Sub-national variation in measles vaccine coverage and outbreak risk: a case study from a 2010 outbreak in Malawi.

BACKGROUND: Despite progress towards increasing global vaccination coverage, measles continues to be one of the leading, preventable causes of death among children worldwide. Whether and how to target sub-national areas for vaccination campaigns continues to remain a question. We analyzed three metrics for prioritizing target areas: vaccination coverage, susceptible birth cohort, and the effective reproductive ratio (RE) in the context of the 2010 measles epidemic in Malawi. METHODS: Using case-based surveillance data from the 2010 measles outbreak in Malawi, we estimated vaccination coverage from the proportion of cases reporting with a history of prior vaccination at the district and health facility catchment scale. Health facility catchments were defined as the set of locations closer to a given health facility than to any other. We combined these estimates with regional birth rates to estimate the size of the annual susceptible birth cohort. We also estimated the effective reproductive ratio, RE, at the health facility polygon scale based on the observed rate of exponential increase of the epidemic. We combined these estimates to identify spatial regions that would be of high priority for supplemental vaccination activities. RESULTS: The estimated vaccination coverage across all districts was 84%, but ranged from 61 to 99%. We found that 8 districts and 354 health facility catchments had estimated vaccination coverage below 80%. Areas that had highest birth cohort size were frequently large urban centers that had high vaccination coverage. The estimated RE ranged between 1 and 2.56. The ranking of districts and health facility catchments as priority areas varied depending on the measure used. CONCLUSIONS: Each metric for prioritization may result in discrete target areas for vaccination campaigns; thus, there are tradeoffs to choosing one metric over another. However, in some cases, certain areas may be prioritized by all three metrics. These areas should be treated with particular concern. Furthermore, the spatial scale at which each metric is calculated impacts the resulting prioritization and should also be considered when prioritizing areas for vaccination campaigns. These methods may be used to allocate effort for prophylactic campaigns or to prioritize response for outbreak response vaccination.

Using simulation to aid trial design: Ring-vaccination trials.

BACKGROUND: The 2014-6 West African Ebola epidemic highlights the need for rigorous, rapid clinical trial methods for vaccines. A challenge for trial design is making sample size calculations based on incidence within the trial, total vaccine effect, and intracluster correlation, when these parameters are uncertain in the presence of indirect effects of vaccination. METHODS AND FINDINGS: We present a stochastic, compartmental model for a ring vaccination trial. After identification of an index case, a ring of contacts is recruited and either vaccinated immediately or after 21 days. The primary outcome of the trial is total vaccine effect, counting cases only from a pre-specified window in which the immediate arm is assumed to be fully protected and the delayed arm is not protected. Simulation results are used to calculate necessary sample size and estimated vaccine effect. Under baseline assumptions about vaccine properties, monthly incidence in unvaccinated rings and trial design, a standard sample-size calculation neglecting dynamic effects estimated that 7,100 participants would be needed to achieve 80% power to detect a difference in attack rate between arms, while incorporating dynamic considerations in the model increased the estimate to 8,900. This approach replaces assumptions about parameters at the ring level with assumptions about disease dynamics and vaccine characteristics at the individual level, so within this framework we were able to describe the sensitivity of the trial power and estimated effect to various parameters. We found that both of these quantities are sensitive to properties of the vaccine, to setting-specific parameters over which investigators have little control, and to parameters that are determined by the study design. CONCLUSIONS: Incorporating simulation into the trial design process can improve robustness of sample size calculations. For this specific trial design, vaccine effectiveness depends on properties of the ring vaccination design and on the measurement window, as well as the epidemiologic setting.

Sentinel site community surveillance of mortality and nutritional status in southwestern Central African Republic, 2010.

BACKGROUND: During 2010, a community-based, sentinel site prospective surveillance system measured mortality, acute malnutrition prevalence, and the coverage of a Médecins Sans Frontières (MSF) intervention in four sous-préfectures of Lobaye prefecture in southwestern Central African Republic. We describe this surveillance system and its evaluation. METHODS: Within 24 randomly selected sentinel sites, home visitors performed a census, weekly demographic surveillance of births, deaths, and in- or out-migration, and weekly anthropometry on a sample of children. We evaluated the system through various methods including capture-recapture analysis and repeat census. RESULTS: The system included 18,081 people at baseline. Over 32 weeks, the crude death rate was 1.0 (95% confidence interval [CI]: 0.8-1.2) deaths per 10,000 person-days (35 deaths per 1,000 person-years), with higher values during the rainy season. The under-5 death rate was approximately double. The prevalence of severe acute malnutrition (SAM) was 3.0% (95% CI: 2.3-4.0), almost half featuring kwashiorkor signs. The coverage of SAM treatment was 29.1%. The system detected >90% of deaths, and >90% of death reports appeared valid. However, demographic surveillance yielded discrepancies with the census and an implausible rate of population growth, while the predictive value of SAM classification was around 60%. DISCUSSION: We found evidence of a chronic health crisis in this remote region. MSF's intervention coverage improved progressively. Mortality data appeared valid, but inaccuracies in population denominators and anthropometric measurements were noted. Similar systems could be implemented in other remote settings and acute emergencies, but with certain technical improvements.

