Thomas Kesteman

Listeria infections associated with infliximab: case reports

Infliximab is a human-murine chimeric monoclonal antibody directed against tumor necrosis factor α (TNFα). Infliximab and other TNF blockers are used to treat inflammatory diseases such as rheumatoid arthritis (RA). TNF blockers are suspected to play a key role in some infections. We report here two cases of Listeria monocytogenes sepsis associated with infliximab treatment for RA. The first patient developed a terminal ileitis and a bacteraemia after three doses of infliximab; the second RA patient presented a bacteraemia associated with a prosthetic joint arthritis of the left hip, both related to Listeria. Those two cases occurred in a population of 518 patients treated with TNF blockers in our hospitals since the year 2000. Those events are of particular interest because of the severity of the infection, because the treatment differs from other infections, and because that, in the rheumatology unit, septic arthritis can mimic RA symptoms. They enhance the likelihood for this drug to increase the risk for infections with germs like Listeria.

“Tazomoka Is Not a Problem”. Local Perspectives on Malaria, Fever Case Management and Bed Net Use in Madagascar

Background Although its incidence has been decreasing during the last decade, malaria is still a major public health issue in Madagascar. The use of Long Lasting Insecticidal Nets (LLIN) remains a key malaria control intervention strategy in Madagascar, however, it encounters some obstacles. The present study aimed to explore the local terminology related to malaria, information channels about malaria, attitude towards bed nets, and health care seeking practices in case of fever. This article presents novel qualitative findings about malaria. Until now, no such data has been published for Madagascar. Methods A comparative qualitative study was carried out at four sites in Madagascar, each differing by malaria epidemiology and socio-cultural background of the populations. Seventy-one semi-structured interviews were conducted with biomedical and traditional caregivers, and members of the local population. In addition, observations of the living conditions and the uses of bed net were conducted. Results Due to the differences between local and biomedical perspectives on malaria, official messages did not have the expected impact on population in terms of prevention and care seeking behaviors. Rather, most information retained about malaria was spread through informal information circulation channels. Most interviewees perceived malaria as a disease that is simple to treat. Tazomoka (“mosquito fever”), the Malagasy biomedical word for malaria, was not used by populations. Tazo (“fever”) and tazomahery (“strong fever”) were the terms more commonly used by members of the local population to refer to malaria related symptoms. According to local perceptions in all areas, tazo and tazomahery were not caused by mosquitos. Each of these symptoms required specific health recourse. The usual fever management strategies consisted of self-medication or recourse to traditional and biomedical caregivers. Usage of bed nets was intermittent and was not directly linked to protection against malaria in the eyes of most Malagasy people. Conclusions This article highlights the conflicting understanding of malaria between local perceptions and the biomedical establishment in Madagascar. Local perceptions of malaria present a holistic vision of the disease that includes various social and cultural dimensions, rather than reflecting one universal understanding, as in the biomedical image. The consideration of this “holistic vision” and other socio-cultural aspects surrounding the understanding of malaria is essential in implementing successful control intervention strategies.

Assessing the impact of vector control interventions by measuring their effectiveness - what has been done in Madagascar

The impact of disease control can be either evaluated by a classical ecological study, or by multiplication of the effectiveness of control intervention and the disease burden. The latter approach has the advantage of circumventing ecological biases. To evaulate the effectiveness of the malaria control program implemented in Madagascar, we conducted a nationwide survey in 2012-2013 in 62 study sites. This survey included (1) a cross-sectional study to measure the effectiveness of each control intervention on reducing the transmission, and (2) a case-control study to measure the effectiveness on reducing the morbidity. We present here the results related to vector control interventions, i.e. Long Lasting Insecticidal Nets (LLIN) distribution and Indoor Residual Spraying (IRS) campaigns. The cross-sectional survey included 15,734 individuals of all age groups among which 3.7% had a positive Rapid Diagnostic Test (RDT). LLIN daily use was 52.3% in areas covered by universal distribution and IRS coverage was 64.8% in targeted areas. 818 uncomplicated clinical malaria cases were compared to 7,767 controls living in the same villages. Multilevel analysis of factors associated with a positive RDT or with the occurrence of an episode of non-complicated malaria revealed that LLIN daily use had a 45% protective effectiveness (PE) against infection (aOR 0.55 [95% CI 0.42, 0.72]) and a 48% PE against morbidity (aOR 0.52 [0.28, 0.96]). The PE of IRS was evaluated to be 23% against infection (aOR 0.77 [0.53, 1.13]) and 49% against morbidity (aOR 0.51 [0.39, 0.66]). In areas where both activities are implemented, coverage of LLIN was 21.3 percentage points lower than in areas where LLIN only were deployed. Combining IRS with LLIN provided almost no gain in preventing infection, but the PE of LLIN use against morbidity increased from 51% (aOR 0.49 [0.20, 1.20]) to 66% (aOR 0.34 [0.16, 0.74]) when IRS was added, although non significantly. Our results indicate that, taken separately, LLIN and IRS perform satisfactorily but that their concurrent use might have a limited benefit as compared with efforts to improve the coverage of a single intervention. Given that in Madagascar, approx. 220,000 clinical malaria cases and 770,000 malaria infections occur each year, we calculated that vector control interventions prevented approx. 96,000 malaria cases and 197,000 malaria infections annually. Distributions of LLIN were implicated in the major part of cases (73.7%) and infections (80.5%) prevented, while IRS campaigns were implicated in 37.3% of cases and 31.2% of infections prevented.

