2012/13 influenza vaccine effectiveness against hospitalised influenza A(H1N1)pdm09, A(H3N2) and B: estimates from a European network of hospitals.

While influenza vaccines aim to decrease the incidence of severe influenza among high-risk groups, evidence of influenza vaccine effectiveness (IVE) among the influenza vaccine target population is sparse. We conducted a multicentre test-negative case-control study to estimate IVE against hospitalised laboratory-confirmed influenza in the target population in 18 hospitals in France, Italy, Lithuania and the Navarre and Valencia regions in Spain. All hospitalised patients aged ≥18 years, belonging to the target population presenting with influenza-like illness symptom onset within seven days were swabbed. Patients positive by reverse transcription polymerase chain reaction for influenza virus were cases and those negative were controls. Using logistic regression, we calculated IVE for each influenza virus subtype and adjusted it for month of symptom onset, study site, age and chronic conditions. Of the 1,972 patients included, 116 were positive for influenza A(H1N1)pdm09, 58 for A(H3N2) and 232 for influenza B. Adjusted IVE was 21.3% (95% confidence interval (CI): -25.2 to 50.6; n=1,628), 61.8% (95% CI: 26.8 to 80.0; n=557) and 43.1% (95% CI: 21.2 to 58.9; n=1,526) against influenza A(H1N1) pdm09, A(H3N2) and B respectively. Our results suggest that the 2012/13 IVE was moderate against influenza A(H3N2) and B and low against influenza A(H1N1) pdm09.

Routine ultrasound examination at 41 weeks of gestation and risk of post-term severe adverse fetal outcome: a retrospective evaluation of two units, within the same hospital, with different guidelines.

OBJECTIVE: To study whether a routine with a routine ultrasound examination (routine scan) at 41 gestational weeks as compared with ultrasound on clinical indication (indicated scan), lowered the risk of severe adverse fetal outcome in post-term period. DESIGN: A retrospective cohort study. SETTING: Karolinska University Hospital, Stockholm, Sweden. POPULATION: Eight years of deliveries, 2002-2009. METHOD: One of the two delivery units at Karolinska University Hospital used a routine scan at 41 week of gestation and the other unit used an indicated scan. Severe adverse fetal outcome were defined: severe asphyxia, death or cerebral damage. The study was analysed using logistic regression with adjustment for potential confounders. MAIN OUTCOME MEASURES: Differences in post-term severe adverse fetal outcome. RESULTS: No increased risk of post-term severe adverse fetal outcome was seen at the unit using a routine scan; conversely, a 48% significantly increased risk was seen at the unit using an indicated scan (OR 0.89, 95% confidence interval, CI, 0.5-1.5 and OR 1.48, 95% CI 1.06-2.1, respectively). Comparing post-term periods, there was no significantly increased risk at the unit using indicated scans (OR 1.6, 95% CI 0.9-3.0). There was a 60% increased prevalence of small-for-gestational age (SGA) newborns in the post-term period at the unit using indicated scans (OR 1.6, 95% CI 1.1-2.4), but no differences in operative delivery. CONCLUSION: A policy to use routine scans at 41 weeks of gestation seems to normalise an increased post-term risk of severe adverse fetal outcome, possible due to increased awareness of SGA and/or oligohydramniosis.

Influenza vaccine effectiveness estimates in Europe in a season with three influenza type/subtypes circulating: the I-MOVE multicentre case-control study, influenza season 2012/13.

In the fifth season of Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE), we undertook a multicentre case-control study (MCCS) in seven European Union (EU) Member States to measure 2012/13 influenza vaccine effectiveness against medically attended influenza-like illness (ILI) laboratory confirmed as influenza. The season was characterised by substantial co-circulation of influenza B, A(H1N1)pdm09 and A(H3N2) viruses. Practitioners systematically selected ILI patients to swab ≤7 days of symptom onset. We compared influenza-positive by type/subtype to influenza-negative patients among those who met the EU ILI case definition. We conducted a complete case analysis using logistic regression with study as fixed effect and calculated adjusted vaccine effectiveness (AVE), controlling for potential confounders (age, sex, symptom onset week and presence of chronic conditions). We calculated AVE by type/subtype. Study sites sent 7,954 ILI/acute respiratory infection records for analysis. After applying exclusion criteria, we included 4,627 ILI patients in the analysis of VE against influenza B (1,937 cases), 3,516 for A(H1N1)pdm09 (1,068 cases) and 3,340 for influenza A(H3N2) (730 cases). AVE was 49.3% (95% confidence interval (CI): 32.4 to 62.0) against influenza B, 50.4% (95% CI: 28.4 to 65.6) against A(H1N1)pdm09 and 42.2% (95% CI: 14.9 to 60.7) against A(H3N2). Our results suggest an overall low to moderate AVE against influenza B, A(H1N1)pdm09 and A(H3N2), between 42 and 50%. In this season with many co-circulating viruses, the high sample size enabled stratified AVE by type/subtype. The low estimates indicate seasonal influenza vaccines should be improved to achieve acceptable protection levels.

