Pathogen Genomics in Public Health.

Rapid advances in DNA sequencing technology ("next-generation sequencing") have inspired optimism about the potential of human genomics for "precision medicine." Meanwhile, pathogen genomics is already delivering "precision public health" through more effective investigations of outbreaks of foodborne illnesses, better-targeted tuberculosis control, and more timely and granular influenza surveillance to inform the selection of vaccine strains. In this article, we describe how public health agencies have been adopting pathogen genomics to improve their effectiveness in almost all domains of infectious disease. This momentum is likely to continue, given the ongoing development in sequencing and sequencing-related technologies.

Emergence of SARS-CoV-2 B.1.1.7 Lineage - United States, December 29, 2020-January 12, 2021.

On December 14, 2020, the United Kingdom reported a SARS-CoV-2 variant of concern (VOC), lineage B.1.1.7, also referred to as VOC 202012/01 or 20I/501Y.V1.* The B.1.1.7 variant is estimated to have emerged in September 2020 and has quickly become the dominant circulating SARS-CoV-2 variant in England (1). B.1.1.7 has been detected in over 30 countries, including the United States. As of January 13, 2021, approximately 76 cases of B.1.1.7 have been detected in 12 U.S. states.† Multiple lines of evidence indicate that B.1.1.7 is more efficiently transmitted than are other SARS-CoV-2 variants (1-3). The modeled trajectory of this variant in the U.S. exhibits rapid growth in early 2021, becoming the predominant variant in March. Increased SARS-CoV-2 transmission might threaten strained health care resources, require extended and more rigorous implementation of public health strategies (4), and increase the percentage of population immunity required for pandemic control. Taking measures to reduce transmission now can lessen the potential impact of B.1.1.7 and allow critical time to increase vaccination coverage. Collectively, enhanced genomic surveillance combined with continued compliance with effective public health measures, including vaccination, physical distancing, use of masks, hand hygiene, and isolation and quarantine, will be essential to limiting the spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). Strategic testing of persons without symptoms but at higher risk of infection, such as those exposed to SARS-CoV-2 or who have frequent unavoidable contact with the public, provides another opportunity to limit ongoing spread.

The intersection of genomics and big data with public health: Opportunities for precision public health.

Muin Khoury and co-authors discuss anticipated contributions of genomics and other forms of large-scale data in public health.

Progress toward global interruption of wild poliovirus transmission, 2010-2013, and tackling the challenges to complete eradication.

Despite substantial progress, global polio eradication has remained elusive. Indigenous wild poliovirus (WPV) transmission in 4 endemic countries (Afghanistan, India, Nigeria, and Pakistan) persisted into 2010 and outbreaks from imported WPV continued. By 2013, most outbreaks in the interim were promptly controlled. The number of polio-affected districts globally has declined by 74% (from 481 in 2009 to 126 in 2013), including a 79% decrease in the number of affected districts in endemic countries (from 304 to 63). India is now polio-free. The challenges to success in the remaining polio-endemic countries include (1) threats to the security of vaccinators in each country and a ban on polio vaccination in areas of Afghanistan and Pakistan; (2) a risk of decreased government commitment; and (3) remaining surveillance gaps. Coordinated efforts under the International Health Regulations and efforts to mitigate the challenges provide a clear opportunity to soon secure global eradication.

Possible eradication of wild poliovirus type 3--worldwide, 2012.

