Species composition and insecticide resistance in malaria vectors in Ellibou, southern Côte d'Ivoire and first finding of; Anopheles arabiensis; in Côte d'Ivoire

Background Knowing the species composition and insecticide resistance status of the target vector population is important to guide malaria vector control. The aim of this study was to characterize the malaria vector population in terms of species composition, insecticide susceptibility status and potential underlying resistance mechanisms in Ellibou, southern Côte d'Ivoire. Methods A 1-year longitudinal entomological survey was conducted using light traps and pyrethroid spray catches to sample adult mosquitoes in combination with larval sampling. The susceptibility status of Anopheles gambiae sensu lato (s.l.) to bendiocarb, deltamethrin, DDT and malathion was assessed using the World Health Organization insecticide susceptibility test. Additionally, An. gambiae specimens were screened for knockdown (kdr) and acetylcholineesterase (ace1) target site resistance alleles, and the expression levels of eight metabolic resistance genes, including seven cytochrome P450 monooxygenases (P450s) and one glutathione S-transferase (GST), measured with reverse transcription quantitative real-time polymerase chain reaction (qPCR). Results Overall, 2383 adult mosquitoes from 12 different taxa were collected with Culex quinquefasciatus and An. gambiae being the predominant taxa. Molecular identification of An. gambiae s.l. revealed the presence of Anopheles arabiensis, Anopheles coluzzii, An. gambiae sensu stricto (s.s.) and Anopheles coluzzii/An. gambiae s.s. hybrids. Anopheles gambiae mosquitoes were resistant to all insecticides except malathion. PCR diagnostics revealed the presence of ace1-G280S and the kdr L995F, L995S and N1570Y target-site mutations. Additionally, several genes were upregulated, including five P450s (i.e., CYP6P3, CYP6M2, CYP9K1, CYP6Z1, CYP6P1) and GSTE2. Conclusion This is the first documented presence of An. arabiensis in Côte d'Ivoire. Its detection - together with a recent finding further north of the country - confirms its existence in the country, which is an early warning sign, as An. arabiensis shows a different biology than the currently documented malaria vectors. Because the local An. gambiae population was still susceptible to malathion, upregulation of P450s, conferring insecticide resistance to pyrethroids, together with the presence of ace1, suggest negative cross-resistance. Therefore, organophosphates could be an alternative insecticide class for indoor residual spraying in the Ellibou area, while additional tools against the outdoor biting An. arabiensis will have to be considered

Use of insecticides in agriculture and the prevention of vector-borne diseases: population knowledge, attitudes, practices and beliefs in Elibou, South Cote d'Ivoire

People's knowledge, attitudes, practices and beliefs (KAPB) pertaining to malaria are generally well described. However, little is known about population knowledge and awareness of insecticide resistance in malaria vectors. The aim of this study was to investigate KAPB related to insecticide resistance in malaria vectors due to the use of insecticides in agriculture and the prevention against mosquitoes. In mid-2017, we carried out a cross-sectional survey in Elibou, South Côte d'Ivoire, employing a mixed methods approach. Quantitative data were obtained with a questionnaire addressed to household heads. Interviews were conducted with key opinion leaders, including village chiefs, traditional healers, heads of health centres and pesticide sellers. Focus group discussions were conducted with youth and elders. A total of 203 individuals participated in the questionnaire survey (132 males, 65%). We found that people had good knowledge about malaria and mosquitoes transmitting the disease, while they felt that preventing measures were ineffective. Pesticides were intensively used by farmers, mainly during the rainy season. Among the pesticides used, insecticides and herbicides were most commonly used. While there was poor knowledge about resistance, the interviewees stated that insecticides were not killing the mosquitoes anymore. The main reason given was that insecticides were diluted by the manufacturers as a marketing strategy to sell larger quantities. More than a third of the farmers used agricultural pesticides for domestic purposes to kill weeds or mosquitoes. We observed a misuse of pesticides among farmers, explained by the lack of specific training. In the community, long-lasting insecticidal nets were the most common preventive measure against malaria, followed by mosquito coils and insecticide sprays. The interviewees felt that the most effective way of dealing with insecticide resistance was to combine at least two preventive measures. In conclusion, population attitudes and practices related to insecticides used in agriculture and the prevention against mosquitoes could lead to resistance in malaria vectors, while people's knowledge about insecticide resistance was limited. There is a need to raise awareness in communities about the presence of resistance in malaria vectors and to involve them in resistance management

