Effectiveness of ertapenem for treatment of infections in children: An evidence mapping and meta-analysis.

Objectives: To assess and summarize current evidence on the effectiveness and safety of ertapenem for treatment of childhood infections, in consideration of high infection prevalence in children and wide use of ertapenem. Methods: The following 8 databases were searched on 13th May 2021: Web of Science, Embase via Ovid SP, PubMed, The Cochrane Library (CENTRAL), Chinese BioMedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), VIP and Wanfang. The primary outcome was treatment success rate. Risk ratios (RRs) and 95% confidence interval (CI) were estimated using random-effect models. Subgroup analysis was conducted where heterogeneity was found. Results: Fifteen studies (8 randomized controlled trials, 1 observational comparative study, and 6 before and after studies) involving 2,528 patients were included in the final review. Ertapenem had similar treatment success rates with ß-lactam antibiotics [relative risk (RR) = 1.08, 95% CI: 0.99-1.19]. In a subgroup analysis, similar efficacy (RR = 1.08, 95% CI: 0.97-1.20) between ertapenem and other carbapenems. Compared with ß-lactam antibiotics, ertapenem did not increase the risk of any adverse events (RR = 1.02, 95%CI: 0.71-1.48), drug-related diarrhea (all non-Asian children, RR = 0.62, 95%CI: 0.31-1.25), or injection site pain (all non-Asian children, RR = 1.66, 95%CI: 0.59-4.68). Subgroup analysis showed no obvious difference between ertapenem group and carbapenems or non-carbapenems group on risk of adverse events. Conclusion: Our findings suggest that ertapenem is effective and safe in treatment for children with infection. Further comparative real-world data is needed to supplement clinical evidence on the overall benefits of ertapenem in this population.

Corrigendum: Effectiveness of ertapenem for treatment of infections in children: An evidence mapping and meta-analysis.

[This corrects the article DOI: 10.3389/fpsyt.2021.706625.].

Use of a district health information system 2 routine immunization dashboard for immunization program monitoring and decision making, Kano State, Nigeria.

Introduction: a district health information system 2 tool with a customized routine immunization (RI) module and indicator dashboard was introduced in Kano State, Nigeria, in November 2014 to improve data management and analysis of RI services. We assessed the use of the module for program monitoring and decision-making, as well as the enabling factors and barriers to data collection and use. Methods: a mixed-methods approach was used to assess user experience with the RI data module and dashboard, including 1) a semi-structured survey questionnaire administered at 60 health facilities administering vaccinations and 2) focus group discussions and 16 in-depth interviews conducted with immunization program staff members at the local government area (LGA) and state levels. Results: in health facilities, a RI monitoring chart was used to review progress toward meeting vaccination coverage targets. At the LGA, staff members used RI dashboard data to prioritize health facilities for additional support. At the State level, immunization program staff members use RI data to make policy decisions. They viewed the provision of real-time data through the RI dashboard as a "game changer". Use of immunization data is facilitated through review meetings and supportive supervision visits. Barriers to data use among LGA staff members included inadequate understanding of the data collection tools and computer illiteracy. Conclusion: the routine immunization data dashboard facilitated access to and use of data for decision-making at the LGA, State and national levels, however, use at the health facility level remains limited. Ongoing data review meetings and training on computer skills and data collection tools are recommended.

Targeted Short Message Service-Based Intervention to Improve Routine Immunization Reporting in Bauchi State, Nigeria, 2016.

Introduction: High quality, timely and complete immunization data are essential for program planning and decision-making. In Nigeria, the National Health Management Information System (NHMIS) Routine Immunization (RI) module and dashboard (on the District Health Information System version 2 (DHIS2) platform) support the use of real time RI data. We deployed an automated short message service (SMS) notification system that works with the existing RI module to facilitate improvements in RI data in the DHIS2. Methods: A pilot project was performed using intervention and control local government areas (LGAs). A mixed methods approach using both qualitative and quantitative methods was used to evaluate the system. We assessed changes in reporting rates across different reports. The evaluation also included baseline and post-intervention surveys of health facility (HF) staff. Results: Reporting timeliness (76% pre and 99% post intervention) and completeness (83% pre and 99% post intervention) were consistently higher during the post-intervention than the pre-intervention period for facilities in the intervention LGA while reporting timeliness (65% pre and 66% post intervention) and completeness (71% and 77% post intervention) for facilities in the control LGA showed no change. Users reported that the SMS system was easy to understand and helped to facilitate improvements in consistency of data and timeliness of reporting. Inability of health care workers to effect changes at the HF level and the lack of immediate feedback were reported as key challenges to timeliness and quality of reports. Conclusion: An SMS-based intervention improved timeliness and completeness of health data reporting. However, the intervention should be evaluated on a larger scale over a longer time period before considering a national implementation.

