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Laboratory and field comparisons of adenosine influx in Plasmodium falciparum and Plasmodium vivax infected erythrocytes with genetic abnormalities from patients in Myanmar.

Influx of the purine nucleoside, adenosine, was assessed in erythrocytes from both normal subjects and from subjects with a range of genetically determined erythrocyte disorders from Myanmar. The latter included alpha-thalassemia major (Myanmar variant), beta-thalassemia major (Myanmar variant), beta-thalassemia trait, HbEE and HbAE erythrocytes and two variants of glucose-6-phosphate dehydrogenase (G6PDH) deficiency. Significant reductions (p < 0.01) of adenosine influx were observed in erythrocytes from individuals with alpha- and beta-thalassemia major and severe G6PDH deficiency. Abnormal erythrocytes infected with the malarial parasites, Plasmodium falciparum or Plasmodium vivax, demonstrated a reduction in adenosine transport which correlated with the proportion of abnormal erythrocytes present in the samples obtained. The effect of nitrobenzylthioinosine (NBMPR) on adenosine influx was explored in normal and abnormal erythrocytes. In all these cases, NBMPR completely inhibited the transport of adenosine. However, transport of adenosine into P. falciparum and P. vivax-infected normal erythrocytes and abnormal cells was only inhibited 50-60% by NBMPR. The combination of tubercidin and NBMPR completely blocked adenosine transport into both normal and abnormal erythrocytes infected with either P. falciparum or P. vivax.

Adenosine↗

Male cross-gender behavior in Myanmar (Burma): a description of the acault.

Cross-gender behavior in Myanmar (formerly Burma) is reported. Western concepts of transsexualism, gynemimesis, transvestism, and homosexuality are not distinct categories by the Burmese. Males with cross-gender behavior are referred to as acaults. Although Myanmar is a profoundly Buddhist society, the people still have strong animistic beliefs with an elaborate system of 37 nats (spirit gods). One of these nats is a female named Manguedon who may take possession of males and impart femininity on them. The cross-gender status of the acaults is sanctioned by their spiritual marriage to Manguedon. The acaults, while not envied, are respected for their roles as shamans and seers.

Adult↗

Sequence and gene structure of the hepatitis E virus isolated from Myanmar.

Hepatitis E virus (HEV) is a causative agent of enterically transmitted non-A, non-B hepatitis. Hepatitis E occurs not only in sporadic forms but also in epidemic outbreaks in the developing world. We have revealed the nucleotide and predicted amino acid sequences of full cDNA of HEV isolated from sporadic hepatitis E of Myanmar. The genome is 7194 nucleotides long, followed by a poly(A) tail, and has three open reading frames. The nonstructural gene is located in the 5' terminus, while the structural gene is situated in the 3' terminus. Our HEV strain has 98.5% nucleic acid identity with the HEV strain cloned by workers at Genelabs Incorporated from Myanmar. The difference is point nucleotide substitutions. There is a high degree of nucleotide relatedness among HEVs isolated from the same geographical location.

Amino Acid Sequence↗

Genetic variations of the dihydrofolate reductase gene of Plasmodium vivax in Mandalay Division, Myanmar.

Dihydrofolate reductase (DHFR; EC1.5.1.3) is a known target enzyme for antifolate agents, which are used as alternative chemotherapeutics for chloroquine-resistant malaria. Mutations in the dhfr gene of Plasmodium vivax are thought to be associated with resistance to the antifolate drugs. In this study, we have analyzed genetic variations in the dhfr genes of clinical isolates of P. vivax (n=21) in Myanmar, to monitor antifolate resistance in this country. Sequence variations within the entire dhfr gene were highly restricted to codons from 57 to 117, and the GGDN tandem repeat region. Double (S58R and S117N/T) or quadruple mutations (F57L/I, S58R, T61M, and S117N/T), which may be closely related to the drug resistance, were recognized in most of the isolates (20/21 cases). Our results suggest that antifolate-resistant P. vivax is becoming widespread in Myanmar, as it also is in the neighboring countries in Southeast Asia. It appears that the drug resistance situation may be worsening in the country.

Amino Acid Sequence↗

Development of a simple indirect enzyme-linked immunosorbent assay for the detection of immunoglobulin M antibody in serum from patients following an outbreak of chikungunya virus infection in Yangon, Myanmar.

