Plasma citrulline concentration and plasma LPS detection among critically ill patients a prospective observational study.

PURPOSE: Gut can be a source of sepsis but sepsis itself can induce gut dysfunction. We aimed to study whether plasma citrulline, a marker of enterocyte mass, was correlated with plasma lipopolysaccharide, a potential marker of bacterial translocation among critically ill patients. MATERIALS AND METHODS: Critically ill patients admitted to the ICU. Plasma citrulline and plasma LPS concentration and activity were measured at ICU admission. Patients were compared according to the presence of sepsis at ICU admission. RESULTS: 109 critically ill patients, with SOFA score 8 [6-12], were prospectively included. Sixty six patients (61%) had sepsis at ICU admission. There was no correlation between plasma citrulline concentration and plasma LPS concentration or activity. However, sepsis at ICU admission was associated with a lower plasma citrulline concentration (13.4 µmol.L-1 vs 21.3 µmol.L-1, p = 0.02). Plasma LPS activity was significantly higher among patients with abdominal sepsis compared to patients with extra-abdominal sepsis (1.04 EU/mL vs 0.63, p = 0.01). CONCLUSIONS: Plasma citrulline is not associated with the level of plasma LPS but is strongly decreased among septic patients. Detection of LPS is ubiquitous among critically ill patients but abdominal sepsis is associated with increased plasma LPS activity compared to extra-abdominal sepsis.

ß-lactam dosing at the early phase of sepsis: Performance of a pragmatic protocol for target concentration achievement in a prospective cohort study.

PURPOSE: We hypothesized that a protocol of standardized fixed dose using prolonged infusion during the early phase of sepsis may avoid insufficient ß-lactam concentrations. METHODS: In this single center prospective study, patients with sepsis and vasopressors were enrolled if they were treated by either piperacillin-tazobactam, meropenem or cefepime. Βeta-lactams were administered at fixed dose by prolonged infusion. Targeted plasma concentrations for piperacillin, meropenem and cefepime were above 80 mg/L, 8 mg/L and 38 mg/L respectively. Three blood samples were collected per patient over the first 48 h of treatment. Primary endpoint was target concentration achievement during the 48 first hours, defined as all plasma concentrations above the targeted threshold. RESULTS: Among the 89 patients completing the three samples, target concentrations were achieved for 61 (69%). Target concentrations were achieved in 20 (53%), 32 (89%), and 9 (60%) of the patients treated with piperacillin, meropenem and cefepime, respectively. By multivariate analysis, lower APACHE 2 score, higher baseline MDRD creatinine clearance, and piperacillin use were independently associated with insufficient ß-lactam concentrations. CONCLUSION: Despite a fixed dose antibiotic administration protocol with prolonged infusion insufficient ß-lactam concentration was frequent at the early phase of sepsis, especially in less severe patients, without renal failure, and treated with piperacillin. In septic patients with vasopressors, piperacillin dosing higher than 16 g may be needed to achieve the recommended target concentration. TRIAL REGISTRATION: NCT02820987.

Daily use of extracorporeal CO2 removal in a critical care unit: indications and results.

BACKGROUND: While outcome improvement with extracorporeal CO2 removal (ECCO2R) is not demonstrated, a strong pathophysiological rational supports its use in the setting of acute respiratory distress syndrome (ARDS) and COPD exacerbation. We aimed to describe our single-center experience of ECCO2R indications and outcome. METHODS: Patients treated with ECCO2R in our medial ICU, from March 2014 to November 2017, were retrospectively enrolled. Primary end point was evolution of ventilator settings during the two first days following ECCO2R start. RESULTS: Thirty-three patients received ECCO2R. Seventeen were managed with Hemolung®, 10 with Prismalung®, 4 with ILA®, and 2 with Cardiohelp®. Indications for ECCO2R were mild or moderate ARDS (n = 16), COPD exacerbation (n = 11), or uncontrolled hypercapnia due to other causes (n = 6). Four patients were not intubated at the time of ECCO2R start. Median duration of ECCO2R treatment was 7 days [5-10]. In ARDS patients, between baseline and day 2, median tidal volume and driving pressure decreased from 5.3 [4.4-5.9] mL/kg and 10 [8-15] to 3.8 [3.3-4.1] mL/kg and 9 [8-11], respectively. Prone positioning was performed in 10 of the 16 patients, without serious adverse event. In COPD patients, between baseline and day 2, median ventilation minute and PaCO2 decreased significantly from respectively 7.6 [6.6-8.7] L/min and 9.4 [8.4-10.1] kPa to 5.8 [4.9-6.2] L/min and 6 [5.3-6.8] kPa. Four out of 11 COPD patients were extubated while on ECCO2R. Device thrombosis occurred in 5 patients (15%). Hemolysis was documented in 16 patients (48%). One patient died of intracranial hemorrhage, while on ECCO2R. Twenty-four patients were discharged from ICU alive. Twenty-eight day mortality was 31% in ARDS, 9% in COPD patients, and 50% in other causes of refractory hypercapnic respiratory failure. CONCLUSION: ECCO2R was useful to apply ultra-protective ventilation among ARDS patients and improved PaCO2, pH, and minute ventilation in COPD patients.

