Hospital for Tropical Diseases

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.

Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barré syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms that will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.

BACKGROUND: Patients with highly drug-resistant forms of tuberculosis have limited treatment options and historically have had poor outcomes. METHODS: In an open-label, single-group study in which follow-up is ongoing at three South African sites, we investigated treatment with three oral drugs - bedaquiline, pretomanid, and linezolid - that have bactericidal activity against tuberculosis and to which there is little preexisting resistance. We evaluated the safety and efficacy of the drug combination for 26 weeks in patients with extensively drug-resistant tuberculosis and patients with multidrug-resistant tuberculosis that was not responsive to treatment or for which a second-line regimen had been discontinued because of side effects. The primary end point was the incidence of an unfavorable outcome, defined as treatment failure (bacteriologic or clinical) or relapse during follow-up, which continued until 6 months after the end of treatment. Patients were classified as having a favorable outcome at 6 months if they had resolution of clinical disease, a negative culture status, and had not already been classified as having had an unfavorable outcome. Other efficacy end points and safety were also evaluated. RESULTS: A total of 109 patients were enrolled in the study and were included in the evaluation of efficacy and safety end points. At 6 months after the end of treatment in the intention-to-treat analysis, 11 patients (10%) had an unfavorable outcome and 98 patients (90%; 95% confidence interval, 83 to 95) had a favorable outcome. The 11 unfavorable outcomes were 7 deaths (6 during treatment and 1 from an unknown cause during follow-up), 1 withdrawal of consent during treatment, 2 relapses during follow-up, and 1 loss to follow-up. The expected linezolid toxic effects of peripheral neuropathy (occurring in 81% of patients) and myelosuppression (48%), although common, were manageable, often leading to dose reductions or interruptions in treatment with linezolid. CONCLUSIONS: The combination of bedaquiline, pretomanid, and linezolid led to a favorable outcome at 6 months after the end of therapy in a high percentage of patients with highly drug-resistant forms of tuberculosis; some associated toxic effects were observed. (Funded by the TB Alliance and others; ClinicalTrials.gov number, NCT02333799.).

BACKGROUND: In May, 2022, several European countries reported autochthonous cases of monkeypox, which rapidly spread globally. Early reports suggest atypical presentations. We aimed to investigate clinical and virological characteristics of cases of human monkeypox in Spain. METHODS: This multicentre, prospective, observational cohort study was done in three sexual health clinics in Madrid and Barcelona, Spain. We enrolled all consecutive patients with laboratory-confirmed monkeypox from May 11 to June 29, 2022. Participants were offered lesion, anal, and oropharynx swabs for PCR testing. Participant data were collected by means of interviews conducted by dermatologists or specialists in sexually transmitted infections and were recorded using a standard case report form. Outcomes assessed in all participants with a confirmed diagnosis were demographics, smallpox vaccination, HIV status, exposure to someone with monkeypox, travel, mass gathering attendance, risk factors for sexually transmitted infections, sexual behaviour, signs and symptoms on first presentation, virological results at multiple body sites, co-infection with other sexually transmitted pathogens, and clinical outcomes 14 days after the initial presentation. Clinical outcomes were followed up until July 13, 2022. FINDINGS: 181 patients had a confirmed monkeypox diagnosis and were enrolled in the study. 166 (92%) identified as gay men, bisexual men, or other men who have sex with men (MSM) and 15 (8%) identified as heterosexual men or heterosexual women. Median age was 37·0 years (IQR 31·0-42·0). 32 (18%) patients reported previous smallpox vaccination, 72 (40%) were HIV-positive, eight (11%) had a CD4 cell count less than 500 cells per μL, and 31 (17%) were diagnosed with a concurrent sexually transmitted infection. Median incubation was 7·0 days (IQR 5·0-10·0). All participants presented with skin lesions; 141 (78%) participants had lesions in the anogenital region, and 78 (43%) in the oral and perioral region. 70 (39%) participants had complications requiring treatment: 45 (25%) had a proctitis, 19 (10%) had tonsillitis, 15 (8%) had penile oedema, six (3%) an abscess, and eight (4%) had an exanthem. Three (2%) patients required hospital admission. 178 (99%) of 180 swabs from skin lesions collected tested positive, as did 82 (70%) of 117 throat swabs. Viral load was higher in lesion swabs than in pharyngeal specimens (mean cycle threshold value 23 [SD 4] vs 32 [6], absolute difference 9 [95% CI 8-10]; p<0·0001). 108 (65%) of 166 MSM reported anal-receptive sex. MSM who engaged in anal-receptive sex presented with proctitis (41 [38%] of 108 vs four [7%] of 58, absolute difference 31% [95% CI 19-44]; p<0·0001) and systemic symptoms before the rash (67 [62%] vs 16 [28%], absolute difference 34% [28-62]; p<0·0001) more frequently than MSM who did not engage in anal-receptive sex. 18 (95%) of 19 participants with tonsillitis reported practising oral-receptive sex. The median time from onset of lesions to formation of a dry crust was 10 days (IQR 7-13). INTERPRETATION: In our cohort, monkeypox caused genital, perianal, and oral lesions and complications including proctitis and tonsillitis. Because of the variability of presentations, clinicians should have a low threshold for suspicion of monkeypox. Lesion swabs showed the highest viral loads, which, combined with the history of sexual exposure and the distribution of lesions, suggests close contact is probably the dominant transmission route in the current outbreak. FUNDING: None.

