A pooled testing strategy for identifying SARS-CoV-2 at low prevalence.

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 groups1-7. 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 test8. 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 studies9-11). 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).

Expansion of artemisinin partial resistance mutations and lack of histidine rich protein-2 and -3 deletions in Plasmodium falciparum infections from Rukara, Rwanda.

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.

The Management of Infectious Diseases in Comorbidity with Tuberculosis.

Tuberculosis (TB) infection is instigated by the bacillus Mycobacterium tuberculosis (MTB) [...].

Risk factors for difficult-to-treat hepatitis C virus genotype 4r in Rwanda and implications for elimination in sub-Saharan Africa.

In sub-Saharan Africa, there exist distinct HCV genotype (GT) subtypes harbouring resistance-associated substitutions to commonly used non-structural protein 5A (NS5A) inhibitor-based direct-acting antiviral (DAA) regimens. In particular, GT4r subtype has demonstrated high rates of treatment failure. In the absence of routine viral sequencing in sub-Saharan Africa, it is important to identify sociodemographic, epidemiologic, and clinical characteristics that may be associated with GT4r infection. Methods: A secondary analysis was performed on data from 300 adults with HCV GT4 enrolled in a prospective trial assessing the safety and efficacy of sofosbuvir-ledipasvir in Rwanda in 2017. The association between characteristics at enrolment and GT subtype was assessed by chi-square analysis and logistic regression. In multivariate analysis, there were a higher proportion of participants with GT4r subtype with age <40 years (OR: 3.6, 95% CI: 1.3-10.5, p = 0.02), previous hospitalization (OR: 2.5, 95% CI: 1.3-5.0, p = 0.006), previous surgery (OR: 2.2, 95% CI: 1.1-4.2, p = 0.03), cirrhosis (OR: 3.2, 95% CI: 1.3-7.5, p = 0.008) and baseline HCV RNA >1 million IU/ml (OR: 3.4, 95% CI: 1.6-6.9, p = 0.001). Rwandan adults with GT4r are more likely to be younger, have a history of hospital admissions and surgeries and have more active or advanced liver disease compared to those with other GT4 subtypes. In the absence of advanced diagnostics to assess GT subtype, patients with these characteristics may warrant closer monitoring for treatment failure or alternative DAA regimens. More treatment experience with diverse DAA regimens is urgently needed for GT subtypes particular to this region.

Improved quality of life following direct-acting antiviral treatment for chronic hepatitis C infection in Rwanda: Results from a clinical trial in sub-Saharan Africa (the SHARED study).

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.

Maternal genitourinary infections and poor nutritional status increase risk of preterm birth in Gasabo District, Rwanda: a prospective, longitudinal, cohort study.

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.

Association between micronutrients and maternal leukocyte telomere length in early pregnancy in Rwanda.

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.

Highly successful treatment outcome of multidrug-resistant and genetic diversity of multidrug-resistant Mycobacterium tuberculosis strains in Rwanda.

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.

OBJECTIF: Déterminer les génotypes prévalents de la TB-MDR et décrire les résultats du traitement et la conversion bactériologique chez les patients atteints de TB-MDR. MÉTHODES: Analyse des dossiers de laboratoire de 173 patients atteints de TB-MDR de l'ensemble du Rwanda qui ont débuté un traitement sous prise en charge programmatique de la TB-MDR (PMDT) entre 2014 et 2015. Cinquante isolats archivés disponibles ont été génotypés pour les unités répétitives intercalées de mycobactéries - nombre variable de tandems répétés (MIRU-VNTR). RÉSULTAT: Sur les 170 patients dont l'issue était connue, 114 (66,3%) étaient guéris et 36 (21%) avaient terminé le traitement, ce qui donne un résultat positif (guéri et complété) de 150 patients (87,3%). Sur 20 patients atteints de TB-MDR dont l'issue du traitement était défavorable, 18 sont décédés, un a eu un échec et le dernier a abandonné/arrêté le traitement. Sur les 18 patients décédés, 11 (61%) étaient coinfectés par le VIH. Le résultat du traitement a été positif pour 93,9% des personnes VIH négatives et 81,8% pour ceux coinfectées par le VIH (p = 0,02). La conversion des frottis d'expectoration est survenue chez 3, 46, 57 et 78 patients respectivement à 2, 3, 4 et 6 mois, avec une durée médiane entre le frottis d'expectoration et la conversion de culture de 3 mois. Les 44 isolats de TB-MDR avec un résultat MIRU-VNTR ont montré une diversité génétique élevée avec un faible taux de regroupement (9,09%) et la sous-famille de la lignée Ouganda II étant la plus prévalente détectée dans 68,2% des isolats. La famille Beijing était le génotype le moins fréquemment détecté (2,3%, 1 isolat). CONCLUSION: Les taux de succès élevés du traitement de la TB-MDR obtenus au Rwanda étaient comparables aux résultats observés dans les régions riches en ressources, le VIH étant un facteur de risque indépendant d'un mauvais résultat du traitement. La diversité génétique élevée et le faible taux de regroupement rapportés ici suggèrent que la réactivation d'une maladie antérieure joue un rôle important dans la transmission de la TB-MDR au Rwanda.

