Search

Outbreaks of monkeypox (mpox) have historically resulted from zoonotic spillover of clade I monkeypox virus (MPXV) in Central Africa and clade II MPXV in West Africa. In 2022, subclade IIb caused a global epidemic linked to transmission through sexual contact. Here we describe the epidemiological and genomic features of an mpox outbreak in a mining region in eastern Democratic Republic of the Congo, caused by clade I MPXV. Surveillance data collected between September 2023 and January 2024 identified 241 suspected cases. Genomic analysis demonstrates a distinct clade I lineage divergent from previously circulating strains in the Democratic Republic of the Congo. Of the 108 polymerase chain reaction-confirmed mpox cases, the median age of individuals was 22 years, 51.9% were female and 29% were sex workers, suggesting a potential role for sexual transmission. The predominance of APOBEC3-type mutations and the estimated emergence time around mid-September 2023 imply recent sustained human-to-human transmission.

Between January and August 2024, mpox cases have been reported in nearly all provinces of the Democratic Republic of the Congo (DRC). Monkeypox virus genome sequences were obtained from 11 mpox cases samples, collected in July-August 2024 in several health zones of Kinshasa. Characterisation of the sequences showed subclades Ia and Ib co-circulating in the Limete health zone, while phylogenetic analyses suggested multiple introductions of the two subclades in Kinshasa. This illustrates the growing complexity of Clade I mpox outbreaks in DRC.

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.

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.

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.

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.).

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

Metagenomic next-generation sequencing (mNGS), the shotgun sequencing of RNA and DNA from clinical samples, has proved useful for broad-spectrum pathogen detection and the genomic surveillance of viral outbreaks. An additional target enrichment step is generally needed for high-sensitivity pathogen identification in low-titre infections, yet available methods using PCR or capture probes can be limited by high cost, narrow scope of detection, lengthy protocols and/or cross-contamination. Here, we developed metagenomic sequencing with spiked primer enrichment (MSSPE), a method for enriching targeted RNA viral sequences while simultaneously retaining metagenomic sensitivity for other pathogens. We evaluated MSSPE for 14 different viruses, yielding a median tenfold enrichment and mean 47% (±16%) increase in the breadth of genome coverage over mNGS alone. Virus detection using MSSPE arboviral or haemorrhagic fever viral panels was comparable in sensitivity to specific PCR, demonstrating 95% accuracy for the detection of Zika, Ebola, dengue, chikungunya and yellow fever viruses in plasma samples from infected patients. Notably, sequences from re-emerging and/or co-infecting viruses that have not been specifically targeted a priori, including Powassan and Usutu, were successfully enriched using MSSPE. MSSPE is simple, low cost, fast and deployable on either benchtop or portable nanopore sequencers, making this method directly applicable for diagnostic laboratory and field use.

Since the ignition of the HIV-1 group M pandemic in the beginning of the 20th century, group M lineages have spread heterogeneously throughout the world. Subtype C spread rapidly through sub-Saharan Africa and is currently the dominant HIV lineage worldwide. Yet the epidemiological and evolutionary circumstances that contributed to its epidemiological expansion remain poorly understood. Here, we analyse 346 novel pol sequences from the DRC to compare the evolutionary dynamics of the main HIV-1 lineages, subtypes A1, C and D. Our results place the origins of subtype C in the 1950s in Mbuji-Mayi, the mining city of southern DRC, while subtypes A1 and D emerged in the capital city of Kinshasa, and subtypes H and J in the less accessible port city of Matadi. Following a 15-year period of local transmission in southern DRC, we find that subtype C spread at least three-fold faster than other subtypes circulating in Central and East Africa. In conclusion, our results shed light on the origins of HIV-1 main lineages and suggest that socio-historical rather than evolutionary factors may have determined the epidemiological fate of subtype C in sub-Saharan Africa.

As of June 16, 2019, an Ebola virus disease (EVD) outbreak has led to 2136 reported cases in the northeastern region of the Democratic Republic of the Congo (DRC). As this outbreak continues to threaten the lives and livelihoods of people already suffering from civil strife and armed conflict, relatively simple mathematical models and their short-term predictions have the potential to inform Ebola response efforts in real time. We applied recently developed non-parametrically estimated Hawkes point processes to model the expected cumulative case count using daily case counts from May 3, 2018, to June 16, 2019, initially reported by the Ministry of Health of DRC and later confirmed in World Health Organization situation reports. We generated probabilistic estimates of the ongoing EVD outbreak in DRC extending both before and after June 16, 2019, and evaluated their accuracy by comparing forecasted vs. actual outbreak sizes, out-of-sample log-likelihood scores and the error per day in the median forecast. The median estimated outbreak sizes for the prospective thee-, six-, and nine-week projections made using data up to June 16, 2019, were, respectively, 2317 (95% PI: 2222, 2464); 2440 (95% PI: 2250, 2790); and 2544 (95% PI: 2273, 3205). The nine-week projection experienced some degradation with a daily error in the median forecast of 6.73 cases, while the six- and three-week projections were more reliable, with corresponding errors of 4.96 and 4.85 cases per day, respectively. Our findings suggest the Hawkes point process may serve as an easily-applied statistical model to predict EVD outbreak trajectories in near real-time to better inform decision-making and resource allocation during Ebola response efforts.

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

IntroductionAs of April 2019, the current Ebola virus disease (EVD) outbreak in the Democratic Republic of the Congo (DRC) is occurring in a longstanding conflict zone and has become the second largest EVD outbreak in history. It is suspected that after violent events occur, EVD transmission will increase; however, empirical studies to understand the impact of violence on transmission are lacking. Here, we use spatial and temporal trends of EVD case counts to compare transmission rates between health zones that have versus have not experienced recent violent events during the outbreak.MethodsWe collected daily EVD case counts from DRC Ministry of Health. A time-varying indicator of recent violence in each health zone was derived from events documented in the WHO situation reports. We used the Wallinga-Teunis technique to estimate the reproduction number R for each case by day per zone in the 2018-2019 outbreak. We fit an exponentially decaying curve to estimates of R overall and by health zone, for comparison to past outbreaks.ResultsAs of 16 April 2019, the mean overall R for the entire outbreak was 1.11. We found evidence of an increase in the estimated transmission rates in health zones with recently reported violent events versus those without (p = 0.008). The average R was estimated as between 0.61 and 0.86 in regions not affected by recent violent events, and between 1.01 and 1.07 in zones affected by violent events within the last 21 days, leading to an increase in R between 0.17 and 0.53. Within zones with recent violent events, the mean estimated quenching rate was lower than for all past outbreaks except the 2013-2016 West African outbreak.ConclusionThe difference in the estimated transmission rates between zones affected by recent violent events suggests that violent events are contributing to increased transmission and the ongoing nature of this outbreak.