Scope and Limits of an anamnestic questionnaire in a control-induced low-endemicity helminthiasis setting in south-central Côte d'Ivoire.

BACKGROUND: Schistosomiasis and soil-transmitted helminthiasis are two high-burden neglected tropical diseases. In highly endemic areas, control efforts emphasize preventive chemotherapy. However, as morbidity, infection, and transmission begin to decrease, more targeted treatment is likely to become more cost-effective, provided that comparatively cheap diagnostic methods with reasonable accuracy are available. METHODOLOGY: Adults were administered an anamnestic questionnaire in mid-2010 during a cross-sectional epidemiological survey in the Taabo health demographic surveillance system in south-central Côte d'Ivoire. Questions pertaining to risk factors and signs and symptoms for schistosomiasis and soil-transmitted helminthiasis were included. The individuals' helminth infection status and their belonging to three different anthelmintic treatment groups were compared with the questionnaire results (i) to inform the local health authorities about the epidemiological and clinical footprint of locally prevailing helminthiases, and (ii) to explore the scope and limits of an anamnestic questionnaire as monitoring tool, which eventually could help guiding the control of neglected tropical diseases in control-induced low-endemicity settings. PRINCIPAL FINDINGS: Our study sample consisted of 195 adults (101 males, 94 females). We found prevalences of hookworm, Trichuris trichiura, Schistosoma haematobium, and Schistosoma mansoni of 39.0%, 2.7%, 2.1%, and 2.1%, respectively. No Ascaris lumbricoides infection was found. Helminth infection intensities were generally very low. Seven, 74 and 79 participants belonged to three different treatment groups. Multivariable logistic regression models revealed statistically significant (p<0.05) associations between some risk factors, signs, and symptoms, and the different helminth infections and treatment groups. However, the risk factors, signs, and symptoms showed weak diagnostic properties. CONCLUSIONS/SIGNIFICANCE: The generally low prevalence and intensity of helminth infection in this part of south-central Côte d'Ivoire indicates that recent control efforts have turned our study area into a low endemicity setting. Our anamnestic questionnaire had low sensitivity and specificity to identify infected individuals or treatment groups.

Patients routinely report more symptoms to experienced field enumerators than physicians in rural Cote d'Ivoire.

Medical history-taking is among the most powerful diagnostic tools for healthcare professionals. However, its accuracy and reliability are underexplored areas. The present post-hoc study compares medical histories from 463 people in a rural part of Côte d'Ivoire. The medical histories of the same individuals were taken by physicians and experienced field enumerators who were blinded to the results of the others. Kappa (κ) statistics for 14 symptoms revealed only poor-to-moderate agreement between physicians and field enumerators (κ = 0.01-0.54). Participants reported consistently more symptoms to field enumerators than physicians. Only 33 (7.1%) participants gave no discordant statement at all. The average number of discordant statements per participant was 3.7. Poisson regression revealed no significant association between the number of discordant statements and participants' age, sex, educational attainment, occupation, or socioeconomic status. Operational research should further explore best practices to obtain reliable medical histories in resource-constrained settings.

Schistosomiasis, soil-transmitted helminthiasis, and sociodemographic factors influence quality of life of adults in Côte d'Ivoire.

BACKGROUND: Burden of disease estimates are widely used for priority setting in public health and disability-adjusted life years are a powerful "currency" nowadays. However, disability weights, which capture the disability incurred by a typical patient of a certain condition, are fundamental to such burden calculation and their determination remains a widely debated issue. METHODOLOGY: A cross-sectional epidemiological survey was conducted in the recently established Taabo health demographic surveillance system (HDSS) in south-central Côte d'Ivoire, to provide new, population-based evidence on the disability caused by schistosomiasis and soil-transmitted helminthiasis. Parasitological results from stool, urine, and blood examinations were juxtaposed to quality of life (QoL) questionnaire results from 187 adults. A multivariable linear regression model with stepwise backward elimination was used to identify significant associations, considering also sociodemographic characteristics obtained from the Taabo HDSS database. PRINCIPAL FINDINGS: Prevalences for hookworm, Plasmodium spp., Trichuris trichiura, Schistosoma haematobium and Schistosoma mansoni were 39.0%, 18.2%, 2.7%, 2.1% and 2.1%, respectively. S. mansoni and T. trichiura infections of any intensity reduced the participants' self-rated QoL by 16 points (95% confidence interval (CI): 4-29 points) and 13 points (95% CI: 1-24 points), respectively, on a scale from 0 (worst QoL) to 100 points (best QoL). The only other statistically significant effect was a 1-point (95% CI: 0.1-2 points) increase on the QoL scale per one unit increase in a calculated wealth index. CONCLUSIONS/SIGNIFICANCE: We found consistent and significant results on the negative effects of schistosomiasis and soil-transmitted helminthiasis on adults' self-rated QoL, also when taking sociodemographic characteristics into account. Our results warrant further investigation on the disability incurred by helmintic infections and the usefulness of generic QoL questionnaires in this endeavor.

