Abstract Important policy questions during infections disease outbreaks include: i) How effective are particular interventions?; ii) When can resource-intensive interventions be removed? We used ...mathematical modelling to address these questions during the 2017 Ebola outbreak in Likati Health Zone, Democratic Republic of the Congo (DRC). Eight cases occurred before 15 May 2017, when the Ebola Response Team (ERT; co-ordinated by the World Health Organisation and DRC Ministry of Health) was deployed to reduce transmission. We used a branching process model to estimate that, pre-ERT arrival, the reproduction number was $$R=1.49$$ R = 1.49 (95% credible interval $$({{{\mathrm{0.67,2.81}}})$$ ( 0.67, 2.81 ) ). The risk of further cases occurring without the ERT was estimated to be 0.97 (97%). However, no cases materialised, suggesting that the ERT’s measures were effective. We also estimated the risk of withdrawing the ERT in real-time. By the actual ERT withdrawal date (2 July 2017), the risk of future cases without the ERT was only 0.01, indicating that the ERT withdrawal decision was safe. We evaluated the sensitivity of our results to the estimated $$R$$ R value and considered different criteria for determining the ERT withdrawal date. This research provides an extensible modelling framework that can be used to guide decisions about when to relax interventions during future outbreaks.
Despite its critical role in containing outbreaks, the efficacy of contact tracing (CT), measured as the sensitivity of case detection, remains an elusive metric. We estimated the sensitivity of CT ...by applying unilist capture-recapture methods on data from the 2018-2020 outbreak of Ebola virus disease in the Democratic Republic of Congo.
We applied different distributional assumptions to the zero-truncated count data to estimate the number of unobserved cases with a) any contacts and b) infected contacts, to compute CT sensitivity. Geometric distributions were the best fitting models.
Our results indicate that CT efforts identified almost all (n=792, 99%) of the cases with any contacts, but only half (n=207, 48%) of the cases with infected contacts, suggesting that CT efforts performed well at identifying contacts during the listing stage, but performed poorly during the contact follow-up stage.
This novel approach can be applied to assess the effectiveness of CT. Importantly, the approach described is disease-agnostic, and can be extended to assess the sensitivity of CT for any disease, including COVID-19, for which CT has been identified as a crucial component of the response activities.
Molecular epidemiological studies revealed that the epicenter of the HIV pandemic was Kinshasa, the capital city of the Democratic Republic of the Congo (DRC) in Central Africa. All known subtypes ...and numerous complex recombinant strains co-circulate in the DRC. Moreover, high intra-subtype diversity has been also documented. During two previous surveys on HIV-1 antiretroviral drug resistance in the DRC, we identified two divergent subtype C lineages in the
and partial
gene regions. We sequenced eight near full-length genomes and classified them using bootscanning and likelihood-based phylogenetic analyses. Four strains are more closely related to subtype C although within the range of inter sub-subtype distances. However, these strains also have small unclassified fragments and thus were named CRF92_C2U. Another strain is a unique recombinant of CRF92_C2U with an additional small unclassified fragment and a small divergent subtype A fragment. The three remaining strains represent a complex mosaic named CRF93_cpx. CRF93_cpx have two fragments of divergent subtype C sequences, which are not conventional subtype C nor the above described C2, and multiple divergent subtype A-like fragments. We then inferred the time-scaled evolutionary history of subtype C following a Bayesian approach and a partitioned analysis using major genomic regions. CRF92_C2U and CRF93_cpx had the most recent common ancestor with conventional subtype C around 1932 and 1928, respectively. A Bayesian demographic reconstruction corroborated that the subtype C transition to a faster phase of exponential growth occurred during the 1950s. Our analysis showed considerable differences between the newly discovered early-divergent strains and the conventional subtype C and therefore suggested that this virus has been diverging in humans for several decades before the HIV/M diversity boom in the 1950s.
The real-time generation of information about pathogen genomes has become a vital goal for transmission analysis and characterisation in rapid outbreak responses. In response to the recently ...established genomic capacity in the Democratic Republic of the Congo, we explored the real-time generation of genomic information at the start of the 2018 Ebola virus disease (EVD) outbreak in North Kivu Province.
