Migration from Epi Info to District Health Information Software 2 for Vaccine-Preventable Disease Surveillance - World Health Organization African Region, 2019-2023.

High-quality vaccine-preventable disease (VPD) surveillance data are critical for timely outbreak detection and response. In 2019, the World Health Organization (WHO) African Regional Office (AFRO) began transitioning from Epi Info, a free, CDC-developed statistical software package with limited capability to integrate with other information systems, affecting reporting timeliness and data use, to District Health Information Software 2 (DHIS2). DHIS2 is a free and open-source software platform for electronic aggregate Integrated Disease Surveillance and Response (IDSR) and case-based surveillance reporting. A national-level reporting system, which provided countries with the option to adopt this new system, was introduced. Regionally, the Epi Info database will be replaced with a DHIS2 regional data platform. This report describes the phased implementation from 2019 to the present. Phase one (2019-2021) involved developing IDSR aggregate and case-based surveillance packages, including pilots in the countries of Mali, Rwanda, and Togo. Phase two (2022) expanded national-level implementation to 27 countries and established the WHO AFRO DHIS2 regional data platform. Phase three (from 2023 to the present) activities have been building local capacity and support for country reporting to the regional platform. By February 2024, eight of 47 AFRO countries had adopted both the aggregate IDSR and case-based surveillance packages, and two had successfully transferred VPD surveillance data to the AFRO regional platform. Challenges included limited human and financial resources, the need to establish data-sharing and governance agreements, technical support for data transfer, and building local capacity to report to the regional platform. Despite these challenges, the transition to DHIS2 will support efficient data transmission to strengthen VPD detection, response, and public health emergencies through improved system integration and interoperability.

CDC's COVID-19 International Vaccine Implementation and Evaluation Program and Lessons from Earlier Vaccine Introductions.

The US Centers for Disease Control and Prevention (CDC) supports international partners in introducing vaccines, including those against SARS-CoV-2 virus. CDC contributes to the development of global technical tools, guidance, and policy for COVID-19 vaccination and has established its COVID-19 International Vaccine Implementation and Evaluation (CIVIE) program. CIVIE supports ministries of health and their partner organizations in developing or strengthening their national capacities for the planning, implementation, and evaluation of COVID-19 vaccination programs. CIVIE's 7 priority areas for country-specific technical assistance are vaccine policy development, program planning, vaccine confidence and demand, data management and use, workforce development, vaccine safety, and evaluation. We discuss CDC's work on global COVID-19 vaccine implementation, including priorities, challenges, opportunities, and applicable lessons learned from prior experiences with Ebola, influenza, and meningococcal serogroup A conjugate vaccine introductions.

Mumps: an Update on Outbreaks, Vaccine Efficacy, and Genomic Diversity.

Mumps is an acute viral infection characterized by inflammation of the parotid and other salivary glands. Persons with mumps are infectious from 2 days before through 5 days after parotitis onset, and transmission is through respiratory droplets. Despite the success of mumps vaccination programs in the United States and parts of Europe, a recent increase in outbreaks of mumps virus infections among fully vaccinated populations has been reported. Although the effectiveness of the mumps virus component of the measles-mumps-rubella (MMR) vaccine is suboptimal, a range of contributing factors has led to these outbreaks occurring in high-vaccination-coverage settings, including the intensity of exposure, the possibility of vaccine strain mismatch, delayed implementation of control measures due to the timeliness of reporting, a lack of use of appropriate laboratory tests (such as reverse transcription-PCR), and time since last vaccination. The resurgence of mumps virus infections among previously vaccinated individuals over the past decade has prompted discussions about new strategies to mitigate the risk of future outbreaks. The decision to implement a third dose of the MMR vaccine in response to an outbreak should be considered in discussions with local public health agencies. Traditional public health measures, including the isolation of infectious persons, timely contact tracing, and effective communication and awareness education for the public and medical community, should remain key interventions for outbreak control. Maintaining high mumps vaccination coverage remains key to U.S. and global efforts to reduce disease incidence and rates of complications.

Oral Cholera Vaccine Coverage during an Outbreak and Humanitarian Crisis, Iraq, 2015.