Low and decreasing vaccine effectiveness against influenza A(H3) in 2011/12 among vaccination target groups in Europe: results from the I-MOVE multicentre case-control study.

Within the Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE) project we conducted a multicentre case­control study in eight European Union (EU) Member States to estimate the 2011/12 influenza vaccine effectiveness against medically attended influenza-like illness (ILI) laboratory-confirmed as influenza A(H3) among the vaccination target groups. Practitioners systematically selected ILI / acute respiratory infection patients to swab within seven days of symptom onset. We restricted the study population to those meeting the EU ILI case definition and compared influenza A(H3) positive to influenza laboratory-negative patients. We used logistic regression with study site as fixed effect and calculated adjusted influenza vaccine effectiveness (IVE), controlling for potential confounders (age group, sex, month of symptom onset, chronic diseases and related hospitalisations, number of practitioner visits in the previous year). Adjusted IVE was 25% (95% confidence intervals (CI): -6 to 47) among all ages (n=1,014), 63% (95% CI: 26 to 82) in adults aged between 15 and 59 years and 15% (95% CI: -33 to 46) among those aged 60 years and above. Adjusted IVE was 38% (95%CI: -8 to 65) in the early influenza season (up to week 6 of 2012) and -1% (95% CI: -60 to 37) in the late phase. The results suggested a low adjusted IVE in 2011/12. The lower IVE in the late season could be due to virus changes through the season or waning immunity. Virological surveillance should be enhanced to quantify change over time and understand its relation with duration of immunological protection. Seasonal influenza vaccines should be improved to achieve acceptable levels of protection.

The case-cohort design in outbreak investigations.

The use of the case-cohort design for outbreak investigations has been limited. Here we discuss its strengths and limitations based on real and fictitious examples. The case-cohort is a case­control study where controls are sampled from the initial population at risk, and may thus include both cases and non-cases. An advantage of the design, compared to traditional case-control studies, is that risk ratios can easily be obtained directly from the cross-product of exposed and unexposed cases and controls (rare disease assumption is not required). We illustrate this in the context of point source gastrointestinal outbreaks and in field studies on vaccine effectiveness. The design is also useful to investigate multiple outcomes with a unique sample of controls or to test hypotheses when different case-definitions (from the most sensitive to the most specific) are used for a particular outcome. Strengths and limitations are presented, and discussed in the context of outbreak investigations.

Applied epidemiology training in Europe: quite a success - but more to be done.

This article describes the development of training in applied epidemiology in Europe and outlines the current situation in Europe with a view of how the system can be improved to meet future challenges.

"I-MOVE" towards monitoring seasonal and pandemic influenza vaccine effectiveness: lessons learnt from a pilot multi-centric case-control study in Europe, 2008-9.

Within I-MOVE (European programme to monitor seasonal and pandemic influenza vaccine effectiveness (IVE)) five countries conducted IVE pilot case-control studies in 2008-9. One hundred and sixty sentinel general practitioners (GP) swabbed all elderly consulting for influenza-like illness (ILI). Influenza confirmed cases were compared to influenza negative controls. We conducted a pooled analysis to obtain a summary IVE in the age group of >or=65 years. We measured IVE in each study and assessed heterogeneity between studies qualitatively and using the I2 index. We used a one-stage pooled model with study as a fixed effect. We adjusted estimates for age-group, sex, chronic diseases, smoking, functional status, previous influenza vaccinations and previous hospitalisations. The pooled analysis included 138 cases and 189 test-negative controls. There was no statistical heterogeneity (I2=0) between studies but ILI case definition, previous hospitalisations and functional status were slightly different. The adjusted IVE was 59.1% (95% CI: 15.3-80.3%). IVE was 65.4% (95% CI: 15.6-85.8%) in the 65-74, 59.6% (95% CI: -72.6 -90.6%) in the age group of >or=75 and 56.4% (95% CI: -0.2-81.3%) for A(H3). Pooled analysis is feasible among European studies. The variables definitions need further standardisation. Larger sample sizes are needed to achieve greater precision for subgroup analysis. For 2009-10, I-MOVE will extend the study to obtain early IVE estimates in groups targeted for pandemic H1N1 influenza vaccination.

