Identification of Prodromal Parkinson Disease: We May Be Able to But Should We?

Parkinson disease (PD) remains a progressive and incurable disease. Research over the past decade provides strong evidence of a detectible phase before the clinical diagnosis, known as the prodromal phase of PD (pPD). In this article, we review the debate about disclosure of risk of progression to PD and related disorders to individuals through the perspectives of the pillars of medical ethics: beneficence, nonmaleficence, autonomy, and justice. There is evidence that lifestyle modification may have positive effects on onset and progression of PD, providing justification of potential benefit. From a societal perspective, a diagnosis of pPD could allow targeted recruitment to disease-modifying trials. Regarding nonmaleficence, direct evidence that catastrophic reactions are scarce is largely derived from studies of monogenic conditions, which may not be generalizable. Diagnosis of PD can be traumatic, and appropriate communication and evaluation of circumstances to weigh up disclosure is crucial. Future research should therefore examine the potential harms of early and of false-positive diagnoses and specifically examine these matters in diverse populations. Autonomy balances the right to know and the right not to know, so an individualized patient-centered approach and shared decision-making is essential, acknowledging that knowledge of being in the prodromal phase could prolong autonomy in the longer term. Distributive justice brings focus toward health care and related planning at the individual and societal level and affects the search for disease modification in PD. We must acknowledge that waiting for established disease states is likely to be too little, too late and results in failures of expensive trials and wasted participant and researcher effort. Ultimately, clinicians must arrive at a decision with the patient that solicits and integrates patients' goals, taking into account their individual life circumstances, perspectives, and philosophies, recognizing that one size cannot fit all.

Post-traumatic amnesia.

Post-traumatic amnesia is the transient state of altered brain function that may follow a traumatic brain injury. At a practical level, an individual has emerged from post-traumatic amnesia when he or she is fully orientated and with return of continuous memory. However, the clinical manifestations are often more complex, with numerous cognitive domains commonly affected, as well as behaviour. In the acute setting, post-traumatic amnesia may easily go unrecognised; this is problematic as it has important implications for both immediate management and for longer-term prognosis. We therefore recommend its careful clinical assessment and prospective evaluation using validated tools. Patients in post-traumatic amnesia who have behavioural disturbance can be particularly challenging to manage. Behavioural and environmental measures form the mainstay of its treatment while avoiding pharmacological interventions where possible, as they may worsen agitation. Patients need assessing regularly to determine their need for further rehabilitation and to facilitate safe discharge planning.

Slow Motion Analysis of Repetitive Tapping (SMART) Test: Measuring Bradykinesia in Recently Diagnosed Parkinson's Disease and Idiopathic Anosmia.

BACKGROUND: Bradykinesia is the defining motor feature of Parkinson's disease (PD). There are limitations to its assessment using standard clinical rating scales, especially in the early stages of PD when a floor effect may be observed. OBJECTIVE: To develop a quantitative method to track repetitive tapping movements and to compare people in the early stages of PD, healthy controls, and individuals with idiopathic anosmia. METHODS: This was a cross-sectional study of 99 participants (early-stage PD = 26, controls = 64, idiopathic anosmia = 9). For each participant, repetitive finger tapping was recorded over 20 seconds using a smartphone at 240 frames per second. From each video, amplitude between fingers, frequency (number of taps per second), and velocity (distance travelled per second) was extracted. Clinical assessment was based on the motor section of the MDS-UPDRS. RESULTS: People in the early stage of PD performed the task with slower velocity (p < 0.001) and with greater frequency slope than controls (p = 0.003). The combination of reduced velocity and greater frequency slope obtained the best accuracy to separate early-stage PD from controls based on metric thresholds alone (AUC = 0.88). Individuals with anosmia exhibited slower velocity (p = 0.001) and smaller amplitude (p < 0.001) compared with controls. CONCLUSION: We present a simple, proof-of-concept method to detect early motor dysfunction in PD. Mean tap velocity appeared to be the best parameter to differentiate patients with PD from controls. Patients with anosmia also showed detectable differences in motor performance compared with controls which may suggest that some were in the prodromal phase of PD.

Improving estimation of Parkinson's disease risk-the enhanced PREDICT-PD algorithm.

