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BackgroundRecent studies suggest measles-induced immune amnesia could have long-term immunosuppressive effects via preferential depletion of memory CD150+ lymphocytes, and associations with a 2-3 year period of increased mortality and morbidity from infectious diseases other than measles has been shown in children from wealthy and low-income countries. To further examine the associations previous measles virus infection may have on immunologic memory among children in the Democratic Republic of the Congo (DRC), we assessed tetanus antibody levels among fully vaccinated children, with and without a history of measles.MethodsWe assessed 711 children 9-59 months of age 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 in the past was completed using maternal recall and measles IgG serostatus obtained from a multiplex chemiluminescent automated immunoassay dried blood spot analysis. Tetanus IgG antibody serostatus was similarly obtained. A logistic regression model was used to identify association of measles and other predictors with subprotective tetanus IgG antibody.ResultsSubprotective geometric mean concentration tetanus IgG antibody values were seen among fully vaccinated children 9-59 months of age, who had a history of measles. Controlling for potential confounding variables, children classified as measles cases were less likely to have seroprotective tetanus toxoid antibody (odds ratio: 0.21; 95% confidence interval: 0.08-0.55) compared with children who had not had measles.ConclusionsHistory of measles was associated with subprotective tetanus antibody among this sample of children in the DRC who were 9-59 months of age and fully vaccinated against tetanus.

BackgroundVaccination 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.MethodsWe 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.ResultsAmong 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.ConclusionsProtection 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.

BackgroundHealth 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.MethodsWe 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.ResultsOverall, 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).DiscussionOur 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.

[This corrects the article DOI: 10.1371/journal.pntd.0009566.].

BackgroundTetanus is a potentially fatal disease that is preventable through vaccination. While the Democratic Republic of the Congo (DRC) has continued to improve implementing routine vaccination activities throughout the country, they have struggled to maintain high childhood vaccine coverage. This study aims to examine the seroprevalence of tetanus in children 6 to 59 months to identify areas for intervention and improvement of vaccination coverage.MethodsIn collaboration with the 2013-2014 Demographic and Health Survey, we assessed the seroprevalence of tetanus antibodies among children in the DRC. Dried blood spot samples collected from children 6-59 months of age were processed using a prototype DYNEX Multiplier® chemiluminescent automated immunoassay instrument with a multiplex measles, mumps, rubella, varicella and tetanus assay. Multivariable logistic regression was used to determine factors associated with tetanus vaccination and seroprotection.ResultsOverall, 36.1% of children 6-59 months of age reported receiving at least 1 dose of tetanus vaccine while 28.7% reported receiving 3 doses; tetanus seroprotection was 40%. Increasing age in children was associated with decreased tetanus seroprotection, but increased number tetanus vaccinations received. Factors related to increased tetanus seroprotection included number of children in the household, wealth index of the family, urban residence compared to rural, level of maternal education, and province and geography.ConclusionsOur findings in this nationally representative sample indicate that serology biomarkers may help identify children who are not fully immunized to tetanus more accurately than reported vaccination. While children may be captured for routine immunization activities, as children age, decreasing seroprevalence may indicate additional need to bolster routine vaccination activities and documentation of vaccination in school aged children. Additionally, the study highlights gaps in rural residential areas and vaccination coverage based on maternal education, indicating that policies targeting maternal education and awareness could improve the coverage and seroprevalence of tetanus antibodies in the DRC.

