Serologic classification of acute viral hepatitis at San Lazaro Hospital, Manila, Philippines.

Sixty-four out of 189 jaundiced patients at San Lazaro Hospital were defined as acute viral hepatitis cases. Of this number, 22 (34.4%) were positive for hepatitis A markers while 26 (40.6%) were positive for hepatitis B markers. Hepatitis D infection accounted for 1.6%, while non-A, non-B hepatitis accounted for 21.9%.

Immune response to cryptosporidiosis in Philippine children.

An ELISA was used to measure the Cryptosporidium-specific IgA, IgG, and IgM antibody levels in serum, stool, and duodenal fluid of 15 Filipino children. Antibody levels were measured on admission to the hospital, 1 week later, and at a 6 week follow-up examination. Delayed type hypersensitivity skin tests were used to assay cell mediated immunity (CMI), iron status was measured by serum iron tests and total iron binding capacity, and the degree of malnutrition was determined by clinical examination. Antibody response to Cryptosporidium was qualitatively and quantitatively strong and maintained over time. All subjects showed impaired CMI early with some reconstitution after 6 weeks. All subjects showed some degree of malnutrition and/or depleted iron status.

Comparison of Tensilon and antivenom for the treatment of cobra-bite paralysis.

We prospectively compared the ability of anti-venom and edrophonium (Tensilon) to improve paralytic symptoms in 8 patients envenomed by the Philippine cobra (Naja naja philippinensis). Twenty, 50 or 100 ml of Philippine cobra antivenom were administered in a double-blind fashion by constant intravenous infusion over 30 min. Even the largest dose of antivenom failed to produce marked improvement within 2 h, though enzyme-linked immunosorbent assays and neutralization tests demonstrated that it possessed high titres of anti-neurotoxin antibodies. Tensilon given at 2 h was significantly more effective than antivenom at increasing the duration of upward gaze (78 +/- 28 vs 43 +/- 26 sec, P less than 0.001), and either completely reversed or markedly decreased paralysis in every patient. The Tensilon test should be given to all patients with paralytic envenoming by cobras, and anticholinesterases administered to those with a positive response.

Symptoms associated with diarrhoeal illness at San Lazaro Hospital, Manila in 1983 and 1984.

The clinical features associated with various agents of diarrhoeal disease were studied using 2,836 patients admitted to San Lazaro Hospital, Manila. Three general patient groups were considered including single pathogen isolations, "multiple pathogen" isolations, and "no pathogen" isolations. In general, symptoms of diarrhoeal illness were found to be non-specific. However, Shigella flexneri. Vibrio parahemolyticus, and rotavirus were significantly associated with a number of prominent symptoms and could sometimes be predictably diagnosed on clinical grounds, especially when age of the patient was considered. Clinical diagnosis cannot be considered an adequate substitute for laboratory methods; other enteric pathogens can sometimes present with the same symptoms. When appropriate laboratory testing is unavailable, as is often the case in developing countries, symptomatologic diagnosis may be of limited value for the organisms mentioned.

Dengue infections in the Philippines: clinical and virological findings in 517 hospitalized patients.

From May 1983 to January 1984, 517 patients with laboratory confirmed dengue were studied at a hospital in Manila. Secondary dengue infections were diagnosed in 78% of these cases. Peak admission (28%) occurred towards the end of the rainy season in November. Most patients (78%) were less than 15 years old but only 3 were infants. Although some type of hemorrhagic finding occurred in 460 cases (89%), only 110 were classified as dengue hemorrhagic fever and the remainder as dengue fever with hemorrhagic manifestations. The clinical course was usually mild. Gastrointestinal bleeding was present in 65 cases, but only 2 patients developed shock. No fatalities occurred. Dengue 2 was the predominant serotype with 53 isolates, followed by dengue 1 with 48 isolates, dengue 3 with 39 isolates, and dengue 4 with only 8 isolates. Dengue 2 was the only serotype with more isolates from sera with a homologous HI antibody titer greater than 1:20 (57%) than from sera with a homologous HI titer less than or equal to 1:20 (43%). In contrast, most of the dengue 1 isolates (63%) were from sera with a homologous HI antibody titer less than 1:10, and this serotype was strongly associated with primary infections. This study shows that dengue infections remain an important cause of pediatric hospitalization in the Philippines; however, the occurrence of life-threatening dengue hemorrhagic fever as has been described in several other large urban areas of Southeast Asia appears to be rare.

