Exploring the association of weather variability on Campylobacter - A systematic review.

BACKGROUND: Previous work has found climate change-induced weather variability is suspected to increase the transmission of enteric pathogens, including Campylobacter, a leading cause of bacterial gastroenteritis. While the relationship between extreme weather events and diarrheal diseases has been documented, the specific impact on Campylobacter infections remains underexplored. OBJECTIVE: To synthesize the peer-reviewed literature exploring the effect of weather variability on Campylobacter infections in humans. METHODS: The review included English language, peer-reviewed articles, published up to September 1, 2022 in PubMed, Embase, GEOBASE, Agriculture and Environmental Science Database, and CABI Global Health exploring the effect of an antecedent weather event on human enteric illness caused by Campylobacter (PROSPERO Protocol # 351884). We extracted study information including data sources, methods, summary measures, and effect sizes. Quality and weight of evidence reported was summarized and bias assessed for each article. RESULTS: After screening 278 articles, 47 articles (34 studies, 13 outbreak reports) were included in the evidence synthesis. Antecedent weather events included precipitation (n = 35), temperature (n = 30), relative humidity (n = 7), sunshine (n = 6), and El Niño and La Niña (n = 3). Reviewed studies demonstrated that increases in precipitation and temperature were correlated with Campylobacter infections under specific conditions, whereas low relative humidity and sunshine were negatively correlated. Articles estimating the effect of animal operations (n = 15) found presence and density of animal operations were significantly associated with infections. However, most of the included articles did not assess confounding by seasonality, presence of animal operations, or describe estimates of risk. DISCUSSION: This review explores what is known about the influence of weather events on Campylobacter and identifies previously underreported negative associations between low relative humidity and sunshine on Campylobacter infections. Future research should explore pathogen-specific estimates of risk, which can be used to influence public health strategies, improve source attribution and causal pathways, and project disease burden due to climate change.

'You have a lot of mirrors': structural and socioecological factors impacting adolescent pregnancy and reproductive health in the Amazon basin, Peru, a qualitative study.

Loreto, in the Peruvian Amazon, has one of the highest adolescent pregnancy rates in the country. However, underlying causes of adolescent pregnancy are not fully understood as data are limited in Indigenous and remote Amazonian communities. This study investigated adolescent reproductive health within Loreto using an ecological systems framework. Forty-one semi-structured interviews were conducted in June 2022: community leaders (n = 12) and adolescent participants between 15 and 17 years of age (pregnant girls, n = 11; never pregnant girls, n = 9; and boys, n = 9). We also conducted focus group discussions with community health workers and educators in October 2022 (three focus groups, n = 15). Adolescent reproductive health is complex with multi-layered factors that put girls at higher risk of pregnancy. We found a paradoxical relationship between expected social and gender norms and individual desires. This research provides a contextual understanding of the lived experience of adolescents and young people in the Amazon region of Peru. Our findings suggest the need for greater exploration of the contradictory ideas surrounding adolescent pregnancy and female sexuality.

Helicobacter pylori treatment knowledge, access and barriers: A cross-sectional study.

BACKGROUND: Helicobacter pylori (Hp) is among the most common bacterial infections in the world and one of the most common infectious agents linked to malignancy, gastric cancer (GC). Within the US there is high disparity in the rates of Hp infection and associated diseases. Hp infection is treatable, and knowledge may influence screening and treatment seeking behaviors. MATERIALS AND METHODS: In this cross-sectional study of 1042 respondents recruited from the Online Amazon MTurk platform, we sought to assess baseline knowledge of Hp and to gain insight into barriers related to Hp care. RESULTS: Just over half (52.3%) reported some prior knowledge of Hp with 11.7% (n = 122) reporting being treated for Hp themselves and 21.4% reporting family members diagnosed with Hp. Of respondents reporting prior treatment, 95 (78%) reported GI upset and 27 (21%) reported not completing medications. Specific to Hp and GC, 70% indicated that a belief that the treatment was worse than the symptoms would affect their willingness to seek care, while 81% indicated knowing Hp can cause GC would affect their treatment decisions and knowing their gastric symptoms were caused by Hp would affect their willingness to receive care. CONCLUSIONS: Knowledge of Hp in this US sample of online respondents is low and self-reported difficulties with treatment compliance is high. Increasing awareness of this infection and addressing the challenges to treatment compliance could potentially reduce rates of Hp antibiotic resistance and progression to GC or other complications of Hp infection.