In 1988, the World Health Assembly resolved to eradicate polio worldwide. Since then, four of the six World Health Organization (WHO) regions have been certified as polio-free: the Americas in 1994, the Western Pacific Region in 2000, the European Region in 2002, and the South-East Asia Region in 2014. Currently, nearly 80% of the world's population lives in areas certified as polio-free. Certification may be considered when ≥3 years have passed since the last isolation of wild poliovirus (WPV) in the presence of sensitive, certification-standard surveillance. Although regional eradication has been validated in the European Region and the Western Pacific Region, outbreaks resulting from WPV type 1 (WPV1) imported from known endemic areas were detected and controlled in these regions in 2010 and 2011, respectively. The last reported case associated with WPV type 2 (WPV2) was in India in 1999, marking global interruption of WPV2 transmission. The completion of polio eradication was declared a programmatic emergency for public health in 2012, and the international spread of WPV1 was declared a public health emergency of international concern in May 2014. The efforts needed to interrupt all indigenous WPV1 transmission are now being focused on the remaining endemic countries: Nigeria, Afghanistan, and Pakistan. WPV type 3 (WPV3) has not been detected in circulation since November 11, 2012. This report summarizes the evidence of possible global interruption of transmission of WPV3, based on surveillance for acute flaccid paralysis (AFP) and environmental surveillance.

An outbreak of wild poliovirus in the Republic of Congo, 2010-2011.

BACKGROUND: The Republic of Congo has had no cases of wild poliovirus type 1 (WPV1) since 2000. In October 2010, a neurologist noted an abnormal number of cases of acute flaccid paralysis (AFP) among adults, which were later confirmed to be caused by WPV1. METHODS: Those presenting with AFP underwent clinical history, physical examination, and clinical specimen collection to determine if they had polio. AFP cases were classified as laboratory-confirmed, clinical, or nonpolio AFP. Epidemiologic features of the outbreak were analyzed. RESULTS: From 19 September 2010 to 22 January 2011, 445 cases of WPV1 were reported in the Republic of Congo; 390 cases were from Pointe Noire. Overall, 331 cases were among adults; 378 cases were clinically confirmed, and 64 cases were laboratory confirmed. The case-fatality ratio (CFR) was 43%. Epidemiologic characteristics differed among polio cases reported in Pointe Noire and cases reported in the rest of the Republic of Congo, including age distribution and CFR. The outbreak stopped after multiple vaccination rounds with oral poliovirus vaccine, which targeted the entire population. CONCLUSIONS: This outbreak underscores the need to maintain high vaccination coverage to prevent outbreaks, the need to maintain timely high-quality surveillance to rapidly identify and respond to any potential cases before an outbreak escalates, and the need to perform ongoing risk assessments of immunity gaps in polio-free countries.

Multidrug-resistant typhoid fever with neurologic findings on the Malawi-Mozambique border.

BACKGROUND: Salmonella enterica serovar Typhi causes an estimated 22 million cases of typhoid fever and 216 000 deaths annually worldwide. We investigated an outbreak of unexplained febrile illnesses with neurologic findings, determined to be typhoid fever, along the Malawi-Mozambique border. METHODS: The investigation included active surveillance, interviews, examinations of ill and convalescent persons, medical chart reviews, and laboratory testing. Classification as a suspected case required fever and ≥1 other finding (eg, headache or abdominal pain); a probable case required fever and a positive rapid immunoglobulin M antibody test for typhoid (TUBEX TF); a confirmed case required isolation of Salmonella Typhi from blood or stool. Isolates underwent antimicrobial susceptibility testing and subtyping by pulsed-field gel electrophoresis (PFGE). RESULTS: We identified 303 cases from 18 villages with onset during March-November 2009; 214 were suspected, 43 were probable, and 46 were confirmed cases. Forty patients presented with focal neurologic abnormalities, including a constellation of upper motor neuron signs (n = 19), ataxia (n = 22), and parkinsonism (n = 8). Eleven patients died. All 42 isolates tested were resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole; 4 were also resistant to nalidixic acid. Thirty-five of 42 isolates were indistinguishable by PFGE. CONCLUSIONS: The unusual neurologic manifestations posed a diagnostic challenge that was resolved through rapid typhoid antibody testing in the field and subsequent blood culture confirmation in the Malawi national reference laboratory. Extending laboratory diagnostic capacity, including blood culture, to populations at risk for typhoid fever in Africa will improve outbreak detection, response, and clinical treatment.

Health care-associated measles outbreak in the United States after an importation: challenges and economic impact.