We used targeted-enrichment sequencing to produce two coding-complete Ebola virus genomes 5 days after declaration of the EVD outbreak in North Kivu. Subsequent sequencing efforts yielded an additional 46 genomes. Genomic information was used to assess early transmission, medical countermeasures, and evolution of Ebola virus.
The genomic information demonstrated that the EVD outbreak in the North Kivu and Ituri Provinces was distinct from the 2018 EVD outbreak in Équateur Province of the Democratic Republic of the Congo. Primer and probe mismatches to Ebola virus were identified in silico for all deployed diagnostic PCR assays, with the exception of the Cepheid GeneXpert GP assay.
The first two coding-complete genomes provided actionable information in real-time for the deployment of the rVSVΔG-ZEBOV-GP Ebola virus envelope glycoprotein vaccine, available therapeutics, and sequence-based diagnostic assays. Based on the mutations identified in the Ebola virus surface glycoprotein (GP12) observed in all 48 genomes, deployed monoclonal antibody therapeutics (mAb114 and ZMapp) should be efficacious against the circulating Ebola virus variant. Rapid Ebola virus genomic characterisation should be included in routine EVD outbreak response procedures to ascertain efficacy of medical countermeasures.
Defense Biological Product Assurance Office.
Plasmodium vivax is the leading cause of human malaria in Asia and Latin America but is absent from most of central Africa due to the near fixation of a mutation that inhibits the expression of its ...receptor, the Duffy antigen, on human erythrocytes. The emergence of this protective allele is not understood because P. vivax is believed to have originated in Asia. Here we show, using a non-invasive approach, that wild chimpanzees and gorillas throughout central Africa are endemically infected with parasites that are closely related to human P. vivax. Sequence analyses reveal that ape parasites lack host specificity and are much more diverse than human parasites, which form a monophyletic lineage within the ape parasite radiation. These findings indicate that human P. vivax is of African origin and likely selected for the Duffy-negative mutation. All extant human P. vivax parasites are derived from a single ancestor that escaped out of Africa.
The 2018 Ebola virus disease (EVD) outbreak in Équateur Province, Democratic Republic of the Congo, began on May 8, and was declared over on July 24; it resulted in 54 documented cases and 33 deaths. ...We did a retrospective genomic characterisation of the outbreak and assessed potential therapeutic agents and vaccine (medical countermeasures).
We used target-enrichment sequencing to produce Ebola virus genomes from samples obtained in the 2018 Équateur Province outbreak. Combining these genomes with genomes associated with known outbreaks from GenBank, we constructed a maximum-likelihood phylogenetic tree. In-silico analyses were used to assess potential mismatches between the outbreak strain and the probes and primers of diagnostic assays and the antigenic sites of the experimental rVSVΔG-ZEBOV-GP vaccine and therapeutics. An in-vitro flow cytometry assay was used to assess the binding capability of the individual components of the monoclonal antibody cocktail ZMapp.
A targeted sequencing approach produced 16 near-complete genomes. Phylogenetic analysis of these genomes and 1011 genomes from GenBank revealed a distinct cluster, confirming a new Ebola virus variant, for which we propose the name “Tumba”. This new variant appears to have evolved at a slower rate than other Ebola virus variants (0·69 × 10−3 substitutions per site per year with “Tumba” vs 1·06 × 10−3 substitutions per site per year without “Tumba”). We found few sequence mismatches in the assessed assay target regions and antigenic sites. We identified nine amino acid changes in the Ebola virus surface glycoprotein, of which one resulted in reduced binding of the 13C6 antibody within the ZMapp cocktail.
Retrospectively, we show the feasibility of using genomics to rapidly characterise a new Ebola virus variant within the timeframe of an outbreak. Phylogenetic analysis provides further indications that these variants are evolving at differing rates. Rapid in-silico analyses can direct in-vitro experiments to quickly assess medical countermeasures.
Defense Biological Product Assurance Office.
