Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-30 (of 74 Records) |
Query Trace: Zaidi A [original query] |
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Spatiotemporal variation in risk of Shigella infection in childhood: a global risk mapping and prediction model using individual participant data
Badr HS , Colston JM , Nguyen NH , Chen YT , Burnett E , Ali SA , Rayamajhi A , Satter SM , Van Trang N , Eibach D , Krumkamp R , May J , Adegnika AA , Manouana GP , Kremsner PG , Chilengi R , Hatyoka L , Debes AK , Ateudjieu J , Faruque ASG , Hossain MJ , Kanungo S , Kotloff KL , Mandomando I , Nisar MI , Omore R , Sow SO , Zaidi AKM , Lambrecht N , Adu B , Page N , Platts-Mills JA , Mavacala Freitas C , Pelkonen T , Ashorn P , Maleta K , Ahmed T , Bessong P , Bhutta ZA , Mason C , Mduma E , Olortegui MP , Peñataro Yori P , Lima AAM , Kang G , Humphrey J , Ntozini R , Prendergast AJ , Okada K , Wongboot W , Langeland N , Moyo SJ , Gaensbauer J , Melgar M , Freeman M , Chard AN , Thongpaseuth V , Houpt E , Zaitchik BF , Kosek MN . Lancet Glob Health 2023 11 (3) e373-e384 BACKGROUND: Diarrhoeal disease is a leading cause of childhood illness and death globally, and Shigella is a major aetiological contributor for which a vaccine might soon be available. The primary objective of this study was to model the spatiotemporal variation in paediatric Shigella infection and map its predicted prevalence across low-income and middle-income countries (LMICs). METHODS: Individual participant data for Shigella positivity in stool samples were sourced from multiple LMIC-based studies of children aged 59 months or younger. Covariates included household-level and participant-level factors ascertained by study investigators and environmental and hydrometeorological variables extracted from various data products at georeferenced child locations. Multivariate models were fitted and prevalence predictions obtained by syndrome and age stratum. FINDINGS: 20 studies from 23 countries (including locations in Central America and South America, sub-Saharan Africa, and south and southeast Asia) contributed 66 563 sample results. Age, symptom status, and study design contributed most to model performance followed by temperature, wind speed, relative humidity, and soil moisture. Probability of Shigella infection exceeded 20% when both precipitation and soil moisture were above average and had a 43% peak in uncomplicated diarrhoea cases at 33°C temperatures, above which it decreased. Compared with unimproved sanitation, improved sanitation decreased the odds of Shigella infection by 19% (odds ratio [OR]=0·81 [95% CI 0·76-0·86]) and open defecation decreased them by 18% (OR=0·82 [0·76-0·88]). INTERPRETATION: The distribution of Shigella is more sensitive to climatological factors, such as temperature, than previously recognised. Conditions in much of sub-Saharan Africa are particularly propitious for Shigella transmission, although hotspots also occur in South America and Central America, the Ganges-Brahmaputra Delta, and the island of New Guinea. These findings can inform prioritisation of populations for future vaccine trials and campaigns. FUNDING: NASA, National Institutes of Health-The National Institute of Allergy and Infectious Diseases, and Bill & Melinda Gates Foundation. |
Risk factors for community-acquired bacterial infection among young infants in South Asia: a longitudinal cohort study with nested case-control analysis
Connor NE , Islam MS , Mullany LC , Shang N , Bhutta ZA , Zaidi AKM , Soofi S , Nisar I , Panigrahi P , Panigrahi K , Satpathy R , Bose A , Isaac R , Baqui AH , Mitra DK , Sadeq-Ur Rahman Q , Hossain T , Schrag SJ , Winchell JM , Arvay ML , Diaz MH , Waller JL , Weber MW , Hamer DH , Hibberd P , Nawshad Uddin Ahmed ASM , Islam M , Hossain MB , Qazi SA , El Arifeen S , Darmstadt GL , Saha SK . BMJ Glob Health 2022 7 (11) OBJECTIVE: Risk factors predisposing infants to community-acquired bacterial infections during the first 2 months of life are poorly understood in South Asia. Identifying risk factors for infection could lead to improved preventive measures and antibiotic stewardship. METHODS: Five sites in Bangladesh, India and Pakistan enrolled mother-child pairs via population-based pregnancy surveillance by community health workers. Medical, sociodemographic and epidemiological risk factor data were collected. Young infants aged 0-59 days with signs of possible serious bacterial infection (pSBI) and age-matched controls provided blood and respiratory specimens that were analysed by blood culture and real-time PCR. These tests were used to build a Bayesian partial latent class model (PLCM) capable of attributing the probable cause of each infant's infection in the ANISA study. The collected risk factors from all mother-child pairs were classified and analysed against the PLCM using bivariate and stepwise logistic multivariable regression modelling to determine risk factors of probable bacterial infection. RESULTS: Among 63 114 infants born, 14 655 were assessed and 6022 had signs of pSBI; of these, 81% (4859) provided blood samples for culture, 71% (4216) provided blood samples for quantitative PCR (qPCR) and 86% (5209) provided respiratory qPCR samples. Risk factors associated with bacterial-attributed infections included: low (relative risk (RR) 1.73, 95% credible interval (CrI) 1.42 to 2.11) and very low birth weight (RR 5.77, 95% CrI 3.73 to 8.94), male sex (RR 1.27, 95% CrI 1.07 to 1.52), breathing problems at birth (RR 2.50, 95% CrI 1.96 to 3.18), premature rupture of membranes (PROMs) (RR 1.27, 95% CrI 1.03 to 1.58) and being in the lowest three socioeconomic status quintiles (first RR 1.52, 95% CrI 1.07 to 2.16; second RR 1.41, 95% CrI 1.00 to 1.97; third RR 1.42, 95% CrI 1.01 to 1.99). CONCLUSION: Distinct risk factors: birth weight, male sex, breathing problems at birth and PROM were significantly associated with the development of bacterial sepsis across South Asian community settings, supporting refined clinical discernment and targeted use of antimicrobials. |
Health care usage among adolescents with congenital heart defects at 5 sites in the United States, 2011 to 2013
Lui GK , Sommerhalter K , Xi Y , Botto LD , Crume T , Farr S , Feldkamp ML , Glidewell J , Hsu D , Khanna A , Krikov S , Li J , Raskind-Hood C , Sarno L , Van Zutphen AR , Zaidi A , Soim A , Book WM . J Am Heart Assoc 2022 11 (18) e026172 Background We sought to characterize health care usage for adolescents with congenital heart defects (CHDs) using population-based multisite surveillance data. Methods and Results Adolescents aged 11 to 18 years with ≥1 CHD-related diagnosis code and residing in 5 US sites were identified in clinical and administrative data sources for the years 2011 to 2013. Sites linked data on all inpatient, emergency department (ED), and outpatient visits. Multivariable log-binomial regression models including age, sex, unweighted Charlson comorbidity index, CHD severity, cardiology visits, and insurance status, were used to identify associations with inpatient, ED, and outpatient visits. Of 9626 eligible adolescents, 26.4% (n=2543) had severe CHDs and 21.4% had Charlson comorbidity index >0. At least 1 inpatient, ED, or outpatient visit was reported for 21%, 25%, and 96% of cases, respectively. Cardiology visits, cardiac imaging, cardiac procedures, and vascular procedures were reported for 38%, 73%, 10%, and 5% of cases, respectively. Inpatient, ED, and outpatient visits were consistently higher for adolescents with severe CHDs compared with nonsevere CHDs. Adolescents with severe and nonsevere CHDs had higher health care usage compared with the 2011 to 2013 general adolescent US population. Adolescents with severe CHDs versus nonsevere CHDs were twice as likely to have at least 1 inpatient visit when Charlson comorbidity index was low (Charlson comorbidity index =0). Adolescents with CHDs and public insurance, compared with private insurance, were more likely to have inpatient (adjusted prevalence ratio, 1.5 [95% CI, 1.3-1.7]) and ED (adjusted prevalence ratio, 1.6 [95% CI, 1.4-1.7]) visits. Conclusions High resource usage by adolescents with CHDs indicates a substantial burden of disease, especially with public insurance, severe CHDs, and more comorbidities. |
