Satellite Based Assessment of Hydroclimatic Conditions Related to Cholera in Zimbabwe

Introduction

Cholera, an infectious diarrheal disease, has been shown to be associated with large scale hydroclimatic processes. The sudden and sporadic occurrence of epidemic cholera is linked with high mortality rates, in part, due to uncertainty in timing and location of outbreaks. Improved understanding of the relationship between pathogenic abundance and climatic processes allows prediction of disease outbreak to be an achievable goal. In this study, we show association of large scale hydroclimatic processes with the cholera epidemic in Zimbabwe reported to have begun in Chitungwiza, a city in Mashonaland East province, in August, 2008.

Principal Findings

Climatic factors in the region were found to be associated with triggering cholera outbreak and are shown to be related to anomalies of temperature and precipitation, validating the hypothesis that poor conditions of sanitation, coupled with elevated temperatures, and followed by heavy rainfall can initiate outbreaks of cholera. Spatial estimation by satellite of precipitation and global gridded air temperature captured sensitivities in hydroclimatic conditions that permitted identification of the location in the region where the disease outbreak began.

Discussion

Satellite derived hydroclimatic processes can be used to capture environmental conditions related to epidemic cholera, as occurred in Zimbabwe, thereby providing an early warning system. Since cholera cannot be eradicated because the causative agent, Vibrio cholerae, is autochthonous to the aquatic environment, prediction of conditions favorable for its growth and estimation of risks of triggering the disease in a given population can be used to alert responders, potentially decreasing infection and saving lives.     

Urban Cholera Transmission Hotspots and Their Implications for Reactive Vaccination: Evidence from Bissau City,Guinea Bissau

Background

Use of cholera vaccines in response to epidemics (reactive vaccination) may provide an effective supplement to traditional control measures. In Haiti, reactive vaccination was considered but, until recently, rejected in part due to limited global supply of vaccine. Using Bissau City, Guinea-Bissau as a case study, we explore neighborhood-level transmission dynamics to understand if, with limited vaccine and likely delays, reactive vaccination can significantly change the course of a cholera epidemic.

Methods and Findings

We fit a spatially explicit meta-population model of cholera transmission within Bissau City to data from 7,551 suspected cholera cases from a 2008 epidemic. We estimated the effect reactive vaccination campaigns would have had on the epidemic under different levels of vaccine coverage and campaign start dates. We compared highly focused and diffuse strategies for distributing vaccine throughout the city. We found wide variation in the efficiency of cholera transmission both within and between areas of the city. “Hotspots”, where transmission was most efficient, appear to drive the epidemic. In particular one area, Bandim, was a necessary driver of the 2008 epidemic in Bissau City. If vaccine supply were limited but could have been distributed within the first 80 days of the epidemic, targeting vaccination at Bandim would have averted the most cases both within this area and throughout the city. Regardless of the distribution strategy used, timely distribution of vaccine in response to an ongoing cholera epidemic can prevent cases and save lives.

Conclusions

Reactive vaccination can be a useful tool for controlling cholera epidemics, especially in urban areas like Bissau City. Particular neighborhoods may be responsible for driving a city''s cholera epidemic; timely and targeted reactive vaccination at such neighborhoods may be the most effective way to prevent cholera cases both within that neighborhood and throughout the city.     

Cholera Epidemics,War and Disasters around Goma and Lake Kivu: An Eight-Year Survey

Background

During the last eight years, North and South Kivu, located in a lake area in Eastern Democratic Republic of Congo, have been the site of a major volcano eruption and of numerous complex emergencies with population displacements. These conditions have been suspected to favour emergence and spread of cholera epidemics.

