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.

Implementation of systematic screening for tuberculosis disease and tuberculosis preventive treatment among people living with HIV attending antiretroviral treatment clinics in Ghana: a national pilot study.

OBJECTIVES: To assess the yield and cost of implementing systematic screening for tuberculosis (TB) disease among people living with HIV (PLHIV) and initiation of TB preventive treatment (TPT) in Ghana. DESIGN: Prospective cohort study from August 2019 to December 2020. SETTING: One hospital from each of Ghana's regions (10 total). PARTICIPANTS: Any PLHIV already receiving or newly initiating antiretroviral treatment were eligible for inclusion. INTERVENTIONS: All participants received TB symptom screening and chest radiography. Those with symptoms and/or an abnormal chest X-ray provided a sputum sample for microbiological testing. All without TB disease were offered TPT. PRIMARY AND SECONDARY OUTCOME MEASURES: We estimated the proportion diagnosed with TB disease and proportion initiating TPT. We used logistic regression to identify factors associated with TB disease diagnosis. We used microcosting to estimate the health system cost per person screened (2020 US$). RESULTS: Of 12 916 PLHIV attending participating clinics, 2639 (20%) were enrolled in the study and screened for TB disease. Overall, 341/2639 (12.9%, 95% CI 11.7% to 14.3%) had TB symptoms and/or an abnormal chest X-ray; 50/2639 (1.9%; 95% CI 1.4% to 2.5%) were diagnosed with TB disease, 20% of which was subclinical. In multivariable analysis, only those newly initiating antiretroviral treatment were at increased odds of TB disease (adjusted OR 4.1, 95% CI 2.0 to 8.2). Among 2589 participants without TB, 2581/2589 (99.7%) initiated TPT. Overall, the average cost per person screened during the study was US$57.32. CONCLUSION: In Ghana, systematic TB disease screening among PLHIV was of high yield and modest cost when combined with TPT. Our findings support WHO recommendations for routine TB disease screening among PLHIV.

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.

Prevalence of Malaria Infection in Pregnant Women Attending Antenatal Clinics in Southern Senegal.

Despite marked progress in Senegal, three regions in the southeast part continue to have a high burden of malaria, but there have been no recent studies assessing the prevalence of malaria associated with pregnancy. This study aimed to determine the prevalence of malaria infection in pregnant women attending antenatal clinics in Senegal. During the malaria transmission season of 2019, pregnant women attending 11 health care facilities for a scheduled visit and those presenting unwell with signs of malaria were invited to participate in a malaria screening study. A finger prick blood sample was taken for malaria diagnosis by rapid diagnosis test (RDT) and polymerase chain reaction (PCR). A total of 877 pregnant women were enrolled, 787 for a scheduled antenatal consultation and 90 for an unscheduled consultation with signs of malaria. The prevalence of Plasmodium falciparum among the first group was 48% by PCR and 20% by RDT, and that among the second group was 86% by PCR and 83% by RDT. RDT sensitivity in capturing asymptomatic, PCR-positive infections was 9.2% but ranged from 83% to 94% among febrile women. The prevalence of infection by PCR in women who reported having received at least three doses of sulfadoxine pyrimethamine (SP) was 41.9% compared with 58.9% in women who reported they had not received any SP doses (prevalence ratio adjusted for gravidity and gestational age, 0.54; 95% CI, 0.41-0.73). The burden of P. falciparum infections remains high among pregnant women, the majority of which are not captured by RDT. More effective measures to prevent malaria infection in pregnancy are needed.

Influence of the new dispersible fixed-dose combination anti-Tuberculosis drug on treatment adherence among children with Tuberculosis in Osun State, Nigeria.