Infectious aetiologies of neonatal illness in South Asia classified using WHO definitions: a primary analysis of the ANISA study
Arvay ML , Shang N , Qazi SA , Darmstadt GL , Islam MS , Roth DE , Liu A , Connor NE , Hossain B , Sadeq-Ur Rahman Q , El Arifeen S , Mullany LC , Zaidi AKM , Bhutta ZA , Soofi SB , Shafiq Y , Baqui AH , Mitra DK , Panigrahi P , Panigrahi K , Bose A , Isaac R , Westreich D , Meshnick SR , Saha SK , Schrag SJ . Lancet Glob Health 2022 10 (9) e1289-e1297 BACKGROUND: Globally, neonatal mortality accounts for almost half of all deaths in children younger than 5 years. Aetiological agents of neonatal infection are difficult to identify because the clinical signs are non-specific. Using data from the Aetiology of Neonatal Infections in south Asia (ANISA) cohort, we aimed to describe the spectrum of infectious aetiologies of acute neonatal illness categorised post-hoc using the 2015 WHO case definitions of critical illness, clinical severe infection, and fast breathing only. METHODS: Eligible infants were aged 0-59 days with possible serious bacterial infection and healthy infants enrolled in the ANISA study in Bangladesh, India, and Pakistan. We applied a partial latent class Bayesian model to estimate the prevalence of 27 pathogens detectable on PCR, pathogens detected by blood culture only, and illness not attributed to any infectious aetiology. Infants with at least one clinical specimen available were included in the analysis. We assessed the prevalence of these aetiologies according to WHO's case definitions of critically ill, clinical severe infection, and infants with late onset, isolated fast breathing. For the clinical severe definition, we compared the prevalence of signs by bacterial versus viral aetiology. FINDINGS: There were 934 infants (992 episodes) in the critically ill category, 3769 (4000 episodes) in the clinical severe infection category, and 738 (771 episodes) in the late-onset isolated fast breathing category. We estimated the proportion of illness attributable to bacterial infection was 32·7% in infants in the critically ill group, 15·6% in the clinical severe infection group, and 8·8% among infants with late-onset isolated fast breathing group. An infectious aetiology was not identified in 58-82% of infants in these categories. Among 4000 episodes of clinical severe infection, those with bacterial versus viral attribution had higher proportions of hypothermia, movement only when stimulated, convulsions, and poor feeding. INTERPRETATION: Our modelled results generally support the revised WHO case definitions, although a revision of the most severe case definition could be considered. Clinical criteria do not clearly differentiate between young infants with and without infectious aetiologies. Our results highlight the need for improved point-of-care diagnostics, and further study into neonatal deaths and episodes with no identified aetiology, to ensure antibiotic stewardship and targeted interventions. FUNDING: The Bill and Melinda Gates Foundation. |
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. |
Associations Between Eight Earth Observation-Derived Climate Variables and Enteropathogen Infection: An Independent Participant Data Meta-Analysis of Surveillance Studies With Broad Spectrum Nucleic Acid Diagnostics.
Colston JM , Zaitchik BF , Badr HS , Burnett E , Ali SA , Rayamajhi A , Satter SM , Eibach D , Krumkamp R , May J , Chilengi R , Howard LM , Sow SO , JahangirHossain M , Saha D , ImranNisar M , Zaidi AKM , Kanungo S , Mandomando I , Faruque ASG , Kotloff KL , Levine MM , Breiman RF , Omore R , Page N , Platts-Mills JA , Ashorn U , Fan YM , Shrestha PS , Ahmed T , Mduma E , Yori PP , Bhutta Z , Bessong P , Olortegui MP , Lima AAM , Kang G , Humphrey J , Prendergast AJ , Ntozini R , Okada K , Wongboot W , Gaensbauer J , Melgar MT , Pelkonen T , Freitas CM , Kosek MN . Geohealth 2022 6 (1) e2021GH000452 Diarrheal disease, still a major cause of childhood illness, is caused by numerous, diverse infectious microorganisms, which are differentially sensitive to environmental conditions. Enteropathogen-specific impacts of climate remain underexplored. Results from 15 studies that diagnosed enteropathogens in 64,788 stool samples from 20,760 children in 19 countries were combined. Infection status for 10 common enteropathogens-adenovirus, astrovirus, norovirus, rotavirus, sapovirus, Campylobacter, ETEC, Shigella, Cryptosporidium and Giardia-was matched by date with hydrometeorological variables from a global Earth observation dataset-precipitation and runoff volume, humidity, soil moisture, solar radiation, air pressure, temperature, and wind speed. Models were fitted for each pathogen, accounting for lags, nonlinearity, confounders, and threshold effects. Different variables showed complex, non-linear associations with infection risk varying in magnitude and direction depending on pathogen species. Rotavirus infection decreased markedly following increasing 7-day average temperatures-a relative risk of 0.76 (95% confidence interval: 0.69-0.85) above 28C-while ETEC risk increased by almost half, 1.43 (1.36-1.50), in the 20-35C range. Risk for all pathogens was highest following soil moistures in the upper range. Humidity was associated with increases in bacterial infections and decreases in most viral infections. Several virus species' risk increased following lower-than-average rainfall, while rotavirus and ETEC increased with heavier runoff. Temperature, soil moisture, and humidity are particularly influential parameters across all enteropathogens, likely impacting pathogen survival outside the host. Precipitation and runoff have divergent associations with different enteric viruses. These effects may engender shifts in the relative burden of diarrhea-causing agents as the global climate changes. |
Access to cardiac surgery centers for cardiac and non-cardiac hospitalizations in adolescents and adults with congenital heart defects- a descriptive case series study
Insaf TZ , Sommerhalter KM , Jaff TA , Farr SL , Downing KF , Zaidi AN , Lui GK , Van Zutphen AR . Am Heart J 2021 236 22-36 BACKGROUND: Individuals with congenital heart defects (CHDs) are recommended to receive all inpatient cardiac and non-cardiac care at facilities that can offer specialized care. We describe geographic accessibility to such centers in New York State and determine several factors associated with receiving care there. METHODS: We used inpatient hospitalization data from the Statewide Planning and Research Cooperative System (SPARCS) in New York State 2008-2013. In the absence of specific adult CHD care center designations during our study period, we identified pediatric/adult and adult-only cardiac surgery centers through the Cardiac Surgery Reporting System to estimate age-based specialized care. We calculated one-way drive and public transit time (in minutes) from residential address to centers using R gmapsdistance package and the Google Maps Distance Application Programming Interface (API). We calculated prevalence ratios using modified Poisson regression with model-based standard errors, fit with generalized estimating equations clustered at the hospital level and sub-clustered at the individual level. RESULTS: Individuals with CHDs were more likely to seek care at pediatric/adult or adult-only cardiac surgery centers if they had severe CHDs, private health insurance, higher severity of illness at encounter, a surgical procedure, cardiac encounter, and shorter drive time. These findings can be used to increase care receipt (especially for non-cardiac care) at pediatric/adult or adult-only cardiac surgery centers, identify areas with limited access, and reduce disparities in access to specialized care among this high-risk population. |
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. |
The Clinical Presentation of Culture-positive and Culture-negative, Quantitative Polymerase Chain Reaction (qPCR)-Attributable Shigellosis in the Global Enteric Multicenter Study and Derivation of a Shigella Severity Score: Implications for Pediatric Shigella Vaccine Trials.
