Last data update: May 06, 2024. (Total: 46732 publications since 2009)
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Reply to Rasmussen and Ringwald, "Continued Low Efficacy of Artemether-Lumefantrine in Angola?"
Dimbu PR , Horth R , Cândido ALM , Ferreira CM , Caquece F , Garcia LEA , André K , Pembele G , Jandondo D , Bondo BJ , Nieto Andrade B , Labuda S , Ponce de León G , Kelley J , Patel D , Svigel SS , Talundzic E , Lucchi N , Morais JFM , Fortes F , Martins JF , Pluciński MM . Antimicrob Agents Chemother 12/28/2021 65 (6) We thank Rasmussen and Ringwald for further highlighting the importance of routine monitoring of antimalarial drug efficacy in sub-Saharan Africa, including Angola (1). Longitudinal monitoring is critical to identify potential new, persistent, and/or expanding foci of parasite resistance to available drugs. In 3 of the last 4 rounds, artemether-lumefantrine (AL) was estimated to have an efficacy of <90% at one of the three sentinel sites in Angola. To our knowledge, in sub-Saharan Africa, only Angola and Burkina Faso (2) have shown AL efficacy of <90% across multiple therapeutic efficacy study (TES) rounds. Thus, we chose a title to highlight this persistent concern. | | We concur that the significance of the high rates of day 2 slide positivity in Lunda Sul Province is not fully known, and as pointed out, there may be various explanations for this finding. Measuring drug levels is resource intensive and not feasible every year, but this could help rule out underdosing in future studies. However, we believe our study procedures, as described in this and previous studies, are robust and thus make systematic underdosing unlikely. We have always strictly adhered to WHO guidelines, including hemoglobin criteria and analysis of day 1 severe cases, to inform our classifications. |
Therapeutic response to four artemisinin-based combination therapies in Angola, 2021
Dimbu PR , Labuda S , Ferreira CM , Caquece F , André K , Pembele G , Pode D , João MF , Pelenda VM , Nieto Andrade B , Horton B , Kennedy C , Svigel SS , Zhou Z , Morais JFM , Rosário Jd , Fortes F , Martins JF , Plucinski MM . Antimicrob Agents Chemother 2024 e0152523 Monitoring antimalarial efficacy is important to detect the emergence of parasite drug resistance. Angola conducts in vivo therapeutic efficacy studies (TESs) every 2 years in its fixed sentinel sites in Benguela, Lunda Sul, and Zaire provinces. Children with uncomplicated Plasmodium falciparum malaria were treated with artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), dihydroartemisinin-piperaquine (DP), or artesunate-pyronaridine (ASPY) and followed for 28 (AL and ASAQ) or 42 days (DP and ASPY) to assess clinical and parasitological response to treatment. Two drugs were sequentially assessed in each site in February-July 2021. The primary indicator was the Kaplan-Meier estimate of the PCR-corrected efficacy at the end of the follow-up period. A total of 622 patients were enrolled in the study and 590 (95%) participants reached a study endpoint. By day 3, ≥98% of participants were slide-negative in all study sites and arms. After PCR correction, day 28 AL efficacy was 88.0% (95% CI: 82%-95%) in Zaire and 94.7% (95% CI: 90%-99%) in Lunda Sul. For ASAQ, day 28 efficacy was 92.0% (95% CI: 87%-98%) in Zaire and 100% in Lunda Sul. Corrected day 42 efficacy was 99.6% (95% CI: 99%-100%) for ASPY and 98.3% (95% CI: 96%-100%) for DP in Benguela. High day 3 clearance rates suggest no clinical evidence of artemisinin resistance. This was the fourth of five rounds of TES in Angola showing a corrected AL efficacy <90% in a site. For Zaire, AL has had an efficacy <90% in 2013, 2015, and 2021. ASAQ, DP, and ASPY are appropriate choices as artemisinin-based combination therapies in Angola. |
Genetics and genomics for the prevention and treatment of cardiovascular disease: update: a scientific statement from the American Heart Association.
Ganesh SK , Arnett DK , Assimes TL , Basson CT , Chakravarti A , Ellinor PT , Engler MB , Goldmuntz E , Herrington DM , Hershberger RE , Hong Y , Johnson JA , Kittner SJ , McDermott DA , Meschia JF , Mestroni L , O'Donnell CJ , Psaty BM , Vasan RS , Ruel M , Shen WK , Terzic A , Waldman SA . Circulation 2013 128 (25) 2813-51 Cardiovascular diseases (CVDs) are a major source of morbidity and mortality worldwide. Despite a decline of ≈30% over the past decade, heart disease remains the leading killer of Americans.1 For rare and familial forms of CVD, we are increasingly recognizing single-gene mutations that impart relatively large effects on individual phenotype. Examples include inherited forms of cardiomyopathy, arrhythmias, and aortic diseases. However, the prevalence of monogenic disorders typically accounts for a small proportion of the total CVD observed in the population. CVDs in the general population are complex diseases, with several contributing genetic and environmental factors. Although recent progress in monogenic disorders has occurred, we have seen a period of intense investigation to identify the genetic architecture of more common forms of CVD and related traits. | | Genomics serves several roles in cardiovascular health and disease, including disease prediction, discovery of genetic loci influencing CVD, functional evaluation of these genetic loci to understand mechanisms, and identification of therapeutic targets. For single-gene CVDs, progress has led to several clinically useful diagnostic tests, extending our ability to inform the management of afflicted patients and their family members. However, there has been little progress in developing genetic testing for complex CVD because individual common variants have only a modest impact on risk. The study of the genomics of complex CVDs is further challenged by the influence of environmental variables, phenotypic heterogeneity, and pathogenic complexity. Characterization of the clinical phenotype requires consideration of the clinical details of the diseases and traits under study. |
Diversity of rotavirus strains circulating in Haiti before and after introduction of monovalent vaccine.
