Three-day treatment of typhoid fever with two different doses of ceftriaxone, compared to 14-day therapy with chloramphenicol: a randomized trial.

Fifty-nine adult Filipino patients suffering from typhoid fever documented by blood culture were randomly allocated to one of three different drug regimens. Nineteen patients received 3 g ceftriaxone iv once daily for three days. Twenty patients received 4 g ceftriaxone iv once daily for three days and 20 patients received oral chloramphenicol 3 g daily in divided doses for two days followed by 2 g daily for 12 days. Eighteen patients were cured (95%) with 3 g of ceftriaxone for three days. All patients receiving 4 g ceftriaxone per day for three days or chloramphenicol for 14 days were cured. In the ceftriaxone groups two patients developed typhoid fever 30 and 45 days respectively after completion of treatment and one further patient had evidence of reinfection. Three patients relapsed within 15 to 17 days in the chloramphenicol group. Fever subsided in most patients between six and eight days, with three patients having a prolonged and moderate fever for 11 days in the ceftriaxone groups. This study suggests that a short treatment of three days of typhoid fever with ceftriaxone (3 or 4 g once daily) is adequate and not hazardous as far as relapses are concerned.

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%.

Rapid diagnosis of malaria by acridine orange staining of centrifuged parasites.

A rapid diagnostic test for malaria based on acridine orange staining of centrifuged parasites in a microhaematocrit tube ('QBC' tube) was compared with the thick blood smear in 12 volunteers experimentally infected with Plasmodium falciparum, 408 residents of a malaria endemic area, and 180 hospital patients with suspected malaria. In the experimentally infected volunteers, the QBC tube test and the thick blood smear were comparable and the QBC tube could detect as few as 4 parasites/microliter blood. When used for mass screening in the field study, the test had a sensitivity of 70% for the diagnosis of malaria compared with 92% for a single thick blood smear. However, when used to diagnose malaria in hospital patients, the test detected as few as 3 parasites/microliter in 91 of 92 patients with asexual parasitaemia. For the three studies, the QBC tube was highly specific (98.4%), indicating malaria in only 8 of 487 subjects with negative blood films. The species of parasite was correctly identified in 77% of species. Processing the QBC tube was easier and much more rapid than was processing a thick blood smear, taking only 5 min for centrifugation and 5 min for examination. The QBC tube is not a substitute for the blood smear, but its speed and ease of use make it an important new tool for the diagnosis of malaria.

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.

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.

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.

A comparative clinical study of mefloquine and chloroquine in the treatment of vivax malaria.

Forty-six patients with Plasmodium vivax malaria were evaluated for their clinical and parasitological response to the two single doses of mefloquine in comparison with the standard 3-day treatment with chloroquine. The patients were randomly distributed into 3 groups. Group 1 with 13 patients were treated with a single dose 250 mg mefloquine, Group 2 with 15 patients were treated with a single dose 500 mg mefloquine and Group 3 with 18 cases were treated with the standard 3-day treatment course of 1,500 mg chloroquine. All patients in the three treatment group showed similar parasite, clearance time, fever clearance time and clearance time of signs and symptoms. There were no statistically significant differences between any of the groups. The age and weight, as well as the initial parasite count of the three groups were comparable. This study shows that mefloquine at the dosages used were as effective as the 3-day standard treatment with 1,500 mg chloroquine.

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.