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Identification of the most significant infectious disease threats to deployed U.S. military forces is important for developing and maintaining an appropriate countermeasure research and development portfolio. We describe a quantitative algorithmic method (the Infectious Diseases Investment Decision Evaluation Algorithm) that uses Armed Forces Medical Intelligence Center information to determine which naturally occurring pathogens pose the most substantial threat to U.S. deployed forces in the absence of specific mitigating countermeasures. The Infectious Diseases Investment Decision Evaluation Algorithm scores the relative importance of various diseases by taking into account both their severity and the likelihood of infection on a country-by-country basis. In such an analysis, the top three endemic disease threats to U.S. deployed forces are malaria, bacteria-caused diarrhea, and dengue fever.

U.S. military physicians and researchers have collaborated in the development of eight U.S.-licensed vaccines since 1934, when product efficacy requirements were added to product safety requirements mandated in 1902. These vaccines include influenza (1945), rubella (1969), adenovirus types 4 and 7 (1980), meningococcus A, C, Y, W-135 (1981), hepatitis B (1981), oral typhoid (1989), Japanese encephalitis (1992), and hepatitis A (1995). Current efforts include new adenovirus and Japanese encephalitis vaccines, and vaccines to prevent dengue, diarrhea due to enterotoxigenic E. coli, Campylobacter, and Shigella, malaria, hemorrhagic fever with renal syndrome, scrub typhus, meningococcus type B, and HIV infection. All vaccines currently administered to U.S. military forces must be licensed by the U.S. Food and Drug Administration (FDA).

US military physicians and researchers helped identify the optimum treatment dose of the naturally occurring compound quinine and collaborated with the pharmaceutical industry in the development and eventual US Food and Drug Administration approval of the synthetic antimalarial drugs chloroquine, primaquine, chloroquine-primaquine, sulfadoxine-pyrimethamine, mefloquine, doxycycline, halofantrine, and atovaquone-proguanil. Because malaria parasites develop drug resistance, the US military must continue to support the creation and testing of new drugs to prevent and treat malaria until an effective malaria vaccine is developed. New antimalarial drugs also benefit civilians residing in and traveling to malarious areas.

Arthropod-borne diseases such as malaria, dengue, scrub typhus, and leishmaniasis continue to pose a significant threat to U.S. military forces deployed in support of operational and humanitarian missions. These diseases are transmitted by a variety of arthropods, including mosquitoes, ticks, chiggers, sand flies, and biting midges. In addition to disease threats, biting arthropods can cause dermatitis, allergic reactions, and sleep loss; therefore, monitoring of vector impact and integrated use of personal protective measures (PPM) and methods to reduce the vector populations are needed to protect service members. The U.S. military has played a vital role in vector identification tools and the development and testing of many of the most effective PPM and vector control products available today, including the topical repellent DEET and the repellent/insecticide permethrin, which is applied to clothing and bed nets. Efforts to develop superior products are ongoing. Although the U.S. military often needs vector control products with rather specific properties (e.g., undetectable, long-lasting in multiple climates) in order to protect its service members, many Department of Defense vector control products have had global impacts on endemic disease control.

Other researchers have found that diethylcarbamazine (DEC) is effective treatment for filariasis despite a lack of demonstrated in vitro antifilarial activity. The results of our previous investigations using feline and murine leukemia virus models encouraged us to investigate the use of DEC with other infections. In the current experiments, DEC treatmentS was associated with (a) increased survival and decreased brain Streptococcus pneumoniae levels following S. pneumoniae challenge in previously immunized mice; (b) increased serum antibody levels to S. pneumoniae, Escherichia coli, and Haemophilus influenzae following inoculation of live bacteria; and (c) lower brain fungal levels following intravenous injection of Aspergillus fumigatus or increasing numbers of Cryptococcus neoformans organisms, and lower brain and kidney levels of Candida albicans following intravenous injection of increasing numbers of C. albicans.

US military physicians and researchers helped identify the optimum treatment dose of the naturally occurring compound quinine and collaborated with the pharmaceutical industry in the development and eventual US Food and Drug Administration approval of the synthetic antimalarial drugs chloroquine, primaquine, chloroquine-primaquine, sulfadoxine-pyrimethamine, mefloquine, doxycycline, halofantrine, and atovaquone-proguanil. Because malaria parasites develop drug resistance, the US military must continue to support the creation and testing of new drugs to prevent and treat malaria until an effective malaria vaccine is developed. New antimalarial drugs also benefit civilians residing in and traveling to malarious areas.

This study was done to assess the size and characteristics of the patient population with bipolar illness treated on the general medical service of two divisions of the Charleston Area Medical Center, the largest hospital complex in West Virginia.A total of 779 admitting and/or discharge summaries were reviewed.The average age of the manic patients (50.5 years) was lower than that of schizophrenic patients (56.1 years) or the general population (58.9 years). The most common reasons for admission in the manic group were chest pain (5 patients) and drug overdose (4 patients). Alcohol abuse was more common in the bipolar group (20%) than in the schizophrenic group (11%) or the general population (12%).Additional studies of the prevalence of bipolar disorder in West Virginia are warranted.

Twenty Strongyloides-infected patients were diagnosed at West Virginia's Charleston Area Medical Center in 1997 and 1998. We recommend that strongyloidiasis, which can be fatal, be a reportable disease in West Virginia.

