Impact of SMS Text Messaging Reminders on Helmet Use Among Motorcycle Drivers in Dar es Salaam, Tanzania: Randomized Controlled Trial.

BACKGROUND: Road traffic injury is a pressing public health issue in Tanzania. Increasing helmet use among motorcycle drivers can help reduce the burden due to road traffic injuries in the country. Helmet adherence can be supported through mobile health interventions. OBJECTIVE: The aim of this study is to evaluate the comparative impact of two different types of SMS text messaging reminders on motorcycle helmet use. METHODS: Participants were 391 commercial motorcycle taxi drivers in Dar es Salaam, Tanzania. Participants were randomized into three groups, each receiving a different set of messages: (1) social norming messages aimed at emphasizing society's positive stance on helmet wearing, (2) fear appeal messages that emphasized the dangers of riding without a helmet, and (3) control group messages, which included basic road safety messages unrelated to helmet use. Every participant received the control messages. Adherence to helmet use was evaluated by self-report through surveys conducted at baseline, 3 weeks, and 6 weeks. RESULTS: At 6 weeks, the odds of self-reporting consistent helmet use were estimated to be 1.58 times higher in the social norming group than in the control group (P=.04), though this difference was not significant after accounting for multiple testing. There was little difference between fear appeal and control group recipients (odds ratio 1.03, P=.47). Subgroup analysis suggests that both fear appeal and social norming message types might have been associated with increased helmet use among participants who did not consistently wear helmets at baseline (odds ratio 1.66 and odds ratio 1.84, respectively), but this was not significant (P=.11 and P=.07, respectively). Among those who were consistent wearers at baseline, the social norming messages performed better than the fear appeal messages, and this difference reached traditional significance (P=.03), but was not significant after accounting for multiple testing. CONCLUSIONS: The use of SMS text messaging reminders may improve helmet use among motorcycle drivers when framed as social norming messages. Given that nearly half of the drivers in our sample did not consistently wear their helmets on every trip, strategies to increase consistent usage could greatly benefit public safety. TRIAL REGISTRATION: ClinicalTrials.gov NCT02120742; https://clinicaltrials.gov/ct2/show/NCT02120742.

Telehealth's New Horizon: Providing Smart Hospital-Level Care in the Home.

During the COVID-19 pandemic, medical providers have expanded telehealth into daily practice, with many medical and behavioral health care visits provided remotely over video or through phone. The telehealth market was already facilitating home health care with increasing levels of sophistication before COVID-19. Among the emerging telehealth practices, telephysical therapy; teleneurology; telemental health; chronic care management of congestive heart failure, chronic obstructive pulmonary disease, diabetes; home hospice; home mechanical ventilation; and home dialysis are some of the most prominent. Home telehealth helps streamline hospital/clinic operations and ensure the safety of health care workers and patients. The authors recommend that we expand home telehealth to a comprehensive delivery of medical care across a distributed network of hospitals and homes, linking patients to health care workers through the Internet of Medical Things using in-home equipment, including smart medical monitoring devices to create a "medical smart home." This expanded telehealth capability will help doctors care for patients flexibly, remotely, and safely as a part of standard operations and during emergencies such as a pandemic. This model of "telehomecare" is already being implemented, as shown herein with examples. The authors envision a future in which providers and hospitals transition medical care delivery to the home just as, during the COVID-19 pandemic, students adapted to distance learning and adults transitioned to remote work from home. Many of our homes in the future may have a "smart medical suite" as well as a "smart home office."

Correction to: Successful implementation of isoniazid preventive therapy at a pediatric HIV clinic in Tanzania.

An amendment to this paper has been published and can be accessed via the original article.

Successful implementation of isoniazid preventive therapy at a pediatric HIV clinic in Tanzania.

