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Background: Existing data on the prevalence of hepatitis C virus (HCV) genotypes and subtypes in Rwanda need to be strengthened. The aim of this study was to identify HCV genotypes and subtypes among HCV-infected patients, as well as their geographical distribution in Rwanda, and to identify the social and economic factors that could influence HCV epidemiology which would make it possible to target national preventive and management actions for infected patients., Methods: This study included 560 patients with confirmed chronic HCV infection. Patients were recruited from various health facilities in the four provinces of Rwanda as well as in the City of Kigali and had never received treatment with direct-acting antiviral (DAAs). HCV viral loads were measured using Cobas® AmpliPrep/Cobas® TaqMan® HCV Quantitative Test, version 2.0. HCV genotyping was performed using an in-house sequencing protocol targeting the NS5B central region. Genotypic HCV prevalence was correlated with patient geographic location, sociodemographic, behavioral, lifestyle, and clinical factors., Results: HCV genotype 4 was detected in 99.3% of the patients, while genotype 3 was identified in 0.7%. A total of eight (8) HCV subtypes were detected, with 4k being the predominant subtype nationwide (49.5%), followed by subtypes 4r (21.2%), 4q (16.2%), 4v (7.9%), 4b (2.0%), 4l (1.8%), 4c and 3h represent 0.7% each. Our findings reveal subtype distribution variations among provinces. Subtype 4k was prevalent across regions, particularly in Kigali (64.0%) and the Eastern Province (61.6%). Subtype 4q was more common in the northern province (40.7%), 4r in the southern (43.9%) and western provinces (37.1%), and 4v in the eastern province (17.8%). Farmers exhibit a distinct infection profile compared to other occupations, showing a lower prevalence of subtype 4k but a higher prevalence of subtype 4r., Conclusions: Our study revealed that HCV infection is unevenly distributed in Rwanda, dominated by HCV genotype 4, with considerable heterogeneity in the repartition of the different subtypes. We found potential associations between rural/urban lifestyles and HCV subtype profiles. Determined HCV distribution and diversity can serve as basis not only for HCV infection awareness and prevention campaigns, but also success and guidance for personalized treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The Africa Centers for Disease Control and Prevention declared mpox a Public Health Emergency of Continental Security (PHECS) in Africa. African public health systems have moved to mobilize a response against a backdrop of inherent significant challenges. With this commentary, we discuss how lessons from past public health emergencies, particularly COVID-19 and Ebola outbreaks, have prepared the region for improved disease surveillance, rapid response strategies, and effective public health communication and how these lessons can be applied to the mpox response, emphasizing the importance of strong healthcare infrastructure, effective data sharing, community engagement, targeted interventions, and robust contact tracing. Additionally, addressing misinformation and building public trust are crucial for controlling the spread of any disease. By leveraging these strategies, African countries can enhance their response to mpox. This includes improving diagnostic capabilities, strengthening cross-border collaborations, and prioritizing vaccination campaigns where needed. Ultimately, by applying the hard-earned lessons from the COVID-19 pandemic and Ebola outbreak, the East Africa region can better address the challenges posed by mpox and safeguard public health.

Objective: To evaluate the use of antigen-based rapid diagnostic tests (Ag-RDTs) alongside a digital tool to deliver household-level COVID-19 testing by community health workers (CHWs), in line with Rwanda's ambition to decentralise COVID-19 testing., Design: This was an operational pilot study to evaluate the impact and operational characteristics of using the digital e-ASCov tool combined with Ag-RDTs to support COVID-19 symptom screening and rapid testing by CHWs across eight districts in Rwanda. A total of 800 CHWs selected from both rural and urban areas were trained in delivering Ag-RDTs for COVID-19 testing and using the e-ASCOV application for data capture on a smartphone. Laboratory technicians repeated a subset of Ag-RDTs to assess the concordance of results obtained by CHWs. The study also assessed CHWs' experience of the intervention using a mixed-methods approach., Setting: Eight rural, urban and semiurban districts in Rwanda., Participants: A total of 19 544 individuals were enrolled and screened for signs and symptoms of COVID-19., Interventions: Community-based screening for COVID-19 by CHWs using the digital tool e-ASCov combined with rapid testing using Ag-RDTs., Main Outcome Measures: Number of participants screened and tested; concordance of Ag-RDT results between CHWs and laboratory technicians; feasibility of study procedures by CHWs and CHWs perceptions of the digital tool and Ag-RDT testing., Results: From February to May 2022, CHWs screened 19 544 participants, of whom 4575 (23.4%) had COVID-19-related symptoms or a history of exposure to the infection. Among them, 86 (1.9%) were positive on Ag-RDTs. Concordance of Ag-RDT results between CHWs and laboratory technicians was 100%. Of the 800 trained CHWs, 746 (93.3%) were independently able to conduct household-based COVID-19 screening, perform the Ag-RDTs and send data to the central server. Most CHWs (>80%) found Ag-RDTs and e-ASCOV easy to use., Conclusions: This study demonstrated the feasibility of deploying a digital tool and Ag-RDTs for household-level SARS-CoV-2 detection in Rwanda. The findings support a broader roll-out of digitally supported rapid testing by CHWs to broaden access to testing for priority diseases., Competing Interests: Competing interests: The authors J-BM, OA, KS, PA and RK disclose that they are employed by FIND. The other authors declare that no conflicts of interest exist., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

A Rift Valley fever epizootic affected livestock in Rwanda during March-October 2022. We confirmed 3,112 infections with the virus, including 1,342 cases, 1,254 abortions, and 516 deaths among cattle, goats, and sheep. We recommend a One Health strategy for investigations and response to protect animal and human health.

Fungal infections (FIs) are spreading globally, raising a significant public health concern. However, its documentation remains sparse in Africa, particularly in Rwanda. This report provides a comprehensive review of FIs in Rwanda based on a systematic review of reports published between 1972 and 2022. The findings reveal a rich diversity of fungal pathogens, including Blastomyces , Candida , Cryptococcus , Histoplasma , Microsporum , Pneumocystis , Rhinosporidium , and Trichophyton caused human infections. Candida infections predominantly affect the vagina mucosa, while Histoplasma duboisi was linked to disseminated infections. Other pathogens, such as Blastomyces dermatitidis and Rhinosporidium seeberi, were associated with cerebellar and nasal mucosa infections, respectively. The widespread observation of soilborne fungi affecting bean crops highlights the pathogens' threat to agricultural productivity, food security, and socioeconomic stability, as well as potential health impacts on humans, animals, and the environment. Of particular importance is that there is no information about FIs among animals in the country. Moreover, the analysis underscores significant limitations in the detection, reporting, and healthcare services related to FIs in the country, indicating gaps in diagnostic capacity and surveillance systems. This is underscored by the predominant use of traditional diagnostic techniques, including culture, cytology, and histopathology in the absence of integrating more sensitive and specific molecular tools in investigating FIs. Developing the diagnostic capacities and national surveillance systems are urgently needed to improve the health of crops, animals, and humans, as well as food security and socioeconomic stability in Rwanda. Also, it is important to indicate severe gaps in the evidence to inform policymaking, guide strategic planning, and improve healthcare and public health services, underscoring the urgent need to build national capacity in fungal diagnosis, surveillance, and research. Raising awareness among the public, scientific community, healthcare providers, and policymakers remains crucial. Furthermore, this report reveals the threats of FIs on public health and food insecurity in Rwanda. A multisectoral one health strategy is essential in research and intervention to determine and reduce the health and safety impacts of fungal pathogens on humans, animals, and the environment.

Background: The core vector control tools used to reduce malaria prevalence are currently long-lasting insecticidal nets (LLINs), and indoor residual spraying (IRS). These interventions are hindered by insecticide resistance and behavioural adaptation by malaria vectors. Thus, for effective interruption of malaria transmission, there is a need to develop novel vector control interventions and technologies to address the above challenges. Larviciding using drones was experimented as an innovative tool that could complement existing indoor interventions to control malaria., Methods: A non-randomized larviciding trial was carried out in irrigated rice fields in sub-urban Kigali, Rwanda. Potential mosquito larval habitats in study sites were mapped and subsequently sprayed using multirotor drones. Application of Bacillus thuringiensis var. israelensis (Bti) (Vectobac ® WDG) was followed by entomological surveys that were performed every two weeks over a ten-month period. Sampling of mosquito larvae was done with dippers while adult mosquitoes were collected using CDC miniature light traps (CDC-LT) and pyrethrum spraying collection (PSC) methods. Malaria cases were routinely monitored through community health workers in villages surrounding the study sites., Results: The abundance of all-species mosquito larvae, Anopheles larvae and all-species pupae declined by 68.1%, 74.6% and 99.6%, respectively. Larval density was reduced by 93.3% for total larvae, 95.3% for the Anopheles larvae and 61.9% for pupae. The total adult mosquitoes and Anopheles gambiae sensu lato collected using CDC-Light trap declined by 60.6% and 80% respectively. Malaria incidence also declined significantly between intervention and control sites (U = 20, z = - 2.268, p = 0.023)., Conclusions: The larviciding using drone technology implemented in Rwanda demonstrated a substantial reduction in abundance and density of mosquito larvae and, concomitant decline in adult mosquito populations and malaria incidences in villages contingent to the treatment sites. The scaling up of larval source management (LSM) has to be integrated in malaria programmes in targeted areas of malaria transmission in order to enhance the gains in malaria control., (© 2024. The Author(s).)