We previously reported a basic algorithm to identify the risk of Parkinson's disease (PD) using published data on risk factors and prodromal features. Using this algorithm, the PREDICT-PD study identified individuals at increased risk of PD and used tapping speed, hyposmia and REM sleep behaviour disorder (RBD) as "intermediate" markers of prodromal PD in the absence of sufficient incident cases. We have now developed and tested an enhanced algorithm which incorporates the intermediate markers into the risk model. Risk estimates were compared using the enhanced and the basic algorithm in members of the PREDICT-PD pilot cohort. The enhanced PREDICT-PD algorithm yielded a much greater range of risk estimates than the basic algorithm (93-609-fold difference between the 10th and 90th centiles vs 10-13-fold respectively). There was a greater increase in the risk of PD with increasing risk scores for the enhanced algorithm than for the basic algorithm (hazard ratios per one standard deviation increase in log risk of 2.75 [95% CI 1.68-4.50; p < 0.001] versus 1.47 [95% CI 0.86-2.51; p = 0.16] respectively). Estimates from the enhanced algorithm also correlated more closely with subclinical striatal DaT-SPECT dopamine depletion (R2 = 0.164, p = 0.005 vs R2 = 0.043, p = 0.17). Incorporating the previous intermediate markers of prodromal PD and using likelihood ratios improved the accuracy of the PREDICT-PD prediction algorithm.

The impact of injury on apparent survival of whale sharks (Rhincodon typus) in South Ari Atoll Marine Protected Area, Maldives.

The whale shark (Rhincodon typus) is an endangered species with a declining global population. The South Ari Atoll Marine Protected Area (SAMPA), Maldives, is one of few locations globally where year-long residency of individuals occurs. This SAMPA aggregation appears to consist almost exclusively of immature males. Due to its year-round residency, this local aggregation is subjected to a high degree of tourism pressure. This ecotourism contributes to the high level of interest and protection offered to whale sharks by the local community. Unfortunately, if regulations are not followed or enforced, tourism can bring with it major stressors, such as accidental injuries. We used POPAN capture-mark-recapture models and lagged identification rate analysis to assess the effect of major injuries on whale shark residency within SAMPA. Injuries may be obtained outside SAMPA. We found individuals with major injuries had a higher apparent survival in the area than those without. Lagged identification rates also demonstrated that sharks with major injuries are more likely to return to the area. We suggest that major injuries result in sharks prolonging their time in the developmental habitat. These findings have implications for individual fitness and the population viability of this endangered species. We propose targeted conservation strategies be considered to protect sharks from further injury. Based on the presented spatio-temporal distributions of sharks, and current local knowledge of sighting patterns, speed limit zones and propeller-exclusion zones should be implemented and enforced. If carried out alongside tourist education, these measures will contribute to the protection of whale sharks within SAMPA and beyond. Furthermore, our results can aid research direction, alongside regulation and enforcement development, at similar sites worldwide.

The prodromes of Parkinson's disease.

Whilst the diagnosis of Parkinson's disease (PD) relies on the motor triad of bradykinesia, rigidity and tremor, the underlying pathological process starts many years before these signs are overt. In this prodromal phase of PD, a diverse range of non-motor and motor features can occur. Individually they do not allow a diagnosis of PD, but when considered together, they reflect the gradual development of the clinical syndrome. Different subgroups within the prodromal phase may exist and reflect different underlying pathology. Here, we summarise the evidence on the prodromal phase of PD in patient groups at increased risk of PD with well described prodromal features: patients with idiopathic rapid eye movement sleep behaviour disorder, patients with idiopathic anosmia and families with monogenic mutations that are closely linked to PD pathology. In addition, we discuss the information on prodromal features from ongoing studies aimed at detecting prodromal PD in the general population. It is likely that better delineation of the clinical prodromes of PD and their progression in these high-risk groups will improve understanding of the underlying pathophysiology.

An early diagnosis is not the same as a timely diagnosis of Parkinson's disease.

Parkinson's disease is a common neurodegenerative condition that has significant costs to the individual patient and to society. The pathology starts up to a decade before symptoms are severe enough to allow a diagnosis using current criteria. Although the search for disease-modifying treatment continues, it is vital to understand what the right time is for diagnosis. Diagnosis of Parkinson's disease is based on the classic clinical criteria, but the presence of other clinical features and disease biomarkers may allow earlier diagnosis, at least in a research setting. In this review, we identify the benefits of an early diagnosis, including before the classic clinical features occur. However, picking the right point for a "timely" diagnosis will vary depending on the preferences of the individual patient, efficacy (or existence) of disease-modifying treatment, and the ability for health systems to provide support and management for individuals at every stage of the disease. Good evidence for the quality-of-life benefits of existing symptomatic treatment supports the argument for earlier diagnosis at a time when symptoms are already present. This argument would be significantly bolstered by the development of disease-modifying treatments. Benefits of early diagnosis and treatment would affect not only the individual (and their families) but also the wider society and the research community. Ultimately, however, shared decision-making and the principles of autonomy, beneficence, and non-maleficence will need to be applied on an individual basis when considering a "timely" diagnosis.

