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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.

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.

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.

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.

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.

Beginning April 8, 2020, we enrolled 1787 frontline heath workers who were asymptomatic for COVID-19 into a longitudinal surveillance study. During that time 4 healthcare workers and 6 first responders tested positive for SARS-CoV-2 by RT-PCR. Additionally, 43 healthcare workers and 55 first responders had detectable IgG antibodies to SARS-CoV-2.

ImportanceHealthcare workers (HCW) are slated to be early recipients of SARS-CoV-2 vaccines due to increased risk of exposure to patients with COVID-19, and will be tasked with administering approved vaccines to the general population. As lynchpins of the vaccination effort, HCWs’ opinions of a vaccine’s safety and efficacy may affect both public perception and uptake of the vaccine. Therefore, it is crucial to understand and address potential hesitancy prior to vaccine administration.ObjectiveTo understand healthcare workers’ attitudes about vaccine safety, efficacy, and acceptability in the context of the COVID-19 pandemic, including acceptance of a novel coronavirus vaccine.Design, Setting, ParticipantsA cross-sectional survey was distributed to participants enrolled in a longitudinal cohort study surveilling SARS-CoV-2 infection among 1,093 volunteer sampled University of California, Los Angeles (UCLA) Health System employees. Surveys were completed online between September 24 and October 16, 2020. In total, 609 participants completed this supplemental survey.ResultsWe averaged a 9-statement Likert scale matrix scored from 1 (“strongly disagree”) to 5 (“strongly agree”) and found respondents overwhelmingly confident about vaccine safety (4.47); effectiveness (4.44); importance, self-protection, and community health (4.67). Notably, 47.3% of respondents reported unwillingness to participate in a coronavirus vaccine trial, and most (66.5%) intend to delay vaccination. The odds of reporting intent to delay coronavirus vaccine uptake were 4.15 times higher among nurses, 2.45 times higher among other personnel with patient contact roles, and 2.15 times higher among those without patient contact compared to doctors. Evolving SARS-CoV-2 science (76.0%), current political climate (57.6%), and fast-tracked vaccine development timeline (83.4%) were cited as primary variables impacting HCW decisions to undergo vaccination. Of note, these results were obtained prior to release of Phase III data from companies manufacturing vaccines in the U.S.Conclusions and RelevanceDespite overall confidence in vaccines, a majority of HCW expressed concerns over a novel coronavirus vaccine. A large proportion plan to delay vaccine uptake due to concerns about expedited development, emerging scientific discoveries, and the political climate. Forthcoming vaccination campaigns must address these unique points of coronavirus vaccine hesitancy in order to achieve adequate vaccine coverage.

The science around the use of masks by the general public to impede COVID-19 transmission is advancing rapidly. Policymakers need guidance on how masks should be used by the general population to combat the COVID-19 pandemic. In this narrative review, we develop an analytical framework to examine mask usage, considering and synthesizing the relevant literature to inform multiple areas: population impact; transmission characteristics; source control; PPE; sociological considerations; and implementation considerations. A primary route of transmission of COVID-19 is via respiratory droplets, and is known to be transmissible from presymptomatic and asymptomatic individuals. Reducing disease spread requires two things: first, limit contacts of infected individuals via physical distancing and other measures, and second, reduce the transmission probability per contact. The preponderance of evidence indicates that mask wearing reduces the transmissibility per contact by reducing transmission of infected droplets in both laboratory and clinical contexts. Public mask wearing is most effective at reducing spread of the virus when compliance is high. The decreased transmissibility could substantially reduce the death toll and economic impact while the cost of the intervention is low. 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 droplets 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 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.

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 nonlinear mixed 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 transformed cumulative case count, borrowing strength across geographic locations and incorporating prior information to obtain a posterior distribution for case trajectory. 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 infections and deaths in U.S. states. We evaluate forecasting accuracy on a two-week holdout set, finding that the model predicts COVID-19 cases and deaths well, with a mean absolute scaled error of 0.40 for cases and 0.32 for deaths throughout the two-week evaluation period. The substantial variation in predicted trajectories and associated uncertainty between states is illustrated by comparing three unique locations: New York, Ohio, and Mississippi. 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 nonlinear mixed model for case velocity 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 also 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.

