Immunogenicity of Different Routine Poliovirus Vaccination Schedules: A Randomized, Controlled Trial in Karachi, Pakistan.

Background: We assessed immunity against polioviruses induced with a new Pakistani poliovirus immunization schedule and compared it to alternative poliovirus immunization schedules. Methods: Newborns were randomized to undergo vaccination based on 1 of 5 vaccination schedules, with doses administered at birth and at 6, 10, and 14 weeks of age. Arm A received inactivated poliovirus vaccine (IPV) at all time points. Arm B received bivalent oral poliovirus vaccine (bOPV) at all time points. Arms C and D received bOPV at the first 3 time points and bOPV plus IPV at the final time point (the current schedule). Arm E received trivalent OPV (tOPV) at all time points. At 22 weeks of age, all children received 1 challenge dose of tOPV, and children in arm D received 1 additional IPV dose. Sera were analyzed for the presence of poliovirus neutralizing antibodies at birth and 14 and 22 weeks of age. Results: Seroconversion for poliovirus type 1 (PV1) at 22 weeks of age was observed in 80% of individuals in arm A, 97% in arm B, 94% in arm C, 96% in arm D, and 94% in arm E; for PV2, seroconversion frequencies were 84%, 19%, 53%, 49%, and 93%, respectively; and for PV3, seroconversion frequencies were 93%, 94%, 98%, 94%, and 85%, respectively. Conclusions: The 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.

Detection of Typhoidal and Paratyphoidal Salmonella in Blood by Real-time Polymerase Chain Reaction.

BACKGROUND: The gold standard for diagnosis of enteric fever caused by Salmonella Typhi or Salmonella Paratyphi A or B is bone marrow culture. However, because bone marrow aspiration is highly invasive, many hospitals and large health centers perform blood culture instead. As blood culture has several limitations, there is a need for novel typhoid diagnostics with improved sensitivity and more rapid time to detection. METHODS: We developed a clyA-based real-time polymerase chain reaction (qPCR) method to detect Salmonella Typhi and Salmonella Paratyphi A simultaneously in blood. The sensitivity and specificity of this probeset was first evaluated in vitro in the laboratory and then in a typhoid-endemic population, in Karachi, Pakistan, and in healthy US volunteers. RESULTS: We optimized a DNA extraction and real-time PCR-based method that could reliably detect 1 colony-forming unit/mL of Salmonella Typhi. The probe set was able to detect clinical Salmonella Typhi and Salmonella Paratyphi A strains and also diarrheagenic Escherichia coli, but not invasive E. coli or other invasive bacteria. In the field, the clyA qPCR diagnostic was 40% as sensitive as blood culture. However, when qPCR-positive specimens were considered to be true positives, blood culture only exhibited 28.57% sensitivity. Specificity was ≥90% for all comparisons and in the healthy US volunteers. qPCR was significantly faster than blood culture in terms of detection of typhoid and paratyphoid. CONCLUSIONS: Based on lessons learned, we recommend that future field trials of this and other novel diagnostics that detect typhoidal and nontyphoidal Salmonella employ multiple methodologies to define a "positive" sample.

Health risk assessment of bread wheat grown under cadmium and nickel stress and impact of silicic acid application on its growth, physiology, and metal uptake.

Heavy metal stress poses a significant threat to the productivity of agricultural systems and human health. Silicon (Si) is widely reported to be very effective against the different heavy metal stresses in crops. According to reports, it can help plants that are under cadmium (Cd) and nickel (Ni) stress. The presented work investigated how silicon interacted in Cd- and Ni-stressed wheat and mitigated metal toxicity. A pot experiment was carried out in which wheat crop was irrigated with Cd- and Ni-contaminated water. Application of Cd and Ni-contaminated water to wheat significantly reduced the root and shoot growth parameters and physiological and biochemical factors while increasing the antioxidant enzymatic activity and bioaccumulation of Cd and Ni metal in shoot and root as compared to the control. Application of Si led to an improvement in physiological parameters, i.e., greenness of leaves, i.e., SPAD values (17% and 26%), membrane stability (26% and 25%), and growth parameters i.e., root surface area (42% and 23%), root length (81% and 79%), root dry weight (456% and 190%), root volume (64% and 32%), shoot length (41% and 35%), shoot dry weight of shoot (111% and 117%), and overall grain weight (62% and 72%) under Cd and Ni stress, respectively. It increased the activity of antioxidant activity (max. up to 20%) whereas decreased the metal bioaccumulation of Cd and Ni in the roots and shoot (max. up to 62%) of wheat. It was concluded that the application of Si potentially increases antioxidant activity and metal chelation resulting in decreased oxidative damage and reducing the effect of Cd and Ni stress on wheat which improves growth and physiological parameters as well as inhibits Cd and Ni inclusion in food chain under Cd and Ni toxicity reducing health risks associated with these metals.

