Tuberculosis: A Challenge to the General Practitioner

Of 157 patients dying of tuberculosis in Ontario (1960) 132 (87.4%) suffered from the pulmonary form of the disease (incidence 2.6 per 100,000). In the same year, 1632 of 1847, or 88.3%, active new cases reported had the pulmonary type and 183 additional cases were reported without details as to type of disease. Thus, in 1960, a total of 2030 new cases of tuberculosis were reported in Ontario.Of 1367 patients with pulmonary tuberculosis (reinfection type), 357 (26.1%) had “far advanced” disease and 613 (44.8%) had “moderately advanced” disease.This high percentage of patients with “moderately advanced” to “far advanced” disease at the time of diagnosis constitutes the real challenge to physicians in private practice, who made the diagnosis in 45% of cases.Emergence of resistant strains of bacteria increases the urgency of prompt diagnosis and treatment. The most vulnerable population segment is the 15-30 year age-group, many of whom are negative intracutaneous reactors. A high index of suspicion is necessary, particularly in certain segments of the population with a high incidence of infection, combined with a careful history, meticulous physical examination, intracutaneous tests, chest and other radiographs, and appropriate bacteriological studies.     

Chest Radiographic Patterns and the Transmission of Tuberculosis: Implications for Automated Systems

BackgroundComputer-aided detection to identify and diagnose pulmonary tuberculosis is being explored. While both cavitation on chest radiograph and smear-positivity on microscopy are independent risk factors for the infectiousness of pulmonary tuberculosis it is unknown which radiographic pattern, were it detectable, would provide the greatest public health benefit; i.e. reduced transmission. Herein we provide that evidence.Objectives1) to determine whether pulmonary tuberculosis in a high income, low incidence country is more likely to present with “typical” adult-type pulmonary tuberculosis radiographic features and 2) to determine whether those with “typical” radiographic features are more likely than those without such features to transmit the organism and/or cause secondary cases.MethodsOver a three-year period beginning January 1, 2006 consecutive adults with smear-positive pulmonary tuberculosis in the Province of Alberta, Canada, were identified and their pre-treatment radiographs scored by three independent readers as “typical” (having an upper lung zone predominant infiltrate, with or without cavitation but no discernable adenopathy) or “atypical” (all others). Each patient’s pre-treatment bacillary burden was carefully documented and, during a 30-month transmission window, each patient’s transmission events were recorded. Mycobacteriology, radiology and transmission were compared in those with “typical” versus “atypical” radiographs.FindingsA total of 97 smear-positive pulmonary tuberculosis cases were identified, 69 (71.1%) with and 28 (28.9%) without “typical” chest radiographs. “Typical” cases were more likely to have high bacillary burdens and cavitation (Odds Ratios and 95% Confidence Intervals: 2.75 [1.04–7.31] and 9.10 [2.51–32.94], respectively). Typical cases were also responsible for most transmission events—78% of tuberculin skin test conversions (p<0.002) and 95% of secondary cases in reported close contacts (p<0.01); 94% of secondary cases in “unreported” contacts (p<0.02).ConclusionAs a group, smear-positive pulmonary tuberculosis patients with typical radiographic features constitute the greatest public health risk. This may have implications for automated detection systems.     

Miliary Tuberculosis in Adults

Of 40 adults with miliary tuberculosis 24 had “overt” disease; in them miliary mottling was usually present on the chest radiograph, and tubercle bacilli were readily isolated from sputum, urine, or cerebrospinal fluid. In the remaining 16 patients the disease was termed “cryptic” because its usual clinical and radiographic features were absent. This cryptic type is as common as the overt type in patients over 60 years. In this series the peak age incidence was in the eighth decade, and possibly this increase in the incidence age is due to the breakdown of old tuberculous foci in patients with diminished immunological mechanisms.Cryptic miliary tuberculosis is a difficult diagnostic problem and should be suspected in any elderly patient, particularly a woman, who has an unexplained pyrexia, pancytopenia, or leukaemoid reaction. In 10 cases it was diagnosed by a therapeutic trial with para-aminosalicylic acid and isoniazid, a fall of temperature to normal (usually within a week), weight gain, a rise in haemoglobin, and increased well-being being the criteria of improvement The use of such a trial is strongly advocated as a specific method of diagnosing cryptic miliary tuberculosis.     