Rwanda is a country in East Africa, a region characterized by highly mobile populations and outbreaks of high-consequence infectious diseases occurring on a regular basis. To increase the level of outbreak preparedness in the region, the Rwandan government and the German Ministry of Health signed a joint agreement to construct a new high-level isolation unit in Rwanda, the first in East Africa, and implement a training program for Rwandan healthcare workers to equip them with the necessary skills and knowledge for medical management of patients under high-level isolation conditions, including intensive care treatment. To better understand the scope and format of the planned training program, a needs assessment was performed based on findings from a standardized survey of 4 intensive care units in Rwanda as well as observations from 2 members of a German high-level isolation unit who completed clinical internships at Rwandan hospitals. In this case study, we describe the necessary steps to promote the sustainability and capabilities of the new high-level isolation unit in Kigali and ensure the successful implementation of the training program.

Antimicrobial resistance (AMR) is a significant global public health threat. This review presents the most recent in-depth review of the situation of the main AMR types in relation to the most commonly prescribed antibiotics in the World Health Organization (WHO) African Region. Underlying genes of resistance have been analyzed where possible. A search to capture published research data on AMR from articles published between 2016 and 2020 was done using PubMed and Google Scholar, with rigorous inclusion/exclusion criteria. Out of 48003 articles, only 167 were included. Among the tested gram-negative bacteria species, Klebsiella spp. remain the most tested, and generally the most resistant. The highest overall phenotypic resistance for imipenem was reported in E. coli , whereas for meropenem, E. coli and Haemophilus spp. showed an equal resistance proportion at 2.5%. For gram-positive bacteria, Streptococcus pneumoniae displayed high resistance percentages to trimethoprim/sulfamethoxazole (64.3%), oxacillin (32.2%), penicillin (23.2%), and tetracycline (28.3%), whereas Staphylococcus aureus contributed to 22.8% and 10% resistance to penicillin and oxacillin, respectively. This review shows that AMR remains a major public health threat. The present findings will help public health decision-makers in developing efficient preventive strategies and adequate policies for antibiotic stewardship and surveillance in line with the global action plan for AMR.

Rift Valley fever (RVF), a mosquito-borne transboundary zoonosis, was first confirmed in Rwanda's livestock in 2012 and since then sporadic cases have been reported almost every year. In 2018, the country experienced its first large outbreak, which was followed by a second one in 2022. To determine the circulating virus lineages and their ancestral origin, two genome sequences from the 2018 outbreak, and thirty-six, forty-one, and thirty-eight sequences of small (S), medium (M), and large (L) genome segments, respectively, from the 2022 outbreak were generated. All of the samples from the 2022 outbreak were collected from slaughterhouses. Both maximum likelihood and Bayesian-based phylogenetic analyses were performed. The findings showed that RVF viruses belonging to a single lineage, C, were circulating during the two outbreaks, and shared a recent common ancestor with RVF viruses isolated in Uganda between 2016 and 2019, and were also linked to the 2006/2007 largest East Africa RVF outbreak reported in Kenya, Tanzania, and Somalia. Alongside the wild-type viruses, genetic evidence of the RVFV Clone 13 vaccine strain was found in slaughterhouse animals, demonstrating a possible occupational risk of exposure with unknown outcome for people working in meat-related industry. These results provide additional evidence of the ongoing wide spread of RVFV lineage C in Africa and emphasize the need for an effective national and international One Health-based collaborative approach in responding to RVF emergencies.

Antimicrobial resistance (AMR) is a major public health threat linked to increased morbidity and mortality. It has the potential to return us to the pre-antibiotic era. Antimicrobial stewardship (AMS) programs are recognized as a key intervention to improve antimicrobial use and combat AMR. However, implementation of AMS remains limited in Africa, particularly in Rwanda. This study aimed to assess prescription practices, identify areas for improvement, and promote adherence to AMS principles. Conducted at King Faisal Hospital in Rwanda, this qualitative study used semi-structured interviews with eight participants until saturation was reached. The interviews were recorded, transcribed, and thematically analyzed, revealing four emerging themes. The first theme was on AMS activities that were working well based on availability of microbiology laboratory results and prescription guidelines as factors influencing antibiotic prescription adjustments. The second theme was related to challenges during the implementation of the AMS program, including the prescription of broad-spectrum antibiotics, limited local data on AMR patterns, and stock-outs of essential antibiotics. The third theme was on the importance of adhering to AMR management guidelines at KFH. The last emerged on recommendations from participants centered on regular training for healthcare workers, widespread dissemination of AMR findings across departments, and the enforcement of antibiotic restriction policies. These actions can improve prescription behaviors, upholding the highest standards of patient care, and strengthening the nascent AMS program.

Background: Emerging artemisinin partial resistance and diagnostic resistance are a threat to malaria control in Africa. Plasmodium falciparum kelch13 (k13) propeller-domain mutations that confer artemisinin partial resistance have emerged in Africa. k13-561H was initially described at a frequency of 7.4% from Masaka in 2014-2015, but not present in nearby Rukara. By 2018, 19.6% of isolates in Masaka and 22% of isolates in Rukara contained the mutation. Longitudinal monitoring is essential to inform control efforts. In Rukara, an assessment was conducted to evaluate recent k13-561H prevalence changes, as well as other key mutations. Prevalence of hrp2/3 deletions was also assessed., Methods: Samples collected in Rukara in 2021 were genotyped for key artemisinin and partner drug resistance mutations using molecular inversion probe assays and for hrp2/3 deletions using qPCR., Results: Clinically validated k13 artemisinin partial resistance mutations continue to increase in prevalence with the overall level of mutant infections reaching 32% in Rwanda. The increase appears to be due to the rapid emergence of k13-675V (6.4%, 6/94 infections), previously not observed, rather than continued expansion of 561H (23.5% 20/85). Mutations to partner drugs and other anti-malarials were variable, with high levels of multidrug resistance 1 (mdr1) N86 (95.5%) associated with lumefantrine decreased susceptibility and dihydrofolate reductase (dhfr) 164L (24.7%) associated with a high level of antifolate resistance, but low levels of amodiaquine resistance polymorphisms with chloroquine resistance transporter (crt) 76T: at 6.1% prevalence. No hrp2 or hrp3 gene deletions associated with diagnostic resistance were found., Conclusions: Increasing prevalence of artemisinin partial resistance due to k13-561H and the rapid expansion of k13-675V is concerning for the longevity of artemisinin effectiveness in the region. False negative RDT results do not appear to be an issue with no hrp2 or hpr3 deletions detected. Continued molecular surveillance in this region and surrounding areas is needed to follow artemisinin partial resistance and provide early detection of partner drug resistance, which would likely compromise control and increase malaria morbidity and mortality in East Africa., (© 2024. The Author(s).)

Introduction: Precision medicine (PM) or personalized medicine is an innovative approach that aims to tailor disease prevention and treatment to consider the differences in people's genes, environments, and lifestyles. Although many efforts have been made to accelerate the universal adoption of PM, several challenges need to be addressed in order to advance PM in Africa. Therefore, our study aimed to establish baseline data on the knowledge and perceptions of the implementation of PM in the Rwandan healthcare setting., Method: A descriptive qualitative study was conducted in five hospitals offering diagnostics and oncology services to cancer patients in Rwanda. To understand the existing policies regarding PM implementation in the country, two additional institutions were surveyed: the Ministry of Health (MOH), which creates and sets policies for the overall vision of the health sector, and the Rwanda Biomedical Center (RBC), which coordinates the implementation of health sector policies in the country. The researchers conducted 32 key informant interviews and assessed the functionality of available PM equipment in the 5 selected health facilities. The data were thematically categorized and analyzed., Results: The study revealed that PM is perceived as a complex and expensive program by most health managers and health providers. The most cited challenges to implementing PM included the following: the lack of policies and guidelines; the lack of supportive infrastructures and limited suppliers of required equipment and laboratory consumables; financial constraints; cultural, behavioral, and religious beliefs; and limited trained, motivated, and specialized healthcare providers. Regarding access to health services for cancer treatment, patients with health insurance pay 10% of their medical costs, which is still too expensive for Rwandans., Conclusion: The study participants highlighted the importance of PM to enhance healthcare delivery if the identified barriers are addressed. For instance, Rwandan health sector leadership might consider the creation of specialized oncology centers in all or some referral hospitals with all the necessary genomic equipment and trained staff to serve the needs of the country and implement a PM program.