Pavlinac PB , Platts-Mills JA , Tickell KD , Liu J , Juma J , Kabir F , Nkeze J , Okoi C , Operario DJ , Uddin MJ , Ahmed S , Alonso PL , Antonio M , Becker SM , Breiman RF , Faruque ASG , Fields B , Gratz J , Haque R , Hossain A , Hossain MJ , Jarju S , Qamar F , Iqbal NT , Kwambana B , Mandomando I , McMurry TL , Ochieng C , Ochieng JB , Ochieng M , Onyango C , Panchalingam S , Kalam A , Aziz F , Qureshi S , Ramamurthy T , Roberts JH , Saha D , Sow SO , Stroup SE , Sur D , Tamboura B , Taniuchi M , Tennant SM , Roose A , Toema D , Wu Y , Zaidi A , Nataro JP , Levine MM , Houpt ER , Kotloff KL . Clin Infect Dis 2020 73 (3) e569-e579 BACKGROUND: Shigella is a leading cause of childhood diarrhea and target for vaccine development. Microbiologic and clinical case definitions are needed for pediatric field vaccine efficacy trials. METHODS: We compared characteristics of moderate to severe diarrhea (MSD) cases in the Global Enteric Multicenter Study (GEMS) between children with culture positive Shigella to those with culture-negative, qPCR-attributable Shigella (defined by an ipaH gene cycle threshold <27.9). Among Shigella MSD cases, we determined risk factors for death and derived a clinical severity score. RESULTS: Compared to culture-positive Shigella MSD cases (n=745), culture-negative/qPCR-attributable Shigella cases (n=852) were more likely to be under 12 months, stunted, have a longer duration of diarrhea, and less likely to have high stool frequency or a fever. There was no difference in dehydration, hospitalization, or severe classification from a modified Vesikari score. Twenty-two (1.8%) Shigella MSD cases died within the 14-days after presentation to health facilities, and 59.1% of these deaths were in culture-negative cases. Age < 12 months, diarrhea duration prior to presentation, vomiting, stunting, wasting, and hospitalization were associated with mortality. A model-derived score assigned points for dehydration, hospital admission, and longer diarrhea duration but was not significantly better at predicting 14-day mortality than a modified Vesikari score. CONCLUSIONS: A composite severity score consistent with severe disease or dysentery may be a pragmatic clinical endpoint for severe shigellosis in vaccine trials. Reliance on culture for microbiologic confirmation may miss a substantial number of Shigella cases but is currently required to measure serotype specific immunity. |
Inpatient admissions and costs for adolescents and young adults with congenital heart defects in New York, 2009-2013
Hsu WH , Sommerhalter KM , McGarry CE , Farr SL , Downing KF , Lui GK , Zaidi AN , Hsu DT , Van Zutphen AR . Birth Defects Res 2020 113 (2) 173-188 OBJECTIVES: Most individuals born with congenital heart defects (CHDs) survive to adulthood, but healthcare utilization patterns for adolescents and adults with CHDs have not been well described. We sought to characterize the healthcare utilization patterns and associated costs for adolescents and young adults with CHDs. METHODS: We examined 2009-2013 New York State inpatient admissions of individuals ages 11-30 years with ≥1 CHD diagnosis codes recorded during any admission. We conducted multivariate linear regression using generalized estimating equations to examine associations between inpatient costs and sociodemographic and clinical variables. RESULTS: We identified 5,100 unique individuals with 9,593 corresponding hospitalizations over the study period. Median inpatient cost and length of stay (LOS) were $10,720 and 3.0 days per admission, respectively; 55.1% were emergency admissions. Admission volume increased 48.7% from 2009 (1,538 admissions) to 2013 (2,287 admissions), while total inpatient costs increased 91.8% from 2009 ($27.2 million) to 2013 ($52.2 million). Inpatient admissions and costs rose more sharply over the study period for those with nonsevere CHDs compared to severe CHDs. Characteristics associated with higher costs were longer LOS, severe CHD, cardiac/vascular hospitalization classification, surgical procedures, greater severity of illness, and admission in New York City. CONCLUSION: This study provides an informative baseline of health care utilization patterns and associated costs among adolescents and young adults with CHDs in New York State. Structured transition programs may aid in keeping this population in appropriate cardiac care as they move to adulthood. |
Characteristics of adults with congenital heart defects in the United States
Gurvitz M , Dunn JE , Bhatt A , Book WM , Glidewell J , Hogue C , Lin AE , Lui G , McGarry C , Raskind-Hood C , Van Zutphen A , Zaidi A , Jenkins K , Riehle-Colarusso T . J Am Coll Cardiol 2020 76 (2) 175-182 BACKGROUND: In the United States, >1 million adults are living with congenital heart defects (CHDs), but gaps exist in understanding the health care needs of this growing population. OBJECTIVES: This study assessed the demographics, comorbidities, and health care use of adults ages 20 to 64 years with CHDs. METHODS: Adults with International Classification of Disease-9th Revision-Clinical Modification CHD-coded health care encounters between January 1, 2008 (January 1, 2009 for Massachusetts) and December 31, 2010 were identified from multiple data sources at 3 U.S. sites: Emory University (EU) in Atlanta, Georgia (5 counties), Massachusetts Department of Public Health (statewide), and New York State Department of Health (11 counties). Demographics, insurance type, comorbidities, and encounter data were collected. CHDs were categorized as severe or not severe, excluding cases with isolated atrial septal defect and/or patent foramen ovale. RESULTS: CHD severity and comorbidities varied across sites, with up to 20% of adults having severe CHD and >50% having ≥1 additional cardiovascular comorbidity. Most adults had ≥1 outpatient encounters (80% EU, 90% Massachusetts, and 53% New York). Insurance type differed across sites, with Massachusetts having a large proportion of Medicaid (75%) and EU and New York having large proportions of private insurance (44% EU, 67% New York). Estimated proportions of adults with CHD-coded health care encounters varied greatly by location, with 1.2 (EU), 10 (Massachusetts), and 0.6 (New York) per 1,000 adults based on 2010 census data. CONCLUSIONS: This was the first surveillance effort of adults with CHD-coded inpatient and outpatient health care encounters in 3 U.S. geographic locations using both administrative and clinical data sources. This information will provide a clearer understanding of health care use in this growing population. |
Investigation of Japanese encephalitis virus as a cause of acute encephalitis in southern Pakistan, April 2015-January 2018
