High-risk Blocks Research Articles

Space–time clusters and co-occurrence of Plasmodium vivax and Plasmodium falciparum malaria in West Bengal, India

BackgroundMalaria, a prominent vector borne disease causing over a million annual cases worldwide, predominantly affects vulnerable populations in the least developed regions. Despite their preventable and treatable nature, malaria remains a global public health concern. In the last decade, India has faced a significant decline in malaria morbidity and mortality. As India pledged to eliminate malaria by 2030, this study examined a decade of surveillance data to uncover space–time clustering and seasonal trends of Plasmodium vivax and Plasmodium falciparum malaria cases in West Bengal.MethodsSeasonal and trend decomposition using Loess (STL) was applied to detect seasonal trend and anomaly of the time series. Univariate and multivariate space–time cluster analysis of both malaria cases were performed at block level using Kulldorff’s space–time scan statistics from April 2011 to March 2021 to detect statistically significant space–time clusters.ResultsFrom the time series decomposition, a clear seasonal pattern is visible for both malaria cases. Statistical analysis indicated considerable high-risk P. vivax clusters, particularly in the northern, central, and lower Gangetic areas. Whereas, P. falciparum was concentrated in the western region with a significant recent transmission towards the lower Gangetic plain. From the multivariate space–time scan statistics, the co-occurrence of both cases were detected with four significant clusters, which signifies the regions experiencing a greater burden of malaria cases.ConclusionsSeasonal trends from the time series decomposition analysis show a gradual decline for both P. vivax and P. falciparum cases in West Bengal. The space–time scan statistics identified high-risk blocks for P. vivax and P. falciparum malaria and its co-occurrence. Both malaria types exhibit significant spatiotemporal variations over the study area. Identifying emerging high-risk areas of P. falciparum malaria over the Gangetic belt indicates the need for more research for its spatial shifting. Addressing the drivers of malaria transmission in these diverse clusters demands regional cooperation and strategic strategies, crucial steps towards overcoming the final obstacles in malaria eradication.

Measurable Residual Disease Results & Survival with Augmented Early Intensification Therapy in Intermediate-Risk & High-Risk Group Pediatric Acute Lymphoblastic Leukemia Patients Treated with ALL IC-BFM 2009 Protocol: A Single-Center Study from India

