The role of provider characteristics on the hepatitis A and B vaccination status of adults in the United States during 2007-2015.

Hepatitis A and B vaccine coverage is suboptimal in US adults, even among those at increased risk for infection, morbidity, or mortality. To understand where medical education and resources might enhance vaccine coverage, it is important to first identify providers and places most commonly associated with the administration of hepatitis vaccinations. We conducted a retrospective analysis of commercial and Medicare insurance claims data from 2007 to 2015 to describe provider types and places of vaccination against hepatitis A and B among adults in the US, and estimated the time to initial vaccination from first diagnosis of a condition for which the Advisory Committee on Immunization Practices (ACIP) recommends hepatitis A and/or B vaccination among at-risk adults. We identified 183,326 adults who received hepatitis A vaccine, 148,119 hepatitis B vaccine, and 64,953 a bivalent vaccine. Mean age was 42.1-45.8 years. Family practice and internal medicine physicians were the main vaccine providers: 38.9% and 20.2% for hepatitis A, 43.7% and 21.4% for hepatitis B, 35.3% and 15.9% for bivalent vaccinations, respectively. ≥90% of initial vaccinations occurred in an office practice. In at-risk patients, median time to first-dose received was 11.8, 20.9, and 20.9 months for hepatitis A, hepatitis B, and hepatitis A/B vaccines, respectively. Primary care and office practices were the most common providers and places of vaccination, respectively, for hepatitis A and B vaccine. For at-risk patients, further research is needed to design vaccination strategies to improve the median time from first ACIP-recommended condition diagnosis to initial vaccination against hepatitis A and B.

Filariasis of the ankle: magnetic resonance imaging.

Filariasis is a world health problem that is frequently seen in tropical and subtropical countries. In endemic areas, the clinical spectrum of extremity swelling, lymphangitis, or elephantiasis is usually recognized as filariasis. In the United States, diagnosis of the disease may be more difficult because of lack of familiarity with this infection. We present a case of filaremic arthropathy of the ankle joint and the magnetic resonance imaging (MRI) findings of this disease. It is the first reported case of MRI findings in a human patient. MRI has been done on animal models with filariasis, and the findings are similar.

Dr. Kiyoshi Shiga: discoverer of the dysentery bacillus.

The clinical manifestations of dysentery have been described for centuries, and the prototypic bacterial agent, Shigella dysenteriae, was identified 100 years ago. In the English language there has been remarkably little written about Dr. Kiyoshi Shiga, discoverer of the dysentery bacillus. We submit a brief biography of Dr. Shiga and the circumstances leading to his discovery, which proved the bacterial etiology of nonamebic dysentery.

Filariasis of the ankle: magnetic resonance imaging

Filariasis is a world health problem that is frequently seen in tropical and subtropical countries. In endemic areas, the clinical spectrum of extremity swelling, lymphangitis, or elephantiasis is usually recognized as filariasis. In the United States, diagnosis of the disease may be more difficult because of lack of familiarity with this infection. We present a case of filaremic anthropathy of the ankle joint and the magnetic resonance imaging (MRI) findings of this disease. It is the first reported case of MRI findings in a human patient. MRI has been done on animal models with filariasis, and the findings are similar. (AU)

A randomized, placebo-controlled study of oral cimetidine as an immunopotentiator of parenteral immunization with a group B meningococcal vaccine.

Cimetidine (CIM) is an H2-receptor antagonist with a long history of clinical use in peptic ulcer disease. In addition to its inhibitory effect upon gastric acid secretion, CIM can also block histamine-mediated immunosuppression by inhibiting H2 receptors on suppressor T cells. CIM results in immunoaugmentation of both cellular and humoral immunity by this mechanism and has been used clinically in the treatment of chronic infectious and neoplastic diseases. We postulated that orally administered CIM, like an adjuvant, could augment the immunologic response to a parenteral vaccine. To test this hypothesis, a randomized placebo (PLB)-controlled, double-blinded study in 14 healthy volunteers was performed using a Group B meningococcal outer membrane protein (OMP) vaccine administered twice, 6 weeks apart. Volunteers were randomized within pairs defined by their screening OMP antibody titers to receive either CIM or PLB which was administered for 5 days, beginning 2 days before each of the two immunizations. All 14 volunteers completed the study with excellent compliance. Sera were tested for anti-OMP and bactericidal antibodies. The groups were comparable in terms of gender distribution, age and baseline anti-OMP titers. Reactogenicity to the vaccine was mild and comparable between groups. There was little effect of CIM (over PLB) on anti-OMP or functional bactericidal antibody levels over time. Geometric means of maximum OMP antibody increase over baseline was 3.3-fold (95% CI: 1.8-6.3) for CIM and 2.4 for PLB (CI: 1.6-3.7). CIM had a corresponding 3.9-fold increase (CI: 1.9-8.3) in bactericidal antibody level compared to 2.2 for PLB (CI: 1.4-3.4). We conclude that oral CIM was not effective as an immunopotentiator of immunization with this group B meningococcal vaccine.

