Tularemia—United States, 1990-2000 FREE

MMWR. 2002;51:181-184

3 figures omitted

Tularemia is a zoonotic disease caused by the gram-negative coccobacillus Francisella tularensis. Known also as "rabbit fever" and "deer fly fever," tularemia was first described in the United States in 1911 and has been reported from all states except Hawaii. Tularemia was removed from the list of nationally notifiable diseases in 1994, but increased concern about potential use of F. tularensis as a biological weapon led to its reinstatement in 2000. This report summarizes tularemia cases reported to CDC during 1990-2000, which indicate a low level of natural transmission. Understanding the epidemiology of tularemia in the United States enables clinicians and public health practitioners to recognize unusual patterns of disease occurrence that might signal an outbreak or a bioterrorism event.

Tularemia characteristically presents as an acute febrile illness. Various clinical manifestations can occur depending on the route of infection and host response, including an ulcer at the site of cutaneous or mucous membrane inoculation, pharyngitis, ocular lesions, regional lymphadenopathy, and pneumonia. A diagnosis of tularemia can be laboratory-confirmed by culture of F. tularensis from clinical specimens or by a fourfold titer change of serum antibodies against F. tularensis. Presumptive diagnosis can be made by detecting F. tularensis antigens with fluorescent assays or by a single elevated antibody level.¹ For purposes of national surveillance, confirmed and probable tularemia cases are defined as clinically compatible illness with confirmatory or presumptive laboratory evidence of F. tularensis infection, respectively. Before September 1996, because of ambiguity in the case definition, some cases of tularemia might have been considered confirmed by fluorescent assay alone. Case status is determined at the state level. For the purposes of this report, any case reported to CDC was assumed to have laboratory evidence of infection. Similar results were obtained when the analysis was limited to cases with documented confirmed or probable status.

During 1990-2000, a total of 1,368 cases of tularemia were reported to CDC from 44 states, averaging 124 cases (range: 86-193) per year; 807 cases (59%) were reported as confirmed and 85 cases (6%) were reported as probable; the status of 476 cases is unknown. Most (91%) unclassified cases were reported during 1990-1992; all cases during 1990-1991 and 54% of cases from 1992 were not classified. The number of cases reported annually did not decrease substantially during the lapse in status as a notifiable disease during 1995-1999, but an increase in reporting occurred during 2000, when notifiable status was restored. Four states accounted for 56% of all reported tularemia cases: Arkansas (315 cases), Missouri (265 cases), South Dakota (96 cases), and Oklahoma (90 cases).

County of residence was available for 1,357 reported cases. Among the 3,143 U.S. counties, 543 (17.3%) reported at least one case during 1990-2000. The counties with the highest number of reported cases were located throughout Arkansas and Missouri, in the eastern parts of Oklahoma and Kansas, in southern South Dakota and Montana, and in Dukes County, Massachusetts (the island of Martha's Vineyard).

During 1990-2000, the average annual incidence of tularemia reported using 1995 population estimates was highest in persons aged 5-9 years and in persons aged ≥75 years. Males had a higher incidence in all age categories. Incidence was highest among American Indians/Alaska Natives (0.5 per 100,000), compared with 0.04 per 100,000 among whites and ≤0.01 per 100,000 among blacks and Asians/Pacific Islanders. Of the 936 cases reported with date of onset, 654 cases (70%) reported onset during May-August, but cases were reported in all months of the year.

E Hayes, MD, S Marshall, MPH, D Dennis, MD, Div of Vector-borne Infectious Diseases, National Center for Infectious Diseases; K Feldman, DVM, EIS Officer, CDC.

The number of tularemia cases reported annually has decreased substantially since the first half of the 1900s. The incidence was highest in 1939, when 2,291 cases were reported² and remained high throughout the 1940s. The number of cases declined substantially in the 1950s and 1960s to the relatively constant number of cases reported since that time.

