Last data update: Nov 11, 2024. (Total: 48109 publications since 2009)
Records 1-30 (of 31 Records) |
Query Trace: Qureshi I[original query] |
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A six-year follow-up of bloodstream infections in hemodialysis facilities in the United States, National Healthcare Safety Network, 2020
Keenan J , Barbre KA , Dollard P , Hoxworth T , Qureshi I , Dunham L , O'Leary E , Nuwoaty SA , Bagchi S , Edwards J , Lu M , Benin A , Bell J . Clin J Am Soc Nephrol 2024 METHODS: Outpatient hemodialysis facilities report BSI events to NHSN. Pooled mean rates with 95% CI were calculated overall and for each type of vascular access (arteriovenous (AV) fistula, AV graft, or a central venous catheter (CVC)). Standardized infection ratios were calculated as observed BSI events divided by the predicted number of events based on national aggregate data. Median facility-level standardized infection ratios and 95% confidence intervals (CIs) were stratified by state and US territory. RESULTS: During 2020, 7,183 outpatient hemodialysis facilities reported data for 5,235,234 patient months with 15,181 BSI events. Pooled mean rates per 100 person-months were 0.29 (95% CI, 0.29-0.30) overall, 0.80 (95% CI, 0.78-0.82) for CVC, 0.12 (95% CI, 0.12-0.12) for AV fistula, 0.21 (95% CI, 0.20-0.22) for AV graft, and 0.28 (95% CI, 0.19-0.40) for other access types. The national standardized infection ratio was 0.40 (95% CI, 0.39-0.41). South Dakota had a standardized infection ratio significantly higher than one (1.34; 95% CI, 1.11 - 1.62). Fifty-one of 54 states and territories had BSI standardized infection ratio significantly lower than one. CONCLUSIONS: In 2020, the median standardized infection ratio for BSI in US outpatient hemodialysis facilities was lower than predicted overall and in almost all states and territories. An elevated standardized infection ratio was identified in South Dakota. |
Declines in influenza vaccination coverage among health care personnel in acute care hospitals during the COVID-19 pandemic - United States, 2017-2023
Lymon H , Meng L , Reses HE , Barbre K , Dubendris H , Shafi S , Wiegand R , Reddy Grty , Woods A , Kuhar DT , Stuckey MJ , Lindley MC , Haas L , Qureshi I , Wong E , Benin A , Bell JM . MMWR Morb Mortal Wkly Rep 2023 72 (45) 1244-1247 Health care personnel (HCP) are recommended to receive annual vaccination against influenza to reduce influenza-related morbidity and mortality. Every year, acute care hospitals report receipt of influenza vaccination among HCP to CDC's National Healthcare Safety Network (NHSN). This analysis used NHSN data to describe changes in influenza vaccination coverage among HCP in acute care hospitals before and during the COVID-19 pandemic. Influenza vaccination among HCP increased during the prepandemic period from 88.6% during 2017-18 to 90.7% during 2019-20. During the COVID-19 pandemic, the percentage of HCP vaccinated against influenza decreased to 85.9% in 2020-21 and 81.1% in 2022-23. Additional efforts are needed to implement evidence-based strategies to increase vaccination coverage among HCP and to identify factors associated with recent declines in influenza vaccination coverage. |
Pneumococcal carriage and changes in serotype distribution post- PCV13 introduction in children in Matiari, Pakistan
Iqbal I , Shahid S , Kanwar S , Kabir F , Umrani F , Ahmed S , Khan W , Qazi MF , Aziz F , Muneer S , Kalam A , Hotwani A , Mehmood J , Qureshi AK , Hasan Z , Shakoor S , Mirza S , McGee L , Lo SW , Kumar N , Azam I , Bentley SD , Jehan F , Nisar MI . Vaccine 2024 42 (23) 126238 BACKGROUND: In early 2021, the 10-valent Pneumococcal conjugate vaccine (PCV10) was replaced with 13-valent (PCV13) by the federal directorate of immunization (FDI), Pakistan. We assessed the impact of a higher valent vaccine, PCV13, on the serotype distribution of nasopharyngeal carriage in rural Pakistan. METHODS: Children <2 years were randomly selected from two rural union councils of Matiari, Sindh in Pakistan between September-October,2022. Clinical, sociodemographic and vaccination histories were recorded. Nasopharyngeal swabs were collected and processed at Infectious Disease Research Laboratory, Aga Khan University, Karachi. Whole genome sequencing was performed on the culture positive isolates. RESULTS: Of the 200 children enrolled, pneumococcus was detected in 140(70 %) isolates. Majority of age-eligible children (60.1 %,110/183) received 3 PCV13 doses. PCV10 carriage declined from 13.2 %(78/590) in 2017/18 to 7.2 % (10/140) in 2022, additional PCV13 serotypes (3, 6A/6C and 19A) decreased from 18.5 %(109/590) to 11.4 %(16/140) while non-PCV13 serotypes increased from 68.3 %(403/590) to 81.4 %(114/140). There were 88.5 %(n = 124), 80.7 %(n = 113), 55.0 %(n = 77), and 46.0 %(n = 65) isolates predicted to be resistant to cotrimoxazole, penicillin(meningitis cut-off), tetracycline, and erythromycin respectively. CONCLUSION: Replacing PCV10 with PCV13 rapidly decreased prevalence of PCV13 carriage among vaccinated children in Matiari, Pakistan. Vaccine-driven selection pressure may have been responsible for the increase of non-PCV13 serotypes. |
SARS-CoV-2 infection and death rates among maintenance dialysis patients during Delta and early Omicron waves - United States, June 30, 2021-September 27, 2022
Navarrete J , Barone G , Qureshi I , Woods A , Barbre K , Meng L , Novosad S , Li Q , Soe MM , Edwards J , Wong E , Reses HE , Guthrie S , Keenan J , Lamping L , Park M , Dumbuya S , Benin AL , Bell J . MMWR Morb Mortal Wkly Rep 2023 72 (32) 871-876 Persons receiving maintenance dialysis are at increased risk for SARS-CoV-2 infection and its severe outcomes, including death. However, rates of SARS-CoV-2 infection and COVID-19-related deaths in this population are not well described. Since November 2020, CDC's National Healthcare Safety Network (NHSN) has collected weekly data monitoring incidence of SARS-CoV-2 infections (defined as a positive SARS-CoV-2 test result) and COVID-19-related deaths (defined as the death of a patient who had not fully recovered from a SARS-CoV-2 infection) among maintenance dialysis patients. This analysis used NHSN dialysis facility COVID-19 data reported during June 30, 2021-September 27, 2022, to describe rates of SARS-CoV-2 infection and COVID-19-related death among maintenance dialysis patients. The overall infection rate was 30.47 per 10,000 patient-weeks (39.64 among unvaccinated patients and 27.24 among patients who had completed a primary COVID-19 vaccination series). The overall death rate was 1.74 per 10,000 patient-weeks. Implementing recommended infection control measures in dialysis facilities and ensuring patients and staff members are up to date with recommended COVID-19 vaccination is critical to limiting COVID-19-associated morbidity and mortality. |
Factors influencing the decision to receive seasonal influenza vaccination among US corporate non-healthcare workers.
