Last data update: Jun 17, 2024. (Total: 47034 publications since 2009)
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Query Trace: Farag N [original query] |
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Cases of meningococcal disease associated with travel to Saudi Arabia for Umrah Pilgrimage - United States, United Kingdom, and France, 2024
Vachon MS , Barret AS , Lucidarme J , Neatherlin J , Rubis AB , Howie RL , Sharma S , Marasini D , Wagle B , Keating P , Antwi M , Chen J , Gu-Templin T , Gahr P , Zipprich J , Dorr F , Kuguru K , Lee S , Halai UA , Martin B , Budd J , Memish Z , Assiri AM , Farag NH , Taha MK , Deghmane AE , Zanetti L , Lefrançois R , Clark SA , Borrow R , Ladhani SN , Campbell H , Ramsay M , Fox L , McNamara LA . MMWR Morb Mortal Wkly Rep 2024 73 (22) 514-516 ![]() Invasive meningococcal disease (IMD), caused by infection with the bacterium Neisseria meningitidis, usually manifests as meningitis or septicemia and can be severe and life-threatening (1). Six serogroups (A, B, C, W, X, and Y) account for most cases (2). N. meningitidis is transmitted person-to-person via respiratory droplets and oropharyngeal secretions. Asymptomatic persons can carry N. meningitidis and transmit the bacteria to others, potentially causing illness among susceptible persons. Outbreaks can occur in conjunction with large gatherings (3,4). Vaccines are available to prevent meningococcal disease. Antibiotic prophylaxis for close contacts of infected persons is critical to preventing secondary cases (2). |
Correction: The One Health High-Level Expert Panel (OHHLEP)
Mettenleiter TC , Markotter W , Charron DF , Adisasmito WB , Almuhairi S , Behravesh CB , Bilivogui P , Bukachi SA , Casas N , Becerra NC , Chaudhary A , Ciacci Zanella JR , Cunningham AA , Dar O , Debnath N , Dungu B , Farag E , Gao GF , Hayman DTS , Khaitsa M , Koopmans MPG , Machalaba C , Mackenzie JS , Morand S , Smolenskiy V , Zhou L . One Health Outlook 2024 6 (1) 6 |
The One Health High-Level Expert Panel (OHHLEP)
Mettenleiter TC , Markotter W , Charron DF , Adisasmito WB , Almuhairi S , Behravesh CB , Bilivogui P , Bukachi SA , Casas N , Becerra NC , Chaudhary A , Zanella JRC , Cunningham AA , Dar O , Debnath N , Dungu B , Farag E , Gao GF , Hayman DTS , Khaitsa M , Koopmans MPG , Machalaba C , Mackenzie JS , Morand S , Smolenskiy V , Zhou L . One Health Outlook 2023 5 (1) 18 One Health is an integrative and systemic approach to health, based on the understanding that human, animal and ecosystem health are inextricably linked. These interconnections and vulnerabilities were once more clearly demonstrated by the COVID-19 pandemic. This led the heads of the United Nations Food and Agriculture Organization (FAO), the United Nations Environment Programme (UNEP), the World Health Organization (WHO), and the World Organization for Animal Health (WOAH; founded as OIE), to enhance their science-based cross-sectoral collaboration by creating a multidisciplinary One Health High-Level Expert Panel (OHHLEP) to provide technical and scientific advice on One Health issues. Out of over 700 applications from all over the world, the four international partners FAO, WHO, WOAH and UNEP selected 26 experts from 24 countries as members of the OHHLEP. The multisectoral and transdisciplinary expertise present in OHHLEP members covers a wide range including animal, human and environmental health, biodiversity conservation and social sciences. The panel was conceived following a proposal by the French and German governments at the Paris Peace Forum in November 2020. It drew on the already existing FAO-OIE-WHO Tripartite intersectoral cooperation on One Health issues. In 2021, UNEP joined to form the Tripartite plus UNEP which was formally transformed into the ‘Quadripartite Collaboration for One Health’ in March 2022 and which now acts as the partner for engaging with OHHLEP. This is the first time that a global advisory panel on One Health has been created as a centre for expert advice. |
Developing One Health surveillance systems
Hayman DTS , Adisasmito WB , Almuhairi S , Behravesh CB , Bilivogui P , Bukachi SA , Casas N , Becerra NC , Charron DF , Chaudhary A , Ciacci Zanella JR , Cunningham AA , Dar O , Debnath N , Dungu B , Farag E , Gao GF , Khaitsa M , Machalaba C , Mackenzie JS , Markotter W , Mettenleiter TC , Morand S , Smolenskiy V , Zhou L , Koopmans M . One Health 2023 17 100617 The health of humans, domestic and wild animals, plants, and the environment are inter-dependent. Global anthropogenic change is a key driver of disease emergence and spread and leads to biodiversity loss and ecosystem function degradation, which are themselves drivers of disease emergence. Pathogen spill-over events and subsequent disease outbreaks, including pandemics, in humans, animals and plants may arise when factors driving disease emergence and spread converge. One Health is an integrated approach that aims to sustainably balance and optimize human, animal and ecosystem health. Conventional disease surveillance has been siloed by sectors, with separate systems addressing the health of humans, domestic animals, cultivated plants, wildlife and the environment. One Health surveillance should include integrated surveillance for known and unknown pathogens, but combined with this more traditional disease-based surveillance, it also must include surveillance of drivers of disease emergence to improve prevention and mitigation of spill-over events. Here, we outline such an approach, including the characteristics and components required to overcome barriers and to optimize an integrated One Health surveillance system. © 2023 The Authors |
One Health: A new definition for a sustainable and healthy future.