In the United States, most persons with tularemia acquire the infection from arthropod bites, particularly tick bites, or from contact with infected mammals, particularly rabbits. Historically, most cases of tularemia occurred in summer, related to arthropod bites, and in winter, related to hunters coming into contact with infected rabbit carcasses. In recent years, a seasonal increase in incidence has occurred only in the late spring and summer months, when arthropod bites are most common. Outbreaks of tularemia in the United States have been associated with muskrat handling,³ tick bites,^4- 5 deerfly bites,⁶ and lawn mowing or cutting brush.⁷ Sporadic cases in the United States have been associated with contaminated drinking water⁸ and various laboratory exposures.⁹ Outbreaks of pneumonic tularemia, particularly in low-incidence areas, should prompt consideration of bioterrorism.¹⁰

The high incidence of tularemia among males and among children aged <10 years might be associated with increased opportunity for exposure to infected ticks or animals, less use of personal protective measures against tick bites, or diagnostic or reporting bias. The high incidence among American Indians/Alaska Natives might be associated with their increased risk for exposure; outbreaks of tularemia have been reported on reservations in Montana and South Dakota, where a high prevalence of tularemia infection was found in ticks and dogs.^4- 5

The findings in this report are subject to several limitations, including underreporting and the lack of documented laboratory confirmation for all cases. Surveillance for tularemia could be improved by documenting laboratory confirmation of diagnosis and by including additional data (e.g., clinical presentation, exposure history, and outcome).

Following a dramatic decline in the second half of the 20th century, the incidence of tularemia in the United States remains low. The epidemiologic characteristics described in this report provide a background against which unusual patterns of disease occurrence, including bioterrorism events, may be recognized more quickly.

This report was based on data contributed by state and local health departments.

MMWR. 2002;51:164-165

Congenitally acquired malaria is rare in the United States; ≤10 cases are reported each year.¹ Congenital infection with Plasmodium malariae is particularly uncommon because distribution of this parasite is focal and sparse in areas where P. falciparum is endemic.² The last case of congenital P. malariae infection in the United States was reported in 1992.³ This report describes the investigation of a case of P. malariae in an infant with no travel history outside of the United States and suggests that health-care providers suspect malaria when treating a neonate or young infant with fever if the mother has traveled or lived in a malarious area.

In September 2000, a previously healthy female infant aged 10 weeks who resided in Raleigh, North Carolina, developed fever and dark urine. A pediatrician examined the infant and found a temperature of 103.7°F (39.8°C) but no other abnormalities. Laboratory evaluation included a white blood cell count of 4,600 µ/L (normal range: 9,000-30,000 µ/L]) and hemoglobin of 8.7 g/dL (normal range: 10.0-14.0 g/dL). The same day, she was admitted to a local hospital for treatment and further evaluation. Laboratory studies were performed, including cultures of blood, urine, and cerebrospinal fluid (CSF). A repeated complete blood count (CBC) demonstrated hemoglobin (6.6 g/dL) and platelets (109,000 µ/L). Intravenous antibiotic therapy was begun with ampicillin and cefotaxime.

Two days after admission, blood films for malaria obtained the previous day were reported to contain Plasmodium malariae parasites; treatment with chloroquine was initiated. Over the next 2 days, the infant received two transfusions of packed red blood cells for anemia. Bacterial cultures of urine, blood, and CSF obtained on admission remained negative.The infant's clinical status improved, and she was discharged home after having completed chloroquine treatment. She had a negative malaria smear on specimens obtained 2 days and 15 days post-therapy.

In July 2000, approximately 42 days before admission, the infant was seen at a local hospital emergency department because her parents were concerned about her breathing pattern; however, physical exam and chest radiograph were normal and no treatment or follow-up was required. The infant had not traveled outside the city or received any blood products before hospitalization.

Both parents had emigrated to the United States from the Democratic Republic of the Congo; the father arrived in 1995 and the mother in 1996. The mother reported being treated for malaria with chloroquine shortly before leaving the Congo and presumptively completed a full course of therapy. Both parents denied any episodes of malaria, febrile illness, foreign travel, or blood transfusion following arrival in the United States. The family lived in a screened apartment in Raleigh, although some mosquitoes were noted indoors during August 2000. A friend from Kinshasa, Congo, stayed with the family during August; he reportedly was well during the visit.

Pretreatment malaria testing of the mother with thick and thin blood films prepared four times over a 2-week period was negative for malaria parasites. Subsequent serologic testing revealed positive IgG titers against P. falciparum and P. malariae (1:16,384), and against P. vivax and P. ovale (1:1,024). Polymerase chain reaction (PCR) analysis on pretreatment blood collected September 22 was negative for these four Plasmodium species. However, the mother was presumptively treated with chloroquine.

NJ D'Avanzo, MD, Blue Ridge Pediatrics; VM Morris, MD, Raleigh Infectious Diseases Associates; TR Carter, MD, Rex Hospital; J-M Maillard, MD, PM Scanlon, MPH, General Communicable Disease Control Br, Div of Public Health, Raleigh, North Carolina. GM Stennies, MD, M Wilson, MS, Div of Parasitic Diseases, National Center for Infectious Diseases; and PDM MacDonald, PhD, RD Newman, MD, EIS Officers, CDC.

