Resurgence of Ebola virus in 2021 in Guinea suggests a new paradigm for outbreaks.

Seven years after the declaration of the first epidemic of Ebola virus disease in Guinea, the country faced a new outbreak-between 14 February and 19 June 2021-near the epicentre of the previous epidemic1,2. Here we use next-generation sequencing to generate complete or near-complete genomes of Zaire ebolavirus from samples obtained from 12 different patients. These genomes form a well-supported phylogenetic cluster with genomes from the previous outbreak, which indicates that the new outbreak was not the result of a new spillover event from an animal reservoir. The 2021 lineage shows considerably lower divergence than would be expected during sustained human-to-human transmission, which suggests a persistent infection with reduced replication or a period of latency. The resurgence of Zaire ebolavirus from humans five years after the end of the previous outbreak of Ebola virus disease reinforces the need for long-term medical and social care for patients who survive the disease, to reduce the risk of re-emergence and to prevent further stigmatization.

Comparison of stochastic and deterministic models for gambiense sleeping sickness at different spatial scales: A health area analysis in the DRC.

The intensification of intervention activities against the fatal vector-borne disease gambiense human African trypanosomiasis (gHAT, sleeping sickness) in the last two decades has led to a large decline in the number of annually reported cases. However, while we move closer to achieving the ambitious target of elimination of transmission (EoT) to humans, pockets of infection remain, and it becomes increasingly important to quantitatively assess if different regions are on track for elimination, and where intervention efforts should be focused. We present a previously developed stochastic mathematical model for gHAT in the Democratic Republic of Congo (DRC) and show that this same formulation is able to capture the dynamics of gHAT observed at the health area level (approximately 10,000 people). This analysis was the first time any stochastic gHAT model has been fitted directly to case data and allows us to better quantify the uncertainty in our results. The analysis focuses on utilising a particle filter Markov chain Monte Carlo (MCMC) methodology to fit the model to the data from 16 health areas of Mosango health zone in Kwilu province as a case study. The spatial heterogeneity in cases is reflected in modelling results, where we predict that under the current intervention strategies, the health area of Kinzamba II, which has approximately one third of the health zone's cases, will have the latest expected year for EoT. We find that fitting the analogous deterministic version of the gHAT model using MCMC has substantially faster computation times than fitting the stochastic model using pMCMC, but produces virtually indistinguishable posterior parameterisation. This suggests that expanding health area fitting, to cover more of the DRC, should be done with deterministic fits for efficiency, but with stochastic projections used to capture both the parameter and stochastic variation in case reporting and elimination year estimations.

Rhabdomyolysis, Acute Kidney Injury, and Mortality in Ebola Virus Disease: Retrospective Analysis of Cases From the Eastern Democratic Republic of the Congo, 2019.

BACKGROUND: Skeletal muscle injury in Ebola virus disease (EVD) has been reported, but its association with morbidity and mortality remains poorly defined. METHODS: This retrospective study included patients admitted to 2 EVD treatment units over an 8-month period in 2019 during an EVD epidemic in the Democratic Republic of the Congo. RESULTS: An overall 333 patients (median age, 30 years; 58% female) had at least 1 creatine kinase (CK) measurement (n = 2229; median, 5/patient [IQR, 1-11]). Among patients, 271 (81%) had an elevated CK level (>380 U/L); 202 (61%) had rhabdomyolysis (CK >1000 IU/L); and 45 (14%) had severe rhabdomyolysis (≥5000 U/L). Among survivors, the maximum CK level was a median 1600 (IQR, 550-3400), peaking 3.4 days after admission (IQR, 2.3-5.5) and decreasing thereafter. Among fatal cases, the CK rose monotonically until death, with a median maximum CK level of 2900 U/L (IQR, 1500-4900). Rhabdomyolysis at admission was an independent predictor of acute kidney injury (adjusted odds ratio, 2.2 [95% CI, 1.2-3.8]; P = .0065) and mortality (adjusted hazard ratio, 1.7 [95% CI, 1.03-2.9]; P = .037). CONCLUSIONS: Rhabdomyolysis is associated with acute kidney injury and mortality in patients with EVD. These findings may inform clinical practice by identifying laboratory monitoring priorities and highlighting the importance of fluid management.