Adisasmito WB , Almuhairi S , Behravesh CB , Bilivogui P , Bukachi SA , Casas N , Cediel Becerra N , Charron DF , Chaudhary A , Ciacci Zanella JR , Cunningham AA , Dar O , Debnath N , Dungu B , Farag E , Gao GF , Hayman DTS , Khaitsa M , Koopmans MPG , Machalaba C , Mackenzie JS , Markotter W , Mettenleiter TC , Morand S , Smolenskiy V , Zhou L . PLoS Pathog 2022 18 (6) e1010537 ![]() ![]() The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic once more demonstrated the close connection between humans, animals, and the shared environment. Although still under investigation, the closest relatives of this virus exist in animals, and the factors leading to spillover remain to be fully understood. This interconnectedness again highlighted the need for a One Health approach. Although the One Health concept is not new and has been at the forefront of interdisciplinary and multisectoral discussions for years, there is now an increased interest for this approach to be applied and translated into action. Following a proposal made by the French and German Ministers for Foreign Affairs at the November 2020 Paris Peace Forum, 4 global partners, the Food and Agriculture Organization (FAO), the World Organization for Animal Health (OIE), the United Nations Environment Programme (UNEP), and the World Health Organization (WHO), in May 2021 established the interdisciplinary One Health High-Level Expert Panel (OHHLEP) (https://www.who.int/groups/one-health-high-level-expert-panel) to enhance their cross-sectoral collaboration. The creation of OHHLEP represents a recognition at the highest level of the urgency and complexities surrounding One Health and the intent to take this concept forward into policies and concrete actions. |
Immunity to poliovirus in Afghanistan: A household sampling method for serological assessment based on geographical information systems
Mendes A , Whiteman A , Nygren B , Kaplan B , Hussain I , Soofi S , Martinez M , Farag NH . Geospat Health 2022 17 (2) Afghanistan continues to experience challenges affecting polio eradication. Mass polio vaccination campaigns, which aim to protect children under the age of 5, are a key eradication strategy. To date, the polio program in Afghanistan has only employed facility-based seroprevalence surveys, which can be subject to sampling bias. We describe the feasibility in implementing a cross-sectional household poliovirus seroprevalence survey based on geographical information systems (GIS) in three districts. Digital maps with randomly selected predetermined starting points were provided to teams, with a total target of 1,632 households. Teams were instructed to navigate to predetermined starting points and enrol the closest household within 60 m. To assess effectiveness of these methods, we calculated percentages for total households enrolled with valid geocoordinates collected within the designated boundary, and whether the Euclidean distance of households were within 60 m of a predetermined starting point. A normalized difference vegetation index (NDVI) image ratio was conducted to further investigate variability in team performances. The study enrolled a total of 78% of the target sample with 52% of all households within 60 m of a pre-selected point and 79% within the designated cluster boundary. Success varied considerably between the four target areas ranging from 42% enrolment of the target sample in one place to 90% enrolment of the target sample in another. Interviews with the field teams revealed that differences in security status and amount of non-residential land cover were key barriers to higher enrolment rates. Our findings indicate household poliovirus seroprevalence surveys using GIS-based sampling can be effectively implemented in polio endemic countries to capture representative samples. We also proposed ways to achieve higher success rates if these methods are to be used in the future, particularly in areas with concerns of insecurity or spatially dispersed residential units. |
Poliovirus immunity among children aged 6-11 and 36-48 months in 14 polio high-risk provinces of Afghanistan: A health-facility-based study
Soofi SB , Martinez M , Farag NH , Hendley WS , Ehrhardt D , Ahmed I , Hussain I , Weldon W , Kassem AM . Vaccines (Basel) 2022 10 (10) Afghanistan is one of two countries where wild poliovirus (WPV) type 1 remains endemic. We conducted a facility-based cross-sectional survey of antipoliovirus antibodies in children in 14 provinces of Afghanistan. The provinces were selected based on programmatic priorities for polio eradication. Children aged 6-11 and 36-48 months attending outpatient clinics were enrolled in the study. We collected venous blood, isolated serum, and conducted neutralization assays to detect poliovirus neutralizing antibodies. A total of 2086 children from the 14 provinces were enrolled. Among the enrolled children, 44.3% were girls; the median age in the 6-11-month group was 9.4 months, and in the 36-48-month group, it was 41.8 months. The most common spoken language was Pashtu (70.8%). Eighty-two percent of children were fully immunized against all the diseases in the vaccination schedule of Afghanistan. In the children aged 6-11 months, seroprevalence to poliovirus type 1 (PV1) was 96.5% and seroprevalence to poliovirus type 3 (PV3) was 93%; in children aged 36-48 months, seroprevalence to PV1 was 99.5% and to PV3 was 98%. Antipoliovirus antibody prevalence for poliovirus type 2 (PV2) was 70.5% in the younger group compared with 90.9% in the older children. Children from Herat and Laghman provinces had almost 100% seroprevalence to PV1, and other provinces also had high prevalence, ranging from 92.0% to 99.0%. A similar finding was seen for antibodies against PV3, ranging from 88% to 100% by province. On the contrary, antibodies to PV2 were low, ranging from 53% for children in the Khost province to around 89% in Kunduz. There was a cluster of 18 seronegative children in the Nuristan province. Overall, the polio eradication program of Afghanistan has been successful in achieving high seroprevalence of poliovirus neutralizing antibodies in the parts of the country included in this study. |
Pathogens associated with linear growth faltering in children with diarrhea and impact of antibiotic treatment: The global enteric multicenter study
Nasrin D , Blackwelder WC , Sommerfelt H , Wu Y , Farag TH , Panchalingam S , Biswas K , Saha D , Jahangir Hossain M , Sow SO , Reiman RFB , Sur D , Faruque ASG , Zaidi AKM , Sanogo D , Tamboura B , Onwuchekwa U , Manna B , Ramamurthy T , Kanungo S , Omore R , Ochieng JB , Oundo JO , Das SK , Ahmed S , Qureshi S , Quadri F , Adegbola RA , Antonio M , Mandomando I , Nhampossa T , Bassat Q , Roose A , O'Reilly CE , Mintz ED , Ramakrishnan U , Powell H , Liang Y , Nataro JP , Levine MM , Kotloff KL . J Infect Dis 2021 224 S848-s855 BACKGROUND: The association between childhood diarrheal disease and linear growth faltering in developing countries is well described. However, the impact attributed to specific pathogens has not been elucidated, nor has the impact of recommended antibiotic treatment. METHODS: The Global Enteric Multicenter Study enrolled children with moderate to severe diarrhea (MSD) seeking healthcare at 7 sites in sub-Saharan Africa and South Asia. At enrollment, we collected stool samples to identify enteropathogens. Length/height was measured at enrollment and follow-up, approximately 60 days later, to calculate change in height-for-age z scores (ΔHAZ). The association of pathogens with ΔHAZ was tested using linear mixed effects regression models. RESULTS: Among 8077 MSD cases analyzed, the proportion with stunting (HAZ below -1) increased from 59% at enrollment to 65% at follow-up (P < .0001). Pathogens significantly associated with linear growth decline included Cryptosporidium (P < .001), typical enteropathogenic Escherichia coli (P = .01), and untreated Shigella (P = .009) among infants (aged 0-11 months) and enterotoxigenic E. coli encoding heat-stable toxin (P < .001) and Cryptosporidium (P = .03) among toddlers (aged 12-23 months). Shigella-infected toddlers given antibiotics had improved linear growth (P = .02). CONCLUSIONS: Linear growth faltering among children aged 0-23 months with MSD is associated with specific pathogens and can be mitigated with targeted treatment strategies, as demonstrated for Shigella. |
Mapathons versus automated feature extraction: a comparative analysis for strengthening immunization microplanning.
Mendes A , Palmer T , Berens A , Espey J , Price R , Mallya A , Brown S , Martinez M , Farag N , Kaplan B . Int J Health Geogr 2021 20 (1) 27 ![]() ![]() BACKGROUND: Social instability and logistical factors like the displacement of vulnerable populations, the difficulty of accessing these populations, and the lack of geographic information for hard-to-reach areas continue to serve as barriers to global essential immunizations (EI). Microplanning, a population-based, healthcare intervention planning method has begun to leverage geographic information system (GIS) technology and geospatial methods to improve the remote identification and mapping of vulnerable populations to ensure inclusion in outreach and immunization services, when feasible. We compare two methods of accomplishing a remote inventory of building locations to assess their accuracy and similarity to currently employed microplan line-lists in the study area. METHODS: The outputs of a crowd-sourced digitization effort, or mapathon, were compared to those of a machine-learning algorithm for digitization, referred to as automatic feature extraction (AFE). The following accuracy assessments were employed to determine the performance of each feature generation method: (1) an agreement analysis of the two methods assessed the occurrence of matches across the two outputs, where agreements were labeled as "befriended" and disagreements as "lonely"; (2) true and false positive percentages of each method were calculated in comparison to satellite imagery; (3) counts of features generated from both the mapathon and AFE were statistically compared to the number of features listed in the microplan line-list for the study area; and (4) population estimates for both feature generation method were determined for every structure identified assuming a total of three households per compound, with each household averaging two adults and 5 children. RESULTS: The mapathon and AFE outputs detected 92,713 and 53,150 features, respectively. A higher proportion (30%) of AFE features were befriended compared with befriended mapathon points (28%). The AFE had a higher true positive rate (90.5%) of identifying structures than the mapathon (84.5%). The difference in the average number of features identified per area between the microplan and mapathon points was larger (t = 3.56) than the microplan and AFE (t = - 2.09) (alpha = 0.05). CONCLUSIONS: Our findings indicate AFE outputs had higher agreement (i.e., befriended), slightly higher likelihood of correctly identifying a structure, and were more similar to the local microplan line-lists than the mapathon outputs. These findings suggest AFE may be more accurate for identifying structures in high-resolution satellite imagery than mapathons. However, they both had their advantages and the ideal method would utilize both methods in tandem. |
CATMoS: Collaborative Acute Toxicity Modeling Suite.
