Serological responses to the MVA-based JYNNEOS monkeypox vaccine in a cohort of participants from the Democratic Republic of Congo.

The current worldwide monkepox outbreak has reaffirmed the continued threat monkeypox virus (MPXV) poses to public health. JYNNEOS, a Modified Vaccinia Ankara (MVA)-based live, non-replicating vaccine, was recently approved for monkeypox prevention for adults at high risk of MPXV infection in the United States. Although the safety and immunogenicity of JYNNEOS have been examined previously, the clinical cohorts studied largely derive from regions where MPXV does not typically circulate. In this study, we assess the quality and longevity of serological responses to two doses of JYNNEOS vaccine in a large cohort of healthcare workers from the Democratic Republic of Congo (DRC). We show that JYNNEOS elicits a strong orthopoxvirus (OPXV)-specific antibody response in participants that peaks around day 42, or 2 weeks after the second vaccine dose. Participants with no prior history of smallpox vaccination or exposure have lower baseline antibody levels, but experience a similar fold-rise in antibody titers by day 42 as those with a prior history of vaccination. Both previously naïve and vaccinated participants generate vaccinia virus and MPXV-neutralizing antibody in response to JYNNEOS vaccination. Finally, even though total OPXV-specific IgG titers and neutralizing antibody titers declined from their peak and returned close to baseline levels by the 2-year mark, most participants remain IgG seropositive at the 2-year timepoint. Taken together, our data demonstrates that JYNNEOS vaccination triggers potent OPXV neutralizing antibody responses in a cohort of healthcare workers in DRC, a monkeypox-endemic region. MPXV vaccination with JYNNEOS may help ameliorate the disease and economic burden associated with monkeypox and combat potential outbreaks in areas with active virus circulation.

Hepatitis C prevalence and quality of health services among HIV-positive mothers in the Democratic Republic of the Congo.

Hepatitis C virus (HCV) contributes to liver-related morbidity and mortality throughout Africa despite effective antivirals. HCV is endemic in the Democratic Republic of the Congo (DRC) but data on HCV/HIV co-infection in pregnancy is limited. We estimated the prevalence of and risk factors for HCV/HIV co-infection among pregnant women in the Kinshasa province of the DRC. This cross-sectional study was conducted as a sub-study of an ongoing randomized trial to assess continuous quality improvement interventions (CQI) for prevention of mother-to-child transmission (PMTCT) of HIV (CQI-PMTCT study, NCT03048669). HIV-infected women in the CQI-PMTCT cohort were tested for HCV, and risk factors were evaluated using logistic regression. The prevalence of HCV/HIV co-infection among Congolese women was 0.83% (95% CI 0.43-1.23). Women who tested positive for HCV were younger, more likely to live in urban areas, and more likely to test positive during pregnancy versus postpartum. HCV-positive women had significantly higher odds of infection with hepatitis B virus (HBV) (aOR 13.87 [3.29,58.6]). An inverse relationship was noted between HCV infection and the overall capacity of the health facility as measured by the service readiness index (SRI) (aOR:0.92 [0.86,0.98] per unit increase). Women who presented to rural, for-profit and PEPFAR-funded health facilities were more likely to test positive for HCV. In summary, this study identified that the prevalence of HCV/HIV co-infection was < 1% among Congolese women. We also identified HBV infection as a major risk factor for HCV/HIV co-infection. Individuals with triple infection should be linked to care and the facility-related differences in HCV prevalence should be addressed in future studies.

Clinical and Epidemiological Findings from Enhanced Monkeypox Surveillance in Tshuapa Province, Democratic Republic of the Congo During 2011-2015.

