Zika Virus Disease in Colombia - Preliminary Report.

BACKGROUND: Colombia began official surveillance for Zika virus disease (ZVD) in August 2015. In October 2015, an outbreak of ZVD was declared after laboratory-confirmed disease was identified in nine patients. METHODS: Using the national population-based surveillance system, we assessed patients with clinical symptoms of ZVD from August 9, 2015, to April 2, 2016. Laboratory test results and pregnancy outcomes were evaluated for a subgroup of pregnant women. Concurrently, we investigated reports of microcephaly for evidence of congenital ZVD. RESULTS: By April 2, 2016, there were 65,726 cases of ZVD reported in Colombia, of which 2485 (4%) were confirmed by means of reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay. The overall reported incidence of ZVD among female patients was twice that in male patients. A total of 11,944 pregnant women with ZVD were reported in Colombia, with 1484 (12%) of these cases confirmed on RT-PCR assay. In a subgroup of 1850 pregnant women, more than 90% of women who were reportedly infected during the third trimester had given birth, and no infants with apparent abnormalities, including microcephaly, have been identified. A majority of the women who contracted ZVD in the first or second trimester were still pregnant at the time of this report. Among the cases of microcephaly investigated from January 2016 through April 2016, four patients had laboratory evidence of congenital ZVD; all were born to asymptomatic mothers who were not included in the ZVD surveillance system. CONCLUSIONS: Preliminary surveillance data in Colombia suggest that maternal infection with the Zika virus during the third trimester of pregnancy is not linked to structural abnormalities in the fetus. However, the monitoring of the effect of ZVD on pregnant women in Colombia is ongoing. (Funded by Colombian Instituto Nacional de Salud and the Centers for Disease Control and Prevention.).

Evaluation of the collaborative integrated surveillance system (ViCo) in Guatemala: a qualitative study on lessons learned and future perspectives.

BACKGROUND: The collaborative integrated surveillance system known as Vigilancia Integrada Comunitaria (ViCo) was implemented in 2007 to better understand and characterize the burden of diarrheal, respiratory and febrile illnesses in Guatemala. METHODS: To evaluate the usefulness of ViCo and inform a redesign of the system and new surveillance activities in the Central American region, personnel from the United States Centers for Disease Control and Prevention (CDC) conducted thirty-nine in-depth interviews from June-December 2018 with key stakeholders responsible for the design and implementation of ViCo in Guatemala. A semi-structured questionnaire adapted from the Updated CDC Guidelines for Evaluating Public Health Surveillance Systems was used for data collection. We used a grounded theory approach to explore stakeholder perceptions of ViCo and generate recommendations for improvement. Primary qualitative findings were organized based on thematic areas using ATLAS.ti version 8 software. RESULTS: Emergent themes relevant to the usefulness of ViCo were organized across strengths, weaknesses, and recommendations pertaining to the: (1) Size and Complexity of ViCo, (2) Stakeholder Expectations About the Objectives of ViCo, (3) Data Management and Structure of the Information System, (4) Local Control of Data, (5) Integration of ViCo within the Ministry of Health, and, (6) Improvement of the Operational and Design Aspects of ViCo across System, Process, and Output levels. CONCLUSIONS: Stakeholders perceived ViCo to be useful. They recommended measures to improve system performance and quality, including simplifying the surveillance system, routine data analysis and feedback, and channeling efforts towards integrating surveillance data into the national health information system. To create a well-performing surveillance system and achieve the intended objective of surveillance for public health action, ongoing evaluation and assessment of surveillance activities are necessary.

Multi-country cross-sectional study of colonization with multidrug-resistant organisms: protocol and methods for the Antibiotic Resistance in Communities and Hospitals (ARCH) studies.