Does bathymetry drive coastal whale shark (Rhincodon typus) aggregations?

BACKGROUND: The whale shark (Rhincodon typus) is known to aggregate in a number of coastal locations globally, however what causes these aggregations to form where they do is largely unknown. This study examines whether bathymetry is an important driver of coastal aggregation locations for R. typus through bathymetry's effect on primary productivity and prey availability. This is a global study taking into account all coastal areas within R. typus' range. METHODS: R. typus aggregation locations were identified through an extensive literature review. Global bathymetric data were compared at R. typus aggregation locations and a large random selection of non-aggregation areas. Generalised linear models were used to assess which bathymetric characteristic had the biggest influence on aggregation presence. RESULTS: Aggregation sites were significantly shallower than non-aggregation sites and in closer proximity to deep water (the mesopelagic zone) by two orders of magnitude. Slope at aggregation sites was significantly steeper than non-aggregation sites. These three bathymetric variables were shown to have the biggest association with aggregation sites, with up to 88% of deviation explained by the GLMs. DISCUSSION: The three key bathymetric characteristics similar at the aggregation sites are known to induce upwelling events, increase primary productivity and consequently attract numerous other filter feeding species. The location of aggregation sites in these key areas can be attributed to this increased prey availability, thought to be the main reason R. typus aggregations occur, extensively outlined in the literature. The proximity of aggregations to shallow areas such as reefs could also be an important factor why whale sharks thermoregulate after deep dives to feed. These findings increase our understanding of whale shark behaviour and may help guide the identification and conservation of further aggregation sites.

Dopamine reuptake transporter-single-photon emission computed tomography and transcranial sonography as imaging markers of prediagnostic Parkinson's disease.

OBJECTIVE: The objective of this study was to examine whether prediagnostic features of Parkinson's disease (PD) were associated with changes in dopamine reuptake transporter-single-photon emission computed tomography and transcranial sonography. METHODS: Prediagnostic features of PD (risk estimates, University of Pennsylvania Smell Identification Test, Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire, and finger-tapping scores) were assessed in a large cohort of older U.K. residents. A total of 46 participants were included in analyses of prediagnostic features and MDS-UPDRS scores with the striatal binding ratio on dopamine reuptake transporter-single-photon emission computed tomography and nigral hyperechogenicity on transcranial sonography. RESULTS: The striatal binding ratio was associated with PD risk estimates (P = .040), University of Pennsylvania Smell Identification Test (P = .002), Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire scores (P = .024), tapping speed (P = .024), and MDS-UPDRS motor scores (P = .009). Remotely collected assessments explained 26% of variation in the striatal binding ratio. The inclusion of MDS-UPDRS motor scores did not explain additional variance. The size of the nigral echogenic area on transcranial sonography was associated with risk estimates (P < .001) and MDS-UPDRS scores (P = .03) only. CONCLUSIONS: The dopamine reuptake transporter-single-photon emission computed tomography results correlated with motor and nonmotor features of prediagnostic PD, supporting its potential use as a marker in the prodromal phase of PD. Transcranial sonography results also correlated with risk scores and motor signs. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Whale shark economics: a valuation of wildlife tourism in South Ari Atoll, Maldives.

Whale sharks attract large numbers of tourists, divers and snorkelers each year to South Ari Atoll in the Republic of Maldives. Yet without information regarding the use and economic extent of the attraction, it is difficult to prioritize conservation or implement effective management plans. We used empirical recreational data and generalized mixed statistical models to conduct the first economic valuation (with direct spend as the primary proxy) of whale shark tourism in Maldives. We estimated that direct expenditures for whale shark focused tourism in the South Ari Marine Protected Area for 2012 and 2013 accounted for US$7.6 and $9.4 million respectively. These expenditures are based on an estimate of 72,000-78,000 tourists who are involved in whale shark excursions annually. That substantial amount of income to resort owners and operators, and tourism businesses in a relatively small area highlights the need to implement regulations and management that safeguard the sustainability of the industry through ensuring guest satisfaction and whale shark conservation.

Improving the quality of prescribing in the emergency department.