BACKGROUND: Monkeypox is a poorly described emerging zoonosis endemic to Central and Western Africa. METHODS: Using surveillance data from Tshuapa Province, Democratic Republic of the Congo during 2011-2015, we evaluated differences in incidence, exposures, and clinical presentation of polymerase chain reaction-confirmed cases by sex and age. RESULTS: We report 1057 confirmed cases. The average annual incidence was 14.1 per 100 000 (95% confidence interval, 13.3-15.0). The incidence was higher in male patients (incidence rate ratio comparing males to females, 1.21; 95% confidence interval, 1.07-1.37), except among those 20-29 years old (0.70; .51-.95). Females aged 20-29 years also reported a high frequency of exposures (26.2%) to people with monkeypox-like symptoms.The highest incidence was among 10-19-year-old males, the cohort reporting the highest proportion of animal exposures (37.5%). The incidence was lower among those presumed to have received smallpox vaccination than among those presumed unvaccinated. No differences were observed by age group in lesion count or lesion severity score. CONCLUSIONS: Monkeypox incidence was twice that reported during 1980-1985, an increase possibly linked to declining immunity provided by smallpox vaccination. The high proportion of cases attributed to human exposures suggests changing exposure patterns. Cases were distributed across age and sex, suggesting frequent exposures that follow sociocultural norms.

Molecular surveillance of anti-malarial drug resistance in Democratic Republic of Congo: high variability of chloroquinoresistance and lack of amodiaquinoresistance.

BACKGROUND: The loss of chloroquine (CQ) effectiveness has led to its withdrawal from national policies as a first-line treatment for uncomplicated malaria in several endemic countries, such as the Democratic Republic of Congo (DRC). The K76T mutation on the pfcrt gene has been identified as a marker of CQ resistance and the SVMNT haplotype in codons 72-76 on the same gene has been associated with resistance to amodiaquine (AQ). In the DRC, the prevalence of K76T has decreased from 100% in 2000 to 63.9% in 2014. The purpose of this study was to determine the prevalence of K76T mutations in circulating strains of Plasmodium falciparum, 16 years after CQ withdrawal in the DRC and to investigate the presence of the SVMNT haplotype. METHODS: In 2017, ten geographical sites across the DRC were selected. Dried blood samples were collected from patients attending health centres. Malaria was first detected by a rapid diagnostic test (RDT) available on site (SD Bioline Malaria Ag Pf or CareStart Malaria Pf) or thick blood smear and then confirmed by a P. falciparum species-specific real-time PCR assay. A pfcrt gene segment containing a fragment that encodes amino acids at positions 72-76 was amplified by conventional PCR before sequencing. RESULTS: A total of 1070 patients were enrolled. Of the 806 PCR-confirmed P. falciparum positive samples, 764 were successfully sequenced. The K76T mutation was detected in 218 samples (28.5%; 95% CI 25.4%-31.9%), mainly (96%) with the CVIET haplotype. Prevalence of CQ resistance marker was unequally distributed across the country, ranging from 1.5% in Fungurume to 89.5% in Katana. The SVMNT haplotype, related to AQ resistance, was not detected. CONCLUSION: Overall, the frequency of the P. falciparum CQ resistance marker has decreased significantly and no resistance marker to AQ was detected in the DRC in 2017. However, the between regions variability of CQ resistance remains high in the country. Further studies are needed for continuous monitoring of the CQ resistance level for its prospective re-use in malaria management. The absence of the AQ resistance marker is in line with the use of this drug in the current DRC malaria treatment policy.

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

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.

Adherence to the referral advice after introduction of rectal artesunate for pre-referral treatment of severe malaria at the community level: a noninferiority trial in the Democratic Republic of the Congo.

BACKGROUND: The Democratic Republic of the Congo adopted the strategy of using, at the community level, a dose of rectal artesunate as a pre-referral treatment for severe malaria amongst children under 5 years who could not quickly reach a health care facility and take oral medication. However, the adherence to referral advice after the integration of this strategy and the acceptability of the strategy were unknown. METHODS: To assess adherence by the mothers/caretakers of children under 5 years to referral advice provided by the community health workers after pre-referral treatment of severe malaria with rectal artesunate, the authors conducted a noninferiority community trial with a pre- and post-intervention design in 63 (pre-intervention) and 51 (post-intervention) community care sites in 4 provinces (Kasaï-Oriental, Kasaï-Central, Lomami, Lualaba) from August 2014 through June 2016. The pre- and post-intervention surveys targets 387 mothers of children under 5 years and 63 community health workers and 346 mothers and 41 community health workers, respectively. A 15% margin was considered for noninferiority analyses due to the expected decrease in adherence to referral advice after the introduction of the new intervention. RESULTS: The mothers acknowledged that the rectal route was often used (60.7%), and medicines given rectally were considered more effective (63.6%) and easy to administer (69.7%). The acceptability of pre-referral rectal artesunate was relatively high: 79.4% (95% CI 75.4-83.3) among mothers, 90.3% (95% CI 82.3-96.8) among community health workers, and 97.8% (95% CI 93.3-100) among nurses. Adherence to referral advice at post-intervention [84.3% (95% CI 80.6-88.1)] was non-inferior to pre-intervention adherence [94.1% (95% CI 91.7-96.4)]. CONCLUSIONS: The integration of pre-referral rectal artesunate for severe malaria into the community care site in the DR Congo is feasible and acceptable. It positively affected adherence to referral advice. However, more health education is needed for parents of children under 5 years and community health workers.

