Publications by authors named "Anne W Rimoin"

77 Publications

Evaluation of bat adenoviruses suggests co-evolution and host roosting behaviour as drivers for diversity.

Microb Genom 2021 Apr;7(4)

Metabiota Inc, Nanaimo, British Columbia, Canada.

Adenoviruses (AdVs) are diverse pathogens of humans and animals, with several dozen bat AdVs already identified. Considering that over 100 human AdVs are known, and the huge diversity of bat species, many bat AdVs likely remain undiscovered. To learn more about AdV prevalence, diversity and evolution, we sampled and tested bats in Cameroon using several PCR assays for viral and host DNA. AdV DNA was detected in 14 % of the 671 sampled animals belonging to 37 different bat species. There was a correlation between species roosting in larger groups and AdV DNA detection. The detected AdV DNA belonged to between 28 and 44 different, mostly previously unknown, mastadenovirus species. The novel isolates are phylogenetically diverse and while some cluster with known viruses, others appear to form divergent new clusters. The phylogenetic tree of novel and previously known bat AdVs does not mirror that of the various host species, but does contain structures consistent with a degree of virus-host co-evolution. Given that closely related isolates were found in different host species, it seems likely that at least some bat AdVs have jumped species barriers, probably in the more recent past; however, the tree is also consistent with such events having taken place throughout bat AdV evolution. AdV diversity was highest in bat species roosting in large groups. The study significantly increased the diversity of AdVs known to be harboured by bats, and suggests that host behaviours, such as roosting size, may be what limits some AdVs to one species rather than an inability of AdVs to infect other related hosts.
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http://dx.doi.org/10.1099/mgen.0.000561DOI Listing
April 2021

Pandemic velocity: Forecasting COVID-19 in the US with a machine learning & Bayesian time series compartmental model.

PLoS Comput Biol 2021 03 29;17(3):e1008837. Epub 2021 Mar 29.

Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, California, United States of America.

Predictions of COVID-19 case growth and mortality are critical to the decisions of political leaders, businesses, and individuals grappling with the pandemic. This predictive task is challenging due to the novelty of the virus, limited data, and dynamic political and societal responses. We embed a Bayesian time series model and a random forest algorithm within an epidemiological compartmental model for empirically grounded COVID-19 predictions. The Bayesian case model fits a location-specific curve to the velocity (first derivative) of the log transformed cumulative case count, borrowing strength across geographic locations and incorporating prior information to obtain a posterior distribution for case trajectories. The compartmental model uses this distribution and predicts deaths using a random forest algorithm trained on COVID-19 data and population-level characteristics, yielding daily projections and interval estimates for cases and deaths in U.S. states. We evaluated the model by training it on progressively longer periods of the pandemic and computing its predictive accuracy over 21-day forecasts. The substantial variation in predicted trajectories and associated uncertainty between states is illustrated by comparing three unique locations: New York, Colorado, and West Virginia. The sophistication and accuracy of this COVID-19 model offer reliable predictions and uncertainty estimates for the current trajectory of the pandemic in the U.S. and provide a platform for future predictions as shifting political and societal responses alter its course.
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http://dx.doi.org/10.1371/journal.pcbi.1008837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8031749PMC
March 2021

Cross-sectional Assessment of COVID-19 Vaccine Acceptance Among Health Care Workers in Los Angeles.

Ann Intern Med 2021 Feb 9. Epub 2021 Feb 9.

Jonathan and Karin Fielding School of Public Health, University of California, Los Angeles, Los Angeles, California (A.G., M.H., A.W.R.).

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http://dx.doi.org/10.7326/M20-7580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926184PMC
February 2021

Human T-cell lymphotropic virus type 1 transmission dynamics in rural villages in the Democratic Republic of the Congo with high nonhuman primate exposure.

PLoS Negl Trop Dis 2021 01 28;15(1):e0008923. Epub 2021 Jan 28.

Laboratory Branch, Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.