Prescribing errors are common and can have a significant negative impact on patients. This article presents an audit and intervention which aimed to improve prescribing safety, documentation and handover in the emergency department. The authors identified shortcomings in the emergency department drug chart, which were subsequently confirmed by audit. To address these shortcomings, a new drug chart was designed and introduced, before repeating the audit. This intervention resulted in significantly more frequent documentation of key aspects of the prescription including date and time, and rate and volume for infusions. This low cost intervention is applicable to other emergency department settings.

Third-line antiepileptic therapy and outcome in status epilepticus: the impact of vasopressor use and prolonged mechanical ventilation.

OBJECTIVES: To characterize associations between antiepileptic drugs with sedating or anesthetic effects (third-line antiepileptic drugs) vs. other antiepileptic agents, and short-term outcomes, in status epilepticus. Furthermore, to evaluate the role of adverse hemodynamic and respiratory effects of these agents in status epilepticus treatment. DESIGN: Retrospective comparative analysis. SETTING: Tertiary academic medical center with two emergency departments and two neurologic intensive care units. PATIENTS: Adults admitted with a diagnosis of status epilepticus defined as seizures lasting continuously >5 mins, or for discrete periods in succession. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 126 patients with 144 separate status epilepticus admissions, 57 were female (45%) with mean age 54.7 ± 15.7 yrs. Status epilepticus was convulsive in 132 cases (92%). Status epilepticus etiologies included subtherapeutic antiepileptic drugs (43%), alcohol or other nonantiepileptic drug (13%), and acute central nervous system disease (12%). Third-line antiepileptic drugs were administered in 47 cases (33%). Seventy-eight status epilepticus episodes (54%) had good outcomes (Glasgow Outcome Score = 1, 2) at the time of hospital discharge. On univariate analysis, poor outcome (Glasgow Outcome Score > 2) was associated with older age (mean 59.8 ± 15.5 vs. 50.5 ± 13.8 yrs, p < .001), acute central nervous system disease (21% vs. 4%, p = .001), mechanical ventilation (76% vs. 53%, p = .004), longer duration of ventilation (median 10 days [range 1-56] vs. 2 days [range 1-10], p < .001), treatment with vasopressors (35% vs. 5%, p < .001), and treatment with third-line antiepileptic drugs (51% vs. 17%, p < .001). Death was associated with acute central nervous system disease, prolonged ventilation, treatment with vasopressors, and treatment with third-line antiepileptic drugs. Predictors of poor outcome among all status epilepticus episodes were older age (odds ratio 1.06; 95% confidence interval 1.03-1.09; p < .001), treatment with third-line antiepileptic therapy (odds ratio 5.64; 95% confidence interval 2.31-13.75; p < .001), and first episode of status epilepticus (odds ratio 3.73; 95% confidence interval 1.38-10.10; p = .010). Among status epilepticus episodes treated by third-line antiepileptic drugs, predictors of poor outcome were older age (odds ratio, 1.09; 95% confidence interval 1.01-1.18; p = .038) and longer ventilation (odds ratio, 1.47; 95% confidence interval 1.08-2.00; p = .015). Predictors of mortality among all status epilepticus episodes were treatment with third-line antiepileptic drugs (odds ratio, 12.08; 95% confidence interval 2.30-63.39; p = .003) and older age (odds ratio, 1.06; 95% confidence interval 1.00-1.12; p = .045). CONCLUSIONS: Third-line antiepileptic drug therapies with sedating or anesthetic effects predicted poor outcome and death in status epilepticus. Hypotension requiring vasopressor therapy and duration of mechanical ventilation induced by these agents may be contributing factors, especially when pentobarbital is used. These findings may inform decision making on drug therapy in status epilepticus and help develop safer and more effective treatment strategies to improve outcome.

Antibiotic treatment for Clostridium difficile-associated diarrhea in adults.

