Where have all the children gone? High HIV prevalence in infants attending nutrition and inpatient entry points:

Journal of the International AIDS Society, Volume 21, No. 2, Year 2018

Interpretation

Introduction: Despite notable progress towards PMTCT, only 50% of HIV-exposed infants in sub-Saharan Africa were tested within the first 2 months of life and only 30% of HIV-infected infants are on antiretroviral treatment. This study assessed HIV prevalence in infants and children receiving care at various service entry points in primary healthcare facilities in Uganda. Methods: A total of 3600 infants up to 24 months of age were systematically enrolled and tested at four regional hospitals across Uganda. Six hundred infants were included and tested from six facility entry points: PMTCT, immunization, inpatient, nutrition, outpatient and community outreach services. Findings: The traditional EID entry point, PMTCT, had a prevalence of 3.8%, representing 19.6% of the total HIV-positive infants identified in the study. Fifty percent of the 117 identified HIV-positive infants were found in the nutrition wards, which had a prevalence of 9.8% (p < 0.001 compared to PMTCT). Inpatient wards had a prevalence of 3.5% and yielded 17.9% of the HIV-positive infants identified. Infants tested at immunization wards and through outreach services identified 0.8% and 1.7% of the HIV-positive infants respectively, and had a prevalence of less than 0.3%. Conclusions: Expanding routine early infant diagnosis screening beyond the traditional PMTCT setting to nutrition and inpatient entry points will increase the identification of HIV-infected infants. Careful reflection for appropriate testing strategies, such as maternal re-testing to identify new HIV infections and HIV-exposed infants in need of follow-up testing and care, at immunization and outreach services should be considered given the expectedly low prevalence rates. These findings may help HIV care programmes significantly expand testing to improve access to early infant diagnosis and paediatric treatment. This was a cross‐sectional prospective study of infants below the age of 2 years presenting at the primary healthcare facility entry points at four hospitals in Uganda. The four healthcare facilities included in this study were: Mulago National Referral Hospital; St. Mary's Hospital, Lacor; Mbale Regional Referral Hospital; and Mbarara Regional Referral Hospital. Infants were recruited from six entry points at each healthcare facility: Immunization (Expanded Programme on Immunization)/well‐child clinic, paediatric outpatient, paediatric inpatient, nutrition, outreach and PMTCT, which is the traditional setting for EID testing. A total of 3600 infants less than 2 years of age were included in the study. One hundred and fifty infants were enrolled at each of the six entry points per hospital. Data collection occurred between September 2014 and August 2015. Patients were systematically sampled and enrolled at each entry point. Due to low daily volumes (<16 infants/day), consecutive enrolment was employed at the nutrition and PMTCT entry points. Systematic sampling across all attending patients was used within the immunization, paediatric outpatient, paediatric inpatient and outreach settings due to high patient volume, to ensure unbiased patient selection. It was predicted that each entry point could enrol 15 infants per day per study nurse; therefore, if an entry point typically had 16 to 30, 31 to 45, or 46 to 60 eligible infants per day each study nurse would enrol every other, third, or fourth infant respectively. Study systems were put in place to ensure no infant was enrolled at multiple entry points. The study objectives and study enrolment processes, including pre‐HIV test counselling, were explained to the mother or guardian of each infant invited to participate in the study at non‐PMTCT entry points before they signed a letter of informed consent. Demographic and clinical data were collected for each infant and mother (if present) using standardized study‐specific forms and study‐specific identification numbers. All enrolled infants underwent both serological and virological testing to determine HIV exposure and HIV infection status respectively. Dried blood spot specimens (DBS) were collected for virological testing and rapid serological diagnostic tests were conducted on each patient. Both tests were conducted on each enrolled infant regardless of the respective results, except for infants at the PMTCT entry point who did not receive a serological screen as their exposure status was already known. Healthcare facility staff, including nurses, clinical officers and laboratory technicians, were trained on study procedures, how to conduct DBS specimen collection and rapid diagnostic testing, and demonstrated proficiency before study commencement. Finally, maternal HIV status was determined if she provided verbal identification or by confirmation from facility records, if her infant included in the study was HIV‐positive, or if her infant was positive by RDT. All mothers were offered HIV testing per the national guidelines. Rapid diagnostic testing was performed using the Alere Determine™ HIV‐1/2 (Waltham, MA, USA). One drop of whole blood was collected using a lancet heel stick, applied to the test strip, and tested per manufacturer's instructions. Either that same lancet heel stick or a fresh draw was used to collect an additional 3 to 5 drops of whole blood that were applied to a filter paper card (Whatman 903, GE Healthcare Biosciences, Pittsburgh, PA). Specimens were dried overnight at room temperature and shipped weekly for testing to the Central Public Health Laboratories in Kampala, Uganda. Dried blood spot specimens were processed and tested with the Roche COBAS AmpliPrep/COBAS TaqMan (CAP/CTM 96) HIV‐1 Qualitative Test (Roche Molecular Diagnostics, Branchburg, NJ, USA) according to the manufacturer's instructions. Any infants with positive rapid diagnostic test or virological test result were referred to PMTCT for post‐test counselling and inclusion in care and treatment per the national standard of care guidelines. This study was approved by the Mildmay Uganda Research Ethics Committee, Uganda National Council for Science and Technology, Mulago Hospital Research and Ethics Committee, Institutional Review Committee at St. Mary's Hospital, Lacor, and the Chesapeake Institutional Review Board in the USA. Statistical analysis was performed with the R statistical software (Version 3.3.2, Free Software Foundation, Boston, MA, USA) and GraphPad Prism (Version 6.0, La Jolla, CA, USA). Infants from like entry points were pooled across hospitals for primary analyses. Two‐sample and multi‐sample comparisons were done using the nonparametric rank‐based Wilcoxon‐Mann–Whitney and Kruskal–Wallis tests respectively. Multi‐testing p‐value adjustment for the p values from logistic regression models was performed according to Hothorn et al. 14 and controls family‐wise error rate. Binomial probability confidence interval was computed using the Wilson method 15.

