Fluctuating selection and global change: a synthesis and review on disentangling the roles of climate amplitude, predictability and novelty.

A formidable challenge for global change biologists is to predict how natural populations will respond to the emergence of conditions not observed at present, termed novel climates. Popular approaches to predict population vulnerability are based on the expected degree of novelty relative to the amplitude of historical climate fluctuations experienced by a population. Here, we argue that predictions focused on amplitude may be inaccurate because they ignore the predictability of environmental fluctuations in driving patterns of evolution and responses to climate change. To address this disconnect, we review major findings of evolutionary theory demonstrating the conditions under which phenotypic plasticity is likely to evolve in natural populations, and how plasticity decreases population vulnerability to novel environments. We outline key criteria that experimental studies should aim for to effectively test theoretical predictions, while controlling for the degree of climate novelty. We show that such targeted tests of evolutionary theory are rare, with marine systems being overall underrepresented in this venture despite exhibiting unique opportunities to test theory. We conclude that with more robust experimental designs that manipulate both the amplitude and predictability of fluctuations, while controlling for the degree of novelty, we may better predict population vulnerability to climate change.

Evaluation of the effectiveness of BCG vaccination using the case-control method in Buenos Aires, Argentina.

A retrospective case-control study was conducted in Argentina to determine the protection conferred by BCG vaccination against tuberculosis in children under six years of age, in an area where coverage is about 55%. A total of 175 tuberculosis patients were included. Five controls selected from patients treated at the same hospital as those under study for reasons other than tuberculosis were matched to each case on the basis of age, socioeconomic origin, nutritional status and place of residence. Information on BCG vaccination status was collected by an independent examiner. Tuberculosis localizations were as follows: 152 pulmonary, pleural and/or miliary; 18 meningitis; 2 lymphadenitis; 2 osteoarticular; and 1 otic. The diagnosis was based on bacteriological and histopathological tests, computerized tomography, radiology, clinical examination, endoscopy, and proved source of infection. The protective effect of BCG among those who were vaccinated was 73.0% with 95% confidence limits of 82% and 62%. According to these results BCG vaccination given early in life is very effective in preventing tuberculosis.

DMSP-consuming bacteria associated with the calanoid copepod Acartia tonsa (Dana).

DMSP-consuming bacteria (DCB) were recovered from the body and fecal pellets of the copepod Acartia tonsa (Dana). The most probable number of DCB associated with starved A. tonsa was 9.2x10(2) cells copepod(-1). The abundance of DCB recovered from the copepod body increased to 1.6-2.8x10(4) after the copepod fed on DMSP-containing alga. DCB abundance associated with fecal pellets averaged 1.2x10(4) cells pellet(-1). In enrichment cultures, the DCB grew with a doubling time of 1.1-2.9 days, and consumed DMSP at a rate of 4.5-7.5 fmol cell(-1) day(-1). The apparent DMSP-to-DMS conversion efficiency was 25-41% for DCB from copepod body, and 99% for DCB from fecal pellets. Our study demonstrated that copepods and their fecal pellets may harbour dense populations of DCB, and that the copepod-bacteria coupling represents a novel mechanism for DMSP consumption in the water column.

Research on BCG vaccination.

BCG vaccination against tuberculosis has been used for many years in practically all national tuberculosis programmes. It is often the mainstay of the programme as regards young children, in whom case-finding and treatment remain deficient, especially regarding the serious meningeal and miliary forms of tuberculosis. Following contradictory reports on the effectiveness of BCG vaccination, a large-scale controlled trial was carried out in south India, under the sponsorship of WHO. The early results of this trial showed that BCG vaccination provided no protection whatsoever against bacillary disease in adults. To examine this unexpected finding WHO convened a Scientific Group, which considered that the reported results per se are valid but might not apply in general. Since the effectiveness of a potentially very useful and generally applied control measure appeared seriously challenged, a Study Group was convened by WHO. The Group considered that under the circumstances BCG vaccination, especially of young children, should be continued, but that the effectiveness of BCG vaccination should be evaluated forthwith. A comprehensive programme has been formulated accordingly. The primary objective of the programme is to evaluate in an expedient manner the effectiveness of BCG vaccination in children. A number of problems inherent to the special situation had to be circumvented. In the case of tuberculosis, community trials of the classical type have to be prolonged and are extremely costly. Moreover, since BCG vaccination has been used widely, it is virtually impossible to find a suitable trial area; many countries are reluctant to conduct such trials for ethical reasons because they require an unvaccinated group. Retrospective studies, although providing no conclusive scientific evidence when carried out in isolation, may give useful information if organized in a comprehensive evaluation programme. Another approach proposed is based on the active follow-up of child contacts of newly detected cases of tuberculosis. This provides information on the magnitude of the tuberculosis problem in children as well as a powerful retrospective evaluation of the protective effect of vaccination; in the case that the results are inconclusive a prospective approach on the same principle would be ethically justified. The study population is only a small fraction of that required in a community trial, and the follow-up of each individual is reduced to a few months. In addition to providing information on the effectiveness of BCG vaccination, the field studies, supported by other research, may clarify the variations in protection observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Pathogenesis of tuberculosis and effectiveness of BCG vaccination.