BACKGROUND: On 12 February 2008, an infected Swiss traveler visited hospital A in Tucson, Arizona, and initiated a predominantly health care-associated measles outbreak involving 14 cases. We investigated risk factors that might have contributed to health care-associated transmission and assessed outbreak-associated hospital costs. METHODS: Epidemiologic data were obtained by case interviews and review of medical records. Health care personnel (HCP) immunization records were reviewed to identify non-measles-immune HCP. Outbreak-associated costs were estimated from 2 hospitals. RESULTS: Of 14 patients with confirmed cases, 7 (50%) were aged ≥ 18 years, 4 (29%) were hospitalized, 7 (50%) acquired measles in health care settings, and all (100%) were unvaccinated or had unknown vaccination status. Of the 11 patients (79%) who had accessed health care services while infectious, 1 (9%) was masked and isolated promptly after rash onset. HCP measles immunity data from 2 hospitals confirmed that 1776 (25%) of 7195 HCP lacked evidence of measles immunity. Among these HCPs, 139 (9%) of 1583 tested seronegative for measles immunoglobulin G, including 1 person who acquired measles. The 2 hospitals spent US$799,136 responding to and containing 7 cases in these facilities. CONCLUSIONS: Suspecting measles as a diagnosis, instituting immediate airborne isolation, and ensuring rapidly retrievable measles immunity records for HCPs are paramount in preventing health care-associated spread and in minimizing hospital outbreak-response costs.

Timely assessment of the severity of the 2009 H1N1 influenza pandemic.

During the 2009 influenza pandemic, weekly mortality data were analyzed to estimate excess mortality above a seasonally adjusted baseline modeled from prior years' data. Between the 1962-1963 and 2008-2009 seasons, among persons ≥ 25 years old, excess mortality had been substantially higher during influenza A(H3N2)-dominant years than during A(H1N1)-dominant years. Among persons ≥ 15 years of age, excess mortality was higher in the 1968-1969 influenza pandemic season than during any other season. During the 2009-2010 pandemic, among all age groups <65 years old, excess mortality increased earlier than during any of the previous 47 seasons, eventually exceeding mortality in any prior non-pandemic season. In the ≥ 65-year-old age group, excess mortality remained relatively low, at rates typical of seasonal influenza A(H1N1) seasons. The model provided a timely assessment of severity during the 2009-2010 influenza pandemic, showing that, compared with prior seasons, mortality was relatively high among persons <65 years old and relatively low among those ≥ 65 years old.

Non-pharmaceutical interventions during an outbreak of 2009 pandemic influenza A (H1N1) virus infection at a large public university, April-May 2009.

Nonpharmaceutical interventions (NPIs), such as home isolation, social distancing, and infection control measures, are recommended by public health agencies as strategies to mitigate transmission during influenza pandemics. However, NPI implementation has rarely been studied in large populations. During an outbreak of 2009 Pandemic Influenza A (H1N1) virus infection at a large public university in April 2009, an online survey was conducted among students, faculty, and staff to assess knowledge of and adherence to university-recommended NPI. Although 3924 (65%) of 6049 student respondents and 1057 (74%) of 1401 faculty respondents reported increased use of self-protective NPI, such as hand washing, only 27 (6.4%) of 423 students and 5 (8.6%) of 58 faculty with acute respiratory infection (ARI) reported staying home while ill. Nearly one-half (46%) of student respondents, including 44.7% of those with ARI, attended social events. Results indicate a need for efforts to increase compliance with home isolation and social distancing measures.

Malaria in Kakuma refugee camp, Turkana, Kenya: facilitation of Anopheles arabiensis vector populations by installed water distribution and catchment systems.

