A survey of gastrointestinal helminth infestation in smallholder backyard pigs and the first molecular identification of the two zoonotic helminths Ascaris suum and Trichuris suis in Myanmar.

BACKGROUND: Parasitic infestations have a substantial economic impact on pig production. This study aimed to investigate the gastrointestinal (GI) helminths in pigs and to molecularly characterise two important nematodes, Ascaris and Trichuris species. MATERIALS AND METHODS: A total of 500 pig faecal samples were collected from small holder backyard pig farms in five townships within Nay Pyi Taw, Myanmar. Microscopic examination was conducted to estimate the prevalence of GI helminth infestation in the pigs. DNA extraction and PCR were performed on faecal samples that were morphologically positive for Ascaris and Trichuris eggs. Molecular analysis was then conducted to characterise A. suum and T. suis, the most common and zoonotic helminths. RESULTS: According to microscopic examination, 69.2% (346/500) were positive for GI helminth eggs. The GI helminth species observed were A. suum, Strongyle, Strongyloides spp., T. suis, Metastrongylus spp., Hyostrongylus spp., Fasciolopsis spp., Paragonimus spp., and Schistosoma spp., with occurrences of 34.8%, 29.6%, 21.4%, 20.0%, 4.0%, 1.6%, 1.0%, 1.0%, and 0.4%, respectively. Mixed infections of GI helminths were noted in 31.0% of the samples. Overall, sampled pigs excreted mostly low levels (< 100 EPG) or moderate levels (> 100-500 EPG) of GI helminth eggs. The highest mean EPG for each parasite species was noted in A. suum. The presence of A. suum and T. suis was confirmed molecularly. The sequences of the internal transcribed spacer 1 (ITS1) region of A. suum showed high similarity with previously reported sequences. Likewise, the sequences of T. suis exhibited high similarity with the sequences reported from humans and pigs. Age was noted as an associated factor (P < 0.05) for GI helminth infection status. CONCLUSIONS: In this report, A. suum and T. suis were molecularly identified for the first time in Myanmar. It is important to extend the information among the farmers to be aware of the necessity of preventing zoonotic parasites by practicing regular deworming, proper use of anthelmintics and maintaining hygienic conditions in their pig farms.

The impact of gender and the social determinants of health on the clinical course of people living with HIV in Myanmar: an observational study.

BACKGROUND: There is a growing recognition of the impact of gender and the social determinants of health on the clinical course of people living with HIV (PLHIV). However, the relative contribution of these factors to clinical outcomes of PLHIV is incompletely defined in many countries. This study was performed to gain a greater understanding of the non-clinical determinants of prognosis of PLHIV in Myanmar. METHODS: Selected demographic, behavioural and socioeconomic characteristics of outpatients at two specialist HIV hospitals and one general hospital in Yangon, Myanmar were correlated with their subsequent clinical course; a poor outcome was defined as death, hospitalisation, loss to follow-up or a detectable viral load at 6 months of follow-up. RESULTS: 221 consecutive individuals with advanced HIV commencing anti-retroviral therapy (ART) were enrolled in the study; their median CD4 T-cell count was 92 (44-158) cells/mm3, 138 (62.4%) were male. Socioeconomic disadvantage was common: the median (interquartile range (IQR) monthly per-capita income in the cohort was US$48 (31-77); 153 (69.9%) had not completed high school. However, in a multivariate analysis that considered demographic, behavioural, clinical factors and social determinants of health, male gender was the only predictor of a poor outcome: odds ratio (95% confidence interval): 2.33 (1.26-4.32, p = 0.007). All eight of the deaths and hospitalisations in the cohort occurred in males (p = 0.03). CONCLUSIONS: Men starting ART in Myanmar have a poorer prognosis than women. Expanded implementation of gender-specific management strategies is likely to be necessary to improve outcomes.

Sequential Helicobacter pylori eradication therapy in Myanmar; a randomized clinical trial of efficacy and tolerability.

