Factors influencing operationalization of Integrated Disease Surveillance in Malawi.

OBJECTIVES: Malawi's disease surveillance system is built on several different data sources and systems and is informed by the Integrated Diseases Surveillance and Response (IDSR) strategy. This study was carried out as part of a larger multicountry study to identify context-specific factors, which influence the operationalization of integrated disease surveillance. STUDY DESIGN AND METHODS: A total of six focus group discussions were conducted with 43 relevant personnel at the primary and secondary healthcare levels in two districts (Lilongwe and Dowa) and at the national level. The discussions were analyzed and sorted into predefined categories based on the domains of the International Association of Public Health conceptual framework. RESULTS: We found ongoing efforts to enhance integrated disease surveillance operationalization, including the establishment of the Public Health Institute of Malawi for coordination, digitalizing the surveillance system through One Health Surveillance Platform, and improving communication among rapid response teams using WhatsApp. The adoption of World Health Organization's third edition IDSR technical guidelines was also underway. Nonetheless, there were major implementation barriers such as parallel and uncoordinated surveillance systems, priority conditions that cannot be diagnosed at the point of reporting, lack of case definitions and diagnostic codes for priority conditions, reporting forms with unexplained acronyms, illegible data sources, unstable electronic data transfers, inadequate supervision and training, poor enforcement of reporting from private health facilities, high reporting burden, and lack of and feedback to those reporting. CONCLUSIONS: The results fit well into the predefined categories used. The study reveals basic problems with the operationalization, tools, and reporting forms used for IDSR. These findings may have implications for practice and policy in Malawi and other countries where IDSR is the national strategy for surveillance.

The state of integrated disease surveillance in seven countries: a synthesis report.

OBJECTIVES: Integrated disease surveillance (IDS) offers the potential for better use of surveillance data to guide responses to public health threats. However, the extent of IDS implementation worldwide is unknown. This study sought to understand how IDS is operationalized, identify implementation challenges and barriers, and identify opportunities for development. STUDY DESIGN: Synthesis of qualitative studies undertaken in seven countries. METHODS: Thirty-four focus group discussions and 48 key informant interviews were undertaken in Pakistan, Mozambique, Malawi, Uganda, Sweden, Canada, and England, with data collection led by the respective national public health institutes. Data were thematically analysed using a conceptual framework that covered governance, system and structure, core functions, finance and resourcing requirements. Emerging themes were then synthesised across countries for comparisons. RESULTS: None of the countries studied had fully integrated surveillance systems. Surveillance was often fragmented, and the conceptualization of integration varied. Barriers and facilitators identified included: 1) the need for clarity of purpose to guide integration activities; 2) challenges arising from unclear or shared ownership; 3) incompatibility of existing IT systems and surveillance infrastructure; 4) workforce and skills requirements; 5) legal environment to facilitate data sharing between agencies; and 6) resourcing to drive integration. In countries dependent on external funding, the focus on single diseases limited integration and created parallel systems. CONCLUSIONS: A plurality of surveillance systems exists globally with varying levels of maturity. While development of an international framework and standards are urgently needed to guide integration efforts, these must be tailored to country contexts and guided by their overarching purpose.

Tuberculosis in the Circumpolar Region, 2006-2012.

SETTING: The northern circumpolar jurisdictions Canada (Northwest Territories, Nunavik, Nunavut, Yukon), Finland, Greenland, Norway, Russian Federation (Arkhangelsk), Sweden and the United States (Alaska). OBJECTIVE: To describe and compare demographic, clinical and laboratory characteristics, including drug resistance and treatment completion, of tuberculosis (TB) cases in the northern circumpolar populations. DESIGN: Descriptive analysis of all active TB cases reported from 2006 to 2012 for incidence rate (IR), age and sex distribution, sputum smear and diagnostic site characteristics, drug resistance and treatment completion rates. RESULTS: The annual IR of TB disease ranged from a low of 4.3 per 100 000 population in Northern Sweden to a high of 199.5/100 000 in Nunavik, QC, Canada. For all jurisdictions, IR was higher for males than for females. Yukon had the highest proportion of new cases compared with retreatment cases (96.6%). Alaska reported the highest percentage of laboratory-confirmed cases (87.4%). Smear-positive pulmonary cases ranged from 25.8% to 65.2%. Multidrug-resistant cases ranged from 0% (Northern Canada) to 46.3% (Arkhangelsk). Treatment outcome data, available up to 2011, demonstrated >80% treatment completion for four of the 10 jurisdictions. CONCLUSION: TB remains a serious public health issue in the circumpolar regions. Surveillance data contribute toward a better understanding and improved control of TB in the north.

