Rapidly building global health security capacity--Uganda demonstration project, 2013.

Increasingly, the need to strengthen global capacity to prevent, detect, and respond to public health threats around the globe is being recognized. CDC, in partnership with the World Health Organization (WHO), has committed to building capacity by assisting member states with strengthening their national capacity for integrated disease surveillance and response as required by International Health Regulations (IHR). CDC and other U.S. agencies have reinforced their pledge through creation of global health security (GHS) demonstration projects. One such project was conducted during March-September 2013, when the Uganda Ministry of Health (MoH) and CDC implemented upgrades in three areas: 1) strengthening the public health laboratory system by increasing the capacity of diagnostic and specimen referral networks, 2) enhancing the existing communications and information systems for outbreak response, and 3) developing a public health emergency operations center (EOC) (Figure 1). The GHS demonstration project outcomes included development of an outbreak response module that allowed reporting of suspected cases of illness caused by priority pathogens via short messaging service (SMS; i.e., text messaging) to the Uganda District Health Information System (DHIS-2) and expansion of the biologic specimen transport and laboratory reporting system supported by the President's Emergency Plan for AIDS Relief (PEPFAR). Other enhancements included strengthening laboratory management, establishing and equipping the EOC, and evaluating these enhancements during an outbreak exercise. In 6 months, the project demonstrated that targeted enhancements resulted in substantial improvements to the ability of Uganda's public health system to detect and respond to health threats.

Uganda's experience in establishing an electronic compendium for public health emergencies.

Uganda has implemented several interventions that have contributed to prevention, early detection, and effective response to Public Health Emergencies (PHEs). However, there are gaps in collecting and documenting data on the overall response to these PHEs. We set out to establish a comprehensive electronic database of PHEs that occurred in Uganda since 2000. We constituted a core development team, developed a data dictionary, and worked with Health Information Systems Program (HISP)-Uganda to develop and customize a compendium of PHEs using the electronic Integrated Disease Surveillance and Response (eIDSR) module on the District Health Information Software version 2 (DHIS2) platform. We reviewed literature for retrospective data on PHEs for the compendium. Working with the Uganda Public Health Emergency Operations Center (PHEOC), we prospectively updated the compendium with real-time data on reported PHEs. We developed a user's guide to support future data entry teams. An operational compendium was developed within the eIDSR module of the DHIS2 platform. The variables for PHEs data collection include those that identify the type, location, nature and time to response of each PHE. The compendium has been updated with retrospective PHE data and real-time prospective data collection is ongoing. Data within this compendium is being used to generate information that can guide future outbreak response and management. The compendium development highlights the importance of documenting outbreak detection and response data in a central location for future reference. This data provides an opportunity to evaluate and inform improvements in PHEs response.

Evaluating a Mobile Phone-Delivered Text Message Reminder Intervention to Reduce Infant Vaccination Dropout in Arua, Uganda: Protocol for a Randomized Controlled Trial.

BACKGROUND: Globally, suboptimal vaccine coverage is a public health concern. According to Uganda's 2016 Demographic and Health Survey, only 49% of 12- to 23-month-old children received all recommended vaccinations by 12 months of age. Innovative ways are needed to increase coverage, reduce dropout, and increase awareness among caregivers to bring children for timely vaccination. OBJECTIVE: This study evaluates a personalized, automated caregiver mobile phone-delivered text message reminder intervention to reduce the proportion of children who start but do not complete the vaccination series for children aged 12 months and younger in select health facilities in Arua district. METHODS: A two-arm, multicenter, parallel group randomized controlled trial was conducted in four health facilities providing vaccination services in and around the town of Arua. Caregivers of children between 6 weeks and 6 months of age at the time of their first dose of pentavalent vaccine (Penta1; containing diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenzae type b antigens) were recruited and interviewed. All participants received the standard of care, defined as the health worker providing child vaccination home-based records to caregivers as available and providing verbal instruction of when to return for the next visit. At the end of each day, caregivers and their children were randomized by computer either to receive or not receive personalized, automated text message reminders for their subsequent vaccination visits according to the national schedule. Text message reminders for Penta2 were sent 2 days before, on the day of, and 2 days after the scheduled vaccination visit. Reminders for Penta3 and the measles-containing vaccine were sent on the scheduled day of vaccination and 5 and 7 days after the scheduled day. Study personnel conducted postintervention follow-up interviews with participants at the health facilities during the children's measles-containing vaccine visit. In addition, focus group discussions were conducted to assess caregiver acceptability of the intervention, economic data were collected to evaluate the incremental costs and cost-effectiveness of the intervention, and health facility record review forms were completed to capture service delivery process indicators. RESULTS: Of the 3485 screened participants, 1961 were enrolled from a sample size of 1962. Enrollment concluded in August 2016. Follow-up interviews of study participants, including data extraction from the children's vaccination cards, data extraction from the health facility immunization registers, completion of the health facility record review forms, and focus group discussions were completed by December 2017. The results are expected to be released in 2021. CONCLUSIONS: Prompting health-seeking behavior with reminders has been shown to improve health intervention uptake. Mobile phone ownership continues to grow in Uganda, so their use in vaccination interventions such as this study is logical and should be evaluated with scientifically rigorous study designs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04177485; https://clinicaltrials.gov/ct2/show/NCT04177485. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/17262.