Among the hypotheses offered to explain the conflicting results of various trials of BCG vaccination, the one invoking gross differences in the immunogenic properties of the various BCG vaccines (strains) has received most attention. Indeed, for many years research in BCG vaccination has been directed almost entirely towards improving the quality of vaccines. the anticipated benefit of this work, however, is not borne out by the results of the latest trial in India. Whereas it cannot be excluded that technological advances may have resulted in the worst vaccines ever, it also remains possible that the basic hypothesis was less relevant than presumed. the quality of the vaccine may be of little importance and a different explanation should be sought for the observed differences in protection. One possible lead is the observation that BCG vaccination consistently appeared to be of poor efficacy under conditions where, in a vaccination programme, even an effective vaccine would have little impact on the tuberculosis problem, i.e. where the majority of cases originated from the population already infected. The hypothesis offered is that in such populations the pathogenesis of tuberculosis is different from that prevailing under the clearly exceptional conditions under which BCG vaccination was effective. Rather than being the direct result of primary infection, tuberculous disease (observed) may be the result of reinfection. In this case BCG vaccination cannot be expected to have a protective effect.

The protective effect of BCG vaccination of the newborn against childhood tuberculosis in an African community.

The latest controlled trial of BCG vaccination in southern India showed that two vaccines failed to confer protection against pulmonary tuberculosis. This result cast serious doubt on the effectiveness of BCG vaccination of the newborn, which is widely applied in developing countries. Therefore, WHO initiated a global research study to evaluate current programmes in developing countries. Part of this study was carried out in Lomé, Togo, in which child contacts of newly detected patients were followed up with clinical and radiological examinations. All observations were recorded according to a scoring system. Concomitant observations were made to verify the comparability of the vaccinated and unvaccinated children. Of the child contacts of 352 index cases, 1421 completed the examinations. The distribution of the final score made it possible to distinguish 175 children likely to suffer from tuberculosis: 113 among the 546 unvaccinated and 62 among the 875 vaccinated children. Significant incomparability was observed in respect of intensity of exposure: the vaccination coverage was relatively low, and the risk of disease relatively high, if a parent was the index case or the child shared the bedroom of the index case (which very often coincided). The other variables studied, including age and sex, turned out to be practically irrelevant as regards comparability. The estimate of the protective effect against all types of tuberculosis combined is 61.5%, which is slightly lower than suggested by the raw data (66%). The protective effect, however, appeared to increase considerably with severity of disease. In children of 5 years and older it was lower than in the younger children. Tuberculin testing failed to reveal any sensitivity induced by BCG in the vaccinated children. The distribution of the tuberculin reactions correlated poorly with the other diagnostic findings. Small reactions were only slightly more frequent in healthy than in sick children; only the very large reactions were associated with a higher risk of disease. This confirms that the tuberculin test is of very limited diagnostic value in young children.

Does BCG vaccination protect the newborn and young infants?