Web-Based Tool Designed to Encourage Supplemental Nutrition Assistance Program Use in Urban College Students: Usability Testing Study.

BACKGROUND: Food insecurity continues to be a risk for college students in the United States. It is associated with numerous problems, such as chronic health conditions, increased stress and anxiety, and a lower grade point average. After COVID-19, the Supplemental Nutrition Assistance Program (SNAP) benefits were extended to college-aged students; however, there were some barriers to participation, which persisted such as lack of perceived food insecurity risk, lack of knowledge regarding the SNAP application process, the complexity of determining eligibility, and stigma associated with needing social assistance. A technology-enhanced tool was developed to address these barriers to SNAP enrollment and encourage at-risk college students to apply for SNAP. OBJECTIVE: The purpose of this study was to test the usability and acceptability of a web-based SNAP screening tool designed for college-aged students. METHODS: College students aged 18-25 years were recruited to participate in 2 rounds of usability testing during fall 2022. Participants tested the prototype of a web-based SNAP screener tool using a standardized think-aloud method. The usability and acceptability of the tool were assessed using a semistructured interview and a 10-item validated System Usability Scale questionnaire. Audio recordings and field notes were systematically reviewed by extracting and sorting feedback as positive or negative comments. System Usability Scale questionnaire data were analyzed using the Wilcoxon signed rank test and sign test. RESULTS: A total of 12 students (mean age 21.8, SD 2.8 years; n=6, 50% undergraduate; n=11, 92% female; n=7, 58% Hispanic or Black or African American; n=9, 78% low or very low food security) participated in both rounds of user testing. Round 1 testing highlighted overall positive experiences with the tool, with most participants (10/12) stating that the website fulfills its primary objective as a support tool to encourage college students to apply for SNAP. However, issues related to user interface design, navigation, and wording of some questions in the screening tool were noted. Key changes after round 1 reflected these concerns, including improved design of response buttons and tool logo and improved clarity of screening questions. The overall system usability showed slight, but not statistically significant, improvement between round 1 and round 2 (91.25 vs 92.50; P=.10, respectively). CONCLUSIONS: Overall usability findings suggest that this web-based tool was highly usable and acceptable to urban college students and could be an effective and appealing approach as a support tool to introduce college students to the SNAP application process. The findings from this study will inform further development of the tool, which could eventually be disseminated publicly among various college campuses.

Impact of postpartum anxiety and depression on child's mental development from two peri-urban communities of Karachi, Pakistan: a quasi-experimental study.

BACKGROUND: Postpartum anxiety and depression has detrimental effects on the overall mental development of children. This study aims to assess the impact of postpartum anxiety and depression on children's mental development on all sub-scales in a Pakistani population. METHODS: A quasi-experimental study was conducted in two peri-urban communities of Karachi, a mega city of Pakistan, to assess the impact of postpartum anxiety and depression on children's growth and mental development. A total of 420 women were enrolled, who had given consent out of 651 pregnant women identified, during February 2004 to December 2005. Data for socio-demographic, home environment and family relationship variables were collected between 36 weeks of pregnancy and within 10 days of childbirth. Mother's levels of anxiety and depression were assessed at 1, 2, 6, 12, 18, 24, and 30 months of childbirth. An indigenous, validated screening instrument- Aga Khan University Anxiety and Depression scale was used and diagnostic confirmation was done through a psychologist's interview, based on DSM IV criteria. Children's growth and development was monitored in the same sequence using an Early Childhood Development tool that consists of five subscales; socio emotional, language, cognitive, gross motor and fine motor development. Physical growth was monitored by measuring height and weight of the child. Data was analyzed using SAS 9.2. Multivariable Generalized Estimating Equations (GEE) logistic regression was conducted to identify association of postpartum anxiety and depression with each early childhood development indicator, adjusting for parental and child factors. RESULTS: A significant association of postpartum anxiety and depression with delayed development on all five subscales of children's mental development was found in our study. Interestingly, our study found that higher maternal age had adverse effects on child's emotional whereas positive impact on child's cognitive development. Children's stunting had an adverse impact on all five subscales of children's development. Male children were at higher risk for delayed language and gross motor development relative to female children. CONCLUSIONS: Our study found that postpartum anxiety and depression is associated with adverse outcomes regarding children's mental development on all sub-scales. The impact was accentuated by low family income or child's increasing age.