BACKGROUND AND AIM: There is little published research to examine the best approach to the management of Helicobacter pylori in Myanmar. This study aimed to determine the relative efficacy and tolerability of sequential eradication therapy compared to Myanmar's current recommendation of a concomitant four drug regimen. METHODS: Patients were screened for H. pylori using monoclonal Stool Antigen Testing (SAT). Those testing positive were randomized 1:1 to receive receive Myanmar's first-line regimen of 14 days of concomitant rabeprazole, clarithromycin, amoxycillin and tinidazole (140 pills, cost US$23) or 10 days of sequential rabeprazole, clarithromycin, amoxycillin and tinidazole (60 pills, cost US$10). Adherence and adverse effects were recorded, and the efficacy of the regimens assessed with repeat SAT. RESULTS: Of the 1011 patients screened for H. pylori infection, 313 (31%) tested positive. There was no statistical difference in the cure rates of the two regimens in either intention-to-treat: 128/157 (82%; 95% confidence interval (CI): 75-87%) receiving sequential therapy versus 123/156 (79%; 95% CI: 72-85%) receiving concomitant therapy (P = 0.55) or per-protocol analysis: 125/131 (95%; 95% CI: 90-98) receiving sequential therapy versus 121/130 (93%; 95% CI: 87-96) receiving concomitant therapy (P = 0.42). Side effects of therapy were reported in 54/157 (47%) patients taking sequential therapy compared with 62/156 (53%) taking concomitant therapy, but this difference did not reach statistical significance (P = 0.33). CONCLUSIONS: In this high-burden, resource-poor setting, less expensive sequential therapy was as effective and as well tolerated as the currently recommended concomitant four drug regimen for eradication of H. pylori.

Biodegradation of Bisphenol A by Sphingobium sp. YC-JY1 and the Essential Role of Cytochrome P450 Monooxygenase.

Bisphenol A (BPA) is a widespread pollutant threatening the ecosystem and human health. An effective BPA degrader YC-JY1 was isolated and identified as Sphingobium sp. The optimal temperature and pH for the degradation of BPA by strain YC-JY1 were 30 °C and 6.5, respectively. The biodegradation pathway was proposed based on the identification of the metabolites. The addition of cytochrome P450 (CYP) inhibitor 1-aminobenzotriazole significantly decreased the degradation of BPA by Sphingobium sp. YC-JY1. Escherichia coli BL21 (DE3) cells harboring pET28a-bisdAB achieved the ability to degrade BPA. The bisdB gene knockout strain YC-JY1ΔbisdB was unable to degrade BPA indicating that P450bisdB was an essential initiator of BPA metabolism in strain YC-JY1. For BPA polluted soil remediation, strain YC-JY1 considerably stimulated biodegradation of BPA associated with the soil microbial community. These results point out that strain YC-JY1 is a promising microbe for BPA removal and possesses great application potential.

Correlation Between Quorum Sensing Signal Molecules and Pseudomonas aeruginosa's Biofilm Development and Virulency.

Bacteria, when adhered to a substratum, can form biofilms. Nevertheless, many factors dictate biofilm formation and virulence factor production, including a response by the bacteria to their surroundings. This system is referred to as Quorum sensing (QS) also known as cell-cell communication. Pseudomonas aeruginosa is an infection causing agent in immune-compromised patients, it uses acyl-homoserine lactone (AHL) to coordinate its QS systems. In this work, the connection between some members of AHL produced by P. aeruginosa PAO1 and its biofilm development and the production of virulence factor was investigated. It was discovered that N-butanoyl-homoserine lactone (C4-HSL) and N-hexanoyl-L-homoserine lactone (C6-HSL) perform a more consequential and eminent function in the biofilm maturation and virulence factor production while N-(3-oxododecanoyl)-L-homoserine lactone (3OC12-HSL) plays a role in biofilm initiation. Because QS has been reported to be required for biofilm development and pathogenesis of P. aeruginosa, the results of this work have great importance and significance for the design of strategies for the control and prevention of biofilms.

First molecular detection of Theileria luwenshuni from goats in Myanmar.

Tick-borne intracellular protozoan parasites of the Theileria genus infect a wide range of both domestic and wild animals. In the present study, we describe the first PCR detection of Theileria luwenshuni in the blood of goats in Myanmar. Nested PCR targeting the Theileria 18S rRNA gene resulted in seven positive goats in central and northern Myanmar. Nucleotide sequencing of the PCR products revealed that all seven sequences were identical and showed 100% identity with T. luwenshuni sequences in GenBank from goats and sheep in China. Since T. luwenshuni parasites have recently been discovered and shown to have nationwide distribution in China, they might have been introduced into Myanmar via transboundary movement of infected domestic small ruminants and/or wild animals from China.

The clinical utility of the urine-based lateral flow lipoarabinomannan assay in HIV-infected adults in Myanmar: an observational study.