BackgroundEbola virus (EBOV) is a zoonotic filovirus spread through exposure to infected bodily fluids of a human or animal. Though EBOV is capable of causing severe disease, referred to as Ebola Virus Disease (EVD), individuals who have never been diagnosed with confirmed, probable or suspected EVD can have detectable EBOV antigen-specific antibodies in their blood. This study aims to identify risk factors associated with detectable antibody levels in the absence of an EVD diagnosis.MethodologyData was collected from September 2015 to August 2017 from 1,366 consenting individuals across four study sites in the DRC (Boende, Kabondo-Dianda, Kikwit, and Yambuku). Seroreactivity was determined to EBOV GP IgG using Zaire Ebola Virus Glycoprotein (EBOV GP antigen) ELISA kits (Alpha Diagnostic International, Inc.) in Kinshasa, DRC; any result above 4.7 units/mL was considered seroreactive. Among the respondents, 113 (8.3%) were considered seroreactive. Several zoonotic exposures were associated with EBOV seroreactivity after controlling for age, sex, healthcare worker status, location, and history of contact with an EVD case, namely: ever having contact with bats, ever having contact with rodents, and ever eating non-human primate meat. Contact with monkeys or non-human primates was not associated with seroreactivity.ConclusionsThis analysis suggests that some zoonotic exposures that have been linked to EVD outbreaks can also be associated with EBOV GP seroreactivity in the absence of diagnosed EVD. Future investigations should seek to clarify the relationships between zoonotic exposures, seroreactivity, asymptomatic infection, and EVD.

BackgroundOur understanding of the different effects of targeted versus nontargeted violence on Ebola virus (EBOV) transmission in Democratic Republic of the Congo (DRC) is limited.MethodsWe used time-series data of case counts to compare individuals in Ebola-affected health zones in DRC, April 2018-August 2019. Exposure was number of violent events per health zone, categorized into Ebola-targeted or Ebola-untargeted, and into civilian-induced, (para)military/political, or protests. Outcome was estimated daily reproduction number (Rt) by health zone. We fit linear time-series regression to model the relationship.ResultsAverage Rt was 1.06 (95% confidence interval [CI], 1.02-1.11). A mean of 2.92 violent events resulted in cumulative absolute increase in Rt of 0.10 (95% CI, .05-.15). More violent events increased EBOV transmission (P = .03). Considering violent events in the 95th percentile over a 21-day interval and its relative impact on Rt, Ebola-targeted events corresponded to Rt of 1.52 (95% CI, 1.30-1.74), while civilian-induced events corresponded to Rt of 1.43 (95% CI, 1.21-1.35). Untargeted events corresponded to Rt of 1.18 (95% CI, 1.02-1.35); among these, militia/political or ville morte events increased transmission.ConclusionsEbola-targeted violence, primarily driven by civilian-induced events, had the largest impact on EBOV transmission.

BackgroundOur understanding of the different effects of targeted versus nontargeted violence on Ebola virus (EBOV) transmission in Democratic Republic of the Congo (DRC) is limited.MethodsWe used time-series data of case counts to compare individuals in Ebola-affected health zones in DRC, April 2018-August 2019. Exposure was number of violent events per health zone, categorized into Ebola-targeted or Ebola-untargeted, and into civilian-induced, (para)military/political, or protests. Outcome was estimated daily reproduction number (Rt) by health zone. We fit linear time-series regression to model the relationship.ResultsAverage Rt was 1.06 (95% confidence interval [CI], 1.02-1.11). A mean of 2.92 violent events resulted in cumulative absolute increase in Rt of 0.10 (95% CI, .05-.15). More violent events increased EBOV transmission (P = .03). Considering violent events in the 95th percentile over a 21-day interval and its relative impact on Rt, Ebola-targeted events corresponded to Rt of 1.52 (95% CI, 1.30-1.74), while civilian-induced events corresponded to Rt of 1.43 (95% CI, 1.21-1.35). Untargeted events corresponded to Rt of 1.18 (95% CI, 1.02-1.35); among these, militia/political or ville morte events increased transmission.ConclusionsEbola-targeted violence, primarily driven by civilian-induced events, had the largest impact on EBOV transmission.

