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.

Gaps in research and capacity development for malaria surveillance and response in the Asia-Pacific: meeting report.

BACKGROUND: This report is based on the 2021 annual meeting of the Asia-Pacific Malaria Elimination Network Surveillance and Response Working Group held online on November 1-3, 2021. In light of the 2030 regional malaria elimination goal, there is an urgency for Asia-Pacific countries to accelerate progress towards national elimination and prevent re-establishment. The Asia Pacific Malaria Elimination Network (APMEN) Surveillance Response Working Group (SRWG) supports elimination goals of national malaria control programmes (NMCPs) by expanding the knowledge base, guiding the region-specific operational research agenda and addressing evidence gaps to improve surveillance and response activities. METHODS: An online annual meeting was hosted from 1 to 3 November 2021, to reflect on research needed to support malaria elimination in the region, challenges with malaria data quality and integration, current surveillance-related technical tools, and training needs of NMCPs to support surveillance and response activities. Facilitator-led breakout groups were held during meeting sessions to encourage discussion and share experience. A list of identified research priorities was voted on by attendees and non-attending NMCP APMEN contacts. FINDINGS: 127 participants from 13 country partners and 44 partner institutions attended the meeting, identifying strategies to address malaria transmission amongst mobile and migrant populations as the top research priority, followed by cost effective surveillance strategies in low resource settings, and integration of malaria surveillance into broader health systems. Key challenges, solutions and best practices for improving data quality and integrating epidemiology and entomology data were identified, including technical solutions to improve surveillance activities, guiding priority themes for hosting informative webinars, training workshops and technical support initiatives. Inter-regional partnerships and SRWG-led training plans were developed in consultation with members to be launched from 2022 onwards. CONCLUSION: The 2021 SRWG annual meeting provided an opportunity for regional stakeholders, both NMCPs and APMEN partner institutions, to highlight remaining challenges and barriers and identify research priorities pertaining to surveillance and response in the region, and advocate for strengthening capacity through training and supportive partnerships.

Extending and Strengthening Routine DHIS2 Surveillance Systems for COVID-19 Responses in Sierra Leone, Sri Lanka, and Uganda.

The COVID-19 pandemic challenged countries to protect their populations from this emerging disease. One aspect of that challenge was to rapidly modify national surveillance systems or create new systems that would effectively detect new cases of COVID-19. Fifty-five countries leveraged past investments in District Health Information Software version 2 (DHIS2) to quickly adapt their national public health surveillance systems for COVID-19 case reporting and response activities. We provide background on DHIS2 and describe case studies from Sierra Leone, Sri Lanka, and Uganda to illustrate how the DHIS2 platform, its community of practice, long-term capacity building, and local autonomy enabled countries to establish an effective COVID-19 response. With these case studies, we provide valuable insights and recommendations for strategies that can be used for national electronic disease surveillance platforms to detect new and emerging pathogens and respond to public health emergencies.

Costing electronic private sector malaria surveillance in the Greater Mekong Subregion.

BACKGROUND: Private sector malaria programmes contribute to government-led malaria elimination strategies in Cambodia, Lao PDR, and Myanmar by increasing access to quality malaria services and surveillance data. However, reporting from private sector providers remains suboptimal in many settings. To support surveillance strengthening for elimination, a key programme strategy is to introduce electronic surveillance tools and systems to integrate private sector data with national systems, and enhance the use of data for decision-making. During 2013-2017, an electronic surveillance system based on open source software, District Health Information System 2 (DHIS2), was implemented as part of a private sector malaria case management and surveillance programme. The electronic surveillance system covered 16,000 private providers in Myanmar (electronic reporting conducted by 200 field officers with tablets), 710 in Cambodia (585 providers reporting through mobile app), and 432 in Laos (250 providers reporting through mobile app). METHODS: The purpose of the study was to document the costs of introducing electronic surveillance systems and mobile reporting solutions in Cambodia, Lao PDR, and Myanmar, comparing the cost in different operational settings, the cost of introduction and maintenance over time, and assessing the affordability and financial sustainability of electronic surveillance. The data collection methods included extracting data from PSI's financial and operational records, collecting data on prices and quantities of resources used, and interviewing key informants in each setting. The costing study used an ingredients-based approach and estimated both financial and economic costs. RESULTS: Annual economic costs of electronic surveillance systems were $152,805 in Laos, $263,224 in Cambodia, and $1,310,912 in Myanmar. The annual economic cost per private provider surveilled was $82 in Myanmar, $371 in Cambodia, and $354 in Laos. Cost drivers varied depending on operational settings and number of private sector outlets covered in each country; whether purchased or personal mobile devices were used; and whether electronic (mobile) reporting was introduced at provider level or among field officers who support multiple providers for case reporting. CONCLUSION: The study found that electronic surveillance comprises about 0.5-1.5% of national malaria strategic plan cost and 7-21% of surveillance budgets and deemed to be affordable and financially sustainable.

