Biotechnological application of Aureobasidium spp. as a promising chassis for biosynthesis of ornithine-urea cycle-derived bioproducts.

The ornithine-urea cycle (OUC) in fungal cells has biotechnological importance and many physiological functions and is closely related to the acetyl glutamate cycle (AGC). Fumarate can be released from argininosuccinate under the catalysis of argininosuccinate lyase in OUC which is regulated by the Ca2+ signaling pathway and over 93.9 ± 0.8 g/L fumarate can be yielded by the engineered strain of Aureobasidium pullulans var. aubasidani in the presence of CaCO3. Furthermore, 2.1 ± 0.02 mg of L-ornithine (L-Orn)/mg of the protein also can be synthesized via OUC by the engineered strains of Aureobasidum melanogenum. Fumarate can be transformed into many drugs and amino acids and L-Orn can be converted into siderophores (1.7 g/L), putrescine (33.4 g/L) and L-piperazic acid (L-Piz) (3.0 g/L), by different recombinant strains of A. melanogenum. All the fumarate, L-Orn, siderophore, putrescine and L-Piz have many applications. As the yeast-like fungi and the promising chassis, Aureobasidium spp, have many advantages over any other fungal strains. Further genetic manipulation and bioengineering will enhance the biosynthesis of fumarate and L-Orn and their derivates.

OUC in fungal cells has biotechnological importance and many physiological functions; OUC is closely related to acetyl glutamate cycle (AGC). Fumarate, L-Orn, siderophore, putrescine and L-Piz produced from OUC have many applications.

The feasibility and acceptability of integrating hepatitis C and HIV diagnostic testing on centralized molecular laboratory platforms in Myanmar.

BACKGROUND: In Myanmar, 1.3 million people have been exposed to hepatitis C (HCV). However, public sector access to viral load (VL) testing for HCV diagnosis remains limited; ten near-point-of-care (POC) devices are available nationally. Myanmar's National Health Laboratory (NHL) has surplus capacity on centralized molecular testing platforms used for HIV diagnostics, presenting an opportunity for integrating HCV testing to expand overall testing capacity. This pilot assessed the operational feasibility and acceptability of HCV/HIV integrated testing implemented with a comprehensive package of supportive interventions. METHODS: HCV VL samples were collected prospectively from consenting participants at five treatment clinics and tested at Myanmar's NHL (October 2019-February 2020) on the Abbott m2000. To optimize integration, laboratory human resources were bolstered, staff trainings were offered, and existing laboratory equipment was serviced/repaired as needed. Diagnostics data during the intervention period were compared against HIV diagnostics data in the seven months prior. We conducted three time and motion analyses at the laboratory and semi-structured interviews with laboratory staff to assess time needs and program acceptability. RESULTS: 715 HCV samples were processed during the intervention period with an average test processing time of 18 days (IQR: 8-28). Despite adding HCV testing, average monthly test volumes were 2,331 for HIV VL and 232 for early infant diagnosis (EID), comparable to the pre-intervention period. Processing times were 7 days for HIV VL and 17 days for EID, also comparable to the pre-intervention period. HCV test error rate was 4.3%. Platforms utilization increased from 18.4% to 24.6%. All staff interviewed were supportive of HCV and HIV diagnostics integration; suggestions were made for broader implementation and expansion. CONCLUSIONS: With a package of supportive interventions, integration of HCV and HIV diagnostics on a centralized platform was operationally feasible, did not adversely impact HIV testing, and was acceptable to laboratory staff. In Myanmar, integrated HCV VL diagnostic testing on centralized platforms may be an important addition to existing near-POC testing in expanding national testing capacity for HCV elimination.

Patient outcomes in public sector hepatitis C treatment programmes: a retrospective cohort analysis across five low- and middle-income countries.

