Steven D. Reid

Background: Guinea reported its first case of COVID-19 on March 12, 2020. Soon thereafter, a national state of emergency was declared, all land borders were closed, schools were shut down, and public gatherings were limited. Many health activities, including field-based activities targeting neglected tropical diseases (NTDs), were paused. The World Health Organization (WHO) issued updated guidance on the resumption of NTD field-based activities on July 27, 2020. In response, the Guinea Ministry of Health (MoH) and its partners planned and resumed mass drug administration (MDA) in mid-August to September 2020 in 19 health districts. Methodology/principal findings: A risk-benefit assessment was conducted to identify potential risks associated with the MDA in the COVID-19 context. Following this assessment, a risk mitigation plan with barrier measures was developed to guide MDA implementation. These measures included COVID-19 testing for all national staff leaving Conakry, mask wearing, social distancing of two meters, and hand washing/sanitizing. A checklist was developed and used to monitor compliance to risk mitigation measures. Data on adherence to risk mitigation measures were collected electronically during the MDA. A total of 120 checklists, representing 120 community drug distributor (CDD) teams (two CDDs per team) and 120 households, were completed. Results indicated that washing or disinfecting hands was practiced by 68.3% of CDD teams, compared to 45.0% among households. Face masks to cover the mouth and nose were worn by 79.2% of CDD teams, while this was low among households (23.3%). In 87.5% of households, participants did not touch the dose pole and in 88.3% of CDD teams, CDDs did not touch the hands of the participants while giving the drugs. A large majority of CDD teams (94.2%) and household members (94.2%) were willing to participate in the MDA despite the pandemic. The epidemiological coverage was ≥65% for lymphatic filariasis, onchocerciasis and soil-transmitted helminths in 10 out of 19 HDs and ≥75% for schistosomiasis for school-aged children in 7 out of 11 HDs. Conclusions/significance: Guinea was one of the first countries in Africa to resume MDA activities during the COVID-19 pandemic without causing an observed increase of transmission. The development of a risk mitigation plan and a method to monitor adherence to barrier measures was critical to this unprecedented effort. The rapid incorporation of COVID-19 barrier measures and their acceptance by CDDs and household members demonstrated both the adaptability of the National NTD Program to respond to emerging issues and the commitment of the MoH to implement NTD programs.

Introduction: Point‐of‐care testing for CD4 cell count is considered a promising way of reducing the time to eligibility assessment for antiretroviral therapy (ART) and of increasing retention in care prior to treatment initiation. In this review, we assess the available evidence on the patient and programme impact of point‐of‐care CD4 testing.Methods: We searched nine databases and two conference sites (up until 26 October 2013) for studies reporting patient and programme outcomes following the introduction of point‐of‐care CD4 testing. Where appropriate, results were pooled using random‐effects methods.Results: Fifteen studies, mainly from sub‐Saharan Africa, were included for review, providing evidence for adults, adolescents, children and pregnant women. Compared to conventional laboratory‐based testing, point‐of‐care CD4 testing increased the likelihood of having CD4 measured [odds ratio (OR) 4.1, 95% CI 3.5–4.9, n=2] and receiving a CD4 result (OR 2.8, 95% CI 1.5–5.6, n=6). Time to being tested was significantly reduced, by a median of nine days; time from CD4 testing to receiving the result was reduced by as much as 17 days. Evidence for increased treatment initiation was mixed.Discussion: The results of this review suggest that point‐of‐care CD4 testing can increase retention in care prior to starting treatment and can also reduce time to eligibility assessment, which may result in more eligible patients being initiated on ART.

Peer reviewed article authored by (Reid SD, Fidler SJ, Cooke GS). Read article or submit your manuscript for publishing.

In this paper, we discuss the reasons why we urgently need a point-of-care (POC) CD4 test, elaborate the problems we have experienced with the current technology which hampers CD4-count coverage and highlight the ideal characteristics of a universal CD4 POC test. It is high-time that CD4 technology is simplified and adapted for wider use in low-income countries to change the current paradigm of restricted access once and for all.

One of the major unresolved questions in B cell biology is how the B cell Ag receptor (BCR) differentially signals to transduce anergy, apoptosis, proliferation, or differentiation during B cell maturation. We now report that extracellularly regulated kinase-mitogen-activated protein kinase (Erk-MAP kinase) can play dual roles in the regulation of the cell fate of the immature B cell lymphoma, WEHI-231, depending on the kinetics and context of Erk-MAP kinase activation. First, we show that the BCR couples to an early (≤2 h) Erk-MAP kinase signal which activates a phospholipase A₂ pathway that we have previously shown to mediate collapse of mitochondrial membrane potential, resulting in depletion of cellular ATP and cathepsin B execution of apoptosis. Rescue of BCR-driven apoptosis by CD40 signaling desensitizes such early extracellularly regulated kinase (Erk) signaling and hence uncouples the BCR from the apoptotic mitochondrial phospholipase A₂ pathway. A second role for Erk-MAP kinase in promoting the growth and proliferation of WEHI-231 immature B cells is evidenced by data showing that proliferating and CD40-stimulated WEHI-231 B cells exhibit a sustained cycling pattern (8–48 h) of Erk activation that correlates with cell growth and proliferation. This growth-promoting role for Erk signaling is supported by three key pieces of evidence: 1) signaling via the BCR, under conditions that induce growth arrest, completely abrogates sustained Erk activation; 2) CD40-mediated rescue from growth arrest correlates with restoration of cycling Erk activation; and 3) sustained inhibition of Erk prevents CD40-mediated rescue of BCR-driven growth arrest of WEHI-231 immature B cells. Erk-MAP kinase can therefore induce diverse biological responses in WEHI-231 cells depending on the context and kinetics of activation.

CD44 comprises a family of type I transmembrane glycoproteins that is expressed on a wide range of cells including those of epithelial, lymphoid and myeloid lineage. Although expression of CD44 in the small intestine is typically localised in the crypts of Lieberkühn, we have reported the expression of CD44 on mature, intestinal villus epithelial cells during the development of small bowel allograft rejection. The mechanisms underlying CD44 up-regulation are unknown, although it may be influenced by localised cytokine production. This study used flow cytometry to assess the effects of recombinant IFN-γ and TNF-α on CD44 expression and hyaluronan binding by the rat small intestinal epithelial cell lines, RIE and IEC 6. IFN-γ upregulated CD44 expression on RIE (155% of unstimulated control) and IEC 6 (209% of unstimulated control) cells, whereas TNF-α had no effect. IFN-γ had no qualitative effect on CD44, as binding of the ubiquitously expressed extracellular matrix polysaccharide hyaluronan was unchanged. RIE and IEC 6 cells expressed the 82 kDa and 130 kDa major isoforms of CD44, however cytokine stimulation did not affect the expression of these, nor did stimulation induce the expression of other variants. In summary, these findings demonstrate that CD44 expression by intestinal epithelial cells can be regulated by cytokines, yet their ability to bind hyaluronan and the isoform of the expressed CD44 remains unaltered. It appears that localised inflammatory conditions and cytokine production may modify epithelial cell expression of CD44, however the physiological role for such a response has yet to be elucidated.