Joseph A. Lewnard

Dynamics and control of Ebola virus transmission in Montserrado, Liberia: a mathematical modelling analysis

BACKGROUND A substantial scale-up in public health response is needed to control the unprecedented Ebola virus disease (EVD) epidemic in west Africa. Current international commitments seek to expand intervention capacity in three areas: new EVD treatment centres, case ascertainment through contact tracing, and household protective kit allocation. We aimed to assess how these interventions could be applied individually and in combination to avert future EVD cases and deaths. METHODS We developed a transmission model of Ebola virus that we fitted to reported EVD cases and deaths in Montserrado County, Liberia. We used this model to assess the effectiveness of expanding EVD treatment centres, increasing case ascertainment, and allocating protective kits for controlling the outbreak in Montserrado. We varied the efficacy of protective kits from 10% to 50%. We compared intervention initiation on Oct 15, 2014, Oct 31, 2014, and Nov 15, 2014. The status quo intervention was defined in terms of case ascertainment and capacity of EVD treatment centres on Sept 23, 2014, and all behaviour and contact patterns relevant to transmission as they were occurring at that time. The primary outcome measure was the expected number of cases averted by Dec 15, 2014. FINDINGS We estimated the basic reproductive number for EVD in Montserrado to be 2·49 (95% CI 2·38-2·60). We expect that allocating 4800 additional beds at EVD treatment centres and increasing case ascertainment five-fold in November, 2014, can avert 77 312 (95% CI 68 400-85 870) cases of EVD relative to the status quo by Dec 15, 2014. Complementing these measures with protective kit allocation raises the expectation as high as 97 940 (90 096-105 606) EVD cases. If deployed by Oct 15, 2014, equivalent interventions would have been expected to avert 137 432 (129 736-145 874) cases of EVD. If delayed to Nov 15, 2014, we expect the interventions will at best avert 53 957 (46 963-60 490) EVD cases. INTERPRETATION The number of beds at EVD treatment centres needed to effectively control EVD in Montserrado substantially exceeds the 1700 pledged by the USA to west Africa. Accelerated case ascertainment is needed to maximise effectiveness of expanding the capacity of EVD treatment centres. Distributing protective kits can further augment prevention of EVD, but it is not an adequate stand-alone measure for controlling the outbreak. Our findings highlight the rapidly closing window of opportunity for controlling the outbreak and averting a catastrophic toll of EVD cases and deaths. FUNDING US National Institutes of Health.

Internet-based partner selection and risk for unprotected anal intercourse in sexual encounters among men who have sex with men: a meta-analysis of observational studies.

Introduction Men who have sex with men (MSM) who identify sex partners over the internet are more likely than other MSM to report having unprotected anal intercourse (UAI). It is unclear whether the internet facilitates pursuit of high-risk sex or whether MSM seeking sex online are a higher-risk population than other MSM. To summarise evidence as to whether internet-based partner selection predisposes MSM to high-risk behaviour, we conducted a meta-analysis of observational studies comparing MSMs UAI risk in online-initiated encounters to their UAI risk in offline-initiated encounters. Methods We systematically searched published, peer-reviewed literature to identify studies reporting MSM participants’ engagement in UAI with online-identified and offline-identified male partners. We calculated pooled odds ratios for any UAI and for seroadaptive UAI practices with partners identified online relative to partners identified offline. Results We included 11 studies representing 39 602 sexual encounters. Odds for any UAI, seroconcordant UAI and serodiscordant UAI with strategic positioning were higher in online-initiated than offline-initiated encounters. Odds for UAI in group sex were higher in online-initiated encounters only among HIV-positive MSM. Effect sizes for all outcomes were greater among HIV-positive than HIV-negative MSM. Effect sizes were greatest when bathhouses, saunas and sex resorts were treated as offline comparison venues. Conclusions Encounters initiated online have elevated odds for entailing UAI and seroadaptive UAI practices. Online-delivered behavioural interventions should address insufficiency of risk-reducing practices involving UAI relative to consistent condom use and promote frequent HIV testing among MSM seeking UAI partners online. http://group.bmj.com/products/journals/instructions-for-authors/licence-forms.