Fatima T , Rais A , Khan E , Hills SL , Chambers TV , Hotwani A , Qureshi S , Shafquat S , Malik S , Qamar F , Mir F , Marfin AA , Zaidi A , Khowaja AR , Shakoor S . PLoS One 2020 15 (6) e0234584 BACKGROUND: Japanese encephalitis (JE) occurs in fewer than 1% of JE virus (JEV) infections, often with catastrophic sequelae including death and neuropsychiatric disability. JEV transmission in Pakistan was documented in 1980s and 1990s, but recent evidence is lacking. Our objective was to investigate JEV as a cause of acute encephalitis in Pakistan. METHODS: Persons aged >/=1 month with possible JE admitted to two acute care hospitals in Karachi, Pakistan from April 2015 to January 2018 were enrolled. Cerebrospinal fluid (CSF) or serum samples were tested for JEV immunoglobulin M (IgM) using the InBios JE DetectTM assay. Positive or equivocal samples had confirmatory testing using plaque reduction neutralization tests. RESULTS: Among 227 patients, testing was performed on CSF in 174 (77%) and on serum in 53 (23%) patients. Six of eight patient samples positive or equivocal for JEV IgM had sufficient volume for confirmatory testing. One patient had evidence of recent West Nile virus (WNV) neurologic infection based on CSF testing. One patient each had recent dengue virus (DENV) infection and WNV infection based on serum results. Recent flavivirus infections were identified in two persons, one each based on CSF and serum results. Specific flaviviruses could not be identified due to serologic cross-reactivity. For the sixth person, JEV neutralizing antibodies were confirmed in CSF but there was insufficient volume for further testing. CONCLUSIONS: Hospital-based JE surveillance in Karachi, Pakistan could not confirm or exclude local JEV transmission. Nonetheless, Pakistan remains at risk for JE due to presence of the mosquito vector, amplifying hosts, and rice irrigation. Laboratory surveillance for JE should continue among persons with acute encephalitis. However, in view of serological cross-reactivity, confirmatory testing of JE IgM positive samples at a reference laboratory is essential. |
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. |
Determinants of linear growth faltering among children with moderate-to-severe diarrhea in the Global Enteric Multicenter Study
Brander RL , Pavlinac PB , Walson JL , John-Stewart GC , Weaver MR , Faruque ASG , Zaidi AKM , Sur D , Sow SO , Hossain MJ , Alonso PL , Breiman RF , Nasrin D , Nataro JP , Levine MM , Kotloff KL . BMC Med 2019 17 (1) 214 BACKGROUND: Moderate-to-severe diarrhea (MSD) in the first 2 years of life can impair linear growth. We sought to determine risk factors for linear growth faltering and to build a clinical prediction tool to identify children most likely to experience growth faltering following an episode of MSD. METHODS: Using data from the Global Enteric Multicenter Study of children 0-23 months old presenting with MSD in Africa and Asia, we performed log-binomial regression to determine clinical and sociodemographic factors associated with severe linear growth faltering (loss of >/= 0.5 length-for-age z-score [LAZ]). Linear regression was used to estimate associations with DeltaLAZ. A clinical prediction tool was developed using backward elimination of potential variables, and Akaike Information Criterion to select the best fit model. RESULTS: Of the 5902 included children, mean age was 10 months and 43.2% were female. Over the 50-90-day follow-up period, 24.2% of children had severe linear growth faltering and the mean DeltaLAZ over follow-up was - 0.17 (standard deviation [SD] 0.54). After adjustment for age, baseline LAZ, and site, several factors were associated with decline in LAZ: young age, acute malnutrition, hospitalization at presentation, non-dysenteric diarrhea, unimproved sanitation, lower wealth, fever, co-morbidity, or an IMCI danger sign. Compared to children 12-23 months old, those 0-6 months were more likely to experience severe linear growth faltering (adjusted prevalence ratio [aPR] 1.97 [95% CI 1.70, 2.28]), as were children 6-12 months of age (aPR 1.72 [95% CI 1.51, 1.95]). A prediction model that included age, wasting, stunting, presentation with fever, and presentation with an IMCI danger sign had an area under the ROC (AUC) of 0.67 (95% CI 0.64, 0.69). Risk scores ranged from 0 to 37, and a cut-off of 21 maximized sensitivity (60.7%) and specificity (63.5%). CONCLUSION: Younger age, acute malnutrition, MSD severity, and sociodemographic factors were associated with short-term linear growth deterioration following MSD. Data routinely obtained at MSD may be useful to predict children at risk for growth deterioration who would benefit from interventions. |
Surveillance of congenital heart defects among adolescents at three U.S. sites
Lui GK , McGarry C , Bhatt A , Book W , Riehle-Colarusso TJ , Dunn JE , Glidewell J , Gurvitz M , Hoffman T , Hogue CJ , Hsu D , Obenhaus S , Raskind-Hood C , Rodriguez FH 3rd , Zaidi A , Van Zutphen AR . Am J Cardiol 2019 124 (1) 137-143 The prevalence, co-morbidities, and healthcare utilization in adolescents with congenital heart defects (CHDs) is not well understood. Adolescents (11 to 19 years old) with a healthcare encounter between January 1, 2008 (January 1, 2009 for MA) and December 31, 2010 with a CHD diagnosis code were identified from multiple administrative data sources compiled at 3 US sites: Emory University, Atlanta, Georgia (EU); Massachusetts Department of Public Health (MA); and New York State Department of Health (NY). The estimated prevalence for any CHD was 4.77 (EU), 17.29 (MA), and 4.22 (NY) and for severe CHDs was 1.34 (EU), 3.04 (MA), and 0.88 (NY) per 1,000 adolescents. Private or commercial insurance was the most common insurance type for EU and NY, and Medicaid for MA. Inpatient encounters were more frequent in severe CHDs. Cardiac co-morbidities included rhythm and conduction disorders at 20% (EU), 46% (MA), and 9% (NY) as well as heart failure at 3% (EU), 15% (MA), and 2% (NY). Leading noncardiac co-morbidities were respiratory/pulmonary (22% EU, 34% MA, 16% NY), infectious disease (17% EU, 22% MA, 20% NY), non-CHD birth defects (12% EU, 23% MA, 14% NY), gastrointestinal (10% EU, 28% MA, 13% NY), musculoskeletal (10% EU, 32% MA, 11% NY), and mental health (9% EU, 30% MA, 11% NY). In conclusion, this study used a novel approach of uniform CHD definition and variable selection across administrative data sources in 3 sites for the first population-based CHD surveillance of adolescents in the United States. High resource utilization and co-morbidities illustrate ongoing significant burden of disease in this vulnerable population. |
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%. |
Effectiveness of ten-valent pneumococcal conjugate vaccine against vaccine type invasive pneumococcal disease in Pakistan
