Filoviruses are negative-sense single-stranded RNA viruses often associated with severe and highly lethal hemorrhagic fever in humans and nonhuman primates, with case fatality rates as high as 90%. Of the known filoviruses, Ebola virus (EBOV), the prototype of the genus Orthoebolavirus, has been a major public health concern as it frequently causes outbreaks and was associated with an unprecedented outbreak in several Western African countries in 2013–2016, affecting 28,610 people, 11,308 of whom died. Thereafter, filovirus research mostly focused on EBOV, paying less attention to other equally deadly orthoebolaviruses (Sudan, Bundibugyo, and Taï Forest viruses) and orthomarburgviruses (Marburg and Ravn viruses). Some of these filoviruses have emerged in nonendemic areas, as exemplified by four Marburg disease outbreaks recorded in Guinea, Ghana, Tanzania, and Equatorial Guinea between 2021 and 2023. Similarly, the Sudan virus has reemerged in Uganda 10 years after the last recorded outbreak. Moreover, several novel bat-derived filoviruses have been discovered in the last 15 years (Lloviu virus, Bombali virus, Měnglà virus, and Dehong virus), most of which are poorly characterized but may display a wide host range. These novel viruses have the potential to cause outbreaks in humans. Several gaps are yet to be addressed regarding known and emerging filoviruses. These gaps include the virus ecology and pathogenicity, mechanisms of zoonotic transmission, host range and susceptibility, and the development of specific medical countermeasures. In this review, we summarize the current knowledge on non-Ebola filoviruses (Bombali virus, Bundibugyo virus, Reston virus, Sudan virus, Tai Forest virus, Marburg virus, Ravn virus, Lloviu virus, Měnglà virus, and Dehong virus) and suggest some strategies to accelerate specific countermeasure development.

Background: Fever with jaundice is a common symptom of some infectious diseases. In public health surveillance within the Democratic Republic of the Congo (DRC), yellow fever is the only recognized cause of fever with jaundice. However, only 5% of the surveillance cases are positive for yellow fever and thus indicate the involvement of other pathogens. Leptospira spp. are the causative agents of leptospirosis, a widespread bacterial zoonosis, a known cause of fever with jaundice. This study aimed to determine the seropositivity of anti-Leptospira antibodies among suspected yellow fever cases and map the geographical distribution of possible leptospirosis in the DRC. Methods: We conducted a retrospective study using 1,300 samples from yellow fever surveillance in the DRC from January 2017 to December 2018. Serum samples were screened for the presence of IgM against Leptospira spp. by a whole cell-based IgM ELISA (Patoc-IgM ELISA) at the Institut National de Recherche Biomedicale in Kinshasa (INRB) according to World Health Organization (WHO) guidance. Exploratory univariable and multivariable logistic regression analyses were undertaken to assess associations between socio-demographic factors and the presence of Leptospira IgM. Results: Of the 1,300 serum samples screened, 88 (7%) showed evidence of IgM against Leptospira spp. Most positive cases (34%) were young adult males in the 20–29-year group. There were statistically significant associations between having Leptospira IgM antibodies, age, sex, and living area. Observed positive cases were mostly located in urban settings, and the majority lived in the province of Kinshasa. There was a statistically significant association between seasonality and IgM Leptospira spp. positivity amongst those living in Kinshasa, where most of the positive cases occurred during the rainy season. Conclusions: This study showed that leptospirosis is likely an overlooked cause of unexplained cases of fever with jaundice in the DRC and highlights the need to consider leptospirosis in the differential diagnosis of fever with jaundice, particularly in young adult males. Further studies are needed to identify animal reservoirs, associated risk factors, and the burden of human leptospirosis in the DRC.

Background: By the end of the third wave of the coronavirus disease 2019 (COVID-19) epidemic (May–October 2021), only 3130 of the 57 268 confirmed cases of coronavirus disease 2019 (COVID-19) in the Democratic Republic of the Congo (DRC) were reported in Kongo Central. This province, and especially its capital city, Matadi, has essential trade and exchanges with Kinshasa, the epicenter of the COVID-19 epidemic in DRC. Kinshasa accounted for 60.0% of all cases during the same period. The true burden of COVID-19 in Matadi is likely underestimated. In this study, we aimed to determine the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence and associated risk factors after the third wave in Matadi. Methods: We conducted a population-based cross-sectional study in October 2021. Consenting participants were interviewed and tested using an enzyme-linked immunosorbent assay commercial kit. We applied univariable and multivariable analysis to evaluate factors associated with seropositivity and adjusted the seroprevalence for the test kit performance. Results: We included 2210 participants from 489 households. Female participants represented 59.1%. The median age was 27 years (interquartile range, 16–45 years). The crude SARS-CoV-2 seroprevalence was 82.3%. Age was identified as the main risk factor as younger age decreased the seropositivity odds. Accounting for clustering at the household level increased the seroprevalence to 83.2%. The seroprevalence increased further to 88.1% (95% confidence interval, 86.2%–90.1%) after correcting for the laboratory test kit performance. Conclusions: The SARS-CoV-2 seroprevalence was very high, contrasting with reported cases. Evidence generated from this population-based survey remains relevant in guiding the local COVID-19 response, especially vaccination strategies.

