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Individuals infected with HIV display varying rates of viral control and disease progression, with a small percentage of individuals being able to spontaneously control infection in the absence of treatment. In attempting to define the correlates associated with natural protection against HIV, extreme heterogeneity in the datasets generated from systems methodologies can be further complicated by the inherent variability encountered at the population, individual, cellular and molecular levels. Furthermore, such studies have been limited by the paucity of well-characterised samples and linked epidemiological data, including duration of infection and clinical outcomes. To address this, we selected 10 volunteers who rapidly and persistently controlled HIV, and 10 volunteers each, from two control groups who failed to control (based on set point viral loads) from an acute and early HIV prospective cohort from East and Southern Africa. A propensity score matching approach was applied to control for the influence of five factors (age, risk group, virus subtype, gender, and country) known to influence disease progression on causal observations. Fifty-two plasma proteins were assessed at two timepoints in the 1st year of infection. We independently confirmed factors known to influence disease progression such as the B*57 HLA Class I allele, and infecting virus Subtype. We demonstrated associations between circulating levels of MIP-1α and IL-17C, and the ability to control infection. IL-17C has not been described previously within the context of HIV control, making it an interesting target for future studies to understand HIV infection and transmission. An in-depth systems analysis is now underway to fully characterise host, viral and immunological factors contributing to control.

This study examined whether CD8+ T-cell responses from coronavirus disease 2019 convalescent individuals (n = 30) potentially maintain recognition of the major severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants (alpha, beta, gamma; n = 45 mutations assessed). Only 1 mutation found in Beta variant-spike overlapped with a previously identified epitope (1/52), suggesting that virtually all anti-SARS-CoV-2 CD8+ T-cell responses should recognize these newly described variants.

Background Understanding the diversity, breadth, magnitude, and functional profile of the T cell response against SARS-CoV-2 in recovered COVID-19 individuals is critical to evaluate the contribution of T cells to produce a potentially protective immune response. Methods We used a multiplexed peptide-MHC tetramer approach to screen a total of 408 SARS-CoV-2 candidate peptide epitopes for CD8+ T cell recognition in a cohort of 30 individuals recovered from COVID-19. The peptides spanned the whole viral genome and were restricted to six prevalent HLA alleles; T cells were simultaneously characterized by a 28-marker phenotypic panel. The evolution of the SARS-CoV-2 T cell responses was then statistically modeled against time from diagnosis, and in relation to humoral and inflammatory response. Workflow for Study. A multiplexed peptide-MHC tetramer approach was used to screen SARS-CoV-2 candidate peptide epitopes in a cohort of 30 COVID-19 recovered patients across 6 prevalent HLA alleles, and T cells profiled with a 28-marker phenotypic panel. Multiplex tetramer screen. One representative COVID-19 recovered patient and one healthy donor were screened for HLA- relevant SARS-CoV-2 epitopes, as well as epitopes for CMV, EBV, Influenza, Adenovirus and MART-1. Shown are the frequencies of tetramer-positive CD8 T cells from 2 technical replicates per subject. Results Almost all individuals screened showed a T cell response against SARS-CoV-2 (29/30): 132 SARS-CoV-2-specific CD8+ T cells hits were detected, corresponding to 52 unique reactive epitopes. Twelve of the 52 unique SARS-CoV-2-specific epitopes were recognized by more than 40% of the individuals screened, indicating high prevalence in the subjects. Importantly, these CD8+ T cell responses were directed against both structural and non-structural viral proteins, with the highest magnitude against nucleocapsid derived peptides, but without any antigen-driven bias in the phenotype of specific T cells. Overall, SARS-CoV-2 T cells showed specific states of differentiation (stem-cell memory and transitional memory), which differed from those of MART-1, influenza, CMV and EBV-specific T cells. UMAP visualization revealed a phenotypic profile of SARS-CoV-2-specific CD8 T cells in COVID-19 convalescent donors that is distinct from other viral specificities, such as influenza, CMV, EBV and Adenovirus. SARS-CoV-2 epitope screening revealed CD8+ T cell responses directed against both structural and non-structural viral proteins, with the highest magnitude response against nucleocapsid derived peptides Conclusion The kinetics modeling demonstrates a dynamic, evolving immune response characterized by a time-dependent decrease in overall inflammation, increase in neutralizing antibody titer, and progressive differentiation of a broad SARS-CoV-2 CD8 T cell response. It could be desirable to aim at recapitulating the hallmarks of this robust CD8 T cell response in the design of protective COVID-19 vaccines. Disclosures Hassen Kared, PhD, ImmunoScape (Shareholder) Alessandra Nardin, DvM, ImmunoScape (Shareholder) Hermi Sumatoh, BSc, Dip MTech, ImmunoScape (Shareholder) Faris Kairi, BSc, ImmunoScape (Shareholder) Daniel Carbajo, PhD, ImmunoScape (Shareholder) Brian Abel, PhD, MBA, ImmunoScape (Shareholder) Evan Newell, PhD, ImmunoScape (Shareholder)