BACKGROUND: The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. METHODS: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9-6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40-59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. INTERPRETATION: We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. FUNDING: UK Research and Innovation and National Institute for Health Research.

ABSTRACT Antibiotic resistance is a major problem in Salmonella enterica serovar Typhi, the causative agent of typhoid. Multidrug-resistant (MDR) isolates are prevalent in parts of Asia and Africa and are often associated with the dominant H58 haplotype. Reduced susceptibility to fluoroquinolones is also widespread, and sporadic cases of resistance to third-generation cephalosporins or azithromycin have also been reported. Here, we report the first large-scale emergence and spread of a novel S . Typhi clone harboring resistance to three first-line drugs (chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole) as well as fluoroquinolones and third-generation cephalosporins in Sindh, Pakistan, which we classify as extensively drug resistant (XDR). Over 300 XDR typhoid cases have emerged in Sindh, Pakistan, since November 2016. Additionally, a single case of travel-associated XDR typhoid has recently been identified in the United Kingdom. Whole-genome sequencing of over 80 of the XDR isolates revealed remarkable genetic clonality and sequence conservation, identified a large number of resistance determinants, and showed that these isolates were of haplotype H58. The XDR S . Typhi clone encodes a chromosomally located resistance region and harbors a plasmid encoding additional resistance elements, including the bla CTX-M-15 extended-spectrum β-lactamase, and carrying the qnrS fluoroquinolone resistance gene. This antibiotic resistance-associated IncY plasmid exhibited high sequence identity to plasmids found in other enteric bacteria isolated from widely distributed geographic locations. This study highlights three concerning problems: the receding antibiotic arsenal for typhoid treatment, the ability of S . Typhi to transform from MDR to XDR in a single step by acquisition of a plasmid, and the ability of XDR clones to spread globally. IMPORTANCE Typhoid fever is a severe disease caused by the Gram-negative bacterium Salmonella enterica serovar Typhi. Antibiotic-resistant S . Typhi strains have become increasingly common. Here, we report the first large-scale emergence and spread of a novel extensively drug-resistant (XDR) S . Typhi clone in Sindh, Pakistan. The XDR S . Typhi is resistant to the majority of drugs available for the treatment of typhoid fever. This study highlights the evolving threat of antibiotic resistance in S . Typhi and the value of antibiotic susceptibility testing and whole-genome sequencing in understanding emerging infectious diseases. We genetically characterized the XDR S . Typhi to investigate the phylogenetic relationship between these isolates and a global collection of S . Typhi isolates and to identify multiple genes linked to antibiotic resistance. This S . Typhi clone harbored a promiscuous antibiotic resistance plasmid previously identified in other enteric bacteria. The increasing antibiotic resistance in S . Typhi observed here adds urgency to the need for typhoid prevention measures.

