Because of concern about the possible reintroduction of malaria transmission in Italy, we analyzed the epidemiologic factors involved and determined the country's malariogenic potential. Some rural areas in central and southern Italy have high receptivity because of the presence of potential malaria vectors. Anopheles labranchiae is probably susceptible to infection with Plasmodium vivax strains, but less likely to be susceptible to infection with P. falciparum. Its vulnerability is low because of the low presence of gametocyte carriers (imported cases) during the season climatically favorable to transmission. The overall malariogenic potential of Italy appears to be low, and reintroduction of malaria is unlikely in most of the country. However, our investigations showed that the malaria situation merits ongoing epidemiologic surveillance.

New stockpiles of smallpox vaccine are required as a contingency for protecting civilian and military personnel against deliberate dissemination of smallpox virus by terrorists or unfriendly governments. The smallpox vaccine in the current stockpile consists of a live animal poxvirus (Vaccinia virus [VACV]) that was grown on the skin of calves. Because of potential issues with controlling this earlier manufacturing process, which included scraping VACV lesions from calfskin, new vaccines are being developed and manufactured by using viral propagation on well-characterized cell substrates. We describe, from a regulatory perspective, the various strains of VACV, the adverse events associated with calf lymph-propagated smallpox vaccine, the issues regarding selection and use of cell substrates for vaccine production, and the issues involved in demonstrating evidence of safety and efficacy.

Trichomonas vaginalis may be emerging as one of the most important cofactors in amplifying HIV transmission, particularly in African-American communities of the United States. In a person co-infected with HIV, the pathology induced by T. vaginalis infection can increase HIV shedding. Trichomonas infection may also act to expand the portal of entry for HIV in an HIV-negative person. Studies from Africa have suggested that T. vaginalis infection may increase the rate of HIV transmission by approximately twofold. Available data indicate that T. vaginalis is highly prevalent among African-Americans in major urban centers of the United States and is often the most common sexually transmitted infection in black women. Even if T. vaginalis increases the risk of HIV transmission by a small amount, this could translate into an important amplifying effect since Trichomonas is so common. Substantial HIV transmission may be attributable to T. vaginalis in African-American communities of the United States.

From October 4 to November 2, 2001, the first 10 confirmed cases of inhalational anthrax caused by intentional release of Bacillus anthracis were identified in the United States. Epidemiologic investigation indicated that the outbreak, in the District of Columbia, Florida, New Jersey, and New York, resulted from intentional delivery of B. anthracis spores through mailed letters or packages. We describe the clinical presentation and course of these cases of bioterrorism-related inhalational anthrax. The median age of patients was 56 years (range 43 to 73 years), 70% were male, and except for one, all were known or believed to have processed, handled, or received letters containing B. anthracis spores. The median incubation period from the time of exposure to onset of symptoms, when known (n=6), was 4 days (range 4 to 6 days). Symptoms at initial presentation included fever or chills (n=10), sweats (n=7), fatigue or malaise (n=10), minimal or nonproductive cough (n=9), dyspnea (n=8), and nausea or vomiting (n=9). The median white blood cell count was 9.8 X 10³ /mm³ (range 7.5 to 13.3), often with increased neutrophils and band forms. Nine patients had elevated serum transaminase levels, and six were hypoxic. All 10 patients had abnormal chest X-rays; abnormalities included infiltrates (n=7), pleural effusion (n=8), and mediastinal widening (seven patients). Computed tomography of the chest was performed on eight patients, and mediastinal lymphadenopathy was present in seven. With multidrug antibiotic regimens and supportive care, survival of patients (60%) was markedly higher (<15%) than previously reported.

In 1998, the Centers for Disease Control and Prevention was notified of severe illnesses and one death, temporally associated with yellow fever (YF) vaccination, in two elderly U.S. residents. Because the cases were unusual and adverse events following YF vaccination had not been studied, we estimated age-related reporting rates for systemic illness following YF vaccination. We found that the rate of reported adverse events among elderly vaccinees was higher than among vaccinees 25 to 44 years of age. We also found two additional deaths among elderly YF vaccinees. These data signal a potential problem but are not sufficient to reliably estimate incidence rates or to understand potential underlying mechanisms; therefore, enhanced surveillance is needed. YF remains an important cause of severe illness and death, and travel to disease-endemic regions is increasing. For elderly travelers, the risk for severe illness and death due to YF infection should be balanced against the risk for systemic illness due to YF vaccine.

