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.

Characteristics of Medical Evacuation by Train in Ukraine, 2022.

Importance: The 2022 war in Ukraine severely affected access to health care for patients in the conflict-affected regions and limited options for medical evacuation. Air transport, a common method of medical evacuation in war zones, was unsafe due to the conflict of 2 modernized military forces that were in possession of aircraft and surface-to-air weapons; therefore, Médecins Sans Frontières, in collaboration with the Ukrainian railway company and Ukrainian health agencies, addressed this by initiating medical evacuation via medically customized trains. Objective: To describe the implementation of medical evacuation trains aimed at improving the access to health care for war-affected patients. Design, Setting, and Participants: This case series describes the remodeling of 2 trains used for medical evacuation in a conflict zone during the war in Ukraine. The study was conducted from March 30 to November 30, 2022. One train had minimal adjustments and could be rapidly deployed to address the most pressing humanitarian needs, while the other underwent major structural modifications to provide intensive care capacity. The report details the medical capabilities of the trains, the organization of referrals, and operational challenges encountered. Additionally, it includes a case series on the characteristics of patients transported in the initial 8 months, based on routinely collected programmatic descriptive data of all patients transported by the medical trains. Results: In 8 months, 2481 patients (male-female ratio, 1.07; male, 1136 [46%]; female 1058 [43%]; missing data, 287 [12%]; median age, 63 years [range, 0-98 years]) were evacuated from 11 cities near the Ukrainian conflict frontline to safer areas. Initially, the trains predominantly evacuated trauma patients, but over the course of the war, the patient characteristics changed with more medical and nonacute conditions, and fewer trauma patients. The main reason for entry into the intensive care unit train carriage was for close monitoring and observation, and the main interventions performed were primarily for respiratory failure. Conclusions and Relevance: The findings of this study suggest that medical evacuation in a war zone by converted trains is possible and can improve access to health care for war-affected patients. The presence of intensive care capacity on board allows for transport of more severely ill or injured individuals. However, the target population should not be limited to trauma patients, as health care institutions affected host a much broader population whose needs and urgency for evacuation may change over time.

Head-to-head comparison of diagnostic accuracy of four Ebola virus disease rapid diagnostic tests versus GeneXpert® in eastern Democratic Republic of the Congo outbreaks: a prospective observational study.

BACKGROUND: Ebola virus disease (EVD) outbreaks have emerged in Central and West Africa. EVD diagnosis relies principally on RT-PCR testing with GeneXpert®, which has logistical and cost restrictions at the peripheral level of the health system. Rapid diagnostic tests (RDTs) would offer a valuable alternative at the point-of-care to reduce the turn-around time, if they show good performance characteristics. We evaluated the performance of four EVD RDTs against the reference standard GeneXpert® on stored EVD positive and negative blood samples collected between 2018 and 2021 from outbreaks in eastern Democratic Republic of the Congo (DRC). METHODS: We conducted a prospective and observational study in the laboratory on QuickNavi-Ebola™, OraQuick® Ebola Rapid Antigen, Coris® EBOLA Ag K-SeT, and Standard® Q Ebola Zaïre Ag RDTs using left-over archived frozen EDTA whole blood samples. We randomly selected 450 positive and 450 negative samples from the EVD biorepositories in DRC, across a range of GeneXpert® cycle threshold values (Ct-values). RDT results were read by three persons and we considered an RDT result as "positive", when it was flagged as positive by at least two out of the three readers. We estimated the sensitivity and specificity through two independent generalized (logistic) linear mixed models (GLMM). FINDINGS: 476 (53%) of 900 samples had a positive GeneXpert Ebola result when retested. The QuickNavi-Ebola™ showed a sensitivity of 56.8% (95% CI 53.6-60.0) and a specificity of 97.5% (95% CI 96.2-98.4), the OraQuick® Ebola Rapid Antigen test displayed 61.6% (95% CI 57.0-65.9) sensitivity and 98.1% (95% CI 96.2-99.1) specificity, the Coris® EBOLA Ag K-SeT showed 25.0% (95% CI 22.3-27.9) sensitivity and 95.9% (95% CI 94.2-97.1) specificity, and the Standard® Q Ebola Zaïre Ag displayed 21.6% (95% CI 18.1-25.7) sensitivity and 99.1% (95% CI 97.4-99.7) specificity. INTERPRETATION: None of the RDTs evaluated approached the "desired or acceptable levels" for sensitivity set out in the WHO target product profile, while all of the tests met the "desired level" for specificity. Nevertheless, the QuickNavi-Ebola™ and OraQuick® Ebola Rapid Antigen Test demonstrated the most favorable profiles, and may be used as frontline tests for triage of suspected-cases while waiting for RT-qPCR confirmatory testing. FUNDING: Institute of Tropical Medicine Antwerp/EDCTP PEAU-EBOV-RDC project.

