Co-circulation of two Alphaviruses in Burkina Faso: Chikungunya and O'nyong nyong viruses.

BACKGROUND: Chikungunya virus (CHIKV) and O'nyong nyong virus (ONNV) are phylogenetically related alphaviruses in the Semliki Forest Virus (SFV) antigenic complex of the Togaviridae family. There are limited data on the circulation of these two viruses in Burkina Faso. The aim of our study was to assess their circulation in the country by determining seroprevalence to each of the viruses in blood donor samples and by retrospective molecular and serological testing of samples collected as part of national measles and rubella surveillance. METHODOLOGY/PRINCIPAL FINDINGS: All blood donor samples were analyzed on the Luminex platform using CHIKV and ONNV E2 antigens. Patient samples collected during national measles-rubella surveillance were screened by an initial ELISA for CHIKV IgM (CHIKjj Detect IgM ELISA) at the national laboratory. The positive samples were then analyzed by a second ELISA test for CHIKV IgM (CDC MAC-ELISA) at the reference laboratory. Finally, samples that had IgM positive results for both ELISA tests and had sufficient residual volume were tested by plaque reduction neutralization testing (PRNT) for CHIKV and ONNV. These same patient samples were also analyzed by rRT-PCR for CHIKV. Among the blood donor specimens, 55.49% of the samples were positive for alphaviruses including both CHIKV and ONNV positive samples. Among patient samples collected as part of national measles and rubella surveillance, 3.09% were IgM positive for CHIKV, including 2.5% confirmed by PRNT. PRNT failed to demonstrate any ONNV infections in these samples. No samples tested by RT-qPCR. had detectable CHIKV RNA. CONCLUSIONS/SIGNIFICANCE: Our results suggest that CHIKV and ONNV have been circulating in the population of Burkina Faso and may have been confused with malaria, dengue fever or other febrile diseases such as measles or rubella. Our study underscores the necessity to enhance arbovirus surveillance systems in Burkina Faso.

Enabling countries to manage outbreaks: statistical, operational, and contextual analysis of the early warning and response system (EWARS-csd) for dengue outbreaks.

Introduction: Dengue is currently the fastest-spreading mosquito-borne viral illness in the world, with over half of the world's population living in areas at risk of dengue. As dengue continues to spread and become more of a health burden, it is essential to have tools that can predict when and where outbreaks might occur to better prepare vector control operations and communities' responses. One such predictive tool, the Early Warning and Response System for climate-sensitive diseases (EWARS-csd), primarily uses climatic data to alert health systems of outbreaks weeks before they occur. EWARS-csd uses the robust Distribution Lag Non-linear Model in combination with the INLA Bayesian regression framework to predict outbreaks, utilizing historical data. This study seeks to validate the tool's performance in two states of Colombia, evaluating how well the tool performed in 11 municipalities of varying dengue endemicity levels. Methods: The validation study used retrospective data with alarm indicators (mean temperature and rain sum) and an outbreak indicator (weekly hospitalizations) from 11 municipalities spanning two states in Colombia from 2015 to 2020. Calibrations of different variables were performed to find the optimal sensitivity and positive predictive value for each municipality. Results: The study demonstrated that the tool produced overall reliable early outbreak alarms. The median of the most optimal calibration for each municipality was very high: sensitivity (97%), specificity (94%), positive predictive value (75%), and negative predictive value (99%; 95% CI). Discussion: The tool worked well across all population sizes and all endemicity levels but had slightly poorer results in the highly endemic municipality at predicting non-outbreak weeks. Migration and/or socioeconomic status are factors that might impact predictive performance and should be further evaluated. Overall EWARS-csd performed very well, providing evidence that it should continue to be implemented in Colombia and other countries for outbreak prediction.

Effectiveness and safety of bedaquiline-based, modified all-oral 9-11-month treatment regimen for rifampicin-resistant tuberculosis in Vietnam.