AI Digest

Study Justification:

– Despite progress in preventing mother-to-child transmission of HIV, there are still challenges in testing and treating HIV-exposed infants in sub-Saharan Africa.
– This study aimed to assess the prevalence of HIV in infants and children at different healthcare entry points in Uganda to identify areas where testing and treatment can be improved.

Highlights:

– The study included 3600 infants up to 24 months of age from four regional hospitals in Uganda.
– Six entry points were examined: PMTCT, immunization, inpatient, nutrition, outpatient, and community outreach services.
– The traditional PMTCT entry point had a prevalence of 3.8% of HIV-positive infants, while the nutrition wards had a prevalence of 9.8%.
– Inpatient wards yielded 17.9% of the HIV-positive infants identified.
– Immunization and outreach services had a prevalence of less than 0.3%.
– Expanding routine early infant diagnosis screening to nutrition and inpatient entry points can increase the identification of HIV-infected infants.
– Maternal re-testing and testing strategies at immunization and outreach services should be considered due to low prevalence rates.

Recommendations:

– Expand routine early infant diagnosis screening beyond the traditional PMTCT setting to include nutrition and inpatient entry points.
– Develop appropriate testing strategies, such as maternal re-testing, at immunization and outreach services to identify new HIV infections and HIV-exposed infants in need of follow-up testing and care.
– HIV care programs should significantly expand testing to improve access to early infant diagnosis and pediatric treatment.

Key Role Players:

– Healthcare facility staff: nurses, clinical officers, and laboratory technicians.
– Policy makers and government officials responsible for healthcare planning and funding.
– HIV care program managers and coordinators.
– Community health workers and outreach teams.

Cost Items for Planning Recommendations:

– Training of healthcare facility staff on study procedures, DBS specimen collection, and rapid diagnostic testing.
– Procurement of testing supplies and equipment.
– Transportation and shipping of dried blood spot specimens for testing.
– Development and implementation of testing strategies at immunization and outreach services.
– Expansion of testing services and infrastructure at nutrition and inpatient entry points.
– Support for post-test counseling and inclusion in care and treatment for HIV-positive infants.
Please note that the provided cost items are general and may vary depending on the specific context and resources available.