HIV viral suppression among pregnant and breastfeeding women in routine care in the Kinshasa province: a baseline evaluation of participants in CQI-PMTCT study.

INTRODUCTION: Published data on viral suppression among pregnant and breastfeeding women in routine care settings are scarce. Here, we report provincial estimates of undetectable and suppressed viral load among pregnant or breastfeeding women in HIV care in Kinshasa, Democratic Republic of Congo (DRC) and associated risk factors. METHODS: This cross-sectional study was conducted as part of a baseline assessment for the CQI-PMTCT study: an ongoing cluster randomized trial to evaluate the effect of continuous quality interventions (CQI) on long-term ART outcomes among pregnant and breastfeeding women (NCT03048669). From November 2016 to June 2018, in each of the 35 Kinshasa provincial health zones (HZ), study teams visited the three busiest maternal and child health clinics, enrolled all HIV-positive pregnant or breastfeeding women (≤1 year post-delivery) receiving ART, and performed viral load testing. Log binomial models with generalized estimating equations to account for clustering at the HZ level, were used to estimate prevalence ratios comparing participants with undetected (<40 copies/mL) or suppressed (<1000 copies/mL) viral load across levels of individual and site characteristics. RESULTS: Of the 1752 eligible women, 1623 had viral load results available, including 38% who had been on ART for <6 months and 74% were on tenofovir-lamivudine-efavirenz. Viral load was undetectable in 53% of women and suppressed in 62%. Among women who were on ART for ≥12 months, only 60% and 67% respectively, had undetectable or suppressed viral load. Viral load was undetectable in 53%, 48% and 58% of women testing during pregnancy, at delivery, and in postpartum respectively. In multivariable log binomial models, duration of ART >12 months, older age, being married, disclosure of HIV status, receiving care in an urban health zone or one supported by PEPFAR were all positively associated with viral suppression. CONCLUSIONS: The observed high level of detectable viral load suggests that high ART coverage alone without substantial efforts to improve the quality of care for pregnant and breastfeeding women, will not be enough to achieve the goal of virtual elimination of vertical HIV transmission in high-burden and limited resources settings like DRC.

Breastfeeding Support Offered at Delivery is Associated with Higher Prevalence of Exclusive Breastfeeding at 6 Weeks Postpartum Among HIV Exposed Infants: A Cross-Sectional Analysis.

Objective HIV-exposed uninfected infants are almost twice as likely to die compared to infants born to HIV-uninfected women. HIV-exposed uninfected children whose mothers are on ART and who are breastfed have the lowest risk of dying by 24 months of age. Interventions to improve breastfeeding among HIV-infected mothers are needed. We aimed to assess the association between support/counseling provided by healthcare workers following delivery and the rate of exclusive breastfeeding (EBF) at 6-week postpartum. Methods This is a secondary analysis of data collected as part of a trial to evaluate the effect of conditional cash transfers on retention in and uptake of PMTCT services. Between April 2013 and August 2014, newly diagnosed HIV-infected women, ≤ 32 weeks pregnant, registering for antenatal care (ANC), in 89 clinics in Kinshasa, Democratic Republic of Congo, were recruited and followed through 6 weeks postpartum. At 6-week, participants were asked if they had given anything other than breastmilk to their infant in the 24 h preceding the interview (No = EBF) and whether a nurse or a doctor talked to them about breastfeeding after they gave birth (YES = received breastfeeding support/counseling). Logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (CI) measuring the strength of the association between EBF and receiving breastfeeding support/counseling by a healthcare provider following delivery. Results Of 433 women enrolled, 328 attended a 6-week postpartum visit including 320 (97%) with complete information on EBF. Of those 320, 202 (63%) reported giving nothing other than breastmilk to their infant in the previous 24 h; 252 (79%) reported that a healthcare provider came to talk to them about breastfeeding following delivery. Mothers who reported receiveing breastfeeding support/counseling from a healthcare provider were more likely to exclusively breastfeed compared to those who did not (69% vs. 38%, OR 3.74; 95% CI 2.14-6.54). Adjustment for baseline sociodemographic characteristics did not change the association substantially, (adjusted OR 3.72; 95% CI 2.06-6.71). Conclusion for Practice Receipt of breastfeeding support/counseling from a healthcare provider after delivery among HIV-infected mothers in care at 6-weeks postpartum in Kinshasa almost quadrupled the odds of EBF.