Riaz A , Mohiuddin S , Husain S , Yousafzai MT , Muhammad S , Kabir F , Ur Rehman N , Mirza W , Salam B , Nadeem N , Pardhan K , Khan KMA , Raza SJ , Arif F , Iqbal K , Zuberi HK , Whitney CG , Omer SB , Zaidi AKM , Ali A . Int J Infect Dis 2018 80 28-33 OBJECTIVE: To assess PCV10 effectiveness against invasive pneumococcal disease (IPD) due to vaccine serotypes of Streptococcus pneumoniae (Sp) post introduction of vaccine in routine immunization program of Pakistan. METHODS: A matched case-control study was conducted at 16 hospitals in Sindh Province, Pakistan. Children <5years of age (eligible to receive PCV10) who presented with radiographic confirmed pneumonia and/or meningitis were enrolled as cases. PCR for Lyt A gene was conducted on blood (for radiographic pneumonia) and cerebrospinal fluid (for meningitis) samples to detect Sp. The proportion of IPD due to vaccine serotypes (including vaccine-related serogroups) was determined through serial multiplex PCR. For each case, at least five controls were enrolled from children hospitalized at the same institution, matched on age, district, and season. RESULTS: From 92 IPD cases enrolled during July 2013-March 2017, 24 cases (26.0%) were vaccine serotypes. Most case (87.5% of 24) and control (66.4% of 134) children had not received any PCV10 doses. Estimated effectiveness for PCV10 against vaccine type IPD was 72.7% (CI -7.2 to 92.6%) with at least one dose, 78.8% (CI -11.9 to 96.0%) for at least two doses and 81.9% (CI -55.7 to 97.9%) for all three doses of vaccine. INTERPRETATION: The VE point estimates for PCV10 were high and increased with increasing number of doses. However, VE estimates did not reach statistical significance, possibly due to low power. The findings indicate likely impact of vaccine in reducing burden of vaccine type IPD if vaccine uptake can be improved. |
Progress in voluntary medical male circumcision for HIV prevention supported by the US President's Emergency Plan for AIDS Relief through 2017: longitudinal and recent cross-sectional programme data
Davis SM , Hines JZ , Habel M , Grund JM , Ridzon R , Baack B , Davitte J , Thomas A , Kiggundu V , Bock N , Pordell P , Cooney C , Zaidi I , Toledo C . BMJ Open 2018 8 (8) e021835 OBJECTIVE: This article provides an overview and interpretation of the performance of the US President's Emergency Plan for AIDS Relief's (PEPFAR's) male circumcision programme which has supported the majority of voluntary medical male circumcisions (VMMCs) performed for HIV prevention, from its 2007 inception to 2017, and client characteristics in 2017. DESIGN: Longitudinal collection of routine programme data and disaggregations. SETTING: 14 countries in sub-Saharan Africa with low baseline male circumcision coverage, high HIV prevalence and PEPFAR-supported VMMC programmes. PARTICIPANTS: Clients of PEPFAR-supported VMMC programmes directed at males aged 10 years and above. MAIN OUTCOME MEASURES: Numbers of circumcisions performed and disaggregations by age band, result of HIV test offer, procedure technique and follow-up visit attendance. RESULTS: PEPFAR supported a total of 15 269 720 circumcisions in 14 countries in Southern and Eastern Africa. In 2017, 45% of clients were under 15 years of age, 8% had unknown HIV status, 1% of those tested were HIV+ and 84% returned for a follow-up visit within 14 days of circumcision. CONCLUSIONS: Over 15 million VMMCs have been supported by PEPFAR since 2007. VMMC continues to attract primarily young clients. The non-trivial proportion of clients not testing for HIV is expected, and may be reassuring that testing is not being presented as mandatory for access to circumcision, or in some cases reflect test kit stockouts or recent testing elsewhere. While VMMC is extremely safe, achieving the highest possible follow-up rates for early diagnosis and intervention on complications is crucial, and programmes continue to work to raise follow-up rates. The VMMC programme has achieved rapid scale-up but continues to face challenges, and new approaches may be needed to achieve the new Joint United Nations Programme on HIV/AIDS goal of 27 million additional circumcisions through 2020. |
Causes and incidence of community-acquired serious infections among young children in south Asia (ANISA): an observational cohort study
Saha SK , Schrag SJ , El Arifeen S , Mullany LC , Shahidul Islam M , Shang N , Qazi SA , Zaidi AKM , Bhutta ZA , Bose A , Panigrahi P , Soofi SB , Connor NE , Mitra DK , Isaac R , Winchell JM , Arvay ML , Islam M , Shafiq Y , Nisar I , Baloch B , Kabir F , Ali M , Diaz MH , Satpathy R , Nanda P , Padhi BK , Parida S , Hotwani A , Hasanuzzaman M , Ahmed S , Belal Hossain M , Ariff S , Ahmed I , Ibne Moin SM , Mahmud A , Waller JL , Rafiqullah I , Quaiyum MA , Begum N , Balaji V , Halen J , Nawshad Uddin Ahmed ASM , Weber MW , Hamer DH , Hibberd PL , Sadeq-Ur Rahman Q , Mogan VR , Hossain T , McGee L , Anandan S , Liu A , Panigrahi K , Abraham AM , Baqui AH . Lancet 2018 392 (10142) 145-159 BACKGROUND: More than 500 000 neonatal deaths per year result from possible serious bacterial infections (pSBIs), but the causes are largely unknown. We investigated the incidence of community-acquired infections caused by specific organisms among neonates in south Asia. METHODS: From 2011 to 2014, we identified babies through population-based pregnancy surveillance at five sites in Bangladesh, India, and Pakistan. Babies were visited at home by community health workers up to ten times from age 0 to 59 days. Illness meeting the WHO definition of pSBI and randomly selected healthy babies were referred to study physicians. The primary objective was to estimate proportions of specific infectious causes by blood culture and Custom TaqMan Array Cards molecular assay (Thermo Fisher, Bartlesville, OK, USA) of blood and respiratory samples. FINDINGS: 6022 pSBI episodes were identified among 63 114 babies (95.4 per 1000 livebirths). Causes were attributed in 28% of episodes (16% bacterial and 12% viral). Mean incidence of bacterial infections was 13.2 (95% credible interval [CrI] 11.2-15.6) per 1000 livebirths and of viral infections was 10.1 (9.4-11.6) per 1000 livebirths. The leading pathogen was respiratory syncytial virus (5.4, 95% CrI 4.8-6.3 episodes per 1000 livebirths), followed by Ureaplasma spp (2.4, 1.6-3.2 episodes per 1000 livebirths). Among babies who died, causes were attributed to 46% of pSBI episodes, among which 92% were bacterial. 85 (83%) of 102 blood culture isolates were susceptible to penicillin, ampicillin, gentamicin, or a combination of these drugs. INTERPRETATION: Non-attribution of a cause in a high proportion of patients suggests that a substantial proportion of pSBI episodes might not have been due to infection. The predominance of bacterial causes among babies who died, however, indicates that appropriate prevention measures and management could substantially affect neonatal mortality. Susceptibility of bacterial isolates to first-line antibiotics emphasises the need for prudent and limited use of newer-generation antibiotics. Furthermore, the predominance of atypical bacteria we found and high incidence of respiratory syncytial virus indicated that changes in management strategies for treatment and prevention are needed. Given the burden of disease, prevention of respiratory syncytial virus would have a notable effect on the overall health system and achievement of Sustainable Development Goal. FUNDING: Bill & Melinda Gates Foundation. |
Seroprevalence of herpes simplex virus types 1 and 2 among pregnant women and sexually active, non-pregnant women in the United States
