The use of dried tube specimens of Plasmodium falciparum in an external quality assessment programme to evaluate health worker performance for malaria rapid diagnostic testing in healthcare centres in Togo.

BACKGROUND: The use of rapid diagnostic tests (RDTs) to diagnose malaria is common in sub-Saharan African laboratories, remote primary health facilities and in the community. Currently, there is a lack of reliable methods to ascertain health worker competency to accurately use RDTs in the testing and diagnosis of malaria. Dried tube specimens (DTS) have been shown to be a consistent and useful method for quality control of malaria RDTs; however, its application in National Quality Management programmes has been limited. METHODS: A Plasmodium falciparum strain was grown in culture and harvested to create DTS of varying parasite density (0, 100, 200, 500 and 1000 parasites/µL). Using the dried tube specimens as quality control material, a proficiency testing (PT) programme was carried out in 80 representative health centres in Togo. Health worker competency for performing malaria RDTs was assessed using five blinded DTS samples, and the DTS were tested in the same manner as a patient sample would be tested by multiple testers per health centre. RESULTS: All the DTS with 100 parasites/µl and 50% of DTS with 200 parasites/µl were classified as non-reactive during the pre-PT quality control step. Therefore, data from these parasite densities were not analysed as part of the PT dataset. PT scores across all 80 facilities and 235 testers was 100% for 0 parasites/µl, 63% for 500 parasites/µl and 93% for 1000 parasites/µl. Overall, 59% of the 80 healthcare centres that participated in the PT programme received a score of 80% or higher on a set of 0, 500 and 1000 parasites/ µl DTS samples. Sixty percent of health workers at these centres recorded correct test results for all three samples. CONCLUSIONS: The use of DTS for a malaria PT programme was the first of its kind ever conducted in Togo. The ease of use and stability of the DTS illustrates that this type of samples can be considered for the assessment of staff competency. The implementation of quality management systems, refresher training and expanded PT at remote testing facilities are essential elements to improve the quality of malaria diagnosis.

Incident HSV-2 infections are common among HIV-1-discordant couples.

BACKGROUND: The synergy between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1) is well known, but lack of knowledge about the epidemiology of HSV-2 acquisition in HIV-1-discordant couples hampers development of HSV-2 prevention interventions that could reduce HIV-1 transmission. METHODS: HIV-1-discordant couples were enrolled in Nairobi, Kenya, and followed for up to 2 years. HSV-2 status was determined using HerpeSelect HSV-2 ELISA. Correlates of prevalence and incidence were assessed. RESULTS.: Of 469 HIV-1-discordant couples, at baseline, 353 (75.3%) were affected by HSV-2, of which 189 (53.5%) were concordantly HSV-2 seropositive and 164 (46.5%) were HSV-2-discordant. Prevalence was lowest among HIV-1-uninfected men (39.9%) compared to HIV-1-infected women (64.8%), HIV-1-infected men (66.7%), and HIV-1-uninfected women (68.5%). During follow-up, HSV-2 seroincidence was 14.9 per 100 person-years. Incidence was 1.6-fold higher among females compared to males (95% confidence interval [CI], 1.00-2.48) and 2.5-fold higher in HIV-1-infected compared to uninfected women (95% CI, 1.12-5.74). At least 30% of incident HSV-2 infections originated from an outside partner. CONCLUSIONS: The high HSV-2 prevalence and incidence in HIV-1-discordant couples in sub-Saharan Africa suggest HSV-2 treatment and prevention could be an effective targeted strategy to reduce HSV-2 and HIV-1 transmission in this high-risk population.

From benchmarking to best practices: Lessons from the laboratory quality improvement programme at the military teaching hospital in Cotonou, Benin.

