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Extensively drug-resistant tuberculosis (XDR TB) has extremely poor treatment outcomes in adults. Limited data are available for children. We report on clinical manifestations, treatment, and outcomes for 37 children (<15 years of age) with bacteriologically confirmed XDR TB in 11 countries. These patients were managed during 1999-2013. For the 37 children, median age was 11 years, 32 (87%) had pulmonary TB, and 29 had a recorded HIV status; 7 (24%) were infected with HIV. Median treatment duration was 7.0 months for the intensive phase and 12.2 months for the continuation phase. Thirty (81%) children had favorable treatment outcomes. Four (11%) died, 1 (3%) failed treatment, and 2 (5%) did not complete treatment. We found a high proportion of favorable treatment outcomes among children, with mortality rates markedly lower than for adults. Regimens and duration of treatment varied considerably. Evaluation of new regimens in children is required. [ABSTRACT FROM AUTHOR]

Background: An estimated 32,000 children develop multidrug-resistant tuberculosis (MDR-TB; Mycobacterium tuberculosis resistant to isoniazid and rifampin) each year. Little is known about the optimal treatment for these children.Methods and Findings: To inform the pediatric aspects of the revised World Health Organization (WHO) MDR-TB treatment guidelines, we performed a systematic review and individual patient data (IPD) meta-analysis, describing treatment outcomes in children treated for MDR-TB. To identify eligible reports we searched PubMed, LILACS, Embase, The Cochrane Library, PsychINFO, and BioMedCentral databases through 1 October 2014. To identify unpublished data, we reviewed conference abstracts, contacted experts in the field, and requested data through other routes, including at national and international conferences and through organizations working in pediatric MDR-TB. A cohort was eligible for inclusion if it included a minimum of three children (aged <15 years) who were treated for bacteriologically confirmed or clinically diagnosed MDR-TB, and if treatment outcomes were reported. The search yielded 2,772 reports; after review, 33 studies were eligible for inclusion, with IPD provided for 28 of these. All data were from published or unpublished observational cohorts. We analyzed demographic, clinical, and treatment factors as predictors of treatment outcome. In order to obtain adjusted estimates, we used a random-effects multivariable logistic regression (random intercept and random slope, unless specified otherwise) adjusted for the following covariates: age, sex, HIV infection, malnutrition, severe extrapulmonary disease, or the presence of severe disease on chest radiograph. We analyzed data from 975 children from 18 countries; 731 (75%) had bacteriologically confirmed and 244 (25%) had clinically diagnosed MDR-TB. The median age was 7.1 years. Of 910 (93%) children with documented HIV status, 359 (39%) were infected with HIV. When compared to clinically diagnosed patients, children with confirmed MDR-TB were more likely to be older, to be infected with HIV, to be malnourished, and to have severe tuberculosis (TB) on chest radiograph (p < 0.001 for all characteristics). Overall, 764 of 975 (78%) had a successful treatment outcome at the conclusion of therapy: 548/731 (75%) of confirmed and 216/244 (89%) of clinically diagnosed children (absolute difference 14%, 95% confidence interval [CI] 8%-19%, p < 0.001). Treatment was successful in only 56% of children with bacteriologically confirmed TB who were infected with HIV who did not receive any antiretroviral treatment (ART) during MDR-TB therapy, compared to 82% in children infected with HIV who received ART during MDR-TB therapy (absolute difference 26%, 95% CI 5%-48%, p = 0.006). In children with confirmed MDR-TB, the use of second-line injectable agents and high-dose isoniazid (15-20 mg/kg/day) were associated with treatment success (adjusted odds ratio [aOR] 2.9, 95% CI 1.0-8.3, p = 0.041 and aOR 5.9, 95% CI 1.7-20.5, p = 0.007, respectively). These findings for high-dose isoniazid may have been affected by site effect, as the majority of patients came from Cape Town. Limitations of this study include the difficulty of estimating the treatment effects of individual drugs within multidrug regimens, only observational cohort studies were available for inclusion, and treatment decisions were based on the clinician's perception of illness, with resulting potential for bias.Conclusions: This study suggests that children respond favorably to MDR-TB treatment. The low success rate in children infected with HIV who did not receive ART during their MDR-TB treatment highlights the need for ART in these children. Our findings of individual drug effects on treatment outcome should be further evaluated. [ABSTRACT FROM AUTHOR]

