Biomedical subjects
T Solomon
Publications and source records attributed to T Solomon.
Clinical research in the tropics: some thoughts for the beginner.
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Comparison of PanBio dengue duo enzyme-linked immunosorbent assay (ELISA) and MRL dengue fever virus immunoglobulin M capture ELISA for diagnosis of dengue virus infections in Southeast Asia.
The performances of the MRL dengue fever virus immunoglobulin M (IgM) capture enzyme-linked immunosorbent assay (ELISA) and the PanBio Dengue Duo IgM capture and IgG capture ELISA were compared. Eighty sera from patients with dengue virus infections, 24 sera from patients with Japanese encephalitis (JE), and 78 sera from patients with nonflavivirus infections, such as malaria, typhoid, leptospirosis, and scrub typhus, were used. The MRL test showed superior sensitivity for dengue virus infections (94 versus 89%), while the PanBio test showed superior specificity for JE (79 versus 25%) and other infections (100 versus 91%). The PanBio ELISA showed better overall performance, as assessed by the sum of sensitivity and specificity (F value). When dengue virus and nonflavivirus infections were compared, F values of 189 and 185 were obtained for the PanBio and MRL tests, respectively, while when dengue virus infections and JE were compared, F values of 168 and 119 were obtained. The results obtained with individual sera in the PanBio and MRL IgM ELISAs showed good correlation, but this analysis revealed that the cutoff value of the MRL test was set well below that of the PanBio test. Comparing the sensitivity and specificity of the tests at different cutoff values (receiver-operator analysis) revealed that the MRL and PanBio IgM ELISAs performed similarly in distinguishing dengue virus from nonflavivirus infections, although the PanBio IgM ELISA showed significantly better distinction between dengue virus infections and JE. The implications of these findings for the laboratory diagnosis of dengue are discussed.
Evaluation of a new commercially available immunoglobulin M capture enzyme-linked immunosorbent assay for diagnosis of Japanese encephalitis infections.
A new commercial enzyme-linked immunosorbent assay (ELISA) for the diagnosis of Japanese encephalitis virus infections showed a sensitivity of 88% with sera and 81% with cerebrospinal fluid and a specificity of 97% with sera from patients with primary and secondary dengue virus infections. Specificity was 100% when samples from nonflavivirus infections were tested.
Rapid serologic diagnosis of dengue virus infection using a commercial capture ELISA that distinguishes primary and secondary infections.
A commercial capture ELISA for specific IgM and IgG antibodies produced during dengue infection (PanBio Dengue Duo) showed excellent sensitivity (99%, n = 78) using sera collected at hospital discharge compared with established ELISA and hemagglutination inhibition (HAI) assays. Furthermore, the ELISA was able to diagnose 79% of the dengue cases using sera collected at hospital admission. The ELISA also showed high specificity (92%) in paired sera from patients without flavivirus infection (n = 26), although 45% of the patients with Japanese encephalitis (n = 20) showed elevation of IgG but not IgM. The IgG capture ELISA showed good correlation with the HAI assay (r = 0.83, P < 0.0001), and IgG levels could be used to distinguish between primary and secondary infection, with 100% of primary infections and 96% of secondary infections being correctly classified. This ELISA should prove useful in the clinical diagnosis of dengue infections.
Poliomyelitis-like illness due to Japanese encephalitis virus.