During November-December 2015, as part of the 2015 cholera outbreak response in Iraq, the Iraqi Ministry of Health targeted ≈255,000 displaced persons >1 year of age with 2 doses of oral cholera vaccine (OCV). All persons who received vaccines were living in selected refugee camps, internally displaced persons camps, and collective centers. We conducted a multistage cluster survey to obtain OCV coverage estimates in 10 governorates that were targeted during the campaign. In total, 1,226 household and 5,007 individual interviews were conducted. Overall, 2-dose OCV coverage in the targeted camps was 87% (95% CI 85%-89%). Two-dose OCV coverage in the 3 northern governorates (91%; 95% CI 87%-94%) was higher than that in the 7 southern and central governorates (80%; 95% CI 77%-82%). The experience in Iraq demonstrates that OCV campaigns can be successfully implemented as part of a comprehensive response to cholera outbreaks among high-risk populations in conflict settings.

Using the World Health Organization Measles Programmatic Risk Assessment Tool for Monitoring of Supplemental Immunization Activities in the Philippines.

In 2012, the World Health Organization Regional Committee for the Western Pacific Region (WPR) reaffirmed its commitment to eliminate measles and urged WPR member states to interrupt endemic measles virus transmission as rapidly as possible. In 2013, a large measles outbreak occurred in the Philippines despite implementation of measles elimination strategies including a nationwide supplemental immunization activity (SIA) in 2011 using measles- and rubella-containing vaccine and targeting children aged nine months to seven years. To prevent future measles outbreaks a new tool was developed to assess district-level risk for measles outbreaks, based on the WPR polio risk assessment tool previously applied in the Philippines. Risk was assessed as a function of combined indicator scores from four data input categories: population immunity, surveillance quality, program performance, and threat assessment. On the basis of the overall score, the tool assigned each district a risk category of low, medium, high, or very high. Of the 122 districts and highly urbanized cities in the Philippines, 58 (48%) were classified as high risk or very high risk, including the district of the Metro Manila area and Region 4A where the outbreak began in 2013. Risk assessment results were used to guide the monitoring and supervision during the nationwide SIA conducted in 2014. The initial tool drafted in the Philippines served as a template for development of the global risk assessment tool. Regular annual measles programmatic risk assessments can be used to help plan risk mitigation activities and measure progress toward measles elimination.

Development of the World Health Organization Measles Programmatic Risk Assessment Tool Using Experience from the 2009 Measles Outbreak in Namibia.

In the World Health Organization (WHO) African region, reported measles cases decreased by 80% and measles mortality declined by 88% during 2000-2012. Based on current performance trends, however, focused efforts will be needed to achieve the regional measles elimination goal. To prioritize efforts to strengthen implementation of elimination strategies, the Centers for Disease Control and Prevention and WHO developed a measles programmatic risk assessment tool to identify high-risk districts and guide and strengthen program activities at the subnational level. This article provides a description of pilot testing of the tool in Namibia using comparisons of high-risk districts identified using 2006-2008 data with reported measles cases and incidence during the 2009 outbreak. Of the 34 health districts in Namibia, 11 (32%) were classified as high risk or very high risk, including the district of Engela where the outbreak began in 2009. The district of Windhoek, including the capital city of Windhoek, had the highest overall risk score-driven primarily by poor population immunity and immunization program performance-and one of the highest incidences during the outbreak. Other high-risk districts were either around the capital district or in the northern part of the country near the border with Angola. Districts categorized as high or very high risk based on the 2006-2008 data generally experienced high measles incidence during the large outbreak in 2009, as did several medium- or low-risk districts. The tool can be used to guide measles elimination strategies and to identify programmatic areas that require strengthening.

Development of a District-Level Programmatic Assessment Tool for Risk of Measles Virus Transmission.