OBJECTIVES: Given limited data on factors associated with hepatitis C virus (HCV) treatment discontinuation and failure in low- and middle-income countries, we aimed to describe patient populations treated for HCV in five countries and identify patient groups that may need additional support. DESIGN: Retrospective cohort analysis using routinely collected data. SETTING: Public sector HCV treatment programmes in India (Punjab), Indonesia, Myanmar, Nigeria (Nasarawa) and Vietnam. PARTICIPANTS: 104 957 patients who initiated treatment in 2016-2022 (89% from Punjab). PRIMARY OUTCOMES: Treatment completion and cure. RESULTS: Patient characteristics and factors associated with outcomes varied across countries and facilities. Across all patients, median age was 40 years (IQR: 29-52), 30.6% were female, 7.0% reported a history of injecting drugs, 18.2% were cirrhotic and 4.9% were coinfected with HIV. 79.8% were prescribed sofosbuvir+daclastasvir. Of patients with adequate follow-up, 90.6% (89,551) completed treatment. 77.5% (69,426) of those who completed treatment also completed sustained virological testing at 12 weeks (SVR12), and of those, 92.6% (64 305) were cured. In multivariable-adjusted models, in most countries, significantly lower treatment completion was observed among patients on 24-week regimens (vs 12-week regimens) and those initiated in later years of the programme. In several countries, males, younger patients <20 years and certain groups of cirrhotic patients were less likely to complete treatment or be cured. In Punjab, treatment completion was also lower in those with a family history of HCV and people who inject drugs (PWID); in other countries, outcomes were comparable for PWID. CONCLUSION: High proportions of patients completed treatment and were cured across patient groups and countries. SVR12 follow-up could be strengthened. Males, younger people and those with decompensated cirrhosis on longer regimens may require additional support to complete treatment and achieve cure. Adequate programme financing, minimal user fees and implementation of evidence-based policies will be critical to close gaps.

Southeast Asia must narrow down the yield gap to continue to be a major rice bowl.

Southeast Asia is a major rice-producing region with a high level of internal consumption and accounting for 40% of global rice exports. Limited land resources, climate change and yield stagnation during recent years have once again raised concerns about the capacity of the region to remain as a large net exporter. Here we use a modelling approach to map rice yield gaps and assess production potential and net exports by 2040. We find that the average yield gap represents 48% of the yield potential estimate for the region, but there are substantial differences among countries. Exploitable yield gaps are relatively large in Cambodia, Myanmar, Philippines and Thailand but comparably smaller in Indonesia and Vietnam. Continuation of current yield trends will not allow Indonesia and Philippines to meet their domestic rice demand. In contrast, closing the exploitable yield gap by half would drastically reduce the need for rice imports with an aggregated annual rice surplus of 54 million tons available for export. Our study provides insights for increasing regional production on existing cropland by narrowing existing yield gaps.

Risk factors for tuberculosis treatment failure among pulmonary tuberculosis patients in four health regions of Burkina Faso, 2009: case control study.

INTRODUCTION: In Burkina Faso, the tuberculosis (TB) treatment failure rate increased from 2.5% in 2000 to 8.3% in 2006. The risk factors for TB treatment failure in the country are not well known. The study aims to determine the risk factors for treatment failure among pulmonary tuberculosis patients in four health region of Burkina Faso and to recommend appropriate interventions. METHODS: A case control study was conducted among pulmonary TB patients who began TB treatment in 2009. A case was any patient who remained smear-positive at fifth month of TB treatment and a control was a patient who tested smear-negative at fifth month of treatment. A structured questionnaire was administered to one hundred cases and one hundred controls to collect information on exposure factors. Odds ratio were calculated using bivariate and multivariate analysis to determine the association between exposures and outcome. RESULTS: Multivariate analysis showed that independent risk factors for TB treatment failure were fail to take TB drugs for more than 14 consecutive days (OR = 18.53; 95% CI:4.56 - 75.22), sputum smear-positive at two months of treatment (OR = 11.52; 95%CI:5.18-25.60), existence of comorbidity (OR = 5.74; 95%CI:1.69-19.44), and use of traditional medicines or herbs (OR = 2.97; 95%CI:1.12-7.85). CONCLUSION: Early identification of patients with the above risk factors for intense case management will improve TB treatment outcome. Patient with smear positive at 2nd(nd) month of treatment require more intense follow-up, and involving traditional healers who provide traditional medicines or herbs in the educational programme on TB are required. The national referral laboratory capacity needs to be strengthened to do drug susceptibility testing and routine drug monitoring on cases of non conversion at 2(nd) month of treatment.

Early warning indicators for HIV drug resistance in adults in South Africa at 2 pilot sites, 2008-2010.

BACKGROUND: Approximately 5.2 million people in South Africa were infected with human immunodeficiency virus (HIV) by the year 2010, with just over 30% initiated on highly active antiretroviral therapy by 2011. With such numbers involved, the potential for the emergence of HIV drug resistance (HIVDR) is high. This study piloted early warning indicators (EWIs) for HIVDR at 2 clinics in South Africa. METHODS: HIV-infected individuals aged ≥15 years and receiving antiretroviral drugs were enrolled into this cohort study between March 2008 and February 2010. All analyses were performed using the 2012 World Health Organization EWI score card. RESULTS: A total of 1144 subjects were enrolled. Clinic A reached the target for 2 of the 5 EWIs but missed the desired target for on-time pill pickup, pharmacy stockouts, and virological suppression. Clinic B reached the target for 1 of 4 EWIs, namely, dispensing practices. Targets were missed for on-time pill pickup, retention in care, and virological suppression. Pharmacy stockouts could not be calculated at this site. CONCLUSIONS: Actual performance against the levels that the pilot sites should reach to minimize HIVDR was low. Improvements in follow-up procedures, internal adherence support, monitoring for drug stockouts, and adherence are all aspects that need support to ensure that all records are complete. This pilot study may help to inform the South African government as EWI monitoring is implemented.