Evaluating the Strength of Association of Human Papillomavirus Infection With Penile Carcinoma: A Meta-Analysis.

BACKGROUND: Human papillomavirus (HPV) is a common sexually transmitted infection that is strongly associated with cervical cancer. A link to penile cancers has been suggested by case series. We sought to assess the strength of the association between HPV infection and penile cancer by meta-analysis. METHODS: A literature search to identify population-based studies evaluating the risk of HPV infection with penile cancer was conducted via PubMed and Google Scholar databases through December 2020. Studies were included in the pooled analyses if they presented relative risk (RR) estimates comparing penile cancer cases with noncases by HPV exposure status. They were stratified by (1) type of HPV, (2) test used to determine past HPV infection, and (3) the penile cancer type. Pooled analyses were conducted for stratum with at least 2 independent studies using fixed-effects and random-effects models. RESULTS: Fourteen articles representing 9 study populations fit the inclusion criteria and were included in the pooled analysis. Based on these studies, the pooled RRs are 2.9 (95% confidence interval [CI], 1.7-5.0; n = 4 studies) for invasive penile cancer and seropositivity to HPV16 L1, 4.5 (95% CI, 1.3-15.5; n = 2) for seropositivity to HPV18, and 8.7 for anogenital warts (95% CI, 5.1-14.8; n = 5). For the 3 studies reporting invasive and in situ penile cancer, the risk was 7.6 for anogenital warts. CONCLUSIONS: The pooled RRs indicate up to a 4.5-fold increased risk between seropositivity for HPV infection and invasive penile cancer. This is much lower than associations seen between HPV and cervical cancer.

Identification and characterization of a mosquito-specific eggshell organizing factor in Aedes aegypti mosquitoes.

Mosquito-borne diseases are responsible for several million human deaths annually around the world. One approach to controlling mosquito populations is to disrupt molecular processes or antagonize novel metabolic targets required for the production of viable eggs. To this end, we focused our efforts on identifying proteins required for completion of embryonic development that are mosquito selective and represent potential targets for vector control. We performed bioinformatic analyses to identify putative protein-coding sequences that are specific to mosquito genomes. Systematic RNA interference (RNAi) screening of 40 mosquito-specific genes was performed by injecting double-stranded RNA (dsRNA) into female Aedes aegypti mosquitoes. This experimental approach led to the identification of eggshell organizing factor 1 (EOF1, AAEL012336), which plays an essential role in the formation and melanization of the eggshell. Eggs deposited by EOF1-deficient mosquitoes have nonmelanized fragile eggshells, and all embryos are nonviable. Scanning electron microscopy (SEM) analysis identified that exochorionic eggshell structures are strongly affected in EOF1-deficient mosquitoes. EOF1 is a potential novel target, to our knowledge, for exploring the identification and development of mosquito-selective and biosafe small-molecule inhibitors.

Improving Undergraduate Epidemiology Education: An Example Using Instructional Teams.

Epidemiology is a core component of the undergraduate public health curriculum and a critical component of a healthy community and a comprehensive education. Evidence-based, collaborative instructional practices improve student success, reach diverse student populations, and improve learning outcomes. Here we describe the pedagogical approach of an instructional team with which we observed an 18% greater learning gain (95% confidence interval: 6.5, 29.5; t = -3.08; P = 0.002), based on pre-/posttesting in a large (approximately 120 students) undergraduate course, than with the prior course offering. There were no differences in DEW rates (defined as receiving a grade of D (scoring 60%-69%) or E (scoring <60%) or withdrawing (W)) between the 2 offerings, but the ratio of "A" to "B" grades was higher (by approximately 10%) after deployment of the instructional team (Pearson's χ2 (1 degree of freedom) = 4.17, P = 0.041). In addition, students reported greater satisfaction with the course deploying an instructional team (80.4% positive sentiment in course evaluation comments compared with 76.1% in the prior offering). As students and faculty become more familiar with effective evidence-based instructional practices, improvements in student learning can be achieved and the goal of creating an educated citizenry ready to build a healthy society will be more attainable.

Community transmission of multidrug-resistant tuberculosis is associated with activity space overlap in Lima, Peru.

