Effectiveness of one dose of killed oral cholera vaccine in an endemic community in the Democratic Republic of the Congo: a matched case-control study.

BACKGROUND: A global shortage of cholera vaccines has increased the use of single-dose regimens, rather than the standard two-dose regimen. There is sparse evidence on single-dose protection, particularly in children. In 2020, a mass vaccination campaign was conducted in Uvira, an endemic urban setting in eastern Democratic Republic of the Congo, resulting in largely single-dose coverage. We examined the effectiveness of a single-dose of the oral cholera vaccine Euvichol-Plus in this high-burden setting. METHODS: In this matched case-control study, we recruited individuals with medically attended confirmed cholera in the two cholera treatment facilities in the city of Uvira. The control group consisted of age-matched, sex-matched, and neighbourhood-matched community individuals. We recruited across two distinct periods: Oct 14, 2021, to March 10, 2022 (12-17 months after vaccination), and Nov 21, 2022, to Oct 18, 2023 (24-36 months after vaccination). Study staff administered structured questionnaires to all participants to capture demographics, household conditions, potential confounding variables, and vaccination status. The odds of vaccination for the case and control groups were contrasted in conditional logistic regression models to estimate unadjusted and adjusted vaccine effectiveness. FINDINGS: We enrolled 658 individuals with confirmed cholera and 2274 matched individuals for the control group. 99 (15·1%) individuals in the case group were younger than 5 years at the time of vaccination. The adjusted single-dose vaccine effectiveness was 52·7% (95% CI 31·4 to 67·4) 12-17 months after vaccination and 44·7% (24·8 to 59·4) 24-36 months after vaccination. Although protection in the first 12-17 months after vaccination was similar for children aged 1-4 years and older individuals, the estimate of protection in children aged 1-4 years appeared to wane during the third year after vaccination (adjusted vaccine effectiveness 32·9%, 95% CI -30·7 to 65·5), with CIs spanning the null. INTERPRETATION: A single dose of Euvichol-Plus provided substantial protection against medically attended cholera for at least 36 months after vaccination in this cholera-endemic setting. Although the evidence provides support for similar levels of protection in young children and others in the short term, protection among children younger than 5 years might wane significantly during the third year after vaccination. FUNDING: Wellcome Trust and Gavi, the Vaccine Alliance.

Risk factors for food contamination among children discharged from community management of acute malnutrition programmes in South Sudan: A cross-sectional study and hazard analysis critical control point approach.

Children under-5 years of age are particularly vulnerable to severe acute malnutrition (SAM), and the risk factors associated with relapse to SAM are poorly understood. Possible causes are asymptomatic or symptomatic infection with enteric pathogens, with contaminated food as a critical transmission route. This cross-sectional study comprised a household survey with samples of child food (n = 382) and structured observations of food preparation (n = 197) among children aged 6-59 months that were discharged from treatment in community management of acute malnutrition (CMAM) programmes in South Sudan. We quantified Escherichia coli and total coliforms (TCs), measured in colony forming units per g of food (CFU/g), as indicators of microbial contamination of child food. A modified hazard analysis critical control point (HACCP) approach was utilised to determine critical control points (CCPs) followed by multivariate logistic regression analysis to understand the risk factors associated with contamination. Over 40% (n = 164) of samples were contaminated with E. coli (43% >0 E. coli CFU/g, 95% CI 38%-48%), and 90% (n = 343) had >10 TCs (CFU/g) (>10 TC CFU/g, 95% CI 87%-93%). Risk factors associated (p < 0.05) with child food contamination included if the child fed themselves (9.05 RR, 95% CI [3.18, 31.16]) and exposure to animals (2.63 RR, 95% CI [1.33, 5.34]). This study highlights the risk factors and potential control strategies that can support interventions that reduce food contamination exposure in young children and help further protect those that are highly vulnerable to recurrent exposure to enteric pathogens.

Evaluating the relationship between community water and sanitation access and the global burden of antibiotic resistance: an ecological study.

