Nutritional Status Link with Polioseronegativity Among Children from Poliomyelitis Transmission High-Risk Area of the Democratic Republic of the Congo (DRC).

Background: Malnutrition is identified as a risk-factor for insufficient polioseroconversion in the context of a vaccine-derived polio virus (VDPV) outbreak prone region. To assess the prevalence of malnutrition and its link to poliovirus insufficient immunity, a cross-sectional household survey was conducted in the regions of Haut- Lomami and Tanganyika, DRC. Methods: In March 2018, we included 968 healthy children aged 6 to 59 months from eight out of 27 districts. Selection of study locations within these districts was done using a stratified random sampling method, where villages were chosen based on habitat characteristics identified from satellite images. Consent was obtained verbally in the preferred language of the participant (French or Swahili) by interviewers who received specific training for this task. Furthermore, participants contributed a dried blood spot sample, collected via finger prick. To assess malnutrition, we measured height and weight, applying WHO criteria to determine rates of underweight, wasting, and stunting. The assessment of immunity to poliovirus types 1, 2, and 3 through the detection of neutralizing antibodies was carried out at the CDC in Atlanta, USA. Results: Of the study population, we found 24.7% underweight, 54.8% stunted, and 15.4% wasted. With IC95%, underweight (OR=1.50; [1.11-2.03]), and the non-administration of vitamin A (OR=1.96; [1.52-2.54]) were significantly associated with seronegativity to polioserotype 1. Underweight (OR=1.64; [1.20-2.24]) and the non-administration of vitamin A (OR=1.55; [1.20-2.01]) were significantly associated with seronegativity to polioserotype 2. Underweight (OR=1.50; [1.11-2.03]), and the non-administration of vitamin A (OR=1.80. [1.38-2.35]) were significantly associated with seronegativity to polioserotype 3. Underweight (OR=1.68; IC95% [1.10-2.57]) and the non-administration of vitamin A (OR=1.82; IC95% [1.30-2.55]) were significantly associated with seronegativity to all polioserotypes. Conclusion: This study reveals a significant association between underweight and polioseronegativity in children. In order to reduce vaccine failures in high-risk areas, an integrated approach by vaccination and nutrition programs should be adopted.

Poliovirus-Neutralizing Antibody Seroprevalence and Vaccine Habits in a Vaccine-Derived Poliovirus Outbreak Region in the Democratic Republic of Congo in 2018: The Impact on the Global Eradication Initiative.

Despite the successes in wild-type polio eradication, poor vaccine coverage in the DRC has led to the occurrence of circulating vaccine-derived poliovirus outbreaks. This cross-sectional population-based survey provides an update to previous poliovirus-neutralizing antibody seroprevalence studies in the DRC and quantifies risk factors for under-immunization and parental knowledge that guide vaccine decision making. Among the 964 children between 6 and 35 months in our survey, 43.8% (95% CI: 40.6-47.0%), 41.1% (38.0-44.2%), and 38.0% (34.9-41.0%) had protective neutralizing titers to polio types 1, 2, and 3, respectively. We found that 60.7% of parents reported knowing about polio, yet 25.6% reported knowing how it spreads. Our data supported the conclusion that polio outreach efforts were successfully connecting with communities-79.4% of participants had someone come to their home with information about polio, and 88.5% had heard of a polio vaccination campaign. Additionally, the odds of seroreactivity to only serotype 2 were far greater in health zones that had a history of supplementary immunization activities (SIAs) compared to health zones that did not. While SIAs may be reaching under-vaccinated communities as a whole, these results are a continuation of the downward trend of seroprevalence rates in this region.

Prediction Model with Validation for Polioseronegativity in Malnourished Children from Poliomyelitis Transmission High-Risk Area of the Democratic Republic of the Congo (DRC).