Epidemiological Markers for Interactions Among Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus in Upper Respiratory Tract Carriage

BACKGROUND Cocolonization by Streptococcus pneumoniae and Haemophilus influenzae among children has been noted in numerous studies, as has an inverse relationship involving colonization with these species and Staphylococcus aureus. Interactions among these pathogens could mediate unanticipated outcomes of clinical interventions, including changes in H. influenzae and S. aureus disease incidence following pneumococcal vaccine introduction. However, it remains unclear whether cocolonization patterns represent true interspecies interactions or whether they result from confounding factors. METHODS We investigated polymicrobial carriage using longitudinal data from 369 Bedouin children and 400 Jewish children in Israel who were enrolled in a 7-valent pneumococcal conjugate vaccine (PCV7) trial. Children were swabbed 10 times between 2 and 30 months of age. RESULTS The pathogens followed distinct age and seasonal distributions, but polymicrobial carriage associations persisted after controlling for these and other confounding factors. Receipt of PCV7 resulted in pneumococcal serotype replacement but did not influence total carriage of S. pneumoniae, H. influenzae, or S. aureus. CONCLUSIONS The fact that S. pneumoniae, H. influenzae, and S. aureus polymicrobial carriage patterns do not result from confounding by age and season supports the idea of active interspecies interactions. However, pneumococcal serotype replacement may prevent changes in H. influenzae and S. aureus carriage among PCV7 recipients.

Forecasting Temporal Dynamics of Cutaneous Leishmaniasis in Northeast Brazil

Introduction Cutaneous leishmaniasis (CL) is a vector-borne disease of increasing importance in northeastern Brazil. It is known that sandflies, which spread the causative parasites, have weather-dependent population dynamics. Routinely-gathered weather data may be useful for anticipating disease risk and planning interventions. Methodology/Principal Findings We fit time series models using meteorological covariates to predict CL cases in a rural region of Bahía, Brazil from 1994 to 2004. We used the models to forecast CL cases for the period 2005 to 2008. Models accounting for meteorological predictors reduced mean squared error in one, two, and three month-ahead forecasts by up to 16% relative to forecasts from a null model accounting only for temporal autocorrelation. Significance These outcomes suggest CL risk in northeastern Brazil might be partially dependent on weather. Responses to forecasted CL epidemics may include bolstering clinical capacity and disease surveillance in at-risk areas. Ecological mechanisms by which weather influences CL risk merit future research attention as public health intervention targets.

Strategies to Prevent Cholera Introduction during International Personnel Deployments: A Computational Modeling Analysis Based on the 2010 Haiti Outbreak

Background Introduction of Vibrio cholerae to Haiti during the deployment of United Nations (UN) peacekeepers in 2010 resulted in one of the largest cholera epidemics of the modern era. Following the outbreak, a UN-commissioned independent panel recommended three pre-deployment intervention strategies to minimize the risk of cholera introduction in future peacekeeping operations: screening for V. cholerae carriage, administering prophylactic antimicrobial chemotherapies, or immunizing with oral cholera vaccines. However, uncertainty regarding the effectiveness of these approaches has forestalled their implementation by the UN. We assessed how the interventions would have impacted the likelihood of the Haiti cholera epidemic. Methods and Findings We developed a stochastic model for cholera importation and transmission, fitted to reported cases during the first weeks of the 2010 outbreak in Haiti. Using this model, we estimated that diagnostic screening reduces the probability of cases occurring by 82% (95% credible interval: 75%, 85%); however, false-positive test outcomes may hamper this approach. Antimicrobial chemoprophylaxis at time of departure and oral cholera vaccination reduce the probability of cases by 50% (41%, 57%) and by up to 61% (58%, 63%), respectively. Chemoprophylaxis beginning 1 wk before departure confers a 91% (78%, 96%) reduction independently, and up to a 98% reduction (94%, 99%) if coupled with vaccination. These results are not sensitive to assumptions about the background cholera incidence rate in the endemic troop-sending country. Further research is needed to (1) validate the sensitivity and specificity of rapid test approaches for detecting asymptomatic carriage, (2) compare prophylactic efficacy across antimicrobial regimens, and (3) quantify the impact of oral cholera vaccine on transmission from asymptomatic carriers. Conclusions Screening, chemoprophylaxis, and vaccination are all effective strategies to prevent cholera introduction during large-scale personnel deployments such as that precipitating the 2010 Haiti outbreak. Antimicrobial chemoprophylaxis was estimated to provide the greatest protection at the lowest cost among the approaches recently evaluated by the UN.

