Risk Factors for Ebola Exposure in Health Care Workers in Boende, Tshuapa Province, Democratic Republic of the Congo.

BACKGROUND: Health care workers (HCW) are more likely to be exposed to Ebola virus (EBOV) during an outbreak compared to people in the general population due to close physical contact with patients and potential exposure to infectious fluids. However, not all will fall ill. Despite evidence of subclinical and paucisymptomatic Ebola virus disease (EVD), prevalence and associated risk factors remain unknown. METHODS: We conducted a serosurvey among HCW in Boende, Tshuapa Province, Democratic Republic of Congo. Human anti-EBOV glycoprotein IgG titers were measured using a commercially available ELISA kit. We assessed associations between anti-EBOV IgG seroreactivity, defined as ≥2.5 units/mL, and risk factors using univariable and multivariable logistic regression. Sensitivity analyses explored a more conservative cutoff, >5 units/mL. RESULTS: Overall, 22.5% of HCWs were seroreactive for EBOV. In multivariable analyses, using any form of personal protective equipment when interacting with a confirmed, probable, or suspect EVD case was negatively associated with seroreactivity (adjusted odds ratio, 0.23; 95% confidence interval, .07-.73). DISCUSSION: Our results suggest high exposure to EBOV among HCWs and provide additional evidence for asymptomatic or minimally symptomatic EVD. Further studies should be conducted to determine the probability of onward transmission and if seroreactivity is associated with immunity.

Poliovirus immunity among adults in the Democratic Republic of the Congo: a cross-sectional serosurvey.

BACKGROUND: Vaccination efforts to eradicate polio currently focus on children under 5 years of age, among whom most cases of poliomyelitis still occur. However, in the Democratic Republic of the Congo (DRC), an outbreak of wild poliovirus type 1 occurred in 2010-2011 in which 16% of cases occurred among adults; in a related outbreak in the neighboring Republic of Congo, 75% of cases occurred among the same adult age-group. Given that infected adults may transmit poliovirus, this study was designed to assess adult immunity against polioviruses. METHODS: We assessed poliovirus seroprevalence using dried blood spots from 5,526 adults aged 15-59 years from the 2013-2014 Demographic and Health Survey in the DRC. RESULTS: Among adults in the DRC, 74%, 72%, and 57% were seropositive for neutralizing antibodies for poliovirus types 1, 2, and 3, respectively. For all three serotypes, seroprevalence tended to be higher among older age groups, those living in households with more children, and among women. CONCLUSIONS: Protection against poliovirus is generally low among adults in the DRC, particularly for type 3 poliovirus. The lack of acquired immunity in adults suggests a potentially limited poliovirus circulation over the lifetime of those surveyed (spanning 1954 through 2014) and transmission of vaccine-derived poliovirus in this age group while underscoring the risk of these outbreaks among adults in the DRC.

Serologic Markers for Ebolavirus Among Healthcare Workers in the Democratic Republic of the Congo.

Healthcare settings have played a major role in propagation of Ebola virus (EBOV) outbreaks. Healthcare workers (HCWs) have elevated risk of contact with EBOV-infected patients, particularly if safety precautions are not rigorously practiced. We conducted a serosurvey to determine seroprevalence against multiple EBOV antigens among HCWs of Boende Health Zone, Democratic Republic of the Congo, the site of a 2014 EBOV outbreak. Interviews and specimens were collected from 565 consenting HCWs. Overall, 234 (41.4%) of enrolled HCWs were reactive to at least 1 EBOV protein: 159 (28.1%) were seroreactive for anti-glycoprotein immunoglobulin G (IgG), 89 (15.8%) were seroreactive for anti-nucleoprotein IgG, and 54 (9.5%) were VP40 positive. Additionally, sera from 16 (2.8%) HCWs demonstrated neutralization capacity. These data demonstrate that a significant proportion of HCWs have the ability to neutralize virus, despite never having developed Ebola virus disease symptoms, highlighting an important and poorly documented aspect of EBOV infection and progression.

Serologic Evidence of Ebolavirus Infection in a Population With No History of Outbreaks in the Democratic Republic of the Congo.