The Democratic Republic of the Congo (DRC) has a history of nonhuman primate (NHP) consumption and exposure to simian retroviruses yet little is known about the extent of zoonotic simian retroviral infections in DRC. We examined the prevalence of human T-lymphotropic viruses (HTLV), a retrovirus group of simian origin, in a large population of persons with frequent NHP exposures and a history of simian foamy virus infection. We screened plasma from 3,051 persons living in rural villages in central DRC using HTLV EIA and western blot (WB). PCR amplification of HTLV tax and LTR sequences from buffy coat DNA was used to confirm infection and to measure proviral loads (pVLs). We used phylogenetic analyses of LTR sequences to infer evolutionary histories and potential transmission clusters. Questionnaire data was analyzed in conjunction with serological and molecular data. A relatively high proportion of the study population (5.4%, n = 165) were WB seropositive: 128 HTLV-1-like, 3 HTLV-2-like, and 34 HTLV-positive but untypeable profiles. 85 persons had HTLV indeterminate WB profiles. HTLV seroreactivity was higher in females, wives, heads of households, and increased with age. HTLV-1 LTR sequences from 109 persons clustered strongly with HTLV-1 and STLV-1 subtype B from humans and simians from DRC, with most sequences more closely related to STLV-1 from Allenopithecus nigroviridis (Allen's swamp monkey). While 18 potential transmission clusters were identified, most were in different households, villages, and health zones. Three HTLV-1-infected persons were co-infected with simian foamy virus. The mean and median percentage of HTLV-1 pVLs were 5.72% and 1.53%, respectively, but were not associated with age, NHP exposure, village, or gender. We document high HTLV prevalence in DRC likely originating from STLV-1. We demonstrate regional spread of HTLV-1 in DRC with pVLs reported to be associated with HTLV disease, supporting local and national public health measures to prevent spread and morbidity.
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http://dx.doi.org/10.1371/journal.pntd.0008923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872225PMC
January 2021

An evidence review of face masks against COVID-19.

Proc Natl Acad Sci U S A 2021 01;118(4)

Department of Epidemiology, Jonathan and Karin Fielding School of Public Health, University of California, Los Angeles, CA 90095.

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.
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http://dx.doi.org/10.1073/pnas.2014564118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848583PMC
January 2021

Risk factors for Ebola exposure in healthcare workers in Boende, Tshuapa Province, Democratic Republic of the Congo.

J Infect Dis 2020 Dec 3. Epub 2020 Dec 3.

Department of Epidemiology, University of California, Los Angeles, Fielding School of Public Health, Los Angeles, CA, USA.

Healthcare 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), the prevalence and associated risk factors remains unknown. We conducted a serosurvey among healthcare workers in the town of Boende in Tshuapa Province, Democratic Republic of Congo (DRC). Human anti-EBOV Glycoprotein (GP) 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. Overall, 22.5% of HCWs were seroreactive for EBOV. In multivariable analyses, using any form of personal protective equipment (PPE) when interacting with a confirmed, probable, or suspect EVD case was negatively associated with seroreactivity [0.23 (95% CI: 0.07, 0.73)]. 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.
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http://dx.doi.org/10.1093/infdis/jiaa747DOI Listing
December 2020

Controlling emerging zoonoses at the animal-human interface.

One Health Outlook 2020 18;2(1):17. Epub 2020 Sep 18.

Department of Ecology and Evolutionary Biology, University of California, 610 Charles E Young Dr S, Los Angeles, CA 90095 USA.

Background: For many emerging or re-emerging pathogens, cases in humans arise from a mixture of introductions (via zoonotic spillover from animal reservoirs or geographic spillover from endemic regions) and secondary human-to-human transmission. Interventions aiming to reduce incidence of these infections can be focused on preventing spillover or reducing human-to-human transmission, or sometimes both at once, and typically are governed by resource constraints that require policymakers to make choices. Despite increasing emphasis on using mathematical models to inform disease control policies, little attention has been paid to guiding rational disease control at the animal-human interface.

Methods: We introduce a modeling framework to analyze the impacts of different disease control policies, focusing on pathogens exhibiting subcritical transmission among humans (i.e. pathogens that cannot establish sustained human-to-human transmission). We quantify the relative effectiveness of measures to reduce spillover (e.g. reducing contact with animal hosts), human-to-human transmission (e.g. case isolation), or both at once (e.g. vaccination), across a range of epidemiological contexts.

Results: We provide guidelines for choosing which mode of control to prioritize in different epidemiological scenarios and considering different levels of resource and relative costs. We contextualize our analysis with current zoonotic pathogens and other subcritical pathogens, such as post-elimination measles, and control policies that have been applied.