Varicella in Tshuapa Province, Democratic Republic of Congo, 2009-2014.

OBJECTIVE: To describe varicella cases in Tshuapa Province of the Democratic Republic of the Congo identified during monkeypox surveillance. METHODS: Demographic, clinical and epidemiological data were collected from each suspected monkeypox case 2009-2014. Samples were tested by PCR for both Orthopoxviruses and varicella-zoster virus (VZV); a subset of VZV-positive samples was genotyped. We defined a varicella case as a rash illness with laboratory-confirmed VZV. RESULTS: There were 366 varicella cases were identified; 66% were ≤19 years old. Most patients had non-typical varicella rash with lesions reported as the same size and stage of evolution (86%), deep and profound (91%), on palms of hands and/or soles of feet (86%) and not itchy (49%). Many had non-typical signs and symptoms, such as lymphadenopathy (70%) and sensitivity to light (23%). A higher proportion of persons aged ≥20 years than persons aged ≤19 years had ≥50 lesions (79% vs. 65%, P = 0.007) and were bedridden (15% vs. 9%, P = 0.056). All VZV isolates genotyped from 79 varicella cases were clade 5. During the surveillance period, one possible VZV-related death occurred in a 7-year-old child. CONCLUSIONS: A large proportion of patients presented with non-typical varicella rash and clinical signs and symptoms, highlighting challenges identifying varicella in an area with endemic monkeypox. Continued surveillance and laboratory diagnosis will help in rapid identification and control of both monkeypox and varicella and improve our understanding of varicella epidemiology in Africa.

OBJECTIF: Décrire les cas de varicelle identifiés dans la province de Tshuapa en République Démocratique du Congo (RDC) au cours de la surveillance de la variole du singe (monkeypox). MÉTHODES: Des données démographiques, cliniques et épidémiologiques ont été recueillies pour chaque cas présumé de monkeypox entre 2009 et 2014. Les échantillons ont été testés par PCR pour les orthopoxvirus et le virus varicelle-zona (VZV); un sous-ensemble d'échantillons positifs au VZV a été génotypé. Nous avons défini un cas de varicelle comme une éruption cutanée avec confirmation du VZV en laboratoire. RÉSULTATS: 366 cas de varicelle ont été identifiés; 66% avaient 19 ans ou moins. La plupart des patients présentaient une éruption non typique de varicelle avec des lésions rapportées de la même taille et le même stade d'évolution (86%), profonds (91%), sur la paume des mains et/ou la plante des pieds (86%), sans démangeaisons (49%). Nombre d'entre eux présentaient des signes et des symptômes inhabituels, tels qu'une adénopathie lymphatique (70%) et une sensibilité à la lumière (23%). Une proportion plus élevée de personnes âgées de 20 ans et plus que de personnes âgées de 19 ans et moins avaient 50 lésions ou plus (79% contre 65%, p = 0,007) et étaient alitées (15% contre 9%; p = 0,056). Tous les isolats de VZV génotypés chez 79 cas de varicelle appartenaient au clade 5. Au cours de la période de surveillance, un décès possible lié au VZV est survenu chez un enfant de 7 ans. CONCLUSIONS: Une forte proportion de patients ont présenté une éruption de varicelle ainsi que des signes et symptômes cliniques non typiques, soulignant les difficultés rencontrées pour identifier la varicelle dans une zone endémique pour le monkeypox. Une surveillance continue et des diagnostics de laboratoire aideront à identifier et à contrôler rapidement le monkeypox et la varicelle et à améliorer notre compréhension sur l'épidémiologie de la varicelle en Afrique.