Key Points Question What are the ophthalmic sequelae in survivors of the 2013 to 2016 Ebola epidemic? Findings In this cohort study, no new Ebola retinal lesions were observed and visual acuity was preserved at 2 years; however, associated retinal dark without pressure did change with regression and expansion of affected zones. New clinical toxoplasmosis chorioretinal lesions occurred in 2 survivors. Meaning Expanding dark without pressure might suggest an ongoing intraretinal stimulus, which may be associated with a viral infection; treatment strategies might take account of the possibility of toxoplasmosis chorioretinitis recurrence within survivors of Ebola., Importance The 2-year ophthalmic sequelae of Ebola virus disease (EVD) in survivors of the 2013 to 2016 epidemic is unknown and may have public health implications for future outbreaks. Objective To assess the potential for uveitis recurrence, the behavior of dark without pressure, and visual outcomes in a cohort of Sierra Leonean survivors of EVD 2 years following the 2013 to 2016 Ebola epidemic. Design, Setting, and Participants Prospective, 1-year observational cohort study performed between 2016 and 2017 at 34 Military Hospital, Freetown, Sierra Leone. Participants included survivors of EVD who reported ocular symptoms since Ebola treatment unit discharge and were participants of a previous case-control study. Participants were invited for ophthalmic reexamination and finger-prick blood sampling for immunoglobulin G (IgG) to Toxoplasma gondii and HIV. Exposures Ebola virus disease. Main Outcomes and Measures Primary outcome measure: comparative ultra-widefield retinal imaging. Secondary outcome measures: visual acuity and detection of IgG to T gondii and HIV. Results Of 57 survivors of EVD who underwent repeated ophthalmic evaluation, 37 were women (64.9%). Mean (SD) age was 31.9 (11.1) years. Median interval between first and last examination was 370 days (interquartile range [IQR], 365-397.5 days), and median time from discharge to last examination was 779 days (IQR, 732-821 days). Fifteen eyes of 10 survivors (17.5%) had retinal lesions secondary to EVD. No new EVD-associated retinal lesions were observed. Two survivors (3.5%) developed new posterior uveitis resembling toxoplasmosis chorioretinitis and 41 (73%) were seropositive for T gondii IgG. Areas of dark without pressure were observed either confined to the perimeter of Ebola retinal lesions (n = 7) and non-Ebola lesions (n = 2), involving extensive retinal areas adjacent to Ebola retinal lesions (n = 4) and non-Ebola lesions (n = 2) or in isolation (n = 6). Both expansion and regression of areas of dark without pressure were observed over the study period. Best eye–presenting visual acuity had mild or no visual impairment in 55 survivors (96.4%) 2 years following discharge. Conclusions and Relevance Vision was maintained in survivors of EVD 2 years following discharge. Evolving regions of dark without pressure may be associated with EVD retinal lesions and might suggest the presence of an ongoing intraretinal stimulus, which may be associated with infective etiology. Treatment strategies should account for the possibility of toxoplasmosis chorioretinitis recurrence within survivors of EVD., This cohort study assesses the potential for uveitis recurrence, the behavior of dark without pressure, and visual outcomes in a cohort of Sierra Leonean survivors of Ebola virus disease 2 years following the 2013 to 2016 Ebola epidemic.

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.

From 2006 to 2007, an active surveillance program for human monkeypox (MPX) in the Democratic Republic of the Congo identified 151 cases of coinfection with monkeypox virus and varicella zoster virus from 1158 suspected cases of human MPX (13%). Using clinical and socio-demographic data collected with standardized instruments by trained, local nurse supervisors, we examined a variety of hypotheses to explain the unexpectedly high proportion of coinfections among the sample, including the hypothesis that the two viruses occur independently. The probabilities of disease incidence and selection necessary to yield the observed sample proportion of coinfections under an assumption of independence are plausible given what is known and assumed about human MPX incidence. Cases of human MPX are expected to be underreported, and more coinfections are expected with improved 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.