Although the infant in this report could have been infected by the bite of a mosquito that had bitten a P. malariae-infected person (e.g., one of the parents or the visitor from Kinshasa), congenital transmission is a much more likely source of infection. P. malariae can persist in humans as an asymptomatic erythrocytic disease for many years following an untreated or incompletely treated primary infection. Symptomatic recrudescence has been reported for up to 70 years following primary infection.⁴ Unlike P. vivax and P. ovale, no dormant form exists in the liver. Recrudescence should not occur following completed treatment with chloroquine; therefore, additional treatment with primaquine as is required for radical cure of P. vivax and P. ovale is not necessary.

Pregnancy can make women more susceptible to infection with malaria and might allow a sufficient increase in the density of parasitemia for passage of parasites through the placenta to the fetus.⁵ Suspected malaria in the neonate should be confirmed using Giemsa-stained thick and thin blood smears. If the infant's smear is positive for malaria parasites, the mother's smears also should be examined for malaria parasites. If the mother's smears are negative, then serologic analysis of her blood for Plasmodium-specific antibodies should be conducted. Negative results demonstrate an absence of current or previous malaria infection and would rule out maternal transmission of malaria. Positive results indicate infection at some time but cannot be used to differentiate current from previous infection or to determine the infecting Plasmodium species. In persons with negative blood films and positive serology, PCR might be useful to detect low-level parasitemia and to determine the infecting species.

In this case, the mother's serology demonstrates previous infection with malaria parasites at some time. The pattern of elevated titers to P. falciparum and P. malariae commonly is seen in persons who have had long-term exposure to malaria in areas of Africa where the disease is endemic. The failure to detect P. malariae in the mother by smear or the more sensitive PCR is expected because most women spontaneously clear parasitemia in the hours following delivery.⁶ The mother in this report was not tested until 10 weeks after delivery, well past the expected period for detecting parasitemia.

U.S. health-care providers should be alert to the diagnosis of malaria in ill neonates and young infants, particularly those with fever. During evaluation, health-care providers should obtain a complete and accurate travel and residency history on the patient and close relatives. Patients should be asked about transfusion of blood products. However, the absence of recent foreign travel or a long interval between immigration of the mother and the birth of the infant being examined should not dissuade clinicians from obtaining blood films on the patient to rule out a potentially life-threatening but easily treatable infection.

Additional information about malaria and its distribution is available from CDC at http://www.cdc.gov/travel. Information about the diagnosis of malaria and the preparation of blood films is available at http://www.dpd.cdc.gov/dpdx.

MMWR. 2002;51:97-101

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Since 1983, when the first infant was conceived from in vitro fertilization (IVF) in the United States, the use of IVF and related procedures (assisted reproductive technology) has increased substantially. In 1998, an estimated 0.7% of the 3.9 million births were the result of ART.¹ ART patients are more likely to deliver multiple infants than women who conceive without treatment, and these multiple-infant births are associated with increased risks for pregnancy complications, premature delivery, low birth-weight infants, and long-term disability among surviving infants.² This report examines state-specific use of ART in 1996 and 1998 and provides data on ART live-born and multiple-infant birth rates in 1998. Findings indicate that the use of ART is increasing in most states and that more than half the infants born as a result of these procedures are multiple births. These high-risk births contribute disproportionately to health-care costs and might negatively affect maternal and child health outcomes, particularly in states where large numbers of ART procedures are performed.

The 1992 Fertility Clinic Success Rate and Certification Act* requires all U.S. clinics performing ART to report data annually to CDC for every ART procedure initiated.³ ART is defined as any procedure in which both oocytes and sperm are handled outside the body; these include IVF and gamete and zygote intrafallopian transfer (gametes or zygotes transferred into the fallopian tubes rather than the uterus). Procedures are classified according to whether the ART patient uses her own eggs or eggs donated by another woman, whether the embryos transferred were freshly fertilized or previously frozen, and whether the embryos were transferred into a gestational surrogate or a new treatment procedure was used. Clinics submit their data to CDC through the Society for Assisted Reproductive Technology reporting system.³ This report uses data from 1996, the first full year CDC collected data, and 1998, the latest year of completed data collection. State-specific comparisons of live-birth and multiple-birth rates as a result of ART require consideration of both ART type and patient age; however, because of insufficient sample sizes, age-adjusted rates could not be calculated for each state. Live-birth delivery (i.e., the percentage of procedures that resulted in the delivery of one or more live-born infants) and multiple birth rates are presented for ART procedures performed on women aged <35 years using fresh, nondonor embryos (excluding gestational surrogate and new treatment procedures).