Methodology/Principal Findings

In order to assess the influence of these conditions on outbreaks, reports of cholera cases were collected weekly from each health district of North Kivu (4,667,699 inhabitants) and South Kivu (4,670,121 inhabitants) from 2000 through 2007. A geographic information system was established, and in each health district, the relationships between environmental variables and the number of cholera cases were assessed using regression techniques and time series analysis. We further checked for a link between complex emergencies and cholera outbreaks. Finally, we analysed data collected during an epidemiological survey that was implemented in Goma after Nyiragongo eruption. A total of 73,605 cases and 1,612 deaths of cholera were reported. Time series decomposition showed a greater number of cases during the rainy season in South Kivu but not in North Kivu. Spatial distribution of cholera cases exhibited a higher number of cases in health districts bordering lakes (Odds Ratio 7.0, Confidence Interval range 3.8–12.9). Four epidemic reactivations were observed in the 12-week periods following war events, but simulations indicate that the number of reactivations was not larger than that expected during any random selection of period with no war. Nyiragongo volcanic eruption was followed by a marked decrease of cholera incidence.

Conclusion/Significance

Our study points out the crucial role of some towns located in lakeside areas in the persistence of cholera in Kivu. Even if complex emergencies were not systematically followed by cholera epidemics, some of them enabled cholera spreading.     

The case for reactive mass oral cholera vaccinations

Introduction

The outbreak of cholera in Zimbabwe intensified interest in the control and prevention of cholera. While there is agreement that safe water, sanitation, and personal hygiene are ideal for the long term control of cholera, there is controversy about the role of newer approaches such as oral cholera vaccines (OCVs). In October 2009 the Strategic Advisory Group of Experts advised the World Health Organization to consider reactive vaccination campaigns in response to large cholera outbreaks. To evaluate the potential benefit of this pivotal change in WHO policy, we used existing data from cholera outbreaks to simulate the number of cholera cases preventable by reactive mass vaccination.

Methods

Datasets of cholera outbreaks from three sites with varying cholera endemicity—Zimbabwe, Kolkata (India), and Zanzibar (Tanzania)—were analysed to estimate the number of cholera cases preventable under differing response times, vaccine coverage, and vaccine doses.

Findings

The large cholera outbreak in Zimbabwe started in mid August 2008 and by July 2009, 98,591 cholera cases had been reported with 4,288 deaths attributed to cholera. If a rapid response had taken place and half of the population had been vaccinated once the first 400 cases had occurred, as many as 34,900 (40%) cholera cases and 1,695 deaths (40%) could have been prevented. In the sites with endemic cholera, Kolkata and Zanzibar, a significant number of cases could have been prevented but the impact would have been less dramatic. A brisk response is required for outbreaks with the majority of cases occurring during the early weeks. Even a delayed response can save a substantial number of cases and deaths in long, drawn-out outbreaks. If circumstances prevent a rapid response there are good reasons to roll out cholera mass vaccination campaigns well into the outbreak. Once a substantial proportion of a population is vaccinated, outbreaks in subsequent years may be reduced if not prevented. A single dose vaccine would be of advantage in short, small outbreaks.

Conclusions

We show that reactive vaccine use can prevent cholera cases and is a rational response to cholera outbreaks in endemic and non-endemic settings. In large and long outbreaks a reactive vaccination with a two-dose vaccine can prevent a substantial proportion of cases. To make mass vaccination campaigns successful, it would be essential to agree when to implement reactive vaccination campaigns and to have a dynamic and determined response team that is familiar with the logistic challenges on standby. Most importantly, the decision makers in donor and recipient countries have to be convinced of the benefit of reactive cholera vaccinations.     

Mortality and Case Fatality Due to Visceral Leishmaniasis in Brazil: A Nationwide Analysis of Epidemiology,Trends and Spatial Patterns

Background

Visceral leishmaniasis (VL) is a significant public health problem in Brazil and several regions of the world. This study investigated the magnitude, temporal trends and spatial distribution of mortality related to VL in Brazil.

Methods

We performed a study based on secondary data obtained from the Brazilian Mortality Information System. We included all deaths in Brazil from 2000 to 2011, in which VL was recorded as cause of death. We present epidemiological characteristics, trend analysis of mortality and case fatality rates by joinpoint regression models, and spatial analysis using municipalities as geographical units of analysis.

