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Background This study aimed to evaluate the feasibility and acceptability of engaging unhoused peer ambassadors (PAs) in coronavirus disease 2019 (COVID-19) vaccination efforts to reach people experiencing unsheltered homelessness in Los Angeles County. Methods From August to December 2021, vaccinated PAs aged ≥18 years who could provide informed consent were recruited during vaccination events for same-day participation. Events were held at encampments, service providers (eg, housing agencies, food lines, and mobile showers), and roving locations around Los Angeles. PAs were asked to join outreach alongside community health workers and shared their experience getting vaccinated, receiving a $25 gift card for each hour they participated. Postevent surveys evaluated how many PAs enrolled and how long they participated. In October 2021, we added a preliminary effectiveness evaluation of how many additional vaccinations were attributable to PAs. Staff who enrolled the PAs estimated the number of additional people vaccinated because of talking with the PA. Results A total of 117 PAs were enrolled at 103 events, participating for an average of 2 hours. At events with the effectiveness evaluation, 197 additional people were vaccinated over 167 PA hours ($21.19 gift card cost per additional person vaccinated), accounting for >25% of all vaccines given at these events. Discussion Recruiting same-day unhoused PAs is a feasible, acceptable, and preliminarily effective technique to increase COVID-19 vaccination in unsheltered settings. The findings can inform delivery of other health services for people experiencing homelessness.

Hesitancy to receive the COVID-19 vaccine among healthcare workers (HCWs) in low-resource settings, such as the Democratic Republic of the Congo (DRC), is a major global health challenge. This study identifies changes in willingness to receive vaccination among 588 HCWs in the DRC and reported influences on COVID-19 vaccination intentions. Up to 25 repeated measures were collected from participants between August 2020 to August 2021. Among the overall cohort, between August 2020 and mid-March 2021, the proportion of HCWs in each period of data collection reporting COVID-19 vaccine hesitancy ranged from 8.6% (95% CI: 5.97, 11.24) to 24.3% (95% CI: 20.12, 28.55). By early April 2021, the proportion reporting hesitancy more than doubled (52.0%; 95% CI: 46.22, 57.83). While hesitancy in the cohort began to decline by late-June 2021, 22.6% (95% CI: 18.05, 27.18) respondents indicated hesitancy in late-August 2021 which remains greater than the proportion of hesitancy at any time prior to early-March 2021. Patterns in reported influences on COVID-19 vaccination were varied with the proportion reporting some influences (e.g., no serious side effects, country of vaccine production) remaining stable throughout the year and other factors (e.g., recommendation of Ministry of Health, ease of vaccination) falling in popularity among respondents. Agreement that the national vaccination schedule should be followed apart from the COVID-19 vaccine remained high among respondents throughout the study period. This study shows that, among a cohort of HCWs in the DRC who have likely been influenced by regional, national, and global factors, COVID-19 vaccine hesitancy has fluctuated during the pandemic and should not be treated as a static factor. Additional research to determine which factors most influence HCWs' willingness to receive the COVID-19 vaccine offers opportunities to reduce vaccine hesitancy among this important population through tailored public health messaging.

Since the establishment of the Global Alignment of Immunization Safety Assessment in pregnancy (GAIA) case definitions in 2015, there has been an urgent need for field validation of pharmacovigilance feasibility in low- and middle-income countries. In this study, we assess the availability and quality of archival medical records at ten randomly selected high-traffic maternity wards in Kinshasa province, Democratic Republic of Congo (DRC).A retrospective cohort of mother-child pairs was established from all recorded births taking place at study sites between July 1, 2019 to February 28, 2020 through digitization of medical records. Adverse birth outcomes and maternal vaccination status, where available and linkable, were defined according to GAIA. Basic demographic information on mothers and newborns was also tabulated; birth outcomes were assessed for both intra-site prevalence and a pooled prevalence.A total of 7,697 mother-newborn pair records were extracted, with 37% of infants screening positive as cases of adverse outcomes. Maternal vaccination information was linkable to 67% of those cases. In total, 51% of stillbirths, 98% of preterm births, 100% of low birthweight infants, 90% of small for gestational age infants, 100% of microcephalic infants, and 0% of neonatal bloodstream infections were classifiable according to GAIA standards following initial screening. Forty percent of case mothers had some indication of tetanus vaccination prior to delivery in their medical records, but only 26% of case mothers met some level of GAIA definition for maternal vaccination during the pregnancy of interest.Archival birth records from delivery centers can be feasibly utilized to screen for stillbirth and maternal tetanus vaccination, and to accurately classify preterm birth, low birthweight, small for gestational age, and congenital microcephaly. Assessment of other neonatal outcomes were limited by inconsistent postpartum infant follow-up and records keeping.