Efficiency of Field Laboratories for Ebola Virus Disease Outbreak during Chronic Insecurity, Eastern Democratic Republic of the Congo, 2018-2020.

During the 10th outbreak of Ebola virus disease in the Democratic Republic of the Congo, the Institut National de Recherche Biomédicale strategically positioned 13 decentralized field laboratories with dedicated equipment to quickly detect cases as the outbreak evolved. The laboratories were operated by national staff, who quickly handed over competencies and skills to local persons to successfully manage future outbreaks. Laboratories analyzed ≈230,000 Ebola diagnostic samples under stringent biosafety measures, documentation, and database management. Field laboratories diversified their activities (diagnosis, chemistry and hematology, survivor follow-up, and genomic sequencing) and shipped 127,993 samples from the field to a biorepository in Kinshasa under good conditions. Deploying decentralized and well-equipped laboratories run by local personnel in at-risk countries for Ebola virus disease outbreaks is an efficient response; all activities are quickly conducted in the field.

Long-lasting insecticidal nets provide protection against malaria for only a single year in Burundi, an African highland setting with marked malaria seasonality.

BACKGROUND: Long-lasting insecticidal nets (LLINs) are one of the key interventions in the global fight against malaria. Since 2014, mass distribution campaigns of LLINs aim for universal access by all citizens of Burundi. In this context, we assess the impact of LLINs mass distribution campaigns on malaria incidence, focusing on the endemic highland health districts. We also explored the possible correlation between observed trends in malaria incidence with any variations in climate conditions. METHODS: Malaria cases for 2011-2019 were obtained from the National Health Information System. We developed a generalised additive model based on a time series of routinely collected data with malaria incidence as the response variable and timing of LLIN distribution as an explanatory variable to investigate the duration and magnitude of the LLIN effect on malaria incidence. We added a seasonal and continuous-time component as further explanatory variables, and health district as a random effect to account for random natural variation in malaria cases between districts. RESULTS: Malaria transmission in Burundian highlands was clearly seasonal and increased non-linearly over the study period. Further, a fast and steep decline of malaria incidence was noted during the first year after mass LLIN distribution (p<0.0001). In years 2 and 3 after distribution, malaria cases started to rise again to levels higher than before the control intervention. CONCLUSION: This study highlights that LLINs did reduce the incidence in the first year after a mass distribution campaign, but in the context of Burundi, LLINs lost their impact after only 1 year.

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.

Persistent Transmission of HCV among Men Who Have Sex with Men despite Widespread Screening and Treatment with Direct-Acting Antivirals.