Results

In the study period, 12,491,280 deaths were recorded in Brazil. VL was mentioned in 3,322 (0.03%) deaths. Average annual age-adjusted mortality rate was 0.15 deaths per 100,000 inhabitants and case fatality rate 8.1%. Highest mortality rates were observed in males (0.19 deaths/100,000 inhabitants), <1 year-olds (1.03 deaths/100,000 inhabitants) and residents in Northeast region (0.30 deaths/100,000 inhabitants). Highest case fatality rates were observed in males (8.8%), ≥70 year-olds (43.8%) and residents in South region (17.7%). Mortality and case fatality rates showed a significant increase in Brazil over the period, with different patterns between regions: increasing mortality rates in the North (Annual Percent Change – APC: 9.4%; 95% confidence interval – CI: 5.3 to 13.6), and Southeast (APC: 8.1%; 95% CI: 2.6 to 13.9); and increasing case fatality rates in the Northeast (APC: 4.0%; 95% CI: 0.8 to 7.4). Spatial analysis identified a major cluster of high mortality encompassing a wide geographic range in North and Northeast Brazil.

Conclusions

Despite ongoing control strategies, mortality related to VL in Brazil is increasing. Mortality and case fatality vary considerably between regions, and surveillance and control measures should be prioritized in high-risk clusters. Early diagnosis and treatment are fundamental strategies for reducing case fatality of VL in Brazil.     

A Statistical Framework for the Adaptive Management of Epidemiological Interventions

Background

Epidemiological interventions aim to control the spread of infectious disease through various mechanisms, each carrying a different associated cost.

Methodology

We describe a flexible statistical framework for generating optimal epidemiological interventions that are designed to minimize the total expected cost of an emerging epidemic while simultaneously propagating uncertainty regarding the underlying disease model parameters through to the decision process. The strategies produced through this framework are adaptive: vaccination schedules are iteratively adjusted to reflect the anticipated trajectory of the epidemic given the current population state and updated parameter estimates.

Conclusions

Using simulation studies based on a classic influenza outbreak, we demonstrate the advantages of adaptive interventions over non-adaptive ones, in terms of cost and resource efficiency, and robustness to model misspecification.     

Disparities in Cervical Cancer Mortality Rates as Determined by the Longitudinal Hyperbolastic Mixed-Effects Type II Model

Background

The main purpose of this study was to model and analyze the dynamics of cervical cancer mortality rates for African American (Black) and White women residing in 13 states located in the eastern half of the United States of America from 1975 through 2010.

Methods

The cervical cancer mortality rates of the Surveillance, Epidemiology, and End Results (SEER) were used to model and analyze the dynamics of cervical cancer mortality. A longitudinal hyperbolastic mixed-effects type II model was used to model the cervical cancer mortality data and SAS PROC NLMIXED and Mathematica were utilized to perform the computations.

Results

Despite decreasing trends in cervical cancer mortality rates for both races, racial disparities in mortality rates still exist. In all 13 states, Black women had higher mortality rates at all times. The degree of disparities and pace of decline in mortality rates over time differed among these states. Determining the paces of decline over 36 years showed that Tennessee had the most rapid decline in cervical cancer mortality for Black women, and Mississippi had the most rapid decline for White Women. In contrast, slow declines in cervical cancer mortality were noted for Black women in Florida and for White women in Maryland.

Conclusions

In all 13 states, cervical cancer mortality rates for both racial groups have fallen. Disparities in the pace of decline in mortality rates in these states may be due to differences in the rates of screening for cervical cancers. Of note, the gap in cervical cancer mortality rates between Black women and White women is narrowing.     

Use of oral cholera vaccines in an outbreak in Vietnam: a case control study

Background

Killed oral cholera vaccines (OCVs) are available but not used routinely for cholera control except in Vietnam, which produces its own vaccine. In 2007–2008, unprecedented cholera outbreaks occurred in the capital, Hanoi, prompting immunization in two districts. In an outbreak investigation, we assessed the effectiveness of killed OCV use after a cholera outbreak began.