Clade I-Associated Mpox Cases Associated with Sexual Contact, the Democratic Republic of the Congo.

We report a cluster of clade I monkeypox virus infections linked to sexual contact in the Democratic Republic of the Congo. Case investigations resulted in 5 reverse transcription PCR-confirmed infections; genome sequencing suggest they belonged to the same transmission chain. This finding demonstrates that mpox transmission through sexual contact extends beyond clade IIb.

Spatiotemporal Modeling of Cholera, Uvira, Democratic Republic of the Congo, 2016-2020.

We evaluated the spatiotemporal clustering of rapid diagnostic test-positive cholera cases in Uvira, eastern Democratic Republic of the Congo. We detected spatiotemporal clusters that consistently overlapped with major rivers, and we outlined the extent of zones of increased risk that are compatible with the radii currently used for targeted interventions.

Co-Circulating Monkeypox and Swinepox Viruses, Democratic Republic of the Congo, 2022.

In September 2022, deaths of pigs manifesting pox-like lesions caused by swinepox virus were reported in Tshuapa Province, Democratic Republic of the Congo. Two human mpox cases were found concurrently in the surrounding community. Specific diagnostics and robust sequencing are needed to characterize multiple poxviruses and prevent potential poxvirus transmission.

Ebola Virus Transmission Initiated by Relapse of Systemic Ebola Virus Disease.

During the 2018-2020 Ebola virus disease (EVD) outbreak in North Kivu province in the Democratic Republic of Congo, EVD was diagnosed in a patient who had received the recombinant vesicular stomatitis virus-based vaccine expressing a ZEBOV glycoprotein (rVSV-ZEBOV) (Merck). His treatment included an Ebola virus (EBOV)-specific monoclonal antibody (mAb114), and he recovered within 14 days. However, 6 months later, he presented again with severe EVD-like illness and EBOV viremia, and he died. We initiated epidemiologic and genomic investigations that showed that the patient had had a relapse of acute EVD that led to a transmission chain resulting in 91 cases across six health zones over 4 months. (Funded by the Bill and Melinda Gates Foundation and others.).

Estimating the relative importance of epidemiological and behavioural parameters for epidemic mpox transmission: a modelling study.

BACKGROUND: Many European countries experienced outbreaks of mpox in 2022, and there was an mpox outbreak in 2023 in the Democratic Republic of Congo. There were many apparent differences between these outbreaks and previous outbreaks of mpox; the recent outbreaks were observed in men who have sex with men after sexual encounters at common events, whereas earlier outbreaks were observed in a wider population with no identifiable link to sexual contacts. These apparent differences meant that data from previous outbreaks could not reliably be used to parametrise infectious disease models during the 2022 and 2023 mpox outbreaks, and modelling efforts were hampered by uncertainty around key transmission and immunity parameters. METHODS: We developed a stochastic, discrete-time metapopulation model for mpox that allowed for sexual and non-sexual transmission and the implementation of non-pharmaceutical interventions, specifically contact tracing and pre- and post-exposure vaccinations. We calibrated the model to case data from Berlin and used Sobol sensitivity analysis to identify parameters that mpox transmission is especially sensitive to. We also briefly analysed the sensitivity of the effectiveness of non-pharmaceutical interventions to various efficacy parameters. RESULTS: We found that variance in the transmission probabilities due to both sexual and non-sexual transmission had a large effect on mpox transmission in the model, as did the level of immunity to mpox conferred by a previous smallpox vaccination. Furthermore, variance in the number of pre-exposure vaccinations offered was the dominant contributor to variance in mpox dynamics in men who have sex with men. If pre-exposure vaccinations were not available, both the accuracy and timeliness of contact tracing had a large impact on mpox transmission in the model. CONCLUSIONS: Our results are valuable for guiding epidemiological studies for parameter ascertainment and identifying key factors for success of non-pharmaceutical interventions.