BACKGROUND: In the Netherlands, unrestricted access to direct-acting antivirals (DAAs) halved the incidence of acute hepatitis C virus (HCV) infections among HIV-infected men who have sex with men (MSM). To develop strategies that can further reduce the spread of HCV, it is important to understand the transmission dynamics of HCV. We used phylogenetic analysis of a dense sample of MSM to provide insight into the impact of unrestricted access to DAAs on HCV transmission in the Netherlands and in Belgium. METHODS: We included 89 MSM that were recently infected with HCV genotype 1a in ten Dutch and one Belgian HIV treatment centers. Sequences were generated using next gene sequencing and Sanger sequencing. Maximum likelihood phylogenetic analysis (general time reversible model) was performed on concatenated NS5A and NS5B sequences and a reference set of 389 highly similar control sequences selected from GenBank. A cluster was based on a minimum bootstrap support of 90% and a 3% genetic distance threshold. RESULTS: We found that 78 (88%) of individuals were part of seven major clusters. All clusters included individuals from across the study region, however, different cities were part of different clusters. In three clusters, HIV-negative MSM clustered with sequences from HIV-positive MSM. All clusters that were observed before the introduction of DAAs persisted after unrestricted access to DAAs became available. CONCLUSION: Recently acquired HCV infections among MSM in the Netherlands and Belgium are strongly clustered and therefore highly suitable for targeted prevention strategies, such as contact tracing and partner notification. Importantly, despite an HCV incidence reduction after high DAA uptake and continuously monitoring, HCV transmission persisted in the same clusters.

Enhanced surveillance of monkeypox in Bas-Uélé, Democratic Republic of Congo: the limitations of symptom-based case definitions.

BACKGROUND: Following an outbreak of cases of vesicular-pustular rash with fever, evocative of human monkeypox, in Bas-Uélé province, Democratic Republic of Congo, surveillance was strengthened. METHODS: Households with at least one active generalized vesicular-pustular rash case were visited, and contact and clinical history information were collected from all household members. Whenever possible, skin lesions were screened by polymerase chain reaction for the monkeypox virus, followed by the varicella-zoster virus, when negative for the former. RESULTS: Polymerase chain reaction results were obtained for 77 suspected cases, distributed in 138 households, of which 27.3% were positive for monkeypox, 58.4% positive for chickenpox, and 14.3% negative for both. Confirmed monkeypox cases presented more often with monomorphic skin lesions on the palms of the hands and on the soles of the feet. Integrating these three features into the case definition raised the specificity to 85% but would miss 50% of true monkeypox cases. A predictive model fit on patient demographics and symptoms had 97% specificity and 80% sensitivity but only 80% and 33% in predicting out-of-sample cases. CONCLUSION: Few discriminating features were identified and the performance of clinical case definitions was suboptimal. Rapid field diagnostics are needed to optimize worldwide early detection and surveillance of monkeypox.

Field performance of three Ebola rapid diagnostic tests used during the 2018-20 outbreak in the eastern Democratic Republic of the Congo: a retrospective, multicentre observational study.

BACKGROUND: The Democratic Republic of the Congo has confronted 13 outbreaks of Ebola virus disease since 1976. Rapid diagnostic tests (RDTs) detecting viral antigens have been developed to circumvent difficulties encountered with RT-PCR for diagnosis in remote low-resource settings, but there is still uncertainty about their performance characteristics and usability during outbreaks. We aimed to assess the field performance of three antigen detection RDTs compared with the gold-standard Cepheid GeneXpert Ebola assay results. METHODS: We conducted a retrospective, multicentre observational study using complete and de-identified databases of five mobile laboratories (managed by the Institut National de Recherche Biomédicale) to assess the performance of three Ebola virus disease RDTs (QuickNavi-Ebola, OraQuick Ebola Rapid Antigen Test, and Coris EBOLA Ag K-SeT rapid test) run on blood samples of patients with suspected Ebola virus disease in direct comparison with the Cepheid GeneXpert Ebola assay reference test during the 2018-20 outbreak in the eastern Democratic Republic of the Congo. We estimated the sensitivity and specificity of each test through generalised linear mixed models against the GeneXpert Ebola assay reference test and corrected for cycle threshold value and random site effects. FINDINGS: 719 (7·9%) of 9157 samples had a positive GeneXpert Ebola assay result. The QuickNavi-Ebola RDT had a sensitivity of 87·4% (95% CI 63·6-96·8) around the mean cycle threshold value and a specificity of 99·6% (99·3-99·8). The OraQuick Ebola Rapid Antigen Test had a sensitivity of 57·4% (95% CI 38·8-75·8) and specificity of 98·3% (97·5-99·0), and the Coris EBOLA Ag K-SeT rapid test had a sensitivity of 38·9% (23·0-63·6) against the GeneXpert Ebola assay reference and specificity of 97·4% (85·3-99·6). The QuickNavi-Ebola RDT showed a robust performance with good sensitivity, particularly with increasing viral loads (ie, low cycle threshold values), and specificity. INTERPRETATION: The three RDTs evaluated did not achieve the desired sensitivity and specificity of the WHO target product profile. Although the RDTs cannot triage and rule out Ebola virus infection among clinical suspects, they can still help to sort people with suspected Ebola virus disease into high-risk and low-risk groups while waiting for GeneXpert Ebola assay reference testing. FUNDING: None. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Two-Year Follow-Up of Trypanosoma brucei gambiense Serology after Successful Treatment of Human African Trypanosomiasis: Results of Four Different Sero-Diagnostic Tests.

