The prevalence of penicillin-nonsusceptible pneumococci is sharply divided between France (43%) and Germany (7%). These differences may be explained on different levels: antibiotic- prescribing practices for respiratory tract infections; patient-demand factors and health-belief differences; social determinants, including differing child-care practices; and differences in regulatory practices. Understanding these determinants is crucial for the success of possible interventions. Finally, we emphasize the overarching importance of a sociocultural approach to preventing antibiotic resistance in the community.

Many infectious agents, especially those that cause emerging diseases, infect more than one host species. Managing reservoirs of multihost pathogens often plays a crucial role in effective disease control. However, reservoirs remain variously and loosely defined. We propose that reservoirs can only be understood with reference to defined target populations. Therefore, we define a reservoir as one or more epidemiologically connected populations or environments in which the pathogen can be permanently maintained and from which infection is transmitted to the defined target population. Existence of a reservoir is confirmed when infection within the target population cannot be sustained after all transmission between target and nontarget populations has been eliminated. When disease can be controlled solely by interventions within target populations, little knowledge of potentially complex reservoir infection dynamics is necessary for effective control. We discuss the practical value of different approaches that may be used to identify reservoirs in the field.

The age distribution of cases of dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) in infants under the age of 1 year are reported from Bangkok, Thailand, and for the first time for Ho Chi Minh City, Vietnam; Yangon, Myanmar; and Surabaya, Indonesia. The four dengue viruses were isolated from Thai infants, all of whom were having a primary dengue infection. Progress studying the immunologically distinct infant DHF/DSS has been limited; most contemporary research has centered on DHF/DSS accompanying secondary dengue infections. In designing research results obtained in studies on a congruent animal model, feline infectious peritonitis virus (FIPV) infections of kittens born to FIPV-immune queens should be considered. Research challenges presented by infant DHF/DSS are discussed.

Zoonotic visceral leishmaniasis (ZVL) is a serious public health problem in several Brazilian cities. Although the proximity of chicken houses is often cited as a risk factor in studies of urban ZVL, the role chickens play in the epidemiology of the disease has not been defined. Chickens attract both male and female sand flies (Lutzomyia longipalpis), but are unable to sustain Leishmania infections, and their presence may exert a zooprophylactic effect. We discuss environmental, physiologic, socioeconomic, and cultural factors related to chicken raising that could influence Le. infantum transmission in Brazilian cities and evaluate whether this practice significantly affects the risk of acquiring ZVL.

Taiwan has one of the highest levels of antibiotic-resistant pneumococcus in the world. Pneumococcal isolates not susceptible to penicillin first appeared in Taiwan in 1986; in 1995 an increase in the prevalence of nonsusceptibility to penicillins, extended-spectrum cephalosporins, trimethoprim-sulfamethoxazole, and macrolides as well as multidrug resistance began to be recognized. With the persistence of antibiotic selective pressure, resistance in some antibiotics reached a high plateau (β-lactam antibiotics) or continued to increase (macrolides), while novel resistance (fluoroquinolones) emerged in the last 3 years. Widespread distribution of some novel resistant 23F and 19F clones (and the international epidemic of 23F clones) contributes further to the rapid increase of resistance. Because Streptococcus pneumoniae is a major pathogen that causes community-acquired lower respiratory tract infections and meningitis in adults and children, antibiotic-resistance in this organism is a serious problem.

West Nile virus (WNV) was isolated from a patient who developed encephalitis while undergoing treatment with CHOP (cyclophosphamide, hydroxydoxorubicin, vincristine [Oncovin], predisone) and rituximab for a non-Hodgkin B-cell lymphoma. Both standard reverse transcription–polymerase chain reaction (RT-PCR) and Taqman RT-PCR established the diagnosis of WNV infection from cerebrospinal fluid (CSF). Several whole blood samples and one serum sample underwent further testing. CSF and serum samples were negative for WNV antibody; however, all samples were positive by both RT-PCR assays. Infectious virus was recovered from a blood sample, and its identity was confirmed by using a WNV-specific immunofluorescence assay. The complete WNV genomes determined from CSF and from the virus isolate adapted from cell culture were the same. The results represent the first complete WNV genome sequence obtained directly from human CSF and the first time that infectious WNV has been recovered from a patient with encephalitis in North America.