BACKGROUND: Transmission of multidrug-resistant tuberculosis (MDRTB) requires spatial proximity between infectious cases and susceptible persons. We assess activity space overlap among MDRTB cases and community controls to identify potential areas of transmission. METHODS: We enrolled 35 MDRTB cases and 64 TB-free community controls in Lima, Peru. Cases were whole genome sequenced and strain clustering was used as a proxy for transmission. GPS data were gathered from participants over seven days. Kernel density estimation methods were used to construct activity spaces from GPS locations and the utilization distribution overlap index (UDOI) was used to quantify activity space overlap. RESULTS: Activity spaces of controls (median = 35.6 km2, IQR = 25.1-54) were larger than cases (median = 21.3 km2, IQR = 17.9-48.6) (P = 0.02). Activity space overlap was greatest among genetically clustered cases (mean UDOI = 0.63, sd = 0.67) and lowest between cases and controls (mean UDOI = 0.13, sd = 0.28). UDOI was positively associated with genetic similarity of MDRTB strains between case pairs (P < 0.001). The odds of two cases being genetically clustered increased by 22% per 0.10 increase in UDOI (OR = 1.22, CI = 1.09-1.36, P < 0.001). CONCLUSIONS: Activity space overlap is associated with MDRTB clustering. MDRTB transmission may be occurring in small, overlapping activity spaces in community settings. GPS studies may be useful in identifying new areas of MDRTB transmission.

A Case-Control Study to Identify Community Venues Associated with Genetically-clustered, Multidrug-resistant Tuberculosis Disease in Lima, Peru.

BACKGROUND: The majority of tuberculosis transmission occurs in community settings. Our primary aim in this study was to assess the association between exposure to community venues and multidrug-resistant (MDR) tuberculosis. Our secondary aim was to describe the social networks of MDR tuberculosis cases and controls. METHODS: We recruited laboratory-confirmed MDR tuberculosis cases and community controls that were matched on age and sex. Whole-genome sequencing was used to identify genetically clustered cases. Venue tracing interviews (nonblinded) were conducted to enumerate community venues frequented by participants. Logistic regression was used to assess the association between MDR tuberculosis and person-time spent in community venues. A location-based social network was constructed, with respondents connected if they reported frequenting the same venue, and an exponential random graph model (ERGM) was fitted to model the network. RESULTS: We enrolled 59 cases and 65 controls. Participants reported 729 unique venues. The mean number of venues reported was similar in both groups (P = .92). Person-time in healthcare venues (adjusted odds ratio [aOR] = 1.67, P = .01), schools (aOR = 1.53, P < .01), and transportation venues (aOR = 1.25, P = .03) was associated with MDR tuberculosis. Healthcare venues, markets, cinemas, and transportation venues were commonly shared among clustered cases. The ERGM indicated significant community segregation between cases and controls. Case networks were more densely connected. CONCLUSIONS: Exposure to healthcare venues, schools, and transportation venues was associated with MDR tuberculosis. Intervention across the segregated network of case venues may be necessary to effectively stem transmission.

Emerging Evidence for Infectious Causes of Cancer in the United States.

Worldwide, infectious agents currently contribute to an estimated 15% of new cancer cases. Most of these (92%, or 2 million new cancer cases) are attributable to 4 infectious agents: Helicobacter pylori, human papillomavirus, and hepatitis B and C viruses. A better understanding of how infectious agents relate to the US cancer burden may assist new diagnostic and treatment efforts. We review US-specific crude mortality rates from infection-associated cancers and describe temporal and spatial trends since 1999. We review the US-specific evidence for infection-cancer associations by reporting available estimates for attributable fractions for the infection-cancer associations. Death due to cancers with established infectious associations varies geographically, but estimates for the US attributable fraction are limited to a few observational studies. To describe the burden of infection-associated cancer in the United States, additional observational studies are necessary to estimate the prevalence of infection nationally and within subpopulations. As infectious associations emerge to explain cancer etiologies, new opportunities and challenges to reducing the burden arise. Improved estimates for the United States would help target interventions to higher-risk subpopulations.

Summary results of the 2014-2015 DARPA Chikungunya challenge.

