Diagnosis of bovine-associated parapoxvirus infections in humans: molecular and epidemiological evidence.

Orf virus, pseudocowpox virus and bovine papular stomatitis virus, are parapoxviruses, associated with domestic ruminants, which are capable of causing cutaneous infections in humans. Owing to virtually identical appearances in humans, clinical differentiation of these viruses is difficult. We discuss three recent occurrences of parapoxvirus infection, involving contact with domestic bovine and use a combination of molecular and epidemiological data in the diagnosis. These cases underscore the utility of modern diagnostic tools, along with species-specific contact information in acquiring a definitive diagnosis, in the case of suspected parapoxvirus infection.

GABA release in the medial preoptic area of cyclic female rats.

GABA is a potent regulator of gonadotropin-releasing hormone neurons in the hypothalamus. To determine the profile of GABA release in the medial preoptic area where the gonadotropin surge generator resides, an in vivo microdialysis study was performed in cyclic female rats. The microdialysis samples were collected and sequential blood samples (150 microl each) were also obtained, at 1-h intervals. During estrus and diestrus 1, GABA release in the medial preoptic area was relatively low. A small increase in the GABA release began in the afternoon of diestrus 1 and attained its peak in the morning of diestrus 2, but declined in the afternoon of that day. The GABA release markedly increased from late in the night of diestrus 2 through the morning of proestrus, when it attained its peak, and thereafter it declined sharply until the critical period of proestrus. A distinct preovulatory luteinizing hormone surge was observed in the afternoon of proestrus in all proestrous rats. From these results we suggest that the preovulatory elevation of the GABA release from the night through to the morning of proestrus, followed by a sharp decline, is closely associated with the onset of the preovulatory luteinizing hormone surge in cyclic female rats. The present study is the first to report the 4-day profile of GABA release in the medial preoptic area during the estrous cycle.

Prediction of 'highly skin smear positive' cases among MB leprosy patients using clinical parameters.

Although 'highly skin smear positive' MB leprosy cases are known to be at high risk of relapse after release from treatment, and have been recommended to receive 'prolonged duration' MDT, government field-based control programmes without skin smear facilities have no simple alternative method to detect such cases. This study reports a significant prevalence of 'highly smear positive' cases amongst 2374 new multibacillary cases recently surveyed by skin smears in Nepal, and retrospectively analyses 555 newly detected, previously untreated BL and LL cases to identify clinical and laboratory parameters that may be associated with a 'highly positive skin smear'. While some parameters showed high sensitivity in predicting 'highly positive smear' status, none showed both high sensitivity and high specificity simultaneously.

Leprosy elimination through integrated basic health services in Myanmar: the role of midwives.

Myanmar is one of the top 16 countries identified by WHO as being hyperendemic for leprosy. Multi-drug therapy (MDT) was introduced in 1988 as a vertical programme and gradually integrated into the basic health services (BHS), achieving 100% coverage over the registered cases by 1995. To achieve maximum coverage of and benefit for patients, both leprosy vertical staff and BHS staff were trained to implement MDT whilst performing routine BHS activities. This included a total of 8615 trained midwives who were mobilized for the nationwide leprosy elimination programme (LEP). They worked at village level in various parts of the country and were willing and able to carry out basic tasks in leprosy management, such as the implementation of MDT using blister-calender packs carrying a month's supply of drugs. This study was performed to assess the workload of midwives and their attitude towards LEP. The authors conclude that midwives in Myanmar show a high level of commitment and reliability, which are essential contributing factors to achieve the current goal of leprosy elimination by the year 2000. Along with the present trend of decreasing prevalence rate, leprosy could no longer be considered as a public health problem at national level by the year 2000 in Myanmar. However, because of its long incubation period, new leprosy patients may arise even after the elimination target is achieved, whilst many other patients may become disabled. A community-based sustainable approach for the post-elimination phase, after the year 2000, will be essential and the contribution of the midwives may be of considerable importance.

Acceptance of short course artesunate plus mefloquine drug combination by malaria patients in rural Myanmar.

A cross sectional study was carried out in a rural area of Myanmar to identify malaria patients' acceptance of artesunate plus mefloquine drug combination and to determine the cost borne by patients. The majority (88.5%) preferred this new regimen rather than the other ones they had used before; conviction of drug efficacy was the reason given for the preference by most of them. Traveling on foot to rural health centers or a health assistant's residence for getting the drugs was found to be the main route. Average cost incurred by a patient to get the drug was found to be 274.22 Kyats. Among the cost items, drug cost was the highest item that they had used.

Influence of blister packaging on the efficacy of artesunate + mefloquine over artesunate alone in community-based treatment of non-severe falciparum malaria in Myanmar.