Aguolu OG , Willebrand K , Elharake JA , Qureshi HM , Kiti MC , Liu CY , Restrepo Mesa A , Nelson K , Jenness S , Melegaro A , Ahmed F , Yildirim I , Malik FA , Lopman B , Omer SB . Hum Vaccin Immunother 2022 18 (6) 2122379 Influenza causes significant mortality and morbidity in the United States (US). Employees are exposed to influenza at work and can spread it to others. The influenza vaccine is safe, effective, and prevents severe outcomes; however, coverage among US adults (50.2%) is below Healthy People 2030 target of 70%. These highlights need for more effective vaccination promotion interventions. Understanding predictors of vaccination acceptance could inform vaccine promotion messages, improve coverage, and reduce illness-related work absences. We aimed to identify factors influencing influenza vaccination among US non-healthcare workers. Using mixed-methods approach, we evaluated factors influencing influenza vaccination among employees in three US companies during April-June 2020. Survey questions were adapted from the WHO seasonal influenza survey. Most respondents (n = 454) were women (272, 59.9%), 20-39 years old (n = 250, 55.1%); white (n = 254, 56.0%); had a college degree (n = 431, 95.0%); and reported receiving influenza vaccine in preceding influenza season (n = 297, 65.4%). Logistic regression model was statistically significant, X (16, N = 450) = 31.6, p = .01. Education [(OR) = 0.3, 95%CI = 0.1-0.6)] and race (OR = 0.4, 95%CI = 0.2-0.8) were significant predictors of influenza vaccine acceptance among participants. The majority had favorable attitudes toward influenza vaccination and reported that physician recommendation would influence their vaccination decisions. Seven themes were identified in qualitative analysis: "Protecting others" (109, 24.0%), "Protecting self" (105, 23.1%), "Vaccine accessibility" (94, 20.7%), "Education/messaging" (71, 15.6%), "Policies/requirements" (15, 3.3%), "Reminders" (9, 2.0%), and "Incentives" (3, 0.7%). Our findings could facilitate the development of effective influenza vaccination promotion messages and programs for employers, and workplace vaccination programs for other diseases such as COVID-19, by public health authorities. | Influenza causes significant mortality and morbidity in the United States (US).The US working-age group (18–64-year-old) bears a huge burden of influenza annually.Influenza vaccination coverage in the working-age group is low.Physicians and employers can influence vaccine acceptance of working adults.Employers can consider practical steps, e.g., incentivizing, or offering vaccine onsite. | eng |
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. |
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. |
Characterization of Reference Materials for Spinal Muscular Atrophy Genetic Testing: A GeT-RM Collaborative Project.
Prior TW , Bayrak-Toydemir P , Lynnes TC , Mao R , Metcalf JD , Muralidharan K , Iwata-Otsubo A , Pham HT , Pratt VM , Qureshi S , Requesens D , Shen J , Vetrini F , Kalman L . J Mol Diagn 2020 23 (1) 103-110 Spinal muscular atrophy (SMA) is an autosomal recessive disorder predominately caused by bi-allelic loss of the SMN1 gene. Increased copies of SMN2, a low functioning nearly identical paralog, is associated with a less severe phenotype. SMA was recently recommended for inclusion in newborn screening. Clinical laboratories must accurately measure SMN1 and SMN2 copy number to identify SMA patients, carriers, and to identify individuals likely to benefit from therapeutic interventions. Having publicly available and appropriately characterized reference materials with various combinations of SMN1 and SMN2 copy number variants is critical to assure accurate SMA clinical testing. To address this need, the Centers for Disease Control and Prevention based Genetic Testing Reference Material Coordination Program (GeT-RM), in collaboration with members of the genetic testing community and the Coriell Institute for Medical Research, have characterized 15 SMA reference materials derived from publicly available cell lines. DNA samples were distributed to four volunteer testing laboratories for genotyping using 3 different methods. The characterized samples had 0-4 copies of SMN1 and 0-5 copies SMN2. The samples also contained clinically important allele combinations (eg. 0 copies SMN1, 3 copies SMN2), and several had markers indicative of a SMA carrier. These and other reference materials characterized by the GeT-RM will support the quality of clinical laboratory testing and are available from the Coriell Institute. |
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. |
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. |
Effects and cost of different strategies to eliminate hepatitis C virus transmission in Pakistan: a modelling analysis
Lim AG , Walker JG , Mafirakureva N , Khalid GG , Qureshi H , Mahmood H , Trickey A , Fraser H , Aslam K , Falq G , Fortas C , Zahid H , Naveed A , Auat R , Saeed Q , Davies CF , Mukandavire C , Glass N , Maman D , Martin NK , Hickman M , May MT , Hamid S , Loarec A , Averhoff F , Vickerman P . Lancet Glob Health 2020 8 (3) e440-e450 BACKGROUND: The WHO elimination strategy for hepatitis C virus advocates scaling up screening and treatment to reduce global hepatitis C incidence by 80% by 2030, but little is known about how this reduction could be achieved and the costs of doing so. We aimed to evaluate the effects and cost of different strategies to scale up screening and treatment of hepatitis C in Pakistan and determine what is required to meet WHO elimination targets for incidence. METHODS: We adapted a previous model of hepatitis C virus transmission, treatment, and disease progression for Pakistan, calibrating using available data to incorporate a detailed cascade of care for hepatitis C with cost data on diagnostics and hepatitis C treatment. We modelled the effect on various outcomes and costs of alternative scenarios for scaling up screening and hepatitis C treatment in 2018-30. We calibrated the model to country-level demographic data for 1960-2015 (including population growth) and to hepatitis C seroprevalence data from a national survey in 2007-08, surveys among people who inject drugs (PWID), and hepatitis C seroprevalence trends among blood donors. The cascade of care in our model begins with diagnosis of hepatitis C infection through antibody screening and RNA confirmation. Diagnosed individuals are then referred to care and started on treatment, which can result in a sustained virological response (effective cure). We report the median and 95% uncertainty interval (UI) from 1151 modelled runs. FINDINGS: One-time screening of 90% of the 2018 population by 2030, with 80% referral to treatment, was projected to lead to 13.8 million (95% UI 13.4-14.1) individuals being screened and 350 000 (315 000-385 000) treatments started annually, decreasing hepatitis C incidence by 26.5% (22.5-30.7) over 2018-30. Prioritised screening of high prevalence groups (PWID and adults aged >/=30 years) and rescreening (annually for PWID, otherwise every 10 years) are likely to increase the number screened and treated by 46.8% and decrease incidence by 50.8% (95% UI 46.1-55.0). Decreasing hepatitis C incidence by 80% is estimated to require a doubling of the primary screening rate, increasing referral to 90%, rescreening the general population every 5 years, and re-engaging those lost to follow-up every 5 years. This approach could cost US$8.1 billion, reducing to $3.9 billion with lowest costs for diagnostic tests and drugs, including health-care savings, and implementing a simplified treatment algorithm. INTERPRETATION: Pakistan will need to invest about 9.0% of its yearly health expenditure to enable sufficient scale up in screening and treatment to achieve the WHO hepatitis C elimination target of an 80% reduction in incidence by 2030. FUNDING: UNITAID. |
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. |
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%. |
Curbing the hepatitis C virus epidemic in Pakistan: the impact of scaling up treatment and prevention for achieving elimination
Lim AG , Qureshi H , Mahmood H , Hamid S , Davies CF , Trickey A , Glass N , Saeed Q , Fraser H , Walker JG , Mukandavire C , Hickman M , Martin NK , May MT , Averhoff F , Vickerman P . Int J Epidemiol 2018 47 (2) 550-560 Background: The World Health Organization (WHO) has developed a global health strategy to eliminate viral hepatitis. We project the treatment and prevention requirements to achieve the WHO HCV elimination target of reducing HCV incidence by 80% and HCV-related mortality by 65% by 2030 in Pakistan, which has the second largest HCV burden worldwide. Methods: We developed an HCV transmission model for Pakistan, and calibrated it to epidemiological data from a national survey (2007), surveys among people who inject drugs (PWID), and blood donor data. Current treatment coverage data came from expert opinion and published reports. The model projected the HCV burden, including incidence, prevalence and deaths through 2030, and estimated the impact of varying prevention and direct-acting antiviral (DAA) treatment interventions necessary for achieving the WHO HCV elimination targets. Results: With no further treatment (currently approximately 150 000 treated annually) during 2016-30, chronic HCV prevalence will increase from 3.9% to 5.1%, estimated annual incident infections will increase from 700 000 to 1 100 000, and 1 400 000 HCV-associated deaths will occur. To reach the WHO HCV elimination targets by 2030, 880 000 annual DAA treatments are required if prevention is not scaled up and no treatment prioritization occurs. By targeting treatment toward persons with cirrhosis (80% treated annually) and PWIDs (double the treatment rate of non-PWIDs), the required annual treatment number decreases to 750 000. If prevention activities also halve transmission risk, this treatment number reduces to 525 000 annually. Conclusions: Substantial HCV prevention and treatment interventions are required to reach the WHO HCV elimination targets in Pakistan, without which Pakistan's HCV burden will increase markedly. |
Importance and contribution of community, social, and healthcare risk factors for hepatitis C infection in Pakistan
Trickey A , May MT , Davies C , Qureshi H , Hamid S , Mahmood H , Saeed Q , Hickman M , Glass N , Averhoff F , Vickerman P . Am J Trop Med Hyg 2017 97 (6) 1920-1928 Pakistan has a high prevalence of hepatitis C virus (HCV) infection, estimated at 4.9% (2,290/46,843) in the 2007 national HCV seroprevalence survey. We used data from this survey to assess the importance of risk factor associations with HCV prevalence in Pakistan. Exposures were grouped as community (going to the barbers, sharing smoking equipment, having an ear/nose piercing, tattoo, or acupuncture), healthcare (ever having hemodialysis, blood transfusion, or ≥ 5 injections in the last year), demographic (marital status and age), and socio-economic (illiterate or laborer). We used mutually adjusted multivariable regression analysis, stratified by sex, to determine associations with HCV infection, their population attributable fraction, and how risk of infection accumulates with multiple exposures. Strength of associations was assessed using adjusted odds ratios (aOR). Community [aOR females 1.5 (95% confidence interval [CI]: 1.2, 1.8); males 1.2 (1.1, 1.4)] and healthcare [females 1.4 (1.2, 1.6); males 1.2 (1.1, 1.4)] exposures, low socio-economic status [females 1.6 (1.3, 1.80); males 1.3 (1.2, 1.5)], and marriage [females 1.5 (1.2, 1.9); males 1.4 (1.1, 1.8)] were associated with increased HCV infection. Among married women, the number of children was associated with an increase in HCV infection; linear trend aOR per child 1.06 (1.01, 1.11). Fewer infections could be attributed to healthcare exposures (females 13%; males 6%) than to community exposures (females 25%; males 9%). Prevalence increased from 3% to 10% when cumulative exposures increased from 1 to ≥ 4 [aOR per additional exposure for females 1.5 (1.4, 1.6); males 1.2 (1.2, 1.3)]. A combination of community, healthcare, and other factors appear to drive the Pakistan HCV epidemic, highlighting the need for a comprehensive array of prevention strategies. |
Use of quantitative molecular diagnostic methods to identify causes of diarrhoea in children: a reanalysis of the GEMS case-control study.