Background: Ebola Virus Disease (EVD) is a severe and often fatal illness that affects humans and has significant public health implications, including high mortality rates, strain on healthcare systems, and social and economic disruption. On 20 September 2022, Uganda declared an Ebola disease outbreak caused by the Sudan ebolavirus species. The neighboring countries of Uganda were classified by World Health Organization (WHO) as being at high risk of Sudan Ebola Virus Disease (SUDV) importation. The country of Rwanda implemented different sustainable strategies and activities to prepare and ensure a timely and effective response to SUDV outbreaks once it has arrived in the country. We aimed to highlight the sustainable strategies and activities implemented for SUDV preparedness and the subsequent lessons learnt in Rwanda., Methods: This paper reviewed the documentation on activities implemented for SUDV preparedness, with a focus on lessons learned from different countries. The paper analyzed the common themes and highlighted the key components of EVD preparedness in Rwanda after declaration of SUDV outbreak in Uganda., Results: The key components of SUDV preparedness include its readiness assessment in Rwanda, effective coordination, collaboration and leadership mechanisms, enhancing the early detection and surveillance system, effective risk communication and community engagement, capacity building of healthcare providers on case management and infection prevention and control (IPC), and continual preparedness. These components were essential to ensure timely and effective preparation and response to SUDV related outbreaks., Conclusion: A multi-sectoral approach involving all stakeholders was necessary to ensure timely and effective preparation and response. Continuous investment in preparedness, strengthening of health systems, and the review of preparedness components provided insights into the best practices for SUDV preparedness, which were essential to prevent future outbreaks and minimize their impact. This will inform other countries about the role of timely development of preparedness plans., (© 2023. The Author(s).)

Salmonella enterica serovar Typhi (S. Typhi) is the cause of typhoid fever, presenting high rates of morbidity and mortality in low- and middle-income countries. The H58 haplotype shows high levels of antimicrobial resistance (AMR) and is the dominant S. Typhi haplotype in endemic areas of Asia and East sub-Saharan Africa. The situation in Rwanda is currently unknown and therefore to reveal the genetic diversity and AMR of S. Typhi in Rwanda, 25 historical (1984-1985) and 26 recent (2010-2018) isolates from Rwanda were analysed using whole genome sequencing (WGS). WGS was locally implemented using Illumina MiniSeq and web-based analysis tools, thereafter complemented with bioinformatic approaches for more in-depth analyses. Whereas historical S. Typhi isolates were found to be fully susceptible to antimicrobials and show a diversity of genotypes, i.e 2.2.2, 2.5, 3.3.1 and 4.1; the recent isolates showed high AMR rates and were predominantly associated with genotype 4.3.1.2 (H58, 22/26; 84,6%), possibly resulting from a single introduction in Rwanda from South Asia before 2010. We identified practical challenges for the use of WGS in endemic regions, including a high cost for shipment of molecular reagents and lack of high-end computational infrastructure for the analyses, but also identified WGS to be feasible in the studied setting and giving opportunity for synergy with other programs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Rutanga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The prevalence of human papillomavirus (HPV) infections in other anatomical sites besides the uterine cervix is unknown in East Africa. Here, we assessed the prevalence and concordance of HPVs in different anatomical sites in HIV concordant couples in Rwanda., Methods: Fifty HIV-positive concordant male-female couples at the HIV clinic at the University Teaching Hospital of Kigali in Rwanda were interviewed, swabbed from the oral cavity (OC), oropharynx (OP), anal canal (AC), vagina (V), uterine cervix (UC) and penis. A pap smear test and a self-collected vaginal swab (Vself) were taken. Twelve high-risk (HR)-HPVs were analyzed., Results: HR-HPVs occurred in 10%/12% in OC, 10%/0% in OP and 2%/24% in AC ( p = 0.002) in men and women, respectively. HR-HPVs occurred in 24% of UC, 32% of Vself, 30% of V and 24% of P samples. Only 22.2% of all HR-HPV infections were shared by both partners (κ -0.34 ± 0.11; p = 0.004). The type-specific HR-HPV concordance was significant between male to female OC-OC (κ 0.56 ± 0.17), V-VSelf (κ 0.70 ± 0.10), UC-V (κ 0.54 ± 0.13), UC-Vself (κ 0.51 ± 0.13) and UC-female AC (κ 0.42 ± 0.15)., Conclusions: HPV infections are prevalent in HIV-positive couples in Rwanda but concordance within couples is low. Vaginal self-sampling for HPV is representative of cervical HPV status.

Background: One of the lessons learned from the coronavirus disease 2019 (COVID-19) pandemic is the importance of early, flexible, and rapidly deployable disease detection methods. Currently, diagnosis of COVID-19 requires the collection of oro/nasopharyngal swabs, nasal turbinate, anterior nares and saliva but as the pandemic continues, disease detection methods that can identify infected individuals earlier and more quickly will be crucial for slowing the spread of the virus. Previous studies have indicated that dogs can be trained to identify volatile organic compounds (VOCs) produced during respiratory infections. We sought to determine whether this approach could be applied for detection of COVID-19 in Rwanda and measured its cost-saving., Methods: Over a period of 5 months, four dogs were trained to detect VOCs in sweat samples collected from human subjects confirmed positive or negative for COVID-19 by reverse transcription polymerase chain reaction (RT-PCR) testing. Dogs were trained using a detection dog training system (DDTS) and in vivo diagnosis. Samples were collected from 5,253 participants using a cotton pad swiped in the underarm to collect sweat samples. Statistical analysis was conducted using R statistical software., Findings: From August to September 2021 during the Delta wave, the sensitivity of the dogs' COVID-19 detection ranged from 75.0 to 89.9% for the lowest- and highest-performing dogs, respectively. Specificity ranged from 96.1 to 98.4%, respectively. In the second phase coinciding with the Omicron wave (January-March 2022), the sensitivity decreased substantially from 36.6 to 41.5%, while specificity remained above 95% for all four dogs. The sensitivity and specificity by any positive sample detected by at least one dog was 83.9, 95% CI: 75.8-90.2 and 94.9%; 95% CI: 93.9-95.8, respectively. The use of scent detection dogs was also found to be cost-saving compared to antigen rapid diagnostic tests, based on a marginal cost of approximately $14,000 USD for testing of the 5,253 samples which makes 2.67 USD per sample. Testing turnaround time was also faster with the scent detection dogs, at 3 h compared to 11 h with routine diagnostic testing., Conclusion: The findings from this study indicate that trained dogs can accurately identify respiratory secretion samples from asymptomatic and symptomatic COVID-19 patients timely and cost-effectively. Our findings recommend further uptake of this approach for COVID-19 detection., Competing Interests: Authors LM, YB, and CM were employed by Center for Human Genetics, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mutesa, Misbah, Remera, Ebbers, Schalke, Tuyisenge, Sindayiheba, Igiraneza, Uwimana, Mbabazi, Kayonga, Twagiramungu, Mugwaneza, Ishema, Butera, Musanabaganwa, Rwagasore, Twele, Meller, Tuyishime, Rutayisire, Murindahabi, Wilson, Bigirimana, Volk, Ndahindwa, Kayijuka, Mills, Muvunyi and Nsanzimana.)