BACKGROUND: Malaria is a major health concern for displaced persons occupying refugee camps in sub-Saharan Africa, yet there is little information on the incidence of infection and nature of transmission in these settings. Kakuma Refugee Camp, located in a dry area of north-western Kenya, has hosted ca. 60,000 to 90,000 refugees since 1992, primarily from Sudan and Somalia. The purpose of this study was to investigate malaria prevalence and attack rate and sources of Anopheles vectors in Kakuma refugee camp, in 2005-2006, after a malaria epidemic was observed by staff at camp clinics. METHODS: Malaria prevalence and attack rate was estimated from cases of fever presenting to camp clinics and the hospital in August 2005, using rapid diagnostic tests and microscopy of blood smears. Larval habitats of vectors were sampled and mapped. Houses were sampled for adult vectors using the pyrethrum knockdown spray method, and mapped. Vectors were identified to species level and their infection with Plasmodium falciparum determined. RESULTS: Prevalence of febrile illness with P. falciparum was highest among the 5 to 17 year olds (62.4%) while malaria attack rate was highest among the two to 4 year olds (5.2/1,000/day). Infected individuals were spatially concentrated in three of the 11 residential zones of the camp. The indoor densities of Anopheles arabiensis, the sole malaria vector, were similar during the wet and dry seasons, but were distributed in an aggregated fashion and predominantly in the same zones where malaria attack rates were high. Larval habitats and larval populations were also concentrated in these zones. Larval habitats were man-made pits of water associated with tap-stands installed as the water delivery system to residents with year round availability in the camp. Three percent of A. arabiensis adult females were infected with P. falciparum sporozoites in the rainy season. CONCLUSIONS: Malaria in Kakuma refugee camp was due mainly to infection with P. falciparum and showed a hyperendemic age-prevalence profile, in an area with otherwise low risk of malaria given prevailing climate. Transmission was sustained by A. arabiensis, whose populations were facilitated by installation of man-made water distribution and catchment systems.

Hepatitis A among international adoptees and their contacts.

We identified 27 cases of hepatitis A among international adoptees (5 persons), their direct or indirect contacts (20 persons), and unvaccinated travelers to the adoptees' countries (2 persons). Most cases occurred among nontraveling contacts of adoptees, suggesting the need to extend prevention guidelines to include hepatitis A vaccination for at-risk nontravelers.

Prevalence of hepatitis C virus infection among injection drug users in the United States, 1994-2004.

OBJECTIVE: To examine hepatitis C virus (HCV) seroprevalence among injection drug users in 4 US cities from 1994 through 2004. METHODS: Demographic characteristics, behaviors, and prevalence of HCV antibody among 5088 injection drug users aged 18-40 years from Baltimore, Maryland; Chicago, Illinois; Los Angeles, California; and New York, New York, enrolled in 3 related studies--Collaborative Injection Drug User Study (CIDUS) I (1994-1996), CIDUS II (1997-1999), and CIDUS III/Drug User Intervention Trial (2002-2004)--were compared using the chi(2) and Mantel-Haenszel tests of significance. Trends over time were assessed by logistic regression. RESULTS: Prevalence of HCV infection was 65%, 35%, and 35% in CIDUS I, CIDUS II, and CIDUS III, respectively. The adjusted prevalence odds ratio (OR) of being HCV antibody positive increased with the number of years of injection drug use (OR, 1.93 [95% confidence interval {CI}, 1.68-2.21] for each year of injecting within the first 2 years; OR, 1.09 [95% CI, 1.07-1.11] for each year of injecting beyond the first 2 years). Significant decreases were observed in the prevalence of HCV antibody between CIDUS I and CIDUS III in Baltimore (OR, 0.30; 95% CI, 0.20-0.43) and Los Angeles (OR, 0.17; 95% CI, 0.09-0.31) and among people of races other than black in Chicago (OR, 0.12; 95% CI, 0.08-0.17). No decrease in prevalence was seen in New York (OR, 1.04; 95% CI, 0.69-1.58) or among blacks in Chicago (OR, 0.55; 95% CI, 0.16-1.90). CONCLUSION: Although regional differences exist, our data suggest that the incidence of HCV infection among injection drug users in the United States decreased from 1994 through 2004.

An outbreak of hepatitis A associated with green onions.