Previous reports suggest that diethylcarbamazine citrate (DEC) could be useful in the treatment of retroviral, bacterial, and fungal infections [1]. In an additional experiment, DEC (25 mg by mouth twice daily) was administered concurrently with oral Zidovudine (20 mg/kg twice daily, later changed to 10 mg/kg, then 15 mg/kg oral Videx twice daily) to a chronically FeLV-infected 18-month-old female domestic shorthair cat (cat S). FeLV serum p27 levels were lowered (by a factor of 10) with no apparent adverse effects or notable changes in serum alanine aminotransferase and creatinine levels, and a weight gain of 0.5 kg was noted over 4 months. Another study indicated that 1 month of oral DEC (10 mg/kg day -~) given to 12 FeLV-infected cats did not significantly alter serum alanine aminotransferase and

Other researchers have found that diethylcarbamazine (DEC) is effective treatment for filariasis despite a lack of demonstrated in vitro antifilarial activity. The results of our previous investigations using feline and murine leukemia virus models encouraged us to investigate the use of DEC with other infections. In our current experiments, DEC treatment was associated with lower brain fungal burden in fluconazole-treated mice following intravenous injection of Aspergillus fumigatus or increasing numbers of Cryptococcus neoformans organisms, and lower brain and kidney levels of Candida albicans following intravenous injection of increasing numbers of C. albicans. Further investigation of combined DEC and fluconazole treatment of fungal infections is warranted.

Notable complications from adenovirus pneumonia in healthy adults are rare. We report a well-documented case of adenovirus type 3 infection in a previously well adult woman that resulted in severe pulmonary complications as well as self-limited ocular, hepatic, and gastrointestinal abnormalities.

A cohort of 63 hemophiliac subjects was followed for clinical and immunologic abnormalities related to the acquired immune deficiency syndrome (AIDS). When evaluated in early 1984, antibody to human T cell leukemia virus type III (HTLV-III) was detected in the serum of 59 percent (24 of 41) of factor VIII or IX concentrate recipients, but in none (0 of six) of the cryoprecipitate/fresh frozen plasma recipients. HTLV-III-seropositive hemophiliac subjects, on average, had been exposed to twice as much concentrate during the previous year as seronegative hemophiliac subjects. The seropositive group had a significantly lower mean helper/suppressor T cell ratio and absolute helper T cell level than the seronegative group. By early 1984, 13 hemophiliac subjects in the study population had lymphadenopathy and one had AIDS. Antibody to HTLV-III was detected in the serum of 13 of these 14 hemophiliac subjects with overt clinical disease. The prevalence of lymphadenopathy or AIDS among HTLV-III-seropositive hemophiliac subjects was 54 percent (13 of 24). It is concluded that HTLV-III antibody occurs with high frequency in hemophiliac subjects, and is related to the amount of factor VIII or IX concentrate infused. Over half of HTLV-III-seropositive hemophiliac subjects in this population had overt clinical disease with either lymphadenopathy or AIDS.

To evaluate the risk of heterosexual transmission of the acquired immunodeficiency syndrome lymphadenopathy and infection with human T-lymphotropic virus type III (HTLV-III) the authors studied 42 hemophiliacs and their wives. By early 1984 9 of the hemophiliacs had asympotomatic lymphadenopathy and 1 had the acquired immunodeficiency syndrome. 21 hemophiliacs including all 10 with clinically overt disease and antibody to HTLV-III. None of the 42 wives had lymphadenopathy or the acquired immunodeficiency syndrome but 2 had HTLV-III antibody. 1 of these women had evidence of immunologic dysfunction with a markedly reduced T-helper/suppressor cell ratio. The husbands of these 2 women both had HTLV-III antibody but neither had overt acquired immunodeficiency syndrome-related disease. Thus as of early 1984 the prevalence of HTLV-III antibody in wives of hemophiliacs seropositive for HTLV-III was 9.5% (2 of 21). The authors conclude that transmission of HTLV-III occurs between hemophiliacs and their heterosexual partners. (authors)

To the Editor.— Schwartz et al 1 recently presented in JAMA a comprehensive summary of the current status of human immunodeficiency virus (HIV) serum antibody testing. However, two points raised by the authors concerning HIV-1 antibody testing by enzyme-linked immunoassay (EI A) warrant further comment. The authors state that "the more reactive the HIV test result, the greater the likelihood of disease. Most false-positive EI A results occur in specimens that have a low specimen-to-control optical density ratio." I suggest that it would be more accurate to say that "the higher the absorbance value corresponding to HIV-1 antibody level, the greater the likelihood of minimally symptomatic HIV-1 infection," since loss of antibody to gag- encoded HIV-1 proteins is frequently associated with development of HIV-related disease among persons in the developed world and may complicate serodiagnosis. 2 I agree that a highly reactive EIA is more likely to represent a true-positive

Ten young adult male patients with chronic hepatitis B virus infection and positive hepatitis B e antigen and DNA polymerase (DNAP) levels were treated with alternating courses of seven to 28 days of 5 to 7.5 mg/kg of vidarabine monophosphate (adenine arabinoside monophosphate) and 28 days of human leukocyte interferon (IFN-α); three different regimens were given on an outpatient basis. All patients responded with a fall in their DNAP level, and the DNAP remained undetectable six months after treatment was stopped in one patient. The major side effect, which most often occurred in those patients receiving 7.5 mg/kg of vidarabine monophosphate, was severe muscular pains. This study demonstrated the feasibility of administering vidarabine monophosphate and interferon to outpatients. Based on data from this and other studies, it is now possible to use a relatively nontoxic regimen that includes 28 days of 5 mg/kg of vidarabine monophosphate in a larger controlled study to answer the question of efficacy. (JAMA1982;247:2261-2265)