Lessons Learned from CDC's Global COVID-19 Early Warning and Response Surveillance System.

Early warning and response surveillance (EWARS) systems were widely used during the early COVID-19 response. Evaluating the effectiveness of EWARS systems is critical to ensuring global health security. We describe the Centers for Disease Control and Prevention (CDC) global COVID-19 EWARS (CDC EWARS) system and the resources CDC used to gather, manage, and analyze publicly available data during the prepandemic period. We evaluated data quality and validity by measuring reporting completeness and compared these with data from Johns Hopkins University, the European Centre for Disease Prevention and Control, and indicator-based data from the World Health Organization. CDC EWARS was integral in guiding CDC's early COVID-19 response but was labor-intensive and became less informative as case-level data decreased and the pandemic evolved. However, CDC EWARS data were similar to those reported by other organizations, confirming the validity of each system and suggesting collaboration could improve EWARS systems during future pandemics.

Global Challenges with Oral Antivirals for COVID-19.

Oral antivirals for COVID-19 can be game changers in low- and middle-income countries (LMICs). Challenges that may hinder current and future oral antiviral rollouts span use in special populations, drug-drug and herb-drug interactions, adverse events, development of resistance, black markets, and equity in access and prescribing. Future antivirals may address some of these barriers; however, health systems around the world should be equipped to receive and administer COVID-19 oral antivirals. Improvements in manufacturing capacity, community engagement, capacity for testing and linkage to care, and systems for surveillance and safety monitoring could "change the game" for LMICs, irrespective of any specific antiviral drug. Investments in health care infrastructure can promote resilience, not only for COVID-19 but also for future local and global health crises.

SARS-CoV-2 Breakthrough Infections among US Embassy Staff Members, Uganda, May-June 2021.

The SARS-CoV-2 Delta variant emerged shortly after COVID-19 vaccines became available in 2021. We describe SARS-CoV-2 breakthrough infections in a highly vaccinated, well-monitored US Embassy community in Kampala, Uganda. Defining breakthrough infection rates in highly vaccinated populations can help determine public health messaging, guidance, and policy globally.

Active surveillance and early detection of community transmission of SARS-CoV-2 Mu variant (B.1.621) in the Brazilian Amazon.

Through active surveillance and contact tracing from outpatients, we aimed to identify and characterize SARS-CoV-2 variants circulating in Porto Velho-Rondônia, a city in the Brazilian Amazon. As part of a prospective cohort, we gathered information from 2,506 individuals among COVID-19 patients and household contacts. Epidemiological data, nasopharyngeal swabs, and blood samples were collected from all participants. Nasopharyngeal swabs were tested for antigen rapid diagnostic test and reverse transcription-polymerase chain reaction (RT-PCR) followed by genomic sequencing. Blood samples underwent ELISA testing for IgA, IgG, and IgM antibody levels. From 757 specimens sequenced, three were identified as Mu variant, none of the individuals carrying this variant had a travel history in the previous 15 days before diagnosis. One case was asymptomatic and two presented mild symptoms. Two infected individuals from different households caring viruses with additional amino acid substitutions ORF7a P45L and ORF1a T1055A compared to the Mu virus reference sequence. One patient presented IgG levels. Our results highlight that genomic surveillance for SARS-CoV-2 variants can assist in detecting the emergency of SARS-CoV-2 variants in the community, before its identification in other parts of the country.

Cluster of SARS-CoV-2 Gamma Variant Infections, Parintins, Brazil, March 2021.

High case counts after the Gamma (P. 1) variant of severe acute respiratory syndrome coronavirus 2 emerged in Brazil raised concerns that previously infected persons might become reinfected. Investigation of a cluster of coronavirus disease cases in Parintins, in the Brazilian Amazon, suggested household transmission but did not identify high rates of reinfection.

Cross-Reactivity of Two SARS-CoV-2 Serological Assays in a Setting Where Malaria Is Endemic.