Mansouri K , Karmaus AL , Fitzpatrick J , Patlewicz G , Pradeep P , Alberga D , Alepee N , Allen TEH , Allen D , Alves VM , Andrade CH , Auernhammer TR , Ballabio D , Bell S , Benfenati E , Bhattacharya S , Bastos JV , Boyd S , Brown JB , Capuzzi SJ , Chushak Y , Ciallella H , Clark AM , Consonni V , Daga PR , Ekins S , Farag S , Fedorov M , Fourches D , Gadaleta D , Gao F , Gearhart JM , Goh G , Goodman JM , Grisoni F , Grulke CM , Hartung T , Hirn M , Karpov P , Korotcov A , Lavado GJ , Lawless M , Li X , Luechtefeld T , Lunghini F , Mangiatordi GF , Marcou G , Marsh D , Martin T , Mauri A , Muratov EN , Myatt GJ , Nguyen DT , Nicolotti O , Note R , Pande P , Parks AK , Peryea T , Polash AH , Rallo R , Roncaglioni A , Rowlands C , Ruiz P , Russo DP , Sayed A , Sayre R , Sheils T , Siegel C , Silva AC , Simeonov A , Sosnin S , Southall N , Strickland J , Tang Y , Teppen B , Tetko IV , Thomas D , Tkachenko V , Todeschini R , Toma C , Tripodi I , Trisciuzzi D , Tropsha A , Varnek A , Vukovic K , Wang Z , Wang L , Waters KM , Wedlake AJ , Wijeyesakere SJ , Wilson D , Xiao Z , Yang H , Zahoranszky-Kohalmi G , Zakharov AV , Zhang FF , Zhang Z , Zhao T , Zhu H , Zorn KM , Casey W , Kleinstreuer NC . Environ Health Perspect 2021 129 (4) 47013 ![]() BACKGROUND: Humans are exposed to tens of thousands of chemical substances that need to be assessed for their potential toxicity. Acute systemic toxicity testing serves as the basis for regulatory hazard classification, labeling, and risk management. However, it is cost- and time-prohibitive to evaluate all new and existing chemicals using traditional rodent acute toxicity tests. In silico models built using existing data facilitate rapid acute toxicity predictions without using animals. OBJECTIVES: The U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Acute Toxicity Workgroup organized an international collaboration to develop in silico models for predicting acute oral toxicity based on five different end points: Lethal Dose 50 (LD50 value, U.S. Environmental Protection Agency hazard (four) categories, Globally Harmonized System for Classification and Labeling hazard (five) categories, very toxic chemicals [LD50 (LD50 ≤ 50 mg/kg)], and nontoxic chemicals (LD50 > 2,000 mg/kg). METHODS: An acute oral toxicity data inventory for 11,992 chemicals was compiled, split into training and evaluation sets, and made available to 35 participating international research groups that submitted a total of 139 predictive models. Predictions that fell within the applicability domains of the submitted models were evaluated using external validation sets. These were then combined into consensus models to leverage strengths of individual approaches. RESULTS: The resulting consensus predictions, which leverage the collective strengths of each individual model, form the Collaborative Acute Toxicity Modeling Suite (CATMoS). CATMoS demonstrated high performance in terms of accuracy and robustness when compared with in vivo results. DISCUSSION: CATMoS is being evaluated by regulatory agencies for its utility and applicability as a potential replacement for in vivo rat acute oral toxicity studies. CATMoS predictions for more than 800,000 chemicals have been made available via the National Toxicology Program's Integrated Chemical Environment tools and data sets (ice.ntp.niehs.nih.gov). The models are also implemented in a free, standalone, open-source tool, OPERA, which allows predictions of new and untested chemicals to be made. https://doi.org/10.1289/EHP8495. |
Characteristics of Salmonella recovered from stools of children enrolled in the Global Enteric Multicenter Study.
Kasumba IN , Pulford CV , Perez-Sepulveda BM , Sen S , Sayed N , Permala-Booth J , Livio S , Heavens D , Low R , Hall N , Roose A , Powell H , Farag T , Panchalingham S , Berkeley L , Nasrin D , Blackwelder WC , Wu Y , Tamboura B , Sanogo D , Onwuchekwa U , Sow SO , Ochieng JB , Omore R , Oundo JO , Breiman RF , Mintz ED , O'Reilly CE , Antonio M , Saha D , Hossain MJ , Mandomando I , Bassat Q , Alonso PL , Ramamurthy T , Sur D , Qureshi S , Zaidi AKM , Hossain A , Faruque ASG , Nataro JP , Kotloff KL , Levine MM , Hinton JCD , Tennant SM . Clin Infect Dis 2021 73 (4) 631-641 ![]() ![]() BACKGROUND: The Global Enteric Multicenter Study (GEMS) determined the etiologic agents of moderate-to-severe diarrhea (MSD) in children under 5 years old in Africa and Asia. Here, we describe the prevalence and antimicrobial susceptibility of non-typhoidal Salmonella (NTS) serovars in GEMS and examine the phylogenetics of Salmonella Typhimurium ST313 isolates. METHODS: Salmonella isolated from children with MSD or diarrhea-free controls were identified by classical clinical microbiology and serotyped using antisera and/or whole genome sequence data. We evaluated antimicrobial susceptibility using the Kirby-Bauer disk diffusion method. Salmonella Typhimurium sequence types were determined using multi-locus sequence typing and whole genome sequencing was performed to assess the phylogeny of ST313. RESULTS: Out of 370 Salmonella-positive individuals, 190 (51.4%) were MSD cases and 180 (48.6%) were diarrhea-free controls. The most frequent Salmonella serovars identified were Salmonella Typhimurium, serogroup O:8 (C2-C3), serogroup O:6,7 (C1), Salmonella Paratyphi B Java and serogroup O:4 (B). The prevalence of NTS was low but similar across sites, regardless of age, and was similar amongst both cases and controls except in Kenya, where Salmonella Typhimurium was more commonly associated with cases than controls. Phylogenetic analysis showed that these Salmonella Typhimurium isolates, all ST313, were highly genetically related to isolates from controls. Generally, Salmonella isolates from Asia were resistant to ciprofloxacin and ceftriaxone but African isolates were susceptible to these antibiotics. CONCLUSION: Our data confirms that NTS is prevalent, albeit at low levels, in Africa and South Asia. Our findings provide further evidence that multi-drug resistant Salmonella Typhimurium ST313 can be carried asymptomatically by humans in sub-Saharan Africa. |
Factors associated with typical enteropathogenic Escherichia coli infection among children <5 years old with moderate-to-severe diarrhoea in rural western Kenya, 2008-2012.
