Inference of Nipah virus evolution, 1999-2015.

Despite near-annual human outbreaks of Nipah virus (NiV) disease in Bangladesh, typically due to individual spillover events from the local bat population, only twenty whole-genome NiV sequences exist from humans and ten from bats. NiV whole-genome sequences from annual outbreaks have been challenging to generate, primarily due to the low viral load in human throat swab and serum specimens. Here, we used targeted enrichment with custom NiV-specific probes and generated thirty-five additional unique full-length genomic sequences directly from human specimens and viral isolates. We inferred the temporal and geographic evolutionary history of NiV in Bangladesh and expanded a tool to visualize NiV spatio-temporal spread from a Bayesian continuous diffusion analysis. We observed that strains from Bangladesh segregated into two distinct clades that have intermingled geographically in Bangladesh over time and space. As these clades expanded geographically and temporally, we did not observe evidence for significant branch and site-specific selection, except for a single site in the Henipavirus L polymerase. However, the Bangladesh 1 and 2 clades are differentiated by mutations initially occurring in the polymerase, with additional mutations accumulating in the N, G, F, P, and L genes on external branches. Modeling the historic geographical and temporal spread demonstrates that while widespread, NiV does not exhibit significant genetic variation in Bangladesh. Thus, future public health measures should address whether NiV within in the bat population also exhibits comparable genetic variation, if zoonotic transmission results in a genetic bottleneck and if surveillance techniques are detecting only a subset of NiV.

Violence and hepatitis C transmission in prison-A modified social ecological model.

BACKGROUND: Transmission of hepatitis C virus (HCV) among the prisoner population is most frequently associated with sharing of non-sterile injecting equipment. Other blood-to-blood contacts such as tattooing and physical violence are also common in the prison environment, and have been associated with HCV transmission. The context of such non-injecting risk behaviours, particularly violence, is poorly studied. The modified social-ecological model (MSEM) was used to examine HCV transmission risk and violence in the prison setting considering individual, network, community and policy factors. METHODS: The Australian Hepatitis C Incidence and Transmission Study in prisons (HITS-p) cohort enrolled HCV uninfected prisoners with injecting and non-injecting risk behaviours, who were followed up for HCV infection from 2004-2014. Qualitative interviews were conducted within 23 participants; of whom 13 had become HCV infected. Deductive analysis was undertaken to identify violence as risk within prisons among individual, network, community, and public policy levels. RESULTS: The risk context for violence and HCV exposure varied across the MSEM. At the individual level, participants were concerned about blood contact during fights, given limited scope to use gloves to prevent blood contamination. At the network level, drug debt and informing on others to correctional authorities, were risk factors for violence and potential HCV transmission. At the community level, racial influence, social groupings, and socially maligned crimes like sexual assault of children were identified as possible triggers for violence. At the policy level, rules and regulations by prison authority influenced the concerns and occurrence of violence and potential HCV transmission. CONCLUSION: Contextual concerns regarding violence and HCV transmission were evident at each level of the MSEM. Further evidence-based interventions targeted across the MSEM may reduce prison violence, provide opportunities for HCV prevention when violence occurs and subsequent HCV exposure.

Hospital-based surveillance for Japanese encephalitis in Bangladesh, 2007-2016: Implications for introduction of immunization.

BACKGROUND: Japanese encephalitis (JE) virus is recognized as a major cause of encephalitis in Bangladesh. The World Health Organization (WHO) recommends human immunization as the most effective means to control JE. Several WHO-prequalified vaccines are available to prevent JE but no vaccination program has been implemented in Bangladesh. METHODS: We conducted hospital-based surveillance for acute meningitis-encephalitis syndrome (AMES) to describe JE epidemiology and help inform policy decisions about possible immunization strategies for Bangladesh. RESULTS: During 2007-2016, a total of 6543 AMES patients were identified at four tertiary hospitals. Of the 6525 patients tested, 548 (8%) were classified as JE cases. These 548 patients resided in 36 (56%) out of 64 districts of Bangladesh, with the highest proportion of JE cases among AMES patients (12% and 7%) presenting at two hospitals in the northwestern part of the country. The median age of JE cases was 30 years, and 193 (35%) were aged ≤15 years. The majority of JE cases (80%) were identified from July through November. CONCLUSIONS: Surveillance results suggest that JE continues to be an important cause of meningo-encephalitis in Bangladesh. Immunization strategies including JE vaccine introduction into the routine childhood immunization program or mass vaccination in certain age groups or geographic areas need to be examined, taking into consideration the cost-effectiveness ratio of the approach and potential for decreasing disease burden.

