Colleen L. Lau

Climate change, flooding, urbanisation and leptospirosis: fuelling the fire?

Flooding and heavy rainfall have been associated with numerous outbreaks of leptospirosis around the world. With global climate change, extreme weather events such as cyclones and floods are expected to occur with increasing frequency and greater intensity and may potentially result in an upsurge in the disease incidence as well as the magnitude of leptospirosis outbreaks. In this paper, we examine mechanisms by which climate change can affect various ecological factors that are likely to drive an increase in the overall incidence as well as the frequency of outbreaks of leptospirosis. We will discuss the geographical areas that are most likely to be at risk of an increase in leptospirosis disease burden owing to the coexistence of climate change hazard risk, environmental drivers of leptospirosis outbreaks, local socioeconomic circumstances, and social and demographic trends. To reduce this disease burden, enhanced surveillance and further research is required to understand the environmental drivers of infection, to build capacity in emergency response and to promote community adaptation to a changing climate.

Leptospirosis: An emerging disease in travellers

A recent upsurge in leptospirosis in travellers has prompted the following review of the epidemiology of this infection in humans. The available data from the published literature as well as laboratory surveillance were examined to determine the possible causes of the apparent change in epidemiology.

Seroprevalence and spatial epidemiology of lymphatic filariasis in American Samoa after successful mass drug administration

Background As part of the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted mass drug administration (MDA) from 2000–2006, and passed transmission assessment surveys in 2011–2012. We examined the seroprevalence and spatial epidemiology of LF post-MDA to inform strategies for ongoing surveillance and to reduce resurgence risk. Methods ELISA for LF antigen (Og4C3) and antibodies (Wb123, Bm14) were performed on a geo-referenced serum bank of 807 adults collected in 2010. Risk factors assessed for association with sero-positivity included age, sex, years lived in American Samoa, and occupation. Geographic clustering of serological indicators was investigated to identify spatial dependence and household-level clustering. Results Og4C3 antigen of >128 units (positive) were found in 0.75% (95% CI 0.3–1.6%) of participants, and >32 units (equivocal plus positive) in 3.2% (95% CI 0.6–4.7%). Seroprevalence of Wb123 and Bm14 antibodies were 8.1% (95% CI 6.3–10.2%) and 17.9% (95% CI 15.3–20.7%) respectively. Antigen-positive individuals were identified in all ages, and antibody prevalence higher in older ages. Prevalence was higher in males, and inversely associated with years lived in American Samoa. Spatial distribution of individuals varied significantly with positive and equivocal levels of Og4C3 antigen, but not with antibodies. Using Og4C3 cutoff points of >128 units and >32 units, average cluster sizes were 1,242 m and 1,498 m, and geographical proximity of households explained 85% and 62% of the spatial variation respectively. Conclusions High-risk populations for LF in American Samoa include adult males and recent migrants. We identified locations and estimated the size of possible residual foci of antigen-positive adults, demonstrating the value of spatial analysis in post-MDA surveillance. Strategies to monitor cluster residents and high-risk groups are needed to reduce resurgence risk. Further research is required to quantify factors contributing to LF transmission at the last stages of elimination to ensure that programme achievements are sustained.

Leptospirosis in American Samoa - Estimating and Mapping Risk Using Environmental Data

Background The recent emergence of leptospirosis has been linked to many environmental drivers of disease transmission. Accurate epidemiological data are lacking because of under-diagnosis, poor laboratory capacity, and inadequate surveillance. Predictive risk maps have been produced for many diseases to identify high-risk areas for infection and guide allocation of public health resources, and are particularly useful where disease surveillance is poor. To date, no predictive risk maps have been produced for leptospirosis. The objectives of this study were to estimate leptospirosis seroprevalence at geographic locations based on environmental factors, produce a predictive disease risk map for American Samoa, and assess the accuracy of the maps in predicting infection risk. Methodology and Principal Findings Data on seroprevalence and risk factors were obtained from a recent study of leptospirosis in American Samoa. Data on environmental variables were obtained from local sources, and included rainfall, altitude, vegetation, soil type, and location of backyard piggeries. Multivariable logistic regression was performed to investigate associations between seropositivity and risk factors. Using the multivariable models, seroprevalence at geographic locations was predicted based on environmental variables. Goodness of fit of models was measured using area under the curve of the receiver operating characteristic, and the percentage of cases correctly classified as seropositive. Environmental predictors of seroprevalence included living below median altitude of a village, in agricultural areas, on clay soil, and higher density of piggeries above the house. Models had acceptable goodness of fit, and correctly classified ∼84% of cases. Conclusions and Significance Environmental variables could be used to identify high-risk areas for leptospirosis. Environmental monitoring could potentially be a valuable strategy for leptospirosis control, and allow us to move from disease surveillance to environmental health hazard surveillance as a more cost-effective tool for directing public health interventions.