Prenatal Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV) infections are associated with adverse birth outcomes. As rapid diagnostic tests become available, it is important to evaluate prenatal sexually transmitted infection (STI) prevalence, as well as the acceptability and feasibility of prenatal screening programs. We recruited 371 pregnant women from four clinics in Kisantu Health Zone, Democratic Republic of Congo (DRC) from October 2016 to March 2017. Trained clinicians collected cervical swabs, and samples were tested by nucleic acid amplification for CT, NG, and TV using a GeneXpert® system. Those testing positive for an STI were treated and asked to return after 4–8 weeks for tests-of-cure. Screening for STIs was widely accepted (99%). STI prevalence at baseline was: CT, 3.2%; NG, 1.5%; and TV, 14%; treatment completion was 97%. Symptoms were reported among 34% of STI-positive women at baseline, compared with 37% of STI-negative women. Upon first test-of-cure, 100% of returning women were cured of CT (n= 10) and NG (n= 5), but only 47% were cured of TV. This study demonstrates the feasibility of implementing diagnostic STI testing for case detection and treatment among expectant mothers in DRC, with implications for maternal and birth outcomes.

A serological survey of 2,430 archived serum samples collected between 1997 and 2012 was conducted to retrospectively determine the prevalence of Marburg virus in five African countries. Serum samples were screened for neutralizing antibodies in a pseudotype micro-neutralization assay and confirmed by enzyme-linked immunosorbent assay (ELISA). Surprisingly, a seroprevalence for Marburg virus of 7.5 and 6.3% was found in Cameroon and Ghana, respectively, suggesting the circulation of filoviruses or related viruses outside of known endemic areas that remain undetected by current surveillance efforts. However, due to the lack of validated assays and appropriate positive controls, these results must be considered preliminary.

BackgroundTransient 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.MethodsWe 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.ResultsThe 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.ConclusionOur 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.

Schistosomiasis afflicts an estimated 10 million pregnant women in Africa annually. With mounting evidence of adverse impacts to reproductive health resulting from urogenital schistosomiasis, including increased transmission of HIV, further research on prenatal disease epidemiology is warranted, with implications for maternal and fetal health. Between October 2016 and March 2017, we conducted a cross-sectional study examining the prevalence of urogenital schistosomiasis and its association with sexually transmitted infections (STIs) other than HIV among pregnant women visiting antenatal clinics in Kisantu health zone, Democratic Republic of Congo. An extensive sociodemographic and clinical survey was administered to consenting participants, with urine samples and vaginal swabs collected to deduce active schistosomiasis and STIs, respectively. In total, 17.4% of expectant mothers were infected with Schistosoma haematobium, 3.1% with Chlamydia trachomatis (CT), 1.4% with Neisseria gonorrhoeae (NG), and 14.6% with Trichomonas vaginalis (TV). Women infected with urogenital schistosomiasis were at significantly increased odds of harboring a CT, NG, or TV infection (adjusted odds ratio = 3.0, 95% CI: 1.5, 6.0), but reports of clinical symptoms were low, ranging from 17.2% of schistosomiasis to 30.8% of TV cases. Laboratory confirmation of schistosomiasis and STIs provided objective evidence of disease in a cohort with low symptomology where syndromic management may not suffice. Shedding light on local risk factors and associated coinfections of urogenital schistosomiasis can identify unique intervention opportunities for prenatal care in trematode-endemic regions and aid in reducing adverse pregnancy outcomes.

As of June 16, 2019, an Ebola virus disease (EVD) outbreak has led to 2136 reported cases in the northeastern region of the Democratic Republic of the Congo (DRC). As this outbreak continues to threaten the lives and livelihoods of people already suffering from civil strife and armed conflict, relatively simple mathematical models and their short-term predictions have the potential to inform Ebola response efforts in real time. We applied recently developed non-parametrically estimated Hawkes point processes to model the expected cumulative case count using daily case counts from May 3, 2018, to June 16, 2019, initially reported by the Ministry of Health of DRC and later confirmed in World Health Organization situation reports. We generated probabilistic estimates of the ongoing EVD outbreak in DRC extending both before and after June 16, 2019, and evaluated their accuracy by comparing forecasted vs. actual outbreak sizes, out-of-sample log-likelihood scores and the error per day in the median forecast. The median estimated outbreak sizes for the prospective thee-, six-, and nine-week projections made using data up to June 16, 2019, were, respectively, 2317 (95% PI: 2222, 2464); 2440 (95% PI: 2250, 2790); and 2544 (95% PI: 2273, 3205). The nine-week projection experienced some degradation with a daily error in the median forecast of 6.73 cases, while the six- and three-week projections were more reliable, with corresponding errors of 4.96 and 4.85 cases per day, respectively. Our findings suggest the Hawkes point process may serve as an easily-applied statistical model to predict EVD outbreak trajectories in near real-time to better inform decision-making and resource allocation during Ebola response efforts.