During the late summer of 1998, veterinary authorities in Tuscany, Italy, received reports of cases of neurologic disease among horses residing in a large wetland area located in the provinces of Florence and Pistoia. West Nile virus was isolated from two of the six horses that died or were euthanized. A retrospective epidemiologic study identified 14 clinical neurologic cases that occurred from August 20 to October 6 (attack rate of 2.8%). A serologic survey conducted over a 700-km2 area in stables with and without apparent clinical cases confirmed a wider spread of the infection, with an overall seroprevalence rate of 38% in the affected area. No significant differences in age-specific prevalence were observed, suggesting that the horses residing in the area had not been exposed previously to West Nile virus and supporting the hypothesis of its introduction in the wetland area during the first half of 1998.

West Nile virus (WNV) is a member of the Flaviviridae family of vector-borne pathogens. Clinical signs of WNV infection include neurologic symptoms, limb weakness, and encephalitis, which can result in paralysis or death. We report that the WNV-capsid (Cp) by itself induces rapid nuclear condensation and cell death in tissue culture. Apoptosis is induced through the mitochondrial pathway resulting in caspase-9 activation and downstream caspase-3 activation. Capsid gene delivery into the striatum of mouse brain or interskeletal muscle resulted in cell death and inflammation, likely through capsid-induced apoptosis in vivo. These studies demonstrate that the capsid protein of WNV may be responsible for aspects of viral pathogenesis through induction of the apoptotic cascade.

To identify the mosquito species competent for West Nile virus (WNV) transmission, we evaluated 10 California species that are known vectors of other arboviruses or major pests: Culex tarsalis, Cx. pipiens pipiens, Cx. p. quinquefasciatus, Cx. stigmatosoma, Cx. erythrothorax, Ochlerotatus dorsalis, Oc. melanimon, Oc. sierrensis, Aedes vexans, and Culiseta inornata. All 10 became infected and were able to transmit WNV at some level. Ochlerotatus, Culiseta, and Aedes were low to moderately efficient vectors. They feed primarily on mammals and could play a secondary role in transmission. Oc. sierrensis, a major pest species, and Cx. p. quinquefasciatus from southern California were the least efficient laboratory vectors. Cx. tarsalis, Cx. stigmatosoma, Cx. erythrothorax, and other populations of Cx. pipiens complex were the most efficient laboratory vectors. Culex species are likely to play the primary role in the enzootic maintenance and transmission of WNV in California.

Results of experiments evaluating the efficacy of three immunization strategies for the prevention of West Nile virus (WNV) encephalitis are reported. Immunization strategies evaluated included a killed virus veterinary vaccine, a live attenuated chimeric virus vaccine candidate, and passive immunization with WNV-immune serum; all were tested by using a hamster model of the disease. Each product protected the animals from clinical illness and death when challenged with a hamster-virulent wild-type WNV strain 1 month after initial immunization. The live attenuated chimeric virus vaccine candidate induced the highest humoral antibody responses, as measured by hemagglutination inhibition, complement fixation, and plaque reduction neutralization tests. Although the duration of protective immunity was not determined in this study, our preliminary results and the cumulative experience of other virus vaccines suggest that the live attenuated chimeric virus provides the longest lasting immunity.

During December 12–29, 1998, seven patients ages 2–18 years were diagnosed with serogroup C meningococcal disease in two neighboring Florida towns with 33,000 residents. We evaluated a mass vaccination campaign implemented to control the outbreak. We maintained vaccination logs and recorded the resources used in the campaign that targeted 2- to 22-year-old residents of the two towns. A total of 13,148 persons received the vaccinations in 3 days. Vaccination coverage in the target population was estimated to be 86% to 99%. Five additional cases of serogroup C meningococcal disease occurred in the community during the year after the campaign began, four in patients who had not received the vaccine. The cost of control efforts was approximately $370,000. Although cases continued to occur, the vaccination campaign appeared to control the outbreak. Rapid implementation, a targeted approach, and high coverage were important to the campaign's success.

