Emergence of new forms of human immunodeficiency virus type 1 intersubtype recombinants in central Myanmar.

We have previously shown that HIV-1 env subtypes B' (a Thai-B cluster within subtype B) and E (CRF01_AE) are distributed in Yangon, the capital city of Myanmar. However, HIV strains from the rest of country have not yet been genetically characterized. In the present study, we determined env (C2/V3) and gag (p17) subtypes of 25 specimens from central Myanmar (Mandalay). Phylogenetic analyses identified 5 subtype C (20%), in addition to 10 CRF01_AE (40%) and 4 subtype B' (16%). Interestingly, the remaining six specimens (24%) showed discordance between gag and env subtypes; three gag subtype B'/env subtype C, one gag subtype B'/env subtype E, one gag subtype C/env subtype B', and one gag subtype C/env subtype E. These discordant specimens were found frequently among injecting drug users (4 of 12, 33%) and female commercial sex workers (2 of 8, 25%) engaging in high-risk behaviors. The recombinant nature of these HIV-1 strains was verified in three specimens, indicating the presence of new forms of HIV-1 intersubtype C/B' and C/B'/E recombinants with different recombination breakpoints. The data suggest that multiple subtypes of B', C, and CRF01_AE are cocirculating in central Myanmar, leading to the evolution of new forms of intersubtype recombinants among the risk populations exhibiting one of the highest HIV infection rates in the region.

Stability of saliva for measuring HIV in the tropics.

If HIV is to be detected among pregnant women in remote regions of the tropics, HIV antibodies need to remain stable until specimens arrive at the laboratory. Our objective was to assess the stability of HIV antibodies in saliva held for up to 1 month at ambient temperature in Yangon, Myanmar. We gathered 10 saliva specimens from each of 102 HIV-infected persons with the Omni-Sal collection device (Saliva Diagnostic Systems, Inc.), and for each subject, divided the saliva into 15 portions. During 33 days, the 102 saliva specimens, kept at ambient temperature, were tested every 2-3 days for HIV antibodies (total 1530 assays) with the GACELISA (Murex Diagnostics Ltd), a highly sensitive test designed for use with saliva. We observed no reduction in test performance over 33 days, indicating that the antimicrobial and antiproteolytic transport medium in the Omni-Sal device can preserve HIV antibodies without refrigeration for up to a month before saliva specimens reach the laboratory.

Genetic and serologic characterization of HIV type 1 prevailing in Myanmar (Burma).

To study the molecular epidemiology of HIV-1 spread in Myanmar and the interplay with the epidemic in surrounding Southeast Asian countries, we determined the HIV-1 subtypes prevailing in Myanmar. Thirty HIV-positive blood specimens were sampled in the capital city, Yangon, and an additional 459 sera were collected nationwide in 1995. Genetic subtyping based on the env C2/V3 sequence and serologic data, using a V3 peptide enzyme immunoassay (PEIA), revealed three patterns of HIV spread in different geographic regions in Myanmar: (1) in the capital city, Yangon, HIV-1 subtype B' ("Thai-B" cluster within subtype B) predominated both in IDUs and heterosexuals; (2) in the cities near the border with Thailand, including Tachelaik and Kawthaung, where heterosexual transmission is a major pathway of HIV-1 spread, HIV-1 subtype E was predominantly distributed among the commercial sex workers and heterosexuals; (3) in central and northeast Myanmar, both HIV-1 subtypes B' and E occurred in a mixed distribution, without showing any significant segregation by risk group. In addition, the PEIA data implied the occurrence of other subtype(s) in these areas. The interperson nucleotide sequence variations in env C2/V3 regions of B' and E, prevailing in Yangon, were 6.7 +/- 2.1 and 7.1 +/- 0.7%, respectively. They were similar to those levels observed in Thailand. These findings are consistent with the view that HIV spread in Myanmar might have taken place at about the same time as that in Thailand, and that multiple entries and exchanges of HIV-1 with neighboring countries are important factors contributing to the current distribution of subtypes in Myanmar.

De novo mutation in CACNA1A caused acetazolamide-responsive episodic ataxia.

With the recent report of mutations in the calcium channel gene CACNA1A in two families with episodic ataxia type 2, we investigated a patient with nonfamilial episodic vertigo and ataxia responsive to acetazolamide for similar mutations. Single-strand conformation polymorphism (SSCP) analysis of exon 23 identified an extra band in the patient that was not present in other relatives or in normal controls. Exon 23 of the patient showed a spontaneous C to T substitution at position 4410 resulting in an early stop codon. Patients with nonfamilial episodic ataxia may respond to acetazolamide and may have mutations in CACNA1A.

The value of the fatty meal in oral cholecystography.

In order to assess the value of the after fatty meal films, 232 oral cholecystograms were reviewed. Gallbladder opacification, duct visualisation, separation of gallbladder from overlying bowel gas shadows, and the demonstration of abnormalities were assessed from the pre-fatty meal films, and then again in conjunction with those taken after fat, when contraction was also assessed. Of the 200 examinations given the fatty meal, 132 were adjudged normal, 63 had gallstones, four had adenomyomatosis (one with stones), and two cholesterolosis. The post-fatty meal films, were found to be essential for the diagnosis of adenomyomatosis and cholesterolosis, and considered to be occasionally helpful in diagnosing small stones. They were of little value in assessing the biliary ducts, or separating the gallbladder from overlying bowel gas, and of no value in the diagnosis of functional biliary tract disorders.

Liver structure and function in cholelithiasis: effect of chenodeoxycholic acid.

Although, in suitable patients, oral chenodeoxycholic acid (CDCA) dissolves gallstones, the results of recent animal studies suggest that it might be hepatotoxic. Liver function was therefore studied in patients with gallstones before and during treatment with CDCA and liver biopsies were carried out both in patients with cholelithiasis given bile acid therapy and in those who had been given no medical treatment. In 25 patients treated with 0.5-1.5 g CDCA/day (7-20 mg kg body weight(-1) day(-1)) there was no significant change in serum bilirubin, albumin, globulin, transaminase, isocitric dehydrogenase, alkaline phosphatase, and gamma glutamyl transpeptidase levels before and at monthly intervals during six months' treatment. The kinetics of bromsulphthalein (BSP) clearance and its apparent transport maximum were not significantly changed during CDCA therapy. The mean fasting serum bile acid concentrations of 18.0 +/- SEM 1.2 mumoles/litre before and 20.0 +/- 3.5 mumoles/litre during treatment were both significantly greater than control values. Liver histology was not appreciably different in 11 patients treated with CDCA from that in eight patients with untreated cholelithiasis and in three patients who had received CDCA three to four months before biopsy. These results suggest that in doses of 0.5 to 1.5 g/day CDCA is not hepatotoxic in man.