e15204 Background: During clinical trial immune monitoring, especially in the field of immunotherapy, it is critical to collect in-depth phenotypic information from multiple immune cell populations in order to assess the biological activity of the immunotherapy, to identify biomarkers of response or disease progression, and/or to identify new drug targets. However, patient samples such as peripheral blood mononuclear cells or tissues, are often scarce and current methods face limitations in either achieving a sufficient depth of analysis and/or cell throughput. Methods: In order to identify therapy-relevant antigens and to facilitate a concurrent in-depth characterization of T cells directed towards these targets, immunoSCAPE leverages the high-dimensional immune profiling capabilities of mass cytometry and a unique methodology allowing the identification and characterization of rare antigen-specific T-cell subsets (targetSCAPE). By implementing a new cutting-edge technology that combines flow and mass cytometry in parallel with a combinatorial live cell barcoding strategy, we further increased the high-dimensional phenotyping capacities to over 100 different marker molecules on up to four different immune cell subsets simultaneously within the same sample. Results: We isolated 4 different immune cell populations from a single sample and combined 3 different phenotypic panels consisting of 35 makers each together with a combinatorial tetramer multiplex and phenotyping panel for deep profiling of myeloid cells, NK cells, B cells and T cells. We demonstrate the potential of this novel immuno-phenotyping method, by tracking virus-specific T cells while simultaneously characterizing 4 immune cell subsets with over 100 distinct phenotypic markers from a single sample, which is currently impossible employing modern flow cytometers or classical mass cytometry methods. Conclusions: With its ability to provide an unprecedented picture of the immune status within a single sample, including T cell specificity information and in-depth profiling of relevant immune cell subsets, ultraSCAPE in combination with targetSCAPE can provide detailed insights on the effects of immunotherapy on the immune cell population. Information learned from in-depth immune phenotyping of several immune cell subsets such as T, B, NK and myeloid cell subsets can be leveraged for the development of novel diagnostics, biomarker discovery and monitoring therapeutic strategies in immunotherapy clinical trials.

BACKGROUND Evidence suggests the pivotal contribution of nutrition as a modifiable risk factor for sarcopenia. The present cross-sectional study characterized the nutritional and metabolic profile of sarcopenia through an extensive exploration of a wide array of blood biomarkers related to muscle protein metabolism and transcriptomic signatures in community-dwelling elderly adults. METHODS Among 189 older individuals with a mean age of 73.2 years, sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia criteria based on appendicular lean mass measured by dual-energy X-ray absorptiometry scan, muscle strength, and gait speed. Nutritional status was evaluated using the mini-nutritional assessment (MNA). In addition, we assessed specific blood biomarkers of nutritional status (plasma essential amino acids [EAAs], vitamins), nicotine-derived metabolites, and an extensive microarray analysis from peripheral blood mononuclear cells. RESULTS Malnutrition defined by low MNA score was independently associated with sarcopenia (p < .001). Sarcopenic elderly showed lower body mass index and leptin and higher adiponectin and high-density lipoproteins. Levels of EAAs including lysine, methionine, phenylalanine, threonine, as well as branched-chain AAs and choline, were inversely associated with sarcopenia. Furthermore, nicotine metabolites (cotinine and trans-3'-hydroxycotine) and vitamin B6 status were linked to one or more clinical and functional measures of sarcopenia. Differentially expressed genes and ingenuity pathway analysis supported the association of nutrition with sarcopenia. CONCLUSIONS Herein, the characterization of a nutritional and metabolic signature of sarcopenia provides a firm basis and potential identification of specific targets and directions for the nutritional approach to the prevention and treatment of sarcopenia in aging populations.

Improving influenza vaccine efficacy is a priority to reduce the burden of influenza-associated morbidity and mortality. By careful selection of individuals based on health we show sustained response to influenza vaccination in older adults. Sustaining health in aging could be an important player in maintaining immune responses to influenza vaccination. NCT03266237. Registered 30 August 2017, https://clinicaltrials.gov/ct2/show/NCT03266237 .

