Papers by Michel Boussinesq
PLOS Neglected Tropical Diseases
Background Ivermectin is known to cause severe encephalopathies in subjects infected with loiasis... more Background Ivermectin is known to cause severe encephalopathies in subjects infected with loiasis, an endemic parasite in Sub-Saharan Africa (SSA). In addition, case reports have described ivermectin-related serious adverse drug reactions (sADRs) such as toxidermias, hepatic and renal disorders. The aim of this study was to identify suspected sADRs reported after ivermectin administration in VigiBase, the World Health Organization’s global individual case safety reports database and analyze their frequency relative to the frequency of these events after other antinematodal drugs reported in SSA and other areas of the world (ROW). Methods All antinematodal-related sADRs were extracted from VigiBase. Disproportionality analyses were conducted to investigate nervous, cutaneous, psychiatric, respiratory, renal, hepatic and cardiac suspected sADRs reported after ivermectin and benzimidazole drug administration across the world, in SSA and RoW. Principal findings 2041 post-ivermectin or p...
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EClinicalMedicine
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Parasite
The availability of a safe macrofilaricidal drug would help to accelerate onchocerciasis eliminat... more The availability of a safe macrofilaricidal drug would help to accelerate onchocerciasis elimination. A trial was conducted in Cameroon to evaluate the effects of a subcutaneous injectable long-acting formulation of ivermectin (LAFI) on the microfilariae (mf) and adult stages of Onchocerca ochengi. Ten zebu cattle naturally infected with the parasite were injected subcutaneously with either 500 mg (group A, N = 4), or 1000 mg long-acting ivermectin (group B, N = 4) or the vehicle (group C, N = 2). Skin samples were collected from each animal before, and 6, 12, and 24 months after treatment to measure microfilarial densities (MFDs). Nodules excised before, and 6 and 12 months after treatment were examined histologically to assess the adult worms’ viability and reproductive status. Blood samples were collected at pre-determined time-points to obtain pharmacokinetic data. Before treatment, the average O. ochengi MFDs were similar in the three groups. Six months after treatment, all ani...
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Clinical Infectious Diseases
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Trends in parasitology, Apr 1, 2018
Endemic to Central Africa, loiasis - or African eye worm (caused by the filarial nematode Loa loa... more Endemic to Central Africa, loiasis - or African eye worm (caused by the filarial nematode Loa loa) - affects more than 10 million people. Despite causing ocular and systemic symptoms, it has typically been considered a benign condition, only of public health relevance because it impedes mass drug administration-based interventions against onchocerciasis and lymphatic filariasis in co-endemic areas. Recent research has challenged this conception, demonstrating excess mortality associated with high levels of infection, implying that loiasis warrants attention as an intrinsic public health problem. This review summarises available information on the key parasitological, entomological, and epidemiological characteristics of the infection and argues for the mobilisation of resources to control the disease, and the development of a mathematical transmission model to guide deployment of interventions.
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Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2018
Great strides have been made toward onchocerciasis elimination by mass drug administration (MDA) ... more Great strides have been made toward onchocerciasis elimination by mass drug administration (MDA) of ivermectin. Focusing on MDA-eligible areas, we investigated where the elimination goal can be achieved by 2025 by continuation of current practice (annual MDA with ivermectin) and where intensification or additional vector control is required. We did not consider areas hypoendemic for onchocerciasis with loiasis coendemicity where MDA is contraindicated. We used 2 previously published mathematical models, ONCHOSIM and EPIONCHO, to simulate future trends in microfilarial prevalence for 80 different settings (defined by precontrol endemicity and past MDA frequency and coverage) under different future treatment scenarios (annual, biannual, or quarterly MDA with different treatment coverage through 2025, with or without vector control strategies), assessing for each strategy whether it eventually leads to elimination. Areas with 40%-50% precontrol microfilarial prevalence and ≥10 years of...
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Infectious diseases of poverty, Jan 22, 2018
Recently, several epidemiological studies performed in Onchocerca volvulus-endemic regions have s... more Recently, several epidemiological studies performed in Onchocerca volvulus-endemic regions have suggested that onchocerciasis-associated epilepsy (OAE) may constitute an important but neglected public health problem in many countries where onchocerciasis is still endemic. On October 12-14 2017, the first international workshop on onchocerciasis-associated epilepsy (OAE) was held in Antwerp, Belgium. The workshop was attended by 79 participants from 20 different countries. Recent research findings strongly suggest that O. volvulus is an important contributor to epilepsy, particularly in meso- and hyperendemic areas for onchocerciasis. Infection with O. volvulus is associated with a spectrum of epileptic seizures, mainly generalised tonic-clonic seizures but also atonic neck seizures (nodding), and stunted growth. OAE is characterised by an onset of seizures between the ages of 3-18 years. Multidisciplinary working groups discussed topics such as how to 1) strengthen the evidence for ...