A Framework to Monitor Changes in Transmission and Epidemiology of Emerging Pathogens: Lessons From Nipah Virus.

It is of uttermost importance that the global health community develops the surveillance capability to effectively monitor emerging zoonotic pathogens that constitute a major and evolving threat for human health. In this study, we propose a comprehensive framework to measure changes in (1) spillover risk, (2) interhuman transmission, and (3) morbidity/mortality associated with infections based on 6 epidemiological key indicators derived from routine surveillance. We demonstrate the indicators' value for the retrospective or real-time assessment of changes in transmission and epidemiological characteristics using data collected through a long-standing, systematic, hospital-based surveillance system for Nipah virus in Bangladesh. We show that although interhuman transmission and morbidity/mortality indicators were stable, the number and geographic extent of spillovers varied significantly over time. This combination of systematic surveillance and active tracking of transmission and epidemiological indicators should be applied to other high-risk emerging pathogens to prevent public health emergencies.

Changing Contact Patterns Over Disease Progression: Nipah Virus as a Case Study.

Contact patterns play a key role in disease transmission, and variation in contacts during the course of illness can influence transmission, particularly when accompanied by changes in host infectiousness. We used surveys among 1642 contacts of 94 Nipah virus case patients in Bangladesh to determine how contact patterns (physical and with bodily fluids) changed as disease progressed in severity. The number of contacts increased with severity and, for case patients who died, peaked on the day of death. Given transmission has only been observed among fatal cases of Nipah virus infection, our findings suggest that changes in contact patterns during illness contribute to risk of infection.

A case of primary amebic meningoencephalitis caused by Naegleria fowleri in Bangladesh.

We present the first recognized case of primary amebic meningoencephalitis (PAM) caused by Naegleria fowleri in a 15-year-old male from Bangladesh. He performed daily nasal rinsing with untreated ground water and bathed in untreated ground water or river water, which likely exposed him to N. fowleri.

Mortality Surveillance Methods to Identify and Characterize Deaths in Child Health and Mortality Prevention Surveillance Network Sites.

Despite reductions over the past 2 decades, childhood mortality remains high in low- and middle-income countries in sub-Saharan Africa and South Asia. In these settings, children often die at home, without contact with the health system, and are neither accounted for, nor attributed with a cause of death. In addition, when cause of death determinations occur, they often use nonspecific methods. Consequently, findings from models currently utilized to build national and global estimates of causes of death are associated with substantial uncertainty. Higher-quality data would enable stakeholders to effectively target interventions for the leading causes of childhood mortality, a critical component to achieving the Sustainable Development Goals by eliminating preventable perinatal and childhood deaths. The Child Health and Mortality Prevention Surveillance (CHAMPS) Network tracks the causes of under-5 mortality and stillbirths at sites in sub-Saharan Africa and South Asia through comprehensive mortality surveillance, utilizing minimally invasive tissue sampling (MITS), postmortem laboratory and pathology testing, verbal autopsy, and clinical and demographic data. CHAMPS sites have established facility- and community-based mortality notification systems, which aim to report potentially eligible deaths, defined as under-5 deaths and stillbirths within a defined catchment area, within 24-36 hours so that MITS can be conducted quickly after death. Where MITS has been conducted, a final cause of death is determined by an expert review panel. Data on cause of death will be provided to local, national, and global stakeholders to inform strategies to reduce perinatal and childhood mortality in sub-Saharan Africa and South Asia.