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.

Understanding and quantifying the transmission of zoonotic pathogens is essential for directing public health responses, especially for pathogens capable of transmission between humans. However, determining a pathogen’s transmission dynamics is complicated by challenges often encountered in zoonotic disease surveillance, including unobserved sources of transmission (both human and zoonotic), limited spatial information, and unknown scope of surveillance. In this work, we present a model-based inference method that addresses these challenges for subcritical zoonotic pathogens using a spatial model with two levels of mixing. After demonstrating the robustness of the method using simulation studies, we apply the new method to a dataset of human monkeypox cases detected during an active surveillance program from 1982-1986 in the Democratic Republic of the Congo (DRC). Our results provide estimates of the reproductive number and spillover rate of monkeypox during this surveillance period and suggest that most human-to-human transmission events occur over distances of 30km or less. Taking advantage of contact-tracing data available for a subset of monkeypox cases, we find that around 80% of contact-traced links could be correctly recovered from transmission trees inferred using only date and location. Our results highlight the importance of identifying the appropriate spatial scale of transmission, and show how even imperfect spatiotemporal data can be incorporated into models to obtain reliable estimates of human-to-human transmission patterns.Author SummarySurveillance datasets are often the only sources of information about the ecology and epidemiology of zoonotic infectious diseases. Methods that can extract as much information as possible from these datasets therefore provide a key advantage for informing our understanding of the disease dynamics and improving our ability to choose the optimal intervention strategy. We developed and tested a likelihood-based inference method based on a mechanistic model of the spillover and human-to-human transmission processes. We first used simulated datasets to explore which information about the disease dynamics of a subcritical zoonotic pathogen could be successfully extracted from a line-list surveillance dataset with non-localized spatial information and unknown geographic coverage. We then applied the method to a dataset of human monkeypox cases detected during an active surveillance program in the Democratic Republic of the Congo between 1982 and 1986 to obtain estimates of the reproductive number, spillover rate, and spatial dispersal of monkeypox in humans.

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

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.

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.

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.

Despite recent declines in HIV incidence, sub-Saharan Africa remains the most heavily affected region in the global HIV/AIDS epidemic. Estimates of HIV prevalence in African military personnel are scarce and inconsistent. We conducted a serosurvey between June and September 2007 among 4043 Armed Forces personnel of the Democratic Republic of Congo (FARDC) stationed in Kinshasa, Democratic Republic of Congo (DRC) to determine the prevalence of HIV and syphilis infections and describe associated risk behaviours. Participants provided blood for HIV and syphilis testing and responded to a demographic and risk factor questionnaire. The prevalence of HIV was 3.8% and the prevalence of syphilis was 11.9%. Women were more likely than men to be HIV positive, (7.5% vs. 3.6% respectively, aOR: 1.66, 95% C.I: 1.21–2.28, p

Smallpox eradication is considered to be one of the most remarkable accomplishments of the 20th century. Lessons learned from the campaign during the 1960s and 1970s in the Democratic Republic of Congo (DRC) can provide important information for the development of other eradication programs including polio. The DRC is the third largest country in Africa; the population suffers from extreme poverty, deteriorating infrastructure and health systems, and long periods of civil strife. Despite these challenges, DRC's smallpox eradication campaign was successful, eradicating smallpox only 41 months after initiation. DRC had been polio free since 2001; however, in 2006, imported cases were identified in the country. Polio transmission has since been re-established and DRC now has the second greatest number of reported polio cases in the world. Challenges which existed during the smallpox campaign in DRC are still present today; additionally, the polio vaccine itself poses unique challenges which include requiring multiple doses to confer immunity. In the fight against polio in DRC, it will be important to draw from the smallpox eradication experience. A number of important themes emerged during the campaign that could be beneficial to eradicating polio and future eradication programs that may follow. During the smallpox campaign, a standard vaccination program was implemented, surveillance was intensified, and there were strong collaborative programs with community involvement. These successful elements of the smallpox campaign should be adapted and applied in DRC in polio eradication programs.