BACKGROUND: In accordance with international guidance for tuberculosis (TB) prevention, the Tanzanian Ministry of Health recommends isoniazid preventive therapy (IPT) for children aged 12 months and older who are living with HIV. Concerns about tolerability, adherence, and potential mistreatment of undiagnosed TB with monotherapy have limited uptake of IPT globally, especially among children, in whom diagnostic confirmation is challenging. We assessed IPT implementation and adherence at a pediatric HIV clinic in Tanzania. METHODS: In this prospective cohort study, eligible children living with HIV aged 1-15 years receiving care at the DarDar Pediatric Program in Dar es Salaam who screened negative for TB disease were offered a 6-month regimen of daily isoniazid. Patients could choose to receive IPT via facility- or community-based care. Parents/caregivers and children provided informed consent and verbal assent respectively. Isoniazid was dispensed with the child's antiretroviral therapy every 1-3 months. IPT adherence and treatment completion was determined by pill counts, appointment attendance, and self-report. Patients underwent TB symptom screening at every visit. RESULTS: We enrolled 66 children between July and December 2017. No patients/caregivers declined IPT. Most participants were female (n = 43, 65.1%) and the median age was 11 years (interquartile range [IQR] 8, 13). 63 (95.5%) participants chose the facility-based model; due to the small number of participants who chose the community-based model, valid comparisons between the two groups could not be made. Forty-nine participants (74.2%) completed IPT within 10 months. Among the remaining 17, 11 had IPT discontinued by their provider due to adverse drug reactions, 5 lacked documentation of completion, and 1 had unknown outcomes due to missing paperwork. Of those who completed IPT, the average monthly adherence was 98.0%. None of the participants were diagnosed with TB while taking IPT or during a median of 4 months of follow-up. CONCLUSIONS: High adherence and treatment completion rates can be achieved when IPT is integrated into routine, self-selected facility-based pediatric HIV care. Improved record-keeping may yield even higher completion rates. IPT was well tolerated and no cases of TB were detected. IPT for children living with HIV is feasible and should be implemented throughout Tanzania.

The future of global health education: training for equity in global health.

BACKGROUND: Among academic institutions in the United States, interest in global health has grown substantially: by the number of students seeking global health opportunities at all stages of training, and by the increase in institutional partnerships and newly established centers, institutes, and initiatives to house global health programs at undergraduate, public health and medical schools. Witnessing this remarkable growth should compel health educators to question whether the training and guidance that we provide to students today is appropriate, and whether it will be applicable in the next decade and beyond. Given that "global health" did not exist as an academic discipline in the United States 20 years ago, what can we expect it will look like 20 years from now and how can we prepare for that future? DISCUSSION: Most clinicians and trainees today recognize the importance of true partnership and capacity building in both directions for successful international collaborations. The challenge is in the execution of these practices. There are projects around the world where this is occurring and equitable partnerships have been established. Based on our experience and observations of the current landscape of academic global health, we share a perspective on principles of engagement, highlighting instances where partnerships have thrived, and examples of where we, as a global community, have fallen short. CONCLUSIONS: As the world moves beyond the charity model of global health (and its colonial roots), it is evident that the issue underlying ethical global health practice is partnership and the pursuit of health equity. Thus, achieving equity in global health education and practice ought to be central to our mission as educators and advisors when preparing trainees for careers in this field. Seeking to eliminate health inequities wherever they are ingrained will reveal the injustices around the globe and in our own cities and towns.

Interventions to improve delivery of isoniazid preventive therapy: an overview of systematic reviews.