Introduction Measurable residual disease (MRD) has proven to be one of the most effective disease monitoring responses in ALL. Multiple treatment groups have demonstrated End-of-Induction (day 33) flow MRD of <0.01% has excellent disease-free survival (DFS). Patients with end-of-consolidation MRD of <0.01% has an overall DFS of 75 % as per COG AALL1131 including the very high-risk B-ALL genotypes. We conducted a study to assess the efficacy & toxicity of augmented early intensification therapy (phase IB) in ALL IC-BFM 2009 protocol for intermediate-risk & high-risk group pediatric ALL patients. Objectives To evaluate efficacy of augmented early intensification therapy (phase IB) in ALL IC-BFM 2009 in terms of achievement of day 78 MRD negative status. To determine the event-free survival in intermediate-risk & high-risk group patients. To appraise the adverse events (AEs) of augmented phase IB Induction. Methodology The study enrolled treatment-naïve ALL patients of 1-25 years' age between April 2021 to February 2023 at AIIMS Rishikesh, India. Patients were risk stratified into Standard (SR), Intermediate (IR) & High risk (HR) groups as per ALL IC BFM 2009 protocol. All patients received Augmented phase IB protocol. The regimen comprised of cyclophosphamide (2 doses), four blocks of cytarabine & 6-mercaptopurine, augmented with vincristine (4 doses), and L-Asparaginase (12 doses). Day 78 bone marrow flowcytometric MRD was performed in all patients irrespective of day 33 marrow morphology & MRD. The study defined complete remission as BM blasts <5% with no extramedullary disease and MRD negativity as <0.01%. The AEs was monitored as per NCI-CTCAE v5. As per the study protocol, patients of B-ALL with day 33 MRD >0.01%, ph-positive ALL, hypodiploidy and T-ALL with day 78 MRD > 0.01% was considered as HR & treated with High-risk blocks consolidation followed by transplant or delayed intensification & maintenance. Results A total of 75 patients enrolled in the study. The M: F ratio was 1.6:1. The median age was 8 years (range 1-25 yrs). B & T-ALL constituted 80% & 20% respectively. ph-positivity accounted 22% of B-ALL. The median Lansky performance was 40 & ECOG was 3 among the participants. The median hb, total white counts, and platelets were 5.9 g/dl, 28 x10 9/L and 30 x10 9/L respectively. At diagnosis, 28% of patients had hyperleukocytosis, 15% with bacterial sepsis, 8% with invasive fungal infections, and 8% with CNS leukemia. At baseline, the distribution of patients in SR, IR & HR was 15%, 68% & 17% respectively. The final risk strata at end-of-induction were 8%, 49% & 43% in SR, IR & HR groups. CNS leukemia accounted for 8% of all patients. Of the total evaluable patients, 86% achieved day 8 good steroid response (absolute blasts count <1000/cu.mm), 73% & 38% achieved day 15 marrow M1 response (<5%blasts) and MRD < 0.1%, 97% & 77% achieved day 33 M1 marrow response and day 33 MRD <0.01% respectively. Among the study participants who were MRD positive on day 15, three-fourths (75%) of them accomplished MRD negativity at day 33. Of the 23% patients with day 33 MRD positivity, 80% achieved day 78 MRD negativity of <0.01% with Augmented phase IB with 3 participants being persistent MRD positive. The median follow-up was 24 months and the overall survival was 74%. The mean survival time was 16.7 months (12.7-20.6) for HR & 21.2 months (18.3-24.1) for IR patients. The subgroup analysis demonstrated an overall survival of 80% for SR, 84% for IR & 64% for HR groups. Nevertheless, the proportion of patients in the SR group (8%) was lower compared to the others. The commonest hematological adverse events were hypofibrinogenemia (22%), followed by febrile neutropenia (19%), anemia (19%), and thrombocytopenia (18%) respectively. The commonest non-hematological AEs were peripheral neuropathy (5%) and typhlitis (5%). Conclusion In our single-center experience, the use of augmented early intensification therapy (phase IB) in ALL IC-BFM 2009 protocol in intermediate-risk & high-risk pediatric ALL patients was associated with achievement of day 78 MRD negative status in 80% patients who had day 33 MRD-positivity without significant treatment-related toxicity, and encouraging event-free survival in this patient population.

Risk source identification and diffusion trends of metal(loid)s in stream sediments from an abandoned arsenic-containing mine

Stream sediments from mine area are a converging source of water and soil pollution. The risk and development trends of metal(loid)s pollution in sediments from an abandoned arsenic-containing mine were studied using modelling techniques. The results showed that the combined techniques of geographic information system (GIS), random forest (RF), and numerical simulation (NS) could identify risk sources and diffusion trends of metal(loid)s in mine sediments. The median values of As, Cd, Hg, and Sb in sediments were 5.01, 3.02, 5.67, and 3.20 times of the background values of stream sediments in China, respectively. As (14.09%) and Hg (18.64%) pollution in mine stream sediments were severe while As is the main potential risk source with a strong spatial correlation. High-risk blocks were concentrated in the landfill area, with the surrounding pollution shows a decreasing trend of “step-type” pollution. The risk correlation between Hg and As (55.37%) in the landfill area is high. As a case of arsenic, the diffusion capacity of As within 500m is strong and stabilizes at 1 km when driven by the flows of 0.05, 0.5, and 5 m3/s, respectively. With the worst-case scenario flow (86 m3/s), it would take only 147 days for the waters within 3 km to become highly polluted. The high pollution levels in a stream under forecast of different distance intervals (500, 1500, 2000 m) within 6.5 km is arrived at approximate 344, 357, and 384 days, respectively. The study suggested the combined technique of GIS, RF, and NS can serve the risk source identification of contaminated sites and risk forecast of toxic element diffusion in emergency situations.