Unveiling mortality risk factors in paediatric sickle cell disease patients during acute crises in the Democratic Republic of the Congo.

Sickle cell disease (SCD) is a significant health burden in the Democratic Republic of the Congo (DRC). This study aims to identify predictive factors of mortality in SCD children admitted to emergency care in Lubumbashi, DRC. We performed a non-interventional cohort follow-up on SCD patients aged 0 to 16 admitted for a "true emergency". Demographic, clinical, and biological data were collected. Univariate and multivariate logistic regression analyses were performed to identify significant risk factors associated with mortality. Among the 121 patients included, 24 died during the follow-up period. Univariate regression revealed age, Mikobi score, referral origin, stroke, and severe infection as significant risk factors. Multivariate analyses identified Hb, WBC, SR, and LDH as predictive factors of mortality. Notably, patients aged 12 to 16 years faced a higher risk, shifting the age of mortality from early to late childhood and adolescence. This study provides valuable insights into mortality risk factors for paediatric SCD patients during acute crises. Early diagnosis, regular follow-up, and therapeutic education are essential to improve patient outcomes and survival rates. These findings contribute to better disease management and targeted interventions, aiming to reduce mortality associated with SCD.

High pre-Delta and early-Omicron SARS-CoV-2 seroprevalence detected in dried blood samples from Kinshasa (D.R. Congo).

Studies on the impact of the COVID-19 pandemic in sub-Saharan Africa have yielded varying results, although authors universally agree the real burden surpasses reported cases. The primary objective of this study was to determine SARS-CoV-2 seroprevalence among patients attending Monkole Hospital in Kinshasa (D.R. Congo). The secondary objective was to evaluate the analytic performance of two chemiluminescence platforms: Elecsys® (Roche) and VirClia® (Vircell) on dried blood spot samples (DBS). The study population (N = 373) was recruited in two stages: a mid-2021 blood donor cohort (15.5% women) and a mid-2022 women cohort. Crude global seroprevalence was 61% (53.9%-67.8%) pre-Delta in 2021 and 90.2% (84.7%-94.2%) post-Omicron in 2022. Anti-spike (S) antibody levels significantly increased from 53.1 (31.8-131.3) U/mL in 2021 to 436.5 (219.3-950.5) U/mL in 2022 and were significantly higher above 45 years old in the 2022 population. Both platforms showed good analytic performance on DBS samples: sensitivity was 96.8% for IgG (antiN/S) (93.9%-98.5%) and 96.0% (93.0%-98.0%) for anti-S quantification. These results provide additional support for the notion that exposure to SARS-CoV-2 is more widespread than indicated by case-based surveillance and will be able to guide the pandemic response and strategy moving forward. Likewise, this study contributes evidence to the reliability of DBS as a tool for serological testing and diagnosis in resource-limited settings.

Epidemiological, anatomoclinical, and therapeutic profile of obstetric fistula in the Democratic Republic of the Congo: About 1267 patients.

OBJECTIVE: Our aim is to describe the epidemiological, anatomoclinical and therapeutic profile of obstetric fistula (OF) in the Democratic Republic of the Congo (DRC). METHODOLOGY: This was a descriptive retrospective study that collected 1416 obstetric fistulas in 1267 patients in seven provinces of the DRC, treated between January 2017 and December 2022. The variables studied were epidemiological, anatomoclinical and therapeutic. RESULTS: The mean age of patients at the time of surgical repair was 33.2 years (range: 15 and 77 years) and 32.8% of patients were aged between 20 and 29 years. The mean age of the fistula at repair was 10 years (range: 3.5 months and 56 years). At the time of fistula, 61.7% of patients had delivered vaginally and 28.7% by caesarean section and 8.2% of patients had a haemostasis hysterectomy. Labour lasted at least 3 days in 47.3% of these patients for the fistula birth. Deliveries took place either at home (27.4%) or in a health facility (72.6%); 83.6% of newborns resulting from these births had died. Taken as a whole, urogenital fistulas are more common than genito-digestive fistulas. Urethro-vaginal (26.2%) and vesico-uterine (24.7%) anatomoclinical entities were predominant among urogenital fistulas. A total of 1416 fistulas were surgically repaired in 1267 patients. These repairs were successful for 1226 (86.6%) fistulas. The main surgical route used was transvaginal (68.8%). CONCLUSION: In the DRC, obstetric fistula is common in young adult women. It often results from vaginal delivery, after prolonged labour. Fistula births often result in the death of newborns. Uro-genital obstetric fistulas are the most frequent with predominance of urethro-vaginal and vesico-uterine anatomoclinical entities. Fistulas remain untreated for a long time. Mostly done transvaginally, surgical repair gives a good result.