During 1996-1998, the number of ART clinics increased nationally from 330 to 390 (18%), of which 315 (95%) reported data in 1996 and 360 (92%) reported data in 1998. The total number of reported ART procedures increased 26.5%, from 64,724 in 1996 to 81,899 in 1998. Increases were reported for 35 of the 38 states that had complete data for 1996 (i.e., no nonreporting clinics). The states where the greatest number of reported ART procedures were performed during 1998 were California (10,615), New York (8,689), Massachusetts (7,236), Illinois (5,145), and New Jersey (5,105). ART was not performed in Alaska, Idaho, Maine, Montana, or Wyoming.

In 1998, a total of 20,143 livebirth deliveries resulted from the 81,899 ART procedures. The national live-birth delivery rate was 24.7%. Nationally, 61,650 (75%) of the 81,899 ART procedures performed in 1998 were fresh nondonor; 11,228 (14%) were frozen nondonor; 5,828 (7%) were fresh donor; 1,928 (2%) were frozen donor; and 1,265 (2%) were procedures involving gestational surrogates, new treatments, or embryo banking. Live-birth delivery rates for the five ART types were 25%, 17%, 37%, 21%, and 30%,† respectively. For 27,858 procedures performed on women aged <35 years using fresh, nondonor embryos, the live-birth rate was 32.0% (95% confidence interval: 31.4%-32.5%).

The 20,143 live-birth deliveries from ART procedures performed in 1998 resulted in 28,873 live-born infants. The number of infants born was higher than the number of live-birth deliveries because of multiple-infant births. The five states with the largest number of ART procedures performed also reported the most infants born by ART procedures. A total of 16,281 (56%) infants were multiple births,‡ 12,598 (44%) were twins. Nationally, 61.6% of the ART infants born to women aged <35 years were multiple births; 16.4% were triplets and higher order multiples. The multiple-infant birth rate for these women was 70%-74% for six states (Connecticut, Hawaii, Louisiana, Nevada, New Mexico, and South Carolina).

LA Schieve, PhD, G Jeng, PhD, LS Wilcox, MD, Div of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion; Div of Applied Public Health Training, Epidemiology Program Office; MA Reynolds, PhD, EIS Officer, CDC.

Data in this report indicate that ART-related multiple births are an increasingly important public health problem nationally and in many states. The proportion of infants born as a result of ART in the United States in 1998 that were multiple births (56%) was substantially higher than the overall national average of 3%.⁴ This rate was even higher (62%) for the most common group receiving ART procedures: women aged <35 years who used fresh nondonor eggs. The triplet and higher-order birth rate for this group was 16%, 100 times higher than the national average of 0.16% among women this age in 1998.⁴

The findings in this report are subject to at least four limitations. First, not all clinics that perform ART procedures in the United States report data. Second, the incompleteness of residency data precludes the calculation of the contribution of ART to total births and multiple births among residents of each state. Some states are more likely to have nonresident ART patients, including states with military hospitals that perform ART (e.g., District of Columbia), states with clinics near borders (e.g., Kansas, Missouri, New Jersey, and Rhode Island), and states neighboring those with no ART clinics. Completeness of residency data was from 5% to 70% for 13 states and from 90% to 100% for 25 states. Among these 25 states, the proportion of ART procedures performed on in-state residents ranged from 74% to 100%. Third, the ART procedure is the unit of analysis for the surveillance data set; it is not possible to link data from multiple ART procedures performed on the same patient in a given year. Finally, these data reflect procedures performed in 1998 and resulting births (i.e., 1998 and 1999). Subsequent changes in ART technology and practice patterns that might have occurred might have affected live-birth and multiple-birth outcomes.

Multiple births disproportionately contribute to infant and maternal morbidity and mortality rates. Data in this report indicate a need to reduce multiple births associated with ART. Professional organizations such as the American Society for Reproductive Medicine have guidelines on the use of judicious limits on the number of embryos transferred.⁵ In addition, maternal residency and other data need to be monitored closely and to be well described to understand the growing impact of ART on maternal and child health.

References: 5 available

*Publication L No. 102-493(42 U.S.C. 263a-1 et seq.) October 24, 1992.

†Calculation excludes embryo banking procedures in which all embryos were frozen for later use.

‡Fetuses delivered with at least one being live-born.