Background: Evaluations of health systems strengthening (HSS) interventions using observational data are rarely used for causal inference due to limited data availability. Routinely collected national data allow use of quasi-experimental designs such as interrupted time series (ITS). Rwanda has invested in a robust electronic health management information system (HMIS) that captures monthly healthcare utilization data. We used ITS to evaluate impact of an HSS intervention to improve primary health care facility readiness on health service utilization in two rural districts of Rwanda. Methods: We used controlled ITS analysis to compare changes in healthcare utilization at health centers (HC) that received the intervention (n = 13) to propensity score matched non-intervention health centers in Rwanda (n = 86) from January 2008 to December 2012. HC support included infrastructure renovation, salary support, medical equipment, referral network strengthening, and clinical training. Baseline quarterly mean outpatient visit rates and population density were used to model propensity scores. The intervention began in May 2010 and was implemented over a twelve-month period. We used monthly healthcare utilization data from the national Rwandan HMIS to study changes in the (1) number of facility deliveries per 10,000 women, (2) number of referrals for high risk pregnancy per 100,000 women, and (3) the number of outpatient visits performed per 1,000 catchment population. Results: PHIT HC experienced significantly higher monthly delivery rates post-HSS during the April-June season than comparison (3.19/10,000, 95% CI: [0.27, 6.10]). In 2010, this represented a 13% relative increase, and in 2011, this represented a 23% relative increase. The post-HSS change in monthly rate of high-risk pregnancies referred increased slightly in intervention compared to control HC (0.03/10,000, 95% CI: [-0.007, 0.06]). There was a small immediate post-HSS increase in outpatient visit rates in intervention compared to control HC (6.64/1,000, 95% CI: [-13.52, 26.81]). Conclusion: We failed to find strong evidence of post-HSS increases in outpatient visit rates or referral rates at health centers, which could be explained by small sample size and high baseline nation-wide health service coverage. However, our findings demonstrate that high quality routinely collected health facility data combined with ITS can be used for rigorous policy evaluation in resource-limited settings. [ABSTRACT FROM AUTHOR]

Background: Cancer services are inaccessible in many low-income countries, and few published examples describe oncology programs within the public sector. In 2011, the Rwanda Ministry of Health (RMOH) established Butaro Cancer Center of Excellence (BCCOE) to expand cancer services nationally. In hopes of informing cancer care delivery in similar settings, we describe program-level experience implementing BCCOE, patient characteristics, and challenges encountered.Methods: Butaro Cancer Center of Excellence was founded on diverse partnerships that emphasize capacity building. Services available include pathology-based diagnosis, basic imaging, chemotherapy, surgery, referral for radiotherapy, palliative care and socioeconomic access supports. Retrospective review of electronic medical records (EMR) of patients enrolled between July 1, 2012 and June 30, 2014 was conducted, supplemented by manual review of paper charts and programmatic records.Results: In the program's first 2 years, 2326 patients presented for cancer-related care. Of these, 70.5% were female, 4.3% children, and 74.3% on public health insurance. In the first year, 66.3% (n = 1144) were diagnosed with cancer. Leading adult diagnoses were breast, cervical, and skin cancer. Among children, nephroblastoma, acute lymphoblastic leukemia, and Hodgkin lymphoma were predominant. As of June 30, 2013, 95 cancer patients had died. Challenges encountered include documentation gaps and staff shortages.Conclusion: Butaro Cancer Center of Excellence demonstrates that complex cancer care can be delivered in the most resource-constrained settings, accessible to vulnerable patients. Key attributes that have made BCCOE possible are: meaningful North-south partnerships, innovative task- and infrastructure-shifting, RMOH leadership, and an equity-driven agenda. Going forward, we will apply our experiences and lessons learned to further strengthen BCCOE, and employ the developed EMR system as a valuable platform to assess long-term clinical outcomes and improve care. [ABSTRACT FROM AUTHOR]