Impact of tourism development upon environmental sustainability: a suggested framework for sustainable ecotourism.

The empirical research investigated the relationship between tourism development and environmental suitability to propose a framework for sustainable ecotourism. The framework suggested a balance between business and environmental interests in maintaining an ecological system with the moderating help of government support and policy interventions. The study population encompasses tourism stakeholders, including tourists, representatives from local communities, members of civil administration, hoteliers, and tour operators serving the areas. A total of 650 questionnaires were distributed to respondents, along with a brief description of key study variables to develop a better understanding. After verifying the instrument's reliability and validity, data analysis was conducted via hierarchical regression. The study findings revealed that a substantial number of people perceive socio-economic benefits, including employment and business openings, infrastructure development from tourism development, and growth. However, the state of the natural and environmental capital was found to be gradually degrading. Alongside the social environment, social vulnerability is reported due to the overutilization of land, intrusion from external cultures, and pollution in air and water due to traffic congestion, accumulation of solid waste, sewage, and carbon emissions. The study suggested a model framework for the development of sustained ecotourism, including supportive government policy interventions to ensure effective conservation of environmental and natural resources without compromising the economic viability and social well-beings of the locals. Furthermore, the variables and the constructs researched can be replicated to other destinations to seek valuable inputs for sustainable destination management elsewhere.

Validating Wave 1 (2014) Urinary Cotinine and TNE-2 Cut-points for Differentiating Wave 4 (2017) Cigarette Use from Non-use in the United States Using Data from the PATH Study.

BACKGROUND: Sex and racial/ethnic identity-specific cut-points for validating tobacco use using Wave 1 (W1) of the Population Assessment of Tobacco and Health (PATH) Study were published in 2020. The current study establishes predictive validity of the W1 (2014) urinary cotinine and total nicotine equivalents-2 (TNE-2) cut-points on estimating Wave 4 (W4; 2017) tobacco use. METHODS: For exclusive and polytobacco cigarette use, weighted prevalence estimates based on W4 self-report alone and with exceeding the W1 cut-point were calculated to identify the percentage missed without biochemical verification. Sensitivity and specificity of W1 cut-points on W4 self-reported tobacco use status were examined. ROC curves were used to determine the optimal W4 cut-points to distinguish past 30-day users from non-users, and evaluate whether the cut-points significantly differed from W1. RESULTS: Agreement between W4 self-reported use and exceeding the W1 cut-points was high overall and when stratified by demographic subgroups (0.7%-4.4% of use was missed if relying on self-report alone). The predictive validity of using the W1 cut-points to classify exclusive cigarette and polytobacco cigarette use at W4 was high (>90% sensitivity and specificity, except among polytobacco Hispanic smokers). Cut-points derived using W4 data did not significantly differ from the W1-derived cut-points [e.g., W1 exclusive = 40.5 ng/mL cotinine (95% confidence interval, CI: 26.1-62.8), W4 exclusive = 29.9 ng/mL cotinine (95% CI: 13.5-66.4)], among most demographic subgroups. CONCLUSIONS: The W1 cut-points remain valid for biochemical verification of self-reported tobacco use in W4. IMPACT: Findings from can be used in clinical and epidemiologic studies to reduce misclassification of cigarette smoking status.

The Gut of Healthy Infants in the Community as a Reservoir of ESBL and Carbapenemase-Producing Bacteria.

The recent rapid rise of multi-drug resistant Enterobacteriaceae (MDR-E) is threatening the treatment of common infectious diseases. Infections with such strains lead to increased mortality and morbidity. Using a cross-sectional study, we aimed to estimate the prevalence of gut colonization with extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae among healthy infants born in Pakistan, a setting with high incidence of MDR-E infections. Stool samples were collected from 104 healthy infants between the ages of 5 and 7 months. Enterobacteriaceae isolates were screened for resistance against several antimicrobial classes. Presence of ESBL and carbapenemase genes was determined using multiplex PCR. Sequence types were assigned to individual strains by multi-locus sequence typing. Phylogenetic analysis of Escherichia coli was done using the triplex PCR method. Forty-three percent of the infants were positive for ESBL-producing Enterobacteriaceae, the majority of which were E. coli. We identified several different ESBL E. coli sequence types most of which belonged to the phylogenetic group B2 (23%) or D (73%). The widespread colonization of infants in a developing country with ESBL-producing Enterobacteriaceae is concerning. The multiple sequence types and reported non-human sources support that multiple non-epidemic MDR lineages are circulating in Pakistan with healthy infants as a common reservoir.