BACKGROUND: Emerging pathogens such as Zika, chikungunya, Ebola, and dengue viruses are serious threats to national and global health security. Accurate forecasts of emerging epidemics and their severity are critical to minimizing subsequent mortality, morbidity, and economic loss. The recent introduction of chikungunya and Zika virus to the Americas underscores the need for better methods for disease surveillance and forecasting. METHODS: To explore the suitability of current approaches to forecasting emerging diseases, the Defense Advanced Research Projects Agency (DARPA) launched the 2014-2015 DARPA Chikungunya Challenge to forecast the number of cases and spread of chikungunya disease in the Americas. Challenge participants (n=38 during final evaluation) provided predictions of chikungunya epidemics across the Americas for a six-month period, from September 1, 2014 to February 16, 2015, to be evaluated by comparison with incidence data reported to the Pan American Health Organization (PAHO). This manuscript presents an overview of the challenge and a summary of the approaches used by the winners. RESULTS: Participant submissions were evaluated by a team of non-competing government subject matter experts based on numerical accuracy and methodology. Although this manuscript does not include in-depth analyses of the results, cursory analyses suggest that simpler models appear to outperform more complex approaches that included, for example, demographic information and transportation dynamics, due to the reporting biases, which can be implicitly captured in statistical models. Mosquito-dynamics, population specific information, and dengue-specific information correlated best with prediction accuracy. CONCLUSION: We conclude that with careful consideration and understanding of the relative advantages and disadvantages of particular methods, implementation of an effective prediction system is feasible. However, there is a need to improve the quality of the data in order to more accurately predict the course of epidemics.

Management of Helicobacter Pylori in the United States: Results from a national survey of gastroenterology physicians.

BACKGROUND AND AIMS: We sought to determine current knowledge and practices among gastroenterology physicians and assess adherence to current guidelines for H. pylori management. METHODS: Online surveys were distributed in 2014 to practicing gastroenterology physicians for information related to the diagnosis and treatment of H. pylori infection. RESULTS: A total of 582 completed surveys were reviewed. The H. pylori screening test used "almost always" was gastric biopsy obtained during endoscopy (histology) (59%) followed by stool antigen test (20%). Standard triple therapy for 14days was commonly prescribed by 53% of respondents. The stool antigen test was most frequently chosen to confirm H. pylori eradication (51%), although only 58% of physicians checked for eradication in patients who underwent treatment. CONCLUSIONS: Adherence to current American College of Gastroenterology guidelines is low. Although more physicians treat patients with a positive H. pylori test, only half ensure eradication after treatment. Improving knowledge of the resistance patterns of H. pylori may be critical to ensure successful eradication.

ATP Acyl Phosphate Reactivity Reveals Native Conformations of Hsp90 Paralogs and Inhibitor Target Engagement.

Hsp90 is an ATP-dependent chaperone of widespread interest as a drug target. Here, using an LC-MS/MS chemoproteomics platform based on a lysine-reactive ATP acyl phosphate probe, several Hsp90 inhibitors were profiled in native cell lysates. Inhibitor specificities for all four human paralogs of Hsp90 were simultaneously monitored at their endogenous relative abundances. Equipotent inhibition of probe labeling in each paralog occurred at sites both proximal to and distal from bound ATP observed in Hsp90 cocrystal structures, suggesting that the ATP probe is assaying a native conformation not predicted by available structures. Inhibitor profiling against a comprehensive panel of protein kinases and other ATP-binding proteins detected in native cell lysates identified PMS2, a member of the GHKL ATPase superfamily as an off-target of NVP-AUY922 and radicicol. Because of the endogenously high levels of Hsp90 paralogs in typical cell lysates, the measured potency of inhibitors was weaker than published IC50 values. Significant inhibition of Hsp90 required inhibitor concentrations above a threshold where off-target activity was detectable. Direct on- and off-target engagement was measured by profiling lysates derived from cells treated with Hsp90 inhibitors. These studies also assessed the downstream cellular pathway effects of Hsp90 inhibition, including the down regulation of several known Hsp90 client proteins and some previously unknown client proteins. Overall, the ATP probe-based assay methodology enabled a broad characterization of Hsp90 inhibitor activity and specificity in native cell lysates.

Monitoring native p38α:MK2/3 complexes via trans delivery of an ATP acyl phosphate probe.

Here we describe a chemical proteomics strategy using ATP acyl phosphates to measure the formation of a protein:protein complex between p38α and mapkap kinases 2 and/or 3. Formation of the protein:protein complex results in a new probe labeling site on p38α that can be used to quantify the extent of interaction in cell lysates and the equilibrium binding constant for the interaction in vitro. We demonstrate through RNA interference that the labeling site is dependent on formation of the protein:protein complex in cells. Further, we identify that active-site-directed, small-molecule inhibitors of MK2/3 selectively inhibit the heterodimer-dependent probe labeling, whereas p38α inhibitors do not. These findings afford a new method to evaluate p38α and MK2/3 inhibitors within native biological systems and a new tool for improved understanding of p38α signaling pathways.

