Estimating seroconversion rates accounting for repeated infections by approximate Bayesian computation.

This study presents a novel approach for inferring the incidence of infections by employing a quantitative model of the serum antibody response. Current methodologies often overlook the cumulative effect of an individual's infection history, making it challenging to obtain a marginal distribution for antibody concentrations. Our proposed approach leverages approximate Bayesian computation to simulate cross-sectional antibody responses and compare these to observed data, factoring in the impact of repeated infections. We then assess the empirical distribution functions of the simulated and observed antibody data utilizing Kolmogorov deviance, thereby incorporating a goodness-of-fit check. This new method not only matches the computational efficiency of preceding likelihood-based analyses but also facilitates the joint estimation of antibody noise parameters. The results affirm that the predictions generated by our within-host model closely align with the observed distributions from cross-sectional samples of a well-characterized population. Our findings mirror those of likelihood-based methodologies in scenarios of low infection pressure, such as the transmission of pertussis in Europe. However, our simulations reveal that in settings of higher infection pressure, likelihood-based approaches tend to underestimate the force of infection. Thus, our novel methodology presents significant advancements in estimating infection incidence, thereby enhancing our understanding of disease dynamics in the field of epidemiology.

Seroincidence of Enteric Fever, Juba, South Sudan.

We applied a new serosurveillance tool to estimate typhoidal Salmonella burden using samples collected during 2020 from a population in Juba, South Sudan. By using dried blood spot testing, we found an enteric fever seroincidence rate of 30/100 person-years and cumulative incidence of 74% over a 4-year period.

Severe Acute Respiratory Syndrome Coronavirus 2 Transmission in Georgia, USA, February 1-July 13, 2020.

The serial interval and effective reproduction number for coronavirus disease (COVID-19) are heterogenous, varying by demographic characteristics, region, and period. During February 1-July 13, 2020, we identified 4,080 transmission pairs in Georgia, USA, by using contact tracing information from COVID-19 cases reported to the Georgia Department of Public Health. We examined how various transmission characteristics were affected by symptoms, demographics, and period (during shelter-in-place and after subsequent reopening) and estimated the time course of reproduction numbers for all 159 Georgia counties. Transmission varied by time and place but also by persons' sex and race. The mean serial interval decreased from 5.97 days in February-April to 4.40 days in June-July. Younger adults (20-50 years of age) were involved in most transmission events occurring during or after reopening. The shelter-in-place period was not long enough to prevent sustained virus transmission in densely populated urban areas connected by major transportation links.

Tracing the Origin of Food-borne Disease Outbreaks: A Network Model Approach.

BACKGROUND: Food-borne disease outbreaks constitute a large health burden on society. One of the challenges when investigating such outbreaks is to trace the origin of the outbreak. In this study, we consider a network model to determine the spatial origin of the contaminated food product that caused the outbreak. METHODS: The network model we use replaces the classic geographic distance of a network by an effective distance so that two nodes connected by a long-range link may be more strongly connected than their geographic distance would suggest. Furthermore, the effective distance transforms complex spatial patterns into regular topological patterns, creating a means for easier identification of the origin of the spreading phenomenon. Because detailed information on food distribution is generally not available, the model uses the gravity model from economics: the flow of goods from one node to another increases with population size and decreases with the geographical distance between them. RESULTS: This effective distance network approach has been shown to perform well in a large Escherichia coli O104:H4 outbreak in Germany in 2011. In this article, we apply the same method to various food-borne disease outbreaks in the Netherlands. We found the effective distance network approach to fail in certain scenarios. CONCLUSIONS: Great care should be taken as to whether the underlying network model correctly captures the spreading mechanism of the outbreak in terms of spatial scale and single or multiple source outbreak.

Quantitative Assessment of the Health Risk for Livestock When Animal Viruses Are Applied in Human Oncolytic Therapy: A Case Study for Seneca Valley Virus.

Some viruses cause tumor regression and can be used to treat cancer patients; these viruses are called oncolytic viruses. To assess whether oncolytic viruses from animal origin excreted by patients pose a health risk for livestock, a quantitative risk assessment (QRA) was performed to estimate the risk for the Dutch pig industry after environmental release of Seneca Valley virus (SVV). The QRA assumed SVV excretion in stool by one cancer patient on Day 1 in the Netherlands, discharge of SVV with treated wastewater into the river Meuse, downstream intake of river water for drinking water production, and consumption of this drinking water by pigs. Dose-response curves for SVV infection and clinical disease in pigs were constructed from experimental data. In the worst scenario (four log10 virus reduction by drinking water treatment and a farm with 10,000 pigs), the infection risk is less than 1% with 95% certainty. The risk of clinical disease is almost seven orders of magnitude lower. Risks may increase proportionally with the numbers of treated patients and days of virus excretion. These data indicate that application of wild-type oncolytic animal viruses may infect susceptible livestock. A QRA regarding the use of oncolytic animal virus is, therefore, highly recommended. For this, data on excretion by patients, and dose-response parameters for infection and clinical disease in livestock, should be studied.

