Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?

Medscape

BACKGROUND: The increasing global burden of tuberculosis (TB) is linked to human immunodeficiency virus (HIV) infection. METHODS: We reviewed data from notifications of TB cases, cohort treatment outcomes, surveys of Mycobacterium tuberculosis infection, and HIV prevalence in patients with TB and other subgroups. Information was collated from published literature and databases held by the World Health Organization (WHO), the Joint United Nations Programme on HIV/Acquired Immunodeficiency Syndrome (UNAIDS), the US Census Bureau, and the US Centers for Disease Control and Prevention. RESULTS: There were an estimated 8.3 million (5th-95th centiles, 7.3-9.2 million) new TB cases in 2000 (137/100,000 population; range, 121/100,000-151/100,000). Tuberculosis incidence rates were highest in the WHO African Region (290/100,000 per year; range, 265/100,000-331/100,000), as was the annual rate of increase in the number of cases (6%). Nine percent (7%-12%) of all new TB cases in adults (aged 15-49 years) were attributable to HIV infection, but the proportion was much greater in the WHO African Region (31%) and some industrialized countries, notably the United States (26%). There were an estimated 1.8 million (5th-95th centiles, 1.6-2.2 million) deaths from TB, of which 12% (226 000) were attributable to HIV. Tuberculosis was the cause of 11% of all adult AIDS deaths. The prevalence of M tuberculosis-HIV coinfection in adults was 0.36% (11 million people). Coinfection prevalence rates equaled or exceeded 5% in 8 African countries. In South Africa alone there were 2 million coinfected adults. CONCLUSIONS: The HIV pandemic presents a massive challenge to global TB control. The prevention of HIV and TB, the extension of WHO DOTS programs, and a focused effort to control HIV-related TB in areas of high HIV prevalence are matters of great urgency.

https://jamanetwork.com/journals/jamainternalmedicine/articlepdf/215525/ira20017.pdf

The growing burden of tuberculosis: global trends and interactions with the HIV epidemic.

Malaria presents a diagnostic challenge to laboratories in most countries. Endemic malaria, population movements, and travelers all contribute to presenting the laboratory with diagnostic problems for which it may have little expertise available. Drug resistance and genetic variation has altered many accepted morphological appearances of malaria species, and new technology has given an opportunity to review available procedures. Concurrently the World Health Organization has opened a dialogue with scientists, clinicians, and manufacturers on the realistic possibilities for developing accurate, sensitive, and cost-effective rapid diagnostic tests for malaria, capable of detecting 100 parasites/microl from all species and with a semiquantitative measurement for monitoring successful drug treatment. New technology has to be compared with an accepted "gold standard" that makes comparisons of sensitivity and specificity between different methods. The majority of malaria is found in countries where cost-effectiveness is an important factor and ease of performance and training is a major consideration. Most new technology for malaria diagnosis incorporates immunochromatographic capture procedures, with conjugated monoclonal antibodies providing the indicator of infection. Preferred targeted antigens are those which are abundant in all asexual and sexual stages of the parasite and are currently centered on detection of HRP-2 from Plasmodium falciparum and parasite-specific lactate dehydrogenase or Plasmodium aldolase from the parasite glycolytic pathway found in all species. Clinical studies allow effective comparisons between different formats, and the reality of nonmicroscopic diagnoses of malaria is considered.

Rapid Diagnostic Tests for Malaria Parasites

https://www.cell.com/cell-host-microbe/pdf/S1931-3128(13)00152-2.pdf

Iron in Infection and Immunity

https://link.springer.com/content/pdf/10.1007%2Fs10156-009-0669-9.pdf

Loop-mediated isothermal amplification (LAMP): a rapid, accurate, and cost-effective diagnostic method for infectious diseases

Malaria causes significant morbidity and mortality worldwide, including countries with mainly imported malaria. In developing nations, scarce resources lead to inadequate diagnostic procedures. In affluent countries, poor familiarity with malaria may cause clinical and laboratory misdiagnosis. Microscopy of Giemsa-stained thick and thin films remains the current standard for diagnosis. Although it has good sensitivity and allows species identification and parasite counts, it is time consuming, requires microscopical expertise and maintenance of equipment. Microscopy with fluorescent stains (QBC), dipstick antigen detection of HRP2 and pLDH (Parasight-F, ICT Malaria Pf, OptiMAL), polymerase chain reaction assays and some automated blood cell analysers offer new approaches and are reviewed here, with emphasis on clinical relevance and their potential to complement conventional microscopy, especially in countries with imported malaria.