Morbidity and mortality due to malaria in Est Mono district, Togo, from 2005 to 2010: a times series analysis.

BACKGROUND: In 2004, Togo adopted a regional strategy for malaria control that made use of insecticide-treated nets (ITNs), followed by the use of rapid diagnostic tests (RDTs), artemisinin-based combination therapy (ACT). Community health workers (CHWs) became involved in 2007. In 2010, the impact of the implementation of these new malaria control strategies had not yet been evaluated. This study sought to assess the trends of malaria incidence and mortality due to malaria in Est Mono district from 2005 to 2010. METHODS: Secondary data on confirmed and suspected malaria cases reported by health facilities from 2005 to 2010 were obtained from the district health information system. Rainfall and temperature data were provided by the national Department of Meteorology. Chi square test or independent student's t-test were used to compare trends of variables at a 95% confidence interval. An interrupted time series analysis was performed to assess the effect of meteorological factors and the use of ACT and CHWs on morbidity and mortality due to malaria. RESULTS: From January 2005 to December 2010, 114,654 malaria cases (annual mean 19,109 ± 6,622) were reported with an increase of all malaria cases from 10,299 in 2005 to 26,678 cases in 2010 (p<0.001). Of the 114,654 malaria cases 52,539 (45.8%) were confirmed cases. The prevalence of confirmed malaria cases increased from 23.1 per 1,000 in 2005 to 257.5 per 1,000 population in 2010 (p <0.001). The mortality rate decreased from 7.2 per 10,000 in 2005 to 3.6 per 10,000 in 2010 (p <0.001), with a significant reduction of 43.9% of annual number of death due to malaria. Rainfall (ß-coefficient = 1.6; p = 0.05) and number of CHWs trained (ß-coefficient = 6.8; p = 0.002) were found to be positively correlated with malaria prevalence. CONCLUSION: This study showed an increase of malaria prevalence despite the implementation of the use of ACT and CHW strategies. Multicentre data analysis over longer periods should be carried out in similar settings to assess the impact of malaria control strategies on the burden of the disease. Integrated malaria vector control management should be implemented in Togo to reduce malaria transmission.

A pharmacovigilance study of adults on highly active antiretroviral therapy, South Africa: 2007 - 2011.

BACKGROUND: Of the 1.6 million South African people infected with human immunodeficiency virus (HIV), approximately 970,000 (55%) have been initiated on HAART. Despite these numbers, very little has been published about the safety profile of antiretroviral (ARV) medicines in the country. This study was performed at the Medunsa National Pharmacovigilance Centre and aimed to describe the demographic characteristics of patients enrolled in the pharmacovigilance surveillance study; highly active antiretroviral therapy (HAART) initiation regimen patterns; reasons for regimen changes; and adverse effects of ARV medicines. METHODS: A cohort study of HIV-infected individuals aged 15 years or older who were on ARV medicines was conducted at four sentinel sites. RESULTS: After HAART initiation, with an average lapse of 17.8 months (range: 0 - 83.8 months), 2,815 patients were enrolled into the study. Results show that patients were observed for 1,606.2 person-years for pharmacy visits (collection of ARV medicines) and 817.1 person-years for clinical visits (consultation with the doctor). Females constituted 69.6% (1,958/2,815) of the study population. Almost all patients initiated HAART on first-line regimens (2,801/2,815). Some patients (6.7%, 190/2,815) dropped out of the study after HAART initiation. Reasons for regimen changes were not recorded for 2.5% (22/891) of the patients who changed regimens. The primary reason for regimen changes was drug-related toxicity (76.1%, 678/891), mostly evident in patients taking first-line regimens. Adverse effects experienced by patients were polyneuropathy (24.0%, 163/678); lipodystrophy (23.9%, 162/678); neuropathy (10.6%, 72/678); and suspected lactic acidosis (3.8%, 26/678). CONCLUSION: The majority of prescribers complied with the HAART guidelines and initiated most patients on first-line regimens. However, adverse effects are evident in patients taking first-line regimens. We recommend that the Department of Health should introduce less toxic first-line ARV regimens. Future efforts will aim to initiate patients on HAART and enrol them into the study simultaneously to determine early risk profiles of ARV medicines.

