High prevalence of IgG antibodies to Ebola virus in the Efé pygmy population in the Watsa region, Democratic Republic of the Congo.

BACKGROUND: Factors related to the natural transmission of Ebola virus (EBOV) to humans are still not well defined. Results of previous sero-prevalence studies suggest that circulation of EBOV in human population is common in sub-Saharan Africa. The Efé pygmies living in Democratic Republic of the Congo are known to be exposed to potential risk factors of EBOV infection such as bush meat hunting, entry into caves, and contact with bats. We studied the pygmy population of Watsa region to determine seroprevalence to EBOV infection and possible risks factors. METHOD: Volunteer participants (N = 300) aged 10 years or above were interviewed about behavior that may constitute risk factors for transmission of EBOV, including exposures to rats, bats, monkeys and entry into caves. Samples of venous blood were collected and tested for IgG antibody against EBOV by enzyme-linked immunosorbent assay (ELISA). The χ2-test and Fisher's exact test were used for the comparison of proportions and the Student's t-test to compare means. The association between age group and anti-EBOV IgG prevalence was analysed by a nonparametric test for trend. RESULTS: The prevalence of anti-EBOV IgG was 18.7 % overall and increased significantly with age (p = 0.023). No association was observed with exposure to risk factors (contacts with rats, bats, monkeys, or entry into caves). CONCLUSIONS: The seroprevalence of IgG antibody to EBOV in pygmies in Watsa region is among the highest ever reported, but it remains unclear which exposures might lead to this high infection rate calling for further ecological and behavioural studies.

Development of a clinical prediction score for Ebola virus disease screening at triage centers in the Democratic Republic of the Congo.

The 2018-2020 Ebola virus disease (EVD) outbreak in the Democratic Republic of the Congo (DRC) was the largest since the disease's discovery in 1976. Rapid identification and isolation of EVD patients are crucial during triage. This study aimed to develop a clinical prediction score for EVD using clinical and epidemiological predictors. We conducted a retrospective cross-sectional study using surveillance data from EVD outbreak, collected during routine clinical care at the Ebola Transit Center (ETC) in Beni, DRC, from 2018 to 2020. The Spiegelhalter and Knill-Jones method was used for score development, including potential predictors with an adjusted likelihood ratio above 2 or below 0.50. Validation was performed using a dataset previously published in PLOSOne by Tshomba et al. Among 3725 patients screened, 3698 fulfilled the inclusion criteria, with 571 (15.4%) testing positive for EVD via RT-PCR Test. Seven predictive factors were identified: asthenia, sore throat, conjunctivitis, bleeding gums, hematemesis, contact with a sick person, and contact with a traditional healer. The prediction score achieved an Area under the receiver operating characteristic (AUROC) of 0.764, with 81.4% sensitivity and 53.6% specificity at a -1 cutoff. External validation demonstrated an AUROC of 0.766, with 80.8% sensitivity and 41.4% specificity at the -1 cutoff. Our study developed a screening tool to assess the risk of suspected patients developing EVD and being admitted to ETUs for RT-PCR testing and treatment. External validation results affirmed the model's reliability and generalizability in similar settings, suggesting its potential integration into clinical practice. Given the severity and urgency of EVD as well as the risk nosocomial EVD transmission, it is essential to continuously update these models with real-time data on symptoms, disease progression, patient outcomes and validated RDT during EVD outbreaks. This approach will enhance model accuracy, enabling more precise risk assessments and more effective outbreak management.

Cost-effectiveness of incorporating Ebola prediction score tools and rapid diagnostic tests into a screening algorithm: A decision analytic model.