Children Are Exposed to Fecal Contamination via Multiple Interconnected Pathways: A Network Model for Exposure Assessment.

In recent decades, quantitative microbial risk assessment (QMRA) has been widely used to assess exposure to fecal microbes and associated health risks. In this study, a multipathway exposure assessment model was developed to evaluate exposure to fecal microbes for children under 5 in highly contaminated urban environments. Children had contact with various environmental compartments. The contamination levels of these compartments were estimated from fecal indicator counts in the environmental samples. Structured observations of child behavior (including activities, locations, and time) were used to model behavioral sequences as a dynamic network. The exposure model combines behavior sequences with environmental contamination, using additional exposure factors when needed, to estimate the number of fecal microbes transferred from environmental sources to human oral ingestion. As fecal exposure in a highly contaminated urban environment consists of contributions from multiple pathways, it is imperative to study their relative importance. The model helps us better understand the characteristics of the exposure pathways that may be driven by variation in contamination and by variable behavior, like hygiene and high-risk activities. Importantly, the model also allows prediction of the quantitative effects of an intervention-the expected reduction in exposure due to infrastructural or behavioral changes-by means of scenario studies. Based on experience with this exposure model, we make specific recommendations for additional studies of child behavior and exposure factors in order to fill critical information gaps and improve the model structure and assumptions.

Spatial Prediction of Coxiella burnetii Outbreak Exposure via Notified Case Counts in a Dose-Response Model.

We develop a novel approach to study an outbreak of Q fever in 2009 in the Netherlands by combining a human dose-response model with geostatistics prediction to relate probability of infection and associated probability of illness to an effective dose of Coxiella burnetii. The spatial distribution of the 220 notified cases in the at-risk population are translated into a smooth spatial field of dose. Based on these symptomatic cases, the dose-response model predicts a median of 611 asymptomatic infections (95% range: 410, 1,084) for the 220 reported symptomatic cases in the at-risk population; 2.78 (95% range: 1.86, 4.93) asymptomatic infections for each reported case. The low attack rates observed during the outbreak range from (Equation is included in full-text article.)to (Equation is included in full-text article.). The estimated peak levels of exposure extend to the north-east from the point source with an increasing proportion of asymptomatic infections further from the source. Our work combines established methodology from model-based geostatistics and dose-response modeling allowing for a novel approach to study outbreaks. Unobserved infections and the spatially varying effective dose can be predicted using the flexible framework without assuming any underlying spatial structure of the outbreak process. Such predictions are important for targeting interventions during an outbreak, estimating future disease burden, and determining acceptable risk levels.

Quantification of exposure to fecal contamination in open drains in four neighborhoods in Accra, Ghana.

In low-income countries, rapid urbanization adds pressure to already stressed water and sanitation systems that are critical to the health of communities. Drainage networks, designed for stormwater but commonly used for disposing of waste, are rarely covered completely, allowing residents to easily come into contact with their contents. This study used spatial mapping, documentation of physical drain characteristics, microbiological analysis of drain samples, and behavioral observation to comprehensively examine drains as a route of exposure to fecal contamination in four low-income neighborhoods in Accra, Ghana. A stochastic model of six likely exposure scenarios was constructed to estimate children's exposure to drain water. Regardless of the age of the child, any exposure scenario considered resulted in exposure to a high level of fecal contamination. Fecal contamination levels in drains were high (Escherichia coli: geometric mean (GM), 8.60 cfu log(10)/100 mL; coliphage: GM, 5.56 pfu log(10)/100 mL), and did not differ by neighborhood or physical drain characteristics, indicating that frequency of contact with drains, and not drain type or location, drives exposure risk. To mitigate health risks associated with this exposure, drains should be covered, with priority given to large concrete and small to medium dirt-lined drains that children were most commonly observed entering.

Estimating seroprevalence of human papillomavirus type 16 using a mixture model with smoothed age-dependent mixing proportions.