Background: Hepatitis C virus (HCV) genotype 4 is the predominant type of HCV found in sub-Saharan Africa. Various genotype 4 subtypes, such as 4r, frequently have resistance-associated substitutions that can increase rates of treatment failure with common direct-acting antiviral regimens. In-vitro studies suggest that the NS5A inhibitor velpatasvir is effective against viral isolates containing such resistance-associated substitutions, but its clinical efficacy against genotype 4 non-a/d subtypes in sub-Saharan Africa remains to be confirmed. We aimed to evaluate the safety and efficacy of sofosbuvir-velpatasvir among adults chronically infected with HCV and naive to direct-acting antiviral treatment in Rwanda, where genotype 4 non-a/d subtypes predominate., Methods: In this single-arm prospective trial, we enrolled adults (age ≥18 years) in Rwanda who had chronic HCV infection and a plasma HCV RNA titre of at least 1000 IU/mL. Patients were referred from hospitals with HCV treatment programmes throughout Rwanda and were sequentially enrolled and assessed for eligibility at a single study site. Individuals with decompensated liver disease or hepatitis B virus co-infection were excluded. Participants were given an oral fixed-dose combination tablet of sofosbuvir (400 mg) and velpatasvir (100 mg) once-daily for 12 weeks. The primary endpoint was the proportion of participants with a sustained virological response 12 weeks after completion of treatment (SVR12) in the intention-to-treat population. Viral sequencing of the NS5A and NS5B genes was done at baseline for all participants and end of follow-up (week 24) for participants who did not have SVR12. This study is registered with ClinicalTrials.gov (NCT03888729) and is completed., Findings: Between Sept 23, 2019, and Jan 10, 2020, 73 individuals were screened for eligibility, of whom 12 (16%) were excluded and 61 (84%) were enrolled. 40 (66%) participants were female, 21 (34%) were male, median age was 64 years (IQR 51-74), and median baseline HCV viral load was 5·7 log 10 IU/mL (5·2-6·2). The genotypes identified among the participants were 4k (28 [46%] participants), 4r (11 [18%]), 4v (eight [13%]), 4q (five [8%]), 4l (three [5%]), 4b (one [2%]), 4c (one [2%]), and one undetermined genotype 4 subtype. Three isolates could not be sequenced and were of indeterminate genotype. Of the 55 HCV isolates that were successfully sequenced, all had at least two NS5A resistance-associated substitutions. 59 (97% [95% CI 89-99]) participants had SVR12. 18 (30%) participants had grade 3 adverse events (including 12 [20%] with hypertension), and none had grade 4 adverse events. Four (7%) participants had serious adverse events, including one asthma exacerbation, one abscess, one uterine myoma, and one pelvic fracture related to a motor vehicle accident. No serious adverse events were attributed to the study drug and no adverse event resulted in discontinuation of the study drug., Interpretation: A 12-week regimen of sofosbuvir-velpatasvir is safe and efficacious in treating chronic HCV genotype 4 infection in patients in Rwanda. This regimen could be an effective treatment option in regions known to have a high prevalence of HCV genotype 4 of diverse non-a/d subtypes., Funding: Gilead Sciences., Competing Interests: Declaration of interests GC is an employee of and holds stock in Gilead Sciences. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Hepatitis C virus (HCV) genotype 4 non-a/d subtypes, which frequently have NS5A resistance-associated substitutions, are highly prevalent in sub-Saharan Africa. These subtypes, particularly genotype 4r, have been associated with higher rates of failure of treatment regimens containing the NS5A inhibitors ledipasvir or daclatasvir, which are the most accessible direct-acting antivirals in low-income countries. Clinical evidence regarding the efficacy of re-treatment options for these subtypes is limited. We aimed to evaluate the safety and efficacy of sofosbuvir-velpatasvir-voxilaprevir for the treatment of adults in Rwanda with chronic HCV infection, predominantly of genotype 4, and a history of direct-acting antiviral treatment failure., Methods: In this single-arm prospective trial, we enrolled adults (aged ≥18 years) with a HCV RNA titre of at least 1000 IU/mL, and a documented history of direct-acting antiviral failure. Patients were assessed for eligibility at a single study site after referral from hospitals with HCV treatment programmes throughout Rwanda, and participants for whom sofosbuvir-ledipasvir treatment had failed in the previous SHARED trial were also included. Participants with decompensated liver disease or hepatitis B virus co-infection were excluded. Participants were treated once daily with an oral fixed-dose combination tablet containing sofosbuvir (400 mg), velpatasvir (100 mg), and voxilaprevir (100 mg) for 12 weeks. The primary endpoint was the proportion of participants with a sustained virological response 12 weeks after completion of treatment (SVR12) in the intention-to-treat population. Viral sequencing of NS3, NS5A, and NS5B genes was done at baseline in all participants and at end of follow-up (week 24) in participants with treatment failure. The study is registered with ClinicalTrials.gov (NCT03888729) and is completed., Findings: Between Sept 23, 2019, and Jan 10, 2020, 49 individuals were screened and 40 participants were enrolled. 20 (50%) were female, 20 (50%) were male, median age was 63 years (IQR 56-68), and median HCV viral load was 6·2 log 10 IU/mL (5·8-6·5) at baseline. The genotype subtypes identified were 4r (18 [45%] participants), 4k (six [15%]), 4b (five [13%]), 4q (four [10%]), 4l (two [5%]), 4a (one [3%]), 4m (one [3%]), and 3h (one [3%]). One (3%) genotype 4 isolate could not be subtyped, and one (3%) isolate was of unknown genotype. All successfully sequenced isolates (33 [83%]) had at least two NS5A resistance-associated substitutions and 25 (63%) had three or more. 39 (98% [95% CI 87-100]) participants had SVR12. Seven (18%) participants had a total of ten grade 3, 4, or 5 adverse events, including three (8%) cases of hypertension, and one (3%) case each of cataract, diabetes, gastrointestinal bleeding, joint pain, low back pain, vaginal cancer, and sudden death. Four of these events were categorised as serious adverse events resulting in hospitalisation. The one sudden death occurred at home from an unknown cause 4 weeks after the completion of treatment. No serious adverse event was determined to be related to the study drug or resulted in treatment discontinuation., Interpretation: A 12 week course of sofosbuvir-velpatasvir-voxilaprevir is safe and efficacious for the re-treatment of individuals infected with HCV genotype 4 non-a/d subtypes with frequent baseline NS5A resistance-associated substitutions, following failure of previous direct-acting antiviral treatment. Improved affordability and access to sofosbuvir-velpatasvir-voxilaprevir in regions with these subtypes is crucial., Funding: Gilead Sciences., Competing Interests: Declaration of interests GC is an employee of and holds stock in Gilead Sciences. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Larval source management (LSM) programs for control of malaria vectors are often vertically organized, while there is much potential for involving local communities in program implementation. To address this, we evaluated the entomological impact of community-based application of Bacillus thuringiensis var. israelensis ( Bti ) in a rice irrigation scheme in Ruhuha, Rwanda. A non-randomized trial with control compared a Bti implementation program that was supervised by the project team (ES) with a program that was led and carried out by local rice farming communities (CB). One other area served as a control to assess mosquito populations without Bti application. Entomological surveys were carried out every two weeks and assessed the presence and abundance of the larval, pupal, and adult stages of Anopheles mosquitoes. In ES, the per round reduction in Anopheles larval habitats was estimated at 49%. This reduction was less in CB (28%) and control (22%) although the per round reduction in CB was still significantly higher than in control. Pupal production was almost completely prevented from round 5 (out of 10) onwards in both CB (average habitat occupancy 0.43%) and ES intervention arms (average habitat occupancy 0.27%), whereas pupal occupancy rates were on average 12.8% from round 5 onwards in the control. Emergence of adult mosquitoes from rice fields was thus prevented although this was not directly noticeable in adult An. gambiae populations in houses nearby the rice fields. Together with our earlier work on the willingness to financially contribute to the LSM program and the high perceived safety and acceptance of the Bti product, the current study demonstrates that, in an environment with limited resources, communities could become more engaged in LSM program implementation and contribute directly to malaria vector control in their environment.

Summary Background: Multidrug-resistant (MDR) tuberculosis (TB) poses an important challenge in TB management and control. Rifampicin resistance (RR) is a solid surrogate marker of MDR-TB. We investigated the RR-TB clustering rates, bacterial population dynamics to infer transmission dynamics, and the impact of changes to patient management on these dynamics over 27 years in Rwanda., Methods: We analysed whole genome sequences of a longitudinal collection of nationwide RR-TB isolates. The collection covered three important periods: before programmatic management of MDR-TB (PMDT; 1991-2005), the early PMDT phase (2006-2013), in which rifampicin drug-susceptibility testing (DST) was offered to retreatment patients only, and the consolidated phase (2014-2018), in which all bacteriologically confirmed TB patients had rifampicin DST done mostly via Xpert MTB/RIF assay. We constructed clusters based on a 5 SNP cut-off and resistance conferring SNPs. We used Bayesian modelling for dating and population size estimations, TransPhylo to estimate the number of secondary cases infected by each patient, and multivariable logistic regression to assess predictors of being infected by the dominant clone., Results: Of 308 baseline RR-TB isolates considered for transmission analysis, the clustering analysis grouped 259 (84.1%) isolates into 13 clusters. Within these clusters, a single dominant clone was discovered containing 213 isolates (82.2% of clustered and 69.1% of all RR-TB), which we named the "Rwanda Rifampicin-Resistant clone" (R3clone). R3clone isolates belonged to Ugandan sub-lineage 4.6.1.2 and its rifampicin and isoniazid resistance were conferred by the Ser450Leu mutation in rpoB and Ser315Thr in katG genes, respectively. All R3clone isolates had Pro481Thr, a putative compensatory mutation in the rpoC gene that likely restored its fitness. The R3clone was estimated to first arise in 1987 and its population size increased exponentially through the 1990s', reaching maximum size (∼84%) in early 2000 s', with a declining trend since 2014. Indeed, the highest proportion of R3clone (129/157; 82·2%, 95%CI: 75·3-87·8%) occurred between 2000 and 13, declining to 64·4% (95%CI: 55·1-73·0%) from 2014 onward. We showed that patients with R3clone detected after an unsuccessful category 2 treatment were more likely to generate secondary cases than patients with R3clone detected after an unsuccessful category 1 treatment regimen., Conclusions: RR-TB in Rwanda is largely transmitted. Xpert MTB/RIF assay as first diagnostic test avoids unnecessary rounds of rifampicin-based TB treatment, thus preventing ongoing transmission of the dominant R3clone. As PMDT was intensified and all TB patients accessed rifampicin-resistance testing, the nationwide R3clone burden declined. To our knowledge, our findings provide the first evidence supporting the impact of universal DST on the transmission of RR-TB., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background: Health education interventions tailored to suit men have the potential to improve health outcomes for this underserved population. HIV self-testing (HIVST) is a promising approach to overcoming challenges associated with low HIV testing rates among men. The primary objective of this study is to assess the feasibility of conducting a definitive trial to determine the effectiveness of a locally adapted and optimized health education program (HEP) on the uptake of HIVST among men in Kigali, Rwanda., Methods: This study employs a pilot pragmatic randomized controlled trial to evaluate an HIVST HEP for men. Participants were randomized to the intervention (HEP) arm or to the control arm. In the intervention group, the adapted HEP was administered in addition to routine health education. In the non-intervention group, only routine health education was offered. Participant data was collected first upon recruitment and then after 3 months' follow-up using interviewer-administered questionnaires., Results: There was a 100% response rate at enrollment and no loss to follow-up at exit. There was significant association between the study arm and knowledge of HIVST. Participants in the control arm had a mean knowledge score of 67% compared to 92% among participants in the intervention arm. There was an association between the study arm and HIVST uptake: 67% of the study participants in the intervention arm self-reported HIVST uptake compared to 23% of the participants in the control arm., Discussion: This pilot study demonstrates the feasibility of a larger trial to assess the effectiveness of an HEP intervention on uptake of HIVST among men. We found preliminary evidence of increased uptake of HIVST in the intervention group., Trial Registration: Pan African Clinical Trial Registry PACTR201908758321490 . Registered on 8 August 2019., (© 2021. The Author(s).)

