foxes against rabies using baits containing rabies vaccine strain. The outbreak area and a wide buffer zone were baited three times. Finland was declared free of rabies again in 1991. Oral vaccination campaign with vaccine baits has been organised along the southeastern border once a year since the beginning of 90s. Continuous surveillance and epidemiological screening is necessary to detect any new outbreaks of rabies at an early stage.     

Leptospirosis outbreak following severe flooding: a rapid assessment and mass prophylaxis campaign; Guyana, January-February 2005

Background

Leptospirosis is a zoonosis usually transmitted through contact with water or soil contaminated with urine from infected animals. Severe flooding can put individuals at greater risk for contracting leptospirosis in endemic areas. Rapid testing for the disease and large-scale interventions are necessary to identify and control infection. We describe a leptospirosis outbreak following severe flooding and a mass chemoprophylaxis campaign in Guyana.

Methodology/Principal Findings

From January–March 2005, we collected data on suspected leptospirosis hospitalizations and deaths. Laboratory testing included anti-leptospiral dot enzyme immunoassay (DST), immunohistochemistry (IHC) staining, and microscopic agglutination testing (MAT). DST testing was conducted for 105 (44%) of 236 patients; 52 (50%) tested positive. Four (57%) paired serum samples tested by MAT were confirmed leptospirosis. Of 34 total deaths attributed to leptospirosis, postmortem samples from 10 (83%) of 12 patients were positive by IHC. Of 201 patients interviewed, 89% reported direct contact with flood waters. A 3-week doxycycline chemoprophylaxis campaign reached over 280,000 people.

Conclusions

A confirmed leptospirosis outbreak in Guyana occurred after severe flooding, resulting in a massive chemoprophylaxis campaign to try to limit morbidity and mortality.     

The Impact of a One-Dose versus Two-Dose Oral Cholera Vaccine Regimen in Outbreak Settings: A Modeling Study

BackgroundIn 2013, a stockpile of oral cholera vaccine (OCV) was created for use in outbreak response, but vaccine availability remains severely limited. Innovative strategies are needed to maximize the health impact and minimize the logistical barriers to using available vaccine. Here we ask under what conditions the use of one dose rather than the internationally licensed two-dose protocol may do both.ConclusionsReactive vaccination campaigns using a single dose of OCV may avert more cases and deaths than a standard two-dose campaign when vaccine supplies are limited, while at the same time reducing logistical complexity. These findings should motivate consideration of the trade-offs between one- and two-dose campaigns in resource-constrained settings, though further field efficacy data are needed and should be a priority in any one-dose campaign.     

Adaptive Management and the Value of Information: Learning Via Intervention in Epidemiology

Optimal intervention for disease outbreaks is often impeded by severe scientific uncertainty. Adaptive management (AM), long-used in natural resource management, is a structured decision-making approach to solving dynamic problems that accounts for the value of resolving uncertainty via real-time evaluation of alternative models. We propose an AM approach to design and evaluate intervention strategies in epidemiology, using real-time surveillance to resolve model uncertainty as management proceeds, with foot-and-mouth disease (FMD) culling and measles vaccination as case studies. We use simulations of alternative intervention strategies under competing models to quantify the effect of model uncertainty on decision making, in terms of the value of information, and quantify the benefit of adaptive versus static intervention strategies. Culling decisions during the 2001 UK FMD outbreak were contentious due to uncertainty about the spatial scale of transmission. The expected benefit of resolving this uncertainty prior to a new outbreak on a UK-like landscape would be £45–£60 million relative to the strategy that minimizes livestock losses averaged over alternate transmission models. AM during the outbreak would be expected to recover up to £20.1 million of this expected benefit. AM would also recommend a more conservative initial approach (culling of infected premises and dangerous contact farms) than would a fixed strategy (which would additionally require culling of contiguous premises). For optimal targeting of measles vaccination, based on an outbreak in Malawi in 2010, AM allows better distribution of resources across the affected region; its utility depends on uncertainty about both the at-risk population and logistical capacity. When daily vaccination rates are highly constrained, the optimal initial strategy is to conduct a small, quick campaign; a reduction in expected burden of approximately 10,000 cases could result if campaign targets can be updated on the basis of the true susceptible population. Formal incorporation of a policy to update future management actions in response to information gained in the course of an outbreak can change the optimal initial response and result in significant cost savings. AM provides a framework for using multiple models to facilitate public-health decision making and an objective basis for updating management actions in response to improved scientific understanding.     