Dengue fever in US military personnel in Haiti.

OBJECTIVE: To describe clinical manifestations and public health implications of an outbreak of dengue fever (DF) during Operation Uphold Democracy, Haiti, 1994. DESIGN: Consecutive sample. SETTING: Military combat support hospital, Port-au-Prince, Haiti. PATIENTS: A total of 101 US military personnel with acute febrile illnesses. INTERVENTIONS: A disease surveillance team collected clinical and epidemiologic data from US military clinics throughout Haiti. Febrile patients admitted to the combat support hospital were evaluated with standardized clinical and laboratory procedures. The surveillance team followed patients daily. MAIN OUTCOME MEASURES: Arbovirus isolation and specific antibody determination and symptoms and physical findings. RESULTS: Febrile illnesses accounted for 103 (25%) of the 406 combat support hospital admissions during the first 6 weeks of deployment. All patients with febrile illness recovered. A total of 30 patients had DF; no patient had evidence of infection with malaria. Dengue virus serotypes 1, 2, and 4 were isolated from 22 patients, and 8 patients developed IgM antibody to dengue virus. Patients with DF could not be distinguished from other febrile patients on clinical grounds alone. No arboviruses other than dengue were identified. CONCLUSIONS: Active surveillance, with clinical and laboratory evaluation directed by an epidemiologic team, led to the timely recognition of an outbreak of febrile illness among US troops in Haiti. Viral isolation and serological studies were essential in confirming DF. During the surveillance period, DF accounted for at least 30% of the febrile illnesses among hospitalized US troops. Dengue fever is a significant threat to military personnel and civilian travelers in Haiti and has the potential for introduction to and transmission in the United States.

Safety, immunogenicity, and efficacy of Plasmodium falciparum repeatless circumsporozoite protein vaccine encapsulated in liposomes.

Seventeen malaria-naive volunteers received a recombinant Plasmodium falciparum vaccine (RLF) containing the carboxy- and the amino-terminal of the circumsporozoite protein (CSP) antigen without the central tetrapeptide repeats. The vaccine was formulated in liposomes with either a low or high dose of 3-deacylated monophosphoryl lipid A (MPL) and administered with alum by intramuscular injection. Both formulations were well tolerated and immunogenic. MPL increased sporozoite antibody titers measured by ELISA, Western blot, and immunofluorescence assay. One high-dose MPL vaccine formulation recipient developed a CSP-specific cytotoxic T lymphocyte response. After homologous sporozoite challenge, immunized volunteers developed patent malaria. There was no correlation between prepatent period and antibody titers to the amino- or carboxy-terminal. The absence of delay in patency argues against inclusion of the amino-terminal in future vaccines. A significant cytotoxic T lymphocyte response may have been suppressed by the inclusion of alum as an adjuvant.

Peru-15, an improved live attenuated oral vaccine candidate for Vibrio cholerae O1.

Cholera vaccine candidate Peru-15 was derived from a Vibrio cholerae O1 El Tor Inaba strain by deleting the cholera toxin genetic element, introducing the gene encoding cholera toxin B subunit into recA, and screening for nonmotility. In a controlled study, Peru-15 (2 x 10(8) cfu) was administered to 11 volunteers. No vaccinee developed diarrhea, and 10 of 11 had > 4-fold rises in vibriocidal antibody titers. One month later, 5 vaccinees and 5 control volunteers were challenged with wild type V. cholerae O1. Four of 5 controls developed diarrhea (mean, 1.9 L). Two Peru-15 vaccinees developed diarrhea, 1 with < 0.3 L and 1 with approximately 1.0 L; this latter volunteer had not developed a significant vibriocidal immune response to vaccination. Peru-15 shows promise as a single-dose, oral cholera vaccine that is safe, immunogenic, and protective.

