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The transition to PEPFAR 2.0 with its focus on country ownership was accompanied by substantial funding cuts. We describe the impact of this transition on HIV care in a large network of HIV clinics in Nigeria. We surveyed 30 comprehensive HIV treatment clinics to assess services supported before (October 2013-September 2014) and after (October 2014-September 2015) the PEPFAR funding policy change, the impact of these policy changes on service delivery areas, and response of clinics to the change. We compared differences in support for staffing, laboratory services, and clinical operations pre- and post-policy change using paired t-tests. We used framework analysis to assess answers to open ended questions describing responses to the policy change. Most sites (83%, n = 25) completed the survey. The majority were public (60%, n = 15) and secondary (68%, n = 17) facilities. Clinics had a median of 989 patients in care (IQR: 543–3326). All clinics continued to receive support for first and second line antiretrovirals and CD4 testing after the policy change, while no clinics received support for other routine drug monitoring labs. We found statistically significant reductions in support for viral load testing, staff employment, defaulter tracking, and prevention services (92% vs. 64%, p = 0.02; 80% vs. 20%, 100% vs. 44%, 84% vs. 16%, respectively, p<0.01 for all) after the policy change. Service delivery was hampered by interrupted laboratory services and reduced wages and staff positions leading to reduced provider morale, and compromised quality of care. Almost all sites (96%) introduced user fees to address funding shortages. Clinics in Nigeria are experiencing major challenges in providing routine HIV services as a result of PEPFAR’s policy changes. Funding cutbacks have been associated with compromised quality of care, staff shortages, and reliance on fee-based care for historically free services. Sustainable HIV services funding models are urgently needed. [ABSTRACT FROM AUTHOR]

Background: Large numbers of young people die yearly due to homicide, but little is known about homicide during adolescence. Research primarily focuses on youth violence among young men and masks important gender-related factors inherent in the adolescent age group. Although young women are less likely to be victims of homicide, violence against women is an important form of violence experienced during adolescence. In this paper, we describe the prevalence of and gender difference in adolescent homicide in South Africa in 2009. Methods: We conducted a retrospective national mortuary-based study to identify all child homicides (boys and girls < 18 years) in 2009 in a proportionate sample of mortuaries. Victim, perpetrator and crime data were collected in three phases: cases were identified from the mortuary register, the autopsy report and from police interviews. In this paper we focus on the adolescent group, aged 10 to 17 years. Findings: We identified 674 (95% CI: 520–823) adolescent homicides for 2009, with more male (520) than female (154) homicides. This gender disparity increased as children aged, with the male homicide rate 27.9/100 000 population (95% CI: 20.3–35.5), nearly 5 times the female rate (4.5:1) of 6.5/ 100 000 population (95% CI: 4.7–8.2) in older adolescents (15–17 year old). Adolescent males were significantly more likely (61.2%) to die in a public space compared to female adolescents (39.3%) but more adolescent females (48.4%) died at home compared to adolescent males (32.9%). Adolescent females (42.1%) were mainly killed by a family member or intimate partner while adolescent males were predominantly (58%) killed by an acquaintance. Conclusion: We found a distinct gender pattern for adolescent homicide in South Africa. This pattern appears to be driven by gender norms that support violence. South Africa requires an investment in developing evidence informed interventions to reduce violence. [ABSTRACT FROM AUTHOR]

Introduction: For HIV-positive individuals on antiretroviral therapy (ART), the World Health Organization (WHO) recommends routine viral load (VL) monitoring. We report on the cascade of care in individuals with unsuppressed VL after introduction of routine VL monitoring in a district in Lesotho. Materials and methods: In Butha-Buthe district 12 clinics (11 rural, 1 hospital) send samples for VL testing to the district laboratory. We included data from patients aged ≥15 years from Dec 1, 2015 to November 1, 2018. As per WHO guidelines VL <1000 copies/mL are considered suppressed, those ≥1000copies/mL unsuppressed. Patients with unsuppressed VL receive adherence counseling and follow-up VL within 8–12 weeks. Two consecutively unsuppressed VLs should trigger switch to second-line ART. For analysis of the VL monitoring cascade we defined care to be “according to guidelines” if patients with unsuppressed VL received a follow-up VL within <180 days and follow-up VL was either re-suppressed, or again unsuppressed and the individual was switched to second-line within 90 days. Results: For 9,949 individuals 24,948 VL tests were available. The majority were female (73%), median age 41 years (interquartile range 33–52), and 58% seen at rural clinics. Overall, 25% (260/1028) of individuals were managed according to guidelines: 40% (410/1028) had a follow-up VL within 180 days of their initial unsuppressed VL and 25% (260/1028) of those either re-suppressed or switched to second-line within 90 days. Female patients were more likely to have a follow-up VL done, (p = 0.015). In rural clinics rates of two consecutively unsuppressed VLs were higher than in the hospital (64% vs. 44%, p<0.001), and rural clinics were less likely to switch these patients to second-line (35% vs. 66%, p<0001). Conclusions: Our data show that in a real-life setting availability of routine VL monitoring may not be exploited to its potential. A lack of timely follow-up after a first unsuppressed VL and reluctance to switch patients with confirmed virological failure, reduce the benefit of VL monitoring, i.e. in the rural clinics. Future studies will have to assess models of care which ensure that VL results are met with an action and make use of scalable innovative approaches. [ABSTRACT FROM AUTHOR]

Introduction: Viral load (VL) monitoring programs have been scaled up rapidly, but are now facing the challenge of providing access to the most remote facilities (the “last mile”). For the hardest-to-reach facilities in Zambia, we compared the cost of placing point of care (POC) viral load instruments at or near facilities to the cost of an expanded sample transportation network (STN) to deliver samples to centralized laboratories. Methods: We extended a previously described geospatial model for Zambia that first optimized a STN for centralized laboratories for 90% of estimated viral load volumes. Amongst the remaining 10% of volumes, facilities were identified as candidates for POC placement, and then instrument placement was optimized such that access and instrument utilization is maximized. We evaluated the full cost per test under three scenarios: 1) POC placement at all facilities identified for POC; 2)an optimized combination of both on-site POC placement and placement at facilities acting as POC hubs; and 3) integration into the centralized STN to allow use of centralized laboratories. Results: For the hardest-to-reach facilities, optimal POC placement covered a quarter of HIV-treating facilities. Scenario 2 resulted in a cost per test of $39.58, 6% less than the cost per test of scenario 1, $41.81. This is due to increased POC instrument utilization in scenario 2 where facilities can act as POC hubs. Scenario 3 was the most costly at $53.40 per test, due to high transport costs under the centralized model ($36 per test compared to $12 per test in scenario 2). Conclusions: POC VL testing may reduce the costs of expanding access to the hardest-to-reach populations, despite the cost of equipment and low patient volumes. An optimal combination of both on-site placement and the use of POC hubs can reduce the cost per test by 6–35% by reducing transport costs and increasing instrument utilization. [ABSTRACT FROM AUTHOR]

Early infant diagnosis (EID) of HIV provides an opportunity for early HIV detection and access to appropriate Antiretroviral treatment (ART). Dried Blood Spot (DBS) samples are used for EID of exposed infants, born to HIV-positive mothers. However, DBS rejection rates in Zimbabwe have been exceeding the target of less than 2% per month set by the National Microbiology Reference Laboratory (NMRL), in Harare. The aim of this study was to determine the DBS sample rejection rate, the reasons for rejection and the possible associations between rejection and level of health facility where the samples were collected. This is an analytical cross-sectional study using routine DBS sample data from the NMRL in Harare, Zimbabwe, between January and December 2017.A total of 34 950 DBS samples were received at the NMRL. Of these, 1291(4%) were rejected. Reasons for rejection were insufficient specimen volume (72%), missing request form (11%), missing sample (6%), cross-contamination (6%), mismatch of information (4%) and clotted sample (1%). Samples collected from clinics/rural health facilities were five times more likely to be rejected compared to those from a central hospital. Rejection rates were above the set target of <2%. The reasons for rejection were ‘pre-analytical’ errors including labelling errors, missing or inconsistent data, and insufficient blood collected. Samples collected at primary healthcare facilities had higher rejection rates. [ABSTRACT FROM AUTHOR]

Background: Considerable upscaling of malaria control efforts have taken place over the last 15 years in the Democratic Republic of Congo, the country with the second highest malaria case load after Nigeria. Malaria control interventions have been strengthened in line with the Millenium Development Goals. We analysed the effects of these interventions on malaria cases at health facility level, using a retrospective trend analysis of malaria cases between 2005 and 2014. Data were collected from outpatient and laboratory registers based on a sample of 175 health facilities that represents all eco-epidemiological malaria settings across the country. Methods: We applied a time series analysis to assess trends of suspected and confirmed malaria cases, by health province and for different age groups. A linear panel regression model controlled for non-malaria outpatient cases, rain fall, nightlight intensity, health province and time fixed effects, was used to examine the relationship between the interventions and malaria case occurrences, as well as test positivity rates. Results: Overall, recorded suspected and confirmed malaria cases in the DRC have increased. The sharp increase in confirmed cases from 2010 coincides with the introduction of the new treatment policy and the resulting scale-up of diagnostic testing. Controlling for confounding factors, the introduction of rapid diagnostic tests (RDTs) was significantly associated with the number of tested and confirmed cases. The test positivity rate fluctuated around 40% without showing any trend. Conclusion: The sharp increase in confirmed malaria cases from 2010 is unlikely to be due to a resurgence of malaria, but is clearly associated with improved diagnostic availability, mainly the introduction of RDTs. Before that, a great part of malaria cases were treated based on clinical suspicion. This finding points to a better detection of cases that potentially contributed to improved case management. Furthermore, the expansion of diagnostic testing along with the increase in confirmed cases implies that before 2010, cases were underreported, and that the accuracy of routine data to describe malaria incidence has improved. [ABSTRACT FROM AUTHOR]