BACKGROUND: Antimicrobial resistance is a global health emergency. Persons colonized with multidrug-resistant organisms (MDROs) are at risk for developing subsequent multidrug-resistant infections, as colonization represents an important precursor to invasive infection. Despite reports documenting the worldwide dissemination of MDROs, fundamental questions remain regarding the burden of resistance, metrics to measure prevalence, and determinants of spread. We describe a multi-site colonization survey protocol that aims to quantify the population-based prevalence and associated risk factors for colonization with high-threat MDROs among community dwelling participants and patients admitted to hospitals within a defined population-catchment area. METHODS: Researchers in five countries (Bangladesh, Chile, Guatemala, Kenya, and India) will conduct a cross-sectional, population-based prevalence survey consisting of a risk factor questionnaire and collection of specimens to evaluate colonization with three high-threat MDROs: extended-spectrum cephalosporin-resistant Enterobacteriaceae (ESCrE), carbapenem-resistant Enterobacteriaceae (CRE), and methicillin-resistant Staphylococcus aureus (MRSA). Healthy adults residing in a household within the sampling area will be enrolled in addition to eligible hospitalized adults. Colonizing isolates of these MDROs will be compared by multilocus sequence typing (MLST) to routinely collected invasive clinical isolates, where available, to determine potential pathogenicity. A colonizing MDRO isolate will be categorized as potentially pathogenic if the MLST pattern of the colonizing isolate matches the MLST pattern of an invasive clinical isolate. The outcomes of this study will be estimates of the population-based prevalence of colonization with ESCrE, CRE, and MRSA; determination of the proportion of colonizing ESCrE, CRE, and MRSA with pathogenic characteristics based on MLST; identification of factors independently associated with ESCrE, CRE, and MRSA colonization; and creation an archive of ESCrE, CRE, and MRSA isolates for future study. DISCUSSION: This is the first study to use a common protocol to evaluate population-based prevalence and risk factors associated with MDRO colonization among community-dwelling and hospitalized adults in multiple countries with diverse epidemiological conditions, including low- and middle-income settings. The results will be used to better describe the global epidemiology of MDROs and guide the development of mitigation strategies in both community and healthcare settings. These standardized baseline surveys can also inform future studies seeking to further characterize MDRO epidemiology globally.

Case-Case Comparison of Candida auris Versus Other Candida Species Bloodstream Infections: Results of an Outbreak Investigation in Colombia.

BACKGROUND: Candida auris is an emerging multidrug-resistant yeast that causes outbreaks in healthcare settings around the world. In 2016, clinicians and public health officials identified patients with C. auris bloodstream infections (BSI) in Colombian healthcare facilities. To evaluate potential risk factors and outcomes for these infections, we investigated epidemiologic and clinical features of patients with C. auris and other Candida species BSI. METHODS: We performed a retrospective case-case investigation in four Colombian acute care hospitals, defining a case as Candida spp. isolated from blood culture during January 2015-September 2016. C. auris BSI cases were compared to other Candida species BSI cases. Odds ratio (OR), estimated using logistic regression, was used to assess the association between risk factors and outcomes. RESULTS: We analyzed 90 patients with BSI, including 40 with C. auris and 50 with other Candida species. All had been admitted to the intensive care unit (ICU). No significant demographic differences existed between the two groups. The following variables were independently associated with C. auris BSI: ≥ 15 days of pre-infection ICU stay (OR: 5.62, CI: 2.04-15.5), evidence of severe sepsis (OR: 3.70, CI 1.19-11.48), and diabetes mellitus (OR 5.69, CI 1.01-31.9). CONCLUSION: Patients with C. auris BSI had longer lengths of ICU stay than those with other candidemias, suggesting that infections are acquired during hospitalization. This is different from other Candida infections, which are usually thought to result from autoinfection with host flora.

Molecular Epidemiology of Candida auris in Colombia Reveals a Highly Related, Countrywide Colonization With Regional Patterns in Amphotericin B Resistance.

Background: Candida auris is a multidrug-resistant yeast associated with hospital outbreaks worldwide. During 2015-2016, multiple outbreaks were reported in Colombia. We aimed to understand the extent of contamination in healthcare settings and to characterize the molecular epidemiology of C. auris in Colombia. Methods: We sampled patients, patient contacts, healthcare workers, and the environment in 4 hospitals with recent C. auris outbreaks. Using standardized protocols, people were swabbed at different body sites. Patient and procedure rooms were sectioned into 4 zones and surfaces were swabbed. We performed whole-genome sequencing (WGS) and antifungal susceptibility testing (AFST) on all isolates. Results: Seven of the 17 (41%) people swabbed were found to be colonized. Candida auris was isolated from 37 of 322 (11%) environmental samples. These were collected from a variety of items in all 4 zones. WGS and AFST revealed that although isolates were similar throughout the country, isolates from the northern region were genetically distinct and more resistant to amphotericin B (AmB) than the isolates from central Colombia. Four novel nonsynonymous mutations were found to be significantly associated with AmB resistance. Conclusions: Our results show that extensive C. auris contamination can occur and highlight the importance of adherence to appropriate infection control practices and disinfection strategies. Observed genetic diversity supports healthcare transmission and a recent expansion of C. auris within Colombia with divergent AmB susceptibility.