BACKGROUND: Acute flaccid paralysis remains common among Vietnamese children despite a pronounced fall in the incidence of poliomyelitis. METHODS: During 1995, all 22 children presenting with acute flaccid paralysis to a referral centre in Ho Chi Minh City, Vietnam, had virological cultures and antibody measurements done on serum, cerebrospinal fluid, and faeces. A year later the children were reassessed and electrophysiological studies were done. FINDINGS: Wild poliovirus type 1 was isolated from the faeces of only one patient, and non-polio enteroviruses from three patients. 12 (55%) of the 22 children with acute flaccid paralysis had evidence of acute Japanese encephalitis virus (JEV) infection, compared with only one (1%) of 88 age-matched hospital controls (children with diphtheria; p<0.0001). Compared with JEV-negative patients, weakness in JEV-infected children was more rapid in onset, tended to be asymmetrical, but was less likely to involve the arms. All 12 children with JEV infection were febrile at the onset of weakness, seven had acute retention of urine, and ten had CSF pleiocytosis. Seven of eight JEV-negative patients met the case-definition of Guillain-Barré syndrome, compared with only one of 12 JEV-positive children. At follow-up, patients with JEV infection had greater disability and were more likely to have muscle wasting than were JEV-negative children. Nerve conduction and electromyographic studies indicated damage to the anterior horn cells. INTERPRETATION: JEV causes an acute flaccid paralysis in children that has similar clinical and pathological features to poliomyelitis. In endemic areas, children with acute flaccid paralysis should be investigated for evidence of JEV infection.
Penicillin vs. erythromycin in the treatment of diphtheria.
In an open-label, randomized trial, 44 Vietnamese children with diphtheria were given penicillin therapy (intramuscular benzylpenicillin, 50,000 U/[kg.d] for 5 days and then oral penicillin, 50 mg/[kg.d] for 5 days), and 42 were given erythromycin therapy (50 mg/[kg.d] orally for 10 days). There were no differences in times to membrane clearance or bacteriologic clearance, but median times to fever clearance were 27 hours (95% confidence interval [CI], 19-30; range, 0-124 hours) for penicillin recipients and 46 hours (95% CI, 34-54; range, 0-148 hours) for erythromycin recipients (P = .0004). In the penicillin group, acute treatment failed for one patient, and one patient relapsed. Three patients in the penicillin group developed diphtheritic myocarditis as evidenced by abnormal electrocardiograms. Erythromycin did not cause prolongation of the QT interval corrected for heart rate. Cultures of specimens from 15 patients (17.4%) were positive for toxigenic Corynebacterium diphtheriae. All isolates were susceptible to penicillin, but for isolates (27%), all of which were from patients who received penicillin treatment, were resistant to erythromycin (minimum inhibitory concentrations, > 64 mg/L). Penicillin is recommended as first-line treatment for diphtheria in Vietnam.
Heart Partners: a strategy for promoting effective diffusion of school health promotion programs.
Heart Partners uses a straightforward, interpersonal approach to increase acceptance and use of innovations in school health promotion. In accord with the linkage model of innovation diffusion, developers of a new program or technology (i.e., resource system) simply designate and train selected members to be recruiters and allies of individual advocates at the campus-level (i.e., user system). Linkage is supported by supplying advocates and allies with guidelines and materials that encourage ongoing, interactive, interpersonal partnerships to promote effective implementation of the new technology at the school. Empirical assessment of this simple strategy implemented by the Texas Affiliate of the American Heart Association showed a twofold to fourfold increase in actual use and reach of school health promotion packages, with an average reported volunteer time of less than three hours per month.
Evaluation of a rapid immunochromatographic test for diagnosis of dengue virus infection.