BACKGROUND: In 2015, the Army Teaching Hospital-University Teaching Hospital (HIA-CHU [Hôpital D'instruction des Armées de Cotonou Centre Hospitalier et Universitaire]) laboratory in Benin launched a quality improvement programme in alignment with the World Health Organization Regional Office for Africa's Stepwise Laboratory Improvement Process Towards Accreditation (SLIPTA). Among the sub-Saharan African laboratories that have used SLIPTA, few have been francophone countries, and fewer have belonged to a military health system. The purpose of this article was to outline the strategy, implementation, outcomes and military-specific challenges of the HIA-CHU laboratory quality improvement programme from 2015 to 2018. INTERVENTION: The strategy for the quality improvement programme included: external baseline SLIPTA evaluation, creation of work plan based on SLIPTA results, execution of improvement projects guided by work plan, assurance of accountability via regular meetings, training of personnel to improve personnel competencies, development of external stakeholder relationships for sustainability and external follow-up post-SLIPTA evaluation. LESSONS LEARNT: Over a period of 3 years, the HIA-CHU laboratory improved its SLIPTA score by 29% through a quality improvement process guided by work plan implementation, quality management system documentation, introduction of new proficiency testing and internal quality control programmes, and enhancement of personnel competencies in technical and quality management through training. RECOMMENDATIONS: The programme has yielded achievements, but consistent improvement efforts are necessary to address programme challenges and ensure continual increases in SLIPTA scores. Despite successes, military-specific challenges such as the high mobility of personnel have hindered programme progress. The authors recommend that further implementation research data be shared from programmes using SLIPTA in under-represented settings such as military health systems.

Reconfirming HIV serostatus in three West African Military ART clinics.

BACKGROUND: HIV rapid diagnostic test (RDT) algorithms have been successfully employed worldwide to accelerate critically important HIV testing. Deviations from the algorithm and processing errors have been associated with inaccurate algorithm results. Positive RDT algorithm results should be confirmed prior to HIV clinic enrollment, but compliance varies. We sought to retest HIV status of patients in three West African military HIV clinics. SETTING: Military HIV clinics in Lome, Togo; Freetown, Sierra Leone; and Monrovia, Liberia METHODS: Patients coming for routine HIV clinic visits were approached for enrollment. Consenting participants completed a 15-minute questionnaire and provided blood samples for both national and WHO-recommended HIV RDT algorithms, and HIV ELISA (plus HIV PCR if HIV ELISA negative). RESULTS: In total, 817 participants provided data: 374 in Togo, 360 in Sierra Leone, and 83 in Liberia. One participant from Liberia was HIV-negative (although follow-up testing was positive). Two of 807 participants on antiretroviral treatment (ART) had inconclusive algorithms, while 2 of 10 participants not on ART had algorithms, for 4 total based on the WHO-approved algorithm. Using the national algorithms, only 3 were inconclusive. A substantial proportion of the cohort had taken ART for over 6 years (25-46%, depending on the site). CONCLUSION: HIV RDT retesting in three military HIV clinics did not uncover significant numbers of misclassified HIV patients. There was no significant difference between national and WHO-recommended RDT algorithms, although the study was underpowered to detect a difference. Antiretroviral treatment was not associated with increased rates of inconclusive RDT algorithm results.

Higher Transplacental Pathogen-Specific Antibody Transfer Among Pregnant Women Randomized to Triple Antiretroviral Treatment Versus Short Course Zidovudine.

BACKGROUND: HIV-1 infection may impair transplacental antibody transfer to infants. The impact of highly active antiretroviral treatment (ART) given during pregnancy on transplacental antibody transport is unknown. METHODS: HIV-1 infected pregnant women with CD4 counts between 200 - 500 were randomized to short-course zidovudine (ZDV) or triple ART at 32 weeks gestation for prevention of mother-to-child HIV-1 transmission. Levels of maternal antibody against measles, pneumococcus and rotavirus at delivery, and antibody transfer to the baby through cord blood, were compared between trial arms. RESULTS: Overall, 141 and 148 women were randomized to triple ART and ZDV, respectively; cord blood was available for a subset (n = 20 in triple ART and n = 22 in ZDV). Maternal antibody levels to all pathogens during pregnancy and at delivery were not significantly different between arms. Within each arm, antibody levels at delivery were lower than at enrolment. For all antibodies, a woman's levels before delivery were an important predictor of amount transferred to her infant. Women on triple ART transferred higher levels of pathogen-specific antibodies when compared with women on short course ZDV. CONCLUSIONS: Women on triple ART transferred higher levels of pathogen-specific antibodies compared with women on ZDV alone.

High Rates of Exclusive Breastfeeding in Both Arms of a Peer Counseling Study Promoting EBF Among HIV-Infected Kenyan Women.