BACKGROUND: The use of the point-of-care lateral flow lipoarabinomannan (LF-LAM) test may expedite tuberculosis (TB) diagnosis in HIV-positive patients. However, the test's clinical utility is poorly defined outside sub-Saharan Africa. METHODS: The study enrolled consecutive HIV-positive adults at a tertiary referral hospital in Yangon, Myanmar. On enrolment, patients had a LF-LAM test performed according to the manufacturer's instructions. Clinicians managing the patients were unaware of the LF-LAM result, which was correlated with the patient's clinical course over the ensuing 6 months. RESULTS: The study enrolled 54 inpatients and 463 outpatients between July 1 and December 31, 2015. On enrolment, the patients' median (interquartile range) CD4 T-cell count was 270 (128-443) cells/mm3. The baseline LF-LAM test was positive in 201/517 (39%). TB was confirmed microbiologically during follow-up in 54/517 (10%), with rifampicin resistance present in 8/54 (15%). In the study's resource-limited setting, extrapulmonary testing for TB was not possible, but after 6 months, 97/201 (48%) with a positive LF-LAM test on enrolment had neither died, required hospitalisation, received a TB diagnosis or received empirical anti-TB therapy, suggesting a high rate of false-positive results. Of the 97 false-positive tests, 89 (92%) were grade 1 positive, suggesting poor test specificity using this cut-off. Only 21/517 (4%) patients were inpatients with TB symptoms and a CD4 T-cell count of < 100 cells/mm3. Five (24%) of these 21 died, three of whom had a positive LF-LAM test on enrolment. However, all three received anti-TB therapy before death - two after diagnosis with Xpert MTB/RIF testing, while the other received empirical treatment. It is unlikely that knowledge of the baseline LF-LAM result would have averted any of the study's other 11 deaths; eight had a negative test, and of the three patients with a positive test, two received anti-TB therapy before death, while one died from laboratory-confirmed cryptococcal meningitis. The test was no better than a simple, clinical history excluding TB during follow-up (negative predictive value (95% confidence interval): 94% (91-97) vs. 94% (91-96)). CONCLUSIONS: The LF-LAM test had limited clinical utility in the management of HIV-positive patients in this Asian referral hospital setting.

HIV care in Yangon, Myanmar; successes, challenges and implications for policy.

BACKGROUND: Approximately 0.8% of adults aged 18-49 in Myanmar are seropositive for Human Immunodeficiency Virus (HIV). Identifying the demographic, epidemiological and clinical characteristics of people living with HIV (PLHIV) is essential to inform optimal management strategies in this resource-limited country. METHODS: To create a "snapshot" of the PLHIV seeking anti-retroviral therapy (ART) in Myanmar, data were collected from the registration cards of all patients who had been prescribed ART at two large referral hospitals in Yangon, prior to March 18, 2016. RESULTS AND DISCUSSION: Anti-retroviral therapy had been prescribed to 2643 patients at the two hospitals. The patients' median [interquartile range (IQR)] age was 37 (31-44) years; 1494 (57%) were male. At registration, injecting drug use was reported in 22 (0.8%), male-to-male sexual contact in eleven (0.4%) and female sex work in eleven (0.4%), suggesting that patients under-report these risk behaviours, that health care workers are uncomfortable enquiring about them or that the two hospitals are under-servicing these populations. All three explanations appear likely. Most patients were symptomatic at registration with 2027 (77%) presenting with WHO stage 3 or 4 disease. In the 2442 patients with a CD4+ T cell count recorded at registration, the median (IQR) count was 169 (59-328) cells/mm3. After a median (IQR) duration of 359 (185-540) days of ART, 151 (5.7%) patients had died, 111 (4.2%) patients had been lost to follow-up, while 2381 were alive on ART. Tuberculosis (TB) co-infection was common: 1083 (41%) were already on anti-TB treatment at registration, while a further 41 (1.7%) required anti-TB treatment during follow-up. Only 21 (0.8%) patients were prescribed isoniazid prophylaxis therapy (IPT); one of these was lost to follow-up, but none of the remaining 20 patients died or required anti-TB treatment during a median (IQR) follow-up of 275 (235-293) days. CONCLUSIONS: People living with HIV in Yangon, Myanmar are generally presenting late in their disease course, increasing their risk of death, disease and transmitting the virus. A centralised model of ART prescription struggles to deliver care to the key affected populations. TB co-infection is very common in Myanmar, but despite the proven efficacy of IPT, it is frequently not prescribed.

Malaria incidence in Myanmar 2005-2014: steady but fragile progress towards elimination.