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Clinical Infectious Diseases
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Background: Treatment of onchocerciasis using mass ivermectin administration has reduced morbidit... more Background: Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana - exposed to more than a decade of regular ivermectin treatment - have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread. Methodology/Principal Findings: Pooled next generation sequencing (Pool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR) and sub-optimal responder (SOR) parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs)...
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Infectious diseases of poverty, Jan 27, 2016
The African Programme for Onchocerciasis Control (APOC) was created in 1995 to establish communit... more The African Programme for Onchocerciasis Control (APOC) was created in 1995 to establish community-directed treatment with ivermectin (CDTi) in order to control onchocerciasis as a public health problem in 20 African countries that had 80 % of the global disease burden. When research showed that CDTi may ultimately eliminate onchocerciasis infection, APOC was given in 2008 the additional objective to determine when and where treatment can be safely stopped. We report the results of epidemiological evaluations undertaken from 2008 to 2014 to assess progress towards elimination in CDTi areas with ≥6 years treatment. Skin snip surveys were undertaken in samples of first-line villages to determine the prevalence of O. volvulus microfilariae. There were two evaluation phases. The decline in prevalence was evaluated in phase 1A. Observed and model-predicted prevalences were compared after correcting for endemicity level and treatment coverage. Bayesian statistics and Monte Carlo simulatio...
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The Lancet. Infectious diseases, 2017
The burden of loiasis has received limited attention and loiasis is still considered a benign con... more The burden of loiasis has received limited attention and loiasis is still considered a benign condition. To assess whether loiasis bears any excess mortality, we did a retrospective cohort study in Cameroon. In 2001, 3627 individuals living in 28 villages were examined for Loa loa infection. In 2016, these villages were revisited and the vital status was determined for 3301 individuals (91%). The data were analysed at community level to assess the relation between the level of L loa infection in 2001 and standardised mortality rates (SMRs), and at individual level to assess the excess mortality relative to the 2001 microfilaraemia and to calculate the population-attributable fraction of mortality associated with L loa microfilaraemia. 915 deaths occurred during the follow-up time (mean time of 12·5 years [IQR 10·2-14·9]) between April, 2001, and March 22, 2016. Crude mortality rate was 20·3 deaths per 1000 person-years. SMRs increased by 4·1% when the proportion of participants infe...
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The Lancet. Infectious diseases, Jan 31, 2017
The standard treatment strategy of mass drug administration with ivermectin plus albendazole for ... more The standard treatment strategy of mass drug administration with ivermectin plus albendazole for lymphatic filariasis cannot be applied in central Africa, because of the risk of serious adverse events in people with high Loa loa microfilaraemia. Thus, alternative strategies are needed. We investigated one such alternative strategy for mass drug administration for elimination of lymphatic filariasis and soil-transmitted helminth infections in Republic of the Congo. In 2012, we started a 3 year community trial of biannual mass administration of albendazole in a village in Republic of the Congo. All volunteering inhabitants aged 2 years or older were offered albendazole (400 mg) every 6 months. Infection with Wuchereria bancrofti was diagnosed with a rapid card immunochromatographic test for antigenaemia. People with antigenaemia were tested for microfilaraemia by night blood smears. Individuals were also tested for soil-transmitted helminth infections (ie, hookworm, Ascaris lumbricoid...
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The Journal of infectious diseases, Aug 15, 2016
The familial recurrence risk of lymphatic filariasis (LF) is unknown. This case study aimed to ev... more The familial recurrence risk of lymphatic filariasis (LF) is unknown. This case study aimed to evaluate the familial susceptibility to infection with Wuchereria bancrofti and to microfilaremia in a village of the Republic of Congo. The heritability and intrafamilial correlation coefficients were assessed for both W. bancrofti infection and microfilaremia by controlling for individual risk factors, environmental influence, and household effects. Pedigree charts were constructed for 829 individuals, including 143 individuals with a diagnosis of W. bancrofti circulating filarial antigens (CFAs) and 44 who also had microfilariae (MF). There was no intrafamilial correlation regarding CFA levels. However, the presence of MF (ρ = 0.45) and microfilarial density (ρ = 0.44) were significantly correlated among parent-offspring pairs. Heritability estimates for CFA positivity and intensity were 0.23 and 0.18, respectively. Heritability estimates were high for microfilarial positivity (h(2) = 0...