Hepatitis B infection among pregnant and post-partum women living with HIV and on antiretroviral therapy in Kinshasa, DR Congo: A cross-sectional study.

BACKGROUND: Hepatitis B virus (HBV) co-infection in HIV-infected individuals increases the risk of hepatic complications and mortality. Further, the risk of perinatal HBV transmission increases among HBV/HIV co-infected pregnant women. Although HBV is endemic in the Democratic Republic of Congo, there is little data on HBV/HIV co-infection. We aimed to assess the burden and risk factors of HBV surface antigen (HBsAg) positivity among HIV-infected pregnant and post-partum women. METHODS: This cross-sectional study was conducted as part of an ongoing trial to assess the effect of data-driven continuous quality improvement interventions (CQI) for optimal prevention of mother-to-child transmission (PMTCT) of HIV (CQI-PMTCT study, NCT03048669). In each of the 35 health zones of Kinshasa province, all HIV-infected pregnant or breastfeeding women (≤1 year post-delivery) presenting for care in one of the three busiest maternal and child health clinics of the health zone were tested for HBsAg using Alere Determine, Japan. We used logistic regression with general estimating equation accounting for within-clinic clustering to assess risk factors of HBsAg positivity. RESULTS: Between November 2016 and June 2018, a total of 1377 women, all on antiretroviral therapy, were tested for HBsAg. Overall, 4.7% [95% binomial confidence interval (CI): 3.7%-5.7%] tested positive for HBsAg. HBsAg prevalence was 3.3% (95% CI: 2.1%-4.8%) for women tested during pregnancy, 4.5% (2.5%-7.4%) for those tested at delivery, and 8.5% (5.6%-12.2%) for those tested post-partum (Ptrend = 0.001). In multivariate models including socio-economic status (SES), type of care facility, duration of antiretroviral therapy, HIV viral load, and self-reported intimate partner violence (IPV), lowest tertile of SES, ≤ 6 months of ART, and IPV were all consistently and positively associated with higher prevalence of HBsAg across pregnancy, delivery, and postpartum period while been tested in a health centre or having a viral load ≥ 1000 copies/mL were consistently associated with lower prevalence. However, only the association with IPV (OR = 2.74, 95% CI: 1.10-6.84) and viral load between 40-1000 copies/ml (OR = 4.28, 95% CI: 1.22-15.01) achieved statistical significance among pregnant women. CONCLUSION: This study revealed an overall high prevalence of HBsAg among HIV-infected pregnant and post-partum women in Kinshasa with the latter showing the highest HBsAg prevalence. Among pregnant women, intimate partner violence was independently and statistically associated with HBsAg positivity, requiring further investigation.

Modeling outbreak data: Analysis of a 2012 Ebola virus disease epidemic in DRC.

We describe two approaches to modeling data from a small to moderate-sized epidemic outbreak. The first approach is based on a branching process approximation and direct analysis of the transmission network, whereas the second one is based on a survival model derived from the classical SIR equations with no explicit transmission information. We compare these approaches using data from a 2012 outbreak of Ebola virus disease caused by Bundibugyo ebolavirus in city of Isiro, Democratic Republic of the Congo. The branching process model allows for a direct comparison of disease transmission across different environments, such as the general community or the Ebola treatment unit. However, the survival model appears to yield parameter estimates with more accuracy and better precision in some circumstances.

Epidemiology of circulating human influenza viruses from the Democratic Republic of Congo, 2015.