Recently, eight allelic variants of the pertactin gene (prn1-8) have been characterized in Bordetella pertussis strains isolated in Europe and the United States. It has been suggested that the divergence of the pertactin types of clinical isolates from those of the B. pertussis vaccine strains is a result of vaccine-driven evolution. Sequencing of the prn, which is relatively time-consuming, has so far been the only method for the differentiation of prn types. We have developed a rapid real-time polymerase chain reaction assay suitable for large-scale screening of the prn type of the circulating strains. This method correctly identified the prn type of all tested 41 clinical isolates and two Finnish vaccine strains. The method is simple and reliable and provides an alternative for sequencing in pertussis research.

We constructed a mathematical model to describe the spread of smallpox after a deliberate release of the virus. Assuming 100 persons initially infected and 3 persons infected per infectious person, quarantine alone could stop disease transmission but would require a minimum daily removal rate of 50% of those with overt symptoms. Vaccination would stop the outbreak within 365 days after release only if disease transmission were reduced to <0.85 persons infected per infectious person. A combined vaccination and quarantine campaign could stop an outbreak if a daily quarantine rate of 25% were achieved and vaccination reduced smallpox transmission by >33%. In such a scenario, approximately 4,200 cases would occur and 365 days would be needed to stop the outbreak. Historical data indicate that a median of 2,155 smallpox vaccine doses per case were given to stop outbreaks, implying that a stockpile of 40 million doses should be adequate.

Hepatitis E virus (HEV), a major cause of viral hepatitis in much of the developing world, has recently been detected in swine in North America and Asia, raising concern about potential for zoonotic transmission. To investigate if HEV is commonly present in swine in the Netherlands, pooled stool samples from 115 swine farms and nine individual pigs with diarrhea were assayed by reverse transcription-polymerase chain reaction (RT-PCR) amplification. HEV RNA was detected by RT-PCR and hybridization in 25 (22%) of the pooled specimens, but in none of the individual samples. RT-PCR amplification products of open reading frames 1 and 2 were sequenced, and the results were compared with published sequences of HEV genotypes from humans and swine. HEV strains from swine in the Netherlands were clustered in at least two groups, together with European and American isolates from swine and humans. Our data show that HEV in swine in the Netherlands are genetically closely related to HEV isolates from humans. Although zoonotic transmission has not been proven, these findings suggest that swine may be reservoir hosts of HEV.

To assess the impact of preventive measures by the food industry, we analyzed food monitoring data as well as trends in the incidence of listeriosis estimated through three independent sources: the National Reference Center of Listeriosis; a laboratory-based active surveillance network; and two consecutive nationwide surveys of public hospital laboratories. From 1987 to 1997, the incidence of listeriosis decreased by an estimated 68%. A substantial reduction in the proportion of Listeria monocytogenes-contaminated products was observed at the retail level. The temporal relationship between prevention measures by the food industry, reduction in L. monocytogenes-contaminated foodstuffs, and reduction in listeriosis incidence suggests a causal relationship and indicates that a substantial part of the reduction in illness is related to prevention efforts.

We reviewed all serologically confirmed cases of leptospirosis from 1985 to 1999 in Israel, where the disease is endemic. There were 59 cases, with an average annual incidence of 0.05/100,000. The dominant serogroup, Leptospira icterohemorrhagica, occurred in 29% of patients; in an earlier study (1970-1979), it accounted for only 2%. Serogroups that occurred mainly in rural areas accounted previously for 79% but had declined to 32%.

Malaria cases reported to the Minnesota Department of Health increased from 5 in 1988 to 76 in 1998, paralleling the number of immigrants to Minnesota. In 20% of cases, the Plasmodium species was not identified; 44% of cases were hospitalized. The public health community needs to reevaluate current recommendations for refugee screening, provider and patient education, and laboratory capacity.