Leptospirosis in American Samoa 2010: epidemiology, environmental drivers, and the management of emergence.

Leptospirosis has recently been reported as an emerging disease worldwide, and a seroprevalence study was undertaken in American Samoa to better understand the drivers of transmission. Antibodies indicative of previous exposure to leptospirosis were found in 15.5% of 807 participants, predominantly against three serovars that were not previously known to occur in American Samoa. Questionnaires and geographic information systems data were used to assess behavioral factors and environmental determinants of disease transmission, and logistic regression was used to identify factors associated with infection. Many statistically significant factors were consistent with previous studies, but we also showed a significant association with living at lower altitudes (odds ratio [OR] = 1.53, 95% confidence interval [CI]: 1.03-2.28), and having higher numbers of piggeries around the home (OR = 2.63, 95% CI: 1.52-4.40). Our findings support a multifaceted approach to combating the emergence of leptospirosis, including modification of individual behavior, but importantly also managing the evolving environmental drivers of risk.

Biodiversity and leptospirosis risk: a case of pathogen regulation?

Well balanced ecosystems have an essential role in disease regulation, and consequently their correct functioning is increasingly recognised as imperative for maintaining human health. Disruptions to ecosystems have been found to increase the risk of several diseases, including Hantavirus, Lyme disease, Ross River virus, malaria and Ciguatera fish poisoning. Leptospirosis is a globally important emerging zoonosis, caused by spirochaete bacteria, borne by many mammalian hosts, and also transmitted environmentally. We propose that leptospirosis incidence in humans is also linked to ecosystem disruption, and that reduced biodiversity (the diversity of species within an ecological community) may be associated with increased leptospirosis incidence. To investigate this hypothesis, the relationship between biodiversity levels of island nations and their annual leptospirosis incidence rates (adjusted for GDP per capita) was examined by linear correlation and regression. Supportive, statistically significant negative associations were obtained between leptospirosis incidence and (a) total number of species (r2=0.69, p<0.001) and (b) number of mammal species (r2=0.80, p<0.001) in univariate analysis. In multivariable analysis only the number of mammal species remained significantly associated (r2=0.81, p=0.007). An association between biodiversity and reduced leptospirosis risk, if supported by further research, would emphasise the importance of managing the emergence of leptospirosis (and other infectious diseases) at a broader, ecosystem level.

Human Leptospirosis Infection in Fiji: An Eco-epidemiological Approach to Identifying Risk Factors and Environmental Drivers for Transmission

Leptospirosis is an important zoonotic disease in the Pacific Islands. In Fiji, two successive cyclones and severe flooding in 2012 resulted in outbreaks with 576 reported cases and 7% case-fatality. We conducted a cross-sectional seroprevalence study and used an eco-epidemiological approach to characterize risk factors and drivers for human leptospirosis infection in Fiji, and aimed to provide an evidence base for improving the effectiveness of public health mitigation and intervention strategies. Antibodies indicative of previous or recent infection were found in 19.4% of 2152 participants (81 communities on the 3 main islands). Questionnaires and geographic information systems data were used to assess variables related to demographics, individual behaviour, contact with animals, socioeconomics, living conditions, land use, and the natural environment. On multivariable logistic regression analysis, variables associated with the presence of Leptospira antibodies included male gender (OR 1.55), iTaukei ethnicity (OR 3.51), living in villages (OR 1.64), lack of treated water at home (OR 1.52), working outdoors (1.64), living in rural areas (OR 1.43), high poverty rate (OR 1.74), living <100m from a major river (OR 1.41), pigs in the community (OR 1.54), high cattle density in the district (OR 1.04 per head/sqkm), and high maximum rainfall in the wettest month (OR 1.003 per mm). Risk factors and drivers for human leptospirosis infection in Fiji are complex and multifactorial, with environmental factors playing crucial roles. With global climate change, severe weather events and flooding are expected to intensify in the South Pacific. Population growth could also lead to more intensive livestock farming; and urbanization in developing countries is often associated with urban and peri-urban slums where diseases of poverty proliferate. Climate change, flooding, population growth, urbanization, poverty and agricultural intensification are important drivers of zoonotic disease transmission; these factors may independently, or potentially synergistically, lead to enhanced leptospirosis transmission in Fiji and other similar settings.