Nephrotic Syndrome Due to Primary Renal Disease in Adults: I. Survey of Incidence in South-east England

In a prospective survey of the nephritic syndrome due to primary renal disease in adult patients in the South-east Metropolitan Region of England 50 patients were seen in a two-year period—a minimum annual incidence of 9·0 new cases per million adult population. The frequency distribution of the three main histological groups was “minimal change” 30%, membranous nephropathy 12%, and proliferative glomerulonephritis 58%. The higher proportion of patients with minimal histological change compared with that found in most previously published series may be explained by the avoidance of selection of patients for inclusion. The much lower incidence of membranous nephropathy probably reflects the use of stricter histological criteria for this diagnosis.     

TAIMA (Stop) TB: The Impact of a Multifaceted TB Awareness and Door-to-Door Campaign in Residential Areas of High Risk for TB in Iqaluit,Nunavut

Background

The incidence rate of active tuberculosis (TB) disease in the Canadian Territory of Nunavut has shown a rising trend over the past 10 years. In 2010 it was 60 times greater than the national incidence rate. The objective of the Taima (translates to “stop” in Inuktitut) TB study was to implement and evaluate a public health campaign to enhance existing TB prevention efforts in Nunavut.

Methods

A TB awareness campaign followed by a door-to-door screening campaign was carried out in Iqaluit, Nunavut. The aim of the campaign was to raise awareness about TB, and to provide in-home screening and treatment for people living in residential areas at high risk for TB. Screening was based on geographic location rather than on individual risk factors.

Results

During the general awareness campaign an increase in the number of people who requested TB testing at the local public health clinic was observed. However, this increase was not sustained following cessation of the awareness campaign. Targeted TB screening in high risk residential areas in Iqaluit resulted in 224 individuals having TSTs read, and detection of 42 previously unidentified cases of latent TB, (overall yield of 18.8% or number needed to screen = 5.3). These cases of latent TB infection (LTBI) were extra cases that had not been picked up by traditional screening practices (34% relative increase within the community). This resulted in a 33% relative increase in the completion of LTBI treatment within the community. The program directly and indirectly identified 5/17 new cases of active TB disease in Iqaluit during the study period (29.5% of all incident cases).

Conclusions

While contact tracing investigations remain a cornerstone of TB prevention, additional awareness, screening, and treatment programs like Taima TB may contribute to the successful control of TB in Aboriginal communities.     

Non-Tuberculous Chest Disease Found in a Mass X-Ray Survey in Vancouver,B.C

In 1964, 219,085 persons were examined during a tuberculosis survey in Vancouver, B.C. One hundred and fifteen new cases of tuberculosis and 929 cases of significant non-tuberculous lung disease were found. In a four-month follow-up of the non-tuberculous cases it was found that of the 742 patients who had named a physician when examined 26.6% had not made contact with him. Of those who did contact the physician, the follow-up was considered “poor” in only 30 patients (2.1%). Seventeen patients had died in the four-month interval and 81 who could not be located after the initial survey were considered “lost”. Rates were determined for 37 diagnoses per 1000 patients screened. The most common diagnosis was localized pulmonary fibrosis (1.69/1000). Carcinoma was found in 0.30/1000 and solitary lung density in 0.17/1000 population screened.     

Medical Assessment of Late Effects of National Socialist Persecution

Emotional involvement of the examiner, hostility and mistrust on the part of the examinees and the long interval since the original events comprise some of the problems facing medical assessors of survivors of National Socialist persecution. Experience with over 100 such persons confirmed the high incidence of irreversible and usually disabling disorders, mainly functional and psychiatric—“late damage” as it has been designated in recent reports on this subject. The most common disorders encountered in the assessments of 70 survivors are reviewed. A number of organic diseases such as organic brain damage, active tuberculosis and fractures were revealed only after careful search. Recent findings by psychiatric assessors are reviewed; their plea for greater familiarity with late effects in survivors of National Socialist persecution is echoed, and the need for medical, psychiatric and social support of these unfortunate individuals is emphasized.     