All six World Health Organization (WHO) regions have now set goals for measles elimination by or before 2020. To prioritize measles elimination efforts and use available resources efficiently, there is a need to identify at-risk areas that are offtrack from meeting performance targets and require strengthening of programmatic efforts. This article describes the development of a WHO measles programmatic risk assessment tool to be used for monitoring, guiding, and sustaining measles elimination efforts at the subnational level. We outline the tool development process; the tool specifications and requirements for data inputs; the framework of risk categories, indicators, and scoring; and the risk category assignment. Overall risk was assessed as a function of indicator scores that fall into four main categories: population immunity, surveillance quality, program performance, and threat assessment. On the basis of the overall score, the tool assigns each district a risk of either low, medium, high, or very high. The cut-off criteria for the risk assignment categories were based on the distribution of scores from all possible combinations of individual indicator cutoffs. The results may be used for advocacy to communicate risk to policymakers, mobilize resources for corrective actions, manage population immunity, and prioritize programmatic activities. Ongoing evaluation of indicators will be needed to evaluate programmatic performance and plan risk mitigation activities effectively. The availability of a comprehensive tool that can identify at-risk districts will enhance efforts to prioritize resources and implement strategies for achieving the Global Vaccine Action Plan goals for measles elimination.

Application of the World Health Organization Programmatic Assessment Tool for Risk of Measles Virus Transmission-Lessons Learned from a Measles Outbreak in Senegal.

The World Health Organization (WHO) African Region set a goal for regional measles elimination by 2020; however, regional measles incidence was 125/1,000,000 in 2012. To support elimination efforts, the WHO and U.S. Centers for Disease Control and Prevention developed a tool to assess performance of measles control activities and identify high-risk areas at the subnational level. The tool uses routinely collected data to generate district-level risk scores across four categories: population immunity, surveillance quality, program performance, and threat assessment. To pilot test this tool, we used retrospective data from 2006 to 2008 to identify high-risk districts in Senegal; results were compared with measles case-based surveillance data from 2009 when Senegal experienced a large measles outbreak. Seventeen (25%) of 69 districts in Senegal were classified as high or very high risk. The tool highlighted how each of the four categories contributed to the total risk scores for high or very high risk districts. Measles case-based surveillance reported 986 cases during 2009, including 368 laboratory-confirmed, 540 epidemiologically linked, and 78 clinically compatible cases. The seven districts with the highest numbers of laboratory-confirmed or epidemiologically linked cases were within the capital region of Dakar. All except one of these seven districts were estimated to be high or very high risk, suggesting that districts identified as high risk by the tool have the potential for measles outbreaks. Prospective use of this tool is recommended to help immunization and surveillance program managers identify high-risk areas in which to strengthen specific programmatic weaknesses and mitigate risk for potential measles outbreaks.

Measles Outbreak Associated with Vaccine Failure in Adults--Federated States of Micronesia, February-August 2014.

On May 15, 2014, CDC was notified of two laboratory-confirmed measles cases in the Federated States of Micronesia (FSM), after 20 years with no reported measles. FSM was assisted by the World Health Organization (WHO), the United Nations Children's Fund (UNICEF), and CDC in investigating suspected cases, identify contacts, conduct analyses to guide outbreak vaccination response, and review vaccine cold chain practices. During February­August, three of FSM's four states reported measles cases: Kosrae (139 cases), Pohnpei (251), and Chuuk (3). Two thirds of cases occurred among adults aged ≥20 years; of these, 49% had received ≥2 doses of measles-containing vaccine (MCV). Apart from infants aged <12 months who were too young for routine vaccination, measles incidence was lower among children than adults. A review of current cold chain practices in Kosrae revealed minor weaknesses; however, an absence of historical cold chain maintenance records precluded an evaluation of earlier problems. Each state implemented vaccination campaigns targeting children as young as age 6 months through adults up to age 57 years. The preponderance of cases in this outbreak associated with vaccine failure in adults highlights the need for both thorough case investigation and epidemiologic analysis to guide outbreak response vaccination. Routine childhood vaccination coverage achieved in recent years limited the transmission of measles among children. Even in areas where transmission has not occurred for years, maintaining high 2-dose MCV coverage through routine and supplemental immunization is needed to prevent outbreaks resulting from increased measles susceptibility in the population.

Use of drug-susceptibility testing for management of drug-resistant tuberculosis, Thailand, 2004-2008.