Methodology/Principal Findings

From 16 to 28 January 2008, vaccination campaigns with the Vietnamese killed OCV were held in two districts of Hanoi. No cholera cases were detected from 5 February to 4 March 2008, after which cases were again identified. Beginning 8 April 2008, residents of four districts of Hanoi admitted to one of five hospitals for acute diarrhea with onset after 5 March 2008 were recruited for a matched, hospital-based, case-control outbreak investigation. Cases were matched by hospital, admission date, district, gender, and age to controls admitted for non-diarrheal conditions. Subjects from the two vaccinated districts were evaluated to determine vaccine effectiveness. 54 case-control pairs from the vaccinated districts were included in the analysis. There were 8 (15%) and 16 (30%) vaccine recipients among cases and controls, respectively. The vaccine was 76% protective against cholera in this setting (95% CI 5% to 94%, P = 0.042) after adjusting for intake of dog meat or raw vegetables and not drinking boiled or bottled water most of the time.

Conclusions/Significance

This is the first study to explore the effectiveness of the reactive use of killed OCVs during a cholera outbreak. Our findings suggest that killed OCVs may have a role in controlling cholera outbreaks.     

The Burden of Cholera in Uganda

Introduction

In 2010, the World Health Organization released a new cholera vaccine position paper, which recommended the use of cholera vaccines in high-risk endemic areas. However, there is a paucity of data on the burden of cholera in endemic countries. This article reviewed available cholera surveillance data from Uganda and assessed the sufficiency of these data to inform country-specific strategies for cholera vaccination.

Methods

The Uganda Ministry of Health conducts cholera surveillance to guide cholera outbreak control activities. This includes reporting the number of cases based on a standardized clinical definition plus systematic laboratory testing of stool samples from suspected cases at the outset and conclusion of outbreaks. This retrospective study analyzes available data by district and by age to estimate incidence rates. Since surveillance activities focus on more severe hospitalized cases and deaths, a sensitivity analysis was conducted to estimate the number of non-severe cases and unrecognized deaths that may not have been captured.

Results

Cholera affected all ages, but the geographic distribution of the disease was very heterogeneous in Uganda. We estimated that an average of about 11,000 cholera cases occurred in Uganda each year, which led to approximately 61–182 deaths. The majority of these cases (81%) occurred in a relatively small number of districts comprising just 24% of Uganda''s total population. These districts included rural areas bordering the Democratic Republic of Congo, South Sudan, and Kenya as well as the slums of Kampala city. When outbreaks occurred, the average duration was about 15 weeks with a range of 4–44 weeks.

Discussion

There is a clear subdivision between high-risk and low-risk districts in Uganda. Vaccination efforts should be focused on the high-risk population. However, enhanced or sentinel surveillance activities should be undertaken to better quantify the endemic disease burden and high-risk populations prior to introducing the vaccine.     

Hospitalization Rates and Post-Operative Mortality for Abdominal Aortic Aneurysm in Italy over the Period 2000–2011

Background

Recent studies have reported declines in incidence, prevalence and mortality for abdominal aortic aneurysms (AAAs) in various countries, but evidence from Mediterranean countries is lacking. The aim of this study is to examine the trend of hospitalization and post-operative mortality rates for AAAs in Italy during the period 2000–2011, taking into account the introduction of endovascular aneurysm repair (EVAR) in 1990s.

Methods

This retrospective cohort study was carried out in Emilia-Romagna, an Italian region with 4.5 million inhabitants. A total of 19,673 patients hospitalized for AAAs between 2000 and 2011, were identified from the hospital discharge records (HDR) database. Hospitalization rates, percentage of OSR and EVAR and 30-day mortality rates were calculated for unruptured (uAAAs) and ruptured AAAs (rAAAs).

