Turning threats into opportunities: how to implement and advance quality TB services for people with HIV during the COVID-19 pandemic and beyond.

INTRODUCTION: Until COVID-19, tuberculosis (TB) was the leading infectious disease killer globally, disproportionally affecting people with HIV. The COVID-19 pandemic is threatening the gains made in the fight against both diseases. DISCUSSION: Although crucial guidance has been released on how to maintain TB and HIV services during the pandemic, it is acknowledged that what was considered normal service pre-pandemic needs to improve to ensure that we rebuild person-centred, inclusive and quality healthcare services. The threat that the pandemic may reverse gains in the response to TB and HIV may be turned into an opportunity by pivoting to using proven differentiated service delivery approaches and innovative technologies that can be used to maintain care during the pandemic and accelerate improved service delivery in the long term. Models of care should be convenient, supportive and sufficiently differentiated to avoid burdensome clinic visits for medication pick-ups or directly observed treatments. Additionally, the pandemic has highlighted the chronic and short-sighted lack of investment in health systems and the need to prioritize research and development to close the gaps in TB diagnosis, treatment and prevention, especially for children and people with HIV. Most importantly, TB-affected communities and civil society must be supported to lead the planning, implementation and monitoring of TB and HIV services, especially in the time of COVID-19 where services have been disrupted, and to report on legal, policy and gender-related barriers to access experienced by affected people. This will help to ensure that TB services are held accountable by affected communities for delivering equitable access to quality, affordable and non-discriminatory services during and beyond the pandemic. CONCLUSIONS: Successfully reaching the related targets of ending TB and AIDS as public health threats by 2030 requires rebuilding of stronger, more inclusive health systems by advancing equitable access to quality TB services, including for people with HIV, both during and after the COVID-19 pandemic. Moreover, services must be rights-based, community-led and community-based, to ensure that no one is left behind.

Towards universal access to HIV prevention, treatment, care, and support: the role of tuberculosis/HIV collaboration.

Tuberculosis is the oldest of the world's current pandemics and causes 8.9 million new cases and 1.7 million deaths annually. The disease is among the most common causes of morbidity and mortality in people living with HIV. However, tuberculosis is more than just part of the global HIV problem; well-resourced tuberculosis programmes are an important part of the solution to scaling-up towards universal access to comprehensive HIV prevention, diagnosis, care, and support. This article reviews the impact of the interactions between tuberculosis and HIV in resource-limited settings; outlines the recommended programmatic and clinical responses to the dual epidemics, highlighting the role of tuberculosis/HIV collaboration in increasing access to prevention, diagnostic, and treatment services; and reviews progress in the global response to the epidemic of HIV-related tuberculosis.

Colinearity and non-colinearity in the expression of Hox genes in developing chick skin.

Hox genes are usually expressed temporally and spatially in a colinear manner with respect to their positions in the Hox complex. We found that these characteristics apply to several Hox genes expressed in developing chick skin (Hoxb-4, Hoxa-7 and Hoxc-8), and we classed this group of genes as regionally restricted. To our surprise, we found that most of the Hox genes we examined are regionally unrestricted in their expression in the embryonic chick skin. This second group includes the Hoxd genes, Hoxd-4 to Hoxd-13, Hoxa-11 and Hoxc-6. Temporally, the expression of the regionally restricted genes can be observed by E5 within the epidermis, whereas the spatially unrestricted genes are not expressed in the epidermis until E6.25. Unexpectedly, we found that all the unrestricted genes are expressed concomitantly and therefore do not conform to temporal colinearity. Moreover, the dermal expression for both groups occurs later, but maintains the same anteroposterior patterning to that seen previously in the epidermis. During embryonic day 7-8, expression for all genes is up-regulated within the dense dermis whilst being reduced within the inter-bud regions. Later expression within the bud mesenchyme is down-regulated whilst high levels of transcriptional activity are detectable within the epidermal sheath of each feather bud. These results indicate that the transcriptional activity of Hox genes in the developing chick skin could be important during embryonic skin patterning both by providing regionally restricted positional cues, and also by imparting generic signals necessary for feather morphology.

Hypokalaemia: common things occur commonly - a retrospective survey.

OBJECTIVES: To define the causes of hypokalaemia in an unselected adult population. DESIGN: Retrospective survey of biochemistry database. SETTING: District general hospital in southwest Scotland. PARTICIPANTS AND MAIN OUTCOME MEASURES: There were 187,704 measurements of urea and electrolytes in 2010. Sixty-one patients had serum potassium <2.5 mmol/L on at least one occasion. RESULTS: Average age of the patients was 71 (range 33-99) years. The most common causes were diarrhoea and/or vomiting (51% of cases), diuretic therapy (47%), nutritional causes including poor dietary intake, re-feeding syndrome and inadequate potassium supplementation when patients were nil by mouth (37%). In 25% of patients a transient and profound fall in serum potassium appeared to coincide with their acute illness. Acute alcohol intoxication and/or alcohol withdrawal were prominent features in 11% of patients. More than one cause was commonly present. There were no cases of Bartter's, Gitelman's or Liddle's syndromes or of hypokalaemic periodic paralysis in this study. CONCLUSIONS: Severe hypokalaemia <2.5 mmol/L occurs at least once a week in a district general hospital with a catchment population of around 150,000, suggesting there may be around 300 cases a week in the UK (population around 50,000,000). Diuretics, vomiting and diarrhoea are commonly implicated as are nutritional causes, acute illness and alcohol. Bartter's, Gitelman's, Liddle's syndrome and hypokalaemic period paralysis are all extremely uncommon.