BACKGROUND: Malaria rapid diagnostic tests (RDTs) offer significant potential to improve the diagnosis of malaria, and are playing an increasing role in malaria case management, control and elimination. Peru, along with other South American countries, is moving to introduce malaria RDTs as components of malaria control programmes supported by the Global Fund for AIDS, TB and malaria. The selection of the most suitable malaria RDTs is critical to the success of the programmes. METHODS: Eight of nine microscopy positive P. falciparum samples collected in Iquitos, Peru tested negative or weak positive using HRP2-detecting RDTs. These samples were tested for the presence of pfhrp2 and pfhrp3 and their flanking genes by PCR, as well as the presence of HRP proteins by ELISA. To investigate for geographic extent of HRP-deleted parasites and their temporal occurrence a retrospective study was undertaken on 148 microscopy positive P. falciparum samples collected in different areas of the Amazon region of Peru. FINDINGS: Eight of the nine isolates lacked the pfhrp2 and/or pfhrp3 genes and one or both flanking genes, and the absence of HRP was confirmed by ELISA. The retrospective study showed that 61 (41%) and 103 (70%) of the 148 samples lacked the pfhrp2 or pfhrp3 genes respectively, with 32 (21.6%) samples lacking both hrp genes. CONCLUSIONS: This is the first documentation of P. falciparum field isolates lacking pfhrp2 and/or pfhrp3. The high frequency and wide distribution of different parasites lacking pfhrp2 and/or pfhrp3 in widely dispersed areas in the Peruvian Amazon implies that malaria RDTs targeting HRP2 will fail to detect a high proportion of P. falciparum in malaria-endemic areas of Peru and should not be used. RDTs detecting parasite LDH or aldolase and quality microscopy should be use for malaria diagnosis in this region. There is an urgent need for investigation of the abundance and geographic distribution of these parasites in Peru and neighbouring countries.

BACKGROUND: Efficient allocation of resources to intervene against malaria requires a detailed understanding of the contemporary spatial distribution of malaria risk. It is exactly 40 y since the last global map of malaria endemicity was published. This paper describes the generation of a new world map of Plasmodium falciparum malaria endemicity for the year 2007. METHODS AND FINDINGS: A total of 8,938 P. falciparum parasite rate (PfPR) surveys were identified using a variety of exhaustive search strategies. Of these, 7,953 passed strict data fidelity tests for inclusion into a global database of PfPR data, age-standardized to 2-10 y for endemicity mapping. A model-based geostatistical procedure was used to create a continuous surface of malaria endemicity within previously defined stable spatial limits of P. falciparum transmission. These procedures were implemented within a Bayesian statistical framework so that the uncertainty of these predictions could be evaluated robustly. The uncertainty was expressed as the probability of predicting correctly one of three endemicity classes; previously stratified to be an informative guide for malaria control. Population at risk estimates, adjusted for the transmission modifying effects of urbanization in Africa, were then derived with reference to human population surfaces in 2007. Of the 1.38 billion people at risk of stable P. falciparum malaria, 0.69 billion were found in Central and South East Asia (CSE Asia), 0.66 billion in Africa, Yemen, and Saudi Arabia (Africa+), and 0.04 billion in the Americas. All those exposed to stable risk in the Americas were in the lowest endemicity class (PfPR2-10 < or = 5%). The vast majority (88%) of those living under stable risk in CSE Asia were also in this low endemicity class; a small remainder (11%) were in the intermediate endemicity class (PfPR2-10 > 5 to < 40%); and the remaining fraction (1%) in high endemicity (PfPR2-10 > or = 40%) areas. High endemicity was widespread in the Africa+ region, where 0.35 billion people are at this level of risk. Most of the rest live at intermediate risk (0.20 billion), with a smaller number (0.11 billion) at low stable risk. CONCLUSIONS: High levels of P. falciparum malaria endemicity are common in Africa. Uniformly low endemic levels are found in the Americas. Low endemicity is also widespread in CSE Asia, but pockets of intermediate and very rarely high transmission remain. There are therefore significant opportunities for malaria control in Africa and for malaria elimination elsewhere. This 2007 global P. falciparum malaria endemicity map is the first of a series with which it will be possible to monitor and evaluate the progress of this intervention process.