Lucien MAB , Esona MD , Pierre M , Joseph G , Rivire C , Leshem E , Aliabadi N , Desormeaux AM , Andre-Alboth J , Fitter DL , Grant-Greene Y , Tate J , Boncy J , Patel R , Burnett E , Juin S , Parashar UD , Bowen MD . IJID Reg 2022 4 146-151 BACKGROUND: Haiti introduced a monovalent human group A rotavirus (RVA) vaccine (Rotarix) into its routine infant immunization program in April 2014. The goal of the surveillance program was to characterize RVA strains circulating in Haiti before and after RVA vaccine introduction. METHODS: Stool samples were collected from children <5 years old presenting with acute gastroenteritis at 16 hospitals in Haiti. RVA antigen enzyme immunoassay (EIA) testing was performed, and G and P genotypes were determined for positive specimens. In this study, genotype data for samples collected from May 2012 through April 2014 (the pre-vaccine introduction era) and May 2014 through July 2019 (post-vaccine introduction era) were analyzed. RESULTS: A total of 809 specimens were tested by the Centers for Disease Control and Prevention. During the pre-vaccine introduction era (May 2012 through April 2014), G12P[8] was the predominant genotype, detected in 88-94% of specimens. There was a high prevalence of the equine-like G3P[8] genotype among Haitian children with RVA after vaccine introduction. CONCLUSIONS: The predominance of equine-like G3P[8] in three of five RVA seasons post-vaccine introduction suggests possible vaccine-specific selection pressure in Haiti. These temporal variations in RVA genotype predominance will require continued monitoring in Haiti as the vaccination program continues. |
The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: a genotypic analysis
Walker TM , Fowler PW , Knaggs J , Hunt M , Peto TE , Walker AS , Crook DW , Walker TM , Miotto P , Cirillo DM , Kser CU , Knaggs J , Iqbal Z , Hunt M , Chindelevitch L , Farhat MR , Comas I , Comas I , Posey J , Omar SV , Peto TE , Walker AS , Crook DW , Suresh A , Uplekar S , Laurent S , Colman RE , Rodwell TC , Nathanson CM , Zignol M , Ismail N , Rodwell TC , Walker AS , Steyn AJC , Lalvani A , Baulard A , Christoffels A , Mendoza-Ticona A , Trovato A , Skrahina A , Lachapelle AS , Brankin A , Piatek A , GibertoniCruz A , Koch A , Cabibbe AM , Spitaleri A , Brandao AP , Chaiprasert A , Suresh A , Barbova A , VanRie A , Ghodousi A , Bainomugisa A , Mandal A , Roohi A , Javid B , Zhu B , Letcher B , Rodrigues C , Nimmo C , Nathanson CM , Duncan C , Coulter C , Utpatel C , Liu C , Grazian C , Kong C , Kser CU , Wilson DJ , Cirillo DM , Matias D , Jorgensen D , Zimenkov D , Chetty D , Moore DA , Clifton DA , Crook DW , vanSoolingen D , Liu D , Kohlerschmidt D , Barreira D , Ngcamu D , SantosLazaro ED , Kelly E , Borroni E , Roycroft E , Andre E , Bttger EC , Robinson E , Menardo F , Mendes FF , Jamieson FB , Coll F , Gao GF , Kasule GW , Rossolini GM , Rodger G , Smith EG , Meintjes G , Thwaites G , Hoffmann H , Albert H , Cox H , Laurenson IF , Comas I , Arandjelovic I , Barilar I , Robledo J , Millard J , Johnston J , Posey J , Andrews JR , Knaggs J , Gardy J , Guthrie J , Taylor J , Werngren J , Metcalfe J , Coronel J , Shea J , Carter J , Pinhata JM , Kus JV , Todt K , Holt K , Nilgiriwala KS , Ghisi KT , Malone KM , Faksri K , Musser KA , Joseph L , Rigouts L , Chindelevitch L , Jarrett L , Grandjean L , Ferrazoli L , Rodrigues M , Farhat M , Schito M , Fitzgibbon MM , Loemb MM , Wijkander M , Ballif M , Rabodoarivelo MS , Mihalic M , Wilcox M , Hunt M , Zignol M , Merker M , Egger M , O'Donnell M , Caws M , Wu MH , Whitfield MG , Inouye M , Mansj M , DangThi MH , Joloba M , Kamal SM , Okozi N , Ismail N , Mistry N , Hoang NN , Rakotosamimanana N , Paton NI , Rancoita PMV , Miotto P , Lapierre P , Hall PJ , Tang P , Claxton P , Wintringer P , Keller PM , Thai PVK , Fowler PW , Supply P , Srilohasin P , Suriyaphol P , Rathod P , Kambli P , Groenheit R , Colman RE , Ong RTH , Warren RM , Wilkinson RJ , Diel R , Oliveira RS , Khot R , Jou R , Tahseen S , Laurent S , Gharbia S , Kouchaki S , Shah S , Plesnik S , Earle SG , Dunstan S , Hoosdally SJ , Mitarai S , Gagneux S , Omar SV , Yao SY , GrandjeanLapierre S , Battaglia S , Niemann S , Pandey S , Uplekar S , Halse TA , Cohen T , Cortes T , Prammananan T , Kohl TA , Thuong NTT , Teo TY , Peto TEA , Rodwell TC , William T , Walker TM , Rogers TR , Surve U , Mathys V , Furi V , Cook V , Vijay S , Escuyer V , Dreyer V , Sintchenko V , Saphonn V , Solano W , Lin WH , vanGemert W , He W , Yang Y , Zhao Y , Qin Y , Xiao YX , Hasan Z , Iqbal Z , Puyen ZM , CryPticConsortium theSeq , Treat Consortium . Lancet Microbe 2022 3 (4) e265-e273 Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (73%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (07%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (914%), moxifloxacin (916%) and ethambutol (933%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation. 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license |
Effectiveness of monovalent rotavirus vaccine against hospitalizations due to all rotavirus and equine-like G3P[8] genotypes in Haiti 2014-2019.
Burnett E , Juin S , Esona MD , Desormeaux AM , Aliabadi N , Pierre M , Andre-Alboth J , Leshem E , Etheart MD , Patel R , Dely P , Fitter D , Jean-Denis G , Kalou M , Katz MA , Bowen MD , Grant-Greene Y , Boncy J , Parashar UD , Joseph GA , Tate JE . Vaccine 2021 39 (32) 4458-4462 BACKGROUND: Rotavirus vaccines are effective in preventing severe rotavirus. Haiti introduced 2-dose monovalent (G1P[8]) rotavirus vaccine recommended for infants at 6 and 10 weeks of age in 2014. We calculated the effectiveness of rotavirus vaccine against hospitalization for acute gastroenteritis in Haiti. METHODS: We enrolled children 6-59 months old admitted May 2014-September 2019 for acute watery diarrhea at any sentinel surveillance hospital. Stool was tested for rotavirus using enzyme immunoassay (EIA) and genotyped with multiplex one-step RT-PCR assay and Sanger sequencing for stratification by genotype. We used a case-negative design where cases were children positive for rotavirus and controls were negative for rotavirus. Only children eligible for vaccination were included and a child was considered vaccinated if vaccine was given ≥ 14 days before enrollment. We used unconditional logistic regression to calculate odds ratios and calculated 2-dose and 1-dose vaccine effectiveness (VE) as (1 - odds ratio) * 100. RESULTS: We included 129 (19%) positive cases and 543 (81%) negative controls. Among cases, 77 (60%) were positive for equine-like G3P[8]. Two doses of rotavirus vaccine were 66% (95% CI: 44, 80) effective against hospitalizations due to any strain of rotavirus and 64% (95% CI: 33, 81) effective against hospitalizations due to the equine-like G3P[8] genotype. CONCLUSIONS: These findings are comparable to other countries in the Americas region. To the best of our knowledge, this is the first VE estimate both against the equine-like G3P[8] genotype and from a Caribbean country. Overall, these results support rotavirus vaccine use and demonstrate the importance of complete vaccination. |
Yersinia enterocolitica Outbreak Associated with Pasteurized Milk
Gruber JF , Morris S , Warren KA , Kline KE , Schroeder B , Dettinger L , Husband B , Pollard K , Davis C , Miller J , Weltman A , Mattioli M , Ray L , Tarr C , Longenberger AH . Foodborne Pathog Dis 2021 18 (7) 448-454 In July 2019, we investigated a cluster of Yersinia enterocolitica cases affecting a youth summer camp and nearby community in northeastern Pennsylvania. After initial telephone interviews with camp owners and community members, we identified pasteurized milk from a small dairy conducting on-site pasteurization, Dairy A, as a shared exposure. We conducted site visits at the camp and Dairy A where we collected milk and other samples. Samples were cultured for Y. enterocolitica. Clinical and nonclinical isolates were compared using molecular subtyping. We performed case finding, conducted telephone interviews for community cases, and conducted a cohort study among adult camp staff by administering an online questionnaire. In total, we identified 109 Y. enterocolitica cases. Consumption of Dairy A milk was known for 37 (34%); of these, Dairy A milk was consumed by 31 (84%). Dairy A had shipped 214 gallons of pasteurized milk in 5 weekly shipments to the camp by mid-July. Dairy A milk was the only shared exposure identified between the camp and community. Y. enterocolitica was isolated from Dairy A unpasteurized milk samples. Five clinical isolates from camp members, two clinical isolates from community members, and nine isolates from unpasteurized milk were indistinguishable by whole-genome sequencing. The risk for yersinosis among camp staff who drank Dairy A milk was 5.3 times the risk for those who did not (95% confidence interval: 1.6-17.3). Because Dairy A only sold pasteurized milk, pasteurized milk was considered the outbreak source. We recommend governmental agencies and small dairies conducting on-site pasteurization collaborate to develop outbreak prevention strategies. |
Intensity and mechanisms of deltamethrin and permethrin resistance in Anopheles gambiae s.l. populations in southern Benin.
