Daniel E. Impoinvil

The effects of human movement on the persistence of vector-borne diseases

With the recent resurgence of vector-borne diseases due to urbanization and development there is an urgent need to understand the dynamics of vector-borne diseases in rapidly changing urban environments. For example, many empirical studies have produced the disturbing finding that diseases continue to persist in modern city centers with zero or low rates of transmission. We develop spatial models of vector-borne disease dynamics on a network of patches to examine how the movement of humans in heterogeneous environments affects transmission. We show that the movement of humans between patches is sufficient to maintain disease persistence in patches with zero transmission. We construct two classes of models using different approaches: (i) Lagrangian models that mimic human commuting behavior and (ii) Eulerian models that mimic human migration. We determine the basic reproduction number R(0) for both modeling approaches. We show that for both approaches that if the disease-free equilibrium is stable (R(0)<1) then it is globally stable and if the disease-free equilibrium is unstable (R(0)>1) then there exists a unique positive (endemic) equilibrium that is globally stable among positive solutions. Finally, we prove in general that Lagrangian and Eulerian modeling approaches are not equivalent. The modeling approaches presented provide a framework to explore spatial vector-borne disease dynamics and control in heterogeneous environments. As an example, we consider two patches in which the disease dies out in both patches when there is no movement between them. Numerical simulations demonstrate that the disease becomes endemic in both patches when humans move between the two patches.

The Spatial Heterogeneity between Japanese Encephalitis Incidence Distribution and Environmental Variables in Nepal

Background To identify potential environmental drivers of Japanese Encephalitis virus (JE) transmission in Nepal, we conducted an ecological study to determine the spatial association between 2005 Nepal JE incidence, and climate, agricultural, and land-cover variables at district level. Methods District-level data on JE cases were examined using Local Indicators of Spatial Association (LISA) analysis to identify spatial clusters from 2004 to 2008 and 2005 data was used to fit a spatial lag regression model with climate, agriculture and land-cover variables. Results Prior to 2006, there was a single large cluster of JE cases located in the Far-West and Mid-West terai regions of Nepal. After 2005, the distribution of JE cases in Nepal shifted with clusters found in the central hill areas. JE incidence during the 2005 epidemic had a stronger association with May mean monthly temperature and April mean monthly total precipitation compared to mean annual temperature and precipitation. A parsimonious spatial lag regression model revealed, 1) a significant negative relationship between JE incidence and April precipitation, 2) a significant positive relationship between JE incidence and percentage of irrigated land 3) a non-significant negative relationship between JE incidence and percentage of grassland cover, and 4) a unimodal non-significant relationship between JE Incidence and pig-to-human ratio. Conclusion JE cases clustered in the terai prior to 2006 where it seemed to shift to the Kathmandu region in subsequent years. The spatial pattern of JE cases during the 2005 epidemic in Nepal was significantly associated with low precipitation and the percentage of irrigated land. Despite the availability of an effective vaccine, it is still important to understand environmental drivers of JEV transmission since the enzootic cycle of JEV transmission is not likely to be totally interrupted. Understanding the spatial dynamics of JE risk factors may be useful in providing important information to the Nepal immunization program.

Expression of metallothionein and α-tubulin in heavy metal-tolerant Anopheles gambiae sensu stricto (Diptera: Culicidae)

Anopheles mosquitoes have been shown to adapt to heavy metals in their natural habitats. In this study we explored the possibility of using Anopheles gambiae sensu stricto as bio-reporters for environmental heavy metal pollution through expressions of their metal-responsive metallothionein and alpha-tubulin genes. The study was undertaken with third instar larvae after selection by cadmium, copper, or lead at LC(30) through five successive generations. Expression levels were determined in the 5th generation by semi-quantitative RT-PCR on the experimental and control populations. The data were analyzed using one-way ANOVA. The highest metallothionein (F(3,11)=4.574, P=0.038) and alpha-tubulin (F(3,11)=12.961, P=0.002) responses were observed in cadmium-tolerant treatments. There was significantly higher expression of metallothionein in cadmium or copper treatments relative to the control (P=0.012), and in cadmium than in lead treatments (P=0.044). Expressions of alpha-tubulin were significantly higher in cadmium than in control treatments (P=0.008). These results demonstrate the capacity of An. gambiae s.s. to develop tolerance to increased levels of heavy metal challenge. The results also confirm the potential of heavy metal-responsive genes in mosquitoes as possible bio-indicators of heavy metal environmental pollution. How the tolerance and expressions relate to An. gambiae s.s. fitness and vectorial capacity in the environment remains to be elucidated.

Evaluation of a temperate climate mosquito, Ochlerotatus detritus (=Aedes detritus), as a potential vector of Japanese encephalitis virus.