Evaluation of vaccine derived poliovirus type 2 outbreak response options: A randomized controlled trial, Karachi, Pakistan.

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 22 weeks 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.

Needle adapters for intradermal administration of fractional dose of inactivated poliovirus vaccine: Evaluation of immunogenicity and programmatic feasibility in Pakistan.

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.

Predictors of diarrheal mortality and patterns of caregiver health seeking behavior in in Karachi, Pakistan.

BACKGROUND: Pakistan is unfortunately among the five countries that contributed to the most deaths due to diarrhea and pneumonia in 2010. To explore factors associated with diarrheal deaths we assessed care-seeking behavior and other predictors of diarrhea-related mortality in children in selected low-income peri-urban communities of Karachi, Pakistan. METHODS: A mixed methods study (qualitative and quantitative) using matched case-control design and focus group discussions with parents of children with moderate to severe diarrhea (MSD) was undertaken. Cases were children <5 years of age who died within 60 days of developing an episode of MSD. Controls were age-matched children who survived after 60 days of an episode of MSD. Demographic, clinical, and care-related behavioral predictors of mortality were assessed. Conditional logistic regression was performed, matched adjusted odds ratios (mOR) are reported. RESULTS: Parents of 77 cases and 154 controls were interviewed. Cases were less likely to receive appropriate care compared to controls (mOR = 0.2, 95% confidence interval (CI) 0.05-0.91). Refusal for hospital admission (OR = 8.9, 95% CI 2.6-30.8), and delays in reaching the health facility (OR = 3.6, 95% CI 1.0-12.9) were significant independent predictors of mortality. We found strong beliefs in traditional and spiritual healing in the population; use of both modern and traditional/spiritual treatments concurrently was common. CONCLUSION: Appropriate care seeking behavior predicts survival in children with diarrhea in Pakistan. There is a complex belief system relating to traditional and standard therapies. Health education for appropriate health care seeking should be implemented in order to achieve a substantial decline in diarrheal disease mortality in Pakistan.

The Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial Pathology Tissue Resource.

BACKGROUND: Pathology tissue specimens with associated epidemiologic and clinical data are valuable for cancer research. The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial undertook a large-scale effort to create a public resource of pathology tissues from PLCO participants who developed a cancer during the trial. METHODS: Formalin-fixed paraffin-embedded tissue blocks were obtained from pathology laboratories on a loan basis for central processing of tissue microarrays, with additional free-standing tissue cores collected for nucleic acid extraction. RESULTS: Pathology tissue specimens were obtained for prostate cancer (n = 1,052), lung cancer (n = 434), colorectal cancer (n = 675) and adenoma (n = 658), ovarian cancer and borderline tumors (n = 212), breast cancer (n = 870), and bladder cancer (n = 204). The process of creating this resource was complex, involving multidisciplinary teams with expertise in pathology, epidemiology, information technology, project management, and specialized laboratories. CONCLUSIONS: Creating the PLCO tissue resource required a multistep process, including obtaining medical records and contacting pathology departments where pathology materials were stored after obtaining necessary patient consent and authorization. The potential to link tissue biomarkers to prospectively collected epidemiologic information, screening and clinical data, and matched blood or buccal samples offers valuable opportunities to study etiologic heterogeneity, mechanisms of carcinogenesis, and biomarkers for early detection and prognosis. IMPACT: The methods and protocols developed for this effort, and the detailed description of this resource provided here, will be useful for those seeking to use PLCO pathology tissue specimens for their research and may also inform future tissue collection efforts in other settings. Cancer Epidemiol Biomarkers Prev; 25(12); 1635-42. ©2016 AACR.

The PLCO Biorepository: Creating, Maintaining, and Administering a Unique Biospecimen Resource.