Background: Elderly adults over 65 years of age are recommended to receive seasonal influenza vaccination as they are at a higher risk of infection and its complications than the younger community. The elderly are often stratified according to frailty status where frail individuals are more susceptible to adverse health outcomes than their non-frail counterparts, however, it is not known whether immunity induced by influenza vaccination is impaired in the frail elderly. Study Design: Two hundred and five elderly subjects of Chinese ethnicity in Singapore (mean age 73.3 ± 5.3 years, 128 females and 77 males) were administered the recommended trivalent inactivated 2013–14 seasonal influenza vaccine (Vaxigrip™) containing A/H1N1, A/H3N2, and B strains. The elderly subjects were stratified into three groups according to Fried's frailty criteria (59 frail, 85 pre-frail, 61 robust) and were also ranked by Rockwood's frailty index (RFI). Statistical associations were evaluated between frailty status and pre- and post-vaccination antibody titres in sera measured by Hemagglutination inhibition (HAI) and microneutralization (MN) assays. Immunological responses across frailty strata were also studied in terms of leukocyte cellular distribution, cytokine levels and gene expression. Results: Post-vaccination, 83.4% of the subjects seroconverted for A/H1N1, 80.5% for A/H3N2, and 81% for the B strain. The seroconversion rates were comparable across frailty groups (A/H1N1, ANOVA, p = 0.7910; A/H3N2, ANOVA, p = 0.8356, B, ANOVA, p = 0.9741). Geometric mean titres of HAI and MN as well as seroprotection rates were also similar in all three frailty groups and uncorrelated with RFI (Spearman, r = 0.023, p = 0.738). No statistically significant differences were observed between the frailty groups in vaccine-induced modulation of leukocyte populations, cytokine responses, and gene expression profiles of peripheral blood mononuclear cells (PBMCs). Whereas, post- and pre-vaccination HAI titres were positively correlated after adjusting for age and gender (A/H1N1, R2 = 0.216, p = 9.1e−11; A/H3N2, R2 = 0.166, p = 3.4e−8; B, R2 = 0.104, p = 3.1e−5). With most subjects lacking previous history of influenza vaccination, the pre-vaccination titres were likely due to natural exposure and seen to match the pattern of influenza subtype prevalence in the time period of vaccination. Conclusion: The majority of the elderly subjects seroconverted for seasonal influenza upon vaccination, and importantly, influenza vaccination-induced humoral immune responses and seroprotection were similar across the frailty strata, indicating that frail individuals may also benefit from influenza vaccination. Pre-existing antibodies due to natural exposure appeared to positively influence vaccine-induced antibody responses.

Rationale: Contacts of patients with tuberculosis (TB) constitute an important target population for preventive measures because they are at high risk of infection with Mycobacterium tuberculosis and progression to disease. Objectives: We investigated bio-signatures with predictive ability for incident TB. Methods: In a case-control study nested within the Grand Challenges 6-74 longitudinal HIV-negative African cohort of exposed household contacts, we employed RNA sequencing, PCR, and the pair ratio algorithm in a training/test set approach. Overall, 79 progressors who developed TB between 3 and 24 months after diagnosis of index case and 328 matched nonprogressors who remained healthy during 24 months of follow-up were investigated. Measurements and Main Results: A four-transcript signature derived from samples in a South African and Gambian training set predicted progression up to two years before onset of disease in blinded test set samples from South Africa, the Gambia, and Ethiopia with little population-associated variability, and it was also validated in an external cohort of South African adolescents with latent M. tuberculosis infection. By contrast, published diagnostic or prognostic TB signatures were predicted in samples from some but not all three countries, indicating site-specific variability. Post hoc meta-analysis identified a single gene pair, C1QC/TRAV27 (complement C1q C-chain / T-cell receptor-a variable gene 27) that would consistently predict TB progression in household contacts from multiple African sites but not in infected adolescents without known recent exposure events. Conclusions: Collectively, we developed a simple whole blood-based PCR test to predict TB in recently exposed household contacts from diverse African populations. This test has potential for implementation in national TB contact investigation programs.

Background Efforts to reduce risk of tuberculosis disease in children include development of effective vaccines. Our aim was to test safety and immunogenicity of the new adenovirus 35-vectored tuberculosis vaccine candidate AERAS-402 in infants, administered as a boost following a prime with the Bacille Calmette-Guerin vaccine. Methods In a phase 1 randomised, double-blind, placebo-controlled, dose-escalation trial, BCG-vaccinated infants aged 6–9 months were sequentially assigned to four study groups, then randomized to receive an increasing dose-strength of AERAS-402, or placebo. The highest dose group received a second dose of vaccine or placebo 56 days after the first. The primary study outcome was safety. Whole blood intracellular cytokine staining assessed immunogenicity. Results Forty-two infants received AERAS-402 and 15 infants received placebo. During follow-up of 182 days, an acceptable safety profile was shown with no serious adverse events or discontinuations related to the vaccine. AERAS-402 induced a specific T cell response. A single dose of AERAS-402 induced CD4T cells predominantly expressing single IFN-γ whereas two doses induced CD4T cells predominantly expressing IFN-γ, TNF-α and IL-2 together. CD8T cells were induced and were more likely to be present after 2 doses of AERAS-402. Conclusions AERAS-402 was safe and immunogenic in healthy infants previously vaccinated with BCG at birth. Administration of the highest dose twice may be the most optimal vaccination strategy, based on the induced immunity. Multiple differences in T cell responses when infants are compared with adults vaccinated with AERAS-402, in the same setting and using the same whole blood intracellular cytokine assay, suggest specific strategies may be important for vaccination for each population.