The U.K. has not yet experienced a confirmed outbreak of mosquito‐borne virus transmission to people or livestock despite numerous autochthonous epizootic and human outbreaks of mosquito‐borne diseases on the European mainland. Indeed, whether or not British mosquitoes are competent to transmit arboviruses has not been established. Therefore, the competence of a local (temperate) British mosquito species, Ochlerotatus detritus (=Aedes detritus) (Diptera: Culicidae) for transmission of a member of the genus Flavivirus, Japanese encephalitis virus (JEV) as a model for mosquito‐borne virus transmission was assessed. The JEV competence in a laboratory strain of Culex quinquefasciatus (Diptera: Culicidae), a previously incriminated JEV vector, was also evaluated as a positive control. Ochlerotatus detritus adults were reared from field‐collected juvenile stages. In oral infection bioassays, adult females developed disseminated infections and were able to transmit virus as determined by the isolation of virus in saliva secretions. When pooled at 7–21 days post‐infection, 13% and 25% of O. detritus were able to transmit JEV when held at 23 °C and 28 °C, respectively. Similar results were obtained for C. quinquefasciatus. To our knowledge, this study is the first to demonstrate that a British mosquito species, O. detritus, is a potential vector of an exotic flavivirus.

New Baseline Environmental Assessment of Mosquito Ecology in Northern Haiti during Increased Urbanization

ABSTRACT: The catastrophic 2010 earthquake in Port-au-Prince, Haiti, led to the large-scale displacement of over 2.3 million people, resulting in rapid and unplanned urbanization in northern Haiti. This study evaluated the impact of this unplanned urbanization on mosquito ecology and vector-borne diseases by assessing land use and change patterns. Land-use classification and change detection were carried out on remotely sensed images of the area for 2010 and 2013. Change detection identified areas that went from agricultural, forest, or bare-land pre-earthquake to newly developed and urbanized areas post-earthquake. Areas to be sampled for mosquito larvae were subsequently identified. Mosquito collections comprised five genera and ten species, with the most abundant species being Culex quinquefasciatus 35% (304/876), Aedes albopictus 27% (238/876), and Aedes aegypti 20% (174/876). All three species were more prevalent in urbanized and newly urbanized areas. Anopheles albimanus, the predominate malaria vector, accounted for less than 1% (8/876) of the collection. A set of spectral indices derived from the recently launched Landsat 8 satellite was used as covariates in a species distribution model. The indices were used to produce probability surfaces maps depicting the likelihood of presence of the three most abundant species within 30 m pixels. Our findings suggest that the rapid urbanization following the 2010 earthquake has increased the amount of area with suitable habitats for urban mosquitoes, likely influencing mosquito ecology and posing a major risk of introducing and establishing emerging vector-borne diseases.

Clinical and prognostic features among children with acute encephalitis syndrome in Nepal; a retrospective study

BackgroundAcute encephalitis syndrome (AES) is commonly seen among hospitalized Nepali children. Japanese Encephalitis (JE) accounts for approximately one-quarter of cases. Although poor prognostic features for JE have been identified, and guide management, relatively little is reported on the remaining three-quarters of AES cases.MethodsChildren with AES (n = 225) were identified through admission records from two hospitals in Kathmandu between 2006 and 2008. Patients without available lumbar puncture results (n = 40) or with bacterial or plasmodium infection (n = 40) were analysed separately. The remaining AES patients with suspected viral aetiology were classified, based on positive IgM antibody in serum or cerebral spinal fluid, as JE (n = 42) or AES of unknown viral aetiology (n = 103); this latter group was sub-classified into Non-JE (n = 44) or JE status unknown (n = 59). Bad outcome was defined as death or neurological sequelae at discharge.ResultsAES patients of suspected viral aetiology more frequently had a bad outcome than those with bacterial or plasmodium infection (31% versus 13%; P = 0.039). JE patients more frequently had a bad outcome than those with AES of unknown viral aetiology (48% versus 24%; P = 0.01). Bad outcome was independently associated in both JE and suspected viral aetiology groups with a longer duration of fever pre-admission (P = 0.007; P = 0.002 respectively) and greater impairment of consciousness (P = 0.02; P < 0.001). A higher proportion of JE patients presented with a focal neurological deficit compared to patients of unknown viral aetiology (13/40 versus 11/103; P = 0.005). JE patients weighed less (P = 0.03) and exhibited a higher respiratory rate (P = 0.003) compared to Non-JE patients.ConclusionsNepali children with AES of suspected viral aetiology or with JE frequently suffered a bad outcome. Despite no specific treatment, patients who experienced a shorter duration of fever before hospital admission more frequently recovered completely. Prompt referral may allow AES patients to receive potentially life-saving supportive management. Previous studies have indicated supportive management, such as fluid provision, is associated with better outcome in JE. The lower weight and higher respiratory rate among JE patients may reflect multiple clinical complications, including dehydration. The findings suggest a more systematic investigation of the influence of supportive management on outcome in AES is warranted.