Accurate SARS-CoV-2 serological assays are critical for COVID-19 serosurveillance. However, previous studies have indicated possible cross-reactivity of these assays, including in areas where malaria is endemic. We tested 213 well-characterized prepandemic samples from Nigeria using two SARS-CoV-2 serological assays, Abbott Architect IgG and Euroimmun NCP IgG assay, both targeting SARS-CoV-2 nucleocapsid protein. To assess antibody binding strength, an avidity assay was performed on these samples and on plasma from SARS-CoV-2 PCR-positive persons. Thirteen (6.1%) of 212 samples run on the Abbott assay and 38 (17.8%) of 213 run on the Euroimmun assay were positive. Anti-Plasmodium IgG levels were significantly higher among false positives for both Abbott and Euroimmun; no association was found with active Plasmodium falciparum infection. An avidity assay using various concentrations of urea wash in the Euroimmun assay reduced loosely bound IgG: of 37 positive/borderline prepandemic samples, 46%, 86%, 89%, and 97% became negative using 2 M, 4 M, 5 M, and 8 M urea washes, respectively. The wash slightly reduced avidity of antibodies from SARS-CoV-2 patients within 28 days of PCR confirmation; thereafter, avidity increased for all urea concentrations except 8 M. This validation found moderate to substantial cross-reactivity on two SARS-CoV-2 serological assays using samples from a setting where malaria is endemic. A simple urea wash appeared to alleviate issues of cross-reactivity.

Use of US Public Health Travel Restrictions during COVID-19 Outbreak on Diamond Princess Ship, Japan, February-April 2020.

Public health travel restrictions (PHTR) are crucial measures during communicable disease outbreaks to prevent transmission during commercial airline travel and mitigate cross-border importation and spread. We evaluated PHTR implementation for US citizens on the Diamond Princess during its coronavirus disease (COVID-19) outbreak in Japan in February 2020 to explore how PHTR reduced importation of COVID-19 to the United States during the early phase of disease containment. Using PHTR required substantial collaboration among the US Centers for Disease Control and Prevention, other US government agencies, the cruise line, and public health authorities in Japan. Original US PHTR removal criteria were modified to reflect international testing protocols and enable removal of PHTR for persons who recovered from illness. The impact of PHTR on epidemic trajectory depends on the risk for transmission during travel and geographic spread of disease. Lessons learned from the Diamond Princess outbreak provide critical information for future PHTR use.

Coronavirus Disease 2019 (COVID-19) in Americans Aboard the Diamond Princess Cruise Ship.

BACKGROUND: The Diamond Princess cruise ship was the site of a large outbreak of coronavirus disease 2019 (COVID-19). Of 437 Americans and their travel companions on the ship, 114 (26%) tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We interviewed 229 American passengers and crew after disembarkation following a ship-based quarantine to identify risk factors for infection and characterize transmission onboard the ship. RESULTS: The attack rate for passengers in single-person cabins or without infected cabinmates was 18% (58/329), compared with 63% (27/43) for those sharing a cabin with an asymptomatic infected cabinmate, and 81% (25/31) for those with a symptomatic infected cabinmate. Whole genome sequences from specimens from passengers who shared cabins clustered together. Of 66 SARS-CoV-2-positive American travelers with complete symptom information, 14 (21%) were asymptomatic while on the ship. Among SARS-CoV-2-positive Americans, 10 (9%) required intensive care, of whom 7 were ≥70 years. CONCLUSIONS: Our findings highlight the high risk of SARS-CoV-2 transmission on cruise ships. High rates of SARS-CoV-2 positivity in cabinmates of individuals with asymptomatic infections suggest that triage by symptom status in shared quarters is insufficient to halt transmission. A high rate of intensive care unit admission among older individuals complicates the prospect of future cruise travel during the pandemic, given typical cruise passenger demographics. The magnitude and severe outcomes of this outbreak were major factors contributing to the Centers for Disease Control and Prevention's decision to halt cruise ship travel in US waters in March 2020.

Observations of the global epidemiology of COVID-19 from the prepandemic period using web-based surveillance: a cross-sectional analysis.