Private Sector Contributions to National Malaria Surveillance Systems in Elimination Settings: Lessons Learned from Cambodia, Lao PDR, Myanmar, and Vietnam.

Comprehensive malaria case surveillance is necessary to achieve and sustain malaria elimination. In the Greater Mekong Subregion (GMS), the private sector plays a substantial role in malaria treatment. Yet, none of the six GMS countries collects complete case data from private sector points-of-care. Between 2016 and 2019, the GMS Elimination of Malaria through Surveillance program supported national malaria programs in Cambodia, Lao PDR, Myanmar, and Vietnam to execute elimination strategies by engaging the private sector in malaria case management, generating private sector case data, and integrating these data into national surveillance systems. The project enrolled 21,903 private sector outlets, covering between 52% and 80% of the private sector in targeted geographies, which were trained and equipped to perform rapid diagnostic tests (RDTs) and report malaria case data. By 2019, the private providers enrolled in the program reported a total of 3,521,586 suspected cases and 96,400 confirmed malaria cases into national surveillance systems, representing 16% of the total reported caseload by these countries (Cambodia, 25%; Lao PDR, 5%; Myanmar, 12%; Vietnam, 8%). Results demonstrated that with comprehensive support, such as training, provision of free or subsidized RDTs, first-line treatments, and routine supportive supervision, private providers can provide quality malaria case management and achieve high reporting rates.

Stretch of human mesothelial cells increases cytokine expression.

Peritoneal dialysis requires large solution volumes that increase abdominal girth and stretch the mesothelial cells of the abdominal wall. To address the hypothesis that stretch stimulates those cells to increase synthesis and production of inflammatory cytokines, we grew MeT-5A human mesothelial cells to confluence and placed the cells in growth arrest on BioFlex Collagen membranes (Flexcell International Corporation, Hillsborough, NC, U.S.A.). After 48 hours, cells were either left stationary (STA) or cycled using a 3000T system (Flexcell International Corporation) with a sinusoidal stretch (STR) frequency of 10 cycles per minute and an amplitude of 30%. The supernatant and cells of individual wells were removed at 0, 4, 12, 24, 48, 72, and 96 hours. Supernatant was assayed by ELISA for transforming growth factor beta (TGF-beta), interleukin 6 (IL-6), and vascular endothelial growth factor (VEGF). After trypsinization, the total number of viable cells in each well was estimated from the lack of trypan blue staining. Total RNA from the cells was extracted, and real-time reverse-transcriptase polymerase chain reaction was used to determine messenger RNA (mRNA) for IL-6, TGF-beta, VEGF, TGF-beta receptors 2 and 3 (TGF-beta-R2, -R3), kinase insert domain receptor (KDR), and FMS-related tyrosine kinase 1 (Flt1). Because of decline of cell numbers and viability, results for STR were compared with those for STA at each time interval up to 72 hours. The mRNA for TGF-beta, VEGF, TGF-beta-R3, and KDR were significantly higher in the STR group throughout the 72 hours, and STR IL-6 mRNA declined nonsignificantly. Normalized to the number of viable cells, supernatant IL-6, TGF-beta, and VEGF were not significantly different between the groups. We conclude that mechanical stress from mesothelial stretch does not enhance mesothelial cell secretion oflL-6, TGF-f, or VEGF, but does increase expression ofTGF-P, VEGF, and their corresponding cell receptors TGF-f-R3 and KDR.