Item does not contain fulltext RATIONALE: Administration of tuberculosis (TB) vaccines in participants with previous or current pulmonary TB may have the potential for causing harmful postvaccination immunologic (Koch-type) reactions. OBJECTIVES: To assess the safety and immunogenicity of three dose levels of the AERAS-402 live, replication-deficient adenovirus 35-vectored TB candidate vaccine, containing three mycobacterial antigens, in individuals with current or previous pulmonary TB. METHODS: We performed a phase II randomized, placebo-controlled, double-blinded dose-escalation study in an HIV-negative adult South African cohort (n = 72) with active pulmonary TB (on treatment for 1-4 mo) or pulmonary TB treated at least 12 months before study entry and considered cured. Safety endpoints included clinical assessment, flow volume curves, diffusing capacity of the lung for carbon monoxide, pulse oximetry, chest radiograph, and high-resolution thoracic computerized tomography scans. Cytokine expression by CD4 and CD8 T cells, after stimulation with Ag85A, Ag85B, and TB10.4 peptide pools, was examined by intracellular cytokine staining. MEASUREMENTS AND MAIN RESULTS: No apparent temporal or dose-related changes in clinical status (specifically acute, Koch phenomenon-like reactions), lung function, or radiology attributable to vaccine were observed. Injection site reactions were mild or moderate. Hematuria (by dipstick only) occurred in 25 (41%) of 61 AERAS-402 recipients and 3 (27%) of 11 placebo recipients, although no gross hematuria was reported. AERAS-402 induced robust CD8+ and moderate CD4+ T-cell responses, mainly to Ag85B in both vaccine groups. CONCLUSIONS: Administration of the AERAS-402 candidate TB vaccine to participants with current or previous pulmonary TB induced a robust immune response and is not associated with clinically significant pulmonary complications. Clinical trial registered with www.clinicaltrials.gov (NCT 02414828) and in the South African National Clinical Trials Register ( www.sanctr.gov.za DOH 27-0808-2060).

RATIONALE: AERAS-402 is a novel tuberculosis vaccine designed to boost immunity primed by bacillus Calmette-Guérin (BCG), the only licensed vaccine. OBJECTIVES: We investigated the safety and immunogenicity of AERAS-402 in healthy Mycobacterium tuberculosis-uninfected BCG-vaccinated adults from a tuberculosis-endemic region of South Africa. METHODS: Escalating doses of AERAS-402 vaccine were administered intramuscularly to each of three groups of healthy South African BCG-vaccinated adults, and a fourth group received two injections of the maximal dose. Participants were monitored for 6 months, with all adverse effects documented. Vaccine-induced CD4(+) and CD8(+) T-cell immunity was characterized by an intracellular cytokine staining assay of whole blood and peripheral blood mononuclear cells. MEASUREMENTS AND MAIN RESULTS: AERAS-402 was well tolerated, and no vaccine-related serious adverse events were recorded. The vaccine induced a robust CD4(+) T-cell response dominated by cells coexpressing IFN-gamma, tumor necrosis factor-alpha, and IL-2 ("polyfunctional" cells). AERAS-402 also induced a potent CD8(+) T-cell response, characterized by cells expressing IFN-gamma and/or tumor necrosis factor-alpha, which persisted for the duration of the study. CONCLUSIONS: Vaccination with AERAS-402 is safe and immunogenic in healthy adults. The immunity induced by the vaccine appears promising: polyfunctional T cells are thought to be important for protection against intracellular pathogens such as Mycobacterium tuberculosis, and evidence is accumulating that CD8(+) T cells are also important. AERAS-402 induced a robust and durable CD8(+) T-cell response, which appears extremely promising. Clinical trial registered with www.sanctr.gov.za (NHREC no. 1381)

Background In most tuberculosis (TB) endemic countries, bacillus Calmette–Guerin (BCG) is usually given around birth to prevent severe TB in infants. The neonatal immune system is immature. Our hypothesis was that delaying BCG vaccination from birth to 10 weeks of age would enhance the vaccine-induced immune response. Methods In a randomized clinical trial, BCG was administered intradermally either at birth ( n = 25) or at 10 weeks of age ( n = 21). Ten weeks after vaccination, and at 1 year of age, vaccine-specific CD4 and CD8 T cell responses were measured with a whole blood intracellular cytokine assay. Results Infants who received delayed BCG vaccination demonstrated higher frequencies of BCG-specific CD4 T cells, particularly polyfunctional T cells co-expressing IFN-γ, TNF-α and IL-2, and most strikingly at 1 year of age. Conclusions Delaying BCG vaccination from birth to 10 weeks of age enhances the quantitative and qualitative BCG-specific T cell response, when measured at 1 year of age.