BACKGROUND: No distinctive clinical signs of Ebola virus disease (EVD) have prompted the development of rapid screening tools or called for a new approach to screening suspected Ebola cases. New screening approaches require evidence of clinical benefit and economic efficiency. As of now, no evidence or defined algorithm exists. OBJECTIVE: To evaluate, from a healthcare perspective, the efficiency of incorporating Ebola prediction scores and rapid diagnostic tests into the EVD screening algorithm during an outbreak. METHODS: We collected data on rapid diagnostic tests (RDTs) and prediction scores' accuracy measurements, e.g., sensitivity and specificity, and the cost of case management and RDT screening in EVD suspect cases. The overall cost of healthcare services (PPE, procedure time, and standard-of-care (SOC) costs) per suspected patient and diagnostic confirmation of EVD were calculated. We also collected the EVD prevalence among suspects from the literature. We created an analytical decision model to assess the efficiency of eight screening strategies: 1) Screening suspect cases with the WHO case definition for Ebola suspects, 2) Screening suspect cases with the ECPS at -3 points of cut-off, 3) Screening suspect cases with the ECPS as a joint test, 4) Screening suspect cases with the ECPS as a conditional test, 5) Screening suspect cases with the WHO case definition, then QuickNavi™-Ebola RDT, 6) Screening suspect cases with the ECPS at -3 points of cut-off and QuickNavi™-Ebola RDT, 7) Screening suspect cases with the ECPS as a conditional test and QuickNavi™-Ebola RDT, and 8) Screening suspect cases with the ECPS as a joint test and QuickNavi™-Ebola RDT. We performed a cost-effectiveness analysis to identify an algorithm that minimizes the cost per patient correctly classified. We performed a one-way and probabilistic sensitivity analysis to test the robustness of our findings. RESULTS: Our analysis found dual ECPS as a conditional test with the QuickNavi™-Ebola RDT algorithm to be the most cost-effective screening algorithm for EVD, with an effectiveness of 0.86. The cost-effectiveness ratio was 106.7 USD per patient correctly classified. The following algorithms, the ECPS as a conditional test with an effectiveness of 0.80 and an efficiency of 111.5 USD per patient correctly classified and the ECPS as a joint test with the QuickNavi™-Ebola RDT algorithm with an effectiveness of 0.81 and a cost-effectiveness ratio of 131.5 USD per patient correctly classified. These findings were sensitive to variations in the prevalence of EVD in suspected population and the sensitivity of the QuickNavi™-Ebola RDT. CONCLUSIONS: Findings from this study showed that prediction scores and RDT could improve Ebola screening. The use of the ECPS as a conditional test algorithm and the dual ECPS as a conditional test and then the QuickNavi™-Ebola RDT algorithm are the best screening choices because they are more efficient and lower the number of confirmation tests and overall care costs during an EBOV epidemic.

Development of Ebola virus disease prediction scores: Screening tools for Ebola suspects at the triage-point during an outbreak.

BACKGROUND: The control of Ebola virus disease (EVD) outbreaks relies on rapid diagnosis and prompt action, a daunting task in limited-resource contexts. This study develops prediction scores that can help healthcare workers improve their decision-making at the triage-point of EVD suspect-cases during EVD outbreaks. METHODS: We computed accuracy measurements of EVD predictors to assess their diagnosing ability compared with the reference standard GeneXpert® results, during the eastern DRC EVD outbreak. We developed predictive scores using the Spiegelhalter-Knill-Jones approach and constructed a clinical prediction score (CPS) and an extended clinical prediction score (ECPS). We plotted the receiver operating characteristic curves (ROCs), estimated the area under the ROC (AUROC) to assess the performance of scores, and computed net benefits (NB) to assess the clinical utility (decision-making ability) of the scores at a given cut-off. We performed decision curve analysis (DCA) to compare, at a range of threshold probabilities, prediction scores' decision-making ability and to quantify the number of unnecessary isolation. RESULTS: The analysis was done on data from 10432 subjects, including 651 EVD cases. The EVD prevalence was 6.2% in the whole dataset, 14.8% in the subgroup of suspects who fitted the WHO Ebola case definition, and 3.2% for the set of suspects who did not fit this case definition. The WHO clinical definition yielded 61.6% sensitivity and 76.4% specificity. Fatigue, difficulty in swallowing, red eyes, gingival bleeding, hematemesis, confusion, hemoptysis, and a history of contact with an EVD case were predictors of EVD. The AUROC for ECPS was 0.88 (95%CI: 0.86-0.89), significantly greater than this for CPS, 0.71 (95%CI: 0.69-0.73) (p < 0.0001). At -1 point of score, the CPS yielded a sensitivity of 85.4% and specificity of 42.3%, and the ECPS yielded sensitivity of 78.8% and specificity of 81.4%. The diagnostic performance of the scores varied in the three disease contexts (the whole, fitting or not fitting the WHO case definition data sets). At 10% of threshold probability, e.g. in disease-adverse context, ECPS gave an NB of 0.033 and a net reduction of unnecessary isolation of 67.1%. Using ECPS as a joint approach to isolate EVD suspects reduces the number of unnecessary isolations by 65.7%. CONCLUSION: The scores developed in our study showed a good performance as EVD case predictors since their use improved the net benefit, i.e., their clinical utility. These rapid and low-cost tools can help in decision-making to isolate EVD-suspicious cases at the triage point during an outbreak. However, these tools still require external validation and cost-effectiveness evaluation before being used on a large scale.

Marburg hemorrhagic fever associated with multiple genetic lineages of virus.