BACKGROUND: Uptake of isoniazid preventive therapy (IPT) to prevent tuberculosis has been poor, particularly in the highest risk populations. Interventions to improve IPT delivery could promote implementation. The large number of existing systematic reviews on treatment adherence has made drawing conclusions a challenge. To provide decision makers with the evidence they need, we performed an overview of systematic reviews to compare different organizational interventions to improve IPT delivery as measured by treatment completion among those at highest risk for the development of TB disease, namely child contacts or HIV-infected individuals. METHODS: We searched the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects (DARE), and MEDLINE up to August 15, 2012. Two authors used a standardized data extraction form and the AMSTAR instrument to independently assess each review. RESULTS: Six reviews met inclusion criteria. Interventions included changes in the setting/site of IPT delivery, use of quality monitoring mechanisms (e.g., directly observed therapy), IPT delivery integration into other healthcare services, and use of lay health workers. Most reviews reported a combination of outcomes related to IPT adherence and treatment completion rate but without a baseline or comparison rate. Generally, we found limited evidence to demonstrate that the studied interventions improved treatment completion. CONCLUSIONS: While most of the interventions were not shown to improve IPT completion, integration of tuberculosis and HIV services yielded high treatment completion rates in some settings. The lack of data from high burden TB settings limits applicability. Further research to assess different IPT delivery interventions, including those that address barriers to care in at-risk populations, is urgently needed to identify the most effective practices for IPT delivery and TB control in high TB burden settings.

Barriers and Enablers to Retention in HIV Care and Adherence to Antiretroviral Therapy: Evidence from Dar es Salaam, Tanzania.

Purpose: To explore the enabling factors, barriers, and strategies to improve retention in HIV care and adherence to antiretroviral therapy (ART) among adults (18 years and above) living with HIV in Dar es Salaam, Tanzania. Methods: We conducted a descriptive qualitative study to better understand and explore enablers, barriers, and strategies to improve retention in HIV care and adherence to antiretroviral therapy (ART) among PLHIV in Dar es Salaam, Tanzania. Focus group discussions (FGD) were conducted with a semi-structured discussion guide between December 2021 and June 2022. A non-random purposive sampling technique was used to select PLHIV and people involved in provision of healthcare and socioeconomic support to PLHIV. Thematic analysis was used to identify and interpret the themes. Results: Three major themes with 10 sub-themes emerged. Participants indicated that family and partner support, peer-support group/adherence clubs, and healthcare provider counselling on medication adherence facilitated retention and adherence to ART. In contrast, stigma and discrimination, financial constraints, disease outbreaks such as the COVID-19 pandemic, myths and misconceptions about HIV, and side effects of antiretrovirals were mentioned as barriers. Strengthening community and patient education about HIV and ART through peer support groups and financial support for poor PLHIV were the proposed mitigation. Conclusion: Addressing the challenges to ART adherence may require a more holistic approach. We recommend the implementation of peer support groups and financial support through small microfinance groups as interventions to increase retention in HIV care and adherence to ART in the study area.

Molecular epidemiology of HIV-associated tuberculosis in Dar es Salaam, Tanzania: strain predominance, clustering, and polyclonal disease.

Molecular typing of Mycobacterium tuberculosis can be used to elucidate the epidemiology of tuberculosis, including the rates of clustering, the frequency of polyclonal disease, and the distribution of genotypic families. We performed IS6110 typing and spoligotyping on M. tuberculosis strains isolated from HIV-infected subjects at baseline or during follow-up in the DarDar Trial in Tanzania and on selected community isolates. Clustering occurred in 203 (74%) of 275 subjects: 124 (80%) of 155 HIV-infected subjects with baseline isolates, 56 (69%) of 81 HIV-infected subjects with endpoint isolates, and 23 (59%) of 39 community controls. Overall, 113 (41%) subjects had an isolate representing the East Indian "GD" family. The rate of clustering was similar among vaccine and placebo recipients and among subjects with or without cellular immune responses to mycobacterial antigens. Polyclonal disease was detected in 6 (43%) of 14 patients with multiple specimens typed. Most cases of HIV-associated tuberculosis among subjects from this study in Dar es Salaam resulted from recently acquired infection. Polyclonal infection was detected and isolates representing the East Indian GD strain family were the most common.

Higher COVID-19 Vaccination Rates Are Associated with Lower COVID-19 Mortality: A Global Analysis.