OBJECTIVES: World Health Organization recommends a 7-drug 9-11-month rifampicin-resistant tuberculosis (RR-TB) short treatment regimen (STR). To reduce the pill burden, we assessed the safety and effectiveness of a 5-drug 9-11-month modified STR (mSTR). METHODS: Prospective cohort study of an all-oral mSTR (comprising bedaquiline, levofloxacin, linezolid [LZD], clofazimine, and/or pyrazinamide) for patients with RR-TB without confirmed fluoroquinolone resistance, enrolled in Vietnam between 2020-2021. RESULTS: A total of 108 patients were enrolled in this study. Overall, 63 of 74 (85%) achieved culture conversion at 2 months. Of 106 evaluated, 95 (90%) were successfully treated, six (6%) were lost-to-follow-up, one (1%) died, and four (4%) had treatment failure, including three with permanent regimen change owing to adverse events (AE) and one with culture reversion. Of 108, 32 (30%) patients encountered at least one AE. Of 45 AEs recorded, 13 (29%) were serious (hospitalization, life threatening, or death). The median time to AE was 3 months (IQR: 2-5). A total of 26 AEs led to regimen adaptation: either dose reduction (N = 1), drug temporary interruption (N = 19), or drug permanent discontinuation (N = 6, 4 attributed to LZD). CONCLUSION: The high treatment success of 5-drug mSTR might replace the 7-drug regimen in routine care. AEs were frequent, but manageable in most patients. Active AEs monitoring is essential, particularly when using LZD throughout.

Health-Related Quality of Life of Tuberculosis Patients during the COVID-19 Pandemic in Conakry, Guinea: A Mixed Methods Study.

The COVID-19 pandemic has had a significant impact on all facets of life and has exacerbated many challenges faced by people living with tuberculosis (TB). This study aimed to assess the health-related quality of life (HRQoL) of TB patients in Guinea during the first wave of the COVID-19 pandemic. A mixed methods study was conducted using two validated tools to assess HRQoL and qualitative interviews among TB patients enrolled in treatment at 11 health centers in Conakry, Guinea. Logistic regression was used to identify factors associated with the deterioration of HRQoL. We included 439 participants in the study, among whom 44% and 31% experienced pain and anxiety, respectively. We found that an increase in the number of household size and the distance from participants' residence to the health centers were significantly associated with lower HRQoL. Qualitative interviews highlighted nutritional and financial issues, which were exacerbated during the COVID-19 pandemic and beliefs that the Guinean Government's assistance plan was insufficient. This study supports the implementation of specific relief plans for TB patients, which includes nutritional and psychological support, especially those whose movements are limited by travel restrictions, preventing access to TB care, reducing work opportunities and exacerbating financial needs and stress.

Evaluating the Effectiveness of a Novel Systematic Screening Approach for Tuberculosis among Individuals Suspected or Recovered from COVID-19: Experiences from Niger and Guinea.

Evidence suggests that the COVID-19 pandemic negatively impacts tuberculosis (TB) activities. As TB and COVID-19 have similar symptoms, we assessed the effectiveness of integrated TB/COVID-19 screening in Guinea and Niger. From May to December 2020, TB screening was offered to symptomatic patients after a negative COVID-19 PCR test or after recovery from COVID-19 in Guinea. From December 2020 to March 2021, all presumptive COVID-19 patients with respiratory symptoms were tested simultaneously for COVID-19 and TB in Niger. We assessed the TB detection yield and used micro-costing to estimate the costs associated with both screening algorithms. A total of 863 individuals (758 in Guinea, and 105 in Niger), who were mostly male (60%) and with a median age of 34 (IQR: 26-45), were screened for TB. Reported symptoms were cough ≥2 weeks (49%), fever (45%), and weight loss (30%). Overall, 61 patients (7%) tested positive for COVID-19 (13 in Guinea, 48 in Niger) and 43 (4.9%) were diagnosed with TB disease (35 or 4.6% in Guinea, and 8 or 7.6% in Niger). The cost per person initiating TB treatment was USD $367 in Guinea and $566 in Niger. Overall, the yield of both approaches was high, and the cost was modest. Optimizing integrated COVID-19/TB screening may support maintaining TB detection during the ongoing pandemic.

Delays in TB Diagnosis and Treatment Initiation in Burkina Faso during the COVID-19 Pandemic.