During 1984, 1548 children were admitted to the Yangon [Rangoon] Children's Hospital in Myanmar [Burma] with haemorrhagic fever. No evidence of recent dengue infection was found in 577 of the 803 children from whom paired sera were obtained, raising the possibility of reappearance of Chikungunya virus infection in Myanmar. An enzyme-linked immunosorbent assay (ELISA) for the detection of anti-Chikungunya virus immunoglobulin M (IgM) antibody was prepared and standardized using only reagents which are commercially available or which could be prepared without the use of sophisticated equipment. While there was 90% agreement between haemagglutination inhibition (HI) tests and the IgM ELISA in the diagnosis of acute Chikungunya virus infections, 12 additional patients with stationary anti-Chikungunya virus HI antibody titres could be identified as having acute Chikungunya infections using the ELISA. Furthermore, the ELISA could identify twice as many patients (31/103) at the time of admission to hospital as the HI test (15/103). There was no false positive IgM reaction with the ELISA which could be attributed to the presence of rheumatoid factor. Using the test, 103 of a sample of 163 children who presented to the Yangon Children's Hospital with fever/haemorrhagic fever were diagnosed as Chikungunya patients, 4 had possible dual Chikungunya and dengue infections, 16 had dengue, 30 had neither Chikungunya nor dengue infections, and a definitive diagnosis could not be made for 10 patients. Routine use of the ELISA would alert authorities to future outbreaks of Chikungunya virus infection and avoid admission to hospital of patients with a non-life-threatening viral disease.

Antibodies, Viral↗

[Imported gnathostomiasis acquired in Myanmar].

We report a case of cutaneous gnathostomiasis acquired in Myanmar where this parasitic zoonosis was considered as non-endemic until a recent outbreak. Myanmar must be added to the list of countries where the infection can be acquired in Southeast Asia. Despite a treatment with ivermectin the patient relapsed after an apparent cure. A double-dose of ivermectin is now recommended for the treatment of gnathostomiasis.

Adult↗

Performance appraisal of rapid on-site malaria diagnosis (ICT malaria Pf/Pv test) in relation to human resources at village level in Myanmar.

Logistic, economic and technical factors limit rapid access to microscopic confirmation of symptomatic diagnosis of malaria in many rural areas in endemic countries such as Myanmar. A study was conducted to evaluate a rapid on-site immunochromatographic test (ICT Malaria Pf/Pv) for detection of Plasmodium falciparum and P. vivax in two villages in the Taikkyi region of Myanmar. The ICT Malaria tests were performed by a volunteer health worker (VHW) in Yae-Aye-San village and by a professionally trained midwife (MW) in Kankone village. A total of 1000 symptomatic patients participated in the study by providing blood samples for an ICT test and for microscopy. The ICT performance indices, relative to microscopy, were better for the trained MW compared with the less experienced VHW. For P. falciparum and/or P. vivax infections, the sensitivities were 82.7% for the VHW compared with 93.7% for the MW. For P. falciparum infections, the sensitivities were 82.2% for the VHW and 91.3% for the MW, while the corresponding values for P. vivax infections were 66.7 and 79%, respectively. Although the test kit appeared to perform better in more experienced hands, this study questions whether this difference is related to the use of the ICT Malaria Pf/Pv test kit, or related to other factors such as differences in the quality of blood slides prepared by the VHW and MW for microscopic examination. Overall, the results suggest that a rapid diagnostic assay such as the ICT Malaria Pf/Pv test kit can be used in rural settings by relatively inexperienced persons, such as VHWs, with a reasonable degree of sensitivity, thus providing on-site confirmation of symptomatic diagnosis of malaria.

Animals↗

Premunition against Plasmodium falciparum in a malaria hyperendemic village in Myanmar.

Premunition, naturally acquired protective immunity against Plasmodium falciparum, has been described in hyperendemic areas of Africa and Papua New Guinea. However, its occurrence in Asia is debatable. In order to elucidate this question, a longitudinal study was undertaken in Oo-Do, a malaria endemic village in Myanmar [Burma] in 1995-97. Only 2 species, Plasmodium falciparum and P. vivax, were detected, with the former predominating. Data from 116 subjects showed that all were infected at one time or another, over a period of 3 years, with a 38% reinfection rate after eradication of patent parasitaemia. The high rate of prevalence (90-100%) of parasite-specific antibodies in the indirect immunofluorescence antibody test and the presence of the primary vector (Anopheles minimus) and 15 other species of Anopheles throughout the year indicated a high level of transmission. The spleen rate was 70% in 5-9 years old children and was inversely related with age. The incidence of parasitaemia was maximal (49%) in children aged 2-4 years, and then declined marginally with age. There was a significant difference (P = 0.001) between the asymptomatic and febrile parasitaemia levels. Also, malarial episodes occurred more frequently in children than in adults (P = 0.001). Taken together, all these facts indicated that the inhabitants of Oo-Do had progressively developed non-sterile partial protective immunity against P. falciparum malaria, or premunition. To our knowledge, this is the first detailed clinico-epidemiological study to document the occurrence of premunition in Myanmar.

