Electronic viral load (VL) Test Ordering and Result Reporting System (ETORRS) was introduced to create data exchange between the existing VL database and the electronic medical record (EMR) system, with the aim of reducing laboratory test results turnaround time (TAT), improving data quality, and supporting timely clinical response for patients with high VL. This use case is an illustrative example of initiating and adopting the principles of health information exchange for a priority health program.

In the version of the article originally published, some of the oligonucleotide sequences in Supplementary Table 4, on the “21 viruses” and “RVP” tabs, were mislabeled. The Supplementary Tables file has now been corrected.

Malaria diagnostic testing in Africa is threatened by Plasmodium falciparum parasites lacking histidine-rich protein 2 (pfhrp2) and 3 (pfhrp3) genes. Among 12,572 subjects enrolled along Ethiopia’s borders with Eritrea, Sudan, and South Sudan and using multiple assays, we estimate HRP2-based rapid diagnostic tests would miss 9.7% (95% CI 8.5-11.1) of falciparum malaria cases due to pfhrp2 deletion. Established and novel genomic tools reveal distinct subtelomeric deletion patterns, well-established pfhrp3 deletions, and recent expansion of pfhrp2 deletion. Current diagnostic strategies need to be urgently reconsidered in Ethiopia, and expanded surveillance is needed throughout the Horn of Africa.Competing Interest StatementJBP reports research support from Gilead Sciences, honoraria from Virology Education for medical education teaching, and non-financial support from Abbott Diagnostics, all outside the scope of the current work. SMF reports research support from AccessBio, outside of the current work.Funding StatementThis work was funded by the Global Fund to Fight AIDS, Tuberculosis, and Malaria through the Ministry of Health-Ethiopia (EPHI5405 to SMF) and the World Health Organization (JAC, JBP). It was also partially supported by MSF Holland, which supported field work in Gambella Region, the Doris Duke Charitable Foundation (JBP), and the US National Institutes of Health (R01AI132547 to JJJ, JAB, OA, and JBP; K24AI134990 to JJJ).Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Ethical approval was obtained from the Ethiopia Public Health Institute (EPHI) Institutional Review Board (IRB; protocol EPHI-IRB-033-2017) and WHO Research Ethics Review Committee (protocol: ERC.0003174 001). Processing of de-identified samples and data at UNC was determined to constitute non-human subjects research by the UNC IRB (study 17-0155). The study was determined to be non-research by the Centers for Disease Control and Prevention Human Subjects office (0900f3eb81bb60b9).All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesGenomic sequencing data will be available through the Sequence Read Archive (BioSample accession numbers pending). De-identified datasets generated during the current study will be available as supplementary files. Code used during data analysis will be made available on GitHub.

The COVID-19 pandemic has demonstrated a clear need for high-throughput, multiplexed, and sensitive assays for detecting SARS-CoV-2 and other respiratory viruses as well as their emerging variants. Here, we present a cost-effective virus and variant detection platform, called microfluidic CARMEN (mCARMEN), that combines CRISPR-based diagnostics and microfluidics with a streamlined workflow for clinical use. We developed the mCARMEN respiratory virus panel (RVP) to test for up to 21 viruses, including SARS-CoV-2, other coronaviruses and both influenza strains, and demonstrated its diagnostic-grade performance on 525 patient specimens in an academic setting and 166 specimens in a clinical setting. We further developed an mCARMEN panel to enable identification of 6 SARS-CoV-2 variant lineages, including Delta and Omicron, and evaluated it on 2,088 patient specimens, with near-perfect concordance to sequencing-based variant classification. Lastly, we implemented a combined Cas13 and Cas12 approach that enables quantitative measurement of SARS-CoV-2 and influenza A viral copies in samples. The mCARMEN platform enables high-throughput surveillance of multiple viruses and variants simultaneously, enabling rapid detection of SARS-CoV-2 variants.