Relative Undernourishment and Food Insecurity Associations with Plasmodium falciparum Among Batwa Pygmies in Uganda: Evidence from a Cross-Sectional Survey

Although malnutrition and malaria co-occur among individuals and populations globally, effects of nutritional status on risk for parasitemia and clinical illness remain poorly understood. We investigated associations between Plasmodium falciparum infection, nutrition, and food security in a cross-sectional survey of 365 Batwa pygmies in Kanungu District, Uganda in January of 2013. We identified 4.1% parasite prevalence among individuals over 5 years old. Severe food insecurity was associated with increased risk for positive rapid immunochromatographic test outcome (adjusted relative risk [ARR] = 13.09; 95% confidence interval [95% CI] = 2.23–76.79). High age/sex-adjusted mid-upper arm circumference was associated with decreased risk for positive test among individuals who were not severely food-insecure (ARR = 0.37; 95% CI = 0.19–0.69). Within Batwa pygmy communities, where malnutrition and food insecurity are common, individuals who are particularly undernourished or severely food-insecure may have elevated risk for P. falciparum parasitemia. This finding may motivate integrated control of malaria and malnutrition in low-transmission settings.

Time series analysis of malaria in Afghanistan: using ARIMA models to predict future trends in incidence

BackgroundMalaria remains endemic in Afghanistan. National control and prevention strategies would be greatly enhanced through a better ability to forecast future trends in disease incidence. It is, therefore, of interest to develop a predictive tool for malaria patterns based on the current passive and affordable surveillance system in this resource-limited region.MethodsThis study employs data from Ministry of Public Health monthly reports from January 2005 to September 2015. Malaria incidence in Afghanistan was forecasted using autoregressive integrated moving average (ARIMA) models in order to build a predictive tool for malaria surveillance. Environmental and climate data were incorporated to assess whether they improve predictive power of models.ResultsTwo models were identified, each appropriate for different time horizons. For near-term forecasts, malaria incidence can be predicted based on the number of cases in the four previous months and 12 months prior (Model 1); for longer-term prediction, malaria incidence can be predicted using the rates 1 and 12 months prior (Model 2). Next, climate and environmental variables were incorporated to assess whether the predictive power of proposed models could be improved. Enhanced vegetation index was found to have increased the predictive accuracy of longer-term forecasts.ConclusionResults indicate ARIMA models can be applied to forecast malaria patterns in Afghanistan, complementing current surveillance systems. The models provide a means to better understand malaria dynamics in a resource-limited context with minimal data input, yielding forecasts that can be used for public health planning at the national level.

Naturally Acquired Immunity Against Rotavirus Infection and Gastroenteritis in Children: Paired Reanalyses of Birth Cohort Studies.

Background Observational studies in socioeconomically distinct populations have yielded conflicting conclusions about the strength of naturally acquired immunity against rotavirus gastroenteritis (RVGE), mirroring vaccine underperformance in low-income countries. We revisited birth cohort studies to understand naturally acquired protection against rotavirus infection and RVGE. Methods We reanalyzed data from 200 Mexican and 373 Indian children followed from birth to 2 and 3 years of age, respectively. We reassessed protection against RVGE, decomposing the incidence rate into the rate of rotavirus infection and the risk of RVGE given infection, and tested for serum antibody correlates of protection using regression models. Results Risk for primary, secondary, and subsequent infections to cause RVGE decreased per log-month of age by 28% (95% confidence interval [CI], 12%-41%), 69% (95% CI, 30%-86%), and 64% (95% CI, -186% to 95%), respectively, in Mexico City, and by 10% (95% CI, -1% to 19%), 51% (95% CI, 41%-59%) and 67% (95% CI, 57%-75%), respectively, in Vellore. Elevated serum immunoglobulin A and immunoglobulin G titers were associated with partial protection against rotavirus infection. Associations between older age and reduced risk for RVGE or moderate-to-severe RVGE given infection persisted after controlling for antibody levels. Conclusions Dissimilar estimates of protection against RVGE may be due in part to age-related, antibody-independent risk for rotavirus infections to cause RVGE.