Patton ME , Bernstein K , Liu G , Zaidi A , Markowitz LE . Clin Infect Dis 2018 67 (10) 1535-1542 Background: Neonatal herpes is a rare, devastating consequence of herpes simplex virus type 1 (HSV-1) or 2 (HSV-2) infection during pregnancy. The risk of neonatal infection is higher among pregnant women seronegative for HSV-1 or HSV-2 who acquire their first HSV infection near delivery. Methods: We estimated HSV-1 and HSV-2 seroprevalence among pregnant women aged 20-39 years in 1999-2014, assessed HSV seroprevalence changes between 1999-2006 and 2007-2014, and compared HSV seroprevalence between pregnant women and sexually active, non-pregnant women aged 20-39 years in 2007-2014 using National Health and Nutrition Examination Survey data. Results: Among pregnant women in 1999-2014, HSV-1 seroprevalence was 59.3%, HSV-2 seroprevalence was 21.1%, and HSV seronegativity was 30.6%. Between 1999-2006 and 2007-2014, HSV-1 and HSV-2 seroprevalence among pregnant women remained stable. However, among pregnant women with </=3 sex partners (approximately 40% of all pregnant women), seronegativity for both HSV-1 and HSV-2 increased from 35.6% to 51.4% (P<.05). In 2007-2014, non-pregnant women who were 1) unmarried, 2) living below poverty level, or 3) had >/=4 sex partners were more likely than pregnant women to be seronegative for both HSV-1 and HSV-2 (P<.05). Conclusions: HSV-1 and HSV-2 seroprevalence among U.S. pregnant women remained stable between 1999-2014. However, pregnant women with fewer sex partners were increasingly seronegative for both HSV-1 and HSV-2, indicating an increasing proportion of pregnant women who are vulnerable to primary HSV acquisition in pregnancy which confers an increased risk of transmitting HSV to their neonates. |
Rotavirus surveillance in Pakistan during 2015-2016 reveals high prevalence of G12P[6]
Umair M , Salman M , Alam MM , Rana MS , Zaidi SSZ , Bowen MD , Aamir UB , Abbasi BH . J Med Virol 2018 90 (7) 1272-1276 The G12 rotavirus genotype has emerged globally since their first detection in 1987 from the Philippines; however it remains a rare cause of gastroenteritis in Pakistan. Rotavirus surveillance conducted during 2015-2016, assessed 3446 children <5 years hospitalized for gastroenteritis and found 802 (23.2%) positive on ELISA. Genotyping of a subset of positive samples (n = 319) revealed G12P[6] (11.28%) as the third most common G/P combination following G3P[8] (28.5%) and G1P[8] (12.5%); G2P[4] (10.65%) and G3P[6] (8.15%) were other frequently detected strains. Phylogenetic analysis of G12 strains from Pakistan revealed high genetic similarity to G12 strains from Italy, Thailand, Korea and Great Britain as well as local strains within G12 lineage III. In conclusion, G12P[6] was a major contributor of RVA gastroenteritis in Pakistani children. Robust surveillance after the introduction of rotavirus vaccines will help determine the evolution of G12 and other circulating genotypes in the country. This article is protected by copyright. All rights reserved. |
A pragmatic approach to monitor and evaluate implementation and impact of differentiated ART delivery for global and national stakeholders
Ehrenkranz PD , Calleja JM , El-Sadr W , Fakoya AO , Ford N , Grimsrud A , Harris KL , Jed SL , Low-Beer D , Patel SV , Rabkin M , Reidy WJ , Reinisch A , Siberry GK , Tally LA , Zulu I , Zaidi I . J Int AIDS Soc 2018 21 (3) INTRODUCTION: The World Health Organization's (WHO) recommendation of "Treat All" has accelerated the call for differentiated antiretroviral therapy (ART) delivery, a method of care that efficiently uses limited resources to increase access to HIV treatment. WHO has further recommended that stable individuals on ART receive refills every 3 to 6 months and attend clinical visits every 3 to 6 months. However, there is not yet consensus on how to ensure that the quality of services is maintained as countries strive to meet these standards. This commentary responds to this gap by defining a pragmatic approach to the monitoring and evaluation (M&E) of the scale up of differentiated ART delivery for global and national stakeholders. DISCUSSION: Programme managers need to demonstrate that the scale up of differentiated ART delivery is achieving the desired effectiveness and efficiency outcomes to justify continued support by national and global stakeholders. To achieve this goal, the two existing global WHO HIV treatment indicators of ART retention and viral suppression should be augmented with two broad aggregate measures. The addition of indicators measuring the frequency of (1) clinical and (2) refill visits by PLHIV per year will allow evaluation of the pace of scale up while monitoring its overall effect on the quality and efficiency of services. The combination of these four routinely collected aggregate indicators will also facilitate the comparison of outcomes among facilities, regions or countries implementing different models of ART delivery. Enhanced monitoring or additional assessments will be required to answer other critical questions on the process of implementation, acceptability, effectiveness and efficiency. CONCLUSIONS: These proposed outcomes are useful markers for the effectiveness and efficiency of the health system's attempts to deliver quality treatment to those who need it-and still reserve as much of the available resource pool as possible for other key elements of the HIV response. |
Evaluation of vaccine derived poliovirus type 2 outbreak response options: A randomized controlled trial, Karachi, Pakistan
Saleem AF , Yousafzai MT , Mach O , Khan A , Quadri F , Weldon WC , Oberste MS , Zaidi SS , Alam MM , Sutter RW , Zaidi AKM . Vaccine 2018 36 (13) 1766-1771 BACKGROUND: Outbreaks of circulating vaccine derived polioviruses type 2 (cVDPV2) remain a risk to poliovirus eradication in an era without live poliovirus vaccine containing type 2 in routine immunization. We evaluated existing outbreak response strategies recommended by the World Health Organization (WHO) for control of cVDPV2 outbreaks. METHODS: Seronegative children for poliovirus type 2 (PV2) at 22weeks of life were assigned to one of four study groups and received respectively (1) one dose of trivalent oral poliovirus vaccine (tOPV); (2) monovalent OPV 2 (mOPV2); (3) tOPV together with a dose of inactivated poliovirus vaccine (IPV); or (4) mOPV2 with monovalent high-potency IPV type 2. Stool and blood samples were collected and assessed for presence of PV2 (stool) and anti-polio antibodies (sera). RESULTS: We analyzed data from 265 children seronegative for PV2. Seroconversion to PV2 was achieved in 48, 76, 98 and 100% in Groups 1-4 respectively. mOPV2 was more immunogenic than tOPV alone (p<0.001); and OPV in combination with IPV was more immunogenic than OPV alone (p<0.001). There were 33%, 67%, 20% and 43% PV2 excretors in Groups 1-4 respectively. mOPV2 resulted in more prevalent shedding of PV2 than when tOPV was used (p<0.001); and tOPV together with IPV resulted in lower excretion of PV2 than tOPV alone (p=0.046). CONCLUSION: mOPV2 was a more potent vaccine than tOPV. Adding IPV to OPV improved immunological response; adding IPV also seemed to have shortened the duration of PV2 shedding. mIPV2 did not provide measurable improvement of immune response when compared to conventional IPV. WHO recommendation to use mOPV2 as a vaccine of first choice in cVDPV2 outbreak response was supported by our findings. Clinical Trial registry number: NCT02189811. |
Diagnostic Assay Development for Poliovirus Eradication.