BACKGROUND: There has been an impressive recent reduction in the global incidence of malaria, but the development of artemisinin resistance in the Greater Mekong Region threatens this progress. Increasing artemisinin resistance is particularly important in Myanmar, as it is the country in the Greater Mekong Region with the greatest malaria burden. If malaria is to be eliminated in the region, it is essential to define the spatial and temporal epidemiology of the disease in Myanmar to inform control strategies optimally. RESULTS: Between the years 2005 and 2014 there was an 81.1 % decline in the reported annual incidence of malaria in Myanmar (1341.8 cases per 100,000 population to 253.3 cases per 100,000 population). In the same period, there was a 93.5 % decline in reported annual mortality from malaria (3.79 deaths per 100,000 population to 0.25 deaths per 100,000 population) and a 87.2 % decline in the proportion of hospitalizations due to malaria (7.8 to 1.0 %). Chin State had the highest reported malaria incidence and mortality at the end of the study period, although socio-economic and geographical factors appear a more likely explanation for this finding than artemisinin resistance. The reduced malaria burden coincided with significant upscaling of disease control measures by the national government with support from international partners. These programmes included the training and deployment of over 40,000 community health care workers, the coverage of over 60 % of the at-risk population with insecticide-treated bed nets and significant efforts to improve access to artemesinin-based combination treatment. Beyond these malaria-specific programmes, increased general investment in the health sector, changing population demographics and deforestation are also likely to have contributed to the decline in malaria incidence seen over this time. CONCLUSIONS: There has been a dramatic fall in the burden of malaria in Myanmar since 2005. However, with the rise of artemisinin resistance, continued political, financial and scientific commitment is required if the ambitious goal of malaria elimination in the country is to be realized.

Auxiliary midwives in hard to reach rural areas of Myanmar: filling MCH gaps.

BACKGROUND: Auxiliary Midwives (AMWs) are community health volunteers supporting the work of midwives, especially maternal and child health services in hard to-reach areas in Myanmar. This paper assessed the contributions of AMW to maternal and child health services, factors influencing their productivity and their willingness to serve the community. METHOD: The study applied quantitative cross-sectional survey using census method. Total of 1,185 AMWs belonging to three batches: trained prior to 2000, between 2000 and 2011, and in 2012, from 21 townships of 17 states and regions in Myanmar participated in the study. Multiple logit regression was used to examine the impact of age, marital status, education, domicile, recruitment pattern and 'batch of training', on AMW's confidence level in providing care, and their intention to serve the community more than 5 years. RESULTS: All AMWs were able to provide essential maternal and child health services including antenatal care, normal delivery and post-natal care. They could identify and refer high-risk pregnancies to larger health facilities for proper management. On average, 9 deliveries, 11 antenatal and 9 postnatal cases were performed by an AMW during the six months prior to this study. AMWs had a comparative advantage for longer service in hard-to-reach villages where they lived, spoke the same dialect as the locals, understood the socio-cultural dimensions, and were well accepted by the community. Despite these contributions, 90 % of the respondents expressed receiving no adequate supervision, refresher training, replenishment of the AMW kits and transportation cost. AMWs in the elder age group are significantly more confident in taking care of the patients than those in the younger groups. Over 90 % of the respondents intended to stay more than five years in the community. The confidence in catering services appeared to have significant association with a longer period of stay in AMW jobs as evidenced by the odds ratio of 3.5, compared to those reporting unconfident. CONCLUSIONS: Comprehensive support system and national policy are needed to sustain and strengthen the contributions of AMWs, in sharing the workload of midwives, particularly in hard-to-reach areas of Myanmar.

The prognostic utility of bedside assessment of adults hospitalized with malaria in Myanmar: a retrospective analysis.

BACKGROUND: Data collected in clinical trials have been used to develop scoring systems that identify adults with malaria at greatest risk of death. One of these, the RCAM score, can be simply determined by measuring a patient's Glasgow Coma Score and respiratory rate on admission to hospital. However the safety of using the RCAM score to define high-risk patients has not been assessed outside of the clinical trial setting. METHODS: A retrospective audit of medical records of all adults admitted with a diagnosis of malaria to two tertiary referral hospitals in Lower Myanmar in 2013 was undertaken. An RCAM score was calculated in all patients and related to their subsequent clinical course. RESULTS: The recent decline in malaria hospitalizations at both sites continued in 2013. During the year 90 adults were hospitalized with malaria; 62 (69%) had Plasmodium falciparum mono-infection, 11 (12%) had Plasmodium vivax mono-infection, 17 (19%) had mixed infection. All seven (7.7%) deaths occurred in patients infected with P. falciparum. An admission RCAM score <2 identified all the patients that would survive to discharge (positive predictive value (95% confidence interval (CI)) 100% (94.9-100%) and also predicted a requirement for less supportive care: 9/70 (13%) patients with an admission RCAM score <2 required supportive care (blood transfusion, vasopressor support or oxygen supplementation) during their hospitalization compared with 12/20 (60%) patients with an admission RCAM score ≥2 (p < 0.0001). No patient with P. vivax mono-infection required supportive care during their hospitalization. Patients with an oxygen saturation ≤95% on room air on admission were more likely to die before discharge (odds ratio 17.3 (95% CI: 2.9-101.2) than patients with a higher oxygen saturation (p = 0.002). CONCLUSIONS: Even outside a clinical trial setting the RCAM score reliably identifies adults with malaria who are at greatest risk of death and can be safely used in the initial triage and management of these patients.