INTRODUCTION: The establishment of the influenza sentinel surveillance system in Kinshasa, Bas Congo, Maniema, Katanga, and Kasai Provinces allowed generation of important data on the molecular epidemiology of human influenza viruses circulating in the Democratic Republic of Congo (DRC). However, some challenges still exist, including the need for extending the influenza surveillance to more provinces. This study describes the pattern of influenza virus circulating in DRC during 2015. METHODOLOGY: Nasopharyngeal swabs were collected from January to December 2015 from outpatients with influenza-like illness (ILI) and in all hospitalized patients with Severe Acute Respiratory Infection (SARI). Molecular analysis was done to determine influenza type and subtype at the National Reference Laboratory (NRL) in Kinshasa using real time reverse transcription-polymerase chain reaction (rRT-PCR). Analysis of antiviral resistance by enzyme inhibition assay and nucleotide sequencing was performed by the Collaborating center in the USA (CDC, Atlanta). RESULTS: Out of 2,376 nasopharyngeal swabs collected from patients, 218 (9.1%) were positive for influenza virus. Among the positive samples, 149 were characterized as influenza virus type A (Flu A), 67 as type B (Flu B) and 2 mixed infections (Flu A and B). Flu A subtypes detected were H3N2 and H1N1. The Yamagata strain of Flu B was detected among patients in the country. Individuals aged between 5 and 14 years accounted for the largest age group affected by influenza virus. All influenza viruses detected were found to be sensitive to antiviral drugs such as oseltamivar, zanamivir, peramivir and laninamivar. CONCLUSION: The present study documented the possible involvement of both circulation of Flu A and B viruses in human respiratory infection in certain DRC provinces during 2015. This study emphasises the need to extend the influenza surveillance to other provinces for a better understanding of the epidemiology of influenza in DRC. It is envisioned that such a system would lead to improved disease control and patient management.

Intimate partner violence and prevention of mother to child transmission of HIV: Evidence from Kinshasa, Democratic Republic of Congo.

Intimate partner violence (IPV) is a risk factor for non-adherence to HIV treatment for women, however the evidence on the impact of IPV on uptake of the prevention of mother to child transmission of HIV (PMTCT) cascade is inconclusive. We examined data from 433 HIV positive pregnant women in Kinshasa, Democratic Republic of Congo, enrolled between April 2013 and August 2014 and followed-up through 6 weeks postpartum. Participants were asked about their IPV experiences in a face-to-face interview at enrollment. Measures of PMTCT cascade included: uptake of clinical appointments and services, viral suppression, and adherence to antiretrovirals (ARV). Approximately half of the sample (51%) had experienced some form of IPV; 35% had experienced emotional abuse, 29% physical abuse, and 19% sexual abuse. There were no statistically significant associations between experiencing any form of IPV and uptake of clinical appointments and services (Adjusted Prevalence Ratio [aPR] = 1.02; 95% [CI]: 0.89-1.17), viral load suppression (aPR = 1.07, 95% CI:0.96-1.19) and ARV adherence (aPR = 1.01, 95% CI: 0.87-1.18). Findings from this study indicate that, among HIV-infected pregnant women enrolled in PMTCT care, experiencing IPV does not reduce adherence to clinic visits and services, adherence to ARV. The high prevalence of IPV in this population suggests that IPV screening and intervention should be included as part of standard care for PMTCT.

Prevalence of Rubella Antibodies Among Children in the Democratic Republic of the Congo.

BACKGROUND: While generally mild in children, rubella infection in early pregnancy can lead to miscarriage, fetal death or congenital rubella syndrome. Rubella vaccination is not yet available as a part of routine immunization in the Democratic Republic of the Congo (DRC), and the burden of infection is unknown. METHODS: In collaboration with the 2013-2014 DRC Demographic and Health Survey, a serosurvey was carried out to assess population immunity to vaccine-preventable diseases. Dry blood spot samples collected from children 6-59 months of age were processed using the Dynex Technologies Multiplier FLEX chemiluminescent immunoassay platform (Dynex Technologies, Chantilly, VA). RESULTS: Among the 7195 6- to 59-month-old children, 33% were positive and <1% indeterminate for rubella antibodies in weighted analyses. Seroprevalence was positively associated with age of the child and province, with seropositivity highest in Bandundu (53%) and lowest in Kasai-Oriental (20%). In multivariate analyses, serologic evidence of infection was associated with age of the mother and child, socioeconomic status and geographic location. CONCLUSIONS: Rubella infection is prevalent among children in the DRC, and while most seroconversion occurs in young children, a significant proportion of children remain at risk and may enter reproductive age susceptible to rubella infection. While not currently in place, implementation of a surveillance program will provide improved estimates of both rubella virus circulation and the burden of congenital rubella syndrome. Such information will play an important role in future policy decisions, vaccine delivery strategies and may provide a basis upon which the effectiveness of rubella antigen introduction may be assessed.

