Impact of HIV treat-all and complementary policies on ART linkage in 13 PEPFAR-supported African countries.

BACKGROUND: In 2015, the World Health Organization recommended that all people living with HIV begin antiretroviral treatment (ART) regardless of immune status, a policy known as 'Treat-All to end AIDS', commonly referred to as Treat-All. Almost all low- and middle-income countries adopted this policy by 2019. This study describes how linkage to treatment of newly diagnosed persons changed between 2015 and 2018 and how complementary policies may have similarly increased linkage for 13 African countries. These countries adopted and implemented Treat-All policies between 2015 and 2018 and were supported by the U.S. Government's President's Emergency Plan for AIDS Relief (PEPFAR). The focuses of this research were to understand 1) linkage rates to ART initiation before and after the adoption of Treat-All in each country; 2) how Treat-All implementation differed across these countries; and 3) whether complementary policies (including same-day treatment initiation, task-shifting, reduced ART visits, and reduced ART pickups) implemented around the same time may have increased ART linkage. METHODS: HIV testing and treatment data were collected by PEPFAR country programs in 13 African countries from 2015 to 2018. These countries were chosen based on the completeness of policy data and availability of program data during the study period. Program data were used to calculate proxy linkage rates. These rates were compared relative to the Treat All adoption period and the adoption of complementary policies. RESULTS: The 13 countries experienced an average increase in ART linkage of 29.3% over the entire study period. In examining individual countries, all but two showed increases in linkage to treatment immediately after Treat All adoption. Across all countries, those that had adopted four or more complementary policies showed an average increased linkage of 39.8% compared to 13.9% in countries with fewer than four complementary policies. CONCLUSIONS: Eleven of 13 country programs examined in this study demonstrated an increase in ART linkage after Treat-All policy adoption. Increases in linkage were associated with complementary policies. When exploring new public health policies, policymakers may consider which complementary policies might also help achieve the desired outcome of the public health policy.

An Epidemiologic Investigation of Potential Risk Factors for Nodding Syndrome in Kitgum District, Uganda.

INTRODUCTION: Nodding Syndrome (NS), an unexplained illness characterized by spells of head bobbing, has been reported in Sudan and Tanzania, perhaps as early as 1962. Hypothesized causes include sorghum consumption, measles, and onchocerciasis infection. In 2009, a couple thousand cases were reportedly in Northern Uganda. METHODS: In December 2009, we identified cases in Kitgum District. The case definition included persons who were previously developmentally normal who had nodding. Cases, further defined as 5- to 15-years-old with an additional neurological deficit, were matched to village controls to assess risk factors and test biological specimens. Logistic regression models were used to evaluate associations. RESULTS: Surveillance identified 224 cases; most (95%) were 5-15-years-old (range = 2-27). Cases were reported in Uganda since 1997. The overall prevalence was 12 cases per 1,000 (range by parish = 0·6-46). The case-control investigation (n = 49 case/village control pairs) showed no association between NS and previously reported measles; sorghum was consumed by most subjects. Positive onchocerciasis serology [age-adjusted odds ratio (AOR1) = 14·4 (2·7, 78·3)], exposure to munitions [AOR1 = 13·9 (1·4, 135·3)], and consumption of crushed roots [AOR1 = 5·4 (1·3, 22·1)] were more likely in cases. Vitamin B6 deficiency was present in the majority of cases (84%) and controls (75%). CONCLUSION: NS appears to be increasing in Uganda since 2000 with 2009 parish prevalence as high as 46 cases per 1,000 5- to 15-year old children. Our results found no supporting evidence for many proposed NS risk factors, revealed association with onchocerciasis, which for the first time was examined with serologic testing, and raised nutritional deficiencies and toxic exposures as possible etiologies.

Clinical, neurological, and electrophysiological features of nodding syndrome in Kitgum, Uganda: an observational case series.