Prognosis of cirrhotic patients admitted to the general ICU.

BACKGROUND: The prognosis of cirrhotic patients admitted to the ICU is considered to be poor but has been mainly reported in liver ICU. We aimed to describe the prognosis of cirrhotic patients admitted to a general ICU, to assess the predictors of mortality in this population, and, finally, to identify a subgroup of patients in whom intensive care escalation might be discussed. RESULTS: We performed a retrospective monocentric study of all cirrhotic patients consecutively admitted between 2002 and 2014 in a general ICU in a regional university hospital. Two hundred and eighteen cirrhotic patients were admitted to the ICU. The 28-day and 6-month mortality rates were 53 and 74 %, respectively. Among the 115 patients who were discharged from ICU, only eight patients underwent liver transplantation, whereas 48 had no clear contraindication. Multivariable analyses on 28-day mortality identified three independent variables, incorporated into a new three-variable prognostic model as follows: SOFA ≥ 12 (OR 4.2 [2.2-8.0]; 2 points), INR ≥ 2.6 (OR 2.5 [1.3-4.8]; 1 point), and renal replacement therapy (OR 2.3 [1.1-5.1]; 1 point). For a value of the score at 4 (16 % of patients), 28-day and 3-month mortality rates were 91 and 100 %, respectively. An external validation of the score among 149 critically ill cirrhotic patients showed a good accuracy for predicting in-ICU mortality. CONCLUSIONS: Mortality of cirrhotic patients admitted to a general ICU was comparable to that of other studies. A pragmatic score integrating the SOFA score, INR, and the need for extrarenal epuration was strongly associated with mortality. Among the 16 % of patients presenting with score 4 at ICU admission, 100 % died in the 3-month follow-up period. The prognostic evaluation on day 3 remains essential for the majority of patients. However, this score calculable at ICU admission might identify patients in whom the benefit of intensive care escalation should be discussed, in particular when liver transplantation is contraindicated.

Sociocultural determinants of anticipated oral cholera vaccine acceptance in three African settings: a meta-analytic approach.

BACKGROUND: Controlling cholera remains a significant challenge in Sub-Saharan Africa. In areas where access to safe water and sanitation are limited, oral cholera vaccine (OCV) can save lives. Establishment of a global stockpile for OCV reflects increasing priority for use of cholera vaccines in endemic settings. Community acceptance of vaccines, however, is critical and sociocultural features of acceptance require attention for effective implementation. This study identifies and compares sociocultural determinants of anticipated OCV acceptance across populations in Southeastern Democratic Republic of Congo, Western Kenya and Zanzibar. METHODS: Cross-sectional studies were conducted using similar but locally-adapted semistructured interviews among 1095 respondents in three African settings. Logistic regression models identified sociocultural determinants of OCV acceptance from these studies in endemic areas of Southeastern Democratic Republic of Congo (SE-DRC), Western Kenya (W-Kenya) and Zanzibar. Meta-analytic techniques highlighted common and distinctive determinants in the three settings. RESULTS: Anticipated OCV acceptance was high in all settings. More than 93% of community respondents overall indicated interest in a no-cost vaccine. Higher anticipated acceptance was observed in areas with less access to public health facilities. In all settings awareness of cholera prevention methods (safe food consumption and garbage disposal) and relating ingestion to cholera causation were associated with greater acceptance. Higher age, larger households, lack of education, social vulnerability and knowledge of oral rehydration solution for self-treatment were negatively associated with anticipated OCV acceptance. Setting-specific determinants of acceptance included reporting a reliable income (W-Kenya and Zanzibar, not SE-DRC). In SE-DRC, intention to purchase an OCV appeared unrelated to ability to pay. Rural residents were less likely than urban counterparts to accept an OCV in W-Kenya, but more likely in Zanzibar. Prayer as a form of self-treatment was associated with vaccine acceptance in SE-DRC and W-Kenya, but not in Zanzibar. CONCLUSIONS: These cholera-endemic African communities are especially interested in no-cost OCVs. Health education and attention to local social and cultural features of cholera and vaccines would likely increase vaccine coverage. High demand and absence of insurmountable sociocultural barriers to vaccination with OCVs indicate potential for mass vaccination in planning for comprehensive control or elimination.