Mouse model of foreign body reaction that alters the submesothelium and transperitoneal transport.

To address the hypothesis that sterile intraperitoneal (ip) catheters alone promote a progressive foreign body reaction (FBR), silicone catheters were surgically implanted in C57BL mice. Controls (CON) underwent sham operations. After 1-5 wk (E1-E5 for catheter-bearing mice), catheters were recovered, and the adherent cell layer (ACL) was separated and cultured to demonstrate sterility. Transperitoneal transport experiments were performed to determine the mass transfer coefficients of mannitol (MTCM) and albumin (MTCA) and the osmotic filtration flux (Josm). After euthanasia, tissue samples were analyzed for submesothelial thickness, angiogenesis, and cytokine immunohistochemistry (IHC). Progressive increases with time were observed in submesothelial thickness (µm: CON, 18.8±12.3; E1, 46.1±20.0; E2, 72.0±17.9; E4, 97.3±20.0; E5, 131.7±10.3; P<0.003), angiogenesis (no. of vessels/mm of peritoneum: CON, 10.7±9.4; E1, 15.4±15.6; E2, 27.0±14.0; E4, 39.8±15.7; E5, 90.1±8.1; P<0.0003), MTCA (6.5±1.5×10(-5) cm/min, mean CON; 18.0±1.1×10(-5) cm/min, mean E1-E5, P<0.0001), Josm (0.0013±0.0001 cm/min, mean CON; 0.0017±0.0001 cm/min, mean E1-E5, P<0.01). No significant differences were found for MTCM. IHC demonstrated strong staining for all treated animals and correlated with the ACL. This mouse model demonstrates that ip silicone catheters result in progressive FBR, altering the submesothelial anatomy and transperitoneal transport, and will form the basis for mechanistic studies in genetically-altered animals.

Foreign-body response to sterile catheters is variable over 20 weeks.

We hypothesized that placement of sterile catheter material into the peritoneal cavity results in a foreign-body response that varies with exposure duration. Sterile medical Silastic catheter material was aseptically implanted into the abdomens of 42 anesthetized Sprague-Dawley rats. Controls (n = 18) underwent sham operations without catheter implantation. After 4, 8, or 20 weeks, the animals were anesthetized, the abdomen was opened, and the catheter material was recovered and processed to separate the cells adhering to the catheters. The cells, abdomen, and catheter material were all cultured to demonstrate sterility, and transport experiments were carried out. After euthanasia of the animals, abdominal wall tissue was examined for submesothelial thickness and vascular density, and immunohistochemistry (IHC) for cytokines was performed. Cells from the catheter material were processed for immunocytochemistry (ICC). The catheter, adherent cells, and abdomen were free of bacteria. Inflammatory changes in peritoneal thickness and angiogenesis were highest at 4 weeks and declined thereafter to 20 weeks. Transport of mannitol was higher at 4 weeks in treated animals than in controls, and albumin transport was higher at 8 weeks in treated animals than in controls. The IHC for cytokines demonstrated changes paralleling the structural alterations (p < 10(-5)). The ICC of the catheter cell layer demonstrated mesothelial cells, macrophages, fibroblasts, and T cells. Over 20 weeks, the foreign-body response to polymer catheters placed intraperitoneally in rats without injection of solution depends on exposure time, with an initial immune response evident at 4 weeks and decreasing thereafter.

Peritoneal inflammation after twenty-week exposure to dialysis solution: effect of solution versus catheter-foreign body reaction.