Due to the Expanded Program on Immunization (EPI) and supplementary immunization activities (SIAs) in China, the incidence of measles in China has decreased extensively. The incidence reached its lowest levels in contemporary history in 2012 and 2017, with incidence rates of 4.6 and 4.3 per million population, respectively. However, more than 147,000 measles cases were reported from 2013 to 2016. Furthermore, the proportions of cases in infants < 8 months and adults have been increasing since 2013, representing a considerable challenge for measles elimination in China. A total of 14,868 measles viruses were isolated from confirmed measles cases from 2011 to 2017, of which 14,631 were identified as the predominant endemic genotype, H1; 87 were identified as genotype A viruses that were vaccine associated strains; and 150 were identified as non-H1 genotype viruses. The non-H1 genotype viruses included 62 D8 viruses, 70 D9 viruses, 3 D11 viruses, 14 B3 viruses, and 1 G3 virus, which were identified as imported or import-related viruses that caused sporadic cases or small outbreaks. Most of the transmission chains detected during the period 2011–2012 were interrupted and were followed by many new transmission chains of unknown origin that spread, causing a large measles resurgence in China during 2013–2016. After 4 years of measles resurgence and continuous implementation of the routine immunization program and SIAs, the population immunity reached a sufficiently high level to interrupt most of the transmission chains; only a few strains survived, which continued to be sporadically detected in China in 2017. In the present study, the results from the combined epidemiological and molecular virological data demonstrated the great progress towards measles elimination in China by the further analysis of circulation dynamics for the endemic H1 genotype measles virus from 2011 to 2017. And this study accumulated critical baseline data on circulating wild-type measles viruses in China and provides comprehensive information to the world. These comprehensive baseline data provide evidence to support measles elimination in the future, not only in China but also in other countries worldwide. In addition, the information will be very useful to other countries for tracing their sources of measles cases and for identifying transmission links, which can help prevent potential measles outbreaks. [ABSTRACT FROM AUTHOR]

Background: We describe CD4 count recovery among HIV positive individuals who initiated antiretroviral therapy (ART) with and without severe immune suppression using complete laboratory data from South Africa’s national HIV treatment programme between 2010 and 2014 and discuss implications for CD4 count monitoring. Methods: Retrospective analysis of routinely collected laboratory data from South Africa’s National Health Laboratory Service (NHLS). A probabilistic record linkage algorithm was used to create a cohort of HIV positive individuals who initiated ART between 2010 and 2014 based on timing of CD4 count and viral load measurements. A CD4 count < 50 copies/μl at ART initiation was considered severe immunosuppression. A multivariable piecewise mixed-effects linear regression model adjusting for age, gender, year of starting ART, viral suppression in follow up and province was used to predict CD4 counts during follow up. Results: 1,070,900 individuals had evidence of starting ART during 2010–2014 and met the criteria for inclusion in the cohort -46.6% starting ART with CD4 < 200 cells/μl and 10.1% with CD4 < 50 cells/ μl. For individuals with CD4 counts < 200 cells/μl, predicted CD4 counts > 200 cells/μl, >350 cells/μl and >500 cells/μl corresponded with mean follow up durations of 1.5 years (standard deviation [s.d] 1.1), 1.9years (s.d 1.2) and 2.1 years (s.d 1.3 years). For those with CD4 counts < 50 cells/μl, predicted CD4 count above these threshold corresponded with mean follow up durations of 2.5 years (s.d 0.9 years), 4.4 years (s.d 0.4 years) and 5.0 years (s.d 0.1years) for recovery to the same thresholds. CD4 count recovery varied mostly with duration on ART, CD4 count at the start of ART and gender. Conclusion: For individuals starting with ART with severe immunosuppression, CD4 recovery to 200cells/μl did not occur or took longer than 12 month for significant proportions. CD4 monitoring and interventions recommended for advanced HIV disease should continue until full recovery. [ABSTRACT FROM AUTHOR]

In a Policy Forum, Peter Ehrenkranz and colleagues discuss the contribution of CD4 and viral load testing to outcomes for people with HIV in low- and middle-income countries. [ABSTRACT FROM AUTHOR]

Background: Outreach and promotion programs are essential to ensuring uptake of new public health interventions and guidelines. We assessed the costs and operation dynamics of outreach and promotion efforts for up front Xpert MTB/RIF (Xpert) testing for pediatric presumptive tuberculosis (TB) patients in four major Indian cities. Methods: Xpert test costs were assessed as weighted average per-test costs based on the daily workload dynamics matched by test volume specific Xpert unit cost at each study site. Costs of outreach programs to recruit health providers to refer pediatric patients for Xpert testing were assessed as cost per referral for each quarter based on total program costs and referral data. All costs were assessed in the health service provider’s perspective and expressed in 2015 USD. Results: Weighted average per-test costs ranged from $14.71 to $17.81 at the four laboratories assessed. Differences between laboratories were associated with unused testing capacity and/or frequencies of overtime work to cope with increasing demand and same-day testing requirements. Outreach activities generated between 825 and 2,065 Xpert testing referrals on average each quarter across the four study sites, translating into $0.63 to $2.55 per patient referred. Overall outreach costs per referral decreased with time, stabilizing at an average cost of $1.10, and demonstrated a clear association with increased referrals. Conclusions: Xpert test and outreach program costs within and across study sites were mainly driven by the dynamics of Xpert testing demand resulting from the combined outreach activities. However, these increases in demand required considerable overtime work resulting in additional costs and operational challenges at the study laboratories. Therefore, careful laboratory operational adjustment should be evaluated at target areas in parallel to the anticipated demand from the Xpert referral outreach program scale-up in other Indian regions. [ABSTRACT FROM AUTHOR]

Aim: We aimed to assess the resistance rates of antimicrobial-resistant, in bacterial pathogens of epidemiological importance in 47 Mexican centers. Material and methods: In this retrospective study, we included a stratified sample of 47 centers, covering 20 Mexican states. Selected isolates considered as potential causatives of disease collected over a 6-month period were included. Laboratories employed their usual methods to perform microbiological studies. The results were deposited into a database and analyzed with the WHONET 5.6 software. Results: In this 6-month study, a total of 22,943 strains were included. Regarding Gram-negatives, carbapenem resistance was detected in ≤ 3% in Escherichia coli, 12.5% in Klebsiella sp. and Enterobacter sp., and up to 40% in Pseudomonas aeruginosa; in the latter, the resistance rate for piperacillin-tazobactam (TZP) was as high as 19.1%. In Acinetobacter sp., resistance rates for cefepime, ciprofloxacin, meropenem, and TZP were higher than 50%. Regarding Gram-positives, methicillin resistance in Staphylococcus aureus (MRSA) was as high as 21.4%, and vancomycin (VAN) resistance reached up to 21% in Enterococcus faecium. Acinetobacter sp. presented the highest multidrug resistance (53%) followed by Klebsiella sp. (22.6%) and E. coli (19.4%). Conclusion: The multidrug resistance of Acinetobacter sp., Klebsiella sp. and E. coli and the carbapenem resistance in specific groups of enterobacteria deserve special attention in Mexico. Vancomycin-resistant enterococci (VRE) and MRSA are common in our hospitals. Our results present valuable information for the implementation of measures to control drug resistance. [ABSTRACT FROM AUTHOR]

Introduction: Measles remains a major public health problem in many developing countries in which vaccination coverage is poor, as is the case in the Central African Republic (CAR). At the beginning of the 2000s, a surveillance system was established in the country, and samples from suspected cases are regularly tested in the laboratory for serological confirmation. Since 2007, when case-by-case monitoring with standardized laboratory databases and monitoring, was set up, no assessment have been performed. Therfore, 9 years later it seemed appropriate to make a first assessment. The aim of the study reported here was to describe the epidemiology of measles in the CAR on the basis of surveillance and laboratory data. Method: A descriptive retrospective study was conducted, based on the databases of the measles surveillance programme and of the Institut Pasteur laboratory in Bangui during the period 2007–2015. Results: During this study period, the surveillance programme notified 3767 cases. Of these, 2795 (75%) were sent for laboratory confirmation, and 24.6% (687/2795) were confirmed serologically. Of the 1797 cases of measles declared during this period by the surveillance programme, 1110 (61.8%) were confirmed clinically or by epidemiological linkage. The majority of confirmed cases (83.7%; 575/687) occurred in children under 10 years, over half of whom (44.2%; 304/687) were aged 1–4 years. Epidemics occurred regularly between 2011 and 2015, with > 10% of laboratory-confirmed cases. The rate of laboratory investigation was < 80% between 2011 and 2013 but nearly 100% in the other years. Conclusion: Measles remains a common, endemic illness in the CAR. Improved detection will require better measles surveillance, increased vaccination coverage, revision of the investigation forms to include the WHO case definition and training of the health personnel involved in case-finding in the field. [ABSTRACT FROM AUTHOR]

Background: Influenza-like Illness (ILI) is a medical diagnosis of possible influenza or another respiratory illness with a common set of symptoms. The deaths of four schoolchildren, during a pandemic influenza outbreak in December 2017 in Ghana, raised doubts about the ILI surveillance system’s performance. We evaluated the ILI surveillance system in the Greater Accra region, Ghana, to assess the system’s attributes and its performance on set objectives. Methods: CDC guidelines were used to evaluate the data of the ILI surveillance system between 2013 and 2017. We interviewed the surveillance personnel on the system’s description and operation. Additionally, routinely entered ILI data from the National Influenza Center provided by the six sentinel sites in Accra was extracted. We sampled and reviewed 120 ILI case-investigation forms from these sites. Surveillance activities were examined on system’s performance indicators, each being scored on a scale of 1 to 3 (poorest to best performance). Results: All population and age groups were under ILI surveillance over the period evaluated. Overall, 2948 suspected case-patients, including 392 (13.3%) children under-five were reported, with 219 being positive for influenza virus (Predictive value positive = 7.4%). The predominant influenza subtype was H3N2, recorded in 90 (41.1%) of positive case-patients. The system only met two out of its four objectives. None of the six sentinel sites consistently met their annual 260 suspected case-detection quota. Samples reached the laboratory on average 48 hours after collection and results were disseminated within 7 days. Of 120 case-investigation forms sampled, 91 (76.3%) were completely filled in. Conclusions: The ILI surveillance system in the Greater Accra region is only partially meeting its objectives. While it is found to be sensitive, representative and timely, the data quality was sub-optimal. We recommend the determination of thresholds for alert and outbreak detection and ensuring that sentinel sites meet their weekly case-detection targets. [ABSTRACT FROM AUTHOR]