Comparing sociocultural features of cholera in three endemic African settings.

BACKGROUND: Cholera mainly affects developing countries where safe water supply and sanitation infrastructure are often rudimentary. Sub-Saharan Africa is a cholera hotspot. Effective cholera control requires not only a professional assessment, but also consideration of community-based priorities. The present work compares local sociocultural features of endemic cholera in urban and rural sites from three field studies in southeastern Democratic Republic of Congo (SE-DRC), western Kenya and Zanzibar. METHODS: A vignette-based semistructured interview was used in 2008 in Zanzibar to study sociocultural features of cholera-related illness among 356 men and women from urban and rural communities. Similar cross-sectional surveys were performed in western Kenya (n = 379) and in SE-DRC (n = 360) in 2010. Systematic comparison across all settings considered the following domains: illness identification; perceived seriousness, potential fatality and past household episodes; illness-related experience; meaning; knowledge of prevention; help-seeking behavior; and perceived vulnerability. RESULTS: Cholera is well known in all three settings and is understood to have a significant impact on people's lives. Its social impact was mainly characterized by financial concerns. Problems with unsafe water, sanitation and dirty environments were the most common perceived causes across settings; nonetheless, non-biomedical explanations were widespread in rural areas of SE-DRC and Zanzibar. Safe food and water and vaccines were prioritized for prevention in SE-DRC. Safe water was prioritized in western Kenya along with sanitation and health education. The latter two were also prioritized in Zanzibar. Use of oral rehydration solutions and rehydration was a top priority everywhere; healthcare facilities were universally reported as a primary source of help. Respondents in SE-DRC and Zanzibar reported cholera as affecting almost everybody without differentiating much for gender, age and class. In contrast, in western Kenya, gender differentiation was pronounced, and children and the poor were regarded as most vulnerable to cholera. CONCLUSIONS: This comprehensive review identified common and distinctive features of local understandings of cholera. Classical treatment (that is, rehydration) was highlighted as a priority for control in the three African study settings and is likely to be identified in the region beyond. Findings indicate the value of insight from community studies to guide local program planning for cholera control and elimination.

Sociocultural determinants of anticipated vaccine acceptance for acute watery diarrhea in early childhood in Katanga Province, Democratic Republic of Congo.

Rotavirus and oral cholera vaccines have the potential to reduce diarrhea-related child mortality in low-income settings and are recommended by the World Health Organization. Uptake of vaccination depends on community support, and is based on local priorities. This study investigates local perceptions of acute watery diarrhea in childhood and anticipated vaccine acceptance in two sites in the Democratic Republic of Congo. In 2010, 360 randomly selected non-affected adults were interviewed by using a semi-structured questionnaire. Witchcraft and breastfeeding were perceived as potential cause of acute watery diarrhea by 51% and 48% of respondents. Despite misperceptions, anticipated vaccine acceptance at no cost was 99%. The strongest predictor of anticipated vaccine acceptance if costs were assumed was the educational level of the respondents. Results suggest that the introduction of vaccines is a local priority and local (mis)perceptions of illness do not compromise vaccine acceptability if the vaccine is affordable.

Distinguishing social and cultural features of cholera in urban and rural areas of Western Kenya: Implications for public health.