In 2004, routine use of culture and drug-susceptibility testing (DST) was implemented for persons in 5 Thailand provinces with a diagnosis of tuberculosis (TB). To determine if DST results were being used to guide treatment, we conducted a retrospective chart review for patients with rifampin-resistant or multidrug-resistant (MDR) TB during 2004-2008. A total of 208 patients were identified. Median time from clinical sample collection to physician review of DST results was 114 days. Only 5.8% of patients with MDR TB were empirically prescribed an appropriate regimen; an additional 31.3% received an appropriate regimen after DST results were reviewed. Most patients with rifampin -resistant or MDR TB had successful treatment outcomes. Patients with HIV co-infection and patients who were unmarried or had received category II treatment before DST results were reviewed had less successful outcomes. Overall, review of available DST results was delayed, and results were rarely used to improve treatment.

Strengthening the WHO Regional Office for Africa (WHO AFRO) COVID-19 vaccination information system.

This manuscript describes the process and impact of strengthening the WHO Regional Office for Africa (WHO AFRO)'s COVID-19 vaccination information system. This system plays a critical role in tracking vaccination coverage, guiding resource allocation and supporting vaccination campaign roll-out for countries in the African region. Recognising existing data management issues, including complex reporting prone to human error, compromised data quality and underutilisation of collected data, WHO AFRO introduced significant system improvements during the COVID-19 pandemic. These improvements include shifting from an Excel-based to an online Azure-based data collection system, automating data processing and validation, and expansion of collected data. These changes have led to improvements in data quality and quantity including a decrease in data non-validity, missingness, and record duplication, and expansion of data collection forms to include a greater number of data fields, offering a more comprehensive understanding of vaccination efforts. Finally, the creation of accessible information products-including an interactive public dashboard, a weekly data pack and a public monthly bulletin-has improved data use and reach to relevant partners. These resources provide crucial insights into the region's vaccination progress at national and subnational levels, thereby enabling data-driven decision-making to improve programme performance. Overall, the strengthening of the WHO AFRO COVID-19 vaccination information system can serve as a model for similar efforts in other WHO regions and contexts. The impact of system strengthening on data quality demonstrated here underscores the vital role of robust data collection, capacity building and management systems in achieving high-quality data on vaccine distribution and coverage. Continued investment in information systems is essential for effective and equitable public health efforts.

Building Data Triangulation Capacity for Routine Immunization and Vaccine Preventable Disease Surveillance Programs to Identify Immunization Coverage Inequities.

The Expanded Programme on Immunization (EPI) and Vaccine Preventable Disease (VPD) Surveillance (VPDS) programs generate multiple data sources (e.g., routine administrative data, VPD case data, and coverage surveys). However, there are challenges with the use of these siloed data for programmatic decision-making, including poor data accessibility and lack of timely analysis, contributing to missed vaccinations, immunity gaps, and, consequently, VPD outbreaks in populations with limited access to immunization and basic healthcare services. Data triangulation, or the integration of multiple data sources, can be used to improve the availability of key indicators for identifying immunization coverage gaps, under-immunized (UI) and un-immunized (zero-dose (ZD)) children, and for assessing program performance at all levels of the healthcare system. Here, we describe the data triangulation processes, prioritization of indicators, and capacity building efforts in Bangladesh, Nigeria, and Rwanda. We also describe the analyses used to generate meaningful data, key indicators used to identify immunization coverage inequities and performance gaps, and key lessons learned. Triangulation processes and lessons learned may be leveraged by other countries, potentially leading to programmatic changes that promote improved access and utilization of vaccination services through the identification of UI and ZD children.

Impact of data editing methods on estimates of smoking prevalence, Global Youth Tobacco Survey, 2007-2009.

Accuracy of self-reported data may be improved by data editing, a mechanism to produce accurate information by excluding inconsistent data based on a set number of predetermined decision rules. We compared data editing methods in the Global Youth Tobacco Survey (GYTS) with other editing approaches and evaluated the effects of these on smoking prevalence estimates. We evaluated 5 approaches for handling inconsistent responses to questions regarding cigarette use: GYTS, do-nothing, gatekeeper, global, and preponderance. Compared with GYTS data edits, the do-nothing and gatekeeper approaches produced similar estimates, whereas the global approach resulted in lower estimates and the preponderance approach, higher estimates. Implications for researchers using GYTS include recognition of the survey's data editing methods and documentation in their study methods to ensure cross-study comparability.