Conclusions: Our work provides a model-based, theoretical foundation to understand and guide policy for subcritical zoonoses, integrating across disciplinary and species boundaries in a manner consistent with One Health principles.
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http://dx.doi.org/10.1186/s42522-020-00024-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550773PMC
September 2020

Race, COVID-19 and deaths of despair.

EClinicalMedicine 2020 Aug 31;25:100485. Epub 2020 Jul 31.

Department of Medicine, University of California San Diego School of Medicine, La Jolla, California, United States.

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http://dx.doi.org/10.1016/j.eclinm.2020.100485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396816PMC
August 2020

The 2019-nCoV pandemic in the global south: A Tsunami ahead.

EClinicalMedicine 2020 Jun 19;23:100384. Epub 2020 May 19.

Department of Medicine, University of California San Diego School of Medicine, La Jolla, California, United States.

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http://dx.doi.org/10.1016/j.eclinm.2020.100384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234938PMC
June 2020

Responding to the Challenge of the Dual COVID-19 and Ebola Epidemics in the Democratic Republic of Congo-Priorities for Achieving Control.

Am J Trop Med Hyg 2020 08 19;103(2):597-602. Epub 2020 Jun 19.

Department of Medical Microbiology and Virology, National Institute of Biomedical Research (INRB), Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of the Congo.

As of June 11, 2020, the Democratic Republic of the Congo (DRC) has reported 4,258 COVID-19 cases with 90 deaths. With other African countries, the DRC faces the challenge of striking a balance between easing public health lockdown measures to curtail the spread of SARS-CoV-2 and minimizing both economic hardships for large sectors of the population and negative impacts on health services for other infectious and noninfectious diseases. The DRC recently controlled its tenth Ebola virus disease (EVD) outbreak, but COVID-19 and a new EVD outbreak beginning on June 1, 2020 in the northwest Équateur Province have added an additional burden to health services. Although the epidemiology and transmission of EVD and COVID-19 differ, leveraging the public health infrastructures and experiences from coordinating the EVD response to guide the public health response to COVID-19 is critical. Building on the DRC's 40 years of experience with 10 previous EVD outbreaks, we highlight the DRC's multi-sectoral public health approach to COVID-19, which includes community-based screening, testing, contact-tracing, risk communication, community engagement, and case management. We also highlight remaining challenges and discuss the way forward for achieving control of both COVID-19 and EVD in the DRC.
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http://dx.doi.org/10.4269/ajtmh.20-0642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410434PMC
August 2020

Human monkeypox - After 40 years, an unintended consequence of smallpox eradication.

Vaccine 2020 07 13;38(33):5077-5081. Epub 2020 May 13.

Regional Head of Emergency Preparedness, Resilience and Response, NHS England (South West & South East), UK. Electronic address:

Smallpox eradication, coordinated by the WHO and certified 40 years ago, led to the cessation of routine smallpox vaccination in most countries. It is estimated that over 70% of the world's population is no longer protected against smallpox, and through cross-immunity, to closely related orthopox viruses such as monkeypox. Monkeypox is now a re-emerging disease. Monkeypox is endemic in as yet unconfirmed animal reservoirs in sub-Saharan Africa, while its human epidemiology appears to be changing. Monkeypox in small animals imported from Ghana as exotic pets was at the origin of an outbreak of human monkeypox in the USA in 2003. Travellers infected in Nigeria were at the origin of monkeypox cases in the UK in 2018 and 2019, Israel in 2018 and Singapore in2019. Together with sporadic reports of human infections with other orthopox viruses, these facts invite speculation that emergent or re-emergent human monkeypox might fill the epidemiological niche vacated by smallpox. An ad-hoc and unofficial group of interested experts met to consider these issues at Chatham House, London in June 2019, in order to review available data and identify monkeypox-related research gaps. Gaps identified by the experts included:The experts further agreed on the need for a better understanding of the genomic evolution and changing epidemiology of orthopox viruses, the usefulness of in-field genomic diagnostics, and the best disease control strategies, including the possibility of vaccination with new generation non-replicating smallpox vaccines and treatment with recently developed antivirals.
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http://dx.doi.org/10.1016/j.vaccine.2020.04.062DOI Listing
July 2020

The Impact of Different Types of Violence on Ebola Virus Transmission During the 2018-2020 Outbreak in the Democratic Republic of the Congo.