Value of Flow Cytometry for MRD-Based Relapse Prediction in B-Cell Precursor Acute Lymphoblastic Leukemia in a Multi-Center Setting

Background: PCR of rearranged antigen receptor genes is the method of choice for MRD quantification in ALL. Although FCM-MRD is faster and biologically more informative than PCR, the analysis requires a high level of training. The only larger published studies using FCM-MRD based stratification (Borowitz, Blood, 2008 and 2015) showed a clear association with clinical outcome in BCP-ALL. However, MRD analyses were centralized and these studies included only one MRD-based stratification (MRD levels at the end of induction). Patients and methods: We examined FCM-MRD as stratification tool in BCP-ALL at various timepoints in a large-scale multicenter (18 MRD centers) study. A total of 1487 patients with BCP-ALL (1298 children (younger than 18 years) and 189 adults (18-45 years) are included in the study and were treated according to the NOPHO ALL2008 protocol between July 2008 and February 2016. The median follow-up time for patients in first remission was 51 months (IQR 32-75). MRD was measured by FCM and/or real time quantitative PCR on days 15, 29 (end of induction) and 79 (for standard (SR) and intermediate risk (IR) patients) and prior to and after high risk blocks. A 6-colour FCM analysis including 3 standardized antibody combinations was used and performed in 18 laboratories. Patients were stratified by FCM-MRD, or by PCR-MRD if no FCM-MRD marker was available. End-of-induction MRD (cut-off 10-3) was used to stratify patients to standard risk (SR) vs intermediate risk (IR) or IR vs high risk consolidation therapy (in case of WBC > 100 x 109/L at diagnosis). Patients with MRD >=2.5x10-1 on day 15 were stratified to high risk block therapy. Patients with MRD >=5x10-2 on day 29 or day 79/post high risk-2 block MRD >=10-3 were stratified to HSCT. Primary outcomes were 5year event-free survival (5y EFS) and 5year cumulative incidence of relapse (5y CIR). Results: Only two patients (0.14% of total) had neither an informative FCM nor a PCR marker, and an informative FCM marker combination for MRD monitoring was identified in 96.2% of patients. There was a significant correlation between FCM- and PCR-MRD levels on day 15 (r=0.77, p<0.0001, n=153) and 29 (r=0.81, p<0.0001, n=140). Based on FCM-MRD only, the median MRD level on day 15, 29 and 79/post high risk-2 block was 5x10-3, 1.1x10-4, and below detection limit, respectively. Adults had significantly higher MRD levels at all time-points (p<0.0001 for day 15 and 29, p=0.0019 for day 79, Mann-Whitney). The 5y EFS was 86.1% (95% CI 84.1-88.1) with a 5y CIR of 9.5% (95% CI 7.8-11.3, n=1487). The day 29 FCM-MRD level was closely associated with clinical outcome and a higher hazard of relapse was seen independently for a FCM-MRD >=10-3 (hazard ratio (HR) 2.4, CI 1.6-3.7, p<0.0001), age>18 year (HR 3.0, CI 1.7-5.3, p<0.0001), WBC>=100 (HR 2.7, CI 1.6-4.6, p=0.0001), and B-other (HR 2.1, CI 1.2-3.5, p=0.0052) or high risk B-ALL cytogenetic aberration (rearranged KMT2A/iAMPchr21/hypodiploid) (HR 3.2, CI 1.6-6.1, p=0.0006) (multivariate cause-specific Cox regression, n=1328). Patients with a day 79 FCM-MRD >=10-4 and <10-3 had a significantly higher CIR (22.1%, CI 10.8-33.5%, n=68) compared to FCM-MRD <10-4 (7.5%, CI 2.1-12.8%, n=110) or undetectable (6.3%, CI 4.5-8.2%, n=999, p=0.0087 for FCM-MRD >=10-4 and <10-3vs <10-4 or undetectable). After adjusting for WBC, age, and the day 29 FCM-MRD level, a day 79 FCM-MRD >=10-4 and <10-3 was still significantly associated with a worse 5y CIR for non-transplanted patients (HR 2.3, CI 1.19-4.36, p=0.012 compared to undetectable FCM-MRD, n=1171). Patients with day 15 FCM-MRD <10-3 had a significantly better 5y EFS (92.0%, CI 89.2-95.0%) and CIR (3.9%, CI 1.7-6.1%, n=432) than patients with FCM-MRD >=10-3 and <2.5x10-1, who had a 5y EFS of 85.5% (CI 82.7-88.3%, p=0.0016, n=837) and a 3-fold higher 5y CIR (11.0%, CI 8.4-13.5%, p<0.0001, n=432). Among patients with day 15 FCM-MRD<10-3, the relapse incidence was comparable for patients with FCM-MRD 10-4 - <10-3 and below 10-4 (CIR 3.6, CI 0.5-6.7 vs. CIR 4.1, CI 1.0-7.2, p=0.83, n=432). Conclusion: FCM-MRD performed in a multi-center setting is a clinically useful method for disease monitoring and MRD-based treatment stratification in BCP-ALL. Moreover, FCM-MRD is a reliable indicator of outcome in BCP-ALL independently of other key risk factors. Residual disease >=10-4 and <10-3 at day 79 in SR/IR patients not allocated to HSCT further identifies patients with a high risk of relapse. Disclosures No relevant conflicts of interest to declare.