Worldwide, most infants born to mothers infected with human immunodeficiency virus (HIV) receive bacille Calmette-Guérin (BCG) vaccine. Tuberculosis is a major cause of death among infants infected with HIV in sub-Saharan Africa, and it should be prevented. However, BCG may itself cause disease (known as "BCGosis") in these infants. Information regarding the immunogenicity of BCG is imperative for the risk/benefit assessment of BCG vaccination in HIV-infected infants; however, no such data exist.We compared BCG-induced CD4 and CD8 T cell responses, as assessed by flow cytometry, in HIV-infected (n=20), HIV-exposed but uninfected (n=25), and HIV-unexposed (n=23) infants, during their first year of life.BCG vaccination of the 2 HIV-uninfected groups induced a robust response, which was characterized by CD4 T cells expressing interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and/or interleukin (IL)-2. In contrast, HIV-infected infants demonstrated a markedly lower response throughout the first year of life. These infants also had significantly reduced numbers of polyfunctional CD4 T cells coexpressing IFN-gamma, TNF-alpha, and IL-2, a finding that is thought to indicate T cell quality.Infection with HIV severely impairs the BCG-specific T cell response during the first year of life. BCG may therefore provide little, if any, vaccine-induced benefit in HIV-infected infants. Considering the significant risk of BCGosis, these data strongly support not giving BCG to HIV-infected infants.

Background Several novel tuberculosis vaccines are currently in clinical trials, including AERAS-402, an adenovector encoding a fusion protein of Mycobacterium tuberculosis antigens 85A, 85B, and TB10.4. A multicentred trial of AERAS-402 safety and immunogenicity in healthy infants was conducted in three countries in sub-Saharan Africa, using an adaptive design. Methods In a double-blind, randomised, placebo-controlled, dose-finding trial, we enrolled BCG-vaccinated, HIV-uninfected infants aged 16–26 weeks. Infants in the safety/dose-finding phase received two doses of AERAS-402 across three dose levels, or placebo, intramuscularly on days 0 and 28. Infants in the expanded safety phase received three doses of the highest dose level, with the 3rd dose at day 280. Follow up for safety and immunogenicity was for up to two years. Results We enrolled 206 infants (52 placebo and 154 AERAS-402 recipients) into the dose-finding phase and 281 (141 placebo and 140 AERAS-402 recipients) into the expanded safety phase. Safety data were acceptable across all dose levels. No vaccine-related deaths were recorded. A single serious adverse event of tachypnoea was deemed related to study vaccine. Antibodies directed largely against Ag85A and Ag85B were detected. Low magnitude CD4+ and CD8+ polyfunctional T cell responses were observed at all dose levels. The addition of a third dose of AERAS-402 at the highest dose level did not increase frequency or magnitude of antibody or CD8+ T cell responses. Conclusions AERAS-402 has an acceptable safety profile in infants and was well tolerated at all dose levels. Response rate was lower than previously seen in BCG vaccinated adults, and frequency and magnitude of antigen-specific T cells were not increased by a third dose of vaccine.

Introduction : Kadoma City experienced cholera outbreaks in 2008-9, and 2010, affecting 6,393 and 123 people, respectively. A study was conducted to compare epidemiology of the cholera outbreaks. Methods : a descriptive cross sectional study was conducted, analyzing line list data for the 2 outbreaks. Proportions, means were generated and compared using the Chi Square test at 5% level of significance. Results : cholera cases were similar by gender and age, with the 20-30 years group being most affected. Rimuka township contributed 80% and 100% of city cases in 2008-9 and 2010, respectively, p value=0.000. In 2008-9, 91% of cholera cases presented within 2 days compared to 98% in 2010. Delay seeking treatment increased from 58% to 73% (p value=0.001), with gender, and place equally affected. The 2010 outbreak evolved faster, resulting in higher proportion being managed in CTU. CFR was 2% in 2008-9, and 3.3% in 2010 (p value =0.31). Conclusion : the 2008-9 and 2010 cholera outbreaks were similar by age and gender. Rimuka Township was most affected by the outbreaks. There was worsening of delay seeking treatment. The 2010 outbreak was more rapid, leading to early opening of CTC. CFR was consistently above 1%.

Introduction: tuberculosis (TB) remains a public health problem and is driven by HIV. Recent studies indicate that anti-retroviral therapy (ART) initiated during the first two months of anti-TB treatment (ATT) reduces risk of HIV morbidity and mortality. In Sanyati district, 14% of TB/HIV coinfected patients were initiated on ART during TB treatment, in 2010. The study was conducted to determine the magnitude and determinants of delay in ART initiation, in TB/HIV co-infected patients. Methods: an analytic cross sectional study was conducted at three study sites in Sanyati district. The outcome was delayed ART initiation, being failure to be initiated on ART during the first two months of ATT. Respondents were interviewed using pre-tested questionnaires. Epi-Info TM was used to generate frequencies, means, odds ratios and 95% confidence intervals. Stratified and logistic regression analysis was done. Results: of the 186 respondents, 63% had delayed ART initiation. Median delay from initiation of ATT to ART was 48 days (Q 1 =20; Q 3 =82). Risk factors for delayed ART initiation were: being treated for TB first time, AOR=2.23 (p=0.03); initially registered for HIV care outside Sanyati, AOR=3.08 (p