IntroductionAs of April 2019, the current Ebola virus disease (EVD) outbreak in the Democratic Republic of the Congo (DRC) is occurring in a longstanding conflict zone and has become the second largest EVD outbreak in history. It is suspected that after violent events occur, EVD transmission will increase; however, empirical studies to understand the impact of violence on transmission are lacking. Here, we use spatial and temporal trends of EVD case counts to compare transmission rates between health zones that have versus have not experienced recent violent events during the outbreak.MethodsWe collected daily EVD case counts from DRC Ministry of Health. A time-varying indicator of recent violence in each health zone was derived from events documented in the WHO situation reports. We used the Wallinga-Teunis technique to estimate the reproduction number R for each case by day per zone in the 2018-2019 outbreak. We fit an exponentially decaying curve to estimates of R overall and by health zone, for comparison to past outbreaks.ResultsAs of 16 April 2019, the mean overall R for the entire outbreak was 1.11. We found evidence of an increase in the estimated transmission rates in health zones with recently reported violent events versus those without (p = 0.008). The average R was estimated as between 0.61 and 0.86 in regions not affected by recent violent events, and between 1.01 and 1.07 in zones affected by violent events within the last 21 days, leading to an increase in R between 0.17 and 0.53. Within zones with recent violent events, the mean estimated quenching rate was lower than for all past outbreaks except the 2013-2016 West African outbreak.ConclusionThe difference in the estimated transmission rates between zones affected by recent violent events suggests that violent events are contributing to increased transmission and the ongoing nature of this outbreak.

Here we describe baseline validation studies and field performance of a research-use-only chemiluminescent multiplex serology panel for measles, mumps, rubella, and varicella-zoster virus used with dried blood spots in support of the 2013-2014 Democratic Republic of the Congo Demographic and Health Survey. Characterization of the panel using U.S. FDA-cleared commercial kits shows good concordance for measles, mumps, rubella, and varicella-zoster with average sensitivity across assays of 94.9% and an average specificity of 91.4%. As expected, performance versus available standards validated for plaque-reduction assays does not provide a 1:1 correspondence with international units and yet demonstrates excellent linearity (average Hill's slope = 1.02) and ∼4 logs of dynamic range. In addition, for the four assays, the multiplexed format allowed for inclusion of three positive and two negative controls for each sample. A prototype Dynex Multiplier chemiluminescent automated immunoassay instrument with a charge-coupled device camera provided a rugged and robust processing and data acquisition platform. Performance of a multiplex instrument for serological testing in a substantially resource-limited environment shows excellent reproducibility, minimal cross-reactivity, and a clear discrimination between specific assays and should be considered a viable option for future serosurveys.IMPORTANCE The critical evaluation of immunization programs is key to identifying areas of suboptimal vaccination coverage, monitoring activities, and aiding development of public health policy. For evaluation of vaccine effectiveness, direct antibody binding assay methods, including enzyme immunoassay, enzyme-linked fluorescence assays, and indirect immunofluorescence assay, are most commonly used for detection of IgG antibodies. However, despite their well-demonstrated, reliable performance, they can be labor-intensive and time-consuming and require separate assays for each individual marker. This necessitates increased sample volumes, processing time, and personnel, which may limit assessment to a few key targets in resource-limited settings, that is, low- and middle-income locations where funding for public health or general infrastructure that directly impacts public health is restricted, limiting access to equipment, infrastructure, and trained personnel. One solution is a multiplexed immunoassay, which allows for the detection of multiple analytes in a single reaction for increased efficiency and rapid surveillance of infectious diseases in limited-resource settings. Thus, the scope of the project precluded a full validation, and here we present abbreviated validation studies demonstrating adequate sensitivity, specificity, and reproducibility.