Liu J , Platts-Mills JA , Juma J , Kabir F , Nkeze J , Okoi C , Operario DJ , Uddin J , Ahmed S , Alonso PL , Antonio M , Becker SM , Blackwelder WC , Breiman RF , Faruque AS , 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 , Toema D , Wu Y , Zaidi A , Nataro JP , Kotloff KL , Levine MM , Houpt ER . Lancet 2016 388 (10051) 1291-301 BACKGROUND: Diarrhoea is the second leading cause of mortality in children worldwide, but establishing the cause can be complicated by diverse diagnostic approaches and varying test characteristics. We used quantitative molecular diagnostic methods to reassess causes of diarrhoea in the Global Enteric Multicenter Study (GEMS). METHODS: GEMS was a study of moderate to severe diarrhoea in children younger than 5 years in Africa and Asia. We used quantitative real-time PCR (qPCR) to test for 32 enteropathogens in stool samples from cases and matched asymptomatic controls from GEMS, and compared pathogen-specific attributable incidences with those found with the original GEMS microbiological methods, including culture, EIA, and reverse-transcriptase PCR. We calculated revised pathogen-specific burdens of disease and assessed causes in individual children. FINDINGS: We analysed 5304 sample pairs. For most pathogens, incidence was greater with qPCR than with the original methods, particularly for adenovirus 40/41 (around five times), Shigella spp or enteroinvasive Escherichia coli (EIEC) and Campylobactor jejuni o C coli (around two times), and heat-stable enterotoxin-producing E coli ([ST-ETEC] around 1.5 times). The six most attributable pathogens became, in descending order, Shigella spp, rotavirus, adenovirus 40/41, ST-ETEC, Cryptosporidium spp, and Campylobacter spp. Pathogen-attributable diarrhoeal burden was 89.3% (95% CI 83.2-96.0) at the population level, compared with 51.5% (48.0-55.0) in the original GEMS analysis. The top six pathogens accounted for 77.8% (74.6-80.9) of all attributable diarrhoea. With use of model-derived quantitative cutoffs to assess individual diarrhoeal cases, 2254 (42.5%) of 5304 cases had one diarrhoea-associated pathogen detected and 2063 (38.9%) had two or more, with Shigella spp and rotavirus being the pathogens most strongly associated with diarrhoea in children with mixed infections. INTERPRETATION: A quantitative molecular diagnostic approach improved population-level and case-level characterisation of the causes of diarrhoea and indicated a high burden of disease associated with six pathogens, for which targeted treatment should be prioritised. FUNDING: Bill & Melinda Gates Foundation. |
A case cluster of variant Creutzfeldt-Jakob disease linked to the Kingdom of Saudi Arabia
Coulthart MB , Geschwind MD , Qureshi S , Phielipp N , Demarsh A , Abrams JY , Belay E , Gambetti P , Jansen GH , Lang AE , Schonberger LB . Brain 2016 139 2609-2616 As of mid-2016, 231 cases of variant Creutzfeldt-Jakob disease-the human form of a prion disease of cattle, bovine spongiform encephalopathy-have been reported from 12 countries. With few exceptions, the affected individuals had histories of extended residence in the UK or other Western European countries during the period (1980-96) of maximum global risk for human exposure to bovine spongiform encephalopathy. However, the possibility remains that other geographic foci of human infection exist, identification of which may help to foreshadow the future of the epidemic. We report results of a quantitative analysis of country-specific relative risks of infection for three individuals diagnosed with variant Creutzfeldt-Jakob disease in the USA and Canada. All were born and raised in Saudi Arabia, but had histories of residence and travel in other countries. To calculate country-specific relative probabilities of infection, we aligned each patient's life history with published estimates of probability distributions of incubation period and age at infection parameters from a UK cohort of 171 variant Creutzfeldt-Jakob disease cases. The distributions were then partitioned into probability density fractions according to time intervals of the patient's residence and travel history, and the density fractions were combined by country. This calculation was performed for incubation period alone, age at infection alone, and jointly for incubation and age at infection. Country-specific fractions were normalized either to the total density between the individual's dates of birth and symptom onset ('lifetime'), or to that between 1980 and 1996, for a total of six combinations of parameter and interval. The country-specific relative probability of infection for Saudi Arabia clearly ranked highest under each of the six combinations of parameter x interval for Patients 1 and 2, with values ranging from 0.572 to 0.998, respectively, for Patient 2 (age at infection x lifetime) and Patient 1 (joint incubation and age at infection x 1980-96). For Patient 3, relative probabilities for Saudi Arabia were not as distinct from those for other countries using the lifetime interval: 0.394, 0.360 and 0.378, respectively, for incubation period, age at infection and jointly for incubation and age at infection. However, for this patient Saudi Arabia clearly ranked highest within the 1980-96 period: 0.859, 0.871 and 0.865, respectively, for incubation period, age at infection and jointly for incubation and age at infection. These findings support the hypothesis that human infection with bovine spongiform encephalopathy occurred in Saudi Arabia. |
Evolution of atypical enteropathogenic E. coli by repeated acquisition of LEE pathogenicity island variants
