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Controlled expression of cloned PhiX174 gene E in Gram-negative bacteria results in lysis of the bacteria by formation of an E-specific transmembrane tunnel structure built through the cell envelope complex. Bacterial ghosts from a variety of bacteria are used as non-living candidate vaccines. In the recombinant ghost system, foreign proteins are attached on the inside of the inner membrane as fusions with specific anchor sequences. Ghosts have a sealed periplasmic space and the export of proteins into this space vastly extends the capacity of ghosts or recombinant ghosts to function as carriers of foreign antigens. In addition, S-layer proteins forming shell-like self assembly structures can be expressed in candidate vaccine strains prior to E-mediated lysis. Such recombinant S-layer proteins carrying foreign epitopes further extend the possibilities of ghosts as carriers of foreign epitopes. As ghosts have inherent adjuvant properties, they can be used as adjuvants in combination with subunit vaccines. Subunits or other ligands can also be coupled to matrixes like dextran which are used to fill the internal lumen of ghosts. Oral, aerogenic or parenteral immunization of experimental animals with recombinant ghosts induced specific humoral and cellular immune responses against bacterial and target components including protective mucosal immunity. The most relevant advantage of recombinant bacterial ghosts as immunogens is that no inactivation procedures that denature relevant immunogenic determinants are employed in this production. This fact explains the superior quality of ghosts when compared to other inactivated vaccines. The endotoxic component of the outer membrane does not limit the use of ghosts as vaccine candidates but triggers the release of several potent immunoregulatory cytokines. As carriers, there is no limitation in the size of foreign antigens that can be inserted in the membrane and the capacity of all spaces including the membranes, peri-plasma and internal lumen of the ghosts can be fully utilized. This extended recombinant ghost system represents a new strategy for adjuvant free combination vaccines.

In 1991 a cholera epidemic occurred in Nigeria. The features of this cholera outbreak in a single hospital in Cross River, Nigeria, were examined. Microbiologic techniques included the use of thiosulphate citrate bile-salts sucrose (TCBS) medium for culture of all stool specimens. Vibrio isolates from diarrheic patients included V. cholerae-O1 (75), V. cholerae non-O1 (10) and V. parahaemolyticus (21). The illnesses were diverse, ranging from mild to severe, and in most instances requiring hospitalization, rehydration as well as antibiotic treatment. Eighty patients were hospitalized and six died mainly from hypovolemic shock and acute renal failure arising from excessive fluid loss. The low vibrio-associated mortality observed in this outbreak may have been influenced by the proximity and easy transit access to the health care facilities offered by the teaching hospital. This contrasts with the high mortality figures reported by Health Centers in the rural areas during the same period. Some features of vibrio diarrheas were comparable with those of other enteric pathogens. Poorly developed water and sewage disposal systems, contact with sea water, consumption of fishery products and leftover foods were the main risk factors identified.