BackgroundThe immunization system in the Democratic Republic of the Congo faces many challenges, including persistent large-scale outbreaks of polio, measles, and yellow fever; a large number of unvaccinated children for all antigens; minimal and delayed funding; and poor use of immunization data at all levels. In response, the Expanded Programme on Immunization within the Ministry of Health (MOH) collaborated with global partners to develop a revitalization strategy for the routine immunization (RI) system called the Mashako Plan.Mashako plan design and developmentThe Mashako Plan aimed to increase full immunization coverage in children aged 12-23 months by 15 percentage points overall in 9 of 26 provinces within 18 months of implementation. In 2018, we conducted a diagnostic review and identified gaps in coordination, service delivery, vaccine availability, real-time monitoring, and evaluation as key areas for intervention to improve the RI system. Five interventions were then implemented in the 9 identified provinces.DiscussionAccording to the 2020 vaccine coverage survey, full immunization coverage increased to 56.4%, and Penta3/DTP3 increased to 71.1% across the Mashako Plan provinces; the initial objective of the plan was reached and additional improvements in key service delivery indicators had been achieved. Increases in immunization sessions held per month, national stock of pentavalent vaccine, and supervision visits conducted demonstrate that simple, measurable changes at all levels can quickly improve immunization systems. Despite short-term improvements in all indicators tracked, challenges remain in vaccine availability, regular funding of immunization activities, systematic provision of immunization services, and ensuring long-term sustainability.ConclusionsStrong commitment of MOH staff combined with partner involvement enabled the improvement of the entire system. A simple set of interventions and indicators focused the energy of managers on discrete actions to improve outcomes. Further exploration of the results is necessary to determine the long-term impact and generate all-level engagement for sustainable success in all provinces.

[This corrects the article DOI: 10.1371/journal.pntd.0008923.].

Background Little research has been conducted on the impact of the coronavirus disease 2019 (COVID-19) pandemic on either birth outcomes or the ability of archival medical records to accurately capture these outcomes. Our study objective is thus to compare the prevalence of preterm birth, stillbirth, low birth weight (LBW), small for gestational age (SGA), congenital microcephaly, and neonatal bloodstream infection (NBSI) before and during the first wave of the COVID-19 pandemic in Kinshasa, Democratic Republic of Congo (DRC). Methods We conducted a facility-based retrospective cohort study in which identified cases of birth outcomes were tabulated at initial screening and subcategorized according to level of diagnostic certainty using Global Alignment of Immunization Safety Assessment in pregnancy (GAIA) definitions. Documentation of any birth complications, delivery type, and maternal vaccination history were also evaluated. The prevalence of each birth outcome was compared in the pre-COVID-19 (i.e., July 2019 to February 2020) and intra-COVID-19 (i.e., March to August 2020) periods via two-sample z-test for equality of proportions. Results In total, 14,300 birth records were abstracted. Adverse birth outcomes were identified among 22.0% and 14.3% of pregnancies in the pre-COVID-19 and intra-COVID-19 periods, respectively. For stillbirth, LBW, SGA, microcephaly, and NBSI, prevalence estimates were similar across study periods. However, the prevalence of preterm birth in the intra-COVID-19 period was significantly lower than that reported during the pre-COVID-19 period (8.6% vs. 11.5%, p Conclusion This study succeeded in providing prevalence estimates for key adverse birth outcomes using GAIA criteria during the COVID-19 pandemic in Kinshasa, DRC. Furthermore, our study adds crucial real-world data to the literature surrounding the impact of the COVID-19 pandemic on maternal and neonatal services and outcomes in Africa.

Background In 2018, the Democratic Republic of the Congo (DRC) declared its 9th and 10th Zaire ebolavirus (EBOV) outbreaks, in the Equateur province (end: July 2018), and in the eastern provinces including North Kivu (end: June 2020). The DRC Ministry of Health deployed the rVSV-vectored glycoprotein (VSV-EBOV) vaccine in response during both outbreaks. Methods A cohort of vaccinated and unvaccinated individuals from the Equateur province were enrolled and followed prospectively for 6 months. Among participants included in this analysis, 505 were vaccinated and 1,418 were unvaccinated. Differences in transmission behaviors pre- and post- outbreak were identified, along with associations between behaviors and vaccination. Results There was an overall increase in the proportion of both unvaccinated and vaccinated individuals in Mbandaka who participated in risky activities post-outbreak. Travel outside of the province pre-outbreak was associated with vaccination. Post-outbreak, vaccinated individuals were less likely to participate in funeral traditions than unvaccinated individuals. Conclusion A net increase in activities considered high risk was observed in both groups despite significant efforts to inform the population of risky behaviors. The absence of a reduction in transmission behavior post-outbreak should be considered for improving future behavior change campaigns in order to prevent recurrent outbreaks.

[This corrects the article DOI: 10.1016/j.jvacx.2021.100127.].

Despite the robust immunogenicity of SARS-CoV-2 mRNA vaccines, emerging data have revealed enhanced neutralizing antibody and T cell cross-reactivity among individuals that previously experienced COVID-19, pointing to a hybrid immune advantage with infection-associated immune priming. Beyond neutralizing antibodies and T cell immunity, mounting data point to a potential role for additional antibody effector functions, including opsinophagocytic activity, in the resolution of symptomatic COVID-19. Whether hybrid immunity modifies the Fc-effector profile of the mRNA vaccine-induced immune response remains incompletely understood. Thus, here we profiled the SARS-CoV-2 specific humoral immune response in a group of individuals with and without prior COVID-19. As expected, hybrid Spike-specific antibody titers were enhanced following the primary dose of the mRNA vaccine but were similar to those achieved by naive vaccinees after the second mRNA vaccine dose. Conversely, Spike-specific vaccine-induced Fc-receptor binding antibody levels were higher after the primary immunization in individuals with prior COVID-19 and remained higher following the second dose compared to those in naive individuals, suggestive of a selective improvement in the quality, rather than the quantity, of the hybrid humoral immune response. Thus, while the magnitude of antibody titers alone may suggest that any two antigen exposures-either hybrid immunity or two doses of vaccine alone-represent a comparable prime/boost immunologic education, we find that hybrid immunity offers a qualitatively improved antibody response able to better leverage Fc-effector functions against conserved regions of the virus. IMPORTANCE Recent data indicates improved immunity to SARS-CoV-2 in individuals who experience a combination of two mRNA vaccine doses and infection, "hybrid immunity," compared to individuals who receive vaccination or experience infection alone. While previous infection accelerates the vaccine-induced immune response following the first dose of mRNA vaccination, subsequent doses demonstrate negligible increases in antibody titers or T cell immunity. Here, using systems serology, we observed a unique antibody profile induced by hybrid immunity, marked by the unique induction of robust Fc-recruiting antibodies directed at the conserved region of the viral Spike antigen, the S2-domain, induced at lower levels in individuals who only received mRNA vaccination. Thus, hybrid immunity clearly redirects vaccine-induced immunodominance, resulting in the induction of a robust functional humoral immune response to the most highly conserved region of the SARS-CoV-2 Spike antigen, which may be key to protection against existing and emerging variants of concern. Thus, next-generation vaccines able to mimic hybrid immunity and drive a balanced response to conserved regions of the Spike antigen may confer enhanced protection against disease.