BACKGROUND: Nodding syndrome is an unexplained illness characterised by head-bobbing spells. The clinical and epidemiological features are incompletely described, and the explanation for the nodding and the underlying cause of nodding syndrome are unknown. We aimed to describe the clinical and neurological diagnostic features of this illness. METHODS: In December, 2009, we did a multifaceted investigation to assess epidemiological and clinical illness features in 13 parishes in Kitgum District, Uganda. We defined a case as a previously healthy child aged 5-15 years with reported nodding and at least one other neurological deficit. Children from a systematic sample of a case-control investigation were enrolled in a clinical case series which included history, physical assessment, and neurological examinations; a subset had electroencephalography (EEG), electromyography, brain MRI, CSF analysis, or a combination of these analyses. We reassessed the available children 8 months later. FINDINGS: We enrolled 23 children (median age 12 years, range 7-15 years) in the case-series investigation, all of whom reported at least daily head nodding. 14 children had reported seizures. Seven (30%) children had gross cognitive impairment, and children with nodding did worse on cognitive tasks than did age-matched controls, with significantly lower scores on tests of short-term recall and attention, semantic fluency and fund of knowledge, and motor praxis. We obtained CSF samples from 16 children, all of which had normal glucose and protein concentrations. EEG of 12 children with nodding syndrome showed disorganised, slow background (n=10), and interictal generalised 2·5-3·0 Hz spike and slow waves (n=10). Two children had nodding episodes during EEG, which showed generalised electrodecrement and paraspinal electromyography dropout consistent with atonic seizures. MRI in four of five children showed generalised cerebral and cerebellar atrophy. Reassessment of 12 children found that six worsened in their clinical condition between the first evaluation and the follow-up evaluation interval, as indicated by more frequent head nodding or seizure episodes, and none had cessation or decrease in frequency of these episodes. INTERPRETATION: Nodding syndrome is an epidemic epilepsy associated with encephalopathy, with head nodding caused by atonic seizures. The natural history, cause, and management of the disorder remain to be determined. FUNDING: Division of Global Disease Detection and Emergency Response, US Centers for Disease Control and Prevention.

Effect of CD4+ T cell count and antiretroviral treatment on two serological HIV incidence assays.

Serological assays are increasingly being used to measure HIV incidence in cross-sectional studies, but their specificity to determine incident infections remains problematic. We estimated the specificity of the BED assay in a cohort of long-term HIV-infected adults before and during antiretroviral treatment (ART) and evaluated an HIV avidity assay to detect BED-based false-recent results. We used the BED assay to test stored specimens from known long-term HIV-1-infected adult Ugandans before and at 3, 12, and 24 months after ART initiation. We evaluated the frequency of false-recent classifications by ART status and CD4(+) T(+) cell count. Specimens classified as BED false-recent were further tested with an avidity assay. In all, 950 blood specimens from 253 adults were tested with the BED assay. Of these, 149 (15.7%) specimens tested false-recent and 64 (24.9%) individuals tested false-recent at least once. Among all specimens tested, the proportion of false-recent rose with increasing CD4(+) cell count (<250 cells/µl: 11.3%, 250-499: 17.8%, ≥500: 21.4%; p for trend=0.002). Of 197 persons with all four BED results available, 75.6% were classified as long-term infected throughout and 8.1% as false-recent throughout; the remainder changed classification once (12.2%) or twice (4.1%). Of 105 false-recent specimens retested with the avidity assay, 101 (96.2%) were correctly classified as "long-term." The BED assay's specificity varied with CD4(+) cell count and use of ART. Knowledge of these parameters for blood samples could improve incidence estimates using the BED assay. The additional use of an avidity assay may help to minimize the proportion of BED false-recent specimens.

Utility of routine viral load, CD4 cell count, and clinical monitoring among adults with HIV receiving antiretroviral therapy in Uganda: randomised trial.