Prevalence and genetic heterogeneity of Borrelia burgdorferi sensu lato in ixodes ticks in Belgium.

Abstract Borrelia burgdorferi sensu lato is a genetically diverse group of spirochetes that includes the agent of Lyme borreliosis in which genospecies tend to be associated with specific clinical features. The aim of the study was to determine the prevalence and genetic diversity of Borrelia burgdorferi sensu lato in 524 ticks collected in woods of a western province of Belgium. Presence of spirochetes in ticks was determined by phase contrast microscopy. The mean infection rate of ticks was 12.0%. Variability was observed in the prevalence of infection among the five sites examined, ranging from 2.8 to 21.6%. Identification to genospecies was determined by PCR and sequencing. The most common genomospecies were Borrelia afzelii (55%) and Borrelia garinii (21%). For the first time in Belgium, we detected Borrelia valaisiana and Borrelia spielmanii, representing 14% and 2%, respectively. Borrelia burgdorferi sensu stricto counted only for 2%. Co-infections were present in 8% of ticks. We emphasize the need for clinical studies to assess the prevalence of specific genospecies-related clinical manifestations of Lyme borreliosis in Belgium.

Clinical bacteriology in low-resource settings: today's solutions

Low-resource settings are disproportionately burdened by infectious diseases and antimicrobial resistance. Good quality clinical bacteriology through a well functioning reference laboratory network is necessary for effective resistance control, but low-resource settings face infrastructural, technical, and behavioural challenges in the implementation of clinical bacteriology. In this Personal View, we explore what constitutes successful implementation of clinical bacteriology in low-resource settings and describe a framework for implementation that is suitable for general referral hospitals in low-income and middle-income countries with a moderate infrastructure. Most microbiological techniques and equipment are not developed for the specific needs of such settings. Pending the arrival of a new generation diagnostics for these settings, we suggest focus on improving, adapting, and implementing conventional, culture-based techniques. Priorities in low-resource settings include harmonised, quality assured, and tropicalised equipment, consumables, and techniques, and rationalised bacterial identification and testing for antimicrobial resistance. Diagnostics should be integrated into clinical care and patient management; clinically relevant specimens must be appropriately selected and prioritised. Open-access training materials and information management tools should be developed. Also important is the need for onsite validation and field adoption of diagnostics in low-resource settings, with considerable shortening of the time between development and implementation of diagnostics. We argue that the implementation of clinical bacteriology in low-resource settings improves patient management, provides valuable surveillance for local antibiotic treatment guidelines and national policies, and supports containment of antimicrobial resistance and the prevention and control of hospital-acquired infections.

Evaluating Effectiveness of Mass and Continuous Long-lasting Insecticidal Net Distributions Over Time in Madagascar: A Sentinel Surveillance Based Epidemiological Study

Background The reduction of global malaria burden over the past 15 years is much attributed to the expansion of mass distribution campaigns (MDCs) of long-lasting insecticidal nets (LLIN). In Madagascar, two LLIN MDCs were implemented and one district also benefited from a community-based continuous distribution (CB-CD). Malaria incidence dropped but eventually rebounded after a decade. Methods Data from a sentinel surveillance network over the 2009–2015 period was analyzed. Alerts were defined as weekly number of malaria cases exceeding the 90th percentile value for three consecutive weeks. Statistical analyses assessed the temporal relationship between LLIN MDCs and (i) number of malaria cases and (ii) malaria alerts detected, and (iii) the effect of a combination of MDCs and a CB-CD in Toamasina District. Findings Analyses showed an increase of 13.6 points and 21.4 points in the percentile value of weekly malaria cases during the second and the third year following the MDC of LLINs respectively. The percentage of alert-free sentinel sites was 98.2% during the first year after LLIN MDC, 56.7% during the second year and 31.5% during the third year. The number of weekly malaria cases decreased by 14% during the CB-CD in Toamasina District. In contrast, sites without continuous distribution had a 12% increase of malaria cases. Interpretation These findings support the malaria-preventive effectiveness of MDCs in Madagascar but highlight their limited duration when not followed by continuous distribution. The resulting policy implications are crucial to sustain reductions in malaria burden in high transmission settings.