Gambiense human African trypanosomiasis (gHAT), also known as gambiense sleeping sickness, is a parasitic infection caused by Trypanosoma brucei gambiense. During the last decades, gHAT incidence has been brought to an all-time low. Newly developed serological tools and drugs for its diagnosis and treatment put the WHO goal of interruption of transmission by 2030 within reach. However, further research is needed to efficiently adapt these new advances to new control strategies. We assessed the serological evolution of cured gHAT patients over a two-year period using four different tests: the rapid diagnostic test (RDT) HAT Sero K-SeT, ELISA/T.b. gambiense, Trypanosoma brucei gambiense inhibition ELISA (iELISA), and the immune trypanolysis test. High seropositive rates were observed in all the tests, although sero-reversion rates were different in each test: ELISA/T.b. gambiense was the test most likely to become negative two years after treatment, whereas RDT HAT Sero-K-SeT was the least likely. iELISA and trypanolysis showed intermediate and comparable probabilities to become negative. Stage 1 patients were also noted to be more likely to become negative than Stage 2 patients in all four serological tests. Our results confirm previous findings that trypanosome-specific antibody concentrations in blood may persist for up to two years, implying that HAT control programs should continue to take the history of past HAT episodes into consideration.

Postmortem Surveillance for Ebola Virus Using OraQuick Ebola Rapid Diagnostic Tests, Eastern Democratic Republic of the Congo, 2019-2020.

After a pilot study, we tested 443 cadavers using OraQuick Ebola rapid diagnostic tests during surveillance after the 10th Ebola outbreak in the Democratic Republic of the Congo. No false negative and 2% false-positive results were reported. Quickly returning results and engaging the community enabled timely public health actions.

Sensitivity and Specificity of Rapid Diagnostic Tests for Hepatitis C Virus With or Without HIV Coinfection: A Multicentre Laboratory Evaluation Study.

BACKGROUND: Hepatitis C virus (HCV) screening is critical to HCV elimination efforts. Simplified diagnostics are required for low-resource settings and difficult-to-reach populations. This retrospective study assessed performance of rapid diagnostic tests (RDTs) for detection of HCV antibodies. METHODS: Two lots of 13 RDTs were evaluated at 3 laboratories using archived plasma samples from 4 countries (Nigeria, Georgia, Cambodia, and Belgium). HCV status was determined using 3 reference tests according to a composite algorithm. Sensitivity and specificity were evaluated in HIV-infected and HIV-uninfected populations. Operational characteristics were also assessed. RESULTS: In total, 1710 samples met inclusion criteria. In HIV-uninfected samples (n = 384), the majority of RDTs had sensitivity ≥98% in 1 or both lots and most RDTs had specificity ≥99%. In HIV-infected samples (n = 264), specificity remained high but sensitivity was markedly lower than in HIV-uninfected samples; only 1 RDT reached >95%. The majority of HIV-infected samples for which sensitivity was low did not have detectable HCV viral load/core antigen. Interreader variability, lot-to-lot variability, and rate of invalid runs were low for all RDTs (<2%). CONCLUSIONS: HCV RDTs should be evaluated in the intended target population, as sensitivity can be impacted by population factors such as HIV status. CLINICAL TRIALS REGISTRATION: NCT04033887.