Sagbohan HW , Kpanou CD , Osse R , Dagnon F , Padonou GG , Sominahouin AA , Salako AS , Sidick A , Sewade W , Akinro B , Ahmed S , Impoinvil D , Agbangla C , Akogbeto M . Parasit Vectors 2021 14 (1) 202 BACKGROUND: Insecticide resistance is threatening the effectiveness of efforts to control malaria vectors in Benin. This study explores the levels and mechanisms of insecticide resistance in An. gambiae s.l. to pyrethroids. METHODS: Larvae were collected from August 2017 to July 2018 in five communes in southern Benin (Adjohoun, Allada, Bohicon, Cotonou, and Porto-Novo) representing diverse ecological regions, and were reared in Benin's insectary. Two- to five-day-old female mosquitoes from each district were exposed to multiple doses of deltamethrin and permethrin (1×, 2×, 5×, and 10×) using the WHO insecticide resistance intensity bioassay. The effect of pre-exposure to the synergist, piperonyl butoxide (PBO), was also tested at different pyrethroid doses. Molecular allele frequencies of kdr (1014F) and ace-1R (119S) insecticide resistance mutations and levels of detoxification enzymes were determined for mosquitoes sampled from each study area. RESULTS: An. gambiae s.l. were resistant to pyrethroid-only exposure up to 10× the diagnostic doses in all the study sites for both deltamethrin and permethrin. Mortality was significantly higher in An. gambiae s.l. pre-exposed to PBO followed by exposure to deltamethrin or permethrin compared to mosquitoes exposed to deltamethrin or permethrin only (p < 0.001). The difference in mortality between deltamethrin only and PBO plus deltamethrin was the smallest in Cotonou (16-64%) and the greatest in Bohicon (12-93%). The mortality difference between permethrin only and PBO plus permethrin was the smallest in Cotonou (44-75%) and the greatest in Bohicon (22-72%). In all the study sites, the kdr resistance allele (1014F) frequency was high (75-100%), while the ace-1 resistance allele (G119S) frequency was low (0-3%). Analysis of the metabolic enzymatic activity of An. gambiae s.l. showed overexpression of nonspecific esterases and glutathione S-transferases (GST) in all study sites. In contrast to the PBO results, oxidase expression was low and was similar to the susceptible An. gambiae s.s. Kisumu strain in all sites. CONCLUSION: There is high-intensity resistance to pyrethroids in southern Benin. However, pre-exposure to PBO significantly increased susceptibility to the pyrethroids in the different An. gambiae s.l. populations sampled. The use of PBO insecticide-treated bed nets may help maintain the gains in An. gambiae (s.l.) control in southern Benin. |
Social distancing policies in 22 African countries during the COVID-19 pandemic: a desk review.
Verani A , Clodfelter C , Menon AN , Chevinsky J , Victory K , Hakim A . Pan Afr Med J 2020 37 46 INTRODUCTION: on January 30, 2020, the World Health Organization declared the novel coronavirus outbreak a Public Health Emergency of International Concern. As of October 5, 2020, there were over 34.8 million reported cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and more than 1 million reported deaths from coronavirus disease 2019 (COVID-19), globally. Non-pharmaceutical interventions, such as social distancing policies, hand hygiene, and mask use, are key public health measures to control COVID-19. In response to, or in some cases even before, the first wave of SARS-CoV-2 infections were reported in their countries, policy makers across Africa issued various social distancing policies. METHODS: we describe social distancing policies issued from March 1 to April 24, 2020 in 22 Anglophone countries of sub-Saharan Africa. We reviewed policies identified online. RESULTS: though all 22 countries closed schools and banned gatherings, they took a variety of approaches to sizes of gatherings banned and to stay-at-home orders, with 13 countries issuing national stay-at-home orders, four issuing subnational stay-at-home orders, and five not issuing stay-at-home orders. Enforcement provisions varied by country, as did funeral and health care exceptions. CONCLUSION: movement restrictions, business restrictions, and school closures can have substantial negative impacts on economies, education, nutrition, and routine health care. Yet easing or lifting of COVID-19 social distancing policies can lead to increased transmission. Our review documents a wide variety of policy alternatives used in Africa and can inform future adjustments as countries ease, lift, and reapply measures in response to their evolving epidemics. |
Susceptibility of Anopheles gambiae from Cte d'Ivoire to insecticides used on insecticide-treated nets: evaluating the additional entomological impact of piperonyl butoxide and chlorfenapyr
Kouassi BL , Edi C , Tia E , Konan LY , Akré MA , Koffi AA , Ouattara AF , Tanoh AM , Zinzindohoue P , Kouadio B , Andre M , Irish SR , Armistead J , Dengela D , Cissé NG , Flatley C , Chabi J . Malar J 2020 19 (1) 454 BACKGROUND: Pyrethroid-treated mosquito nets are currently the mainstay of vector control in Côte d'Ivoire. However, resistance to pyrethroids has been reported across the country, limiting options for insecticide resistance management due to the paucity of alternative insecticides. Two types of insecticide-treated nets (ITNs), ITNs with pyrethroids and the synergist piperonyl butoxide (PBO), and Interceptor®G2 nets, a net treated with a combination of chlorfenapyr and alpha-cypermethrin, are believed to help in the control of pyrethroid-resistant mosquitoes. METHODS: The susceptibility of Anopheles gambiae sensu lato (s.l.) to pyrethroid insecticides with and without pre-exposure to PBO as well as to chlorfenapyr was investigated in fifteen sites across the country. Susceptibility tests were conducted on 2- to 4-day old adult female An. gambiae s.l. reared from larval collections. The resistance status, intensity, and effects of PBO on mortality after exposure to different concentrations of deltamethrin, permethrin and alpha-cypermethrin were determined using WHO susceptibility test kits. In the absence of a WHO-recommended standard protocol for chlorfenapyr, two interim doses (100 and 200 µg/bottle) were used to test the susceptibility of mosquitoes using the CDC bottle assay method. RESULTS: Pre-exposure to PBO did not result in full restoration of susceptibility to any of the three pyrethroids for the An. gambiae s.l. populations from any of the sites surveyed. However, PBO pre-exposure did increase mortality for all three pyrethroids, particularly deltamethrin (from 4.4 to 48.9%). Anopheles gambiae s.l. from only one site (Bettie) were susceptible to chlorfenapyr at the dose of 100 µg active ingredient (a.i.)/bottle. At the dose of 200 µg (a.i.)/bottle, susceptibility was only recorded in 10 of the 15 sites. CONCLUSION: Low mosquito mortality was found for pyrethroids alone, and while PBO increased mortality, it did not restore full susceptibility. The vector was not fully susceptible to chlorfenapyr in one third of the sites tested. However, vector susceptibility to chlorfenapyr seems to be considerably higher than for pyrethroids alone or with PBO. These data should be used cautiously when making ITN procurement decisions, noting that bioassays are conducted in controlled conditions and may not fully represent field efficacy where the host-seeking behaviours, which include free-flying activity are known to enhance pro-insecticide chlorfenapyr intoxication to mosquitoes. |
Identifying septic pollution exposure routes during a waterborne norovirus outbreak - A new application for human-associated microbial source tracking qPCR.