The strong influence of management factors on coccidian infections in smallholder pig farms and the first molecular identification of Cystoisospora suis in Myanmar.

A cross-sectional study was conducted to investigate coccidian infection and associated factors in smallholder pigs, and to identify Cystoisospora oocysts by PCR. A total of 500 pig faecal samples from 330 smallholder farms were collected in Nay Pyi Taw, Myanmar. The faecal flotation method was used to identify Eimeria and Cystoisospora species, and oocyst counts per gram (OPG) of faeces were recorded. Oocysts were differentiated after sporulation. Oocyst DNA was subjected to ITS1-targeted Cystoisospora-specific PCR. The overall coccidian oocyst detection rate by microscopic was 89.0% (445/500). Among the studied samples, 74.0% (370/500) and 70.6% (353/500), were found to be positive with Eimeria spp. and Cystoisospora suis oocysts, respectively. The sequences of C. suis detected were 100% identical to those of C. suis reported from Japan, and had 99.5% resemblance to sequences from Australia and China. Weaner pigs showed the significantly highest (p < 0.05) OPG when compared to other age groups. The highest intensity of coccidian infection (p < 0.05) was found in pigs fed local feed, pigs raised on earthen floors and pigs under poor hygienic conditions. Factors such as age, breed, feed type, and housing floors were found to be significantly associated with coccidian infection (p < 0.05). Age, as well as management factors including floor type, feed type, and hygiene practices on the farm, had a strong influence on the occurrence of coccidian infection in pigs. This is the first study in Myanmar on coccidian infection in pigs and molecular detection of C. suis.

TITLE: Forte influence des facteurs de gestion sur les infections à coccidies dans les petites exploitations porcines et première identification moléculaire de Cystoisospora suis au Myanmar. ABSTRACT: Une étude transversale a été menée pour étudier l'infection coccidienne et les facteurs associés chez les porcs dans des petites exploitations, et pour identifier les oocystes de Cystoisospora par PCR. Au total, 500 échantillons de matières fécales de porcs provenant de 330 petites exploitations agricoles ont été collectés dans la région de Nay Pyi Taw, au Myanmar. La méthode de flottation fécale a été utilisée pour identifier les espèces d'Eimeria et de Cystoisospora, et le nombre d'oocystes par gramme (OPG) de matières fécales a été déterminé. Les oocystes ont été différenciés après sporulation. L'ADN des oocystes a été soumis à une PCR spécifique à Cystoisospora, ciblée sur ITS1. Le taux global de détection d'oocystes de coccidies au microscope était de 89,0 % (445/500). Parmi les échantillons étudiés, respectivement 74,0 % (370/500) et 70,6 % (353/500) ont été trouvés positifs pour Eimeria spp. et les oocystes de Cystoisospora suis. Les séquences de C. suis détectées étaient identiques à 100 % à celles de C. suis signalées au Japon, et avaient 99,5 % de ressemblance avec des séquences d'Australie et de Chine. Les porcs sevrés ont montré un OPG significativement plus élevé (p < 0,05) par rapport aux autres groupes d'âge. L'intensité la plus élevée de l'infection coccidienne (p < 0,05) a été observée chez les porcs nourris avec des aliments locaux, les porcs élevés sur des sols en terre battue et les porcs dans de mauvaises conditions d'hygiène. Des facteurs tels que l'âge, la race, le type d'alimentation et les étages se sont avérés être significativement (p < 0,05) associés à l'infection coccidienne. L'âge, ainsi que les facteurs de gestion, notamment le type de sol, le type d'alimentation et les pratiques d'hygiène dans la ferme, ont eu une forte influence sur la survenue d'une infection coccidienne chez les porcs. Il s'agit de la première étude au Myanmar sur l'infection coccidienne chez le porc et la détection moléculaire de C. suis.

Diagnostic accuracy of WHO screening criteria to guide lateral-flow lipoarabinomannan testing among HIV-positive inpatients: A systematic review and individual participant data meta-analysis.