BACKGROUND: Exclusive breastfeeding (EBF) is recommended for 6 months after delivery as the optimal infant feeding method and is especially important for prevention of mother-to-child HIV transmission (PMTCT). However, EBF promotion efforts among HIV-infected mothers in sub-Saharan Africa have achieved mixed success and require context-specific interventions. METHODS: HIV-positive, pregnant women from six clinics in Nairobi were enrolled into a clinic-level, before-after counseling intervention study. All women received standard perinatal and HIV care. Women in the intervention arm were offered three counseling sessions that promoted EBF, described its benefits, and explained breastfeeding techniques. Mother-infant pairs were followed until 14 weeks postpartum, with infant HIV testing at 6 weeks. EBF prevalence at 14 weeks postpartum was compared between study arms using log-binomial regression. Proportions of 6-week HIV-free survival and 14-week infant survival were assessed using Cox regression. Risk estimates were adjusted for clinic, relationship status, and antiretroviral therapy. RESULTS: Between 2009 and 2013, 833 women were enrolled of whom 94% planned to practice EBF for 6 months and 95% were taking therapeutic or prophylactic antiretrovirals. Median age was 27 years; median CD4 count was 403 cells/µL. EBF prevalence at 14 weeks postpartum was 86% in the control and 81% in the intervention group (p = 0.19). No differences were observed between groups for 6-week HIV-free survival and 14-week infant survival. CONCLUSION: Women who received breastfeeding counseling were not more likely to breastfeed exclusively, in part due to high overall EBF prevalence in this study population. The high EBF prevalence is an important finding, given recent efforts to promote EBF in Kenya.

Seroprevalence of measles IgG among HIV-1-infected and uninfected Kenyan adults.

Despite global efforts to reduce measles incidence, outbreaks continue to occur in developing countries where HIV-1-infected adults represent a vulnerable population. Immunization campaigns have targeted children, although little is known about the levels of measles protection in adult populations in Kenya. The objective of this study was to determine seroprevalence and titers of measles IgG among HIV-1-infected and uninfected adults in Nairobi, Kenya. The presence of anti-measles IgG was measured in cryopreserved serum of 257 HIV-1-infected and 367 uninfected adults using a commercial ELISA (Enzygnost, Germany). The measles IgG concentration was calculated for those samples that were positive. Overall, 96% of adults were measles seropositive and the mean measles IgG concentration among those who were seropositive was 4134 mIU/ml, which is well above previously reported protective levels. There was no statistical difference in seroprevalence or antibody concentration between the HIV-infected and HIV-uninfected groups. While local vaccination efforts and circulating measles infection likely contribute to this high measles seroprevalence rate, these data are unique to an urban population and may not reflect a country-wide distribution. Our results suggest that reduced immunity among HIV-1-infected adults is not a major contributor to measles resurgence in Kenya.

Measles seropositivity in HIV-infected Kenyan children on antiretroviral therapy.

This article describes results from a cross-sectional study among HIV-infected children 15 months to 12 years of age who were receiving antiretroviral therapy. We found a low prevalence of measles IgG seropositivity (45.7%) and identified CD4% ≥ 25 as a predictor. Most HIV-infected children on ART were not measles seropositive and might benefit from revaccination.

Pooled HIV-1 RNA viral load testing for detection of antiretroviral treatment failure in Kenyan children.

BACKGROUND: Pooled viral load (VL) testing with 2 different testing strategies was evaluated as a potential cost saving method to monitor antiretroviral therapy (ART) in HIV-infected children receiving ART in a resource-limited setting. METHODS: Archived samples collected from 250 HIV-1-infected children on first-line ART at various time points post-ART initiation were evaluated for pooled VL testing using a minipool + algorithm strategy. Additionally, samples collected in real time from 125 children on ART were assessed for virologic failure using a minipool strategy for pooled VL testing. Virologic failure was determined as HIV-1 RNA VLs >1500 copies/mL. RESULTS: Minipool + algorithm strategy for pooled VL testing of archived samples had estimated viral failure of 13.6%, with a relative efficiency (RE) of 23.6% (95% CI: 18.5 to 29.4), and negative predictive value of 88%. This testing strategy would have resulted in 24% fewer assays needed for a cost savings of $1180 per 100 samples. The minipool strategy for pooled VL testing of samples obtained in real time yielded an estimated 23.2% of samples with viral failure and a RE of 8.0% (95% CI: 3.9 to 14.2); however, had a minipool + algorithm pooling strategy been used, the RE would have increased to 20%. CONCLUSIONS: The minipool + algorithm strategy for pooled VL testing to detect virologic failure in HIV-1-infected children on ART was determined to be relatively efficient in detecting virologic failure, have high negative predictive value, with substantial cost savings. Pooling strategies may be important components of cost-effect strategies to reduce rates of viral failure and resistance, thus, improving clinical outcomes.