The Sixty Second Film and Video Festival

An innovative curatorial experiment and exhibition of International artists' new video and film works

The isolation of orientia tsutsugamushi and rickettsia typhi from human blood through mammalian cell culture: a descriptive series of 3,227 samples and outcomes in the Lao People’s Democratic Republic

In the Lao People’s Democratic Republic (Laos), rickettsial infections, including scrub and murine typhus, account for a significant burden of fevers. The Mahosot Hospital Microbiology Laboratory in Vientiane, Laos, routinely performs rickettsial isolation from hospitalized patients with suspected rickettsioses using mammalian cell culture systems. We review the clinical and laboratory factors associated with successful Orientia tsutsugamushi and Rickettsia typhi isolations from this laboratory over a period of 6 years between 2008 and 2014. The overall isolation success was 7.9% for all samples submitted and 17.3% for samples for which the patient had a positive O. tsutsugamushi or R. typhi rapid diagnostic test (RDT), serology, or PCR. The frequency of successful isolation was highest for samples submitted in November, at the end of the wet season (28.3%). A longer median duration of reported illness, a positive result for a concurrent Orientia or Rickettsia spp. quantitative PCR, and the use of antibiotics by the patient in the week before admission were significantly associated with isolation success (P 0.05). Buffy coat inoculation and a shorter interval between sample collection and inoculation in the laboratory were associated with a higher frequency of isolation (both P 0.05). This frequency was highest if cell culture inoculation occurred on the same day as blood sample collection. Factors related to the initial rickettsial bacterial concentration are likely the main contributors to isolation success. However, modifiable factors do contribute to the rickettsial isolation success, especially delays in inoculating patient samples into culture

Antimicrobial resistance in commensal opportunistic pathogens isolated from non-sterile sites can be an effective proxy for surveillance in bloodstream infections

Antimicrobial resistance (AMR) surveillance in bloodstream infections (BSIs) is challenging in low/middle-income countries (LMICs) given limited laboratory capacity. Other specimens are easier to collect and process and are more likely to be culture-positive. In 8102 E. coli BSIs, 322,087 E. coli urinary tract infections, 6952 S. aureus BSIs and 112,074 S. aureus non-sterile site cultures from Oxfordshire (1998–2018), and other (55,296 isolates) rarer commensal opportunistic pathogens, antibiotic resistance trends over time in blood were strongly associated with those in other specimens (maximum cross-correlation per drug 0.51–0.99). Resistance prevalence was congruent across drug-years for each species (276/312 (88%) species-drug-years with prevalence within ± 10% between blood/other isolates). Results were similar across multiple countries in high/middle/low income-settings in the independent ATLAS dataset (103,559 isolates, 2004–2017) and three further LMIC hospitals/programmes (6154 isolates, 2008–2019). AMR in commensal opportunistic pathogens cultured from BSIs is strongly associated with AMR in commensal opportunistic pathogens cultured from non-sterile sites over calendar time, suggesting the latter could be used as an effective proxy for AMR surveillance in BSIs

Nitrofurantoin and glucose-6-phosphate dehydrogenase deficiency: a safety review

Nitrofurantoin, a broad-spectrum antibiotic available since 1953, is used widely for the treatment of urinary tract infections as it often retains activity against drug-resistant uropathogens. It is contraindicated in pregnant women at term, and in neonates. Like trimethoprim/sulfamethoxazole, nitrofurantoin carries a warning for patients with known sensitivity to oxidant drugs, notably glucose-6-phosphate dehydrogenase (G6PD) deficiency, in whom it may cause haemolytic anaemia. This is a barrier to uptake in tropical regions where there is a high burden of antimicrobial resistance and where G6PD deficiency is common. Early studies of erythrocyte survival following nitrofurantoin suggest it is less likely to cause oxidant haemolysis in individuals with G6PD deficiency than primaquine. Here we review reports of haemolysis associated with nitrofurantoin from the published literature and from USA (FDA Adverse Event Reporting System; FAERS) and European (VigiBase) pharmacovigilance databases. In total, 318 episodes of haemolytic anaemia were reported and 10 deaths, with 42 (13%) in individuals with confirmed or highly probable G6PD deficiency, out of at least 245 million exposures. A causal link between death and exposure was not reported and a precise risk estimation in G6PD-deficient individuals was not possible as there are few reports from regions where this enzymopathy is most prevalent. The evidence suggests a total daily dose of 200 mg nitrofurantoin may be used for short (3–5 day) course urinary tract infection treatment without G6PD screening when accompanied by appropriate advice. Pharmacovigilance in countries with high prevalence of G6PD-deficiency is recommended to monitor for serious adverse events

Enrolling pregnant women in research: ethical challenges encountered in Lao PDR (Laos)