Outbreak of Rift Valley fever affecting veterinarians and farmers in South Africa, 2008.

BACKGROUND: During 2008, Rift Valley fever (RVF) virus re-emerged in South Africa as focal outbreaks in several provinces. AIMS: To investigate an outbreak affecting cattle farmers and farm workers, and the staff and students of a veterinary school, assess the prevalence of infection during the outbreak, document the clinical presentation of cases, and identify potential risk factors. METHODS: We conducted a cross-sectional serological survey of exposed veterinarians and farmers, who were examined to determine the presence of current or recent illness. Blood specimens were collected for virus isolation, nucleic acid detection and serology. A subset was interviewed using a standardised questionnaire to obtain data on recent exposures and risk factors for infection. RESULTS: Of 53 participants potentially exposed to infected domestic ruminants, 15% had evidence of recent infection and 4% evidence of past exposure to the RVF virus. The prevalence of acute infection was 21% in veterinarians compared with 9% in farmers and farm workers. After a mean incubation period of 4.3 days, the most frequent symptoms experienced included myalgia (100%), headache (88%) and malaise (75%). No asymptomatic cases were identified. Transmission, by direct contact with infected animals was the major risk factor in these professional groups. Performing animal autopsies was significantly associated with acute infection (risk ratio 16.3, 95% confidence interval 2.3 - 114.2). CONCLUSIONS: Increased risks associated with veterinary practices highlight a need for the use of personal protective equipment, and identify veterinarians as a primary target group for future vaccination.

Public health systems strengthening in Africa: the role of South Africa Field Epidemiology and Laboratory Training Programme.

The South Africa Field Epidemiology and Laboratory Training Programme (SAFELTP) was created in 2006 after recognizing the need to build and sustain the country's human resource capacity in field (applied) epidemiology and public health practice. The programme was formed as a collaboration between the South Africa Department of Health (DoH), the National Institute for Communicable Diseases (NICD), the National Health Laboratory Services (NHLS), the US Centers for Disease Control and Prevention (CDC) and the University of Pretoria. The primary goal of the programme was to produce field-trained epidemiologists equipped with knowledge and practical skills to effectively and efficiently address the public health priorities of South Africa. SAFELTP is a 2-year full-time training, consisting of a combination of classroom-based instruction (30%) and mentored field work (70%). The training places emphasis on public health surveillance, investigation of disease epidemics, public health laboratory practice and communication of epidemiologic information, among other aspects of epidemiology research. At completion, residents are awarded a Master of Public Health (MPH) degree from the University of Pretoria. Since its inception in 2006, 48 residents have enrolled onto the programme and 30 (62%) of them have completed the training. Over the past 5 years, the residents have conducted more than 92 outbreak investigations, 47 surveillance evaluations, 19 planned studies, analyzed 37 large databases and presented more than 56 papers at local and international conferences. In recognition of the high-quality work, at least five SAFELTP residents have received awards at various international scientific conferences during the 5 years. In conclusion, the South Africa FELTP is now fully established and making valuable contributions to the country's public health system, albeit with innumerable challenges.

Socio-Demographic Determinants of Condom Use Among Sexually Active Young Adults in Rural KwaZulu-Natal, South Africa.

AIM: To investigate patterns, levels and socio-demographic determinants of condom use and consistency of use among young adults aged 15-24 years. BACKGROUND: Condoms are known to prevent HIV infection. However, HIV prevalence and incidence remain high. METHODS: This study was conducted in the Africa Centre Demographic Surveillance Area (ACDSA) in rural KwaZulu-Natal. Analysis focused on resident young adults aged 15-24 years in 2005. In univariable and multivariable analyses, determinants of condom use and consistency of use among 15-24 year olds were estimated using data collected in 2005. 'Ever' condom use was defined as the proportion who reported having used a condom; consistent use among those ever using as "always" using condoms with most recent partner in the last year. RESULTS: 3,914 participants aged 15-24 years reported ever having sex, of whom 52% reported condom use. Adjusting for age, sex, number of partners, residence of partner, partner age difference, type of partner and socio-economic status (SES), having an older partner decreased likelihood (aOR=0.69, p<0.01), while belonging to a household in a higher SES increased likelihood of ever using condoms (aOR=1.82, p<0.01). Being female (aOR=0.61 p<0.01) and having a regular partner (aOR=0.65 p<0.01) were independently associated with low consistent condom use. CONCLUSIONS: In this rural South African setting, condom use remains low, especially among females and with an older partner, situations commonly associated with increased HIV acquisition. Targeted supportive interventions to increase condom use need to be developed if HIV prevention programmes are to be successful.