BACKGROUND: Clostridium difficile is recognized as a frequent cause of antibiotic-associated diarrhea and colitis. OBJECTIVES: The aim of this review is to investigate the efficacy of antibiotic therapy for C. difficile-associated diarrhea (CDAD). SEARCH STRATEGY: MEDLINE (1966 to March 24, 2010), EMBASE (1980 to March 24, 2010), Cochrane Central Register of Controlled Trials and the Cochrane IBD/FBD Review Group Specialized Trials Register were searched using the following search terms: "pseudomembranous colitis and randomized trial"; "Clostridium difficile and randomized trial"; "antibiotic associated diarrhea and randomized trial". SELECTION CRITERIA: Only randomized, controlled trials assessing antibiotic treatment for CDAD were included in the review. The following outcomes were sought: initial resolution of diarrhea; initial conversion of stool to cytotoxin and/or culture negative; recurrence of diarrhea; recurrence of fecal evidence of CDAD; patient response to cessation of prior antibiotic therapy; emergent surgery; and death. DATA COLLECTION AND ANALYSIS: Three authors independently assessed abstracts and full text articles for inclusion. The risk of bias was independently rated by two authors. For dichotomous outcomes, relative risks (RR) and 95% confidence intervals (CI) were derived from each study and summary statistics obtained when appropriate, using a fixed effects model, except where significant heterogeneity was detected, at which time a random effects model was used. MAIN RESULTS: Fifteen studies (total of 1152 participants) with CDAD were included. Nine different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin and fidaxomicin (OPT-80). Most of the studies were active comparator studies comparing vancomycin with other antibiotics. The risk of bias was rated as high for 12 of 15 included studies. Patients with severe CDAD were often excluded from the included studies. In the only placebo-controlled trial vancomycin was found to be superior to placebo for treatment of CDAD for initial symptomatic cure. Initial symptomatic cure was achieved in 41% of vancomycin patients compared to 4% of placebo patients (1 study; 44 patients; RR 9.00; 95% CI 1.24 to 65.16). Vancomycin was significantly superior to placebo for initial bacteriologic response. Initial bacteriologic response was achieved in 45% of vancomycin patients compared to 4% of placebo patients (1 study; 44 patients; RR 10.00; 95% CI 1.40 to 71.62). The results of this study should be interpreted with caution due to the small number of patients and high risk of bias. No statistically significant differences in efficacy were found between vancomycin and metronidazole, vancomycin and fusidic acid, vancomycin and nitazoxanide, or vancomycin and rifaximin. No statistically significant differences in efficacy were found between metronidazole and nitazoxanide or metronidazole and fusidic acid. Vancomycin was significantly superior to bacitracin for initial bacteriologic response. Initial bacteriologic response was achieved in 48% of vancomycin patients compared to 25% of bacitracin patients (2 studies; 104 patients; RR 0.52; 95% CI 0.31 to 0.86). Teicoplanin, an antibiotic of limited availability and great cost, was significantly superior to vancomycin for initial bacteriologic response and cure. Initial bacteriologic response was achieved in 62% of vancomycin patients compared to 87% of teicoplanin patients (2 studies; 110 patients; RR 1.43; 95% CI 1.14 to 1.81). Bacteriologic cure was achieved in 45% of vancomycin patients compared to 82% of teicoplanin patients (2 studies; 110 patients; RR 1.82; 95% CI 1.19 to 2.78). These results should be interpreted with caution due to the small number of patients and the high risk of bias in the two studies in the pooled analysis. Teicoplanin was significantly superior to metronidazole for initial bacteriologic response. Initial bacteriologic response was achieved in 71% of metronidazole patients compared to 93% of teicoplanin patients (1 study; 59 patients; RR 0.76; 95% CI 0.60 to 0.98). This result should be interpreted with caution due to the small number of patients and high risk of bias in the study. Only one study investigated synergistic antibiotic combination, metronidazole and rifampin, and no advantage was demonstrated for the drug combination. This result should be interpreted with caution due to the small number of patients and high risk of bias in the study. Adverse events including surgery and death occurred infrequently in the included studies. There was a total of 18 deaths among 1152 patients in this systematic review. Among the studies that commented on the cause of mortality the deaths were attributed to underlying disease rather than CDAD or antibiotic treatment. One study reported a partial colectomy after failed CDAD treatment. AUTHORS' CONCLUSIONS: Current evidence leads to uncertainty whether mild CDAD needs to be treated. The studies provide little evidence for antibiotic treatment of severe CDAD as many studies excluded these patients. Considering the two goals of therapy: improvement of the patient's clinical condition and prevention of spread of C. difficile infection to other patients, one should choose the antibiotic that brings both symptomatic cure and bacteriologic cure. A recommendation to achieve these goals cannot be made because of the small numbers of patients in the included studies and the high risk of bias in these studies, especially related to dropouts. Most of the active comparator studies found no statistically significant difference in efficacy between vancomycin and other antibiotics including metronidazole, fusidic acid, nitazoxanide or rifaximin. Teicoplanin may be an attractive choice but for its limited availability (Teicoplanin is not available in the USA) and great cost relative to the other options. More research of antibiotic treatment and other treatment modalities of CDAD is required.