Recent epidemics of Plasmodium falciparum malaria have been observed in high-altitude areas of East Africa. Increased malaria incidence in these areas of unstable malaria transmission has been attributed to a variety of changes including global warming. To determine whether the reemergence of malaria in western Kenya could be attributed to changes in meteorologic conditions, we tested for trends in a continuous 30-year monthly malaria incidence dataset (1966–1995) obtained from complete hospital registers at a Kenyan tea plantation. Contemporary monthly meteorologic data (1966–1995) that originated from the tea estate meteorologic station and from global climatology records were also tested for trends. We found that total hospital admissions (malaria and nonmalaria) remained unchanged while malaria admissions increased significantly during the period. We also found that all meteorologic variables showed no trends for significance, even when combined into a monthly suitability index for malaria transmission. We conclude that climate changes have not caused the highland malaria resurgence in western Kenya.

Susceptibilities to fourteen antimicrobial agents important in clinical medicine and agriculture were determined for 752 Escherichia coli isolates of serotypes O26, O103, O111, O128, and O145. Strains of these serotypes may cause urinary tract and enteric infections in humans and have been implicated in infections with Shiga toxin–producing E. coli (STEC). Approximately 50% of the 137 isolates from humans were resistant to ampicillin, sulfamethoxazole, cephalothin, tetracycline, or streptomycin, and approximately 25% were resistant to chloramphenicol, trimethoprim-sulfamethoxazole, or amoxicillin-clavulanic acid. Approximately 50% of the 534 isolates from food animals were resistant to sulfamethoxazole, tetracycline, or streptomycin. Of 195 isolates with STEC-related virulence genes, approximately 40% were resistant to sulfamethoxazole, tetracycline, or streptomycin. Findings from this study suggest antimicrobial resistance is widespread among E. coli O26, O103, O111, O128, and O145 inhabiting humans and food animals.

The first confirmed Rift Valley fever outbreak outside Africa was reported in September 2000, in the Arabian Peninsula. As of February 2001, a total of 884 hospitalized patients were identified in Saudi Arabia, with 124 deaths. In Yemen, 1,087 cases occurred, with 121 deaths. Laboratory diagnosis of Rift Valley fever virus (RVFV) infections included virus genetic detection and characterization of clinical specimens by reverse transcription-polymerase chain reaction, in addition to serologic tests and virus isolation. Genetic analysis of selected regions of virus S, M, and L RNA genome segments indicated little genetic variation among the viruses associated with disease. The Saudi Arabia and Yemen viruses were almost identical to those associated with earlier RVF epidemics in East Africa. Analysis of S, M, and L RNA genome segment sequence differences showed similar phylogenetic relationships among these viruses, indicating that genetic reassortment did not play an important role in the emergence of this virus in the Arabian Peninsula. These results are consistent with the recent introduction of RVFV into the Arabian Peninsula from East Africa.

To determine whether direct passage of spirochetes between co-feeding vector ticks contributes to the likelihood that the Lyme disease spirochete Borrelia afzelii will perpetuate in nature, we compared the effects of time and space on transmission efficiency between simultaneously feeding ticks. The likelihood of co-feeding transmission increases with duration of attachment of the infecting tick. Co-feeding transmission becomes less efficient as distance from the infecting tick increases. Approximately 6 times as many ticks acquire infection when feeding on infected mice than when co-feeding with infected ticks. Both subadult stages of the wood tick Ixodes ricinus infrequently co-infest mice and voles in nature; on approximately 1 in 20 small rodents, larvae co-feed with spirochete-infected nymphs. Because only 1 in 100 larvae in nature appear to acquire spirochetal infection when co-feeding with infected nymphs, perpetuation of B. afzelii depends largely on horizontal transmission of such pathogens from previously infected mice to noninfected larvae.