Urban and rural areas have distinctive health problems, which require consideration. To examine sociocultural features of cholera and its community context, a semi-structured explanatory model interview based on vignettes depicting typical clinical features of cholera was used to interview 379 urban and rural respondents in Western Kenya. Findings included common and distinctive urban and rural ideas about cholera, and its prevention and treatment. The three most commonly perceived causes among urban and rural respondents collectively were drinking contaminated water, living in a dirty environment and lacking latrines. However, a dirty environment and flies were more prominently perceived causes among urban respondents. Rural respondents were less likely to identify additional symptoms and more likely to identify biomedically irrelevant perceived causes of cholera. Oral rehydration therapy was the most frequently reported home treatment. Health facilities were recommended unanimously at both sites. For prevention, rural respondents were more likely to suggest medicines, and urban respondents were more likely to suggest health education and clean food. Findings indicate community priority, demand for and potential effectiveness of enhanced efforts to control cholera in Western Kenya, and they suggest strategies that are particularly well suited for control of cholera in urban and rural areas.

Local perceptions of cholera and anticipated vaccine acceptance in Katanga province, Democratic Republic of Congo.

BACKGROUND: In regions where access to clean water and the provision of a sanitary infrastructure has not been sustainable, cholera continues to pose an important public health burden. Although oral cholera vaccines (OCV) are effective means to complement classical cholera control efforts, still relatively little is known about their acceptability in targeted communities. Clarification of vaccine acceptability prior to the introduction of a new vaccine provides important information for future policy and planning. METHODS: In a cross-sectional study in Katanga province, Democratic Republic of Congo (DRC), local perceptions of cholera and anticipated acceptance of an OCV were investigated. A random sample of 360 unaffected adults from a rural town and a remote fishing island was interviewed in 2010. In-depth interviews with a purposive sample of key informants and focus-group discussions provided contextual information. Socio-cultural determinants of anticipated OCV acceptance were assessed with logistic regression. RESULTS: Most respondents perceived contaminated water (63%) and food (61%) as main causes of cholera. Vaccines (28%), health education (18%) and the provision of clean water (15%) were considered the most effective measures of cholera control. Anticipated vaccine acceptance reached 97% if an OCV would be provided for free. Cholera-specific knowledge of hygiene and self-help in form of praying for healing were positively associated with anticipated OCV acceptance if costs of USD 5 were assumed. Conversely, respondents who feared negative social implications of cholera were less likely to anticipate acceptance of OCVs. These fears were especially prominent among respondents who generated their income through fishing. With an increase of assumed costs to USD 10.5, fear of financial constraints was negatively associated with anticipated vaccine acceptance as well. CONCLUSIONS: Results suggest a high motivation to use an OCV as long as it seems affordable. The needs of socially marginalized groups such as fishermen may have to be explicitly addressed when preparing for a mass vaccination campaign.

Review of two decades of cholera diagnostics--how far have we really come?

BACKGROUND: Cholera, an ancient scourge, continues to inflict high rates of mortality today. The rising incidence of epidemics in areas of poor sanitation and crowding highlight the need for better epidemic prevention and early response. Such interventions require the availability of rapid and accurate diagnostic techniques to trigger timely response and mitigate the scale of the outbreak. The current gold standard of bacterial culture is inadequate for rapid diagnosis, highlighting the overarching neglect of field diagnostic needs. This paper was written to support the World Health Organisation's Global Task Force on Cholera Control mandated Cholera and diarrhoeal disease laboratory Network (CholdiNet) in devising a protocol for the validation of Rapid Diagnostic Tests (RDTs) for Vibrio cholerae. The status of diagnostic tools for Vibrio cholerae is assessed, describing products that have been commercialised over the last two decades and discussing their peer-reviewed evaluation. METHOD: Review of post-1990 peer-reviewed and grey literature on rapid diagnostic tests for Vibrio cholerae. RESULTS: Since 1990, twenty four diagnostic tests have been developed for the detection of Vibrio cholerae in human faecal samples. Fourteen of these have also been described in the literature, with rapid chromatographic-immuno assays (CIA) featuring strongly. Polymerase chain reaction (PCR) assays maintain the ability to detect the lowest amount of bacteria; however CIAs achieve both low detection thresholds and high sensitivity and specificity, making them possible candidates for use in field conditions. Field and laboratory studies were performed in a wide range of settings demonstrating variability in performance, however only a few of these studies were sufficiently stringent, highlighting five RDTs that showed promise in field conditions; COAT, IP cholera dipstick, SMART, IP dipstick and Medicos. In light of non-independent reporting, the authors would like to see these five products undergoing additional studies, with further technical improvements if needed and commercial production. The authors hope that public health use of such a RDT in limited-resource field conditions on stool samples may contribute to effective reduction in cholera epidemic spread.