Results

Adjusted hospitalization rates decreased on average by 2.9% per year for uAAAs and 3.2% for rAAAs (p<0.001). The temporal trend of 30-day mortality rates remained stable for both groups. The percentage of EVAR for uAAAs increased significantly from 2006 to 2011 (42.7 versus 60.9% respectively, mean change of 3.9% per year, p<0.001). No significant difference in mortality was found between OSR and EVAR for uAAAs and rAAAs.

Conclusions

The incidence and trend of hospitalization rates for rAAAs and uAAAs decreased significantly in the last decade, while 30-day mortality rates in operated patients remained stable. OSR continued to be the most common surgery in rAAAs, although the gap between OSR and EVAR recently declined. The EVAR technique became the preferred surgery for uAAAs since 2008.     

Epidemiology of Cholera in the Philippines

Background

Despite being a cholera-endemic country, data on cholera in the Philippines remain sparse. Knowing the areas where cholera is known to occur and the factors that lead to its occurrence will assist in planning preventive measures and disaster mitigation.

Methods

Using sentinel surveillance data, PubMed and ProMED searches covering information from 2008–2013 and event-based surveillance reports from 2010–2013, we assessed the epidemiology of cholera in the Philippines. Using spatial log regression, we assessed the role of water, sanitation and population density on the incidence of cholera.

Results and Discussion

We identified 12 articles from ProMED and none from PubMed that reported on cholera in the Philippines from 2008 to 2013. Data from ProMed and surveillance revealed 42,071 suspected and confirmed cholera cases reported from 2008 to 2013, among which only 5,006 were confirmed. 38 (47%) of 81 provinces and metropolitan regions reported at least one confirmed case of cholera and 32 (40%) reported at least one suspected case. The overall case fatality ratio in sentinel sites was 0.62%, but was 2% in outbreaks. All age groups were affected. Using both confirmed and suspected cholera cases, the average annual incidence in 2010–2013 was 9.1 per 100,000 population. Poor access to improved sanitation was consistently associated with higher cholera incidence. Paradoxically, access to improved water sources was associated with higher cholera incidence using both suspected and confirmed cholera data sources. This finding may have been due to the breakdown in the infrastructure and non-chlorination of water supplies, emphasizing the need to maintain public water systems.

Conclusion

Our findings confirm that cholera affects a large proportion of the provinces in the country. Identifying areas most at risk for cholera will support the development and implementation of policies to minimize the morbidity and mortality due to this disease.     

Maiden outbreak of chikungunya in dongguan city, guangdong province, china: epidemiological characteristics

Background

This study was conducted to identify epidemiological characteristics of the first documented CHIK fever outbreak in China and evaluate the effect of the preventive measures taken.

Methodology/Principal Findings

From September 1 to October 29, 2010, China''s first documented outbreak of CHIK fever occurred in the Xincun community of Wanjiang District of Dongguan city, Guangdong province; 253 case-patients were recorded, of which 129 were laboratory confirmed, with an attack rate of 1%. Before September 18^th the number of CHIK fever cases remained relatively low in the Xincun community; from September 19^th onwards, the number of cases increased drastically, with an outbreak peak on October 4^th. Cases were distributed across nine small village groups in the Xincun community, with an attack rate of 0–12% at the village level. The household attack rates ranged between 20% and 100%. No significant difference was found in the attack rate between males and females. There was a significant difference in the attack rate in different age groups (chi-square = 18.35, p = 0.005); highest in patients aged 60 years or older and the lowest in patients aged under 10. The major clinical characteristics of patients are fever (100%), joint pain (79%) and rash (54%). Phylogenetic analysis of the E1 gene on the five earliest confirmed cases showed that the strains of CHIKV isolated from their sera were highly homologous (up to 99%) with isogeneic strains isolated in Thailand in 2009. After control measures were taken, including killing adult mosquitoes and cleaning breeding habitats of Aedes mosquitoes, the Breteau index and Mosq-ovitrap index decreased rapidly, and the outbreak ended on October 29.

Conclusion/Significance

The infection source of the outbreak was imported. Cases showed obvious temporal, spatial, and population aggregation during the outbreak. Comprehensive control measures based on reducing the density of Aedes mosquitoes were effective in controlling the epidemic.     