Seroprevalence of Zika virus and Rubella virus IgG among blood donors in Rwanda and in Sweden.

Seroprevalence studies provide information on the susceptibility to infection of certain populations, including women of childbearing age. Such data from Central Africa are scarce regarding two viruses that cause congenital infections: Zika virus (ZIKV), an emerging mosquito-borne infection, and Rubella virus (RuV), a vaccine-preventable infection. We report on the seroprevalence of both ZIKV and RuV from Rwanda, a country without any known cases of ZIKV, but bordering Uganda where this virus was isolated in 1947. Anti-ZIKV-specific and anti-RuV-specific immunoglobulin G (IgG) antibodies were analyzed by enzyme-linked immunosorbent assay (ELISA) in serum samples from 874 Rwandan and 215 Swedish blood donors. Samples positive for IgG antibodies against ZIKV were examined for viral RNA using real-time reverse transcription polymerase chain reaction (RT-qPCR). The seroprevalence of ZIKV IgG in Rwanda was 1.4% (12/874), of which the predominance of positive findings came from the Southeastern region. All anti-ZIKV IgG-positive samples were PCR-negative. Among 297 female blood donors of childbearing age, 295 (99.3%) were seronegative and thus susceptible to ZIKV. All Swedish blood donors were IgG-negative to ZIKV. In contrast, blood donors from both countries showed high seroprevalence of IgG to RuV: 91.2% for Rwandan and 92.1% for Swedish donors. Only 10.5% (31/294) of female donors of childbearing age from Rwanda were seronegative for RuV. In Rwanda, seroprevalence for ZIKV IgG antibodies was low, but high for RuV. Hence, women of childbearing age were susceptible to ZIKV. These data may be of value for decision-making regarding prophylactic measures.

Community-based biological control of malaria mosquitoes using Bacillus thuringiensis var. israelensis (Bti) in Rwanda: community awareness, acceptance and participation.

BACKGROUND: Targeting the aquatic stages of malaria vectors via larval source management (LSM) in collaboration with local communities could accelerate progress towards malaria elimination when deployed in addition to existing vector control strategies. However, the precise role that communities can assume in implementing such an intervention has not been fully investigated. This study investigated community awareness, acceptance and participation in a study that incorporated the socio-economic and entomological impact of LSM using Bacillus thuringiensis var. israelensis (Bti) in eastern Rwanda, and identified challenges and recommendations for future scale-up. METHODS: The implementation of the community-based LSM intervention took place in Ruhuha, Rwanda, from February to July 2015. The intervention included three arms: control, community-based (CB) and project-supervised (PS). Mixed methods were used to collect baseline and endline socio-economic data in January and October 2015. RESULTS: A high perceived safety and effectiveness of Bti was reported at the start of the intervention. Being aware of malaria symptoms and perceiving Bti as safe on other living organisms increased the likelihood of community participation through investment of labour time for Bti application. On the other hand, the likelihood for community participation was lower if respondents: (1) perceived rice farming as very profitable; (2) provided more money to the cooperative as a capital; and, (3) were already involved in rice farming for more than 6 years. After 6 months of implementation, an increase in knowledge and skills regarding Bti application was reported. The community perceived a reduction in mosquito density and nuisance biting on treated arms. Main operational, seasonal and geographical challenges included manual application of Bti, long working hours, and need for transportation for reaching the fields. Recommendations were made for future scale-up, including addressing above-mentioned concerns and government adoption of LSM as part of its vector control strategies. CONCLUSIONS: Community awareness and support for LSM increased following Bti application. A high effectiveness of Bti in terms of reduction of mosquito abundance and nuisance biting was perceived. The study confirmed the feasibility of community-based LSM interventions and served as evidence for future scale-up of Bti application and adoption into Rwandan malaria vector control strategies.

Using an intervention mapping approach for planning, implementing and assessing a community-led project towards malaria elimination in the Eastern Province of Rwanda.