PS948 EXCELLENT RESPONSE TO BLINATUMOMAB IN REFRACTORY B LINEAGE ACUTE LYMPHOBLASTIC LEUKAEMIA IN CHILDREN AND YOUNG ADULTS AFTER DEBULKING CHEMOTHERAPY TO ACHIEVE PARTIAL REMISSION

Background:A recent phase I/II study of blinatumomab in children with relapsed/refractory B cell acute lymphoblastic leukaemia (B‐ALL), found 39–51% achieved complete, often MRD negative, remission after two cycles of therapy. Higher responses were observed in patients with less than 50% bone marrow blasts, compared to greater than 50% (55.6% vs 32.7% (95% CI 30.8–78.5 and 20.3–47.1 respectively). Furthermore, an adult study showed complete minimal residual disease (MRD) response rates of 78% when blinatumomab was used to treat MRD‐positive ALL in haematological remission. Hence response rates (and toxicity) to blinatumomab are highly correlated with pre‐treatment disease burden.Aims:We aimed to determine the outcome of children and young adults who received blinatumomab for primary refractory or relapsed B‐ALL, who had persistent MRD, or after debulking chemotherapy to achieve a partial remission.Methods:Eighteen patients were identified through a national survey. The mean age of patients was 8 years (range 0.5‐ 22), 4 infants and 1 Down syndrome ALL). All patients had B‐lineage ALL which was CD19 positive. None had active CNS disease at the point of receiving blinatumomab. Prior to administration of blinatumomab, all patients either had persistent MRD following several courses of intensive chemotherapy or received debulking chemotherapy for heavier marrow infiltrates. Pre‐blinatumomab chemotherapy to which the patients had failed to obtain an adequate MRD response included UKALL 2011 Regimens A or C, UKALL R3, Interfant 06, FLA‐IDA or NOPHO high risk blocks. Patients received 5–15 μg/m2 of blinatumomab for 1–2 cycles prior to definitive therapy.Results:Pre‐blinatumomab, all patients except two were in morphological remission with MRD measurable by PCR (0.003–6%), the remaining patient had 15 and 32% marrow disease by morphology. After 1–2 cycles of blinatumomab all patients had negative MRD when measured by flow cytometry and/or by PCR, giving a 100% response rate. This was followed by haemopoietic stem cell transplant (HSCT) in 17 patients, and of these, 11 are currently alive and disease‐free. Three patients died from transplant‐related complications, without evidence of disease recurrence. One patient had a lineage switch relapse post‐transplant and 2 with CD19 positive relapse 3–7 months post‐transplant have received CART cells. One patient is awaiting CART cells having relapsed 2 weeks after 1 cycle of blinatumomab.Minimal toxicity was observed; 6 patients had grade 1–2 CRS, which resolved spontaneously without interruption of therapy or treatment with corticosteroids or Tocilizumab. Two patients reported grade neurotoxicity (grade 1+3).Summary/Conclusion:This preliminary UK experience demonstrates that excellent MRD response is observed with minimal toxicity in children and young adults who receive blinatumomab for persistent MRD or after debulking chemotherapy which provides an opportunity for transplant in otherwise ineligible patients.

Low burden of minimal residual disease prior to transplantation in children with very high risk acute lymphoblastic leukaemia: The NOPHO ALL2008 experience.