Costs of illness due to cholera, costs of immunization and cost-effectiveness of an oral cholera mass vaccination campaign in Zanzibar.

BACKGROUND: The World Health Organization (WHO) recommends oral cholera vaccines (OCVs) as a supplementary tool to conventional prevention of cholera. Dukoral, a killed whole-cell two-dose OCV, was used in a mass vaccination campaign in 2009 in Zanzibar. Public and private costs of illness (COI) due to endemic cholera and costs of the mass vaccination campaign were estimated to assess the cost-effectiveness of OCV for this particular campaign from both the health care provider and the societal perspective. METHODOLOGY/PRINCIPAL FINDINGS: Public and private COI were obtained from interviews with local experts, with patients from three outbreaks and from reports and record review. Cost data for the vaccination campaign were collected based on actual expenditure and planned budget data. A static cohort of 50,000 individuals was examined, including herd protection. Primary outcome measures were incremental cost-effectiveness ratios (ICER) per death, per case and per disability-adjusted life-year (DALY) averted. One-way sensitivity and threshold analyses were conducted. The ICER was evaluated with regard to WHO criteria for cost-effectiveness. Base-case ICERs were USD 750,000 per death averted, USD 6,000 per case averted and USD 30,000 per DALY averted, without differences between the health care provider and the societal perspective. Threshold analyses using Shanchol and assuming high incidence and case-fatality rate indicated that the purchase price per course would have to be as low as USD 1.2 to render the mass vaccination campaign cost-effective from a health care provider perspective (societal perspective: USD 1.3). CONCLUSIONS/SIGNIFICANCE: Based on empirical and site-specific cost and effectiveness data from Zanzibar, the 2009 mass vaccination campaign was cost-ineffective mainly due to the relatively high OCV purchase price and a relatively low incidence. However, mass vaccination campaigns in Zanzibar to control endemic cholera may meet criteria for cost-effectiveness under certain circumstances, especially in high-incidence areas and at OCV prices below USD 1.3.

Social and cultural determinants of oral cholera vaccine uptake in Zanzibar.

Effectiveness of mass cholera vaccination campaigns requires not only technical and financial capacity but also consideration of social and cultural factors affecting vaccine acceptance. This study examined the influence of local community views of cholera on oral cholera vaccine (OCV) uptake in a mass vaccination campaign in 2009 in peri-urban and rural areas of Zanzibar. It used data from interviews conducted before the campaign and followed previous research assessing determinants of anticipated OCV acceptance. OCV uptake was lower than the reported anticipated acceptance. Less than half of the 356 adult respondents (49.7%) drank the required two doses of OCV. Variables referring to socio-cultural features of diarrheal illness that respondents identified with a cholera case vignette explained uptake better than analysis only of socio-demographic characteristics. Somatic features of illness not specific for cholera were negative determinants. Recognition of unconsciousness as a serious sign of dehydration and concern that cholera outbreaks would overwhelm the local healthcare system in the rural area were positive determinants of acceptance. Female gender, rural residence and older age were also positive determinants of OCV uptake. For further vaccine action with OCVs, cholera as a cause of severe dehydration should be distinguished from other causes of diarrhea. Planning should acknowledge rural concern about the relationship of limited capacity of the healthcare system to cope with cholera outbreaks and the priority of a cholera vaccine. Findings recommend particular efforts to increase cholera immunization coverage among young adults, in peri-urban areas and for men.

Improving community coverage of oral cholera mass vaccination campaigns: lessons learned in Zanzibar.