Use of azithromycin for the treatment of Campylobacter enteritis in travelers to Thailand, an area where ciprofloxacin resistance is prevalent.

We evaluated the use of azithromycin (500 mg) or ciprofloxacin (500 mg) daily for 3 days for the treatment of acute diarrhea among United States military personnel in Thailand. Stool cultures were obtained and symptoms were recorded on study days 0, 1, 2, 3, and 10. Campylobacter species were the most common pathogen isolated (44 isolates from 42 patients). All Campylobacter isolates were susceptible to azithromycin; 22 were resistant to ciprofloxacin. Among the 42 patients with campylobacter infection, there were 2 clinical and 6 bacteriologic treatment failures in the ciprofloxacin group and no treatment failures in the azithromycin group (P = .021 for bacteriologic failures). Overall, azithromycin was as effective as ciprofloxacin in decreasing the duration of illness (36.9 hours vs. 38.2 hours, respectively) and the number of stools (6.4 vs. 7.8, respectively). Among those not infected with Campylobacter species (n = 30), the duration of illness was 32.9 hours vs. 20.7 hours (P = .03) for the azithromycin and ciprofloxacin groups, respectively. Azithromycin is superior to ciprofloxacin in decreasing the excretion of Campylobacter species and as effective as ciprofloxacin in shortening the duration of illness. Azithromycin therapy may be an effective alternative to ciprofloxacin therapy in areas where ciprofloxacin-resistant Campylobacter species are prevalent.

Safety, immunogenicity, and efficacy of live attenuated Vibrio cholerae O139 vaccine prototype.

New vaccines are needed to prevent cholera caused by Vibrio cholerae O139. Attenuated V cholerae O139 vaccines were made by deleting multiple copies of the cholera-toxin genetic element from two virulent strains of the organism, MO10 and AI4456. The deletion mutants were further modified by insertion of a construct that encoded the B subunit of cholera toxin, thus generating strains Bengal-3 and VRI-16. A stable spontaneous non-motile derivative of Bengal-3 was isolated and designated Bengal-15; VRI-16 is naturally non-motile. Bengal-3, Bengal-15, and VRI-16 were evaluated as oral single-dose cholera vaccine candidates in 4 volunteers each, and MO10 was given to 3 volunteers. 1 of 4 volunteers who received Bengal-3 and all 3 who received MO10 had diarrhoea. VRI-16 caused no significant symptoms but was not immunogenic. Bengal-15 produced few symptoms and was nearly as immunogenic as MO10. Subsequently, Bengal-15 was given to 10 volunteers at a dose of 10(8) colony-forming units. No volunteers had diarrhoea, and other subjective symptoms were as common in vaccinees as in 3 buffer recipients. 1 month after vaccination, 7 vaccinees, the 3 buffer recipients, and 3 unimmunised subjects were challenged with 5 x 10(6) colony-forming units of V cholerae O139. 5 of 6 controls had cholera-like diarrhoea. By contrast, 1 of 7 vaccinees had diarrhoea, which was mild and had a long incubation period. Vaccine protective efficacy was 83%. Our results indicate the Bengal-15 is a safe live attenuated vaccine candidate for cholera caused by the O139 serogroup.

Epidemiology of Norwalk virus during an outbreak of acute gastroenteritis aboard a US aircraft carrier.

A large outbreak of acute gastroenteritis occurred over a 5-week period aboard an aircraft carrier. The estimated cumulative attack rate was 13% among the 4,500-man crew. Eight percent of the crew sought medical attention, nearly all of whom missed 1 day or more of work. The risk of developing illness was 2 to 3 times greater for individuals living in more crowded sleeping quarters (> 50 persons per compartment). Occurrence of gastroenteritis was associated with a fourfold or more rise in Norwalk virus antibody levels, as measured by an enzyme-linked immunoassay utilizing a baculovirus expressed recombinant antigen. In addition, 27 nm Norwalk virus-like particles were visualized in two of six stools examined by immune electron microscopy. The presence of a low (< 1:50) or a high (> or = 1:6,400) pre-illness antibody level was associated with a lower incidence of illness. This investigation indicates that Norwalk virus can adversely impact operations of a military vessel and that crowding is a major risk factor in transmission.