BACKGROUND: A century after its discovery, Chagas disease still represents a major neglected tropical threat. Accurate diagnostics tools as well as surrogate markers of parasitological response to treatment are research priorities in the field. The purpose of this study was to evaluate the performance of PCR methods in detection of Trypanosoma cruzi DNA by an external quality evaluation. METHODOLOGY/FINDINGS: An international collaborative study was launched by expert PCR laboratories from 16 countries. Currently used strategies were challenged against serial dilutions of purified DNA from stocks representing T. cruzi discrete typing units (DTU) I, IV and VI (set A), human blood spiked with parasite cells (set B) and Guanidine Hidrochloride-EDTA blood samples from 32 seropositive and 10 seronegative patients from Southern Cone countries (set C). Forty eight PCR tests were reported for set A and 44 for sets B and C; 28 targeted minicircle DNA (kDNA), 13 satellite DNA (Sat-DNA) and the remainder low copy number sequences. In set A, commercial master mixes and Sat-DNA Real Time PCR showed better specificity, but kDNA-PCR was more sensitive to detect DTU I DNA. In set B, commercial DNA extraction kits presented better specificity than solvent extraction protocols. Sat-DNA PCR tests had higher specificity, with sensitivities of 0.05-0.5 parasites/mL whereas specific kDNA tests detected 5.10(-3) par/mL. Sixteen specific and coherent methods had a Good Performance in both sets A and B (10 fg/µl of DNA from all stocks, 5 par/mL spiked blood). The median values of sensitivities, specificities and accuracies obtained in testing the Set C samples with the 16 tests determined to be good performing by analyzing Sets A and B samples varied considerably. Out of them, four methods depicted the best performing parameters in all three sets of samples, detecting at least 10 fg/µl for each DNA stock, 0.5 par/mL and a sensitivity between 83.3-94.4%, specificity of 85-95%, accuracy of 86.8-89.5% and kappa index of 0.7-0.8 compared to consensus PCR reports of the 16 good performing tests and 63-69%, 100%, 71.4-76.2% and 0.4-0.5, respectively compared to serodiagnosis. Method LbD2 used solvent extraction followed by Sybr-Green based Real time PCR targeted to Sat-DNA; method LbD3 used solvent DNA extraction followed by conventional PCR targeted to Sat-DNA. The third method (LbF1) used glass fiber column based DNA extraction followed by TaqMan Real Time PCR targeted to Sat-DNA (cruzi 1/cruzi 2 and cruzi 3 TaqMan probe) and the fourth method (LbQ) used solvent DNA extraction followed by conventional hot-start PCR targeted to kDNA (primer pairs 121/122). These four methods were further evaluated at the coordinating laboratory in a subset of human blood samples, confirming the performance obtained by the participating laboratories. CONCLUSION/SIGNIFICANCE: This study represents a first crucial step towards international validation of PCR procedures for detection of T. cruzi in human blood samples.