During 1995 to 1999, we collected 1,210 Salmonella isolates; 629 were from Finnish travelers returning from abroad. These isolates were tested for susceptibility by determining MICs to ciprofloxacin, nalidixic acid, and seven additional antimicrobial agents. From 1995 to 1999, the annual proportion of reduced ciprofloxacin susceptibility (MIC > 0.125 µg/mL) among all travelers' isolates increased from 3.9% to 23.5% (p<0.001). The increasing trend was outstanding among the isolates from Southeast Asia; isolates from Thailand alone increased from 5.6% to 50.0% (p<0.001). The reduced fluoroquinolone susceptibility was nonclonal in character and significantly associated with multidrug resistance. A point mutation in the quinolone resistance-determining region of gyrA was present in all isolates with reduced susceptibility. These data provide further evidence for the rapid spread of multidrug-resistant pathogens from one continent to another.

Advances in serologic assays for Cryptosporidium parvum have made serology an attractive surveillance tool. The sensitivity, specificity, and predictive value of these new assays for surveillance of immunocompromised populations, however, have not been reported. Using stored serum specimens collected for the San Francisco Men's Health Study, we conducted a case-control study with 11 clinically confirmed cases of cryptosporidiosis. Based on assays using a 27-kDa antigen (CP23), the serum specimens from cases had a median response immunoglobulin (Ig) G level following clinical diagnosis (1,334) and a net response (433, change in IgG level from baseline) that were significantly higher than their respective control values (329 and -32, Wilcoxon p value = 0.01). Receiver operator curves estimated a cutoff of 625 U as the optimal sensitivity (0.86 [0.37, 1.0]) and specificity (0.86 [0.37, 1.0]) for predicting Cryptosporidium infection. These data suggest that the enzyme-linked immunosorbent assay technique can be an effective epidemiologic tool to monitor Cryptosporidium infection in immunocompromised populations.

The use of polymerase chain reaction-single-stranded conformational polymorphism (PCR-SSCP) to study rpoB gene mutations in rifampin-resistant (RIFr) Mycobacterium tuberculosis has yielded contradictory results. To determine the sensitivity of this method, we analyzed 35 RIFr strains and 11 rifampin-susceptible (RIFs) strains, using the DNA sequencing of the core region of rpoB for comparison. Of the RIFr, 24 had a PCR-SSCP pattern identical to that of H37Rv; the other 11 had four different patterns. The 11 RIFs had PCR-SSCP patterns identical to that of H37Rv. The sensitivity of the assay was 31.4%; its specificity was 100%. We observed a strong correlation between the degree of resistance and the type of mutation.

Rickettsia africae, a recently identified pathogen, was detected for the first time in Amblyomma ticks from Niger, Mali, Burundi, and Sudan, and "R. mongolotimonae" was identified for the first time in Africa. Rickettsiae of unknown pathogenicity and two new ehrlichiae of the Ehrlichia canis group were identified in ticks from Mali and Niger.

To control West Nile virus (WNV), it is necessary to know which mosquitoes are able to transmit this virus. Therefore, we evaluated the WNV vector potential of several North American mosquito species. Culex restuans and Cx. salinarius, two species from which WNV was isolated in New York in 2000, were efficient laboratory vectors. Cx. quinquefasciatus and Cx. nigripalpus from Florida were competent but only moderately efficient vectors. Coquillettidia perturbans was an inefficient laboratory vector. As WNV extends its range, exposure of additional mosquito species may alter its epidemiology.

A multistate outbreak of Escherichia coli O157:H7 infections occurred in the United States in June and July 1997. Two concurrent outbreaks were investigated through independent case-control studies in Michigan and Virginia and by subtyping isolates with pulsed-field gel electrophoresis (PFGE). Isolates from 85 persons were indistinguishable by PFGE. Alfalfa sprouts were the only exposure associated with E. coli O157:H7 infection in both Michigan and Virginia. Seeds used for sprouting were traced back to one common lot harvested in Idaho. New subtyping tools such as PFGE used in this investigation are essential to link isolated infections to a single outbreak.

In June 2000, vancomycin-intermediate Staphylococcus aureus (VISA) was isolated from a 27-year-old home health-care patient following a complicated cholecystectomy. Two VISA strains were identified with identical MICs to all antimicrobials tested except oxacillin and with closely related pulsed-field gel electrophoresis types. The patient was treated successfully with antimicrobial therapy, biliary drainage, and reconstruction. Standard precautions in the home health setting appear successful in preventing transmission.