BACKGROUND: An outbreak of Marburg hemorrhagic fever was first observed in a gold-mining village in northeastern Democratic Republic of the Congo in October 1998. METHODS: We investigated the outbreak of Marburg hemorrhagic fever most intensively in May and October 1999. Sporadic cases and short chains of human-to-human transmission continued to occur until September 2000. Suspected cases were identified on the basis of a case definition; cases were confirmed by the detection of virus antigen and nucleic acid in blood, cell culture, antibody responses, and immunohistochemical analysis. RESULTS: A total of 154 cases (48 laboratory-confirmed and 106 suspected) were identified (case fatality rate, 83 percent); 52 percent of cases were in young male miners. Only 27 percent of these men reported having had contact with other affected persons, whereas 67 percent of patients who were not miners reported such contact (P<0.001). Most of the affected miners (94 percent) worked in an underground mine. Cessation of the outbreak coincided with flooding of the mine. Epidemiologic evidence of multiple introductions of infection into the population was substantiated by the detection of at least nine genetically distinct lineages of virus in circulation during the outbreak. CONCLUSIONS: Marburg hemorrhagic fever can have a very high case fatality rate. Since multiple genetic variants of virus were identified, ongoing introduction of virus into the population helped perpetuate this outbreak. The findings imply that reservoir hosts of Marburg virus inhabit caves, mines, or similar habitats.

Organisation of health care during an outbreak of Marburg haemorrhagic fever in the Democratic Republic of Congo, 1999.

Organising health care was one of the tasks of the International Scientific and Technical Committee during the 1998-1999 outbreak in Durba/Watsa, in the north-eastern province (Province Orientale), Democratic Republic of Congo. With the logistical support of Médecins sans Frontières (MSF), two isolation units were created: one at the Durba Reference Health Centre and the other at the Okimo Hospital in Watsa. Between May 6th, the day the isolation unit was installed and May 19th, 15 patients were admitted to the Durba Health Centre. In only four of them were the diagnosis of Marburg haemorrhagic fever (MHF) confirmed by laboratory examination. Protective equipment was distributed to health care workers and family members caring for patients. Information about MHF, modes of transmission and the use of barrier nursing techniques was provided to health care workers and sterilisation procedures were reviewed. In contrast to Ebola outbreaks, there was little panic among health care workers and the general public in Durba and all health services remained operational.

Use of protective gear and the occurrence of occupational Marburg hemorrhagic fever in health workers from Watsa health zone, Democratic Republic of the Congo.

BACKGROUND: Occupational transmission to health workers (HWs) has been a typical feature of Marburg hemorrhagic fever (MHF) outbreaks. The goal of this study was to identify cases of occupational MHF in HWs from Durba and Watsa, Democratic Republic of the Congo; to assess levels of exposure and protection; and to explore reasons for inconsistent use of protective gear. METHODS: A serosurvey of 48 HWs who cared for patients with MHF was performed. In addition, HWs were given a questionnaire on types of exposure, use of protective gear, and symptoms after contact. Informal and in-depth interviews with HWs were also performed. RESULTS: We found 1 HW who was seropositive for MHF, in addition to 5 cases of occupational MHF known beforehand; 4 infections had occurred after the introduction of infection control. HWs protected themselves better during invasive procedures (injections, venipuncture, and surgery) than during noninvasive procedures, but the overall level of protection in the hospital remained insufficient, particularly outside of isolation wards. The reasons for inconsistent use of protective gear included insufficient availability of the gear, adherence to traditional explanatory models of the origin of disease, and peer bonding with sick colleagues. CONCLUSIONS: Infection control must not focus too exclusively on the establishment of isolation wards but should aim at improving overall hospital hygiene. Training of HWs should allow them to voice and discuss their doubts and prepare them for the peculiarities of caring for ill colleagues.

Marburg hemorrhagic fever in Durba and Watsa, Democratic Republic of the Congo: clinical documentation, features of illness, and treatment.

The objective of the present study was to describe day of onset and duration of symptoms of Marburg hemorrhagic fever (MHF), to summarize the treatments applied, and to assess the quality of clinical documentation. Surveillance and clinical records of 77 patients with MHF cases were reviewed. Initial symptoms included fever, headache, general pain, nausea, vomiting, and anorexia (median day of onset, day 1-2), followed by hemorrhagic manifestations (day 5-8+), and terminal symptoms included confusion, agitation, coma, anuria, and shock. Treatment in isolation wards was acceptable, but the quality of clinical documentation was unsatisfactory. Improved clinical documentation is necessary for a basic evaluation of supportive treatment.

Serosurvey on household contacts of Marburg hemorrhagic fever patients.

The first major outbreak of Marburg hemorrhagic fever (MHF) outside a laboratory environment occurred in the subdistrict of Watsa, Democratic Republic of Congo, from October 1998 to August 2000. We performed a serosurvey of household contacts of MHF patients to identify undetected cases, ascertain the frequency of asymptomatic Marburg infection, and estimate secondary attack risk and postintervention reproduction number. Contacts were interviewed about their exposure and symptoms consistent with MHF. Blood samples were tested for anti-Marburg immunoglobulin G (IgG). One hundred twenty-one (51%) of 237 identified contacts participated; 72 (60%) were not known to the health authorities. Two participating contacts were seropositive and reported becoming ill after the contact; no serologic evidence for asymptomatic or mild Marburg infection was found. The secondary attack risk was 21%; the postintervention reproduction number was 0.9, consistent with an outbreak sustained by repeated primary transmission, rather than large-scale secondary transmission.