Serological Evaluation of Onchocerciasis and Lymphatic Filariasis Elimination in the Bakoye and Falémé foci, Mali

In Mali, ivermectin-based onchocerciasis elimination from the Bakoye and Falémé foci, reported in 2009–2012, was a beacon leading to policy shifting from morbidity control to elimination of transmission (EOT). These foci are also endemic for lymphatic filariasis (LF). In 2007–2016 mass ivermectin plus albendazole administration was implemented. We report Ov16 (onchocerciasis) and Wb123 (LF) seroprevalence after 24–25 years of treatment to evaluate if onchocerciasis EOT and LF elimination as a public health problem (EPHP) have been achieved

Health facility-based prevalence and potential risk factors of autism spectrum disorders in Mali

Background: The prevalence of autism spectrum disorders (ASD) is 1-2% worldwide, 1 in 68 in the U.S, and unknown in Africa. ASD is under-diagnosed in Mali due to stigma and the lack of appropriate human resources and infrastructure.Objective: To determine the ASD frequency and potential risk factors in Mali.Methods: We identified all the health facilities and community-based organizations involved in the ASD diagnosis and management in Bamako. We established an ASD research and awareness platform in Mali, which encompasses community-based organizations and a multidisciplinary team including psychiatrists, psychologists, pediatricians, geneticists, and public health and social science specialists. Through this platform, we performed a survey in health facilities and organizations where patients with ASD are likely to seek care in Bamako. We reviewed the psychiatric patient registry to obtain basic epidemiological profiles of children with ASD, epilepsy and other psychiatric disorders.Results: We found a health facility-based prevalence of ASD of 4.5% (105/2,343) in Bamako. The mean age at the first outpatient visit was 7.64 ± 3.85 years old. First degree consanguinity of 29.5% (31/105) was more frequent in parents of ASD children versus age and sex matched controls OR= 4.37 [1.96-9.76] p=0.0001.Conclusion: Our data suggest that ASD is more common than expected in Mali. The established ASD awareness and research platform may improve the diagnosis and management of ASD by raising ASD awareness, training of Malian clinicians and researchers in early ASD screening and diagnosis, and strengthening research capacity in genomics of ASD and other mental disorders.Keywords: ASD, prevalence, consanguinity, health facilit

Changes in the levels of cytokines, chemokines and malaria-specific antibodies in response to Plasmodium falciparum infection in children living in sympatry in Mali

<p>Abstract</p> <p>Background</p> <p>The Fulani are known to be less susceptible to <it>Plasmodium falciparum </it>malaria as reflected by lower parasitaemia and fewer clinical symptoms than other sympatric ethnic groups. So far most studies in these groups have been performed on adults, which is why little is known about these responses in children. This study was designed to provide more information on this gap.</p> <p>Methods</p> <p>Circulating inflammatory factors and antibody levels in children from the Fulani and Dogon ethnic groups were measured. The inflammatory cytokines; interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12p70, tumor necrosis factor (TNF) and the chemokines; regulated on activation normal T cell expressed and secreted (RANTES), monokine-induced by IFN-gamma (MIG), monocyte chemotactic protein (MCP)-1 and IFN-gamma-inducible protein (IP)-10 were measured by cytometric bead arrays. The levels of interferon (IFN)-alpha, IFN-gamma and malaria-specific antibodies; immunoglobulin (Ig) G, IgM and IgG subclasses (IgG1-IgG4) were measured by ELISA.</p> <p>Results</p> <p>The results revealed that the Fulani children had higher levels of all tested cytokines compared to the Dogon, in particular IFN-gamma, a cytokine known to be involved in parasite clearance. Out of all the tested chemokines, only MCP-1 was increased in the Fulani compared to the Dogon. When dividing the children into infected and uninfected individuals, infected Dogon had significantly lower levels of RANTES compared to their uninfected peers, and significantly higher levels of MIG and IP-10 as well as MCP-1, although the latter did not reach statistical significance. In contrast, such patterns were not seen in the infected Fulani children and their chemokine levels remained unchanged upon infection compared to uninfected counterparts. Furthermore, the Fulani also had higher titres of malaria-specific IgG and IgM as well as IgG1-3 subclasses compared to the Dogon.</p> <p>Conclusions</p> <p>Taken together, this study demonstrates, in accordance with previous work, that Fulani children mount a stronger inflammatory and antibody response against <it>P. falciparum </it>parasites compared to the Dogon and that these differences are evident already at an early age. The inflammatory responses in the Fulani were not influenced by an active infection which could explain why less clinical symptoms are seen in this group.</p