Adolescent↗

Plasmodium falciparum: sensitivity in vivo to chloroquine, pyrimethamine/sulfadoxine and mefloquine in western Myanmar.

In Rakhine State, on the western border of Myanmar, the efficacy of chloroquine (CQ) and pyrimethamine/ sulfadoxine (PS), the current treatments for uncomplicated Plasmodium falciparum malaria in this area, was evaluated in an open comparative study of 289 patients, stratified prospectively into 3 age groups. Chloroquine treatment was associated with more rapid clinical recovery (P = 0.03), but the overall cure rates were worse than for PS treatment; failure to clear parasitaemia or recrudescence within 14 d occurred in 72% (102/141) of cases treated with CQ compared to 47% (69/148) of those who received PS (P < 0.0001, adjusted for age). Failure rates at day 28 increased to 82% (116/141) in the CQ group and 67% (99/148) in the PS group (P = 0.003). The risk of treatment failure was significantly higher in children under 15 years old than in adults for both CQ (relative risk [RR] = 2.6; 95% confidence interval [95% CI] 1.3-5.2) and PS (RR = 2.2; 95% CI 1.4-3.3). Mefloquine (15 mg base/kg) proved to be highly effective as a treatment for CQ and PS resistant P. falciparum; only 2 of 75 patients (3%) had early treatment failures (< or = day 7), and the overall failure rate by day 42 was 7%. There is a very high level of chloroquine and PS resistance in P.falciparum on the western border of Myanmar, but mefloquine was effective in the area.

Adult↗

High prevalence of Plasmodium malariae and Plasmodium ovale in malaria patients along the Thai-Myanmar border, as revealed by acridine orange staining and PCR-based diagnoses.

The prevalence of the four human malaria parasites was investigated among malaria patients at northern, central and southern towns in Thailand along the border with Myanmar between September 1995 and May 1996. Thin smears obtained from 548 Thai and Burmese patients were reviewed by an acridine orange staining method, and many mixed infections with two to four species, including P. malariae and P. ovale, were detected. These diagnostic results were compared with those by two PCR-based diagnoses, microtitre plate hybridization (MPH) and a nested PCR method, both of which targets the same, species-specific regions in the 18S rRNA genes. In both PCR diagnoses, many P. malariae and P. ovale infections were also detected. Detection sensitivity of P. malariae infection was higher in nested PCR than MPH, and a total prevalence of P. malariae infection estimated by nested PCR reached 24.3% (133/548). In 16 of them, the size of PCR products amplified by the P. malariae-specific primer was about 20-bp shorter than the expected size of 115-bp. Four of 16 possessed two different bands with normal and shorter sizes, suggesting that P. malariae isolates may be separated into two types, and that those with shorter products may be new variant form (s) with a nucleotide deletion in the target region. On the other hand, 21 P. ovale infections (3.8%) were detected by nested PCR, but four of them were MPH-negative because of the sequence variation at the probe region. These results indicated that the prevalence of P. malariae and P. ovale along the Thai-Myanmar border may be substantially higher than previously reported.

Acridine Orange↗

Wide distribution of Plasmodium ovale in Myanmar.

The presence of Plasmodium ovale has never been previously reported in Myanmar. Using blood samples obtained in many villages across the country between 1996 and 2000, molecular diagnosis of Plasmodium species was made with semi- or full-nested polymerase chain reaction (PCR) with species-specific primers, followed by agarose gel electrophoresis to detect amplification products. The presence of P. ovale was also confirmed with the another PCR-based diagnosis, the microtiterplate hybridization (MPH) method using species-specific probes. Both methods target the A type of the small subunit ribosomal RNA gene of the four human malaria parasites. Plasmodium ovale DNA was amplified in samples from 65 (4.9%) of 1323 PCR-positive patients, with perfect agreement between results obtained by nested PCR and MPH. Only four P. ovale-infected patients had single-species infection; all others were coinfected with P. falciparum, P. vivax and/or P. malariae. Quadruple infections were observed in six subjects. Parasites with typical P. ovale morphology were found in only 19 patients by conventional microscopy of Giemsa-stained thin smears or fluorescence microscopy of acridine orange-stained thin smears. Plasmodium ovale infections were found in villages situated in the southern, central and western regions of Myanmar, suggesting that P. ovale may be widely distributed in this country.