Mass vaccination initiatives are underway worldwide, and a considerable percentage of the world's population is now vaccinated. This study examined the association of COVID-19 deaths per 1000 cases with a fully vaccinated population. The global median deaths per 1000 cases were 15.68 (IQR 9.84, 25.87) after 6 months of vaccinations and 11.96 (IQR 6.08, 20.63) after 12 months. Across 164 countries, we found significant variations in vaccination levels of populations, booster doses, and mortality, with higher vaccine coverage and lower mortality in high-income countries. Several regression models were performed to test the association between vaccination and COVID-19 mortality. Control variables were used to account for confounding variables. A 10-percentage-point increase in vaccination was associated with an 18.1% decrease in mortality after 6 months (95%CI, 7.4-28.8%) and a 16.8% decrease after 12 months (95%CI, 6.9-26.7%). A 10-percentage-point increase in booster vaccination rates was associated with a 33.1% decrease in COVID-19 mortality (95%CI, 16.0-50.2%). This relationship is present in most analyses by country income groups with variations in the effect size. Efforts are needed to reduce vaccine hesitancy while ensuring suitable infrastructure and supply to enable all countries to increase their vaccination rates.

Testing for Drug-Related Infectious Diseases and Determinants among People Who Use Drugs in a Low-Resource Setting: A Respondent-Driven Cross-Sectional Survey.

(1) Background: There is a dearth of data on the levels and determinants of testing for drug-related infectious diseases among people who use drugs (PWUD). We assessed the proportions and determinants of testing for drug-related infectious diseases to inform ongoing interventions for PWUD. (2) Methods: A cross-sectional study involving 599 PWUD was conducted in Dar es Salaam and Tanga between January and February 2019. Data were collected through a researcher-administered questionnaire using handheld tablets. Logistic regression models were used to identify independent testing determinants for drug-related infectious diseases. (3) Results: A majority (98.0%) of participants were males, with a mean age of 36.8 (SD = 7.8) years. 75.0%, 40.6%, 38.6%, and 8.2% reported having ever tested for HIV, tuberculosis (TB), sexually transmitted infections (STIs), and viral hepatitis, respectively. The likelihood of HIV testing was higher among those living with someone (AOR = 2.18, 95% CI: 1.09-4.68) compared with those who were homeless and perceived treatment was appropriate (AOR = 2.18, 95% CI: 1.05-4.46), but was lower among those who experienced mild to moderate (AOR = 0.44, 95% CI: 0.21-0.95) and severe internalized stigma (AOR = 0.44, 95% CI: 0.22-0.94) compared with those reporting no internalized stigma, and among those who experienced financial difficulties resulting from spending on health care services (AOR = 0.60, 95% CI: 0.40-0.89). Perception of treatment appropriateness (AOR = 2.29, 96% CI: 1.10-5.06) and severe enacted stigma (AOR = 1.90, 95% CI: 1.06-3.42) were associated with increased odds of TB testing. The odds of STIs testing increased among those who were married (AOR = 2.31, 95% CI: 1.45-3.72) compared with those who were single and those who had experienced mild (AOR = 2.39, 95% CI: 1.28-4.53) or severe (AOR = 6.20, 95% CI: 1.99-23.83) sexual violence, compared with those who had not experienced sexual violence. However, the odds decreased among those who had been remanded in the past month (AOR = 0.64, 95% CI: 0.43-0.95) compared with those who were not remanded and among those who had financial difficulties resulting from spending on health care services (AOR = 0.66, 95% CI: 0.47-0.94). The likelihood of testing for viral hepatitis testing increased among those who had heard about the comprehensive HIV intervention package (CHIP) (AOR = 2.59, 95% CI: 1.40-4.94); however, it decreased among those who had financial difficulties resulting from spending on health care services (AOR = 0.48, 95% CI: 0.24-0.92). (4) Conclusions: Except for HIV, PWUD had undergone limited testing for drug-related infectious diseases. The study findings highlight some factors influencing testing for the selected infectious diseases investigated, which should be targeted for tailored interventions to improve diagnosis and treatment.