Around 71 million people are living with chronic hepatitis C virus (HCV) infection, with approximately 14% residing in sub-Saharan Africa. Direct-acting antiviral (DAA) therapies offer clear benefits for liver-related morbidity and mortality, and data from high-income settings suggest that DAA treatments also provide significant benefits in terms of health-related quality of life (HRQL). In this study, we assessed the effect of DAA treatment on HRQL for individuals treated for HCV in a clinical trial in Rwanda. We assessed the HRQL of participants using an 83-question composite survey at Day 0 ('baseline') and Week 24 ('endpoint'). Data were analysed in R. A total of 296 participants were included in this analysis. Their ages ranged from 19 to 90, and 184 (62.2%) were female. There were significant improvements from baseline to endpoint median scores for all physical and mental quality of life sub-scales. Additionally, a reduction-before and after treatment-in the proportion of those classified as depressed and needing social support was statistically significant (both P < .001). Economic productivity increased after treatment (P < .001), and households classified as food secure increased from baseline to endpoint (P < .001). These results demonstrate that Rwandans with chronic HCV infection experience both clinical and HRQL benefits, including household-level benefits like substantial gains in workforce stability, economic productivity, and poverty alleviation, from DAA treatment. A stronger demonstration of accurate and broader household-level benefits achieved through treatment of HCV with DAAs will help financing and investment for HCV in resource-constrained settings become an urgent priority., (© 2020 John Wiley & Sons Ltd.)

Suppressing infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will probably require the rapid identification and isolation of individuals infected with the virus on an ongoing basis. Reverse-transcription polymerase chain reaction (RT-PCR) tests are accurate but costly, which makes the regular testing of every individual expensive. These costs are a challenge for all countries around the world, but particularly for low-to-middle-income countries. Cost reductions can be achieved by pooling (or combining) subsamples and testing them in groups 1-7 . A balance must be struck between increasing the group size and retaining test sensitivity, as sample dilution increases the likelihood of false-negative test results for individuals with a low viral load in the sampled region at the time of the test 8 . Similarly, minimizing the number of tests to reduce costs must be balanced against minimizing the time that testing takes, to reduce the spread of the infection. Here we propose an algorithm for pooling subsamples based on the geometry of a hypercube that, at low prevalence, accurately identifies individuals infected with SARS-CoV-2 in a small number of tests and few rounds of testing. We discuss the optimal group size and explain why, given the highly infectious nature of the disease, largely parallel searches are preferred. We report proof-of-concept experiments in which a positive subsample was detected even when diluted 100-fold with negative subsamples (compared with 30-48-fold dilutions described in previous studies 9-11 ). We quantify the loss of sensitivity due to dilution and discuss how it may be mitigated by the frequent re-testing of groups, for example. With the use of these methods, the cost of mass testing could be reduced by a large factor. At low prevalence, the costs decrease in rough proportion to the prevalence. Field trials of our approach are under way in Rwanda and South Africa. The use of group testing on a massive scale to monitor infection rates closely and continually in a population, along with the rapid and effective isolation of people with SARS-CoV-2 infections, provides a promising pathway towards the long-term control of coronavirus disease 2019 (COVID-19).

An estimated 71 million people live with hepatitis C virus (HCV) and without an effective vaccination, control efforts depend entirely on prevention, early diagnosis, and treatment with direct acting antiviral medication. The experiences of accessing care and treatment, as well as how HCV is locally perceived, are context specific and require an understanding of local epidemics. The objectives of this study were to explore the experiences and demand-side barriers for people with chronic HCV infection, as well as describe the social and cultural landscapes in which they experienced, managed, and perceived HCV in Rwanda. Eleven participants provided consent to participate and all completed two semi-structured interviews during treatment within a clinical trial. We identified four themes: (1) diagnosis and use of traditional medicine, (2) access and financial barriers, (3) complex social networks (4) proactivity in care-seeking. Results demonstrate the complex ways in which Rwandans understand HCV, utilise parallel health systems, activate social networks, and the importance of active agency in the opportunities and outcomes for their own health in the context of an early response to a major epidemic. Without recognising communities' understanding and expectations, it is impossible to build a sustainable and successful public health response to HCV.

Background: Exposure to environmental stressors can lead to shorter leukocyte telomere length and increase the risk of chronic diseases. Preservation of leukocyte telomere length by reducing oxidative stress exposure and reinforcing immunity may be a mechanism by which nutritional factors delay or prevent chronic disease development., Methods: Healthy pregnant women (aged 18-45 years) at 9-15 weeks of gestation living in Gasabo District, Kigali, Rwanda, were recruited from 10 health centers for a prospective, longitudinal study from September to October 2017 to determine possible associations between nutrition health, infectious disease and leukocyte telomere length. Anthropometric and laboratory measurements were performed using standard procedures; sociodemographic parameters and health histories were assessed via surveys, and leukocyte telomere length was assessed using quantitative PCR expressed as the ratio of a telomeric product to a single-copy gene product (T/S)., Results: Mean gestational age of participants (n = 297) at enrollment was 13.04 ± 3.50 weeks, age was 28.16 ± 6.10 years and leukocyte telomere length was 1.16 ± 0.22 (T/S). Younger age; no schooling vs. primary schooling; and lower levels of ferritin, soluble transferrin receptors and retinol-binding protein were independent predictors of longer telomere length in multivariable models., Conclusions: Leukocyte telomere length is an indicator of biological aging in pregnant Rwandan women. Maternal micronutrient status, specifically lower ferritin, soluble transferrin receptor levels, and retinol-binding protein levels were associated with longer maternal telomere length in contrast with some studies from North America and Europe. There were no associations between inflammation and infectious disease status and maternal leukocyte telomere length. Further studies are needed to enhance our understanding of the interplay between maternal nutritional status and infectious disease in relation to leukocyte telomere length in developing countries.

Regimens of current drugs for tuberculosis are lengthy and are associated with many adverse effects. Currently, the emergence of different resistant strains has been observed. This urges a need for the discovery and development of novel drugs. The main sources of drug lead candidates are based on natural products. Zanthoxylum leprieurii, Lantana camara, and Cryptolepis Sanguinolenta are among the plants that have antimycobacterial activity. Recent technological methods, such as metabolomics, can rapidly detect and identify active compounds from medicinal plants. In this review, we aim to provide an overview and discussion of the antimycobacterial activity, phytochemical analysis and toxicity profile of these plants and their products as well as the potential of metabolomic fingerprinting of medicinal plants with a given activity on microbes, in the search for the potential drug hit molecules. The information for this review was extracted from databases such as Excerpta Medica Database, Google Scholar, Springer, and PubMed Central. Primary studies, using a combination of the keywords antimycobacterial medicinal plant, multidrug-resistant tuberculosis, phytochemistry, toxicity, Zanthoxylum leprieurii, Lantana camara, Cryptolepis sanguinolenta, and plant metabolomics/metabolic fingerprinting of plant extracts, have been considered. The above-mentioned plant species showed antimycobacterial activity against drug-resistant strains of M. tuberculosis. They may provide potential candidates for novel drugs against multidrug-resistant tuberculosis. However, extensive work is still needed. To our knowledge, there is no or limited literature that reports the metabolic fingerprints of these plants. The analysis of the metabolite fingerprints of medicinal plants with similar antimicrobial activity could be important to determine whether the activity results from common metabolites within different plant species. This review shows that these plants are potential candidates to provide drug hits against multidrug-resistant tuberculosis strains. Future studies of compound optimization, in vivo safety and efficacy, as well as of the specific mechanisms of action are however required., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Preterm birth (PTB) is a leading cause of early childhood mortality and morbidity, including long-term physical and mental impairment. The risk factors for PTB are complex and include maternal nutritional status and infections. This study aimed to identify potentially modifiable risk factors for targeted interventions to reduce the occurrence of PTB in Rwanda., Methods: We conducted a prospective, longitudinal cohort study of healthy pregnant women aged 18 to 49 years. Women at 9-15 gestational weeks were recruited from 10 health centers in Gasabo District, Kigali Province between September and October 2017. Pregnancy age was estimated using ultrasonography and date of last menstruation. Anthropometric and laboratory measurements were performed using standard procedures for both mothers and newborns. Surveys were administered to assess demographic and health histories. Categorical and continuous variables were depicted as proportions and means, respectively. Variables with p <  0.25 in bivariate analyses were included in multivariable logistic regression models to determine independent predictors of PTB. The results were reported as odds ratios (ORs) and 95% confidence intervals (CI), with statistical significance set at p <  0.05., Results: Among 367 participants who delivered at a mean of 38.0 ± 2.2 gestational weeks, the overall PTB rate was 10.1%. After adjusting for potential confounders, we identified the following independent risk factors for PTB: anemia (hemoglobin < 11 g/dl) (OR: 4.27; 95%CI: 1.85-9.85), urinary tract infection (UTI) (OR:9.82; 95%CI: 3.88-24.83), chlamydia infection (OR: 2.79; 95%CI: 1.17-6.63), inadequate minimum dietary diversity for women (MDD-W) score (OR:3.94; CI: 1.57-9.91) and low mid-upper arm circumference (MUAC) < 23 cm (OR: 3.12, 95%CI; 1.31-7.43). indicators of nutritional inadequacy (low MDD-W and MUAC) predicted risk for low birth weight (LBW) but only UTI was associated with LBW in contrast with PTB., Conclusion: Targeted interventions are needed to improve the nutritional status of pregnant women, such as maternal education on dietary diversity and prevention of anemia pre-pregnancy. Additionally, prevention and treatment of maternal infections, especially sexually transmitted infections and UTIs should be reinforced during standard antenatal care screening which currently only includes HIV and syphilis testing.