Tuberculosis and latent tuberculous infection screening of migrants in Europe: comparative analysis of policies, surveillance systems and results.

Migration patterns into and within Europe have changed over the last decade. In 2015, European Union (EU) countries received over 1.2 million asylum requests, more than double the number registered in the previous year. This review compares the published literature on policies for tuberculosis (TB) and latent tuberculous infection (LTBI) screening in EU and European Free Trade Association (EFTA) countries with the existing TB/LTBI screening programmes for migrants in 11 EU/EFTA countries based on a survey of policy and surveillance systems. In addition, we provide a systematic review of the literature on the yield of screening migrants for active TB and LTBI in Europe. Published studies provide limited information about screening coverage and the yield of screening evaluations in EU/EFTA countries. Furthermore, countries use different screening strategies and settings, and different definitions for coverage and yield of screening for active TB and LTBI. We recommend harmonising case definitions, reporting standards and policies for TB/LTBI screening. To achieve TB elimination targets, a European platform for multi-country data collection and analysis, sharing of countries' policies and practices, and harmonisation of migrant screening strategies is needed.

Outbreak of wound botulism in people who inject drugs, Norway, October to November 2013.

In October and November 2013, four cases of wound botulism were confirmed in people who inject drugs (PWID) in Norway. Two additional cases are suspected. Because of the international distribution pathways for heroin ­ the likely source of the outbreak ­ healthcare workers and public health authorities in other countries should remain vigilant for wound botulism in PWID. This outbreak serves as a reminder that countries should ensure access to botulinum antitoxin in case of outbreak situations.

Protein N-terminal acetyltransferases in cancer.

The human N-terminal acetyltransferases (NATs) catalyze the transfer of acetyl moieties to the N-termini of 80-90% of all human proteins. Six NAT types are present in humans, NatA-NatF, each is composed of specific subunits and each acetylates a set of substrates defined by the N-terminal amino-acid sequence. NATs have been suggested to act as oncoproteins as well as tumor suppressors in human cancers, and NAT expression may be both elevated and decreased in cancer versus non-cancer tissues. Manipulation of NATs in cancer cells induced cell-cycle arrest, apoptosis or autophagy, implying that these enzymes target a variety of pathways. Of particular interest is hNaa10p (human ARD1), the catalytic subunit of the NatA complex, which was coupled to a number of signaling molecules including hypoxia inducible factor-1α, ß-catenin/cyclin D1, TSC2/mammalian target of rapamycin, myosin light chain kinase , DNA methyltransferase1/E-cadherin and p21-activated kinase-interacting exchange factors (PIX)/Cdc42/Rac1. The variety of mechanistic links where hNaa10p acts as a NAT, a lysine acetyltransferase or displaying a non-catalytic role, provide insights to how hNaa10p may act as both a tumor suppressor and oncoprotein.

Measles virus genotyping an important tool in measles outbreak investigation in Norway, 2011.