Mortality in HIV-infected Ugandan adults receiving antiretroviral treatment and survival of their HIV-uninfected children: a prospective cohort study.

BACKGROUND: Antiretroviral therapy (ART) is increasingly available in Africa, but physicians and clinical services are few. We therefore assessed the effect of a home-based ART programme in Uganda on mortality, hospital admissions, and orphanhood in people with HIV-1 and their household members. METHODS: In 2001, we enrolled and followed up 466 HIV-infected adults and 1481 HIV-uninfected household members in a prospective cohort study. After 5 months, we provided daily co-trimoxazole (160 mg trimethoprim and 800 mg sulfamethoxazole) prophylaxis to HIV-infected participants. Between May, 2003, and December, 2005, we followed up 138 infected adults who were eligible and 907 new HIV-infected participants and their HIV-negative household members in a study of ART (mainly stavudine, lamivudine, and nevirapine). Households were visited every week by lay providers, and no clinic visits were scheduled after enrolment. We compared rates of death, hospitalisation, and orphanhood during different study periods and calculated the number needed to treat to prevent an outcome. FINDINGS: 233 (17%) of 1373 participants with HIV and 40 (1%) of 4601 HIV-uninfected household members died. During the first 16 weeks of ART and co-trimoxazole, mortality in HIV-infected participants was 55% lower than that during co-trimoxazole alone (14 vs 16 deaths per 100 person-years; adjusted hazard ratio 0.45, 95% CI 0.27-0.74, p=0.0018), and after 16 weeks, was reduced by 92% (3 vs 16 deaths per 100 person-years; 0.08, 0.06-0.13, p<0.0001). Compared with no intervention, ART and co-trimoxazole were associated with a 95% reduction in mortality in HIV-infected participants (5 vs 27 deaths per 100 person-years; 0.05, 0.03-0.08, p<0.0001), 81% reduction in mortality in their uninfected children younger than 10 years (0.2 vs 1.2 deaths per 100 person-years; 0.19, 0.06-0.59, p=0.004), and a 93% estimated reduction in orphanhood (0.9 vs 12.8 per 100 person-years of adults treated; 0.07, 0.04-0.13, p<0.0001). INTERPRETATION: Expansion of access to ART and co-trimoxazole prophylaxis could substantially reduce mortality and orphanhood among adults with HIV and their families living in resource-poor settings.

A Cross-Cutting Approach to Surveillance and Laboratory Capacity as a Platform to Improve Health Security in Uganda.

Global health security depends on effective surveillance for infectious diseases. In Uganda, resources are inadequate to support collection and reporting of data necessary for an effective and responsive surveillance system. We used a cross-cutting approach to improve surveillance and laboratory capacity in Uganda by leveraging an existing pediatric inpatient malaria sentinel surveillance system to collect data on expanded causes of illness, facilitate development of real-time surveillance, and provide data on antimicrobial resistance. Capacity for blood culture collection was established, along with options for serologic testing for select zoonotic conditions, including arboviral infection, brucellosis, and leptospirosis. Detailed demographic, clinical, and laboratory data for all admissions were captured through a web-based system accessible at participating hospitals, laboratories, and the Uganda Public Health Emergency Operations Center. Between July 2016 and December 2017, the expanded system was activated in pediatric wards of 6 regional government hospitals. During that time, patient data were collected from 30,500 pediatric admissions, half of whom were febrile but lacked evidence of malaria. More than 5,000 blood cultures were performed; 4% yielded bacterial pathogens, and another 4% yielded likely contaminants. Several WHO antimicrobial resistance priority pathogens were identified, some with multidrug-resistant phenotypes, including Acinetobacter spp., Citrobacter spp., Escherichia coli, Staphylococcus aureus, and typhoidal and nontyphoidal Salmonella spp. Leptospirosis and arboviral infections (alphaviruses and flaviviruses) were documented. The lessons learned and early results from the development of this multisectoral surveillance system provide the knowledge, infrastructure, and workforce capacity to serve as a foundation to enhance the capacity to detect, report, and rapidly respond to wide-ranging public health concerns in Uganda.

Adherence to antiretroviral therapy in a home-based AIDS care programme in rural Uganda.