BACKGROUND: WHO recommends urine lateral-flow lipoarabinomannan (LF-LAM) testing with AlereLAM in HIV-positive inpatients only if screening criteria are met. We assessed the performance of WHO screening criteria and alternative screening tests/strategies to guide LF-LAM testing and compared diagnostic accuracy of the WHO AlereLAM algorithm (WHO screening criteria followed by AlereLAM if screen positive) with AlereLAM and FujiLAM (a novel LF-LAM test) testing in all HIV-positive inpatients. METHODS: We searched MEDLINE, Embase, and Cochrane Library from Jan 1, 2011 to March 1, 2020 for studies among adult/adolescent HIV-positive inpatients regardless of tuberculosis signs and symptoms. The reference standards were (1) AlereLAM or FujiLAM for screening tests/strategies and (2) culture or Xpert for AlereLAM/FujiLAM. We determined proportion of inpatients eligible for AlereLAM using WHO screening criteria; assessed accuracy of WHO criteria and alternative screening tests/strategies to guide LF-LAM testing; compared accuracy of WHO AlereLAM algorithm with AlereLAM/FujiLAM testing in all; and determined diagnostic yield of AlereLAM, FujiLAM, and Xpert MTB/RIF (Xpert). We estimated pooled proportions with a random-effects model, assessed diagnostic accuracy using random-effects bivariate models, and assessed diagnostic yield descriptively. FINDINGS: We obtained data from all 5 identified studies (n = 3,504). The pooled proportion of inpatients eligible for AlereLAM using WHO criteria was 93% (95%CI 91, 95). Among screening tests/strategies to guide LF-LAM testing, WHO criteria, C-reactive protein (≥5 mg/L), and CD4 count (<200 cells/µL) had high sensitivities but low specificities; cough (≥2 weeks), hemoglobin (<8 g/dL), body mass index (<18.5 kg/m2), lymphadenopathy, and WHO-defined danger signs had higher specificities but suboptimal sensitivities. AlereLAM in all had the same sensitivity (62%) and specificity (88%) as WHO AlereLAM algorithm. Sensitivity of FujiLAM and AlereLAM was 69% and 48%, while specificity was 88% and 96%, respectively. In 2 studies that collected sputum and non-sputum samples for Xpert and/or culture, diagnostic yield of sputum Xpert was 40-41%, AlereLAM was 39-76%, and urine Xpert was 35-62%. In one study, FujiLAM diagnosed 80% of tuberculosis cases (vs 39% for AlereLAM), and sputum Xpert combined with AlereLAM, urine Xpert, or FujiLAM diagnosed 61%, 81%, and 92% of all cases, respectively. INTERPRETATION: WHO criteria and alternative screening tests/strategies have limited utility in guiding LF-LAM testing, suggesting that AlereLAM testing in all HIV-positive medical inpatients be implemented. Routine FujiLAM may improve tuberculosis diagnosis. FUNDING: None.

Tuberculosis screening among HIV-positive inpatients: a systematic review and individual participant data meta-analysis.

BACKGROUND: Since 2011, WHO has recommended that HIV-positive inpatients be routinely screened for tuberculosis with the WHO four-symptom screen (W4SS) and, if screened positive, receive a molecular WHO-recommended rapid diagnostic test (eg, Xpert MTB/RIF [Xpert] assay). To inform updated WHO tuberculosis screening guidelines, we conducted a systematic review and individual participant data meta-analysis to assess the performance of W4SS and alternative screening tests to guide Xpert testing and compare the diagnostic accuracy of the WHO Xpert algorithm (ie, W4SS followed by Xpert) with Xpert for all HIV-positive inpatients. METHODS: We searched MEDLINE, Embase, and Cochrane Library from Jan 1, 2011, to March 1, 2020, for studies of adult and adolescent HIV-positive inpatients enrolled regardless of tuberculosis signs and symptoms. The separate reference standards were culture and Xpert. Xpert was selected since it is most likely to be the confirmatory test used in practice. We assessed the proportion of inpatients eligible for Xpert testing using the WHO algorithm; assessed the accuracy of W4SS and alternative screening tests or strategies to guide diagnostic testing; and compared the accuracy of the WHO Xpert algorithm (W4SS followed by Xpert) with Xpert for all. We obtained pooled proportion estimates with a random-effects model, assessed diagnostic accuracy by fitting random-effects bivariate models, and assessed diagnostic yield descriptively. This systematic review has been registered on PROSPERO (CRD42020155895). FINDINGS: Of 6162 potentially eligible publications, six were eligible and we obtained data for all of the six publications (n=3660 participants). The pooled proportion of inpatients eligible for an Xpert was 90% (95% CI 89-91; n=3658). Among screening tests to guide diagnostic testing, W4SS and C-reactive protein (≥5 mg/L) had highest sensitivities (≥96%) but low specificities (≤12%); cough (≥2 weeks), haemoglobin concentration (<8 g/dL), body-mass index (<18·5 kg/m2), and lymphadenopathy had higher specificities (61-90%) but suboptimal sensitivities (12-57%). The WHO Xpert algorithm (W4SS followed by Xpert) had a sensitivity of 76% (95% CI 67-84) and specificity of 93% (88-96; n=637). Xpert for all had similar accuracy to the WHO Xpert algorithm: sensitivity was 78% (95% CI 69-85) and specificity was 93% (87-96; n=639). In two cohorts that had sputum and non-sputum samples collected for culture or Xpert, diagnostic yield of sputum Xpert was 41-70% and 61-64% for urine Xpert. INTERPRETATION: The W4SS and other potential screening tests to guide Xpert testing have suboptimal accuracy in HIV-positive inpatients. On the basis of these findings, WHO now strongly recommends molecular rapid diagnostic testing in all medical HIV-positive inpatients in settings where tuberculosis prevalence is higher than 10%. FUNDING: World Health Organization.