BACKGROUND: Antibiotic resistance is a leading cause of death, with the highest burden occurring in low-resource settings. There is little evidence on the potential for water, sanitation, and hygiene (WASH) access to reduce antibiotic resistance in humans. We aimed to determine the relationship between the burden of antibiotic resistance in humans and community access to drinking water and sanitation. METHODS: In this ecological study, we linked publicly available, geospatially tagged human faecal metagenomes (from the US National Center for Biotechnology Information Sequence Read Archive) with georeferenced household survey datasets that reported access to drinking water sources and sanitation facility types. We used generalised linear models with robust SEs to estimate the relationship between the abundance of antibiotic resistance genes (ARGs) in human faecal metagenomes and community-level coverage of improved drinking water and sanitation within a defined radii of faecal metagenome coordinates. FINDINGS: We identified 1589 metagenomes from 26 countries. The mean abundance of ARGs, in units of log10 ARG fragments per kilobase per million mapped reads classified as bacteria, was highest in Africa compared with Europe (p=0·014), North America (p=0·0032), and the Western Pacific (p=0·011), and second highest in South-East Asia compared with Europe (p=0·047) and North America (p=0·014). Increased access to improved water and sanitation was associated with lower ARG abundance (effect estimate -0·22, [95% CI -0·39 to -0·05]) and the association was stronger in urban (-0·32 [-0·63 to 0·00]) than in rural (-0·16 [-0·38 to 0·07]) areas. INTERPRETATION: Although additional studies to investigate causal effects are needed, increasing access to water and sanitation could be an effective strategy to curb the proliferation of antibiotic resistance in low-income and middle-income countries. FUNDING: Bill & Melinda Gates Foundation.

Water, Sanitation, and Cholera in Sub-Saharan Africa.

Improvements in water and sanitation should reduce cholera risk though the associations between cholera and specific water and sanitation access measures remain unclear. We estimated the association between eight water and sanitation measures and annual cholera incidence access across sub-Saharan Africa (2010-2016) for data aggregated at the country and district levels. We fit random forest regression and classification models to understand how well these measures combined might be able to predict cholera incidence rates and identify high cholera incidence areas. Across spatial scales, piped or "other improved" water access was inversely associated with cholera incidence. Access to piped water, septic or sewer sanitation, and septic, sewer, or "other improved" sanitation were associated with decreased district-level cholera incidence. The classification model had moderate performance in identifying high cholera incidence areas (cross-validated-AUC 0.81, 95% CI 0.78-0.83) with high negative predictive values (93-100%) indicating the utility of water and sanitation measures for screening out areas that are unlikely to be at high cholera risk. While comprehensive cholera risk assessments must incorporate other data sources (e.g., historical incidence), our results suggest that water and sanitation measures could alone be useful in narrowing the geographic focus for detailed risk assessments.

A fuzzy inference-based index for piped water supply service quality in a complex, low-income urban setting.

Sustainable Development Goal (SDG) 6 calls for universal access to safely managed drinking water services. We studied the evolution of the water supply service between January 2017 and December 2021 in the town of Uvira (South Kivu, Democratic Republic of the Congo) where large investments were made to improve the water supply infrastructure during this period, including a new 2,000-m3 tank, 56 community taps and 1,191 private taps. Across 16 geographic clusters in the town, we assessed water service accessibility, water quantity, continuity, and affordability, based on data provided by the construction team and the utility. We combined these dimensions into a single index ranging 0-100% according to rules defined using the fuzzy inference Mamdani method. Our results show that despite substantial increases in accessibility (i.e. proportion of households with a private tap or within 200 m of a community tap), overall service quality remained unsatisfactory, with a maximum index value of 38.1%, and worsened in many parts of the town due to limitations of the water production capacity after major flooding events and persistent electricity supply issues. The estimated amount of water supplied per user per day remained under 20 L during >95% of the observation period, with a decreasing trend. Pumps operated 58% of the time on average and the frequency of days without electricity supply increased over time. Our study highlights the important gap between upgrades in water supply infrastructure and improvements in the quality of service. The analysis of potential future scenarios for Uvira indicates that increasing production capacity is priority to improve overall service quality. Our results demonstrate that meeting SDG6 will be challenging in complex urban settings and will not only require sustained investments in water supply infrastructure but also in systems management and in energy supply.

Genomic Microevolution of Vibrio cholerae O1, Lake Tanganyika Basin, Africa.

Africa's Lake Tanganyika basin is a cholera hotspot. During 2001-2020, Vibrio cholerae O1 isolates obtained from the Democratic Republic of the Congo side of the lake belonged to 2 of the 5 clades of the AFR10 sublineage. One clade became predominant after acquiring a parC mutation that decreased susceptibility to ciprofloxacin.