Low Varicella Zoster Virus Seroprevalence Among Young Children in the Democratic Republic of the Congo.

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.

Enhancing case definitions for surveillance of human monkeypox in the Democratic Republic of Congo.

BACKGROUND: Human monkeypox (MPX) occurs at appreciable rates in the Democratic Republic of Congo (DRC). Infection with varicella zoster virus (VZV) has a similar presentation to that of MPX, and in areas where MPX is endemic these two illnesses are commonly mistaken. This study evaluated the diagnostic utility of two surveillance case definitions for MPX and specific clinical characteristics associated with laboratory-confirmed MPX cases. METHODOLOGY/PRINCIPAL FINDINGS: Data from a cohort of suspect MPX cases (identified by surveillance over the course of a 42 month period during 2009-2014) from DRC were used; real-time PCR diagnostic test results were used to establish MPX and VZV diagnoses. A total of 333 laboratory-confirmed MPX cases, 383 laboratory-confirmed VZV cases, and 36 cases that were determined to not be either MPX or VZV were included in the analyses. Significant (p<0.05) differences between laboratory-confirmed MPX and VZV cases were noted for several signs/symptoms including key rash characteristics. Both surveillance case definitions had high sensitivity and low specificities for individuals that had suspected MPX virus infections. Using 12 signs/symptoms with high sensitivity and/or specificity values, a receiver operator characteristic analysis showed that models for MPX cases that had the presence of 'fever before rash' plus at least 7 or 8 of the 12 signs/symptoms demonstrated a more balanced performance between sensitivity and specificity. CONCLUSIONS: Laboratory-confirmed MPX and VZV cases presented with many of the same signs and symptoms, and the analysis here emphasized the utility of including 12 specific signs/symptoms when investigating MPX cases. In order to document and detect endemic human MPX cases, a surveillance case definition with more specificity is needed for accurate case detection. In the absence of a more specific case definition, continued emphasis on confirmatory laboratory-based diagnostics is warranted.

Human Exposure to Wild Animals in the Sankuru Province of the Democratic Republic of the Congo.

Due to the high level of biological diversity in the Congo Basin and human population dependence on bushmeat, the DRC represents an ideal location for expanding knowledge on wild animal exposures and thus the potential for transmission of zoonotic pathogens. However, limited information exists on patterns and extent of contact with wildlife in such communities. Using a cross-sectional study, 14 villages in the Sankuru Province of the DRC were surveyed between August and September 2007. Villagers ≥ 1 year of age and at home of the time of the survey were eligible and enrolled to describe and assess factors associated with animal exposures (both activity and type of animal). Among respondents, 91% reported exposure to rodents, 89% to duikers, 78% to non-human primates (NHPs), and 32% reported contact with bats in the month prior to the survey. The most frequently reported activities included eating (95%), cooking (70%), and butchering or skinning of animals (55%). The activities and animals to which subjects had contact varied by sex and age. Moreover, we observed a high correlation of the same activities across animal types. In this and other populations that rely on bushmeat, there is a high frequency of exposure to multiple animal species through various modalities. In the event of future zoonotic disease outbreaks, effective public health interventions and campaigns that mitigate the risk of animal contact during outbreaks need to be broad to include various modes of contact and should be directed to both men and women across all age groups. As available information is limited, further studies are necessary to better understand the complex relationships and exposures individuals have with animals.

Continuous quality improvement interventions to improve long-term outcomes of antiretroviral therapy in women who initiated therapy during pregnancy or breastfeeding in the Democratic Republic of Congo: design of an open-label, parallel, group randomized trial.