The Past and Future of Tuberculosis Research

Renewed efforts in tuberculosis (TB) research have led to important new insights into the biology and epidemiology of this devastating disease. Yet, in the face of the modern epidemics of HIV/AIDS, diabetes, and multidrug resistance—all of which contribute to susceptibility to TB—global control of the disease will remain a formidable challenge for years to come. New high-throughput genomics technologies are already contributing to studies of TB''s epidemiology, comparative genomics, evolution, and host–pathogen interaction. We argue here, however, that new multidisciplinary approaches—especially the integration of epidemiology with systems biology in what we call “systems epidemiology”—will be required to eliminate TB.     

High Utility of Contact Investigation for Latent and Active Tuberculosis Case Detection among the Contacts: A Retrospective Cohort Study in Tbilisi,Georgia, 2010–2011

Setting

The study was conducted at the National Center for Tuberculosis and Lung Diseases (NCTBLD) in Tbilisi, Georgia.

Objective

To assess the utility of contact investigation for tuberculosis (TB) case detection. We also assessed the prevalence and risk factors for active TB disease and latent TB infection (LTBI) among contacts of active pulmonary TB cases.

Design

A retrospective cohort study was conducted among the contacts of active pulmonary TB cases registered in 2010–2011 at the NCTBLD in Tbilisi, Georgia. Contacts of active TB patients were investigated according to an “invitation model”: they were referred to the NCTBLD by the index case; were queried about clinical symptoms suggestive of active TB disease; tuberculin skin testing and chest radiographs were performed. Demographic, laboratory, and clinical data of TB patients and their contacts were abstracted from existing records up to February 2013.

Results

869 contacts of 396 index cases were enrolled in the study; a median of 2 contacts were referred per index case. Among the 869 contacts, 47 (5.4%) were found to have or developed active TB disease: 30 (63.8%) were diagnosed with TB during the baseline period (co-prevalent cases) and 17 (36.2%) developed active TB disease during the follow-up period (mean follow up of 21 months) (incident TB cases). The incidence rate of active TB disease among contacts was 1126.0 per 100 000 person years (95% CI 655.7–1802.0 per 100,000 person-years). Among the 402 contacts who had a tuberculin skin test (TST) performed, 52.7% (95% CI 47.7–57.7%) had LTBI.

Conclusions

A high prevalence of LTBI and active TB disease was found among the contacts of TB cases in Tbilisi, Georgia. Our findings demonstrated that an “invitation” model of contact investigation was an effective method of case detection. Therefore, contact investigation should be scaled up in Georgia.     

MULTIPLE SCLEROSIS—Its Frequency and Distribution,with Special Reference to San Francisco

Epidemiologic surveys of multiple sclerosis were conducted in 1949 in San Francisco, Winnipeg, Boston, New Orleans, and Denver. Reports of cases for 1939 through 1948 were obtained from record offices, hospitals and clinics, and private physicians. The basis for the observations was the group of “probable” cases among residents.In San Francisco these probable cases in residents numbered 415; however, in only 146 of these was the onset between 1939 and 1948. Of the 143 patients who were white, 51 were male and 92 female. The average annual incidence based on these figures was 2.1 per 100,000—1.5 for males and 2.6 for females.Prevalence, based on probable cases in residents on January 1, 1949, was 29.7 cases per 100,000 population—21.2 for males and 38.1 for females.Mortality was 0.7 per 100,000 population—0.9 for females and 0.6 for males.In comparison of the findings for San Francisco with those of other cities, both the incidence and the severity of the disease appear to decrease from north to south.     