Fagerli K , Omore R , Kim S , Ochieng JB , Ayers TL , Juma J , Farag TH , Nasrin D , Panchalingam S , Robins-Browne RM , Nataro JP , Kotloff KL , Levine MM , Oundo J , Parsons MB , Laserson KF , Mintz ED , Breiman RF , O'Reilly CE . Epidemiol Infect 2020 148 1-37 ![]() Typical enteropathogenic Escherichia coli (tEPEC) infection is a major cause of diarrhoea and contributor to mortality in children <5 years old in developing countries. Data were analysed from the Global Enteric Multicenter Study examining children <5 years old seeking care for moderate-to-severe diarrhoea (MSD) in Kenya. Stool specimens were tested for enteric pathogens, including by multiplex polymerase chain reaction for gene targets of tEPEC. Demographic, clinical and anthropometric data were collected at enrolment and ~60-days later; multivariable logistic regressions were constructed. Of 1778 MSD cases enrolled from 2008 to 2012, 135 (7.6%) children tested positive for tEPEC. In a case-to-case comparison among MSD cases, tEPEC was independently associated with presentation at enrolment with a loss of skin turgor (adjusted odds ratio (aOR) 2.08, 95% confidence interval (CI) 1.37-3.17), and convulsions (aOR 2.83, 95% CI 1.12-7.14). At follow-up, infants with tEPEC compared to those without were associated with being underweight (OR 2.2, 95% CI 1.3-3.6) and wasted (OR 2.5, 95% CI 1.3-4.6). Among MSD cases, tEPEC was associated with mortality (aOR 2.85, 95% CI 1.47-5.55). This study suggests that tEPEC contributes to morbidity and mortality in children. Interventions aimed at defining and reducing the burden of tEPEC and its sequelae should be urgently investigated, prioritised and implemented. |
Update on immunodeficiency-associated vaccine-derived polioviruses - worldwide, July 2018-December 2019
Macklin G , Diop OM , Humayun A , Shahmahmoodi S , El-Sayed ZA , Triki H , Rey G , Avagyan T , Grabovac V , Jorba J , Farag N , Mach O . MMWR Morb Mortal Wkly Rep 2020 69 (28) 913-917 Since establishment of the Global Polio Eradication Initiative* in 1988, polio cases have declined >99.9% worldwide; extensive use of live, attenuated oral poliovirus vaccine (OPV) in routine childhood immunization programs and mass campaigns has led to eradication of two of the three wild poliovirus (WPV) serotypes (types 2 and 3) (1). Despite its safety record, OPV can lead to rare emergence of vaccine-derived polioviruses (VDPVs) when there is prolonged circulation or replication of the vaccine virus. In areas with inadequate OPV coverage, circulating VDPVs (cVDPVs) that have reverted to neurovirulence can cause outbreaks of paralytic polio (2). Immunodeficiency-associated VDPVs (iVDPVs) are isolated from persons with primary immunodeficiency (PID). Infection with iVDPV can progress to paralysis or death of patients with PID, and excretion risks seeding cVDPV outbreaks; both risks might be reduced through antiviral treatment, which is currently under development. This report updates previous reports and includes details of iVDPV cases detected during July 2018-December 2019 (3). During this time, 16 new iVDPV cases were reported from five countries (Argentina, Egypt, Iran, Philippines, and Tunisia). Alongside acute flaccid paralysis (AFP) surveillance (4), surveillance for poliovirus infections among patients with PID has identified an increased number of persons excreting iVDPVs (5). Expansion of PID surveillance will facilitate early detection and follow-up of iVDPV excretion among patients with PID to mitigate the risk for iVDPV spread. This will be critical to help identify all poliovirus excretors and thus achieve and maintain eradication of all polioviruses. |
Estimating population immunity to poliovirus in Lebanon: Results from a seroprevalence survey, 2016
Mansour Z , Said R , Wannemuehler K , Weldon W , Estephan J , Khachan J , Warrak R , Hendley W , Ehrhardt D , Farag NH . Vaccine 2020 38 (31) 4846-4852 INTRODUCTION: Circulation of poliovirus in neighboring countries and mass population movement places Lebanon at risk of polio and other vaccine-preventable disease outbreaks. Determining population immunity levels is essential for guiding program planning and implementation of targeted supplementary immunization activities (SIAs) in governorates and subpopulations with low seroprevalence. METHODS: A cross-sectional multi-stage cluster survey was conducted during February-December 2016 in all six governorates of Lebanon adapted from the World Health Organization (WHO) recommended Expanded Progamme on Immunization (EPI) methodology. Sera from selected children aged 12-59 months were tested for poliovirus neutralizing antibodies. RESULTS: Of 2,164 children recruited in this study, 1,893 provided sufficient quantity of serum samples for laboratory testing. Seroprevalence for all three poliovirus serotypes was greater than 90% in all six governorates. Poliovirus vaccine coverage with three or more doses, based on vaccination cards or parental recall, ranged between 54.1% for children aged 36-47 months in the North and 83.5% for children aged 48-59 months in Beirut. CONCLUSION: Immunity to polioviruses was high in Lebanon in 2016 following a series of supplementary immunization activities. It is essential to continue strategies that increase vaccination coverage in order to sustain the considerably high immunity levels and prevent reintroduction and transmission of poliovirus. Educating caregivers and training health care workers on the standardized usage of home-based vaccination records is needed to guarantee the accuracy of records on children's vaccination status. |
Using nonpolio enterovirus detection to assess the integrity of stool specimens collected from acute flaccid paralysis cases in Somalia during 2014-2017
Ben Hamida A , Mohamed Ali K , Mdodo R , Mohamed A , Mengistu K , Nzunza RM , Farag NH , Ehrhardt DT , Elfakki E , Mbaeyi C . Open Forum Infect Dis 2020 7 (5) ofaa135 Background: Despite insecurity challenges in Somalia, key indicators for acute flaccid paralysis (AFP) surveillance have met recommended targets. However, recent outbreaks of vaccine-derived polioviruses have raised concerns about possible gaps. We analyzed nonpolio enterovirus (NPEV) and Sabin poliovirus isolation rates to investigate whether comparing these rates can inform about the integrity of stool specimens from inaccessible areas and the likelihood of detecting circulating polioviruses. Methods: Using logistic regression, we analyzed case-based AFP surveillance data for 1348 cases with onset during 2014-2017. We assessed the adjusted impacts of variables including age, accessibility, and Sabin-like virus isolation on NPEV detection. Results: NPEVs were more likely to be isolated from AFP case patients reported from inaccessible areas than accessible areas (23% vs 15%; P = .01). In a multivariable model, inaccessibility and detection of Sabin-like virus were positively associated with NPEV detection (adjusted odds ratio [AOR], 1.75; 95% confidence interval [CI], 1.14-2.65; and AOR, 1.79; 95% CI, 1.07-2.90; respectively), while being aged >/=5 years was negatively associated (AOR, 0.42; 95% CI, 0.20-0.85). Conclusions: Rates of NPEV and Sabin poliovirus detection in inaccessible areas suggest that the integrity of fecal specimens tested for AFP surveillance in Somalia can generate useful AFP data, but uncertainties remain about surveillance system quality. |
CoMPARA: Collaborative Modeling Project for Androgen Receptor Activity.