BACKGROUND: In November 2003, a large hepatitis A outbreak was identified among patrons of a single Pennsylvania restaurant. We investigated the cause of the outbreak and factors that contributed to its unprecedented size. METHODS: Demographic and clinical outcome data were collected from patients with laboratory confirmation of hepatitis A, and restaurant workers were tested for hepatitis A. A case-control study was conducted among patrons who dined at the restaurant between October 3 and October 6, 2003. Sequence analysis was performed on a 315-nucleotide region of viral RNA extracted from serum specimens. RESULTS: Of 601 patients identified, 3 died; at least 124 were hospitalized. Of 425 patients who recalled a single dining date at the restaurant, 356 (84 percent) had dined there between October 3 and October 6. Among 240 patients in the case-control study, 218 had eaten mild salsa (91 percent), as compared with 45 of 130 controls (35 percent) (odds ratio, 19.6; 95 percent confidence interval, 11.0 to 34.9) for whom data were available. A total of 98 percent of patients and 58 percent of controls reported having eaten a menu item containing green onions (odds ratio, 33.3; 95 percent confidence interval, 12.8 to 86.2). All restaurant workers were tested, but none were identified who could have been the source of the outbreak. Sequences of hepatitis A virus from all 170 patients who were tested were identical. Mild salsa, which contained green onions grown in Mexico, was prepared in large batches at the restaurant and provided to all patrons. CONCLUSIONS: Green onions that were apparently contaminated before arrival at the restaurant caused this unusually large foodborne outbreak of hepatitis A. The inclusion of contaminated green onions in large batches that were served to all customers contributed to the size of the outbreak.

Injection drug users in the United States, 1979-2002: an aging population.

BACKGROUND: Injection drug use (IDU) is important in the epidemiology of blood-borne pathogens. Herein, trends in IDU from 1979 to 2002 are analyzed. METHODS: The National Household Survey on Drug Abuse is an ongoing survey of drug use among the US population 12 years and older. Participants were chosen using a multistage sampling design and interviewed by written questionnaire (1979-1998) or audio computer-assisted self-interviewing (1999-2002). Herein, we examine the prevalence of a history of IDU at any time in the past (IDU-ever) or within the past year. RESULTS: In the 2000-2002 surveys, 1.5% (95% confidence interval [CI], 1.4%-1.6%) reported IDU-ever (weighted estimate, 3.4 million persons). Prevalence was highest in persons aged 35 to 49 years (3.1%; 95% CI, 2.8%-3.4%), was higher in men (2.0%; 95% CI, 1.8%-2.2%) than women (1.0%; 95% CI, 0.9%-1.1%), and was higher in whites (1.7%; 95% CI, 1.5%-1.8%) than blacks (0.8%; 95% CI, 0.7%-1.1%) or Hispanics (1.1%; 95% CI, 0.8%-1.4%). Prevalence decreased with increasing annual income and educational level. Of all participants, 0.19% (95% CI, 0.16%-0.23%) reported IDU within the past year (weighted estimate, 440 000 persons). Ten years earlier (1990-1992), 1.6% (95% CI, 1.5%-1.8%) reported IDU-ever; prevalence did not differ by race. From 1979 through 2002, the mean age of participants with IDU within the past year increased from 21 to 36 years; the age of participants with IDU-ever increased from 26 to 42 years. From 2000 to 2002, 59.4% of all persons with IDU-ever were aged 35 to 49 years. CONCLUSIONS: The mean age of injection drug users has increased substantially. Persons born between the late 1940s and early 1960s have the highest prevalence of IDU-ever. Self-reported IDU rates are now lower among young blacks than young whites.

The prevalence of hepatitis C virus infection in the United States, 1999 through 2002.