A rapid (<7-min) immunochromatographic test for immunoglobulin M (IgM) and IgG antibodies to dengue viruses was evaluated by using hospital admission and discharge sera from 124 patients. The reference laboratory diagnosis was based on the results of virus isolation, hemagglutination-inhibition assay (HAI), and enzyme immunoassay (EIA). By the standard assays, patients experienced primary dengue virus infection (n = 30), secondary dengue virus infection (n = 48), Japanese encephalitis (JE) virus infection (n = 20), or no flavivirus infection (n = 26). The rapid test demonstrated 100% sensitivity in the diagnosis of dengue virus infection and was able to distinguish between primary and secondary dengue virus infections through the separate determinations of IgM and IgG. For all patients with primary dengue virus infection a positive test for IgM to dengue virus and a negative test for IgG to dengue virus were obtained, whereas for 46 of 48 patients (96%) with secondary dengue virus infection, a positive test for IgG to dengue virus with or without a positive test for IgM to dengue virus was obtained. The remaining two patients with secondary dengue virus infection had positive IgM test results and negative IgG test results. Furthermore, the rapid test was positive for patients confirmed to be infected with different dengue virus serotypes (12 infected with dengue virus serotype 1, 4 infected with dengue virus serotype 2, 3 infected with dengue virus serotype 3, and 2 infected with dengue virus serotype 4). The specificity of the test for nonflavivirus infections was 88% (3 of 26 positive), while for JE virus infections the specificity of the test was only 50% (10 of 20). However, most patients with secondary dengue virus infection were positive for both IgM and IgG antibodies to dengue virus, while no patients with JE virus infection had this profile, so cross-reactivity was only a concern for a small proportion of patients with secondary dengue infections. The rapid test demonstrated a good correlation with the reference EIA and HAI and should be useful for the rapid diagnosis of dengue virus infections.
Rapid diagnosis of Japanese encephalitis by using an immunoglobulin M dot enzyme immunoassay.
Japanese encephalitis (JE) occurs in rural settings in southern and eastern Asia, where diagnostic facilities are limited. For the diagnosis of JE virus (JEV) infection, we developed a nitrocellulose membrane-based immunoglobulin M (IgM) capture dot enzyme immunoassay (MAC DOT) that is rapid, simple to use, requires no specialized equipment, and can distinguish JEV from dengue infection. In a prospective field study in southern Vietnam, 155 cerebrospinal fluid (CSF) and 341 serum samples were collected from 111 children and 83 adults with suspected encephalitis. The JEV MAC DOT, performed on site, was scored visually from negative to strongly positive by two observers, and the results were compared subsequently with those of the standard IgM capture enzyme-linked immunosorbent assay. For the 179 patients with adequate specimens, the MAC DOT correctly identified 59 of 60 JEV-positive patients and 118 of 119 JEV-negative patients (sensitivity [95% confidence intervals], 98.3% [92.1 to 99.91%]; specificity, 99.2% [95.9 to 100.0%]; positive predictive value, 0.98; negative predictive value, 0.99). The MAC DOT also correctly identified three patients with dengue encephalopathy. Admission specimens were positive for 73% of JE patients. Interobserver agreement for MAC DOT diagnosis was excellent (kappa = 0.94). The JEV MAC DOT is a simple and reliable rapid diagnostic test for JE in rural hospitals.
Hong Kong, 1894: the role of James A Lowson in the controversial discovery of the plague bacillus.
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Quinolone-resistant Salmonella typhi in Viet Nam: molecular basis of resistance and clinical response to treatment.
Nalidixic acid-resistant Salmonella typhi (NARST) was first isolated in Viet Nam in 1993. Analysis of the quinolone resistance-determining region of gyrA in 20 NARST isolates by polymerase chain reaction and single-stranded conformational polymorphism yielded two novel patterns: pattern II corresponding to a point mutation at nucleotide 87 Asp-->Gly (n = 17), and pattern III corresponding to a point mutation at nucleotide 83 Ser-->Phe (n = 3). In trials of short-course ofloxacin therapy for uncomplicated typhoid, 117 (78%) of 150 patients were infected with multidrug-resistant S. typhi, 18 (15%) of which were NARST. The median time to fever clearance was 156 hours (range, 30-366 hours) for patients infected with NARST and 84 hours (range, 12-378 hours) for those infected with nalidixic acid-susceptible strains (P < .001). Six (33.3%) of 18 NARST infections required retreatment, whereas 1 (0.8%) of 132 infections due to susceptible strains required retreatment (relative risk = 44; 95% confidence interval = 5.6-345; P < .0001). We recommend that short courses of quinolones not be used in patients infected with NARST.
Alexandre Yersin and the plague bacillus.
