The impact of sub-national heterogeneities in demography and epidemiology on the introduction of rubella vaccination programs in Nigeria.

Rubella infection during pregnancy can result in miscarriage or infants with a constellation of birth defects known as congenital rubella syndrome (CRS). When coverage is inadequate, rubella vaccination can increase CRS cases by increasing the average age of infection. Thus, the World Health Organisation recommends that countries introducing rubella vaccine be able to vaccinate at least 80% of each birth cohort. Previous studies have focused on national-level analyses and have overlooked sub-national variation in introduction risk. We characterised the sub-national heterogeneity in rubella transmission within Nigeria and modelled local rubella vaccine introduction under different scenarios to refine the set of conditions and strategies required for safe rubella vaccine use. Across Nigeria, the basic reproduction number ranged from 2.6 to 6.2. Consequently, the conditions for safe vaccination varied across states with low-risk areas requiring coverage levels well below 80 %. In high-risk settings, inadequate routine coverage needed to be supplemented by campaigns that allowed for gradual improvements in vaccination coverage over time. Understanding local heterogeneities in both short-term and long-term epidemic dynamics can permit earlier nationwide introduction of rubella vaccination and identify sub-national areas suitable for program monitoring, program improvement and campaign support.

Lessons learnt from assessing and improving accuracy and positive predictive value of the national HIV testing algorithm in Nigeria.

Background: HIV testing remains an entry point into HIV care and treatment services. In 2007, Nigeria adopted and implemented a two-test rapid HIV testing algorithm of three HIV rapid test kits, following the sequence: Alere Determine (first test), UnigoldTM (second test), and STAT-PAK® as the tie-breaker. Sub-analysis of the 2018 Nigeria HIV/AIDS Indicator and Impact Survey data showed significant discordance between the first and second tests, necessitating an evaluation of the algorithm. This manuscript highlights lessons learnt from that evaluation. Intervention: A two-phased evaluation method was employed, including abstraction and analysis of retrospective HIV testing data from January 2017 to December 2019 from 24 selected sites supported by the United States President's Emergency Plan for AIDS Relief programme. A prospective evaluation of HIV testing was done among 2895 consecutively enrolled and consented adults, aged 15-64 years, accessing HIV testing services from three selected sites per state across the six geopolitical zones of Nigeria between July 2020 and September 2020. The prospective evaluation was performed both in the field and at the National Reference Laboratory under controlled laboratory conditions. Stakeholder engagements, strategic selection and training of study personnel, and integrated supportive supervision were employed to assure the quality of evaluation procedures and outcomes. Lessons learnt: The algorithm showed higher sensitivity and specificity in the National Reference Laboratory compared with the field. The approaches to quality assurance were integral to the high-quality study outcomes. Recommendations: We recommend comparison of testing algorithms under evaluation against a gold standard. What this study adds: This study provides context-specific considerations in using World Health Organization recommendations to evaluate the Nigerian national HIV rapid testing algorithm.

Performance of HIV rapid testing algorithm in Nigeria: Findings from a household-based Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS).

BACKGROUND: The Nigeria AIDS Indicator and Impact Survey (NAIIS), a cross-sectional household survey, was conducted in 2018 with primary objectives to estimate HIV prevalence, HIV-1 incidence, and status of UNAIDS 90-90-90 cascade. We conducted retrospective analysis of the performance of HIV rapid tests and the national HIV testing algorithm used in Nigeria. METHODS: The national algorithm included Determine HIV-1/2 as test 1 (T1), Unigold HIV-1/2 as test 2 (T2), and StatPak HIV-1/2 as the tie-breaker test (T3). Individuals reactive with T1 and either T2 or T3 were considered HIV-positive. HIV-positive specimens from the algorithm were further confirmed for the survey using supplemental test Geenius HIV-1/2. If Geenius did not confirm HIV-positive status, HIV-1 Western blot was performed. We calculated the concordance between tests and positive predictive value (PPV) of the algorithm on unweighted data. RESULTS: Of 204,930 participants (ages ≥18 months) 5,103 (2.5%) were reactive on T1. Serial testing of T1 reactive specimens with T2 or if needed by tiebreaker T3 identified 2958 (1.44%) persons as HIV-positive. Supplemental testing confirmed 2,800 (95%) as HIV-positive (HIV-1 = 2,767 [98.8%]; HIV-2 = 5 [0.2%]; dual infections = 22 [0.8%]). Concordance between T1 and T2 was 56.6% while PPV of the national algorithm was 94.5%. CONCLUSIONS: Our results show high discordant rates and poor PPV of the national algorithm with a false-positive rate of about 5.5% in the NAIIS survey. Considering our findings have major implications for HIV diagnosis in routine HIV testing services, additional evaluation of testing algorithm is warranted in Nigeria.

