Nicole A. Hoff

Novel simian foamy virus infections from multiple monkey species in women from the Democratic Republic of Congo.

BackgroundZoonotic transmission of simian retroviruses in Central Africa is ongoing and can result in pandemic human infection. While simian foamy virus (SFV) infection was reported in primate hunters in Cameroon and Gabon, little is known about the distribution of SFV in Africa and whether human-to-human transmission and disease occur. We screened 3,334 plasmas from persons living in rural villages in central Democratic Republic of Congo (DRC) using SFV-specific EIA and Western blot (WB) tests. PCR amplification of SFV polymerase sequences from DNA extracted from buffy coats was used to measure proviral loads. Phylogenetic analysis was used to define the NHP species origin of SFV. Participants completed questionnaires to capture NHP exposure information.ResultsSixteen (0.5%) samples were WB-positive; 12 of 16 were from women (75%, 95% confidence limits 47.6%, 92.7%). Sequence analysis detected SFV in three women originating from Angolan colobus or red-tailed monkeys; both monkeys are hunted frequently in DRC. NHP exposure varied and infected women lived in distant villages suggesting a wide and potentially diverse distribution of SFV infections across DRC. Plasmas from 22 contacts of 8 WB-positive participants were all WB negative suggesting no secondary viral transmission. Proviral loads in the three women ranged from 14 – 1,755 copies/105 cells.ConclusionsOur study documents SFV infection in rural DRC for the first time and identifies infections with novel SFV variants from Colobus and red-tailed monkeys. Unlike previous studies, women were not at lower risk for SFV infection in our population, providing opportunities for spread of SFV both horizontally and vertically. However, limited testing of close contacts of WB-positive persons did not identify human-to-human transmission. Combined with the broad behavioral risk and distribution of NHPs across DRC, our results suggest that SFV infection may have a wider geographic distribution within DRC. These results also reinforce the potential for an increased SFV prevalence throughout the forested regions of Africa where humans and simians co-exist. Our finding of endemic foci of SFV infection in DRC will facilitate longitudinal studies to determine the potential for person-to-person transmissibility and pathogenicity of these zoonotic retroviral infections.

The effect of immunization on measles incidence in the Democratic Republic of Congo: Results from a model of surveillance data.

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 DRCs 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.

Ebola Virus Neutralizing Antibodies Detectable in Survivors of theYambuku, Zaire Outbreak 40 Years after Infection

Duration of immunity against Ebola virus among survivors remains unclear. We assessed serological immune profiles and retention of Ebola virus neutralizing antibodies in 14 survivors of the 1976 Yambuku outbreak 40 years postinfection, providing the longest documentation of such measures reported.

Evidence of Mumps Infection Among Children in the Democratic Republic of Congo

Background: 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. Methods: 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. Results: 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). Conclusion: 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.

Field evaluation of measles vaccine effectiveness among children in the Democratic Republic of Congo

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.

Smallpox and its eradication in the Democratic Republic of Congo: lessons learned.

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, DRCs 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.

Predictors of measles vaccination coverage among children 6–59 months of age in the Democratic Republic of the Congo

Highlights • DRC’s overall measles vaccination coverage level of 70% is too low to halt the spread of measles.• Socioeconomic variables and residence are associated with vaccination coverage disparities.• Vaccination coverage and data quality are linked, and as such, dated records must be increased.

Multifunctional Pan-ebolavirus Antibody Recognizes a Site of Broad Vulnerability on the Ebolavirus Glycoprotein

SUMMARY Ebolaviruses cause severe disease in humans, and identification of monoclonal antibodies (mAbs) that are effective against multiple ebolaviruses are important for therapeutics development. Here we describe a distinct class of broadly neutralizing human mAbs with protective capacity against three ebolaviruses infectious for humans: Ebola (EBOV), Sudan (SUDV), and Bundibugyo (BDBV) viruses. We isolated mAbs from human survivors of ebolavirus disease and identified a potent mAb, EBOV‐520, which bound to an epitope in the glycoprotein (GP) base region. EBOV‐520 efficiently neutralized EBOV, BDBV, and SUDV and also showed protective capacity in relevant animal models of these infections. EBOV‐520 mediated protection principally by direct virus neutralization and exhibited multifunctional properties. This study identified a potent naturally occurring mAb and defined key features of the human antibody response that may contribute to broad protection. This multifunctional mAb and related clones are promising candidates for development as broadly protective pan‐ebolavirus therapeutic molecules. Graphical Abstract Figure. No caption available. HighlightsBroad human antibody recognizes a quaternary site of vulnerability on ebolavirus GPThe antibody possesses pan‐ebolavirus neutralizing and protective capacityThe antibody mediates protection principally by direct virus neutralizationThe antibody uses several mechanisms for contributing to broad immunity &NA; Gilchuk et al. isolated and characterized new broadly neutralizing human monoclonal antibodies active against all three clinically relevant ebolaviruses. Some potent antibodies bind to the glycoprotein base region, act principally by direct virus neutralization, and exploit several mechanisms for contributing to pan‐ebolavirus protective immunity.

Treatment of Streptococcal Pharyngitis With Once-Daily Amoxicillin Versus Intramuscular Benzathine Penicillin G in Low-Resource Settings: A Randomized Controlled Trial

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.

Serologic Evidence of Ebolavirus Infection in a Population With No History of Outbreaks in the Democratic Republic of the Congo

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.