BACKGROUND: The dispersible fixed-dose combination drug has been recommended as the mainstay of treatment for TB in children. However, more needs to be known about its effect on treatment. This study aimed to assess the effectiveness of the formulation on treatment adherence among children with TB. METHODS: A historical cohort design was used to assess and compare adherences of old loose non-dispersible and new dispersible fixed-dose anti-TB drugs, using a convergent parallel mixed-method approach for data collection. Determinants of treatment adherence were assessed using binary logistic regression. RESULTS: The proportion of children with good treatment adherence was higher in the new dispersible formulation group (82 [64.6%]) relative to the proportion among the loose non-dispersible formulation group (29 [23.4%]). Reports of forgetfulness, travelling and pill burden were significantly higher among those with poor adherence in the loose non-dispersible formulation group. Significant predictors of treatment adherence were acceptability (adjusted OR [AOR]=4.1, p=0.013, 95% CI 1.342 to 12.756), travelling from treatment areas (AOR=8.9, p=0.002, 95% CI 2.211 to 35.771) and forgetfulness (AOR=74.0, p<0.001, 95% CI 23.319 to 234.725). CONCLUSIONS: The determinants of treatment adherence are multifactorial. In addition to ensuring universal access to the drug, flexible referral in case of travelling and ensuring treatment partners' participation to minimise forgetfulness to take pills, are essential.

First results from the lessons learnt from the deployment of the Med Safety App for reporting adverse drug reactions in Ghana.

Background: The use of mobile phone technology for reporting adverse drug reactions (ADRs) in pharmacovigilance is relatively new.The objective of the study was to explore challenges and facilitators for the use of the Med Safety App for reporting ADRs in Ghana. A comparative evaluation of ADR reports received through the app and the standard paper-based form was also conducted. Methods: This was a cross-sectional study with a purposive sampling technique. The study population was persons who had downloaded the Med Safety App launched in Ghana 18 months before the study. Results: Of the 350 participants, 121 provided answers to the questionnaire sent as a Google form, representing a response rate of 34.6%.Ninety-five (78.5%) of the participants were healthcare professionals, and the remaining were patients. Seventy-five (64.7%) of the participants were using the app after initial installation because they thought it had helpful features. However, only 33 (27.3%) participants used the app to report ADRs, and of these, seven (21.2%) participants indicated that they would continue to use the app because it was easier than the other means of reporting ADRs. Most of the respondents, 109 (94%), indicated that they would recommend the app to someone else. There were some differences between the reports received through the app and between the paper-based Council for International Organizations of Medical Sciences (CIOMS) 1 form and the app, which warrant further exploration. Conclusion: Most participants indicated that the app is a useful tool and easy to use, and they were satisfied with the features of the app. Given that only just under one-third of participants had used the app to report ADRs, more time and training may be required to fully evaluate the feasibility of the use of the app going forward. The findings will help improve introduction of the app in other countries.

Challenges in engaging the private sector for tuberculosis prevention and care in Nigeria: a mixed methods study.

OBJECTIVES: This study aimed to assess the practices of private practitioners regarding tuberculosis (TB), and to ascertain factors related to the low contribution of private healthcare providers to TB prevention and care in Nigeria. DESIGN: This is a mixed methods study comprising a quantitative retrospective review and qualitative study. SETTING: Private health facilities (HF) in Oyo State and the Federal Capital Territory (FCT), Nigeria. PARTICIPANTS: We used routinely collected data on patients with tuberculosis (TB) notified between 1 January 2017 and 31 December 2018. In-depth interviews were also conducted with the clinical staff of the facilities. PRIMARY AND SECONDARY OUTCOME MEASURES: The study outcomes are practices of TB case notification and treatment outcome, as well as the barriers and enablers of TB notification. RESULTS: A total of 13 (11.0%) out of 118 private HF were designated as 'engaged' TB care facilities in Oyo State and none (0%) of the 198 private HF in the FCT held this designation. From the 214 patients with presumptive TB, 75 (35%) were diagnosed with TB, 42 (56%) had a bacteriological test done, 12 (16%) had an X-ray of the chest alone and 21 (28%) had other non-specific investigations. Most patients diagnosed were referred to a public HF, while 19 (25%) patients were managed at the private HF. Among them, 2 (10.5%) patients were treated with unconventional regimens, 4 (21%) were cured, 2 (11%) died, 3 (16%) lost to follow-up and 10 (53%) were not evaluated. The general practitioners did not have up-to-date knowledge of TB with a majority not trained on TB. Most referred patients with presumptive and confirmed TB to the public sector without feedback and were unclear regarding diagnostic algorithm and relevant tests to confirm TB. CONCLUSION: Most private facilities were not engaged to provide TB services although with knowledge and practice gaps. The study has been used to develop plans for strategic engagement of the private sector in Nigeria.

Early warning and response system for dengue outbreaks: Moving from research to operational implementation in Mexico.