A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa

BACKGROUND: In sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast. METHODS: We included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non-AIDS-defining cancer, non-AIDS-defining invasive bacterial disease, or death from any cause at 30 months. We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies. RESULTS: A total of 2056 patients (41% with a baseline CD4+ count of ≥500 cells per cubic millimeter) were followed for 4757 patient-years. A total of 204 primary end-point events were observed (3.8 events per 100 person-years; 95% confidence interval [CI], 3.3 to 4.4), including 68 in patients with a baseline CD4+ count of at least 500 cells per cubic millimeter (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0). Tuberculosis and invasive bacterial diseases accounted for 42% and 27% of primary end-point events, respectively. The risk of death or severe HIV-related illness was lower with early ART than with deferred ART (adjusted hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.56; 95% CI, 0.33 to 0.94) and lower with IPT than with no IPT (adjusted hazard ratio, 0.65; 95% CI, 0.48 to 0.88; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.61; 95% CI, 0.36 to 1.01). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies. CONCLUSIONS: In this African country, immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis; TEMPRANO ANRS 12136 ClinicalTrials.gov number, NCT00495651.)

Effect of isoniazid preventive therapy on risk of death in west African, HIV-infected adults with high CD4 cell counts: long-term follow-up of the Temprano ANRS 12136 trial.

BACKGROUND: Temprano ANRS 12136 was a factorial 2 × 2 trial that assessed the benefits of early antiretroviral therapy (ART; ie, in patients who had not reached the CD4 cell count threshold used to recommend starting ART, as per the WHO guidelines that were the standard during the study period) and 6-month isoniazid preventive therapy (IPT) in HIV-infected adults in Côte d'Ivoire. Early ART and IPT were shown to independently reduce the risk of severe morbidity at 30 months. Here, we present the efficacy of IPT in reducing mortality from the long-term follow-up of Temprano. METHODS: For Temprano, participants were randomly assigned to four groups (deferred ART, deferred ART plus IPT, early ART, or early ART plus IPT). Participants who completed the trial follow-up were invited to participate in a post-trial phase. The primary post-trial phase endpoint was death, as analysed by the intention-to-treat principle. We used Cox proportional models to compare all-cause mortality between the IPT and no IPT strategies from inclusion in Temprano to the end of the follow-up period. FINDINGS: Between March 18, 2008, and Jan 5, 2015, 2056 patients (mean baseline CD4 count 477 cells per μL) were followed up for 9404 patient-years (Temprano 4757; post-trial phase 4647). The median follow-up time was 4·9 years (IQR 3·3-5·8). 86 deaths were recorded (Temprano 47 deaths; post-trial phase 39 deaths), of which 34 were in patients randomly assigned IPT (6-year probability 4·1%, 95% CI 2·9-5·7) and 52 were in those randomly assigned no IPT (6·9%, 5·1-9·2). The hazard ratio of death in patients who had IPT compared with those who did not have IPT was 0·63 (95% CI, 0·41 to 0·97) after adjusting for the ART strategy (early vs deferred), and 0·61 (0·39-0·94) after adjustment for the ART strategy, baseline CD4 cell count, and other key characteristics. There was no evidence for statistical interaction between IPT and ART (pinteraction=0·77) or between IPT and time (pinteraction=0·94) on mortality. INTERPRETATION: In Côte d'Ivoire, where the incidence of tuberculosis was last reported as 159 per 100 000 people, 6 months of IPT has a durable protective effect in reducing mortality in HIV-infected people, even in people with high CD4 cell counts and who have started ART. FUNDING: National Research Agency on AIDS and Viral Hepatitis (ANRS)

Basic considerations in the dermatokinetics of topical formulations

Assessing the bioavailability of drug molecules at the site of action provides better insight into the efficiency of a dosage form. However, determining drug concentration in the skin layers following topical application of dermatological formulations is a great challenge. The protocols followed in oral formulations could not be applied for topical dosage forms. The regulatory agencies are considering several possible approaches such as tape stripping, microdialysis etc. On the other hand, the skin bioavailability assessment of xenobiotics is equally important for topical formulations in order to evaluate the toxicity. It is always possible that drug molecules applied on the skin surface may transport thorough the skin and reaches systemic circulation. Thus the real time measurement of molecules in the skin layer has become obligatory. In the last two decades, quite a few investigations have been carried out to assess the skin bioavailability and toxicity of topical/dermatological products. This review provides current understanding on the basics of dermatokinetics, drug depot formation, skin metabolism and clearance of drug molecules from the skin layers following application of topical formulations