Background: Antimicrobial resistance (AMR) is an imminent threat to modern medicine. As the efficacy of treatment regimens is reduced, mortality and morbidity attributed to infectious diseases is expected to rise dramatically across the globe. Antimicrobial stewardship and good prescription practices are critical to conserving available therapeutics; it is appropriate, therefore, to appraise our attitudes and knowledge of antimicrobial resistance, particularly for the future healthcare practitioners., Methods: This is a descriptive cross-sectional study that was conducted among 282 medicals, dental and pharmacy students from the University of Rwanda. Questionnaires were used to collect data from the 4th to 29th March 2017., Results: Students from Level 3 to level 6 have demonstrated a good knowledge on antibiotics and antimicrobial resistance. Generally, 95% ( n  = 218) agreed that the inappropriate use of antibiotics could lead to antibiotic resistance. It was found that 96% ( n  = 220) of the respondents had heard about AMR outside their degree courses. 49% ( n  = 112) of the participants reported that they are able to purchase antibiotics without a prescription. 96% (n = 220) agreed that it was important for healthcare students to be knowledgeable about antimicrobial resistance. Perhaps most surprisingly, it was found that 83% ( n  = 191) of participants were unfamiliar with the concept of antimicrobial stewardship and 49% ( n  = 21) had not yet discussed antimicrobial resistance as part of their education, albeit only 1% ( n  = 3) was completely unfamiliar with the term. Furthermore, 38% ( n  = 86) did not support that the antibiotics were overused in Rwanda, 23% ( n  = 10) did not agree that inappropriate antimicrobial use contributed to antimicrobial resistance, and 50% ( n  = 22) of participants agreed that antibiotics were indicated in the treatment of pain and inflammation., Conclusions: The present study reports a moderate knowledge on AMR among the healthcare students. The gaps in the current formal training of healthcare individuals have been identified as well. We highlight the necessity to enhance educational approaches to introduce the key concepts of AMR and antimicrobial stewardship to the curriculum of healthcare students., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Background: The Rwandan Ministry of Health recently (in February 2017) recommended the use of HIV self-testing (HIVST) as an additional strategy for hard-to-reach populations such as men. However, the level of awareness and acceptability of this testing strategy among this population in Rwanda is not known. The main objective of this study is to assess the level of awareness and acceptability of HIVST among male clinic attendees in Kigali, Rwanda., Methods: A cross-sectional survey was employed to systematically sample and interview 579 male health-facility attendees over a seven-week period. We employed a pretested interviewer questionnaire to collect data. The chi-square test was used to determine associations between explanatory variables. Univariate binary logistic regression analysis was carried out to obtain preliminary insight into the unconditional association of each independent variable and dependent variables (awareness and acceptability). Multiple logistic regression was employed to determine explanatory variables associated with awareness or acceptability status while adjusting for other study variables. All statistical analyses were performed using Stata version 11.2., Results: Of the 579 men interviewed, only 21% were aware of HIVST, while 74% found it acceptable. Logistic regression analysis identified the following as factors significantly (p < 0.05) associated with HIVST awareness: having paid or received money for sex in the past month, health-seeking behavior, HIVST knowledge, HIVST attitude, and HIV risk perception. Factors associated with HIVST acceptability include the following: health-seeking behavior, HIVST knowledge, HIVST attitude, and condom use after taking drugs and alcohol., Conclusion: The findings reveal low awareness and high acceptability of HIVST among men in Rwanda. Our findings accentuate the need to promote awareness of HIVST as an important intervention for improving the uptake of HIV testing among men, a traditionally hard-to-reach population in Rwanda., (© 2020 The Author(s).)

SETTING: In 2005, in response to the increasing prevalence of rifampicin-resistant tuberculosis (RR-TB) and poor treatment outcomes, Rwanda initiated the programmatic management of RR-TB, including expanded access to systematic rifampicin drug susceptibility testing (DST) and standardised treatment. OBJECTIVE: To describe trends in diagnostic and treatment delays and estimate their effect on RR-TB mortality. DESIGN: Retrospective analysis of individual-level data including 748 (85.4%) of 876 patients diagnosed with RR-TB notified to the World Health Organization between 1 July 2005 and 31 December 2016 in Rwanda. Logistic regression was used to estimate the effect of diagnostic and therapeutic delays on RR-TB mortality. RESULTS: Between 2006 and 2016, the median diagnostic delay significantly decreased from 88 days to 1 day, and the therapeutic delay from 76 days to 3 days. Simultaneously, RR-TB mortality significantly decreased from 30.8% in 2006 to 6.9% in 2016. Total delay in starting multidrug-resistant TB (MDR-TB) treatment of more than 100 days was associated with more than two-fold higher odds for dying. When delays were long, empirical RR-TB treatment initiation was associated with a lower mortality. CONCLUSION: The reduction of diagnostic and treatment delays reduced RR-TB mortality. We anticipate that universal testing for RR-TB, short diagnostic and therapeutic delays and effective standardised MDR-TB treatment will further decrease RR-TB mortality in Rwanda.

Direct-acting antivirals for hepatitis C virus (HCV) are highly effective and well-tolerated. However, only a small percentage of HCV-infected individuals globally have received therapy. Reducing the complexity of monitoring during HCV therapy, if shown to be safe, could facilitate greater access to HCV services, particularly in resource-limited settings such as sub-Saharan Africa. We enrolled a total of 300 patients who were chronically infected with genotype 4 HCV in Rwanda and treated them with fixed-dose ledispasvir/sofosbuvir for 12 weeks. For 60 consecutive participants enrolled, we blinded the study clinician to on-treatment laboratory results. We compared the efficacy, safety, and tolerability in those with blinded laboratory results to those with standard laboratory monitoring. Baseline characteristics among those with blinded laboratory values were comparable to those with standard monitoring. Among both groups, the median age was 63 years, and the median HCV viral load was 5.9 log (versus 64 years and 6.0 log, respectively). Sustained virologic response rates at 12 weeks after treatment completion were similar in those with blinded laboratories (87%) compared to those with standard laboratory monitoring (87%). There was no increase in adverse events in those with blinded laboratory results, and no participants discontinued the study medication because of an adverse event. Conclusion: On-treatment laboratory monitoring did not improve patient outcomes in those treated with ledispasvir/sofosbuvir. Eliminating this monitoring in treatment programs in resource-limited settings may facilitate and accelerate scale-up of HCV therapy., (© 2020 The Authors. Hepatology Communications published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.)