The population-based Nordic/Baltic acute lymphoblastic leukaemia (ALL) Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol combined minimal residual disease (MRD)-driven treatment stratification with very intense first line chemotherapy for patients with high risk ALL. Patients with MRD ≥5% at end of induction or ≥10-3 at end of consolidation or following two high risk blocks were eligible for haematopoietic cell transplantation (HCT) in first remission. After at least three high risk blocks a total of 71 children received HCT, of which 46 had MRD ≥5% at end of induction. Ten patients stratified to HCT were not transplanted; 12 received HCT without protocol indication. Among 69 patients with evaluable pre-HCT MRD results, 22 were MRD-positive, one with MRD ≥10-3 . After a median follow-up of 5·5years, the cumulative incidence of relapse was 23·5% (95% confidence interval [CI]: 10·5-47·7) for MRD-positive versus 5·1% (95% CI: 1·3-19·2), P=0·02) for MRD-negative patients. MRD was the only variable significantly associated with relapse (hazard ratio 9·1, 95% CI: 1·6-51·0, P=0·012). Non-relapse mortality did not differ between the two groups, resulting in disease-free survival of 85·6% (95% CI: 75·4-97·2) and 67·4% (95% CI: 50·2-90·5), respectively. In conclusion, NOPHO block treatment efficiently reduced residual leukaemia which, combined with modern transplant procedures, provided high survival rates, also among pre-HCT MRD-positive patients.

Excellent Response to Blinatumomab in Children and Young Adults with Refractory B Lineage Acute Lymphoblastic Leukaemia for Persistent MRD or after Debulking Chemotherapy for Higher Disease Burden

Introduction: A recent phase I/II study of blinatumomab in children with relapsed/refractory B cell acute lymphoblastic leukaemia (B-ALL), found 39-51% achieved complete, often MRD negative, remission after two cycles of therapy. Higher responses were observed in patients with less than 50% bone marrow blasts, compared to greater than 50% (55.6% vs 32.7% (95% CI 30.8-78.5 and 20.3-47.1 respectively)1. Furthermore, an adult study showed complete minimal residual disease (MRD) response rates of 78% when blinatumomab was used to treat MRD-positive ALL in haematological remission 2. Hence response rates (and toxicity) to blinatumomab are highly correlated with pre-treatment disease burden. We present preliminary data showing an excellent response to blinatumomab in children and young adults with resistant B-ALL who had persistent MRD, or after debulking chemotherapy to achieve a partial remission.Methods: Eleven patients were identified through a national survey. The mean age of patients was 10 years (range 0.7-22 years, 3 infants and 1 Down syndrome ALL). All patients had B-lineage ALL which was CD19 positive. None had active CNS disease at the point of receiving blinatumomab. Prior to administration of blinatumomab, all patients either had persistent MRD following several courses of intensive chemotherapy or received debulking chemotherapy for heavier marrow infiltrates. Pre-blinatumomab chemotherapy to which the patients had failed to obtain an adequate MRD response included UKALL 2011 Regimens A or C, UKALL R3, Interfant 06 or NOPHO high risk blocks. Patients received 5-15 µg/m2 of blinatumomab for 1-2 cycles prior to definitive therapy.Results: Pre-blinatumomab, all patients except one were in morphological remission with MRD measurable by PCR (0.003-1%), the remaining patient had 9% marrow disease by morphology. After 1-2 cycles of blinatumomab all patients had negative MRD when measured by flow cytometry and/or by PCR, giving a 100% response rate. This was followed by Haemopoietic stem cell transplant (HSCT) in nine patients and the remaining two are awaiting transplant. Further data on patient characteristics, CNS status, relapse and survival outcome are being collected and will be presented at the meeting.Minimal toxicity was observed; of the seven patients in whom toxicity data were available, three had grade 1 CRS, which resolved spontaneously without interruption of therapy or treatment with corticosteroids or Tocilizumab. One patient reported grade 1 neurotoxicity.This preliminary UK experience demonstrates that excellent MRD response is observed with minimal toxicity in children and young adults who receive blinatumomab for persistent MRD or after debulking chemotherapy. This provided a bridge to transplant in patients who would otherwise not have benefited from the procedure because of persistent MRD. We are planning to extend these observations by undertaking a study of this strategy in first high-risk B-ALL relapse.Stackelberg Av, Locatelli F, Zugmaier G, et al. Phase I/Phase II Study of Blinatumomab in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia. Journal of Clinical Oncology. 2016;34(36):4381-4389.Gokbuget N, Dombret H, Bonifacio M, et al. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. 2018;131(14):1522-1531. DisclosuresGhorashian:Celgene: Other: travel support; Novartis: Honoraria. Marks:Novartis: Consultancy; Pfizer: Consultancy; Amgen: Consultancy. Vora:Amgen: Other: Advisory board; Novartis: Other: Advisory board; Jazz: Other: Advisory board; Medac: Other: Advisory board; Pfizer: Other: Advisory board.