Hospital-Associated Multicenter Outbreak of Emerging Fungus Candida auris, Colombia, 2016.

Candida auris is an emerging multidrug-resistant fungus that causes hospital-associated outbreaks of invasive infections with high death rates. During 2015-2016, health authorities in Colombia detected an outbreak of C. auris. We conducted an investigation to characterize the epidemiology, transmission mechanisms, and reservoirs of this organism. We investigated 4 hospitals with confirmed cases of C. auris candidemia in 3 cities in Colombia. We abstracted medical records and collected swabs from contemporaneously hospitalized patients to assess for skin colonization. We identified 40 cases; median patient age was 23 years (IQR 4 months-56 years). Twelve (30%) patients were <1 year of age, and 24 (60%) were male. The 30-day mortality was 43%. Cases clustered in time and location; axilla and groin were the most commonly colonized sites. Temporal and spatial clustering of cases and skin colonization suggest person-to-person transmission of C. auris. These cases highlight the importance of adherence to infection control recommendations.

Emerging Multidrug-Resistant Candida duobushaemulonii Infections in Panama Hospitals: Importance of Laboratory Surveillance and Accurate Identification.

Candida duobushaemulonii, a yeast closely related to Candida auris, is thought to cause infections in rare cases and is often misidentified. In October 2016, the Panamanian Ministry of Health implemented laboratory surveillance for C. auris Suspected C. auris isolates were forwarded to the national reference laboratory for identification by matrix-assisted laser desorption ionization-time of flight mass spectrometry and antifungal susceptibility testing. Between November 2016 and May 2017, 17 of 36 (47%) isolates suspected to be C. auris were identified as C. duobushaemulonii. These 17 isolates were obtained from 14 patients at six hospitals. Ten patients, including three children, had bloodstream infections, and MICs for fluconazole, voriconazole, and amphotericin B were elevated. No resistance to echinocandins was observed. C. duobushaemulonii causes more invasive infections than previously appreciated and poses a substantial problem, given its resistance to multiple antifungals. Expanded laboratory surveillance is an important step in the detection and control of such emerging pathogens.

Isolation of Candida auris from 9 patients in Central America: Importance of accurate diagnosis and susceptibility testing.

Candida auris is an emerging multidrug-resistant (MDR) fungus associated with invasive infections and high mortality. This report describes 9 patients from whom C. auris was isolated at a hospital in Panama City, Panama, the first such cases in Central America, and highlights the challenges of accurate identification and methods for susceptibility testing.

Seroprevalence of high incidence congenital infections among pregnant women in Coatepeque, Guatemala and surrounding areas, 2017-2018.

Maternal infections during pregnancy can potentially cause birth defects and severe adverse effects in infants. From 2017 to 2018, we investigated the seroprevalence of five antibodies among 436 mother-infant pairs enrolled in a pregnancy cohort study in Coatepeque, Guatemala. Upon enrollment (< 20 weeks gestational age) and shortly after delivery, we measured the prevalence of IgG and IgM antibodies against Toxoplasma gondii (T. gondii), rubella, and cytomegalovirus (CMV) in mothers and newborns and used rapid tests to detect HIV and syphilis (Treponema pallidum) in mothers. The mean cohort age was 24.5 years. Maternal T. gondii IgM and IgG seropositivity was 1.9% and 69.7%, respectively. No women were positive for HIV, syphilis, or rubella IgM. Maternal rubella IgG seropositivity was 80.8% and significantly increased with age. Maternal CMV IgM and IgG seropositivity were 2.3% and 99.5%, respectively. Of the 323 women tested at both timepoints, IgM reactivation occurred in one woman for T. gondii infection and in eight for CMV. No newborn was seropositive for CMV IgM or rubella IgM. One newborn was seropositive for T. gondii IgM. Congenital T. gondii and CMV infections are important public health issues for pregnant women, newborns, and healthcare providers in Coatepeque and Guatemala.

Epidemiological and Clinical Characteristics of Acute Dengue Virus Infections Detected through Acute Febrile Illness Surveillance, Belize 2020.