Costs of Illness Due to Cholera, Costs of Immunization and Cost-Effectiveness of an Oral Cholera Mass Vaccination Campaign in Zanzibar

Background

The World Health Organization (WHO) recommends oral cholera vaccines (OCVs) as a supplementary tool to conventional prevention of cholera. Dukoral, a killed whole-cell two-dose OCV, was used in a mass vaccination campaign in 2009 in Zanzibar. Public and private costs of illness (COI) due to endemic cholera and costs of the mass vaccination campaign were estimated to assess the cost-effectiveness of OCV for this particular campaign from both the health care provider and the societal perspective.

Methodology/Principal Findings

Public and private COI were obtained from interviews with local experts, with patients from three outbreaks and from reports and record review. Cost data for the vaccination campaign were collected based on actual expenditure and planned budget data. A static cohort of 50,000 individuals was examined, including herd protection. Primary outcome measures were incremental cost-effectiveness ratios (ICER) per death, per case and per disability-adjusted life-year (DALY) averted. One-way sensitivity and threshold analyses were conducted. The ICER was evaluated with regard to WHO criteria for cost-effectiveness. Base-case ICERs were USD 750,000 per death averted, USD 6,000 per case averted and USD 30,000 per DALY averted, without differences between the health care provider and the societal perspective. Threshold analyses using Shanchol and assuming high incidence and case-fatality rate indicated that the purchase price per course would have to be as low as USD 1.2 to render the mass vaccination campaign cost-effective from a health care provider perspective (societal perspective: USD 1.3).

Conclusions/Significance

Based on empirical and site-specific cost and effectiveness data from Zanzibar, the 2009 mass vaccination campaign was cost-ineffective mainly due to the relatively high OCV purchase price and a relatively low incidence. However, mass vaccination campaigns in Zanzibar to control endemic cholera may meet criteria for cost-effectiveness under certain circumstances, especially in high-incidence areas and at OCV prices below USD 1.3.     

A Model for a Chikungunya Outbreak in a Rural Cambodian Setting: Implications for Disease Control in Uninfected Areas

Following almost 30 years of relative silence, chikungunya fever reemerged in Kenya in 2004. It subsequently spread to the islands of the Indian Ocean, reaching Southeast Asia in 2006. The virus was first detected in Cambodia in 2011 and a large outbreak occurred in the village of Trapeang Roka Kampong Speu Province in March 2012, in which 44% of the villagers had a recent infection biologically confirmed. The epidemic curve was constructed from the number of biologically-confirmed CHIKV cases per day determined from the date of fever onset, which was self-reported during a data collection campaign conducted in the village after the outbreak. All individuals participating in the campaign had infections confirmed by laboratory analysis, allowing for the identification of asymptomatic cases and those with an unreported date of fever onset. We develop a stochastic model explicitly including such cases, all of whom do not appear on the epidemic curve. We estimate the basic reproduction number of the outbreak to be 6.46 (95% C.I. [6.24, 6.78]). We show that this estimate is particularly sensitive to changes in the biting rate and mosquito longevity. Our model also indicates that the infection was more widespread within the population on the reported epidemic start date. We show that the exclusion of asymptomatic cases and cases with undocumented onset dates can lead to an underestimation of the reproduction number which, in turn, could negatively impact control strategies implemented by public health authorities. We highlight the need for properly documenting newly emerging pathogens in immunologically naive populations and the importance of identifying the route of disease introduction.     