PIP: BCG vaccination has been applied on an increasing scale during the last few decades. This vaccination is now being applied to the newborn despite the fact that there is little direct evidence concerning the degree of protection afforded to very young infants. This discussion reviews the evidence that is available regarding vaccination of the newborn from 3 controlled trials that were carried out in the 1930s and the only recent evidence that is available on this question which comes from retrospective studies. The 1st effort to examine the efficacy of BCG vaccination of young infants in a controlled trial was begun in New York City in 1926. Up to 1933, half of the infants (under 1 year old, many under 4 weeks) referred from tuberculosis homes were vaccinated, the others serving as control. There were 3 deaths from tuberculosis among 445 vaccinated children but 18 deaths among 545 controls. During the 14 years of the controlled trial in Saskatchewan Indian infants (begun in 1933), there were 53 deaths among those vaccinated with BCG and 63 among the controls. Among the 306 vaccinated children there were 6 cases of tuberculosis, 2 of whom died. Among the 303 controls, there were 29 cases, 9 of whom died. A study of BCG vaccination of the newborn by a percutaneous multiple puncture method was started by Rosenthal et al. in 1937. It comprised 3381 infants of whom about half were vaccinated during the 1st week after birth if the household members were free of tuberculosis. As regards tuberculosis, the difference in morbidity was highly significant. There were 17 cases among the 1716 vaccinated and 65 cases among the 1665 controls. An interesting analysis of morbidity statistics for different countries was made by Bjartveit and Waaler, who studied the association between the decline of tuberculosis in various age groups and the age at which vaccination was given. This association was pronounced and thus provided evidence of the efficacy of BCG vaccination. Results have been recently published of a retrospective study that concerned 6364 infants who were vaccinated at birth, in Hamburg in 1954, and 9524 who were not. Up to 1971, 9 of the vaccinated and 130 of the unvaccinated children had developed tuberculosis. Of the 30,370 children born in 1963, 27,371 were vaccinated and 2999 were not. There were 11 cases of tuberculosis among the vaccinated and 16 cases among the unvaccinated children over the 8 year follow-up period. At face value, the evidence suggests that BCG vaccination of the newborn confers considerable protection against tuberculosis in infants and young children, yet it must be remembered that the evidence is both scanty and superficial.^ieng

Determining the prevalence of tuberculosis infection in populations with non-specific tuberculin sensitivity.

In tropical countries, where there is generally a high prevalence of non-specific sensitivity, the tuberculin test is inadequate for detecting tuberculosis infection. A method is proposed by which the prevalence of infection in the population can be determined under such circumstances thus making possible meaningful epidemiological surveillance of the disease. This method compares levels of tuberculin sensitivity in individuals before and after BCG vaccination. If BCG vaccination fails to produce an increase in tuberculin sensitivity, the individual must have been infected with human or bovine tubercle bacilli.

Epidemiological significance of the local reaction to direct BCG vaccination as assessed from a study in Mongolia.

Direct BCG vaccination has considerable operational advantages over the classical method of vaccinating only persons who do not react to tuberculin. In the present study it is shown that the direct method as applied in Mongolia does not cause any untoward reactions in persons who react to tuberculin and therefore can be considered a rational public health procedure.By reason of the repeated follow-up examinations, it was possible to obtain a clear picture of the development of the local BCG reactions and to test the hypothesis that these reactions may give information on pre-existing tuberculin sensitivity. It appeared impossible to deduce with any accuracy from either the local induration or the tissue destruction at the site of vaccination whether a person had tuberculin sensitivity before vaccination or not, and the results obtained with 2 different vaccines were inconsistent. It is therefore concluded that the local BCG reaction has no epidemiological significance in this respect.

The effectiveness of BCG vaccination of the newborn against childhood tuberculosis in Bangkok.