Background: Previous studies suggest that cases of Ebola virus disease (EVD) may go unreported because they are asymptomatic or unrecognized, but evidence is limited by study designs and sample size. Methods: A large population-based survey was conducted (n = 3415) to assess animal exposures and behaviors associated with Ebolavirus antibody prevalence in rural Kasai Oriental province of the Democratic Republic of Congo (DRC). Fourteen villages were randomly selected and all healthy individuals ≥1 year of age were eligible. Results: Overall, 11% of subjects tested positive for Zaire Ebolavirus (EBOV) immunoglobulin G antibodies. Odds of seropositivity were higher for study participants older than 15 years of age and for males. Those residing in Kole (closer to the outbreak site) tested positive at a rate 1.6× higher than Lomela, with seropositivity peaking at a site located between Kole and Lomela. Multivariate analyses of behaviors and animal exposures showed that visits to the forest or hunting and exposure to rodents or duikers predicted a higher likelihood of EBOV seropositivity. Conclusions: These results provide serologic evidence of Ebolavirus exposure in a population residing in non-EBOV outbreak locations in the DRC and define statistically significant activities and animal exposures that associate with EBOV seropositivity.

Ebola Virus Neutralizing Antibodies Detectable in Survivors of theYambuku, Zaire Outbreak 40 Years after Infection.

The first reported outbreak of Ebola virus disease occurred in 1976 in Yambuku, Democratic Republic of Congo. Antibody responses in survivors 11 years after infection have been documented. However, this report is the first characterization of anti-Ebola virus antibody persistence and neutralization capacity 40 years after infection. Using ELISAs we measured survivor's immunological response to Ebola virus Zaire (EBOV) glycoprotein and nucleoprotein, and assessed VP40 reactivity. Neutralization of EBOV was measured using a pseudovirus approach and plaque reduction neutralization test with live EBOV. Some survivors from the original EBOV outbreak still harbor antibodies against all 3 measures. Interestingly, a subset of these survivors' serum antibodies could still neutralize live virus 40 years postinitial infection. These data provide the longest documentation of both anti-Ebola serological response and neutralization capacity within any survivor cohort, extending the known duration of response from 11 years postinfection to at least 40 years after symptomatic infection.

Early Folic Acid Supplement Initiation and Risk of Adverse Early Childhood Respiratory Health: A Population-based Study.

Objectives Folate plays a vital role in biologic functions yet women often do not meet the recommended dietary intake in pregnancy. It has been suggested that high folic acid intake during pregnancy may increase the risk of respiratory diseases in offspring. However, findings from observational studies in human populations are inconclusive. Methods In this population-based study, we collected self-reported folic acid and prenatal vitamin supplement use during pregnancy 3-6 months postpartum from mothers in Los Angeles whose children were born in 2003. Supplement initiation was based on whichever supplement, either folic acid or prenatal supplements, the women initiated first. In a 2006 follow-up survey, approximately 50% of women were re-contacted to gather information on the child's respiratory health, including symptoms and diagnoses, at approximately 3.5 years of age. Results Overall, timing of folic acid supplement initiation was not associated with wheeze or lower respiratory tract infection, even after accounting for preterm births and censoring at follow-up. However, children born to mothers with a history of atopy (hay fever, eczema or asthma) who initiate folic acid supplements in late pregnancy, compared to first trimester initiators, have 1.67 (95% CI 1.12, 2.49) times the risk of wheeze in the first 3 years of life and 1.88 (95% CI 1.05, 3.34) times the risk of wheeze in the past year. No association was found among children of non-atopic mothers. Conclusions These findings suggest that early folic acid or prenatal supplementation among atopic women may be important to prevent wheeze among offspring.

Detecting Ebola with limited laboratory access in the Democratic Republic of Congo: evaluation of a clinical passive surveillance reporting system.

BACKGROUND: Ebola virus disease (EVD) can be clinically severe and highly fatal, making surveillance efforts for early disease detection of paramount importance. In areas with limited access to laboratory testing, the Integrated Disease Surveillance and Response (IDSR) strategy in the Democratic Republic of Congo (DRC) may be a vital tool in improving outbreak response. METHODS: Using DRC IDSR data from the nation's four EVD outbreak periods from 2007-2014, we assessed trends of Viral Hemorrhagic Fever (VHF) and EVD differential diagnoses reportable through IDSR. With official case counts from active surveillance of EVD outbreaks, we assessed accuracy of reporting through the IDSR passive surveillance system. RESULTS: Although the active and passive surveillance represent distinct sets of data, the two were correlated, suggesting that passive surveillance based only on clinical evaluation may be a useful predictor of true cases prior to laboratory confirmation. There were 438 suspect VHF cases reported through the IDSR system and 416 EVD cases officially recorded across the outbreaks examined. CONCLUSION: Although collected prior to official active surveillance cases, case reporting through the IDSR during the 2007, 2008 and 2012 outbreaks coincided with official EVD epidemic curves. Additionally, all outbreak areas experienced increases in suspected cases for both malaria and typhoid fever during EVD outbreaks, underscoring the importance of training health care workers in recognising EVD differential diagnoses and the potential for co-morbidities.