J Infect Dis 2020 11;222(12):2021-2029

Harvard Medical School, Boston, Massachusetts, USA.

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.
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http://dx.doi.org/10.1093/infdis/jiaa163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661768PMC
November 2020

The coronavirus 2019-nCoV epidemic: Is hindsight 20/20?

EClinicalMedicine 2020 Mar 3;20:100289. Epub 2020 Mar 3.

Department of Medicine, University of California San Diego School of Medicine, La Jolla, CA, USA.

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http://dx.doi.org/10.1016/j.eclinm.2020.100289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057189PMC
March 2020

Further Considerations About the Ophthalmic Sequelae of Ebola.

JAMA Ophthalmol 2020 04;138(4):403-404

Ocular Inflammatory Disease Center, UCLA Stein Eye Institute, David Geffen School of Medicine at UCLA, Los Angeles, California.

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http://dx.doi.org/10.1001/jamaophthalmol.2020.0185DOI Listing
April 2020

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

Vaccine 2020 02;38(9):2258-2265

Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA 90095, United States. Electronic address:

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.
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http://dx.doi.org/10.1016/j.vaccine.2019.09.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026690PMC
February 2020

Seroreactivity against Marburg or related filoviruses in West and Central Africa.

Emerg Microbes Infect 2020 8;9(1):124-128. Epub 2020 Jan 8.

Vitalant Research Institute, San Francisco, CA, USA.

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.
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http://dx.doi.org/10.1080/22221751.2019.1709563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968259PMC
September 2020

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

Ecohealth 2020 03 24;17(1):64-73. Epub 2019 Dec 24.

Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, USA.

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.
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http://dx.doi.org/10.1007/s10393-019-01459-7DOI Listing
March 2020

Field Test and Validation of the Multiplier Measles, Mumps, Rubella, and Varicella-Zoster Multiplexed Assay System in the Democratic Republic of the Congo by Using Dried Blood Spots.

mSphere 2019 08 14;4(4). Epub 2019 Aug 14.

Department of Epidemiology, University of California, Los Angeles, Fielding School of Public Health, Los Angeles, California, USA.

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. 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.
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http://dx.doi.org/10.1128/mSphere.00112-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6695516PMC
August 2019

Real-time predictions of the 2018-2019 Ebola virus disease outbreak in the Democratic Republic of the Congo using Hawkes point process models.

Epidemics 2019 09 23;28:100354. Epub 2019 Jul 23.

Department of Statistics, University of California, Los Angeles, CA, USA.

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.
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http://dx.doi.org/10.1016/j.epidem.2019.100354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358183PMC
September 2019

Urogenital Schistosomiasis and Sexually Transmitted Coinfections among Pregnant Women in a Schistosome-Endemic Region of the Democratic Republic of Congo.

Am J Trop Med Hyg 2019 10;101(4):828-836

Department of Epidemiology, Jonathan and Karin Fielding School of Public Health, University of California Los Angeles, Los Angeles, California.

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 , 3.1% with (CT), 1.4% with (NG), and 14.6% with (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.
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http://dx.doi.org/10.4269/ajtmh.19-0024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779196PMC
October 2019

Projections of epidemic transmission and estimation of vaccination impact during an ongoing Ebola virus disease outbreak in Northeastern Democratic Republic of Congo, as of Feb. 25, 2019.

PLoS Negl Trop Dis 2019 08 5;13(8):e0007512. Epub 2019 Aug 5.

F. I. Proctor Foundation, University of California, San Francisco (UCSF), San Francisco, California, United States of America.

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.
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http://dx.doi.org/10.1371/journal.pntd.0007512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6695208PMC
August 2019

Estimating the impact of violent events on transmission in Ebola virus disease outbreak, Democratic Republic of the Congo, 2018-2019.

Epidemics 2019 09 26;28:100353. Epub 2019 Jul 26.

Francis I. Proctor Foundation for Research in Ophthalmology, San Francisco, University of California, CA, USA; Department of Epidemiology and Biostatistics, School of Medicine, University of California, San Francisco, San Francisco, CA, USA. Electronic address:

Introduction: As of April 2019, the current Ebola virus disease (EVD) outbreak in the Democratic Republic of the Congo (DRC) is occurring in a longstanding conflict zone and has become the second largest EVD outbreak in history. It is suspected that after violent events occur, EVD transmission will increase; however, empirical studies to understand the impact of violence on transmission are lacking. Here, we use spatial and temporal trends of EVD case counts to compare transmission rates between health zones that have versus have not experienced recent violent events during the outbreak.