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.

Although multiple antigenically distinct ebolavirus species can cause human disease, previous serosurveys focused on only Zaire ebolavirus (EBOV). Thus, the extent of reactivity or exposure to other ebolaviruses, and which sociodemographic factors are linked to this seroreactivity, are unclear. We conducted a serosurvey of 539 healthcare workers (HCW) in Mbandaka, Democratic Republic of the Congo, using ELISA-based analysis of serum IgG against EBOV, Sudan ebolavirus (SUDV) and Bundibugyo ebolavirus (BDBV) glycoproteins (GP). We compared seroreactivity to risk factors for viral exposure using univariate and multivariable logistic regression. Seroreactivity against different GPs ranged from 2.2–4.6%. Samples from six individuals reacted to all three species of ebolavirus and 27 samples showed a species-specific IgG response. We find that community health volunteers are more likely to be seroreactive against each antigen than nurses, and in general, that HCWs with indirect patient contact have higher anti-EBOV GP IgG levels than those with direct contact. Seroreactivity against ebolavirus GP may be associated with positions that offer less occupational training and access to PPE. Those individuals with broadly reactive responses may have had multiple ebolavirus exposures or developed cross-reactive antibodies. In contrast, those individuals with species-specific BDBV or SUDV GP seroreactivity may have been exposed to an ebolavirus not previously known to circulate in the region.

As of June 11, 2020, the Democratic Republic of the Congo (DRC) has reported 4,258 COVID-19 cases with 90 deaths. With other African countries, the DRC faces the challenge of striking a balance between easing public health lockdown measures to curtail the spread of SARS-CoV-2 and minimizing both economic hardships for large sectors of the population and negative impacts on health services for other infectious and noninfectious diseases. The DRC recently controlled its tenth Ebola virus disease (EVD) outbreak, but COVID-19 and a new EVD outbreak beginning on June 1, 2020 in the northwest Équateur Province have added an additional burden to health services. Although the epidemiology and transmission of EVD and COVID-19 differ, leveraging the public health infrastructures and experiences from coordinating the EVD response to guide the public health response to COVID-19 is critical. Building on the DRC’s 40 years of experience with 10 previous EVD outbreaks, we highlight the DRC’s multi-sectoral public health approach to COVID-19, which includes community-based screening, testing, contact-tracing, risk communication, community engagement, and case management. We also highlight remaining challenges and discuss the way forward for achieving control of both COVID-19 and EVD in the DRC.

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.

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.

Despite more than 300,000 rVSVΔG-ZEBOV-glycoprotein (GP) vaccine doses having been administered during Ebola virus disease (EVD) outbreaks in the Democratic Republic of the Congo (DRC) between 2018 and 2020, seroepidemiologic studies of vaccinated Congolese populations are lacking. This study examines the antibody response at 21 d and 6 mo postvaccination after single-dose rVSVΔG-ZEBOV-GP vaccination among EVD-exposed and potentially exposed populations in the DRC. We conducted a longitudinal cohort study of 608 rVSVΔG-ZEBOV-GP-vaccinated individuals during an EVD outbreak in North Kivu Province, DRC. Participants provided questionnaires and blood samples at three study visits (day 0, visit 1; day 21, visit 2; and month 6, visit 3). Anti-GP immunoglobulin G (IgG) antibody titers were measured in serum by the Filovirus Animal Nonclinical Group anti-Ebola virus GP IgG enzyme-linked immunosorbent assay. Antibody response was defined as an antibody titer that had increased fourfold from visit 1 to visit 2 and was above four times the lower limit of quantification at visit 2; antibody persistence was defined as a similar increase from visit 1 to visit 3. We then examined demographics for associations with follow-up antibody titers using generalized linear mixed models. A majority of the sample, 87.2%, had an antibody response at visit 2, and 95.6% demonstrated antibody persistence at visit 3. Being female and of young age was predictive of a higher antibody titer postvaccination. Antibody response and persistence after Ebola vaccination was robust in this cohort, confirming findings from outside of the DRC.

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.

Background Tetanus 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. Methods In 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. Results Overall, 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. Conclusions Our 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.