Hospital-based zoonotic disease surveillance in Bangladesh: design, field data and difficulties.

Early detection of zoonotic diseases allows for the implementation of early response measures, reducing loss of human life and economic disruption. We implemented a surveillance system in hospitals in Bangladesh to screen acutely ill hospitalized patients with severe respiratory infection and meningoencephalitis for zoonotic exposures. Patients were screened for the risk of zoonotic exposures with five questions covering vocational exposures, sick domestic animal and wild animal contact, and date palm sap consumption in the three weeks preceding illness onset. Patients giving at least one positive response were considered a potential zoonotic exposure. From September 2013 to March 2017, a total of 11 429 hospitalized patients across 14 participating hospitals were screened for exposures. Overall, 2% of patients reported a potential zoonotic exposure in the three-week period prior to becoming ill. Sixteen per cent of hospitalized patients with reported exposures died. After routine surveillance diagnostic testing, 88% of patients admitted to the hospital after a potential zoonotic exposure did not have a laboratory diagnosed aetiology for their illness. Hospital-based surveillance systems such as the Bangladeshi example presented here could play an important future role in the early detection of zoonotic spillover diseases. This article is part of the theme issue 'Dynamic and integrative approaches to understanding pathogen spillover'.

Transmission of Nipah Virus - 14 Years of Investigations in Bangladesh.

BACKGROUND: Nipah virus is a highly virulent zoonotic pathogen that can be transmitted between humans. Understanding the dynamics of person-to-person transmission is key to designing effective interventions. METHODS: We used data from all Nipah virus cases identified during outbreak investigations in Bangladesh from April 2001 through April 2014 to investigate case-patient characteristics associated with onward transmission and factors associated with the risk of infection among patient contacts. RESULTS: Of 248 Nipah virus cases identified, 82 were caused by person-to-person transmission, corresponding to a reproduction number (i.e., the average number of secondary cases per case patient) of 0.33 (95% confidence interval [CI], 0.19 to 0.59). The predicted reproduction number increased with the case patient's age and was highest among patients 45 years of age or older who had difficulty breathing (1.1; 95% CI, 0.4 to 3.2). Case patients who did not have difficulty breathing infected 0.05 times as many contacts (95% CI, 0.01 to 0.3) as other case patients did. Serologic testing of 1863 asymptomatic contacts revealed no infections. Spouses of case patients were more often infected (8 of 56 [14%]) than other close family members (7 of 547 [1.3%]) or other contacts (18 of 1996 [0.9%]). The risk of infection increased with increased duration of exposure of the contacts (adjusted odds ratio for exposure of >48 hours vs. ≤1 hour, 13; 95% CI, 2.6 to 62) and with exposure to body fluids (adjusted odds ratio, 4.3; 95% CI, 1.6 to 11). CONCLUSIONS: Increasing age and respiratory symptoms were indicators of infectivity of Nipah virus. Interventions to control person-to-person transmission should aim to reduce exposure to body fluids. (Funded by the National Institutes of Health and others.).

Using healthcare-seeking behaviour to estimate the number of Nipah outbreaks missed by hospital-based surveillance in Bangladesh.

BACKGROUND: Understanding the true burden of emergent diseases is critical for assessing public-health impact. However, surveillance often relies on hospital systems that only capture a minority of cases. We use the example of Nipah-virus infection in Bangladesh, which has a high case-fatality ratio and frequent person-to-person transmission, to demonstrate how healthcare-seeking data can estimate true burden. METHODS: We fit logistic-regression models to data from a population-based, healthcare-seeking study of encephalitis cases to characterize the impact of distance and mortality on attending one of three surveillance hospital sites. The resulting estimates of detection probabilities, as a function of distance and outcome, are applied to all observed Nipah outbreaks between 2007 and 2014 to estimate the true burden. RESULTS: The probability of attending a surveillance hospital fell from 82% for people with fatal encephalitis living 10 km away from a surveillance hospital to 54% at 50 km away. The odds of attending a surveillance hospital are 3.2 (95% confidence interval: 1.6, 6.6) times greater for patients who eventually died (i.e. who were more severely ill) compared with those who survived. Using these probabilities, we estimated that 119 Nipah outbreaks (95% confidence interval: 103, 140)-an average of 15 outbreaks per Nipah season-occurred during 2007-14; 62 (52%) were detected. CONCLUSIONS: Our findings suggest hospital-based surveillance missed nearly half of all Nipah outbreaks. This analytical method allowed us to estimate the underlying burden of disease, which is important for emerging diseases where healthcare access may be limited.