BackgroundAs of February 25, 2019, 875 cases of Ebola virus disease (EVD) were reported in North Kivu and Ituri Provinces, Democratic Republic of Congo. Since the beginning of October 2018, the outbreak has largely shifted into regions in which active armed conflict has occurred, and in which EVD cases and their contacts have been difficult for health workers to reach. We used available data on the current outbreak, with case-count time series from prior outbreaks, to project the short-term and long-term course of the outbreak.MethodsFor short- and long-term projections, we modeled Ebola virus transmission using a stochastic branching process that assumes gradually quenching transmission rates estimated from past EVD outbreaks, with outbreak trajectories conditioned on agreement with the course of the current outbreak, and with multiple levels of vaccination coverage. We used two regression models to estimate similar projection periods. Short- and long-term projections were estimated using negative binomial autoregression and Theil-Sen regression, respectively. We also used Gott's rule to estimate a baseline minimum-information projection. We then constructed an ensemble of forecasts to be compared and recorded for future evaluation against final outcomes. From August 20, 2018 to February 25, 2019, short-term model projections were validated against known case counts.ResultsDuring validation of short-term projections, from one week to four weeks, we found models consistently scored higher on shorter-term forecasts. Based on case counts as of February 25, the stochastic model projected a median case count of 933 cases by February 18 (95% prediction interval: 872-1054) and 955 cases by March 4 (95% prediction interval: 874-1105), while the auto-regression model projects median case counts of 889 (95% prediction interval: 876-933) and 898 (95% prediction interval: 877-983) cases for those dates, respectively. Projected median final counts range from 953 to 1,749. Although the outbreak is already larger than all past Ebola outbreaks other than the 2013-2016 outbreak of over 26,000 cases, our models do not project that it is likely to grow to that scale. The stochastic model estimates that vaccination coverage in this outbreak is lower than reported in its trial setting in Sierra Leone.ConclusionsOur projections are concentrated in a range up to about 300 cases beyond those already reported. While a catastrophic outbreak is not projected, it is not ruled out, and prevention and vigilance are warranted. Prospective validation of our models in real time allowed us to generate more accurate short-term forecasts, and this process may prove useful for future real-time short-term forecasting. We estimate that transmission rates are higher than would be seen under target levels of 62% coverage due to contact tracing and vaccination, and this model estimate may offer a surrogate indicator for the outbreak response challenges.

BackgroundClinical sequelae of Ebola virus disease (EVD) have not been described more than 3 years postoutbreak. We examined survivors and close contacts from the 1995 Ebola outbreak in Kikwit, Democratic Republic of Congo (DRC), and determined prevalence of abnormal neurological, cognitive, and psychological findings and their association with EVD survivorship.MethodsFrom August to September 2017, we conducted a cross-sectional study in Kikwit, DRC. Over 2 decades after the EVD outbreak, we recruited EVD survivors and close contacts from the outbreak to undergo physical examination and culturally adapted versions of the Folstein mini-mental status exam (MMSE) and Goldberg anxiety and depression scale (GADS). We estimated the strength of relationships between EVD survivorship and health outcomes using linear regression models by comparing survivors versus close contacts, adjusting for age, sex, educational level, marital status, and healthcare worker status.ResultsWe enrolled 20 EVD survivors and 187 close contacts. Among the 20 EVD survivors, 4 (20%) reported at least 1 abnormal neurological symptom, and 3 (15%) had an abnormal neurological examination. Among the 187 close contacts, 14 (11%) reported at least 1 abnormal neurologic symptom, and 9 (5%) had an abnormal neurological examination. EVD survivors had lower mean MMSE and higher mean GADS scores as compared to close contacts (MMSE: adjusted coefficient: -1.85; 95% confidence interval [CI]: -3.63, -0.07; GADS: adjusted coefficient: 3.91; 95% CI: 1.76, 6.04).ConclusionsEVD survivors can have lower cognitive scores and more symptoms of depression and anxiety than close contacts more than 2 decades after Ebola virus outbreaks.

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.