BACKGROUND: Poverty and limited health services in rural Africa present barriers to adherence to antiretroviral therapy that necessitate innovative options other than facility-based methods for delivery and monitoring of such therapy. We assessed adherence to antiretroviral therapy in a cohort of HIV-infected people in a home-based AIDS care programme that provides the therapy and other AIDS care, prevention, and support services in rural Uganda. METHODS: HIV-infected individuals with advanced HIV disease or a CD4-cell count of less than 250 cells per muL were eligible for antiretroviral therapy. Adherence interventions included group education, personal adherence plans developed with trained counsellors, a medicine companion, and weekly home delivery of antiretroviral therapy by trained lay field officers. We analysed factors associated with pill count adherence (PCA) of less than 95%, medication possession ratio (MPR) of less than 95%, and HIV viral load of 1000 copies per mL or more at 6 months (second quarter) and 12 months (fourth quarter) of follow-up. FINDINGS: 987 adults who had received no previous antiretroviral therapy (median CD4-cell count 124 cells per muL, median viral load 217,000 copies per mL) were enrolled between July, 2003, and May, 2004. PCA of less than 95% was calculated for 0.7-2.6% of participants in any quarter and MPR of less than 95% for 3.3-11.1%. Viral load was below 1000 copies per mL for 894 (98%) of 913 participants in the second quarter and for 860 (96%) of 894 of participants in the fourth quarter. In separate multivariate models, viral load of at least 1000 copies per mL was associated with both PCA below 95% (second quarter odds ratio 10.6 [95% CI 2.45-45.7]; fourth quarter 14.5 [2.51-83.6]) and MPR less than 95% (second quarter 9.44 [3.40-26.2]; fourth quarter 10.5 [4.22-25.9]). INTERPRETATION: Good adherence and response to antiretroviral therapy can be achieved in a home-based AIDS care programme in a resource-limited rural African setting. Health-care systems must continue to implement, evaluate, and modify interventions to overcome barriers to comprehensive AIDS care programmes, especially the barriers to adherence with antiretroviral therapy.

Confronting Challenges in Monitoring and Evaluation: Innovation in the Context of the Global Plan Towards the Elimination of New HIV Infections Among Children by 2015 and Keeping Their Mothers Alive.

The Global Plan Towards the Elimination of New HIV Infections Among Children by 2015 and Keeping Their Mothers Alive (Global Plan), which was launched in 2011, set a series of ambitious targets, including a reduction of new HIV infections among children by 90% by 2015 (from a baseline year of 2009) and AIDS-related maternal mortality by 50% by 2015. To reach these targets, the Global Plan called for unprecedented investments in the prevention of mother-to-child transmission of HIV (PMTCT), innovative new approaches to service delivery, immense collective effort on the programmatic and policy fronts, and importantly, a renewed focus on data collection and use. We provide an overview of major achievements in monitoring and evaluation across Global Plan countries and highlight key challenges and innovative country-driven solutions using PMTCT program data. Specifically, we describe the following: (1) Uganda's development and use of a weekly reporting system for PMTCT using short message service technology that facilitates real-time monitoring and programmatic adjustments throughout the transition to a "treat all" approach for pregnant and breastfeeding women living with HIV (Option B+); (2) Uganda's work to eliminate parallel reporting systems while strengthening the national electronic district health information system; and (3) how routine PMTCT program data in Nigeria can be used to estimate HIV prevalence at the local level and address a critical gap in local descriptive epidemiologic data to better target limited resources. We also identify several ongoing challenges in data collection, analysis, and use, and we suggest potential solutions.

Clinical toxicity of highly active antiretroviral therapy in a home-based AIDS care program in rural Uganda.

BACKGROUND: We evaluated clinical toxicity in HIV-infected persons receiving antiretroviral therapy (ART) in Uganda. METHODS: From May 2003 through December 2004, adults with a CD4 cell count < or =250 cells/microL or World Health Organization stage 3/4 HIV disease were prescribed ART. We calculated probabilities for time to toxicity and single-drug substitution as well as multivariate-adjusted hazard ratios for development of toxicity. RESULTS: ART (stavudine plus lamivudine with nevirapine [96%] or efavirenz [4%]) was prescribed for 1029 adults, contributing 11,268 person-months of observation. Toxicities developed in 543 instances in 411 (40%) patients (incidence rate = 4.47/100 person-months): 36% peripheral neuropathy (9% severe); 6% rash (2% severe); 2% hypersensitivity reaction; < or =0.5% acute hepatitis, anemia, acute pancreatitis, or lactic acidosis; and 13% other. Probabilities of remaining free from any toxicity at 6, 12, and 18 months were 0.76, 0.59, and 0.47 and from any severe toxicity at 6, 12, and 18 months were 0.92, 0.86, and 0.85, respectively. For 217 patients (21%), 222 single-drug substitutions were made, mostly because of peripheral neuropathy or rash. CONCLUSIONS: Clinical toxicities were common, but no patients discontinued ART because of toxicity. The most common toxicities, peripheral neuropathy and rash, were managed with single-drug substitutions. In resource-limited settings, toxicity from ART regimens containing stavudine or nevirapine is manageable but more tolerable regimens are needed.