BACKGROUND: We hypothesized that both sterile solutions and foreign body reaction to the peritoneal dialysis catheter are associated with inflammatory changes in rats exposed to hypertonic solution. METHODS: Four hypertonic solutions (30 - 40 mL) were injected daily via needle and syringe over 20 weeks in 4 groups of rats: 4.25% standard clinical solution (LAC), LAC plus pyridoxamine (PYR), LAC plus ethyl pyruvate (EP), and a biocompatible 4% dextrose solution (BIC). Two groups received catheters: a non-injected 4-week catheter group (C4) and a group injected for 20 weeks with the BIC solution (CI). Control animals (CON) were not injected. In the C4 group, adherent cells were separated from the catheter and examined by culture and electron microscopy to ensure that animals were bacteria free prior to exposure to solution. Animals underwent transport experiments to determine mass transfer coefficients of mannitol (MTC(M)) and albumin (MTC(A)), osmotic filtration flux (J(osm)), and hydrostatic pressure-driven flux (J(p)). After euthanasia, tissues were examined for submesothelial thickness, vascular density, and immunohistochemistry for various cytokines. RESULTS: The catheter cell layer was free of bacteria and consisted of macrophages, lymphocytes, mesothelial cells, and fibroblastic cells. Marked differences in angiogenesis and submesothelial thickening were noted for the catheter groups. Transport differences were mixed: MTC(M) was significantly less for the CI group and MTC(A) was variable among the groups. There were no differences among groups for J(osm) or J(p). Inflammatory markers in the catheter-adherent cells correlated with inflammatory changes in the tissue. These data demonstrate significant changes in submesothelial thickness, angiogenesis, transport function, and inflammatory markers between animals injected with sterile solutions over 20 weeks with and without catheters. CONCLUSION: An indwelling catheter amplifies peritoneal inflammation from dialysis solutions through a foreign body reaction. Our data also suggest that additives to existing solutions may have limited the effect on inflammatory response to non-biocompatible solutions.

Peritoneal changes after exposure to sterile solutions by catheter.

Most current animal models that are used to study effects of long-term peritoneal exposure to dialysis solutions use an indwelling catheter for daily injections. It was hypothesized that the presence of a foreign body in the peritoneal cavity (PC) might alter the inflammatory response to the solutions and that the response would depend on exposure duration. For addressing these, long-term injections were carried out for 2 to 8 wk in 90 Sprague-Dawley rats: 40 via a subcutaneous port connected to a silicone catheter tunneled to the PC, 40 via direct needle injection, and 10 noninjected, age-control rats. Daily volumes were 30 to 40 ml of filter-sterilized, bicarbonate-buffered solutions that contained 4% dextrose. After 2, 4, 6, and 8 wk, anesthetized rats underwent transport experiments with a chamber affixed to the abdominal wall to determine mass transfer coefficients of mannitol (MTC(mannitol)) and albumin (MTC(BSA)), osmotic filtration flux (J(osm)), and hydrostatic pressure-driven flux. After the rats were killed, tissues were collected for measurement of peritoneal thickness, vascular density, and immunohistochemical staining. ANOVA demonstrated significant (P < 0.01) differences in thickness, vessel density, MTC(mannitol), and MTC(BSA) among the groups at the various time intervals and in overall means. Differences among the groups were less pronounced for hydrostatic pressure-driven flux and J(osm). Vessel density, MTC(mannitol), MTC(BSA), and J(osm) were dependent on injection duration (P < 0.01). There were marked differences between the needle injection and catheter injection groups at various intervals in the expression of three cytokines. It is concluded that the histologic and functional response depends on the duration of injection with animals that are exposed for as little as 2 wk demonstrating alterations. These findings confirm the hypothesis that the presence of a PC catheter increases inflammatory response to sterile solutions as evidenced by the structural and functional changes in the peritoneal barrier.

Host adaptation and immune modulation are mediated by homologous recombination in Helicobacter pylori.

Rearrangement of genomic DNA via homologous recombination provides an alternative mechanism of gene regulation that is essential for successful colonization of the gastric mucosa by Helicobacter pylori. Inoculation of outbred mice with the H. pylori SS1 wild-type strain elicited a T helper (Th) 2 response and established a persistent infection. In contrast, inoculation with an isogenic H. pylori strain defective for homologous recombination elicited a Th1-mediated immune response and clearance of infection within 70 days. We, therefore, demonstrate that recombination is critical for mediating persistence of a microbial pathogen through the induction of ineffective immune responses.