Pan-serotype Reduction in Progression of Streptococcus pneumoniae to Otitis Media After Rollout of Pneumococcal Conjugate Vaccines

Background Reductions in otitis media (OM) burden following rollout of pneumococcal conjugate vaccines (PCVs) have exceeded predictions of vaccine impact. In settings with active surveillance, reductions in OM caused by vaccine-targeted pneumococcal serotypes have co-occurred with reductions in OM caused by other pathogens carried in the upper-respiratory tract of children. To understand these changes, we investigated the progression of vaccine-targeted and non-vaccine pneumococcal serotypes from carriage to OM before and after vaccine rollout. Methods Nasopharyngeal carriage prevalence of pneumococcus was monitored in prospective studies of Bedouin and Jewish children <3 years old in southern Israel between 2004 and 2016. Incidence of OM necessitating middle-ear fluid culture (predominantly complex OM including recurrent, spontaneously-draining, non-responsive, and chronic cases) was monitored via prospective, population-based active surveillance. We estimated rates of pneumococcal serotype-specific progression from carriage to disease before and after rollout of PCV7/13, measured as OM incidence per carrier. We pooled serotype-specific estimates using Bayesian random-effects models. Results On average, rates of progression declined 92% (95% credible interval: 79-97%) and 80% (46-93%) for PCV7/13 serotypes among Bedouin and Jewish children <12 months old, respectively, and 32% (-58-71%) and 61% (-5-86%) among children aged 12-35m. For non-vaccine serotypes, rates of progression among Bedouin and Jewish children aged <12m declined 74% (55-85%) and 43% (4-68%), respectively. Conclusions Vaccine-targeted and non-vaccine pneumococcal serotypes showed lower rates of progression to complex OM after rollout of PCV7/13. Early-life OM episodes historically associated with vaccine-serotype pneumococci may impact the susceptibility of children to OM progression.

A live vaccine rapidly protects against cholera in an infant rabbit model

An engineered cholera vaccine candidate mediates colonization resistance and disease protection within 1 day in an infant rabbit model. Designer bugs as drugs The endemic persistence and outbreaks of Vibrio cholerae indicate a need for new methods of control; in this issue, two groups investigated the potential of engineered bacteria to mediate cholera resistance in animal models. Mao et al. discovered that lactic acid production by the probiotic Lactococcus lactis rendered the infant mouse gut hostile to V. cholerae and engineered L. lactis to detect breakthrough infection. Hubbard et al. extensively modified a contemporary V. cholerae strain for a live oral vaccine, which resulted in an attenuated strain that could protect infant rabbits from V. cholerae challenge within 24 hours of vaccine administration, indicating that the protective effects were not dependent on adaptive immunity. These papers showcase innovative approaches to tackling cholera. Outbreaks of cholera, a rapidly fatal diarrheal disease, often spread explosively. The efficacy of reactive vaccination campaigns—deploying Vibrio cholerae vaccines during epidemics—is partially limited by the time required for vaccine recipients to develop adaptive immunity. We created HaitiV, a live attenuated cholera vaccine candidate, by deleting diarrheagenic factors from a recent clinical isolate of V. cholerae and incorporating safeguards against vaccine reversion. We demonstrate that administration of HaitiV 24 hours before lethal challenge with wild-type V. cholerae reduced intestinal colonization by the wild-type strain, slowed disease progression, and reduced mortality in an infant rabbit model of cholera. HaitiV-mediated protection required viable vaccine, and rapid protection kinetics are not consistent with development of adaptive immunity. These features suggest that HaitiV mediates probiotic-like protection from cholera, a mechanism that is not known to be elicited by traditional vaccines. Mathematical modeling indicates that an intervention that works at the speed of HaitiV-mediated protection could improve the public health impact of reactive vaccination.