Dengue disease epidemics have increased in time and space due to climatic and non-climatic factors such as urbanization. In the absence of an effective vaccine, preventing dengue outbreak relies on vector control activities. Employing computerized tools to predict outbreaks and respond in advance has great potential for improving dengue disease control. Evidence of integrating or implementing such applications into control programs and their impact are scarce, and endemic countries demand for experience sharing and know-how transfer. Mexico has extensive experience of pre-validated EWARS (Early Warning And Response System), a tool that was developed in 2012 as part of a collaboration with the Special Program for Research and Training in Tropical Diseases Unit (TDR) at the World Health Organization and used at national level. The advancement of EWARS since 2014 and its stepwise integration into the national surveillance system has increased the appreciation of the need for integrated surveillance (including disease, vector and climate surveillance), and for linking inter-institutional and trans-sectoral information for holistic epidemiological intelligence. The integration of the EWARS software into the national surveillance platform in Mexico was a remarkable milestone and a successful experience. This manuscript describes the implementation process of EWARS in Mexico, which started in 2012 and further demonstrates benefits, threats, and opportunities of integrating EWARS into existing national surveillance programs.

Implementation strategies for the introduction of the RTS,S/AS01 (RTS,S) malaria vaccine in countries with areas of highly seasonal transmission: workshop meeting report.

A workshop on implementation strategies for the introduction of the RTS,S/AS01 (RTS,S) malaria vaccine in countries with areas of highly seasonal transmission, was held as a hybrid meeting in Dakar, Senegal, and online, 23-25 January 2023. Delegates from Expanded Programmes on Immunization (EPI) and National Malaria Control Programmes (NMCPs) from 13 African countries, and representatives from key stakeholders participated. RTS,S is the first malaria vaccine to be recommended by the World Health Organization (WHO). The recommendation followed pilot implementation of the vaccine in Ghana, Kenya and Malawi, which showed that introduction of the vaccine was highly effective at scale, and was associated with a 30% reduction in hospital admissions with severe malaria in age groups eligible to have received the vaccine and no evidence of the safety signals that had been observed in the phase 3 trial. Clinical trials in Mali and Burkina Faso, showed that in children receiving Seasonal Malaria Chemoprevention (SMC), providing the vaccine just prior to high transmission seasons, matching the period of highest efficacy to the peak transmission season, resulted in substantial reduction in the incidence of clinical malaria and of severe malaria. While SMC has been successfully scaled-up despite the challenges of delivery, there is no established platform for seasonal vaccine delivery and no real-world experience. The objectives of this workshop were, therefore, to share experiences from countries that have introduced the RTS,S vaccine in routine child vaccination programmes, with SMC-implementing countries as they consider malaria vaccine introduction, and to explore implementation strategies in countries with seasonal transmission and where EPI coverage may be low especially in the second year of life. Practical implementation challenges, lessons learned for vaccine introduction, and research questions, towards facilitating the introduction of the RTS,S (and other malaria vaccines) in countries with seasonal malaria transmission were discussed.

Developing African arbovirus networks and capacity strengthening in arbovirus surveillance and response: findings from a virtual workshop.

This meeting report presents the key findings and discussion points of a 3-h virtual workshop, held on 21 September 2022, and organized by the "Resilience Against Future Threats through Vector Control (RAFT)" research consortium. The workshop aimed to identify priorities for advancing arbovirus research, network and capacity strengthening in Africa. Due to increasing human population growth, urbanization and global movement (trade, tourism, travel), mosquito-borne arboviral diseases, such as dengue, Chikungunya and Zika, are increasing globally in their distribution and prevalence. This report summarizes the presentations that reviewed the current status of arboviruses in Africa, including: (i) key findings from the recent WHO/Special Programme for Research & Training in Tropical Diseases (WHO/TDR) survey in 47 African countries that revealed deep and widespread shortfalls in the capacity to cope with arbovirus outbreak preparedness, surveillance and control; (ii) the value of networking in this context, with examples of African countries regarding arbovirus surveillance; and (iii) the main priorities identified by the breakout groups on "research gaps", "networks" and "capacity strengthening".

Facilitators and barriers to seasonal malaria chemoprevention (SMC) uptake in Nigeria: a qualitative approach.