A multi-country, prospective cohort study to measure rate and risk of relapse among children recovered from severe acute malnutrition in Mali, Somalia, and South Sudan: a study protocol.

BACKGROUND: The Community-Based Management of Acute Malnutrition (CMAM) model transformed the treatment of severe acute malnutrition (SAM) by shifting treatment from inpatient facilities to the community. Evidence shows that while CMAM programs are effective in the initial recovery from SAM, recovery is not sustained for some children requiring them to receive treatment repeatedly. This indicates a potential gap in the model, yet little evidence is available on the incidence of relapse, the determinants of the phenomena, or its financial implications on program delivery. METHODS: This study is a multi-country prospective cohort study following "post-SAM" children (defined as children following anthropometric recovery from SAM through treatment in CMAM) and matched community controls (defined as children not previously experiencing acute malnutrition (AM)) monthly for six months. The aim is to assess the burden and determinants of relapse to SAM. This study design enables the quantification of relapse among post-SAM children, but also to determine the relative risk for, and excess burden of, AM between post-SAM children and their matched community controls. Individual -, household-, and community-level information will be analyzed to identify potential risk-factors for relapse, with a focus on associations between water, sanitation, and hygiene (WASH) related exposures, and post-discharge outcomes. The study combines a microbiological assessment of post-SAM children's drinking water, food, stool via rectal swabs, dried blood spots (DBS), and assess for indicators of enteric pathogens and immune function, to explore different exposures and potential associations with treatment and post-treatment outcomes. DISCUSSION: This study is the first of its kind to systematically track children after recovery from SAM in CMAM programs using uniform methods across multiple countries. The design allows the use of results to: 1) facilitate understandings of the burden of relapse; 2) identify risk factors for relapse and 3) elucidate financial costs associated with relapse in CMAM programs. This protocol's publication aims to support similar studies and evaluations of CMAM programs and provides opportunities for comparability of an evidence-based set of indicators for relapse to SAM.

Household Disinfection Interventions to Prevent Cholera Transmission: Facilitators, Barriers, Training, and Evidence Needs.

There are two common household disinfection interventions to prevent interhousehold transmission of cholera: household spraying, whereby a team disinfects cholera patients' households, and household disinfection kits (HDKs), whereby cleaning materials are provided to cholera patients' family members. Currently, both interventions lack evidence, and international agencies recommend HDK distribution; however, household spraying remains widely implemented. To understand this disconnect, we conducted 14 key informant interviews with international and national responders and a study in Haiti assessing HDK efficacy using two training modules including 20 household surveys and 327 surfaces samples before and after cleaning. During interviews, 80% of the international-level informants discussed evidence gaps for both interventions, and 60% preferred HDKs. Conversely, no national-level informants knew what an HDK was; therefore, they all preferred spraying. Informants discussed behavior changes, bleach perceptions, and implementation as facilitators and/or barriers to implementing both interventions. In households, training with demonstrations regarding the use of HDK led to increased reductions of Escherichia coli (P < 0.001) and Vibrio spp. (P < 0.001) on surfaces after participants cleaned the household compared with a hygiene promotion session only. These results emphasize the gap between the current international-level policy and the realities of cholera response programs, highlight the need for evidence to align household disinfection recommendations, and underscore the importance of the dissemination and training of responders and affected populations regarding methods to prevent intrahousehold cholera transmission.

The impact of improved water supply on cholera and diarrhoeal diseases in Uvira, Democratic Republic of the Congo: a protocol for a pragmatic stepped-wedge cluster randomised trial and economic evaluation.