Inclusion of biospecimens in population-based studies is an integral part of understanding disease etiology, identifying biomarkers and developing prevention and treatment strategies. The Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial collected, processed and stored biospecimens from participants to create a biorepository of specimens which serves as a useful resource for a broad research community. PLCO collected blood samples from consented screening arm participants at six screening rounds and a buccal sample from consented control arm participants. In addition, formalin-fixed paraffin embedded tumor tissue specimens were collected for participants in both arms for selected cancer sites. Collection of biospecimens at multiple timepoints (i.e. serial samples) and prior to cancer diagnosis, paired with rich epidemiologic and screening data, makes the PLCO collection of biospecimens a uniquely valuable resource. As such, access to the PLCO biorepository is granted to investigators by a rigorous scientific review process and guided by a steering committee which is responsible for developing and implementing the biospecimen use policies. Here, we describe the procedures for biospecimen collection, processing, storage, requisition, and distribution, as well as data management employed in PLCO. We also provide examples of how the biospecimens have been used to advance cancer research and describe relevant lessons learned to help inform cohorts wishing to add or modify biospecimen collection.

Monovalent type-1 oral poliovirus vaccine given at short intervals in Pakistan: a randomised controlled, four-arm, open-label, non-inferiority trial.

BACKGROUND: Supplementary immunisation activities with oral poliovirus vaccines (OPVs) are usually separated by 4 week intervals; however, shorter intervals have been used in security-compromised areas and for rapid outbreak responses. We assessed the immunogenicity of monovalent type-1 oral poliovirus vaccine (mOPV1) given at shorter than usual intervals in Karachi, Pakistan. METHODS: This was a multicentre, randomised, controlled, four-arm, open-label, non-inferiority trial done at five primary health-care centres in low-income communities in and around Karachi, Pakistan. Eligible participants were healthy newborn babies with a birthweight of at least 2·5 kg, for whom informed consent was provided by their parent or guardian, and lived less than 30 km from the study clinic. After receiving a birth dose of trivalent OPV, we enrolled and randomly assigned newborn babies (1:1:1:1) to receive two doses of mOPV1 with an interval of 1 week (mOPV1-1 week), 2 weeks (mOPV1-2 weeks), or 4 weeks (mOPV1-4 weeks) between doses, or two doses of bivalent OPV (bOPV) with an interval of 4 weeks between doses (bOPV-4 weeks). We gave the first study dose of OPV at age 6 weeks. We did the randomisation with a centrally generated, computerised allocation sequence with blocks of 16; participants' families and study physicians could not feasibly be masked to the allocations. Trial participants were excluded from local supplementary immunisation activities during the study period. The primary outcome was non-inferiority (within a 20% margin) between groups in seroconversion to type-1 poliovirus. The primary and safety analyses were done in the per-protocol population of infants who received all three doses of vaccine. This trial is registered with ClinicalTrials.gov, number NCT01586572, and is closed to new participants. FINDINGS: Between March 1, 2012, and May 31, 2013, we enrolled 1009 newborn babies, and randomly assigned 829 (82%) to treatment. 554 (67%) of the 829 babies were included in the per-protocol analysis. Proportions of seroconversion to type-1 poliovirus were 107/135 (79%, 95% CI 72·4-86·1) with mOPV1-1 week, 108/135 (80%, 73·2-86·8) with mOPV1-2 weeks, 129/148 (87%, 80·9-92·0) with mOPV1-4 weeks, and 107/136 (79%, 71·8-85·6) with bOPV-4 weeks. Non-inferiority was shown between groups and no significant differences were noted. Ten participants died during the trial. Seven of these deaths occurred during the lead-in period before randomisation (two from diarrhoea, five from unknown causes). Three infants died from sepsis after random assignment. No deaths were attributed to the procedures or vaccines. Additionally, we noted no events of vaccine-associated paralysis. INTERPRETATION: We identified no significant differences in responses to mOPV1 given with shorter intervals between doses than with the standard 4 week intervals. The short-interval strategy could be particularly beneficial when temporary windows of opportunity for safe access can be granted in areas of conflict--eg, during cease-fire periods. In such situations, we recommend shortening the interval between OPV doses to 7 days. FUNDING: World Health Organization.

Immunogenicity of poliovirus vaccines in chronically malnourished infants: a randomized controlled trial in Pakistan.