Investigating Pneumonia Etiology Among Refugees and the Lebanese population (PEARL): A study protocol

Background: Community-acquired pneumonia (CAP), a leading cause of mortality, mainly affects children in developing countries. The harsh circumstances experienced by refugees include various factors associated with respiratory pathogen transmission, and clinical progression of CAP. Consequently, the etiology of CAP in humanitarian crisis situations may differ to that of settled populations, which would impact appropriate case management. Therefore, the Pneumonia Etiology Among Refugees and the Lebanese population (PEARL) study was initiated with the objective of identifying the causal pathogenic microorganisms in the respiratory tract of children and adults from both the refugee and host country population presenting with signs of CAP during a humanitarian crisis. Methods: PEARL, a prospective, multicentric, case-control study, will be conducted at four primary healthcare facilities in Tripoli and the Bekaa valley over 15 months (including two high-transmission seasons/winters). Sociodemographic and medical data, and biological samples will be collected from at least 600 CAP cases and 600 controls. Nasopharyngeal swabs, sputum, urine and blood samples will be analyzed at five clinical pathology laboratories in Lebanon to identify the bacterial and viral etiological agents of CAP. Transcriptomic profiling of host leukocytes will be performed. Conclusions: PEARL is an original observational study that will provide important new information on the etiology of pneumonia among refugees, which may improve case management, help design antimicrobial stewardship interventions, and reduce morbidity and mortality due to CAP in a humanitarian crisis.

The protective effectiveness of control interventions for malaria prevention: a systematic review of the literature

Background: Thanks to a considerable increase in funding, malaria control interventions (MCI) whose efficacy had been demonstrated by controlled trials have been largely scaled up during the last decade. Nevertheless, it was not systematically investigated whether this efficacy had been preserved once deployed on the field. Therefore, we sought the literature to assess the disparities between efficacy and effectiveness and the effort to measure the protective effectiveness (PE) of MCI. Methods: The PubMed database was searched for references with keywords related to malaria, to control interventions for prevention and to study designs that allow for the measure of the PE against parasitemia or against clinical outcomes. Results: Our search retrieved 1423 references, and 162 articles were included in the review. Publications were scarce before the year 2000 but dramatically increased afterwards. Bed nets was the MCI most studied (82.1%). The study design most used was a cross-sectional study (65.4%). Two thirds (67.3%) were conducted at the district level or below, and the majority (56.8%) included only children even if the MCI didn’t target only children. Not all studies demonstrated a significant PE from exposure to MCI: 60.6% of studies evaluating bed nets, 50.0% of those evaluating indoor residual spraying, and 4/8 showed an added PE of using both interventions as compared with one only; this proportion was 62.5% for intermittent preventive treatment of pregnant women, and 20.0% for domestic use of insecticides. Conclusions: This review identified numerous local findings of low, non-significant PE –or even the absence of a protective effect provided by these MCIs. The identification of such failures in the effectiveness of MCIs advocates for the investigation of the causes of the problem found. Ideal evaluations of the PE of MCIs should incorporate both a large representativeness and an evaluation of the PE stratified by subpopulations.

The importance of historical data in simulating malaria epidemiology and control interventions: application to multiple sites in Madagascar

Planning malaria interventions requires the prediction of likely impacts of different intervention strategies. Simulation models can provide such predictions but weak information about pre-control levels of transmission, intervention coverage and access to care often makes it challenging to correctly parameterize them. We consider a number of low malaria transmission sites in Madagascar, with available historical prevalence and entomological inoculation rate (EIR) estimates (by mosquito sampling), giving disparate estimates of historical exposure. Information about implementation of Long Lasting Insecticide Nets (LLINs) and Indoor Residual Spraying (IRS), and access to healthcare, collated from malaria surveys and on-going cross-sectional studies were used to parameterise simulations of malaria transmission, prevalence and burden within the OpenMalaria platform. Multiple parameterisations were considered using various sources of data for pre-intervention transmission level, intervention coverage and access to healthcare. In some sites the simulated impact of existing vector control programs matches reasonably well the malaria prevalence measured in a recent national survey. In others it predicts lower than observed prevalence, very likely because the models do not capture residual local transmission foci. The simulations suggest that the most cost-effective vector control strategy would be to scale-up LLINs or IRS only, depending on the transmission level. Indeed, preliminary results show no additional benefit of IRS where LLINs were used. These preliminary results suggest that historical prevalence data, combined with current coverage information are potentially adequate for planning intervention strategies. The outcome of intervention scale-up is essentially unpredictable if baseline information is poor. Reproducing the observed epidemiology of malaria through simulations both provides confidence in the use of the model but serves as a basis for prospective studies that support decision-making, including cost-effectiveness analyses.