Clusters of nosocomial infection often occur undetected, at substantial cost to the medical system and individual patients. We evaluated binary cumulative sum (CUSUM) and moving average (MA) control charts for automated detection of nosocomial clusters. We selected two outbreaks with genotyped strains and used resistance as inputs to the control charts. We identified design parameters for the CUSUM and MA (window size, k, α, β, p₀, p₁) that detected both outbreaks, then calculated an associated positive predictive value (PPV) and time until detection (TUD) for sensitive charts. For CUSUM, optimal performance (high PPV, low TUD, fully sensitive) was for 0.1 <α ≤0.25 and 0.2 <β <0.25, with p₀ = 0.05, with a mean TUD of 20 (range 8–43) isolates. Mean PPV was 96.5% (relaxed criteria) to 82.6% (strict criteria). MAs had a mean PPV of 88.5% (relaxed criteria) to 46.1% (strict criteria). CUSUM and MA may be useful techniques for automated surveillance of resistant infections.

We determined if infection indicators were sufficiently consistent across health plans to allow comparison of hospitals’ risks of infection after coronary artery bypass surgery. Three managed care organizations accounted for 90% of managed care in eastern Massachusetts, from October 1996 through March 1999. We searched automated inpatient and outpatient claims and outpatient pharmacy dispensing files for indicator codes suggestive of postoperative surgical site infection. We reviewed full text medical records of patients with indicator codes to confirm infection status. We compared the hospital-specific proportions of cases with an indicator code, adjusting for health plan, age, sex, and chronic disease score. A total of 536 (27%) of 1,953 patients had infection indicators. Infection was confirmed in 79 (53%) of 149 reviewed records with adequate documentation. The proportion of patients with an indicator of infection varied significantly (p<0.001) between hospitals (19% to 36%) and health plans (22% to 33%). The difference between hospitals persisted after adjustment for health plan and patients’ age and sex. Similar relationships were observed when postoperative antibiotic information was ignored. Automated claims and pharmacy data from different health plans can be used together to allow inexpensive, routine monitoring of indicators of postoperative infection, with the goal of identifying institutions that can be further evaluated to determine if risks for infection can be reduced.

To assess influenza vaccination coverage in Germany, we conducted a nationwide telephone survey in November 1999 in adults (>18 yrs) using random-digit dialing. Overall, 23% of 1,190 survey participants reported having been vaccinated (adjusted 18%) with 16% (adjusted 15%) in former West Germany versus 35% (adjusted 32%) in former East Germany. Immunization rates for vaccination target groups were lower in West Germany (21%) than in East Germany (40%). Seven percent of health-care workers were immunized. Previous influenza vaccination, positive attitudes towards immunization, and having a family physician increased the rate of vaccination; fear of adverse effects lowered the rate. Family physicians performed 93% of the vaccinations, which suggests their key role in improving low vaccination coverage in Germany. The fact that >71% (850/1,190) of participants belonged to at least one of the vaccination target groups recommended by the German Standing Commission on Immunization emphasizes the need to focus the definition of target groups.

After a large outbreak of Legionnaires’ disease in the Netherlands, we determined risk factors for intensive care unit (ICU) admission and death and the impact of adequate therapy on ICU-free survival among 141 hospitalized patients. Overall mortality rate was 13%, and ICU mortality rate was 36%. Smoking, temperature >38.5°C, and bilateral infiltrates shown on chest x-ray were independent risk factors for ICU admission or death (all p<0.05). Starting adequate therapy within 24 hours after admission resulted in a higher ICU-free survival rate compared to therapy initiation after 24 hours: 78% versus 54%, respectively (p=0.005). However, delay in providing therapy to patients with urinary antigen tests with negative results did not influence outcome. These data suggest that by using the urinary antigen test on admission a more tailored approach to patients with community-acquired pneumonia may be applied.