Climate-based models for understanding and forecasting dengue epidemics

Background

Dengue dynamics are driven by complex interactions between human-hosts, mosquito-vectors and viruses that are influenced by environmental and climatic factors. The objectives of this study were to analyze and model the relationships between climate, Aedes aegypti vectors and dengue outbreaks in Noumea (New Caledonia), and to provide an early warning system.

Methodology/Principal Findings

Epidemiological and meteorological data were analyzed from 1971 to 2010 in Noumea. Entomological surveillance indices were available from March 2000 to December 2009. During epidemic years, the distribution of dengue cases was highly seasonal. The epidemic peak (March–April) lagged the warmest temperature by 1–2 months and was in phase with maximum precipitations, relative humidity and entomological indices. Significant inter-annual correlations were observed between the risk of outbreak and summertime temperature, precipitations or relative humidity but not ENSO. Climate-based multivariate non-linear models were developed to estimate the yearly risk of dengue outbreak in Noumea. The best explicative meteorological variables were the number of days with maximal temperature exceeding 32°C during January–February–March and the number of days with maximal relative humidity exceeding 95% during January. The best predictive variables were the maximal temperature in December and maximal relative humidity during October–November–December of the previous year. For a probability of dengue outbreak above 65% in leave-one-out cross validation, the explicative model predicted 94% of the epidemic years and 79% of the non epidemic years, and the predictive model 79% and 65%, respectively.

Conclusions/Significance

The epidemic dynamics of dengue in Noumea were essentially driven by climate during the last forty years. Specific conditions based on maximal temperature and relative humidity thresholds were determinant in outbreaks occurrence. Their persistence was also crucial. An operational model that will enable health authorities to anticipate the outbreak risk was successfully developed. Similar models may be developed to improve dengue management in other countries.     

Review of Two Decades of Cholera Diagnostics – How Far Have We Really Come?

Background

Cholera, an ancient scourge, continues to inflict high rates of mortality today. The rising incidence of epidemics in areas of poor sanitation and crowding highlight the need for better epidemic prevention and early response. Such interventions require the availability of rapid and accurate diagnostic techniques to trigger timely response and mitigate the scale of the outbreak. The current gold standard of bacterial culture is inadequate for rapid diagnosis, highlighting the overarching neglect of field diagnostic needs. This paper was written to support the World Health Organisation''s Global Task Force on Cholera Control mandated Cholera and diarrhoeal disease laboratory Network (CholdiNet) in devising a protocol for the validation of Rapid Diagnostic Tests (RDTs) for Vibrio cholerae. The status of diagnostic tools for Vibrio cholerae is assessed, describing products that have been commercialised over the last two decades and discussing their peer-reviewed evaluation.

Method

Review of post-1990 peer-reviewed and grey literature on rapid diagnostic tests for Vibrio cholerae.

Results

Since 1990, twenty four diagnostic tests have been developed for the detection of Vibrio cholerae in human faecal samples. Fourteen of these have also been described in the literature, with rapid chromatographic-immuno assays (CIA) featuring strongly. Polymerase chain reaction (PCR) assays maintain the ability to detect the lowest amount of bacteria; however CIAs achieve both low detection thresholds and high sensitivity and specificity, making them possible candidates for use in field conditions. Field and laboratory studies were performed in a wide range of settings demonstrating variability in performance, however only a few of these studies were sufficiently stringent, highlighting five RDTs that showed promise in field conditions; COAT, IP cholera dipstick, SMART, IP dipstick and Medicos. In light of non-independent reporting, the authors would like to see these five products undergoing additional studies, with further technical improvements if needed and commercial production. The authors hope that public health use of such a RDT in limited-resource field conditions on stool samples may contribute to effective reduction in cholera epidemic spread.     

The Evolution of the Epidemic of Charcoal-Burning Suicide in Taiwan: A Spatial and Temporal Analysis

Background

An epidemic of carbon monoxide poisoning suicide by burning barbecue charcoal has occurred in East Asia in the last decade. We investigated the spatial and temporal evolution of the epidemic to assess its impact on the epidemiology of suicide in Taiwan.