Evaluation of a rapid diagnostic test for detection of Vibrio cholerae O1 in the Democratic Republic of the Congo: Preventative intervention for cholera for 7 days (PICHA7 program).

OBJECTIVE: Globally, there are estimated to be 2.9 million cholera cases annually. Early detection of cholera outbreaks is crucial for resource allocation for case management and for targeted interventions to be delivered to stop the spread of cholera. In resource limited settings such as Eastern Democratic Republic of the Congo (DRC), there is often limited laboratory capacity for analysing stool samples for cholera by bacterial culture. Therefore, rapid diagnostic tests (RDTs) for cholera present a promising tool to rapidly test stool samples in a health facility setting for cholera. Our objective is to evaluate the Crystal VC O1 RDT for cholera detection compared with bacterial culture and polymerase chain reaction (PCR) for Vibrio cholerae. METHODS: From March 2020 to December 2022, stool samples were collected from 644 diarrhoea patients admitted to 94 health facilities in Bukavu in Eastern DRC. Patient stool samples were analysed by Crystal VC O1 RDT for cholera and by bacterial culture and PCR for V. cholerae O1. RESULTS: Twenty six percent of diarrhoea patients (166/644) had stool samples positive for cholera by RDT, and 24% (152/644) had stool samples positive for V. cholerae O1 by bacterial culture or PCR. The overall specificity and sensitivity of the Crystal VC O1 RDT by direct testing was 94% (95% confidence interval [CI]: 92%-96%) and 90% (95% CI, 84%-94%), respectively, when compared with either a positive result by bacterial culture or PCR. CONCLUSION: Our findings suggest that the Crystal VC O1 RDT presents a promising tool for cholera surveillance in this cholera endemic setting in sub-Saharan Africa.

Completion of isoniazid preventive therapy for latent tuberculosis infection among children and adolescents compared to adults living with HIV in Kinshasa, Democratic Republic of the Congo.

BACKGROUND: Little is known about isoniazid preventive therapy (IPT) completion rates among children or adolescents compared to adults living with HIV in Kinshasa, Democratic Republic of the Congo (DRC). METHODS: We conducted a retrospective cohort analysis including children, adolescents, and adults living with HIV who were treated at FHI360 and partners-implemented HIV care programs at six health zones in Kinshasa, DRC, from 2004 to 2020. The primary outcome was the proportion of children, adolescents versus adults who did complete 6 months of daily self-administered IPT. Log-binomial regression assessed independent predictors of IPT non-completion and Kaplan-Meier technique for survival analysis. RESULTS: Of 11,691 eligible patients on ART who initiated IPT, 429 were children (<11 years), 804 adolescents (11-19 years), and 10,458 adults (≥20 years). The median age was 7 (IQR: 3-9) years for children, 15 (IQR: 13-17) years for adolescents, and 43 (35-51) years for adults. Among those who were initiated on IPT, 5625 out of 11,691 people living with HIV (PLHIV) had IPT completion outcome results, and an overall 3457/5625 (61.5%) completion rate was documented. Compared to adults, children and adolescents were less likely to complete IPT [104/199 (52.3%) and 268/525 (51.0%), respectively, vs. 3085/4901 (62.9%)]. After adjustment, the only independent predictors for IPT non-completion were health zone of residence and type of ART regimen. Kaplan-Meier analysis showed comparable poor survival among patients who completed IPT versus those who did not (p-value for log-rank test, 0.15). CONCLUSIONS: The overall sub-optimal IPT completion rate in adults as well as children/adolescents in this setting is of great concern. Prospective studies are needed to elucidate the specific barriers to IPT completion among children, adolescents, and adults in DRC as well as the scale-up of evidence-informed interventions to improve IPT completion, such as adoption of shorter TB preventive regimens.