This study describes 33 laboratory-confirmed cases of measles that occurred in Norway in 2011, mainly among unvaccinated children between seven months and 10 years of age. Laboratory testing included detection of anti-measles IgM- and IgG antibodies by enzyme-linked immunosorbent assay (ELISA) and molecular detection and characterisation of measles virus by polymerase chain reaction (PCR) and sequencing. Epidemiological data and genotyping revealed that the measles cases originated from eight separate importations, resulting in four outbreaks and four sporadic cases. Except for the first outbreak which affected 18 cases, limited secondary spread occurred in each of the three other outbreaks. The outbreaks were caused by measles virus genotypes B3, D4 and D9, whereas genotypes D8 and B3 were detected in the sporadic cases. This study highlights that genetic characterisation of measles virus is an essential tool in the laboratory surveillance of measles, especially in countries like Norway which are approaching the measles elimination goal. The investigation revealed that importation of measles resulted in subsequent transmission within Norway to non-vaccinated individuals, and twelve cases occurred in healthcare settings, involving both staff and children. The four cases detected among healthcare workers (HCWs) emphasised that the coverage of measles-mumps-rubella (MMR) vaccination among healthcare personnel needs to be improved and both primary and secondary vaccine failure was demonstrated in two fully immunised HCWs.

Ongoing outbreak of measles in Oslo, Norway, January-February 2011.

Between 19 January and 17 February 2011, 10 cases of measles (eight laboratory-confirmed and two probable) were reported in Oslo with the majority of cases in a mainly unvaccinated immigrant community. Of these, two cases were identified outside the immigrant community, in Norwegian children.

Induction of apoptosis in human cells by RNAi-mediated knockdown of hARD1 and NATH, components of the protein N-alpha-acetyltransferase complex.

Protein N-epsilon-acetylation is recognized as an important modification influencing many biological processes, and protein deacetylase inhibitors leading to N-epsilon-hyperacetylation of histones are being clinically tested for their potential as anticancer drugs. In contrast to N-epsilon-acetyltransferases, the N-alpha-acetyltransferases transferring acetyl groups to the alpha-amino groups of protein N-termini have only been briefly described in mammalians. Human arrest defective 1 (hARD1), the only described human enzyme in this class, complexes with N-acetyltransferase human (NATH) and cotranslationally transfers acetyl groups to the N-termini of nascent polypeptides. Here, we demonstrate that knockdown of NATH and/or hARD1 triggers apoptosis in human cell lines. Knockdown of hARD1 also sensitized cells to daunorubicin-induced apoptosis, potentially pointing at the NATH-hARD1 acetyltransferase complex as a novel target for chemotherapy. Our results argue for an essential role of the NATH-hARD1 complex in cell survival and underscore the importance of protein N-alpha-acetylation in mammalian cells.

Resection margins in conization as prognostic marker for relapse in high-grade dysplasia of the uterine cervix in northern Norway: a retrospective long-term follow-up material.

OBJECTIVE: The main intention of the current study was to evaluate free resection margins in cervical conization specimens as prognostic marker by investigating the statistical association between clear or unclear resection margins of cervical cones and the risk of recurrence. METHODS: In a retrospective material, 459 women with moderate (CIN II) and severe dysplasia (CIN III) were included. Fifty of the patients were diagnosed with CIN II (10.9%) and 409 with CIN III (89.1%). Cold knife conization was performed in 371 (81%) patients, the rest were treated with CO(2) laser (19%). All the patients had been treated with conization between 1980 and 1984, follow-up time being from 19 to 23 years. Mean age of the patients was 35.2 years (range 18-81 years) at operation. The histopathological material and the results of the follow-up biopsies and smears were accessible as archival material. RESULTS: A total of 379 (82.6%) patients had clear margins in the primary operation specimens, in 80 patients margins were unclear (17.4%). There were three recurrences in the CIN II group (6%) and 39 (9.5%) in the CIN III group. Further there were 42 (9.2%) relapses in the total group, 36 relapses in the cold-knife group and 6 in the laser group. When univariate analysis was performed to investigate the statistical relation between the resection margins and recurrences, there was no significant correlation (P = 0.7, P > 0.05). Nor did variables like CIN group, surgical procedure, age at disease, age at recurrence, and years till recurrence prove to be predictors of relapses. CONCLUSION: In our material, the relation between free margins and relapse was not statistically significant. According to the literature-free resection margin is not an optimal prognostic criterion for recurrence. The search for new prognostic markers for high-risk cases are important to give these patients adequate therapy and avoiding over-treatment of the low risk groups.