We tested serum specimens from three groups of patients with pneumonia by indirect immunofluorescence against Legionella-like amoebal pathogens (LLAPs) 1-7, 9, 10, 12, 13; Parachlamydia acanthamoeba strains BN 9 and Hall's coccus; and Afipia felis. We found that LLAPs play a role (albeit an infrequent one) in community-acquired pneumonia, usually as a co-pathogen but sometimes as the sole identified pathogen.

Enterococci isolated from packaging areas of meat-processing facilities that produce ready-to-eat meat products were examined for high-level vancomycin resistance. A total of 406 enterococci isolates from the plants' packaging areas were examined for vancomycin resistance. High-level vancomycin resistance was not demonstrated in any enterococci isolated from 12 meat-processing plants.

We describe the first case of community-acquired bacteremia caused by Acinetobacter radioresistens; the patient was a 32-year-old HIV-positive neutropenic woman. Ambiguous Gram staining and poor biochemical reactivity of blood culture isolates misguided early diagnosis and therapy. Bacterial identification was based on 16S rDNA sequence analysis. A. radioresistens can be considered as a cause of opportunistic infection in immunodeficient patients.

We compared the characteristics of a cultured human "Helicobacter heilmannii" isolate with those of other helicobacters found in animals. Phenotypic, protein profile, 16S rDNA sequence, and DNA-DNA hybridization analyses identified the human strain as H. bizzozeronii, a species frequently found in dogs. Thus, H. bizzozeronii may have zoonotic potential.

Nontuberculous mycobacteria (NTM) have been recognized as an important cause of disease in immunocompromised hosts. Pulmonary disease caused by NTM is increasingly recognized in previously healthy persons. Investigation of pulmonary disease affecting a family of five identified an indoor hot tub as the source of NTM-related disease.

Streptomyces species are rare causes of invasive infection in humans. We report the first documented case of a catheter-associated bacteremia due to Streptomyces. The most likely source of infection was unlicensed, injectable holistic preparations that the patient had received. We review reported cases of invasive infections caused by Streptomyces and comment on the potential infectious complications of parenteral holistic treatments.

Salmonella enterica serotype Baildon, a rare serotype, was recovered from 86 persons in eight states; 87% of illnesses began during a 3-week period ending January 9, 1999. Raw restaurant-prepared tomatoes were implicated in multiple case-control studies. Contamination likely occurred on the farm or during packing; more effective disinfection and prevention strategies are needed.

In a prospective, unmatched case-control study of sporadic Shiga toxin (Vero cytotoxin)-producing Escherichia coli O157 (STEC O157) infection in England, exposure to the farming environment emerged strongly as a risk factor (adjusted odds ratio = 2.45; 95% confidence intervals = 1.49-4.02; p=0.0004) posing further challenges and opportunities for prevention.

A Rift Valley fever outbreak occurred in Mauritania in 1998. Seroepidemiologic and virologic investigation showed active circulation of the Rift Valley fever virus, with 13 strains isolated, and 16% (range 1.5%-38%) immunoglobulin (Ig) M-positivity in sera from 90 humans and 343 animals (sheep, goats, camels, cattle, and donkeys). One human case was fatal.

A cluster of 22 imported malaria cases, 21 caused by Plasmodium falciparum, was observed among illegal Chinese immigrants in northern Italy in the summer of 2000. The rate of severe disease was high because the patients were not immune and they sought health-care services late in their illness because of their clandestine status. Recognition of the outbreak was delayed because no regional alert system among infectious diseases hospitals was in place.

We report three fatal cases of bacteremia (two adults, one neonate) caused by Vibrio cholerae O1 (Ogawa), which occurred in the context of a community outbreak of cholera diarrhea in Blantyre, Malawi. Only four cases of invasive disease caused by V. cholerae O1 have previously been reported. We describe the clinical features associated with these rare cases and discuss their significance.

A new Rabies virus variant, with no close antigenic or genetic relationship to any known rabies variants found in bats or terrestrial mammals in the Americas, was identified in association with human rabies cases reported from the state of Ceará, Brazil, from 1991 to 1998. The marmoset, Callithrix jacchus jacchus, was determined to be the source of exposure.

Aedes albopictus, a mosquito vector of Dengue virus, has been recorded for the first time in Cameroon. Entomologic surveys in 2000 demonstrated that it is widespread in southern Cameroon, colonizing a wide variety of breeding sites and biting humans in every district surveyed. The presence of this vector increases the risk for emergence of dengue in Cameroon.