Implementation of data triangulation and dashboard development for COVID-19 vaccine adverse event following immunisation (AEFI) data in Nigeria.

Nigeria began administering COVID-19 vaccines on 5 March 2021 and is working towards the WHO's African regional goal to fully vaccinate 70% of their eligible population by December 2022. Nigeria's COVID-19 vaccination information system includes a surveillance system for COVID-19 adverse events following immunisation (AEFI), but as of April 2021, AEFI data were being collected and managed by multiple groups and lacked routine analysis and use for action. To fill this gap in COVID-19 vaccine safety monitoring, between April 2021 and June 2022, the US Centers for Disease Control and Prevention, in collaboration with other implementing partners led by the Institute of Human Virology Nigeria, supported the Government of Nigeria to triangulate existing COVID-19 AEFI data. This paper describes the process of implementing published draft guidelines for data triangulation for COVID-19 AEFI data in Nigeria. Here, we focus on the process of implementing data triangulation rather than analysing the results and impacts of triangulation. Work began by mapping the flow of COVID-19 AEFI data, engaging stakeholders and building a data management system to intake and store all shared data. These datasets were used to create an online dashboard with key indicators selected based on existing WHO guidelines and national guidance. The dashboard went through an iterative review before dissemination to stakeholders. This case study highlights a successful example of implementing data triangulation for rapid use of AEFI data for decision-making and emphasises the importance of stakeholder engagement and strong data governance structures to make data triangulation successful.

Lessons learned from early implementation of the Growing Expertise in E-health Knowledge and Skills (GEEKS) program in Nigeria, 2019 - 2021.

Introduction: the Growing Expertise in E-health Knowledge and Skills (GEEKS) program is an applied apprenticeship program that aims to improve informatics capacity at various levels of the national health system and create a sustainable informatics workforce. Nigeria adapted the GEEKS model in 2019 as a mechanism to strengthen data quality and use of routine immunization (RI) and vaccine-preventable disease (VPD) surveillance data among Expanded Programme on Immunization (EPI) staff. Since the start of the GEEKS-EPI program, there has not been a formal assessment conducted to measure the extent to which GEEKS-EPI has been able to build local informatics workforce capacity and strengthen RI and VPD surveillance (VPDS) data quality and use in Nigeria. Methods: we conducted a qualitative assessment to inform the extent to which GEEKS-EPI has been able to build informatics skillsets to enhance local workforce capacity, foster collaboration across government agencies, and create a sustainable informatics workforce in Nigeria. In-Depth Interviews (IDIs) and Focus Group Discussions (FGDs) were held with GEEKS-EPI supervisors, mentors, and mentees from previous GEEKS-EPI cohorts. Results: while there were challenges reported during early implementation of the GEEKS-EPI program in Nigeria, particularly early on in the COVID-19 pandemic, participants and supervisors reported that the fellowship provided a framework for building a sustainable RI and VPDS informatics workforce through regular mentorship, peer-to-peer exchanges and Subject Matter Expert (SME)-led trainings. Conclusion: lessons learned from early implementation of GEEKS-EPI in Nigeria will help to inform its implementation in other countries, where strengthened national RI and VPDS informatics capacity is the primary objective.

Outbreak of influenza A (H3N2) variant virus infection among attendees of an agricultural fair, Pennsylvania, USA, 2011.