Mao Zedong's fight against schistosomiasis

In 1956, Mao Zedong began a mass campaign against schistosomiasis in the People's Republic of China. The campaign, which integrated mass mobilization, science, agricultural production, local construction projects, and prophylactic measures, was fueled primarily by a determination to accelerate China's agricultural development. The initial success of this campaign encouraged Mao to embark on the next stage of socialism, the Great Leap Forward. As attention was diverted away from schistosomiasis, however, the disease has again become a major burden to the health of the country.     

Molecular epidemiological study of a mass outbreak caused by enteropathogenic Escherichia coli O157:H45.

We made a molecular analysis of O157:H45 Escherichia coli isolated from a mass outbreak that occurred in Obihiro City. Using DNA analysis, we confirmed this infection case as a mass outbreak. Although the isolates expressed O157 antigen, they did not produce Vero toxin. We concluded they were enteropathogenic E. coli (EPEC) because they had a bfp gene and an EAF plasmid, and further they exhibited local adherence to HEp-2 cells. We believe this is the first report of a mass outbreak by O157 EPEC, and we suggest that PCR using eae- and bfp-specific primers and HEp-2 adherence assay are useful to identify EPEC.     

Viruses in sewage waters during and after a poliomyelitis outbreak and subsequent nationwide oral poliovirus vaccination campaign in Finland.

During an outbreak of paralytic poliomyelitis in Finland in 1984 and 1985 the widespread circulation of the causative wild-type serotype 3 poliovirus in the population was documented by demonstrating the virus in sewage water specimens in 13 different locations in the greater Helsinki district and in 13 other cities or towns all over the country. After the nationwide campaign with oral poliovirus vaccine in 1985, poliovirus serotypes 2 and 3 were readily isolated from sewage waters for up to 2 months, whereas type 1 poliovirus seemed to disappear from the sewage more rapidly. All of these isolates were temperature sensitive and therefore most likely vaccine related. The efficacy of the vaccination campaign in regard to elimination of the epidemic type 3 strain was evaluated by a follow-up study on viruses in sewage waters continued for 12 months through the subsequent expected season of poliomyelitis. Several types of enteroviruses, including five vaccine-related poliovirus strains, were identified in the 72 virus-positive specimens out of 93 studied. No wild-type polioviruses were found, indicating the success of the campaign.     

An integral equation model for the control of a smallpox outbreak

An integral equation model of a smallpox epidemic is proposed. The model structures the incidence of infection among the household, the workplace, the wider community and a health-care facility; and incorporates a finite incubation period and plausible infectivity functions. Linearisation of the model is appropriate for small epidemics, and enables analytic expressions to be derived for the basic reproduction number and the size of the epidemic. The effects of control interventions (vaccination, isolation, quarantine and public education) are explored for a smallpox epidemic following an imported case. It is found that the rapid identification and isolation of cases, the quarantine of affected households and a public education campaign to reduce contact would be capable of bringing an epidemic under control. This could be used in conjunction with the vaccination of healthcare workers and contacts. Our results suggest that prior mass vaccination would be an inefficient method of containing an outbreak.     

Viruses in sewage waters during and after a poliomyelitis outbreak and subsequent nationwide oral poliovirus vaccination campaign in Finland

During an outbreak of paralytic poliomyelitis in Finland in 1984 and 1985 the widespread circulation of the causative wild-type serotype 3 poliovirus in the population was documented by demonstrating the virus in sewage water specimens in 13 different locations in the greater Helsinki district and in 13 other cities or towns all over the country. After the nationwide campaign with oral poliovirus vaccine in 1985, poliovirus serotypes 2 and 3 were readily isolated from sewage waters for up to 2 months, whereas type 1 poliovirus seemed to disappear from the sewage more rapidly. All of these isolates were temperature sensitive and therefore most likely vaccine related. The efficacy of the vaccination campaign in regard to elimination of the epidemic type 3 strain was evaluated by a follow-up study on viruses in sewage waters continued for 12 months through the subsequent expected season of poliomyelitis. Several types of enteroviruses, including five vaccine-related poliovirus strains, were identified in the 72 virus-positive specimens out of 93 studied. No wild-type polioviruses were found, indicating the success of the campaign.     