Methods: We collected daily EVD case counts from DRC Ministry of Health. A time-varying indicator of recent violence in each health zone was derived from events documented in the WHO situation reports. We used the Wallinga-Teunis technique to estimate the reproduction number R for each case by day per zone in the 2018-2019 outbreak. We fit an exponentially decaying curve to estimates of R overall and by health zone, for comparison to past outbreaks.

Results: As of 16 April 2019, the mean overall R for the entire outbreak was 1.11. We found evidence of an increase in the estimated transmission rates in health zones with recently reported violent events versus those without (p = 0.008). The average R was estimated as between 0.61 and 0.86 in regions not affected by recent violent events, and between 1.01 and 1.07 in zones affected by violent events within the last 21 days, leading to an increase in R between 0.17 and 0.53. Within zones with recent violent events, the mean estimated quenching rate was lower than for all past outbreaks except the 2013-2016 West African outbreak.

Conclusion: The difference in the estimated transmission rates between zones affected by recent violent events suggests that violent events are contributing to increased transmission and the ongoing nature of this outbreak.
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http://dx.doi.org/10.1016/j.epidem.2019.100353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363034PMC
September 2019

Metagenomic Next-Generation Sequencing of the 2014 Ebola Virus Disease Outbreak in the Democratic Republic of the Congo.

J Clin Microbiol 2019 09 26;57(9). Epub 2019 Aug 26.

Department of Laboratory Medicine, University of California, San Francisco, San Francisco, California, USA

We applied metagenomic next-generation sequencing (mNGS) to detect Zaire Ebola virus (EBOV) and other potential pathogens from whole-blood samples from 70 patients with suspected Ebola hemorrhagic fever during a 2014 outbreak in Boende, Democratic Republic of the Congo (DRC) and correlated these findings with clinical symptoms. Twenty of 31 patients (64.5%) tested in Kinshasa, DRC, were EBOV positive by quantitative reverse transcriptase PCR (qRT-PCR). Despite partial degradation of sample RNA during shipping and handling, mNGS followed by EBOV-specific capture probe enrichment in a U.S. genomics laboratory identified EBOV reads in 22 of 70 samples (31.4%) versus in 21 of 70 (30.0%) EBOV-positive samples by repeat qRT-PCR (overall concordance = 87.1%). Reads from (malaria) were detected in 21 patients, of which at least 9 (42.9%) were coinfected with EBOV. Other positive viral detections included hepatitis B virus ( = 2), human pegivirus 1 ( = 2), Epstein-Barr virus ( = 9), and Orungo virus ( = 1), a virus in the family. The patient with Orungo virus infection presented with an acute febrile illness and died rapidly from massive hemorrhage and dehydration. Although the patient's blood sample was negative by EBOV qRT-PCR testing, identification of viral reads by mNGS confirmed the presence of EBOV coinfection. In total, 9 new EBOV genomes (3 complete genomes, and an additional 6 ≥50% complete) were assembled. Relaxed molecular clock phylogenetic analysis demonstrated a molecular evolutionary rate for the Boende strain 4 to 10× slower than that of other Ebola lineages. These results demonstrate the utility of mNGS in broad-based pathogen detection and outbreak surveillance.
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http://dx.doi.org/10.1128/JCM.00827-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711896PMC
September 2019

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

PLoS One 2019 24;14(5):e0217426. Epub 2019 May 24.

Department of Epidemiology, University of California Los Angeles, Los Angeles, California, United States of America.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0217426PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534301PMC
January 2020

Serologic Prevalence of Ebola Virus in Equatorial Africa.

Emerg Infect Dis 2019 05;25(5):911-918

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.
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http://dx.doi.org/10.3201/eid2505.180115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478206PMC
May 2019

Projections of Ebola outbreak size and duration with and without vaccine use in Équateur, Democratic Republic of Congo, as of May 27, 2018.

PLoS One 2019 7;14(3):e0213190. Epub 2019 Mar 7.

School of Medicine, University of California, San Francisco (UCSF), San Francisco, CA, United States of America.