Mansouri K , Kleinstreuer N , Abdelaziz AM , Alberga D , Alves VM , Andersson PL , Andrade CH , Bai F , Balabin I , Ballabio D , Benfenati E , Bhhatarai B , Boyer S , Chen J , Consonni V , Farag S , Fourches D , Garcia-Sosa AT , Gramatica P , Grisoni F , Grulke CM , Hong H , Horvath D , Hu X , Huang R , Jeliazkova N , Li J , Li X , Liu H , Manganelli S , Mangiatordi GF , Maran U , Marcou G , Martin T , Muratov E , Nguyen DT , Nicolotti O , Nikolov NG , Norinder U , Papa E , Petitjean M , Piir G , Pogodin P , Poroikov V , Qiao X , Richard AM , Roncaglioni A , Ruiz P , Rupakheti C , Sakkiah S , Sangion A , Schramm KW , Selvaraj C , Shah I , Sild S , Sun L , Taboureau O , Tang Y , Tetko IV , Todeschini R , Tong W , Trisciuzzi D , Tropsha A , Van Den Driessche G , Varnek A , Wang Z , Wedebye EB , Williams AJ , Xie H , Zakharov AV , Zheng Z , Judson RS . Environ Health Perspect 2020 128 (2) 27002 ![]() BACKGROUND: Endocrine disrupting chemicals (EDCs) are xenobiotics that mimic the interaction of natural hormones and alter synthesis, transport, or metabolic pathways. The prospect of EDCs causing adverse health effects in humans and wildlife has led to the development of scientific and regulatory approaches for evaluating bioactivity. This need is being addressed using high-throughput screening (HTS) in vitro approaches and computational modeling. OBJECTIVES: In support of the Endocrine Disruptor Screening Program, the U.S. Environmental Protection Agency (EPA) led two worldwide consortiums to virtually screen chemicals for their potential estrogenic and androgenic activities. Here, we describe the Collaborative Modeling Project for Androgen Receptor Activity (CoMPARA) efforts, which follows the steps of the Collaborative Estrogen Receptor Activity Prediction Project (CERAPP). METHODS: The CoMPARA list of screened chemicals built on CERAPP's list of 32,464 chemicals to include additional chemicals of interest, as well as simulated ToxCast metabolites, totaling 55,450 chemical structures. Computational toxicology scientists from 25 international groups contributed 91 predictive models for binding, agonist, and antagonist activity predictions. Models were underpinned by a common training set of 1,746 chemicals compiled from a combined data set of 11 ToxCast/Tox21 HTS in vitro assays. RESULTS: The resulting models were evaluated using curated literature data extracted from different sources. To overcome the limitations of single-model approaches, CoMPARA predictions were combined into consensus models that provided averaged predictive accuracy of approximately 80% for the evaluation set. DISCUSSION: The strengths and limitations of the consensus predictions were discussed with example chemicals; then, the models were implemented into the free and open-source OPERA application to enable screening of new chemicals with a defined applicability domain and accuracy assessment. This implementation was used to screen the entire EPA DSSTox database of approximately 875,000 chemicals, and their predicted AR activities have been made available on the EPA CompTox Chemicals dashboard and National Toxicology Program's Integrated Chemical Environment. https://doi.org/10.1289/EHP5580. |
Diarrhoeal disease and subsequent risk of death in infants and children residing in low-income and middle-income countries: analysis of the GEMS case-control study and 12-month GEMS-1A follow-on study
Levine MM , Nasrin D , Acacio S , Bassat Q , Powell H , Tennant SM , Sow SO , Sur D , Zaidi AKM , Faruque ASG , Hossain MJ , Alonso PL , Breiman RF , O'Reilly CE , Mintz ED , Omore R , Ochieng JB , Oundo JO , Tamboura B , Sanogo D , Onwuchekwa U , Manna B , Ramamurthy T , Kanungo S , Ahmed S , Qureshi S , Quadri F , Hossain A , Das SK , Antonio M , Saha D , Mandomando I , Blackwelder WC , Farag T , Wu Y , Houpt ER , Verweiij JJ , Sommerfelt H , Nataro JP , Robins-Browne RM , Kotloff KL . Lancet Glob Health 2019 8 (2) e204-e214 BACKGROUND: The Global Enteric Multicenter Study (GEMS) was a 3-year case-control study that measured the burden, aetiology, and consequences of moderate-to-severe diarrhoea (MSD) in children aged 0-59 months. GEMS-1A, a 12-month follow-on study, comprised two parallel case-control studies, one assessing MSD and the other less-severe diarrhoea (LSD). In this report, we analyse the risk of death with each diarrhoea type and the specific pathogens associated with fatal outcomes. METHODS: GEMS was a prospective, age-stratified, matched case-control study done at seven sites in Africa and Asia. Children aged 0-59 months with MSD seeking care at sentinel health centres were recruited along with one to three randomly selected matched community control children without diarrhoea. In the 12-month GEMS-1A follow-on study, children with LSD and matched controls, in addition to children with MSD and matched controls, were recruited at six of the seven sites; only cases of MSD and controls were enrolled at the seventh site. We compared risk of death during the period between enrolment and one follow-up household visit done about 60 days later (range 50-90 days) in children with MSD and LSD and in their respective controls. Approximately 50 pathogens were detected using, as appropriate, classic bacteriology, immunoassays, gel-based PCR and reverse transcriptase PCR, and quantitative real-time PCR (qPCR). Specimens from a subset of GEMS cases and controls were also tested by a TaqMan Array Card that compartmentalised probe-based qPCR for 32 enteropathogens. FINDINGS: 223 (2.0%) of 11 108 children with MSD and 43 (0.3%) of 16 369 matched controls died between study enrolment and the follow-up visit at about 60 days (hazard ratio [HR] 8.16, 95% CI 5.69-11.68, p<0.0001). 12 (0.4%) of 2962 children with LSD and seven (0.2%) of 4074 matched controls died during the follow-up period (HR 2.78, 95% CI 0.95-8.11, p=0.061). Risk of death was lower in children with dysenteric MSD than in children with non-dysenteric MSD (HR 0.20, 95% CI 0.05-0.87, p=0.032), and lower in children with LSD than in those with non-dysenteric MSD (HR 0.29, 0.14-0.59, p=0.0006). In children younger than 24 months with MSD, infection with typical enteropathogenic Escherichia coli, enterotoxigenic E coli encoding heat-stable toxin, enteroaggregative E coli, Shigella spp (non-dysentery cases), Aeromonas spp, Cryptosporidium spp, and Entamoeba histolytica increased risk of death. Of 61 deaths in children aged 12-59 months with non-dysenteric MSD, 31 occurred among 942 children qPCR-positive for Shigella spp and 30 deaths occurred in 1384 qPCR-negative children (HR 2.2, 95% CI 1.2-3.9, p=0.0090), showing that Shigella was strongly associated with increased risk of death. INTERPRETATION: Risk of death is increased following MSD and, to a lesser extent, LSD. Considering there are approximately three times more cases of LSD than MSD in the population, more deaths are expected among children with LSD than in those with MSD. Because the major attributable LSD-associated and MSD-associated pathogens are the same, implementing vaccines and rapid diagnosis and treatment interventions against these major pathogens are rational investments. FUNDING: Bill & Melinda Gates Foundation. |
Assessment of in-country capacity to maintain communicable disease surveillance and response services after polio eradication-Somalia
Hsu CH , Harvey B , Mohamed A , Elfakki E , Ehrhardt D , Farag NH . Vaccine 2019 38 (5) 1220-1224 One objective of the 2013-2018 Global Polio Eradication Initiative (GPEI) Strategic Plan was the transition of GPEI polio essential functions to other public health programs [1]. For many developing countries, in addition to polio essential functions, GPEI funding has been supporting integrated communicable disease surveillance and routine immunization programs. As GPEI progresses toward polio eradication, GPEI funding for some polio-free countries is being scaled back. The Somalia Polio Eradication Program, led by international organizations in collaboration with local authorities, is a critical source of immunizations for >2.5 million children. In addition, the polio program has been supporting a range of communicable disease surveillance, basic health services (e.g. routine immunizations) as well as emergency response activities (e.g. outbreak response). To assess current capacities in Somalia, interviews were conducted with representatives of relief organizations and ministries of health (MoHs) from Somaliland, Puntland, and South-Central political zones to elicit their opinions on their agency's capacity to assume public health activities currently supported by GPEI funds. Seventy percent of international and 62% of representatives of domestic relief agencies reported low capacity to conduct communicable disease surveillance without GPEI funds. Responses from MoH representatives for the three zones in Somalia ranged from "very weak" to "strong" regarding capacity to conduct both polio and non-polio related communicable disease surveillance and outbreak response activities. Zones programs are unprepared to provide communicable diseases services if GPEI funding were substantially reduced abruptly. Polio transition planning must strategically plan for shifting of GPEI staffing, operational assets and funding to support identified gaps in Somalia's public health infrastructure. |