The dynamics of hollowing in annually burnt savanna trees and its effect on adult tree mortality

Savanna trees often display significant hollows due to the combined action of fire and termites (N'Dri et al., J Trop Ecol 27:269-278, 2011). Observations have shown that internal cavities caused by termites in tree stems often result in external hollows under annual fire regimes, and it is quite possible that such hollows/fire interaction may increase the probability of trunk or big branch breakage and/or tree mortality. A study of individual tree and branch mortality as a function of prior termite and fire damage was undertaken in a West African savanna (Lamto, Cte d'Ivoire) where most of the trees naturally have hollows in their stems due to termite and fire interaction. Our goal was to examine the dynamics of hollowing and to determine whether hollowing significantly affected tree mortality. Branch and whole plant mortality were quantified for dominant tree species according to their initial hollow state and height. Four different responses were obtained depending on tree species: (1) mortality increased with cavity severity and tree size (Piliostigma thonningii), (2) mortality depended on tree size only (Bridelia ferruginea), (3) no mortality even after being hollowed by termites and externally damaged by fire (Crossopteryx febrifuga, the species with the highest proportion of individuals with hollows yet the greatest background survival time, 14 +/- A 2 years) and (4) high mortality, but few hollow trees suggesting a weak resistance to hollowing (Cussonia arborea which was insensitive to all the factors examined in this study). For species resistant to hollowing, tree mortality was rare; alternatively, for species prone to hollowing, whole trees died quickly and before the most severe hollow classes could be observed. Long-term demographic data yielded population-level mortality estimates of adult trees at least four times lower in fire-exclusion zones than that in fire-prone areas. Because hollow dynamics interact with fire in affecting adult mortality of some dominant tree species, fire management is important for a sustainable woody component of these savannas

ABCES ET EMPYEMES INTRACRANIENS CHEZ L’ENFANT OBSERVES A ABIDJAN (CÔTE D'IVOIRE) (CEREBRAL ABCESS AND INTRACRANIAL EMPYEMAS IN CHILDREN.)

BACKGROUND Abcess and empyemas are frequent intracranial lesions in children. OBJECTIVES : The authors report the clinicals, radiologicals bacteriologicals and therapeuticals aspects of these intracranial suppurations observed in Abidjan. METHOD A retrospective analysis has been led in the neurosurgical department of university teaching hospital of Yopougon on 5 years period (December' 93 to december' 98). That study were based on 34 clinical observations on patients between 7 months and 15 years of age. RESULTS The authors reported 34 cases of abscess and intracranial empyemas on children subdural empyemas cases represented 44,1 %, abcess 20,5 % and the two lesions were associated in 17,6 %. Bacteriological agents isolated on 12 patients were gram positif cocci (3 cases) heamophilus (2 cases) flora mixed (2 cases) and a combination of pseudomonas acinetobacter (1 cases). The predisposing factors were ENT diseases. CONCLUSION : Intracranial subdural empyemas are most common form of intracranial suppurations seen on child in our unit. This study can be considered as a speech for the defense of the use one cerebral abcess and intracranial empyemas surgical drainage via burrhole. The author stress the interest of eradication of primary source of the sepsis and the appropriate treatment of head trauma

On the dispersal of bottle gourd [Lagenaria siceraria (Mol.) Standl.] out of Africa : a contribution from the analysis of nuclear ribosomal DNA haplotypes, divergent paralogs and variants of 5.8S protein sequences