BACKGROUND: SMC was adopted in Nigeria in 2014 and by 2021 was being implemented in 18 states, over four months between June and October by 143000 community drug distributors (CDDs) to a target population of 23million children. Further expansion of SMC is planned, extending to 21 states with four or five monthly cycles. In view of this massive scale-up, the National Malaria Elimination Programme undertook qualitative research in five states shortly after the 2021 campaign to understand community attitudes to SMC so that these perspectives inform future planning of SMC delivery in Nigeria. METHODS: In 20 wards representing urban and rural areas with low and high SMC coverage in five states, focus group discussions were held with caregivers, and in-depth interviews conducted with community leaders and community drug distributors. Interviews were also held with local government area and State malaria focal persons and at national level with the NMEP coordinator, and representatives of partners working on SMC in Nigeria. Interviews were recorded and transcribed, those in local languages translated into English, and transcripts analysed using NVivo software. RESULTS: In total, 84 focus groups and 106 interviews were completed. Malaria was seen as a major health concern, SMC was widely accepted as a key preventive measure, and community drug distributors (CDDs) were generally trusted. Caregivers preferred SMC delivered door-to-door to the fixed-point approach, because it allowed them to continue daily tasks, and allowed time for the CDD to answer questions. Barriers to SMC uptake included perceived side-effects of SMC drugs, a lack of understanding of the purpose of SMC, mistrust and suspicions that medicines provided free may be unsafe or ineffective, and local shortages of drugs. CONCLUSIONS: Recommendations from this study were shared with all community drug distributors and others involved in SMC campaigns during cascade training in 2022, including the need to strengthen communication about the safety and effectiveness of SMC, recruiting distributors from the local community, greater involvement of state and national level pharmacovigilance coordinators, and stricter adherence to the planned medicine allocations to avoid local shortages. The findings reinforce the importance of retaining door-to-door delivery of SMC.

A new online toolkit to support implementation research to enhance the use of digital innovations to End TB.

Digital technologies are playing an increasing role in the global response to tuberculosis (TB), however their effectiveness and impact are often shaped in the context in which they are implemented. Implementation research can help facilitate the effective introduction of digital health technologies in TB programmes. In 2020, the Implementation Research for Digital Technologies and TB online toolkit (IR4DTB) was developed and launched by the Special Programme for Research and Training in Tropical Diseases, and the Global TB Programme at the World Health Organization (WHO), to build local capacity for IR and promote the effective use of digital technologies within TB programmes. This paper describes the development and piloting of the IR4DTB toolkit, a self-learning tool designed for TB programme implementers. The toolkit comprises six modules reflecting key steps of the IR process, practical instructions and guidance on how to complete these steps, and real-word case studies to illustrate key learning points. This paper also describes the launch of the IR4DTB during a five-day training workshop with TB staff from China, Uzbekistan, Pakistan, Malaysia. The workshop included facilitated sessions on the IR4DTB modules, and provided an opportunity for participants to work with facilitators to develop a comprehensive IR proposal addressing an identified challenge related to the implementation and/or scale-up of digital health technologies for TB care in their home country. Post-workshop evaluation revealed high level of satisfaction among participants with the workshop content and format. The IR4DTB toolkit is a replicable model which can be used to strengthen the TB staff capacity to innovate within a culture of continuous collection of evidence. Through continued trainings and adaptation of the toolkit alongside the integration of digital technologies within TB prevention and care, this model has the potential to contribute directly to all components of the End TB Strategy.

Prevalence of Plasmodium falciparum haplotypes associated with resistance to sulfadoxine-pyrimethamine and amodiaquine before and after upscaling of seasonal malaria chemoprevention in seven African countries: a genomic surveillance study.