Methods and Findings

Age-standardised rates of suicide and undetermined death by charcoal burning were mapped across townships (median population aged 15 y or over = 27,000) in Taiwan for the periods 1999–2001, 2002–2004, and 2005–2007. Smoothed standardised mortality ratios of charcoal-burning and non-charcoal-burning suicide and undetermined death across townships were estimated using Bayesian hierarchical models. Trends in overall and method-specific rates were compared between urban and rural areas for the period 1991–2007. The epidemic of charcoal-burning suicide in Taiwan emerged more prominently in urban than rural areas, without a single point of origin, and rates of charcoal-burning suicide remained highest in the metropolitan regions throughout the epidemic. The rural excess in overall suicide rates prior to 1998 diminished as rates of charcoal-burning suicide increased to a greater extent in urban than rural areas.

Conclusions

The charcoal-burning epidemic has altered the geography of suicide in Taiwan. The observed pattern and its changes in the past decade suggest that widespread media coverage of this suicide method and easy access to barbecue charcoal may have contributed to the epidemic. Prevention strategies targeted at these factors, such as introducing and enforcing guidelines on media reporting and restricting access to charcoal, may help tackle the increase of charcoal-burning suicides. Please see later in the article for the Editors'' Summary     

The spatial and temporal dynamics of rabies in China

Background and Objectives

Recent years have seen a rapid increase in the number of rabies cases in China and an expansion in the geographic distribution of the virus. In spite of the seriousness of the outbreak and increasing number of fatalities, little is known about the phylogeography of the disease in China. In this study, we report an analysis of a set of Nucleocapsid sequences consisting of samples collected through the trial Chinese National Surveillance System as well as publicly available sequences. This sequence set represents the most comprehensive dataset from China to date, comprising 210 sequences (including 57 new samples) from 15 provinces and covering all epidemic regions. Using this dataset we investigated genetic diversity, patterns of distribution, and evolutionary history.

Results

Our analysis indicates that the rabies virus in China is primarily defined by two clades that exhibit distinct population subdivision and translocation patterns and that contributed to the epidemic in different ways. The younger clade originated around 1992 and has properties that closely match the observed spread of the recent epidemic. The older clade originated around 1960 and has a dispersion pattern that suggests it represents a strain associated with a previous outbreak that remained at low levels throughout the country and reemerged in the current epidemic.

Conclusions

Our findings provide new insight into factors associated with the recent epidemic and are relevant to determining an effective policy for controlling the virus.     

Outcomes and Impact of HIV Prevention,ART and TB Programs in Swaziland – Early Evidence from Public Health Triangulation

Introduction

Swaziland’s severe HIV epidemic inspired an early national response since the late 1980s, and regular reporting of program outcomes since the onset of a national antiretroviral treatment (ART) program in 2004. We assessed effectiveness outcomes and mortality trends in relation to ART, HIV testing and counseling (HTC), tuberculosis (TB) and prevention of mother to child transmission (PMTCT).

Methods

Data triangulated include intervention coverage and outcomes according to program registries (2001-2010), hospital admissions and deaths disaggregated by age and sex (2001-2010) and population mortality estimates from the 1997 and 2007 censuses and the 2007 demographic and health survey.

Results

By 2010, ART reached 70% of the estimated number of people living with HIV/AIDS with CD4<350/mm³, with progressively improving patient retention and survival. As of 2010, 88% of health facilities providing antenatal care offered comprehensive PMTCT services. The HTC program recorded a halving in the proportion of adults tested who were HIV-infected; similarly HIV infection rates among HIV-exposed babies halved from 2007 to 2010. Case fatality rates among hospital patients diagnosed with HIV/AIDS started to decrease from 2005–6 in adults and especially in children, contrasting with stable case fatality for other causes including TB. All-cause child in-patient case fatality rates started to decrease from 2005–6. TB case notifications as well as rates of HIV/TB co-infection among notified TB patients continued a steady increase through 2010, while coverage of HIV testing and CPT for co-infected patients increased to above 80%.