The triglyceride glucose (TyG) index, a product of triglyceride and fasting glucose, is a reliable marker for insulin resistance (IR). Obesity is also known to be closely related with IR. Recently, the efficiency of TyG-related markers that combine obesity markers with TyG index has been studied; however, earlier studies were limited in number and the results were inconsistent. Therefore, in this study, we investigated the efficiency of several combinations of TyG index and obesity indices, namely, body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR), in reflecting IR. Data were obtained from the Korean National Health and Nutrition Examination Survey from 2007–2010. A total of 11,149 subjects (4,777 men and 6,372 women) were included. IR was defined as the homeostasis model assessment for IR (HOMA-IR) of above the 75th percentile for each gender. Logistic regression analysis was performed after adjusting for confounding factors, to compare and identify the associations of the 4 parameters (TyG index, TyG-BMI, TyG-WC, and TyG-WHtR) with IR. For each parameter, odds ratios (OR) and 95% confidence intervals (CIs) of quartiles 2–4 were calculated and compared with quartile 1 as a reference. A receiver operating characteristic (ROC) curve analysis was conducted to evaluate the ability of each parameter to predict IR. The adjusted ORs of quartile 4 in comparison with quartile 1 (95% CIs) for IR were 7.60 (6.52–8.87) for TyG index, 12.82 (10.89–15.10) for TyG-BMI, 16.29 (13.70–19.38) for TyG-WC, and 14.86 (12.53–17.62) for TyG-WHtR. The areas under the ROC curve for each parameter were 0.690 for TyG index, 0.748 for TyG-BMI, 0.731 for TyG-WC, and 0.733 for TyG-WHtR. In conclusion, TyG-BMI was found to be superior to other parameters for IR prediction. We propose TyG-BMI as an alternative marker for assessing IR in clinical settings. [ABSTRACT FROM AUTHOR]

Background: In lymphangioleiomyomatosis (LAM), tuberous sclerosis gene mutations activate the mechanistic target of the rapamycin pathway, resulting in vascular endothelial growth factor-D (VEGF-D) overproduction. While the utility of serum VEGF-D testing for the diagnosis of LAM is outlined in ATS/JRS LAM Guidelines, the assay has not been fully validated for Asian populations. Our aims were to validate serum VEGF-D testing in Japan, by directly comparing measurements in Japan and the U.S., determining the diagnostic cut-off for serum VEGF-D levels among the Japanese women with typical thin walled cystic change on CT, and determining the performance of VEGF-D as a prognostic biomarker. Subjects and methods: We determined serum VEGF-D levels from 108 LAM patients, 14 disease controls, and 51 healthy volunteers from the Japanese population. Measurements of 61 LAM patients were compared to those from the principal VEGF-D laboratory in the U.S at Cincinnati Children’s Hospital Medical Center. We correlated baseline serum VEGF-D levels with baseline and longitudinal clinical data to determine how pregnancy, sirolimus or gonadotrophin-releasing hormone (GnRH) agonists influence serum VEGF-D levels. Results: Serum VEGF-D measurements in Japan and the U.S. were very similar. Baseline serum VEGF-D levels effectively distinguished LAM from other diseases and healthy volunteers at a cut-off level of 645 pg/ml and were diagnostically specific at 800 pg/ml, consistent with the recommendations of the ATS/JRS LAM Guidelines. Baseline serum VEGF-D correlated negatively with the DLco baseline % predicted and with the annual decrease in DLco % predicted. There was no significant association between baseline serum VEGF-D level and the outcomes of death or transplant. Serum VEGF-D levels markedly decreased during treatment with sirolimus, but not with GnRH analogues. Serum VEGF-D levels of most LAM patients did not increase over time, and neither pregnancy nor menopause significantly modulated serum VEGF-D levels. Conclusions: Serum VEGF-D is a useful diagnostic and therapeutic biomarker for LAM. Satisfactory precision and international inter-laboratory agreement of the clinical assay support VEGF-D recommendations in the ATS/JRS LAM Guidelines for the Japanese population. [ABSTRACT FROM AUTHOR]

Background: Routine surveillance is required to monitor the performance of tuberculosis diagnostic programme and is essential for the rapid detection of drug resistance. The main objective of this study was to explore the effectiveness and stakeholder perception of the current routine surveillance system for previously treated tuberculosis cases in Tanzania with a view to identify interventions to improve and accelerate positive patient outcomes. Methods: A study using quantitative and qualitative methods of data collection including in-depth interviews and focus group discussions with health care service providers was conducted in four regions. Quantitative data were extracted from the routine databases to assess performance. Results: Quantitative findings from 2011 to 2013 showed 2,750 specimens from previously treated TB cases were received at the reference laboratory. The number increased year on year, but even in the most recent year was only 61% of that expected. The median and interquartile range of turnaround time in days from specimen reception to results reported for smear microscopy, culture and drug susceptibility testing were 1(1, 1), 61(43, 71) and 129(72, 170) respectively. Contaminated specimens were reported in 3.6% of cases. The qualitative analysis showed the system of sending specimens using postal services was seen to be efficient by participants. However, there were many challenges and significant delays in specimens reaching the reference laboratory associated with lack of funds to transfer specimens, weak form completion, inadequate training and poor supervision. These all adversely affected the implementation of the routine surveillance system. Conclusions: Many issues limit the effectiveness of the routine surveillance system in Tanzania. Priority areas for strengthening are; specimen transportation, supervision and availability of commodities. A pilot study of a revised routine surveillance system that takes into account the observations from this study alongside improved access to drug susceptibility testing using Xpert MTB/RIF should be considered. [ABSTRACT FROM AUTHOR]

Dengue is a national priority disease in Cambodia. The Cambodian National Dengue Surveillance System is based on passive surveillance of dengue-like inpatients reported by public hospitals and on a sentinel, pediatric hospital-based active surveillance system. This system works well to assess trends but the sensitivity of the early warning and time-lag to usefully inform hospitals can be improved. During The ECOnomic development, ECOsystem MOdifications, and emerging infectious diseases Risk Evaluation (ECOMORE) project’s knowledge translation platforms, Cambodian hospital staff requested an early warning tool to prepare for major outbreaks. Our objective was therefore to find adapted tools to improve the early warning system and preparedness. Dengue data was provided by the National Dengue Control Program (NDCP) and are routinely obtained through passive surveillance. The data were analyzed at the provincial level for eight Cambodian provinces during 2008–2015. The R surveillance package was used for the analysis. We evaluated the effectiveness of Bayesian algorithms to detect outbreaks using count data series, comparing the current count to an expected distribution obtained from observations of past years. The analyses bore on 78,759 patients with dengue-like syndromes. The algorithm maximizing sensitivity and specificity for the detection of major dengue outbreaks was selected in each province. The overall sensitivity and specificity were 73% and 97%, respectively, for the detection of significant outbreaks during 2008–2015. Depending on the province, sensitivity and specificity ranged from 50% to 100% and 75% to 100%, respectively. The final algorithm meets clinicians’ and decisionmakers’ needs, is cost-free and is easy to implement at the provincial level. [ABSTRACT FROM AUTHOR]

Background: Cystic echinococcosis (CE) is a globally occurring zoonosis, whereas alveolar echinococcosis (AE) is endemic only in certain parts of the Northern Hemisphere. The socioeconomic impact of human echinococcosis has been shown to be considerable in highly endemic regions. However, detailed data on direct healthcare-related costs associated with CE and AE are scarce for high income countries. The aim of this study was to evaluate direct costs of human disease caused by CE and AE in Austria. Methods: Clinical data from a registry maintained at a national reference center for echinococcosis at the Medical University of Vienna were obtained for the years 2012–2014. These data were used in conjunction with epidemiological data from Austria’s national disease reporting system and diagnostic reference laboratory for echinococcosis to assess nationwide costs attributable to CE and AE. Results: In Austria, total modelled direct costs were 486,598€ (95%CI 341,825€ – 631,372€) per year for CE, and 683,824€ (95%CI 469,161€ - 898,486€) for AE. Median costs per patient with AE from diagnosis until the end of a 10-year follow-up period were 30,832€ (25th– 75th percentile: 23,197€ - 31,220€) and 62,777€ (25th– 75th percentile: 60,806€ - 67,867€) for inoperable and operable patients, respectively. Median costs per patients with CE from diagnosis until end of follow-up after 10 years were 16,253€ (25th– 75th percentile: 8,555€ - 24,832€) and 1,786€ (25th– 75th percentile: 736€ - 2,146€) for patients with active and inactive cyst stages, respectively. The first year after inclusion was the most cost-intense year in the observed period, with hospitalizations and albendazole therapy the main contributors to direct costs. Conclusions: This study provides detailed information on direct healthcare-related costs associated with CE and AE in Austria, which may reflect trends for other high-income countries. Surgery and albendazole therapy, due to surprisingly high drug prices, were identified as important cost-drivers. These data will be important for cost-effectiveness analyses of possible prevention programs. [ABSTRACT FROM AUTHOR]