A Bayesian Approach to Quantifying the Effects of Mass Poultry Vaccination upon the Spatial and Temporal Dynamics of H5N1 in Northern Vietnam

Outbreaks of H5N1 in poultry in Vietnam continue to threaten the livelihoods of those reliant on poultry production whilst simultaneously posing a severe public health risk given the high mortality associated with human infection. Authorities have invested significant resources in order to control these outbreaks. Of particular interest is the decision, following a second wave of outbreaks, to move from a “stamping out” approach to the implementation of a nationwide mass vaccination campaign. Outbreaks which occurred around this shift in policy provide a unique opportunity to evaluate the relative effectiveness of these approaches and to help other countries make informed judgements when developing control strategies. Here we use Bayesian Markov Chain Monte Carlo (MCMC) data augmentation techniques to derive the first quantitative estimates of the impact of the vaccination campaign on the spread of outbreaks of H5N1 in northern Vietnam. We find a substantial decrease in the transmissibility of infection between communes following vaccination. This was coupled with a significant increase in the time from infection to detection of the outbreak. Using a cladistic approach we estimated that, according to the posterior mean effect of pruning the reconstructed epidemic tree, two thirds of the outbreaks in 2007 could be attributed to this decrease in the rate of reporting. The net impact of these two effects was a less intense but longer-lasting wave and, whilst not sufficient to prevent the sustained spread of outbreaks, an overall reduction in the likelihood of the transmission of infection between communes. These findings highlight the need for more effectively targeted surveillance in order to help ensure that the effective coverage achieved by mass vaccination is converted into a reduction in the likelihood of outbreaks occurring which is sufficient to control the spread of H5N1 in Vietnam.     

Design and development of oral drugs for the prophylaxis and treatment of smallpox infection

Smallpox was eradicated by the World Health Organization (WHO) vaccination campaign in the 1970s and the variola virus was restricted to repositories in the United States and Russia. Recently, however, concerns have arisen about the possible existence of variola outside these sites and the potential for using the virus as a weapon of bioterror. The world population now has little residual immunity to smallpox and supplies of the smallpox vaccine are being reconstituted. Large numbers of individuals with various skin diseases or immunosuppression owing to AIDS or organ transplantation medications, or who are pregnant or have heart disease might not be ideal candidates for vaccination with the current live vaccines. It would be useful to have an orally active drug that could be self-administered in case of an outbreak of smallpox.     

Spatial analysis of gypsy moth populations in Sardinia using geostatistical and climate models

• 1 Spatial fluctuations of the Sardinian population of the gypsy moth Lymantria dispar (L.) (Lepidoptera: Lymantriidae) were characterized using geostatistical and climate models. Data on gypsy moth egg mass abundance recorded at 282 permanent monitoring sites from 1980 to 2004 were incorporated in a geographic information system with the vegetational, geomorphological and pedological features of the sites.
• 2 Statistical analyses revealed that the relative outbreak frequency was related to the predominant host tree, slope and elevation of the monitoring sites, whereas there was no correlation between outbreak frequency and exposure and soil type.
• 3 By using bioclimatic modelling, probability maps of gypsy moth outbreaks were generated. The model identified a probability surface with climatic conditions favourable to gypsy moth outbreaks and thus potentially subject to defoliation. The maps included 92 sites where outbreaks never occurred, suggesting that the Sardinian climate may not be a determinant factor for gypsy moth outbreaks.
• 4 The geostatistical method cokriging with outbreak frequency as a covariate was found to be the most suitable technique to estimate gypsy moth egg mass abundance. Semivariograms showed spatial correlation of egg mass abundance within the range 18.5–53 km. The results obtained were used to create regional gypsy moth distribution maps by cokriging, which demonstrated the outbreak foci and different infestation levels at each monitoring area. These results can help to delimit the treatment areas and develop rational gypsy moth management programmes.