Conclusion

Against a background of high, but stable HIV prevalence and decreasing HIV incidence, we documented early evidence of a mortality decline associated with the expanded national HIV response since 2004. Attribution of impact to specific interventions (versus natural epidemic dynamics) will require additional data from future household surveys, and improved routine (program, surveillance, and hospital) data at district level.     

Excess mortality associated with influenza epidemics in Portugal, 1980 to 2004

Background

Influenza epidemics have a substantial impact on human health, by increasing the mortality from pneumonia and influenza, respiratory and circulatory diseases, and all causes. This paper provides estimates of excess mortality rates associated with influenza virus circulation for 7 causes of death and 8 age groups in Portugal during the period of 1980–2004.

Methodology/Principal Findings

We compiled monthly mortality time series data by age for all-cause mortality, cerebrovascular diseases, ischemic heart diseases, diseases of the respiratory system, chronic respiratory diseases, pneumonia and influenza. We also used a control outcome, deaths from injuries. Age- and cause-specific baseline mortality was modelled by the ARIMA approach; excess deaths attributable to influenza were calculated by subtracting expected deaths from observed deaths during influenza epidemic periods. Influenza was associated with a seasonal average of 24.7 all-cause excess deaths per 100,000 inhabitants, approximately 90% of which were among seniors over 65 yrs. Excess mortality was 3–6 fold higher during seasons dominated by the A(H3N2) subtype than seasons dominated by A(H1N1)/B. High excess mortality impact was also seen in children under the age of four years. Seasonal excess mortality rates from all the studied causes of death were highly correlated with each other (Pearson correlation range, 0.65 to 0.95, P<0.001) and with seasonal rates of influenza-like-illness (ILI) among seniors over 65 years (Pearson correlation rho>0.64, P<0.05). By contrast, there was no correlation with excess mortality from injuries.

Conclusions/Significance

Our excess mortality approach is specific to influenza virus activity and produces influenza-related mortality rates for Portugal that are similar to those published for other countries. Our results indicate that all-cause excess mortality is a robust indicator of influenza burden in Portugal, and could be used to monitor the impact of influenza epidemics in this country. Additional studies are warranted to confirm these findings in other settings.     

Changing Mortality Profile among HIV-Infected Patients in Rio de Janeiro,Brazil: Shifting from AIDS to Non-AIDS Related Conditions in the HAART Era

Introduction

We describe temporal trends in the mortality rates and factors associated with AIDS and non-AIDS related mortality at the Evandro Chagas Clinical Research Institute (IPEC), Oswaldo Cruz Foundation (FIOCRUZ).

Methods

Adult patients enrolling from 1986 through 2009 with a minimum follow up of 60 days were included. Vital status was exhaustively checked using patients’ medical charts, through active contact with individuals and family members and by linkage with the Rio de Janeiro Mortality database using a previously validated algorithm. The CoDe protocol was used to establish the cause of death. Extended Cox proportional hazards models were used for multivariate modeling.

Results

A total of 3530 individuals met the inclusion criteria, out of which 868 (24.6%) deceased; median follow up per patient was 3.9 years (interquartile range 1.7–9.2 years). The dramatic decrease in the overall mortality rates was driven by AIDS-related causes that decreased from 9.19 deaths/100PYs n 1986–1991 to 1.35/100PYs in 2007–2009. Non-AIDS related mortality rates remained stable overtime, at around 1 death/100PYs. Immunodeficiency significantly increased the hazard of both AIDS-related and non-AIDS-related causes of death, while HAART use was strongly associated with a lower hazard of death from either cause.

Conclusions

Our results confirm the remarkable decrease in AIDS-related mortality as the HIV epidemic evolved and alerts to the conditions not traditionally related to HIV/AIDS which are now becoming more frequent, needing careful monitoring.