Evaluation of the Nigeria national HIV rapid testing algorithm.

Human Immunodeficiency Virus (HIV) diagnosis remains the gateway to HIV care and treatment. However, due to changes in HIV prevalence and testing coverage across different geopolitical zones, it is crucial to evaluate the national HIV testing algorithm as false positivity due to low prevalence could be detrimental to both the client and the service delivery. Therefore, we evaluated the performance of the national HIV rapid testing algorithm using specimens collected from multiple HIV testing services (HTS) sites and compared the results from different HIV prevalence levels across the six geopolitical zones of Nigeria. The evaluation employed a dual approach, retrospective, and prospective. The retrospective evaluation focused on a desktop review of program data (n = 492,880) collated from patients attending routine HTS from six geopolitical zones of Nigeria between January 2017 and December 2019. The prospective component utilized samples (n = 2,895) collected from the field at the HTS and tested using the current national serial HIV rapid testing algorithm. These samples were transported to the National Reference Laboratory (NRL), Abuja, and were re-tested using the national HIV rapid testing algorithm and HIV-1/2 supplementary assays (Geenius to confirm positives and resolve discordance and multiplex assay). The retrospective component of the study revealed that the overall proportion of HIV positives, based on the selected areas, was 5.7% (28,319/492,880) within the study period, and the discordant rate between tests 1 and 2 was 1.1%. The prospective component of the study indicated no significant differences between the test performed at the field using the national HIV rapid testing algorithm and the re-testing performed at the NRL. The comparison between the test performed at the field using the national HIV rapid testing algorithm and Geenius HIV-1/2 supplementary assay showed an agreement rate of 95.2%, while that of the NRL was 99.3%. In addition, the comparison of the field results with HIV multiplex assay indicated a sensitivity of 96.6%, the specificity of 98.2%, PPV of 97.0%, and Kappa Statistic of 0.95, and that of the NRL with HIV multiplex assay was 99.2%, 99.4%, 99.0%, and 0.99, respectively. Results show that the Nigeria national serial HIV rapid testing algorithm performed very well across the target settings. However, the algorithm's performance in the field was lower than the performance outcomes under a controlled environment in the NRL. There is a need to target testers in the field for routine continuous quality improvement implementation, including refresher trainings as necessary.

Considerations for quality assurance of multiplex malaria antigen detection assays with large sample sets.

Multiplex assays for malaria antigen detection can gather data from large sample sets, but considerations for the consistency and quality assurance (QA) of mass testing lack evaluation. We present a QA framework for a study occurring November 2019 to March 2020 involving 504 assay plates detecting four Plasmodium antigens: pan-Plasmodium aldolase and lactate dehydrogenase (LDH), histidine-rich protein 2 (HRP2), P. vivax LDH (PvLDH). Controls on each plate included buffer blank, antigen negative blood, and 4-point positive dilution curve. The blank and negative blood provided consistently low signal for all targets except for pAldolase, which showed variability. Positive curve signals decreased throughout the 5-month study duration but retained a coefficient of variation (CV) of < 5%, with the exception of HRP2 in month 5 (CV of 11%). Regression fittings for inter-plate control signals provided mean and standard deviations (SDs), and of 504 assay plates, 6 (1.2%) violated the acceptable deviation limits and were repeated. For the 40,272 human blood samples assayed in this study, of 161,088 potential data points (each sample × 4 antigens), 160,641 (99.7%) successfully passed quality checks. The QA framework presented here can be utilized to ensure quality of laboratory antigen detection for large sample sets.