Objective Integrated Management of Childhood Illness (IMCI) is the leading clinical protocol designed to decrease under-five mortality globally. However, impact is threatened by gaps in IMCI quality of care (QOC). In 2010, Partners In Health and the Rwanda Ministry of Health implemented a nurse mentorship intervention Mentoring and Enhanced Supervision at Health Centres (MESH) in two rural districts. This study measures change in QOC following the addition of MESH to didactic training. Design Prepost intervention study of change in QOC after 12 months of MESH support measured by case observation using a standardised checklist. Study sample was children age 2 months to 5 years presenting on the days of data collection (292 baseline, 413 endpoint). Setting 21 rural health centres in Rwanda. Outcomes Primary outcome was a validated index of key IMCI assessments. Secondary outcomes included assessment, classification and treatment indicators, and QOC variability across providers. A mixed-effects regression model of the index was created. Results In multivariate analyses, the index significantly improved in southern Kayonza (ß-coefficient 0.17, 95% CI 0.12 to 0.22) and Kirehe (ß-coefficient 0.29, 95% CI 0.23 to 0.34) districts. Children seen by IMCI-trained nurses increased from 83.2% to 100% (p<0.001) and use of IMCI case recording forms improved from 65.9% to 97.1% (p<0.001). Correct classification improved (56.0% to 91.5%, p<0.001), as did correct treatment (78.3% to 98.2%, p<0.001). Variability in QOC decreased (intracluster correlation coefficient 0.613- 0.346). Conclusions MESH was associated with significant improvements in all domains of IMCI quality. MESH could be an innovative strategy to improve IMCI implementation in resource-limited settings working to decrease under-five mortality. [ABSTRACT FROM AUTHOR]

The notion of "reverse innovation"-that some insights from low-income countries might offer transferable lessons for wealthier contexts—is increasingly common in the global health and business strategy literature. Yet the perspectives of researchers and policymakers in settings where these innovations are developed have been largely absent from the discussion to date. In this Commentary, we present examples of programmatic, technological, and research-based innovations from Rwanda, and offer reflections on how the global health community might leverage innovative partnerships for shared learning and improved health outcomes in all countries. [ABSTRACT FROM AUTHOR]

Background: Nationally, health in Rwanda has been improving since 2000, with considerable improvement since 2005. Despite improvements, rural areas continue to lag behind urban sectors with regard to key health outcomes. Partners In Health (PIH) has been supporting the Rwanda Ministry of Health (MOH) in two rural districts in Rwanda since 2005. Since 2009, the MOH and PIH have spearheaded a health systems strengthening (HSS) intervention in these districts as part of the Rwanda Population Health Implementation and Training (PHIT) Partnership. The partnership is guided by the belief that HSS interventions should be comprehensive, integrated, responsive to local conditions, and address health care access, cost, and quality. The PHIT Partnership represents a collaboration between the MOH and PIH, with support from the National University of Rwanda School of Public Health, the National Institute of Statistics, Harvard Medical School, and Brigham and Women's Hospital. Description of intervention: The PHIT Partnership's health systems support aligns with the World Health Organization's six health systems building blocks. HSS activities focus across all levels of the health system -- community, health center, hospital, and district leadership -- to improve health care access, quality, delivery, and health outcomes. Interventions are concentrated on three main areas: targeted support for health facilities, quality improvement initiatives, and a strengthened network of community health workers. Evaluation design: The impact of activities will be assessed using population-level outcomes data collected through oversampling of the demographic and health survey (DHS) in the intervention districts. The overall impact evaluation is complemented by an analysis of trends in facility health care utilization. A comprehensive costing project captures the total expenditures and financial inputs of the health care system to determine the cost of systems improvement. Targeted evaluations and operational research pieces focus on specific programmatic components, supported by partnership-supported work to build in-country research capacity. Discussion: Building on early successes, the work of the Rwanda PHIT Partnership approach to HSS has already seen noticeable increases in facility capacity and quality of care. The rigorous planned evaluation of the Partnership's HSS activities will contribute to global knowledge about intervention methodology, cost, and population health impact. [ABSTRACT FROM AUTHOR]