Summary Objectives To evaluate the utility of rapid antigen detection testing (RADT) for the diagnosis of group A streptococcal (GAS) pharyngitis in pediatric outpatient clinics in four countries with varied socio-economic and geographic profiles. Methods We prospectively evaluated the utility of a commercial RADT in children aged 2–12 years presenting with symptoms of pharyngitis to urban outpatient clinics in Brazil, Croatia, Egypt, and Latvia between August 2001 and December 2005. We compared the performance of the RADT to culture using diagnostic and agreement statistics, including sensitivity, specificity, and positive and negative predictive values. The Centor scores for GAS diagnosis were used to assess the potential effect of spectrum bias on RADT results. Results Two thousand four hundred and seventy-two children were enrolled at four sites. The prevalence of GAS by throat culture varied by country (range 24.5–39.4%) and by RADT (range 23.9–41.8%). Compared to culture, RADT sensitivity ranged from 72.4% to 91.8% and specificity ranged from 85.7% to 96.4%. The positive predictive value ranged from 67.9% to 88.6% and negative predictive value ranged from 88.1% to 95.7%. Conclusions In limited-resource regions where microbiological diagnosis is not feasible or practical, RADTs should be considered an option that can be performed in a clinic and provide timely results.

Despite the fact that most emerging diseases stem from the transmission of pathogenic agents from animals to humans, the factors that mediate this process are still ill defined. What is known, however, is that the interface between humans and animals is of paramount importance in the process. This review will discuss the importance of the human-animal interface to the disease emergence process. We also provide an overview of factors that are believed to contribute to the origin and global spread of emerging infectious diseases and offer suggestions that may serve as future prevention strategies, such as social mobilization, public health education, behavioral change, and communication strategies. Because there exists no comprehensive global surveillance system to monitor zoonotic disease emergence, the intervention measures discussed herein may prove effective temporary alternatives.

SUMMARYThis study examined the prevalence of HIV and other sexually transmitted infections (STIs) in pregnant women in Kinshasa, the Democratic Republic of the Congo (DRC). Between April and July 2004, antenatal attendees at two of the largest maternity clinics in Kinshasa were tested to identify HIV status, syphilis, Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). HIV seroprevalence was 1·9% in 2082 women. With PCR techniques, CT and NG infections were also uncommon in the first 529 women (1·7% and 0·4%, respectively). No active syphilis infection case was identified by Treponema pallidum haemagglutination assay (TPHA) and rapid plasma reagin test (RPR). A woman's risk of HIV infection was significantly associated with her reporting a male partner having had other female sexual partners (OR 2·7, 95% CI 1·2–6·2). The continuing low seroprevalence of HIV in pregnant women from Kinshasa was confirmed. Understanding factors associated with this phenomenon could help prevent a future HIV epidemic in low HIV transmission areas in Africa.

Objective To compare the effectiveness of several clinical prediction rules for culture-positive streptococcal pharyngitis in a single group of patients in a setting in which clinicians routinely treat all cases of pharyngitis presumptively, without laboratory data. Study design A MEDLINE search identified clinical prediction rules for streptococcal pharyngitis in children. Each rule was applied analytically to data from 410 children in Cairo, Egypt with clinical pharyngitis, in whom throat cultures were performed. The diagnostic effectiveness of these rules for predicting a positive culture were assessed and compared. Results Seven prediction rules were identified. Of these 7 rules, 4 were developed in North American children, 1 was recommended by the World Health Organization (WHO), and 2 were developed in Egypt. In the Cairo children, the WHO rule was the least sensitive, at 12%. The 6 other rules had sensitivities ranging from 81% to 99% and specificities ranging from 4% to 40%; 2 rules seemed to be effective, with diagnostic odds ratios of 5.2 and 6.1. Conclusions The prediction rules demonstrated variable diagnostic effectiveness in the Egyptian children. Without laboratory testing, 2 clinical rules detected > 90% of cases of pharyngitis with positive culture for group A streptococcus and reduced overtreatment of culture-negative cases by ∼40%. Selected clinical prediction rules have useful characteristics in settings of limited resources and need further validation.