The Influence of Pre-natal Supplement Initiation on Preterm Birth Among Majority Hispanic Women in Los Angeles County: The Role of Nativity.

Objectives Despite being encouraged to take pre-natal supplements, suboptimal micronutrient intake is common in pregnancy, especially among Hispanic women. In this study, we assessed whether initiation and timing of pre-natal vitamin use influences the risk of preterm birth. Methods Women who gave birth to singletons in 2003 in Los Angeles County, California, were enrolled into a population-based case-control study. Focusing on non-Hispanic white and Hispanic women, associations between timing of pre-natal supplement use and preterm birth were assessed using logistic regression. Results Among Hispanic mothers, the odds of preterm birth increased the later a woman initiated pre-natal supplement use in pregnancy. The magnitude of this association was larger in US-born compared to foreign-born Hispanic women. Conclusions These findings suggest that nativity may modify the relationship between pre-natal supplement use and preterm birth possibly due to underlying differences in diet composition of Hispanic women by place of birth.

Validity of child anthropometric measurements in the Special Supplemental Nutrition Program for Women, Infants, and Children.

INTRODUCTION: The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) serves 50% of infants and 25% of preschool-aged children in the United States and collects height and weight measurements from eligible children every 6 mo, making WIC data a valuable resource for studying childhood growth and obesity. We assessed the accuracy of measurements collected by WIC staff by comparing them to "gold standard" measurements collected by trained research staff. RESULTS: Intraclass correlation coefficients (ICCs) measuring agreement between WIC and research protocol measurements for height, weight, and BMI were 0.96, 0.99, and 0.93, respectively. Although WIC measurements overestimated height by 0.6 cm and weight by 0.05 kg on average, BMI was underestimated by only 0.15 kg/m(2) on average. WIC BMI percentiles classified children as overweight/obese vs. underweight/normal with 86% sensitivity and 92% specificity. DISCUSSION: We conclude that height, weight, and BMI measurements of children aged 2-5 y collected by trained WIC staff are sufficiently accurate for monitoring and research purposes. METHODS: At seven WIC clinics in southern California, 287 children aged 2-5 y measured for height and weight by WIC staff using WIC standard protocol were remeasured by research staff using a research protocol (duplicate measurements with shoes and outerwear removed were taken by trained personnel).

Measles antibody levels among vaccinated and unvaccinated children 6-59 months of age in the Democratic Republic of the Congo, 2013-2014.

BACKGROUND: Measles is endemic in the Democratic Republic of the Congo (DRC), and 89-94% herd immunity is required to halt its transmission. Much of the World Health Organization African Region, including the DRC, has vaccination coverage below the 95% level required to eliminate measles, heightening concern of inadequate measles immunity. METHODS: We assessed 6706 children aged 6-59 months whose mothers were selected for interview in the 2013-2014 DRC Demographic and Health Survey. History of measles was obtained by maternal report, and classification of children who had measles was completed using maternal recall and measles immunoglobulin G serostatus obtained from a multiplex chemiluminescent automated immunoassay dried blood spot analysis. A logistic regression model was used to identify associations of covariates with measles and seroprotection, and vaccine effectiveness (VE) was calculated. RESULTS: Out of our sample, 64% of children were seroprotected. Measles vaccination was associated with protection against measles (OR: 0.15, 95% CI: 0.03, 0.81) when administered to children 12 months of age or older. Vaccination was predictive of seroprotection at all ages. VE was highest (88%) among children 12-24 months of age. CONCLUSION: Our results demonstrated lower than expected seroprotection against measles among vaccinated children. Understanding the factors that affect host immunity to measles will aid in developing more efficient and effective immunization programs in DRC.

Monkeypox Rash Severity and Animal Exposures in the Democratic Republic of the Congo.

Experimental studies have suggested a larger inoculum of monkeypox virus may be associated with increased rash severity; however, little data are available on the relationship between specific animal exposures and rash severity in endemic regions. Using cross-sectional data from an active surveillance program conducted between 2005 and 2007 in the Sankuru Province of the Democratic Republic of the Congo, we explored the possible relationship between rash severity and exposures to rodents and non-human primates among confirmed MPX cases. Among the 223 PCR-confirmed MPX cases identified during active surveillance, the majority of cases (n = 149) presented with mild rash (5-100 lesions) and 33% had a more serious presentation (> 100 lesions). No association between exposure to rodents and rash severity was found in the multivariable analysis. Those that self-reported hunting NHP 3 weeks prior to onset of MPX symptoms had 2.78 times the odds of severe rash than those that did not report such exposure (95% CI: 1.18, 6.58). This study provides a preliminary step in understanding the association between animal exposure and rash severity and demonstrates correlation with exposure to NHPs and human MPX presentation. Additional research exploring the relationship between rash severity and NHPs is warranted.