BACKGROUND: The presence in serum of antibodies to viral antigens is generally considered a well-defined marker of past infection or vaccination. However, analyses of serological data that use a cut-off value to classify individuals as seropositive are prone to misclassification bias, in particular when studying infections with a weak serological response, such as the sexually transmitted human papillomavirus (HPV). METHODS: We analyzed the serological concentrations of HPV type 16 (HPV16) antibodies in the general Dutch population in 2006-2007, before the introduction of mass vaccination against HPV. We used a 2-component mixture model to represent persons who were seronegative or seropositive for HPV16. Component densities were assumed to be log-normally distributed, with parameters possibly dependent on sex. The age-dependent mixing proportions were smoothed using penalized splines to obtain a flexible seroprevalence profile. RESULTS: Our results suggest that HPV16 seropositivity is associated with higher antibody concentrations in women as compared with men. Seroprevalence shows an increase starting from adolescence in men and women alike, coinciding with the age of sexual debut. Seroprevalence stabilizes in men around age 40, whereas it has a decreasing trend from age 50 onwards in women. Analyses that rely on a cut-off value to classify persons as seropositive yield substantially different seroprevalence profiles, leading to a qualitatively different interpretation of HPV16 infection dynamics. CONCLUSIONS: Our results provide a benchmark for examining the effect of HPV16 vaccination in future serological surveys. Our method may prove useful for estimating seroprevalence of other infections with a weak serological response.

An evidence synthesis approach to estimating the incidence of symptomatic pertussis infection in the Netherlands, 2005-2011.

BACKGROUND: Despite high vaccination coverage, infection with Bordetella pertussis is a current public health concern in the Netherlands and other European Union member states. Because surveillance data are subject to extensive under-ascertainment and under-reporting, incidence is difficult to determine. Our objective was to estimate the age-group specific incidence of symptomatic pertussis infection in the Netherlands over the period 2005-2011, using multi-parameter evidence synthesis. METHODS: Age-specific seroconversion probabilities were estimated for 2007 using Netherlands population data stratified by age-group and cross-sectional population-wide serosurvey (PIENTER-2) data, with a sero-diagnostic cut-off of 125 EU/ml as a proxy for recent infection. Symptomatic probabilities were derived from a study of household contacts and from PIENTER-2. The annual number of symptomatic infected (SI) persons was estimated using evidence synthesis methods in a Bayesian framework, by combining the estimated incidence of infection with notification data and symptomatic probabilities. RESULTS: An incidence rate of 128 SI cases per 10,000 population (95 % credible interval [CrI]: 110-150) was estimated for 2005, which decreased to 107 per 10,000 (95 % CrI: 91-126) for 2011. The degree of underestimation in statutory notified cases was age-dependent, ranging from 10-fold (10-19 years) to 69-fold (60+ years). The largest annual decreases in SI incidence rate over the study period were in the 1-4 and 5-9 years age-groups (24.3 %, 15.9 % per year, respectively). CONCLUSIONS: By synthesising all available data, the incidence of symptomatic pertussis and the extent to which SI is underrepresented by notification data can be estimated. Such estimates are essential for disease burden computation and for informing public health priority-setting.

Was the increase in culture-confirmed Campylobacter infections in Denmark during the 1990s a surveillance artefact?

In 1991, 1999 and 2006, randomly selected individuals from the Danish Central Personal Register provided a serum sample. From individuals aged 30 years and above, 500 samples from each year were analysed for Campylobacter IgG, IgA and IgM antibodies using a direct ELISA method. We applied a seroincidence calculator available from the European Centre for Disease Prevention and Control to perform a mathematical back-calculation to estimate the annual Campylobacter seroincidence in the Danish population. The estimated Campylobacter seroincidence did not differ significantly between the 1991, 1999 and 2006 studies although the reported number of culture-confirmed cases of Campylobacter infection increased 2.5 fold from 1993 to 1999 among individuals aged 30 years and above. This suggests that Campylobacter was widely present in the Danish population before the increase in poultry-associated clinical Campylobacter infections observed from 1993 to 2001 among individuals of this age groups.

Kinetics of the long-term antibody response after meningococcal C vaccination in patients with juvenile idiopathic arthritis: a retrospective cohort study.