Human monkeypox is a viral zoonotic disease that occurs mostly in the rain forests of central and western Africa. However, the disease recently emerged in the United States in imported wild rodents from Africa. Monkeypox has a clinical presentation very similar to that of ordinary forms of smallpox, including flulike symptoms, fever, malaise, back pain, headache, and characteristic rash. Given this clinical spectrum, differential diagnosis to rule out smallpox is very important. There are no licensed therapies for human monkeypox; however, the smallpox vaccine can protect against the disease. The discontinuation of general vaccination in the 1980s has given rise to increasing susceptibility to monkeypox virus infection in the human population. This has led to fears that monkeypox virus could be used as a bioterrorism agent. Effective prevention relies on limiting the contact with infected patients or animals and limiting the respiratory exposure to infected patients.

Background Recent studies suggest a measles-induced immune amnesia that could have long-term immunosuppressive effects via preferential depletion of memory B and T CD150+ lymphocytes. Methods We examined the association between past measles and tetanus antibody levels among children participating in the 2013–2014 Democratic Republic of Congo (DRC) Demographic and Health Survey (DHS). Our sample consisted of 833 children aged 6–59 months whose mothers were selected for interview. Mothers reported (via recall) history of measles within the lifetime of the child. Classification of children who previously had measles was completed using maternal recall and measles immunoglobulin G (IgG) serostatus obtained via dried blood spot (DBS) analysis. A multiplex chemiluminescent immunoassay platform was used to obtain serologic results and Assay Score (AS) was calculated as a ratio to a positive control included in each run. Tetanus serostatus was categorized as being above or below the sample median serology AS value. Tetanus vaccination status was obtained via dated vaccination card and limited to children receiving the complete 3-dose vaccination series. Results The median AS for tetanus serology among the entire sample of 833 children was 0.085, while children with history of measles had a median AS of 0.053 (N = 41) and children with no history of measles had a median AS of 0.088 (N = 792), chi-square P-value < 0.05. A random intercept logistic regression model was used to examine the association between previous measles disease and odds of having below median levels of tetanus antibody. Controlling for potential confounding variables, the odds of a child with past history of measles having less than the median level of tetanus antibody was 3.86 (95% CI: 1.70, 8.78) among children fully vaccinated for tetanus. Conclusion The results suggest that, among children 6–59 months in DRC, measles may have a long-term impact on levels of pre-existing, vaccine-induced immunity to tetanus. These findings suggest the need for laboratory studies examining measles’ impact on pre-existing, vaccine-induced immunity and underscore the need for continued evaluation and improvement of DRC’s measles vaccination program. Disclosures All authors: No reported disclosures.

Human parvovirus 4 infections are primarily associated with parenteral exposure in western countries. By ELISA, we demonstrate frequent seropositivity for antibody to parvovirus 4 viral protein 2 among adult populations throughout sub-Saharan Africa (Burkina Faso, 37%; Cameroon, 25%; Democratic Republic of the Congo, 35%; South Africa, 20%), which implies existence of alternative transmission routes.

Background: Primary prevention of acute rheumatic fever is achieved by proper antibiotic treatment of group A β -hemolytic streptococcal (GAS) pharyngitis. Methods: To assess noninferiority of oral amoxicillin to intramuscular benzathine penicillin G (IM BPG). Children (2 to 12 years) meeting enrollment criteria were randomized 1:1 to receive antibiotic treatment in 2 urban outpatient clinics in Egypt and Croatia. Results: A total of 558 children (Croatia = 166, Egypt = 392) were randomized, with 368 evaluable in an intention-to-treat (ITT) analysis, and 272 evaluable in the per protocol (PP) analysis. In Croatia, ITT and PP treatment success rates were comparable for IM BPG and amoxicillin (2.5% difference vs 1.1% difference, respectively). In Egypt, amoxicillin was not comparable with IM BPG in ITT analysis (15.1% difference), but was comparable in PP analysis (-9.3% difference). Conclusion: If compliance is a major issue, a single dose of IM BPG may be preferable for treatment of GAS pharyngitis.