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Parasites & vectors, Jan 14, 2016
After more than a decade of community-directed treatment with ivermectin (CDTI) in Centre and Lit... more After more than a decade of community-directed treatment with ivermectin (CDTI) in Centre and Littoral Regions of Cameroon, onchocerciasis endemicity was still high in some communities according to the 2011 epidemiological evaluations. Some corrective measures were undertaken to improve the CDTI process and therefore reduce the burden of the disease. The objective of the present study was to assess the progress made towards the elimination of onchocerciasis in the Centre 1 and Littoral 2 CDTI projects where the worst performances were found in 2011. To this end, a cross-sectional survey was conducted in April 2015 in eight communities in two health districts (HD), Bafia in Centre 1 and Yabassi in Littoral 2, chosen because assessed at baseline and in 2011. All volunteers living for at least five years in the community, aged five years or more, underwent clinical and parasitological examinations. Individual compliance to ivermectin treatment was also assessed. Analyses of data were w...
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The American journal of tropical medicine and hygiene, Jan 10, 2016
Since the mid-2000s, the immunochromatographic card test (ICT), a point-of-care test for detectin... more Since the mid-2000s, the immunochromatographic card test (ICT), a point-of-care test for detecting Wuchereria bancrofti circulating filarial antigens (CFAs), has been the backbone for mapping and monitoring lymphatic filariasis (LF) worldwide. Recently, there have been instances in which CFA positivity has been associated with Loa loa microfilaremia. Here, we examined the association, at both the community and individual levels, between L. loa and CFA using additional diagnostic tools (quantitative polymerase chain reaction [qPCR], Og4C3 enzyme-linked immunosorbent assay, and IgG4 antibodies to Wb123 assays) to demonstrate the relationship between L. loa microfilaremia and ICT positivity. In May 2013, peripheral blood was collected during the day from 1,812 individuals living in southern Cameroon. ICT tests were done on the spot, and positive individuals were resampled at night. Results of qPCR and Wb123 assays concurred proving the absence of W. bancrofti infection. Og4C3 assays in...
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The American journal of tropical medicine and hygiene, Jun 1, 2016
The Alere Filariasis Test Strip (FTS) is a qualitative, point-of-care diagnostic tool that detect... more The Alere Filariasis Test Strip (FTS) is a qualitative, point-of-care diagnostic tool that detects Wuchereria bancrofti circulating filarial antigen (CFA) in human blood, serum, or plasma. The Global Program to Eliminate Lymphatic Filariasis employs the FTS for mapping filariasis-endemic areas and assessing the success of elimination efforts. The objective of this study was to explore the relationship between the intensity of positive test lines obtained by FTS with CFA levels as determined by enzyme-linked immunosorbent assay (ELISA) with blood and plasma samples from 188 individuals who live in a filariasis-endemic area. The intensity of the FTS test line was assessed visually to provide a semiquantitative score (visual Filariasis Test Strip [vFTS]), and line intensity was measured with a portable spectrodensitometer (quantitative Filariasis Test Strip [qFTS]). These results were compared with antigen levels measured by ELISA in plasma from the same subjects. qFTS measurements wer...
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Epilepsia, 2003
To evaluate the demographic impact of epilepsy a rural area of Africa. A cohort study was conduct... more To evaluate the demographic impact of epilepsy a rural area of Africa. A cohort study was conducted between 1991 and 2001 in the Mbam Valley (Cameroon) on two groups of subjects (one of persons with epilepsy, and the other of control individuals matched for sex, age, and village of residence). At the end of the follow-up, information on mortality, marital status, and numbers of offspring was obtained from 128 pairs of subjects. Thirty-seven (28.9%) persons with epilepsy and six (4.7%) controls died between 1991 and 2001. The relative risk of dying during the follow-up among the group of people with epilepsy, compared with the controls, was 6.2 (95% CI, 2.7-14.1). The most frequent causes of death in the persons with epilepsy were status epilepticus, sudden unexpected death in epilepsy (SUDEP), and drowning. Of the 90 pairs, of which both members were still alive in 2001, 15 (16.7%) persons with epilepsy were married as compared with 53 (58.9%) controls. The mean number of children was 0.9 in the subjects with epilepsy, and 1.7 in the controls (p < 0.0001). Health personnel should be trained and sensitized about the devastating effect of this neglected disease in developing countries. In those areas where onchocerciasis control programs are organized by using the community-directed-treatment approach, the possibility that the ivermectin distributors could also be responsible for distributing antiepileptic drugs should be considered.
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Bulletin De La Societe De Pathologie Exotique, 2001
... Ann Trop Med Parasitol, 2001, 95, 495-507. 7 . BUCK AA, ANDERSON RI, SASAKI TT & KAWATA K... more ... Ann Trop Med Parasitol, 2001, 95, 495-507. 7 . BUCK AA, ANDERSON RI, SASAKI TT & KAWATA K Health and disease in Chad. Epidemiology, culture, and environment in five villages. ... Lancet, 2000, 356 , 1077-1078. 23. UFOMADU GO, NWOKE BEB, AKOH JI et al. ...
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Medecine Tropicale, 1999
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Papers by Michel Boussinesq