The BRCA Challenge is a long-term data-sharing project initiated within the Global Alliance for Genomics and Health (GA4GH) to aggregate BRCA1 and BRCA2 data to support highly collaborative research activities. Its goal is to generate an informed and current understanding of the impact of genetic variation on cancer risk across the iconic cancer predisposition genes, BRCA1 and BRCA2. Initially, reported variants in BRCA1 and BRCA2 available from public databases were integrated into a single, newly created site, . The purpose of the BRCA Exchange is to provide the community with a reliable and easily accessible record of variants interpreted for a high-penetrance phenotype. More than 20,000 variants have been aggregated, three times the number found in the next-largest public database at the project’s outset, of which approximately 6,150 have expert classifications. The data set is based on shared information from existing clinical databases—Breast Cancer Information Core (BIC), ClinVar, and the Leiden Open Variation Database (LOVD)—as well as population databases, all linked to a single point of access. The BRCA Challenge has brought together the existing international Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium expert panel, along with expert clinicians, diagnosticians, researchers, and database providers, all with a common goal of advancing our understanding of BRCA1 and BRCA2 variation. Ongoing work includes direct contact with national centers with access to BRCA1 and BRCA2 diagnostic data to encourage data sharing, development of methods suitable for extraction of genetic variation at the level of individual laboratory reports, and engagement with participant communities to enable a more comprehensive understanding of the clinical significance of genetic variation in BRCA1 and BRCA2. [ABSTRACT FROM AUTHOR]

Introduction: Internal and external quality control (QC) of rapid diagnostic tests (RDTs) is important to increase reliability of RDTs currently used to diagnose malaria. However, cross-checking of used RDTs as part of quality assurance can rarely be done by off-site personnel because there is no guarantee of retaining visible test lines after manufacturers’ recommended reading time. Therefore, this study examined the potential of using Fionet™ technology for remote RDT quality monitoring at seven clinics, identifying reasons for making RDT processing and interpretation errors, and taking corrective actions for improvement of diagnosis and consequently improved management of febrile patients Methods: The study was conducted at seven military health facilities in Mainland Tanzania and utilized RDTs capable of detecting Plasmodium falciparum specific Histidine-rich protein 2 (Pf-HRP2) and the genus specific Plasmodium lactate dehydrogenase (pLDH) for other species of plasmodium (P. vivax, P. malariae or P. ovale; pan-pLDH). Patients’ data and images of processed RDTs from seven clinics were uploaded on a Fionet web portal and reviewed regularly to monitor preparation procedures and visual interpretation of test results compared to automated analysis using the Deki reader of RDT. Problems detected were rapidly communicated to remote laboratory personnel at the clinic for corrective action and follow-up of patients who were falsely diagnosed as negative and missed treatment. Factors contributing to making errors in visual interpretation of RDT results were analyzed during visits to the health facilities. Results: A total of 1,367 (1.6%) out of 83,294 RDT test images uploaded to the Fionet portal had discordant test results of which 822 (60.1%) and 545 (39.9%) were falsely reported as negative and positive, respectively. False negative and false positive test results were common for a single test line in 515 (62.7%) and 741 (54.2%) tests, respectively. Out of 1,367 RDT images assessed, 98 (7.2%) had quality problems related to preparation procedures of which 95(96.9%) errors were due to putting too much blood on the sample well or insufficient buffer in the respective wells. The reasons for discrepant results included, false reporting of none existent lines in 526 (38.5%) tests, missing a faint positive line in 493 (36.1%), missing a strong positive line in 248(18.1%) and errors caused by poorly processed RDTs in 96 (7.2%) tests. Among the false negative tests (n = 822), 669 (48.9%) patients were eligible for follow–up and only 339 (48.5%) were reached and 291 (85.8%) received appropriate anti-malaria therapy. Conclusion: Fionet technology enabled remote monitoring of RDT quality issues, identifying reasons contributing to laboratory personnel making errors and provided a rapid method to implement corrective actions at remote sites to improve malaria diagnosis and consequently improved health care management of febrile patients infected with malaria. [ABSTRACT FROM AUTHOR]

Background: To enable incremental optimization of screening, regular reporting of quality indicators is required. Aim: To report key quality indicators and basic statistics about cervical screening in Sweden. Methods: We collected individual level data on all cervical cytologies, histopathologies, human papillomavirus tests and all invitations for cervical screening in Sweden during 2013–2016. Results: There were over 2,278,000 cervical samples collected in Sweden in 2014–2016. Organized samples (resulting from an invitation) constituted 69% of samples. The screening test coverage of all resident women aged 23–60 was 82%. The coverage has slowly increased for >10 years. There is large variability between counties (from 71% to 92%) over time. There were 25,725 women with high-grade lesions in cytology during 2013–2015. Only 96% of these women had a follow-up histopathology within a year. Cervical cancer incidence showed an increasing trend. Conclusion: Key quality indicators such as population coverage and follow-up rates were stable or improving, but there was nevertheless an unexplained cervical cancer increase. [ABSTRACT FROM AUTHOR]

Background: The knowledge of circulating HCV genotypes and subtypes in a country is crucial to guide antiviral therapy and to understand local epidemiology. Studies investigating circulating HCV genotypes and their trends have been conducted in Belgium. However they are outdated, lack nationwide representativeness or were not conducted in the general population. Methods: In order to determine the distribution of different circulating HCV genotypes in Belgium, we conducted a multicentre study with all the 19 Belgian laboratories performing reimbursed HCV genotyping assays. Available genotype and subtype data were collected for the period from 2008 till 2015. Furthermore, a limited number of other variables were collected: some demographic characteristics from the patients and the laboratory technique used for the determination of the HCV genotype. Results: For the study period, 11,033 unique records collected by the participating laboratories were used for further investigation. HCV genotype 1 was the most prevalent (53.6%) genotype in Belgium, with G1a and G1b representing 19.7% and 31.6%, respectively. Genotype 3 was the next most prevalent (22.0%). Further, genotype 4, 2, and 5 were responsible for respectively 16.1%, 6.2%, and 1.9% of HCV infections. Genotype 6 and 7 comprise the remaining <1%. Throughout the years, a stable distribution was observed for most genotypes. Only for genotype 5, a decrease as a function of the year of analysis was observed, with respectively 3.6% for 2008, 2.3% for 2009 and 1.6% for the remaining years. The overall M:F ratio was 1.59 and was mainly driven by the high M:F ratio of 3.03 for patients infected with genotype 3. Patients infected with genotype 3 are also younger (mean age 41.7 years) than patients infected with other genotypes (mean age above 50 years for all genotypes). The patients for whom a genotyping assay was performed in 2008 were younger than those from 2015. Geographical distribution demonstrates that an important number of genotyped HCV patients live outside the Belgian metropolitan cities. Conclusion: This national monitoring study allowed a clear and objective view of the circulating HCV genotypes in Belgium and will help health authorities in the establishment of cost effectiveness determinations before implementation of new treatment strategies. This baseline characterization of the circulating genotypes is indispensable for a continuous surveillance, especially for the investigation of the possible impact of migration from endemic regions and prior to the increasing use of highly potent direct-acting antiviral (DAA) agents. [ABSTRACT FROM AUTHOR]

The discovery of the life-threatening zoonotic infection Plasmodium knowlesi has added to the challenges of prompt and accurate malaria diagnosis and surveillance. In this study from Aceh Province, Indonesia, a malaria elimination setting where P. knowlesi endemicity was not previously known, we report the laboratory investigation and difficulties encountered when using molecular detection methods for quality assurance of microscopically identified clinical cases. From 2014 to 2015, 20 (49%) P. falciparum, 16 (39%) P. vivax, 3 (7%) P. malariae, and 2 (5%) indeterminate species were identified by microscopy from four sentinel health facilities. At a provincial-level reference laboratory, loop-mediated isothermal amplification (LAMP), a field-friendly molecular method, was performed and confirmed Plasmodium in all samples though further species-identification was limited by the unavailability of non-falciparum species-specific testing with the platform used. At a national reference laboratory, several molecular methods including nested PCR (nPCR) targeting the 18 small sub-unit (18S) ribosomal RNA, nPCR targeting the cytochrome-b (cytb) gene, a P. knowlesi-specific nPCR, and finally sequencing, were necessary to ultimately classify the samples as: 19 (46%) P. knowlesi, 8 (20%) P. falciparum, 14 (34%) P. vivax. Microscopy was unable to identify or mis-classified up to 56% of confirmed cases, including all cases of P. knowlesi. With the nPCR methods targeting the four human-only species, P. knowlesi was missed (18S rRNA method) or showed cross-reactivity for P. vivax (cytb method). To facilitate diagnosis and management of potentially fatal P. knowlesi infection and surveillance for elimination of human-only malaria in Indonesia and other affected settings, new detection methods are needed for testing at the point-of-care and in local reference laboratories. [ABSTRACT FROM AUTHOR]

In addition to high vaccination coverage, timely and accurate laboratory confirmation of measles cases is critical to interrupt measles transmission. To evaluate the role of real-time reverse transcription-polymerase chain reaction (RT-PCR) in the diagnosis of measles cases, 46,363 suspected measles cases with rash and 395 suspected measles cases without rash were analyzed in this study; the cases were obtained from the Chinese measles surveillance system (MSS) during 2014–2017 and simultaneously detected by measles-specific IgM enzyme-linked immunosorbent assay (ELISA) and real-time RT-PCR. However, some IgM-negative measles cases were identified by real-time RT-PCR. The proportion of these IgM-negative and viral nucleic acid-positive measles cases was high among measles cases with measles vaccination history, cases without rash symptoms, and cases within 3 days of specimen collection after onset. The proportion of IgM-negative and viral nucleic acid-positive measles cases in the 0–3 day group was up to 14.4% for measles cases with rash and 40% for measles cases without rash. Moreover, the proportions of IgM-negative and nucleic acid-positive measles cases gradually increased with the increase in the measles vaccination dose. Therefore, integrated with IgM ELISA, real-time RT-PCR would greatly improve the accurate diagnosis of measles cases and avoid missing the measles cases, especially for measles cases during the first few days after onset when the patients were highly contagious and for measles cases with secondary vaccine failure. In conclusion, our study reconfirmed that IgM ELISA is the gold-standard detection assay for measles cases confirmation. However, real-time RT-PCR should be introduced and used to supplement the laboratory diagnosis, especially in the setting of pre-elimination and/or elimination wherever appropriate. [ABSTRACT FROM AUTHOR]