Mattioli MC , Benedict KM , Murphy J , Kahler A , Kline KE , Longenberger A , Mitchell PK , Watkins S , Berger P , Shanks OC , Barrett CE , Barclay L , Hall AJ , Hill V , Weltman A . J Microbiol Methods 2020 180 106091 In June 2017, the Pennsylvania Department of Health (PADOH) was notified of multiple norovirus outbreaks associated with 179 ill individuals who attended separate events held at an outdoor venue and campground over a month period. Epidemiologic investigations were unable to identify a single exposure route and therefore unable to determine whether there was a persistent contamination source to target for exposure mitigation. Norovirus was detected in a fresh recreational water designated swimming area and a drinking water well. A hydrogeological site evaluation suggested a nearby septic leach field as a potential contamination source via ground water infiltration. Geological characterization revealed a steep dip of the bedrock beneath the septic leach field toward the well, providing a viral transport pathway in a geologic medium not previously documented as high risk for viral ground water contamination. The human-associated microbial source tracking (MST) genetic marker, HF183, was used as a microbial tracer to demonstrate the hydrogeological connection between the malfunctioning septic system, drinking water well, and recreational water area. Based on environmental investigation findings, venue management and local public health officials implemented a series of outbreak prevention strategies including discontinuing the use of the contaminated well, issuing a permit for a new drinking water well, increasing portable toilet and handwashing station availability, and promoting proper hand hygiene. Despite the outbreaks at the venue and evidence of ground water contamination impacting nearby recreational water and the drinking water well, no new norovirus cases were reported during a large event one week after implementing prevention practices. This investigation highlights a new application for human-associated MST methods to trace hydrological connections between multiple fecal pollutant exposure routes in an outbreak scenario. In turn, pollutant source information can be used to develop effective intervention practices to mitigate exposure and prevent future outbreaks associated with human fecal contaminated waters. |
Risk Assessment and Management of COVID-19 Among Travelers Arriving at Designated U.S. Airports, January 17-September 13, 2020.
Dollard P , Griffin I , Berro A , Cohen NJ , Singler K , Haber Y , de la Motte Hurst C , Stolp A , Atti S , Hausman L , Shockey CE , Roohi S , Brown CM , Rotz LD , Cetron MS , Alvarado-Ramy F . MMWR Morb Mortal Wkly Rep 2020 69 (45) 1681-1685 In January 2020, with support from the U.S. Department of Homeland Security (DHS), CDC instituted an enhanced entry risk assessment and management (screening) program for air passengers arriving from certain countries with widespread, sustained transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). The objectives of the screening program were to reduce the importation of COVID-19 cases into the United States and slow subsequent spread within states. Screening aimed to identify travelers with COVID-19-like illness or who had a known exposure to a person with COVID-19 and separate them from others. Screening also aimed to inform all screened travelers about self-monitoring and other recommendations to prevent disease spread and obtain their contact information to share with public health authorities in destination states. CDC delegated postarrival management of crew members to airline occupational health programs by issuing joint guidance with the Federal Aviation Administration.* During January 17-September 13, 2020, a total of 766,044 travelers were screened, 298 (0.04%) of whom met criteria for public health assessment; 35 (0.005%) were tested for SARS-CoV-2, and nine (0.001%) had a positive test result. CDC shared contact information with states for approximately 68% of screened travelers because of data collection challenges and some states' opting out of receiving data. The low case detection rate of this resource-intensive program highlighted the need for fundamental change in the U.S. border health strategy. Because SARS-CoV-2 infection and transmission can occur in the absence of symptoms and because the symptoms of COVID-19 are nonspecific, symptom-based screening programs are ineffective for case detection. Since the screening program ended on September 14, 2020, efforts to reduce COVID-19 importation have focused on enhancing communications with travelers to promote recommended preventive measures, reinforcing mechanisms to refer overtly ill travelers to CDC, and enhancing public health response capacity at ports of entry. More efficient collection of contact information for international air passengers before arrival and real-time transfer of data to U.S. health departments would facilitate timely postarrival public health management, including contact tracing, when indicated. Incorporating health attestations, predeparture and postarrival testing, and a period of limited movement after higher-risk travel, might reduce risk for transmission during travel and translocation of SARS-CoV-2 between geographic areas and help guide more individualized postarrival recommendations. |
Continued low efficacy of artemether-lumefantrine in Angola, 2019.
Dimbu PR , Horth R , Cândido ALM , Ferreira CM , Caquece F , Garcia LEA , André K , Pembele G , Jandondo D , Bondo BJ , Nieto Andrade B , Labuda S , Ponce de León G , Kelley J , Patel D , Svigel SS , Talundzic E , Lucchi N , Morais JFM , Fortes F , Martins JF , Pluciński MM . Antimicrob Agents Chemother 2020 65 (2) BACKGROUND: Biennial therapeutic efficacy monitoring is a crucial activity for ensuring efficacy of currently used artemisinin-based combination therapy in Angola. METHODS: Children with acute uncomplicated P. falciparum infection in sentinel sites in Benguela, Zaire, and Lunda Sul Provinces were treated with artemether-lumefantrine (AL) or artesunate amodiaquine (ASAQ) and followed for 28 days to assess clinical and parasitological response. Molecular correction was performed using seven microsatellite markers. Samples from treatment failures were genotyped for the pfk13, pfcrt, and pfmdr1 genes. RESULTS: Day 3 clearance rates were ≥95% in all arms. Uncorrected Day-28 Kaplan-Meier efficacy estimates ranged from 84.2 to 90.1% for the AL arms, and 84.7 to 100% for the ASAQ arms. Corrected Day-28 estimates were 87.6% (95% Confidence interval [CI]: 81-95%) for the AL arm in Lunda Sul, 92.2% (95%CI: 87-98%) for AL in Zaire, 95.6% (95%CI: 91-100%) for ASAQ in Zaire, 98.4% (95%CI: 96-100%) for AL in Benguela, and 100% for ASAQ in Benguela and Lunda Sul. All 103 analyzed samples had wildtype pfk13 sequences. The 76T pfcrt allele was found in most (92%, 11/12) ASAQ late failure samples but only 16% (4/25) of AL failure samples. The N86 pfmdr1 allele was found in 97% (34/35) of treatment failures. CONCLUSION: AL efficacy in Lunda Sul was below the 90% World Health Organization threshold, the third time in four rounds that this threshold was crossed for an AL arm in Angola. In contrast, observed ASAQ efficacy has not been below 95% to date in Angola, including this latest round. |
STROBE-metagenomics: a STROBE extension statement to guide the reporting of metagenomics studies.