Characterization of the Spatial and Temporal Distribution of Nipah Virus Spillover Events in Bangladesh, 2007-2013.

Nipah virus is a zoonotic virus harbored by bats and lethal to humans. Bat-to-human spillovers occur every winter in Bangladesh. However, there is significant heterogeneity in the number of spillovers detected by district and year that remains unexplained. We analyzed data from all 57 spillovers during 2007-2013 and found that temperature differences explained 36% of the year-to-year variation in the total number of spillovers each winter and that distance to surveillance hospitals explained 45% of spatial heterogeneity. Interventions to prevent human infections may be most important during colder winters. Further work is needed to understand how dynamics of bat infections explains spillover risk.

Nipah Virus Contamination of Hospital Surfaces during Outbreaks, Bangladesh, 2013-2014.

Nipah virus (NiV) has been transmitted from patient to caregivers in Bangladesh presumably through oral secretions. We aimed to detect whether NiV-infected patients contaminate hospital surfaces with the virus. During December 2013-April 2014, we collected 1 swab sample from 5 surfaces near NiV-infected patients and tested surface and oral swab samples by real-time reverse transcription PCR for NiV RNA. We identified 16 Nipah patients; 12 cases were laboratory-confirmed and 4 probable. Of the 12 laboratory-confirmed cases, 10 showed NiV RNA in oral swab specimens. We obtained surface swab samples for 6 Nipah patients; 5 had evidence of NiV RNA on >1 surface: 4 patients contaminated towels, 3 bed sheets, and 1 the bed rail. Patients with NiV RNA in oral swab samples were significantly more likely than other Nipah patients to die. To reduce the risk for fomite transmission of NiV, infection control should target hospital surfaces.

Convergence of Humans, Bats, Trees, and Culture in Nipah Virus Transmission, Bangladesh.

Preventing emergence of new zoonotic viruses depends on understanding determinants for human risk. Nipah virus (NiV) is a lethal zoonotic pathogen that has spilled over from bats into human populations, with limited person-to-person transmission. We examined ecologic and human behavioral drivers of geographic variation for risk of NiV infection in Bangladesh. We visited 60 villages during 2011-2013 where cases of infection with NiV were identified and 147 control villages. We compared case villages with control villages for most likely drivers for risk of infection, including number of bats, persons, and date palm sap trees, and human date palm sap consumption behavior. Case villages were similar to control villages in many ways, including number of bats, persons, and date palm sap trees, but had a higher proportion of households in which someone drank sap. Reducing human consumption of sap could reduce virus transmission and risk for emergence of a more highly transmissible NiV strain.

Risk Factors Associated with Blood Exposure for Sporadic Hepatitis E in Dhaka, Bangladesh.