Background: Malaria rapid diagnostic tests have become a primary and critical tool for malaria diagnosis in malaria-endemic countries where Plasmodium falciparum Histidine Rich Protein 2-based rapid diagnostic tests (PfHRP2-based RDTs) are widely used. However, in the last decade, the accuracy of PfHRP2-based RDTs has been challenged by the emergence of P. falciparum strains harbouring deletions of the P. falciparum histidine rich protein 2 (pfhrp2) gene, resulting in false-negative results. In the Democratic Republic of Congo (D.R. Congo), little is known about the prevalence of the pfhrp2 gene deletion among P. falciparum isolates infecting symptomatic patients, especially in low to moderate transmission areas where pfhrp2 deletion parasites are assumed to emerge and spread. Here we determine the local prevalence and factors associated with pfhrp2 gene deletions among symptomatic malaria patients in the Kwilu Province of the D.R. Congo. Methods: We used secondary data from a prospective health facility-based cross-sectional study conducted in 2018. Blood was collected for microscopy, PfHRP2-RDT, and spotted onto Whatman filter paper for downstream genetic analysis. Genomic DNA was extracted and used to perform PCR assays for the detection and confirmation of pfhrp2 gene deletions. Fischer’s exact and the Kruskal–Wallis tests were applied to look for associations between potential explanatory variables and the pfhrp2 gene deletion with a level of statistical significance set at P < 0.05. Results: Of the 684 enrolled symptomatic patients, 391 (57.7%) were female. The majority (87.7%) reported the presence of mosquito breeding sites within the household’s compound, and fever was the most reported symptom (81.6%). The overall prevalence of the pfhrp2 gene deletion was 9.2% (95% CI: 6.7%–12.1%). The deletion of the pfhrp2 gene was associated with health zone of origin (P = 0.012) and age (P = 0.019). Among false-negative PfHRP2-RDT results, only 9.9% were due to pfhrp2 gene deletion. Conclusions: P. falciparum isolates with pfhrp2 gene deletions are relatively common among symptomatic patients in Kwilu province. Further investigations are needed to provide enough evidence for policy change. Meanwhile, the use of RDTs targeting PfHRP2 and parasite lactate dehydrogenase (pLDH) antigens could limit the spread of deleted isolates. Graphic

Tibroviruses are novel rhabdoviruses detected in humans, cattle, and arthropods. Four tibroviruses are known to infect humans: Bas-Congo virus (BASV), Ekpoma virus 1 (EKV-1), Ekpoma virus 2, and Mundri virus. However, since none of them has been isolated, their biological properties are largely unknown. We aimed to characterize the human tibrovirus glycoprotein (G), which likely plays a pivotal role in viral tropism and pathogenicity. Human tibrovirus Gs were found to share some primary structures and display 14 conserved cysteine residues, although their overall amino acid homology was low (29%–48%). Multiple potential glycosylation sites were found on the G molecules, and endoglycosidase H- and peptide-N-glycosidase F-sensitive glycosylation was confirmed. AlphaFold-predicted three-dimensional (3D) structures of human tibrovirus Gs were overall similar. Membrane fusion mediated by these tibrovirus Gs was induced by acidic pH. The low pH-induced conformational change that triggers fusion was reversible. Virus-like particles (VLPs) were produced by transient expression of Gs in cultured cells and used to produce mouse antisera. Using vesicular stomatitis Indiana virus pseudotyped with Gs, we found that the antisera to the respective tibrovirus VLPs showed limited cross-neutralizing activity. It was also found that human C-type lectins and T-cell immunoglobulin mucin 1 acted as attachment factors for G-mediated entry into cells. Interestingly, BASV-G showed the highest ability to utilize these molecules. The viruses infected a wide range of cell lines with preferential tropism for human-derived cells whereas the preference of EKV-1 was unique compared with the other human tibroviruses. These findings provide fundamental information to understand the biological properties of the human tibroviruses. IMPORTANCE: Human tibroviruses are poorly characterized emerging rhabdoviruses associated with either asymptomatic infection or severe disease with a case fatality rate as high as 60% in humans. However, the extent and burden of human infection as well as factors behind differences in infection outcomes are largely unknown. In this study, we characterized human tibrovirus glycoproteins, which play a key role in virus-host interactions, mainly focusing on their structural and antigenic differences and cellular tropism. Our results provide critical information for understanding the biological properties of these novel viruses and for developing appropriate preparedness interventions such as diagnostic tools, vaccines, and effective therapies.

A community-based coronavirus disease (COVID-19) active case-finding strategy using an antigen-detecting rapid diagnostic test (Ag-RDT) was implemented in the Democratic Republic of Congo (DRC) to enhance COVID-19 case detection. With this pilot community-based active case finding and response program that was designed as a clinical, prospective testing performance, and implementation study, we aimed to identify insights to improve community diagnosis and rapid response to COVID-19. This pilot study was modeled on the DRC’s National COVID-19 Response Plan and the COVID-19 Ag-RDT screening algorithm defined by the World Health Organization (WHO), with case findings implemented in 259 health areas, 39 health zones, and 9 provinces. In each health area, a 7-member interdisciplinary field team tested the close contacts (ring strategy) and applied preventive and control measures to each confirmed case. The COVID-19 testing capacity increased from 0.3 tests per 10,000 inhabitants per week in the first wave to 0.4, 1.6, and 2.2 in the second, third, and fourth waves, respectively. From January to November 2021, this capacity increase contributed to an average of 10.5% of COVID-19 tests in the DRC, with 7,110 positive Ag-RDT results for 40,226 suspected cases and close contacts who were tested (53.6% female, median age: 37 years [interquartile range: 26.0–50.0)]. Overall, 79.7% (n = 32,071) of the participants were symptomatic and 7.6% (n = 3,073) had comorbidities. The Ag-RDT sensitivity and specificity were 55.5% and 99.0%, respectively, based on reverse transcription polymerase chain reaction analysis, and there was substantial agreement between the tests (k = 0.63). Despite its limited sensitivity, the Ag-RDT has improved COVID-19 testing capacity, enabling earlier detection, isolation, and treatment of COVID-19 cases. Our findings support the community testing of suspected cases and asymptomatic close contacts of confirmed cases to reduce disease spread and virus transmission.