Country Immunization Information System Assessments - Kenya, 2015 and Ghana, 2016.

The collection, analysis, and use of data to measure and improve immunization program performance are priorities for the World Health Organization (WHO), global partners, and national immunization programs (NIPs). High quality data are essential for evidence-based decision-making to support successful NIPs. Consistent recording and reporting practices, optimal access to and use of health information systems, and rigorous interpretation and use of data for decision-making are characteristics of high-quality immunization information systems. In 2015 and 2016, immunization information system assessments (IISAs) were conducted in Kenya and Ghana using a new WHO and CDC assessment methodology designed to identify root causes of immunization data quality problems and facilitate development of plans for improvement. Data quality challenges common to both countries included low confidence in facility-level target population data (Kenya = 50%, Ghana = 53%) and poor data concordance between child registers and facility tally sheets (Kenya = 0%, Ghana = 3%). In Kenya, systemic challenges included limited supportive supervision and lack of resources to access electronic reporting systems; in Ghana, challenges included a poorly defined subdistrict administrative level. Data quality improvement plans (DQIPs) based on assessment findings are being implemented in both countries. IISAs can help countries identify and address root causes of poor immunization data to provide a stronger evidence base for future investments in immunization programs.

Enhancing case definitions for surveillance of human monkeypox in the Democratic Republic of Congo.

BACKGROUND: Human monkeypox (MPX) occurs at appreciable rates in the Democratic Republic of Congo (DRC). Infection with varicella zoster virus (VZV) has a similar presentation to that of MPX, and in areas where MPX is endemic these two illnesses are commonly mistaken. This study evaluated the diagnostic utility of two surveillance case definitions for MPX and specific clinical characteristics associated with laboratory-confirmed MPX cases. METHODOLOGY/PRINCIPAL FINDINGS: Data from a cohort of suspect MPX cases (identified by surveillance over the course of a 42 month period during 2009-2014) from DRC were used; real-time PCR diagnostic test results were used to establish MPX and VZV diagnoses. A total of 333 laboratory-confirmed MPX cases, 383 laboratory-confirmed VZV cases, and 36 cases that were determined to not be either MPX or VZV were included in the analyses. Significant (p<0.05) differences between laboratory-confirmed MPX and VZV cases were noted for several signs/symptoms including key rash characteristics. Both surveillance case definitions had high sensitivity and low specificities for individuals that had suspected MPX virus infections. Using 12 signs/symptoms with high sensitivity and/or specificity values, a receiver operator characteristic analysis showed that models for MPX cases that had the presence of 'fever before rash' plus at least 7 or 8 of the 12 signs/symptoms demonstrated a more balanced performance between sensitivity and specificity. CONCLUSIONS: Laboratory-confirmed MPX and VZV cases presented with many of the same signs and symptoms, and the analysis here emphasized the utility of including 12 specific signs/symptoms when investigating MPX cases. In order to document and detect endemic human MPX cases, a surveillance case definition with more specificity is needed for accurate case detection. In the absence of a more specific case definition, continued emphasis on confirmatory laboratory-based diagnostics is warranted.

Assessing Inactivated Polio Vaccine Introduction and Utilization in Kano State, Nigeria, April-November 2015.