Praziquantel pharmacokinetics and side effects in Schistosoma japonicum-infected patients with liver disease.

Praziquantel undergoes extensive first-pass hepatic biotransformation, but there is little information on its disposition or toxicity when administered to patients with liver disease. To define the influence of liver disease on the pharmacokinetics of praziquantel, we administered it orally to 30 patients with proven Schistosoma japonicum infection whose liver disease was carefully assessed as being severe, moderate, or absent. Both the peak plasma concentration of praziquantel and the bioavailability (measured as the area under the plasma concentration time curve) were significantly greater in the two groups of patients with liver disease (P less than .005), as were the concentrations of the two identified metabolites of praziquantel. Mild side effects were associated with high peak concentrations of praziquantel, but a syndrome of severe abdominal pain followed by bloody diarrhea was not. Our results indicate that the side effects and bioavailability of praziquantel are increased in the presence of liver disease.

Placebo-controlled trial of intravenous penicillin for severe and late leptospirosis.

The effect of a 7-day course of intravenous penicillin (6 million units/day) on severe, advanced leptospirosis was examined in a randomised, placebo-controlled, double-blind trial involving 42 patients. Every measurable aspect of the disease was favourably affected by penicillin. Fever lasted more than twice as long in the placebo group (11.6 [SD 8.34] days vs 4.7 [4.19] days, p less than 0.005), and by the fourth day after starting penicillin more than half the treatment group, but only 1 of 19 in the placebo group, were afebrile (p less than 0.005). Creatinine rises persisted more than thrice as long in the patients receiving only placebo (8.3 [8.46] days vs 2.7 [1.90] days; p less than 0.01). Penicillin also shortened the hospital stay and prevented leptospiruria. Intravenous penicillin should be given to patients with severe leptospirosis, even if therapy can be begun only late in the course of their disease.

Chloroquine and quinine: a randomized, double-blind comparison of efficacy and side effects in the treatment of Plasmodium falciparum malaria in the Philippines.

Chloroquine (25 mg/kg over 3 d) was compared to quinine (10 mg/kg 3 times daily for 5 d) in 20 adult Filipino males with uncomplicated Plasmodium falciparum malaria in a double-blind, randomized trial. Asexual parasitaemia was cleared in all patients, with no statistically significant difference (P = 0.13) in the rate of clearance between the chloroquine-treated patients (76.1 +/- 29.3 h) and those receiving quinine (60.3 +/- 12.5 h). The duration of fever was also comparable (chloroquine 46.3 +/- 24.7 h; quinine 43.2 +/- 20.0 h; P = 0.76) and 40% of patients in each treatment group experienced mild side effects. Chloroquine, however, is cheaper and easier to administer. In vitro results were strikingly different. P. falciparum parasites from 4 quinine-treated patients were all sensitive to this compound in vitro, whereas 4 of the 5 isolates from the chloroquine group were resistant. Further comparisons of these two antimalarials are indicated, especially in cerebral malaria, and drug use policies should be based on clinical and parasitological response to treatment.

Comparison of washed and unwashed specimens in the Plasmodium falciparum in vitro microculture drug assay.

The dose response of Plasmodium falciparum isolates in the standard in vitro assay for drug resistance was compared using blood specimens which were centrifuged and washed before cultivation. Washing of the cultures increased the success of cultivation by greater than 100%. Eight cultures which grew using both methods gave similar results in the determination of resistance or sensitivity. The ED50 as determined by probit analysis, was approximately 50% higher in parasites which had been washed before cultivation.

In vitro drug response of Plasmodium falciparum in the Philippines: increased resistance to amodiaquine.