Ingle DJ , Tauschek M , Edwards DJ , Hocking DM , Pickard DJ , Azzopardi KI , Amarasena T , Bennett-Wood V , Pearson JS , Tamboura B , Antonio M , Ochieng JB , Oundo J , Mandomando I , Qureshi S , Ramamurthy T , Hossain A , Kotloff KL , Nataro JP , Dougan G , Levine MM , Robins-Browne RM , Holt KE . Nat Microbiol 2016 1 15010 Atypical enteropathogenic Escherichia coli (aEPEC) is an umbrella term given to E. coli that possess a type III secretion system encoded in the locus of enterocyte effacement (LEE), but lack the virulence factors (stx, bfpA) that characterize enterohaemorrhagic E. coli and typical EPEC, respectively. The burden of disease caused by aEPEC has recently increased in industrialized and developing nations, yet the population structure and virulence profile of this emerging pathogen are poorly understood. Here, we generated whole-genome sequences of 185 aEPEC isolates collected during the Global Enteric Multicenter Study from seven study sites in Asia and Africa, and compared them with publicly available E. coli genomes. Phylogenomic analysis revealed ten distinct widely distributed aEPEC clones. Analysis of genetic variation in the LEE pathogenicity island identified 30 distinct LEE subtypes divided into three major lineages. Each LEE lineage demonstrated a preferred chromosomal insertion site and different complements of non-LEE encoded effector genes, indicating distinct patterns of evolution of these lineages. This study provides the first detailed genomic framework for aEPEC in the context of the EPEC pathotype and will facilitate further studies into the epidemiology and pathogenicity of EPEC by enabling the detection and tracking of specific clones and LEE variants. |
Aeromonas-associated diarrhea in children under 5 years: The GEMS experience
Qamar FN , Nisar MI , Quadri F , Shakoor S , Sow SO , Nasrin D , Blackwelder WC , Wu Y , Farag T , Panchalingham S , Sur D , Qureshi S , Faruque AS , Saha D , Alonso PL , Breiman RF , Bassat Q , Tamboura B , Ramamurthy T , Kanungo S , Ahmed S , Hossain A , Das SK , Antonio M , Hossain MJ , Mandomando I , Mintz ED , Tennant SM , Kotloff KL , Levine MM , Zaidi AK . Am J Trop Med Hyg 2016 95 (4) 774-780 We report the clinical findings, epidemiology, and risk factors for moderate-to-severe diarrhea (MSD) associated with Aeromonas species in children 0-59 months of age, from the Global Enteric Multicenter Study, conducted at three sites in south Asia and four sites in sub-Saharan Africa. Children with MSD were enrolled along with controls matched for age, gender, and neighborhood. Pooled, age-stratified conditional logistic regression models were applied to evaluate the association of Aeromonas infection controlling for coinfecting pathogens and sociodemographic variables. A pooled, age-stratified, multivariate logistic regression analysis was done to identify risk factors associated with Aeromonas positivity in MSD cases. A total of 12,110 cases and 17,291 matched controls were enrolled over a period of 48 months. Aeromonas was identified as a significant pathogen in 736 cases of MSD in Pakistan and Bangladesh (22.2%). Aeromonas remained a significant pathogen even after adjustment for the presence of other pathogens and sociodemographic factors. Odds ratio (OR) for Aeromonas were higher in the presence of Shigella (matched OR: 6.2, 95% confidence interval [CI]: 1.9-20.2). Cases of Aeromonas were likely to present with dysentery, particularly in the 0-11 months (OR: 1.4, 95% CI 1.0-2.0) and 12-23 months (OR: 1.8, 95% CI: 1.3-2.5) age group. The odds of Aeromonas increased with increasing degree of stunting, being highest for severe stunting (OR: 10.1, 95% CI: 3.6-28.9). Aeromonas is a significant pathogen for MSD in Pakistan and Bangladesh. Presence of dysentery and co-occurrence with other pathogens, notably Shigella spp. are significant features of Aeromonas-associated diarrhea. |
The burden of cryptosporidium diarrheal disease among children < 24 months of age in moderate/high mortality regions of Sub-Saharan Africa and South Asia, utilizing data from the Global Enteric Multicenter Study (GEMS)
Sow SO , Muhsen K , Nasrin D , Blackwelder WC , Wu Y , Farag TH , Panchalingam S , Sur D , Zaidi AK , Faruque AS , Saha D , Adegbola R , 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 , Hossain MJ , Mandomando I , Nhampossa T , Acacio S , Omore R , Oundo JO , Ochieng JB , Mintz ED , O'Reilly CE , Berkeley LY , Livio S , Tennant SM , Sommerfelt H , Nataro JP , Ziv-Baran T , Robins-Browne RM , Mishcherkin V , Zhang J , Liu J , Houpt ER , Kotloff KL , Levine MM . PLoS Negl Trop Dis 2016 10 (5) e0004729 BACKGROUND: The importance of Cryptosporidium as a pediatric enteropathogen in developing countries is recognized. METHODS: Data from the Global Enteric Multicenter Study (GEMS), a 3-year, 7-site, case-control study of moderate-to-severe diarrhea (MSD) and GEMS-1A (1-year study of MSD and less-severe diarrhea [LSD]) were analyzed. Stools from 12,110 MSD and 3,174 LSD cases among children aged <60 months and from 21,527 randomly-selected controls matched by age, sex and community were immunoassay-tested for Cryptosporidium. Species of a subset of Cryptosporidium-positive specimens were identified by PCR; GP60 sequencing identified anthroponotic C. parvum. Combined annual Cryptosporidium-attributable diarrhea incidences among children aged <24 months for African and Asian GEMS sites were extrapolated to sub-Saharan Africa and South Asian regions to estimate region-wide MSD and LSD burdens. Attributable and excess mortality due to Cryptosporidium diarrhea were estimated. FINDINGS: Cryptosporidium