Reaching high population immunity against polioviruses (PV) is essential to achieving global polio eradication. Efficacy of oral poliovirus vaccine (OPV) varies and is lower among children living in tropical areas with impoverished environments. Malnutrition found as a risk factor for lower serological protection against PV. We compared whether inactivated polio vaccine (IPV) can be used to rapidly close the immunity gap among chronically malnourished (stunted) infants in Pakistan who will not be eligible for the 14 week IPV dose in routine EPI schedule. A phase 3, multicenter 4-arm randomized controlled trial conducted at five Primary Health Care (PHC) centers in Karachi, Pakistan. Infants, 9-12 months were stratified by length for age Z score into chronically malnourished and normally nourished. Infants were randomized to receive one dose of either bivalent OPV (bOPV) alone or bOPV+IPV. Baseline seroprevalence of PV antibodies and serum immune response to study vaccine dose were assessed by neutralization assay. Vaccine PV shedding in stool was evaluated 7 days after a bOPV challenge dose. Sera and stool were analyzed from 852/928 (92%) enrolled children. At baseline, the seroprevalence was 85.6% (n=386), 73.6% (n=332), and 70.7% (n=319) in malnourished children against PV types 1, 2 and 3 respectively; and 94.1% (n=448), 87.0% (n=441) and 83.6% (n=397) in the normally nourished group (p<0.05). Children had previously received 9-10 doses of bOPV (80%) or tOPV (20%). One dose of IPV+bOPV given to malnourished children increased their serological protection (PV1, n=201, 97.6%; PV2, n=198, 96.1% and PV3, n=189, 91.7%) to parity with normally nourished children who had not received IPV (p=<0.001). Seroconversion and boosting for all three serotypes was significantly more frequent in children who received IPV+bOPV than in those with bOPV only (p<0.001) in both strata. Shedding of polioviruses in stool did not differ between study groups and ranged from 2.4% (n=5) to 7.1% (n=15). In malnourished children the shedding was reduced after bOPV+IPV compared to bOPV only. Chronically malnourished infants were more likely to be unprotected against polioviruses than normal infants. bOPV+IPV helped close the immunity gap better than bOPV alone.

Mean bone mineral density and frequency of occurrence of osteopenia and osteoporosis in patients on hemodialysis: a single-center study.

Chronic renal disease changes both quality and quantity of bone through multi-factorial influences on bone metabolism, leading to osteopenia, osteoporosis and increased risk of fracture. The objectives of our present cross-sectional study were to determine the mean bone mineral density (BMD) and frequency of occurrence of osteoporosis and osteopenia in Saudi patients on hemodialysis (HD) for longer than 1 year. Forty-two male and 78 female patients with age between 20 and 50 years were enrolled in this study. The BMD of the lumbar vertebral spine (LV) and the neck of femur (FN) were measured in all patients. Data were analyzed using SPSS version 17.0 software and the level of significance was considered as P <0.05. The mean BMD in the LV (L2-L4) was 1.155 ± 0.026 g/cm 2 in male and 1.050 ± 0.025 g/cm 2 in female patients (P = 0.016). The mean BMD in the FN was 1.010 ± 0.023 g/cm 2 in male and 0.784 ± 0.020 g/cm 2 in female patients (P = 0.00). Based on the World Health Organization criteria, 73.8% of the male and 44.9% of the female patients in our study had normal BMD (P = 0.002); 16.7% male and 28.2% female patients had osteopenia (P = 0.14), while 9.5% male and 26.9% female patients had osteoporosis (P = 0.01). This study showed a marked decrease in mean BMD in the cortical bone (FN) compared with trabecular bone (LV) (P = 0.00) as well as in female patients on HD compared with male patients (P = 0.016 for LV and P = 0.00 for FN).

Health care use patterns for diarrhea in children in low-income periurban communities of Karachi, Pakistan.

Diarrhea causes 16% of all child deaths in Pakistan. We assessed patterns of healthcare use among caretakers of a randomly selected sample of 959 children ages 0-59 months in low-income periurban settlements of Karachi through a cross-sectional survey. A diarrheal episode was reported to have occurred in the previous 2 weeks among 298 (31.1%) children. Overall, 280 (80.3%) children sought care. Oral rehydration solution and zinc were used by 40.8% and 2%, respectively; 11% were admitted or received intravenous rehydration, and 29% sought care at health centers identified as sentinel centers for recruiting cases of diarrhea for a planned multicenter diarrheal etiology case-control study. Odds ratios for independent predictors of care-seeking behavior were lethargy, 4.14 (95% confidence interval = 1.45-11.77); fever, 2.67 (1.27-5.59); and stool frequency more than six per day, 2.29 (1.03-5.09). Perception of high cost of care and use of home antibiotics were associated with reduced care seeking: odds ratio = 0.28 (0.1-0.78) and 0.29 (0.11-0.82), respectively. There is a need for standardized, affordable, and accessible treatment of diarrhea as well as community education regarding appropriate care in areas with high diarrheal burden.