Decolonizing Global Health Education: Rethinking Institutional Partnerships and Approaches.

Global health often entails partnerships between institutions in low- and middle-income countries (LMICs) that were previously colonized and high-income countries (HICs) that were colonizers. Little attention has been paid to the legacy of former colonial relationships and the influence they have on global health initiatives. There have been recent calls for the decolonization of global health education and the reexamination of assumptions and practices under pinning global health partnerships. Medicine's role in colonialism cannot be ignored and requires critical review. There is a growing awareness of how knowledge generated in HICs defines practices and informs thinking to the detriment of knowledge systems in LMICs. Additionally, research partnerships often benefit the better-resourced partner. In this article, the authors offer a brief analysis of the intersections between colonialism, medicine, and global health education and explore the lingering impact of colonialist legacies on current global health programs and partnerships. They describe how "decolonized" perspectives have not gained sufficient traction and how inequitable power dynamics and neocolonialist assumptions continue to dominate. They discuss 5 approaches, and highlight resources, that challenge colonial paradigms in the global health arena. Furthermore, they argue for the inclusion of more transfor mative learning approaches to promote change in attitudes and practice. They call for critical reflection and concomitant action to shift colonial paradigms toward more equitable partnerships in global education.

Last mile research: a conceptual map.

Background: The term 'last mile' has been used across disciplines to refer to populations who are farthest away, most difficult to reach, or last to benefit from a program or service. However, last mile research lacks a shared understanding around its conceptualization.Objectives: This project used a concept mapping process to answer the questions: what is last mile research in global health and, how can it be used to make positive change for health equity in the last mile?Methods: Between July and December 2019, a five-stage concept mapping exercise was undertaken using online concept mapping software and an in-person consensus meeting. The stages were: establishment of an expert group and focus prompt; idea generation; sorting and rating; initial analysis and final consensus meeting.Results: A group of 15 health researchers with experience working with populations in last mile contexts and who were based at the Matariki Network institutions of Queen's University, CAN and Dartmouth College, USA took part. The resulting concept map had 64 unique idea statements and the process resulted in a map with five clusters. These included: (1) Last mile populations; (2) Research methods and approaches; (3) Structural and systemic factors; (4) Health system factors, and (5) Broader environmental factors. Central to the map were the ideas of equity, human rights, health systems, and contextual sensitivity.Conclusion: This is the first time 'last mile research' has been the focus of a formal concept mapping exercise. The resulting map showed consensus about who last mile populations are, how research should be undertaken in the last mile and why last mile health disparities exist. The map can be used to inform research training programs, however, repeating this process with researchers and members from different last mile populations would also add further insight.

The adverse health effects of punitive immigrant policies in the United States: A systematic review.

BACKGROUND: Immigrants in the United States (US) today are facing a dynamic policy landscape. The Trump administration has threatened or curtailed access to basic services for 10.5 million undocumented immigrants currently in the US. We sought to examine the historical effects that punitive laws have had on health outcomes in US immigrant communities. METHODS: In this systematic review, we searched the following databases from inception-May 2020 for original research articles with no language restrictions: Ovid MEDLINE, Ovid EMBASE, Cochrane Library (Wiley), Web of Science Core Collection (Clarivate), CINAHL (EBSCO), and Social Work Abstracts (Ovid). This study is registered with PROSPERO, CRD42019138817. Articles with cohort sizes >10 that directly evaluated the health-related effects of a punitive immigrant law or policy within the US were included. FINDINGS: 6,357 studies were screened for eligibility. Of these, 32 studies were selected for inclusion and qualitatively synthesized based upon four themes that appeared throughout our analysis: (1) impact on healthcare utilization, (2) impact on women's and children's health, (3) impact on mental health services, and (4) impact on public health. The impact of each law, policy, mandate, and directive since 1990 is briefly discussed, as are the limitations and risk of bias of each study. INTERPRETATION: Many punitive immigrant policies have decreased immigrant access to and utilization of basic healthcare services, while instilling fear, confusion, and anxiety in these communities. The federal government should preserve and expand access for undocumented individuals without threat of deportation to improve health outcomes for US citizens and noncitizens.