Estimating population immunity to poliovirus in Jordan's high-risk areas
Farag NH , Wannemuehler K , Weldon W , Arbaji A , Belbaisi A , Khuri-Bulos N , Ehrhardt D , Surour MR , ElhajQasem NS , Al-Abdallat MM . Hum Vaccin Immunother 2019 16 (3) 548-553 A community-based serosurvey was conducted among children ages 6-59 to assess population immunity in Jordan's high-risk areas following the Middle East polio outbreak response. The survey was a two-stage cluster-quota sample with high risk areas as the primary sampling units. High-risk areas included border and hard-to-reach areas, and areas with a high proportion of refugees, mobile communities and/or low coverage during previous immunization campaigns. Population immunity to poliovirus was high overall. In high-risk areas, Type 1 seroprevalence = 98% (95% CI = 96, 99), Type 2= 98 (95% CI = 96, 99) and Type 3= 96 (95% CI = 94, 98). Seroprevalence was higher in the refugee camps: Type 1 seroprevalence = 99.6 (95% CI = 97.9, 100); Type 2: 99.6 (95% CI = 97.9, 99.9), and Type 3: 100 (95% CI = 100,100). The vigilance that the Jordan Ministry of Health has placed on locating and vaccinating high-risk populations has been successful in maintaining high population immunity and averting polio outbreaks despite the influx of refugees from Syria. |
Water, sanitation, and hygiene characteristics among HIV-positive households participating in the Global Enteric Multicenter Study in Rural Western Kenya, 2008-2012
Schilling KA , Awuor AO , Rajasingham A , Moke F , Omore R , Amollo M , Farag TH , Nasrin D , Nataro JP , Kotloff KL , Levine MM , Ayers T , Laserson K , Blackstock A , Rothenberg R , Stauber CE , Mintz ED , Breiman RF , O'Reilly CE . Am J Trop Med Hyg 2018 99 (4) 905-915 Diarrheal illness, a common occurrence among people living with human immunodeficiency virus (PLHIV), is largely preventable through access to safe drinking water quality, sanitation, and hygiene (WASH) facilities. We examined WASH characteristics among households with and without HIV-positive residents enrolled in the Global Enteric Multicenter Study (GEMS) in rural Western Kenya. Using univariable logistic regression, we examined differences between HIV-positive and HIV-negative households in regard to WASH practices. Among HIV-positive households, we explored the relationship between the length of time knowing their HIV status and GEMS enrollment. No statistically significant differences were apparent in the WASH characteristics among HIV-positive and HIV-negative households. However, we found differences in the WASH characteristics among HIV-positive households who were aware of their HIV status >/= 30 days before enrollment compared with HIV-positive households who found out their status < 30 days before enrollment or thereafter. Significantly more households aware of their HIV-positive status before enrollment reported treating their drinking water (odds ratio [OR] confidence interval [CI]: 2.34 [1.12, 4.86]) and using effective water treatment methods (OR [CI]: 9.6 [3.09, 29.86]), and had better drinking water storage practices. This suggests that within this region of Kenya, HIV programs are effective in promoting the importance of practicing positive WASH-related behaviors among PLHIV. |
Poliovirus immunity among children under five years-old in accessible areas of Afghanistan, 2013
Hsu CH , Wannemuehler KA , Soofi S , Mashal M , Hussain I , Bhutta ZA , McDuffie L , Weldon W , Farag NH . Vaccine 2019 37 (12) 1577-1583 BACKGROUND: Afghanistan remains among the three countries with endemic wild poliovirus transmission, and high population immunity levels are required to interrupt transmission and prevent outbreaks. Surveillance and vaccination of children in Afghanistan have been challenging due to security issues limiting accessibility in certain areas. METHODS: A serosurvey was conducted in 2013 within accessible enumeration areas (EAs) among children aged <5years using samples collected for a national micronutrient assessment survey to assess poliovirus immunity in Afghanistan. Of 21194 total EAs in Afghanistan, 107 were inaccessible and therefore were excluded from the sampling frame. RESULTS: Population immunity was high overall but varied for the poliovirus serotypes, and was lowest for type 3 (95% [95% CI: 93%, 96%]) compared to type 1 (99% [95% CI:97%, 99%]) and type 2 (98% [95% CI:96%, 99%]). The proportion of the population immune to all three types was 93% (95% CI: 91%, 95%), and the proportion seronegative for all three types was 0.5% (95% CI: 0.2%, 1.7%). CONCLUSION: Except for regional differences in immunity to type 3 virus, there were no other apparent differences in seroprevalence by region or by any of the demographic or nutritional characteristics assessed in this study. The study was not powered to provide provincial level seroprevalence estimates, but Paktika Province, in the South region, had the largest proportion of seronegative specimens for type 1 (4 seronegative of 17 serum specimens compared to 14 seronegative of 673 for the remainder of the areas). Among accessible children in Afghanistan, seroprevalence of antibodies to poliovirus was high, with most seroprevalence reported at 95% or greater. Despite high seroprevalence in areas assessed in this study, the continued detection of poliovirus cases in the South and East regions indicate that overall regional vaccination coverage and performance is not sufficient to stop polio transmission. |
Colonization factors among enterotoxigenic Escherichia coli isolates from children with moderate-to-severe diarrhea and from matched controls in the Global Enteric Multicenter Study (GEMS).
Vidal RM , Muhsen K , Tennant SM , Svennerholm AM , Sow SO , Sur D , Zaidi AKM , Faruque ASG , Saha D , Adegbola R , Hossain MJ , Alonso PL , Breiman RF , Bassat Q , Tamboura B , Sanogo D , Onwuchekwa U , Manna B , Ramamurthy T , Kanungo S , Ahmed S , Qureshi S , Quadri F , Hossain A , Das SK , Antonio M , Mandomando I , Nhampossa T , Acacio S , Omore R , Ochieng JB , Oundo JO , Mintz ED , O'Reilly CE , Berkeley LY , Livio S , Panchalingam S , Nasrin D , Farag TH , Wu Y , Sommerfelt H , Robins-Browne RM , Del Canto F , Hazen TH , Rasko DA , Kotloff KL , Nataro JP , Levine MM . PLoS Negl Trop Dis 2019 13 (1) e0007037 ![]() BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) encoding heat-stable enterotoxin (ST) alone or with heat-labile enterotoxin (LT) cause moderate-to-severe diarrhea (MSD) in developing country children. The Global Enteric Multicenter Study (GEMS) identified ETEC encoding ST among the top four enteropathogens. Since the GEMS objective was to provide evidence to guide development and implementation of enteric vaccines and other interventions to diminish diarrheal disease morbidity and mortality, we examined colonization factor (CF) prevalence among ETEC isolates from children age <5 years with MSD and from matched controls in four African and three Asian sites. We also assessed strength of association of specific CFs with MSD. METHODOLOGY/PRINCIPAL FINDINGS: MSD cases enrolled at healthcare facilities over three years and matched controls were tested in a standardized manner for many enteropathogens. To identify ETEC, three E. coli colonies per child were tested by polymerase chain reaction (PCR) to detect genes encoding LT, ST; confirmed ETEC were examined by PCR for major CFs (Colonization Factor Antigen I [CFA/I] or Coli Surface [CS] antigens CS1-CS6) and minor CFs (CS7, CS12, CS13, CS14, CS17, CS18, CS19, CS20, CS21, CS30). ETEC from 806 cases had a single toxin/CF profile in three tested strains per child. Major CFs, components of multiple ETEC vaccine candidates, were detected in 66.0% of LT/ST and ST-only cases and were associated with MSD versus matched controls by conditional logistic regression (p</=0.006); major CFs detected in only 25.0% of LT-only cases weren't associated with MSD. ETEC encoding exclusively CS14, identified among 19.9% of 291 ST-only and 1.5% of 259 LT/ST strains, were associated with MSD (p = 0.0011). No other minor CF exhibited prevalence >/=5% and significant association with MSD. CONCLUSIONS/SIGNIFICANCE: Major CF-based efficacious ETEC vaccines could potentially prevent up to 66% of pediatric MSD cases due to ST-encoding ETEC in developing countries; adding CS14 extends coverage to ~77%. |