The downstream effects of COVID-19 on adolescent girls in the Peruvian Amazon: qualitative findings on how the pandemic affected education and reproductive health.

Due to COVID-19, schools were closed to mitigate disease spread. Past studies have shown that disruptions in education have unintended consequences for adolescents, including increasing their risk of school dropout, exploitation, gender-based violence, pregnancy and early unions. In Peru, the government closed schools from March 2020 to March 2022, declaring a national emergency that affected an estimated 8 million children. These closures may have unintended consequences, including increased adolescent pregnancy, particularly in Peru's rural, largely indigenous regions. Loreto, located in the Peruvian Amazon, has one of the highest adolescent pregnancy rates in the country and poor maternal and child health outcomes. The underlying causes may not be fully understood as data are limited, especially as we transition out of the pandemic. This qualitative study investigated the downstream effects of COVID-19 on adolescent education and reproductive health in Loreto's districts of Nauta and Parinari. In-depth interviews (n=41) were conducted with adolescents and community leaders. These were held in June 2022, 3 months after the reinstitution of in-person classes throughout Peru. Focus group discussions (FGDs) were also completed with community health workers and educators from the same study area in October 2022 to supplement our findings (3 FGDs, n=15). We observed that the economic, educational and health effects of the COVID-19 pandemic contributed to reduced contraceptive use, and increased school abandonment, early unions and adolescent pregnancy. The interplay between adolescent pregnancy and both early unions and school abandonment was bidirectional, with each acting as both a cause and consequence of the other.

Amides of 4-hydroxy-8-methanesulfonylamino-quinoline-2-carboxylic acid as zinc-dependent inhibitors of Lp-PLA2.

AX10479, the phenyl amide of 4-hydroxy-8-methanesulfonylamino-quinoline-2-carboxylic acid, was identified as a Zn(2+)-dependent, 27nM inhibitor of human plasma Lp-PLA(2). Structure-activity relationship studies focused on the AX10479 2-phenylamide group identified equipotent cycloaliphatic amides, an enantioselective preference for chiral amides, and phenyl substitution patterns (e.g., 2-methyl-3-fluoro) that increased potency.

The malaria transmission in Anhui province China.

Plasmodium vivax and Plasmodium falciparum cases have opposite trends in Anhui China in the past decade. Long term and seasonal trends in the transmission rate of P. falciparum in Africa has been well studied, however that of P. vivax transmitted by Anopheles sinensis in China has not been investigated. There is a lot of work on the relationship between P. vivax cases and climatic factors in China, with sometimes contradicting results. However, how climatic factors affect transmission rate of P. vivax in China is unknown. We used Anhui province as an example to analyze the recent transmission dynamics where two types of malaria have been reported with differing etiologies. We examined breakpoints of the P. vivax and P. falciparum malaria long term dynamics in the recent decade. For locally transmitted P. vivax malaria, we analyzed the transmission rate and its seasonality using the combined human and mosquitos SIR-SI model with time-varied mosquito biting rate. We identified the effects of meteorological factors on the seasonality in transmission rate using a GAM model. For the imported P. falciparum malaria, we analyzed the potential reason for the observed increase in cases. The breakpoints of P. vivax and P. falciparum dynamics happened in a same year, 2010. The seasonality in the transmission rate of P. vivax malaria was high (42.4%) and was linearly associated with temperature and nonlinearly with rainfall. The abrupt increase in imported P. falciparum cases after the breakpoint was significantly related to the increased annual Chinese investment in Africa. Under the conditions of the existing vectors of malaria, long-term trends in climatic factors, and increasing trend in migration to/from endemic areas and imported malaria cases, we should be cautious of the possibility of the reestablishment of malaria in regions where it has been eliminated or the establishment of other vector-borne diseases.

Comparison of Prognostic Factors for Merkel Cell Carcinoma, Mucosal Melanoma and Cutaneous Malignant Melanoma: Insights into Their Etiologies.