Development of a live, oral, attenuated vaccine against El Tor cholera.

Vibrio cholerae El Tor strains from Peru, Bangladesh, and Bahrain were attenuated by deletion of a genetic element that encodes virulence factors and RS1. The B subunit of ctx (ctxB) was reintroduced into the recA gene of the deletion mutants, rendering them unable to recombine with exogenous genetic elements and generating Peru-3, Bang-3, and Bah-3. Fifteen volunteers received one dose of various vaccine strains at 4 x 10(6) to 1 x 10(8) cfu. All strains colonized the gut. A > or = 4-fold rise in vibriocidal titer was observed in 14 volunteers, with titers of > or = 1600 in 13. Peru-3 was the least reactogenic, but 2 of 6 volunteers had loose stools. Peru-14, a filamentous motility-deficient mutant of Peru-3, was well tolerated and colonized 18 of 21 volunteers at doses of 2 x 10(6) to 1 x 10(9) cfu. Also, when 8 Peru-3 or Peru-5 vaccinees, 5 Peru-14 vaccinees, and 8 controls were challenged with 2 x 10(6) cfu V. cholerae El Tor Inaba (N16961), 11 vaccinees were protected compared with no controls. Peru-14 shows promise as a safe, effective, single-dose oral vaccine against El Tor cholera.

Laboratory and preliminary clinical characterization of Vi capsular polysaccharide-protein conjugate vaccines.

To improve its immunogenicity for children and adults and to make it suitable for routine immunization of infants against typhoid fever, the capsular polysaccharide of Salmonella typhi (Vi) was bound to the B subunit of the heat-labile toxin (LT-B) of Escherichia coli or the recombinant exoprotein A (rEPA) of Pseudomonas aeruginosa. The conjugates elicited higher levels of antibodies (micrograms per milliliter of serum) in mice and in guinea pigs than did Vi and, unlike Vi alone, elicited booster antibody responses in both species. In adult volunteers, Vi-LT-B and Vi-rEPA, respectively, elicited higher levels of antibodies than Vi alone after the first injection (4.74 versus 1.77 and 4.91 versus 1.77; P < 0.005) and 26 weeks later (2.32 and 2.69 versus 0.54; P < 0.04); a second injection of the conjugates did not elicit a booster response of Vi antibodies. None of the 51 vaccinees had fever or significant local reactions. Vi-rEPA elicited slightly higher levels of Vi antibodies than did Vi-LT-B at all intervals after injection, but these differences were not significant. Each conjugate elicited antibodies to its carrier protein. The antibody responses elicited in adults by Vi bound to LT-B and rEPA are similar to those of other polysaccharide-protein conjugates. These conjugates promise to be an improved Vi vaccine. Studies of Vi conjugates with adults and infants in areas where typhoid is endemic are planned.

Outpatient studies of the safety and immunogenicity of an auxotrophic Escherichia coli K-12-Shigella flexneri 2a hybrid vaccine candidate, EcSf2a-2.

A phase II study was conducted in 244 volunteers at Fort Ord, CA, to determine the safety and immunogenicity of EcSf2a-2, a live, oral Shigella vaccine constructed by transfer of genes from Shigella flexneri to Escherichia coli K-12. In this placebo-controlled study, four doses of vaccine ranging from 2.3 to 9.0 x 10(8) colony-forming units were given on days 0, 3, 14 and 17. Vaccine shedding occurred from 1 to 3 days after each dose. The vaccine was well tolerated at every dose tested. Significant levels of IgA, IgG or IgM antibody-secreting cells (ASC) recognizing S. flexneri 2a lipopolysaccharide (LPS) were found in 94% of a volunteer subset tested 7 days after the first dose of EcSf2a-2. Seven days after the third dose, ASC were detected less often (57%), and were mainly IgA. Significant rises in serum antibody to LPS were detected in 37% of vaccine recipients.

Hypokalemia associated with ticarcillin-clavulanic acid.

Charts of 16 patients on ticarcillin-clavulanic acid were examined. Eight patients were found to have hypokalemia, yet not all were screened routinely for potassium imbalance. Some physicians prescribing ticarcillin-clavulanic acid seem unaware of the drug's side effect.