During August 2011, influenza A (H3N2) variant [A(H3N2)v] virus infection developed in a child who attended an agricultural fair in Pennsylvania, USA; the virus resulted from reassortment of a swine influenza virus with influenza A(H1N1)pdm09. We interviewed fair attendees and conducted a retrospective cohort study among members of an agricultural club who attended the fair. Probable and confirmed cases of A(H3N2)v virus infection were defined by serology and genomic sequencing results, respectively. We identified 82 suspected, 4 probable, and 3 confirmed case-patients who attended the fair. Among 127 cohort study members, the risk for suspected case status increased as swine exposure increased from none (4%; referent) to visiting swine exhibits (8%; relative risk 2.1; 95% CI 0.2-53.4) to touching swine (16%; relative risk 4.4; 95% CI 0.8-116.3). Fairs may be venues for zoonotic transmission of viruses with epidemic potential; thus, health officials should investigate respiratory illness outbreaks associated with agricultural events.

Highly active anti-retroviral therapy in the prevention of mother-to-child transmission of HIV in rural Zimbabwe during the socio-economic crisis.

The purpose of this study is to evaluate the effectiveness of highly active antiretroviral therapy (HAART) in preventing mother-to-child transmission (PMTCT) of HIV in breastfeeding women in rural Zimbabwe. During a severe socio-economic crisis in 2005-2007, 82 eligible HIV-positive pregnant women between 14-36 weeks gestation were initiated on HAART with AZT/3TC/nelfinavir combination therapy at a rural hospital and continued through to six months post-partum. In addition, mothers also received intrapartum single-dose nevirapine (sdNVP). Infants received sdNVP/AZT in the first 72 hours and were assessed for HIV infection at six weeks of age. Results were compared to historical controls of HIV-positive pregnant women who received sdNVP only at the same center. Of the 67 infants with available data on HIV status at six weeks postpartum, three (4.4%) were HIV positive by HIV RNA assay in the HAART + sdNVP group compared to 49/297 (16.5%) in the sdNVP group (p = 0.01). HAART given to HIV-infected mothers in pregnancy and during breastfeeding along with intrapartum sdNVP resulted in a lower postnatal HIV transmission at six weeks postpartum compared to sdNVP treatment. Our HAART regimen demonstrates that PMTCT of HIV can be effective even during times of socioeconomic crisis in resource-poor rural settings.

Cost-effectiveness of birth-dose hepatitis B vaccination among refugee populations in the African region: a series of case studies.

BACKGROUND: Hepatitis B affects 257 million people worldwide. Mother-to-child hepatitis B virus (HBV) transmission is a preventable cause of substantial morbidity and mortality and poses greatest risk for developing chronic HBV infection. The World Health Organization recommends that all countries institute universal hepatitis B birth dose (HepB BD) vaccination during the first 24 h of life, followed by timely completion of routine immunization. The objective of this analysis was to assess the cost-effectiveness of adding HepB BD vaccination among sub-Saharan African refugee populations where the host country's national immunization policy includes HepB BD. METHODS: We performed a cost-effectiveness analysis of three hepatitis B vaccination strategy scenarios for camp-based refugee populations in the African Region (AFR): routine immunization (RI), RI plus universal HepB BD, and RI plus HepB BD only for newborns of hepatitis B surface antigen-positive mothers identified through rapid diagnostic testing (RDT). We focused analyses on refugee populations living in countries that include HepB BD in national immunization schedules: Djibouti, Algeria and Mauritania. We used a decision tree model to estimate costs of vaccination and testing, and costs of life-years lost due to complications of chronic hepatitis B. RESULTS: Compared with RI alone, addition of HepB BD among displaced Somali refugees in Djibouti camps would save 9807 life-years/year, with an incremental cost-effectiveness ratio (ICER) of 0.15 USD (US dollars) per life-year saved. The RI plus HepB BD strategy among Western Saharan refugees in Algerian camps and Malian refugees in Mauritania camps would save 27,108 life-years/year with an ICER of 0.11 USD and 18,417 life-years/year with an ICER of 0.16 USD, respectively. The RI plus RDT-directed HepB BD was less cost-effective than RI plus delivery of universal HepB BD vaccination or RI alone. CONCLUSIONS: Based on our model, addition of HepB BD vaccination is very cost-effective among three sub-Saharan refugee populations, using relative life-years saved. This analysis shows the potential benefit of implementing HepB BD vaccination among other camp-based refugee populations as more AFR countries introduce national HepB BD policies.

A digital microfluidic system for serological immunoassays in remote settings.