was significantly associated with MSD and LSD below age 24 months. Among Cryptosporidium-positive MSD cases, C. hominis was detected in 77.8% (95% CI, 73.0%-81.9%) and C. parvum in 9.9% (95% CI, 7.1%-13.6%); 92% of C. parvum tested were anthroponotic genotypes. Annual Cryptosporidium-attributable MSD incidence was 3.48 (95% CI, 2.27-4.67) and 3.18 (95% CI, 1.85-4.52) per 100 child-years in African and Asian infants, respectively, and 1.41 (95% CI, 0.73-2.08) and 1.36 (95% CI, 0.66-2.05) per 100 child-years in toddlers. Corresponding Cryptosporidium-attributable LSD incidences per 100 child-years were 2.52 (95% CI, 0.33-5.01) and 4.88 (95% CI, 0.82-8.92) in infants and 4.04 (95% CI, 0.56-7.51) and 4.71 (95% CI, 0.24-9.18) in toddlers. We estimate 2.9 and 4.7 million Cryptosporidium-attributable cases annually in children aged <24 months in the sub-Saharan Africa and India/Pakistan/Bangladesh/Nepal/Afghanistan regions, respectively, and ~202,000 Cryptosporidium-attributable deaths (regions combined). ~59,000 excess deaths occurred among Cryptosporidium-attributable diarrhea cases over expected if cases had been Cryptosporidium-negative. CONCLUSIONS: The enormous African/Asian Cryptosporidium disease burden warrants investments to develop vaccines, diagnostics and therapies. |
Classification of blood culture isolates into contaminants and pathogens on the basis of clinical and laboratory data
Hossain B , Weber MW , Hamer DH , Hibberd PL , Ahmed AS , Marzan M , Islam M , Connor NE , Islam MS , Zaidi AK , Baqui AH , Bhutta ZA , Qureshi SM , Rafiqullah I , McGee L , Saha SK . Pediatr Infect Dis J 2016 35 S52-4 The multisite community-based study, Aetiology of Neonatal Infection in South Asia (ANISA), uses blood culture as the gold standard for identifying the etiology of neonatal infection. Considering the importance of this age-old diagnostic tool and the risk of contamination, ANISA has employed rigorous measures to prevent contamination at all stages of blood collection, processing and culture. Because contamination may still occur, an independent expert group evaluates the routinely collected clinical and laboratory data to determine whether a blood culture isolate is a contaminant or a true pathogen. This article describes the methodology used by ANISA to determine whether a blood culture isolate is likely to be a true pathogen or a contaminant in neonatal sepsis. |
Laboratory methods for determining etiology of neonatal infection at population-based sites in South Asia: The ANISA study
Saha SK , Islam MS , Qureshi SM , Hossain B , Islam M , Zaidi AK , Modak JK , Al-Emran HM , Diaz MH , McGee L , Winchell JM . Pediatr Infect Dis J 2016 35 S16-22 BACKGROUND: The Aetiology of Neonatal Infection in South Asia (ANISA) study aims to determine the etiology of neonatal infections in 5 population-based sites in Bangladesh, India and Pakistan. METHODS: The main laboratory challenges in ANISA were selection and consistent implementation of laboratory methods at participating sites with varied infrastructure. The other specific challenges included (1) specimen collection and transport to designated study laboratories and timely processing in rural settings; (2) minimal or nonexistent laboratory facilities at the field sites; (3) obtaining sufficient volumes of blood from enrolled infants aged 0-59 days and (4) caregivers' concerns about collection of clinical specimens from young infants. An additional challenge was selecting an appropriate molecular platform from multiple available options, all with limited field validation, for use in determining infection in young infants. CONCLUSIONS: This article describes how the challenges of specimen collection, transport and processing and implementation of laboratory methods have been addressed in the ANISA study. It also describes the measures taken to improve detection of microorganisms causing young infant infections by enhancing the sensitivity of existing laboratory methods for pathogen detection. |
Impact of human mobility on the emergence of dengue epidemics in Pakistan
Wesolowski A , Qureshi T , Boni MF , Sundsoy PR , Johansson MA , Rasheed SB , Engo-Monsen K , Buckee CO . Proc Natl Acad Sci U S A 2015 112 (38) 11887-92 The recent emergence of dengue viruses into new susceptible human populations throughout Asia and the Middle East, driven in part by human travel on both local and global scales, represents a significant global health risk, particularly in areas with changing climatic suitability for the mosquito vector. In Pakistan, dengue has been endemic for decades in the southern port city of Karachi, but large epidemics in the northeast have emerged only since 2011. Pakistan is therefore representative of many countries on the verge of countrywide endemic dengue transmission, where prevention, surveillance, and preparedness are key priorities in previously dengue-free regions. We analyze spatially explicit dengue case data from a large outbreak in Pakistan in 2013 and compare the dynamics of the epidemic to an epidemiological model of dengue virus transmission based on climate and mobility data from approximately 40 million mobile phone subscribers. We find that mobile phone-based mobility estimates predict the geographic spread and timing of epidemics in both recently epidemic and emerging locations. We combine transmission suitability maps with estimates of seasonal dengue virus importation to generate fine-scale dynamic risk maps with direct application to dengue containment and epidemic preparedness. |
Genetic characterization of norovirus strains in hospitalized children from Pakistan.