Imatinib treatment of paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (EsPhALL2010): a prospective, intergroup, open-label, single-arm clinical trial

The EsPhALL2004 randomised trial showed a 10% advantage in disease-free survival for short, discontinuous use of imatinib after induction compared with no use of imatinib in patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia receiving Berlin-Frankfurt-Münster chemotherapy and haemopoietic stem-cell transplantation (HSCT). Other contemporary studies showed an advantage from continuous protracted exposure to imatinib, challenging the indications to transplant. The EsPhALL2010 study was designed to assess whether imatinib given from day 15 of induction and continuously throughout chemotherapy led to a different outcome to that obtained in EsPhALL2004, despite decreasing the number of patients having HSCT. This prospective, intergroup, open-label, single-arm clinical trial (EsPhALL2010) was done at 11 study groups across Europe, Chile, and Hong Kong. Patients aged 1-17 years with the translocation t(9;22)(q34;q11) who were recruited into national front-line trials for acute lymphoblastic leukaemia were eligible for this trial. Patients with abnormal renal or hepatic function or an active systemic infection were ineligible. Patients received imatinib 300 mg/m2 continuously from day 15 of induction during chemotherapy. Eligibility to HSCT depended on early morphological response and minimal residual disease. Imatinib was recommended throughout the first year after transplant. The co-primary endpoints were event-free survival and overall survival. All analyses were done in the intention-to-treat population. The trial is registered with the European Clinical Trials Database (EudraCT 2004-001647-30) and with ClinicalTrials.gov (NCT00287105) and is completed. 158 patients were screened for eligibility, of whom 155 were enrolled between Jan 1, 2010, and Dec 31, 2014. 151 (97%) patients achieved first complete remission after induction and four after the consolidation phase, with 102 (66%) patients categorised as good risk and 53 (34%) as poor risk according to EsPhALL risk stratification criteria. 59 (38%) patients had HSCT during their first complete remission. 40 (26%) patients relapsed and 41 (26%) patients died during the study (25 [61%] during complete continuous remission, and 16 [39%] after relapse). The 5-year event-free survival was 57·0% (95% CI 48·5-64·6) and 5-year overall survival was 71·8% (63·5-78·5). 154 serious adverse events were reported in 80 (52%) of 155 patients. The most common toxicity was infection (61 [39%] patients, mostly bacterial); gastrointestinal disorders occurred in ten (6%) patients and osteonecrosis in eight (5%). Serious adverse events occurred mainly during high-risk blocks and delayed intensifications, including 14 fatal events (one in the consolidation phase, six in high-risk blocks, six in first delayed intensification, and one in second delayed intensification). Although HSCT was done in a smaller proportion of patients in EsPhALL2010 than in EsPhALL2004, event-free and overall survival were similar between the two studies. Our data suggest that imatinib given early and continuously with intensive chemotherapy might increase toxicity. Projet Hospitalier de Recherche Clinique-Cancer and Novartis France; Bloodwise and Cancer Research UK; Ministry of Health, Czech Republic.

Does India need national child mortality surveillance project to reduce child mortality? An opportunity from National Polio Surveillance Project (NPSP)