After an outbreak of leptospirosis in workers who participated in cleaning a pond during September 1999 in Thailand, a serologic survey was conducted. Among a cohort of 104 persons from one village who participated in pond cleaning activity, 43 (41.3%) were seropositive for immunoglobulin M antibodies against Leptospira, indicating recent infection. Only 17 (39.5%) of 43 seropositive persons reported a recent febrile illness; the remaining seropositive persons were considered asymptomatic, suggesting that asymptomatic leptospirosis infection may be common where leptospirosis is endemic. Multivariable logistic regression indicated that wearing long pants or skirts was independently protective against leptospirosis infection (OR_adjusted = 0.217), while the presence of more than two wounds on the body was independently associated with infection (OR_adjusted = 3.97). Educational efforts should be enhanced in areas where leptospirosis is endemic to encourage the use of protective clothing. In addition wound management and avoidance of potentially contaminated water when skin wounds are present should be included in health education programs.

An outbreak of Rift Valley fever in the Kingdom of Saudi Arabia and Yemen in 2000 was the first recognized occurrence of the illness outside of Africa and Madagascar. An assessment of potential mosquito vectors in the region yielded an isolate from Aedes vexans arabiensis, most closely related to strains from Madagascar (1991) and Kenya (1997).

We isolated Cowpox virus (CPXV) from the ulcerative eyelid lesions of a 14-year-old girl, who had cared for a clinically ill wild rat that later died. CPXV isolated from the rat (Rattus norvegicus) showed complete homology with the girl’s virus. Our case is the first proven rat-to-human transmission of cowpox.

A naturally occurring infection of Ehrlichia chaffeensis in lemurs is described. DNA of Ehrlichia chaffeensis was identified by polymerase chain reaction in peripheral blood from six of eight clinically ill lemurs. Organisms were cultured from the blood of one lemur exhibiting clinical and hematologic abnormalities similar to those of humans infected with E. chaffeensis.

Fluoroquinolone-resistant Campylobacter jejuni has been observed worldwide and is now being seen in the United States. Among patients in our health-care system in Pennsylvania, fluoroquinolone-resistant C. jejuni were not observed from 1982 to 1992; however, resistance increased to 40.5% in 2001. Resistance to erythromycin remains at a low level (<5%).

In 1998, a varicella-zoster virus glycoprotein E (gE) mutant virus (VZV-MSP) was isolated from a child with chickenpox. VZV-MSP, representing a second VZV serotype, was considered a rarity. We isolated another VZV-MSP-like virus from an elderly man with herpes zoster. These gE mutant viruses may have arisen through independent mutation or may represent a distinct VZV subpopulation that emerged more than 50 years ago.

We describe a case of locally acquired Plasmodium ovale malaria in Spain. The patient was a Spanish woman who had never traveled out of Spain and had no other risk factors for malaria. Because patients with malaria may never have visited endemic areas, occasional transmission of malaria to European hosts is a diagnostic and clinical challenge.

We compared the occurrence of nephropathia epidemica cases, over a multi-annual population cycle, in northeastern France with the hantavirus serology for bank voles captured in the same area. We discuss hypotheses to explain the pattern of infection in both humans and rodents and their synchrony.

A mass immunization campaign for 18-month to 19-year-olds was undertaken in Spain in 1996–1997 because of an epidemic of serogroup C meningococcal disease associated with a C:2b:P1.2,5 strain belonging to the A4 lineage. Surveillance for the “capsule-switching” phenomenon producing B:2b:P1.2,5 isolates was undertaken. Of 2,975 meningococci characterized, B:2b:P1.2,5 and B:2b:P1.2 antigenic combinations were found in 18 isolates; 15 meningococci were defined as serogroup B belonging to the A4 lineage.

Using polymerase chain reaction and sequencing, we investigated the prevalence of Rickettsia prowazekii, Bartonella quintana, and Borrelia recurrentis in 841 body lice collected from various countries. We detected R. prowazekii in body lice from Burundi in 1997 and in lice from Burundi and Rwanda in 2001; B. quintana infections of body lice were widespread. We did not detect B. recurrentis in any lice.