Quantifying quality of life for economic analysis: time out for time tradeoff.

The "Time trade-off" (TTO), is the most widely used method to "quality adjust" life years for "QALYs" in cost utility analysis. In this paper we ask if it is theoretically likely that the TTO is valid for this use. The TTO consists in a trade off between longevity and quality of life. Firstly, we argue that it is impossible to control for all factors that may influence one's willingness to sacrifice lifetime. Secondly, that longevity and quality of life are too closely interrelated for the hypothetical trade off to reveal real preferences. Thirdly, that the TTO handles the value of a life year inconsistently because it simultaneously assumes that it changes (as an outcome measure) and that it doesn't change (as a currency unit). Lastly, we ask whether the difficulties stem from an inherent contradiction in trying to quantify quality of life. The problems theoretical validity an internal consistency, contrast the use of the results as exact measurements. We conclude that cost utility analysis based on TTO cannot be trusted as a tool for setting priorities in health.

Coping with obligations towards patient and society: an empirical study of attitudes and practice among Norwegian physicians.

A questionnaire relating to attitudes towards setting economic priorities within the health care system was sent to all 151 general practitioners in Northern Norway. Of these, 109 (72 per cent) responded. Ninety-six per cent of the respondents agreed or partly agreed that the setting of economic priorities within the health care system was necessary. Ninety-three per cent had experienced a conflict between their responsibility towards the individual patient and the requirement for them to manage the health budget. The responses suggest that doctors act more in the interests of their patient than the interests of society. However, 68 per cent reported having refrained from giving the best treatment to patients because it was too expensive. As many as 60 per cent of the respondents wanted more public guidelines. Only 10 per cent wanted doctors to have more influence in difficult questions arising from setting priorities.

[Is the main goal of the health care services to produce health?]. / Er helsevesenets viktigste oppgave å produsere helse?

A questionnaire on the relative weight attached to severity of disease and health gain when allocating scarce resources between patient groups was answered by 99 doctors in general practice. The same questionnaire had been previously answered by politicians. Doctors and politicians alike tended to emphasize severity of disease rather than health gain when allocating scarce resources. Furthermore, many did not emphasize either of these factors, but distributed the resources equally between the different patient groups. If the patients were equally ill, the doctors attached greater weight than the politicians did to health gain. The answers to the questionnaire indicate that the obligation to help the most seriously ill and to uphold the ideal of equality are regarded as more fundamental than the goal of producing health effectively.

[Immuno-filtration. A new principle of analysis exemplified by the determination of HCG]. / Immunfiltrering. Et nytt analyseprinsipp belyst ved eksemplet HCG-Bestemmelse.

PIP: A rapid quantitative test for human chorionic gonadotropin (HCG) is useful for diagnosis of extra-Uterine pregnancy. The development of monoclonal antibodies has made it possible to produce immuno-filters of very high specific sensitivity. The reported tests were performed on samples from 90 patients with varying diagnoses. The HCG levels determined in the tests were checked against radioimmunoassay tests standardized to World Health Organization 1st international standard. Urine has traditionally been the sample material for simple tests of HCG, but early tests were easily spoiled by any protein present in the urine, for example, from weak hematuria. The new immuno-filtration technique washes protein and other interfering materials away. The new technique is better suited for measuring HCG concentration in serum since the HCG concentration does not vary so much as it does in urine. The Tandem Icon HCG Hybritech test has been found to be nearly 100% specific and 100% sensitive. The extremely high sensitivity which will show a positive test many days before expected menstruation for normal pregnancy. There is a disadvantage in that perhaps 50% of all initial pregnancies are spontaneously aborted in the course of the 1st few weeks of pregnancy. False hopes can be aroused. By timing the development of the blue indicator spot with a stopwatch, changes in HCG concentration may be plotted over time for a patient for better control of the pregnancy diagnosis.^ieng