Adolescent↗

The anthropoid status of a primate from the late middle Eocene Pondaung Formation (Central Myanmar): tarsal evidence.

Primate dental and postcranial remains from the Eocene Pondaung Formation (Myanmar) have been the subject of considerable confusion since their initial discoveries, and their anthropoid status has been widely debated. We report here a well preserved primate talus discovered in the Segyauk locality near Mogaung that displays derived anatomical features typical of haplorhines, notably anthropoids, and lacks strepsirhine synapomorphies. Linear discriminant and parsimony analyses indicate that the talus from Myanmar is more similar structurally to those of living and extinct anthropoids than to those of adapiforms, and its overall osteological characteristics further point to arboreal quadrupedalism. Regressions of talar dimensions versus body mass in living primates indicate that this foot bone might have belonged to Amphipithecus. This evidence supports hypotheses favoring anthropoid affinities for the large-bodied primates from Pondaung and runs contrary to the hypothesis that Pondaungia and Amphipithecus are strepsirhine adapiforms.

Animals↗

A lower jaw of Pondaungia cotteri from the Late Middle Eocene Pondaung Formation (Myanmar) confirms its anthropoid status.

Pondaungia cotteri is the largest primate known from the Late Middle Eocene Pondaung Formation, Myanmar. Its taxonomic status has been the subject of much debate because of the fragmentary nature of its remains. Initially described as an anthropoid, some authors recently have associated it with adapid primates. These debates have been fueled not only by the incompleteness of the fossils attributed to Pondaungia but also by the reticence of many authors to regard Asia as an important evolutionary theater for Eocene anthropoids. During the November 1998 Myanmar-French Pondaung Expedition, a right lower jaw was discovered that yields the most nearly complete dentition of Pondaungia cotteri ever found: it shows the complete horizontal ramus, alveoli for the second incisor and canine, three premolars, and three molars. The symphysis showed all characteristics of anthropoids but was unfused. The canine root is large, the first premolar is absent, and the second premolar is single-rooted, reduced, and oblique in the tooth row, as in anthropoids. The premolars show a reduced mesio-distal length compared with the tooth row, and their morphology is very similar to that of Amphipithecus mogaungensis. Therefore, the two Pondaung taxa appear to be closely related to each other, with Siamopithecus as their sister taxon.

Animals↗

Mental health and psychosocial aspects of disaster preparedness in Myanmar.

Myanmar as a country in South-East Asia is vulnerable to disasters including storms, floods, fire, earth fall, earthquakes, depending on the geographical nature and climate of the area. The National Health Committee (NHC) of Myanmar has formed under it an Emergency Healthcare Committee. After the Asian tsunami, the Ministry of Health (MoH) formed the National Disaster Preparedness and Response Committee which developed the National Guidelines for Disasters Preparedness and Response. The experience of dealing with the tsunami has shown that psychosocial support to the affected community not only reduces its psychological distress but can also facilitate physical rehabilitation. Thus mental health and psychosocial aspects have been included in disaster preparedness and management plans of the MoH.

Disaster Planning↗

Hospital-based surveillance for rotavirus diarrhea in children in Yangon, Myanmar.

Diarrhea is a common childhood illness in Myanmar, and rotavirus is the single most important etiological agent of diarrhea. Surveillance for rotavirus diarrhea in children <5 years of age was conducted in a tertiary pediatric hospital in Yangon, Myanmar, from January 2002 through December 2003. Stool specimens obtained from children admitted to the hospital for acute diarrhea were tested for the presence of rotavirus by use of an enzyme-linked immunosorbent assay. Diarrhea was the cause of 5671 (18%) of all hospitalizations of children <5 years of age during the 2-year study period (n = 30,869). Rotavirus was identified in 923 (53%) of the 1736 stool specimens tested, and rotavirus infection was associated with approximately 10% of all hospitalizations of children. Rotavirus diarrhea most frequently occurred in children 6-17 months of age, and it was more commonly identified in boys (62% of children with rotavirus diarrhea were boys). The seasonal pattern of rotavirus disease mimicked that of diarrheal illness due to all causes, with the peak season for rotavirus disease occurring from November through February (i.e., during the cool, dry season). During the study period, 53 of the children who were hospitalized for diarrhea died. The present study confirms the importance of the etiological role that rotavirus plays in childhood diarrhea.