Background Scant data are available about global patterns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread and global epidemiology of early confirmed cases of COVID-19 outside mainland China. We describe the global spread of SARS-CoV-2 and characteristics of COVID-19 cases and clusters before the characterisation of COVID-19 as a pandemic. METHODS: Cases of COVID-19 reported between Dec 31, 2019, and March 10, 2020 (ie, the prepandemic period), were identified daily from official websites, press releases, press conference transcripts, and social media feeds of national ministries of health or other government agencies. Case characteristics, travel history, and exposures to other cases were abstracted. Countries with at least one case were classified as affected. Early cases were defined as those among the first 100 cases reported from each country. Later cases were defined as those after the first 100 cases. We analysed reported travel to affected countries among the first case reported from each country outside mainland China, demographic and exposure characteristics among cases with age or sex information, and cluster frequencies and sizes by transmission settings. FINDINGS: Among the first case reported from each of 99 affected countries outside of mainland China, 75 (76%) had recent travel to affected countries; 60 (61%) had travelled to China, Italy, or Iran. Among 1200 cases with age or sex information, 874 (73%) were early cases. Among 762 early cases with age information, the median age was 51 years (IQR 35-63); 25 (3%) of 762 early cases occurred in children younger than 18 years. Overall, 21 (2%) of 1200 cases were in health-care workers and none were in pregnant women. 101 clusters were identified, of which the most commonly identified transmission setting was households (76 [75%]; mean 2·6 cases per cluster [range 2-7]), followed by non-health-care occupational settings (14 [14%]; mean 4·3 cases per cluster [2-14]), and community gatherings (11 [11%]; mean 14·2 cases per cluster [4-36]). INTERPRETATION: Cases with travel links to China, Italy, or Iran accounted for almost two-thirds of the first reported COVID-19 cases from affected countries. Among cases with age information available, most were among adults aged 18 years and older. Although there were many clusters of household transmission among early cases, clusters in occupational or community settings tended to be larger, supporting a possible role for physical distancing to slow the progression of SARS-CoV-2 spread. FUNDING: None.

Evidence of behaviour change during an Ebola virus disease outbreak, Sierra Leone.

OBJECTIVE: To evaluate changes in Ebola-related knowledge, attitudes and prevention practices during the Sierra Leone outbreak between 2014 and 2015. METHODS: Four cluster surveys were conducted: two before the outbreak peak (3499 participants) and two after (7104 participants). We assessed the effect of temporal and geographical factors on 16 knowledge, attitude and practice outcomes. FINDINGS: Fourteen of 16 knowledge, attitude and prevention practice outcomes improved across all regions from before to after the outbreak peak. The proportion of respondents willing to: (i) welcome Ebola survivors back into the community increased from 60.0% to 89.4% (adjusted odds ratio, aOR: 6.0; 95% confidence interval, CI: 3.9-9.1); and (ii) wait for a burial team following a relative's death increased from 86.0% to 95.9% (aOR: 4.4; 95% CI: 3.2-6.0). The proportion avoiding unsafe traditional burials increased from 27.3% to 48.2% (aOR: 3.1; 95% CI: 2.4-4.2) and the proportion believing spiritual healers can treat Ebola decreased from 15.9% to 5.0% (aOR: 0.2; 95% CI: 0.1-0.3). The likelihood respondents would wait for burial teams increased more in high-transmission (aOR: 6.2; 95% CI: 4.2-9.1) than low-transmission (aOR: 2.3; 95% CI: 1.4-3.8) regions. Self-reported avoidance of physical contact with corpses increased in high but not low-transmission regions, aOR: 1.9 (95% CI: 1.4-2.5) and aOR: 0.8 (95% CI: 0.6-1.2), respectively. CONCLUSION: Ebola knowledge, attitudes and prevention practices improved during the Sierra Leone outbreak, especially in high-transmission regions. Behaviourally-targeted community engagement should be prioritized early during outbreaks.

Public Health Responses to COVID-19 Outbreaks on Cruise Ships - Worldwide, February-March 2020.