Studies of two SARS-CoV-2 mRNA vaccines suggested that they yield ∼95% protection from symptomatic infection at least short-term, but important clinical questions remain. It is unclear how vaccine-induced antibody levels quantitatively compare to the wide spectrum induced by natural SARS-CoV-2 infection. Vaccine response kinetics and magnitudes in persons with prior COVID-19 compared to virus-naı̈ve persons are not well-defined. The relative stability of vaccine-induced versus infection-induced antibody levels is unclear. We addressed these issues with longitudinal assessments of vaccinees with and without prior SARS-CoV-2 infection using quantitative enzyme-linked immunosorbent assay (ELISA) of anti-RBD antibodies. SARS-CoV-2-naı̈ve individuals achieved levels similar to mild natural infection after the first vaccination; a second dose generated levels approaching severe natural infection. In persons with prior COVID-19, one dose boosted levels to the high end of severe natural infection even in those who never had robust responses from infection, increasing no further after the second dose. Antiviral neutralizing assessments using a spike-pseudovirus assay revealed that virus-naı̈ve vaccinees did not develop physiologic neutralizing potency until the second dose, while previously infected persons exhibited maximal neutralization after one dose. Finally, antibodies from vaccination waned similarly to natural infection, resulting in an average of ∼90% loss within 90 days. In summary, our findings suggest that two doses are important for quantity and quality of humoral immunity in SARS-CoV-2-naı̈ve persons, while a single dose has maximal effects in those with past infection. Antibodies from vaccination wane with kinetics very similar to that seen after mild natural infection; booster vaccinations will likely be required.

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.

We conducted a serologic survey of 2,430 serum samples collected during 1997-2012 for various studies to determine the prevalence of the hemorrhagic fever virus Ebola virus (EBOV) in equatorial Africa. We screened serum samples for neutralizing antibodies by using a pseudotype microneutralization assay and a newly developed luciferase immunoprecipitation system assay. Specimens seroreactive for EBOV were confirmed by using an ELISA. Our results suggest a serologic prevalence of 2%-3.5% in the Republic of the Congo and the Democratic Republic of the Congo, which have reported outbreaks of infection with EBOV. In addition we detected a seroprevalence of 1.3% in southern Cameroon, which indicated a low risk for exposure in this region.

Background Sentiments of vaccine hesitancy and distrust in public health institutions have complicated the government-led coronavirus disease 2019 (COVID-19) vaccine control strategy in the United States. As the first to receive the vaccine, COVID-19 vaccine attitudes among frontline workers are consequential for COVID-19 control and public opinion of the vaccine. Methods In this study, we used a repeated cross-sectional survey administered at 3 time points between 24 September 2020 and 6 February 2021 to a cohort of employees of the University of California, Los Angeles Health and the Los Angeles County Fire Department. The primary outcome of interest was COVID-19 vaccination intent and vaccine uptake. Results Confidence in COVID-19 vaccines and vaccine uptake rose significantly over time. At survey 1, confidence in vaccine protection was 46.4% among healthcare workers (HCWs) and 34.6% among first responders (FRs); by survey 3, this had risen to 90.0% and 75.7%, respectively. At survey 1, about one-third of participants intended to receive a vaccine as soon as possible. By survey 3, 96.0% of HCWs and 87.5% of FRs had received a COVID-19 vaccine. Conclusions Attitudes toward vaccine uptake increased over the study period, likely a result of increased public confidence in COVID-19 vaccines, targeted communications, a COVID-19 winter surge in Los Angeles County, and ease of access from employer-sponsored vaccine distribution.

Predictions of COVID-19 case growth and mortality are critical to the decisions of political leaders, businesses, and individuals grappling with the pandemic. This predictive task is challenging due to the novelty of the virus, limited data, and dynamic political and societal responses. We embed a Bayesian time series model and a random forest algorithm within an epidemiological compartmental model for empirically grounded COVID-19 predictions. The Bayesian case model fits a location-specific curve to the velocity (first derivative) of the log transformed cumulative case count, borrowing strength across geographic locations and incorporating prior information to obtain a posterior distribution for case trajectories. The compartmental model uses this distribution and predicts deaths using a random forest algorithm trained on COVID-19 data and population-level characteristics, yielding daily projections and interval estimates for cases and deaths in U.S. states. We evaluated the model by training it on progressively longer periods of the pandemic and computing its predictive accuracy over 21-day forecasts. The substantial variation in predicted trajectories and associated uncertainty between states is illustrated by comparing three unique locations: New York, Colorado, and West Virginia. The sophistication and accuracy of this COVID-19 model offer reliable predictions and uncertainty estimates for the current trajectory of the pandemic in the U.S. and provide a platform for future predictions as shifting political and societal responses alter its course., Author summary COVID-19 models can be roughly classified as mathematical models that simulate disease within a population, including epidemiological compartmental models, or statistical curve-fitting models that fit a function to observed data and extrapolate forward into the future. Bridging this divide, we combine the strengths of curve-fitting statistical models and the structure of epidemiological models, by embedding a Bayesian velocity model and a machine learning algorithm (random forest) into the framework of a compartmental model. Fusing these models together exploits the particular strengths of each to glean as much information as possible from the currently available data. We identify the velocity of log cumulative cases as an excellent target for modeling and extrapolating COVID-19 case trajectories. We empirically evaluate the predictive performance of the model and provide predicted trajectories with credible intervals for cumulative confirmed case count, active confirmed infections and COVID-19 deaths for each of the 50 U.S. states. Combining sophisticated data analytic methods with proven epidemiological models offers an empirically grounded strategy for making realistic predictions and quantifying their uncertainty. These predictions indicate substantial variation in the COVID-19 trajectories of U.S. states.