Genetic testing availability in the health care system is rapidly increasing, along with the diffusion of next-generation sequencing (NGS) into diagnostics. These issues make imperative the knowledge-drive optimization of testing in the clinical setting. Time estimations of wet laboratory procedure in Italian molecular laboratories offering genetic diagnosis were evaluated to provide data suitable to adjust efficiency and optimize health policies and costs. A survey was undertaken by the Italian Society of Human Genetics (SIGU). Forty-two laboratories participated. For most molecular techniques, the most time-consuming steps are those requiring an intensive manual intervention or in which the human bias can affect the global process time-performances. For NGS, for which the study surveyed also the interpretation time, the latter represented the step that requiring longer times. We report the first survey describing the hands-on times requested for different molecular diagnostics procedures, including NGS. The analysis of this survey suggests the need of some improvements to optimize some analytical processes, such as the implementation of laboratory information management systems to minimize manual procedures in pre-analytical steps which may affect accuracy that represents the major challenge to be faced in the future setting of molecular genetics laboratory. [ABSTRACT FROM AUTHOR]

The rates of pulmonary colonization and disease due to nontuberculous mycobacteria (NTM) appear to be increasing globally, but diversity of species recovered as well as clinical relevance of NTM isolates differ considerably by geographic region. The first nationwide study of isolation frequency and clinical significance of NTM in Serbia included all patients with respiratory specimens yielding a positive NTM culture over the six-year period, 2010–2015. We analyzed trends in annual NTM isolation and NTM pulmonary disease (PD) incidence rates, with NTM PD cases defined in accordance with microbiological criteria established by the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA). 777 pulmonary NTM isolates were collected from 565 patients, of whom 126 (22.3%) met the ATS/IDSA criteria. The annual NTM isolation and NTM PD incidence rates per 100,000 changed over 2010–2015 from 0.9 to 1.6 (p = 0.1746) and from 0.18 to 0.48 (p = f0.0040), respectively. Both isolation and disease rates increased considerably with age, while higher NTM PD rates were also associated with residence in urbanized areas. Diversity of NTM species isolated was shown to be region-specific, with M. xenopi as the most prevalent species (17.3%), and increasing isolation rates of rapid growing mycobacteria (RGM) (p = 0.0072). M. xenopi was also the most common cause of NTM PD (28.6%), followed by RGM (27.8%). With 73% clinically relevant isolates, M. abscessus was identified as the most clinically relevant NTM species. While NTM PD obviously remains a rare disease in Serbia, the overall results justify recognition of NTM as pathogens of rising importance, and require further characterization of their epidemiology in the country. [ABSTRACT FROM AUTHOR]

Measurement of pH in IVF-media using the blood gas analyzer (BGA) requires validation, because IVF-media is outside the intended scope of the BGA. To determine whether the Siemens Rapidpoint 500 BGA is suitable for pH measurements in IVF-media this study will validate the BGA and assess its accuracy. In this method comparison study, the pH of over three hundred IVF-media samples was measured with the BGA and a pH electrode (Hanna pH checker). The precision of both the BGA and the pH electrode were excellent (coefficient variation <1.4%). However, the closeness of agreement between measured values of both devices were not equivalent to each other in the tested IVF-media, showing 15% to 85% accordance between devices. The pH measured with the blood gas analyzer was also significantly higher in the tested media, compared to that measured by the pH electrode. One of the tested media did not reach its target pH when it was measured with the BGA, even at 9% CO2. The results show that the validated blood gas analyzer produces excellent results in terms of precision but not in terms of accuracy. Inaccurate measurement may lead to misinterpretation of results and consequently to suboptimal culture conditions. Therefore, each laboratory is encouraged to perform a validation of their BGA. [ABSTRACT FROM AUTHOR]

Introduction: HIV and AIDS care requires frequent visits to the hospital. Patient satisfaction with care services during hospital visits is important in considering quality and outcome of care. Increasing number of patients needing treatment led to the decentralization of care to lower level hospitals without documented patient perception on the quality of services. The study determined and compared patient satisfaction with HIV and AIDS care services in public and private hospitals and identified the factors that influence it. Method: This was a cross-sectional comparative study of patients receiving antiretroviral treatment in public and private hospitals in Anambra State. The sampling frame for the hospitals consisted of all registered public and private hospitals that have rendered antiretroviral services for at least one year. There were three public urban, nine public rural, eleven private urban and ten private rural hospitals that met the criteria. One hospital was selected by simple random sampling (balloting) from each group. Out of a total of 6334 eligible patients (had received ART for at least 12 months), 1270 were recruited by simple random sampling from the hospitals proportionate to size of patient in each hospital. Adapted, validated and pretested Patient Satisfaction Questionnaire (PSQ18) was interviewer-administered on consenting patients as an exit interview. A Chi-square test and logistic regression analysis were conducted at 5% level of significance. Result: There were 635 participants each in public and private hospitals. Of the 408 patients who had primary education or less, 265(65.0%) accessed care in public hospitals compared to 143(35.0%) who accessed care in private hospital (p<0.001). Similarly, of the 851 patients who were currently married, 371 (43.6%) accessed their care in public compared to 480 (56.4%) who accessed care in private (p<0.001). The proportion of participants who were satisfied were more in public hospitals (71.5%) compared to private hospitals (41.4%). The difference in proportion was statistically significant (χ2 = 116.85, p <0.001). Good retention in care [AOR: 2.3, 95%CI: 1.5–3.5] was the only predictor of satisfaction in public hospitals while primary education [adjusted odds ratio (AOR); 2.3, 95%CI: 1.5–3.4], residing in rural area [AOR: 2.0, 95%CI: 1.4–2.9], and once-daily dosing [AOR: 3.2, 95%CI: 2.1–4.8] were independent predictors of patient' satisfaction among private hospital respondents. Conclusion: Satisfaction was higher among patients attending public hospitals. Patient’s satisfaction was strongly associated with retention in care among patients in public hospitals. However, in private hospitals, it was influenced by the patient’s level of education, place of residence, and antiretroviral medication dosing frequency. [ABSTRACT FROM AUTHOR]

Although most countries in the WHO European Region were verified in 2017 as having interrupted endemic measles transmission, nine countries were still endemic. Among these, Italy accounted for the second highest number of measles cases reported in Europe in 2017. The elimination of measles is verified at national level by each country’s National Verification Committee (NVC) through the production of an Annual Status Update (ASU). Since in Italy decentralization has led to an inhomogeneous implementation of immunization strategies among the 21 administrative Regions, the Italian NVC proposed that measles elimination should also be documented at the subnational level through regional ASUs and Synthetic Regional Reports (SRRs). The regional ASUs and the SRRs for 2014, 2015 and 2016 were produced and appraised by the NVC to evaluate the Regions’ performances in each individual year as well as over the whole period. A specific analysis of vaccination coverage, including official immunization data for 2017, was performed. Moreover, the measles epidemic of 2017 was examined. Firstly, in the period 2014–2016, low immunization rates were registered in most Regions. Sixty-three per cent of southern Regions reported rates below the national mean and an overall low-quality performance. The approval of Italy’s mandatory vaccination law in 2017 resulted in a marked increase in vaccination coverage; however, this increase was not homogeneous among Regions. Secondly, more than 50% of Regions did not report any supplemental immunization activity (SIA) for the period 2014–2016. Thirdly, from 2014 to 2016, fewer than one-third of Regions improved their reporting of outbreaks. Finally, over the study period, only two Regions reached the target required by the WHO for measles laboratory investigations. In countries with decentralized health policies, subnational monitoring can help identify local barriers to measles elimination. In Italy it has highlighted the need for further SIAs and a stronger surveillance system. [ABSTRACT FROM AUTHOR]

In this study we aimed at identifying main demographic, laboratory and environmental factors influencing the level of urinary biomarkers (DNA-derived 8-oxodG and lipid membrane-derived 8-isoprostane), and deriving their adjusted 95% reference intervals (RI) in a sample of healthy people from the general population. Data from 281 healthy subjects from the Gene Environment Interactions in Respiratory Diseases survey were used in this study. Generalized additive models for location, scale and shape (GAMLSS) were used to find determinants of the biomarkers among gender, age, season and distance from collection (DFC), and to predict their RI. The RI of the biomarkers stratified by season and adjusted for DFC showed a slight statistically significant decrease in the biomarkers at the increasing DFC in two seasons, except the 8-oxodG during the warm season: median levels at the min and max values of DFC were (ng/mgcreat) 7.0–1.1 in the cold and 3.9–3.9 in the warm seasons for 8-oxodG, 0.7–0.2 in the cold and 1.3–0.6 in the warm seasons for 8-isoprostane. Both the biomarkers should be evaluated in association with the DFC and season in large epidemiological studies. The (semi)parametric GAMLSS method is a useful and flexible technique, which makes it possible to estimate adjusted RI. [ABSTRACT FROM AUTHOR]