Bharucha T , Oeser C , Balloux F , Brown JR , Carbo EC , Charlett A , Chiu CY , Claas ECJ , de Goffau MC , de Vries JJC , Eloit M , Hopkins S , Huggett JF , MacCannell D , Morfopoulou S , Nath A , O'Sullivan DM , Reoma LB , Shaw LP , Sidorov I , Simner PJ , Van Tan L , Thomson EC , van Dorp L , Wilson MR , Breuer J , Field N . Lancet Infect Dis 2020 20 (10) e251-e260 The term metagenomics refers to the use of sequencing methods to simultaneously identify genomic material from all organisms present in a sample, with the advantage of greater taxonomic resolution than culture or other methods. Applications include pathogen detection and discovery, species characterisation, antimicrobial resistance detection, virulence profiling, and study of the microbiome and microecological factors affecting health. However, metagenomics involves complex and multistep processes and there are important technical and methodological challenges that require careful consideration to support valid inference. We co-ordinated a multidisciplinary, international expert group to establish reporting guidelines that address specimen processing, nucleic acid extraction, sequencing platforms, bioinformatics considerations, quality assurance, limits of detection, power and sample size, confirmatory testing, causality criteria, cost, and ethical issues. The guidance recognises that metagenomics research requires pragmatism and caution in interpretation, and that this field is rapidly evolving. |
Seroprevalence of measles, rubella, tetanus, and diphtheria antibodies among children in Haiti, 2017
Minta AA , Andre-Alboth J , Childs L , Nace D , Rey-Benito G , Boncy J , Adrien P , Francois J , Phaimyr Jn Charles N , Blot V , Vanden Eng J , Priest JW , Rogier E , Tohme RA . Am J Trop Med Hyg 2020 103 (4) 1717-1725 In Haiti, measles, rubella, and maternal and neonatal tetanus have been eliminated, but a diphtheria outbreak is ongoing as of 2019. We conducted a national representative, household-based, two-stage cluster survey among children aged 5-7 years in 2017 to assess progress toward maintenance of control and elimination of selected vaccine-preventable diseases (VPDs). We stratified Haiti into west region (west department, including the capital city) and non-west region (all other departments). We obtained vaccination history and dried blood spots, and measured antibody concentrations to VPDs on a multiplex bead assay. Among 1,146 children, national seropositivity was 83% (95% CI: 80-86%) for tetanus, 83% (95% CI: 81-85%) for diphtheria, 87% (95% CI: 85-89%) for measles, and 84% (95% CI: 81-87%) for rubella. None of the children had long-term immunity to tetanus or diphtheria (IgG concentration >/= 1 international unit/mL). Seropositivity in the west region was lower than that in the non-west region. Vaccination coverage was 68% (95% CI: 61-74%) for >/= 3 doses of tetanus- and diphtheria-containing vaccine (DTP3), 84% (95% CI: 80-87%) for one dose of measles-rubella (MR1) vaccine, and 20% (95% CI: 16-24%) for MR2. The seroprevalence of measles, rubella, and diphtheria antibodies is lower than population immunity levels needed to prevent disease transmission, particularly in the west region; reintroduction of these diseases could lead to an outbreak. To maintain VPD control and elimination, Haiti should achieve DTP3 and MR2 coverage >/= 95%, and include tetanus and diphtheria booster doses in the routine immunization schedule. |
Serum elimination half-lives adjusted for ongoing exposure of tri-to hexabrominated diphenyl ethers: Determined in persons moving from North America to Australia.
Sjodin A , Mueller JF , Jones R , Schutze A , Wong LY , Caudill SP , Harden FA , Webster TF , Toms LM . Chemosphere 2020 248 125905 The objective of the study was to determine the human serum elimination half-life of polybrominated diphenyl ethers (PBDEs) adjusted for ongoing exposure in subjects moving from a higher exposure region (North America) to a lower exposure region (Australia). The study population was comprised of exchange students and long-term visitors from North America moving to Brisbane, Australia (N = 27) and local residents (N = 23) who were followed by repeated serum sampling every other month. The local residents were sampled to adjust for ongoing exposure in Australia. Only one visitor remained in Australia for a period of time similar to the elimination half-life and had a sufficiently high initial concentration of PBDEs to derive a half-life. This visitor arrived in Australia in March of 2011 and remained in the country for 1.5 years. Since the magnitude of PBDE exposure is lower in Australia than in North America we observed an apparent 1st order elimination curve over time from which we have estimated the serum elimination half-lives for BDE28, BDE47, BDE99, BDE100, and BDE153 to be 0.942, 1.19, 1.03, 2.16, and 4.12 years, respectively. Uncertainty in the estimates were estimated using a Monte Carlo simulation. The human serum elimination half-life adjusted for ongoing exposure can allow us to assess the effectiveness and reduction in exposure in the general population following phase out of commercial penta- and octaBDE in 2004 in the United States. |
Identification and Characterization of Shigella with Decreased Susceptibility to Azithromycin in the United States, 2005 to 2014.
Campbell D , Bowen A , Bhatnagar A , McCullough A , Grass J , Chen J , Folster JP . J Glob Antimicrob Resist 2019 21 417-419 OBJECTIVES: To identify Shigella isolates in the U.S. with decreased susceptibility to azithromycin (DSA) and characterized the genetic mechanisms responsible for this resistance. METHODS: The National Antimicrobial Resistance Monitoring System (NARMS) at Centers for Disease Control and Prevention (CDC) collects and conducts broth microdilution antimicrobial susceptibility testing on Shigella to determine minimum inhibitory concentrations (MIC) for up to 15 drugs, including azithromycin. Isolates with decreased susceptibility to azithromycin were subjected to molecular methods (PCR, whole genome sequencing, and plasmid typing/transformation) to identify the genetic mechanisms of resistance. RESULTS: A total of 118 isolates with decreased susceptibility to azithromycin were tested; 65 (55%) isolates contained only mphA, one (<1%) isolate contained only ermB, and 51 (43%) isolates contained both mechanisms. Seven isolates contained IncFII plasmids with mphA, ermB, or mphA and ermB, while one isolate contained an IncB/O plasmid with mphA. One (<1%) isolate that contained neither mphA nor ermB contained mutations in rrlH, rplD, and rplV genes, and an insertion in rplV, the function of which are not yet known. CONCLUSIONS: Additional studies are needed to understand the effect on treatment outcomes, epidemiology, and possible additional mechanisms responsible for decreased susceptibility of azithromycin in Shigella. |
Short communication: Multistate outbreak of Listeria monocytogenes infections retrospectively linked to unpasteurized milk using whole-genome sequencing.
Nichols M , Conrad A , Whitlock L , Stroika S , Strain E , Weltman A , Johnson L , DeMent J , Reporter R , Williams I . J Dairy Sci 2019 103 (1) 176-178 Unpasteurized milk can contain harmful bacteria such as Listeria monocytogenes. In 2016, the US Food and Drug Administration notified the Centers for Disease Control and Prevention (Atlanta, GA) that L. monocytogenes isolated from unpasteurized chocolate milk from a Pennsylvania dairy was closely related, by whole-genome sequencing, to L. monocytogenes isolates collected from blood specimens of 2 patients (in California and Florida) in 2014. The California and Florida patients consumed unpasteurized milk from the Pennsylvania dairy. Both were >65 yr old and were hospitalized in 2014; the Florida patient died. Isolates from the 2 patients had indistinguishable pulsed-field gel electrophoresis patterns and were closely related by whole-genome multilocus sequence typing analysis (by 2 alleles) to the isolate from unpasteurized chocolate milk produced by the Pennsylvania dairy in 2015. Together, epidemiologic and laboratory information indicated a common origin. This is the first multistate listeriosis outbreak linked to unpasteurized milk in the United States detected using whole-genome multilocus sequence analysis. |
The efficacy of dihydroartemisinin-piperaquine and artemether-lumefantrine with and without primaquine on Plasmodium vivax recurrence: A systematic review and individual patient data meta-analysis.