Diarrhoea, enteric pathogen detection and nutritional indicators among controls in the Global Enteric Multicenter Study, Kenya site: an opportunity to understand reference populations in case-control studies of diarrhoea
Berendes DM , O'Reilly CE , Kim S , Omore R , Ochieng JB , Ayers T , Fagerli K , Farag TH , Nasrin D , Panchalingam S , Nataro JP , Kotloff KL , Levine MM , Oundo J , Laserson K , Breiman RF , Mintz ED . Epidemiol Infect 2018 147 1-9 Given the challenges in accurately identifying unexposed controls in case-control studies of diarrhoea, we examined diarrhoea incidence, subclinical enteric infections and growth stunting within a reference population in the Global Enteric Multicenter Study, Kenya site. Within 'control' children (0-59 months old without diarrhoea in the 7 days before enrolment, n = 2384), we examined surveys at enrolment and 60-day follow-up, stool at enrolment and a 14-day post-enrolment memory aid for diarrhoea incidence. At enrolment, 19% of controls had 1 enteric pathogen associated with moderate-to-severe diarrhoea ('MSD pathogens') in stool; following enrolment, many reported diarrhoea (27% in 7 days, 39% in 14 days). Controls with and without reported diarrhoea had similar carriage of MSD pathogens at enrolment; however, controls reporting diarrhoea were more likely to report visiting a health facility for diarrhoea (27% vs. 7%) or fever (23% vs. 16%) at follow-up than controls without diarrhoea. Odds of stunting differed by both MSD and 'any' (including non-MSD pathogens) enteric pathogen carriage, but not diarrhoea, suggesting control classification may warrant modification when assessing long-term outcomes. High diarrhoea incidence following enrolment and prevalent carriage of enteric pathogens have implications for sequelae associated with subclinical enteric infections and for design and interpretation of case-control studies examining diarrhoea. |
Poliovirus excretion following vaccination with live poliovirus vaccine in patients with primary immunodeficiency disorders: clinicians' perspectives in the endgame plan for polio eradication
Galal NM , Meshaal S , ElHawary R , Nasr E , Bassiouni L , Ashghar H , Farag NH , Mach O , Burns C , Iber J , Chen Q , ElMarsafy A . BMC Res Notes 2018 11 (1) 717 OBJECTIVE: Primary immunodeficiency (PID) patients are prone to developing viral infections and should not be vaccinated with live vaccines. In such patients, prolonged excretion and viral divergence may occur and they may subsequently act as reservoirs in the community introducing mutated virus and jeopardizing polio eradication. One hundred and thirty PID cases were included for poliovirus detection in stool with assessment of divergence of detected polioviruses from oral polio vaccine (OPV) virus. Clinical presentations of PID patients with detectable poliovirus in stool specimens are described. RESULTS: Six PID patients (4.5%) had detectable vaccine-derived poliovirus (VDPV) excretion in stool specimens; of these, five patients had severe combined immunodeficiency (two with acute flaccid paralysis, one with meningoencephalitis and two without neurological manifestations), and one patient had X-linked agammaglobulinemia (paralysis developed shortly after diagnosis of immunodeficiency). All six case-patients received trivalent OPV. Five case-patients had type 2 immunodeficiency-related vaccine-derived polioviruses (iVDPV2) excretion; one had concomitant excretion of Sabin like type 3 virus and one was identified as iVDPV1 excretor. Surveillance for poliovirus excretion among PID patients is critical as these patients represent a potential source to reseed polioviruses into populations. |
Clinical, environmental, and behavioral characteristics associated with Cryptosporidium infection among children with moderate-to-severe diarrhea in rural western Kenya, 2008-2012: The Global Enteric Multicenter Study (GEMS)
Delahoy MJ , Omore R , Ayers TL , Schilling KA , Blackstock AJ , Ochieng JB , Moke F , Jaron P , Awuor A , Okonji C , Juma J , Farag TH , Nasrin D , Panchalingam S , Nataro JP , Kotloff KL , Levine MM , Oundo J , Roellig DM , Xiao L , Parsons MB , Laserson K , Mintz ED , Breiman RF , O'Reilly CE . PLoS Negl Trop Dis 2018 12 (7) e0006640 BACKGROUND: Cryptosporidium is a leading cause of moderate-to-severe diarrhea (MSD) in young children in Africa. We examined factors associated with Cryptosporidium infection in MSD cases enrolled at the rural western Kenya Global Enteric Multicenter Study (GEMS) site from 2008-2012. METHODOLOGY/PRINCIPAL FINDINGS: At health facility enrollment, stool samples were tested for enteric pathogens and data on clinical, environmental, and behavioral characteristics collected. Each child's health status was recorded at 60-day follow-up. Data were analyzed using logistic regression. Of the 1,778 children with MSD enrolled as cases in the GEMS-Kenya case-control study, 11% had Cryptosporidium detected in stool by enzyme immunoassay; in a genotyped subset, 81% were C. hominis. Among MSD cases, being an infant, having mucus in stool, and having prolonged/persistent duration diarrhea were associated with being Cryptosporidium-positive. Both boiling drinking water and using rainwater as the main drinking water source were protective factors for being Cryptosporidium-positive. At follow-up, Cryptosporidium-positive cases had increased odds of being stunted (adjusted odds ratio [aOR] = 1.65, 95% CI: 1.06-2.57), underweight (aOR = 2.08, 95% CI: 1.34-3.22), or wasted (aOR = 2.04, 95% CI: 1.21-3.43), and had significantly larger negative changes in height- and weight-for-age z-scores from enrollment. CONCLUSIONS/SIGNIFICANCE: Cryptosporidium contributes significantly to diarrheal illness in young children in western Kenya. Advances in point of care detection, prevention/control approaches, effective water treatment technologies, and clinical management options for children with cryptosporidiosis are needed. |
Feasibility of jet injector use during inactivated poliovirus vaccine house-to-house vaccination campaigns
Farag NH , Mansour Z , Torossian L , Said R , Snider CJ , Ehrhardt D . Vaccine 2018 36 4935-4938 BACKGROUND: To attain high coverage during polio vaccination campaigns, an outreach house-to-house strategy is used to administer oral poliovirus vaccine. Administering an injectable vaccine house-to-house requires a skilled work force and increases risks of needle stick injuries. Needle-free injection devices provide a safer alternative to needles and syringes for administering injectable vaccines. We evaluated the feasibility and acceptability of a needle-free injection device to administer injectable poliovirus vaccine during a house-to-house vaccination outreach activity. METHODS: Vaccination teams administered injectable poliovirus vaccine using the Pharmajet(R) needle-free intramuscular jet injector to children ages 6-59months in 766 homes. Data on the feasibility of using the jet injector in an outreach campaign setting and the acceptability of the jet injector by caregivers and vaccinators were collected. RESULTS: A total of 993 injections were administered. Vaccinators faced challenges during device preparation in 16% (n=158) of injections; challenges were related to problems loading the injector and not having a flat surface to use for setup of the injector. Among 32 vaccinators interviewed after the vaccination campaign, the main reported advantage of the device was absence of sharps disposal (91%) while the main reported disadvantage was unacceptability by parents (90%) which was related to the vaccine, not the device. CONCLUSIONS: The needle-free jet injector was feasible for use in house-to-house campaigns. Acceptability by vaccinators was low as 81% stated that the jet injector was not easier to use than needle and syringe. Parental refusal related to frequent polio vaccination campaigns was the biggest challenge. In addition, novelty of the device posed a challenge to teams as they needed to reassure parents about safety of the device. To take full advantage of the ability to take injectable vaccines door-to-door during vaccination campaigns using a needle-free jet injector device, tailored social mobilization efforts are needed ahead of campaigns. |
The effect of costs on Kenyan households' demand for medical care: why time and distance matter