OBJECTIVE: To evaluate the use of routine laboratory monitoring in terms of clinical outcomes among patients receiving antiretroviral therapy (ART) in Uganda. DESIGN: Randomised clinical trial SETTING: A home based ART programme in rural Uganda. PARTICIPANTS: All participants were people with HIV who were members of the AIDS Support Organisation. Participants had CD4 cell counts <250 cells × 10(6)/L or World Health Organization stage 3 or 4 disease. INTERVENTIONS: Participants were randomised to one of three different monitoring arms: a viral load arm (clinical monitoring, quarterly CD4 counts, and viral load measurements), CD4 arm (clinical monitoring and CD4 counts), or clinical arm (clinical monitoring alone). MAIN OUTCOME MEASURES: Serious morbidity (newly diagnosed AIDS defining illness) and mortality. RESULTS: 1094 participants started ART; median CD4 count at baseline was 129 cells × 10(6)/L. Median follow-up was three years. In total, 126 participants died (12%), 148 (14%) experienced new AIDS defining illnesses, and 61(6%) experienced virological failure, defined as two consecutive viral loads >500 copies/mL occurring more than three months after the start of ART. After adjustment for age, sex, baseline CD4 count, viral load, and body mass index, the rate of new AIDS defining events or death was higher in the clinical arm than the viral load arm (adjusted hazard ratio 1.83, P = 0.002) or the CD4 arm (1.49, P = 0.032). There was no significant difference between the CD4 arm and the viral load arm (1.23, P = 0.31). CONCLUSION: In patients receiving ART for HIV infection in Uganda, routine laboratory monitoring is associated with improved health and survival compared with clinical monitoring alone. Trial registration Clinical Trials NCT00119093.

Determinants of early and late mortality among HIV-infected individuals receiving home-based antiretroviral therapy in rural Uganda.

BACKGROUND: Up to 20% of people initiating antiretroviral therapy (ART) in sub-Saharan Africa die during the first year of treatment. Understanding the clinical conditions associated with mortality could potentially lead to effective interventions to prevent these deaths. METHODS: We examined data from participants aged ≥18 years in the Home-Based AIDS Care project in Tororo, Uganda, to describe mortality over time and to determine clinical conditions associated with death. Survival analysis was used to examine variables associated with mortality at baseline and during follow-up. RESULTS: A total of 112 (9.4%) deaths occurred in 1132 subjects (73% women) during a median of 3.0 years of ART. Mortality was 15.9 per 100 person-years during the first 3 months and declined to 0.3 per 100 person-years beyond 24 months after ART initiation. Tuberculosis (TB) was the most common condition associated with death (21% of deaths), followed by Candida disease (15%). In 43% of deaths, no specific clinical diagnosis was identified. Deaths within 3 months after ART initiation were associated with World Health Organization clinical stage III or IV at baseline, diagnosis of TB at baseline, a diagnosis of a non-TB opportunistic infection in follow-up and a body mass index ≤17 kg/m² during follow-up. Mortality after 3 months of ART was associated with CD4 cell counts <200 cells per microliter, a diagnosis of TB or other opportunistic infection, adherence to therapy <95%, and low hemoglobin levels during follow-up. CONCLUSION: Potentially remediable conditions and preventable infections were associated with mortality while receiving ART in Uganda.

10 Guiding principles of a comprehensive Internet-based public health preparedness training and education program.

Distance learning is an effective strategy to address the many barriers to continuing education faced by the public health workforce. With the proliferation of online learning programs focused on public health, there is a need to develop and adopt a common set of principles and practices for distance learning. In this article, we discuss the 10 principles that guide the development, design, and delivery of the various training modules and courses offered by the North Carolina Center for Public Health Preparedness (NCCPHP). These principles are the result of 10 years of experience in Internet-based public health preparedness educational programming. In this article, we focus on three representative components of NCCPHP's overall training and education program to illustrate how the principles are implemented and help others in the field plan and develop similar programs.

Partnering to meet training needs: a communicable-disease continuing education course for public health nurses in North Carolina.