Two mRNA vaccines (BNT162b2 and mRNA-1273) against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) are globally authorized as a two-dose regimen. Understanding the magnitude and duration of protective immune responses is vital to curbing the pandemic. We enrolled 461 high-risk health services workers at the University of California, Los Angeles (UCLA) and first responders in the Los Angeles County Fire Department (LACoFD) to assess the humoral responses in previously infected (PI) and infection naïve (NPI) individuals to mRNA-based vaccines (BNT162b2/Pfizer- BioNTech or mRNA-1273/Moderna). A chemiluminescent microparticle immunoassay was used to detect antibodies against SARS-CoV-2 Spike in vaccinees prior to (n = 21) and following each vaccine dose (n = 246 following dose 1 and n = 315 following dose 2), and at days 31–60 (n = 110) and 61–90 (n = 190) following completion of the 2-dose series. Both vaccines induced robust antibody responses in all immunocompetent individuals. Previously infected individuals achieved higher median peak titers (p = 0.002) and had a slower rate of decay (p = 0.047) than infection-naïve individuals. mRNA-1273 vaccinated infection-naïve individuals demonstrated modestly higher titers following each dose (p = 0.005 and p = 0.029, respectively) and slower rates of antibody decay (p = 0.003) than those who received BNT162b2. A subset of previously infected individuals (25%) required both doses in order to reach peak antibody titers. The biologic significance of the differences between previously infected individuals and between the mRNA-1273 and BNT162b2 vaccines remains uncertain, but may have important implications for booster strategies.

Background Our understanding of the different effects of targeted versus nontargeted violence on Ebola virus (EBOV) transmission in Democratic Republic of the Congo (DRC) is limited. Methods We 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. Results Average 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. Conclusions Ebola-targeted violence, primarily driven by civilian-induced events, had the largest impact on EBOV transmission., A time-series study of the 2018–2020 Ebola virus disease outbreak in the Democratic Republic of the Congo found both Ebola-targeted and untargeted violence increased transmission, though targeted violence, primarily driven by civilian-involved events, had the largest impact.

The Democratic Republic of the Congo (DRC) has a history of nonhuman primate (NHP) consumption and exposure to simian retroviruses yet little is known about the extent of zoonotic simian retroviral infections in DRC. We examined the prevalence of human T-lymphotropic viruses (HTLV), a retrovirus group of simian origin, in a large population of persons with frequent NHP exposures and a history of simian foamy virus infection. We screened plasma from 3,051 persons living in rural villages in central DRC using HTLV EIA and western blot (WB). PCR amplification of HTLV tax and LTR sequences from buffy coat DNA was used to confirm infection and to measure proviral loads (pVLs). We used phylogenetic analyses of LTR sequences to infer evolutionary histories and potential transmission clusters. Questionnaire data was analyzed in conjunction with serological and molecular data. A relatively high proportion of the study population (5.4%, n = 165) were WB seropositive: 128 HTLV-1-like, 3 HTLV-2-like, and 34 HTLV-positive but untypeable profiles. 85 persons had HTLV indeterminate WB profiles. HTLV seroreactivity was higher in females, wives, heads of households, and increased with age. HTLV-1 LTR sequences from 109 persons clustered strongly with HTLV-1 and STLV-1 subtype B from humans and simians from DRC, with most sequences more closely related to STLV-1 from Allenopithecus nigroviridis (Allen’s swamp monkey). While 18 potential transmission clusters were identified, most were in different households, villages, and health zones. Three HTLV-1-infected persons were co-infected with simian foamy virus. The mean and median percentage of HTLV-1 pVLs were 5.72% and 1.53%, respectively, but were not associated with age, NHP exposure, village, or gender. We document high HTLV prevalence in DRC likely originating from STLV-1. We demonstrate regional spread of HTLV-1 in DRC with pVLs reported to be associated with HTLV disease, supporting local and national public health measures to prevent spread and morbidity., Author summary HTLV-1 is a human retrovirus of zoonotic simian origin that has spread globally causing inflammatory and carcinogenic disease. We previously showed that persons with high nonhuman primate (NHP) exposure in the Democratic Republic of the Congo (DRC) can be infected with another simian retrovirus, simian foamy virus (SFV), suggesting they are also at risk for infection with STLV-1. We conducted follow-up analysis of the same persons from rural villages of central DRC to determine exposure and transmission risks for STLV-1 and HTLV-1 infection. Most persons, especially women, reported high levels of NHP exposure. We identified possible introduction and spread of STLV-1 from a local monkey species across households, villages, and health zones in DRC. Most persons had HTLV-1 levels above those reported in previous studies for persons with disease. Our findings reveal that coordinated public health strategies are needed at both local and national levels to prevent further spread and morbidity of HTLV-1.

Smallpox eradication, coordinated by the WHO and certified 40 years ago, led to the cessation of routine smallpox vaccination in most countries. It is estimated that over 70% of the world's population is no longer protected against smallpox, and through cross-immunity, to closely related orthopox viruses such as monkeypox. Monkeypox is now a re-emerging disease. Monkeypox is endemic in as yet unconfirmed animal reservoirs in sub-Saharan Africa, while its human epidemiology appears to be changing. Monkeypox in small animals imported from Ghana as exotic pets was at the origin of an outbreak of human monkeypox in the USA in 2003. Travellers infected in Nigeria were at the origin of monkeypox cases in the UK in 2018 and 2019, Israel in 2018 and Singapore in2019. Together with sporadic reports of human infections with other orthopox viruses, these facts invite speculation that emergent or re-emergent human monkeypox might fill the epidemiological niche vacated by smallpox. An ad-hoc and unofficial group of interested experts met to consider these issues at Chatham House, London in June 2019, in order to review available data and identify monkeypox-related research gaps. Gaps identified by the experts included:The experts further agreed on the need for a better understanding of the genomic evolution and changing epidemiology of orthopox viruses, the usefulness of in-field genomic diagnostics, and the best disease control strategies, including the possibility of vaccination with new generation non-replicating smallpox vaccines and treatment with recently developed antivirals.