Kukla M , McKay N , Rheingans R , Harman J , Schumacher J , Kotloff KL , Levine MM , Breiman R , Farag T , Walker D , Nasrin D , Omore R , O'Reilly C , Mintz E . Health Policy Plan 2017 32 (10) 1397-1406 In an environment of constrained resources, policymakers must identify solutions for financing and delivering health services that are efficient and sustainable. However, such solutions require that policymakers understand the complex interaction between household utilization patterns, factors influencing household medical decisions, and provider performance. This study examined whether and under what conditions out-of-pocket, transportation, and time costs influenced Kenyan households' choice of medical provider for childhood diarrhoeal illnesses. It compared these decisions with the actual cost and quality of those providers to assess strategies for increasing the utilization of high quality, low-cost primary care. This study analyzed nationally-representative survey data through several multinomial nested logit models. On average, time costs accounted for the greatest share of total costs. Households spent the most time and transportation costs utilizing public care, yet were more likely to incur catastrophic time and out-of-pocket costs seeking private care for their child's diarrhoeal illness. Out-of-pocket, transportation, and time costs influenced households' choice of provider, though demand was cost inelastic and households were most responsive to transportation costs. Poorer households were the most responsive to changes in all cost types and most likely to self-treat or utilize informal care. Many households utilized informal care that, relative to formal care, cost the same but was of worse quality-suggesting that such households were making poor medical decisions for their children. To achieve public policy objectives, such as financial risk protection for childhood illnesses and equitable access to primary care, policymakers could focus on three areas: (1) refine financing strategies for further reducing household out-of-pocket costs; (2) reduce or subsidize time and transportation costs for households seeking public and private care; and (3) increase transparency of costs and quality to improve household decisions. |
Modeling poliovirus transmission in Pakistan and Afghanistan to inform vaccination strategies in undervaccinated subpopulations
Duintjer Tebbens RJ , Pallansch MA , Cochi SL , Ehrhardt DT , Farag NH , Hadler SC , Hampton LM , Martinez M , Wassilak SGF , Thompson KM . Risk Anal 2018 38 (8) 1701-1717 Due to security, access, and programmatic challenges in areas of Pakistan and Afghanistan, both countries continue to sustain indigenous wild poliovirus (WPV) transmission and threaten the success of global polio eradication and oral poliovirus vaccine (OPV) cessation. We fitted an existing differential-equation-based poliovirus transmission and OPV evolution model to Pakistan and Afghanistan using four subpopulations to characterize the well-vaccinated and undervaccinated subpopulations in each country. We explored retrospective and prospective scenarios for using inactivated poliovirus vaccine (IPV) in routine immunization or supplemental immunization activities (SIAs). The undervaccinated subpopulations sustain the circulation of serotype 1 WPV and serotype 2 circulating vaccine-derived poliovirus. We find a moderate impact of past IPV use on polio incidence and population immunity to transmission mainly due to (1) the boosting effect of IPV for individuals with preexisting immunity from a live poliovirus infection and (2) the effect of IPV-only on oropharyngeal transmission for individuals without preexisting immunity from a live poliovirus infection. Future IPV use may similarly yield moderate benefits, particularly if access to undervaccinated subpopulations dramatically improves. However, OPV provides a much greater impact on transmission and the incremental benefit of IPV in addition to OPV remains limited. This study suggests that despite the moderate effect of using IPV in SIAs, using OPV in SIAs remains the most effective means to stop transmission, while limited IPV resources should prioritize IPV use in routine immunization. |
Fractional-dose inactivated poliovirus vaccine campaign - Sindh Province, Pakistan, 2016
Pervaiz A , Mbaeyi C , Baig MA , Burman A , Ahmed JA , Akter S , Jatoi FA , Mahamud A , Asghar RJ , Azam N , Shah MN , Laghari MA , Soomro K , Wadood MZ , Ehrhardt D , Safdar RM , Farag N . MMWR Morb Mortal Wkly Rep 2017 66 (47) 1295-1299 Following the declaration of eradication of wild poliovirus (WPV) type 2 in September 2015, trivalent oral poliovirus vaccine (tOPV) was withdrawn globally to reduce the risk for type 2 vaccine-derived poliovirus (VDPV2) transmission; all countries implemented a synchronized switch to bivalent OPV (type 1 and 3) in April 2016 (1,2). Any isolation of VDPV2 after the switch is to be treated as a potential public health emergency and might indicate the need for supplementary immunization activities (3,4). On August 9, 2016, VDPV2 was isolated from a sewage sample taken from an environmental surveillance site in Hyderabad, Sindh province, Pakistan. Possible vaccination activities in response to VDPV2 isolation include the use of injectable inactivated polio vaccine (IPV), which poses no risk for vaccine-derived poliovirus transmission. Fractional-dose, intradermal IPV (fIPV), one fifth of the standard intramuscular dose, has been developed to more efficiently manage limited IPV supplies. fIPV has been shown in some studies to be noninferior to full-dose IPV (5,6) and was used successfully in response to a similar detection of a single VDPV2 isolate from sewage in India (7). Injectable fIPV was used for response activities in Hyderabad and three neighboring districts. This report describes the findings of an assessment of preparatory activities and subsequent implementation of the fIPV campaign. Despite achieving high coverage (>80%), several operational challenges were noted. The lessons learned from this campaign could help to guide the planning and implementation of future fIPV vaccination activities. |
Animal-related factors associated with moderate-to-severe diarrhea in children younger than five years in western Kenya: A matched case-control study
Conan A , O'Reilly CE , Ogola E , Ochieng JB , Blackstock AJ , Omore R , Ochieng L , Moke F , Parsons MB , Xiao L , Roellig D , Farag TH , Nataro JP , Kotloff KL , Levine MM , Mintz ED , Breiman RF , Cleaveland S , Knobel DL . PLoS Negl Trop Dis 2017 11 (8) e0005795 BACKGROUND: Diarrheal disease remains among the leading causes of global mortality in children younger than 5 years. Exposure to domestic animals may be a risk factor for diarrheal disease. The objectives of this study were to identify animal-related exposures associated with cases of moderate-to-severe diarrhea (MSD) in children in rural western Kenya, and to identify the major zoonotic enteric pathogens present in domestic animals residing in the homesteads of case and control children. METHODOLOGY/PRINCIPAL FINDINGS: We characterized animal-related exposures in a subset of case and control children (n = 73 pairs matched on age, sex and location) with reported animal presence at home enrolled in the Global Enteric Multicenter Study in western Kenya, and analysed these for an association with MSD. We identified potentially zoonotic enteric pathogens in pooled fecal specimens collected from domestic animals resident at children's homesteads. Variables that were associated with decreased risk of MSD were washing hands after animal contact (matched odds ratio [MOR] = 0.2; 95% CI 0.08-0.7), and presence of adult sheep that were not confined in a pen overnight (MOR = 0.1; 0.02-0.5). Variables that were associated with increased risk of MSD were increasing number of sheep owned (MOR = 1.2; 1.0-1.5), frequent observation of fresh rodent excreta (feces/urine) outside the house (MOR = 7.5; 1.5-37.2), and participation of the child in providing water to chickens (MOR = 3.8; 1.2-12.2). Of 691 pooled specimens collected from 2,174 domestic animals, 159 pools (23%) tested positive for one or more potentially zoonotic enteric pathogens (Campylobacter jejuni, C. coli, non-typhoidal Salmonella, diarrheagenic E. coli, Giardia, Cryptosporidium, or rotavirus). We did not find any association between the presence of particular pathogens in household animals, and MSD in children. CONCLUSIONS AND SIGNIFICANCE: Public health agencies should continue to promote frequent hand washing, including after animal contact, to reduce the risk of MSD. Future studies should address specific causal relations of MSD with sheep and chicken husbandry practices, and with the presence of rodents. |
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