OBJECTIVES: The kinetics of the antibody response induced by meningococcal serogroup C (MenC) conjugate vaccination was analysed in patients with juvenile idiopathic arthritis (JIA) to assess their long-term protection against MenC disease. METHODS: In The Netherlands, a nationwide catch-up campaign was performed in 2002 during which children aged 1-19 years, including JIA patients, received the MenC conjugate vaccination. From 127 JIA patients, IgG antibody concentrations against MenC-polysaccharide were determined by a fluorescent-bead-based immunoassay in 402 serum samples collected between 2002 and 2010. Using a hierarchical linear regression model, the 8 years course of MenC-specific antibodies was analysed in four age groups (13-19, 9-12.9, 5-8.9 and 1-4.9 years), and in patients starting with methotrexate or biologicals. In 65 randomly selected samples, the correlation of MenC-specific IgG concentrations with serum bactericidal assay (SBA) titres was assessed. MenC-specific IgG concentrations at 4.2 years after vaccination were compared with those of 1527 age-matched healthy controls. RESULTS: MenC-specific IgG concentrations postvaccination were highest in patients aged 13-19 years at time of vaccination. Antibodies gradually waned over time in patients, but their estimated concentrations at 4.2 years postvaccination were similar to those measured in controls. MenC-specific IgG concentrations correlated well with SBA titres (r=0.72, p<0.001). By contrast with methotrexate, starting treatment with biologicals induced a trend towards accelerated decline of MenC-specific antibodies. CONCLUSIONS: Persistence of MenC-specific IgG antibodies in JIA patients is similar to healthy controls, but treatment with biologicals may induce accelerated antibody waning, resulting in unprotected patients who may need revaccination.

Estimating the Seroincidence of Scrub Typhus using Antibody Dynamics after Infection.

Scrub typhus, a vector-borne bacterial infection, is an important but neglected disease globally. Accurately characterizing the burden is challenging because of nonspecific symptoms and limited diagnostics. Prior seroepidemiology studies have struggled to find consensus cutoffs that permit comparisons of estimates across contexts and time. In this study, we present a novel approach that does not require a cutoff and instead uses information about antibody kinetics after infection to estimate seroincidence. We use data from three cohorts of scrub typhus patients in Chiang Rai, Thailand, and Vellore, India, to characterize antibody kinetics after infection and two population serosurveys in the Kathmandu Valley, Nepal, and Tamil Nadu, India, to estimate seroincidence. The samples were tested for IgM and IgG responses to Orientia tsutsugamushi-derived recombinant 56-kDa antigen using commercial enzyme-linked immunosorbent assay kits. We used Bayesian hierarchical models to characterize antibody responses after scrub typhus infection and used the joint distributions of the peak antibody titers and decay rates to estimate population-level incidence rates in the cross-sectional serosurveys. Median responses persisted above an optical density (OD) of 1.8 for 23.6 months for IgG and an OD of 1 for 4.5 months for IgM. Among 18- to 29-year-olds, the seroincidence was 10 per 1,000 person-years (95% CI, 5-19) in Tamil Nadu, India, and 14 per 1,000 person-years (95% CI: 10-20) in the Kathmandu Valley, Nepal. When seroincidence was calculated with antibody decay ignored, the disease burden was underestimated by more than 50%. The approach can be deployed prospectively, coupled with existing serosurveys, or leverage banked samples to efficiently generate scrub typhus seroincidence estimates.

Human dose response relation for airborne exposure to Coxiella burnetii.

BACKGROUND: The recent outbreak of Q fever in the Netherlands between 2007 and 2009 is the largest recorded Q fever outbreak. Exposure to Coxiella burnetii may cause Q fever but the size of the population exposed during the outbreak remained uncertain as little is known of the infectivity of this pathogen. The quantification of the infectiousness and the corresponding response is necessary for assessing the risk to the population. METHODS: A human challenge study was published in the 1950s but this study quantified the dose of C. burnetii in relative units. Data from a concurrent guinea pig challenge study were combined with a recent study in which guinea pigs were challenged with a similar aerosol route to quantify human exposure. Concentration estimates for C. burnetii are made jointly with estimates of the dose response parameters in a hierarchical Bayesian framework. RESULTS: The dose for 50% infection (InfD50%) in human subjects is 1.18 bacteria (95% credible interval (CI) 0.76-40.2). The dose for 50% illness (IllD50) in challenged humans is 5.58 (95%CI 0.89-89.0) bacteria. The probability of a single viable C. burnetii causing infection in humans is 0.44 (95%CI 0.044-0.59) and for illness 0.12 (95%CI 0.0006-0.55). CONCLUSIONS: To our knowledge this is the first human dose-response model for C. burnetii. The estimated dose response relation demonstrates high infectivity in humans. In many published papers the proportion of infected individuals developing illness is reported to be 40%. Our model shows that the proportion of symptomatic infections may vary with the exposure dose. This implies that presence of these bacteria in the environment, even in small numbers, poses a serious health risk to the population.