The COVID-19 pandemic has significantly disrupted TB services, particularly in low resource settings. In Burkina Faso, a cross-sectional 'before and after' study was conducted to assess the impact of COVID-19 on access to TB services. Data was collected in two phases (Phase 1: December 2017−March 2018, and 2: October−December 2020) to estimate and compare various patient and system delays among TB patients before and during COVID-19 and explore changes in treatment seeking behaviors and practices. 331 TB patients were recruited across the two phases. A significant increase in median time between first symptom and contact with TB service (45 days vs. 26 days; p < 0.01) and decrease in median time between first contact and diagnosis, and treatment initiation, respectively, during COVID-19 compared to before. Fewer patients reported using public health centers and more patients reporting using private facilities as the point of first contact following TB symptom onset during the COVID-19 period compared to before. These findings suggest that COVID-19 has created barriers to TB service access and health seeking among symptomatic individuals, yet also led to some efficiencies in TB diagnostic and treatment services. Our findings can be help target efforts along specific points of the TB patient pathway to minimize the overall disruption of COVID-19 and future public health emergencies on TB control in Burkina Faso.

Prevalence and drivers of false-positive rifampicin-resistant Xpert MTB/RIF results: a prospective observational study in Rwanda.

BACKGROUND: The Xpert MTB/RIF (Xpert) assay is used globally to rapidly diagnose tuberculosis and resistance to rifampicin. We investigated the frequency and predictors of false-positive findings of rifampicin resistance with Xpert. METHODS: We did a prospective, observational study of individuals who were enrolled in a Rwandan nationwide diagnostic cohort study (DIAMA trial; NCT03303963). We included patients identified to have rifampicin resistance on initial Xpert testing. We did a repeat Xpert assay and used rpoB Sanger and deep sequencing alongside phenotypic drug susceptibility testing (pDST) to ascertain final rifampicin susceptibility status, with any (hetero)resistant result overriding. We used multivariable logistic regression to assess predictors of false rifampicin resistance on initial Xpert testing, adjusted for HIV status, tuberculosis treatment history, initial Xpert semi-quantitative bacillary load, and initial Xpert probe. FINDINGS: Between May 4, 2017, and April 30, 2019, 175 people were identified with rifampicin resistance at initial Xpert testing, of whom 154 (88%) underwent repeat Xpert assay. 54 (35%) patients were confirmed as rifampicin resistant on repeat testing and 100 (65%) were not confirmed with resistance. After further testing and sequencing, 121 (79%) of 154 patients had a final confirmed status for rifampicin susceptibility. 57 (47%) of 121 patients were confirmed to have a false rifampicin resistance result and 64 (53%) had true rifampicin resistance. A high pretest probability of rifampicin resistance did not decrease the odds of false rifampicin resistance (adjusted odds ratio [aOR] 6·0, 95% CI 1·0-35·0, for new tuberculosis patients vs patients who needed retreatment). Ten (16%) of the 64 patients with true rifampicin resistance did not have confirmed rifampicin resistance on repeat Xpert testing, of whom four had heteroresistance. Of 63 patients with a very low bacillary load on Xpert testing, 54 (86%) were falsely diagnosed with rifampicin-resistant tuberculosis. Having a very low bacillary load on Xpert testing was strongly associated with false rifampicin resistance at the initial Xpert assay (aOR 63·6, 95% CI 9·9-410·4). INTERPRETATION: The Xpert testing algorithm should include an assessment of bacillary load and retesting in case rifampicin resistance is detected on a paucibacillary sputum sample. Only when rifampicin resistance has been confirmed on repeat testing should multidrug-resistant tuberculosis treatment be started. When rifampicin resistance has not been confirmed on repeat testing, we propose that patients should be given first-line anti-tuberculosis drugs and monitored closely during treatment, including by baseline culture, pDST, and further Xpert testing. FUNDING: The European & Developing Countries Clinical Trials Partnership 2 programme, and Belgian Directorate General for Development Cooperation.

Prevalence of asymptomatic malaria parasitaemia following mass testing and treatment in Pakro sub-district of Ghana.