Fecal contamination of drinking water is associated with large hepatitis E virus (HEV) outbreaks of genotypes 1 and 2 in endemic areas. Sporadic transmission of HEV genotypes 3 and 4 in high-income countries has been associated with exposure to blood and animal contact. The objective of the study was to identify the risk factors for hepatitis E and the genotype(s) causing sporadic hepatitis E in Dhaka, Bangladesh. We selected, from a diagnostic center in Dhaka between November 2008 and November 2009, cases presenting with jaundice and anti-HEV IgM antibodies and age-matched controls were defined as those with no history of jaundice and normal blood test results. Serum samples were tested for HEV RNA using real-time reverse transcriptase polymerase chain reaction followed by a sequencing and phylogenetic analysis. A total of 109 cases and 109 controls were enrolled. The cases were more likely to be male (adjusted matched odds ratios [mOR] 2.2, 95% CI: 1.2-3.9; P = 0.01), or have reported contact with another person's blood or blood product, or contact with blood-contaminated sharp instruments (adjusted mOR 2.1, 95% CI: 1.1-4.1; P = 0.03) than controls. There were no significant differences between the cases and the controls in terms of reported high-risk sexual intercourse, consumption of undercooked meat, or contact or drinking fecally-contaminated water. The sera from three cases carried HEV RNA, all belonging to genotype 1. Findings from this study suggest that contact with human blood and sharing sharp instruments may transmit sporadic hepatitis E in Dhaka, Bangladesh. Efforts to prevent the transmission of blood-borne pathogens may also prevent sporadic HEV transmission in this endemic setting.

Outbreak of Sudden Death with Acute Encephalitis Syndrome Among Children Associated with Exposure to Lychee Orchards in Northern Bangladesh, 2012.

Recurrent outbreaks of acute encephalitis syndrome (AES) among children in lychee growing areas in Asia highlight the need to better understand the etiology and the context. We conducted a mixed-methods study to identify risk factors for disease, and behaviors and practices around lychee cultivation in an AES outbreak community in northern Bangladesh in 2012. The outbreak affected 14 children; 13 died. The major symptoms included unconsciousness, convulsion, excessive sweating, and frothy discharge. The median time from illness onset to unconsciousness was 2.5 hours. The outbreak corresponded with lychee harvesting season. Multiple pesticides including some banned in Bangladesh were frequently used in the orchards. Visiting a lychee orchard within 24 hours before onset (age-adjusted odds ratio [aOR] = 11.6 [1.02-109.8]) and 3 days (aOR = 7.2 [1.4-37.6]), and family members working in a lychee orchard (aOR = 7.2 [1.7-29.4]) and visiting any garden while pesticides were being applied (aOR = 4.9 [1.0-19.4]) in 3 days preceding illness onset were associated with illness in nearby village analysis. In neighborhood analysis, visiting an orchard that used pesticides (aOR = 8.4 [1.4-49.9]) within 3 days preceding illness onset was associated with illness. Eating lychees was not associated with illness in the case-control study. The outbreak was linked to lychee orchard exposures where agrochemicals were routinely used, but not to consumption of lychees. Lack of acute specimens was a major limitation. Future studies should target collection of environmental and food samples, acute specimens, and rigorous assessment of community use of pesticides to determine etiology.

A large-scale behavior change intervention to prevent Nipah transmission in Bangladesh: components and costs.

BACKGROUND: Nipah virus infection (NiV) is a bat-borne zoonosis transmitted to humans through consumption of NiV-contaminated raw date palm sap in Bangladesh. The objective of this analysis was to measure the cost of an NiV prevention intervention and estimate the cost of scaling it up to districts where spillover had been identified. METHODS: We implemented a behavior change communication intervention in two districts, testing different approaches to reduce the risk of NiV transmission using community mobilization, interpersonal communication, posters and TV public service announcements on local television during the 2012-2014 sap harvesting seasons. In one district, we implemented a "no raw sap" approach recommending to stop drinking raw date palm sap. In another district, we implemented an "only safe sap" approach, recommending to stop drinking raw date palm sap but offering the option of drinking safe sap. This is sap covered with a barrier, locally called bana, to interrupt bats' access during collection. We conducted surveys among randomly selected respondents two months after the intervention to measure the proportion of people reached. We used an activity-based costing method to calculate the cost of the intervention. RESULTS: The implementation cost of the "no raw sap" intervention was $30,000 and the "only safe sap" intervention was $55,000. The highest cost was conducting meetings and interpersonal communication efforts. The lowest cost was broadcasting the public service announcements on local TV channels. To scale up a similar intervention in 30 districts where NiV spillover has occurred, would cost between $2.6 and $3.5 million for one season. Placing the posters would cost $96,000 and only broadcasting the public service announcement through local channels in 30 districts would cost $26,000. CONCLUSIONS: Broadcasting a TV public service announcement is a potential low cost option to advance NiV prevention. It could be supplemented with posters and targeted interpersonal communication, in districts with a high risk of NiV spillover.