Statins control oxidized LDL-mediated histone modifications and gene expression in cultured human endothelial cells.

OBJECTIVE: Activation of the endothelium by oxidized low-density lipoprotein (oxLDL) has been implicated in the development of atherosclerosis. Histone modifications impact on the transcriptional activity state of genes. We tested the hypothesis that oxLDL-induced inflammatory gene expression is regulated by histone modifications and experienced the effect of statins on these alterations. METHODS AND RESULTS: OxLDL-related interleukin-8 (IL-8) and monocyte-chemoattractant protein-1 (MCP-1) secretion in endothelial cells was reduced by statins but enhanced by histone deacetylase inhibitors. OxLDL induced lectin-like oxidized LDL receptor-1 (LOX-1) and extracellular regulated kinases (ERK1/2)-dependent acetylation of histone H3 and H4 as well as phosphorylation of histone H3, both globally and on the promoters of il8 and mcp1. Pretreatment of oxLDL-exposed cells with statins reduced the above mentioned histone modification, as well as recruitment of CREB binding protein (CBP) 300, NF-kappaB, and of RNA polymerase II but prevented loss of binding of histone deacetylase (HDAC)-1 and -2 at the il8 and mcp1 gene promoters. OxLDL reduced HDAC1 and 2 expression, and statins partly restored global HDAC-activity. Statin-related effects were reverted with mevalonate. In situ experiments indicated decreased expression of HDAC2 in endothelial cells in atherosclerotic plaques of human coronary arteries. CONCLUSIONS: Histone modifications seem to play an important role in atherosclerosis.

[The impact of war on the evolution of sleeping sickness in west-central Côte d'Ivoire]. / L'impact de la guerre sur l'evolution de la THA dans le centre-ouest de la Côte d'Ivoire.

OBJECTIVE: To evaluate the situation of sleeping sickness in west-central Côte d'Ivoire from 2000 to 2003, in view of the war which broke out in September 2002. METHODS: Active surveys by medical teams and passive case detection. RESULTS: Between 2000 and 2003, 250 patients were diagnosed with sleeping sickness. At first it appeared that sleeping sickness prevalence had fallen since the beginning of political troubles. But this apparent drop was due to poor population coverage. Participation in medical surveys differed according to ethnic group, reflecting land use conflicts between ethnic communities. Such conflicts are common in this area, but have been exacerbated by the war. CONCLUSION: In war, assessing the importance of sleeping sickness by medical surveys only is very difficult. But detection of sleeping sickness cases by passive surveillance increased.

Human African trypanosomiasis: quantitative and qualitative assessment of intrathecal immune response.

Quantitative and qualitative techniques for assessment of the intrathecal humoral immune response in human African trypanosomiasis were compared, and their diagnostic potential for detection of the meningo-encephalitic stage of the disease was evaluated. Total and trypanosome specific immunoglobulin G (IgG) and IgM intrathecal synthesis were studied in paired cerebrospinal fluid (CSF) and blood samples of 38 trypanosomiasis patients and in three controls using Reiber's formulae. The presence of CSF-specific oligoclonal IgG and of trypanosome-specific antibodies was determined using iso-electric focusing followed by immunoblotting and antigen-driven immunoblots. The intrathecal IgG fraction (16% positive) and oligoclonal IgG detection (24% positive) were insensitive for detection of an intrathecal humoral immune response. Trypanosome-specific IgG synthesis, reflected by the IgG antibody index (AI) (26% positive), was confirmed by the presence of oligoclonal specific IgG (47% positive), but the latter was more sensitive. Although the detection technique failed for oligoclonal IgM, the intrathecal IgM fraction (42% positive) and the IgM AI (32% positive) indicated that the meningo-encephalitic stage of the disease is characterized by a dominant intrathecal IgM response, which was higher than the IgG response. The highest combination of diagnostic sensitivity and specificity for the meningo-encephalitic stage of trypanosomiasis was observed for quantitative IgM determinations.

Stage determination and therapeutic decision in human African trypanosomiasis: value of polymerase chain reaction and immunoglobulin M quantification on the cerebrospinal fluid of sleeping sickness patients in Côte d'Ivoire.

In human African trypanosomiasis (HAT), two disease stages are defined: the first, or haemo-lymphatic stage, and the second, or meningo-encephalitic stage. Stage determination forms the basis of therapeutic decision and is of prime importance, as the drug used to cure second-stage patients has considerable side-effects. However, the tests currently used for stage determination have low sensitivity or specificity. Two new tests for stage determination in the cerebrospinal fluid (CSF) were evaluated on 73 patients diagnosed with HAT in Côte d'Ivoire. The polymerase chain reaction (PCR) detecting trypanosome DNA (PCR/CSF) is an indirect test for trypanosome detection whereas the latex agglutination test detecting immunoglobulin M (LATEX/IgM) is an indicator for neuro-inflammation. Both tests were compared with classically used tests, double centrifugation and white blood cell count of the CSF. PCR/CSF appeared to be the most sensitive test (96%), and may be of use to improve stage determination. However, its value for therapeutic decision appears limited, as patients whose CSF was positive with PCR were successfully treated with pentamidine. This result confirms those of previous works that showed that some patients with trypanosomes in the CSF could be treated successfully with pentamidine. LATEX/IgM, which depending on the cut-off, showed lower sensitivity of 76% and 88%, but higher specificity of 83% and 71% for LATEX/IgM 16 and LATEX/IgM 8 respectively, appears more appropriate for therapeutic decision making.