Little is known about the epidemiology of Merkel cell carcinoma (MCC) and mucosal melanoma (MM). Using the United States (US) National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program data, we compared MCC and MM with cutaneous malignant melanoma (CMM) with respect to incidence rates and prognostic factors to better understand disease etiologies. We describe the proportional incidences of the three cancers along with their survival rates based on 20 years of national data. The incidence rates in 2000-2019 were 203.7 per 1,000,000 people for CMM, 5.9 per 1,000,000 people for MCC and 0.1 per 1,000,000 people for MM. The rates of these cancers increased over time, with the rate of MM tripling between 2000-2009 and 2010-2019. The incidences of these cancers increased with age and rates were highest among non-Hispanic Whites. Fewer MCCs and MMS were diagnosed at the local stage compared with CMM. The cases in the 22 SEER registries in California were not proportional to the 2020 population census but instead were higher than expected for CMM and MCC and lower than expected for MM. Conversely, MM rates were higher than expected in Texas and New York. These analyses highlight similarities in the incidence rates of CMM and MCC-and differences between them and MM rates-by state. Understanding more about MCC and MM is important because of their higher potential for late diagnosis and metastasis, which lead to poor survival.

Antibiotic Resistance Rates for Helicobacter pylori in Rural Arizona: A Molecular-Based Study.

Helicobacter pylori (H. pylori) is a common bacterial infection linked to gastric malignancies. While H. pylori infection and gastric cancer rates are decreasing, antibiotic resistance varies greatly by community. Little is known about resistance rates among rural Indigenous populations in the United States. From 2018 to 2021, 396 endoscopy patients were recruited from a Northern Arizona clinic, where community H. pylori prevalence is near 60%. Gastric biopsy samples positive for H. pylori (n = 67) were sequenced for clarithromycin- and metronidazole-associated mutations, 23S ribosomal RNA (23S), and oxygen-insensitive NADPH nitroreductase (rdxA) regions. Medical record data were extracted for endoscopic findings and prior H. pylori history. Data analysis was restricted to individuals with no history of H. pylori infection. Of 49 individuals, representing 64 samples which amplified in the 23S region, a clarithromycin-associated mutation was present in 38.8%, with T2182C being the most common mutation at 90%. While the prevalence of metronidazole-resistance-associated mutations was higher at 93.9%, the mutations were more variable, with D95N being the most common followed by L62V. No statistically significant sex differences were observed for either antibiotic. Given the risk of treatment failure with antibiotic resistance, there is a need to consider resistance profile during treatment selection. The resistance rates in this population of American Indian patients undergoing endoscopy are similar to other high-risk populations. This is concerning given the high H. pylori prevalence and low rates of resistance testing in clinical settings. The mutations reported are associated with antibiotic resistance, but clinical resistance must be confirmed.

A new algorithm quantifies the roles of wind and midge flight activity in the bluetongue epizootic in northwest Europe.

The 2006 bluetongue (BT) outbreak in northwestern Europe had devastating effects on cattle and sheep in that intensively farmed area. The role of wind in disease spread, through its effect on Culicoides dispersal, is still uncertain, and remains unquantified. We examine here the relationship between farm-level infection dates and wind speed and direction within the framework of a novel model involving both mechanistic and stochastic steps. We consider wind as both a carrier of host semio-chemicals, to which midges might respond by upwind flight, and as a transporter of the midges themselves, in a more or less downwind direction. For completeness, we also consider midge movement independent of wind and various combinations of upwind, downwind and random movements. Using stochastic simulation, we are able to explain infection onset at 94 per cent of the 2025 affected farms. We conclude that 54 per cent of outbreaks occurred through (presumably midge) movement of infections over distances of no more than 5 km, 92 per cent over distances of no more than 31 km and only 2 per cent over any greater distances. The modal value for all infections combined is less than 1 km. Our analysis suggests that previous claims for a higher frequency of long-distance infections are unfounded. We suggest that many apparent long-distance infections resulted from sequences of shorter-range infections; a 'stepping stone' effect. Our analysis also found that downwind movement (the only sort so far considered in explanations of BT epidemics) is responsible for only 39 per cent of all infections, and highlights the effective contribution to disease spread of upwind midge movement, which accounted for 38 per cent of all infections. The importance of midge flight speed is also investigated. Within the same model framework, lower midge active flight speed (of 0.13 rather than 0.5 m s(-1)) reduced virtually to zero the role of upwind movement, mainly because modelled wind speeds in the area concerned were usually greater than such flight speed. Our analysis, therefore, highlights the need to improve our knowledge of midge flight speed in field situations, which is still very poorly understood. Finally, the model returned an intrinsic incubation period of 8 days, in accordance with the values reported in the literature. We argue that better understanding of the movement of infected insect vectors is an important ingredient in the management of future outbreaks of BT in Europe, and other devastating vector-borne diseases elsewhere.