BACKGROUND: Despite the rapid adoption of the World Health Organization's 2013 guidelines, children continue to be infected with HIV perinatally because of sub-optimal adherence to the continuum of HIV care in maternal and child health (MCH) clinics. To achieve the UNAIDS goal of eliminating mother-to-child HIV transmission, multiple, adaptive interventions need to be implemented to improve adherence to the HIV continuum. METHODS: The aim of this open label, parallel, group randomized trial is to evaluate the effectiveness of Continuous Quality Improvement (CQI) interventions implemented at facility and health district levels to improve retention in care and virological suppression through 24 months postpartum among pregnant and breastfeeding women receiving ART in MCH clinics in Kinshasa, Democratic Republic of Congo. Prior to randomization, the current monitoring and evaluation system will be strengthened to enable collection of high quality individual patient-level data necessary for timely indicators production and program outcomes monitoring to inform CQI interventions. Following randomization, in health districts randomized to CQI, quality improvement (QI) teams will be established at the district level and at MCH clinics level. For 18 months, QI teams will be brought together quarterly to identify key bottlenecks in the care delivery system using data from the monitoring system, develop an action plan to address those bottlenecks, and implement the action plan at the level of their district or clinics. DISCUSSION: If proven to be effective, CQI as designed here, could be scaled up rapidly in resource-scarce settings to accelerate progress towards the goal of an AIDS free generation. TRIAL REGISTRATION: The protocol was retrospectively registered on February 7, 2017. ClinicalTrials.gov Identifier: NCT03048669 .

Presumptive risk factors for monkeypox in rural communities in the Democratic Republic of the Congo.

Monkeypox virus (MPXV), a close relative of Variola virus, is a zoonotic virus with an unknown reservoir. Interaction with infected wildlife, bites from peri-domestic animals, and bushmeat hunting are hypothesized routes of infection from wildlife to humans. Using a Risk Questionnaire, performed in monkeypox-affected areas of rural Democratic Republic of the Congo, we describe the lifestyles and demographics associated with presumptive risk factors for MPXV infection. We generated two indices to assess risk: Household Materials Index (HMI), a proxy for socioeconomic status of households and Risk Activity Index (RAI), which describes presumptive risk for animal-to-human transmission of MPXV. Based on participant self-reported activity patterns, we found that people in this population are more likely to visit the forest than a market to fulfill material needs, and that the reported occupation is limited in describing behavior of individuals may participate. Being bitten by rodents in the home was commonly reported, and this was significantly associated with a low HMI. The highest scoring RAI sub-groups were 'hunters' and males aged ≥ 18 years; however, several activities involving MPXV-implicated animals were distributed across all sub-groups. The current analysis may be useful in identifying at-risk groups and help to direct education, outreach and prevention efforts more efficiently.

Evaluation of the GeneXpert for Human Monkeypox Diagnosis.

Monkeypox virus (MPXV), a zoonotic orthopoxvirus (OPX), is endemic in the Democratic Republic of Congo (DRC). Currently, diagnostic assays for human monkeypox (MPX) focus on real-time quantitative polymerase chain reaction (PCR) assays, which are typically performed in sophisticated laboratory settings. Herein, we evaluated the accuracy and utility of a multiplex MPX assay using the GeneXpert platform, a portable rapid diagnostic device that may serve as a point-of-care test to diagnose infections in endemic areas. The multiplex MPX/OPX assay includes a MPX-specific PCR test, OPX-generic PCR test, and an internal control PCR test. In total, 164 diagnostic specimens (50 crusts and 114 vesicular swabs) were collected from suspected MPX cases in Tshuapa Province, DRC, under national surveillance guidelines. The specimens were tested with the GeneXpert MPX/OPX assay and an OPX PCR assay at the Institut National de Recherche Biomedicale (INRB) in Kinshasa. Aliquots of each specimen were tested in parallel with a MPX-specific PCR assay at the Centers for Disease Control and Prevention. The results of the MPX PCR were used as the gold standard for all analyses. The GeneXpert MPX/OPX assay performed at INRB had a sensitivity of 98.8% and specificity of 100%. The GeneXpert assay performed well with both crust and vesicle samples. The GeneXpert MPX/OPX test incorporates a simple methodology that performs well in both laboratory and field conditions, suggesting its viability as a diagnostic platform that may expand and expedite current MPX detection capabilities.