First steps in the design of a system to monitor vaccine effectiveness during seasonal and pandemic influenza in EU/EEA Member States.

Estimating influenza vaccine effectiveness (IVE) early in the season helps measuring the consequences of a mismatch between the vaccine and the circulating strain and guiding alternative or complementary interventions. The European Centre for Disease Prevention and Control is funding a project to develop pilot studies to monitor IVE in the Member States (MS) of the European Union and European Economic Area (EU/EEA) during seasonal and pandemic influenza. To identify key methodological and practical issues in developing protocols for pilot studies, we conducted a survey among EU/EEA MS, a literature review on IVE methods, and consultations of experts. The survey and literature review highlighted the variety of the data sources used to estimate IVE and the difficulty to interpret data on IVE, which varies with age, risk group, outcome specificity and virus-vaccine mismatch. We also found that negative and positive confounding can bias IVE. The experts consultations lead to the following recommendations: to measure IVE in the same population in various seasons; to control for positive/negative confounding (including pre- and post-influenza season IVE estimates); and to include laboratory confirmation as outcome in various study designs. In the 2008-9 influenza season, two cohort studies using general practitioners' databases and six case control studies will be piloted in EU/EEA MS and will adhere to the above recommendations. The pilot studies will be the basis for the development of robust methods to monitor IVE in EU/EEA MS.

cDNA cloning and expression of a human platelet-derived growth factor (PDGF) receptor specific for B-chain-containing PDGF molecules.

The structure of the human receptor for platelet-derived growth factor (PDGF) has been deduced through cDNA cloning. A 5.45-kilobase-pair cDNA clone predicts a 1,106-amino-acid polypeptide, including the cleavable signal sequence. The overall amino acid sequence similarity with the murine PDGF receptor is 85%. After transcription of the cDNA and translation in vitro, a PDGF receptor antiserum was used to immunoprecipitate a product of predicted size, which also could be phosphorylated in vitro. Stable introduction of the cDNA into Chinese hamster ovary (CHO) cells led to the expression of a 190-kilodalton component, which was immunoprecipitated by the PDGF receptor antiserum; this most probably represents the mature PDGF receptor. Binding assays with different 125I-labeled dimeric forms of PDGF A and B chains showed that the PDGF receptor expressed in CHO cells bound PDGF-BB and, to a lesser extent, PDGF-AB, but not PDGF-AA.

Moderate influenza vaccine effectiveness against hospitalisation with A(H3N2) and A(H1N1) influenza in 2013-14: Results from the InNHOVE network.

We conducted a multicentre test negative case control study to estimate the 2013-14 influenza vaccine effectiveness (IVE) against hospitalised laboratory confirmed influenza in 12 hospitals in France, Italy and Spain. We included all ≥18 years hospitalised patients targeted by local influenza vaccination campaign reporting an influenza-like illness within 7 days before admission. We defined as cases patients RT-PCR positive for influenza and as controls those negative for all influenza virus. We used a logistic regression to calculate IVE adjusted for country, month of onset, chronic diseases and age. We included 104 A(H1N1)pdm09, 157 A(H3N2) cases and 585 controls. The adjusted IVE was 42.8% (95%CI: 6.3;65;0) against A(H1N1)pdm09. It was respectively 61.4% (95%CI: -1.9;85.4), 39.4% (95%CI: -32.2;72.2) and 19.7% (95%CI:-148.1;74.0) among patients aged 18-64, 65-79 and ≥80 years. The adjusted IVE against A(H3N2) was 38.1% (95%CI: 8.3;58.2) overall. It was respectively 7.8% (95%CI: -145.3;65.4), 25.6% (95%CI: -36.0;59.2) and 55.2% (95%CI: 15.4;76.3) among patients aged 18-64, 65-79 and ≥80 years. These results suggest a moderate and age varying effectiveness of the 2013-14 influenza vaccine to prevent hospitalised laboratory-confirmed influenza. While vaccination remains the most effective prevention measure, developing more immunogenic influenza vaccines is needed to prevent severe outcomes among target groups.

Functional consequences of tumorigenic missense mutations in the amino-terminal domain of Smad4.

