Accuracy in HIV Rapid Testing among Laboratory and Non-laboratory Personnel in Zambia: Observations from the National HIV Proficiency Testing System.

BACKGROUND: Despite rapid task-shifting and scale-up of HIV testing services in high HIV prevalence countries, studies evaluating accuracy remain limited. This study aimed to assess overall accuracy level and factors associated with accuracy in HIV rapid testing in Zambia. METHODS: Accuracy was investigated among rural and urban HIV testing sites participating in two annual national HIV proficiency testing (PT) exercises conducted in 2009 (n = 282 sites) and 2010 (n = 488 sites). Testers included lay counselors, nurses, laboratory personnel and others. PT panels of five dry tube specimens (DTS) were issued to testing sites by the national reference laboratory (NRL). Site accuracy level was assessed by comparison of reported results to the expected results. Non-parametric rank tests and multiple linear regression models were used to assess variation in accuracy between PT cycles and between tester groups, and to examine factors associated with accuracy respectively. RESULTS: Overall accuracy level was 93.1% (95% CI: 91.2-94.9) in 2009 and 96.9% (95% CI: 96.1-97.8) in 2010. Differences in accuracy were seen between the tester groups in 2009 with laboratory personnel being more accurate than non-laboratory personnel, while in 2010 no differences were seen. In both PT exercises, lay counselors and nurses had more difficulties interpreting results, with more occurrences of false-negative, false-positive and indeterminate results. Having received the standard HIV rapid testing training and adherence to the national HIV testing algorithm were positively associated with accuracy. CONCLUSION: The study showed an improvement in tester group and overall accuracy from the first PT exercise to the next. Average number of incorrect test results per 1000 tests performed was reduced from 69 to 31. Further improvement is needed, however, and the national HIV proficiency testing system seems to be an important tool in this regard, which should be continued and needs to be urgently strengthened

Task-Shifting and Quality of HIV Testing Services: Experiences from a National Reference Hospital in Zambia.

BACKGROUND: With new testing technologies, task-shifting and rapid scale-up of HIV testing services in high HIV prevalence countries, assuring quality of HIV testing is paramount. This study aimed to explore various cadres of providers' experiences in providing HIV testing services and their understanding of elements that impact on quality of service in Zambia. METHODS: Sixteen in-depth interviews and two focus group discussions were conducted with HIV testing service providers including lay counselors, nurses and laboratory personnel at purposively selected HIV testing sites at a national reference hospital in Lusaka. Qualitative content analysis was adopted for data analysis. RESULTS: Lay counselors and nurses reported confidentiality and privacy to be greatly compromised due to limited space in both in- and out-patient settings. Difficulties in upholding consent were reported in provider-initiated testing in in-patient settings. The providers identified non-adherence to testing procedures, high workload and inadequate training and supervision as key elements impacting on quality of testing. Difficulties related to testing varied by sub-groups of providers: lay counselors, in finger pricking and obtaining adequate volumes of specimen; non-laboratory providers in general, in interpreting invalid, false-negative and false-positive results. The providers had been participating in a recently established national HIV quality assurance program, i.e. proficiency testing, but rarely received site supervisory visits. CONCLUSION: Task-shifting coupled with policy shifts in service provision has seriously challenged HIV testing quality, protection of confidentiality and the process of informed consent. Ways to better protect confidentiality and informed consent need careful attention. Training, supervision and quality assurance need strengthening tailored to the needs of the different cadres of providers

Universal combination antiretroviral regimens to prevent mother-to-child transmission of HIV in rural Zambia: a two-round cross-sectional study

To evaluate if a pilot programme to prevent mother-to-child transmission (PMTCT) of the human immunodeficiency virus (HIV) was associated with changes in early childhood survival at the population level in rural Zambia