In 2004, the General Communicable Disease Control Branch of the North Carolina Division of Public Health and the North Carolina Center for Public Health Preparedness partnered to create a free continuing education course in communicable-disease surveillance and outbreak investigations for public health nurses. The course was a competency-based curriculum with 14 weeks of Internet-based instruction, culminating in a two-day classroom-based skills demonstration. In spring 2006, the course became mandatory for all public health nurses who spend at least three-fourths of their time on tasks related to communicable diseases. As of December 2006, 177 nurses specializing in communicable diseases from 74 North Carolina counties had completed the course. Evaluations indicated that participants showed statistically significant improvements in self-perceived confidence to perform competencies addressed by the course. This course has become a successful model that combines academic expertise in curriculum development and teaching technologies with practical expertise in course content and audience needs. Through a combination of Internet and classroom instruction, this course has delivered competency-based training to the public health professionals who perform as frontline epidemiologists throughout North Carolina.

Serologic response to inactivated poliovirus vaccine: a randomized clinical trial comparing 2 vaccination schedules in Puerto Rico.

BACKGROUND: The World Health Organization (WHO) recommends the discontinuation of oral poliovirus vaccine after eradication of wild poliovirus. Studies assessing inactivated poliovirus vaccine (IPV) immunogenicity in tropical countries, using the WHO Expanded Programme on Immunization (EPI) schedule, have been limited. METHODS: We conducted a randomized clinical trial in Ponce, Puerto Rico. Infants were assigned to 1 of 2 study arms: those in the EPI arm received IPV at 6, 10, and 14 weeks of age, and those in the US arm received IPV at 2, 4, and 6 months of age. Neutralizing antibody titers against poliovirus types 1, 2, and 3 were tested on serum specimens obtained before administration of the first dose of IPV and 28-45 days after administration of the last dose of IPV. RESULTS: Seroconversion rates for the EPI (n=225) and US (n=230) arms, respectively, were 85.8% and 99.6% for poliovirus type 1 (P<.001), 86.2% and 100% for poliovirus type 2 (P<.001), and 96.9% and 99.1% for poliovirus type 3 (P=.08). Seroconversion rates were lower among infants in the EPI arm who had high maternal antibody levels for all 3 poliovirus types (P<.001). CONCLUSIONS: The EPI schedule resulted in lower seroconversion rates for poliovirus types 1 and 2. These results are relevant for tropical countries planning to use IPV in a posteradication environment.

Competency-based preparedness training for public health practitioners.

The bioterrorism preparedness training needs of the public health workforce have been described in several studies, assessments, and surveys. To meet these needs, the North Carolina Center for Public Health Preparedness (NCCPHP) and the Public Health Leadership Program (PHLP) at the University of North Carolina School of Public Health developed a new distance learning course, Introduction to Public Health Preparedness for Disasters and Emergencies. After a review of assessment data to identify training needs, we conducted a literature review of methodology and concluded that a distance learning course would be the best approach. The course curriculum is based on the Bioterrorism and Emergency Readiness Competencies for All Public Health Workers. This paper describes the course development process and methods used to make this course an effective training tool.

User patterns and satisfaction with on-line trainings completed on the North Carolina Center for Public Health Preparedness Training Web Site.

Short online training modules have been developed by the North Carolina Center for Public Health Preparedness (NCCPHP) and provided to registered users for free on its Training Web Site. Use of these modules can improve the knowledge, skills, and awareness of public health professionals in topics related to public health preparedness. According to the results of a survey implemented in October 2004, the NCCPHP Training Web Site is effectively reaching its target audience of local and state public health workers. The utilization of distance learning technology allows for broad distribution of training materials, with registered users in all 50 US states and 122 foreign countries. In addition, the NCCPHP Training Web Site is providing training materials in topics most requested by the public health workforce. According to the findings of this survey, online training in public health preparedness and response is an efficient way to improve the knowledge and skills of our public health workforce to increase competency.

Development and implementation of a public health workforce training needs assessment survey in North Carolina.