Background: Kano State, Nigeria, introduced inactivated polio vaccine (IPV) into its routine immunization (RI) schedule in March 2015 and was the pilot site for an RI data module for the National Health Management Information System (NHMIS). We determined factors impacting IPV introduction and the value of the RI module on monitoring new vaccine introduction. Methods: Two assessment approaches were used: (1) analysis of IPV vaccinations reported in NHMIS, and (2) survey of 20 local government areas (LGAs) and 60 associated health facilities (HF). Results: By April 2015, 66% of LGAs had at least 20% of HFs administering IPV, by June all LGAs had HFs administering IPV and by July, 91% of the HFs in Kano reported administering IPV. Among surveyed staff, most rated training and implementation as successful. Among HFs, 97% had updated RI reporting tools, although only 50% had updated microplans. Challenges among HFs included: IPV shortages (20%), hesitancy to administer 2 injectable vaccines (28%), lack of knowledge on multi-dose vial policy (30%) and age of IPV administration (8%). Conclusion: The introduction of IPV was largely successful in Kano and the RI module was effective in monitoring progress, although certain gaps were noted, which should be used to inform plans for future vaccine introductions.

Evaluation of the GeneXpert for Human Monkeypox Diagnosis.

Monkeypox virus (MPXV), a zoonotic orthopoxvirus (OPX), is endemic in the Democratic Republic of Congo (DRC). Currently, diagnostic assays for human monkeypox (MPX) focus on real-time quantitative polymerase chain reaction (PCR) assays, which are typically performed in sophisticated laboratory settings. Herein, we evaluated the accuracy and utility of a multiplex MPX assay using the GeneXpert platform, a portable rapid diagnostic device that may serve as a point-of-care test to diagnose infections in endemic areas. The multiplex MPX/OPX assay includes a MPX-specific PCR test, OPX-generic PCR test, and an internal control PCR test. In total, 164 diagnostic specimens (50 crusts and 114 vesicular swabs) were collected from suspected MPX cases in Tshuapa Province, DRC, under national surveillance guidelines. The specimens were tested with the GeneXpert MPX/OPX assay and an OPX PCR assay at the Institut National de Recherche Biomedicale (INRB) in Kinshasa. Aliquots of each specimen were tested in parallel with a MPX-specific PCR assay at the Centers for Disease Control and Prevention. The results of the MPX PCR were used as the gold standard for all analyses. The GeneXpert MPX/OPX assay performed at INRB had a sensitivity of 98.8% and specificity of 100%. The GeneXpert assay performed well with both crust and vesicle samples. The GeneXpert MPX/OPX test incorporates a simple methodology that performs well in both laboratory and field conditions, suggesting its viability as a diagnostic platform that may expand and expedite current MPX detection capabilities.

Extended Human-to-Human Transmission during a Monkeypox Outbreak in the Democratic Republic of the Congo.

A >600% increase in monkeypox cases occurred in the Bokungu Health Zone of the Democratic Republic of the Congo during the second half of 2013; this increase prompted an outbreak investigation. A total of 104 possible cases were reported from this health zone; among 60 suspected cases that were tested, 50 (48.1%) cases were confirmed by laboratory testing, and 10 (9.6%) tested negative for monkeypox virus (MPXV) infection. The household attack rate (i.e., rate of persons living with an infected person that develop symptoms of MPXV infection) was 50%. Nine families showed >1 transmission event, and >6 transmission events occurred within this health zone. Mean incubation period was 8 days (range 4-14 days). The high attack rate and transmission observed in this study reinforce the importance of surveillance and rapid identification of monkeypox cases. Community education and training are needed to prevent transmission of MPXV infection during outbreaks.

Laboratory-acquired vaccinia virus infection in a recently immunized person--Massachusetts, 2013.

On November 26, 2013, the CDC poxvirus laboratory was notified by the Boston Public Health Commission (BPHC) of an inadvertent inoculation of a recently vaccinated (ACAM2000 smallpox vaccine) laboratory worker with wild type vaccinia virus (VACV) Western Reserve. A joint investigation by CDC and BPHC confirmed orthopoxvirus infection in the worker, who had reported a needle stick in his thumb while inoculating a mouse with VACV. He experienced a non-tender, red rash on his arm, diagnosed at a local emergency department as cellulitis. He subsequently developed a necrotic lesion on his thumb, diagnosed as VACV infection. Three weeks after the injury, the thumb lesion was surgically debrided and at 2 months post-injury, the skin lesion had resolved. The investigation confirmed that the infection was the first reported VACV infection in the United States in a laboratory worker vaccinated according to the Advisory Committee on Immunization Practices (ACIP) recommendations. The incident prompted the academic institution to outline biosafety measures for working with biologic agents, such as biosafety training of laboratory personnel, vaccination (if appropriate), and steps in incident reporting. Though vaccination has been shown to be an effective measure in protecting personnel in the laboratory setting, this case report underscores the importance of proper safety measures and incident reporting.