Background: Malnutrition is identified as a risk factor for insufficient polio seroconversion in the context of a vaccine-derived poliovirus (VDPV) outbreak-prone region. In the Democratic Republic of Congo (DRC), underweight decreased from 31% (in 2001) to 26% (in 2018). Since 2004, VDPV serotype 2 outbreaks (cVDPV2) have been documented and were geographically limited around the Haut-Lomami and Tanganyika Provinces. Methods: To develop and validate a predictive model for poliomyelitis vaccine response in malnourished infants, a cross-sectional household study was carried out in the Haut-Lomami and Tanganyika provinces. Healthy children aged 6 to 59 months (n=968) were enrolled from eight health zones (HZ) out of 27, in March 2018. We performed a bivariate and multivariate logistics analysis. Final models were selected using a stepwise Wald method, and variables were selected based on the criterion p < 0.05. The association between nutritional variables, explaining polio seronegativity for the three serotypes, was assessed using the receiver operating characteristic curve (ROC curve). Results: Factors significantly associated with seronegativity to the three polio serotypes were underweight, non-administration of vitamin A, and the age group of 12 to 59 months. The sensitivity was 10.5%, and its specificity was 96.4% while the positive predictive values (PPV) and negative (PNV) were 62.7% and 65.3%, respectively. We found a convergence of the curves of the initial sample and two split samples. Based on the comparison of the overlapping confidence intervals of the ROC curve, we concluded that our prediction model is valid. Conclusion: This study proposed the first tool which variables are easy to collect by any health worker in charge of vaccination or in charge of nutrition. It will bring on top, the collaboration between the Immunization and the Nutritional programs in DRC integration policy, and its replicability in other low- and middle-income countries with endemic poliovirus.

Hesitancy to receive the novel coronavirus vaccine and potential influences on vaccination among a cohort of healthcare workers in the Democratic Republic of the Congo.

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

Pan-ebolavirus serology study of healthcare workers in the Mbandaka Health Region, Democratic Republic of the Congo.

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

High-resolution population estimation using household survey data and building footprints.

The national census is an essential data source to support decision-making in many areas of public interest. However, this data may become outdated during the intercensal period, which can stretch up to several decades. In this study, we develop a Bayesian hierarchical model leveraging recent household surveys and building footprints to produce up-to-date population estimates. We estimate population totals and age and sex breakdowns with associated uncertainty measures within grid cells of approximately 100 m in five provinces of the Democratic Republic of the Congo, a country where the last census was completed in 1984. The model exhibits a very good fit, with an R2 value of 0.79 for out-of-sample predictions of population totals at the microcensus-cluster level and 1.00 for age and sex proportions at the province level. This work confirms the benefits of combining household surveys and building footprints for high-resolution population estimation in countries with outdated censuses.

Immunogenicity of rVSVΔG-ZEBOV-GP Ebola vaccination in exposed and potentially exposed persons in the Democratic Republic of the Congo.

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

Increasing Ebola transmission behaviors 6 months post-vaccination: Comparing vaccinated and unvaccinated populations near 2018 Mbandaka Ebola outbreak in the Democratic Republic of Congo.

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.

Zoonotic risk factors associated with seroprevalence of Ebola virus GP antibodies in the absence of diagnosed Ebola virus disease in the Democratic Republic of Congo.

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.

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

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.

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.

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.

Neurological, Cognitive, and Psychological Findings Among Survivors of Ebola Virus Disease From the 1995 Ebola Outbreak in Kikwit, Democratic Republic of Congo: A Cross-sectional Study.

BACKGROUND: Clinical sequelae of Ebola virus disease (EVD) have not been described more than 3 years postoutbreak. We examined survivors and close contacts from the 1995 Ebola outbreak in Kikwit, Democratic Republic of Congo (DRC), and determined prevalence of abnormal neurological, cognitive, and psychological findings and their association with EVD survivorship. METHODS: From August to September 2017, we conducted a cross-sectional study in Kikwit, DRC. Over 2 decades after the EVD outbreak, we recruited EVD survivors and close contacts from the outbreak to undergo physical examination and culturally adapted versions of the Folstein mini-mental status exam (MMSE) and Goldberg anxiety and depression scale (GADS). We estimated the strength of relationships between EVD survivorship and health outcomes using linear regression models by comparing survivors versus close contacts, adjusting for age, sex, educational level, marital status, and healthcare worker status. RESULTS: We enrolled 20 EVD survivors and 187 close contacts. Among the 20 EVD survivors, 4 (20%) reported at least 1 abnormal neurological symptom, and 3 (15%) had an abnormal neurological examination. Among the 187 close contacts, 14 (11%) reported at least 1 abnormal neurologic symptom, and 9 (5%) had an abnormal neurological examination. EVD survivors had lower mean MMSE and higher mean GADS scores as compared to close contacts (MMSE: adjusted coefficient: -1.85; 95% confidence interval [CI]: -3.63, -0.07; GADS: adjusted coefficient: 3.91; 95% CI: 1.76, 6.04). CONCLUSIONS: EVD survivors can have lower cognitive scores and more symptoms of depression and anxiety than close contacts more than 2 decades after Ebola virus outbreaks.