Tuberculosis screening among ambulatory people living with HIV: a systematic review and individual participant data meta-analysis.

BACKGROUND: The WHO-recommended tuberculosis screening and diagnostic algorithm in ambulatory people living with HIV is a four-symptom screen (known as the WHO-recommended four symptom screen [W4SS]) followed by a WHO-recommended molecular rapid diagnostic test (eg Xpert MTB/RIF [hereafter referred to as Xpert]) if W4SS is positive. To inform updated WHO guidelines, we aimed to assess the diagnostic accuracy of alternative screening tests and strategies for tuberculosis in this population. METHODS: In this systematic review and individual participant data meta-analysis, we updated a search of PubMed (MEDLINE), Embase, the Cochrane Library, and conference abstracts for publications from Jan 1, 2011, to March 12, 2018, done in a previous systematic review to include the period up to Aug 2, 2019. We screened the reference lists of identified pieces and contacted experts in the field. We included prospective cross-sectional, observational studies and randomised trials among adult and adolescent (age ≥10 years) ambulatory people living with HIV, irrespective of signs and symptoms of tuberculosis. We extracted study-level data using a standardised data extraction form, and we requested individual participant data from study authors. We aimed to compare the W4SS with alternative screening tests and strategies and the WHO-recommended algorithm (ie, W4SS followed by Xpert) with Xpert for all in terms of diagnostic accuracy (sensitivity and specificity), overall and in key subgroups (eg, by antiretroviral therapy [ART] status). The reference standard was culture. This study is registered with PROSPERO, CRD42020155895. FINDINGS: We identified 25 studies, and obtained data from 22 studies (including 15 666 participants; 4347 [27·7%] of 15 663 participants with data were on ART). W4SS sensitivity was 82% (95% CI 72-89) and specificity was 42% (29-57). C-reactive protein (≥10 mg/L) had similar sensitivity to (77% [61-88]), but higher specificity (74% [61-83]; n=3571) than, W4SS. Cough (lasting ≥2 weeks), haemoglobin (<10 g/dL), body-mass index (<18·5 kg/m2), and lymphadenopathy had high specificities (80-90%) but low sensitivities (29-43%). The WHO-recommended algorithm had a sensitivity of 58% (50-66) and a specificity of 99% (98-100); Xpert for all had a sensitivity of 68% (57-76) and a specificity of 99% (98-99). In the one study that assessed both, the sensitivity of sputum Xpert Ultra was higher than sputum Xpert (73% [62-81] vs 57% [47-67]) and specificities were similar (98% [96-98] vs 99% [98-100]). Among outpatients on ART (4309 [99·1%] of 4347 people on ART), W4SS sensitivity was 53% (35-71) and specificity was 71% (51-85). In this population, a parallel strategy (two tests done at the same time) of W4SS with any chest x-ray abnormality had higher sensitivity (89% [70-97]) and lower specificity (33% [17-54]; n=2670) than W4SS alone; at a tuberculosis prevalence of 5%, this strategy would require 379 more rapid diagnostic tests per 1000 people living with HIV than W4SS but detect 18 more tuberculosis cases. Among outpatients not on ART (11 160 [71·8%] of 15 541 outpatients), W4SS sensitivity was 85% (76-91) and specificity was 37% (25-51). C-reactive protein (≥10 mg/L) alone had a similar sensitivity to (83% [79-86]), but higher specificity (67% [60-73]; n=3187) than, W4SS and a sequential strategy (both test positive) of W4SS then C-reactive protein (≥5 mg/L) had a similar sensitivity to (84% [75-90]), but higher specificity than (64% [57-71]; n=3187), W4SS alone; at 10% tuberculosis prevalence, these strategies would require 272 and 244 fewer rapid diagnostic tests per 1000 people living with HIV than W4SS but miss two and one more tuberculosis cases, respectively. INTERPRETATION: C-reactive protein reduces the need for further rapid diagnostic tests without compromising sensitivity and has been included in the updated WHO tuberculosis screening guidelines. However, C-reactive protein data were scarce for outpatients on ART, necessitating future research regarding the utility of C-reactive protein in this group. Chest x-ray can be useful in outpatients on ART when combined with W4SS. The WHO-recommended algorithm has suboptimal sensitivity; Xpert for all offers slight sensitivity gains and would have major resource implications. FUNDING: World Health Organization.