Tuberculosis and HIV infection: the global setting.

Tuberculosis (TB) and human immunodeficiency virus (HIV) infection make each other's control significantly more difficult. Coordination in addressing this "cursed duet" is insufficient at both global and national levels. However, global policy for TB/HIV coordination has been set, and there is consensus around this policy from both the TB and HIV control communities. The policy aims to provide all necessary care for the prevention and management of HIV-associated TB, but its implementation is hindered by real technical difficulties and shortages of resources. All major global-level institutions involved in HIV care and prevention must include TB control as part of their corporate policy. Country-level decision makers need to work together to expand both TB and HIV services, and civil society and community representatives need to hold those responsible accountable for their delivery. The TB and HIV communities should join forces to address the health-sector weaknesses that confront them both.

Planning to improve global health: the next decade of tuberculosis control.

The Global Plan to Stop TB 2006-2015 is a road map for policy-makers and managers of national programmes. It sets out the key actions needed to achieve the targets of the Millennium Development Goals relating to tuberculosis (TB): to halve the prevalence and deaths by 2015 relative to 1990 levels and to save 14 million lives. Developed by a broad coalition of partners, the plan presents a model approach combining interventions that can feasibly be supplied on the ground. The main areas of activity set out in the plan are: scaling up interventions to control tuberculosis; promoting the research and development of improved diagnostics, drugs and vaccines; and engaging in related activities for advocacy, communications and social mobilization. Scenarios for the planning process were developed; these looked at issues both globally and in seven epidemiological regions. The scenarios made ambitious but realistic assumptions about the pace of scale-up and implementation coverage of the activities. A mathematical model was used to estimate the impact of scaling up current interventions based on data from studies of tuberculosis biology and from experience with tuberculosis control in diverse settings. The estimated costs of the activities set out in the Global Plan were based on implementing interventions and researching and developing drugs, diagnostics and vaccines; these costs were US$ 56 billion over 10 years. When translated into cost per disability adjusted life year averted, these costs compare favourably with those of other public health interventions. This approach to planning for global tuberculosis control is a valuable example of developing plans to improve global health that has relevance for other health issues.

Trends in adult medical admissions in a rural South African hospital between 1991 and 2002.

South Africa is one of the countries most severely affected by the global HIV/AIDS pandemic. The effects of increased numbers of sick patients on rural district hospitals are not well documented. This study summarizes the changes in number and type of hospital admissions to the medical wards of a small rural district hospital in Northern KwaZulu/Natal, South Africa, between 1991 and 2002. For the same 2-month period, across the study period total admissions rose by 228 to 626 patients with no increase in hospital staff or capacity. Length of inpatient stay fell from 10.9 to 7.9 days, and inpatient mortality rose from 8% to 20%. The median age of female patients fell from 50 to 34 years, and the median male patient's age fell from 45 from 39 years over the study period. After 1991, tuberculosis became the most frequent diagnosis, and in 2002 it was the leading cause of death. The HIV epidemic has increased the number of medical hospital admissions, primarily infectious diseases such as tuberculosis, lower respiratory infection, and diarrheal illness. Comprehensive strategies are needed to reduce the community burden of disease and minimize the impact of HIV on the health services.

Clonal analysis of patterns of growth, stem cell activity, and cell movement during the development and maintenance of the murine corneal epithelium.

Patterns of growth and cell movement in the developing and adult corneal epithelium were investigated by analysing clonal patches of LacZ-expressing cells in chimeric and X-inactivation mosaic mice. It was found that cell proliferation throughout the basal corneal epithelium during embryogenesis and early postnatal life creates a disordered mosaic pattern of LacZ(+) clones that contrasts with patterns of proliferation and striping produced during the later embryonic stages of retinal pigmented epithelium development. The early mosaic pattern in the corneal epithelium is replaced in the first 12 postnatal weeks by an ordered pattern of radial stripes or sectors that reflects migration without mixing of the progeny of clones of limbal stem cells. In contrast to previous assumptions, it was found that maturation of the activity of limbal stem cells and the pattern of migration of their progeny are delayed for several weeks postnatally. No evidence was found for immigration of the progeny of stem cells until the 5th postnatal week. There are approximately 100 clones of limbal stem cells initially, and clones are lost during postnatal life. Our studies provide a new assay for limbal and corneal defects in mutant mice.