UK national clinical audit: Management of pregnancies in women with HIV

BACKGROUND: The potential for HIV transmission between a pregnant woman and her unborn child was first recognized in 1982. Since then a complex package of measures to reduce risk has been developed. This project aims to review UK management of HIV in pregnancy as part of the British HIV Association (BHIVA) audit programme. METHODS: The National Study of HIV in Pregnancy and Childhood (NSHPC), a population-based surveillance study, provided data for pregnancies with an expected delivery date from 1/1/13 - 30/6/14. Services also completed a survey on local management policies. Data were audited against the 2012 BHIVA pregnancy guidelines. RESULTS: During the audit period 1483 pregnancies were reported and 112 services completed the survey. Use of dedicated multidisciplinary teams was reported by 99% although 26% included neither a specialist midwife nor nurse. 17% of services reported delays >1 week for HIV specialist review of women diagnosed antenatally. Problematic urgent HIV testing had been experienced by 9% of services although in a further 49% the need for urgent testing had not arisen. Delays of >2 h in obtaining urgent results were common. Antiretroviral therapy (ART) was started during pregnancy in 37% women with >94% regimens in accordance with guidelines. Late ART initiation was common, particularly in those with a low CD4 count or high viral load. Eleven percent of services reported local policy contrary to guidelines regarding delivery mode for women with a VL <50 copies/mL at ≥36 weeks. According to NSHPC reports 27% of women virologically eligible for vaginal delivery planned to deliver by CS. CONCLUSIONS: Pregnant women in the UK are managed largely in accordance with BHIVA guidelines. Improvements are needed to ensure timely referral and ART initiation to ensure the best possible outcomes

Methylphenidate and the risk of psychotic disorders and hallucinations in children and adolescents in a large health system

Previous studies have suggested that risk of psychotic events may be increased in children exposed to methylphenidate (MPH). However, this risk has not been fully examined and the possibility of confounding factors has not been excluded. Patients aged 6-19 years who received at least one MPH prescription were identified using Hong Kong population-based electronic medical records on the Clinical Data Analysis & Reporting System (2001-2014). Using the self-controlled case series design, relative incidence of psychotic events was calculated comparing periods when patients were exposed to MPH with non-exposed periods. Of 20 586 patients prescribed MPH, 103 had an incident psychotic event; 72 (69.9%) were male and 31 (30.1%) female. The mean age at commencement of observation was 6.95 years and the mean follow-up per participant was 10.16 years. On average, each participant was exposed to MPH for 2.17 years. The overall incidence of psychotic events during the MPH exposure period was 6.14 per 10 000 patient-years. No increased risk was found during MPH exposed compared to non-exposed periods (incidence rate ratio (IRR) 1.02 (0.53-1.97)). However, an increased risk was found during the pre-exposure period (IRR 4.64 (2.17-9.92)). Results were consistent across all sensitivity analyses. This study does not support the hypothesis that MPH increases risk of incident psychotic events. It does indicate an increased risk of psychotic events prior to the first prescription of MPH, which may be due to an association between psychotic events and the behavioural and attentional symptoms that led to psychiatric assessment and initiation of MPH treatment

Can urban coffee consumption help predict US inflation?

Motivated by the importance of coffee to Americans and the significance of the coffee subsector to the US economy, we pursue three notable innovations. First, we augment the traditional Phillips curve model with the coffee price as a predictor, and show that the resulting model outperforms the traditional variant in both in-sample and out-of-sample predictability of US inflation. Second, we demonstrate the need to account for the inherent statistical features of predictors such as persistence, endogeneity, and conditional heteroskedasticity effects when dealing with US inflation. Consequently, we offer robust illustrations to show that the choice of estimator matters for improved US inflation forecasts. Third, the proposed augmented Phillips curve also outperforms time series models such as autoregressive integrated moving average and the fractionally integrated version for both in-sample and out-of-sample forecasts. Our results show that augmenting the traditional Phillips curve with the urban coffee price will produce better forecast results for US inflation only when the statistical effects are captured in the estimation process. Our results are robust to alternative measures of inflation, different data frequencies, higher order moments, multiple data samples and multiple forecast horizons

Antimalarial Activity and Mechanisms of Action of Two Novel 4-Aminoquinolines against Chloroquine-Resistant Parasites

Chloroquine (CQ) is a cost effective antimalarial drug with a relatively good safety profile (or therapeutic index). However, CQ is no longer used alone to treat patients with Plasmodium falciparum due to the emergence and spread of CQ-resistant strains, also reported for P. vivax. Despite CQ resistance, novel drug candidates based on the structure of CQ continue to be considered, as in the present work. One CQ analog was synthesized as monoquinoline (MAQ) and compared with a previously synthesized bisquinoline (BAQ), both tested against P. falciparum in vitro and against P. berghei in mice, then evaluated in vitro for their cytotoxicity and ability to inhibit hemozoin formation. Their interactions with residues present in the NADH binding site of P falciparum lactate dehydrogenase were evaluated using docking analysis software. Both compounds were active in the nanomolar range evaluated through the HRPII and hypoxanthine tests. MAQ and BAQ derivatives were not toxic, and both compounds significantly inhibited hemozoin formation, in a dose-dependent manner. MAQ had a higher selectivity index than BAQ and both compounds were weak PfLDH inhibitors, a result previously reported also for CQ. Taken together, the two CQ analogues represent promising molecules which seem to act in a crucial point for the parasite, inhibiting hemozoin formation