Serosurveys are useful for assessing population susceptibility to vaccine-preventable disease outbreaks. Although at-risk populations in remote areas could benefit from this type of information, they face several logistical barriers to implementation, such as lack of access to centralized laboratories, cold storage, and transport of samples. We describe a potential solution: a compact and portable, field-deployable, point-of-care system relying on digital microfluidics that can rapidly test a small volume of capillary blood for disease-specific antibodies. This system uses inexpensive, inkjet-printed digital microfluidic cartridges together with an integrated instrument to perform enzyme-linked immunosorbent assays (ELISAs). We performed a field validation of the system's analytical performance at Kakuma refugee camp, a remote setting in northwestern Kenya, where we tested children aged 9 to 59 months and caregivers for measles and rubella immunoglobulin G (IgG). The IgG assays were determined to have sensitivities of 86% [95% confidence interval (CI), 79 to 91% (measles)] and 81% [95% CI, 73 to 88% (rubella)] and specificities of 80% [95% CI, 49 to 94% (measles)] and 91% [95% CI, 76 to 97% (rubella)] (measles, n = 140; rubella, n = 135) compared with reference tests (measles IgG and rubella IgG ELISAs from Siemens Enzygnost) conducted in a centralized laboratory. These results demonstrate a potential role for this point-of-care system in global serological surveillance, particularly in remote areas with limited access to centralized laboratories.

Inhibition of cyclooxygenase-2 by rofecoxib attenuates the growth and metastatic potential of colorectal carcinoma in mice.

A large number of epidemiological studies have shown that regular use of aspirinor other nonsteroidal anti-inflammatory drugs (NSAIDs) results in a 40-50% reduced risk of colorectal cancer (CRC). Furthermore, NSAIDs cause the regression of preexisting adenomas in patients with familial adenomatous polyposis and significantly inhibit tumor growth in animal models of CRC. To establish a CRC liver metastasis model, we implanted mouse colon tumor MC-26 cells into the splenic subcapsule of BALB/c mice, after which mice were given either standard chow or chow containing the cyclooxygenase (COX)-2-specific inhibitor rofecoxib, alone or in combination with the standard antineoplastic agents, 5-fluoruracil or irinotecan. After 14 days, mice that were given rofecoxib or irinotecan, but not 5-fluoruracil, had significantly smaller primary tumors and fewer metastases. Rofecoxib, at clinical anti-inflammatory plasma concentrations, enhanced the effects of both antineoplastic agents when used in combination. Biochemical analyses of the primary splenic tumor in rofecoxib-treated mice showed no alteration in COX-1 expression, but significant decreases in the expression of the tumor-promoting proteins COX-2, cyclin D1, cytosolic beta-catenin, matrix metalloproteinases-2 and -9, and vascular endothelial cell- derived growth factor. Rofecoxib also decreased growth-enhancing prostaglandin E(2) and tumor-suppressive interleukin-10, whereas antineoplastic interleukin-12 was increased. Two separate survival studies were performed. When mice were fed chow containing 0.01% rofecoxib beginning on day 0 after tumor cell implantation, which achieved clinical anti-inflammatory plasma concentrations, survival time was significantly longer compared with mice given control chow. After 30 days, mortality in the control group was 90%, whereas only one mouse (5%) treated with rofecoxib had died after 30 days. In the second survival study, all of the mice were initially fed with regular chow after tumor cell implantation. On day 7, mice were randomly divided into three dietary groups: control chow, low-dose (0.01%) rofecoxib chow, and high-dose (0.025%) rofecoxib chow. After 28 days, mortality was 100%, 20%, and 10% in control, low-, and high-dose rofecoxib fed groups, respectively. These studies demonstrate that rofecoxib decreases the growth and metastatic potential of CRC in mice through multiple mechanisms. These studies in mice also provide important information that supports the benefit of COX-2 inhibition, not only in the prevention of CRC, but also potentially in the treatment of this common malignancy. Clinical trials will be necessary to assess the utility of COX-2 inhibitors as adjuvant therapy for early-stage disease and as potential agents, either alone or in combination, with more established drugs, for the treatment of refractory CRC.