Bottle gourd (Lagenaria siceraria), a multipurpose crop, is among the first domesticates of humans. This study analyses nuclear ribosomal DNA (nrDNA) of the two cultivated subspecies to improve our understanding on the African origin and the dispersal to Asia. A total of 146 nrDNA sequences representing 79 individuals from African cultivars and 67 individuals from Asian cultivars were compared; the resulting nrDNA sequences were composed of 35 and 16 haplotypes specific to Africa and Asia, respectively, and two additional haplotypes shared by both continents. When all the rDNA haplotypes were bulked, the genetic differentiation (F (ST) ) was significant between the subspecies (P < 0.001), within Africa (P < 0.001) and within Asia (P < 0.05), and the nucleotide diversity was 2.5-fold higher in Africa. Sorting the haplotypes by classes of paralogs revealed more classes in Africa, and in classes where African and Asian cultivars were represented, the diversity was higher in Africa, in general. The 5.8S-coding regions showed two to four amino acid differences resulting to nine protein sequence variants, one of which encompassed all the Asian cultivars. The nucleotide diversity at that shared variant was 1.43-fold higher in Africa than in Asia. Analyses of phylogenetic networks revealed major shared haplotypes containing 23.91 % of the cultivars and having founder locations. We suggest that African cultivars reached Asia. The study tags for the first time nrDNA haplotypes capable of discriminating between and within the subspecies. Thirty single nucleotide polymorphisms (SNPs) and five insertion-deletions (Indels) derived from the haplotypes and registered in GenBank are provided

ABCES ET EMPYEMES INTRACRANIENS CHEZ L’ENFANT OBSERVES A ABIDJAN (CÔTE D'IVOIRE) (CEREBRAL ABCESS AND INTRACRANIAL EMPYEMAS IN CHILDREN.)

BACKGROUND Abcess and empyemas are frequent intracranial lesions in children. OBJECTIVES : The authors report the clinicals, radiologicals bacteriologicals and therapeuticals aspects of these intracranial suppurations observed in Abidjan. METHOD A retrospective analysis has been led in the neurosurgical department of university teaching hospital of Yopougon on 5 years period (December' 93 to december' 98). That study were based on 34 clinical observations on patients between 7 months and 15 years of age. RESULTS The authors reported 34 cases of abscess and intracranial empyemas on children subdural empyemas cases represented 44,1 %, abcess 20,5 % and the two lesions were associated in 17,6 %. Bacteriological agents isolated on 12 patients were gram positif cocci (3 cases) heamophilus (2 cases) flora mixed (2 cases) and a combination of pseudomonas acinetobacter (1 cases). The predisposing factors were ENT diseases. CONCLUSION : Intracranial subdural empyemas are most common form of intracranial suppurations seen on child in our unit. This study can be considered as a speech for the defense of the use one cerebral abcess and intracranial empyemas surgical drainage via burrhole. The author stress the interest of eradication of primary source of the sepsis and the appropriate treatment of head trauma

The complex health seeking pathway of a human African trypanosomiasis patient in Cote d'Ivoire underlines the need of setting up passive surveillance systems

Background Significant efforts to control human African trypanosomiasis (HAT) over the two past decades have resulted in drastic decrease of its prevalence in Cote d'Ivoire. In this context, passive surveillance, integrated in the national health system and based on clinical suspicion, was reinforced. We describe here the health-seeking pathway of a girl who was the first HAT patient diagnosed through this strategy in August 2017. Methods After definitive diagnosis of this patient, epidemiological investigations were carried out into the clinical evolution and the health and therapeutic itinerary of the patient before diagnosis. Results At the time of diagnosis, the patient was positive in both serological and molecular tests and trypanosomes were detected in blood and cerebrospinal fluid. She suffered from important neurological disorders. The first disease symptoms had appeared three years earlier, and the patient had visited several public and private peripheral health care centres and hospitals in different cities. The failure to diagnose HAT for such a long time caused significant health deterioration and was an important financial burden for the family. Conclusion This description illustrates the complexity of detecting the last HAT cases due to complex diagnosis and the progressive disinterest and unawareness by both health professionals and the population. It confirms the need of implementing passive surveillance in combination with continued sensitization and health staff training. Author summary Human African trypanosomiasis (HAT) or sleeping sickness is a parasitic disease caused byTrypanosoma bruceithat is transmitted by tsetse flies. In 2012, HAT was included in the World Health Organization roadmap for the control of neglected tropical diseases with the objective of elimination as a public health problem by 2020. In Cote d'Ivoire, HAT prevalence has dropped sharply the last decade. A passive HAT surveillance was therefore integrated in the national health system, which allowed to detect a first patient in 2017. This article describes the complex health seeking pathway and suffering before diagnosis of this patient, an 11 years old girl, and illustrates the challenge when health agents and population no longer consider HAT as a threat in an elimination context. Our results show the need to install a solid surveillance system, in combination with continued sensitization and repeated health staff training