Strength of Evidence

The strength of evidence for this abstract is 7 out of 10.
The evidence in the abstract is based on a cross-sectional prospective study with a large sample size of 3600 infants. The study was conducted at four hospitals in Uganda and included six different entry points for enrollment. The prevalence of HIV in infants was assessed at each entry point, and the findings suggest that expanding routine early infant diagnosis screening to nutrition and inpatient entry points could increase the identification of HIV-infected infants. The study used standardized forms and identification numbers to collect demographic and clinical data, and both serological and virological testing were conducted on each enrolled infant. The study was approved by multiple research ethics committees and statistical analysis was performed using appropriate methods. To improve the strength of the evidence, future studies could consider using a longitudinal design to assess the long-term impact of expanding testing to different entry points, and could also include a control group for comparison. Additionally, conducting the study at a larger number of healthcare facilities could increase the generalizability of the findings.

Abstract

This was a cross‐sectional prospective study of infants below the age of 2 years presenting at the primary healthcare facility entry points at four hospitals in Uganda. The four healthcare facilities included in this study were: Mulago National Referral Hospital; St. Mary's Hospital, Lacor; Mbale Regional Referral Hospital; and Mbarara Regional Referral Hospital. Infants were recruited from six entry points at each healthcare facility: Immunization (Expanded Programme on Immunization)/well‐child clinic, paediatric outpatient, paediatric inpatient, nutrition, outreach and PMTCT, which is the traditional setting for EID testing. A total of 3600 infants less than 2 years of age were included in the study. One hundred and fifty infants were enrolled at each of the six entry points per hospital. Data collection occurred between September 2014 and August 2015. Patients were systematically sampled and enrolled at each entry point. Due to low daily volumes (<16 infants/day), consecutive enrolment was employed at the nutrition and PMTCT entry points. Systematic sampling across all attending patients was used within the immunization, paediatric outpatient, paediatric inpatient and outreach settings due to high patient volume, to ensure unbiased patient selection. It was predicted that each entry point could enrol 15 infants per day per study nurse; therefore, if an entry point typically had 16 to 30, 31 to 45, or 46 to 60 eligible infants per day each study nurse would enrol every other, third, or fourth infant respectively. Study systems were put in place to ensure no infant was enrolled at multiple entry points. The study objectives and study enrolment processes, including pre‐HIV test counselling, were explained to the mother or guardian of each infant invited to participate in the study at non‐PMTCT entry points before they signed a letter of informed consent. Demographic and clinical data were collected for each infant and mother (if present) using standardized study‐specific forms and study‐specific identification numbers. All enrolled infants underwent both serological and virological testing to determine HIV exposure and HIV infection status respectively. Dried blood spot specimens (DBS) were collected for virological testing and rapid serological diagnostic tests were conducted on each patient. Both tests were conducted on each enrolled infant regardless of the respective results, except for infants at the PMTCT entry point who did not receive a serological screen as their exposure status was already known. Healthcare facility staff, including nurses, clinical officers and laboratory technicians, were trained on study procedures, how to conduct DBS specimen collection and rapid diagnostic testing, and demonstrated proficiency before study commencement. Finally, maternal HIV status was determined if she provided verbal identification or by confirmation from facility records, if her infant included in the study was HIV‐positive, or if her infant was positive by RDT. All mothers were offered HIV testing per the national guidelines. Rapid diagnostic testing was performed using the Alere Determine™ HIV‐1/2 (Waltham, MA, USA). One drop of whole blood was collected using a lancet heel stick, applied to the test strip, and tested per manufacturer's instructions. Either that same lancet heel stick or a fresh draw was used to collect an additional 3 to 5 drops of whole blood that were applied to a filter paper card (Whatman 903, GE Healthcare Biosciences, Pittsburgh, PA). Specimens were dried overnight at room temperature and shipped weekly for testing to the Central Public Health Laboratories in Kampala, Uganda. Dried blood spot specimens were processed and tested with the Roche COBAS AmpliPrep/COBAS TaqMan (CAP/CTM 96) HIV‐1 Qualitative Test (Roche Molecular Diagnostics, Branchburg, NJ, USA) according to the manufacturer's instructions. Any infants with positive rapid diagnostic test or virological test result were referred to PMTCT for post‐test counselling and inclusion in care and treatment per the national standard of care guidelines. This study was approved by the Mildmay Uganda Research Ethics Committee, Uganda National Council for Science and Technology, Mulago Hospital Research and Ethics Committee, Institutional Review Committee at St. Mary's Hospital, Lacor, and the Chesapeake Institutional Review Board in the USA. Statistical analysis was performed with the R statistical software (Version 3.3.2, Free Software Foundation, Boston, MA, USA) and GraphPad Prism (Version 6.0, La Jolla, CA, USA). Infants from like entry points were pooled across hospitals for primary analyses. Two‐sample and multi‐sample comparisons were done using the nonparametric rank‐based Wilcoxon‐Mann–Whitney and Kruskal–Wallis tests respectively. Multi‐testing p‐value adjustment for the p values from logistic regression models was performed according to Hothorn et al. 14 and controls family‐wise error rate. Binomial probability confidence interval was computed using the Wilson method 15.