The Acute Febrile Illness (AFI) Surveillance Network in Belize is a country-wide active surveillance program aimed at diagnosing vector-borne, respiratory, and enteric pathogens among patients presenting to 11 participating hospitals and clinics with new onset fever. This study describes the epidemiology of dengue virus (DENV) infections in Belize diagnosed through AFI surveillance in 2020. Of the 894 patients enrolled and PCR-tested for DENV in this period, 44 DENV-positive cases (5%) were identified. All four DENV serotypes were detected, with two cases testing positive for DENV serotype 4, which is the first report of this serotype in Belize since 2004. The majority of DENV cases (66%) were diagnosed in the Belize District, which contains the largest urban center in the country (Belize City). Positive cases were detected between January 2020 and September 2020, with the majority (89%) diagnosed during the dry season between January and April, unlike years prior when cases were more often diagnosed during the wet season. Clinical signs and symptoms varied slightly between DENV serotypes. Active surveillance of DENV among AFI cases provides insight into the epidemiologic and clinical characteristics of DENV in Belize. This information is important for informing public health interventions to mitigate DENV transmission.

SARS-CoV-2 seroprevalence, cumulative infections, and immunity to symptomatic infection - A multistage national household survey and modelling study, Dominican Republic, June-October 2021.

Background: Population-level SARS-CoV-2 immunological protection is poorly understood but can guide vaccination and non-pharmaceutical intervention priorities. Our objective was to characterise cumulative infections and immunological protection in the Dominican Republic. Methods: Household members ≥5 years were enrolled in a three-stage national household cluster serosurvey in the Dominican Republic. We measured pan-immunoglobulin antibodies against the SARS-CoV-2 spike (anti-S) and nucleocapsid glycoproteins, and pseudovirus neutralising activity against the ancestral and B.1.617.2 (Delta) strains. Seroprevalence and cumulative prior infections were weighted and adjusted for assay performance and seroreversion. Binary classification machine learning methods and pseudovirus neutralising correlates of protection were used to estimate 50% and 80% protection against symptomatic infection. Findings: Between 30 Jun and 12 Oct 2021 we enrolled 6683 individuals from 3832 households. We estimate that 85.0% (CI 82.1-88.0) of the ≥5 years population had been immunologically exposed and 77.5% (CI 71.3-83) had been previously infected. Protective immunity sufficient to provide at least 50% protection against symptomatic SARS-CoV-2 infection was estimated in 78.1% (CI 74.3-82) and 66.3% (CI 62.8-70) of the population for the ancestral and Delta strains respectively. Younger (5-14 years, OR 0.47 [CI 0.36-0.61]) and older (≥75-years, 0.40 [CI 0.28-0.56]) age, working outdoors (0.53 [0.39-0.73]), smoking (0.66 [0.52-0.84]), urban setting (1.30 [1.14-1.49]), and three vs no vaccine doses (18.41 [10.69-35.04]) were associated with 50% protection against the ancestral strain. Interpretation: Cumulative infections substantially exceeded prior estimates and overall immunological exposure was high. After controlling for confounders, markedly lower immunological protection was observed to the ancestral and Delta strains across certain subgroups, findings that can guide public health interventions and may be generalisable to other settings and viral strains. Funding: This study was funded by the US CDC.

Urine Bisphenol A and Arsenic Levels in Residents of the Cheyenne River Sioux Tribe, South Dakota, with and without Diabetes.

INTRODUCTION: Diabetes disproportionately affects American Indians/Alaskan Natives (AI/AN). Bisphenol A (BPA) and arsenic (As), environmental toxicants which may be associated with diabetes, have not been well studied in this population. Our objectives were to determine if urinary BPA and As are associated with diabetes among adults in the Cheyenne River Sioux Tribe (CRST), and to compare their urinary levels with the general US population. METHODS: We performed a case-control study among 276 volunteers. We matched our cases (persons with diabetes) and controls (persons without diabetes) using age. We collected questionnaire data and urine samples which were tested for BPA and speciated As analytes. We used paired t tests and McNemar's chi-square test to compare continuous and categorical variables, respectively, between cases and controls and linear regression to assess the association between self-reported exposures and BPA and As levels. We used conditional logistic regression to investigate the association between case status and BPA and As levels. BPA and As levels among participants were compared with those from the 2011-2012 National Health and Nutrition Examination Survey (NHANES). RESULTS: The average age of participants was 46 years. The majority identified as AI/AN race (97%) and 58% were female. The geometric means from CRST participant urine specimens were 1.83 ug/L for BPA and 3.89 ug/L for total As. BPA geometric means of CRST participants were higher than NHANES participants while total As geometric means were lower. BPA and As were not associated with case status. CONCLUSION: The results of this study are consistent with others that have reported no association between diabetes and exposure to BPA or As.