U.S. Preparedness and Response to Increasing Clade I Mpox Cases in the Democratic Republic of the Congo - United States, 2024.

Clade I monkeypox virus (MPXV), which can cause severe illness in more people than clade II MPXVs, is endemic in the Democratic Republic of the Congo (DRC), but the country has experienced an increase in suspected cases during 2023-2024. In light of the 2022 global outbreak of clade II mpox, the increase in suspected clade I cases in DRC raises concerns that the virus could spread to other countries and underscores the importance of coordinated, urgent global action to support DRC's efforts to contain the virus. To date, no cases of clade I mpox have been detected outside of countries in Central Africa where the virus is endemic. CDC and other partners are working to support DRC's response. In addition, CDC is enhancing U.S. preparedness by raising awareness, strengthening surveillance, expanding diagnostic testing capacity for clade I MPXV, ensuring appropriate specimen handling and waste management, emphasizing the importance of appropriate medical treatment, and communicating guidance on the recommended contact tracing, containment, behavior modification, and vaccination strategies.

Malaria infection among adults residing in a highly endemic region from the Democratic Republic of the Congo.

BACKGROUND: Adults infected with Plasmodium spp. in endemic areas need to be re-evaluated in light of global malaria elimination goals. They potentially undermine malaria interventions but remain an overlooked aspect of public health strategies. METHODS: This study aimed to estimate the prevalence of Plasmodium spp. infections, to identify underlying parasite species, and to assess predicting factors among adults residing in an endemic area from the Democratic Republic of Congo (DRC). A community-based cross-sectional survey in subjects aged 18 years and above was therefore carried out. Study participants were interviewed using a standard questionnaire and tested for Plasmodium spp. using a rapid diagnostic test and a nested polymerase chain reaction assay. Logistic regression models were fitted to assess the effect of potential predictive factors for infections with different Plasmodium spp. RESULTS: Overall, 420 adults with an estimated prevalence of Plasmodium spp. infections of 60.2% [95% CI 55.5; 64.8] were included. Non-falciparum species infected 26.2% [95% CI 22.2; 30.5] of the study population. Among infected participants, three parasite species were identified, including Plasmodium falciparum (88.5%), Plasmodium malariae (39.9%), and Plasmodium ovale (7.5%) but no Plasmodium vivax. Mixed species accounted for 42.3% of infections while single-species infections predominated with P. falciparum (56.5%) among infected participants. All infected participants were asymptomatic at the time of the survey. Adults belonging to the "most economically disadvantaged" households had increased risks of infections with any Plasmodium spp. (adjusted odds ratio, aOR = 2.87 [95% CI 1.66, 20.07]; p < 0.001), compared to those from the "less economically disadvantaged" households. Conversely, each 1 year increase in age reduced the risk of infections with any Plasmodium spp. (aOR = 0.99 [95% CI 0.97, 0.99]; p = 0.048). Specifically for non-falciparum spp., males had increased risks of infection than females (aOR = 1.83 [95% CI 1.13, 2.96]; p = 0.014). CONCLUSION: Adults infected with malaria constitute a potentially important latent reservoir for the transmission of the disease in the study setting. They should specifically be taken into account in public health measures and translational research.

G-formula for observational studies under stratified interference, with application to bed net use on malaria.