Predictors of suboptimal adherence to isoniazid preventive therapy among adolescents and children living with HIV.

This study identified factors associated with adherence to a 6-month isoniazid preventive therapy (IPT) course among adolescents and children living with HIV. Forty adolescents living with HIV and 48 primary caregivers of children living with HIV completed a Likert-based survey to measure respondent opinions regarding access to care, quality of care, preferred regimens, perceived stigma, and confidence in self-efficacy. Sociodemographic data were collected and adherence measured as the average of pill counts obtained while on IPT. The rates of suboptimal adherence (< 95% adherent) were 22.5% among adolescents and 37.5% among the children of primary caregivers. Univariate logistic regression was used to model the change in the odds of suboptimal adherence. Independent factors associated with suboptimal adherence among adolescents included age, education level, the cost of coming to clinic, stigma from community members, and two variables relating to self-efficacy. Among primary caregivers, child age, concerns about stigma, and location preference for meeting a community-health worker were associated with suboptimal adherence. To determine whether these combined factors contributed different information to the prediction of suboptimal adherence, a risk score containing these predictors was constructed for each group. The risk score had an AUC of 0.87 (95% CI: 0.76, 0.99) among adolescents and an AUC of 0.76 (95% CI: 0.62, 0.90), among primary caregivers suggesting that these variables may have complementary predictive utility. The heterogeneous scope and associations of these variables in different populations suggests that interventions aiming to increase optimal adherence will need to be tailored to specific populations and multifaceted in nature. Ideally interventions should address both long-established barriers to adherence such as cost of transportation to attend clinic and more nuanced psychosocial barriers such as perceived community stigma and confidence in self-efficacy.

DAR-901 vaccine for the prevention of infection with Mycobacterium tuberculosis among BCG-immunized adolescents in Tanzania: A randomized controlled, double-blind phase 2b trial.

BACKGROUND: SRL172 prevented disease due to Mycobacterium tuberculosis in a Phase 3 trial. DAR-901 represents a scalable manufacturing process for SRL172. We sought to determine if DAR-901 would prevent infection with M. tuberculosis among BCG-primed adolescents age 13-15 years in Tanzania. METHODS: Adolescents with a negative T- SPOT.TBR interferon gamma release assay (IGRA) were randomized 1:1 to three intradermal injections of DAR-901 or saline placebo at 0, 2 and 4 months. Repeat IGRAs were performed at 2 months, and at 1, 2, and 3 years. The primary efficacy outcome was time to new TB infection (IGRA conversion to positive); the secondary outcome was time to persistent TB infection (IGRA conversion with repeat positive IGRA). RESULTS: Among 936 participants screened 667 were eligible and randomized to their first dose of vaccine or placebo (safety cohort). At 2 months, 625 participants remained IGRA-negative and were scheduled for the additional two doses (efficacy cohort). DAR-901 was safe and well-tolerated. One DAR-901 recipient developed a vaccine site abscess. Neither the primary nor secondary endpoints differed between the two treatment arms (p = 0.90 and p = 0.20, respectively). DAR-901 IGRA converters had median responses to ESAT-6 of 50.1 spot-forming cells (SFCs) vs. 19.6 SFCs in placebo IGRA converters (p = 0.03). CONCLUSIONS: A three-dose series of 1 mg DAR-901 was safe and well-tolerated but did not prevent initial or persistent IGRA conversion. DAR-901 recipients with IGRA conversion demonstrated enhanced immune responses to ESAT-6. Since protection against disease may require different immunologic responses than protection against infection a trial of DAR-901 to prevent TB disease is warranted. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov as NCT02712424.