In Africa, most rapid diagnostic tests (RDTs) for falciparum malaria recognize histidine-rich protein 2 antigen. Plasmodium falciparum parasites lacking histidine-rich protein 2 (pfhrp2) and 3 (pfhrp3) genes escape detection by these RDTs, but it is not known whether these deletions confer sufficient selective advantage to drive rapid population expansion. By studying blood samples from a cohort of 12,572 participants enroled in a prospective, cross-sectional survey along Ethiopia's borders with Eritrea, Sudan and South Sudan using RDTs, PCR, an ultrasensitive bead-based immunoassay for antigen detection and next-generation sequencing, we estimate that histidine-rich protein 2-based RDTs would miss 9.7% (95% confidence interval 8.5-11.1) of P. falciparum malaria cases owing to pfhrp2 deletion. We applied a molecular inversion probe-targeted deep sequencing approach to identify distinct subtelomeric deletion patterns and well-established pfhrp3 deletions and to uncover recent expansion of a singular pfhrp2 deletion in all regions sampled. We propose a model in which pfhrp3 deletions have arisen independently multiple times, followed by strong positive selection for pfhrp2 deletion owing to RDT-based test-and-treatment. Existing diagnostic strategies need to be urgently reconsidered in Ethiopia, and improved surveillance for pfhrp2 deletion is needed throughout the Horn of Africa.

BACKGROUND: Sixty percent of the Ethiopia population is at risk of malaria, with the highest prevalence reported in Gambella (6%) and Benishangul-Gumuz (3%) regions. Within these regions are large agricultural developments with high numbers of seasonal migrant workers. The migrant workers are believed to be at increased risk for malaria infection due to their poor living conditions and outdoor activities, but there is little information on their specific behaviours and health risks. This study was conducted to address this gap. METHODS: Quantitative observations were conducted from September to December 2017 in the Benishangul-Gumuz Region. The nightly routines of mobile migrant workers were observed every month for 4 consecutive months. The study team collected quantitative data including nocturnal behavioural observations of worker living conditions, malaria prevention efforts, and work activities and surveys of worker representatives. Qualitative data was collected from migrant workers, farm managers and local health providers using focus group discussions and semi-structured interviews. RESULTS: Migrant workers arrived in the study area during the peak malaria transmission season and the workers in focus groups reported repeated cases of malaria during their stay on the farms. Overall, less than a quarter of the migrant workers were sleeping under a mosquito net by midnight in all 4 observation months. Some work activities also took place outdoors at night. The study additionally found a lack of access to malaria prevention and treatment at the farms and challenges in utilizing local public health facilities. CONCLUSIONS: There is a need to better address malaria prevention and treatment needs among migrant workers in Ethiopia through outreach from existing healthcare infrastructure and within the farms themselves. This will help prevent malaria transmission both within this population and prevent transmission of malaria back to home communities in lower burden areas in Ethiopia.

OBJECTIVE: We assessed the practices of U.S. population-based birth defects surveillance programs in addressing current and emergent public health needs. METHODS: Using the CDC Strategic Framework considerations for public health surveillance (i.e., lexicon and standards, legal authority, technological advances, workforce, and analytic capacity), during 2012 and 2013, we conducted a survey of all U.S. operational birth defects programs (n=43) soliciting information on legal authorities, case definition and clinical information collected, types of data sources, and workforce staffing. In addition, we conducted semi-structured interviews with nine program directors to further understand how programs are addressing current and emergent needs. RESULTS: Three-quarters of birth defects surveillance programs used national guidelines for case definition. Most birth defects surveillance programs (86%) had a legislative mandate to conduct surveillance, and many relied on a range of prenatal, postnatal, public health, and pediatric data sources for case ascertainment. Programs reported that the transition from paper to electronic formats was altering the information collected, offering an opportunity for remote access to improve timeliness for case review and verification. Programs also reported the growth of pooled, multistate data collaborations as a positive development. Needs identified included ongoing workforce development to improve information technology and analytic skills, more emphasis on data utility and birth defects-specific standards for health information exchange, and support to develop channels for sharing ideas on data interpretation and dissemination. CONCLUSION: The CDC Strategic Framework provided a useful tool to determine the birth defects surveillance areas with positive developments, such as multi-state collaborative epidemiologic studies, and areas for improvement, such as preparation for health information exchanges and workforce database and analytic skills. Our findings may inform strategic deliberations for enhancing the effectiveness of birth defects surveillance programs.