A long term study was carried out at San Lazaro Hospital, Manila, Philippines, monitoring the in vitro response of Plasmodium falciparum to chloroquine, amodiaquine, mefloquine, and quinine. The in vitro effective dose giving 50% inhibition of schizogony was: 0.68 X 10(-6) M/liter blood for chloroquine; 0.18 X 10(-6) for amodiaquine; 0.2 X 10(-6) for mefloquine; and 1.12 X 10(-6) for quinine. The percent of isolates determined to be resistant in vitro was 85.2% for chloroquine, and 1.2% for both mefloquine and quinine. These figures were relatively unchanged over the course of 3 years studied. The in vitro resistance rate to amodiaquine increased from 5.1% in 1982 to 22.2% in 1984.

Amodiaquine less effective than chloroquine in the treatment of falciparum malaria in the Philippines.

Amodiaquine was compared to chloroquine in two groups of Filipino patients with uncomplicated falciparum malaria. Every patient received 25 mg/kg of base orally given over three days. In a hospital study, all eight patients receiving chloroquine cleared their parasitemia by day 6, but six of eight patients receiving amodiaquine failed to clear parasitemia and in four patients there was no response at all (RIII resistance); this difference was significant (P less than 0.01). In a village based study, there was initial clearing of parasitemia in each patient. However, recrudescent infection occurred in all five patients receiving amodiaquine (RI resistance). Five of six falciparum infections were sensitive to chloroquine, while parasitemia reappeared in one patient. In this village, resistance to amodiaquine was significantly more common than resistance to chloroquine (P less than 0.05). To our knowledge, this is the first report of amodiaquine being substantially worse than chloroquine in the treatment of Plasmodium falciparum infection.

Prevalence of renal involvement in Schistosoma japonicum infection.

244 outpatients and 100 hospitalized patients with confirmed Schistosoma japonicum infection were prospectively surveyed for the presence of nephropathy. There was no association between schistosomiasis and renal disease in the outpatient group. Three hospitalized patients had evidence of significant nephropathy, but this number was not significantly higher than in a control group of 100 hospitalized age and sex-matched control patients without schistosomiasis. One schistosomiasis patient with severe nephrotic syndrome underwent percutaneous renal biopsy. Neither S. japonicum antigen nor antibody was found in the biopsy specimen. 64 of the 100 hospitalized patients had portal hypertension; in 28 patients there was hepatic decompensation. Only one of these hepatosplenic patients had evidence of renal disease. Thus renal involvement was uncommon in patients presenting various manifestations of chronic S. japonicum infection, including those with severe hepatosplenic disease. These results contrast markedly with S. mansoni infection, in which nephropathy associated with advanced liver disease is a distinct, well-recognized clinical entity.

Diagnostic value of a single, pre-treatment Widal test in suspected enteric fever cases in the Philippines.

101 patients with a clinical suspicion of typhoid or paratyphoid (enteric) fever admitted to San Lazaro Hospital, Manila, Philippines, were studied by bacteriological culture of blood, rectal swab, urine and duodenal string capsule; 35 also had bacteriological culture of bone marrow aspirate. 44 of the patients were culture-confirmed as having enteric fever; the remainder were classified as non-enteric fever cases. Analysis of the pretreatment Widal agglutination titres of all patients revealed that using as a diagnostic criterion an antibody titre of greater than or equal to 1:80 to the O antigen of Salmonella typhi yielded a test specificity of 100%, although the corresponding sensitivity was only 64%. The sensitivity of the test could be increased to 80% by using different cut-off values for titres to flagellar antigens, but this concomitantly decreased the test specificity from 100 to 82%. The data indicate that a single pretreatment Widal test in suspected enteric fever cases is of definite diagnostic value, but that the results must be interpreted with caution and foreknowledge of the test's shortcomings and limitations.

Positive response to edrophonium in patients with neurotoxic envenoming by cobras (Naja naja philippinensis). A placebo-controlled study.