Background: Microscopic diagnosis of Giemsa stained thick and thin blood films by skilled microscopists has remained the gold standard laboratory method for the diagnosis of malaria. However, there is a scarcity of qualified laboratory professionals for correctly diagnosing malaria using microscopy. The aim of this study was to evaluate the performance of laboratory professionals on malaria microscopy at health facilities in Bahir Dar city administration, Northwest Ethiopia. Methods: A cross-sectional study was conducted from January to March 2017 in Bahir Dar City. A total of 87 laboratory professionals participated in the selected health facilities, with a response rate of (100%). Standardized pre-validated slide panels and questionnaire were distributed to laboratory professionals by the principal investigator. The panel slides were comprised of 5 positives and 3 negative blood films. The laboratory professionals were requested to report the parasite density using semi-quantitative (+) and per micro-liter methods. Their performances of slide readings were compared with the experts’ readings. Agreement in detecting malaria parasites between laboratory professionals and expert was estimated using the kappa score. Results: The overall sensitivity and specificity of the laboratory professionals in detecting malaria parasites were 83% and 97%, respectively. Similarly, positive predictive values of 98.1% and negative predictive values of 77.7% were reported. The percent agreement between laboratory professionals and expert microscopist in the detection of malaria parasites was 88.5% with a Kappa index of 0.78. Percent agreement in species identification and reporting of Pf/Pv mixed infections were 27.2% and 22.4%, respectively. About 62.2% of the laboratory professionals reported parasite density using semi-quantitative method. While none of them reported per micro-liter method. Conclusions: The current study showed that laboratory professionals had good performance in parasite detection. However, poor performance was seen in both species identification and reporting of Pf/Pv mixed infections. [ABSTRACT FROM AUTHOR]

Antimalarial drug resistance is a major constraint for malaria control and elimination efforts. Artemisinin-based combination therapy is now the mainstay for malaria treatment. However, delayed parasite clearance following treatment with artemisinin derivatives has now spread in the Greater Mekong Sub region and may emerge or spread to other malaria endemic regions. This spread is of great concern for malaria control programmes, as no alternatives to artemisinin-based combination therapies are expected to be available in the near future. There is a need to strengthen surveillance systems for early detection and response to the antimalarial drug resistance threat. Current surveillance is mainly done through therapeutic efficacy studies; however these studies are complex and both time- and resource-intensive. For multiple common antimalarials, parasite drug resistance has been correlated with specific genetic mutations, and the molecular markers associated with antimalarial drug resistance offer a simple and powerful tool to monitor the emergence and spread of resistant parasites. Different techniques to analyse molecular markers associated with antimalarial drug resistance are available, each with advantages and disadvantages. However, procedures are not adequately harmonized to facilitate comparisons between sites. Here we describe the target product profiles for tests to analyse molecular markers associated with antimalarial drug resistance, discuss how use of current techniques can be standardised, and identify the requirements for an ideal product that would allow malaria endemic countries to provide useful spatial and temporal information on the spread of resistance. [ABSTRACT FROM AUTHOR]

In a Perspective on the research article from Jacobson and colleagues, Amitabh Suthar and colleagues from the Centers for Disease Control and Prevention discuss the importance of and considerations for developing real-time and large-scale reporting systems for tracking and controlling antimicrobial resistance. [ABSTRACT FROM AUTHOR]

The article discusses the use of digital medical technology in the diagnosis of African trypanosomiasis in humans and mentions the authors views on its benefits in providing quality assurance in diagnostic procedures. The use of technologies such as smartphone application, and digital imaging system as well as algorithms in diagnostic screening is discussed.

The article reflects on the need to bolster human rabies surveillance in Africa to eliminate canine-mediated rabies. It mentions that several organizations such as World Health Organization, World Organization for Animal Health, and Food and Agriculture Organization of the United Nations have proposed a feasible, strategic global plan to end canine-mediated human rabies by 2030. It highlights challenges in implementing an active surveillance system in rural areas of developing countries.

Background: South Africa has the highest tuberculosis incidence globally (781/100,000), with an estimated 4.3% of cases being rifampicin resistant (RR). Control and elimination strategies will require detailed spatial information to understand where drug-resistant tuberculosis exists and why it persists in those communities. We demonstrate a method to enable drug-resistant tuberculosis monitoring by identifying high-burden communities in the Western Cape Province using routinely collected laboratory data.Methods and Findings: We retrospectively identified cases of microbiologically confirmed tuberculosis and RR-tuberculosis from all biological samples submitted for tuberculosis testing (n = 2,219,891) to the Western Cape National Health Laboratory Services (NHLS) between January 1, 2008, and June 30, 2013. Because the NHLS database lacks unique patient identifiers, we performed a series of record-linking processes to match specimen records to individual patients. We counted an individual as having a single disease episode if their positive samples came from within two years of each other. Cases were aggregated by clinic location (n = 302) to estimate the percentage of tuberculosis cases with rifampicin resistance per clinic. We used inverse distance weighting (IDW) to produce heatmaps of the RR-tuberculosis percentage across the province. Regression was used to estimate annual changes in the RR-tuberculosis percentage by clinic, and estimated average size and direction of change was mapped. We identified 799,779 individuals who had specimens submitted from mappable clinics for testing, of whom 222,735 (27.8%) had microbiologically confirmed tuberculosis. The study population was 43% female, the median age was 36 years (IQR 27-44), and 10,255 (4.6%, 95% CI: 4.6-4.7) cases had documented rifampicin resistance. Among individuals with microbiologically confirmed tuberculosis, 8,947 (4.0%) had more than one disease episode during the study period. The percentage of tuberculosis cases with rifampicin resistance documented among these individuals was 11.4% (95% CI: 10.7-12.0). Overall, the percentage of tuberculosis cases that were RR-tuberculosis was spatially heterogeneous, ranging from 0% to 25% across the province. Our maps reveal significant yearly fluctuations in RR-tuberculosis percentages at several locations. Additionally, the directions of change over time in RR-tuberculosis percentage were not uniform. The main limitation of this study is the lack of unique patient identifiers in the NHLS database, rendering findings to be estimates reliant on the accuracy of the person-matching algorithm.Conclusions: Our maps reveal striking spatial and temporal heterogeneity in RR-tuberculosis percentages across this province. We demonstrate the potential to monitor RR-tuberculosis spatially and temporally with routinely collected laboratory data, enabling improved resource targeting and more rapid locally appropriate interventions. [ABSTRACT FROM AUTHOR]

Critical medium column theory has typically been used to predict the scope of caved rock zone (CRZ) caused by caving mining method. It is essential to understand the distribution laws of lateral pressure induced by caving mining method with different dipping angles. In this study, a self-designed scaled physical model was used to investigate the distribution laws with angles ranging from 80° to 90°, and ore drawing was employed in experiments to simulate caving mining method. The experimental results indicated that the distribution laws were divided into the reductive region and the extensive region during ore drawing. The reductive region was close to the drawing hole, and its scope was smaller than the other part. Moreover, decreasing the dipping angle was an effective way of controlling the maximum reduction rates and the scope of reductive region. By varying laws of lateral pressure, the predictive model of CRZs’ scope was established. Additionally, the rock mass located outside the predictive CRZs’ scope did not rupture based on the monitoring of Digital Optical Televiewing (OPTV), which was verified by the field test in Dabeishan Iron Mine, China. The results of the field test demonstrated that the prediction method used in this study was valid and could be used in practice. [ABSTRACT FROM AUTHOR]

Background: To determine the validity of the lactate threshold (LT) and maximal oxygen uptake () determined during graded exercise test (GXT) of different durations and using different LT calculations. Trained male cyclists (n = 17) completed five GXTs of varying stage length (1, 3, 4, 7 and 10 min) to establish the LT, and a series of 30-min constant power bouts to establish the maximal lactate steady state (MLSS). was assessed during each GXT and a subsequent verification exhaustive bout (VEB), and 14 different LTs were calculated from four of the GXTs (3, 4, 7 and 10 min)—yielding a total 56 LTs. Agreement was assessed between the highest measured during each GXT () as well as between each LT and MLSS. and LT data were analysed using mean difference (MD) and intraclass correlation (ICC). Results: The value from GXT1 was 61.0 ± 5.3 mL.kg-1.min-1 and the peak power 420 ± 55 W (mean ± SD). The power at the MLSS was 264 ± 39 W. from GXT3, 4, 7, 10 underestimated by ~1–5 mL.kg-1.min-1. Many of the traditional LT methods were not valid and a newly developed Modified Dmax method derived from GXT4 provided the most valid estimate of the MLSS (MD = 1.1 W; ICC = 0.96). Conclusion: The data highlight how GXT protocol design and data analysis influence the determination of both and LT. It is also apparent that and LT cannot be determined in a single GXT, even with the inclusion of a VEB. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) is an established cause of serious lower respiratory disease in infants, elderly and high-risk populations. The OUTSMART surveillance program aims to characterize patient populations and currently circulating RSV strains, and monitor temporal and geographic evolution of RSV F and G proteins in the U.S. Methods: The OUTSMART 2016–17 study collected RSV-positive samples from 25 RSVAlert® laboratories from 4 U.S. regions and Puerto Rico during November 2016 through March 2017. Frequencies of A and B subtypes and genotypes were determined for several demographic and geographic variables. To gauge the representativeness of the OUTSMART patients, results were compared to discharge data from the NEDS and NIS databases. Results: A total of 1,041 RSV-positive samples with associated demographic data were obtained and the RSV F gene and second variable region of the G gene were sequenced. The majority of samples (76.0%) came from children under 2 years old: <1 year (48.4%), 1–2 years (27.6%). The OUTSMART patient sample was similar to NEDS and NIS for age, gender, and geographic location. Both OUTSMART and national RSV cases peaked in January. Of OUTSMART samples, 45.3% were subtype A, 53.7% were subtype B and 1.0% were mixed A and B. The percentage of RSV B cases increased with increasing age. Hospitalization (length of hospital stay, LOS, >24 hrs) occurred in 29.0% of patients of which 52.0% had RSV B. Outpatients (LOS <24 hrs) were 64.4% of total of which 73.3% were diagnosed in the ER and discharged, while only 6% were diagnosed in other outpatient settings. Conclusions: The OUTSMART 2016–17 study was representative of the U.S. RSV experience. Geographic and temporal information from the RSV surveillance program will be used to establish a molecular baseline of RSV F and G sequence variability and to help inform development of novel agents for RSV prophylaxis and treatment. [ABSTRACT FROM AUTHOR]