Development of a risk score to guide targeted hepatitis C testing among human immunodeficiency virus patients in Cambodia.

BACKGROUND: The World Health Organization recommends testing all human immunodeficiency virus (HIV) patients for hepatitis C virus (HCV). In resource-constrained contexts with low-to-intermediate HCV prevalence among HIV patients, as in Cambodia, targeted testing is, in the short-term, potentially more feasible and cost-effective. AIM: To develop a clinical prediction score (CPS) to risk-stratify HIV patients for HCV coinfection (HCV RNA detected), and derive a decision rule to guide prioritization of HCV testing in settings where 'testing all' is not feasible or unaffordable in the short term. METHODS: We used data of a cross-sectional HCV diagnostic study in the HIV cohort of Sihanouk Hospital Center of Hope in Phnom Penh. Key populations were very rare in this cohort. Score development relied on the Spiegelhalter and Knill-Jones method. Predictors with an adjusted likelihood ratio ≥ 1.5 or ≤ 0.67 were retained, transformed to natural logarithms, and rounded to integers as score items. CPS performance was evaluated by the area-under-the-ROC curve (AUROC) with 95% confidence intervals (CI), and diagnostic accuracy at the different cut-offs. For the decision rule, HCV coinfection probability ≥1% was agreed as test-threshold. RESULTS: Among the 3045 enrolled HIV patients, 106 had an HCV coinfection. Of the 11 candidate predictors (from history-taking, laboratory testing), seven had an adjusted likelihood ratio ≥ 1.5 or ≤ 0.67: ≥ 50 years (+1 point), diabetes mellitus (+1), partner/household member with liver disease (+1), generalized pruritus (+1), platelets < 200 × 109/L (+1), aspartate transaminase (AST) < 30 IU/L (-1), AST-to-platelet ratio index (APRI) ≥ 0.45 (+1), and APRI < 0.45 (-1). The AUROC was 0.84 (95%CI: 0.80-0.89), indicating good discrimination of HCV/HIV coinfection and HIV mono-infection. The CPS result ≥0 best fits the test-threshold (negative predictive value: 99.2%, 95%CI: 98.8-99.6). Applying this threshold, 30% (n = 926) would be tested. Sixteen coinfections (15%) would have been missed, none with advanced fibrosis. CONCLUSION: The CPS performed well in the derivation cohort, and bears potential for other contexts of low-to-intermediate prevalence and little onward risk of transmission(i.e. cohorts without major risk factors as injecting drug use, men having sex with men), and where available resources do not allow to test all HIV patients as recommended by WHO. However, the score requires external validation in other patient cohorts before any wider use can be considered.

A Multidisciplinary Investigation of the First Chikungunya Virus Outbreak in Matadi in the Democratic Republic of the Congo.

Early March 2019, health authorities of Matadi in the Democratic Republic of the Congo alerted a sudden increase in acute fever/arthralgia cases, prompting an outbreak investigation. We collected surveillance data, clinical data, and laboratory specimens from clinical suspects (for CHIKV-PCR/ELISA, malaria RDT), semi-structured interviews with patients/caregivers about perceptions and health seeking behavior, and mosquito sampling (adult/larvae) for CHIKV-PCR and estimation of infestation levels. The investigations confirmed a large CHIKV outbreak that lasted February-June 2019. The total caseload remained unknown due to a lack of systematic surveillance, but one of the two health zones of Matadi notified 2686 suspects. Of the clinical suspects we investigated (n = 220), 83.2% were CHIKV-PCR or IgM positive (acute infection). One patient had an isolated IgG-positive result (while PCR/IgM negative), suggestive of past infection. In total, 15% had acute CHIKV and malaria. Most adult mosquitoes and larvae (>95%) were Aedes albopictus. High infestation levels were noted. CHIKV was detected in 6/11 adult mosquito pools, and in 2/15 of the larvae pools. This latter and the fact that 2/6 of the CHIKV-positive adult pools contained only males suggests transovarial transmission. Interviews revealed that healthcare seeking shifted quickly toward the informal sector and self-medication. Caregivers reported difficulties to differentiate CHIKV, malaria, and other infectious diseases resulting in polypharmacy and high out-of-pocket expenditure. We confirmed a first major CHIKV outbreak in Matadi, with main vector Aedes albopictus. The health sector was ill-prepared for the information, surveillance, and treatment needs for such an explosive outbreak in a CHIKV-naïve population. Better surveillance systems (national level/sentinel sites) and point-of-care diagnostics for arboviruses are needed.