INTRODUCTION: Diarrhoeal disease remains a leading cause of mortality and morbidity worldwide. Cholera alone is estimated to cause 95,000 deaths per year, most of which occur in endemic settings with inadequate water access. Whilst a global strategy to eliminate cholera by 2030 calls for investment in improved drinking water services, there is limited rigorous evidence for the impact of improved water supply on endemic cholera transmission in low-income urban settings. Our protocol is designed to deliver a pragmatic health impact evaluation of a large-scale water supply intervention in Uvira (Democratic Republic of the Congo), a cholera transmission hotspot. METHODS/DESIGN: A stepped-wedge cluster randomised trial (SW-CRT) was designed to evaluate the impact of a large-scale drinking water supply intervention on cholera incidence among the 280,000 inhabitants of Uvira. The city was divided into 16 clusters, where new community and household taps will be installed following a randomised sequence over a transition period of up to 8 weeks in each cluster. The primary trial outcomes are the monthly incidence of "confirmed" cholera cases (patients testing positive by rapid detection kit) and of "suspected" cholera cases (patients admitted to the cholera treatment centre). Concurrent process and economic evaluations will provide further information on the context, costs, and efficiency of the intervention. DISCUSSION: In this protocol, we describe a pragmatic approach to conducting rigorous research to assess the impacts of a complex water supply intervention on severe diarrhoeal disease and cholera in an unstable, low-resource setting representative of cholera-affected areas. In particular, we discuss a series of pre-identified risks and linked mitigation strategies as well as the value of combining different data collection methods and preparation of multiple analysis scenarios to account for possible deviations from the protocol. The study described here has the potential to provide robust evidence to support more effective cholera control in challenging, high-burden settings. TRIAL REGISTRATION: This trial is registered on clinicaltrials.gov ( NCT02928341 , 10th October 2016) and has received ethics approval from the London School of Hygiene and Tropical Medicine (8913, 10603) and from the Ethics Committee from the School of Public Health, University of Kinshasa, Democratic Republic of the Congo (ESP/CE/088/2015).

RESUME (VERSION FRANçAISE): Please note this translation has been generated by the authors and has not been checked against the original, peer-reviewed English version by the Journal. Any discrepancies between the two versions should be raised with the authors. Cette traduction a été préparée par les auteurs et sa conformité avec la version anglaise revue par les pairs n'a pas été vérifiée par le journal. Toute différence entre les deux versions doit être signalée aux auteurs. INTRODUCTION: Les maladies diarrhéiques restent une cause majeure de mortalité et morbidité dans le monde. Le choléra seul cause environ 95'000 morts par an, dont la plupart dans des contextes endémiques où l'accès à l'eau est inadéquat. Tandis qu'une stratégie globale pour l'élimination du choléra d'ici à 2030 appelle des investissements dans l'amélioration des services d'approvisionnement en eau, il y a peu de données probantes et rigoureuses sur l'impact d'un approvisionnement en eau amélioré sur la transmission endémique du choléra dans les contextes urbains à faibles ressources. Notre protocole d'étude est conçu pour livrer une évaluation d'impact épidémiologique pragmatique d'une intervention d'approvisionnement en eau à large échelle à Uvira, République Démocratique du Congo, un point focal de transmission du choléra. MéTHODES/CONCEPTION: Un essai randomisé par grappes par échelons (stepped-wedge cluster randomised trial, SW-CRT) a été conçu pour évaluer l'impact d'une intervention d'approvisionnement en eau potable à large échelle sur l'incidence du choléra parmi les 280'000 habitants d'Uvira. La ville a été divisée en 16 grappes, dans lesquelles de nouvelles bornes fontaines et branchements individuels seront installés suivant une séquence randomisée sur une période allant jusqu'à 8 semaines par grappe. Le principal résultat de l'essai sera l'incidence mensuelle des cas de choléra « confirmés ¼ (patients positifs par tests de détection rapide) et des cas « suspects ¼ (patients admis au centre de traitement du choléra). Des évaluations de processus et économique menées en parallèle fourniront des informations complémentaires sur le contexte, les coûts et l'efficience de l'intervention. DISCUSSION: Dans ce protocole, nous présentons une approche pragmatique pour effectuer une recherche rigoureuse visant à évaluer les impacts d'une intervention complexe d'approvisionnement en eau sur la diarrhée sévère et le choléra dans un contexte instable et à faibles ressources, représentatif des zones affectées par le choléra. En particulier, nous considérons une série de risques pré-identifiés et les stratégies de mitigation associées ainsi que la valeur de combiner différentes méthodes de collecte de données et de préparer de multiples scénarios d'analyse pour tenir compte d'éventuelles déviations du protocole. L'étude présentée ici a le potentiel de fournir des évidences scientifiques robustes pour soutenir des stratégies de contrôle du choléra plus efficientes dans les contextes difficiles qui sont fortement affectés. ENREGISTREMENT DE L'ESSAI: Cet essai est enregistré sur clinicaltrials.gov ( NCT02928341 , 10 octobre 2016) et a reçu les approbations éthiques de la London School of Hygiene and Tropical Medicine (8913, 10603) ainsi que de l'Ecole de Santé Publique de l'Université de Kinshasa, République Démocratique du Congo (ESP/CE/088/2015).