Alam A , Qureshi SA , Vinje J , Zaidi A . J Med Virol 2015 88 (2) 216-23 Norovirus is one of the most common causes of acute gastroenteritis among children in developing countries. No data on the prevalence and genetic variability of norovirus are available for Pakistan, where early childhood mortality due to acute gastroenteritis is common. We tested 255 fecal specimens from children under 5 years of age hospitalized between April 2006 and March 2008 with severe acute gastroenteritis in five hospitals in the four largest cities in Pakistan for norovirus by real-time RT-PCR. Positive samples were further genotyped by conventional RT-PCR targeting the 5'-end of the capsid gene followed by sequencing of the positive PCR products. Overall, 41 (16.1%) samples tested positive for norovirus with an equal frequency in rotavirus-positive and rotavirus-negative samples. Nine (22%) samples were genogroup (G)I positive, 30 (73%) GII positive and two (5%) samples contained a mixture of GI and GII viruses. Sequence analyses demonstrated co-circulation of 14 norovirus genotypes including 4 GI genotypes (GI.3, GI.5, GI.7, GI.8) and 10 GII genotypes (GII.2, GII.3, GII.4, GII.5, GII.6, GII.7, GII.9, GII.13, GII.16, and GII.21). The most prevalent genotypes were GI.7 and GII.4 both causing 12.2% of the infections. This report confirms the presence of multiple norovirus genotypes in hospitalized children with acute gastroenteritis in Pakistan and a lack of clear predominance of GII.4 viruses. |
Shigella isolates from the Global Enteric Multicenter Study (GEMS) inform vaccine development
Livio S , Strockbine N , Panchalingam S , Tennant SM , Barry EM , Marohn ME , Antonio M , Hossain A , Mandomando I , Ochieng JB , Oundo JO , Qureshi S , Ramamurthy T , Tamboura B , Adegbola RA , Hossain MJ , Saha D , Sen S , Faruque AS , Alonso PL , Breiman RF , Zaidi AK , Sur D , Sow SO , Berkeley LY , O'Reilly C , Mintz ED , Biswas K , Cohen D , Farag TH , Nasrin D , Wu Y , Blackwelder WC , Kotloff KL , Nataro JP , Levine MM . Clin Infect Dis 2014 59 (7) 933-41 BACKGROUND: Shigella, a major diarrheal disease pathogen worldwide, is the target of vaccine development. The Global Enteric Multicenter Study (GEMS) investigated burden and etiology of moderate-to-severe diarrheal disease in children age<60 months and matched controls without diarrhea during three years in four sites in Africa and three in Asia. Shigella was one of the four most common pathogens across sites and age strata. GEMS Shigella serotypes are reviewed to guide vaccine development. METHODS: Subjects' stool specimens/rectal swabs were transported to site laboratories in transport media and plated onto XLD and MacConkey's agar. Suspect Shigella colonies were identified by biochemical tests and agglutination with antisera. Shigella isolates were shipped to the GEMS Reference Laboratory (Baltimore) for confirmation and serotyping of S. flexneri; one-third of isolates were sent to Centers for Disease Control and Prevention for quality control. RESULTS: S. dysenteriae and S. boydii accounted for only 5.0% and 5.4%, respectively, of 1130 Shigella case isolates; S. flexneri comprised 65.9% and S. sonnei 23.7%. Five serotypes/subserotypes comprised 89.4% of S. flexneri, including S. flexneri 2a, S. flexneri 6, S. flexneri 3a, S. flexneri 2b and S. flexneri 1b. CONCLUSIONS: A broad spectrum Shigella vaccine must protect against S. sonnei and 15 serotypes/subserotypes of S. flexneri. A quadrivalent vaccine including O antigens from S. sonnei, S. flexneri 2a, S. flexneri 3a and S. flexneri 6 can provide broad direct coverage against these most common serotypes and indirect coverage against all but one (rare) remaining subserotype through shared S. flexneri group antigens. |
Pneumococcal serotypes and serogroups causing invasive disease in Pakistan, 2005-2013
Shakoor S , Kabir F , Khowaja AR , Qureshi SM , Jehan F , Qamar F , Whitney CG , Zaidi AK . PLoS One 2014 9 (6) e98796 While pneumococcal conjugate vaccines have been implemented in most countries worldwide, use in Asia has lagged in part because of a lack of data on the amount of disease that is vaccine preventable in the region. We describe pneumococcal serotypes elicited from 111 episodes of invasive pneumococcal disease (IPD) from 2005 to 2013 among children and adults in Pakistan. Seventy-three percent (n = 81) of 111 IPD episodes were cases of meningitis (n = 76 in children 0-15 years and n = 5 among adults). Serotypes were determined by target amplification of DNA extracted from pneumococcal isolates (n = 52) or CSF specimens (n = 59). Serogroup 18 was the most common serogroup causing meningitis in children <5 years, accounting for 21% of cases (n = 13). The 10-valent pneumococcal conjugate vaccine (PCV 10) or PCV10- related serotypes were found in 61% (n = 47) of childhood (age 0-15 years) meningitis episodes. PCV-13 increased this coverage to 63% (one additional serotype 19A; n = 48). Our data indicate that use of PCVs would prevent a large proportion of serious pneumococcal disease. |
Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study
Kotloff KL , Nataro JP , Blackwelder WC , Nasrin D , Farag TH , Panchalingam S , Wu Y , Sow SO , Sur D , Breiman RF , Faruque AS , Zaidi AK , Saha D , Alonso PL , Tamboura B , Sanogo D , Onwuchekwa U , Manna B , Ramamurthy T , Kanungo S , Ochieng JB , Omore R , Oundo JO , Hossain A , Das SK , Ahmed S , Qureshi S , Quadri F , Adegbola RA , Antonio M , Hossain MJ , Akinsola A , Mandomando I , Nhampossa T , Acacio S , Biswas K , O'Reilly CE , Mintz ED , Berkeley LY , Muhsen K , Sommerfelt H , Robins-Browne RM , Levine MM . Lancet 2013 382 (9888) 209-22 BACKGROUND: Diarrhoeal diseases cause illness and death among children younger than 5 years in low-income countries. We designed the Global Enteric Multicenter Study (GEMS) to identify the aetiology and population-based burden of paediatric diarrhoeal disease in sub-Saharan Africa and south Asia. METHODS: The GEMS is a 3-year, prospective, age-stratified, matched case-control study of moderate-to-severe diarrhoea in children aged 0-59 months residing in censused populations at four sites in Africa and three in Asia. We recruited children with moderate-to-severe diarrhoea seeking care at health centres along with one to three randomly selected matched community control children without diarrhoea. From patients with moderate-to-severe diarrhoea and controls, we obtained clinical and epidemiological data, anthropometric measurements, and a faecal sample to identify enteropathogens at enrolment; one follow-up home visit was made about 60 days later to ascertain vital status, clinical outcome, and interval growth. FINDINGS: We enrolled 9439 children with moderate-to-severe diarrhoea and 13,129 control children without diarrhoea. By analysing adjusted