BACKGROUND: Seasonal malaria chemoprevention is used in 13 countries in the Sahel region of Africa to prevent malaria in children younger than 5 years. Resistance of Plasmodium falciparum to seasonal malaria chemoprevention drugs across the region is a potential threat to this intervention. METHODS: Between December, 2015, and March, 2016, and between December, 2017, and March, 2018, immediately following the 2015 and 2017 malaria transmission seasons, community surveys were done among children younger than 5 years and individuals aged 10-30 years in districts implementing seasonal malaria chemoprevention with sulfadoxine-pyrimethamine and amodiaquine in Burkina Faso, Chad, Guinea, Mali, Nigeria, Niger and The Gambia. Dried blood samples were collected and tested for P falciparum DNA by PCR. Resistance-associated haplotypes of the P falciparum genes crt, mdr1, dhfr, and dhps were identified by quantitative PCR and sequencing of isolates from the collected samples, and survey-weighted prevalence and prevalence ratio between the first and second surveys were estimated for each variant. FINDINGS: 5130 (17·5%) of 29 274 samples from 2016 and 2176 (7·6%) of 28 546 samples from 2018 were positive for P falciparum on quantitative PCR. Among children younger than 5 years, parasite carriage decreased from 2844 of 14 345 samples (19·8% [95% CI 19·2-20·5]) in 2016 to 801 of 14 019 samples (5·7% [5·3-6·1]) in 2018 (prevalence ratio 0·27 [95% CI 0·24-0·31], p<0·0001). Genotyping found no consistent evidence of increasing prevalence of amodiaquine resistance-associated variants of crt and mdr1 between 2016 and 2018. The dhfr haplotype IRN (consisting of 51Ile-59Arg-108Asn) was common at both survey timepoints, but the dhps haplotype ISGEAA (431Ile-436Ser-437Gly-540Glu-581Ala-613Ala), crucial for resistance to sulfadoxine-pyrimethamine, was always rare. Parasites carrying amodiaquine resistance-associated variants of both crt and mdr1 together with dhfr IRN and dhps ISGEAA occurred in 0·05% of isolates. The emerging dhps haplotype VAGKGS (431Val-436Ala-437Gly-540Lys-581Gly-613Ser) was present in four countries. INTERPRETATION: In seven African countries, evidence of a significant reduction in parasite carriage among children receiving seasonal malaria chemoprevention was found 2 years after intervention scale-up. Combined resistance-associated haplotypes remained rare, and seasonal malaria chemoprevention with sulfadoxine-pyrimethamine and amodiaquine is expected to retain effectiveness. The threat of future erosion of effectiveness due to dhps variant haplotypes requires further monitoring. FUNDING: Unitaid.

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.

TB-PRACTECAL: study protocol for a randomised, controlled, open-label, phase II-III trial to evaluate the safety and efficacy of regimens containing bedaquiline and pretomanid for the treatment of adult patients with pulmonary multidrug-resistant tuberculosis.

BACKGROUND: Globally rifampicin-resistant tuberculosis disease affects around 460,000 people each year. Currently recommended regimens are 9-24 months duration, have poor efficacy and carry significant toxicity. A shorter, less toxic and more efficacious regimen would improve outcomes for people with rifampicin-resistant tuberculosis. METHODS: TB-PRACTECAL is an open-label, randomised, controlled, phase II/III non-inferiority trial evaluating the safety and efficacy of 24-week regimens containing bedaquiline and pretomanid to treat rifampicin-resistant tuberculosis. Conducted in Uzbekistan, South Africa and Belarus, patients aged 15 and above with rifampicin-resistant pulmonary tuberculosis and requiring a new course of therapy were eligible for inclusion irrespective of HIV status. In the first stage, equivalent to a phase IIB trial, patients were randomly assigned one of four regimens, stratified by site. Investigational regimens include oral bedaquiline, pretomanid and linezolid. Additionally, two of the regimens also included moxifloxacin (arm 1) and clofazimine (arm 2) respectively. Treatment was administered under direct observation for 24 weeks in investigational arms and 36 to 96 weeks in the standard of care arm. The second stage of the study was equivalent to a phase III trial, investigating the safety and efficacy of the most promising regimen/s. The primary outcome was the percentage of unfavourable outcomes at 72 weeks post-randomisation. This was a composite of early treatment discontinuation, treatment failure, recurrence, lost-to-follow-up and death. The study is being conducted in accordance with ICH-GCP and full ethical approval was obtained from Médecins sans Frontières ethical review board, London School of Hygiene and Tropical Medicine ethical review board as well as ERBs and regulatory authorities at each site. DISCUSSION: TB-PRACTECAL is an ambitious trial using adaptive design to accelerate regimen assessment and bring novel treatments that are effective and safe to patients quicker. The trial took a patient-centred approach, adapting to best practice guidelines throughout recruitment. The implementation faced significant challenges from the COVID-19 pandemic. The trial was terminated early for efficacy on the advice of the DSMB and will report on data collected up to the end of recruitment and, additionally, the planned final analysis at 72 weeks after the end of recruitment. TRIAL REGISTRATION: Clinicaltrials.gov NCT02589782. Registered on 28 October 2015.

