Steyn et al. (pp 415-424) have provided a detailed summary of recent research on mycobacteria. For those readers who would like an overview of the powerful new genetic and molecular technologies that are being applied to infectious organisms and to their interactions with host cells, this review is an encyclopedia.
The complete sequence of a strain of Mycobacterium tuberculosis, and soon to be available complete sequences for five other members of the family, promise a cascade of new knowledge on the organization of this large genome (4 411 529 base pairs). It is already known that the M. tuberculosis gene can be translated to produce 250 enzymes that are involved in fatty-acid metabolism. Also, 10% of the genome may be dedicated to promote antigenic variation.
Another remarkable genetic tool has been the follow-on development of genome microarrays, which are available in some cases on microchips. DNA microarrays measure gene expression in eukaryotes or prokaryotes. In effect, the whole process of infection can be studied by detecting which microorganism or host cell genes are ‘turned on’. By studying the process through time, the sequence of microorganism and host gene expression can be identified.
Another powerful molecular tool being applied to study the process of infection is proteomics. Studies are designed to detect the appearance of proteins as they are actively translated from genes. Steyn et al. describe how proteomics has been applied to fundamental questions such as the nature of virulence, mycobacterial defense mechanisms, and the process of latency. The same techniques are used to study host resistance and susceptibility to tuberculosis, the immune response, and strategies for producing effective vaccines.
Three other reviews bring the reader to a different reality. Kay (pp. 425-432) provides an admirable update on the present status of knowledge of and techniques for the control of Aedes aegypti. This adaptable and successful species evolved from purely sylvatic ancestors in Africa to its present worldwide distribution and its niche as the most domesticated mosquito. As an efficient vector of three human viral pathogens, each capable of pandemic disease, A. aegypti merits serious attention by the public health community. Not surprisingly, in some locales the species is demonstrating an extension of its habitat to include underground sites such as sewers in Colombia, and wells and service pits in northern Australia. Whether this is in response to increased mosquito population or to mosquito control pressure being placed upon indoor and more traditional breeding sites was not stated. More surprising is the admission by entomologists that after one century of attempting to control this species, there is little agreement as to how to enumerate populations. A group led by Florida entomologist Focks argues that pupal densities most accurately reflect populations of adult mosquitoes. A group in Trinidad, however, found the search for immature stages of A. aegypti to be time-consuming and fatiguing. They suggest wider use of a passive surveillance method such as ovitraps. On the subject of control, public health workers are battered by lack of funds and the generally low priority assigned to A. aegypti control. As Kay points out, A. aegypti control is not likely to succeed until someone learns how to make money in the process. The good news is that an inexpensive small crustacean, Mesocyclops, can be grown in large numbers and distributed around habitats by motivated humans. In north Vietnam, A. aegypti has been eradicated from a cluster of villages. We will soon learn whether this technology is transferrable. It has been adopted for a country-wide effort. Finally, viral resistance genes continue to be engineered into A. aegypti. If they can be endowed with a survival advantage, we might have mosquitoes that bite, but do not transmit.
Wolfe (pp 433-438) provides a comprehensive review of the field of travel medicine from the perspective of the practitioner. He provides an update on the new Lyme disease vaccine, the latest on rotavirus vaccines, and new information on already licensed vaccines. The section contains a clear discussion of current prophylaxis and treatment of malaria.
Finally, Hyams (pp 439-443) provides an insight into one of the enigmas of our era, the Gulf War syndrome (GWS). A review of the GWS is included in this section because the putative causal agent was located in an area of the world normally considered endemic for exotic or tropical diseases. Among factors initially considered as an etiology of GWS was visceral leishmaniasis. Hyams describes the evolution of GWS as a health and political problem, noting that the ‘syndrome’ was never defined by physicians, but by reporters. Furthermore, cases have largely been self-reported. Comprehensive toxicologic studies have been negative. Importantly, no overall increase was found in hospitalization rates among US veterans or in birth defects among children born after the war. Gulf War veterans were found to have less than half the mortality rate of an age- and sex-controlled civilian cohort. Nonetheless, among self-reported patients there were increased levels of depression, post-traumatic stress disorder, and neurological abnormalities. Numerous causative factors have been considered, the most important being stress.
The most interesting section is the description of very similar illnesses after each US war since the Civil War, but not after large-scale peacetime deployments. The constants in this syndrome are the deployment of humans into a stressful environment and a political culture that encourages the identification and possible amplification of cases. Hyams points out that over US$100 million has been spent to find the ‘cause’ of GWS. Possibly some of the powerful techniques described in the first paragraph of this discussion might have been used to identify genes activated in GWS sufferers. It was left to Hyams to point to the universal nature of this condition, however. Gulf War veterans are not alone. More importantly, a repetitive phenomenon that adversely affects human health suggests the constructive possibility of prevention, early identification, or intervention. In other words we might never fully understand the molecular mechanisms of GWS, but, with insight, sensitivity and patience, we might be able to intervene and prevent future suffering.