Background: Screening pregnant women for HIV and syphilis is recommended by WHO in order to reduce mother-to-child transmission. We evaluated the field performance, feasibility, and acceptability of a dual rapid diagnostic test (RDT) for HIV and syphilis test in antenatal clinic settings in Nigeria. Methods and findings: Participants were recruited at 12 antenatal clinic sites in three states of Nigeria. All consenting individuals were tested according to the national HIV testing algorithm, as well as a dual RDT, the SD BIOLINE HIV/Syphilis Duo Test (Alere, USA), in the clinic. To determine sensitivity, specificity and concordance, whole blood samples were obtained for repeat RDT performance in the laboratory, as well as reference tests for HIV and syphilis. Dual test acceptability and operational characteristics were assessed among participants and clinic staff. The prevalence of HIV among the 4,551 enrollees was 3.0% (138/4551) using the national clinic-based HIV testing algorithm. Positive and negative percent agreement of the HIV component of the dual RDT were 100.0% (95% CI 99.7–100.0) and 99.9% (95% CI 99.7–100.0) respectively, when compared with the national rapid testing algorithm. The prevalence of syphilis, using TPHA as the reference test, was low at 0.09% (4/4550). The sensitivity of the syphilis component of the dual RDT could not be calculated as no positive results were observed for patients that were positive for syphilis by TPHA. Each of the only four TPHA-positive specimens had RPR titers of 1:1 (neat), indicative of non-active syphilis. The specificity of the syphilis component of the dual RDT was 99.9% (95% CI 99.8–100.0). The dual RDT received favorable feasibility ratings among antenatal care clinic staff. Acceptability among study participants was high with most women reporting preference for rapid dual HIV/syphilis testing. Conclusions: The SD BIOLINE HIV/Syphilis Duo Test showed a high overall diagnostic accuracy for HIV and a high specificity for syphilis diagnosis in antenatal clinic settings. This study adds to a growing body of evidence that supports the clinic-based use of dual tests for HIV and syphilis among pregnant women. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) incidence in South Africa is among the highest globally. Initial loss to follow-up (ILFU), defined as not starting on TB treatment within 28 days of testing positive, is undermining control efforts. We assessed the feasibility, acceptability, and potential of a mHealth application to reduce ILFU. Methods: An mHealth application was developed to capture patients TB investigation data, provide results and monitor treatment initiation. This was implemented in two primary health clinics (PHC) in inner-city Johannesburg. Feasibility was assessed by comparing documentation of personal details, specimen results for same individuals during implementation period (paper register and Mhealth application). Effectiveness was assessed by comparing proportion of patients with results within 48 hours, and proportion started on treatment within 28 days of testing TB positive during pre- implementation (paper register) and implementation (mHealth application) periods. In-depth interviews with patients and providers were conducted to assess acceptability of application. Results: Pre-implementation, 457 patients were recorded in paper registers [195 (42.7%) male, median age 34 years (interquartile range IQR (28–40), 45 (10.5%) sputum Xpert positive]. During implementation, 319 patients were recorded in paper register and the mHealth application [131 (41.1%) male, median age 32 years (IQR 27–38), 33 (10.3%) sputum Xpert positive]. The proportion with complete personal details: [mHealth 95.0% versus paper register 94.0%, (p = 0.54)] and proportion with documented results: [mHealth 97.4% versus paper register 97.8%, (p = 0.79)] were not different in the two methods. The proportion of results available within 48 hours: [mHealth 96.8% versus paper register 68.6%), (p <0.001)], and the proportion on treatment within 28 days [mHealth 28/33 (84.8%) versus paper register 30/44 (68.2%), (p = 0.08)] increased during implementation but was not statistically significant. In-depth interviews showed that providers easily integrated the mHealth application into routine TB investigation and patients positively received the delivery of results via text message. Time from sputum collection to TB treatment initiation decreased from 4 days (pre-implementation) to 3 days but was not statistically significant. Conclusions: We demonstrated that implementation of the mHealth application was feasible, acceptable to health care providers and patients, and has potential to reduce the time to TB treatment initiation and ILFU in PHC settings. [ABSTRACT FROM AUTHOR]

Objective: Since 1987 all fecal samples referred to the clinical microbiology laboratory of the UZ Brussel were screened for the presence of Shiga toxin-producing E. coli (STEC). In this study all STEC strains isolated over a period of 27 years (1987–2014) were reexamined to achieve deeper insight in the STEC infections in our patient population. Methods: A total of 606 STEC strains from 604 patients were subjected to molecular methods for shiga toxin (stx) subtyping, detection of additional virulence genes, typing of the O-serogroups, and phylogenetic relatedness assessment of STEC O157:H7/H-. Results: Since the introduction of PCR in 1991 the annual positivity rates varied between 1.1% and 2.7%. The isolation rate of STEC O157:H7/H- remained stable over the years while the isolation rate of non-O157 serotypes increased, mainly since 2011. The majority of the patients were children. Uncomplicated- and bloody diarrhea were the most prevalent gastrointestinal manifestations (respectively 51.9% and 13.6%), 4.3% of the strains were related to the hemolytic uremic syndrome (HUS), and 30.2% of the patients showed none of these symptoms. The strains were very diverse; they belonged to 72 different O-serovars and all stx subtypes except stx1d and stx2g were identified. Out of the 23 stx2f-positives one was associated with HUS and one belonged to the E. albertii species. As seen in other studies, the frequency of strains of the O157:H7/H- serotype and strains carrying stx2a, eaeA and ehxA was higher in patients with HUS. Conclusions: The characteristics and trends of STEC infection seen in our patient population are similar to those noted in other countries. STEC infections in our hospital are mainly sporadic, and a substantial portion of the patients were asymptomatic carriers. Human STEC Stx2f infection was less rare than previously assumed and we report the first Belgian STEC stx2f HUS case and stx2f positive E. albertii infection. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis is a major public health problem in Liberia. According to the World Health Organization (WHO), the incidence of tuberculosis in Liberia is significantly increasing from year to year. However, little is known about the performance of the programme and the challenges after the 14 years of civil war which ended in 2003.The purpose of the study was to evaluate the performance of the TB programme of Liberia. Methods: The study utilised mixed research design; both quantitative and qualitative methods were used in this study conducted from 2013 to 2014. For the quantitative part of the study, a questionnaire, laboratory performance and eleven years TB programme data (2003–2013) were used. For the performance of tuberculosis laboratory testing, all the 107 functional tuberculosis microscopy centers in Liberia were included. For the qualitative part of the study, an interview of 10 informants and two focus group discussions (FGDs) were also conducted, each comprising of eight people. Themes and subthemes emerged from the two FGDs. Data was analysed in line with the Donabedian model. Quantitative findings were analysed and presented using both descriptive and inferential statistics. Results: The study findings pointed out that there was overall improvement in the performance of the tuberculosis control programme in Liberia from 2003 to 2013. The percentage of cured patients was 60% in 2005 and 62% in 2013. Percentage of treatment completed was 16% in 2005 and 21% in 2013. The case detection rate was 57% and treatment success rate 80% in 2013. The default rate was 11% in 2013. Of the 139 participants, 120 (86%) completed TB treatment while 19 (14%) did not. Conclusion: Between 2003 and 2013, the National Leprosy and Tuberculosis Control Programme (NLTCP) succeeded in restoring the TB services and improving some of the TB treatment outcomes including the Directly observed treatment short courses(DOTS) coverage. Despite these improvements, the TB treatment, laboratory services and human resource capacity lagged behind. The TB programme of Liberia needs to develop new strategies to address its challenges. [ABSTRACT FROM AUTHOR]

Objectives: Quality of tuberculosis (TB) microscopy diagnosis is not a guarantee despite implementation of External Quality Assurance (EQA) service in all laboratories of health facilities. Hence, we aimed at evaluating the technical quality and the findings of sputum smear microscopy for acid fast bacilli (AFB) at health centers in Hararge Zone, Oromia Region, Ethiopia. Methods: A cross-sectional study was carried out between July 8, 2014 and July 7, 2015.A pre-tested structured questionnaire was used to collect data. Lot Quality Assurance Sampling (LQAS) method was put into practice for collecting all necessary sample slides. Data were analyzed by using SPSS (Statistical Package for Social Sciences) version 20 software. P-value < 0.05 was considered as statistically significant. Results: Of the total55 health center laboratories which had been assessed during the study period, 20 (36.4%) had major technical errors; 13 (23.6%) had 15 false negative results and 17 (30.9%) had 22 false positive results. Moreover, poor specimen quality, smear size, smear thickness, staining and evenness were indicated in 40 (72.7%), 39 (70.9%), 37 (67.3%), 27(49.1%) and 37 (67.3%) of the collected samples, respectively. False negative AFB findings were significantly associated with lack of Internal Quality Control (IQC) measures (AOR (Adjusted Odds Ratio): 2.90 (95% CI (Confidence Interval): 1.25,6.75) and poor staining procedures (AOR: 2.16(95% CI: 1.01, 5.11). Conclusions: The qualities of AFB smear microscopy reading and smearing were low in most of the laboratories of the health centers. Therefore, it is essential to strength EQA program through building the capacity of laboratory professionals. [ABSTRACT FROM AUTHOR]