Localization of uPAR and MMP-9 in lipid rafts is critical for migration, invasion and angiogenesis in human breast cancer cells

<p>Abstract</p> <p>Background</p> <p>uPAR and MMP-9, which play critical roles in tumor cell invasion, migration and angiogenesis, have been shown to be associated with lipid rafts.</p> <p>Methods</p> <p>To investigate whether cholesterol could regulate uPAR and MMP-9 in breast carcinoma, we used MβCD (methyl beta cyclodextrin, which extracts cholesterol from lipid rafts) to disrupt lipid rafts and studied its effect on breast cancer cell migration, invasion, angiogenesis and signaling.</p> <p>Results</p> <p>Morphological evidence showed the association of uPAR with lipid rafts in breast carcinoma cells. MβCD treatment significantly reduced the colocalization of uPAR and MMP-9 with lipid raft markers and also significantly reduced uPAR and MMP-9 at both the protein and mRNA levels. Spheroid migration and invasion assays showed inhibition of breast carcinoma cell migration and invasion after MβCD treatment. <it>In vitro </it>angiogenesis studies showed a significant decrease in the angiogenic potential of cells pretreated with MβCD. MβCD treatment significantly reduced the levels of MMP-9 and uPAR in raft fractions of MDA-MB-231 and ZR 751 cells. Phosphorylated forms of Src, FAK, Cav, Akt and ERK were significantly inhibited upon MβCD treatment. Increased levels of soluble uPAR were observed upon MβCD treatment. Cholesterol supplementation restored uPAR expression to basal levels in breast carcinoma cell lines. Increased colocalization of uPAR with the lysosomal marker LAMP1 was observed in MβCD-treated cells when compared with untreated cells.</p> <p>Conclusion</p> <p>Taken together, our results suggest that cholesterol levels in lipid rafts are critical for the migration, invasion, and angiogenesis of breast carcinoma cells and could be a critical regulatory factor in these cancer cell processes mediated by uPAR and MMP-9.</p

Trends in malaria morbidity among health care-seeking children under age five in Mopti and Sévaré, Mali between 1998 and 2006

<p>Abstract</p> <p>Background</p> <p>In Mali, malaria is the leading cause of death and the primary cause of outpatient visits for children under five. The twin towns of Mopti and Sévaré have historically had high under-five mortality. This paper investigates the changing malaria burden in children under five in these two towns for the years 1998-2006, and the likely contribution of previous interventions aimed at reducing malaria.</p> <p>Methods</p> <p>A retrospective analysis of daily outpatient consultation records from urban community health centres (CSCOMs) located in Mopti and Sévaré for the years 1998-2006 was conducted. Risk factors for a diagnosis of presumptive malaria, using logistic regression and trends in presumptive malaria diagnostic rates, were assessed using multilevel analysis.</p> <p>Results</p> <p>Between 1998-2006, presumptive malaria accounted for 33.8% of all recorded consultation diagnoses (10,123 out of 29,915). The monthly presumptive malaria diagnostic rate for children under five decreased by 66% (average of 8 diagnoses per month per 1,000 children in 1998 to 2.7 diagnoses per month in 2006). The multi-level analysis related 37% of this decrease to the distribution of bed net treatment kits initiated in May of 2001. Children of the Fulani (Peuhl) ethnicity had significantly lower odds of a presumptive malaria diagnosis when compared to children of other ethnic groups.</p> <p>Conclusions</p> <p>Presumptive malaria diagnostic rates have decreased between 1998-2006 among health care-seeking children under five in Mopti and Sévaré. A bed net treatment kit intervention conducted in 2001 is likely to have contributed to this decline. The results corroborate previous findings that suggest that the Fulani ethnicity is protective against malaria. The findings are useful to encourage dialogue around the urban malaria situation in Mali, particularly in the context of achieving the target of reducing malaria morbidity in children younger than five by 50% by 2011 as compared to levels in 2000.</p

Statistical methodology for the evaluation of vaccine efficacy in a phase III multi-centre trial of the RTS,S/AS01 malaria vaccine in African children