Smads, the intracellular effectors of transforming growth factor-beta (TGF-beta) family members, are somatically mutated at high frequency in particular types of human cancers. Certain of these mutations affect the Smad amino-terminal domain, which, in the case of Smad3 and Smad4, binds DNA. We investigated the functional consequences of four missense mutations in the Smad4 amino-terminal domain found in human tumors. The mutant proteins were found to have impaired abilities to bind DNA although they were fully capable of forming complexes with Smad3. All four Smad4 mutants showed decreased protein stability compared to wild-type Smad4. Two of the Smad4 mutants (G65V and P130S) were translocated to the nucleus and were capable of transactivating a Smad-dependent promoter in a ligand-dependent manner. In contrast, the L43S and R100T mutants were not translocated efficiently to the nucleus and consequently resulted in severely defective transcriptional responses to TGF-beta. Moreover, we demonstrate here the critical importance of two basic residues in the beta-hairpin loop of Smad3 or Smad4 for DNA binding, consistent with predictions from the Smad3 crystal structure. In addition, our results reveal that in the TGF-beta-induced heteromeric signaling complex, loss of DNA binding of Smad4 can be compensated by Smad3, however, both Smad3 and Smad4 are needed for efficient DNA binding and signaling. In conclusion, mutations in the amino-terminal domain of Smad4, that are found in cancer, show loss of multiple functional properties which may contribute to tumorigenesis.

Structural properties of 3.0 kb and 3.2 kb transcripts encoding platelet-derived endothelial cell growth factor/thymidine phosphorylase in A431 cells.

Platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) is a 90 kDa protein consisting of two non-covalently associated subunits. In addition to the previously identified 1.8 kilobase (kb) PD-ECGF/TP mRNA, the human epidermoid carcinoma cell line A431 was found to express 3.0 kb and 3.2 kb transcripts. cDNA cloning of the larger transcripts revealed that they contain long 5' leader sequences of 1.5 kb and 1.7 kb, respectively, and the same open reading frame encoding PD-ECGF/TP as that of the 1.8 kb transcript. Comparison with the published PD-ECGF/TP genomic sequence shows that the long 5' leader sequence contain 7 of 8 copies of Sp-1 binding sites present in the transcription promoter region of the 1.8 kb transcript.

Expression of type I and type IB receptors for activin in midgestation mouse embryos suggests distinct functions in organogenesis.

Activins exert their effects by inducing heteromeric complexes of either of two different type I receptors, ActR-I or ActR-IB, and either of two type II receptors, ActR-II or ActR-IIB. We describe the cDNA cloning of the mouse homologue of human ActR-IB and analyze binding of radio-iodinated activin on type I/type II combinations of mouse receptors expressed from cDNA. We studied the distribution of ActR-I and ActR-IB mRNAs in postimplantation mouse embryos by in situ hybridization. In the 12.5-day postcoitum embryo, both mRNAs are found in the brain, spinal cord, some ganglia, vibrissae, lungs, body wall, stomach, gonads, ribs, limbs and shoulders. ActR-I mRNA, but not ActR-IB, is expressed in blood vessels, the heart, tongue, intervertebral discs and diaphragm. Conversely, only ActR-IB mRNA is detected in the olfactory region, eye, tooth primordium, esophagus, mesonephros, dorsal root ganglia and is strongly expressed in the spinal cord. Our results demonstrate similarities, but also differences and complementarities (mesenchymal versus epithelial expression) between the expression patterns of these type I receptors. Moreover, their expression patterns overlap with at least one of the type II activin receptors and/or one of activin subunits in some regions of the embryo, such as the brain, spinal cord, pituitary, whisker follicles, and the inner nuclear neuroblastic layer of the eye.

Distinct spatial and temporal expression patterns of two type I receptors for bone morphogenetic proteins during mouse embryogenesis.