Introduction: Health education programmes (HEPs) have been associated with a number of benefits. These include providing individuals with information on matters related to their mental, social, physical as well as emotional health. HEPs also play a major role in preventing diseases and reducing the level of engagement of individuals in risky behaviours. While this is the case, there are barriers to the effective implementation of HEPs, especially in low-income and middle-income countries (LMICs) where resources are scarce. Available evidence has revealed socioeconomic challenges ranging from literacy issues, discomfort about issues of sexuality, and cultural barriers to financial constraints as key barriers to the implementation of sexual and reproductive health HEPs in LMICs. We will focus on HEPs related to sexual and reproductive health; all age groups will be considered with no restrictions on geographical setting nor model of HEP delivery. This review will map literature on the barriers to the effective implementation of HEPs in LMICs to guide future implementation research., Methods: Arksey and O'Malley's 2005 scoping methodological framework will act as the guide for this review. We will search the following electronic databases: EBSCOhost (Academic search complete, PsycINFO, Health Sources, CINAHL and MEDLINE with full text), Google Scholar, PubMed, SCOPUS, Science Direct and Web of Science. Grey literature from Mount Kenya University theses and dissertations, governments' as well as international organisations' reports, such as WHO, and reference lists of included studies will be searched for eligible studies. We will limit our search to publications from 1 January 2000 to 30 September 2019. Using thematic content analysis, we will employ NVivo V.12 to extract the relevant outcomes from the included articles. We will conduct a quality appraisal of the included articles using the mixed methods appraisal tool (MMAT) version 2018., Ethics and Dissemination: No ethical approval is needed for the study as it will not include animal nor human participants. The results of the proposed scoping review will be disseminated electronically, in print and through conference presentation as well as at key stakeholder meetings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Chikungunya virus (CHIKV) and West Nile virus (WNV) have previously been reported from several African countries, including those bordering Rwanda where they may have originated. However, there have been no serosurveillance reports from Rwanda regarding these two viral pathogens. In this article, we present the first study of immunoglobulin G (IgG) seroreactivity of CHIKV and WNV in Rwandan blood donor samples. Methods: Blood donors from Rwanda ( n  = 874) and Sweden ( n  = 199) were tested for IgG reactivity against CHIKV, using an in-house enzyme-linked immunosorbent assay with the E1 envelope protein fused with p62 as antigen, and against WNV using a commercial kit. Data on mosquito distribution were obtained from the 2012 assessment of yellow fever virus circulation in Rwanda. Results: Seroreactivity to CHIKV was high in Rwanda (63.0%), when compared with Swedish donors, where only 8.5% were IgG positive. However, a cross-reactivity to O'nyong'nyong virus in neutralization test was noted in Rwandan donors. No significant difference in WNV seroreactivity was found (10.4% for Rwandan and 14.1% for Swedish donors). The relatively high seroreactivity to WNV among Swedish donors could partly be explained by cross-reactivity with tick-borne encephalitis virus prevalent in Sweden. Donors from the Eastern Province of Rwanda had the highest IgG reactivity to the two investigated viruses (86.7% for CHIKV and 33.3% for WNV). Five genera of mosquitoes were found in Rwanda where Culex was the most common (82.5%). The vector of CHIKV, Aedes , accounted for 9.6% of mosquitoes and this species was most commonly found in the Eastern Province. Conclusions: Our results showed high seroreactivity to CHIKV in Rwandan donors. The highest IgG reactivity to CHIKV, and to WNV, was found in the Eastern Province, the area reporting the highest number of mosquito vectors for these two viruses. Infection control by eliminating mosquito-breeding sites in population-dense areas is recommended, especially in eastern Rwanda.

Background: Resistance among bacterial infections is increasingly well-documented in high-income countries; however, relatively little is known about bacterial antimicrobial resistance in low-income countries, where the burden of infections is high., Methods: We prospectively screened all adult inpatients at a referral hospital in Rwanda for suspected infection for seven months. Blood, urine, wound and sputum samples were cultured and tested for antibiotic susceptibility. We examined factors associated with resistance and compared hospital outcomes for participants with and without resistant isolates., Results: We screened 19,178 patient-days, and enrolled 647 unique participants with suspected infection. We obtained 942 culture specimens, of which 357 were culture-positive specimens. Of these positive specimens, 155 (43.4%) were wound, 83 (23.2%) urine, 64 (17.9%) blood, and 55 (15.4%) sputum. Gram-negative bacteria comprised 323 (88.7%) of all isolates. Of 241 Gram-negative isolates tested for ceftriaxone, 183 (75.9%) were resistant. Of 92 Gram-negative isolates tested for the extended spectrum beta-lactamase (ESBL) positive phenotype, 66 (71.7%) were ESBL positive phenotype. Transfer from another facility, recent surgery or antibiotic exposure, and hospital-acquired infection were each associated with resistance. Mortality was 19.6% for all enrolled participants., Conclusions: This is the first published prospective hospital-wide antibiogram of multiple specimen types from East Africa with ESBL testing. Our study suggests that low-resource settings with limited and inconsistent access to the full range of antibiotic classes may bear the highest burden of resistant infections. Hospital-acquired infections and recent antibiotic exposure are associated with a high proportion of resistant infections. Efforts to slow the development of resistance and supply effective antibiotics are urgently needed., Competing Interests: The authors have declared that no competing interests exist.

Objective: To determine prevalent MDR-TB genotypes and describe treatment outcome and bacteriology conversion in MDR-TB patients., Methods: Review of laboratory records of 173 MDR-TB patients from all over Rwanda who initiated treatment under programmatic management of MDR-TB (PMDT) between 2014 and 2015. Fifty available archived isolates were genotyped by mycobacterial interspersed repetitive units - variable number of tandem repeats (MIRU-VNTR) genotyping., Result: Of the 170 patients whose outcome was known, 114 (66.3%) were cured and 36 (21%) completed the treatment, giving a successful outcome (cured and completed) of 150 (87.3%) patients. Of 20 MDR-TB patients with unfavourable treatment outcome, 18 died, one failed and one defaulted/stopped treatment. Of the 18 patients who died, 11 (61%) were HIV-coinfected. The treatment outcome was successful for 93.9% among HIV negative and 81.8% among HIV-coinfected patients (P = 0.02). Sputum smear conversion occurred in 3, 46, 57 and 78 patients before 2, 3, 4 and 6 months, respectively, with median time of sputum smear and culture conversion at 3 months. The 44 MDR-TB isolates with MIRU-VNTR result, showed high genetic diversity with low clustering rate (9.09%) and Uganda II being the most prevalent sub-family lineage detected in 68.2% of isolates. Beijing family was the least common genotype detected (2.3%, 1 isolate)., Conclusion: The high success rates for MDR-TB treatment achieved in Rwanda were comparable to outcomes observed in resource-rich settings with HIV being an independent risk factor for poor treatment outcome. High genetic diversity and low clustering rate reported here suggest that reactivation of previous disease plays an important role in the transmission of MDR-TB in Rwanda., (© 2019 John Wiley & Sons Ltd.)

Background: Artemisinin-based combination therapies (ACTs) have proven highly effective in reducing malaria morbidity in sub-Saharan Africa. Artemether-lumefantrine (AL) was introduced in 2005 as a first-line ACT for the treatment of uncomplicated malaria in Rwanda. Monitoring the therapeutic efficacy of ACTs is necessary to ensure effective malaria case management., Methods: A comparative study on the efficacy of AL and dihydroartemisinin-piperaquine (DHP) was conducted in two sites, Masaka and Ruhuha, between September 2013 and December 2015. Clinical and parasitological responses were assessed at days 28 and 42., Results: A total of 534 children were treated with AL (n=267) or DHP (n=267). After polymerase chain reaction (PCR) adjustment, 98.3% and 98.9% of children in the AL and DHP arms, respectively, achieved an adequate clinical and parasitological response (ACPR) at day 28. At day 42, PCR-adjusted ACPR proportions were 97.3% and 98.4% for AL and DHP, respectively. PCR-adjusted ACPR was 99% for both drugs at days 28 and 42 in Ruhuha. The PCR-adjusted ACPR proportions in Masaka were 97.3% for AL and 98.5% for DHP at day 28 and 95.2% for AL and 97.5% for DHP at day 42., Conclusions: AL remains efficacious in Rwanda 10 y after its adoption. The probability of new infections occurring among patients in the DHP arm was significantly lower than those in the AL arm. DHP also demonstrated a greater post-treatment prophylactic effect against new infections compared with AL., (© The Author(s) 2019. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The Presto combined qualitative real-time assay for Chlamydia trachomatis and Neisseria gonorrhoeae (Presto CT/NG PCR assay) is appealing for developing countries, because it can be used with multiple DNA extraction methods and polymerase chain reaction (PCR) platforms., Objectives: The objective of the study was to implement and evaluate the Presto CT/NG PCR assay at the National Reference Laboratory (NRL) in Kigali, Rwanda, where no real-time PCR assays for the detection of C. trachomatis or N. gonorrhoeae were available., Methods: The Presto CT/NG PCR assay was first evaluated at the Institute of Tropical Medicine (ITM) in Antwerp, Belgium. Next, NRL laboratory technicians were trained to use the assay on their ABI PRISM 7500 real-time PCR instrument and their competencies were assessed prior to trial initiation. During the trial, endocervical swabs were tested at the NRL, with bi-monthly external quality control testing monitored by the ITM. The final NRL results were evaluated against extended gold standard testing at the ITM, consisting of the Abbott m 2000 RealTi m e System with confirmation of positive results by an in-house real-time PCR assay for C. trachomatis or N. gonorrhoeae ., Results: Of the 192 samples analysed using the Presto assay at the NRL, 16 samples tested positive for C. trachomatis and 17 tested positive for N. gonorrhoeae ; four of these were infected with both. The sensitivity and specificity of the Presto assay were 93.3% (95% confidence interval [CI]: 68.1% - 99.8%) and 99.4% (95% CI: 96.8% - 100%) for C. trachomatis and 100% (95% CI: 76.8% - 100%) and 98.8% (95% CI: 95.8% - 99.9%) for N. gonorrhoeae ., Conclusion: C. trachomatis and N. gonorrhoeae testing with the Presto assay was feasible in Kigali, Rwanda, and good performance was achieved., Keywords: qPCR; Chlamydia trachomatis ; Neisseria gonorrhoeae ., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article.

