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.
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%.
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.
We prospectively compared the ability of antivenom 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<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.
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.
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.
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.
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<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<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<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.
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.
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.
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.
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.
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.
Journal Article The diagnosis of Schistosoma japonicum infection. Areas of uncertainty Get access George Watt, George Watt 1U.S. Naval Medical Research Unit No. 2, APO San Francisco, California 96528, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Gary W Long, Gary W Long 1U.S. Naval Medical Research Unit No. 2, APO San Francisco, California 96528, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Catherine P Ranoa, Catherine P Ranoa 2San Lazaro Hospital, Manila, Republic of the Phillippines Search for other works by this author on: Oxford Academic PubMed Google Scholar John H Cross John H Cross 1U.S. Naval Medical Research Unit No. 2, APO San Francisco, California 96528, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Transactions of The Royal Society of Tropical Medicine and Hygiene, Volume 80, Issue 1, 1986, Pages 10–11, https://doi.org/10.1016/0035-9203(86)90184-7 Published: 01 January 1986 Article history Accepted: 05 November 1984 Published: 01 January 1986
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.
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.
Journal Article Bloody diarrhoea after praziquantel therapy Get access George Watt, George Watt U.S. Naval Medical Research Unit No. 2, APO San Francisco, California 96528, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Pelagio C. Baldovino, Pelagio C. Baldovino San Lazaro Hospital, Manila, Philippines Search for other works by this author on: Oxford Academic PubMed Google Scholar Josefina T. Castro, Josefina T. Castro San Lazaro Hospital, Manila, Philippines Search for other works by this author on: Oxford Academic PubMed Google Scholar Marcelino T. Fernando, Marcelino T. Fernando San Lazaro Hospital, Manila, Philippines Search for other works by this author on: Oxford Academic PubMed Google Scholar Catherine P. Ranoa Catherine P. Ranoa San Lazaro Hospital, Manila, Philippines Search for other works by this author on: Oxford Academic PubMed Google Scholar Transactions of The Royal Society of Tropical Medicine and Hygiene, Volume 80, Issue 2, 1986, Page 345, https://doi.org/10.1016/0035-9203(86)90053-2 Published: 01 January 1986 Article history Accepted: 07 May 1985 Published: 01 January 1986
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.
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.
Human leucocyte antigens (HLA) were used as genetic markers in an attempt to determine possible host genetic susceptibility or resistance to malarial infections. HLA-A and B typing on lymphocytes from 68 confirmed P. falciparum and 77 P. vivax cases was compared with that found in 66 control subjects with no known history of malaria. A significant deviation was observed in the distribution of HLA-B27. This phenotype was absent in the P. falciparum group although found present in the P. vivax group (10%) and the control group (11%). Also, the combination of A9(w24) and B5 was significantly higher among the P. falciparum group than that found in the P. vivax and control groups. These findings require confirmation but do suggest the possibility of genetic susceptibility and that extensive genetic studies might be worth investigating.