Bone morphogenetic proteins (BMPs) are multifunctional proteins structurally related to transforming growth factor-beta (TGF beta) and activin that can induce cartilage and bone growth in vivo. Members of the TGF beta superfamily exert their biological effects via heteromeric serine/threonine kinase complexes of type I and type II receptors. We previously obtained six different type I receptors, termed activin receptor-like kinase-1 (ALK-1) to -6. ALK-5 is a TGF beta type I receptor, ALK-2 and ALK-4 are activin type I receptors, and ALK-3 and ALK-6 are type I receptors for osteogenic protein-1 (OP-1)/bone morphogenetic protein-7 (BMP-7) and BMP-4. Here we report the complementary DNA cloning of the mouse homolog of ALK-3, which is highly conserved between mouse and man. ALK-3 messenger RNA (mRNA) is ubiquitously expressed in various adult mouse tissues, whereas ALK-6 mRNA is only found in brain and lung. The distribution of ALK-3 and ALK-6 mRNA in the postimplantation mouse embryo [6.5-15.5 days postcoitum (pc)] was studied by in situ hybridization. ALK-3 was nearly ubiquitously expressed throughout these stages of development, but was notably absent in the liver. In contrast, ALK-6 showed a more restricted expression pattern. ALK-6 mRNA was absent in early postimplantation embryos, was detected first in 9.5 days pc embryos, and persisted until 15.5 days pc. In midgestation embryos, ALK-6 transcripts were detected in mesenchymal precartilage condensations, premuscle masses, blood vessels, central nervous system, parts of the developing ear and eye, and epithelium. The expression in sites of developing cartilage and bone supports the idea that ALK-3 and -6 are receptors for BMPs in vivo. In addition, the expression of these genes in many soft tissues suggests broader functions for BMPs in embryogenesis.

Measles epidemic in the urban community of Niamey: transmission patterns, vaccine efficacy and immunization strategies, Niger, 1990 to 1991.

From October 1, 1990, until April 28, 1991, 13,578 cases of measles were reported in the urban community of Niamey, Niger. Vaccine coverages (one dose of Schwarz vaccine given after 9 months) in urban community of Niamey were, respectively, 63% at the age of 12 months and 73% at 24 months before the epidemic. Incidence rates were the highest among children ages 6 to 8 months and 9 to 11 months and 22% of the cases were less than 1 year old. Vaccine efficacy estimates ranged from 86 to 94% according to age groups and the method used (screening method, case control study, retrospective cohort study). The risk of transmission of illness increased with the intensity of contact with a case. Contact with a health facility 7 to 22 days before onset of rash was not a risk factor. Seasonal migrants in Niamey were more likely to develop measles. Recommendations included implementation of an early two dose schedule of measles immunization during the outbreak, vaccination offered at each contact with a health facility, radio and television advertising for measles immunization and distribution of vitamin A to all measles cases.

Measles vaccine effectiveness in standard and early immunization strategies, Niger, 1995.

BACKGROUND: An Expanded Programme on Immunization was started in late 1987 in Niger, including vaccination against measles with one dose of standard titer Schwarz vaccine given to infants after 9 months of age. During epidemics an early two-dose strategy was implemented (one dose between 6 and 8 months and one dose after 9 months). From January 1, 1995, until May 7, 1995, 13 892 measles cases were reported in Niamey, Niger. METHODS: A retrospective cohort study was conducted in a crowded area of Niamey at the end of the outbreak to assess the effectiveness of measles vaccine in standard (after 9 months) and early (before 9 months) immunization strategies under field conditions. RESULTS: Highest measles incidence rates were observed among children <1 year of age. Vaccine effectiveness estimates increased with age at vaccination from 78% with a single dose administered at 6 months of age to 95% at 9 months. Vaccine effectiveness with the early two dose strategy was 93%. CONCLUSIONS: Immunization with a single dose of standard titer Schwarz vaccine before 9 months of age provided higher clinical protection than expected from seropositivity studies. The early two dose strategy is justified in contexts where measles incidence is high before 9 months of age. Our results raise the issue of lowering the recommended age for measles vaccination in developing countries.

Measles outbreaks in the Mozambican refugee camps in Malawi: the continued need for an effective vaccine.

Between November 1988 and January 1989, measles outbreaks occurred in 11 Mozambican refugee camps in Malawi with five camps principally affected. A total of 1214 cases were reported. Despite the reduction of the age of measles vaccination to six months in 1987, attack rates were highest in children aged 6-9 months (10-26%); rates were also high in the 0-5 month age group (3-21%). The case-fatality rate was high among children less than five years old (15-21%). Children were being inappropriately vaccinated, either being vaccinated at less than six months of age (2-29%) or failing to receive a second dose if vaccinated at six months (0-25%). With vaccine coverage between 66-87%, vaccine efficacy in children less than five years old was estimated to be more than 90% in the camps principally affected. Reduction of the age of vaccination leads to logistical problems in vaccine delivery in refugee situations. These outbreaks again indicate the need to improve vaccine coverage with the existing Schwarz vaccine, and also highlight the urgent need for an effective single dose measles vaccine for children less than nine months of age.