Background: Failure to timely diagnose HIV in infants is a major barrier for scaling-up paediatric antiretroviral treatment (ART). WHO recommends birth testing for earlier diagnosis and to improve test coverage, but current diagnosis takes 2–3 weeks to complete, thereby limiting the ability of care givers to provide follow-on care, especially in low-resource settings. We evaluated the benefit of implementing rapid diagnosis of HIV at birth in primary health care maternity wards in Mozambique. Methods and findings: Infants born to HIV-infected mothers delivering consecutively at eight primary health care clinics were tested within 24 hours of delivery using on-site POC (Alere q HIV1/2 Detect) and standard laboratory (Roche COBAS AmpliPrep/TaqMan HIV-1 qualitative assay v2.0) testing. Infants were also tested at 4–6 weeks of age with both assays. Of 2,350 HIV-exposed infants enrolled in this implementation research study, 33 tested HIV-positive at birth on both assays. Sensitivity and specificity of POC testing compared with laboratory testing at birth were 100% (95% CI 89·4–100·0) and 100% (95% CI 99·8–100·0), respectively. At 4–6 weeks of age, 61 infants were identified as HIV-positive; of these 29 (47·5%) had a positive test at birth. Testing at both birth and 4–6 weeks identified 71 HIV-positive infants compared with 61 infants by testing at 4–6 weeks alone, a 16% increase. Two infants tested positive at birth but tested HIV-negative during follow-up. Conclusions: Adding POC birth testing to the 4–6 week screen may increase access to HIV diagnosis and expedite ART initiation in primary health care settings within low resource settings. Guidance on appropriate confirmatory HIV testing algorithms for birth testing is needed. [ABSTRACT FROM AUTHOR]

Introduction: Timely notification of infectious diseases is crucial for prompt response by public health services. Adequate notification systems facilitate timely notification. A systematic literature review was performed to assess outcomes of studies on notification timeliness and to determine which aspects of notification systems are associated with timely notification. Methodology: Articles reviewing timeliness of notifications published between 2000 and 2017 were searched in Pubmed and Scopus. Using a standardized notification chain, timeliness of reporting system for each article was defined as either sufficient (≥ 80% notifications in time), partly sufficient (≥ 50–80%), or insufficient (< 50%) according to the article’s predefined timeframe, a standardized timeframe for all articles, and a disease specific timeframe. Electronic notification systems were compared with conventional methods (postal mail, fax, telephone, email) and mobile phone reporting. Results: 48 articles were identified. In almost one third of the studies with a predefined timeframe (39), timeliness of notification systems was either sufficient or insufficient (11/39, 28% and 12/39, 31% resp.). Applying the standardized timeframe (45 studies) revealed similar outcomes (13/45, 29%, sufficient notification timeframe, vs 15/45, 33%, insufficient). The disease specific timeframe was not met by any study. Systems involving reporting by laboratories most often complied sufficiently with predefined or standardized timeframes. Outcomes were not related to electronic, conventional notification systems or mobile phone reporting. Electronic systems were faster in comparative studies (10/13); this hardly resulted in sufficient timeliness, neither according to predefined nor to standardized timeframes. Conclusion: A minority of notification systems meets either predefined, standardized or disease specific timeframes. Systems including laboratory reporting are associated with timely notification. Electronic systems reduce reporting delay, but implementation needs considerable effort to comply with notification timeframes. During outbreak threats, patient, doctors and laboratory testing delays need to be reduced to achieve timely detection and notification. Public health authorities should incorporate procedures for this in their preparedness plans. [ABSTRACT FROM AUTHOR]

Background: Systematic reviews have described high rates of attrition in patients with HIV receiving antiretroviral therapy (ART). However, migration and clinical transfer may lead to an overestimation of attrition (death and loss to follow-up). Using a newly linked national laboratory database in South Africa, we assessed national retention in South Africa's national HIV program.Methods and Findings: Patients receiving care in South Africa's national HIV program are monitored through regular CD4 count and viral load testing. South Africa's National Health Laboratory Service has maintained a database of all public-sector CD4 count and viral load results since 2004. We linked individual laboratory results to patients using probabilistic matching techniques, creating a national HIV cohort. Validation of our approach in comparison to a manually matched dataset showed 9.0% undermatching and 9.5% overmatching. We analyzed data on patients initiating ART in the public sector from April 1, 2004, to December 31, 2006, when ART initiation could be determined based on first viral load among those whose treatment followed guidelines. Attrition occurred on the date of a patient's last observed laboratory measure, allowing patients to exit and reenter care prior to that date. All patients had 6 potential years of follow-up, with an additional 2 years to have a final laboratory measurement to be retained at 6 years. Data were censored at December 31, 2012. We assessed (a) national retention including all laboratory tests regardless of testing facility and (b) initiating facility retention, where laboratory tests at other facilities were ignored. We followed 55,836 patients initiating ART between 2004 and 2006. At ART initiation, median age was 36 years (IQR: 30-43), median CD4 count was 150 cells/mm3 (IQR: 81-230), and 66.7% were female. Six-year initiating clinic retention was 29.1% (95% CI: 28.7%-29.5%). After allowing for transfers, national 6-year retention was 63.3% (95% CI: 62.9%-63.7%). Results differed little when tightening or relaxing matching procedures. We found strong differences in retention by province, ranging from 74.2% (95% CI: 73.2%-75.2%) in Western Cape to 52.2% (95% CI: 50.6%-53.7%) in Mpumalanga at 6 years. National attrition was higher among patients initiating at lower CD4 counts and higher viral loads, and among patients initiating ART at larger facilities. The study's main limitation is lack of perfect cohort matching, which may lead to over- or underestimation of retention. We also did not have data from KwaZulu-Natal province prior to 2010.Conclusions: In this study, HIV care retention was substantially higher when viewed from a national perspective than from a facility perspective. Our results suggest that traditional clinical cohorts underestimate retention. [ABSTRACT FROM AUTHOR]

Introduction: Cryptococcal meningitis (CM) is an opportunistic fungal disease with a high mortality among HIV-positive patients with severe immunosuppression (CD4 count <100 cells/μl). Reflexed screening for cryptococcal antigen (CrAg) in remnant blood samples was initially piloted at selected CD4 testing laboratories of the National Health Laboratory Service (NHLS) prior to the implementation of a national screening programme using a lateral flow assay (LFA) (IMMY, Norman, OK, USA). The aim of this study was to assess CrAg positivity nationally, per province and district in combination with the percentage of CD4 samples tested with a CD4 count <100 cells/μl to identify areas with advanced HIV/CrAg disease burden. Methods: CrAg and CD4 laboratory result data were extracted from the NHLS corporate data warehouse. Monthly test volumes were used to assess CrAg test volumes and coverage, while bubble charts were used to display the relationship between CD4 <100 cells/μl, CrAg positivity and number of positive CrAg samples by district. ArcGIS software was used to spatially report CrAg positivity. Results: CrAg screening coverage was stable at around 96% after November 2016. Samples with a CD4 <100 cell/μl and CrAg positivity were also stable over the study period at 10% and ~5% respectively. The highest CrAg positivity was reported for the Kwa-Zulu Natal province (7.3%), which also had the lowest percentage of samples with a CD4 <100 cells/μl (7.2%). Uthungulu and Umkhanyakude districts had the highest CrAg positivity (9.3% and 8.9% respectively). Ethekwini and Johannesburg Metro districts contributed to 22% of the total number of CrAg-positive samples tested across South Africa for the period reported. Conclusion: Existing CD4 testing services were used to rapidly scale up CrAg reflex testing in South Africa. Districts with advanced HIV and CrAg disease burden were identified that need further investigation of patient management interventions. [ABSTRACT FROM AUTHOR]

Background: There are racial, ethnic and geographical differences in complete blood count (CBC) reference intervals (RIs) and therefore it is necessary to establish RIs that are population specific. Several studies have been carried out in Africa to derive CBC RIs but many were not conducted with the rigor recommended for RI studies hence limiting the adoption and generalizability of the results. Method: By use of a Beckman Coulter ACT 5 DIFF CP analyser, we measured CBC parameters in samples collected from 528 healthy black African volunteers in a largely urban population. The latent abnormal values exclusion (LAVE) method was used for secondary exclusion of individuals who may have had sub-clinical diseases. The RIs were derived by both parametric and non-parametric methods with and without LAVE for comparative purposes. Results: Haemoglobin (Hb) levels were lower while platelet counts were higher in females across the 4 age stratifications. The lower limits for Hb and red blood cell parameters significantly increased after applying the LAVE method which eliminated individuals with latent anemia and inflammation. We adopted RIs by parametric method because 90% confidence intervals of the RI limits were invariably narrower than those by the non-parametric method. The male and female RIs for Hb after applying the LAVE method were 14.5–18.7 g/dL and 12.0–16.5 g/dL respectively while the platelet count RIs were 133–356 and 152–443 x103 per μL respectively. Conclusion: Consistent with other studies from Sub-Saharan Africa, Hb and neutrophil counts were lower than Caucasian values. Our finding of higher Hb and lower eosinophil counts compared to other studies conducted in rural Kenya most likely reflects the strict recruitment criteria and healthier reference population after secondary exclusion of individuals with possible sub-clinical diseases. [ABSTRACT FROM AUTHOR]

Between August-2016 and April-2017, Solomon Islands experienced the largest and longest-running dengue outbreak on record in the country, with 12,329 suspected cases, 877 hospitalisations and 16 deaths. We conducted a retrospective review of related data and documents, and conducted key informant interviews to characterise the event and investigate the adaptability of syndromic surveillance for enhanced and expanded data collection during a public health emergency in a low resource country setting. While the outbreak quickly consumed available public and clinical resources, we found that authorities were able to scale up the conventional national syndrome-based early warning surveillance system to support the increased information demands during the event demonstrating the flexibility of the system and syndromic surveillance more broadly. Challenges in scaling up included upskilling and assisting staff with no previous experience of the tasks required; managing large volumes of data; maintaining data quality for the duration of the outbreak; harmonising routine and enhanced surveillance data and maintaining surveillance for other diseases; producing information optimally useful for response planning; and managing staff fatigue. Solomon Islands, along with other countries of the region remains vulnerable to outbreaks of dengue and other communicable diseases. Ensuring surveillance systems are robust and able to adapt to changing demands during emergencies should be a health protection priority. [ABSTRACT FROM AUTHOR]