Commons RJ , Simpson JA , Thriemer K , Abreha T , Adam I , Anstey NM , Assefa A , Awab GR , Baird JK , Barber BE , Chu CS , Dahal P , Daher A , Davis TME , Dondorp AM , Grigg MJ , Humphreys GS , Hwang J , Karunajeewa H , Laman M , Lidia K , Moore BR , Mueller I , Nosten F , Pasaribu AP , Pereira DB , Phyo AP , Poespoprodjo JR , Sibley CH , Stepniewska K , Sutanto I , Thwaites G , Hien TT , White NJ , William T , Woodrow CJ , Guerin PJ , Price RN . PLoS Med 2019 16 (10) e1002928 BACKGROUND: Artemisinin-based combination therapy (ACT) is recommended for uncomplicated Plasmodium vivax malaria in areas of emerging chloroquine resistance. We undertook a systematic review and individual patient data meta-analysis to compare the efficacies of dihydroartemisinin-piperaquine (DP) and artemether-lumefantrine (AL) with or without primaquine (PQ) on the risk of recurrent P. vivax. METHODS AND FINDINGS: Clinical efficacy studies of uncomplicated P. vivax treated with DP or AL and published between January 1, 2000, and January 31, 2018, were identified by conducting a systematic review registered with the International Prospective Register of Systematic Reviews (PROSPERO): CRD42016053310. Investigators of eligible studies were invited to contribute individual patient data that were pooled using standardised methodology. The effect of mg/kg dose of piperaquine/lumefantrine, ACT administered, and PQ on the rate of P. vivax recurrence between days 7 and 42 after starting treatment were investigated by Cox regression analyses according to an a priori analysis plan. Secondary outcomes were the risk of recurrence assessed on days 28 and 63. Nineteen studies enrolling 2,017 patients were included in the analysis. The risk of recurrent P. vivax at day 42 was significantly higher in the 384 patients treated with AL alone (44.0%, 95% confidence interval [CI] 38.7-49.8) compared with the 812 patients treated with DP alone (9.3%, 95% CI 7.1-12.2): adjusted hazard ratio (AHR) 12.63 (95% CI 6.40-24.92), p < 0.001. The rates of recurrence assessed at days 42 and 63 were associated inversely with the dose of piperaquine: AHRs (95% CI) for every 5-mg/kg increase 0.63 (0.48-0.84), p = 0.0013 and 0.83 (0.73-0.94), p = 0.0033, respectively. The dose of lumefantrine was not significantly associated with the rate of recurrence (1.07 for every 5-mg/kg increase, 95% CI 0.99-1.16, p = 0.0869). In a post hoc analysis, in patients with symptomatic recurrence after AL, the mean haemoglobin increased 0.13 g/dL (95% CI 0.01-0.26) for every 5 days that recurrence was delayed, p = 0.0407. Coadministration of PQ reduced substantially the rate of recurrence assessed at day 42 after AL (AHR = 0.20, 95% CI 0.10-0.41, p < 0.001) and at day 63 after DP (AHR = 0.08, 95% CI 0.01-0.70, p = 0.0233). Results were limited by follow-up of patients to 63 days or less and nonrandomised treatment groups. CONCLUSIONS: In this study, we observed the risk of P. vivax recurrence at day 42 to be significantly lower following treatment with DP compared with AL, reflecting the longer period of post-treatment prophylaxis; this risk was reduced substantially by coadministration with PQ. We found that delaying P. vivax recurrence was associated with a small but significant improvement in haemoglobin. These results highlight the benefits of PQ radical cure and also the provision of blood-stage antimalarial agents with prolonged post-treatment prophylaxis. |
The haematological consequences of Plasmodium vivax malaria after chloroquine treatment with and without primaquine: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis.
Commons RJ , Simpson JA , Thriemer K , Chu CS , Douglas NM , Abreha T , Alemu SG , Anez A , Anstey NM , Aseffa A , Assefa A , Awab GR , Baird JK , Barber BE , Borghini-Fuhrer I , D'Alessandro U , Dahal P , Daher A , de Vries PJ , Erhart A , Gomes MSM , Grigg MJ , Hwang J , Kager PA , Ketema T , Khan WA , Lacerda MVG , Leslie T , Ley B , Lidia K , Monteiro WM , Pereira DB , Phan GT , Phyo AP , Rowland M , Saravu K , Sibley CH , Siqueira AM , Stepniewska K , Taylor WRJ , Thwaites G , Tran BQ , Hien TT , Vieira JLF , Wangchuk S , Watson J , William T , Woodrow CJ , Nosten F , Guerin PJ , White NJ , Price RN . BMC Med 2019 17 (1) 151 BACKGROUND: Malaria causes a reduction in haemoglobin that is compounded by primaquine, particularly in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. The aim of this study was to determine the relative contributions to red cell loss of malaria and primaquine in patients with uncomplicated Plasmodium vivax. METHODS: A systematic review identified P. vivax efficacy studies of chloroquine with or without primaquine published between January 2000 and March 2017. Individual patient data were pooled using standardised methodology, and the haematological response versus time was quantified using a multivariable linear mixed effects model with non-linear terms for time. Mean differences in haemoglobin between treatment groups at day of nadir and day 42 were estimated from this model. RESULTS: In total, 3421 patients from 29 studies were included: 1692 (49.5%) with normal G6PD status, 1701 (49.7%) with unknown status and 28 (0.8%) deficient or borderline individuals. Of 1975 patients treated with chloroquine alone, the mean haemoglobin fell from 12.22 g/dL [95% CI 11.93, 12.50] on day 0 to a nadir of 11.64 g/dL [11.36, 11.93] on day 2, before rising to 12.88 g/dL [12.60, 13.17] on day 42. In comparison to chloroquine alone, the mean haemoglobin in 1446 patients treated with chloroquine plus primaquine was - 0.13 g/dL [- 0.27, 0.01] lower at day of nadir (p = 0.072), but 0.49 g/dL [0.28, 0.69] higher by day 42 (p < 0.001). On day 42, patients with recurrent parasitaemia had a mean haemoglobin concentration - 0.72 g/dL [- 0.90, - 0.54] lower than patients without recurrence (p < 0.001). Seven days after starting primaquine, G6PD normal patients had a 0.3% (1/389) risk of clinically significant haemolysis (fall in haemoglobin > 25% to < 7 g/dL) and a 1% (4/389) risk of a fall in haemoglobin > 5 g/dL. CONCLUSIONS: Primaquine has the potential to reduce malaria-related anaemia at day 42 and beyond by preventing recurrent parasitaemia. Its widespread implementation will require accurate diagnosis of G6PD deficiency to reduce the risk of drug-induced haemolysis in vulnerable individuals. TRIAL REGISTRATION: This trial was registered with PROSPERO: CRD42016053312. The date of the first registration was 23 December 2016. |
Seroprevalence of hepatitis A and hepatitis E viruses among pregnant women in Haiti
Tejada-Strop A , Tohme RA , Andre-Alboth J , Childs L , Ji X , de Oliveira Landgraf de Castro V , Boncy J , Kamili S . Am J Trop Med Hyg 2019 101 (1) 230-232 Hepatitis E virus (HEV) infection is associated with a high fatality rate among pregnant women, and gestational complications have been reported among pregnant women infected with hepatitis A virus (HAV). The aim of this study was to determine the seroprevalence of HAV and HEV infections among pregnant women in Haiti. We stratified the population (n = 1,307) between West and non-West regions. Specimens were tested for total HAV antibody (anti-HAV), and IgM and IgG HEV antibody (anti-HEV). Overall, 96.8% pregnant women were positive for total anti-HAV, 10.3% for IgG anti-HEV, and 0.3% for IgM anti-HEV. The prevalence of IgG anti-HEV in the non-West region (12.3%) was significantly greater than that in the West region (5.3%) (P < 0.0001). Most pregnant women in Haiti had evidence of past exposure and immunity to HAV. The non-West region had a higher prevalence of HEV. Improvement in water and sanitation will help in the prevention and control of these infections in Haiti. |
New filovirus disease classification and nomenclature.