Implementation of a peer support intervention to promote the detection, reporting and management of adverse drug reactions in people living with HIV in Uganda: a protocol for a quasi-experimental study.

INTRODUCTION: Patients have contributed <1% of spontaneous adverse drug reaction (ADR) reports in Uganda's pharmacovigilance database. Peer support combined with mobile technologies could empower people living with HIV (PLHIV) to report ADRs and improve ADR management through linkage to care. We seek to test the feasibility and effect of a peer support intervention on ADR reporting by PLHIV receiving combination antiretroviral therapy (cART) in Uganda; identify barriers and facilitators to the intervention; and characterise ADR reporting and management. METHODS AND ANALYSIS: This is a quasi-experimental study to be implemented over 4 months at 12 intervention and 12 comparison cART sites from four geographical regions of Uganda. Per region, two blocks each with a tertiary, secondary and primary care cART site will be selected by simple random sampling. Blocks per region will be randomly assigned to intervention and comparison arms.Study units will include cART sites and PLHIV receiving cART. PLHIV at intervention sites will be assigned to peer supporters to empower them to report ADRs directly to the National Pharmacovigilance Centre (NPC). Peer supporters will be expert clients from among PLHIV and/or recognised community health workers.Direct patient reporting of ADRs to NPC will leverage the Med Safety App and toll-free unstructured supplementary service data interface to augment traditional pharmacovigilance methods.The primary outcomes are attrition rate measured by number of study participants who remain in the study until the end of follow-up at 4 months; and number of ADR reports submitted to NPC by PLHIV as measured by questionnaire and data abstraction from the national pharmacovigilance database at baseline and 4 months. ETHICS AND DISSEMINATION: The study received ethical approval from: School of Health Sciences Research and Ethics Committee at Makerere University (MAKSHSREC-2020-64) and Uganda National Council for Science and Technology (HS1206ES). Results will be shared with PLHIV, policy-makers, the public and academia. TRIAL REGISTRATION NUMBER: ISRCTN75989485.

Prevalence, acceptability, and cost of routine screening for pulmonary tuberculosis among pregnant women in Cotonou, Benin.

OBJECTIVES: We sought to evaluate the yield, cost, feasibility, and acceptability of routine tuberculosis (TB) screening of pregnant women in Cotonou, Benin. DESIGN: Mixed-methods, cross-sectional study with a cost assessment. SETTING: Eight participating health facilities in Cotonou, Benin. PARTICIPANTS: Consecutive pregnant women presenting for antenatal care at any participating site who were not in labor or currently being treated for TB from April 2017 to April 2018. INTERVENTIONS: Screening for the presence of TB symptoms by midwives and Xpert MTB/RIF for those with cough for at least two weeks. Semi-structured interviews with 14 midwives and 16 pregnant women about experiences with TB screening. PRIMARY AND SECONDARY OUTCOME MEASURES: Proportion of pregnant women with cough of at least two weeks and/or microbiologically confirmed TB. The cost per pregnant woman screened and per TB case diagnosed in 2019 USD from the health system perspective. RESULTS: Out of 4,070 pregnant women enrolled in the study, 94 (2.3%) had a cough for at least two weeks at the time of screening. The average (standard deviation) age of symptomatic women was 26 ± 5 years and 5 (5.3%) had HIV. Among the 94 symptomatic women, 2 (2.3%) had microbiologically confirmed TB for a TB prevalence of 49 per 100,000 (95% CI: 6 to 177 per 100,000) among pregnant women enrolled in the study. The average cost to screen one pregnant woman for TB was $1.12 USD and the cost per TB case diagnosed was $2271 USD. Thematic analysis suggested knowledge of TB complications in pregnancy was low, but that routine TB screening was acceptable to both midwives and pregnant women. CONCLUSION: Enhanced screening for TB among pregnant women is feasible, acceptable, and inexpensive per woman screened, however in this setting has suboptimal yield even if it can contribute to enhance TB case finding.