BACKGROUND: Active community participation in malaria control is key to achieving malaria pre-elimination in Rwanda. This paper describes development, implementation and evaluation of a community-based malaria elimination project in Ruhuha sector, Bugesera district, Eastern province of Rwanda. METHODS: Guided by an intervention mapping approach, a needs assessment was conducted using household and entomological surveys and focus group interviews. Data related to behavioural, epidemiological, entomological and economical aspects were collected. Desired behavioural and environmental outcomes were identified concurrently with behavioural and environmental determinants. Theoretical methods and their practical applications were enumerated to guide programme development and implementation. An operational plan including the scope and sequence as well as programme materials was developed. Two project components were subsequently implemented following community trainings: (1) community malaria action teams (CMATs) were initiated in mid-2014 as platforms to deliver malaria preventive messages at village level, and (2) a mosquito larval source control programme using biological substances was deployed for a duration of 6 months, implemented from January to July 2015. Process and outcome evaluation has been conducted for both programme components to inform future scale up. RESULTS: The project highlighted malaria patterns in the area and underpinned behavioural and environmental factors contributing to malaria transmission. Active involvement of the community in collaboration with CMATs contributed to health literacy, particularly increasing ability to make knowledgeable decisions in regards to malaria prevention and control. A follow up survey conducted six months following the establishment of CMATs reported a reduction of presumed malaria cases at the end of 2014. The changes were related to an increase in the acceptance and use of available preventive measures, such as indoor residual spraying and increase in community-based health insurance membership, also considered as a predictor of prompt and adequate care. The innovative larval source control intervention contributed to reduction in mosquito density and nuisance bites, increased knowledge and skills for malaria control as well as programme ownership. CONCLUSION: This community-based programme demonstrated the feasibility and effectiveness of active community participation in malaria control activities, which largely contributed to community empowerment and reduction of presumed malaria in the area. Further studies should explore how gains may be sustained to achieve the goal of malaria pre-elimination.

Determinants of prompt and adequate care among presumed malaria cases in a community in eastern Rwanda: a cross sectional study.

BACKGROUND: In order to understand factors influencing fever/malaria management practices among community-based individuals, the study evaluated psychosocial, socio-demographic and environmental determinants of prompt and adequate healthcare-seeking behaviours. METHODS: A quantitative household (HH) survey was conducted from December 2014 to February 2015 in Ruhuha sector, Bugesera district in the Eastern province of Rwanda. HHs that reported having had at least one member who experienced a fever and/or malaria episode in the previous 3 months prior to the study were included in the analysis. Healthcare-seeking behaviours associated with the last episode of illness were analysed. Socio-demographic, health facility access, long-lasting insecticidal-treated nets (LLINs), data on malaria knowledge, data and theory of planned behaviour (TPB) related variables (attitudes, subjective norms, perceived behavioural control) with regard to fever/malaria healthcare seeking, were collected. The primary outcome was prompt and adequate care defined as: (1) seeking advice or treatment at a health facility (health centre or hospital) or from a community health worker (CHW); (2) advice or treatment seeking within same/next day of symptoms onset; (3) received a laboratory diagnosis; (4) received advice or treatment; and, (5) reported completing the prescribed dose of medication. Determinants of prompt and adequate care among presumed malaria cases were evaluated using a logistic regression analysis. RESULTS: Overall, 302 (21 %) of the 1410 interviewed HHs reported at least one member as having experienced a fever or malaria within the 3 months prior to the survey. The number of HHs (where at least one member reported fever/malaria) that reported seeking advice or treatment at a health facility (health centre or hospital) or from a CHW was 249 (82.4 %). Of those who sought advice or treatment, 87.3 % had done so on same/next day of symptoms developing, 82.8 % received a laboratory diagnosis, and more than 90 % who received treatment reported completing the prescribed dosage. Prompt and adequate care was reported from 162 of the 302 HHs (53.6 %) that experienced fever or malaria for one or more HH members. Bivariate analyses showed that head of household (HoH)-related characteristics including reported knowledge of three or more malaria symptoms, having health insurance, being able to pay for medical services, use of LLINs the night before the survey, having a positive attitude, perceiving social support, as well as a high-perceived behavioural control with regard to healthcare seeking, were all significantly associated with prompt and adequate care. In the final logistic regression model, a high-perceived behavioural control (odds ratio (OR) 5.068, p = 0.042), having a health insurance (OR 2.410, p = 0.044) and having knowledge of malaria symptoms (OR 1.654, p = 0.049) significantly predicted prompt and adequate care. CONCLUSIONS: To promote prompt and adequate care seeking for malaria in the area, particular emphasis should be placed on community-focused strategies that promote early malaria symptom recognition, increased health insurance coverage and enhanced perceived behavioural control with regard to healthcare-seeking.