Introduction:the Notifiable disease surveillance system (NDSS) was established in Zimbabwe through the Public Health Act. Between January and August 2011, 14 dog bites were treated at Kadoma Hospital. Eighty-six doses of anti-rabies vaccine were dispensed. One suspected rabies case was reported, without epidemiological investigations. The discrepancy may imply under reporting of Notifiable Diseases. The study was conducted to evaluate the NDSS in Sanyati district. Methods:a descriptive cross sectional study was conducted. Healthcare workers in selected health facilities in urban, rural, and private and public sector were interviewed using questionnaires. Checklists were used to assess resource availability and guide records review of notification forms. Epi InfoTMwas used to generate frequencies, proportions and Chi Square tests at 5% level. Results:we recruited 69 participants, from 16 facilities. Twenty six percent recalled at least 9 Notifiable diseases, 72% correctly mentioned the T1 form for notification, 39% correctly mentioned the forms completed in triplicate and 20% knew it was a legal requirement to notify. Ninety six percent of respondents indicated willingness to participate, whilst 41% had ever received feedback. Three out of 16 health facilities had T1 forms. Conclusion:NDSS is useful, acceptable, simple, and sensitive. NDSS is threatened by lack of T1 forms, poor feedback and knowledge of health workers on NDSS. T1 forms and guidelines for completing the forms were distributed to all health facilities, public and private sector. On the job training of health workers through tutorials, supervision and feedback was conducted.

This paper examines major trends in healthcare reforms in the European Union Member States during the last decade. It focuses on managed care developments and shows that, to a certain extent, managed care in Europe is moving towards a consensus. The paper analyses major trends observed across the European Union including the establishment of overall budgets for health services, separation of purchasers from providers, competition between providers, capitation payments for doctors, budget controls on pharmaceutical expenditure and priority-setting methodologies. It then discusses the potential introduction of new forms of managed care and the current weaknesses in information needs and systems. Finally, the policy-makers' dilemmas for resource allocation are examined and a frame-work for policy debate is suggested.

Background Kadoma City experienced an increase in watery diarrhoea from 27 cases during week beginning 5th September, to 107 cases during week beginning 26th September 2011. The weekly diarrhoea cases crossed the threshold action line during week beginning 5th September at the children’s clinic in Rimuka Township, and the remaining four clinics reported cases crossing threshold action lines between week beginning 12th September and week beginning 26th September. Eighty-two percent of the cases were children less than 5 years old. We conducted a case controlstudy to determine risk factorsfor contracting watery diarrhoea in children less than 5 years in Kadoma City. Methods An unmatched 1:1 case control study was conducted in Ngezi and Rimuka townships in Kadoma City, Zimbabwe. A case was a child less than 5 years old, who developed acute watery diarrhoea between 5th September and 1st October 2011. A control was a child less than 5 years old who stayed in the same township and did not suffer from diarrhoea. A structured questionnaire was administered to caregivers of cases and controls.Laboratory water quality tests and stool test results were reviewed.Epi Info™ statistical software was used to analyse data. Results A total of 109 cases and 109 controls were enrolled. Independent protective factors were: having been exclusively breastfed for six months [AOR = 0.44; 95% CI (0.24-0.82)]; using municipal water [AOR = 0.38; 95% CI (0.18-0.80)]; using aqua tablets, [AOR = 0.49; 95% CI (0.26–0.94)] and; storing water in closed containers, [AOR = 0.24; 95% CI (0.07–0.0.83). The only independent risk factor for contracting watery diarrhoea was hand washing in a single bowl, [AOR = 2.89; 95% CI (1.33–6.28)]. Salmonella, Shigella, Rotavirus, and Enteropathogenic Escherichia coli were isolated in the stool specimens. None of the 33 municipal water samples tested showed contamination with Escherichia coli, whilst 23 of 44 (52%) shallow well water samples and 3 of 15(20%) borehole water samples tested were positive for Escherichia coli. Conclusions The outbreak resulted from inadequate clean water and use of contaminated water. Evidence from this study was used to guide public health response to the outbreak.

Immunogenicity of new tuberculosis (TB) vaccines is commonly assessed by measuring the frequency and cytokine expression profile of T cells.We tested whether this outcome correlates with protection against childhood TB disease after newborn vaccination with bacillus Calmette-Guérin (BCG).Whole blood from 10-week-old infants, routinely vaccinated with BCG at birth, was incubated with BCG for 12 hours, followed by cryopreservation for intracellular cytokine analysis. Infants were followed for 2 years to identify those who developed culture-positive TB-these infants were regarded as not protected against TB. Infants who did not develop TB disease despite exposure to TB in the household, and another group of randomly selected infants who were never evaluated for TB, were also identified-these groups were regarded as protected against TB. Cells from these groups were thawed, and CD4, CD8, and γδ T cell-specific expression of IFN-γ, TNF-α, IL-2, and IL-17 measured by flow cytometry.A total of 5,662 infants were enrolled; 29 unprotected and two groups of 55 protected infants were identified. There was no difference in frequencies of BCG-specific CD4, CD8, and γδ T cells between the three groups of infants. Although BCG induced complex patterns of intracellular cytokine expression, there were no differences between protected and unprotected infants.The frequency and cytokine profile of mycobacteria-specific T cells did not correlate with protection against TB. Critical components of immunity against Mycobacterium tuberculosis, such as CD4 T cell IFN-γ production, may not necessarily translate into immune correlates of protection against TB disease.