Time for pragmatic, prospective clinical trials to determine the role of empirical antibacterial therapy in critically ill adults hospitalized with malaria.

BACKGROUND: Children with severe falciparum malaria in malaria-endemic regions are predisposed to developing life-threatening bacterial co-infection. International guidelines therefore recommend empirical broad-spectrum antibacterial therapy in these children. Few studies have examined co-infection in adults, although it has been believed to be relatively rare; antibacterial therapy is therefore not routinely recommended in adults with falciparum malaria. DISCUSSION: However, the fundamental pathophysiology of falciparum malaria in adults and children is the same; it is therefore unclear why adults would not also be predisposed to bacterial infection. Indeed, recent studies have identified bacteraemia in >10% of adults hospitalized with malaria. Some have suggested that these adults probably had bacterial sepsis, with the parasitaemia an incidental finding. However, it is usually impossible in resource-limited settings to determine-at presentation-whether critically ill, parasitaemic adults have severe malaria, bacterial sepsis, or both. Given the significant case-fatality rates of severe malaria and bacterial sepsis, the pragmatic initial approach would be to cover both possibilities. CONCLUSIONS: Life-threatening bacterial co-infection may be more common in critically ill adults with malaria than previously believed. While further prospective data are awaited to confirm these findings, it might be more appropriate to provide empirical aantibacterial cover in these patients than current guidelines suggest.

Sustainable Laboratory Capacity Building After the 2014 Ebola Outbreak in the Republic of Guinea.

Background: The 2014-2016 West Africa Ebola virus disease outbreak heavily impacted the Republics of Guinea, Sierra Leone, and Liberia. The outbreak uncovered the weaknesses of the public health systems, including inadequately trained and insufficient health personnel as well as limited and poorly equipped health infrastructures. These weaknesses represent significant threats to global health security. In the wake of the outbreak, affected countries made urgent requests for international engagement to help strengthening the public health systems. Methods: This work describes the successful multi-year implementation of a laboratory capacity building program in the Republic of Guinea. The program integrated biorisk and quality management systems training, infectious diseases diagnostic training, facility engineering and maintenance training, and mentorship to strengthen Guinea's bio-surveillance capacity. Results: The major outcome of these efforts was an established and local staff-operated public health laboratory that performs disease surveillance and reporting and diagnostic of priority diseases and pathogens of security concerns. Conclusions: This work has improved the Guinea country's capabilities to address country public health issues and preparedness to respond to future infectious disease threats.

Primary biodegradation and mineralization of aryl organophosphate flame retardants by Rhodococcus-Sphingopyxis consortium.

In this study, the biodegradation towards aryl organophosphate flame retardants (aryl-OPFRs) was investigated by the Rhodococcus-Sphingopyxis consortium, mixture of strain Rhodococcus sp. YC-JH2 and Sphingopyxis sp. YC-JH3. The optimal ratio between the two composition strains was determined as 1:1. Under the optimum condition (pH 8, 35 °C and 0% salinity), the consortium could utilize aryl-OPFRs as sole carbon source and degrade them rapidly with half-life of 4.53, 21.11 and 23.0 h for triphenyl phosphate (TPhP), tricresyl phosphate (TCrP) and 2-ethylhexyl diphenyl phosphate (EHDPP) respectively. The consortium maintained high degrading efficiency under a wide of range of pH (6-10), temperature (20-40 °C) and salinity (0-6%). Besides, the consortium could rapidly degrade high concentration of TPhP and no inhibitory effect towards degradation speed was observed up to 500 mg/L. The effect of metal ions and surfactants was estimated. Most metal ions exhibited significant inhibition, except Zn2+ and Pb2+, which showed no effect or slight promotion. Ionic surfactants could severely reduce the degrading capacity, while nonionic surfactants showed no effect. With abundant inoculation of the consortium, mineralization higher than 75% could be achieved within a week. This study provides efficient microorganisms for bioremediation of aryl-OPFRs contamination.