CONTEXT: Birth defects remain a leading cause of infant mortality in the United States and contribute substantially to health care costs and lifelong disabilities. State population-based surveillance systems have been established to monitor birth defects, yet no recent systematic examination of their efforts in the United States has been conducted. OBJECTIVE: To understand the current population-based birth defects surveillance practices in the United States. DESIGN: The National Birth Defects Prevention Network conducted a survey of US population-based birth defects activities that included questions about operational status, case ascertainment methodology, program infrastructure, data collection and utilization, as well as priorities and challenges for surveillance programs. Birth defects contacts in the United States, including District of Columbia and Puerto Rico, received the survey via e-mail; follow-up reminders via e-mails and telephone were used to ensure a 100% response rate. RESULTS: Forty-three states perform population-based surveillance for birth defects, covering approximately 80% of the live births in the United States. Seventeen primarily use an active case-finding approach and 26 use a passive case-finding approach. These programs all monitor major structural malformations; however, passive case-finding programs more often monitor a broader list of conditions, including developmental conditions and newborn screening conditions. Active case-finding programs more often use clinical reviewers, cover broader pregnancy outcomes, and collect more extensive information, such as family history. More than half of the programs (24 of 43) reported an ability to conduct follow-up studies of children with birth defects. CONCLUSIONS: The breadth and depth of information collected at a population level by birth defects surveillance programs in the United States serve as an important data source to guide public health action. Collaborative efforts at the state and national levels can help harmonize data collection and increase utility of birth defects programs.

BACKGROUND: Cryptosporidiosis is an important cause for chronic diarrhea and death in HIV/AIDS patients. Among common Cryptosporidium species in humans, C. parvum is responsible for most zoonotic infections in industrialized nations. Nevertheless, the clinical significance of C. parvum and role of zoonotic transmission in cryptosporidiosis epidemiology in developing countries remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: In this cross-sectional study, 520 HIV/AIDS patients were examined for Cryptosporidium presence in stool samples using genotyping and subtyping techniques. Altogether, 140 (26.9%) patients were positive for Cryptosporidium spp. by PCR-RFLP analysis of the small subunit rRNA gene, belonging to C. parvum (92 patients), C. hominis (25 patients), C. viatorum (10 patients), C. felis (5 patients), C. meleagridis (3 patients), C. canis (2 patients), C. xiaoi (2 patients), and mixture of C. parvum and C. hominis (1 patient). Sequence analyses of the 60 kDa glycoprotein gene revealed a high genetic diversity within the 82 C. parvum and 19 C. hominis specimens subtyped, including C. parvum zoonotic subtype families IIa (71) and IId (5) and anthroponotic subtype families IIc (2), IIb (1), IIe (1) and If-like (2), and C. hominis subtype families Id (13), Ie (5), and Ib (1). Overall, Cryptosporidium infection was associated with the occurrence of diarrhea and vomiting. Diarrhea was attributable mostly to C. parvum subtype family IIa and C. hominis, whereas vomiting was largely attributable to C. hominis and rare Cryptosporidium species. Calf contact was identified as a significant risk factor for infection with Cryptosporidium spp., especially C. parvum subtype family IIa. CONCLUSIONS/SIGNIFICANCE: Results of the study indicate that C. parvum is a major cause of cryptosporidiosis in HIV-positive patients and zoonotic transmission is important in cryptosporidiosis epidemiology in Ethiopia. In addition, they confirm that different Cryptosporidium species and subtypes are linked to different clinical manifestations.