Introduction of Monkeypox into a Community and Household: Risk Factors and Zoonotic Reservoirs in the Democratic Republic of the Congo.

An increased incidence of monkeypox (MPX) infections in the Democratic Republic of the Congo was noted by the regional surveillance system in October 2013. Little information exists regarding how MPX is introduced into the community and the factors associated with transmission within the household. Sixty-eight wild animals were collected and tested for Orthopoxvirus. Two of three rope squirrels (Funisciurus sp.) were positive for antibodies to Orthopoxviruses; however, no increased risk was associated with the consumption or preparation of rope squirrels. A retrospective cohort investigation and a case-control investigation were performed to identify risk factors affecting the introduction of monkeypox virus (MPXV) into the community and transmission within the home. School-age males were the individuals most frequently identified as the first person infected in the household and were the group most frequently affected overall. Risk factors of acquiring MPXV in a household included sleeping in the same room or bed, or using the same plate or cup as the primary case. There was no significant risk associated with eating or processing of wild animals. Activities associated with an increased risk of MPXV transmission all have potential for virus exposure to the mucosa.

Novel poxvirus infection in 2 patients from the United States.

BACKGROUND: Some human poxvirus infections can be acquired through zoonotic transmission. We report a previously unknown poxvirus infection in 2 patients, 1 of whom was immunocompromised; both patients had known equine contact. METHODS: The patients were interviewed and clinical information was abstracted from the patients' medical files. Biopsies of the skin lesions were collected from both patients for histopathology, immunohistochemistry, and transmission electron microscopy analysis. Oral and skin swabs were collected from animals with frequent contact with the patients, and environmental sampling including rodent trapping was performed on the farm where the immunosuppressed patient was employed. "Pan-pox and high Guanine-cytosine" polymerase chain reaction assays were performed on patient, animal, and environmental isolates. Amplicon sequences of the viral DNA were used for agent identification and phylogenetic analysis. RESULTS: Specimens from both human cases revealed a novel poxvirus. The agent shares 88% similarity to viruses in the Parapoxvirus genus and 78% to those in the Molluscipoxvirus genus but is sufficiently divergent to resist classification as either. All animal and environmental specimens were negative for poxvirus and both patients had complete resolution of lesions. CONCLUSIONS: This report serves as a reminder that poxviruses should be considered in cutaneous human infections, especially in individuals with known barnyard exposures. The clinical course of the patients was similar to that of parapoxvirus infections, and the source of this virus is currently unknown but is presumed to be zoonotic. This report also demonstrates the importance of a comprehensive approach to diagnosis of human infections caused by previously unknown pathogens.

Hantavirus infections among overnight visitors to Yosemite National Park, California, USA, 2012.

In summer 2012, an outbreak of hantavirus infections occurred among overnight visitors to Yosemite National Park in California, USA. An investigation encompassing clinical, epidemiologic, laboratory, and environmental factors identified 10 cases among residents of 3 states. Eight case-patients experienced hantavirus pulmonary syndrome, of whom 5 required intensive care with ventilatory support and 3 died. Staying overnight in a signature tent cabin (9 case-patients) was significantly associated with becoming infected with hantavirus (p<0.001). Rodent nests and tunnels were observed in the foam insulation of the cabin walls. Rodent trapping in the implicated area resulted in high trap success rate (51%), and antibodies reactive to Sin Nombre virus were detected in 10 (14%) of 73 captured deer mice. All signature tent cabins were closed and subsequently dismantled. Continuous public awareness and rodent control and exclusion are key measures in minimizing the risk for hantavirus infection in areas inhabited by deer mice.