This research was concerned with the feasibility of government charges for health services. The aim was to test the validity of charging individuals not using special facilities and to determine acceptable and equitable charges for specified services. Surveys were conducted for: 1) 29518 prescriptions dispensed at 28 health units in 7 different regions; 2) 892 outpatients at 3 referral hospitals 2 regional hospitals and 4 district hospitals; and 3) 1820 households in 3 urban cities or in locations between mission and government hospitals in 26 rural districts and 15 regions. Current medical services reach 93% of the population within 10 km and 72% within 5 km. Health services are free except for charges for patients in special or private wards at referral and regional hospitals for dental appointments and for immunization for travel. Public expenditure has been declining and there is underfinancing for drugs medical equipment and vehicles building maintenance salaries support staff and an information system. Findings are presented for hospital waiting timetravel costs choices of facilities (traditional services mission services and government services) costs admissions and costs reasons for choice of services willingness to pay improvements desired financial constraints and rationale for charges. The justification for government charges stems from concerns about frivolous use the presence of charges at mission facilities and improvements to services. It is argued that long waiting lines are sufficient to stop frivolous use. Patients used missions because of access to drugs. Government services were used because of inexpense and convenience. Most were willing to pay for services at hospitals if there were improvements in drug and food availability for instance; i.e. about 50% would pay Tsh 200 (Tanzanian shillings) at referral and regional hospitals and Tsh 100 at district hospitals. Waiting times could be 3-4 hours. 84% of rural patients and 55% of urban patients walked to facilities. Travel costs were Tsh 673 at the lowest and Tsh 4741 at the highest; the mean cost for a consultation was Tsh 440. 59% in the outpatient survey were willing to pay Tsh 200.

After a long period of growth and relative organizational stability, the last 10 years have been a period of reappraisal. One driving force has been the desire of governments simply to contain health care costs. Another has been the search to find ways of obtaining better value for money. Thus, the reforms of the British National Health Service should be seen in an international context. Britain is by no means alone in introducing changes which would have been thought inconceivable only 10 years ago. Sweden has, of course, also been introducing changes. And it may be that there will be more to follow. The changes in Britain should be seen as a process, starting essentially from 1984. The Thatcher White Paper in 1989 was the culmination of it. Essentially the changes consist of an attempt to bring private business methods into the running of the health services while still retaining the essential principles of medical services being largely free at the point of use and intended to offer equal access to all citizens. It has been, in part, a change of control from bodies representing different interests to control by bodies established on similar lines to the Board of Directors of a public company and acting as such.

This article reports on the author's survey of the cost-control measures for health care in 12 European countries during the period from 1983 to 1990. Among these countries the greatest convergence was in the use of the budget as a system of control, reinforced by manpower controls. Budgets were constructed to restrict hospital costs and payments to doctors practicing outside of hospitals. Another strategy was cost sharing for purchase of drugs and, in some cases, for dentistry. Most countries took steps to control expensive medical equipment; others, to restrict entry to medical schools. The European experience demonstrates the technical feasibility of the government's controlling health care costs by regulating supply rather than demand. The key to Europe's success in the use of monopsony power, whereby one purchaser dominates the market. The author contends that regulation works in Europe and questions whether the United States can exert similar control over its coalition of insurers and providers in order to rein in its health care expenses.

The changes in fortunes of the developing world affect the acquisition of technology for these countries. A shrewd minister of health needs to find out 2 things about scientific advances: 1) how many people will it help where and at what cost and 2) whether the additional expenditure provides a less expensive way of getting better results than the present technology. The scale of the investment is also a consideration as is the evaluation research available on efficacy of treatments. The equipment of hospitals and health centers and the training of specialists primary care physicians paramedics workers and midwives also affect the decision to acquire new technology. The nature of the economic climate of developing countries is described as exporting more to maintain the same level of earnings. The dilemma is how to balance export costs with debt payments and how to balance collection of taxes needed for debt service payments with maintaining public services. Devaluation means the country has made itself poorer. 17 African countries devalued their currency and cut public expenditures reduced subsidies and postponed capital investments. Poverty increased. An assessment based on statistical records of how health has been affected is not available because: 1) ministries of health finance only part of public expenditure on health; 2) private expenditure on health is larger than public expenditure; 3) the proportion of the budget on health may be the same but the budget may have decreased; and 4) prices paid for health are variable and not easily available. The inferences drawn are that developing countries were heavily involved in the 1970s in construction of hospitals but the economic crisis of the 1980s meant possibly leaving new hospitals unused. Foreign exchange has contributed to investment in physicians and not replacement or repair of equipment buildings or vehicles and an inadequate supply of drugs. The health sector crunch has not been eased by foreign aid which has remained about the same since 1980 at about 4% from Organization for Economic Cooperation and Development countries. There has also been diversion of aid to countries with greater political or commercial interests. A free trade policy would help as would easing foreign debt. Countries might help themselves by implementing insurance schemes for curative care priorities expenditures and combat poverty malnutrition unsafe water and promote sanitation female education and a better life style. There are no quick solutions.