Tuberculosis Prevention in South Africa

Background

South Africa has one of the highest per capita rates of tuberculosis (TB) incidence in the world. In 2012, the South African government produced a National Strategic Plan (NSP) to control the spread of TB with the ambitious aim of zero new TB infections and deaths by 2032, and a halving of the 2012 rates by 2016.

Methods

We used a transmission model to investigate whether the NSP targets could be reached if immediate scale up of control methods had happened in 2014. We explored the potential impact of four intervention portfolios; 1) “NSP” represents the NSP strategy, 2) “WHO” investigates increasing antiretroviral therapy eligibility, 3) “Novel Strategies” considers new isoniazid preventive therapy strategies and HIV “Universal Test and Treat” and 4) “Optimised” contains the most effective interventions.

Findings

We find that even with this scale-up, the NSP targets are unlikely to be achieved. The portfolio that achieved the greatest impact was “Optimised”, followed closely by “NSP”. The “WHO” and “Novel Strategies” had little impact on TB incidence by 2050. Of the individual interventions explored, the most effective were active case finding and reductions in pre-treatment loss to follow up which would have a large impact on TB burden.

Conclusion

Use of existing control strategies has the potential to have a large impact on TB disease burden in South Africa. However, our results suggest that the South African TB targets are unlikely to be reached without new technologies. Despite this, TB incidence could be dramatically reduced by finding and starting more TB cases on treatment.     

Prevalence and Correlates of HIV Testing among Young People Enrolled in Non-Formal Education Centers in Urban Chiang Mai,Thailand: A Cross-Sectional Study

BackgroundHIV testing is the gateway to HIV prevention, treatment, and care. Despite the established vulnerability of young Thai people to HIV infection, studies examining the prevalence and correlates of HIV testing among the general population of Thai youth are still very limited. This study investigates socio-demographic, behavioral, and psychosocial factors associated with HIV testing among young Thai people enrolled in Non-formal Education Centers (NFEC) in urban Chiang Mai, Northern Thailand.MethodsThis was a cross-sectional quantitative study conducted among young unmarried Thai youth—between the ages of 15 and 24—who were enrolled in NFEC in urban Chiang Mai. Multiple logistic regressions were used to identify correlates of “ever tested for HIV” among the sexually active participants.FindingsOf the 295 sexually active participants, 27.3% reported “ever tested for HIV;” 65.4% “did not consistently use condom;” and 61.7% “had at least 2 lifetime partners.” We found that “self-efficacy” (AOR, 4.92; CI, 1.22–19.73); “perception that it is easy to find a location nearby to test for HIV” (AOR, 4.67; CI, 1.21–18.06); “having at least 2 lifetime sexual partners” (AOR, 2.05; CI, 1.09–3.85); and “ever been pregnant or made someone pregnant” (AOR, 4.06; CI, 2.69–9.15); were associated with increased odds of having ever been tested. On the other hand, “fear of HIV test results” (AOR, 0.21; CI, 0.08–0.57) was associated with lower odds of ever having been tested for HIV.ConclusionThe main finding is that a substantially high proportion of Thai youth is engaged in risky sexual behaviors—yet reports low rates of ever having been tested for HIV. This highlights an urgent need to develop appropriate interventions—based on the identified correlates of HIV testing. There is also an urgent need to enhance HIV testing and to promote safer sexual behaviors among young Thai people—particularly those who are out-of-school.     

Consultant Surgeons and Vasectomy

In late 1971 410 consultant general surgeons and urologists—74% of a national random sample—responded to a postal survey about vasectomy. Probably about 50,000 vasectomies were performed by surgeons in England and Wales in 1970. The service was largely a private one: 60% of consultants'' hospital vasectomies were not done under the National Health Service, and, in addition, 26% of the consultants who worked in relevant specialties performed vasectomies elsewhere than in hospital (usually in private nursing homes). Based again on consultants'' estimates, probably 6,000 men in 1970 had their requests for vasectomy turned down by surgeons, or more than one turned down for every 10 done. The most common reason was that patients were “too young.”About 90% of the consultants thought vasectomy could normally be performed safely and adequately as an outpatient procedure, yet only 64% said that 90% or more of their hospital vasectomies were done on this basis. While 69% regarded services in their areas as adequate, most were in favour of more special vasectomy clinics.     