Hormone therapy and intraocular pressure in nonglaucomatous eyes.

OBJECTIVE: The influence of sex hormones on intraocular pressure (IOP) has been the focus of recent debate. Previous studies investigating the effects of hormone therapy (HT) on IOP in postmenopausal women have produced conflicting results but have been limited by small numbers of participants. The aim of our study was to compare IOP in women without glaucoma taking HT with those not taking HT. METHODS: A prospective cross-sectional study of postmenopausal women visiting a single ophthalmic medical practitioner was conducted. All women with a history of intraocular disease, a family history of glaucoma, or refractive error exceeding +/-5 diopters were excluded. Applanation tonometry was used to measure IOP, and participants were then asked if they were current HT users. RESULTS: A total of 263 participants were recruited, of whom 91 reported current use of HT; 172 had never used HT. Within the HT group, 33 were taking an estrogen-therapy and 58 were taking a estrogen-progesterone therapy. Mean IOP in the HT group was significantly lower than that in the non-HT group; the mean difference was 1.41 mm Hg (P < 0.001). This difference remained statistically significant after statistical correction for age, use of systemic beta-blockers, and time of IOP measurement. There was no significant difference in mean IOP between women taking combined versus those taking estrogen-only preparations. CONCLUSIONS: Our study showed that IOP was significantly lower in women taking HT than in those who had never taken HT, even after removing other possible influences on IOP. The IOP-lowering effect of HT deserves further investigation to explore whether it may represent a possible new therapeutic modality for glaucoma.

Levels of childhood vaccination coverage and the impact of maternal HIV status on child vaccination status in rural KwaZulu-Natal, South Africa*.

OBJECTIVES: To analyse coverage of childhood vaccinations in a rural South African population and investigate whether maternal HIV status is associated with children's vaccination status. METHODS: 2 431 children with complete information, 12-23 months of age at some point during the period January 2005 through December 2006 and resident in the Africa Centre Demographic Surveillance Area at the time of their birth were investigated. We examined the relationship between maternal HIV status and child vaccination status for five vaccinations [Bacillus Calmette-Guérin (BCG), diphtheria-tetanus-pertussis (DTP3), poliomyelitis (polio3), hepatitis B (HepB3), and measles] in multiple logistic regressions, controlling for household wealth, maternal age, maternal education and distances to roads, fixed and mobile clinics. RESULTS: Coverage of the five vaccinations ranged from 89.3% (95% CI 81.7-93.9) for BCG to 77.3% (67.1-83.6) for measles. Multivariably, maternal HIV-positive status was significantly associated with lower adjusted odds ratios (AOR) of child vaccination for all vaccines [(AOR) 0.60-0.74, all P < or = 0.036] except measles (0.75, P = 0.073), distance to mobile clinic was negatively associated with vaccination status (all P < or = 0.029), household wealth was positively (all P < or = 0.013) and distance to nearest road negatively (all P < or = 0.004) associated with vaccination status. CONCLUSION: Positive maternal HIV status independently reduces children's probability to receive child vaccinations, which likely contributes to the morbidity and mortality differential between children of HIV-positive and HIV-negative mothers. As a means of increasing vaccination coverage, policy makers should consider increasing the number of mobile clinics in this and similar communities in rural Africa.

Making systems work: the hard part of improving maternal health services in South Africa.

As part of a multi-country study, maternal health services were reviewed in one health district in Gauteng Province, South Africa. Poor record-keeping, inadequate supervision, poor levels of clinical knowledge and under-utilisation of midwife obstetric units were found. Interventions identified by local health service personnel to improve maternity care were developed, implemented and evaluated, included programme-specific (training in prevention of mother-to-child transmission of HIV and neonatal resuscitation) and system interventions (improving interpersonal relations and system functioning, use of routine data for monitoring purposes, improving supervision skills). This resulted in some positive outputs. Health worker knowledge and patient records improved, and there was some indication that supervision improved. However, system-wide interventions that could improve programmes were less successful. To build a learning organisation, a new culture of monitoring and evaluation, including routine self-evaluation, is required as core skills for all health workers. These data should be used at the point of collection. Changing reporting lines between programme and district managers may improve co-ordination between different authorities, and there is a need to enhance the manner in which staff are assessed, appraised, promoted and rewarded. Professional bodies who oversee training curricula, institutions that offer training, and institutions that provide funding for training and development need to take on the challenge of health systems development and avoid promoting programme-specific interventions only.