Kuhn JH , Adachi T , Adhikari NKJ , Arribas JR , Bah IE , Bausch DG , Bhadelia N , Borchert M , Brantsaeter AB , Brett-Major DM , Burgess TH , Chertow DS , Chute CG , Cieslak TJ , Colebunders R , Crozier I , Davey RT , de Clerck H , Delgado R , Evans L , Fallah M , Fischer WA 2nd , Fletcher TE , Fowler RA , Grunewald T , Hall A , Hewlett A , Hoepelman AIM , Houlihan CF , Ippolito G , Jacob ST , Jacobs M , Jakob R , Jacquerioz FA , Kaiser L , Kalil AC , Kamara RF , Kapetshi J , Klenk HD , Kobinger G , Kortepeter MG , Kraft CS , Kratz T , Bosa HSK , Lado M , Lamontagne F , Lane HC , Lobel L , Lutwama J , Lyon GM 3rd , Massaquoi MBF , Massaquoi TA , Mehta AK , Makuma VM , Murthy S , Musoke TS , Muyembe-Tamfum JJ , Nakyeyune P , Nanclares C , Nanyunja M , Nsio-Mbeta J , O'Dempsey T , Paweska JT , Peters CJ , Piot P , Rapp C , Renaud B , Ribner B , Sabeti PC , Schieffelin JS , Slenczka W , Soka MJ , Sprecher A , Strong J , Swanepoel R , Uyeki TM , van Herp M , Vetter P , Wohl DA , Wolf T , Wolz A , Wurie AH , Yoti Z . Nat Rev Microbiol 2019 17 (5) 261-263 The recent large outbreak of Ebola virus disease (EVD) in Western Africa resulted in greatly increased accumulation of human genotypic, phenotypic and clinical data, and improved our understanding of the spectrum of clinical manifestations. As a result, the WHO disease classification of EVD underwent major revision. |
Genome wide characterization of enterotoxigenic Escherichia coli serogroup O6 isolates from multiple outbreaks and sporadic infections from 1975-2016.
Pattabiraman V , Katz LS , Chen JC , McCullough AE , Trees E . PLoS One 2018 13 (12) e0208735 Enterotoxigenic Escherichia coli (ETEC) are an important cause of diarrhea globally, particularly among children under the age of five in developing countries. ETEC O6 is the most common ETEC serogroup, yet the genome wide population structure of isolates of this serogroup is yet to be determined. In this study, we have characterized 40 ETEC O6 isolates collected between 1975-2016 by whole genome sequencing (WGS) and by phenotypic antimicrobial susceptibility testing. To determine the relatedness of isolates, we evaluated two methods-whole genome high-quality single nucleotide polymorphism (whole genome-hqSNP) and core genome SNP analyses using Lyve-SET and Parsnp respectively. All isolates were tested for antimicrobial susceptibility using a panel of 14 antibiotics. ResFinder 2.1 and a custom quinolone resistance determinants workflow were used for resistance determinant detection. VirulenceFinder 1.5 was used for prediction of the virulence genes. Thirty-seven isolates clustered into three major clades (I, II, III) by whole genome-hqSNP and core genome SNP analyses, while three isolates included in the whole genome-hqSNP analysis only did not cluster with clades I-III by both analyses and formed a distantly related outgroup, designated clade IV. Median number of pairwise whole genome-hqSNPs in clonal ETEC O6 outbreaks ranged from 0 to 5. Of the 40 isolates tested for antimicrobial susceptibility, 18 isolates were pansusceptible. Twenty-two isolates were resistant to at least one antibiotic, nine of which were multidrug resistant. Phenotypic antimicrobial resistance (AR) correlated with AR determinants in 22 isolates. Thirty-two isolates harbored both enterotoxin virulence genes while the remaining 8 isolates had only one of the two virulence genes. In summary, whole genome-hqSNP and core genome SNP analyses from this study revealed similar evolutionary relationships and an overall diversity of ETEC O6 isolates independent of time of isolation. Less than 5 pairwise hqSNPs between ETEC O6 isolates is circumstantially indicative of an outbreak cluster. Findings from this study will be a basis for quicker outbreak detection and control by efficient subtyping by WGS. |
Clinical and Molecular Features of Feline Foamy Virus and Feline Leukemia Virus Co-Infection in Naturally-Infected Cats.
Cavalcante LTF , Muniz CP , Jia H , Augusto AM , Troccoli F , Medeiros SO , Dias CGA , Switzer WM , Soares MA , Santos AF . Viruses 2018 10 (12) Feline foamy virus (FFV) and feline leukemia virus (FeLV) belong to the Retroviridae family. While disease has not been reported for FFV infection, FeLV infection can cause anemia and immunosuppression (progressive infection). Co-infection with FFV/FeLV allows evaluation of the pathogenic potential and epidemiology of FFV infection in cats with FeLV pathology. Blood and buccal swab samples from 81 cats were collected in Rio de Janeiro. Plasma was serologically tested for FeLV. DNA extracted from peripheral blood mononuclear cells and buccal swabs was used to PCR detect FFV and FeLV. A qPCR was developed to detect and measure FFV proviral loads (pVLs) in cats. FeLV qPCR was performed using previous methods. The median log10 pVL of FFV mono-infected individuals was lower than found in FFV/FeLV co-infected cats in buccal swabs (p = 0.003). We found 78% of cats had detectable buccal FFV DNA in FFV mono-infected and FFV co-infected FeLV-progressive cats, while in FeLV-regressive cats (those without signs of disease) 22% of cats had detectable buccal FFV DNA (p = 0.004). Our results suggest that regressive FeLV infection may reduce FFV saliva transmission, the main mode of FV transmission. We did not find evidence of differences in pathogenicity in FFV mono- and -dually infected cats. In summary, we show that FVs may interact with FeLV within the same host. Our study supports the utility of cats naturally co-infected with retroviruses as a model to investigate the impact of FV on immunocompromised mammalian hosts. |
Frontline field epidemiology training programs as a strategy to improve disease surveillance and response
Andre AM , Lopez A , Perkins S , Lambert S , Chace L , Noudeke N , Fall A , Pedalino B . Emerg Infect Dis 2017 23 (13) S166-73 Since 1980, Field Epidemiology Training Programs (FETPs) have trained highly qualified field epidemiologists to work for ministries of health (MOH) around the world. However, the 2013-2015 Ebola epidemic in West Africa, which primarily affected Guinea, Liberia, and Sierra Leone, demonstrated a lack of field epidemiologists at the local levels. Trained epidemiologists at these levels could have detected the Ebola outbreak earlier. In 2015, the US Centers for Disease Control and Prevention (CDC) launched FETP-Frontline, a 3-month field training program targeting local MOH staff in 24 countries to augment local public health capacity. As of December 2016, FETP-Frontline has trained 1,354 graduates in 24 countries. FETP-Frontline enhances global health security by training local public health staff to improve surveillance quality in their jurisdictions, which can be a valuable strategy to strengthen the capacity of countries to more rapidly detect, respond to, and contain public health emergencies at the source. |
Surveillance training for Ebola preparedness in Cote d'Ivoire, Guinea-Bissau, Senegal, and Mali
Caceres VM , Sidibe S , Andre M , Traicoff D , Lambert S , King M , Kazambu D , Lopez A , Pedalino B , Guibert DJH , Wassawa P , Cardoso P , Assi B , Ly A , Traore B , Angulo FJ , Quick L . Emerg Infect Dis 2017 23 (13) S174-82 The 2014-2015 epidemic of Ebola virus disease in West Africa primarily affected Guinea, Liberia, and Sierra Leone. Several countries, including Mali, Nigeria, and Senegal, experienced Ebola importations. Realizing the importance of a trained field epidemiology workforce in neighboring countries to respond to Ebola importations, the Centers for Disease Control and Prevention Field Epidemiology Training Program unit implemented the Surveillance Training for Ebola Preparedness (STEP) initiative. STEP was a mentored, competency-based initiative to rapidly build up surveillance capacity along the borders of the at-risk neighboring countries Cote d'Ivoire, Mali, Senegal, and Guinea-Bissau. The target audience was district surveillance officers. STEP was delivered to 185 participants from 72 health units (districts or regions). Timeliness of reporting and the quality of surveillance analyses improved 3 months after training. STEP demonstrated that mentored, competency-based training, where learners attain competencies while delivering essential public health services, can be successfully implemented in an emergency response setting. |
Zoonotic infection of Brazilian primate workers with New World simian foamy virus.