The evolving SARS-CoV-2 epidemic in Africa: insights from rapidly expanding genomic surveillance

Investment in SARS-CoV-2 sequencing in Africa over the past year has led to a major increase in the number of sequences generated, now exceeding 100,000 genomes, used to track the pandemic on the continent. Our results show an increase in the number of African countries able to sequence domestically, and highlight that local sequencing enables faster turnaround time and more regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and shed light on the distinct dispersal dynamics of Variants of Concern, particularly Alpha, Beta, Delta, and Omicron, on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve, while the continent faces many emerging and re-emerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Second Generation Steroidal 4-Aminoquinolines Are Potent, Dual-Target Inhibitors of the Botulinum Neurotoxin Serotype A Metalloprotease and P. falciparum Malaria

Significantly more potent second generation 4-amino-7-chloroquinoline (4,7-ACQ) based inhibitors of the botulinum neurotoxin serotype A (BoNT/A) light chain were synthesized. Introducing an amino group at the C(3) position of the cholate component markedly increased potency (IC50 values for such derivatives ranged from 0.81 to 2.27 mu M). Two additional subclasses were prepared: bis(steroidal)-4,7-ACQ derivatives and bis(4,7-ACQ)cholate derivatives; both classes provided inhibitors with nanomolar-range potencies (e.g., the K-i of compound 67 is 0.10 mu M). During BoNT/A challenge using primary neurons, select derivatives protected SNAP-25 by up to 89%. Docking simulations were performed to rationalize the compounds' in vitro potencies. In addition to specific residue contacts, coordination of the enzyme's catalytic zinc and expulsion of the enzyme's catalytic water were a consistent theme. With respect to antimalarial activity, the compounds provided better IC90 activities against chloroquine resistant (CQR) malaria than CQ, and seven compounds were more active than mefloquine against CQR strain W2

Association of maternal prenatal copper concentration with gestational duration and preterm birth: a multicountry meta-analysis

Background Copper (Cu), an essential trace mineral regulating multiple actions of inflammation and oxidative stress, has been implicated in risk for preterm birth (PTB). Objectives This study aimed to determine the association of maternal Cu concentration during pregnancy with PTB risk and gestational duration in a large multicohort study including diverse populations. Methods Maternal plasma or serum samples of 10,449 singleton live births were obtained from 18 geographically diverse study cohorts. Maternal Cu concentrations were determined using inductively coupled plasma mass spectrometry. The associations of maternal Cu with PTB and gestational duration were analyzed using logistic and linear regressions for each cohort. The estimates were then combined using meta-analysis. Associations between maternal Cu and acute-phase reactants (APRs) and infection status were analyzed in 1239 samples from the Malawi cohort. Results The maternal prenatal Cu concentration in our study samples followed normal distribution with mean of 1.92 μg/mL and standard deviation of 0.43 μg/mL, and Cu concentrations increased with gestational age up to 20 wk. The random-effect meta-analysis across 18 cohorts revealed that 1 μg/mL increase in maternal Cu concentration was associated with higher risk of PTB with odds ratio of 1.30 (95% confidence interval [CI]: 1.08, 1.57) and shorter gestational duration of 1.64 d (95% CI: 0.56, 2.73). In the Malawi cohort, higher maternal Cu concentration, concentrations of multiple APRs, and infections (malaria and HIV) were correlated and associated with greater risk of PTB and shorter gestational duration. Conclusions Our study supports robust negative association between maternal Cu and gestational duration and positive association with risk for PTB. Cu concentration was strongly correlated with APRs and infection status suggesting its potential role in inflammation, a pathway implicated in the mechanisms of PTB. Therefore, maternal Cu could be used as potential marker of integrated inflammatory pathways during pregnancy and risk for PTB