Lessons learned from conducting six multi-country mixed-methods effectiveness research studies on water, sanitation, and hygiene (WASH) interventions in humanitarian response.

BACKGROUND: Provision of safe water, sanitation, and hygiene (WASH) to affected populations in humanitarian emergencies is necessary for dignity and communicable disease control. Additional evidence on WASH interventions is needed in humanitarian settings. Between 2008 and 2019, we completed six multi-country, mixed-methods effectiveness studies in humanitarian response on six different WASH interventions. In each evaluation, we conducted: key informant interviews; water point observations and water quality testing; household surveys with recipients, including survey and water quality testing; focus group discussions; and/or, secondary data analysis. The research questions were: "What is the effectiveness of [intervention] in reducing the risk of diarrhea/cholera transmission; and, what programmatic factors lead to higher effectiveness?" DISCUSSION: In all six multi-country, mixed-methods evaluations, policy-relevant outcomes were obtained. We found, in our individual research results, that: interventions could reduce the risk of disease in humanitarian contexts; this reduction of risk did not always occur, as there were large ranges in effectiveness; and, implementation factors were crucial to intervention effectiveness. When collaboratively reviewing our research process across evaluations, we found strategies for successfully conducting this research included: 1) working with partners to identify and evaluate programs; 2) rapidly obtaining approvals to deploy; and, 3) conducting research methodologies consistently. Personal connections, in-person communication, trust, and experience working together were key factors for success in identifying partners for evaluation. Successes in evaluation deployment occurred with flexibility, patience, commitment of adequate time, and understanding of processes; although we note access and security concerns in insecure contexts precluded deployment. Consistent and robust protocols, flexibility, and a consistent researcher on the ground in each context allowed for methodological consistency and high-quality results. CONCLUSIONS: In conclusion, we have found multi-country, mixed-methods results to be one crucial piece of the WASH evidence base in humanitarian contexts. This is particularly because evaluations of reductions in risk from real-world programming are policy-relevant, and are directly used to improve programming. In future, we need to flexibly work with donors, agencies, institutions, responders, local governments, local responders, and beneficiaries to design safe and ethical research protocols to answer questions related to WASH interventions effectiveness in humanitarian response, and, improve WASH programming.

Antimicrobial resistance and COVID-19: Intersections and implications.

Before the coronavirus 2019 (COVID-19) pandemic began, antimicrobial resistance (AMR) was among the top priorities for global public health. Already a complex challenge, AMR now needs to be addressed in a changing healthcare landscape. Here, we analyse how changes due to COVID-19 in terms of antimicrobial usage, infection prevention, and health systems affect the emergence, transmission, and burden of AMR. Increased hand hygiene, decreased international travel, and decreased elective hospital procedures may reduce AMR pathogen selection and spread in the short term. However, the opposite effects may be seen if antibiotics are more widely used as standard healthcare pathways break down. Over 6 months into the COVID-19 pandemic, the dynamics of AMR remain uncertain. We call for the AMR community to keep a global perspective while designing finely tuned surveillance and research to continue to improve our preparedness and response to these intersecting public health challenges.

A systematic review of chlorine-based surface disinfection efficacy to inform recommendations for low-resource outbreak settings.

BACKGROUND: Infectious diseases can be transmitted via fomites (contaminated surfaces/objects); disinfection can interrupt this transmission route. However, disinfection guidelines for low-resource outbreak settings are inconsistent and not evidence-based. METHODS: A systematic review of surface disinfection efficacy studies was conducted to inform low-resource outbreak guideline development. Due to variation in experimental procedures, outcomes were synthesized in a narrative summary focusing on chlorine-based disinfection against 7 pathogens with potential to produce outbreaks in low-resource settings (Mycobacterium tuberculosis, Vibrio cholerae, Salmonella spp., hepatitis A virus, rotavirus, norovirus, and Ebola virus). RESULTS: Data were extracted from 89 laboratory studies and made available, including 20 studies on relevant pathogens used in combination with surrogate data to determine minimum target concentration × time ("CT") factors. Stainless steel (68%) and chlorine-based disinfectants (56%) were most commonly tested. No consistent trend was seen in the influence of chlorine concentration and exposure time on disinfection efficacy. Disinfectant application mode; soil load; and surface type were frequently identified as influential factors in included studies. CONCLUSIONS: This review highlights that surface disinfection efficacy estimates are strongly influenced by each study's experimental conditions. We therefore recommend laboratory testing to be followed by field-based testing/monitoring to ensure effectiveness is achieved in situ.

