Assessment of vaccine management in cold chain points of Jashpur and Sarguja districts of Chhattisgarh

Background: It has been observed that besides intensification of routine immunization, more strategic interventions are essential to strengthen the different aspects of immunization services like cold-chain management and monitoring/supportive supervision. The present study was considered as a part of ongoing UNICEF funded project on Supportive Supervision of Routine Immunization in Jashpur and Sarguja districts undertaken by the Department of Community Medicine, GMC Rajnandgaon with the objectives to assess the status of cold chain equipment and logistics management practices, knowledge and practice of cold chain handler (CCHs) about cold chain equipment and logistics management.Methods: A cross-sectional facility based study was conducted from August 2017 to February 2018. Among 18 cold chain points (CCPs), 9 from Jashpur and 9 from Sarguja district were considered for analysis using structured questionnaires provided by UNICEF.Results: In 83.33% CCPs cold chain technician or annual maintenance contract/computer-mediated communication service provider visit for preventive maintenance in the last 4 months. Vaccine CCHs carries out the daily and weekly planned preventive measures as per the checklist in 83.33% CCPs during our visit. In all CCPs iced line refrigerator (ILR) and deep freezer (DF) were placed as per specified guidelines. In 66.66% CCPs there was documentation of monthly review of temperature records. In all CCPs visited standard vaccine and logistics stock/issue registers were available.Conclusions: Most of the components of cold chain and logistics management practices were satisfactory while there is a gap in other components which needs to be improved by means of ongoing project of strengthening of SSRI in both districts.

Evaluation of vaccine storage and cold chain management practices during intensified mission Indradhanush in community health centers of Tikamgarh district of Madhya Pradesh

Background: Vaccination is one of the most effective disease prevention strategies and potency of vaccine is dependent on effective management of cold chain at all levels of vaccine handling. An effective cold chain maintenance system is the backbone of success of any immunization program. This study was done to assess the cold chain management and vaccine storage practices in Tikamgarh district of Madhya Pradesh.Methods: Cross-sectional study was carried out using a structured questionnaire.Results: Dedicated room/space for dry storage not available in any of 03 CHCs. Dedicated table for conditioning of icepacks, dedicated clean clothes for wiping of icepacks after conditioning and power back up was available, ILR and DF were connected to separate functional voltage stabilizer and thermometers were placed correctly only in 66.6% CHCs. ILRs and DFs were properly placed, cabinet temperature of ILR and DFs was maintained in normal range in all the three (100%) CHCs. Record of power failure, records of defrosting/cleaning was maintained in temperature log book and cold chain handlers had knowledge of shake test in only 33.3% CHC.Conclusions: Proper vaccine storage and management of cold chain system is essential for immunization. In order to improve quality of immunization services there is a need of space, temperature monitoring and regular defrosting with record keeping and regular training of cold chain handlers to keep their knowledge and skills updated. Monitoring and supervision of cold chain points by DIO should be on regular basis.

Investigação do papel de SIGIRR/IL-1R8 no crosstalk entre células tumorais e o infiltrado leucocitário / Investigating the role of SIGIRR/IL-1R8 in the crosstalk between tumor cells and the immune system