Efficient Synthesis and Anti-Tubercular Activity of a Series of Spirocycles: An Exercise in Open Science

Tuberculosis afflicts an estimated 2 billion people worldwide and causes 1.3 million deaths annually. Chemotherapeutic solutions rely on drugs developed many years ago, with only one new therapeutic having been approved in the last 40 years. Given the rise of drug-resistant strains, there is an urgent need for the development of a more robust drug development pipeline. GlaxoSmithKline recently placed the structures and activities of 177 novel anti-tubercular leads in the public domain, as well as the results of ongoing optimisation of some of the series. Since many of the compounds arose from screening campaigns, their provenance was unclear and synthetic routes were in many cases not reported. Here we present the efficient synthesis of several novel analogues of one family of the GSK compounds—termed “Spiros”—using an oxa-Pictet–Spengler reaction. The new compounds are attractive from a medicinal chemistry standpoint and some were potent against the virulent strain, suggesting this class is worthy of further study. The research was carried out using open source methodology, providing the community with full access to all raw experimental data in real time.     

Obesity and Respiratory Infection in Infants and Young Children

A controlled trial has been carried out to test the widely held “clinical impression” that overweight infants have a greater liability to respiratory infections than those of normal weight. Two matched groups of children aged between 3 months and 2 years were studied, containing children whose weight was above the 90th percentile, or was between the 25th and 75th percentiles, at the start of the trial.Data from 120 children of the overweight group were available for analysis, of whom 47 experienced at least one respiratory infection during the trial and 73 did not. Of children remaining over the 90th percentile at the end of the trial 19 had suffered respiratory infections and 28 had not. One baby in the overweight group suffered a “cot death” from acute bronchiolitis. In the control group, 103 cases were analysed—23 had suffered a respiratory infection and 80 had remained free of respiratory infection throughout the trial. These figures are statistically significant and suggest that obesity in infants and young children is associated with an increased incidence of acute respiratory infections.     

Use of artificial genomes in assessing methods for atypical gene detection

Parametric methods for identifying laterally transferred genes exploit the directional mutational biases unique to each genome. Yet the development of new, more robust methods—as well as the evaluation and proper implementation of existing methods—relies on an arbitrary assessment of performance using real genomes, where the evolutionary histories of genes are not known. We have used the framework of a generalized hidden Markov model to create artificial genomes modeled after genuine genomes. To model a genome, “core” genes—those displaying patterns of mutational biases shared among large numbers of genes—are identified by a novel gene clustering approach based on the Akaike information criterion. Gene models derived from multiple “core” gene clusters are used to generate an artificial genome that models the properties of a genuine genome. Chimeric artificial genomes—representing those having experienced lateral gene transfer—were created by combining genes from multiple artificial genomes, and the performance of the parametric methods for identifying “atypical” genes was assessed directly. We found that a hidden Markov model that included multiple gene models, each trained on sets of genes representing the range of genotypic variability within a genome, could produce artificial genomes that mimicked the properties of genuine genomes. Moreover, different methods for detecting foreign genes performed differently—i.e., they had different sets of strengths and weaknesses—when identifying atypical genes within chimeric artificial genomes.     

We need to address ableism in science

In science, technology, engineering, and mathematics (STEM) fields, disabled people remain a significantly underrepresented part of the workforce. Recent data suggests that about 20% of undergraduates in the United States have disabilities, but representation in STEM fields is consistently lower than in the general population. Of those earning STEM degrees, only about 10% of undergraduates, 6% of graduate students, and 2% of doctoral students identify as disabled. This suggests that STEM fields have difficulty recruiting and retaining disabled students, which ultimately hurts the field, because disabled scientists bring unique problem-solving perspectives and input. This essay briefly explores the ways in which ableism—prejudice against disabled people based on the assumption that they are “less than” their nondisabled peers—in research contributes to the exclusion of disabled scientists and suggests ways in which the scientific community can improve accessibility and promote the inclusion of disabled scientists in academic science.     