The Role of Unused Swimming Pools as a Habitat for Anopheles Immature Stages in Urban Malindi, Kenya

ABSTRACT We conducted larval surveys in habitats located in urban Malindi, Kenya, in 2005 and 2006 with the goal of determining the productivity of unused swimming pools in relation to other habitats. Of the 250 habitats sampled, 66 were unused swimming pools, 93 were wells, 60 were drainage troughs, and 31 were miscellaneous areas, such as septic tanks, swamps, concrete tanks, fish ponds, car-track depressions, and drainage ponds. Anopheles gambiae s.l. was the only anophelines species found in the habitats, whereas Culex quinquefasciatus made up >95% of all culicine immature stages found. Of the 110 habitats found to be positive for mosquitoes, unused swimming pools represented 42.7%. One hundred and forty-eight anopheline pupae were found in 8 of the 66 unused swimming pools, but none was found in the other habitats. Using a nonparametric test, Kruskal–Wallis H test, there was no significant difference in the abundance of culicine pupae found in the 4 habitat types (χ2 = 7.350, df = 3, p = 0.062). Unused swimming pools in Malindi provide ideal habitats that should be targeted for mosquito control.

The effect of vaccination coverage and climate on Japanese encephalitis in Sarawak, Malaysia

Background Japanese encephalitis (JE) is the leading cause of viral encephalitis across Asia with approximately 70,000 cases a year and 10,000 to 15,000 deaths. Because JE incidence varies widely over time, partly due to inter-annual climate variability effects on mosquito vector abundance, it becomes more complex to assess the effects of a vaccination programme since more or less climatically favourable years could also contribute to a change in incidence post-vaccination. Therefore, the objective of this study was to quantify vaccination effect on confirmed Japanese encephalitis (JE) cases in Sarawak, Malaysia after controlling for climate variability to better understand temporal dynamics of JE virus transmission and control. Methodology/principal findings Monthly data on serologically confirmed JE cases were acquired from Sibu Hospital in Sarawak from 1997 to 2006. JE vaccine coverage (non-vaccine years vs. vaccine years) and meteorological predictor variables, including temperature, rainfall and the Southern Oscillation index (SOI) were tested for their association with JE cases using Poisson time series analysis and controlling for seasonality and long-term trend. Over the 10-years surveillance period, 133 confirmed JE cases were identified. There was an estimated 61% reduction in JE risk after the introduction of vaccination, when no account is taken of the effects of climate. This reduction is only approximately 45% when the effects of inter-annual variability in climate are controlled for in the model. The Poisson model indicated that rainfall (lag 1-month), minimum temperature (lag 6-months) and SOI (lag 6-months) were positively associated with JE cases. Conclusions/significance This study provides the first improved estimate of JE reduction through vaccination by taking account of climate inter-annual variability. Our analysis confirms that vaccination has substantially reduced JE risk in Sarawak but this benefit may be overestimated if climate effects are ignored.

Effectiveness of insecticide-treated bednets in malaria prevention in Haiti: a case-control study

BACKGROUND Insecticide-treated bednets (ITNs) are effective in preventing malaria where vectors primarily bite indoors and late at night, but their effectiveness is uncertain where vectors bite outdoors and earlier in the evening. We studied the effectiveness of ITNs following a mass distribution in Haiti from May to September, 2012, where the Anopheles albimanus vector bites primarily outdoors and often when people are awake. METHODS In this case-control study, we enrolled febrile patients presenting to outpatient departments at 17 health facilities throughout Haiti from Sept 4, 2012, to Feb 27, 2014, who were tested with malaria rapid diagnostic tests (RDTs), and administered questionnaires on ITN use and other risk factors. Cases were defined by positive RDT and controls were febrile patients from the same clinic with a negative RDT. Our primary analysis retrospectively matched cases and controls by age, sex, location, and date, and used conditional logistic regression on the matched sample. A sensitivity analysis used propensity scores to match patients on ITN use propensity and analyse malaria among ITN users and non-users. Additional ITN bioefficacy and entomological data were collected. FINDINGS We enrolled 9317 patients, including 378 (4%) RDT-positive cases. 1202 (13%) patients reported ITN use. Post-hoc matching of cases and controls yielded 362 cases and 1201 matched controls, 19% (333) of whom reported consistent campaign net use. After using propensity scores to match on consistent campaign ITN use, 2298 patients, including 138 (7%) RDT-positive cases, were included: 1149 consistent campaign ITN users and 1149 non-consistent campaign ITN users. Both analyses revealed that ITNs did not significantly protect against clinical malaria (odds ratio [OR]=0·95, 95% CI 0·68-1·32, p=0·745 for case-control analysis; OR=0·95, 95% CI 0·45-1·97, p=0·884 for propensity score analysis). ITN and entomological data indicated good ITN physical integrity and bioefficacy, and no permethrin resistance among local mosquitoes. INTERPRETATION We found no evidence that mass ITN campaigns reduce clinical malaria in this observational study in Haiti; alternative malaria control strategies should be prioritised. FUNDING The Global Fund to Fight AIDS, Tuberculosis, and Malaria, and the US-based Centers for Disease Control and Prevention (CDC).

Emergence or improved detection of Japanese encephalitis virus in the Himalayan highlands

The emergence of Japanese encephalitis virus (JEV) in the Himalayan highlands is of significant veterinary and public health concern and may be related to climate warming and anthropogenic landscape change, or simply improved surveillance. To investigate this phenomenon, a One Health approach focusing on the phylogeography of JEV, the distribution and abundance of the mosquito vectors, and seroprevalence in humans and animal reservoirs would be useful to understand the epidemiology of Japanese encephalitis in highland areas.