BACKGROUND: Acyclovir given for 7 to 10 days is of proved benefit in acute herpes zoster, but studies of its effectiveness in preventing postherpetic neuralgia have had conflicting results. The role of corticosteroids in the treatment of herpes zoster is also controversial. METHODS: We conducted a double-blind, controlled trial in patients with acute herpes zoster to determine whether either 21 days of acyclovir therapy or the addition of prednisolone offered any improvement over 7 days of acyclovir therapy. Patients with a rash of less than 72 hours' duration were assigned to receive acyclovir (800 mg orally, five times daily) for 7 days with either prednisolone or placebo, or acyclovir for 21 days with either prednisolone or placebo. Prednisolone therapy was initiated at a dose of 40 mg per day and tapered over a three-week period. Patients were assessed frequently through day 28 and then monthly through month 6 to assess postherpetic neuralgia. RESULTS: Of 400 patients recruited, 349 completed the study. No significant differences were detected between the four groups in the progression of the rash (P > 0.1). With steroid therapy, a significantly higher proportion of the rash area had healed on days 7 and 14 (P = 0.02). Pain reduction was greater during the acute phase of disease in patients treated with steroids or 21 days of acyclovir (P < 0.01 and P = 0.02, respectively, on day 7; P < 0.01 for steroid therapy on day 14). However, on follow-up there were no significant differences between any of the groups in the time to a first or a complete cessation of pain. The steroid recipients reported more adverse events. CONCLUSIONS: In acute herpes zoster, treatment with acyclovir for 21 days or the addition of prednisolone to acyclovir therapy confers only slight benefits over standard 7-day treatment with acyclovir. Neither additional treatment reduces the frequency of postherpetic neuralgia.

Clinical management of cystic echinococcosis (CE) has evolved over decades without adequate evaluation of important features such as efficacy, effectiveness, rate of adverse reactions, relapse rate, and cost. CE occurs in health care environments as different as Europe/North America and resource-poor countries of the South and the East. This creates setting-specific problems in the management of patients. Furthermore, studies carried out in either of the two fundamentally different environments lack external validity, i.e., results obtained in one setting may be different from those in the other and practices that can work in one may not be applicable to the other. In this paper, we review the current management procedures of CE with particular emphasis on the evidence base and setting-specific problems.

BACKGROUND: Strongyloidiasis is frequently under diagnosed since many infections remain asymptomatic and conventional diagnostic tests based on parasitological examination are not sufficiently sensitive. Serology is useful but is still only available in reference laboratories. The need for improved diagnostic tests in terms of sensitivity and specificity is clear, particularly in immunocompromised patients or candidates to immunosuppressive treatments. This review aims to evaluate both conventional and novel techniques for the diagnosis of strongyloidiasis as well as available cure markers for this parasitic infection. METHODOLOGY/PRINCIPAL FINDINGS: The search strategy was based on the data-base sources MEDLINE, Cochrane Library Register for systematic review, EmBase, Global Health and LILACS and was limited in the search string to articles published from 1960 to August 2012 and to English, Spanish, French, Portuguese and German languages. Case reports, case series and animal studies were excluded. 2003 potentially relevant citations were selected for retrieval, of which 1649 were selected for review of the abstract. 143 were eligible for final inclusion. CONCLUSIONS: Sensitivity of microscopic-based techniques is not good enough, particularly in chronic infections. Furthermore, techniques such as Baermann or agar plate culture are cumbersome and time-consuming and several specimens should be collected on different days to improve the detection rate. Serology is a useful tool but it might overestimate the prevalence of disease due to cross-reactivity with other nematode infections and its difficulty distinguishing recent from past (and cured) infections. To evaluate treatment efficacy is still a major concern because direct parasitological methods might overestimate it and the serology has not yet been well evaluated; even if there is a decline in antibody titres after treatment, it is slow and it needs to be done at 6 to 12 months after treatment which can cause a substantial loss to follow-up in a clinical trial.

Journal Article John Snow: Anaesthetist to a queen and epidemiologist to a nation. A biography. D. A. E. Shephard, Cornwall, PE, Canada: York Point Publishing, 1995. 374 pp. Price not known. ISBN 1-57087-103-5 Get access John Snow: Anaesthetist to a queen and epidemiologist to a nation. A biography. Shephard D. A. E., Cornwall, PE, Canada: York Point Publishing, 1995. 374 pp. Price not known. ISBN 1-57087-103-5. G.C. Cook G.C. Cook Hospital for Tropical Diseases St Pancras Way London, NW1 0PE, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Transactions of The Royal Society of Tropical Medicine and Hygiene, Volume 90, Issue 5, September-October 1996, Page 592, https://doi.org/10.1016/S0035-9203(96)90349-1 Published: 01 September 1996