Four types of human T cell lymphotropic viruses (HTLV) have been described (HTLV-1 to HTLV-4) with three of them having closely related simian virus analogues named STLV-1, -2, and -3. To assess the ...risk of cross-species transmissions of STLVs from nonhuman primates to humans in the Democratic Republic of Congo, a total of 330 samples, derived from primate bushmeat, were collected at remote forest sites where people rely on bushmeat for subsistence. STLV prevalences and genetic diversity were estimated by PCR and sequence analysis of tax-rex and LTR fragments. Overall, 7.9% of nonhuman primate bushmeat is infected with STLVs. We documented new STLV-1 and STLV-3 variants in six out of the seven species tested and showed for the first time STLV infection in C. mona wolfi, C. ascanius whitesidei, L. aterrimus aterrimus, C. angolensis, and P. tholloni. Our results provide increasing evidence that the diversity and geographic distribution of PTLVs are much greater than previously thought.
Le dépistage des anticorps anti-virus de l’immunodéficience humaine est obligatoire chez tout donneur de sang admis à la Banque de sang des Cliniques Universitaires de Kinshasa depuis 1984. Cependant ...aucune donnée compilée n’est disponible à ce jour. L’objectif de la présente étude était de dresser la tendance, la prévalence, les co-infections, anti-virus, et les déterminants de la séropositivité anti-virus de l’immunodéficience humaine chez les donneurs de sang admis entre 2003–2006 et 2008–2013.
Une analyse rétrospective des données a été réalisée chez les donneurs de sang des cliniques universitaires de Kinshasa entre 2003–2006 et 2008–2013. Les fréquences populationnelles d’infection par le virus de l’immunodéficience humaine par année, âge, sexe et type de donneur de sang ont été estimées.
Sur 26 341 donneurs de sang, 2,2 % (n=576/26 341) étaient séropositifs pour le virus de l’immunodéficience humaine. L’âge<25 ans (OR=1,7 ; IC 95 % : 1,4–2 ; p<0,0001) et la séropositivité du virus de l’hépatite C (OR=3 ; IC 95 % : 1,8–4,9 ; p<0,001) ont été identifiés comme des marqueurs indépendants mais associés à la séropositivité du virus de l’immunodéficience humaine.
Cette étude montre une forte association (avec un pic en 2003) entre l’infection par le virus de l’immunodéficience humaine, l’infection par le virus de l’hépatite C et le jeune âge. Des recherches plus approfondies doivent être menées pour sécuriser la transfusion en République démocratique du Congo.
The screening of anti-Human Immunodeficiency Virus antibodies is mandatory in every blood donor admitted to the Blood Bank of Kinshasa University Clinics since 1984. However, no compiled data are available to date. The objective of this study was to establish the trend, prevalence, viral co-infections, and determinants of Human Immunodeficiency anti-Virus serology in blood donors admitted between 2003–2006 and 2008–2013.
A retrospective analysis was carried out at University Kinshasa Clinics, using blood donors’ records during 2003–2006 and 2008–2013. The prevalence of the human immunodeficiency virus per year, age, sex and type of blood donors were estimated. Independent predictors of human immunodeficiency virus seropositivity were also identified.
Out of 26,341 blood donors, 2.2% (n=576/26,341) were seropositive for Human Immunodeficiency Virus. Age<25 years (OR=1.7; 95% CI: 1.4–2; P<0.0001) and Hepatitis C virus seropositivity (OR=3; 95% CI; 1.8–4.9; P<0.001) emerged as independent predictors of Human Immunodeficiency Virus seropositivity.
This study shows a strong association between the Human Immunodeficiency Virus and hepatitis C and younger age respectively. Further studies are needed to ensure safety of Blood donation in Democratic Republic of Congo.
Simian immunodeficiency viruses (SIVs) are lentiviruses that infect an extensive number of wild African primate species. Here we describe for the first time SIV infection in a captive agile mangabey ...(Cercocebus agilis) from Cameroon. Phylogenetic analysis of the full-length genome sequence of SIVagi-00CM312 showed that this novel virus fell into the SIVrcm lineage and was most closely related to a newly characterized SIVrcm strain (SIVrcm-02CM8081) from a wild-caught red-capped mangabey (Cercocebus torquatus) from Cameroon. In contrast to red-capped mangabeys, no 24 bp deletion in CCR5 has been observed in the agile mangabey. Further studies on wild agile mangabeys are needed to determine whether agile and red-capped mangabeys are naturally infected with the same SIV lineage, or whether this agile mangabey became infected with an SIVrcm strain in captivity. However, our study shows that agile mangabeys are susceptible to SIV infection.
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