Muniz CP , Cavalcante LTF , Jia H , Zheng H , Tang S , Augusto AM , Pissinatti A , Fedullo LP , Santos AF , Soares MA , Switzer WM . PLoS One 2017 12 (9) e0184502 Simian foamy viruses (SFVs) are retroviruses present in nearly all nonhuman primates (NHPs), including Old World primates (OWP) and New World primates (NWP). While all confirmed human infections with SFV are from zoonotic transmissions originating from OWP, little is known about the zoonotic transmission potential of NWP SFV. We conducted a longitudinal, prospective study of 56 workers occupationally exposed to NWP in Brazil. Plasma from these workers was tested using Western blot (WB) assays containing NWP SFV antigens. Genomic DNA from blood and buccal swabs was analyzed for the presence of proviral SFV sequences by three nested PCR tests and a new quantitative PCR assay. Exposure histories were obtained and analyzed for associations with possible SFV infection. Ten persons (18%) tested seropositive and two persons were seroindeterminate (3.6%) for NWP SFV. Six persons had seroreactivity over 2-3 years suggestive of persistent infection. All SFV NWP WB-positive workers reported at least one incident involving NWP, including six reporting NWP bites. NWP SFV viral DNA was not detected in the blood or buccal swabs from all 12 NWP SFV seroreactive workers. We also found evidence of SFV seroreversion in three workers suggestive of possible clearance of infection. Our findings suggest that NWP SFV can be transmitted to occupationally-exposed humans and can elicit specific humoral immune responses but infection remains well-controlled resulting in latent infection and may occasionally clear. |
A non-invasive specimen collection method and a novel simian foamy virus (SFV) DNA quantification assay in New World primates reveal aspects of tissue tropism and improved SFV detection.
Muniz CP , Zheng H , Jia H , Cavalcante LTF , Augusto AM , Fedullo LP , Pissinatti A , Soares MA , Switzer WM , Santos AF . PLoS One 2017 12 (9) e0184251 Simian foamy viruses (SFVs) co-evolved with a wide range of Old World and New World primates (OWPs and NWPs, respectively) and occasionally transmit to humans. Previous studies of OWPs showed that the predominant site of SFV replication is the oral mucosa. However, very little is known about SFV viral loads (VLs) in the oral mucosa or blood of NWPs. NWPs have smaller body sizes, limiting collection of sufficient whole blood volumes to molecularly detect and quantify SFV. Our study evaluated the use of noninvasively collected buccal swabs to detect NWP SFV compared with detection in blood using a new NWP SFV quantitative PCR (qPCR) assay. Buccal and blood samples were collected from 107 captive NWPs in Brazil comprising eleven distinct genera at the Primate Center of Rio de Janeiro (n = 58) and at Fundacao Jardim Zoologico da Cidade do Rio Janeiro (n = 49). NWP SFV western blot (WB) testing was performed on a subset of animals for comparison with PCR results. The qPCR assay was validated using distinct SFV polymerase sequences from seven NWP genera (Callithrix, Sapajus, Saimiri, Ateles, Alouatta, Cacajao and Pithecia). Assay sensitivity was 20 copies/106 cells, detectable in 90% of replicates. SFV DNA VLs were higher in buccal swabs (5 log copies/106 cells) compared to peripheral blood mononuclear cells (PBMCs) (3 log copies/106 cells). The qPCR assay was also more sensitive than nested PCR for detection of NWP SFV infection and identified an additional 27 SFV-infected monkeys of which 18 (90%) were WB-positive and three that were WB-negative. We show the utility of using both blood and buccal swabs and our new qPCR assay for detection and quantification of diverse NWP SFV, which will assist a better understanding of the epidemiology of SFV in NWPs and any potential zoonotic infection risk for humans exposed to NWPs. |
Seroprevalence of herpes simplex virus type-2 (HSV-2) among pregnant women who participated in a national HIV surveillance activity in Haiti
Domercant JW , Jean Louis F , Hulland E , Griswold M , Andre-Alboth J , Ye T , Marston BJ . BMC Infect Dis 2017 17 (1) 577 BACKGROUND: Herpes simplex virus type 2 (HSV-2), one the most common causes of genital ulcers, appears to increase both the risk of HIV acquisition and HIV transmission. HSV-2/HIV co-infection among pregnant women may increase the risk of perinatal transmission of HIV. This study describes rates of HSV-2 among pregnant women in Haiti and HSV-2 test performance in this population. METHODS: Unlinked residual serum specimens from the 2012 National HIV and Syphilis Sentinel Surveillance Survey among pregnant women in Haiti were tested using two commercial kits (Focus HerpeSelect, Kalon) for HSV-2 antibodies. We evaluated rates of HSV-2 seropositivity and HSV-2/HIV co-infection, associations between HSV-2 and demographic characteristics using multivariable Cox proportional hazards modeling, and HSV-2 test performance in this population. RESULTS: Serum samples from 1000 pregnant women (all 164 HIV positive and 836 random HIV negative) were selected. The overall weighted prevalence of HSV-2 was 31.4% (95% CI: 27.7-35.4) and the prevalence of HIV-positivity among HSV-2 positive pregnant women was five times higher than the prevalence among HSV-2 negative women (4.8% [95% CI: 3.9-6.0] vs. 0.9% [95% CI: 0.6-1.3], respectively). Factors significantly associated with HSV-2 positivity were HIV-positivity (PR: 2.27 [95% CI: 1.94-2.65]) and older age (PRs: 1.41 [95% CI: 1.05-1.91] for 20-24 years, 1.71 [95% CI:1.13-2.60] for 30-34 years, and 1.55 [95% CI: 1.10-2.19] for 35 years or greater]), while rural residence was negatively associated with HSV-2 positivity (PR 0.83 [95% CI: 0.69-1.00]), after controlling for other covariables. For this study a conservative Focus index cutoff of 3.5 was used, but among samples with a Focus index value ≥2.5, 98.4% had positive Kalon tests. CONCLUSION: The prevalence of HSV-2 is relatively high among pregnant women in Haiti. Public health interventions to increase access to HSV-2 screening in antenatal services are warranted. |
Metabolic differentiation of early Lyme disease from southern tick-associated rash illness (STARI).
Molins CR , Ashton LV , Wormser GP , Andre BG , Hess AM , Delorey MJ , Pilgard MA , Johnson BJ , Webb K , Islam MN , Pegalajar-Jurado A , Molla I , Jewett MW , Belisle JT . Sci Transl Med 2017 9 (403) Lyme disease, the most commonly reported vector-borne disease in the United States, results from infection with Borrelia burgdorferi. Early clinical diagnosis of this disease is largely based on the presence of an erythematous skin lesion for individuals in high-risk regions. This, however, can be confused with other illnesses including southern tick-associated rash illness (STARI), an illness that lacks a defined etiological agent or laboratory diagnostic test, and is coprevalent with Lyme disease in portions of the eastern United States. By applying an unbiased metabolomics approach with sera retrospectively obtained from well-characterized patients, we defined biochemical and diagnostic differences between early Lyme disease and STARI. Specifically, a metabolic biosignature consisting of 261 molecular features (MFs) revealed that altered N-acyl ethanolamine and primary fatty acid amide metabolism discriminated early Lyme disease from STARI. Development of classification models with the 261-MF biosignature and testing against validation samples differentiated early Lyme disease from STARI with an accuracy of 85 to 98%. These findings revealed metabolic dissimilarity between early Lyme disease and STARI, and provide a powerful and new approach to inform patient management by objectively distinguishing early Lyme disease from an illness with nearly identical symptoms. |
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