Child, Preschool↗

High prevalence of diverse forms of HIV-1 intersubtype recombinants in Central Myanmar: geographical hot spot of extensive recombination.

OBJECTIVES: To investigate the molecular epidemiology and genetic structure of HIV-1s causing the epidemic in Central Myanmar and to explore the genesis of HIV epidemic in this area. DESIGN: A molecular epidemiological investigation was conducted in 1999-2000 in the city of Mandalay among high-risk populations and the structural features of circulating HIV-1s were analyzed. METHODS: HIV-1 genotypes of 59 specimens were screened based on gag (p17) and env (C2/V3) regions. Near full-length nucleotide sequences of HIV-1 isolates with subtype discordance were determined and their recombinant structures were characterized. RESULTS: Three lineages of HIV-1 strains, including CRF01_AE (27, 45.8%), subtype B' (Thailand variant of subtype B) (15, 25.4%) and subtype C (8, 13.6%), were distributed in Mandalay, while substantial portions (9, 15.3%) of specimens showed various patterns of subtype discordance in different regions of HIV-1 genomes. The study on six HIV-1 isolates with subtype discordance revealed that they were highly diverse types of unique recombinant forms (URFs) comprised of various combinations of three circulating subtypes. One URF was a particularly complex mosaic that contained 13 recombination breakpoints between three HIV-1 subtypes. Approximately half of recombinants showed 'pseudotype' virion structures, in which the external portions of envelope glycoproteins were exchanged with different lineages of HIV-1 strains, suggesting the potential selective advantage of 'pseudotype' viruses over parental strains. CONCLUSION: The study revealed the unique geographical hot spot in Central Myanmar where extensive recombination events appeared to be taking place continually. This reflects the presence of highly exposed individuals and social networks of HIV-1 transmission.

Adolescent↗

Quality control of antibiotics before the implementation of an STD program in Northern Myanmar.

BACKGROUND: The ready availability of poor-quality drugs in developing countries leads to treatment failure and, consequently, excess mortality and morbidity. Moreover, the widespread availability of substandard drugs plays a key role in increasing the resistance to antimicrobial drugs.GOAL As a prerequisite to the establishment of a sexually transmitted disease (STD) control program, this study aimed to evaluate the quality of antibiotics recommended for treatment of STDs that were locally available in the capital of a province of Northern Myanmar. STUDY DESIGN: In addition to the hospital pharmacy, we selected at random 5 of the 41 drug sellers and 5 of the 40 general practitioners who sell antibiotics in the city of Myitkyina. Twenty-one marketing products corresponding to nine different antibiotics used for STD treatment were purchased (benzathine benzylpenicillin, benzylpenicillin, ceftriaxone, chlortetracycline, ciprofloxacin, clotrimazole, co-trimoxazole, doxycycline, and erythromycin). Drugs were sent to France, where they were analyzed according to the WHO guidelines. Drugs were considered to be standard if their dosage remained in the 10% range of the expected value. RESULTS: Among the 21 different specialty products, only three displayed the official "registered" label. Three drugs were expired and the expiration date was not available for six others. One product did not contain the active drug declared (chlortetracycline; Lombisin, Unicorn, China) and did not show any in vitro activity against bacteria. Seven of 21 products (33%) did not contain the stated dosage (1, more than stated dosage; 6, less than stated dosage). The highest deficit observed was 48% in two products (co-trimoxazole, Yong Fong, Myanmar; benzylpenicillin, China [city and manufacturer unknown]). The dosage was not available for five drugs. As a result, only 8 of 21 products (38%) did not contain the stated dosage of active drug. CONCLUSION: These findings suggest that public health policies based on national treatment guidelines should rigorously include the monitoring of quality control of available antimicrobial products. In the absence of such measures, specific treatment strategies are likely to fail and to generate drug resistance.

Anti-Bacterial Agents↗

Different subtype distributions in two cities in Myanmar: evidence for independent clusters of HIV-1 transmission.

A molecular epidemiological investigation was conducted in two major cities in Myanmar (Yangon and Mandalay). The study revealed a unique predominance of HIV-1 subtype B' (Thailand variant of subtype B) among injecting drug users in Yangon, indicating the strong founder effect of this variant. In contrast, multiple lineages of HIV-1 strains were found in Mandalay, leading to the evolution of various forms of intersubtype recombinants. The results showed independent clusters of HIV-1 transmission in Myanmar.

Female↗