Células tumorais desenvolvem diversas estratégias para escapar da identificação e eliminação pelo sistema imune. Dessa forma, a investigação dos mecanismos envolvidos na comunicação celular no microambiente tumoral e na desregulação local do sistema imune é crítica para uma melhor compreensão da progressão da doença e para o desenvolvimento de alternativas terapêuticas mais eficazes. Nós aqui demonstramos que SIGIRR/IL-1R8, um importante regulador negativo de receptores de Interleucina-1 (ILRs) e receptores do tipo Toll (TLRs), apresenta expressão aumentada em uma linhagem celular epitelial mamária transformada pela superexpressão do oncogene HER2 e em tumores primários de mama, e promove o crescimento tumoral e metástase através da modulação da inflamação associada ao câncer e da atenuação da resposta imune antitumoral. Observamos que IL-1R8 tem sua expressão correlacionada com HER2 em tecidos mamários e sua alta expressão é fator de pior prognóstico em câncer de mama de baixo grau. Notavelmente, níveis aumentados de IL-1R8 foram observados especialmente nos subtipos HER2+ e Luminais de tumores de mama, e sua expressão aumentada em células epiteliais de mama transformadas por HER2 diminui a ativação da via de NF-κB e a expressão de diferentes citocinas pro-inflamatórias (IL-6, IL-8, TNF, CSF2, CSF3 e IFN-ß1). Meio condicionado de células transformadas por HER2, mas não de variantes celulares com o gene IL-1R8 silenciado, induz a polarização de macrófagos para o fenótipo M2 e inibe a ativação de células NK. Em um modelo murino transgênico de tumorigênese espontânea mediada por HER2, MMTV-neu, verificamos que a deficiência de IL-1R8 (IL-1R8-/-neu) retardou o aparecimento de tumores e reduziu a incidência, a carga tumoral e a disseminação metastática. Contudo, não foram observadas diferenças significativas no crescimento tumoral quando animais IL-1R8-/-neu receberam medula óssea de animais IL-1R8+/+, confirmando um papel importante da expressão de IL-1R8 em células não hematopoiéticas na tumorigênese da mama. Tumores IL-1R8+/+neu apresentaram maiores níveis de citocinas pró-inflamatórias como IL-1ß e VEGF, e menores níveis da citocina imunomodulatória IFN-γ. Além disso, tumores que expressavam IL-1R8 apresentaram menor infiltrado de células NK maduras, células dendríticas (DCs) e linfócitos T-CD8+ e um maior infiltrado de macrófagos M2 e linfócitos T-CD4+. Coletivamente, esses resultados indicam que a expressão de IL-1R8 em tumores de mama pode representar um novo mecanismo de escape da resposta imune e suportam IL-1R8 como potencial alvo terapêutico

Tumor cells develop numerous strategies to fine-tune inflammation and avoid detection and eradication by the immune system. Identification of new players that regulate the cellular crosstalk within the tumor microenvironment and promote local immune dysregulation is critical to understand disease progression and to improve therapeutic strategies. Here, we demonstrate that SIGIRR/IL-1R8, a negative regulator of IL-1R and TLRs, is up-regulated in a HER2-transformed epithelial mammary cell line and in primary breast tumors and promotes tumor growth and metastasis by modulating cancer-related inflammation and impairing anti-tumor immunity. IL-1R8 expression is correlated with HER2 in mammary tissue, and higher tumor IL-1R8 expression is a poor prognostic factor in lower grade breast tumors. Notably, higher levels of IL-1R8 expression were observed in HER2+ and Luminal breast tumor subtypes and IL-1R8 up-regulation in HER2-transformed mammary epithelial cells inhibited NF-κB activation and the expression of pro-inflammatory cytokines (IL-6, IL-8, TNFα, CSF2, CSF3, IFN-ß1). Conditioned medium from HER2-transformed cells, but not from IL-1R8 knockdown variants, induced M2-macrophage polarization and inhibited natural-killer (NK) cell activation. IL-1R8 deficiency in a transgenic mouse model of breast tumorigenesis (MMTV-neu) significantly delayed tumor onset and reduced tumor incidence, burden and metastasis. No significant differences in tumor growth were observed when IL-1R8-/-neu mice were transplanted with bone marrow from IL-1R8+/+ animals, confirming an important role for IL-1R8 expression in non-hematopoietic cells during breast tumorigenesis. IL-1R8+/+neu mammary tumors presented higher levels of pro-inflammatory cytokines such as IL-1ß and VEGF, but lower levels of IFN-γ. Besides, a lower infiltrate of mature NK cells, dendritic cells (DCs) and CD8+ T cells but higher infiltrate of M2-macrophages and CD4+ T cells were present in IL-1R8 expressing tumors. Collectively, our results support IL-1R8 expression as a novel tumor immune escape mechanism in breast cancer and putative target for immunotherapy