Materials

N/A

Innovations

Based on the information provided, a recommendation to improve access to maternal health would be to expand routine early infant diagnosis (EID) screening beyond the traditional prevention of mother-to-child transmission (PMTCT) setting to include nutrition and inpatient entry points. This recommendation is based on the finding that the nutrition wards had the highest prevalence of HIV-positive infants, followed by the inpatient wards. By implementing EID screening in these additional entry points, healthcare facilities can increase the identification of HIV-infected infants and ensure they receive appropriate care and treatment.

Furthermore, it is suggested to consider appropriate testing strategies, such as maternal re-testing to identify new HIV infections and HIV-exposed infants in need of follow-up testing and care, at immunization and outreach services. Although these entry points had lower prevalence rates, expanding testing in these settings can still contribute to improving access to early infant diagnosis and pediatric treatment.

Implementing these recommendations can help HIV care programs significantly expand testing and improve access to maternal health services, ultimately leading to better health outcomes for both mothers and infants.

AI Innovations Description

Implementing these recommendations can help HIV care programs significantly expand testing and improve access to maternal health services, ultimately leading to better health outcomes for both mothers and infants.

AI Innovations Methodology

To simulate the impact of the main recommendations on improving access to maternal health, the following methodology can be employed:

1. Identify the target population: Determine the population that will be included in the simulation, such as pregnant women and infants in a specific region or healthcare facility.

2. Define the intervention: Clearly outline the recommended interventions, including expanding routine early infant diagnosis (EID) screening to nutrition and inpatient entry points, and implementing appropriate testing strategies at immunization and outreach services.

3. Collect baseline data: Gather relevant data on the current access to maternal health services, including the number of pregnant women and infants accessing different entry points, the prevalence of HIV-positive infants, and the availability of testing and treatment services.

4. Model the impact: Use statistical modeling techniques to simulate the impact of the recommended interventions on improving access to maternal health. This can involve creating a mathematical model that takes into account factors such as population size, prevalence rates, and the effectiveness of the interventions.

5. Run the simulation: Input the collected data and parameters into the model and run the simulation to generate results. This can include estimating the number of additional HIV-positive infants that would be identified through expanded EID screening and the potential increase in access to treatment and care.

6. Analyze the results: Evaluate the outcomes of the simulation to assess the potential impact of the recommended interventions on improving access to maternal health. This can involve analyzing the changes in prevalence rates, the number of identified HIV-positive infants, and the overall improvement in access to testing and treatment services.

7. Interpret the findings: Interpret the results of the simulation and draw conclusions about the potential benefits of implementing the recommended interventions. This can include discussing the implications for healthcare facilities, policymakers, and other stakeholders involved in maternal health.

It is important to note that the methodology described above is a general framework and can be adapted based on the specific context and available data. Additionally, the accuracy of the simulation results will depend on the quality and reliability of the input data and the assumptions made in the modeling process.

Author

Dima Health

Statistics:

Citations: 6

Identifiers:

DOI: 10.1002/jia2.25089

Research Areas:

Community Interventions, Food Security, Health System and Policy, Infectious Diseases, Maternal Access, Maternal and Child Health, Quality of Care, Social Determinants, Technology and Innovations

Study Countries:

Uganda

Study Design:

Cohort Study, Cross Sectional Study, Grounded Theory

Study Approach:

Mixed-methods, Qualitative, Quantitative