The resurgence of malaria in areas where it had been controlled previously and the concurrent emergence of drug-resistant malaria strains contribute to the current recommendations concerning malaria chemoprophylaxis. Chloroquine (e.g., Aralen), the former standard for malaria prevention and treatment,is now effective only in limited areas, and multidrug resistance has made chemoprophylaxis with mefloquine (e.g., Lariam) less effective in some regions. This has complicated the decision-making process with regard to selection of optimal antimalarial drug regimens for international travelers. Guidelines from the Centers for Disease Control and Prevention (CDC) provide recommendations for the use of three currently available drugs for malaria prophylaxis in chloroquine-resistant areas: mefloquine, doxycycline (e.g., Vibramycin, Doryx), and atovaquone/proguanil (e.g., Malarone). Guidelines from the World Health Organization (WHO) include the three drugs above, and in addition, consider proguanil (e.g., Paludrine) coadministered or in fixed-dose combination with chloroquine, and also primaquine among current choices for malaria prophylaxis. This article presents a concise review of current knowledge about use of these drug regimens for prophylaxis against malaria. Given the increase in international travel and the spread of malaria into previously disease-free areas,growing numbers of travelers now face the risk of contracting this disease. 1 The number of cases of imported malaria has been rising in the United States,Canada,and other developed countries since the 1970s. In 1997, over 1,500 cases of imported malaria, including 6 fatalities, were reported in the United States, whereas in Canada, 1,036 cases of imported malaria were reported that year. 2‐5 Compounding the problem of increased incidence of malaria,parasite resis

Journal Article Discussion: Who Should Receive Hepatitis A Vaccine? A Strategy for Controlling Hepatitis A in the United States Get access F. Blaine Hollinger, F. Blaine Hollinger Reprints or correspondence: Dr. F. Blaine Hollinger. Baylor College of Medicine, One Baylor Plaza, Houston. TX 77030. Search for other works by this author on: Oxford Academic PubMed Google Scholar Moderator, Moderator Search for other works by this author on: Oxford Academic PubMed Google Scholar Theodore Eickhoff, Theodore Eickhoff Search for other works by this author on: Oxford Academic PubMed Google Scholar Anne Gershon, Anne Gershon Search for other works by this author on: Oxford Academic PubMed Google Scholar Elaine C. Jong, Elaine C. Jong Search for other works by this author on: Oxford Academic PubMed Google Scholar Raymond S. Koff Raymond S. Koff Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 171, Issue Supplement_1, March 1995, Pages S73–S77, https://doi.org/10.1093/infdis/171.Supplement_1.S73 Published: 01 March 1995

Some 15 million Americans travel abroad each year, half of them to developing countries. Not only are they venturing farther afield than ever before but they are more inclined to be adventurous. A high percentage of these hardy souls acquire some form of infection. Physicians should know the risks, their geographic distribution, and both prophylactic and therapeutic strategies.

A sensitive and specific immunoblot assay was used to rapidly and accurately diagnose paragonimiasis. The immunoreactivity of a complex Paragonimus westermani Chaffee antigen was evaluated by SDS-PAGE and Western blot analysis. Initial probing with pooled human serum from proven Paragonimus infections revealed many bands, including a significant antibody response to an approximately 8,000 molecular weight (8 kDa) protein. Forty-three of 45 proven paragonimiasis serum specimens had antibodies to this diagnostic band. Of 29 normal serum specimens and 210 serum specimens from patients with other parasitic and nonparasitic infections, only 1 serum, from a schistosomiasis haematobium patient, reacted positively. These results indicate that our immunoblot for paragonimiasis, which uses a comparatively crude antigen, is highly sensitive (96%) and specific (99%).

Mast cells, when incubated in vitro with hydrogen peroxide (H2O2) and iodide, are cytotoxic to schistosomula of Schistosoma mansoni, as determined morphologically by dye exclusion, motility, and refractility and by transmission and scanning electron microscopy. When intact mast cells were incubated with schistosomula, mast cell degranulation with extracellular release of mast cell granules (MCG) was only observed in the presence of added H2O2 (10(-4) M). The secreted MCG, which contain small amounts of endogenous peroxidase activity, adhered to the surface of schistosomula. By 15 to 30 min, the mast cell-H2O2 system in the presence of iodide (10(-4) M) produced marked disruption of the tegumental and internal structures of the schistosomula. No helminthic damage was noted if any component of the incubation mixture (mast cells, H2O2 or iodide) was omitted. MCG could substitute for intact mast cells in the H2O2 and iodide-dependent cytotoxic system; MCG-mediated killing of schistosomula was inhibited by the hemeprotein inhibitor azide, suggesting that the cytotoxic reaction required endogenous peroxidase. The cytotoxicity was increased by eosinophil peroxidase bound to the MCG surface. These findings suggest a mechanism by which mast cells may contribute to the host cytotoxic response to helminths. H2O2 formed by nearby inflammatory cells may induce mast cell secretion, and the released MCG, through their endogenous peroxidase content (or bound eosinophil or neutrophil peroxidase), may react with H2O2 and a halide to form a system toxic to the adjacent helminth.