As outlined in the first part of this article in the last issue of the journal, many countries are facing severe constraints on health expenditure at the same time as they are trying to work towards Health for All by the Year 2000. Health manpower needs to be planned to secure maximum benefits from the limited resources available. Many medical schools train more doctors than are needed because quotas on medical places are either non-existent or set too high. Medical training may be oriented to high-technology, curative care and produce doctors ill equipped to fulfil the role demanded of them in the primary health care approach. Educational courses for paramedics and nurses are often insufficient and inappropriate. Countries which have previously lost trained doctors to attractive posts abroad now face the prospect of a flood of doctors looking for work in their home countries, now that opportunities for work abroad are being reduced. Such countries will find it difficult to reverse the bias in policy towards medical professionals, despite the waste caused by unemployment and inappropriate training among doctors. With limited budgets, there is a need for countries to plan ahead. To do this they must find ways of estimating future effective demand. The future balance of staff can then be planned on the basis of resources available and the relative costs of deploying various categories of health staff.

There are extraordinarily few countries in the world where there has been less public control in the medical care market than in the United States. The phrase 'public control' as distinct from 'public regulation' is used here to cover two separate developments. The first is the ownership of medical care facilities by public authorities. The second is the use of tax or compulsory insurance financing. Data currently being collected by WHO will show the pattern of ownership of hospital facilities in different countries of the world. Though there may be occasional exceptions, I am confident that the data from Africa, Asia, Australasia and Europe as a whole will show that well over half the hospital beds for the physically sick are publicly owned. Among the high-income countries of Europe, with which the United States can most readily be compared, only the Netherlands has less than half its beds (about 30 per cent) owned by public authorities. While public authorities in the United States pay for the bulk of mental hospitals and offer services to the armed forces, veterans, Presidents and other categories, there is no compulsory health insurance. The vast majority of other high-income countries have some form of compulsory health insurance, and taxation pays for a considerable proportion, and usually a majority, of medical care services in the United Kingdom, Scandinavia, Eastern Europe, Africa and S.E. Asia.

Economic, demographic, and technological pressures have led at the same time to increased demands upon health services and the need to contain spending on health care. As the United States has focused singularly on an array of market mechanisms, Western European countries have each adopted a broader set of strategies along with limited de-insurance: innovative regulatory approaches and a move from compulsory health insurance models to flexible national health service models of providing health care. Pursuit of cost-containment in Western Europe has proceeded along with pursuit of quality and, above all else, equity.

Are there new sources of finance which Third World countries can tap to pay for Health for All? Is there anything valuable to be learnt in this respect from the experience of countries which are now developed? Countries have drifted into different ways of paying for health services, often without foreseeing the long run consequences. In many Third World countries the financing of services has been strongly influenced by their colonial past. This explains why many of them attempt to provide wholly free services and provide privileged services not only to the armed forces but to public servants as well. Introducing charges is one way of securing more revenue. It is noticeable that in some countries which were never colonized, there is a greater willingness to use charging and that this stimulates the growth of informal systems of voluntary health insurance. While many developed countries have made a transition from health insurance to universal services while retaining a considerable element of contributions from employers and employees, it is more difficult in political terms to introduce contributions unless those who contribute get something specific for them. The problem for developing countries contemplating the introduction of compulsory health insurance is to design systems which avoid all the problems which have manifested themselves in Europe, North America and on a wider scale in Latin America. These problems include the escalation of costs, failure to collect contributions due, the provision of ‘paper’ rights, bureaucratic obstacles to receiving care, different funds with varying rights, wholly separated services for insured persons, the bias to urban curative services and the separation of curative from preventive services. World experience suggests that services provided under compulsory health insurance need to be closely coordinated with governmental services and the policy governing them should be kept under the close supervision of Ministers of Health.

Paying for health services: a study of the costs and sources of finance in six countries , Paying for health services: a study of the costs and sources of finance in six countries , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی

By giving everyone paper rights to health care, Americans may end up doing little better, at much greater cost, and feeling worse about it. The key to providing greater equity may be to find a way of defining the minimum that all should have. Most countries somehow define these limits for publicly provided services from education to cash assistance. But for health care benefits there are no simple limiting criteria--especially when professionals have the exceptional luxury of using whatever resources they choose. A realistic floor requires toughly maintained ceilings.