Diagnosis of malaria: a review of alternatives to conventional microscopy.

How useful is PCR in the diagnosis of malaria

Plasmodium spp produce a pigment (haemozoin) to detoxify the free haem that is generated by haemoglobin degradation. Haemozoin was originally thought to be an inert waste byproduct of the parasite. However, recent research has led to the recognition that haemozoin is possibly of great importance in various aspects of malaria. Haemozoin is the target of many antimalarial drugs, and the unravelling of the exact modes of action may allow the design of novel antimalarial compounds. The detection of haemozoin in erythrocytes or leucocytes facilitates the diagnosis of malaria. The number of haemozoin-containing monocytes and granulocytes has been shown to correlate well with disease severity and may hold the potential for becoming a novel, automated laboratory marker in the assessment of patients. Finally, haemozoin has a substantial effect on the immune system. Further research is needed to clarify these aspects, many of which are important in clinical practice.

https://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(07)70238-4.pdf

Haemozoin: from melatonin pigment to drug target, diagnostic tool, and immune modulator

Objective: To examine differences in progression to AIDS and death between HIV-1-positive Africans (most infected in sub-Saharan Africa and therefore with non-B subtypes) and HIV-I-positive non-Africans in London.Design: Retrospective cohort study of 2048 HIV-1-positive individuals.Setting: HIV-l-infected individuals attending 11 of the largest HIV/AIDS units in London.Patients: Subjects were 1056 Africans and 992 non-Africans seen between 1982-1995.Results: There were no differences in crude survival from presentation to death between Africans and non-Africans (median 82 and 78 months, respectively; P = 0.22). Africans progressed more rapidly to AIDS [hazard ratio (HR), 1.21; 95% confidence interval (CI), 1.02-1.45] but after adjustment for age, sex, Centers for Disease Control and Prevention category B symptoms and CD4+ lymphocyte count at presentation, year of HIV diagnosis and hospital attended, this difference was no longer significant (adjusted HR, 1.15; 95% CI, 0.93-1.43). Africans with AIDS had a reduced risk of death compared with non-Africans (HR, 0.78; 95% CI, 0.63-0.96) but not after adjustment for age, CD4+ lymphocyte count at AIDS, initial AIDS-defining conditions (ADC) and hospital attended (HR, 0.98; 95% CI, 0.76-1.27). Tuberculosis as the first ADC was associated with a 64% reduction in the risk of death. CD4+ lymphocyte decline was not significantly different between Africans and non-Africans (P = 0.18).Conclusions: Differences in progression to AIDS and death and CD4+ lymphocyte decline between HIV-l-infected Africans and non-Africans in London could not be attributed to ethnicity or different viral subtypes. Age and the clinical and immunological stage at presentation, or AIDS, were the major determinants of outcome. Compared with other diagnoses, tuberculosis as the initial ADC was associated with increased survival. Lack of access to health care and exposure to environmental pathogens are the most likely causes of reduced survival with AIDS in Africa, rather than inherently different rates of progression of immune deficiency due to racial differences or viral subtypes. (C) 1998 Lippincott-Raven Publishers.

Thomas Hänscheid

Papers

Diagnosis of malaria: a review of alternatives to conventional microscopy.

How useful is PCR in the diagnosis of malaria

Haemozoin: from melatonin pigment to drug target, diagnostic tool, and immune modulator

Disease progression and survival in HIV-1-infected Africans in London.

Current strategies to avoid misdiagnosis of malaria.