To most doctors, the name Yersin is known only for its eponymous connection with the plague bacillus, Yersinia pestis. In Vietnam, where he lived for over 50 years, Alexandre Yersin is a legendary figure. On the 100th anniversary of the identification of the plague bacillus, a review of this extraordinary man and his controversial discovery is timely.
Hypoglycaemia in paediatric admissions in Mozambique.
We studied the incidence and clinical associations of hypoglycaemia in an acute medical paediatric service in Maputo, Mozambique. Of 603 children, 43 (7.1%) were hypoglycaemic. 16 of these with Plasmodium falciparum malaria had a shorter illness, and a higher incidence of convulsions and focal neurological signs than those with other diagnoses, but were less likely to die. Hypoglycaemia also complicated protein energy malnutrition, pneumonia, encephalitis, intestinal parasite infection, and nephrotic syndrome. 25 of the 603 children died: 7 (16.3%) of 43 with hypoglycaemia and 18 (3.2%) of 560 who were normoglycaemic, (relative risk of death 5.8 [95% confidence interval 2.25 to 14.93]). Hypoglycaemia is common in children in hospital in Mozambique, and should be suspected in any acutely-ill child regardless of the primary disease.
A case of methaemoglobinaemia.
Methaemoglobinaemia is rare but should be considered in cases of cyanosis unresponsive to oxygen therapy. An example of this is given involving the accidental ingestion of Amyl Nitrite.
Physiological and cytotoxic effects of Ca(2+) ionophores on Caco-2 paracellular permeability: relationship of 45Ca(2+) efflux to 51 Cr release.
The human intestinal cell line, Caco-2, and the Ca2+ ionophores, A23187 and ionomycin, were used to determine the interrelationships of 45Ca(2+) efflux, transepithelial electrical resistance (Rt), and [3H]-mannitol flux to changes in 51Cr release and lactate dehydrogenase (LDH) activity. Treatment of Caco-2 monolayers with ionomycin at concentrations of between 0.25 and 2.50 mumol/l showed similar 45Ca(2+) efflux rate constants and coefficients. Analysis of the control and ionomycin-induced 45Ca(2+) efflux values showed the data to best fit a three Ca(2+) compartmental model. All changes in Caco-2 Rt and [3H]-mannitol flux were reversible with no significant increases in 51Cr release with ionomycin concentrations of less than or equal to 2.5 mumols/l. Caco-2 monolayers treated with ionomycin at concentrations of between 5.0 and 50.0 mumols/l showed rapid non-exponential 45Ca(2+) effluxes with irreversible changes in Rt, [3H]-mannitol flux, and significant increases in 51Cr release. There was no changes in media LDH activity using either ionomycin or A23187 at concentrations of up to 50 mumols/l for 60 min. The results of our study show that: (1) disruption of Ca(2+) homeostasis in Caco-2 cells will occur with the addition of Ca(2+) ionophores at concentrations of greater than 2.50 mumols/l; (2) high concentrations (greater than 2.5 mumols/l) of ionomycin will cause non-exponential 45Ca(2+) efflux rates with irreversible changes in intracellular Rt and 14C-mannitol flux, and (3) early signs of Ca(2+) ionophore-induced damage can be detected by 51Cr release from Caco-2 cells into the media and not by changes in LDH media activity.
Cerebral malaria in children.
Cerebral malaria is a rapidly progressive encephalopathy with up to 50% mortality. A cardinal feature is the massing of red cells containing mature Plasmodium falciparum within the cerebral capillaries. Adhesion of these parasitised red cells to endothelium, an event which may initiate cerebral malaria, is being studied at the molecular level. However, the relevance of these studies to the pathophysiology and treatment of human cerebral malaria is uncertain. Although chloroquine is still widely used to treat falciparum malaria, resistance has spread to most of the endemic zone. Quinine is emerging as the only effective treatment for cerebral malaria, though resistance to this drug threatens to become a problem. Alternative drugs are urgently needed.