Background: Surgical Site Infections (SSI) are the most reported health acquired infection and common surgical complication in both developed and developing countries. In developing countries such as Rwanda, there is a paucity of published reports on the pattern of SSI, therefore this study aimed at assessing the incidence, risk factors and the antibiotic profile of pathogens responsible of SSI., Methods: This prospective study included 294 patients admitted between October 10, 2017 and February 12, 2018 to the surgical department of the University Teaching Hospital of Kigali. Patients data were collected using a structured and pretested questionnaire in English version. Regular follow-up was maintained until at least 30 days postoperatively. Samples were collected from suspected wounds and identified using different bacteria culture media. Data were analyzed using Statistical Package for the Social Sciences (SPSS) software word version 20.0. P -value < 0.05 was considered statistically significant., Results: The overall incidence of SSI was 10.9%. The associated risk factors were found to be an increased age, ASA class, wound classification, skills and experience of the surgeon, longer duration of surgery (> 2 h), prolonged duration of hospital stay, blood transfusion and emergency surgery. The most common pathogens isolated were Klebsiella ssp (55%), followed by Escherichia coli (15%) and Proteus ssp (12%), Acinectobacter (9%), Staphylococcus aureus (6%) and coagulase-negative staphylococc i (3%).The pathogens revealed different levels of antibiotic resistance; amoxy-clavilinic acid (98.8%), gentamicin (92.6%), ciprofloxacin (78.1%) and ceftriaxone (53.3%). On the other hand, Amikacin and imipinem were the only two most effective antibiotics for all isolated pathogens with 100% sensitivity., Conclusion: SSI incidence rate was revealed to be within acceptable international ranges. However, multi drug resistance was seen in half of the isolates leaving clinicians with few choices of drugs for the treatment of patients with SSI. Periodic surveillance of bacteria and antibiotic susceptibility coupled with the implementation of strict protocol for antibiotic administration and operative room regulations are important to minimize the burden of SSI with resistant bacteria pathogens., Competing Interests: The study was approved by the Kigali University Teaching Hospital Ethics committee. Written informed consent was obtained from the participants.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Limited treatment data are available for hepatitis C virus (HCV) in sub-Saharan Africa, especially for genotype 4. Our objective was to establish the safety and efficacy of ledipasvir-sofosbuvir for chronic HCV genotype 1 or 4 infection in adults in Rwanda., Methods: We did a single-arm trial to evaluate the safety and efficacy of ledipasvir-sofosbuvir in Rwandan adults with chronic HCV infection at a single study site (Rwanda Military Hospital, Kigali, Rwanda). We enrolled individuals aged 18 years or older with HCV genotype 1 or 4 infection and a plasma HCV RNA concentration of more than 1000 IU/mL at screening. All participants were given ledipasvir (90 mg) and sofosbuvir (400 mg) in a single combination tablet once daily for 12 weeks. We established HCV genotype using an Abbott platform, and HCV subtype with PCR amplification. The primary endpoint was the proportion of participants with a sustained virological response 12 weeks after therapy (SVR12). All patients enrolled in the study were included in the primary endpoint analyses. This study is registered with ClinicalTrials.gov, number NCT02964091., Findings: 300 participants were enrolled between Feb 6, 2017, and Sept 18, 2017, and the follow-up period was completed on March 1, 2018. On genotyping, 248 (83%) participants were reported as having genotype 4, four (1%) genotype 1, and 48 (16%) both genotype 1 and genotype 4. Subsequent viral sequencing showed all participants actually had genotype 4 infection with subtype 4k (134 [45%]), subtype 4r (48 [16%]), subtype 4q (42 [14%]), and subtype 4v (24 [8%]) predominating. Overall, 261 (87%, 95% CI 83-91) participants achieved SVR12. In participants with genotype 4r, SVR12 was observed in 27 (56%, 95% CI 41-71) participants versus 234 (93%, 90-96) individuals with other subtypes. There were no drug-related treatment discontinuations due to ledipasvir-sofosbuvir. The most common adverse events were hypertension (97 [32%]), headache (78 [26%]), dizziness (61 [20%]), and fatigue (56 [19%]). There were six serious adverse events; none were assessed to be due to the study drug. 296 participants had data for pill counts at week 4 and 8; 271 (92%) had 100% adherence and only one (<1%) had an adherence of less than 90%., Interpretation: This is the first large-scale prospective study reporting direct-acting antiviral outcomes in sub-Saharan Africa. The high adherence and treatment success without intensive support measures or highly specialised clinical providers, and lack of treatment discontinuations due to adverse events support the feasibility of HCV treatment decentralisation and scale-up in sub-Saharan Africa. Genotype 4r is uniquely expressed in this region and associated with high rates of treatment failure, suggesting a need for rigorous test-of-cure in clinical practice and consideration of the use of newer pangenotypic direct-acting antiviral regimens in this region., Funding: Gilead Sciences., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: We evaluated post-vaccination immunity status and describe potential risk factors associated with the lack of response among healthcare workers (HCWs) at a tertiary care hospital in Kigali, Rwanda., Results: Of 373 HCWs, 291 (78.2%) were female and 81 (21.8%) were male. The mean age of the study participants was 40.2 years (standard deviation [SD], 7.7 years), within a range of 24-41 years. Participants' mean BMI was 25.4 ± 6.6 kg/m 2 , with more than half of patients (60.3%) being overweight. 96% received all three doses of vaccination. A total of 36 participants (9.6%) were considered non responders as they did not develop a sufficient anti-HBs response post vaccination. The anti-HBs response was significantly higher in females when compared to males (p = 0.02). Interestingly, there was no significant association between decline in antibody levels with age (p = 0.242) and BMI (p = 0.516) of the participants. The anti-HBs titers were similar in the group of participants who had received two doses and those who had received three doses of the HBV vaccination. Overall the findings of our study provide a basis for testing for anti-HBs in all HCWs post vaccination in Rwanda.

The escalating burden of infections attributable to methicillin-resistant Staphylococcus aureus (MRSA) in East African countries is calling for interventional strategies to control the spread of this strain. The present study aimed at determining the prevalence, antimicrobial profiles, and staphylococcal cassette chromosome mec (SCC mec ) typing of MRSA strains. This was a cross-sectional laboratory-based study involving 226 non-duplicated S. aureus isolates from different clinical samples of patients attending a referral hospital in Kigali. Kirby-Bauer disk diffusion method was used for drug susceptibility testing. Methicillin-resistant S. aureus were confirmed using polymerase chain reaction (PCR) assay for the mec A gene and SCC mec type PCR assay was used for genotyping. Of 138 S. aureus , 39 (31.2%) were found to be MRSA strains. The mean age of the patients was 21.9 years. The incidence of MRSA increases with age and was 27.1% in patient age group younger than 18 years, 33.3% in the age group between 19 and 65 years, and 66.7% in patient age group older than 65 years. There was a significant association between geographic regions and incidence of MRSA ( P = 0.02) with the high MRSA isolates from Northern (61.5%) and Western (50%) provinces. Methicillin-resistant S. aureus strains were found to be mostly susceptible to linezolid (93.5%). Among the MRSA strains, SCC mec type I and SCC mec type IV were the most prevalent at 56.4% and 17.9%, respectively. A high prevalence of MRSA was found in Rwanda. Staphylococcal cassette chromosome mec type I (52.2%) was the most predominant. A continuous surveillance of MRSA strains, particularly in the hospital settings, should be an enduring exercise in Rwanda.

Human tuberculosis (TB) is amongst the oldest and deadliest human bacterial diseases that pose major health, social and economic burden at a global level. Current regimens for TB treatment are lengthy, expensive and ineffective to emerging drug resistant strains. Thus, there is an urgent need for identification and development of novel TB drugs and drug regimens with comprehensive and specific mechanisms of action. Many medicinal plants are traditionally used for TB treatment. While some of their phytochemical composition has been elucidated, their mechanisms of action are not well understood. Insufficient knowledge on Mycobacterium tuberculosis (M.tb) biology and the complex nature of its infection limit the effectiveness of current screening-based methods used for TB drug discovery. Nonetheless, application of metabolomics tools within the 'omics' approaches, could provide an alternative method of elucidating the mechanism of action of medicinal plants. Metabolomics aims at high throughput detection, quantification and identification of metabolites in biological samples. Changes in the concentration of specific metabolites in a biological sample indicate changes in the metabolic pathways. In this paper review and discuss novel methods that involve application of metabolomics to drug discovery and the understanding of mechanisms of action of medicinal plants with anti-TB activity. Current knowledge on TB infection, anti-TB drugs and mechanisms of action are also included. We further highlight metabolism of M. tuberculosis and the potential drug targets, as well as current approaches in the development of anti-TB drugs.