Diagnostic performance of smear microscopy and incremental yield of Xpert in detection of pulmonary tuberculosis in Rwanda.

BACKGROUND: Tuberculosis control program of Rwanda is currently phasing in light emitting diode-fluorescent microscopy (LED-FM) as an alternative to Ziehl-Neelsen (ZN) smear microscopy. This, alongside the newly introduced Xpert (Cepheid, Sunnyvale, CA, USA) is expected to improve diagnosis of tuberculosis and detection of rifampicin resistance in patients at health facilities. We assessed the accuracy of smear microscopy and the incremental sensitivity of Xpert at tuberculosis laboratories in Rwanda. METHODS: This was a cross-sectional study involving four laboratories performing ZN and four laboratories performing LED-FM microscopy. The laboratories include four intermediate (ILs) and four peripheral (PLs) laboratories. After smear microscopy, the left-over of samples, of a single early-morning sputum from 648 participants, were tested using Xpert and mycobacterial culture as a reference standard. Sensitivity of each test was compared and the incremental sensitivity of Xpert after a negative smear was assessed. RESULTS: A total of 96 presumptive pulmonary tuberculosis participants were culture positive for M. tuberculosis. The overall sensitivity in PL of ZN was 55.1 % (40.2-69.3 %), LED-FM was 37 % (19.4-57.6 %) and Xpert was 77.6 % (66.6-86.4 %) whereas in ILs the same value for ZN was 58.3 % (27.7-84.8 %), LED-FM was 62.5 % (24.5-91.5 %) and Xpert was 90 (68.3-98.8 %). The sensitivity for all tests was significantly higher among HIV-negative individuals (all test p <0.05). The overall incremental sensitivity of Xpert over smear microscopy was 32.3 %; p < 0.0001. The incremental sensitivity of Xpert was statistically significant for both smear methods at PL (32.9 %; p = 0.001) but not at the ILs (30 %; p = 0.125) for both smear methods. CONCLUSIONS: Our study findings of the early implementation of the LED-FM did not reveal significant increment in sensitivity compared to the method being phased out (ZN). This study showed a significant incremental sensitivity for Xpert from both smear methods at peripheral centers where majority of TB patients are diagnosed. Overall our findings support the recommendation for Xpert as an initial diagnostic test in adults and children presumed to have TB.

Factors impeding the acceptability and use of malaria preventive measures: implications for malaria elimination in eastern Rwanda.

BACKGROUND: Long-lasting insecticidal nets (LLIN), indoor residual spraying (IRS) and malaria case treatment with artemisinin-based combination therapy (ACT) have been proven to significantly reduce malaria, but may not necessarily lead to malaria elimination. This study explored factors hindering the acceptability and use of available malaria preventive measures to better inform area specific strategies that can lead to malaria elimination. METHODS: Nine focus group discussions (FGD) covering a cross-section of 81 lay community members and local leaders were conducted in Ruhuha, Southern Eastern Rwanda in December 2013 to determine: community perceptions on malaria disease, acceptability of LLIN and IRS, health care-seeking behaviours and other malaria elimination strategies deployed at household and environmental levels. Discussions were recorded in Kinyarwanda, transcribed into English and coded using Nvivo 10 software. RESULTS: Participants ranked malaria as the top among five common diseases in the Ruhuha sector. Participants expressed comprehensive knowledge and understanding of malaria transmission and symptoms. The concept of malaria elimination was acknowledged, but challenges were reported. Sleeping under a bed net was negatively affected by increase of bedbugs (and the associated irritability) as well as discomfortable warmness particularly during the dry season. These two factors were reported as common hindrances of the use of LLIN. Also, widespread use of LLIN in constructing chicken pens or as fences around vegetable gardens was reported. Participants also reported that IRS appeared to lead to an increase in number of mosquitoes and other household bugs rather than kill them. Prompt health centre utilization among participants with presumed malaria was reported to be common particularly among subscribers to the subsidized community-based health insurance (CBHI) scheme. In contrast, the lack of CBHI and/or perceptions that health centre visits were time consuming were common reasons for the use of over-the-counter medicines for malaria management. CONCLUSION: In this study, identification of behavioural determinants in relation to LLIN use, IRS acceptability and health care seeking is a critical step in the development of effective, targeted interventions aiming to further reduce malaria transmission and elimination in the area.