As of May 27, 2018, 6 suspected, 13 probable and 35 confirmed cases of Ebola virus disease (EVD) had been reported in Équateur Province, Democratic Republic of Congo. We used reported case counts and time series from prior outbreaks to estimate the total outbreak size and duration with and without vaccine use. We modeled Ebola virus transmission using a stochastic branching process model that included reproduction numbers from past Ebola outbreaks and a particle filtering method to generate a probabilistic projection of the outbreak size and duration conditioned on its reported trajectory to date; modeled using high (62%), low (44%), and zero (0%) estimates of vaccination coverage (after deployment). Additionally, we used the time series for 18 prior Ebola outbreaks from 1976 to 2016 to parameterize the Thiel-Sen regression model predicting the outbreak size from the number of observed cases from April 4 to May 27. We used these techniques on probable and confirmed case counts with and without inclusion of suspected cases. Probabilistic projections were scored against the actual outbreak size of 54 EVD cases, using a log-likelihood score. With the stochastic model, using high, low, and zero estimates of vaccination coverage, the median outbreak sizes for probable and confirmed cases were 82 cases (95% prediction interval [PI]: 55, 156), 104 cases (95% PI: 58, 271), and 213 cases (95% PI: 64, 1450), respectively. With the Thiel-Sen regression model, the median outbreak size was estimated to be 65.0 probable and confirmed cases (95% PI: 48.8, 119.7). Among our three mathematical models, the stochastic model with suspected cases and high vaccine coverage predicted total outbreak sizes closest to the true outcome. Relatively simple mathematical models updated in real time may inform outbreak response teams with projections of total outbreak size and duration.

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.

BackgroundMeasles 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).MethodsWe 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.ResultsUrban 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.ConclusionsResults 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.

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.

Evaluating the effectiveness of a surveillance system, and how it improves over time has significant implications for disease control and prevention. In the Democratic Republic of Congo (DRC), the Integrated Disease Surveillance and Response (IDSR) was implemented to estimate the burden of disease, monitor changes in disease occurrence, and inform resource allocation. For this effort we utilized national passive surveillance data from DRC's IDSR to explore reporting trends of human monkeypox (MPX) from 2001 to 2013. We obtained surveillance data on MPX cases occurring between January 2001 and December 2013 from the DRC Ministry of Health (MoH). Phases of the surveillance system, yearly trends in reporting and estimated incidence for MPX were analyzed using SAS v9.2 and Health Mapper. Between 2001 and 2013, three discrete surveillance phases were identified that described the evolution of the surveillance system. Overall, an increase in suspected MPX cases was reported, beyond what would be expected from simply an improved reporting system. When restricting the analysis to the "stable phase," national estimated incidence increased from 2.13 per 100,000 in 2008 to 2.84 per 100,000 in 2013. The reported increase in MPX, based on an evolving surveillance system, is likely to be a true increase in disease occurrence rather than simply improvements to the surveillance system. Further analyses should provide critical information for improved prevention and control strategies and highlight areas of improvement for future data collection efforts.

Recent enhanced monkeypox (MPX) surveillance in the Democratic Republic of Congo, where MPX is endemic, has uncovered multiple cases of MPX and varicella zoster virus (VZV) coinfections. The purpose of this study was to verify if coinfections occur and to characterize the clinical nature of these cases. Clinical, epidemiological, and laboratory results were used to investigate MPX/VZV coinfections. A coinfection was defined as a patient with at least one Orthopoxvirus/MPX-positive sample and at least one VZV-positive sample within the same disease event. Between September 2009 and April 2014, 134 of the 1,107 (12.1%) suspected MPX cases were confirmed as MPX/VZV coinfections. Coinfections were more likely to report symptoms than VZV-alone cases and less likely than MPX-alone cases. Significantly higher lesion counts were observed for coinfection cases than for VZV-alone but less than MPX-alone cases. Discernible differences in symptom and rash severity were detected for coinfection cases compared with those with MPX or VZV alone. Findings indicate infection with both MPX and VZV could modulate infection severity. Collection of multiple lesion samples allows for the opportunity to detect coinfections. As this program continues, it will be important to continue these procedures to assess variations in the proportion of coinfected cases over time.