Maternity waiting homes as an intervention to increase facility delivery in rural Zambia

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150534/1/ijgo12864_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150534/2/ijgo12864.pd

tat Exon 1 Exhibits Functional Diversity during HIV-1 Subtype C Primary Infection

Human immunodeficiency virus type 1 (HIV-1) Tat is a mediator of viral transcription and is involved in the control of virus replication. However, associations between HIV-1 Tat diversity and functional effects during primary HIV-1 infection are still unclear. We estimated selection pressures in tat exon 1 using the mixed-effects model of evolution with 672 viral sequences generated from 20 patients infected with HIV-1 subtype C (HIV-1C) over 500 days postseroconversion. tat exon 1 residues 3, 4, 21, 24, 29, 39, and 68 were under positive selection, and we established that specific amino acid signature patterns were apparent in primary HIV-1C infection compared with chronic infection. We assessed the impact of these mutations on long terminal repeat (LTR) activity and found that Tat activity was negatively affected by the Ala21 substitution identified in 13/20 (65%) of patients, which reduced LTR activity by 88% (±1%) (P < 0.001). The greatest increase in Tat activity was seen with the Gln35/Lys39 double mutant that resulted in an additional 49% (±14%) production of LTR-driven luciferase (P = 0.012). There was a moderate positive correlation between Tat-mediated LTR activity and HIV-1 RNA in plasma (P = 0.026; r = 0.400) after 180 days postseroconversion that was reduced by 500 days postseroconversion (P = 0.043; r = 0.266). Although Tat activation of the LTR is not a strong predictor of these clinical variables, there are significant linear relationships between Tat transactivation and patients' plasma viral loads and CD4 counts, highlighting the complex interplay between Tat mutations in early HIV-1C infection

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

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

First COVID-19 Case in Zambia - Comparative phylogenomic analyses of SARS-CoV-2 detected in African countries

Since its first discovery in December 2019 in Wuhan, China, COVID-19, caused by the novel coronavirus SARS-CoV-2, has spread rapidly worldwide. Whilst African countries were relatively spared initially, the initial low incidence of COVID-19 cases was not sustained for long due to continuing travel links between China, Europe and Africa.. In preparation, Zambia had applied a multisectoral national epidemic disease surveillance and response system resulting in the identification of the first case within 48 hours of the individual entering the country by air travel from a trip to France. Contact tracing showed that SARS-CoV-2 infection was contained within the patient's household, with no further spread to attending health care workers or community members. Phylogenomic analysis of the patient's SARS-CoV-2 strain showed it belonged to lineage B.1.1., sharing the last common ancestor with SARS-CoV-2 strains recovered from South Africa. At the African continental level, our analysis showed that lineage B.1 and B.1.1 lineages appear to be predominant in Africa. Whole genome sequence analysis should be part of all surveillance and case detection activities in order to monitor the origin and evolution of SARS-CoV-2 lineages across Africa

Assessing the impact of a food supplement on the nutritional status and body composition of HIV-infected Zambian women on ARVs

Background Zambia is a sub-Saharan country with one of the highest prevalence rates of HIV, currently estimated at 14%. Poor nutritional status due to both protein-energy and micronutrient malnutrition has worsened this situation. In an attempt to address this combined problem, the government has instigated a number of strategies, including the provision of antiretroviral (ARV) treatment coupled with the promotion of good nutrition. High-energy protein supplement (HEPS) is particularly promoted; however, the impact of this food supplement on the nutritional status of people living with HIV/AIDS (PLHA) beyond weight gain has not been assessed. Techniques for the assessment of nutritional status utilising objective measures of body composition are not commonly available in Zambia. The aim of this study is therefore to assess the impact of a food supplement on nutritional status using a comprehensive anthropometric protocol including measures of skinfold thickness and circumferences, plus the criterion deuterium dilution technique to assess total body water (TBW) and derive fat-free mass (FFM) and fat mass (FM). Methods/Design This community-based controlled and longitudinal study aims to recruit 200 HIV-infected females commencing ARV treatment at two clinics in Lusaka, Zambia. Data will be collected at four time points: baseline, 4-month, 8-month and 12-month follow-up visits. Outcome measures to be assessed include body height and weight, body mass index (BMI), body composition, CD4, viral load and micronutrient status. Discussion This protocol describes a study that will provide a longitudinal assessment of the impact of a food supplement on the nutritional status of HIV-infected females initiating ARVs using a range of anthropometric and body composition assessment techniques

Meeting human resources for health staffing goals by 2018: a quantitative analysis of policy options in Zambia

<p>Abstract</p> <p>Background</p> <p>The Ministry of Health (MOH) in Zambia is currently operating with fewer than half of the health workers required to deliver basic health services. The MOH has developed a human resources for health (HRH) strategic plan to address the crisis through improved training, hiring, and retention. However, the projected success of each strategy or combination of strategies is unclear.</p> <p>Methods</p> <p>We developed a model to forecast the size of the public sector health workforce in Zambia over the next ten years to identify a combination of interventions that would expand the workforce to meet staffing targets. The key forecasting variables are training enrolment, graduation rates, public sector entry rates for graduates, and attrition of workforce staff. We model, using Excel (Office, Microsoft; 2007), the effects of changes in these variables on the projected number of doctors, clinical officers, nurses and midwives in the public sector workforce in 2018.</p> <p>Results</p> <p>With no changes to current training, hiring, and attrition conditions, the total number of doctors, clinical officers, nurses, and midwives will increase from 44% to 59% of the minimum necessary staff by 2018. No combination of changes in staff retention, graduation rates, and public sector entry rates of graduates by 2010, without including training expansion, is sufficient to meet staffing targets by 2018 for any cadre except midwives. Training enrolment needs to increase by a factor of between three and thirteen for doctors, three and four for clinical officers, two and three for nurses, and one and two for midwives by 2010 to reach staffing targets by 2018. Necessary enrolment increases can be held to a minimum if the rates of retention, graduation, and public sector entry increase to 100% by 2010, but will need to increase if these rates remain at 2008 levels.</p> <p>Conclusions</p> <p>Meeting the minimum need for health workers in Zambia this decade will require an increase in health training school enrolment. Supplemental interventions targeting attrition, graduation and public sector entry rates can help close the gap. HRH modelling can help MOH policy makers determine the relative priority and level of investment needed to expand Zambia's workforce to target staffing levels.</p

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