An estimated 30 million passengers are transported on 272 cruise ships worldwide each year* (1). Cruise ships bring diverse populations into proximity for many days, facilitating transmission of respiratory illness (2). SARS-CoV-2, the virus that causes coronavirus disease (COVID-19) was first identified in Wuhan, China, in December 2019 and has since spread worldwide to at least 187 countries and territories. Widespread COVID-19 transmission on cruise ships has been reported as well (3). Passengers on certain cruise ship voyages might be aged ≥65 years, which places them at greater risk for severe consequences of SARS-CoV-2 infection (4). During February-March 2020, COVID-19 outbreaks associated with three cruise ship voyages have caused more than 800 laboratory-confirmed cases among passengers and crew, including 10 deaths. Transmission occurred across multiple voyages of several ships. This report describes public health responses to COVID-19 outbreaks on these ships. COVID-19 on cruise ships poses a risk for rapid spread of disease, causing outbreaks in a vulnerable population, and aggressive efforts are required to contain spread. All persons should defer all cruise travel worldwide during the COVID-19 pandemic.

High Levels of HIV-1 Drug Resistance in Children Who Acquired HIV Infection Through Mother to Child Transmission in the Era of Option B+, Haiti, 2013 to 2014.

BACKGROUND: The main objective of this study was to determine the frequency and patterns of HIV drug resistance-associated mutations among children under 18 months of age born to HIV-1-positive mothers enrolled in the prevention of mother-to-child transmission services in Haiti. METHODS: Between January 1, 2013 and December 31, 2014, HIV-positive remnant dried blood spots collected from children under 18 months of age for Early Infant Diagnosis at the National Public Health Laboratory were used for HIV-1 genotyping. HIV drug resistance mutations were analyzed using the Stanford Drug Resistance HIVdb program. RESULTS: Of the 3555 dried blood spots collected for Early Infant Diagnosis, 360 (10.1%) were HIV-positive and 355 were available for genotyping. Of these, 304 (85.6%) were successfully genotyped and 217 (71.4%) had ≥1 drug resistance mutation. Mutations conferring resistance to nucleoside reverse transcriptase inhibitor (NRTIs) and non-NRTIs were present in 40.5% (123) and 69.1% (210), respectively. The most frequent mutations were K103N/S (48.0%), M184V (37.5%), G190A/S (15.1%), and Y181C/G/V (14.1%). Predicted drug resistance analysis revealed that 68.8% of the children had high-level resistance to non-NRTIs and 11.5% had intermediate to high-level resistance to abacavir. CONCLUSIONS: This study showed high rates of resistance to NRTIs and non-NRTIs among newly HIV-diagnosed children in Haiti, suggesting that in the era of "Option B+" (initiation of lifelong combination antiretroviral therapy to pregnant women with HIV), the majority of children who acquire HIV infection through mother-to-child transmission of HIV have resistant HIV. These results have led the National HIV Program to revise the pediatric guidelines to include protease inhibitors in first-line regimens for all HIV-positive newborns.

Ebola Virus Infection Associated with Transmission from Survivors.

Ebola virus (EBOV) can persist in immunologically protected body sites in survivors of Ebola virus disease, creating the potential to initiate new chains of transmission. From the outbreak in West Africa during 2014-2016, we identified 13 possible events of viral persistence-derived transmission of EBOV (VPDTe) and applied predefined criteria to classify transmission events based on the strength of evidence for VPDTe and source and route of transmission. For 8 events, a recipient case was identified; possible source cases were identified for 5 of these 8. For 5 events, a recipient case or chain of transmission could not be confidently determined. Five events met our criteria for sexual transmission (male-to-female). One VPDTe event led to at least 4 generations of cases; transmission was limited after the other events. VPDTe has increased the importance of Ebola survivor services and sustained surveillance and response capacity in regions with previously widespread transmission.

Resources needed for US CDC's support to the response to post-epidemic clusters of Ebola in West Africa, 2016.