In 2015, India had 20 percent share of global under-five deaths (1.2 million), highest number of deaths in the world. In the era of Sustainable Development Goal (SDG), to accomplish goal 3, target 3.2 to reduce child mortality to 25 per 1,000 live births, India needs to accelerate to achieve the same. India was taken off from the list of polio endemic countries by World Health Organization in February 2012. In 1997 the National Polio Surveillance Project (NPSP) was established as a joint partnership between the World Health Organization and the Ministry of Health and Family Welfare (MoHFW), Government of India. As in Polio eradication program interaction between the health care providers and Surveillance Medical Officer (SMO), had provided the foundation for successful Acute Flaccid Paralysis (AFP) surveillance, same opportunity can be used for every child death. Each child death reported by reporting unit (RU) needs to be investigated in case investigation form (CIF) and the factors related to continuum of care for maternal, newborn and child health whichever responsible for child death needs to be identified for action. Another aim of this project will be to capture each and every child death occurring in the district and identifying the high risk blocks and accordingly training of health workers and private practitioner can be undertaken for capacity building. The feedback of factors identified for child death can be given to health officers of concerned district and same can be discussed in District Task Force meeting, so appropriate corrective action is initiated; also same can be reviewed at regional, state and national level meetings. National Child Mortality Surveillance Project can take the advantage of network of SMO already available with NPSP along with training modules and forms.

Cross-sectional serologic assessment of immunity to poliovirus infection in high-risk areas of northern India.

The objectives of this survey were to assess the seroprevalence of antibodies to poliovirus types 1 and 3 and the impact of bivalent (types 1 and 3) oral poliovirus vaccine (bOPV) use in immunization campaigns in northern India. In August 2010, a 2-stage stratified cluster sampling method identified infants aged 6-7 months in high-risk blocks for wild poliovirus infection. Vaccination history, weight and length, and serum were collected to test for neutralizing antibodies to poliovirus types 1, 2, and 3. Seroprevalences of antibodies to poliovirus types 1, 2, and 3 were 98% (95% confidence interval [CI], 97%-99%), 66% (95% CI, 62%-69%), and 77% (95% CI, 75%-79%), respectively, among 664 infants from Bihar and 616 infants from Uttar Pradesh. Infants had received a median of 3 bOPV doses and 2 monovalent type 1 OPV (mOPV1) doses through campaigns and 3 trivalent OPV (tOPV) doses through routine immunization. Among subjects with 0 tOPV doses, the seroprevalences of antibodies to type 3 were 50%, 77%, and 82% after 2, 3, and 4 bOPV doses, respectively. In multivariable analysis, malnutrition was associated with a lower seroprevalence of type 3 antibodies. This study confirmed that replacing mOPV1 with bOPV in campaigns was successful in maintaining very high population immunity to type 1 poliovirus and substantially decreasing the immunity gap to type 3 poliovirus.

Outcomes of polio eradication activities in Uttar Pradesh, India: the Social Mobilization Network (SM Net) and Core Group Polio Project (CGPP)

BackgroundThe primary strategy to interrupt transmission of wild poliovirus in India is to improve supplemental immunization activities and routine immunization coverage in priority districts with a focus on 107 high-risk blocks of western Uttar Pradesh and central Bihar. Villages or urban areas with a history of wild poliovirus transmission, or hard-to-reach or resistant populations are categorized as high-risk areas within blocks. The Social Mobilization Network (SM Net) was formed in Uttar Pradesh in 2003 to support polio eradication efforts through improved planning, implementation and monitoring of social mobilization activities in those high-risk areas. In this paper, we examine the vaccination outcomes in districts of SM Net where the CORE Group works.MethodsWe carried out a secondary data analysis of routine monitoring information collected by the SM Net and the Government of India. These data include information about vaccination outcomes in SM Net areas and non-SM Net areas within the districts where the CORE Group operates. Statistical analysis was used to compare, between SM Net and non-SM Net areas, vaccination outcomes considered sensitive to social mobilization efforts of the SM Net. We employed Generalized Estimating Equations (GEE) statistical method to account for Intra-cluster Correlation (ICC), and used 'Quasi-likelihood under the independence model criterion (QIC)' as the model selection method.ResultsVaccination outcomes in SM Net areas were as high as or higher than in non-SM Net areas. There was considerable variation in vaccination outcomes between districts.ConclusionsWhile not conclusive, the results suggest that the social mobilization efforts of the SM Net and the CORE Group are helping to increase vaccination levels in high-risk areas of Uttar Pradesh. Vaccination outcomes in CORE Group areas were equal or higher than in non-CORE, non-SM Net areas. This occurred even though SM Net areas are those with more community resistance to polio vaccination and/or are have harder-to-reach populations than non-SM Net areas. Other likely explanations for the relatively good vaccination performance in SM Net areas are not apparent.