Search

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.

[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.

ObjectivesTo describe face mask use among pregnant women seeking antenatal care (ANC) in Kinshasa, Democratic Republic of Congo and to identify factors associated with masking adherence in this population.DesignFacility-based cross-sectional study nested within a prospective cohort study.SettingRandom sample of 10 health facilities, including 5 primary health centers and 5 secondary facilities or hospitals.ParticipantsA total of 934 pregnant women aged 18 years or above with a gestational age of at least 32 weeks were consecutively surveyed from 17 August 2020 to 31 January 2021.Primary and secondary outcome measuresWe estimated the proportions of pregnant women wearing a face mask and masking correctly (ie, over the mouth and nose), and assessed their knowledge regarding the COVID-19 pandemic. Multivariable logistic regression was employed to identify factors associated with overall and correct face mask use.ResultsOverall, 309 (33.1%) women wore a mask during the interview after their antenatal appointments, but only 33 (10.7%) wore a mask correctly. The odds of masking and correct mask use were significantly higher among women who had their ANC visit in a facility that provided COVID-19 care. Additionally, women who experienced COVID-19-like symptoms in the past 6 months had higher odds of wearing a mask correctly compared with those reporting no recent symptoms. Although 908 (97.2%) women were aware of the COVID-19 pandemic, only 611 (67.3%) thought that COVID-19 was circulating locally in Kinshasa.ConclusionOverall and correct face mask adherence levels were low among pregnant women attending ANC in Kinshasa. Our study highlights the need for improving adherence to correct face mask use in order to help control the spread of COVID-19 within Kinshasa alongside other control measures, like vaccination.

The national census is an essential data source to support decision-making in many areas of public interest. However, this data may become outdated during the intercensal period, which can stretch up to several decades. We developed a Bayesian hierarchical model leveraging recent household surveys with probabilistic sampling designs and building footprints to produce up-to-date population estimates. We estimated population totals and age and sex breakdowns with associated uncertainty measures within grid cells of approximately 100m in five provinces of the Democratic Republic of the Congo, a country where the last census was completed in 1984. The model exhibited a very good fit, with an R^2 value of 0.79 for out-of-sample predictions of population totals at the microcensus-cluster level and 1.00 for age and sex proportions at the province level. The results confirm the benefits of combining household surveys and building footprints for high-resolution population estimation in countries with outdated censuses., Comment: 27 pages, 6 figures

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.

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.

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.

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.

The science around the use of masks by the public to impede COVID-19 transmission is advancing rapidly. In this narrative review, we develop an analytical framework to examine mask usage, synthesizing the relevant literature to inform multiple areas: population impact, transmission characteristics, source control, wearer protection, sociological considerations, and implementation considerations. A primary route of transmission of COVID-19 is via respiratory particles, and it is known to be transmissible from presymptomatic, paucisymptomatic, and asymptomatic individuals. Reducing disease spread requires two things: limiting contacts of infected individuals via physical distancing and other measures and reducing the transmission probability per contact. The preponderance of evidence indicates that mask wearing reduces transmissibility per contact by reducing transmission of infected respiratory particles in both laboratory and clinical contexts. Public mask wearing is most effective at reducing spread of the virus when compliance is high. Given the current shortages of medical masks, we recommend the adoption of public cloth mask wearing, as an effective form of source control, in conjunction with existing hygiene, distancing, and contact tracing strategies. Because many respiratory particles become smaller due to evaporation, we recommend increasing focus on a previously overlooked aspect of mask usage: mask wearing by infectious people (“source control”) with benefits at the population level, rather than only mask wearing by susceptible people, such as health care workers, with focus on individual outcomes. We recommend that public officials and governments strongly encourage the use of widespread face masks in public, including the use of appropriate regulation.

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.

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.

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.

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.

Deep sequencing was used to discover a novel rhabdovirus (Bas-Congo virus, or BASV) associated with a 2009 outbreak of 3 human cases of acute hemorrhagic fever in Mangala village, Democratic Republic of Congo (DRC), Africa. The cases, presenting over a 3-week period, were characterized by abrupt disease onset, high fever, mucosal hemorrhage, and, in two patients, death within 3 days. BASV was detected in an acute serum sample from the lone survivor at a concentration of 1.09×106 RNA copies/mL, and 98.2% of the genome was subsequently de novo assembled from ∼140 million sequence reads. Phylogenetic analysis revealed that BASV is highly divergent and shares less than 34% amino acid identity with any other rhabdovirus. High convalescent neutralizing antibody titers of >1∶1000 were detected in the survivor and an asymptomatic nurse directly caring for him, both of whom were health care workers, suggesting the potential for human-to-human transmission of BASV. The natural animal reservoir host or arthropod vector and precise mode of transmission for the virus remain unclear. BASV is an emerging human pathogen associated with acute hemorrhagic fever in Africa., Author Summary We used deep sequencing, a method for generating millions of DNA sequence reads from clinical samples, to discover a novel rhabdovirus (Bas-Congo virus, or BASV) associated with a 2009 outbreak of 3 human cases of acute hemorrhagic fever in Mangala village, Democratic Republic of Congo (DRC), Africa. The cases, presenting over a 3-week period, were characterized by abrupt disease onset, high fever, bloody vomiting and diarrhea, and, in two patients, death within 3 days. BASV was present in the blood of the lone survivor at a concentration of over a million copies per milliliter. The genome of BASV, assembled from over 140 million sequence reads, reveals that it is very different from any other rhabdovirus. The lone survivor and a nurse caring for him (with no symptoms), both health care workers, were found to have high levels of antibodies to BASV, indicating that they both had been infected by the virus. Although the source of the virus remains unclear, our study findings suggest that BASV may be spread by human-to-human contact and is an emerging pathogen associated with acute hemorrhagic fever in Africa.