Outbreaks remain an important but infrequent public health issue, representing <2% of all cases of meningococcal disease. However, given the increased case-fatality rate found among outbreak-related cases of N. meningitidis infection, additional investigation of factors that favor the transmission and virulence of outbreak-related strains is warranted.

Like many physiological ligands, several viruses and toxins enter mammalian cells through receptor-mediated endocytosis. Once internalized, the nucleic acids of several viruses and the toxic subunit of diphtheria toxin gain access to the cytosol of the host cell through an acidic intracellular compartment. In this report, we present evidence that one class of mutants of Chinese hamster ovary (CHO)-K1 cells, which is "cross-resistant" to Pseudomonas exotoxin A, diphtheria toxin, and several animal viruses, has a defect in acidification of the endosome. Cells were allowed to internalize fluorescein isothiocyanate-conjugated dextran before subcellular fractionation. Fluorescence measurements on subcellular fractions permitted measurement of the internal pH of the isolated endosomes and lysosomes. Our results show that (i) endosomes and lysosomes from CHO-KI cells maintain an acidic pH, (ii) acidification of both endosomes and lysosomes is mediated by a Mg2"/ATP-dependent process, (iii) GTP can satisfy the ATP requirement for acidification of lysosomes but not of endosomes, and (iv) at leastone class of mutants thatis cross-resistant to toxins and animal viruses has a defect in the ATP-dependent acidification of their endosomes. These studies provide biochemical and genetic evidence that the mechanisms of acidification of endosomes and lysosomes are distinct and that a defect in acidification of endosomes is one biochemical basis for cross-resistance to toxins and viruses.Receptor-mediated endocytosis is a specific cell-directed mechanism by which extracellular substances can enter the intracellular vesicular system (1, 2). Steps in the entry pathway include (i) binding to cell surface receptors; (ii) internalization within coated vesicles, (iii) distribution of ligand to appropriate intracellular compartments; and (iv) in many-cases, return of the receptor to the cell surface. For some pathogenic viruses and toxins, step iii includes transfer of a portion of the ligand to the cytosol (3-8). Recently, it has become apparent that this transfer, which is critical for the biologic activity of these viruses and toxins, requires an acidic environment (7-13). Although lysosomes are known to be acidic (14,15), recent evidence (16) 5315The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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The high rates of occupationally related injuries, accidents, and deaths in rural Thailand are of particular concern to public health officials, as well as the residents and workers living in these areas. In response to specific concerns raised by local residents and local health officials in Chainat Province, Thailand, the Work Improvement in Neighborhood Development (WIND) programme was introduced and implemented by means of the local Primary Care Unit (PCU). The objective was to improve farmers' knowledge of methods to improve occupational safety and to reduce the occurrence of occupationally related injuries, accidents, and deaths in the area. Local farmers, public health officers, and health volunteers from the PCU played a primary role in the programme, serving as trainers in the initial training of trainer session. Major activities included visiting a local farm to carry out a check-list improvement activity and active discussion among participants about potential improvements. Following the implementation of WIND in Chainat, a number of significant improvements in work conditions were noted, including construction of resting corners, plans to build toilets in the fields, improved knowledge about the dangers of chemical fertilizers and pesticides, and increased use of personal protective equipment. Furthermore, participants began making organic fertilizer and had independently developed an organic anti-snail pesticide. This integrative approach, achieved by including many different members of the community, in combination with government support and diligent follow-up, has proved to be particularly successful.