Inverse association between dengue, chikungunya, and Zika virus infection and indicators of household air pollution in Santa Rosa, Guatemala: A case-control study, 2011-2018.

BACKGROUND: Dengue, chikungunya, and Zika viruses are increasingly important public health problems. Burning vegetation, leaves, and other plant products have been shown to be effective mosquito repellents for their vector, Aedes spp., but there has been scant research on whether firewood cooking smoke in households influences mosquito populations or mosquito-borne diseases. About 2.9 billion people worldwide use biomass fuel for household cooking and heating, resulting in an estimated 1.6 million deaths annually from household air pollution (HAP)-related diseases. Global health agencies now encourage households to transition from biomass to clean fuels, but it is unclear whether such interventions may actually increase risk for mosquito-borne diseases. This retrospective case-control study evaluated associations between arboviral infections and cooking with firewood in Santa Rosa, Guatemala. METHOD: Vigilancia Integrada Comunitaria (VICo) was a prospective public health surveillance system for bacterial, parasitic, and viral causes of diarrheal, neurological, respiratory, and febrile illnesses in hospitals and clinics in the department of Santa Rosa, Guatemala. Enrolled VICo in-patients and out-patients during 2011-2018 were interviewed using standardized questionnaires on demographics and household characteristics. Blood and stool specimens were collected and tested to identify the etiologies presenting symptoms. Cases were defined as laboratory-positive for dengue, chikungunya, or Zika virus infections. Controls were laboratory-positive for bacterial and viral diarrheal illnesses (e.g., Salmonella, Shigella, Campylobacter, Escherichia coli, rotavirus, norovirus, sapovirus, or astrovirus). Cooking with firewood, kitchen location, stove type, and firewood cooking frequency were the independent exposure variables. Logistic regression models were used to analyze unadjusted and adjusted associations between arboviral infections and exposures of interest. RESULT: There were 311 arboviral cases and 1,239 diarrheal controls. Arboviral infections were inversely associated with cooking with firewood in the main house (AOR: 0.22; 95% CI: 0.08-0.57), cooking with firewood on an open hearth (AOR: 0.50; 95% CI: 0.33-0.78), and cooking with firewood ≥5 times per week (AOR: 0.54; 95% CI: 0.36-0.81), adjusting for age, sex, ethnicity, socioeconomic status index, number of people per household, community population density, community elevation, recruitment location, season, and admission year. CONCLUSION: Several primary determinants of HAP exposure were inversely associated with arboviral infections. Additional studies are needed to understand whether interventions to reduce HAP might actually increase risk for mosquito-borne infectious diseases, which would warrant improved education and mosquito control efforts in conjunction with fuel interventions.

Understanding the Emergence of Multidrug-Resistant Candida: Using Whole-Genome Sequencing to Describe the Population Structure of Candida haemulonii Species Complex.

The recent emergence of a multidrug-resistant yeast, Candida auris, has drawn attention to the closely related species from the Candida haemulonii complex that include C. haemulonii, Candida duobushaemulonii, Candida pseudohaemulonii, and the recently identified Candida vulturna. Here, we used antifungal susceptibility testing and whole-genome sequencing (WGS) to investigate drug resistance and genetic diversity among isolates of C. haemulonii complex from different geographic areas in order to assess population structure and the extent of clonality among strains. Although most isolates of all four species were genetically distinct, we detected evidence of the in-hospital transmission of C. haemulonii and C. duobushaemulonii in one hospital in Panama, indicating that these species are also capable of causing outbreaks in healthcare settings. We also detected evidence of the rising azole resistance among isolates of C. haemulonii and C. duobushaemulonii in Colombia, Panama, and Venezuela linked to substitutions in ERG11 gene as well as amplification of this gene in C. haemulonii in isolates in Colombia suggesting the presence of evolutionary pressure for developing azole resistance in this region. Our results demonstrate that these species need to be monitored as possible causes of outbreaks of invasive infection.