Because of turnover, protein synthesis and breakdown can each be involved in the regulation of the growth of tissue protein. To investigate the regulation of skeletal-muscle-protein growth we measured rates of protein synthesis and breakdown in growing rats during development on a good diet, during development on a marginally low-protein diet and during rehabilitation on a good diet after a period of severe protein deficiency. Rates of protein synthesis were measured in vivo with a constant intravenous infusion of [14C]tyrosine. The growth rate of muscle protein was measured and the rate of breakdown calculated as breakdown rate=synthesis rate-growth rate. These measurements showed that during development on a good diet there was a fall with age in the rate of protein synthesis resulting from a fall in capacity (RNA concentration) and activity (synthesis rate per unit of RNA). There was a fall with age in the breakdown rate so that the rate was highest in the weaning rats, with a half-life of 3 days. There was a direct correlation between the fractional growth and breakdown rates. During rehabilitation on the good diet, rapid growth was also accompanied by high rates of protein breakdown. During growth on the inadequate diet protein synthesis rates were lesss than in controls, but growth occurred because of decreased rates of protein breakdown. This compression was not complete, however, since ultimate muscle size was only one-half that of controls. It is suggested that increased rates of protein breakdown are a necessary accompaniment to muscle growth and may result from the way in which myofibrils proliferate.

The effects of growth-suppressing and muscle-wasting treatments on muscle protein turnover and amino acid concentrations were determined in vivo. All treatments depressed protein synthesis and some treatments depressed protein breakdown. Only prolonged starvation increased protein breakdown. Muscle protein mass is regulated primarily through alterations in protein synthesis in all except emergency conditions. The increased concentrations of the branched-chain amino acids indicate that they are unlikely to be involved in this regulation.

Health is central to the development of any country. Nigeria’s gross domestic product is the largest in Africa, but its per capita income of about ₦770 000 (US$2000) is low with a highly inequitable distribution of income, wealth, and therefore, health. It is a picture of poverty amidst plenty. Nigeria is both a wealthy country and a very poor one. About 40% of Nigerians live in poverty, in social conditions that create ill health, and with the ever-present risk of catastrophic expenditures from high out-of-pocket spending for health. Even compared with countries of similar income levels in Africa, Nigeria’s population health outcomes are poor, with national statistics masking drastic differences between rich and poor, urban and rural populations, and different regions.

BACKGROUND: Scabies is a common parasitic skin condition that causes considerable morbidity globally. Clinical and epidemiological research for scabies has been limited by a lack of standardization of diagnostic methods. OBJECTIVES: To develop consensus criteria for the diagnosis of common scabies that could be implemented in a variety of settings. METHODS: Consensus diagnostic criteria were developed through a Delphi study with international experts. Detailed recommendations were collected from the expert panel to define the criteria features and guide their implementation. These comments were then combined with a comprehensive review of the available literature and the opinion of an expanded group of international experts to develop detailed, evidence-based definitions and diagnostic methods. RESULTS: The 2020 International Alliance for the Control of Scabies (IACS) Consensus Criteria for the Diagnosis of Scabies include three levels of diagnostic certainty and eight subcategories. Confirmed scabies (level A) requires direct visualization of the mite or its products. Clinical scabies (level B) and suspected scabies (level C) rely on clinical assessment of signs and symptoms. Evidence-based, consensus methods for microscopy, visualization and clinical symptoms and signs were developed, along with a media library. CONCLUSIONS: The 2020 IACS Criteria represent a pragmatic yet robust set of diagnostic features and methods. The criteria may be implemented in a range of research, public health and clinical settings by selecting the appropriate diagnostic levels and subcategories. These criteria may provide greater consistency and standardization for scabies diagnosis. Validation studies, development of training materials and development of survey methods are now required. What is already known about this topic? The diagnosis of scabies is limited by the lack of accurate, objective tests. Microscopy of skin scrapings can confirm the diagnosis, but it is insensitive, invasive and often impractical. Diagnosis usually relies on clinical assessment, although visualization using dermoscopy is becoming increasingly common. These diagnostic methods have not been standardized, hampering the interpretation of findings from clinical research and epidemiological surveys, and the development of scabies control strategies. What does this study add? International consensus diagnostic criteria for common scabies were developed through a Delphi study with global experts. The 2020 International Alliance for the Control of Scabies (IACS) Criteria categorize diagnosis at three levels of diagnostic certainty (confirmed, clinical and suspected scabies) and eight subcategories, and can be adapted to a range of research and public health settings. Detailed definitions and figures are included to aid training and implementation. The 2020 IACS Criteria may facilitate the standardization of scabies diagnosis.