Community mobilization for malaria elimination: application of an open space methodology in Ruhuha sector, Rwanda.

BACKGROUND: Despite the significant reduction of malaria transmission in Rwanda, Ruhuha sector is still a highly endemic area for malaria. The objective of this activity was to explore and brainstorm the potential roles of various community stakeholders in malaria elimination. METHODS: Horizontal participatory approaches such as 'open space' have been deployed to explore local priorities, stimulate community contribution to project planning, and to promote local capacity to manage programmes. Two open space meetings were conducted with 62 and 82 participants in years 1 and 2, respectively. Participants included purposively selected community and local organizations' representatives. RESULTS: Malaria was perceived as a health concern by the respondents despite the reported reduction in prevalence from 60 to 20% for cases at the local health centre. Some misconceptions of the cause of malaria and misuse of preventive strategies were noted. Poverty was deemed to be a contributing factor to malaria transmission, with suggestions that improvement of living conditions for poor families might help malaria reduction. Participants expressed willingness to contribute to malaria elimination and underscored the need for constant education, sensitization and mobilization towards malaria control in general. Active diagnosis, preventative strategies and prompt treatment of malaria cases were all mentioned by participants as ways to reduce malaria. Participants suggested that partnership of stakeholders at various levels could speed up programme activities. A community rewards system was deemed important to motivate engaged participants, i.e., community health workers and households. Establishment of malaria clubs in schools settings was also suggested as crucial to speed up community awareness and increase skills towards further malaria reduction. CONCLUSIONS: This bottom-up approach was found useful in engaging the local community, enabling them to explore issues related to malaria in the area and suggest solutions for sustainable malaria elimination gains.

Measles Vaccine Coverage and Disease Outbreaks: A Systematic Review of the Early Impact of COVID-19 in Low and Lower-Middle Income Countries.

Objectives: We aimed to evaluate changes to measles-containing vaccine (MCV) provision and subsequent measles disease cases in low- and lower-middle income countries (LICs, LMICs) in relation to the COVID-19 pandemic. Methods: A systematic search was conducted of MEDLINE, OVID EMBASE and PubMed records. Primary quantitative and qualitative research studies published from January 2020 were included if they reported on COVID-19 impact on MCV provision and/or measles outbreak rates within LICs and LMICs. Results: 45 studies were included. The change in MCV1 vaccination coverage in national and international regions ranged -13% to +44.4% from pre-COVID time periods. In local regions, the median MCV1 and overall EPI rate changed by -23.3% and -28.5% respectively. Median MCV2 rate was disproportionally impacted in local areas during COVID-interruption time-periods (-48.2%) with ongoing disruption in early-recovery time-periods (-17.7%). 8.9% of studies reported on vaccination status of confirmed measles cases; from these, 71%-91% had received no MCV dose. Conclusion: MCV vaccination coverage experienced ongoing disruption during the recovery periods after initial COVID-19 disruption. Vaccination in local area datasets notably experienced longer-term disruption compared to nationally reported figures.

Exploring Prescription Practices: Insights from an Antimicrobial Stewardship Program at a Tertiary Healthcare Facility, Rwanda.

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.

Prevalence of Falciparum and non-Falciparum Malaria in the 2014-15 Rwanda Demographic Health Survey.

Background: Malaria remains a major cause of morbidity in sub-Saharan Africa. Undetected asymptomatic falciparum malaria results in a large transmission reservoir and there is evidence of increasing non-falciparum malaria as malaria is controlled in Africa, both resulting in challenges for malaria control programs. Methods: We performed quantitative real time PCR for 4 malaria species in 4,596 individuals from the 2014-2015 Rwanda Demographic Health Survey. Bivariate models were used to determine species-specific associations with risk factors. Results: Asymptomatic falciparum malaria, P. ovale spp., and P. malariae infection had broad spatial distribution across Rwanda. P. vivax infection was rare. Overall infection prevalence was 23.6% (95%CI [21.7%, 26.0%]), with falciparum and non-falciparum at 17.6% [15.9%, 19.0%] and 8.3% [7.0%, 10.0%], respectively. Parasitemias tended to be low and mixed species infections were common, especially where malaria transmission was the highest. Falciparum infection was associated with socio-econiomic status, rural residence and low altitude. Few risk factors were associated with non-falciparum malaria. Conclusions: Asymptomatic falciparum malaria and non-falciparum malaria are common and widely distributed across Rwanda. Continued molecular monitoring of Plasmodium spp. is needed to monitor these threats to malaria control in Africa.