Assessing population-level effects of vaccines and other infectious disease prevention measures is important to the field of public health. In infectious disease studies, one person's treatment may affect another individual's outcome, that is, there may be interference between units. For example, the use of bed nets to prevent malaria by one individual may have an indirect effect on other individuals living in close proximity. In some settings, individuals may form groups or clusters where interference only occurs within groups, that is, there is partial interference. Inverse probability weighted estimators have previously been developed for observational studies with partial interference. Unfortunately, these estimators are not well suited for studies with large clusters. Therefore, in this paper, the parametric g-formula is extended to allow for partial interference. G-formula estimators are proposed for overall effects, effects when treated, and effects when untreated. The proposed estimators can accommodate large clusters and do not suffer from the g-null paradox that may occur in the absence of interference. The large sample properties of the proposed estimators are derived assuming no unmeasured confounders and that the partial interference takes a particular form (referred to as 'weak stratified interference'). Simulation studies are presented demonstrating the finite-sample performance of the proposed estimators. The Demographic and Health Survey from the Democratic Republic of the Congo is then analyzed using the proposed g-formula estimators to assess the effects of bed net use on malaria.

Indicator-condition-guided HIV testing in rural DRC.

BACKGROUND: HIV testing services are a key component of the 95-95-95-0 goals. In many parts of the Democratic Republic of the Congo the availability of test kits is limited for multiple reasons. Targeted testing of patients with HIV indicator conditions is therefore the only feasible option in these settings. METHODS: We introduced an indicator condition-guided HIV testing project in the Emergency Room of the Hôpital Géneral de Référence de Kikwit, DRC. RESULTS: We screened 1274 patients for indicator condition. In 94 (7.4%) patients, the treating physician diagnosed at least one HIV indicator. 34 (36.2%) tested HIV-positive (2.7% of screened patients). 52% of the newly diagnosed patients were lost to follow-up two months after the first diagnosis of HIV. CONCLUSION: In a resource-limited setting with insufficient availability of HIV-Tests, indicator-triggered testing is a useful tool to find a high number of HIV-positive patients. Loss to follow-up is one of the major challenges.

Spatiotemporal dynamics of cholera hotspots in the Democratic Republic of the Congo from 1973 to 2022.

BACKGROUND: Since the early 1970s, cholera outbreaks have been a major public health burden in the Democratic Republic of Congo (DRC). Cholera cases have been reported in a quasi-continuous manner in certain lakeside areas in the Great Lakes Region. As these cholera-endemic health zones constitute a starting point for outbreaks and diffusion towards other at-risk areas, they play a major role in cholera dynamics in the country. Monitoring the spatiotemporal dynamics of cholera hotspots and adjusting interventions accordingly thus reduces the disease burden in an efficient and cost-effective manner. METHODS: A literature review was conducted to describe the spatiotemporal dynamics of cholera in the DRC at the province level from 1973 to 1999. We then identified and classified cholera hotspots at the provincial and health zone levels from 2003 to 2022 and described the spatiotemporal evolution of hotspots. We also applied and compared three different classification methods to ensure that cholera hotspots are identified and classified according to the DRC context. RESULTS: According to all three methods, high-priority hotspots were concentrated in the eastern Great Lakes Region. Overall, hotspots largely remained unchanged over the course of the study period, although slight improvements were observed in some eastern hotspots, while other non-endemic areas in the west experienced an increase in cholera outbreaks. The Global Task Force on Cholera Control (GTFCC) and the Department of Ecology and Infectious Disease Control (DEIDC) methods largely yielded similar results for the high-risk hotspots. However, the medium-priority hotspots identified by the GTFCC method were further sub-classified by the DEIDC method, thereby providing a more detailed ranking for priority targeting. CONCLUSIONS: Overall, the findings of this comprehensive study shed light on the dynamics of cholera hotspots in the DRC from 1973 to 2022. These results may serve as an evidence-based foundation for public health officials and policymakers to improve the implementation of the Multisectoral Cholera Elimination Plan, guiding targeted interventions and resource allocation to mitigate the impact of cholera in vulnerable communities.