The Immunogenicity of a Modified Intradermal Pre-exposure Rabies Vaccination Schedule—A Case Series of 420 Travelers

BACKGROUND Current Australian recommendations for rabies pre-exposure vaccination involve the use of cell-culture-based rabies vaccines, which are administered via intramuscular (IM) or intradermal (ID) routes. ID vaccination is more affordable for travelers, but is only recommended if there is sufficient time to perform serology 2 to 3 weeks post-vaccination and confirm immunity prior to travel. We report the immunogenicity of a modified ID schedule that can be completed in less time than the standard ID schedule, and allow more travelers to be vaccinated prior to departure. METHODS Travelers were offered a modified schedule if they were unable to afford standard IM vaccinations, and did not have time to complete a standard ID course. The modified schedule consisted of two ID injections of 0.1 mL of human diploid cell rabies vaccine administered on days 0 and 7, and serology was performed to determine immune status at a time between day 21 and 28. RESULTS A total of 420 travelers aged between 10 and 65 years were vaccinated using the modified ID course. The overall seroconversion rate was 94.5%, with 397 travelers developing antibody levels of >0.5 IU/mL when tested at approximately 21 days post-vaccination. CONCLUSION The modified ID schedule used in this case series was highly effective, had similar immunogenicity to the standard ID schedule, and should be considered in travelers who are unable to complete standard IM or standard ID courses of rabies vaccines.

The Effectiveness of Intradermal Pre-exposure Rabies Vaccination in an Australian Travel Medicine Clinic

BACKGROUND The objective of the study was to assess the effectiveness of intradermal (ID) rabies vaccination and to determine whether any difference in response with age or gender exists. No published Australian data on the subject is available and controversy continues to surround the use of ID rabies vaccination for pre-exposure prophylaxis. Vaccinated travelers requiring postexposure treatment are sometimes considered unvaccinated. By confirming their immunity prior to travel, this problem may be avoided. METHODS The data was collected by retrospective analysis over 2 years at a specialized travel medicine clinic in Perth, Western Australia. The standard protocol is three ID injections of 0.1 mL, given on days 0, 7, and 28 with a booster after 12 months. The vaccine used was the Pasteur Merieux human diploid cell vaccine. Serology was performed 3 weeks after completion of the primary course or after a booster. Antibody levels were measured using the rapid fluorescent focus inhibition test, and levels of >0.5 IU/mL were considered protective. RESULTS A total of 164 travelers were included in the study, of which 144 had completed the three primary ID doses, and 20 had received an ID booster after a previous primary ID course. The mean age was 34.75 years, and gender distribution was equal. The median time between vaccination and serology was 23 days. The antibody levels ranged from 0 to 50 IU/mL with a mean of 8.42 IU/mL. Three travelers had no detectable antibodies giving a seroconversion rate of 98.2%. No statistically significant correlation between age or gender and antibody levels was present. CONCLUSION We have found that ID rabies vaccination is effective in a travel clinic with nurses experienced in the technique. The lower cost of ID rabies vaccination makes it accessible to a larger number of travelers. Further studies will be required to determine the duration of protection after ID vaccination and antibody response after postexposure boosters. We will continue to recommend ID rabies vaccination if there is sufficient time for serology to be performed and for results to be available prior to departure.

Distribution of rickettsioses in Oceania: past patterns and implications for the future.

Rickettsioses present a threat to human health worldwide, but relatively little is known on their epidemiology and ecology in Oceania. These bacteria are the cause of potentially fatal febrile illnesses in humans (categorized into scrub typhus, typhus group and spotted fever group rickettsioses). They are transmitted by arthropod vectors such as ticks, mites, fleas and lice, which are associated with vertebrate host animals including rodents and companion animals. We conducted a search in the scientific and grey literature of Rickettsia spp. and Orientia tsutsugamushi within the Oceania region. Human case reports, human serosurveys and PCR-based testing of vectors and host animals reviewed here highlight the widespread distribution of these pathogens in the region, with the majority of human serological and vector surveys reporting positive results. These findings suggest that rickettsioses may have a significantly higher burden of disease in Oceania than is currently appreciated due to diagnostic challenges. Furthermore, consideration of the ecology and risk factors for rickettsioses reported for Oceania suggests that their importance as a cause of undifferentiated acute febrile illness may grow in the future: environmental and social changes driven by predicted climate change and population growth have the potential to lead to the emergence of rickettsioses as a significant public health problem in Oceania.