Synthesis, characterization, and clinical evaluation of conjugate vaccines composed of the O-specific polysaccharides of Shigella dysenteriae type 1, Shigella flexneri type 2a, and Shigella sonnei (Plesiomonas shigelloides) bound to bacterial toxoids.

The theoretic basis for developing conjugate vaccines, to induce immunoglobulin G (IgG) lipopolysaccharide (LPS) antibodies for the prevention of shigellosis, has been described (J. B. Robbins, C.-Y. Chu, and R. Schneerson, Clin. Infect. Dis. 15:346-361, 1992). The O-specific polysaccharides (O-SPs) of Shigella dysenteriae type 1, S. flexneri type 2a, and S. sonnei were covalently bound to carrier proteins. Alone, the O-SPs were not immunogenic in mice. Conjugates of these O-SPs, injected into young outbred mice subcutaneously as saline solutions containing 2.5 micrograms of saccharide, elicited serum IgG and IgM antibodies with booster responses; adsorption onto alum enhanced their immunogenicity. Injection of 25 micrograms of these conjugates into adult volunteers elicited mild local reactions only. Each conjugate induced a significant rise of the geometric mean serum IgG, IgM, and IgA LPS antibody levels. A second injection 6 weeks later did not elicit booster responses, and adsorption of the conjugates onto alum did not enhance their immunogenicity. Conjugate-induced levels of IgA, but not IgG or IgM, declined to preimmunization levels at day 56. The levels of postimmunization antibodies of the three immunoglobulin classes were similar to or higher than those of recruits in the Israel Defense Force following shigellosis caused by S. flexneri type 2a or S. sonnei. These data provide the basis for evaluating these conjugates to prevent shigellosis.

Safety and immunogenicity of the oral, whole cell/recombinant B subunit cholera vaccine in North American volunteers.

A newly formulated, oral, inactivated whole cell plus recombinant B subunit (WC/rBS) cholera vaccine was evaluated in US military personnel. In the first study, 74 subjects were given two doses 14 days apart. In the second study, 186 subjects were randomized into four groups; two groups received vaccine with either full (4 g) or half (2 g) strength bicarbonate buffer, and two groups received either full or half strength buffer without vaccine. Mild gastrointestinal symptoms were associated with full buffer (P = .02) but not with the vaccine. In the first study, 36% of all subjects and 55% with low prevaccination titers (< 1:40) had a > or = 2-fold rise in vibriocidal antibody level; > 80% of subjects developed a 4-fold rise in anti-cholera toxin (CT) titers. Post-vaccination IgA and IgG anti-CT titers were approximately 1.5-fold higher among persons receiving full strength buffer (P = .05). The WC/rBS vaccine is safe and immunogenic in North Americans, although some mild gastrointestinal symptoms occur with the high concentration of buffer necessary to protect the B subunit from gastric acid denaturation. Prior immunity to cholera conferred by parenteral vaccine decreased vibriocidal antibody response.

Safety and immunogenicity of different immunization regimens of CVD 103-HgR live oral cholera vaccine in soldiers and civilians in Thailand.

Attenuated Vibrio cholerae oral vaccine CVD 103-HgR was well tolerated by 324 Thai soldiers and civilians. Most received a single 5 x 10(8) cfu dose, while 40 each received one or two 5 x 10(9) cfu doses. Vibriocidal antibody (the best correlate of immunity) seroconversion was lower in soldiers than civilians (P less than .001). Increasing the vaccine dose to 5 x 10(9) cfu raised the geometric mean titer (P less than .001). A second 5 x 10(9) cfu dose one week later did not notably increase seroconversions. Likelihood of seroconversion was inversely correlated with baseline vibriocidal titer (P less than .001). CVD 103-HgR caused seroconversion in most subjects with baseline titers less than or equal to 1:40, including 100% of civilians after one 5 x 10(8) cfu dose, 79% of soldiers after one 5 x 10(9) cfu dose, and 45% of soldiers after one 5 x 10(8) cfu dose. In persons with elevated baseline titers, vibriocidal antibody seroconversion is not a sensitive measure of whether vaccine has boosted intestinal immunity; for such subjects, other measurements must be used. Study regimens in endemic areas should use a single 5 x 10(9) cfu dose.

Phenytoin hypersensitivity.

Phenytoin hypersensitivity is a potentially fatal reaction to the chemical diphenylhydantoin. It is important to inform patients of possible complications and early sentinel signs of adverse drug reactions.