BACKGROUND\ud \ud There has been much debate about the appropriate statistical methodology for the evaluation of malaria field studies and the challenges in interpreting data arising from these trials.\ud \ud METHODS\ud \ud The present paper describes, for a pivotal phase III efficacy of the RTS, S/AS01 malaria vaccine, the methods of the statistical analysis and the rationale for their selection. The methods used to estimate efficacy of the primary course of vaccination, and of a booster dose, in preventing clinical episodes of uncomplicated and severe malaria, and to determine the duration of protection, are described. The interpretation of various measures of efficacy in terms of the potential public health impact of the vaccine is discussed.\ud \ud CONCLUSIONS\ud \ud The methodology selected to analyse the clinical trial must be scientifically sound, acceptable to regulatory authorities and meaningful to those responsible for malaria control and public health policy

Malaria vector control practices in an irrigated rice agro-ecosystem in central Kenya and implications for malaria control

<p>Abstract</p> <p>Background</p> <p>Malaria transmission in most agricultural ecosystems is complex and hence the need for developing a holistic malaria control strategy with adequate consideration of socio-economic factors driving transmission at community level. A cross-sectional household survey was conducted in an irrigated ecosystem with the aim of investigating vector control practices applied and factors affecting their application both at household and community level.</p> <p>Methods</p> <p>Four villages representing the socio-economic, demographic and geographical diversity within the study area were purposefully selected. A total of 400 households were randomly sampled from the four study villages. Both semi-structured questionnaires and focus group discussions were used to gather both qualitative and quantitative data.</p> <p>Results</p> <p>The results showed that malaria was perceived to be a major public health problem in the area and the role of the vector <it>Anopheles </it>mosquitoes in malaria transmission was generally recognized. More than 80% of respondents were aware of the major breeding sites of the vector. Reported personal protection methods applied to prevent mosquito bites included; use of treated bed nets (57%), untreated bed nets (35%), insecticide coils (21%), traditional methods such as burning of cow dung (8%), insecticide sprays (6%), and use of skin repellents (2%). However, 39% of respondents could not apply some of the known vector control methods due to unaffordability (50.5%), side effects (19.9%), perceived lack of effectiveness (16%), and lack of time to apply (2.6%). Lack of time was the main reason (56.3%) reported for non-application of environmental management practices, such as draining of stagnant water (77%) and clearing of vegetations along water canals (67%).</p> <p>Conclusion</p> <p>The study provides relevant information necessary for the management, prevention and control of malaria in irrigated agro-ecosystems, where vectors of malaria are abundant and disease transmission is stable.</p

Phase 1 Study of a Combination AMA1 Blood Stage Malaria Vaccine in Malian Children

Apical Membrane Antigen-1 (AMA1) is one of the leading blood stage malaria vaccine candidates. AMA1-C1/Alhydrogel consists of an equal mixture of recombinant AMA1 from FVO and 3D7 clones of P. falciparum, adsorbed onto Alhydrogel. A Phase 1 study in semi-immune adults in Mali showed that the vaccine was safe and immunogenic, with higher antibody responses in those who received the 80 microg dose. The aim of this study was to assess the safety and immunogenicity of this vaccine in young children in a malaria endemic area.This was a Phase 1 dose escalating study in 36 healthy children aged 2-3 years started in March 2006 in Donéguébougou, Mali. Eighteen children in the first cohort were randomized 2 ratio 1 to receive either 20 microg AMA1-C1/Alhydrogel or Haemophilus influenzae type b Hiberix vaccine. Two weeks later 18 children in the second cohort were randomized 2 ratio 1 to receive either 80 microg AMA1-C1/Alhydrogel or Haemophilus influenzae type b Hiberix vaccine. Vaccinations were administered on Days 0 and 28 and participants were examined on Days 1, 2, 3, 7, and 14 after vaccination and then about every two months. Results to Day 154 are reported in this manuscript.Of 36 volunteers enrolled, 33 received both vaccinations. There were 9 adverse events related to the vaccination in subjects who received AMA1-C1 vaccine and 7 in those who received Hiberix. All were mild to moderate. No vaccine-related serious or grade 3 adverse events were observed. There was no increase in adverse events with increasing dose of vaccine or number of immunizations. In subjects who received the test vaccine, antibodies to AMA1 increased on Day 14 and peaked at Day 42, with changes from baseline significantly different from subjects who received control vaccine.AMA-C1 vaccine is well tolerated and immunogenic in children in this endemic area although the antibody response was short lived.Clinicaltrials.gov NCT00341250