Locating the Elderly in a General Practice

A preliminary survey undertaken before compiling a geriatric register showed that about 90% of the information on the practice files for patients over 65 was accurate. It is emphasized that such a register—which should be as accurate and up-to-date as possible—is important for the successful organization of a preventive geriatric clinic, or to any project designed to “screen” a defined population.     

The Grand Convergence: Closing the Divide between Public Health Funding and Global Health Needs

The Global Health 2035 report notes that the “grand convergence”—closure of the infectious, maternal, and child mortality gap between rich and poor countries—is dependent on research and development (R&D) of new drugs, vaccines, diagnostics, and other health tools. However, this convergence (and the R&D underpinning it) will first require an even more fundamental convergence of the different worlds of public health and innovation, where a largely historical gap between global health experts and innovation experts is hindering achievement of the grand convergence in health.The Global Health 2035 report notes that the “grand convergence”—closure of the infectious, maternal, and child mortality gap between rich and poor countries—is dependent on research and development (R&D) of new drugs, vaccines, diagnostics, and other health tools. New tools alone are estimated to deliver a 2% decline each year in the under-5 mortality rate, maternal mortality ratio, and deaths from HIV/AIDS and tuberculosis (TB) [1].However, this convergence (and the R&D underpinning it) is unlikely unless we first have an even more fundamental convergence of the parallel worlds of public health and innovation. At the moment, these worlds are often disconnected, with major gaps to be bridged at both the intellectual and practical levels before we can truly reach a grand convergence in health.     

Leprosy in a prison population: A new active search strategy and a prospective clinical analysis

BackgroundThis study evaluates an active search strategy for leprosy diagnosis based on responses to a Leprosy Suspicion Questionnaire (LSQ), and analyzing the clinical, immunoepidemiological and follow-up aspects for individuals living in a prison population.MethodsA cross-sectional study based on a questionnaire posing 14 questions about leprosy symptoms and signs that was distributed to 1,400 prisoners. This was followed by dermatoneurological examination, anti-PGL-I serology and RLEP-PCR. Those without leprosy were placed in the Non-leprosy Group (NLG, n = 1,216) and those diagnosed with clinical symptoms of leprosy were placed in the Leprosy Group (LG, n = 34).FindingsIn total, 896 LSQ were returned (64%), and 187 (20.9%) of the responses were deemed as positive for signs/symptoms, answering 2.7 questions on average. Clinically, 1,250 (89.3%) of the prisoners were evaluated resulting in the diagnosis of 34 new cases (LG), based on well-accepted clinical signs and symptoms, a new case detection rate of 2.7% within this population, while the NLG were comprised of 1,216 individuals. The confinement time medians were 39 months in the LG while it was 36 months in the NLG (p>0.05). The 31 leprosy cases who responded to the questionnaire (LSQ+) had an average of 1.5 responses. The symptoms “anesthetized skin area” and “pain in nerves” were most commonly mentioned in the LG while “tingling, numbness in the hands/feet”, “sensation of pricks and needles”, “pain in nerves” and “spots on the skin” responses were found in more than 30% of questionnaires in the NLG. Clinically, 88.2% had dysesthetic macular skin lesions and 97.1% presented some peripheral nerve impairment, 71.9% with some degree of disability. All cases were multibacillary, confirming a late diagnosis. Anti-PGL-I results in the LG were higher than in the NLG (p<0.0001), while the RLEP-PCR was positive in 11.8% of the patients.InterpretationOur findings within the penitentiary demonstrated a hidden prevalence of leprosy, although the individuals diagnosed were likely infected while living in their former communities and not as a result of exposure in the prison. The LSQ proved to be an important screening tool to help identify leprosy cases in prisons.