DOTS implementation in a post-war, United Nations-administered territory: lessons from Kosovo.

SETTING: The WHO-recommended strategy of tuberculosis control (DOTS strategy) has been shown to be effective in reducing tuberculosis incidence in a variety of countries/ settings. Little evidence exists on the implementation, and effectiveness of DOTS in a transitional, post-war setting OBJECTIVE: To describe the process of establishing a National Tuberculosis Control Program (NTP) and implementing DOTS throughout Kosovo, and the outcomes achieved by this international collaboration in a post-war transitional setting during 1999-2005. METHODS: In 1999, as part of the re-organization of health services, a DOTS-based NTP was established and operationalized through a collaboration of several international partners in Kosovo. Five key steps supported these activities. RESULTS: Kosovo has reached the World Health Assembly targets, having achieved 75% case detection rate (sputum smear-positive cases) and 93% treatment success rate. During 2000-2005, new smear-positive tuberculosis case notifications decreased by 44.5% (median annual decrease for all cases: 7.6%). CONCLUSIONS: Kosovo's success story is a collaborative tale, each partner involved playing a unique role in supporting NTP activities. The Kosovo example provides yet another setting in which DOTS implementation has resulted in successful patient outcomes. The international TB control community would be well-served by formal guidelines for implementing DOTS and the new STOP TB Strategy in these settings.

Health Professional Training and Capacity Strengthening Through International Academic Partnerships: The First Five Years of the Human Resources for Health Program in Rwanda.

BACKGROUND: The Rwanda Human Resources for Health Program (HRH Program) is a 7-year (2012-2019) health professional training initiative led by the Government of Rwanda with the goals of training a large, diverse, and competent health workforce and strengthening the capacity of academic institutions in Rwanda. METHODS: The data for this organizational case study was collected through official reports from the Rwanda Ministry of Health (MoH) and 22 participating US academic institutions, databases from the MoH and the College of Medicine and Health Sciences (CMHS) in Rwanda, and surveys completed by the co-authors. RESULTS: In the first 5 years of the HRH Program, a consortium of US academic institutions has deployed an average of 99 visiting faculty per year to support 22 training programs, which are on track to graduate almost 4600 students by 2019. The HRH Program has also built capacity within the CMHS by promoting the recruitment of Rwandan faculty and the establishment of additional partnerships and collaborations with the US academic institutions. CONCLUSION: The milestones achieved by the HRH Program have been substantial although some challenges persist. These challenges include adequately supporting the visiting faculty; pairing them with Rwandan faculty (twinning); ensuring strong communication and coordination among stakeholders; addressing mismatches in priorities between donors and implementers; the execution of a sustainability strategy; and the decision by one of the donors not to renew funding beyond March 2017. Over the next 2 academic years, it is critical for the sustainability of the 22 training programs supported by the HRH Program that the health-related Schools at the CMHS significantly scale up recruitment of new Rwandan faculty. The HRH Program can serve as a model for other training initiatives implemented in countries affected by a severe shortage of health professionals.

Safety and immunogenicity of an inactivated whole cell tuberculosis vaccine booster in adults primed with BCG: A randomized, controlled trial of DAR-901.