BACKGROUND: West African countries Liberia, Sierra Leone, and Guinea experienced the largest and longest epidemic of Ebola virus disease from 2014 to 2016; after the epidemic was declared to be over, Liberia, Guinea, and Sierra Leone still experienced Ebola cases/clusters. The United States Centers for Disease Control and Prevention (US CDC) participated in the response efforts to the latter Ebola clusters, by assisting with case investigation, contact identification, and monitoring. This study aims to estimate the cost to the US CDC of responding to three different Ebola clusters after the end of the Ebola epidemic in 2015: i) Sierra Leone, Tonkolili (Jan 2016, 2 Ebola cases, 5 affected regions); ii) Guinea, Nzerekore (Mar-May 2016, 10 Ebola cases, 2 affected regions); iii) Liberia, Somali Drive (Mar 2016, 3 Ebola cases, 1 affected region). MAIN TEXT: After interviewing team members that had participated in the response, we estimated total costs (expressed in 2016 US Dollars [USD]), where total costs correspond to travel costs, deployed personnel costs, costs to prepare for deployment, procurement and interagency collaboration costs, among others. We also estimated cost per cluster case (corresponding to the total costs divided by the total number of cluster cases); and cost per case-affected-region (equal to the total costs divided by the product of the number of cases times the number of regions affected). We found that the response cost varied sixteenfold between USD 113 166 in Liberia and USD 1 764 271 in Guinea, where the main cost drivers were travel and personnel costs. The cost per cluster case varied tenfold between 37 722 in Liberia (three cases) and USD 347 226 in Sierra Leone, and the cost per case-affected-region varied threefold between USD 37 722 in Liberia and USD 88 214 in Guinea. CONCLUSIONS: Costs vary with the characteristics of each cluster, with those spanning more regions and cases requiring more resources for case investigation and contact identification and monitoring. These data will assist policy makers plan for similar post-epidemic responses.

Impact of Ebola experiences and risk perceptions on mental health in Sierra Leone, July 2015.

BACKGROUND: The mental health impact of the 2014-2016 Ebola epidemic has been described among survivors, family members and healthcare workers, but little is known about its impact on the general population of affected countries. We assessed symptoms of anxiety, depression and post-traumatic stress disorder (PTSD) in the general population in Sierra Leone after over a year of outbreak response. METHODS: We administered a cross-sectional survey in July 2015 to a national sample of 3564 consenting participants selected through multistaged cluster sampling. Symptoms of anxiety and depression were measured by Patient Health Questionnaire-4. PTSD symptoms were measured by six items from the Impact of Events Scale-revised. Relationships among Ebola experience, perceived Ebola threat and mental health symptoms were examined through binary logistic regression. RESULTS: Prevalence of any anxiety-depression symptom was 48% (95% CI 46.8% to 50.0%), and of any PTSD symptom 76% (95% CI 75.0% to 77.8%). In addition, 6% (95% CI 5.4% to 7.0%) met the clinical cut-off for anxiety-depression, 27% (95% CI 25.8% to 28.8%) met levels of clinical concern for PTSD and 16% (95% CI 14.7% to 17.1%) met levels of probable PTSD diagnosis. Factors associated with higher reporting of any symptoms in bivariate analysis included region of residence, experiences with Ebola and perceived Ebola threat. Knowing someone quarantined for Ebola was independently associated with anxiety-depression (adjusted OR (AOR) 2.3, 95% CI 1.7 to 2.9) and PTSD (AOR 2.095% CI 1.5 to 2.8) symptoms. Perceiving Ebola as a threat was independently associated with anxiety-depression (AOR 1.69 95% CI 1.44 to 1.98) and PTSD (AOR 1.86 95% CI 1.56 to 2.21) symptoms. CONCLUSION: Symptoms of PTSD and anxiety-depression were common after one year of Ebola response; psychosocial support may be needed for people with Ebola-related experiences. Preventing, detecting, and responding to mental health conditions should be an important component of global health security efforts.

Ebola Response Impact on Public Health Programs, West Africa, 2014-2017.

Events such as the 2014-2015 West Africa epidemic of Ebola virus disease highlight the importance of the capacity to detect and respond to public health threats. We describe capacity-building efforts during and after the Ebola epidemic in Liberia, Sierra Leone, and Guinea and public health progress that was made as a result of the Ebola response in 4 key areas: emergency response, laboratory capacity, surveillance, and workforce development. We further highlight ways in which capacity-building efforts such as those used in West Africa can be accelerated after a public health crisis to improve preparedness for future events.