Three studies were carried out to determine the need, acceptability, and efficacy of adding mefloquine to artemisinin derivatives (AD) for the first-line treatment of uncomplicated falciparum malaria. The first was a retrospective study of 255 basic health workers which showed that their recommendation of AD to patients depended on their level of training. None of the paramedics/midwives and only 9% of 129 doctors had prescribed AD, and no one had recommended AD in combination with mefloquine; 72% of patients used courses that were too short for parasitological cure. To promote the addition of mefloquine to AD regimens we conducted intervention workshops with health care providers and subsidized the cost of mefloquine to patients. In the second study, we interviewed 200 patients before and after the intervention to evaluate drug compliance with full doses of AD and use of subsidized mefloquine. After the intervention, we found that only 3.6% had used mefloquine and 62% had taken non-curative doses of AD. In the third study, we provided blister packs of medication in daily doses and compared the intake of AD + placebo (158 patients) with that of AD + mefloquine (222 patients) for 5 days. The compliance with both regimens was 99%. Blood smears for parasites on day 28 showed one positive in the AD + mefloquine group and 7 positive in the AD group. We conclude that provision of blister packs of daily doses is a very effective way to improve compliance with short courses and drug combinations, but the efficacy of the combination in Myanmar in this particular study was only marginally higher than that of AD alone.

Serum cortisol levels in patients with uncomplicated and cerebral malaria.

Ten patients with uncomplicated malaria, ten with cerebral malaria and 37 controls (blood donors from blood bank) were included in the study. The serum cortisol levels of the patients were determined daily for 7 days while they were at the hospital. A radio-immunoassay method was used for quantitative measurement of cortisol in human serum. The mean serum cortisol level of patients with uncomplicated malaria was 528.2 +/- 123.9 nmol/l, with cerebral malaria was 516.0 +/- 80.5 nmol/l, and in controls was 393.8 +/- 141.0 nmol/l. There was a significant rise of serum cortisol levels in patients with malaria when compared to controls at the day of admission to hospital. There was no significant difference between uncomplicated malaria patients and those with cerebral malaria. There was also no significant difference between the different days of treatment up till day 7. We found no cortisol insufficiency in cases with falciparum malaria during acute and convalescent stages of illness.

A comparative study of intervention methods (full, partial and non-integration) on late case detection and treatment irregularity in Yangon, Myanmar.

The high percentage (20%) of new cases with grade 2 disabilities, and a low treatment regularity of 47% indicated problems in case detection and case holding in Urban Yangon. The fact that Urban Health Centers (UHCs) were not involved in leprosy control programme might have had an adverse influence. To compare the effectiveness of two methods of integration (full and partial) of urban leprosy services in terms of early case detection and regularity of treatment this study was conducted, in an urban area. Two townships with similar leprosy prevalence, staff infrastructure, socio-economic status, transport, communication and working capacity of the Township Medical Officers (TMOs) were chosen for this intervention study: UHC-A(Thingangyun) for full integration and UHC-B(Tamwe) for partial integration and the remaining 14 townships as non-integrated areas served by the Central Special Skin Clinic (CSSC). This study has shown that it was possible to fully integrate Leprosy Control Programme (LCP) into the Urban Health Centres [Basic Health Services (BHS)] in Urban Yangon. Case detection could be improved by active case finding such as contact examination and school examination conducted by the personnel of UHCs. Treatment regularity was found to be directly proportional to prompt defaulter retrieval action and the motivational level of the TMO and peripheral BHS workers. There were more complaints from patients (8.1%) treated at UHC-A when compared to CSSC (6.7%). Among defaulters there were more adults than children, more males than females and more PB than MB patients.

Risk factors in dengue shock syndrome.

Despite a growing body of evidence predominantly, but not exclusively, from Thailand suggesting that the risk of developing dengue shock syndrome (DSS) is greatest following an anamnestic dengue infection, particularly if the most recent infection was with dengue 2 virus, there continues to be debate about the justification for these claims. This report describes a five-year, prospective study in two townships (suburbs) in Yangon (Rangoon) Myanmar (Burma) in which attempts were made to confirm the data from an earlier prospective study in Thailand and to address some of the criticism of earlier studies. This investigation found the incidence of anamnestic dengue infections in DSS patients to be significantly higher than in the community from which they were drawn and a significantly higher risk of developing DSS following an anamnestic infection (particularly with dengue 2 virus) than following a primary infection with any serotype.

Changes in levels of anti-dengue virus IgG subclasses in patients with disease of varying severity.