More than one century later, the key issues regarding this parasite (subsequently renamed Strongyloides stercoralis) are essentially the same, and although researchers have recently given more attention to this infection, systematic action plans still lag behind. There is widespread agreement in the scientific community that its prevalence is largely underestimated [2]. The current estimate of 30 to 100 million infected persons in the world dates back to review articles published between 1989 and 1996 [3], [4], and is cited by most subsequent papers. These figures were mostly based on surveys aimed at defining the prevalence of parasitic infections, without using adequate diagnostic techniques for S. stercoralis. For example, Kato-Katz, a technique that is commonly used in surveys aiming to assess intestinal helminth infections [5], is poorly sensitive for this parasite. Larvae of S. stercoralis in stool are often scanty, and therefore they are most often missed by this technique that examines a small amount of faeces (between 20 and 50 mg, depending on the template). Larvae can be detected by this technique only occasionally, when the larval output is particularly high [6]. More reliable prevalence estimates have been made by geographically confined surveys, using alternative faecal-based diagnostic methods that are much more sensitive such as Baermann or Koga agar plate culture [7], [8]. Serology (ELISA or IFAT) is even more sensitive, but its specificity is less well defined. Problems of cross-reactivity seem to arise especially in areas where other nematodes, particularly filariae, are also endemic. New and promising tools such as serologic methods based on recombinant antigens or PCR are also available in some referral centers. However, the optimal diagnostic strategy, both for epidemiological surveys and for individual diagnosis and screening, has yet to be defined and certainly deserves further research

Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29 - 9.78, P < 0.001) and increased pfmdr1 copy number (adjusted hazards ratio = 6.52, 95% confidence interval = 2.36-17.97, P < 0.001 : were significant independent risk factors for recrudescence in patients treated with AL. AL and ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in pfcrt and pfmdr1. Monitoring selection and responding to emerging signs of drug resistance are critical tools for preserving efficacy of artemisinin combination therapies; determination of the prevalence of at least pfcrt K76T and pfmdr1 N86Y should now be routine.

A study of aggregate data collected from the literature and official sources was undertaken to estimate expected and observed prevalence of Trypanosoma cruzi infection, annual incidence of congenital transmission and rate of underdiagnosis of Chagas disease among Latin American migrants in the nine European countries with the highest prevalence of Chagas disease. Formal and informal data sources were used to estimate the population from endemic countries resident in Europe in 2009, diagnosed cases of Chagas disease and births from mothers originating from endemic countries. By 2009, 4,290 cases had been diagnosed in Europe, compared with an estimated 68,000 to 122,000 expected cases. The expected prevalence was very high in undocumented migrants (on average 45% of total expected cases) while the observed prevalence rate was 1.3 cases per 1,000 resident migrants from endemic countries. An estimated 20 to 183 babies with congenital Chagas disease are born annually in the study countries. The annual incidence rate of congenital transmission per 1,000 pregnancies in women from endemic countries was between none and three cases. The index of under diagnosis of T. cruzi infection was between 94% and 96%. Chagas disease is a public health challenge in the studied European countries. Urgent measures need to be taken to detect new cases of congenital transmission and take care of the existing cases with a focus on migrants without legal residency permit and potential difficulty accessing care.