To study the ability of anticholinesterase drugs to reverse the potentially fatal paralytic effects of cobra venom, we conducted a placebo-controlled, double-blind crossover trial of intravenous edrophonium (Tensilon) in 10 adults with neurotoxic envenoming caused by bites of the Philippine cobra (Naja naja philippinensis). There was significantly more improvement in ptosis and endurance of upward gaze after edrophonium than after placebo. Five minutes after injection, the mean difference (+/- SD) in the percentage of the iris that was uncovered was 39 +/- 5.47 (70 vs. 31 percent; P less than 0.01), and the mean difference in the number of seconds of upward gaze was 33.1 +/- 9.29 (39.7 vs. 6.6 seconds; P less than 0.01). The expiratory and inspiratory pressures, forced vital capacity, and ability to cough, speak, and swallow also improved after edrophonium. In both the patients who were studied electromyographically, pretreatment and postplacebo responses were typical of myasthenia gravis and became normal after edrophonium. We conclude that anticholinesterases are beneficial in the management of neurotoxic envenoming by Asian cobras (Naja naja), and we recommended a test of edrophonium in any patient with signs of neurotoxic envenoming after snakebite.

Cardiopulmonary involvement rare in severe Schistosoma japonicum infection.

In a prospective study, 65 consecutive patients hospitalized with Schistosoma japonicum infection were evaluated for evidence of cardiopulmonary involvement. Thirty-two patients had evidence of severe liver dysfunction while 11 patients had portal hypertension only. Of these 43 patients with hepatosplenic disease, only one patient had pulmonary hypertension. Cardiopulmonary involvement is relatively uncommon in severe S. japonicum infections.

Evaluation of a synthetic oligonucleotide probe for diagnosis of Plasmodium falciparum infections.

A radiolabeled synthetic oligonucleotide was evaluated as a diagnostic probe specific for Plasmodium falciparum using blood samples lysed directly on nitrocellulose filters. The probe technique successfully diagnosed malaria in experimentally infected chimpanzees that had 0.001% parasitemias (50 parasites/microliter) as determined by blood smears, and in 1 chimpanzee whose blood smear was negative, but whose blood was culture-positive for P. falciparum. In a double blind study of 50 patient samples from the Philippines, the probe results correlated well with blood smear results when the autoradiographs were read after 4-8 hr exposure. The results indicate that the oligonucleotide probe may be useful in the rapid and specific diagnosis of P. falciparum infection.

Praziquantel in treatment of cerebral schistosomiasis.

The effectiveness of standard single-day praziquantel treatment (60 mg/kg) was prospectively evaluated in nine patients with seizures caused by cerebral Schistosoma japonicum infection. Eight patients were cured when discharged from the study, an average of 6 months after receiving praziquantel. They were seizure-free in the absence of anticonvulsants, their electroencephalograms were normal, and no major abnormalities could be detected on neurological examination. Serial computed tomography scanning revealed rapid dissipation of cerebral oedema and complete or near-complete resolution of mass lesions. No serious adverse effects of praziquantel were encountered. The ninth patient was not cured but improved greatly in the months after treatment. Thus, single-day treatment with praziquantel is safe and effective in cerebral schistosomiasis.

Comparative study of three blood culture systems for isolation of enteric fever Salmonella.

Eight hundred blood cultures were tested in parallel in three conventional systems: tryptic soy broth containing 0.05% sodium polyanethosulfonate (TSB-SPS), whole blood in bile (BILE-BLOOD), and blood clots in bile (BILE-CLOT). Sixty-eight cultures were Salmonella typhi positive and 29 were positive for S. paratyphi A in at least one of the systems. Analysis of the isolation rates of the 97 Salmonella-positive specimens showed that BILE-BLOOD was significantly more sensitive (p less than 0.05) than either TSB-SPS or BILE-CLOTS, and that the latter two were not significantly different. The time required for positive results was shortest in BLOOD-BILE which was significantly quicker than BILE-CLOTs (p less than 0.05), but not TSB-SPS (p greater than 0.05). Possible explanations for the observed, superior performance of the BILE-BLOOD system are discussed and recommendations for efficient recovery of enteric fever salmonellae from blood are presented.