When case reporting becomes untenable: Can sewer networks tell us where COVID-19 transmission occurs?

Monitoring SARS-CoV-2 in wastewater is a valuable approach to track COVID-19 transmission. Designing wastewater surveillance (WWS) with representative sampling sites and quantifiable results requires knowledge of the sewerage system and virus fate and transport. We developed a multi-level WWS system to track COVID-19 in Atlanta using an adaptive nested sampling strategy. From March 2021 to April 2022, 868 wastewater samples were collected from influent lines to wastewater treatment facilities and upstream community manholes. Variations in SARS-CoV-2 concentrations in influent line samples preceded similar variations in numbers of reported COVID-19 cases in the corresponding catchment areas. Community sites under nested sampling represented mutually-exclusive catchment areas. Community sites with high SARS-CoV-2 detection rates in wastewater covered high COVID-19 incidence areas, and adaptive sampling enabled identification and tracing of COVID-19 hotspots. This study demonstrates how a well-designed WWS provides actionable information including early warning of surges in cases and identification of disease hotspots.

Nosocomial transmission of norovirus is mainly caused by symptomatic cases.

BACKGROUND: Nosocomial norovirus (NoV) infection is common and may increase the burden of disease in healthcare settings, particularly in vulnerable hospitalized patients. Implementing effective infection control during and after admission may limit further spread, but evidence-based measures are lacking. METHODS: In this study, we performed a systematic evaluation of sources and modes of transmission during NoV outbreaks within 2 types of healthcare facilities. An outbreak protocol was developed to sample all patients and healthcare workers (HCWs) with and without symptoms on wards involved in outbreaks. Data on clinical history and possible high-risk exposures were collected. Five outbreaks were investigated, involving 28 patients with recognized symptomatic NoV infection. RESULTS: Enhanced sampling, however, yielded 65 additional cases, of whom 14% (n = 9) were asymptomatic patients, 57% (n = 37) were symptomatic HCWs, and 17% (n = 11) were asymptomatic HCWs. For 12% (n = 8), clinical data were not provided (2 HCWs and 6 patients). On the basis of the shedding kinetics, the onset of infection was estimated for each case. The generation interval was then used to construct plausible transmission pathways and reproduction numbers for symptomatic and asymptomatic patients and HCWs. CONCLUSIONS: We found that symptomatic patients and HCWs were more often involved in transmission events than asymptomatic shedders. Asymptomatic HCWs rarely contributed to transmission, despite high levels of fecal virus shedding.

Quantifying transmission of norovirus during an outbreak.

BACKGROUND: Healthcare workers are thought to play a role in nosocomial transmission of norovirus, but the level and direction of norovirus transmission between patients and healthcare workers in sustaining transmission during an outbreak have not been quantified. METHODS: We developed a method for finding plausible transmission trees of who acquired their infection from whom. We applied the method to data from an outbreak of norovirus in 4 wards of a psychiatric institution in the Netherlands in 2008. The simulated transmission trees were based on serial intervals for time between symptom onsets, weighted for the number of days that healthcare workers were present. The obtained transmission trees were linked to the Barthel Index, a measure of patient reliance on healthcare in their basic daily activities. RESULTS: The dominant recognized transmission route was from patient to patient (64%), followed by patient to healthcare worker (29%). The overall estimated reproduction number for healthcare workers was low compared with patients (0.25 vs. 1.20; mean difference = 0.95 [95% confidence interval (CI) = 0.60 to 1.30]). The average number of all subsequent cases attributable to the downstream branch of one single infected healthcare worker in the transmission tree was 4.4 compared with 6.5 for cases attributable to one single infected patient (mean difference = 2.1 [95% CI = -4.7 to 8.9]). In the ward with patients requiring the highest level of care from healthcare workers, the attack rate among healthcare workers was highest. CONCLUSION: This approach provides a framework to quantify the magnitude and direction of transmission between healthcare workers and patients during a norovirus outbreak. The utility of this method in outbreaks of other infections and in different settings should be explored.

Serological cross-sectional studies on salmonella incidence in eight European countries: no correlation with incidence of reported cases.