Paragonimiasis was diagnosed in eight patients: five with sputum specimens positive for characteristic ova and three with only stool specimens positive for ova. Clinical symptoms, roentgenograms and serologic findings appeared to correlate with severity of disease. All eight patients were treated with praziquantel (oral dose, 75 mg/kg of body weight daily for two consecutive days). Of seven patients who completed the treatment, six had ova-negative sputum and stool specimens by day 90; the seventh patient's specimens became ova negative by day 120. The eighth patient, who had failed to respond to prior treatment with bithionol, could not tolerate the daily dosage of 75 mg/kg because of nausea. Although he received the same total dose (150 mg/kg) over four days his specimens remained ova positive on day 90. Adverse effects included nausea (two patients), headache (one patient), and urticaria (two), the last effect possibly secondary to release of antigen from drug-damaged parasites. A review of the epidemiology, clinical presentation, and treatment of pulmonary paragonimiasis is presented.

Eosinophil peroxidase (EPO) is a major component of the large cytoplasmic granules of eosinophils, and is released onto the surface of schistosomula when eosinophils adhere to antibody and complement coated organisms. EPO is a strongly cationic protein, which can bind to the surface of schistosomula with retention of peroxidatic activity. The binding per se was not toxic to the organisms under our conditions, but EPO-coated schistosomula were rapidly killed when H2O2 and halide were added, under conditions in which uncoated schistosomula were unaffected. The toxicity of the surface-bound EPO system was not significantly inhibited by albumin (20 mg/ml), in contrast to the complete inhibition by this concentration of protein when the EPO was free in solution. Purified polymorphonuclear leukocytes (PMNs) from normal donors were toxic to uncoated schistosomula in medium containing antischistosomal antibody and complement, and this toxicity was significantly increased when EPO was bound to the surface of the organisms. The toxicity of PMNs to EPO-coated schistosomula was inhibited but not abolished by the hemeprotein inhibitor azide. This is compatible with the involvement of surface-bound EPO in an enzymatic attack on the organism, utilizing H2O2 generated by PMNs stimulated by adherence to antibody and complement-coated schistosomula. PMN adherence to schistosomula is increased by surface-bound EPO, and this also may contribute to the enhancement of neutrophil-mediated toxicity by EPO. These findings indicate a mechanism by which two inflammatory cells, the eosinophil and neutrophil, may interact to enhance the destruction of a target organism.

A patient from Southeast Asia with cough and hemoptysis was documented to have pulmonary paragonimiasis. Initial treatment with bithionol failed. The patient was then treated with praziquantel 75 mg/kg body weight a day for 2 days under an investigational protocol. Subsequent follow-up studies showed clinical improvement and indicated parasitologic cure. A concurrent asymptomatic Clonorchis infection was also cured following praziquantel treatment. Side effects were minor.

Guinea pig eosinophil peroxidase (EPO) was capable of killing schistosomula of Schistosoma mansoni in vitro when combined with hydrogen peroxide and a halide. Killing was measured by 51Cr release, by microscopic evaluation of viability, and by reinfection experiments in mice. Parasite killing was dependent on each component of the EPO-H2O2-halide system, was completely inhibited by catalase and azide, and was partially inhibited by cyanide. The EPO-mediated system required 10(-4) M H2O2 and 10(-4) M iodide at pH 7.0, and the schistosomula were killed with exposure to this system of less than 30 min at 37 degrees C. At pH 6.0, the EPO-mediated system showed significant cidal activity with 10(-6) M iodide. Canine neutrophil peroxidase (myeloperoxidase [MPO]) was also able to kill schistosomula in vitro in the presence of 10(-4) M H2O2 and 10(-4) iodide at pH 7.0 and pH 6.0. Physiologic concentrations of chloride (0.1 M) could substitute for iodide at pH 7.0 and pH 6.0 as the halide cofactor; however, at pH 7.0, a higher concentration of enzyme was required. These findings with isolated enzyme systems are compatible with a role for peroxidase in the host defense against schistosomula.

A partially purified preparation of guinea pig eosinophil peroxidase was found to be bactericidal when combined with H2O2 and either iodide, bromide, chloride, or thiocyanate ions. The EPO-H2O2-halide bactericidal system had an acid pH optimum and was inhibited by the proteins albumin and gelatin and by the hemeprotein inhibitors azide, cyanide, and aminotriazole. When the EPO concentration of the reaction mixture was lowered, the bactericidal effect at pH 7.0 was lost first with chloride, then with bromide, and finally with iodide as the halide. Activity with physiologic concentrations of chloride was favored by a relatively high EPO level, a decrease in pH below neutrality and an absence of extraneous protein. These findings are discussed in relation to the potential role of the peroxidase system in the intracellular and extracellular toxic reactions of eosinophils.

Mast cells, when supplemented with H2O2 and iodide, are cytotoxic to mammalian tumor cells as determined by 51Cr release, and transmission and scanning electron microscopy. H2O2 at the concentration employed (10(-4) M) initiates mast cell degranulation, and mast cell granules (MCG), which contain a small amount of endogenous peroxidase activity, are toxic to tumor cells when combined with H2O2 and iodide. This toxicity is greatly increased by binding eosinophil peroxidase (EPO) to the MCG surface. Each component of the mast cell, MCG, or MCG-EPO system was required and toxicity was inhibited by the addition of the hemeprotein inhibitors azide or aminotriazole, which is compatible with a requirement for peroxidase in the cytotoxic reaction. A sequence of reactions is proposed in which mast cells, stimulated to release their granules by H2O2 generated by adjacent phagocytes, react with H2O2 and a halide to damage tumor cells. EPO release from eosinophils may contribute to this sequence of reactions, both by stimulation of H2O2-induced mast cell secretion and by combination with MCG to form a complex with augmented tumoricidal activity. These rections may play a role in the host defense against neoplasms.