Bioterrorism-related inhalational anthrax: the first 10 cases reported in 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 10(3)/mm(3) (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 vitro activity of antimalarial compounds on the exoerythrocytic stages of Plasmodium cynomolgi and P. knowlesi.

Primary cultures of Macaca mulatta hepatocytes infected with sporozoites of Plasmodium knowlesi, P. cynomolgi (Cambodian strain), and P. cynomolgi bastianellii were exposed in vitro to 7 antimalarial compounds. The number of exoerythrocytic schizonts present after 4-7 days of culture was used to assess the activity. With pyrimethamine, proguanil, cycloguanil, primaquine, and 2 of its analogues (WR242511 and WR238605), marked inhibition of schizont formation could be achieved at concentrations below those causing a cytotoxic effect on the host hepatocytes. Chloroquine had only minimal schizonticidal activity at a concentration that produced severe hepatocyte toxicity. This simian in vitro system provides a reliable model for screening antimalarial compounds and for investigating their effects on the hepatic stage of malaria parasites.

Cultivation of exoerythrocytic stages of Plasmodium cynomolgi, P. knowlesi, P. coatneyi, and P. inui in Macaca mulatta hepatocytes.

Exoerythrocytic stage parasites of Plasmodium cynomolgi, P. knowlesi, P. coatneyi, and P. inui were cultured by inoculating primary cultures of hepatocytes from Macaca mulatta with sporozoites. Less than 1% of inoculated sporozoites survived. Morphology and size of the liver stages in all 4 species were similar to in vivo descriptions and the time required for in vitro maturation correlated well with prepatent periods described.

In vitro cultivation of exoerythrocytic stages of the human malaria parasite Plasmodium malariae.

Exoerythrocytic stage parasites of Plasmodium malariae were obtained in vitro by inoculating primary cultures of hepatocytes from a chimpanzee (Pan troglodytes) and a monkey (Aotus lemurinus griseimembra) with sporozoites. Schizonts were observed in chimpanzee hepatocytes 8, 11, and 13 days after inoculation. Only 1 schizont was seen in Aotus hepatocytes at day 13. The morphology and development rates of P. malariae exoerythrocytic stages obtained in vitro were similar to those previously described in vivo.