Laos has the highest maternal mortality ratio in mainland Southeast Asia but there has been little research conducted with pregnant women. We aim to discuss ethical challenges in enrolling pregnant women in research as a part of large pregnancy cohort study in Laos. From 2013 to 2015, a prospective cohort study was conducted with 1000 pregnant women in a rural area of Vientiane, Laos, to determine whether fevers were associated with maternal morbidity and small for gestational age. Incidence of fever was 10% and incidence of small for gestational age was 12%. Level of education, cultural norms about family decision-making, and misconceptions about healthcare during pregnancy were three common issues encountered in enrolling pregnant women to this study. Only 47% of recruited women had completed primary school with no further education, which could affect the decisions women make to participate and remain in the study. Family decision-making is common in Laos; in some cases, we could not recruit pregnant women without agreement from their families. In Laos, many pregnant women and their families had strong beliefs in travelling during late pregnancy or losing small amount of blood (giving ~5 ml blood sample) could negatively impact their pregnancies. These misconceptions affected not only the quality of the study but also the women’s opportunities to access healthcare. Good engagement between the research team and study participants, and the provision of more health information to the community, were essential to reducing issues experienced in enrolling pregnant women in this study

The isolation of Orientia tsutsugamushi and Rickettsia typhi from human blood through mammalian cell culture – a descriptive series of 3,227 samples and outcomes in the Lao PDR

In the Lao People's Democratic Republic (Laos) rickettsial infections, including scrub and murine typhus, account for a significant burden of fevers. The Mahosot Hospital Microbiology Laboratory in Vientiane, Laos, routinely performs rickettsial isolation from hospitalised patients with suspected rickettsioses using mammalian cell culture systems. We review the clinical and laboratory factors associated with successful Orientia tsutsugamushi and Rickettsia typhi isolations over a period of six years between 2008 and 2014 from this laboratory. The overall isolation success was 7.9% for all samples submitted, and 17.3% for samples for which the patient had positive O. tsutsugamushi or R. typhi RDT, serology or PCR. The frequency of successful isolation was highest for samples submitted in November, at the end of the wet season (28.3%). A longer median duration of reported illness and a positive result for a concurrent Orientia or Rickettsia spp. quantitative PCR, and the use of antibiotics by the patient in the week before admission were significantly associated with isolation success (p<0.05). Buffy coat inoculation and a shorter interval between sample collection and inoculation in the laboratory were associated with a higher frequency of isolation (both p<0.05). This frequency was highest if cell culture inoculation occurred on the same day as blood sample collection. Factors related to the initial rickettsial bacterial concentration are likely the main contributors to isolation success. However, modifiable factors do contribute to the rickettsial isolation success, especially delays in inoculating patient samples into culture

Inter- and intra-operator variability in the reading of indirect immunofluorescence assays for the serological diagnosis of scrub typhus and murine typhus.

Inter- and intra-observer variation was examined among six microscopists who read 50 scrub typhus (ST) and murine typhus (MT) indirect immunofluorescence assay (IFA) immunoglobulin M (IgM) slides. Inter-observer agreement was moderate (κ = 0.45) for MT and fair (κ = 0.32) for ST, and was significantly correlated with experience (P = 0.03 and P = 0.004, respectively); κ-scores for intra-observer agreement between morning and afternoon readings (range = 0.35-0.86) were not correlated between years of experience for ST and MT IFAs (Spearman's ρ = 0.31, P = 0.54 and P = 0.14, respectively; P = 0.78). Storage at 4°C for 2 days showed a change from positive to negative in 20-32% of slides. Although the titers did not dramatically change after 14 days of storage, the final interpretation (positive to negative) did change in 36-50% of samples, and it, therefore, recommended that slides should be read as soon as possible after processing

Typhoid in Laos: An 18-year perspective

Although typhoid is endemic to Southeast Asia, very little is known about the disease in Laos. Typhoid vaccination is not included in the national immunization program. Although sanitation has improved, one million people still do not have access to basic clean water sources. We describe the epidemiology and antimicrobial susceptibility patterns of Salmonella enterica serovar Typhi (S. Typhi) infection in Laos based on isolates accrued over 18 years at Mahosot Hospital, Vientiane. All blood cultures collected from patients presenting with fever submitted to the Microbiology Laboratory at Mahosot Hospital (February 2000–December 2018) were included. This included patients from Vientiane and four provincial hospitals and one typhoid outbreak investigation. A total of 913 (1.5%) of 60,384 blood cultures were positive for S. Typhi. The majority of isolates with data available (712/898, 79.3%) were susceptible to all antibiotics tested, with 59 (6.5%) multidrug-resistant (MDR) isolates, mostly from one outbreak. Of 854 isolates, 12 (1.4%) were fluoroquinolone resistant. Patient admissions peaked between March and June at the end of the dry season. Although there are key limitations, these data give the first detailed epidemiological evidence of typhoid in Laos. However, estimates will be greatly influenced by access to blood culture services and health-seeking behavior. Although typhoid multidrug resistance and fluoroquinolone resistance are not currently major issues in Laos, continued surveillance and improved antibiotic stewardship are necessary to forestall worsening of the situation. Cost-effectiveness analysis is needed to inform decisions regarding typhoid vaccine introduction