Background Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV) infections during pregnancy are linked with adverse birth outcomes. However, few countries have prenatal CT, NG, or TV screening programs. In this study, we aimed to evaluate the acceptability and feasibility of CT, NG, and TV screening and treatment among pregnant women across 6 low- to middle-income countries. Methods A total of 1817 pregnant women were screened for CT, NG, and TV in Botswana, the Democratic Republic of Congo, Haiti, South Africa, and Vietnam. An additional 640 pregnant women were screened for CT in Peru. Screening occurred between December 2012 and October 2017. Acceptability of screening was evaluated at each site as the proportion of eligible women who agreed to participate in screening. Feasibility of treatment was calculated as the proportion of women who tested positive that received treatment. Results Acceptability of screening and feasibility of treatment was high across all 6 sites. Acceptability of screening ranged from 85% to 99%, and feasibility of treatment ranged from 91% to 100%. Discussion The high acceptability and feasibility of screening and treatment of CT, NG, and TV among pregnant women supports further research to evaluate the cost-effectiveness of prenatal CT, NG, and TV screening programs.

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.

Highlights • Serosurvey data suggest R0 values for rubella in the DRC on the range 3 to 8. • Supplementary immunization activities provide multi-decade reduction in burden. • Post-vaccine introduction, burden will likely be concentrated in outbreaks., Background Rubella vaccine has yet to be introduced into the national immunization schedule of the Democratic Republic of the Congo (DRC); the current burden of congenital rubella syndrome (CRS) is unknown and likely to be high. An important consideration prior to introducing rubella containing vaccine (RCV) is the potential inverse relationship between RCV coverage and CRS incidence. Increasing RCV coverage will also increase in the average age of infection. Cumulative infections across all age groups will decrease, but the number of infections in age groups vulnerable to CRS may increase. Methods Rubella transmission dynamics in the DRC were simulated using a stochastic agent-based model of transmission. Input parameter values for known properties, demographic variables, and interventions were fixed; infectivity was inferred from seropositivity profiles in survey data. Results Our simulations of RCV introduction for the DRC demonstrate that an increase in CRS burden is unlikely. Continued endemic transmission is only plausible when routine immunization coverage is less than 40% and follow-up supplemental immunization activities have poor coverage for decades. Conclusion Increased vaccination coverage tends to increase the annual variability of CRS burden. Simulations examining low vaccination coverage and high mean CRS burden are outbreak prone, with multiple years of reduced burden followed by acute outbreaks. These outcomes contrast simulations with no vaccination coverage and high mean CRS burden, which have more consistent burden from year to year.

While investigating a signal of adaptive evolution in humans at the gene LARGE, we encountered an intriguing finding by Dr. Stefan Kunz that the gene plays a critical role in Lassa virus binding and entry. This led us to pursue field work to test our hypothesis that natural selection acting on LARGE—detected in the Yoruba population of Nigeria—conferred resistance to Lassa Fever in some West African populations. As we delved further, we conjectured that the “emerging” nature of recently discovered diseases like Lassa fever is related to a newfound capacity for detection, rather than a novel viral presence, and that humans have in fact been exposed to the viruses that cause such diseases for much longer than previously suspected. Dr. Stefan Kunz’s critical efforts not only laid the groundwork for this discovery, but also inspired and catalyzed a series of events that birthed Sentinel, an ambitious and large-scale pandemic prevention effort in West Africa. Sentinel aims to detect and characterize deadly pathogens before they spread across the globe, through implementation of its three fundamental pillars: Detect, Connect, and Empower. More specifically, Sentinel is designed to detect known and novel infections rapidly, connect and share information in real time to identify emerging threats, and empower the public health community to improve pandemic preparedness and response anywhere in the world. We are proud to dedicate this work to Stefan Kunz, and eagerly invite new collaborators, experts, and others to join us in our efforts.

Background Ebola 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. Methodology Data 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. Conclusions This 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., Author summary Ebola virus (EBOV) is spread through exposure to infected bodily fluids of a human or animal. While EBOV can lead to a severe disease, Ebola Virus Disease (EVD), it is possible for individuals to have anti-EBOV antibodies without ever getting sick with EVD. Seroreactivity (the detection of antigen-specific antibodies) suggests that that person has been exposed to EBOV or a similar virus in the past. Our study looked for seroreactive individuals who have never received an EVD diagnosis in four sites across the Democratic Republic of the Congo. Then we checked if animal exposures previously linked to EVD were more common among seroreactive individuals than non-seroreactive individuals. Among respondents from all four sites, 113 (8.3%) were seroreactive to EBOV. Additionally, contact with bats, rodents, and eating non-human primate meat were associated with seroreactivity, indicating these factors may be predictors of undocumented EBOV exposure events. These findings show that some EVD risk factors may be associated with EBOV seroreactivity without EVD diagnosis. Future research is needed to clarify the relationships between zoonotic exposures, seroreactivity, asymptomatic infection, and EVD.