Building and Rebuilding: The National Public Health Laboratory Systems and Services Before and After the Earthquake and Cholera Epidemic, Haiti, 2009-2015.

Before the 2010 devastating earthquake and cholera outbreak, Haiti's public health laboratory systems were weak and services were limited. There was no national laboratory strategic plan and only minimal coordination across the laboratory network. Laboratory capacity was further weakened by the destruction of over 25 laboratories and testing sites at the departmental and peripheral levels and the loss of life among the laboratory health-care workers. However, since 2010, tremendous progress has been made in building stronger laboratory infrastructure and training a qualified public health laboratory workforce across the country, allowing for decentralization of access to quality-assured services. Major achievements include development and implementation of a national laboratory strategic plan with a formalized and strengthened laboratory network; introduction of automation of testing to ensure better quality of results and diversify the menu of tests to effectively respond to outbreaks; expansion of molecular testing for tuberculosis, human immunodeficiency virus, malaria, diarrheal and respiratory diseases; establishment of laboratory-based surveillance of epidemic-prone diseases; and improvement of the overall quality of testing. Nonetheless, the progress and gains made remain fragile and require the full ownership and continuous investment from the Haitian government to sustain these successes and achievements.

Trends in Tuberculosis Case Notification and Treatment Success, Haiti, 2010-2015.

Since the 2010 earthquake, tuberculosis (TB) control has been a major priority for health sector response and recovery efforts in Haiti. The goal of this study was to analyze trends in TB case notification in Haiti from the aggregate data reported by the National TB Control Program to understand the effects of such efforts. A total of 95,745 TB patients were registered for treatment in Haiti between 2010 and 2015. Three regions, the West, Artibonite, and North departments accounted for 68% of the TB cases notified during the period. Patients in the 15-34 age groups represented 53% (50,560) of all cases. Case notification rates of all forms of TB increased from 142.7/100,000 in 2010 to 153.4 in 2015, peaking at 163.4 cases/100,000 in 2013. Case notification for smear-positive pulmonary TB increased from 85.5 cases/100,000 to 105.7 cases/100,000, whereas treatment success rates remained stable at 79-80% during the period. Active TB case finding efforts in high-risk communities and the introduction of new diagnostics have contributed to increasing TB case notification trends in Haiti from 2010 to 2015. Targeted interventions and novel strategies are being implemented to reach high-risk populations and underserved communities.

Implementation of broad screening with Ebola rapid diagnostic tests in Forécariah, Guinea.

BACKGROUND: Laboratory-enhanced surveillance is critical for rapidly detecting the potential re-emergence of Ebola virus disease. Rapid diagnostic tests (RDT) for Ebola antigens could expand diagnostic capacity for Ebola virus disease. OBJECTIVES: The Guinean National Coordination for Ebola Response conducted a pilot implementation to determine the feasibility of broad screening of patients and corpses with the OraQuick® Ebola RDT. METHODS: The implementation team developed protocols and trained healthcare workers to screen patients and corpses in Forécariah prefecture, Guinea, from 15 October to 30 November 2015. Data collected included number of consultations, number of fevers reported or measured, number of tests performed for patients or corpses and results of confirmatory RT-PCR testing. Data on malaria RDT results were collected for comparison. Feedback from Ebola RDT users was collected informally during supervision visits and forums. RESULTS: There were 3738 consultations at the 15 selected healthcare facilities; 74.6% of consultations were for febrile illness. Among 2787 eligible febrile patients, 2633 were tested for malaria and 1628 OraQuick® Ebola RDTs were performed. A total of 322 OraQuick® Ebola RDTs were conducted on corpses. All Ebola tests on eligible patients were negative. CONCLUSIONS: Access to Ebola testing was expanded by the implementation of RDTs in an emergency situation. Feedback from Ebola RDT users and lessons learned will contribute to improving quality for RDT expansion.