PIP: The Central Chest Clinic, Bangkok, Thailand, undertook a study among child contacts of newly discovered sputum-smear-positive patients with pulmonary tuberculosis to determine the effectiveness of BCG vaccination in young children. The study design resembled that of a controlled trial except that it was retrospective for vaccination, i.e., the vaccinated and control groups were not randomly selected. For this reason a number of measures were taken to allow for the comparability of groups to be verified and for adjustments to be made if necessary. The study was initiated in September 1981 and terminated in June 1984, after 971 index cases who reported contact with young children had been registered. Registration and initial examinations were completed for 1506 child contacts. The field teams could not trace 124 reported child contacts. In the case of 8 children, the initial examination was refused. Within a week of the detection of the index case, a visit was made to the household and personal data were collected. The contact children then were offered a clinical and X-ray examination at the Central Chest Clinic for the examinations. A clinical record was prepared for each child contact, the site of BCG vaccination was covered with a dressing (even if there had been no vaccination or scar), and the pediatrician administered a clinical examination and made a full-plate postero-anterior X-ray. The X-ray picture was examined by 2 readers. Suspect children were followed up for as long as there were medical indications. When indicated by the clinical or X-ray examination, a laryngeal swab was taken for culture and gland biopsies were made and examined by histopathology and culture. If tuberculosis was strongly suspected, treatment was initiated at once with rifampicin and isoniazid. For each child a final diagnosis was made at the end of the study. A scoring system proposed by WHO was used to obtain an indication of the probability of tuberculosis. As many as 1218 (81%) of the children had a BCG scar, and among those without a scar, 35 had a record of vaccination. Vaccination coverage as well as disease risk appeared to be associated with age. Stratification by age showed that this did not affect the calculated effectiveness of BCG vaccination. Apart from age, no differences between the vaccinated and the unvaccinated children were observed that call for stratification of the material. 284 tuberculosis suspects were found, 218 among the 1253 vaccinated and 66 among the 253 unvaccinated participants. The total incidence of tuberculosis was 14.5%; it was 12.6% among the vaccinated and 23.6% among the unvaccinated. Based on the data presented in Tables 1 and 8, and adjusting for the estimated 55 vaccinated children included among those without a scar or a vaccination record, the observed efficacy is 53% with 95% confidence limits of 64% and 38%; the observed number of cases among the vaccinated is 185 less than expected. Thus, although efficacy appears less, the effectiveness is far higher than with a more stringent diagnostic criteria.^ieng

Present knowledge of immunization against tuberculosis.

This is a selective review, which, after recalling some immunological aspects, analyses the present knowledge on the protective efficacy of BCG vaccination, the vaccination reactions and complications that may be observed, and current methods of vaccine production and control. As regards the application of BCG vaccination, particular attention is given to dosage and vaccination techniques, direct and simultaneous vaccination, and revaccination. Finally, the evaluation of BCG vaccination programmes is briefly discussed.

The duration of BCG-induced tuberculin sensitivity in children, and its irrelevance for revaccination. Results of two 5-year prospective studies.

It had been shown earlier, in a retrospective study, that tuberculin sensitivity is stronger in children tested for the second time after vaccination than in those tested for the first time after vaccination. The hypothesis that the tuberculin test itself may reinforce sensitivity to a further test has now been confirmed in 2 strictly controlled prospective studies, which are reported here. The results refer to the tuberculin reactions 5 years after vaccination. These reactions were significantly larger in children who had had an intermediate test (less than 5 years after vaccination) than in those tested for the first time at 5 years. This was found equally for several BCG products, but there was a significant tendency for the PPD batch RT 19-20-21 to have a more pronounced effect than the other tuberculins.It follows from the results of these studies that a possible waning of tuberculin sensitivity cannot be revealed by regular tuberculin testing. Moreover, experiments in guinea-pigs have shown that restoration of sensitivity by means of an injection of tuberculin does not influence the acquired resistance; there are no particular reasons to believe that this should be different in man. Thus the authors consider the very common practice of giving regular tuberculin tests to vaccinated children, in order to decide on possible revaccination, to be devoid of any scientific basis.

BCG vaccination by bifurcated needle in a pilot vaccination programme.

The bifurcated needle technique for BCG vaccination was compared with intradermal injection in a mass BCG and smallpox vaccination programme in Afghanistan. In all population groups the bifurcated needle technique produced substantial tuberculin sensitivity, which however was significantly inferior to that following intradermal injection. The advantages of the bifurcated needle technique did not result in a significant increase in vaccination coverage and output. Under the present circumstances vaccination by bifurcated needle would probably be more expensive than intradermal vaccination.

Tuberculosis control in refugee settlements.

Tuberculosis and its management in refugees and other displaced persons in temporary settlements poses a challenge to organisations coordinating and providing care in refugee emergencies. This paper offers a consensus of the co-sponsoring agencies on practical recommendations for implementing measures aimed at both interrupting transmission of tuberculosis and treatment of individual patients.

The use of jet-injectors in BCG vaccination.

In mass vaccination programmes, the jet-injection of vaccine may have considerable operational advantages over the classical techniques. The technical performance of two models of jet-injector, the Dermo-Jet and the Ped-O-Jet, in BCG vaccination was assessed in a number of studies which are reviewed by the authors. It is shown that the jet-injectors do not administer the full dose for which they are calibrated and that the size of the vaccination lesion varies more than after vaccination by syringe.By increasing the dosage considerably, the results of vaccination by jet-injection may be improved to a certain extent but the risk of unpleasant reactions is also increased.