Household spraying in cholera outbreaks: Insights from three exploratory, mixed-methods field effectiveness evaluations.

Household spraying is a commonly implemented, yet an under-researched, cholera response intervention where a response team sprays surfaces in cholera patients' houses with chlorine. We conducted mixed-methods evaluations of three household spraying programs in the Democratic Republic of Congo and Haiti, including 18 key informant interviews, 14 household surveys and observations, and 418 surface samples collected before spraying, 30 minutes and 24 hours after spraying. The surfaces consistently most contaminated with Vibrio cholerae were food preparation areas, near the patient's bed and the latrine. Effectiveness varied between programs, with statistically significant reductions in V. cholerae concentrations 30 minutes after spraying in two programs. Surface contamination after 24 hours was variable between households and programs. Program challenges included difficulty locating households, transportation and funding limitations, and reaching households quickly after case presentation (disinfection occurred 2-6 days after reported cholera onset). Program advantages included the concurrent deployment of hygiene promotion activities. Further research is indicated on perception, recontamination, cost-effectiveness, viable but nonculturable V. cholerae, and epidemiological coverage. We recommend that, if spraying is implemented, spraying agents should: disinfect surfaces systematically until wet using 0.2/2.0% chlorine solution, including kitchen spaces, patients' beds, and latrines; arrive at households quickly; and, concurrently deploy hygiene promotion activities.

Prevention and control of cholera with household and community water, sanitation and hygiene (WASH) interventions: A scoping review of current international guidelines.

INTRODUCTION: Cholera remains a frequent cause of outbreaks globally, particularly in areas with inadequate water, sanitation and hygiene (WASH) services. Cholera is spread through faecal-oral routes, and studies demonstrate that ingestion of Vibrio cholerae occurs from consuming contaminated food and water, contact with cholera cases and transmission from contaminated environmental point sources. WASH guidelines recommending interventions for the prevention and control of cholera are numerous and vary considerably in their recommendations. To date, there has been no review of practice guidelines used in cholera prevention and control programmes. METHODS: We systematically searched international agency websites to identify WASH intervention guidelines used in cholera programmes in endemic and epidemic settings. Recommendations listed in the guidelines were extracted, categorised and analysed. Analysis was based on consistency, concordance and recommendations were classified on the basis of whether the interventions targeted within-household or community-level transmission. RESULTS: Eight international guidelines were included in this review: three by non-governmental organisations (NGOs), one from a non-profit organisation (NPO), three from multilateral organisations and one from a research institution. There were 95 distinct recommendations identified, and concordance among guidelines was poor to fair. All categories of WASH interventions were featured in the guidelines. The majority of recommendations targeted community-level transmission (45%), 35% targeted within-household transmission and 20% both. CONCLUSIONS: Recent evidence suggests that interventions for effective cholera control and response to epidemics should focus on case-centred approaches and within-household transmission. Guidelines did consistently propose interventions targeting transmission within households. However, the majority of recommendations listed in guidelines targeted community-level transmission and tended to be more focused on preventing contamination of the environment by cases or recurrent outbreaks, and the level of service required to interrupt community-level transmission was often not specified. The guidelines in current use were varied and interpretation may be difficult when conflicting recommendations are provided. Future editions of guidelines should reflect on the inclusion of evidence-based approaches, cholera transmission models and resource-efficient strategies.

Selection of a Biosafety Level 1 (BSL-1) surrogate to evaluate surface disinfection efficacy in Ebola outbreaks: Comparison of four bacteriophages.