BACKGROUND: Development of a tuberculosis vaccine to boost BCG is a major international health priority. SRL172, an inactivated whole cell booster derived from a non-tuberculous mycobacterium, is the only new vaccine against tuberculosis to have demonstrated efficacy in a Phase 3 trial. In the present study we sought to determine if a three-dose series of DAR-901 manufactured from the SRL172 master cell bank by a new, scalable method was safe and immunogenic. METHODS: We performed a single site, randomized, double-blind, controlled, Phase 1 dose escalation trial of DAR-901 at Dartmouth-Hitchcock Medical Center in the United States. Healthy adult subjects age 18-65 with prior BCG immunization and a negative interferon-gamma release assay (IGRA) were enrolled in cohorts of 16 subjects and randomized to three injections of DAR-901 (n = 10 per cohort), or saline placebo (n = 3 per cohort), or two injections of saline followed by an injection of BCG (n = 3 per cohort; 1-8 x 106 CFU). Three successive cohorts were enrolled representing DAR-901 at 0.1, 0.3, and 1 mg per dose. Randomization was performed centrally and treatments were masked from staff and volunteers. Subsequent open label cohorts of HIV-negative/IGRA-positive subjects (n = 5) and HIV-positive subjects (n = 6) received three doses of 1 mg DAR-901. All subjects received three immunizations at 0, 2 and 4 months administered as 0.1 mL injections over the deltoid muscle alternating between right and left arms. The primary outcomes were safety and immunogenicity. Subjects were followed for 6 months after dose 3 for safety and had phlebotomy performed for safety studies and immune assays before and after each injection. Immune assays using peripheral blood mononuclear cells included cell-mediated IFN-γ responses to DAR-901 lysate and to Mycobacterium tuberculosis (MTB) lysate; serum antibody to M. tuberculosis lipoarabinomannan was assayed by ELISA. RESULTS: DAR-901 had an acceptable safety profile and was well-tolerated at all dose levels in all treated subjects. No serious adverse events were reported. Median (range) 7-day erythema and induration at the injection site for 1 mg DAR-901 were 10 (4-20) mm and 10 (4-16) mm, respectively, and for BCG, 30 (10-107) mm and 38 (15-55) mm, respectively. Three mild AEs, all headaches, were considered possibly related to DAR-901. No laboratory or vital signs abnormalities were related to immunization. Compared to pre-vaccination responses, three 1 mg doses of DAR-901 induced statistically significant increases in IFN-γ response to DAR-901 lysate and MTB lysate, and in antibody responses to M. tuberculosis lipoarabinomannan. Ten subjects who received 1 mg DAR-901 remained IFN-γ release assay (IGRA) negative after three doses of vaccine. CONCLUSIONS: A three-injection series of DAR-901 was well-tolerated, had an acceptable safety profile, and induced cellular and humoral immune responses to mycobacterial antigens. DAR-901 is advancing to efficacy trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT02063555.

Beyond Visas and Vaccines: Preparing Students for Domestic and Global Health Engagement.

At campuses across the United States, scores of students are embarking on global health experiences in low- and middle-income countries. The desire to improve the health of poor communities while preparing for future health careers is often the main driver. The spotlight on domestic health issues also has fueled a resurgence of interest in underserved communities in the United States. Regardless of the destination, rigorous preparation is needed to ensure that the students' presence benefits the communities they aim to serve. Development of mutually beneficial programs with host communities coupled with thoughtful preparation of students is essential to the future of these university programs but, more importantly, to achieve the goal of shared learning and capacity building across borders. US program leaders may not fully consider the potential risks that can occur to their programs from involving poorly prepared students, or these risks may appear largely theoretical. However, many experienced practitioners and their international collaborators can relate examples of damaged partnerships, adverse consequences on community structures, dangers to patient safety, and harmed professional reputations and credibility. Domestic health experiences do not require a visa or vaccines but bring students in contact with many of the same ethical, professional, and cross-cultural challenges as overseas endeavors. Fortunately, best practices for preparing students to confront these challenges have emerged from years of experience in domestic and global contexts alike. It all begins with establishing institutional partnerships built on principles of reciprocity and respect. Through careful program design, universities can align missions, goals, and expectations to best serve all invested parties: local partners, students, faculty, staff, and the communities where they will be working. A second critical component is appropriate student selection. Matching student skills with partner needs can optimize benefits for both the host organization and student. Finally, universities can prepare students to navigate in cross-cultural settings in a professional and ethical manner through careful training. Just as negative experiences can have lasting negative consequences, the best ones can lead to strengthened partnerships; durable benefits for local and global communities; and optimal learning for students, their supervisors, and hosts.