Skin test studies on close contacts of leprosy patients in India

Skin-test studies with a series of tuberculins have been carried out in close contacts of multibacillary (MB) leprosy patients around three leprosy centers in India, and casual contacts of the disease around two centers. The results show that the rate of acquisition of leprosin A positivity is associated with age and the closeness of contact with MB leprosy. At the age of 15 years, the differences between the two types of contact were highly significant (p less than 0.00001). Many responses to leprosin A are directed toward the group iv species-specific, antigens of the leprosy bacillus, and the significance of positivity is discussed in relation to protective immunity from leprosy. The differences from Iran show that positivity to leprosin A is not solely the effect of the degree of contact with the disease, but must also have a genetic or environmental element, the latter being favored. The results from Miraj show that the high levels of tuberculin, scrofulin, and vaccin positivity seen in Fathimanagar, and to a lesser extent in Karigiri, are not a consequence of contact with leprosy. BCG vaccination made little difference to the leprosin A positivity of close contacts of leprosy patients, although it significantly enhanced positivity among casual contacts around Miraj (p less than 0.002). BCG vaccination significantly increased tuberculin positivity in Miraj and Karigri, and in those under 11 years of age in Fathimanagar. It made no difference to the already high level of positivity found in older persons around Fathimanagar

Vaccination and skin test studies on the children of leprosy patients

The purpose of this study carried out in Iranian Azerbaijan was to determine the pattern of skin-test positivity to mycobacterial antigens in children living in the valley, and to assess the effect on this of a series of vaccines against mycobacterial disease. Set up in 1978, 1707 tuberculin-negative children without scars of previous BCG vaccination were vaccinated with BCG Glaxo alone (vaccine A) or with the addition of a suspension of killed Mycobacterium vaccae (vaccine B). One hundred children were vaccinated with BCG Glaxo plus a suspension of M. leprae (vaccine C). Eight to 10 years later about half of the children were found for follow up. At this time further children were skin tested, and the results obtained were related to whether or not they had scars of vaccination with BCG Pasteur (Teheran) given by the local health authorities. Between setting up the study and the first follow up, cases of leprosy or tuberculosis had occurred in some of the villages, although not among those we had vaccinated. Differences between the effects of the vaccines were only found in villages with cases of leprosy. In these villages positivity to leprosin A was significantly greater after vaccine B (49%) than after vaccine A (36%; p less than 0.04). The results for scrofulin and vaccine were the same after both vaccines, and significantly lower than in the villages without cases of leprosy. The general reduction in skin-test positivity in the villages with leprosy cases was mainly due to a loss of category 1 responders to group i, common mycobacterial, antigens. It was concluded that where casual contact with cases of leprosy occurs the combination of BCG with killed M. vaccae is likely to be a better vaccine for leprosy than is BCG alone. Although few children received the combination with M. leprae, the results obtained were not particularly promising

Vaccination and skin test studies on children living in villages with differing endemicity for leprosy and tuberculosis

The purpose of this study carried out in Iranian Azerbaijan was to determine the pattern of skin-test positivity to mycobacterial antigens in children living in the valley, and to assess the effect on this of a series of vaccines against mycobacterial disease. Set up in 1978, 1707 tuberculin-negative children without scars of previous BCG vaccination were vaccinated with BCG Glaxo alone (vaccine A) or with the addition of a suspension of killed Mycobacterium vaccae (vaccine B). One hundred children were vaccinated with BCG Glaxo plus a suspension of M. leprae (vaccine C). Eight to 10 years later about half of the children were found for follow up. At this time further children were skin tested, and the results obtained were related to whether or not they had scars of vaccination with BCG Pasteur (Teheran) given by the local health authorities. Between setting up the study and the first follow up, cases of leprosy or tuberculosis had occurred in some of the villages, although not among those we had vaccinated. Differences between the effects of the vaccines were only found in villages with cases of leprosy. In these villages positivity to leprosin A was significantly greater after vaccine B (49%) than after vaccine A (36%; p less than 0.04). The results for scrofulin and vaccine were the same after both vaccines, and significantly lower than in the villages without cases of leprosy. The general reduction in skin-test positivity in the villages with leprosy cases was mainly due to a loss of category 1 responders to group i, common mycobacterial, antigens. It was concluded that where casual contact with cases of leprosy occurs the combination of BCG with killed M. vaccae is likely to be a better vaccine for leprosy than is BCG alone. Although few children received the combination with M. leprae, the results obtained were not particularly promising