Changes in childhood vaccination coverage over time in the Democratic Republic of the Congo.

Despite increased vaccination rates, the burden, morbidity and mortality associated with vaccine preventable diseases remains high. In the Democratic Republic of the Congo (DRC), potentially unreliable data and geographically varied program provision call for a better understanding of vaccination coverage and its changes over time at the country and province level. To assess changes in the proportion of children who were fully vaccinated over time in the DRC, vaccination histories for children 12-59 months of age were obtained from both the 2007 and 2013-2014 Demographic and Health Surveys (DHS). Changes were assessed, both at the country- and province-levels, to identify potential geographic variations. Vaccination coverage improved 70% between the DHS waves: 26% compared to 44% of 12-59 month-old children met full vaccination criteria in 2007 and 2013-2014, respectively (n2007 = 3032 and n2013-14 = 6619). Similarly, there was an overall trend across both DHS waves where as year of birth increased, so did vaccination coverage. There was geographic variation in immunization changes with most central and eastern provinces increasing in coverage and most northern, western and southern provinces having decreased vaccination coverage at the second time point. Using nationally representative data, we identified significant changes over time in vaccination coverage which may help to inform future policy, interventions and research to improve vaccination rates among children in the DRC. This study is the first of its kind for the population of DRC and provides an important initial step towards better understanding trends in vaccination coverage over time.

Association of Previous Measles Infection With Markers of Acute Infectious Disease Among 9- to 59-Month-Old Children in the Democratic Republic of the Congo.

BACKGROUND: Transient immunosuppression and increased susceptibility to other infections after measles infection is well known, but recent studies have suggested the occurrence of an "immune amnesia" that could have long-term immunosuppressive effects. METHODS: We examined the association between past measles infection and acute episodes of fever, cough, and diarrhea among 2350 children aged 9 to 59 months whose mothers were selected for interview in the 2013-2014 Democratic Republic of the Congo (DRC) Demographic and Health Survey (DHS). Classification of children who had had measles was completed using maternal recall and measles immunoglobulin G serostatus obtained via dried-blood-spot analysis with a multiplex immunoassay. The association with time since measles infection and fever, cough, and diarrhea outcomes was also examined. RESULTS: The odds of fever in the previous 2 weeks were 1.80 (95% confidence interval [CI], 1.25-2.60) among children for whom measles was reported compared to children with no history of measles. Measles vaccination demonstrated a protective association against selected clinical markers of acute infectious diseases. CONCLUSION: Our results suggest that measles might have a long-term effect on selected clinical markers of acute infectious diseases among children aged 9 to 59 months in the DRC. These findings support the immune-amnesia hypothesis suggested by others and underscore the need for continued evaluation and improvement of the DRC's measles vaccination program.

Prevalence of Rubella Antibodies Among Children in the Democratic Republic of the Congo.

BACKGROUND: While generally mild in children, rubella infection in early pregnancy can lead to miscarriage, fetal death or congenital rubella syndrome. Rubella vaccination is not yet available as a part of routine immunization in the Democratic Republic of the Congo (DRC), and the burden of infection is unknown. METHODS: In collaboration with the 2013-2014 DRC Demographic and Health Survey, a serosurvey was carried out to assess population immunity to vaccine-preventable diseases. Dry blood spot samples collected from children 6-59 months of age were processed using the Dynex Technologies Multiplier FLEX chemiluminescent immunoassay platform (Dynex Technologies, Chantilly, VA). RESULTS: Among the 7195 6- to 59-month-old children, 33% were positive and <1% indeterminate for rubella antibodies in weighted analyses. Seroprevalence was positively associated with age of the child and province, with seropositivity highest in Bandundu (53%) and lowest in Kasai-Oriental (20%). In multivariate analyses, serologic evidence of infection was associated with age of the mother and child, socioeconomic status and geographic location. CONCLUSIONS: Rubella infection is prevalent among children in the DRC, and while most seroconversion occurs in young children, a significant proportion of children remain at risk and may enter reproductive age susceptible to rubella infection. While not currently in place, implementation of a surveillance program will provide improved estimates of both rubella virus circulation and the burden of congenital rubella syndrome. Such information will play an important role in future policy decisions, vaccine delivery strategies and may provide a basis upon which the effectiveness of rubella antigen introduction may be assessed.