Hepatitis C Prevalence and Validation of a Clinical Prediction Score for Targeted Screening among People Living with HIV in Ghana.

WHO recommends hepatitis C (HCV) screening for all people living with HIV (PLHIV). Yet, HCV coinfection was shown to be rare in some Sub-Saharan HIV cohorts, and targeted testing was suggested more efficient for such settings. We studied HCV prevalence among Ghanaian PLHIV, and assessed the external validity of a score to guide targeted testing. This score was initially derived from a Cambodian HIV cohort, and uses as predictors: age, household member/partner with liver disease, diabetes, generalized pruritus, AST, platelets, and AST-to-platelet ratio index. We enrolled 4,023 PLHIV, most from Greater Accra and Central regions, 28.4% were male, median age was 47 years, and high-risk behavior was reported to be rare. HCV seroprevalence was 0.57%, and HCV-RNA was detectable in 0.5%. Sequencing revealed genotype 1(b) and 2(q/r) infections. The discriminatory performance of the score was suboptimal in the Ghanaian setting. The area under the curve was 0.69 (95% CI 0.59-0.79). HCV coinfection prevalence was very low in this Ghanaian PLHIV cohort with reported low-risk of onward transmission. To avoid the cost of screening all PLHIV in similar cohorts in resource-constrained settings, further research to develop better tools/scores to guide targeted HCV testing is needed.

Feasibility of a dried blood spot strategy for serological screening and surveillance to monitor elimination of Human African Trypanosomiasis in the Democratic Republic of the Congo.

In recent years, the number of reported Human African Trypanosomiasis (HAT) cases caused by Trypanosoma brucei (T.b.) gambiense has been markedly declining, and the goal of 'elimination as a public health problem' is within reach. For the next stage, i.e. interruption of HAT transmission by 2030, intensive screening and surveillance will need to be maintained, but with tools and strategies more efficiently tailored to the very low prevalence. We assessed the sequential use of ELISA and Immune Trypanolysis (ITL) on dried blood spot (DBS) samples as an alternative to the traditional HAT field testing and confirmation approach. A cross-sectional study was conducted in HAT endemic and previously endemic zones in Kongo Central province, and a non-endemic zone in Haut Katanga province in the Democratic Republic of the Congo (DRC). Door-to-door visits were performed to collect dried blood spot (DBS) samples on filter paper. ELISA/T.b. gambiense was conducted followed by ITL for those testing positive by ELISA and in a subset of ELISA negatives. In total, 11,642 participants were enrolled. Of these, 11,535 DBS were collected and stored in appropriate condition for ELISA testing. Ninety-seven DBS samples tested positive on ELISA. In the endemic zone, ELISA positivity was 1.34% (95%CI: 1.04-1.64). In the previously endemic zone and non-endemic zone, ELISA positivity was 0.34% (95% CI: 0.13-0.55) and 0.37% (95% CI: 0.15-0.60) respectively. Among the ELISA positives, only two samples had a positive ITL result, both from the endemic zone. One of those was from a former HAT patient treated in 2008 and the other from an individual who unfortunately had deceased prior to the follow-up visit. Our study showed that a surveillance strategy, based on DBS samples and centralized testing with retracing of patients if needed, is feasible in DRC. ELISA seems well suited as initial test with a similar positivity rate as traditional screening tests, but ITL remains complex. Alternatives for the latter, also analyzable on DBS, should be further explored.