Extensive complement activation precedes onset of shock in dengue patients and complement "split products" C3a and C5a could be responsible, directly or indirectly, for the increased vascular permeability and disseminated intravascular coagulation which characterises dengue haemorrhagic fever (DHF) dengue shock syndrome (DSS). As IgG subclasses vary in their capacity to activate the classical complement pathway after combining with antigen, we have used an indirect enzyme linked immunosorbent assay (ELISA) to assess levels of IgG1-4 against each dengue serotype in acute and convalescent sera from patients with disease of varying severity. Acute phase sera from patients with dengue haemorrhagic fever (DHF) or dengue shock syndrome (DSS) contained higher levels of anti-dengue antibodies of the IgG1, complement fixing, subclass than similar sera from dengue fever (DF) patients. Conversely, acute phase sera from DHF and DSS patients contained lower levels of anti-dengue antibodies of the poor complement activating IgG2 subclass than acute phase sera from DF patients. No significant differences were detected between the levels of anti-dengue IgG3 and IgG4 antibody in acute phase sera from DF, DHF, and DSS patients. With the exception of levels of anti-dengue IgG2 antibody from DHF patients which were lower than those from DF and DSS patients, levels of anti-dengue IgG1, IgG2, IgG3, and IgG4 were similar in convalescent sera from all patients. These results provide a possible explanation for the activation of the serum complement system which precedes onset of shock in severe dengue infections.

Prevalence of colour blindness among patients with leprosy.

Using Ishihara test plates the prevalence of colour blindness was studied on six hundred and ninety-seven leprosy patients and two hundred and ninety-two normal healthy controls. 7.88% of male patients with tuberculoid leprosy, 12.18% of male patients with lepromatous leprosy, and 0.67% of male controls were detected to be colour blind (red-green deficiency or total colour weakness). The differences between the different groups are significant. Among female patients and controls, only one lepromatous leprosy patient was detected to have red-green deficiency. This suggests the possibility of a genetic predisposition to Mycobacterium leprae infection in patients with leprosy.

The effect of artemether plus mefloquine on Myanmar patients with complicated falciparum malaria.

The effect of artemether plus mefloquine versus quinine on 35 patients with complicated falciparum malaria including 5 patients with cerebral malaria were studied. All patients treated with the artemether-mefloquine combination survived and all were free from toxic effects of the drugs. Three patients on quinine therapy died. The mortality rate was 8.5%. The mean parasite clearance time of patients treated with artemether plus mefloquine was significantly shorter than those treated with quinine but there was no significant difference in the mean fever clearance of the two groups of patients. There was no recrudescence with artemether and mefloquine; the recrudescence rate was 5.5% with quinine. The study showed that the artemether-mefloquine combination is superior to quinine for the treatment of patients with complicated falciparum malaria, including cerebral malaria.

Estimation of leprosy prevalence in Bago and Kawa townships using two-stage probability proportionate to size sampling technique.

Two surveys to estimate leprosy prevalence using two-stage probability proportionate to size sampling technique were conducted in Bago and Kawa townships. A total of 3519 and 3739 individuals were examined in each township. The two surveys were finished within 25 (Bago) and 30 (Kawa) working days at a cost of Kyats 10,000 (US $1500) for each survey. The estimated leprosy prevalence obtained in Bago was 9.95 per 1000 population (95% confidence interval (CI): 7.11-12.78) and in Kawa it was 12.04 per 1000 population (95% CI: 8.85-15.22). A total of 30 (Bago) and 34 (Kawa) new leprosy cases were detected in the two surveys. Grade I disability was seen to be 20% in Bago and 18.78% in Kawa, whereas grade II disability was 17.14% in Bago and 15.56% in Kawa.

The effect of tetanus toxoid in leprosy patients.

Since cases of lepra reaction following smallpox vaccination and BCG vaccination had been reported the effect of tetanus immunisation on leprosy patients (whether it may provoke a lepra reaction or not) was studied. Three doses of purified tetanus toxoid (one ml initially, one ml after six weeks and one ml after six months) were given to 357 leprosy patients and 60 patients living in the same environ were followed as controls. The antibody response following immunisation was followed in six lepromatous leprosy patients using toxin antitoxin neutralisation test at the Lf/1000 level in mice and in three of them the antibody titre of leprosy patients rose to satisfactory level. The number of lepra reactions in these patients was monitored for nine months (two months before vaccination, during the six months period of vaccination and one month after the last dose of vaccine). There was no significant rise in the number of patients with reaction following the vaccination.

The effect of mefloquine-sulfadoxine-pyrimethamine vs quinine on patients with complicated falciparum malaria.

Sixty-six patients with complicated falciparum malaria (defined as anaemia, hyperpyrexia, jaundice, or more than 2% of RBC parasitised) were studied. Patients with cerebral signs and symptoms were not included in the study. Patients were randomised in pairs to receive either mefloquine 750 mg, sulfadoxine 1500 mg and pyrimethamine 75 mg (MSP) single oral dose or quinine (10 mg/kg tds X 7 days oral therapy). All the patients were admitted in hospital for 7 days and were followed on days 14, 21 and 28. All patients survived. The parasite clearance times in MSP treated patients were significantly shorter then those treated with quinine. There was no difference in fever clearance time in the two groups of patients. One patient was resistant to MSP at RII level and 5 patients were resistant at RI level. Among patients treated with quinine 3 patients were resistant at RI level.