Gerloff N , Sun H , Mandelbaum M , Maher C , Nix WA , Zaidi S , Shaukat S , Seakamela L , Nalavade UP , Sharma DK , Oberste MS , Vega E . J Clin Microbiol 2017 56 (2) With poliovirus eradication nearing, few pockets of active wild poliovirus (WPV) transmission remain in the world. Intratypic differentiation (ITD) plays a crucial part in laboratory surveillance as the molecular detection method that can identify and distinguish wild and vaccine-like polioviruses isolated from acute flaccid paralysis cases or environmental sources. The need to detect new variants of WPV serotype 1 (WPV1), and the containment of all serotype 2 polioviruses (PV2) in 2015 required changes to the previous version of the method. The ITD version 5.0 is a set of six real-time RT-PCR (rRT-PCR) assays that serve as accurate diagnostic tools to easily detect and differentiate PV serotypes and genotypes. We describe the creation and properties of quantitation standards, including 16 control RNA transcripts, and nine plaque-isolated viruses. All ITD rRT-PCR assays were validated using these standards and the limits of detection were determined for each assay. We designed and pilot-tested two new assays targeting recently circulating WPV1 genotypes and all PV2. The WPV1 assay specificity was 99.1%, and sensitivity 100%, and the PV2 assay had 97.7% specificity, and 92% sensitivity.Before proceeding to the next step in the global poliovirus eradication program we needed to gain a better understanding of the performance of the ITD 5.0 suite of molecular assays and their limits of detection and specificities. The findings and conclusions in this evaluation serve as building blocks for future development work. |
HIV surveillance among pregnant women attending antenatal clinics: Evolution and current direction
Dee J , Garcia Calleja JM , Marsh K , Zaidi I , Murrill C , Swaminathan M . JMIR Public Health Surveill 2017 3 (4) e85 Since the late 1980s, human immunodeficiency virus (HIV) sentinel serosurveillance among pregnant women attending select antenatal clinics (ANCs) based on unlinked anonymous testing (UAT) has provided invaluable information for tracking HIV prevalence and trends and informing global and national HIV models in most countries with generalized HIV epidemics. However, increased coverage of HIV testing, prevention of mother-to-child transmission (PMTCT), and antiretroviral therapy has heightened ethical concerns about UAT. PMTCT programs now routinely collect demographic and HIV testing information from the same pregnant women as serosurveillance and therefore present an alternative to UAT-based ANC serosurveillance. This paper reports on the evolution and current direction of the global approach to HIV surveillance among pregnant women attending ANCs, including the transition away from traditional UAT-based serosurveillance and toward new guidance from the World Health Organization and the Joint United Nations Programme on HIV/AIDS on the implementation of surveillance among pregnant women attending ANCs based on routine PMTCT program data. |
Proximity to pediatric cardiac surgical care among adolescents with congenital heart defects in 11 New York counties
Sommerhalter KM , Insaf TZ , Akkaya-Hocagil T , McGarry CE , Farr SL , Downing KF , Lui GK , Zaidi AN , Van Zutphen AR . Birth Defects Res 2017 109 (18) 1494-1503 BACKGROUND: Many individuals with congenital heart defects (CHDs) discontinue cardiac care in adolescence, putting them at risk of adverse health outcomes. Because geographic barriers may contribute to cessation of care, we sought to characterize geographic access to comprehensive cardiac care among adolescents with CHDs. METHODS: Using a population-based, 11-county surveillance system of CHDs in New York, we characterized proximity to the nearest pediatric cardiac surgical care center among adolescents aged 11 to 19 years with CHDs. Residential addresses were extracted from surveillance records documenting 2008 to 2010 healthcare encounters. Addresses were geocoded using ArcGIS and the New York State Street and Address Maintenance Program, a statewide address point database. One-way drive and public transit time from residence to nearest center were calculated using R packages gmapsdistance and rgeos with the Google Maps Distance Matrix application programming interface. A marginal model was constructed to identify predictors associated with one-way travel time. RESULTS: We identified 2522 adolescents with 3058 corresponding residential addresses and 12 pediatric cardiac surgical care centers. The median drive time from residence to nearest center was 18.3 min, and drive time was 30 min or less for 2475 (80.9%) addresses. Predicted drive time was longest for rural western addresses in high poverty census tracts (68.7 min). Public transit was available for most residences in urban areas but for few in rural areas. CONCLUSION: We identified areas with geographic barriers to surgical care. Future research is needed to determine how these barriers influence continuity of care among adolescents with CHDs. Birth Defects Research 109:1494-1503, 2017.(c) 2017 Wiley Periodicals, Inc. |
Immunogenicity of different routine poliovirus vaccination schedules: A randomized controlled trial, Karachi, Pakistan
Saleem AF , Mach O , Yousafzai MT , Khan A , Weldon WC , Oberste MS , Zaidi SS , Alam MM , Quadri F , Sutter RW , Zaidi AKM . J Infect Dis 2017 217 (3) 443-450 Background: We assessed immunity against polioviruses induced with new Pakistani immunization schedule and compared it with alternative immunization schedules. Methods: Newborns were randomized to receive one of the following vaccination schedules, administered at birth, 6, 10, and 14 weeks of age. Arm A: 4x IPV; Arm B: 4x bOPV; Arm C and D: bOPV, bOPV, bOPV, bOPV+ inactivated poliovirus vaccine (IPV); Arm E: 4x trivalent oral poliovirus vaccine (tOPV). At 22 weeks of age, children received one challenge dose of tOPV, and children in arm D received one additional IPV dose. Sera were analyzed for presence of polio neutralizing antibodies at birth, 14, and 22 weeks of age. Results: Study arms A-E, the seroconversion for PV1 at 22 weeks of age was 80%, 97%, 94%, 96%, 94% respectively; for PV2: 84%, 19%, 53%, 49%, 93%; and for PV3: 93%, 94%, 98%, 94%, 85%. Interpretation: Current immunization schedule in Pakistan induced high seroconversion rates for PV1 and PV3; however, it induced PV2 seroconversion in only half of study subjects. There is a growing cohort of young children in Pakistan who are unprotected against PV2; and this creates an increasing risk of a large-scale outbreak of poliomyelitis caused by circulating vaccine-derived PV2. |
The role of supplementary environmental surveillance to complement acute flaccid paralysis surveillance for wild poliovirus in Pakistan - 2011-2013.