The 2014 West African Ebola virus disease outbreak was the largest to date, and conflicting, chlorine-based surface disinfection protocols to interrupt disease transmission were recommended. We identified only one study documenting surface disinfection efficacy against the Ebola virus, showing a >6.6 log reduction after 5-minute exposure to 0.5% sodium hypochlorite (NaOCl) based on small-scale tests (Cook et al. (2015)). In preparation for future extensive, large-scale disinfection efficacy experiments, we replicated the Cook et al. experiment using four potential BSL-1 surrogates selected based on similarities to the Ebola virus: bacteriophages MS2, M13, Phi6, and PR772. Each bacteriophage was exposed to 0.1% and 0.5% NaOCl for 1, 5, and 10 minutes on stainless steel. MS2 and M13 were only reduced by 3.4 log and 3.5 log after a 10-minute exposure to 0.5% NaOCl, and would be overly conservative surrogates. Conversely, PR772 was too easily inactivated for surrogate use, as it was reduced by >4.8 log after only 1-minute exposure to 0.5% NaOCl. Phi6 was slightly more resistant than the Ebola virus, with 4.1 log reduction after a 5-minute exposure and not detected after a 10-minute exposure to 0.5% NaOCl. We therefore recommend Phi6 as a surrogate for evaluating the efficacy of chlorine-based surface disinfectants against the Ebola virus.

Surface Cleaning and Disinfection: Efficacy Assessment of Four Chlorine Types Using Escherichia coli and the Ebola Surrogate Phi6.

In the 2014 West African Ebola outbreak, international organizations provided conflicting recommendations for disinfecting surfaces contaminated by uncontrolled patient spills. We compared the efficacy of four chlorine solutions (sodium hypochlorite, sodium dichloroisocyanurate, high-test hypochlorite, and generated hypochlorite) for disinfection of three surface types (stainless steel, heavy-duty tarp, and nitrile) with and without pre-cleaning practices (prewiping, covering, or both) and soil load. The test organisms were Escherichia coli and the Ebola surrogate Phi6. All tests achieved a minimum of 5.9 and 3.1 log removal in E. coli and Phi6, respectively. A 15 min exposure to 0.5% chlorine was sufficient to ensure <8 Phi6 plaque-forming unit (PFU)/cm2 in all tests. While chlorine types were equally efficacious with and without soil load, variation was seen by surface type. Wiping did not increase disinfection efficacy and is not recommended because it generates infectious waste. Covering spills decreased disinfection efficacy against E. coli on heavy-duty tarp but does prevent splashing, which is critical in Ebola contexts. Our results support the recommendation of a 15 min exposure to 0.5% chlorine, independently of chlorine type, surface, pre-cleaning practices, and organic matter, as an efficacious measure to interrupt disease transmission from uncontrolled spills in Ebola outbreaks.

Handwashing and Ebola virus disease outbreaks: A randomized comparison of soap, hand sanitizer, and 0.05% chlorine solutions on the inactivation and removal of model organisms Phi6 and E. coli from hands and persistence in rinse water.

To prevent Ebola transmission, frequent handwashing is recommended in Ebola Treatment Units and communities. However, little is known about which handwashing protocol is most efficacious. We evaluated six handwashing protocols (soap and water, alcohol-based hand sanitizer (ABHS), and 0.05% sodium dichloroisocyanurate, high-test hypochlorite, and stabilized and non-stabilized sodium hypochlorite solutions) for 1) efficacy of handwashing on the removal and inactivation of non-pathogenic model organisms and, 2) persistence of organisms in rinse water. Model organisms E. coli and bacteriophage Phi6 were used to evaluate handwashing with and without organic load added to simulate bodily fluids. Hands were inoculated with test organisms, washed, and rinsed using a glove juice method to retrieve remaining organisms. Impact was estimated by comparing the log reduction in organisms after handwashing to the log reduction without handwashing. Rinse water was collected to test for persistence of organisms. Handwashing resulted in a 1.94-3.01 log reduction in E. coli concentration without, and 2.18-3.34 with, soil load; and a 2.44-3.06 log reduction in Phi6 without, and 2.71-3.69 with, soil load. HTH performed most consistently well, with significantly greater log reductions than other handwashing protocols in three models. However, the magnitude of handwashing efficacy differences was small, suggesting protocols are similarly efficacious. Rinse water demonstrated a 0.28-4.77 log reduction in remaining E. coli without, and 0.21-4.49 with, soil load and a 1.26-2.02 log reduction in Phi6 without, and 1.30-2.20 with, soil load. Chlorine resulted in significantly less persistence of E. coli in both conditions and Phi6 without soil load in rinse water (p<0.001). Thus, chlorine-based methods may offer a benefit of reducing persistence in rinse water. We recommend responders use the most practical handwashing method to ensure hand hygiene in Ebola contexts, considering the potential benefit of chlorine-based methods in rinse water persistence.