BACKGROUND: Defining the primary characteristics of persons infected with hepatitis C virus (HCV) enables physicians to more easily identify persons who are most likely to benefit from testing for the disease. OBJECTIVE: To describe the HCV-infected population in the United States. DESIGN: Nationally representative household survey. SETTING: U.S. civilian, noninstitutionalized population. PARTICIPANTS: 15,079 participants in the National Health and Nutrition Examination Survey between 1999 and 2002. MEASUREMENTS: All participants provided medical histories, and those who were 20 to 59 years of age provided histories of drug use and sexual practices. Participants were tested for antibodies to HCV (anti-HCV) and HCV RNA, and their serum alanine aminotransferase (ALT) levels were measured. RESULTS: The prevalence of anti-HCV in the United States was 1.6% (95% CI, 1.3% to 1.9%), equating to an estimated 4.1 million (CI, 3.4 million to 4.9 million) anti-HCV-positive persons nationwide; 1.3% or 3.2 million (CI, 2.7 million to 3.9 million) persons had chronic HCV infection. Peak prevalence of anti-HCV (4.3%) was observed among persons 40 to 49 years of age. A total of 48.4% of anti-HCV-positive persons between 20 and 59 years of age reported a history of injection drug use, the strongest risk factor for HCV infection. Of all persons reporting such a history, 83.3% had not used injection drugs for at least 1 year before the survey. Other significant risk factors included 20 or more lifetime sex partners and blood transfusion before 1992. Abnormal serum ALT levels were found in 58.7% of HCV RNA-positive persons. Three characteristics (abnormal serum ALT level, any history of injection drug use, and history of blood transfusion before 1992) identified 85.1% of HCV RNA-positive participants between 20 and 59 years of age. LIMITATIONS: Incarcerated and homeless persons were not included in the survey. CONCLUSIONS: Many Americans are infected with HCV. Most were born between 1945 and 1964 and can be identified with current screening criteria. History of injection drug use is the strongest risk factor for infection.

Hepatitis C virus infection in Samoa and American Samoa.

Little is known about the prevalence of hepatitis C virus (HCV) in Pacific islands. In this study, serum specimens collected in 1985 and 2002 among the general populations of Samoa and American Samoa were tested for antibody to HCV by a third-generation enzyme immunoassay and a recombinant immunoblot assay. Of the 3,466 specimens tested, 8 (0.2%; 95% confidence interval = 0.07-0.4%) were positive for antibody to HCV. Prevalence did not vary by location or demographic characteristic. Thus, HCV is present in the Samoas but at a low prevalence.

Human Metapneumovirus Circulation in the United States, 2008 to 2014.

BACKGROUND: Human metapneumovirus (HMPV) infection causes respiratory illness, including bronchiolitis and pneumonia. However, national HMPV seasonality, as it compares with respiratory syncytial virus (RSV) and influenza seasonality patterns, has not been well described. METHODS: Hospital and clinical laboratories reported weekly aggregates of specimens tested and positive detections for HMPV, RSV, and influenza to the National Respiratory and Enteric Virus Surveillance System from 2008 to 2014. A season was defined as consecutive weeks with ≥3% positivity for HMPV and ≥10% positivity for RSV and influenza during a surveillance year (June through July). For each virus, the season, onset, offset, duration, peak, and 6-season medians were calculated. RESULTS: Among consistently reporting laboratories, 33 583 (3.6%) specimens were positive for HMPV, 281 581 (15.3%) for RSV, and 401 342 (18.2%) for influenza. Annually, 6 distinct HMPV seasons occurred from 2008 to 2014, with onsets ranging from November to February and offsets from April to July. Based on the 6-season medians, RSV, influenza, and HMPV onsets occurred sequentially and season durations were similar at 21 to 22 weeks. HMPV demonstrated a unique biennial pattern of early and late seasonal onsets. RSV seasons (onset, offset, peak) were most consistent and occurred before HMPV seasons. There were no consistent patterns between HMPV and influenza circulations. CONCLUSIONS: HMPV circulation begins in winter and lasts until spring and demonstrates distinct seasons each year, with the onset beginning after that of RSV. HMPV, RSV, and influenza can circulate simultaneously during the respiratory season.