Sensitivity and specificity of rapid hepatitis C antibody assays in freshly collected whole blood, plasma and serum samples: A multicentre prospective study.

BACKGROUND: This study evaluated performance of two hepatitis C virus (HCV) rapid diagnostic tests (RDTs) performed by intended users in resource-limited settings. METHODS: Testing was conducted at three facilities in two countries (Georgia, Cambodia) using matched fingerstick whole blood, plasma and serum samples. Investigational RDTs were compared with a composite reference standard (CRS) comprised of three laboratory tests, and a reference RDT. RESULTS: In matched samples from 489 HCV positive and 967 HCV negative participants, specificity with both investigational RDTs was high using either reference method (≥98.4% in all sample types). Sensitivity was lower in whole blood versus plasma and serum for both RDTs compared with the CRS (86.5-91.4% vs 97.5-98.0% and 97.3-97.1%) and reference RDT (93.6-97.8% vs 100% and 99.4%). Sensitivity improved when considering only samples with detectable HCV viral load. CONCLUSION: Sensitivity was highest in serum and plasma versus whole blood. The World Health Organization prequalification criterion (≥98%) was narrowly missed by both RDTs in serum, and one in plasma, possibly due to the intended user factor. Performance in whole blood was considered adequate, given potential roles of HCV infection history, improved sensitivity with detectable viral load and performance similarities to the reference RDT.

Molecular characterization of chikungunya virus during the 2019 outbreak in the Democratic Republic of the Congo.

Early 2019, a chikungunya virus (CHIKV) outbreak hit the Democratic Republic of the Congo (DRC). Though seldomly deadly, this mosquito-borne disease presents as an acute febrile (poly)arthralgia often followed by long-term sequelae. Although Aedes aegypti is the primary vector, an amino acid substitution in the viral envelope gene E1 (A226V) is causing concern as it results in increased transmission by Aedes albopictus, a mosquito with a much wider geographical distribution. Between January and March 2019, we collected human and mosquito samples in Kinshasa and Kongo Central province (Kasangulu and Matadi). Of the patients that were tested within 7 days of symptom onset, 49.7% (87/175) were RT-qPCR positive, while in the mosquito samples CHIKV was found in 1/2 pools in Kinshasa, 5/6 pools in Kasangulu, and 8/26 pools in Matadi. Phylogenetic analysis on whole-genome sequences showed that the circulating strain formed a monophyletic group within the ECSA2 lineage and harboured the A226V mutation. Our sequences did not cluster with sequences from previously reported outbreaks in the DRC nor with other known A226V-containing ECSA2 strains. This indicates a scenario of convergent evolution where A226V was acquired independently in response to a similar selection pressure for transmission by Ae. albopictus. This is in line with our entomological data where we detected Ae. albopictus more frequently than Ae. aegypti in two out of three affected areas. In conclusion, our findings suggest that CHIKV is adapting to the increased presence of Aedes albopictus in DRC.

Point-of-Care Biomarkers to Guide Antibiotic Prescription for Acute Febrile Illness in Sub-Saharan Africa: Promises and Caveats.

Empiric malaria treatment in Sub-Saharan Africa has significantly decreased with the scaling-up of malaria rapid diagnostic tests; this coincided with a pronounced increase in empiric antibiotic prescriptions. In high-income countries, guidance for antibiotic prescriptions using biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) has reduced antibiotic use while safe-guarding patient safety. Importantly, several low-cost point-of-care CRP/PCT tests are currently available. However, only a few studies on the role of CRP/PCT in differentiating bacterial vs viral infections in acute febrile illness have been conducted in Sub-Saharan Africa. Studies from Central and West Africa (most of which is malaria-endemic) are particularly scarce, and only 1 has included adults. The evidence base for point-of-care use of CRP/PCT biomarkers in acute fever in Sub-Saharan Africa should be urgently built. Before engaging in clinical trials to assess clinical impact, pilot studies should be conducted to address key knowledge gaps including recommended CRP/PCT cutoff values and the effect of malaria coinfection.