Assessing the training needs of local public health workers is an important step toward providing appropriate training programs in emergency preparedness and core public health competencies. The North Carolina Public Health Workforce Training Needs Assessment survey was implemented through the collaboration of several organizations, including the North Carolina Center for Public Health Preparedness at the North Carolina Institute for Public Health, the outreach and service unit of the University of North Carolina School of Public Health, the Office of Public Health Preparedness and Response in the North Carolina Division of Public Health Epidemiology Section, and local health departments across the state.

Ensuring preparedness for potential poliomyelitis outbreaks: Recommendations for the US poliovirus vaccine stockpile from the National Vaccine Advisory Committee (NVAC) and the Advisory Committee on Immunization Practices (ACIP).

Paralytic poliomyelitis was once endemic in the United States; however, because of high vaccination levels, the last case of wild disease occurred in 1979. Although worldwide polio eradication may be achieved in the near future, the presence of undervaccinated children in urban areas and among groups who refuse vaccination creates an outbreak risk, should importation of wild virus occur. In 1999, the Advisory Committee on Immunization Practices (ACIP) recommended that inactivated poliovirus vaccine (IPV) be used for routine immunization of the US population and that oral poliovirus vaccine (OPV) be reserved for "mass vaccination campaigns to control outbreaks of paralytic polio." Subsequently, the sole US manufacturer of OPV withdrew from the market. In 2003, a joint National Vaccine Advisory Committee (NVAC)/ACIP working group was charged with reporting to its parent bodies concerning the need for a poliovirus vaccine stockpile. Based on that working group's report, the NVAC and ACIP have concluded that stockpiles of both IPV and OPV should be maintained. In the event of an outbreak in which OPV continues not to be available, IPV should be used for control, and a stockpile of 8 million doses seems to be sufficient. Should IPV be manufactured only in combination with other vaccines, appropriate procurement actions should be taken to ensure that uncombined IPV continues to be stockpiled. Under circumstances of diminished population immunity, OPV may offer outbreak control advantages. The NVAC and ACIP recommend that the United States collaborate with international agencies to provide guaranteed and rapid access to at least 8 million doses of trivalent OPV or 8 million doses of each of the 3 types of monovalent OPV. The regulatory and practical obstacles to implementation of this recommendation will require assertive facilitation at high levels of the federal government and careful planning at the state and local levels.

Vaccine policy changes and epidemiology of poliomyelitis in the United States.

CONTEXT: The last case of poliomyelitis in the United States due to indigenously acquired wild poliovirus occurred in 1979; however, as a consequence of oral poliovirus vaccine (OPV) use that began in 1961, an average of 9 cases of vaccine-associated paralytic poliomyelitis (VAPP) were confirmed each year from 1961 through 1989. To reduce the VAPP burden, national vaccination policy changed in 1997 from reliance on OPV to options for a sequential schedule of inactivated poliovirus vaccine (IPV) followed by OPV. In 2000, an exclusive IPV schedule was adopted. OBJECTIVE: To review the epidemiology of paralytic poliomyelitis and document the association between the vaccine schedule changes and VAPP in the United States. DESIGN AND SETTING: Review of national surveillance data from 1990 through 2003 for cases of confirmed paralytic poliomyelitis. MAIN OUTCOME MEASURES: Number of confirmed paralytic poliomyelitis cases, including VAPP, and ratio of VAPP cases to number of doses of OPV distributed that occurred before, during, and after implementation of policy changes. RESULTS: From 1990 through 1999, 61 cases of paralytic poliomyelitis were reported; 59 (97%) of these were VAPP (1 case per 2.9 million OPV doses distributed), 1 case was imported, and 1 case was indeterminate. Thirteen cases occurred during the 1997-1999 transitional policy period and were associated with the all-OPV schedule; none occurred with the IPV-OPV schedule. No cases occurred after the United States implemented the all-IPV policy in 2000. The last imported poliomyelitis case occurred in 1993 and the last case of VAPP occurred in 1999. CONCLUSION: The change in polio vaccination policy from OPV to exclusive use of IPV was successfully implemented; this change led to the elimination of VAPP in the United States.