Background: Rwanda's National PMTCT program aims to achieve elimination of new HIV infections in children by 2015. In November 2010, Rwanda adopted the WHO 2010 ARV guidelines for PMTCT recommending Option B (HAART) for all HIV-positive pregnant women extended throughout breastfeeding and discontinued (short course-HAART) only for those not eligible for life treatment. The current study aims to assess the cost-effectiveness of this policy choice. Methods: Based on a cohort of HIV-infected pregnant women in Rwanda, we modelled the cost-effectiveness of six regimens: dual ARV prophylaxis with either 12 months breastfeeding or replacement feeding; short course HAART (Sc-HAART) prophylaxis with either 6 months breastfeeding, 12 months breastfeeding, or 18 months breastfeeding; and Sc-HAART prophylaxis with replacement feeding. Direct costs were modelled based on all inputs in each scenario and related unit costs. Effectiveness was evaluated by measuring HIV-free survival at 18 months. Savings correspond to the lifetime costs of HIV treatment and care avoided as a result of all vertical HIV infections averted. Results: All PMTCT scenarios considered are cost saving compared to “no intervention.” Sc-HAART with 12 months breastfeeding or 6 months breastfeeding dominate all other scenarios. Sc-HAART with 12 months breastfeeding allows for more children to be alive and HIV-uninfected by 18 months than Sc-HAART with 6 months breastfeeding for an incremental cost per child alive and uninfected of 11,882 USD. This conclusion is sensitive to changes in the relative risk of mortality by 18 months for exposed HIV-uninfected children on replacement feeding from birth and those who were breastfed for only 6 months compared to those breastfeeding for 12 months or more. Conclusion: Our findings support the earlier decision by Rwanda to adopt WHO Option B and could inform alternatives for breastfeeding duration. Local contexts and existing care delivery models should be part of national policy decisions. [ABSTRACT FROM AUTHOR]

Treatment of gestationat multidrug-resistant tuberculosis (MDR-TB) is controversial. We describe follow-up of 6 children exposed to second-line antituberculous agents in utero. Each child (average age, 3.7 years) underwent comprehensive clinical evaluation. One child had MDR-TB diagnosed. There was no evidence of significant late-presentation toxicity among the children. The results suggest that aggressive management of gestational MDR-TB may benefit both mother and child. [ABSTRACT FROM AUTHOR]

The article discusses the transformation of the Rwandan healthcare system in the wake of the genocide of 1994. Implementation of policies aimed at equalization in the health sector, has led to a substantial decrease in premature deaths related to Human Immunodeficiency Virus (HIV) and associated diseases like tuberculosis. External funds such as the Global fund and strategies such as the "mutuelles de santé" universal health coverage were instrumental in resurrecting the healthcare system.

While health systems strengthening (HSS) interventions are recommended by global health policy experts to improve population health in resource-limited settings, few examples exist of evaluations of HSS interventions conducted at the district level. In 2009, a partnership between Partners In Health (PIH), a non-governmental organization, and the Rwandan Ministry of Health (RMOH) was provided funds to implement and evaluate a district-level HSS intervention in two rural districts of Rwanda. The partnership provided limited funds to 14 health centers for targeted systems support in 2010; six others received support prior to the intervention (reference). RMOH health systems norms were mapped across the WHO HSS framework, scored from 0 to 10 and incorporated into a rapid survey assessing 11 domains of facility readiness. Stakeholder meetings allowed partnership leaders to review results, set priorities, and allocate resources. Investments included salary support, infrastructure improvements, medical equipment, and social support for patients. We compared facility domain scores from the start of the intervention to 12 months and tested for correlation between change in score and change in funding allocation to assess equity in our approach. We found significant improvements among intervention facilities from baseline to 12 months across several domains [infrastructure (+4, p=0.0001), clinical services (+1.2, p=0.03), infection and sanitation control (+0.6, p=0.03), medical equipment (+1.0, p=0.02), information use (+2, p=0.002)]. Composite score across domains improved from 6.2 at baseline to 7.4 at 12 months (p=0.002). Across facilities, 50% had composite scores greater than the average score among reference facilities (7.4) at 12 months compared to none at baseline. Rapid facility surveys, stakeholder engagement, and information feedback can be used for gap analysis and resource allocation. This approach can achieve effective use of limited resources, improve facility readiness, and ensure consistency of facility capacity to provide quality care at the district level. [ABSTRACT FROM AUTHOR]