Coronaviruses play an important role as pathogens of humans and animals, and the emergence of epidemics like SARS, MERS and COVID-19 is closely linked to zoonotic transmission events primarily from wild animals. Bats have been found to be an important source of coronaviruses with some of them having the potential to infect humans, with other animals serving as intermediate or alternate hosts or reservoirs. Host diversity may be an important contributor to viral diversity and thus the potential for zoonotic events. To date, limited research has been done in Africa on this topic, in particular in the Congo Basin despite frequent contact between humans and wildlife in this region. We sampled and, using consensus coronavirus PCR-primers, tested 3,561 wild animals for coronavirus RNA. The focus was on bats (38%), rodents (38%), and primates (23%) that posed an elevated risk for contact with people, and we found coronavirus RNA in 121 animals, of which all but two were bats. Depending on the taxonomic family, bats were significantly more likely to be coronavirus RNA-positive when sampled either in the wet (Pteropodidae and Rhinolophidae) or dry season (Hipposideridae, Miniopteridae, Molossidae, and Vespertilionidae). The detected RNA sequences correspond to 15 alpha- and 6 betacoronaviruses, with some of them being very similar (>95% nucleotide identities) to known coronaviruses and others being more unique and potentially representing novel viruses. In seven of the bats, we detected RNA most closely related to sequences of the human common cold coronaviruses 229E or NL63 (>80% nucleotide identities). The findings highlight the potential for coronavirus spillover, especially in regions with a high diversity of bats and close human contact, and reinforces the need for ongoing surveillance.

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.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.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).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.

Objective 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. Methods 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. Results 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. Conclusions 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.

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. Keywords: Ebola virus disease, Hawkes point process, Mathematical modeling, Democratic Republic of Congo, Compartmental models

Background As 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. Methods For 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. Results During 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. Conclusions Our 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., Author summary As 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 been reported, and in which EVD cases and their contacts have been difficult for health workers to reach. We used an ensemble of models to estimate EVD transmission rates and to forecast the short- and long-term course of the outbreak. Our models project that a final size of roughly up to 300 additional cases is most likely, and estimate that transmission rates are higher than would be seen under optimal levels of contact tracing and vaccination. While a catastrophic outbreak is not projected, is it not ruled out, and prevention and vigilance are warranted.

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., 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.

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.

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.

Different species of adenoviruses (AdVs) infect humans and animals and are known for their role as pathogens, especially in humans, with animals, primarily rodents, often serving as model systems. However, although we know over 100 types of human AdVs, we know comparatively little about the diversity of animal AdVs. Due to the fact that rodents are the most diverse family of mammals and a standard model system for human disease, we set out to sample African rodents native to the Democratic Republic of the Congo and test them for AdV DNA using a semi-nested consensus PCR. A total of 775 animals were tested, and viral DNA was detected in four of them. The AdV DNA found belongs to three different AdVs, all being closely related to murine adenovirus 2 (MAdV-2). Considering the genetic differences of the amplicon were 9%, 11% and 19% from MAdV-2 and at least 10% from each other, they seem to belong to up to three different novel types within the Murine mastadenovirus B species. This evidence of genetic diversity highlights the opportunities to isolate and study additional AdVs that infect rodents as models for AdV biology and pathology. Keywords: Adenovirus, Africa, Murine adenovirus 2, PCR, Rodent

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.

Background Measles continues to be a leading cause of vaccine-preventable disease mortality among children under five despite a safe and efficacious vaccine being readily available. While global vaccination coverage has improved tremendously, measles outbreaks persist throughout sub-Saharan Africa. Since 2010, the Democratic Republic of Congo (DRC) has seen a resurgence of measles outbreaks affecting all 11 provinces. These outbreaks are mainly attributed to gaps in routine immunization (RI) coverage compounded with missed supplementary immunization activities (SIAs). We utilized national passive surveillance data from DRC's Integrated Disease Surveillance and Response (IDSR) system to estimate the effect of immunization on measles incidence in DRC. Methods We investigated the decline in measles incidence post-immunization with one dose of measles containing vaccine (MCV1) with and without the addition of supplementary immunization activities (SIAs) and outbreak response immunization (ORI) campaigns. Measles case counts by health zone were obtained from the IDSR system between January 1, 2010 and December 31, 2013. The impact of measles immunization was modeled using a random effects multi-level model for count data with RI coverage levels and mass campaign activities from one year prior. Results The presence of an SIA (aIRR [95% CI] 0.86 [0.60–1.25]) and ORI (0.28 [0.20–0.39]) in the year prior were both associated with a decrease in measles incidence. When interaction terms were included, our results suggested that the high levels of MCV1 reported in the year prior and the presence of either mass campaign was associated with a decrease in measles incidence. Conclusions Our results highlight the importance of a two-dose measles vaccine schedule and the need for a strong routine immunization program coupled with frequent SIAs. Repeated occurrences of large-scale outbreaks in DRC suggest that vaccination coverage rates are grossly overestimated and signify the importance of the evaluation and modification of measles prevention and control strategies.