Low Varicella Zoster Virus Seroprevalence Among Young Children in the Democratic Republic of the Congo.

BACKGROUND: Varicella zoster virus (VZV) causes both varicella (chickenpox) and herpes zoster (shingles) and is associated with significant global morbidity. Most epidemiological data on VZV come from high-income countries, and to date there are limited data on the burden of VZV in Africa. METHODS: We assessed the seroprevalence of VZV antibodies among children in the Democratic Republic of Congo in collaboration with the 2013-2014 Demographic and Health Survey. Dried blood spot samples collected from children 6-59 months of age were run on Dynex™ Technologies Multiplier FLEX® chemiluminescent immunoassay platform to assess serologic response. Multivariate logistic regression was then used to determine risk factors for VZV seropositivity. RESULTS: Serologic and survey data were matched for 7,195 children 6-59 months of age, among whom 8% were positive and 2% indeterminate for VZV antibodies in weighted analyses. In multivariate analyses, the odds of seropositivity increased with increasing age, increasing socioeconomic status, mother's education level, rural residence, and province (South Kivu, North Kivu, Bandundu, Bas Congo had the highest odds of a positive test result compared with Kinshasa). CONCLUSION: Our data suggest that VZV is circulating in DRC, and seropositivity is low among children 6-59 months. Seropositivity increased with age and varied by other sociodemographic factors, such as geographic location. This study provides the first nationally representative estimates of VZV infection among children in the DRC.

Predictors of measles vaccination coverage among children 6-59 months of age in the Democratic Republic of the Congo.

BACKGROUND: Measles is a significant contributor to child mortality in the Democratic Republic of the Congo (DRC), despite routine immunization programs and supplementary immunization activities (SIA). Further, national immunization coverage levels may hide disparities among certain groups of children, making effective measles control even more challenging. This study describes measles vaccination coverage and reporting methods and identifies predictors of vaccination among children participating in the 2013-2014 DRC Demographic and Health Survey (DHS). METHODS: We examined vaccination coverage of 6947 children aged 6-59 months. A multivariate logistic regression model was used to identify predictors of vaccination among children reporting vaccination via dated card in order to identify least reached children. We also assessed spatial distribution of vaccination report type by rural versus urban residence. RESULTS: Urban children with educated mothers were more likely to be vaccinated (OR = 4.1, 95% CI: 1.6, 10.7) versus children of mothers with no education, as were children in wealthier rural families (OR = 2.9, 95% CI: 1.9, 4.4). At the provincial level, urban areas more frequently reported vaccination via dated card than rural areas. CONCLUSIONS: Results indicate that, while the overall coverage level of 70% is too low, socioeconomic and geographic disparities also exist which could make some children even less likely to be vaccinated. Dated records of measles vaccination must be increased, and groups of children with the greatest need should be targeted. As access to routine vaccination services is limited in DRC, identifying and targeting under-reached children should be a strategic means of increasing country-wide effective measles control.

Evidence of Mumps Infection Among Children in the Democratic Republic of Congo.

BACKGROUND: Mumps is an acute viral infection and while the infection is usually mild, complications can lead to permanent sequelae including brain damage and deafness. The burden of mumps is currently unknown the Democratic Republic of Congo (DRC), we therefore assessed susceptibility to mumps infection among children 6-59 months of age. METHODS: In collaboration with the 2013-2014 DRC Demographic and Health Survey, we conducted a serosurvey to assess population immunity to vaccine preventable diseases. Dried blood spot samples were collected from children 6 to 59 months of age and processed at the UCLA-DRC laboratory in Kinshasa, DRC using the Dynex Technologies Multiplier FLEX chemiluminescent immunoassay platform (Dynex multiplex assay, Chantilly, VA). Logistic multivariate analyses were used to determine risk factors for mumps seropositivity. RESULTS: Serologic and survey data were matched for 7195, 6-59 month-old children, among whom 22% were positive and 3% indeterminate for mumps antibodies in weighted analyses. In multivariate analyses, the odds of seropositivity increased with increasing age, female gender, number of children in household, increasing socioeconomic status and province (Kinshasa with the highest odds of positive test result compared with all other provinces). CONCLUSION: These data suggest that mumps virus is circulating in DRC and risk of exposure increases with age. At present, the introduction of a combined measles-mumps-rubella vaccine remains unlikely, as the capacity to maintain adequate vaccine coverage levels for routine immunization must be improved before additional antigens can be considered for the routine immunization schedule.