Mortality trends in systemic sclerosis in France and USA, 1980-1998: an age-period-cohort analysis.

We compared trends of Systemic Sclerosis (SS) mortality in France and the USA over the period 1980-1998 and used an Age-Period-Cohort (APC) model to adjust on the age at death of SS patients. All deaths coded with SS as an underlying primary or secondary cause in the national French and US mortality databases from 1980 to 1998 were included in the analysis. SS age-standardized mortality rates increased from 7.2 to 10.3/million in US women (+43%), and from 3 to 3.9/million in French women (+22%). Most of the increase occurred in senior women. In contrast, SS age-standardized death rates remained stable among US men (around 3/million) and French men (around 2/million). In US women, the APC analysis shows a growing cohort effect between 1900 and 1940, tending to stabilize for following cohorts. Similar findings were obtained to a lesser extent in French women. In conclusion, SS mortality rates increased by more than 40% between 1980 and 1998 in the USA, mostly in women born between 1900 and 1940. Whether these trends reflect rising incidence of SS need to be documented. The observed dissimilarity between genders and countries underline that environmental exposure and gender-related factors likely play a major etiological role. Stabilization in the following birth cohorts suggests that the increase of mortality observed since 1980 may slow down in the near future.

Using European travellers as an early alert to detect emerging pathogens in countries with limited laboratory resources.

BACKGROUND: The volume, extent and speed of travel have dramatically increased in the past decades, providing the potential for an infectious disease to spread through the transportation network. By collecting information on the suspected place of infection, existing surveillance systems in industrialized countries may provide timely information for areas of the world without adequate surveillance currently in place. We present the results of a case study using reported cases of Shigella dysenteriae serotype 1 (Sd1) in European travellers to detect "events" of Sd1, related to either epidemic cases or endemic cases in developing countries. METHODS: We identified papers from a Medline search for reported events of Sd1 from 1940 to 2002. We requested data on shigella infections reported to the responsible surveillance entities in 17 European countries. Reports of Sd1 from the published literature were then compared with Sd1 notified cases among European travellers from 1990 to 2002. RESULTS: Prior to a large epidemic in 1999-2000, no cases of Sd1 had been identified in West Africa. However, if travellers had been used as an early warning, Sd1 could have been identified in this region as earlier as 1992. CONCLUSION: This project demonstrates that tracking diseases in European travellers could be used to detect emerging disease in developing countries. This approach should be further tested with a view to the continuous improvement of national health surveillance systems and existing European networks, and may play a significant role in aiding the international public health community to improve infectious disease control.

A large outbreak of hepatitis E among a displaced population in Darfur, Sudan, 2004: the role of water treatment methods.

BACKGROUND: The conflict in Darfur, Sudan, was responsible for the displacement of 1.8 million civilians. We investigated a large outbreak of hepatitis E virus (HEV) infection in Mornay camp (78,800 inhabitants) in western Darfur. METHODS: To describe the outbreak, we used clinical and demographic information from cases recorded at the camp between 26 July and 31 December 2004. We conducted a case-cohort study and a retrospective cohort study to identify risk factors for clinical and asymptomatic hepatitis E, respectively. We collected stool and serum samples from animals and performed a bacteriological analysis of water samples. Human samples were tested for immunoglobulin G and immunoglobulin M antibody to HEV (for serum samples) and for amplification of the HEV genome (for serum and stool samples). RESULTS: In 6 months, 2621 hepatitis E cases were recorded (attack rate, 3.3%), with a case-fatality rate of 1.7% (45 deaths, 19 of which involved were pregnant women). Risk factors for clinical HEV infection included age of 15-45 years (odds ratio, 2.13; 95% confidence interval, 1.02-4.46) and drinking chlorinated surface water (odds ratio, 2.49; 95% confidence interval, 1.22-5.08). Both factors were also suggestive of increased risk for asymptomatic HEV infection, although this was not found to be statistically significant. HEV RNA was positively identified in serum samples obtained from 2 donkeys. No bacteria were identified from any sample of chlorinated water tested. CONCLUSIONS: Current recommendations to ensure a safe water supply may have been insufficient to inactivate HEV and control this epidemic. This research highlights the need to evaluate current water treatment methods and to identify alternative solutions adapted to complex emergencies.