Background Large-scale measles outbreaks in areas with high administrative vaccine coverage rates suggest the need to re-evaluate measles prevention and control in the Democratic Republic of Congo (DRC). Monitoring of measles Vaccine Effectiveness (VE) is a useful measure of quality control in immunization programs. We estimated measles VE among children aged 12–59 months in the Democratic Republic of Congo (DRC) using laboratory surveillance data from 2010–2012. Methods We used the case-based surveillance system with laboratory confirmation to conduct a case-control study using the test negative design. Cases and controls were selected based on presence ( n = 1044) or absence ( n = 1335) of measles specific antibody IgM or epidemiologic linkage. Risk factors for measles were assessed using unconditional logistic regression, stratified by age. Results Among children 12–59 months, measles vaccination was protective against measles [aOR (95% C)], 0.20 (0.15–0.26) and estimated VE was 80% (95% CI 74–85%). Year of diagnosis, 2011: 6.02 (4.16–8.72) and 2012; 8.31 (5.57–12.40) was a risk factor for measles when compared to 2010. Compared to Kinshasa, children in Bas-Congo, Kasai-Oriental, Maniema and South Kivu provinces all had higher odds of developing measles. Measles VE was similar for children 12–23 months and 24–59 months (80% and 81% respectively). Conclusions Repeated occurrences of measles outbreaks and lower than expected VE estimates suggest the need to further evaluate measles vaccine efficacy and improve vaccine delivery strategies in DRC.

Background Human monkeypox is a zoonotic disease endemic to parts of Africa. Similar to other orthopoxviruses, virus and host have considerable interactions through immunomodulation. These interactions likely drive the establishment of a productive infection and disease progression, resulting in the range of disease presentations and case fatality rates observed for members of the Orthopoxvirus genus. Objectives Much of our understanding about the immune response to orthopoxvirus infection comes from either in vitro or in vivo studies performed in small animals or non-human primates. Here, we conducted a detailed assessment of cytokine responses to monkeypox virus using serum from acutely ill humans collected during monkeypox active disease surveillance (2005–2007) in the Democratic Republic of the Congo. Study design Nineteen serum samples that were from patients with confirmed monkeypox virus infections were selected for cytokine profiling. Cytokine profiling was performed on the Bio-Rad Bioplex 100 system using a 30-plex human cytokine panel. Results Cytokine profiling revealed elevated cytokine concentrations in all samples. Overproduction of certain cytokines (interleukin [IL]-2R, IL-10, and granulocyte macrophage-colony stimulating factor were observed in patients with serious disease (defined as >250 lesions based on the World Health Organization scoring system). Conclusions The data suggest that cytokine modulation affects monkeypox disease severity in humans.

IntroductionOne of the goals of the Global Measles and Rubella Strategic Plan is the reduction in global measles mortality, with high measles vaccination coverage as one of its core components. While measles mortality has been reduced more than 79%, the disease remains a major cause of childhood vaccine preventable disease burden globally. Measles immunization requires a two-dose schedule and only countries with strong, stable immunization programs can rely on routine services to deliver the second dose. In the Democratic Republic of Congo (DRC), weak health infrastructure and lack of provision of the second dose of measles vaccine necessitates the use of supplementary immunization activities (SIAs) to administer the second dose.MethodsWe modeled three vaccination strategies using an age-structured SIR (Susceptible-Infectious-Recovered) model to simulate natural measles dynamics along with the effect of immunization. We compared the cost-effectiveness of two different strategies for the second dose of Measles Containing Vaccine (MCV) to one dose of MCV through routine immunization services over a 15-year time period for a hypothetical birth cohort of 3 million children.ResultsCompared to strategy 1 (MCV1 only), strategy 2 (MCV2 by SIA) would prevent a total of 5,808,750 measles cases, 156,836 measles-related deaths and save U.S. $199 million. Compared to strategy 1, strategy 3 (MCV2 by RI) would prevent a total of 13,232,250 measles cases, 166,475 measles-related deaths and save U.S. $408 million.DiscussionVaccination recommendations should be tailored to each country, offering a framework where countries can adapt to local epidemiological and economical circumstances in the context of other health priorities. Our results reflect the synergistic effect of two doses of MCV and demonstrate that the most cost-effective approach to measles vaccination in DRC is to incorporate the second dose of MCV in the RI schedule provided that high enough coverage can be achieved.

Objective: Herpesviruses belong to a diverse order of large DNA viruses that can cause diseases in humans and animals. With the goal of gathering information about the distribution and diversity of herpesviruses in wild rodent and shrew species in central Africa, animals in Cameroon and the Democratic Republic of the Congo were sampled and tested by PCR for the presence of herpesvirus DNA. Methods: A broad range PCRs targeting either the Polymerase or the terminase gene were used for virus detection. Amplified products from PCR were sequenced and isolates analysed for phylogenetic placement. Results: Overall, samples of 1,004 animals of various rodent and shrew species were tested and 24 were found to be positive for herpesvirus DNA. Six of these samples contained strains of known viruses, while the other positive samples revealed DNA sequences putatively belonging to 11 previously undescribed herpesviruses. The new isolates are beta- and gammaherpesviruses and the shrew isolates appear to form a separate cluster within the Betaherpesvirinae subfamily. Conclusion: The diversity of viruses detected is higher than in similar studies in Europe and Asia. The high diversity of rodent and shrew species occurring in central Africa may be the reason for a higher diversity in herpesviruses in this area.

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.

Human monkeypox is an endemic disease in rain-forested regions of central Democratic Republic of Congo. We report fetal outcomes for 1 of 4 pregnant women who participated in an observational study at the General Hospital of Kole (Sankuru Province), where 222 symptomatic subjects were followed between 2007 and 2011. Of the 4 pregnant women, 1 gave birth to a healthy infant, 2 had miscarriages in the first trimester, and 1 had fetal death, with the macerated stillborn showing diffuse cutaneous maculopapillary skin lesions involving the head, trunk and extremities, including palms of hands and soles of feet.