Objective:To investigate the accuracy of three clinical scales for predicting severe disease (severe dehydration or death) in children with diarrhea in a resource-limited setting. Methods:Participants included 178 children admitted to three Rwandan hospitals with diarrhea. A local physician or nurse assessed each child on arrival using the World Health Organization (WHO) severe dehydration scale and the Centers for Disease Control (CDC) scale. Children were weighed on arrival and daily until they achieved a stable weight, with a 10% increase between admission weight and stable weight considered severe dehydration. The Clinical Dehydration Scale was then constructed post-hoc using the data collected for the other two scales. Receiver Operator Characteristic (ROC) curves were constructed for each scale compared to the composite outcome of severe dehydration or death. Results:The WHO severe dehydration scale, CDC scale, and Clinical Dehydration Scale had areas under the ROC curves (AUCs) of 0.72 (95% CI 0.60, 0.85), 0.73 (95% CI 0.62, 0.84), and 0.80 (95% CI 0.71, 0.89), respectively, in the full cohort. Only the Clinical Dehydration Scale was a significant predictor of severe disease when used in infants, with an AUC of 0.77 (95% CI 0.61, 0.93), and when used by nurses, with an AUC of 0.78 (95% CI 0.63, 0.93). Conclusions:While all three scales were moderate predictors of severe disease in children with diarrhea, scale accuracy varied based on provider training and age of the child. Future research should focus on developing or validating clinical tools that can be used accurately by nurses and other less-skilled providers to assess all children with diarrhea in resource-limited settings. [ABSTRACT FROM AUTHOR]

Background: Nationally, health in Rwanda has been improving since 2000, with considerable improvement since 2005. Despite improvements, rural areas continue to lag behind urban sectors with regard to key health outcomes. Partners In Health (PIH) has been supporting the Rwanda Ministry of Health (MOH) in two rural districts in Rwanda since 2005. Since 2009, the MOH and PIH have spearheaded a health systems strengthening (HSS) intervention in these districts as part of the Rwanda Population Health Implementation and Training (PHIT) Partnership. The partnership is guided by the belief that HSS interventions should be comprehensive, integrated, responsive to local conditions, and address health care access, cost, and quality. The PHIT Partnership represents a collaboration between the MOH and PIH, with support from the National University of Rwanda School of Public Health, the National Institute of Statistics, Harvard Medical School, and Brigham and Women's Hospital.Description Of Intervention: The PHIT Partnership's health systems support aligns with the World Health Organization's six health systems building blocks. HSS activities focus across all levels of the health system - community, health center, hospital, and district leadership - to improve health care access, quality, delivery, and health outcomes. Interventions are concentrated on three main areas: targeted support for health facilities, quality improvement initiatives, and a strengthened network of community health workers.Evaluation Design: The impact of activities will be assessed using population-level outcomes data collected through oversampling of the demographic and health survey (DHS) in the intervention districts. The overall impact evaluation is complemented by an analysis of trends in facility health care utilization. A comprehensive costing project captures the total expenditures and financial inputs of the health care system to determine the cost of systems improvement. Targeted evaluations and operational research pieces focus on specific programmatic components, supported by partnership-supported work to build in-country research capacity.Discussion: Building on early successes, the work of the Rwanda PHIT Partnership approach to HSS has already seen noticeable increases in facility capacity and quality of care. The rigorous planned evaluation of the Partnership's HSS activities will contribute to global knowledge about intervention methodology, cost, and population health impact. [ABSTRACT FROM AUTHOR]

The notion of "reverse innovation"--that some insights from low-income countries might offer transferable lessons for wealthier contexts--is increasingly common in the global health and business strategy literature. Yet the perspectives of researchers and policymakers in settings where these innovations are developed have been largely absent from the discussion to date. In this Commentary, we present examples of programmatic, technological, and research-based innovations from Rwanda, and offer reflections on how the global health community might leverage innovative partnerships for shared learning and improved health outcomes in all countries. [ABSTRACT FROM AUTHOR]