An outbreak of pellagra related to changes in dietary niacin among Mozambican refugees in Malawi.

Between February and October 1990, 18,276 cases of pellagra dermatitis (due to niacin deficiency) were reported among 285,942 Mozambican refugees in Malawi. Overall, 6.3% of the refugee population developed pellagra and the attack rate was 7.8 times higher among women than men. This outbreak followed a 5-month cessation of groundnut distribution (the major source of niacin) to refugees. A matched-pair case-control study confirmed the protective role of the daily consumption of groundnuts (Odds Ratio [OR] = 0.08), as well as the independent role of garden ownership (OR = 0.34), and home maize milling (OR = 0.3). Recommended corrective action included early case finding and treatment, distribution of niacin tablets, prompt identification of groundnut supply on the world market, fortification with niacin of the food ration and diversification of the food basket through access to local markets.

PIP: Between February and October 1990, health workers in Malawi noted 18,276 cases of pellagra among 285,942 Mozambican refugees. This represented a significant increase in pellagra cases (compared with just 1169 cases in 1989). 5 months before each outbreak, the UN High Commission for Refugees and the World Food Program could not obtain groundnuts, a source of niacin, to include in food rations. The food ration distributed to refugees had an average of just 4 mg available niacin equivalent (or 2 mg/1000 kcal) which was considerably less than the recommended daily allowance of 6.6 mg/1000 kcal. The overall attack rate stood at 6.4% (4.9-13.2%. It was higher among refugees living in camps than it was among those living in Malawian villages near the border (10.1% vs. 0.8%). The attack rate was 7.8 times higher in females than males (6.1/1000 vs. 0.78/1000). It was lowest among children under 5 years old (1.7% vs. 7.5% for = or 5 year olds). No infant had pellagra. Researchers compared 126 pellagra cases with 126 controls. The conditional logistic regression indicated that pellagra cases were less likely to eat groundnuts and fish at least once a day within the last 6 months (odds ratio [OR] = .07 and .56, respectively). They tended not to have a garden (OR = .32) and to mill maize at home (OR = .26). Thus, eating groundnuts, milling maize at home, and garden ownership protected the refugees from developing pellagra. In August 1990, relief workers distributed niacin tablets to refugees. The health workers recommended other corrective actions such as early case finding and treatment, identification of groundnut supply on the world market, and diversification of the food basket through access to local markets.

A multifocal outbreak of trichinellosis linked to horse meat imported from North America to France in 1993.

An outbreak of 538 cases of trichinellosis occurred in France in December 1993. Seven cases developed neurotrichinosis and 23 had cardiologic complications. No deaths were recorded. Two patients had a positive muscle biopsy showing living Trichinella larvae. One of them was typed as Trichinella spiralis. A case-control study showed that horse meat was the only meat associated with illness (odds ratio = 80.7). The risk of illness increased with the amount of horse meat eaten and when it was consumed raw. The cases, which were spread out in five foci, bought horse meat from five butchers who had received parts of a single horse carcass imported in November 1993 from Canada. The Trichinella International Screening Program, implemented since 1985 after two similar episodes involving a thousand cases, failed to detect the incriminated horse carcass. This new horse meat-related outbreak led to modifications of the internationally recommended screening methods whereby the weight of meat samples tested was increased.

Visceral leishmaniasis in southern Sudan.

Reports made by Médecins Sans Frontières in Khartoum on an outbreak of visceral leishmaniasis among displaced people from the western Upper Nile prompted an investigation at Ler Hospital, the second largest in the region. In a 10 d period during April 1989, 100 persons with visceral leishmaniasis were identified. Of these, 82% were men; 67% were aged 20 to 39 years. Except for the absence of ulcerated skin lesions, the clinical features corresponded to those traditionally described in the Sudan. A cross-sectional serological survey was conducted in Kuernyang (400 inhabitants), 40 km north of Ler. The anti-Leishmania antibody prevalence was 18.2%, being higher among those older than 15 years, and higher among adult women (28%) than among men (18%). The overall prevalence of splenomegaly was 16.4%. 33% of seropositive cases presented with splenomegaly, compared with 11.6% of those who were seronegative. Three serological surveys conducted on the eastern side of the Nile showed no seropositive cases. However, 2 autochthonous cases were clinically diagnosed and confirmed by serological assays. The war conflicts and population movements appear to be the main cause of this large outbreak that may have killed thousands of tribespeople in southern Sudan. There is a risk of the disease spreading into other areas with devastating consequences for the population, should energetic measures not be immediately taken.