IgM quantification in the cerebrospinal fluid of sleeping sickness patients by a latex card agglutination test.

An increased IgM concentration in cerebrospinal fluid (CSF), occurring as a consequence of massive intrathecal IgM synthesis, is a marker of interest for diagnosis of the meningo-encephalitic stage in human African trypanosomiasis. However, in current practice, IgM in CSF is not determined because of the lack of a simple and robust test that is applicable in African rural regions where the disease prevails. We describe the development of a sensitive semiquantitative card agglutination test, LATEX/IgM, for IgM quantification in CSF. The test is simple and fast and the lyophilized reagent remains stable even at 45 degrees C. CSF end-titres obtained with LATEX/IgM parallel the IgM concentrations determined by nephelometry and enzyme-linked immunosorbent assay. Detection of intrathecal IgM synthesis is the most sensitive marker for CNS involvement in sleeping sickness. At a cut-off value of >or= 8, the sensitivity and specificity of LATEX/IgM for intrathecal IgM synthesis are 89.4 and 92.7%. As a consequence, patients with LATEX/IgM end-titres >or= 8 are likely to have intrathecal IgM synthesis, thus central nervous system involvement and therefore should be treated accordingly. Further studies should concentrate on the relationship between the LATEX/IgM end-titres, presence of intrathecal IgM synthesis and occurrence of treatment failures in patients treated with pentamidine.

Comparison of different DNA preparation protocols for PCR diagnosis of Human African Trypanosomosis in Côte d'Ivoire.

During a medical survey the sleeping sickness focus in Bonon, Ivory Coast, PCR with Trypanosoma brucei specific primers (TBR 1-2 from Parasitology 99 (1989) 57) was tested on DNA derived from blood samples. DNA purification using a chelating resin was performed either on whole blood or on the buffy coat prepared in two different ways. The preparation based on whole blood performed better than those using the buffy-coat. Using this first method, the sensitivity was 100% on parasitologically confirmed patients, and the specificity was 92%. However, problems of reproducibility of the technique were pointed out, particularly on samples from serologically positive but apparently aparasitemic individuals. It is suggested that the PCR could help in the diagnosis of Human African Trypanosomosis, but the use of other primers should be investigated.

[Human African trypanosomiasis in Ivory Coast: biological characteristics after treatment. 812 cases treated in the Daloa focus (Ivory Coast)]. / Trypanosomose humaine africaine en Côte d'Ivoire: caractéristiques biologiques après traitement. A propos de 812 cas traités dans le foyer de Daloa (Côte d'Ivoire).

The treatment and post therapeutic follow up of patients diagnosed with HAT are important for HAT control. A longitudinal survey was implemented in the focus of Daloa (Côte d'Ivoire). A total of 812 patients infected with Trypanosoma brucei gambiense in meningoencephalitic stage and treated with melarsoprol were included, this study pointed out the biological characteristics of patients after treatment. The relapse occurs between 1 and 24 months after treatment. It is essentially neurological, and characterised by the presence in the CSF of antibodies, by the increase of cell count compared with value immediately after treatment, or by the presence of trypanosomes. The cure can be confirmed from 18 months after treatment, and is characterised by the absence of antibodies and trypanosomes in the CSF, by a normal cell count and a normal proteinorachy. Biological scares were recorded on some of the patients after 18 months of follow up, but no relapse occurred among them.

[Geographic distribution of trypanosomiasis treated in Ivory Coast from 1993 to 2000]. / Distribution géographique des trypanosomés pris en charge en Côte d'Ivoire de 1993 à 2000.

Human African Trypanosomosis (HAT, or sleeping sickness) caused by Trypanosoma brucei gambiense develops chronically in Côte d'Ivoire. From 1993 to 2000, a total of 1616 patients were taken in charge in the three treatment centres of the country, which means an average of 202 patients a year. The patients came from two main areas in the Centre West of the country in the Marahoué region: the districts of Sinfra, South of Bouaflé, and Bonon, West of Bouaflé. In the Centre West and in the South East of the country (Aboisso-Ayamé), patients are still struck by the disease, although these foci are less active. The remaining foci seem to be controlled, although no active survey has been carried out. The areas where the greatest number of patients were recorded are the ones where rental crops are located (cocoa and coffee mainly) and where rural activities tend to bring humans and tsetse flies in contact. In this study, are figured the number of treated patients, the endemic and risk areas. It will help to design control strategies and decision makers to know where priority control programs should be implemented.