population attributable fractions, most attributable cases of moderate-to-severe diarrhoea were due to four pathogens: rotavirus, Cryptosporidium, enterotoxigenic Escherichia coli producing heat-stable toxin (ST-ETEC; with or without co-expression of heat-labile enterotoxin), and Shigella. Other pathogens were important in selected sites (eg, Aeromonas, Vibrio cholerae O1, Campylobacter jejuni). Odds of dying during follow-up were 8.5-fold higher in patients with moderate-to-severe diarrhoea than in controls (odd ratio 8.5, 95% CI 5.8-12.5, p<0.0001); most deaths (167 [87.9%]) occurred during the first 2 years of life. Pathogens associated with increased risk of case death were ST-ETEC (hazard ratio [HR] 1.9; 0.99-3.5) and typical enteropathogenic E coli (HR 2.6; 1.6-4.1) in infants aged 0-11 months, and Cryptosporidium (HR 2.3; 1.3-4.3) in toddlers aged 12-23 months. INTERPRETATION: Interventions targeting five pathogens (rotavirus, Shigella, ST-ETEC, Cryptosporidium, typical enteropathogenic E coli) can substantially reduce the burden of moderate-to-severe diarrhoea. New methods and accelerated implementation of existing interventions (rotavirus vaccine and zinc) are needed to prevent disease and improve outcomes. FUNDING: The Bill & Melinda Gates Foundation. |
A study evaluating poliovirus antibodies and risk factors associated with polio seropositivity in low socioeconomic areas of Pakistan
Habib M , Soofi S , Ali N , Sutter RW , Palansch M , Qureshi H , Akhtar T , Molodecky NA , Okayasu H , Bhutta ZA . Vaccine 2013 31 (15) 1987-93 BACKGROUND: Seroprevalence studies provide important data on performance of immunization programs, susceptible groups and populations at-risk of future outbreaks. Identifying risk factors that affect seroconversion of the oral polio vaccine (OPV) will enable the polio eradication initiatives to increase seroprevalence. This paper describes the first population-based seroprevalence survey in Pakistan. METHODS: This study evaluated the seroprevalence of poliovirus (PV) types 1, 2, and 3 antibodies to OPV in an illustrative sample of 554 subjects 6-11 months of age in three geographic locations of Pakistan (Lahore, Karachi, and Peshawar) representing a low socioeconomic at-risk populations. Antibody titers were measured and sero protection rates and geometric median titers were compared among different geographic regions and populations, as were demographics and OPV vaccination history collected by questionnaire. Univariate and multivariate analyses were conducted on subject characteristics to assess for potential risk factors for failure to sero-convert. RESULTS: The average seroprevalence of PV1, PV2, and PV3 was 96.0%, 87.9% and 86.7%, respectively. The lowest sero protection rate for all three serotypes was for Karachi with 90.2%, 73.8%, and 78.8% for PV1, PV2, and PV3, respectively. Significant regional variation in PV3 seroprevalence was found (range: 74.2-100%). In the univariate analysis, age, total and campaign OPV doses were associated with higher seroprevalence, whereas stunting, respondent education and diarrhea in the past six months were significant risk factors for failure to sero-convert. CONCLUSIONS: These findings demonstrate consistently high levels of antibody response to PV1 and more geographically varied response to PV2 and PV3. Additionally, important risk factors affecting seropositivity were identified. |
Parental and peer factors associated with body image discrepancy among fifth-grade boys and girls
Michael SL , Wentzel K , Elliott MN , Dittus PJ , Kanouse DE , Wallander JL , Pasch KE , Franzini L , Taylor WC , Qureshi T , Franklin FA , Schuster MA . J Youth Adolesc 2013 43 (1) 15-29 Many young adolescents are dissatisfied with their body due to a discrepancy between their ideal and actual body size, which can lead to weight cycling, eating disorders, depression, and obesity. The current study examined the associations of parental and peer factors with fifth-graders' body image discrepancy, physical self-worth as a mediator between parental and peer factors and body image discrepancy, and how these associations vary by child's sex. Body image discrepancy was defined as the difference between young adolescents' self-perceived body size and the size they believe a person their age should be. Data for this study came from Healthy Passages, which surveyed 5,147 fifth graders (51 % females; 34 % African American, 35 % Latino, 24 % White, and 6 % other) and their primary caregivers from the United States. Path analyses were conducted separately for boys and girls. The findings for boys suggest father nurturance and getting along with peers are related negatively to body image discrepancy; however, for girls, fear of negative evaluation by peers is related positively to body image discrepancy. For both boys and girls, getting along with peers and fear of negative evaluation by peers are related directly to physical self-worth. In addition, mother nurturance is related positively to physical self-worth for girls, and father nurturance is related positively to physical self-worth for boys. In turn, physical self-worth, for both boys and girls, is related negatively to body image discrepancy. The findings highlight the potential of parental and peer factors to reduce fifth graders' body image discrepancy. |
Family history in public health practice: a genomic tool for disease prevention and health promotion.
Valdez R , Yoon PW , Qureshi N , Green RF , Khoury MJ . Annu Rev Public Health 2010 31 69-87 1 p following 87 Family history is a risk factor for many chronic diseases, including cancer, cardiovascular disease, and diabetes. Professional guidelines usually include family history to assess health risk, initiate interventions, and motivate behavioral changes. The advantages of family history over other genomic tools include a lower cost, greater acceptability, and a reflection of shared genetic and environmental factors. However, the utility of family history in public health has been poorly explored. To establish family history as a public health tool, it needs to be evaluated within the ACCE framework (analytical validity, clinical validity; clinical utility; and ethical, legal, and social issues). Currently, private and public organizations are developing tools to collect standardized family histories of many diseases. Their goal is to create family history tools that have decision support capabilities and are compatible with electronic health records. These advances will help realize the potential of family history as a public health tool. Expected final online publication date for the Annual Review of Public Health Volume 31 is March 17, 2010. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates. |
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