BACKGROUND: Recent research in two cholera-endemic communities of Zanzibar has shown that a majority (∼94%) of the adult population was willing to receive free oral cholera vaccines (OCVs). Since OCV uptake in the 2009 campaign reached only ∼50% in these communities, an evaluation of social and cultural factors and of barriers was conducted to understand this difference for future cholera control planning. METHODOLOGY/PRINCIPAL FINDINGS: A random sample of 367 adult peri-urban and rural community residents (46.6% immunized vs. 53.4% unimmunized) was studied with a semi-structured interview that inquired about social and cultural features of cholera depicted in a vignette and barriers to OCV uptake. Symptoms (rectal pain, loose skin only in rural community) and perceived causes (uncovered food, contact with contaminated water) specific for severe diarrhea were associated with uptake. Purchasing drugs from pharmacies to stop diarrhea and vomiting was negatively associated with uptake. Increasing household size, age and previous enteric illness episode were positively related to uptake, the latter only at the rural site. The most prominent barrier to uptake was competing obligations or priorities (reported by 74.5%, identified as most important barrier by 49.5%). Next most prominent barriers were lacking information about the campaign (29.6%, 12.2%), sickness (14.3%, 13.3%) and fear of possible vaccine side effects (15.3%, 5.6%). The majority of unvaccinated respondents requested repetition of the vaccination with free OCVs. CONCLUSIONS/SIGNIFICANCE: Factors associated with uptake indicated a positive impact of the vaccination campaign and of sensitization activities on vaccine acceptance behavior. Unlike communities opposed to cholera control or settings where public confidence in vaccines is lacking, identified barriers to uptake indicated a good campaign implementation and trust in the health system. Despite prospects and demand for repeating the vaccination, local decision-makers should reconsider how careful logistical arrangements may improve community coverage and thus effectiveness of vaccination campaigns.

Social and cultural determinants of anticipated acceptance of an oral cholera vaccine prior to a mass vaccination campaign in Zanzibar.

Despite improvements in sanitation and water supply, cholera remains a serious public health burden. Vaccination is included among recommendations for cholera control. Cultural concepts of illness are likely to affect vaccine acceptance. This study examined social and cultural determinants of anticipated acceptance of an oral cholera vaccine (OCV) prior to a mass vaccination campaign in Zanzibar. Using a cultural epidemiological approach, 356 unaffected adult residents were studied with vignette-based semi-structured interviews. Anticipated acceptance was high for a free OCV (94%), but declined with increasing price. Logistic regression models examined social and cultural determinants of anticipated acceptance at low (USD 0.9), medium (USD 4.5) and high (USD 9) price. Models including somatic symptoms (low and high price), social impact (low and medium) and perceived causes (medium and high) explained anticipated OCV acceptance better than models containing only socio-demographic characteristics. Identifying thirst with cholera was positively associated with anticipated acceptance of the low-priced OCV, but acknowledging the value of home-based rehydration was negatively associated. Concern about spreading the infection to others was positively associated at low price among rural respondents. Confidence in the health system response to cholera outbreaks was negatively associated at medium price among peri-urban respondents. Identifying witchcraft as cause of cholera was negatively associated at medium and high price. Anticipated acceptance of free OCVs is nearly universal in cholera-endemic areas of Zanzibar; pre-intervention assessments of community demand for OCV should not only consider the social epidemiology, but also examine local socio-cultural features of cholera-like illness that explain vaccine acceptance.

Sensitivity and specificity of typhoid fever rapid antibody tests for laboratory diagnosis at two sub-Saharan African sites.