BACKGROUND: Published incidence rates of human salmonella infections are mostly based on numbers of stool culture-confirmed cases reported to public health surveillance. These cases constitute only a small fraction of all cases occurring in the community. The extent of underascertainment is influenced by health care seeking behaviour and sensitivity of surveillance systems, so that reported incidence rates from different countries are not comparable. We performed serological cross-sectional studies to compare infection risks in eight European countries independent of underascertainment. METHODS: A total of 6,393 sera from adults in Denmark, Finland, France, Italy, Poland, Romania, Sweden, and The Netherlands were analysed, mostly from existing serum banks collected in the years 2003 to 2008. Immunoglobulin A (IgA), IgM, and IgG against salmonella lipopolysaccharides were measured by in-house mixed ELISA. We converted antibody concentrations to estimates of infection incidence ('sero-incidence') using a Bayesian backcalculation model, based on previously studied antibody decay profiles in persons with culture-confirmed salmonella infections. We compared sero-incidence with incidence of cases reported through routine public health surveillance and with published incidence estimates derived from infection risks in Swedish travellers to those countries. RESULTS: Sero-incidence of salmonella infections ranged from 56 (95% credible interval 8-151) infections per 1,000 person-years in Finland to 547 (343-813) in Poland. Depending on country, sero-incidence was approximately 100 to 2,000 times higher than incidence of culture-confirmed cases reported through routine surveillance, with a trend for an inverse correlation. Sero-incidence was significantly correlated with incidence estimated from infection risks in Swedish travellers. CONCLUSIONS: Sero-incidence estimation is a new method to estimate and compare the incidence of salmonella infections in human populations independent of surveillance artefacts. Our results confirm that comparison of reported incidence between countries can be grossly misleading, even within the European Union. Because sero-incidence includes asymptomatic infections, it is not a direct measure of burden of illness. But, pending further validation of this novel method, it may be a promising and cost-effective way to assess infection risks and to evaluate the effectiveness of salmonella control programmes across countries or over time.

Dose response for Salmonella Typhimurium and Enteritidis and other nontyphoid enteric salmonellae.

This dose response assessment combines data from 6 human challenge studies and 44 outbreaks to determine infectivity and pathogenicity of several serotypes of nontyphoid Salmonella. Outcomes focus on the major serotypes Salmonella Enteritidis and Typhimurium, showing that Typhimurium is less infectious and has a lower probability of causing acute illness in infected subjects. The dose response relation of Salmonella Enteritidis is less steep than that of Typhimurium, indicating greater heterogeneity in infectivity and pathogenicity. This study revisits an older study with less flexible methods that could not combine the widely different outcomes of challenge studies and outbreaks, and had limited capability for dealing with missing information. Reported outcomes are in a format that allows use in calculations of uncertainty for quantitative risk assessment.

Dose-response relationship of Ralstonia solanacearum and potato in greenhouse and in vitro experiments.

Ralstonia solanacearum is the causative agent of bacterial wilt of potato and other vegetable crops. Contaminated irrigation water contributes to the dissemination of this pathogen but the exact concentration or biological threshold to cause an infection is unknown. In two greenhouse experiments, potted potato plants (Solanum tuberosum) were exposed to a single irrigation with 50 mL water (non-invasive soil-soak inoculation) containing no or 102 - 108 CFU/mL R. solanacearum. The disease response of two cultivars, Kondor and HB, were compared. Disease development was monitored over a three-month period after which stems, roots and tubers of asymptomatic plants were analyzed for latent infections. First wilting symptoms were observed 15 days post inoculation in a plant inoculated with 5x109 CFU and a mean disease index was used to monitor disease development over time. An inoculum of 5x105 CFU per pot (1.3x102 CFU/g soil) was the minimum dose required to cause wilting symptoms, while one latent infection was detected at the lowest dose of 5x102 CFU per pot (0.13 CFU/g). In a second set of experiments, stem-inoculated potato plants grown in vitro were used to investigate the dose-response relationship under optimal conditions for pathogen growth and disease development. Plants were inoculated with doses between 0.5 and 5x105 CFU/plant which resulted in visible symptoms at all doses. The results led to a dose-response model describing the relationship between R. solanacearum exposure and probability of infection or illness of potato plants. Cultivar Kondor was more susceptible to brown-rot infections than HB in greenhouse experiments while there was no significant difference between the dose-response models of both cultivars in in vitro experiments. The ED50 for infection of cv Kondor was 1.1x107 CFU. Results can be used in management strategies aimed to reduce or eliminate the risk of bacterial wilt infection when using treated water in irrigation.