As of May 27, 2018, 6 suspected, 13 probable and 35 confirmed cases of Ebola virus disease (EVD) had been reported in Équateur Province, Democratic Republic of Congo. We used reported case counts and time series from prior outbreaks to estimate the total outbreak size and duration with and without vaccine use. We modeled Ebola virus transmission using a stochastic branching process model that included reproduction numbers from past Ebola outbreaks and a particle filtering method to generate a probabilistic projection of the outbreak size and duration conditioned on its reported trajectory to date; modeled using high (62%), low (44%), and zero (0%) estimates of vaccination coverage (after deployment). Additionally, we used the time series for 18 prior Ebola outbreaks from 1976 to 2016 to parameterize the Thiel-Sen regression model predicting the outbreak size from the number of observed cases from April 4 to May 27. We used these techniques on probable and confirmed case counts with and without inclusion of suspected cases. Probabilistic projections were scored against the actual outbreak size of 54 EVD cases, using a log-likelihood score. With the stochastic model, using high, low, and zero estimates of vaccination coverage, the median outbreak sizes for probable and confirmed cases were 82 cases (95% prediction interval [PI]: 55, 156), 104 cases (95% PI: 58, 271), and 213 cases (95% PI: 64, 1450), respectively. With the Thiel-Sen regression model, the median outbreak size was estimated to be 65.0 probable and confirmed cases (95% PI: 48.8, 119.7). Among our three mathematical models, the stochastic model with suspected cases and high vaccine coverage predicted total outbreak sizes closest to the true outcome. Relatively simple mathematical models updated in real time may inform outbreak response teams with projections of total outbreak size and duration.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213190PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405095PMC
December 2019

High Herpesvirus Diversity in Wild Rodent and Shrew Species in Central Africa.

Intervirology 2018 16;61(4):155-165. Epub 2018 Nov 16.

Metabiota, San Francisco, California, USA,

Objective: Herpesviruses belong to a diverse order of large DNA viruses that can cause diseases in humans and animals. With the goal of gathering information about the distribution and diversity of herpesviruses in wild rodent and shrew species in central Africa, animals in Cameroon and the Democratic Republic of the Congo were sampled and tested by PCR for the presence of herpesvirus DNA.

Methods: A broad range PCRs targeting either the Polymerase or the terminase gene were used for virus detection. Amplified products from PCR were sequenced and isolates analysed for phylogenetic placement.

Results: Overall, samples of 1,004 animals of various rodent and shrew species were tested and 24 were found to be positive for herpesvirus DNA. Six of these samples contained strains of known viruses, while the other positive samples revealed DNA sequences putatively belonging to 11 previously undescribed herpesviruses. The new isolates are beta- and gammaherpesviruses and the shrew isolates appear to form a separate cluster within the Betaherpesvirinae subfamily.

Conclusion: The diversity of viruses detected is higher than in similar studies in Europe and Asia. The high diversity of rodent and shrew species occurring in central Africa may be the reason for a higher diversity in herpesviruses in this area.
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http://dx.doi.org/10.1159/000493796DOI Listing
May 2019

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

J Pediatric Infect Dis Soc 2019 Dec;8(6):531-538

Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles.

Background: Transient immunosuppression and increased susceptibility to other infections after measles infection is well known, but recent studies have suggested the occurrence of an "immune amnesia" that could have long-term immunosuppressive effects.

Methods: We examined the association between past measles infection and acute episodes of fever, cough, and diarrhea among 2350 children aged 9 to 59 months whose mothers were selected for interview in the 2013-2014 Democratic Republic of the Congo (DRC) Demographic and Health Survey (DHS). Classification of children who had had measles was completed using maternal recall and measles immunoglobulin G serostatus obtained via dried-blood-spot analysis with a multiplex immunoassay. The association with time since measles infection and fever, cough, and diarrhea outcomes was also examined.

Results: The odds of fever in the previous 2 weeks were 1.80 (95% confidence interval [CI], 1.25-2.60) among children for whom measles was reported compared to children with no history of measles. Measles vaccination demonstrated a protective association against selected clinical markers of acute infectious diseases.

Conclusion: Our results suggest that measles might have a long-term effect on selected clinical markers of acute infectious diseases among children aged 9 to 59 months in the DRC. These findings support the immune-amnesia hypothesis suggested by others and underscore the need for continued evaluation and improvement of the DRC's measles vaccination program.
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http://dx.doi.org/10.1093/jpids/piy099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933309PMC
December 2019