OBJECTIVE: To evaluate three commercial typhoid rapid antibody tests for Salmonella Typhi antibodies in patients suspected of having typhoid fever in Mpumalanga, South Africa, and Moshi, United Republic of Tanzania. METHODS: The diagnostic accuracy of Cromotest(®) (semiquantitative slide agglutination and single tube Widal test), TUBEX(®) and Typhidot(®) was assessed against that of blood culture. Performance was modelled for scenarios with pretest probabilities of 5% and 50%. FINDINGS: In total 92 patients enrolled: 53 (57.6%) from South Africa and 39 (42.4%) from the United Republic of Tanzania. Salmonella Typhi was isolated from the blood of 28 (30.4%) patients. The semiquantitative slide agglutination and single-tube Widal tests had positive predictive values (PPVs) of 25.0% (95% confidence interval, CI: 0.6-80.6) and 20.0% (95% CI: 2.5-55.6), respectively. The newer typhoid rapid antibody tests had comparable PPVs: TUBEX(®), 54.1% (95% CI: 36.9-70.5); Typhidot(®) IgM, 56.7% (95% CI: 37.4-74.5); and Typhidot(®) IgG, 54.3% (95% CI: 36.6-71.2). For a pretest probability of 5%, PPVs were: TUBEX(®), 11.0% (95% CI: 6.6-17.9); Typhidot(®) IgM, 9.1% (95% CI: 5.8-14.0); and Typhidot(®) IgG, 11.0% (6.3-18.4). For a pretest probability of 50%, PPVs were: TUBEX(®), 70.2% (95% CI: 57.3-80.5); Typhidot(®) IgM, 65.6% (95% CI: 54.0-75.6); and Typhidot(®) IgG, 70.0% (95% CI: 56.0-81.1). CONCLUSION: Semiquantitative slide agglutination and single-tube Widal tests performed poorly. TUBEX(®) and Typhidot(®) may be suitable when pretest probability is high and blood cultures are unavailable, but their performance does not justify deployment in routine care settings in sub-Saharan Africa.

Zoonoses and marginalised infectious diseases of poverty: where do we stand?

Despite growing awareness of the importance of controlling neglected tropical diseases as a contribution to poverty alleviation and achieving the Millennium Development Goals, there is a need to up-scale programmes to achieve wider public health benefits. This implementation deficit is attributable to several factors but one often overlooked is the specific difficulty in tackling diseases that involve both people and animals - the zoonoses. A Disease Reference Group on Zoonoses and Marginalised Infectious Diseases (DRG6) was convened by the Special Programme for Research and Training in Tropical Diseases (TDR), a programme executed by the World Health Organization and co-sponsored by UNICEF, UNDP, the World Bank and WHO. The key considerations included: (a) the general lack of reliable quantitative data on their public health burden; (b) the need to evaluate livestock production losses and their additional impacts on health and poverty; (c) the relevance of cross-sectoral issues essential to designing and implementing public health interventions for zoonotic diseases; and (d) identifying priority areas for research and interventions to harness resources most effectively. Beyond disease specific research issues, a set of common macro-priorities and interventions were identified which, if implemented through a more integrated approach by countries, would have a significant impact on human health of the most marginalised populations characteristically dependent on livestock.

Social and cultural features of cholera and shigellosis in peri-urban and rural communities of Zanzibar.

BACKGROUND: Responding to the high burden of cholera in developing countries, the WHO now considers vaccination as a supplement to the provision of safe drinking water and improved sanitation in the strategy for cholera control in endemic settings. Cultural concepts of illness affect many aspects of public health. In the first step of a two-step strategy to examine determinants of cholera vaccine acceptance, this study identified social and cultural features of diarrhoeal illness for cholera control in endemic communities. METHODS: A cultural epidemiological study with locally adapted vignette-based interviews was conducted in two cholera-endemic communities of Zanzibar. A random sample of unaffected peri-urban (n = 179) and rural (n = 177) adults was interviewed to study community ideas of cholera and shigellosis, considering categories of distress, perceived causes, and help-seeking behaviour. RESULTS: Cholera was recognised by 88%. Symptoms of dehydration were most prominent in reports at the peri-urban site. Interference with work leading to strain on household finances was frequently emphasised. Dirty environment was the most prominent perceived cause, followed by unsafe drinking water and germ-carrying flies. Causes unrelated to the biomedical basis of cholera were reported more often by rural respondents. Rural women had more difficulty (20%) to identify a cause than men (7.1%, p = 0.016). Peri-urban self treatment emphasised rehydration; the rural community preferred herbal treatment and antibiotics. Shigellosis was recognised by 70%. Fewer regarded it as very serious compared with cholera (76% vs. 97%, p < 0.001) and regarded it as less likely to be fatal (48% vs. 78%, p < 0.001). More respondents could not explain causes of shigellosis (23%) compared with cholera (7.3%, p < 0.001). Community respondents less frequently identified dehydration and contagiousness for shigellosis. Government facilities were preferred healthcare providers for both conditions. CONCLUSIONS: This study clarified local views of cholera and shigellosis relevant for diarrhoeal disease control in Zanzibar. The finding that rural women were less likely than men to specify causes of cholera suggests more attention to them is required. Better health education is needed for cholera in rural areas and for shigellosis in general. This study also identified variables for subsequent analysis of social and cultural determinants of cholera vaccine acceptance.