Cowger TL , Burns CC , Sharif S , Gary HE Jr , Iber J , Henderson E , Malik F , Zahoor Zaidi SS , Shaukat S , Rehman L , Pallansch MA , Orenstein WA . PLoS One 2017 12 (7) e0180608 BACKGROUND: More than 99% of poliovirus infections are non-paralytic and therefore, not detected by acute flaccid paralysis (AFP) surveillance. Environmental surveillance (ES) can detect circulating polioviruses from sewage without relying on clinical presentation. With extensive ES and continued circulation of polioviruses, Pakistan presents a unique opportunity to quantify the impact of ES as a supplement to AFP surveillance on overall completeness and timeliness of poliovirus detection. METHODS: Genetic, geographic and temporal data were obtained for all wild poliovirus (WPV) isolates detected in Pakistan from January 2011 through December 2013. We used viral genetics to assess gaps in AFP surveillance and ES as measured by detection of 'orphan viruses' (≥1.5% different in VP1 capsid nucleotide sequence). We compared preceding detection of closely related circulating isolates (≥99% identity) detected by AFP surveillance or ES to determine which surveillance system first detected circulation before the presentation of each polio case. FINDINGS: A total of 1,127 WPV isolates were detected by AFP surveillance and ES in Pakistan from 2011-2013. AFP surveillance and ES combined exhibited fewer gaps (i.e., % orphan viruses) in detection than AFP surveillance alone (3.3% vs. 7.7%, respectively). ES detected circulation before AFP surveillance in nearly 60% of polio cases (200 of 346). For polio cases reported from provinces conducting ES, ES detected circulation nearly four months sooner on average (117.6 days) than did AFP surveillance. INTERPRETATION: Our findings suggest ES in Pakistan is providing earlier, more sensitive detection of wild polioviruses than AFP surveillance alone. Overall, targeted ES through strategic selection of sites has important implications in the eradication endgame strategy. |
Needle adapters for intradermal administration of fractional dose of inactivated poliovirus vaccine: Evaluation of immunogenicity and programmatic feasibility in Pakistan
Saleem AF , Mach O , Yousafzai MT , Khan A , Weldon WC , Oberste MS , Sutter RW , Zaidi AKM . Vaccine 2017 35 (24) 3209-3214 Administration of 1/5th dose of Inactivated poliovirus vaccine intradermally (fIPV) provides similar immune response as full-dose intramuscular IPV, however, fIPV administration with BCG needle and syringe (BCG NS) is technically difficult. We compared immune response after one fIPV dose administered with BCG NS to administration with intradermal devices, referred to as Device A and B; and assessed feasibility of conducting a door-to-door vaccination campaign with fIPV. In Phase I, 452 children 6-12months old from Karachi were randomized to receive one fIPV dose either with BCG NS, Device A or Device B in a health facility. Immune response was defined as seroconversion or fourfold rise in polio neutralizing antibody titer 28days after fIPV among children whose baseline titer ≤362. In Phase II, fIPV was administered during one-day door-to-door campaign to assess programmatic feasibility by evaluating vaccinators' experience. For all three poliovirus (PV) serotypes, the immune response after BCG NS and Device A was similar, however it was lower with Device B (34/44 (77%), 31/45 (69%), 16/30 (53%) respectively for PV1; 53/78 (68%), 61/83 (74%), 42/80 (53%) for PV2; and; 58/76 (76%), 56/80 (70%), 43/77 (56%) for PV3; p<0.05 for all three serotypes). Vaccinators reported problems filling Device B in both Phases; no other operational challenges were reported during Phase II. Use of fIPV offers a dose-saving alternative to full-dose IPV. |
Case-control vaccine effectiveness studies: Data collection, analysis and reporting results
Verani JR , Baqui AH , Broome CV , Cherian T , Cohen C , Farrar JL , Feikin DR , Groome MJ , Hajjeh RA , Johnson HL , Madhi SA , Mulholland K , O'Brien KL , Parashar UD , Patel MM , Rodrigues LC , Santosham M , Scott JA , Smith PG , Sommerfelt H , Tate JE , Victor JC , Whitney CG , Zaidi AK , Zell ER . Vaccine 2017 35 (25) 3303-3308 The case-control methodology is frequently used to evaluate vaccine effectiveness post-licensure. The results of such studies provide important insight into the level of protection afforded by vaccines in a 'real world' context, and are commonly used to guide vaccine policy decisions. However, the potential for bias and confounding are important limitations to this method, and the results of a poorly conducted or incorrectly interpreted case-control study can mislead policies. In 2012, a group of experts met to review recent experience with case-control studies evaluating vaccine effectiveness; we summarize the recommendations of that group regarding best practices for data collection, analysis, and presentation of the results of case-control vaccine effectiveness studies. Vaccination status is the primary exposure of interest, but can be challenging to assess accurately and with minimal bias. Investigators should understand factors associated with vaccination as well as the availability of documented vaccination status in the study context; case-control studies may not be a valid method for evaluating vaccine effectiveness in settings where many children lack a documented immunization history. To avoid bias, it is essential to use the same methods and effort gathering vaccination data from cases and controls. Variables that may confound the association between illness and vaccination are also important to capture as completely as possible, and where relevant, adjust for in the analysis according to the analytic plan. In presenting results from case-control vaccine effectiveness studies, investigators should describe enrollment among eligible cases and controls as well as the proportion with no documented vaccine history. Emphasis should be placed on confidence intervals, rather than point estimates, of vaccine effectiveness. Case-control studies are a useful approach for evaluating vaccine effectiveness; however careful attention must be paid to the collection, analysis and presentation of the data in order to best inform evidence-based vaccine policies. |
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