Surveillance at Private Laboratories Identifies Small Outbreaks of Hepatitis E in Urban Bangladesh.

Although large outbreaks of hepatitis E are regularly identified in south Asia, the majority of south Asian countries lack surveillance systems for this disease, which has hindered burden of disease estimates and prioritization of resources for prevention. Our study aimed to identify small hepatitis E outbreaks through a sentinel private laboratory in Dhaka, Bangladesh. We identified patients with detectable IgM antibody against hepatitis E virus. We defined a small outbreak as at least two laboratory-confirmed cases or ≥ 2 acute jaundice cases from the sentinel cases' family, neighborhood, or workplace. From November 2008 to November 2009, we identified 29 small outbreaks of hepatitis E from one private laboratory. The median number of cases in each outbreak was three. Cases were identified every month. Eighteen outbreaks occurred among families or neighbors, and 11 in the workplace. Among 103 cases identified as part of outbreaks, 31 (30%) sought care for diagnosis. In Bangladesh, collaboration between government public health surveillance and private laboratories can strengthen capacity for outbreak detection and improve estimates of disease burden.

Investigating Rare Risk Factors for Nipah Virus in Bangladesh: 2001-2012.

Human Nipah encephalitis outbreaks have been identified almost yearly in Bangladesh since 2001. Though raw date palm sap consumption and person-to-person contact are recognized as major transmission pathways, alternative pathways of transmission are plausible and may not have been identified due to limited statistical power in each outbreak. We conducted a risk factor analysis using all 157 cases and 632 controls surveyed in previous investigations during 2004-2012 to identify exposures independently associated with Nipah, since date palm sap was first asked about as an exposure in 2004. To further explore possible rare exposures, we also conducted in-depth interviews with all cases, or proxies, since 2001 that reported no exposure to date palm sap or contact with another case. Cases were 4.9 (95% 3.2-7.7) times more likely to consume raw date palm sap and 7.3 (95% 4.0-13.4) times more likely to have contact with a Nipah case than controls. In-depth interviews revealed that 39/182 (21%) of Nipah cases reporting neither date palm sap consumption nor contact with another case were misclassified. Prevention efforts should be focused on interventions to interrupt transmission through date palm sap consumption and person-to-person contact. Furthermore, pooling outbreak investigation data is a good method for assessing rare exposures.

It's not only what you say, it's also how you say it: communicating nipah virus prevention messages during an outbreak in Bangladesh.

BACKGROUND: During a fatal Nipah virus (NiV) outbreak in Bangladesh, residents rejected biomedical explanations of NiV transmission and treatment and lost trust in the public healthcare system. Field anthropologists developed and communicated a prevention strategy to bridge the gap between the biomedical and local explanation of the outbreak. METHODS: We explored residents' beliefs and perceptions about the illness and care-seeking practices and explained prevention messages following an interactive strategy with the aid of photos showed the types of contact that can lead to NiV transmission from bats to humans by drinking raw date palm sap and from person-to-person. RESULTS: The residents initially believed that the outbreak was caused by supernatural forces and continued drinking raw date palm sap despite messages from local health authorities to stop. Participants in community meetings stated that the initial messages did not explain that bats were the source of this virus. After our intervention, participants responded that they now understood how NiV could be transmitted and would abstain from raw sap consumption and maintain safer behaviours while caring for patients. CONCLUSIONS: During outbreaks, one-way behaviour change communication without meaningful causal explanations is unlikely to be effective. Based on the cultural context, interactive communication strategies in lay language with supporting evidence can make biomedical prevention messages credible in affected communities, even among those who initially invoke supernatural causal explanations.