A comprehensive approach to risk assessment and surveillance guiding public health interventions.

Tools are required to identify 'multi-endemic' population segments - in order to benefit the most vulnerable people and to make public health interventions cost-effective. The article suggests a comprehensive risk assessment and surveillance system approach based on a combination of epidemiological, environmental and social determinants. Such a cross-disciplinary approach will combine the advantages of forecasting upcoming disease 'hot spots' with provision of evidence for long-term planning under more stable conditions, and it may in principle apply to any combination of public health problems depending on the local context.

Oral cholera vaccine use in Zanzibar: socioeconomic and behavioural features affecting demand and acceptance.

BACKGROUND: Cholera remains a serious public health problem in low-income countries despite efforts in the past to promote oral rehydration therapy as major treatment. In 2007, the majority of worldwide cases (94%) and deaths (99%) were reported from Africa. To improve cholera control efforts in addition to maintaining and improving existing water supply, sanitation and hygiene behaviour measures, the World Health Organization has recently started to consider the use of vaccines as an additional public health tool. To assess this new approach in endemic settings, a project was launched in Zanzibar to vaccinate 50,000 individuals living in communities at high risk of cholera with an oral two-dose vaccine (Dukoral). Immunisation programmes in low-income countries have suffered a reduced coverage or were even brought to a halt because of an ignorance of local realities. To ensure the success of vaccination campaigns, implementers have to consider community-held perceptions and behaviours regarding the infectious disease and the vaccine of interest. The main aim of this study is to provide advice to the Ministry of Health and Social Welfare of Zanzibar regarding routine introduction of an oral cholera vaccine from a socioeconomic and behavioural perspective as part of a long-term development for a sustained cholera prevention strategy. METHODS AND DESIGN: Qualitative and quantitative methods of health social science research will be applied on four stakeholder levels before and after the mass vaccination campaign. Rapid assessment individual interviews and focus groups will be used to describe cholera- and vaccine-related views of policy makers, health care professionals and community representatives. The cultural epidemiological approach will be employed on the individual household resident level in a repeated cross-sectional design to estimate determinants of anticipated and actual oral cholera vaccine acceptance. DISCUSSION: The study presented here is designed to inform about people's perceptions regarding cholera and about socioeconomic and behavioural factors determining anticipated and actual oral cholera vaccine acceptance in Zanzibar. Its pre- and post-intervention design using a mixed-methods approach on different stakeholder levels in communities at high risk of cholera outbreaks will ensure the collection of locally valid data relevant for public health action and planning.

Characteristics of a pandemic clone of O3 : K6 and O4 : K68 Vibrio parahaemolyticus isolated in Beira, Mozambique.

The genetic characteristics of Vibrio parahaemolyticus strains isolated in 2004 and 2005 in Mozambique were assessed in this study to determine whether the pandemic clone of V. parahaemolyticus O3 : K6 and O4 : K68 serotypes has spread to Mozambique. Fifty-eight V. parahaemolyticus strains isolated from hospitalized diarrhoea patients in Beira, Mozambique, were serotyped for O : K antigens and genotyped for toxR, tdh and trh genes. A group-specific PCR, a PCR that detects the presence of ORF8 of the filamentous phage f237, arbitrarily primed PCR, PFGE and multilocus sequence typing were performed to determine the pandemic status of the strains and their ancestry. All strains of serovars O3 : K6 (n=38) and O4 : K68 (n=4) were identified as a pandemic clonal group by these analyses. These strains are closely related to the pandemic reference strains of O3 : K6 and O4 : K68, which emerged in Asia in 1996 and were later found globally. The pandemic serotypes O3 : K6 and O4 : K68 including reference strains grouped into a single cluster indicating emergence from a common ancestor. The O3 : K58 (n=8), O4 : K13 (n=6), O3 : KUT (n=1) and O8 : K41 (n=1) strains showed unique characteristics different from the pandemic clone.