BACKGROUND: Global efforts to scale-up malaria control interventions are gaining steam. These include the use of Long-Lasting Insecticide Nets, Indoor Residual Spraying, Intermittent Preventive Treatment and Test, Treat and Track. Despite these, the drive for malaria elimination is far from being realistic in endemic communities in Africa. This is partly due to the fact that asymptomatic parasite carriage, not specifically targeted by most interventions, remains the bedrock that fuels transmission. This has led to mass testing, treatment and tracking (MTTT) as an alternative strategy to target asymptomatic individuals. We report the impact of MTTT on the prevalence of asymptomatic malaria parasitaemia over a one-year period in Ghana, hypothesizing that implementing MTTT could reduce the rate of asymptomatic parasitaemia. METHODS: A population of about 5000 individuals in seven communities in the Pakro sub-district of Ghana participated in this study. A register was developed for each community following a census. MTTT engaged trained community-based health volunteers who conducted house-to-house testing using RDTs every 4 months and treated positive cases with Artemisinin-based Combination Therapy. Between interventions, community-based management of malaria was implemented for symptomatic cases. RESULTS: MTTT Coverage was 98.8% in July 2017 and 79.3% in July 2018. Of those tested, asymptomatic infection with malaria parasites reduced from 36.3% (1795/4941) in July 2017 to 32.9% (1303/3966) in July 2018 (p = 0.001). Prevalence of asymptomatic parasitaemia among children under 15 years declined from 52.6% (1043/1984) in July 2017 to 47.5% (820/1728) in July 2018 (p = 0.002). Implementing MTTT significantly reduced asymptomatic parasitaemia by 24% from July 2017 to July 2018 after adjusting for age, ITN use and axillary temperature (OR = 0.76, CI = 0.67, 0.85 p ≤ 0.001). CONCLUSION: This study has demonstrated that implementing MTTT is feasible and could reduce the prevalence of asymptomatic malaria parasitaemia in children under 15 years of age. Furthermore, the use of community-based health volunteers could ensure high coverage at lower cost of implementation. TRIAL REGISTRATION: NCT04167566, Date 14/11/2019. Retrospective registration.

Challenges and perceptions of implementing mass testing, treatment and tracking in malaria control: a qualitative study in Pakro sub-district of Ghana.

BACKGROUND: Malaria remains endemic in Ghana despite several interventions. Studies have demonstrated very high levels of asymptomatic malaria parasitaemia in both under-five and school-age children. Mass testing, treatment and tracking (MTTT) of malaria in communities is being proposed for implementation with the argument that it can reduce parasite load, amplify gains from the other control interventions and consequently lead to elimination. However, challenges associated with implementing MTTT such as feasibility, levels of coverage to be achieved for effectiveness, community perceptions and cost implications need to be clearly understood. This qualitative study was therefore conducted in an area with on-going MTTT to assess community and health workers' perceptions about feasibility of scale-up and effectiveness to guide scale-up decisions. METHODS: This qualitative study employed purposive sampling to select the study participants. Ten focus group discussions (FGDs) were conducted in seven communities; eight with community members (n = 80) and two with health workers (n = 14). In addition, two in-depth interviews (IDI) were conducted, one with a Physician Assistant and another with a Laboratory Technician at the health facility. All interviews were recorded, transcribed, translated and analyzed using QSR NVivo 12. RESULTS: Both health workers and community members expressed positive perceptions about the feasibility of implementation and effectiveness of MTTT as an intervention that could reduce the burden of malaria in the community. MTTT implementation was perceived to have increased sensitisation about malaria, reduced the incidence of malaria, reduced household expenditure on malaria and alleviated the need to travel long distances for healthcare. Key challenges to implementation were doubts about the expertise of trained Community-Based Health Volunteers (CBHVs) to diagnose and treat malaria appropriately, side effects of Artemisinin-based Combination Therapies (ACTs) and misconceptions that CBHVs could infect children with epilepsy. CONCLUSION: The study demonstrated that MTTT was perceived to be effective in reducing malaria incidence and related hospital visits in participating communities. MTTT was deemed useful in breaking financial and geographical barriers to accessing healthcare. The interventions were feasible and acceptable to community members, despite observed challenges to implementation such as concerns about CBHVs' knowledge and skills and reduced revenue from internally generated funds (IGF) of the health facility.