     

Hepatitis a outbreak in a public school in Rio de Janeiro,Brazil

From June 1 to July 1 1999, an outbreak involving 25 cases of hepatitis A occurred in a public school in Rio de Janeiro, Brazil. Since these cases were notified to the State Health Department, the National Reference Center for Hepatitis Viruses (CNRHV) was required to investigate the extent of hepatitis A virus (HAV) dissemination. Blood samples from all students were tested for IgM and total anti-HAV antibodies using a commercial enzyme-linked immunoassay (ELISA). At the same time, a questionnaire was completed in order to identify possible risk factors for HAV infection. The environmental investigation showed that there was no fecal contamination of the water supply. The epidemiological investigation demonstrated that almost 50% of this population was susceptible to HAV infection and probably person-to-person transmission was the principal mode of virus dissemination. In this situation, a massive vaccination campaign could control the HAV infection.     

Mapping perceptions related to acceptance of smallpox vaccination by hospital emergency room personnel

Emergency department personnel would be first responders in the event of a bioterror smallpox outbreak, yet few were willing to be vaccinated during the 2002 federal campaign. To better understand vaccination concerns, perceptual mapping methods were used to create multidimensional models of how emergency department personnel (N= 73) in the Philadelphia area perceive the risks and benefits of smallpox vaccination under 4 levels of threat: (1) today; (2) if another terrorist attack happened anywhere in the U.S.; (3) if a smallpox attack happened somewhere in the U.S.; (4) if a smallpox attack happened locally. The perceptual maps show significant shifts in factors that are important for motivating respondents to accept vaccination under increasingly higher levels of threat. In the today scenario, endorsement of vaccination from a credible source, such as a major hospital in the area, was a very important factor (mean =7.10 on a 0-10 scale).However, endorsement was not as important under the 2 higher levels of threat. Under these conditions, respondents'sense of wanting to help in a disaster emerged as an important element the closer the hypothetical attack was to the respondent,ranging in importance from 3.87 under the least threat to 7.35 under the greatest threat scenario. The perceptual maps yield information that would assist planners in designing more effective risk communication strategies tailored to particular audiences and levels of threat. Such communications are important to prepare for a smallpox event or other uncertain outbreak, where it is essential to rapidly vaccinate a critical mass of healthcare workers.     

Imported Genotype 2B Rubella Virus Caused the 2012 Outbreak in Anqing City,China

A rubella outbreak occurred in Anqing city of Anhui province, China, from February to July of 2012, and a total of 241 clinically diagnosed or lab-confirmed patients were reported. The highest number of rubella cases during this outbreak was recorded in teenagers between 10 and 19 years of age who had not previously received the rubella vaccine. Genotyping results indicated that the genotype 2B rubella virus (RV) was responsible for the outbreak. However, a phylogenetic analysis showed that the genotype 2B RVs isolated in Anqing City were not related to 2B RVs found in other cities of Anhui province and in other provinces of China, thus providing evidence for importation. After importation, the transmission of Anqing RVs was interrupted owing to an effective immunization campaign against rubella, suggesting the timeliness and effectiveness of contingency vaccination. Strengthening rubella surveillance, including the integration of epidemiologic information and laboratory data, is a vital strategy for rubella control and elimination. In addition, except for routine immunization, targeted supplementary immunization activities aimed at susceptible groups according to sero-epidemiological surveillance data also play a key role in stopping the continuous transmission of rubella viruses and in preventing further congenital rubella syndrome cases.     

Modeling epidemics dynamics on heterogenous networks

The dynamics of the SIS process on heterogenous networks, where different local communities are connected by airlines, is studied. We suggest a new modeling technique for travelers movement, in which the movement does not affect the demographic parameters characterizing the metapopulation. A solution to the deterministic reaction-diffusion equations that emerges from this model on a general network is presented. A typical example of a heterogenous network, the star structure, is studied in detail both analytically and using agent-based simulations. The interplay between demographic stochasticity, spatial heterogeneity and the infection dynamics is shown to produce some counterintuitive effects. In particular it was found that, while movement always increases the chance of an outbreak, it may decrease the steady-state fraction of sick individuals. The importance of the modeling technique in estimating the outcomes of a vaccination campaign is demonstrated.