Spatial mapping and prediction of Plasmodium falciparum infection risk among school-aged children in Côte d'Ivoire

BACKGROUND: In Côte d'Ivoire, malaria remains a major public health issue, and thus a priority to be tackled. The aim of this study was to identify spatially explicit indicators of Plasmodium falciparum infection among school-aged children and to undertake a model-based spatial prediction of P. falciparum infection risk using environmental predictors. METHODS: A cross-sectional survey was conducted, including parasitological examinations and interviews with more than 5,000 children from 93 schools across Côte d'Ivoire. A finger-prick blood sample was obtained from each child to determine Plasmodium species-specific infection and parasitaemia using Giemsa-stained thick and thin blood films. Household socioeconomic status was assessed through asset ownership and household characteristics. Children were interviewed for preventive measures against malaria. Environmental data were gathered from satellite images and digitized maps. A Bayesian geostatistical stochastic search variable selection procedure was employed to identify factors related to P. falciparum infection risk. Bayesian geostatistical logistic regression models were used to map the spatial distribution of P. falciparum infection and to predict the infection prevalence at non-sampled locations via Bayesian kriging. RESULTS: Complete data sets were available from 5,322 children aged 5-16 years across Côte d'Ivoire. P. falciparum was the predominant species (94.5 %). The Bayesian geostatistical variable selection procedure identified land cover and socioeconomic status as important predictors for infection risk with P. falciparum. Model-based prediction identified high P. falciparum infection risk in the north, central-east, south-east, west and south-west of Côte d'Ivoire. Low-risk areas were found in the south-eastern area close to Abidjan and the south-central and west-central part of the country. CONCLUSIONS: The P. falciparum infection risk and related uncertainty estimates for school-aged children in Côte d'Ivoire represent the most up-to-date malaria risk maps. These tools can be used for spatial targeting of malaria control interventions

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)

Effect of deworming on school-aged children's physical fitness, cognition and clinical parameters in a malaria-helminth co-endemic area of Côte d'Ivoire

Malaria and helminth infections are thought to negatively affect children's nutritional status and to impair their physical and cognitive development. Yet, the current evidence-base is weak. The purpose of this study was to determine the effect of deworming against soil-transmitted helminthiasis and schistosomiasis on children's physical fitness, cognition and clinical parameters in a malaria-helminth co-endemic setting of Côte d'Ivoire.; We designed an intervention study with a 5-month follow-up among schoolchildren aged 5-14 years from Niablé, eastern Côte d'Ivoire. In late 2012, a baseline cross-sectional survey was conducted. Finger-prick blood, stool and urine samples were subjected to standardised, quality-controlled techniques for the diagnosis of Plasmodium spp., Schistosoma spp., soil-transmitted helminths and intestinal protozoa infections. Haemoglobin level was determined and anthropometric measurements were taken for appraisal of anaemia and nutritional status. Children underwent memory (digit span) and attention (code transmission) cognitive testing, and their physical fitness and strength were determined (20 m shuttle run, standing broad jump and grip strength test). All children were treated with albendazole (against soil-transmitted helminthiasis) and praziquantel (against schistosomiasis) after the baseline cross-sectional survey and again 2 months later. Five months after the initial deworming, the same battery of clinical, cognitive and physical fitness tests was performed on the same children.; Lower scores in strength tests were significantly associated with children with harbouring nutritional deficiencies. Surprisingly, boys infected with Schistosoma mansoni achieved longer jumping distances than their non-infected counterparts. Light-intensity infection with S. mansoni was associated with slightly better aerobic capacity. Deworming showed no effect on haemoglobin levels and anaemia, but children with moderate- to heavy-intensity Schistosoma infection at baseline gained weight more pronouncedly than non-infected children. Interestingly, children with soil-transmitted helminth or Schistosoma infection at baseline performed significantly better in the sustained attention test than their non-infected counterparts at the 5-month follow-up.; This study revealed conflicting results regarding clinical parameters and cognitive behaviour of children after two rounds of deworming. We speculate that potential beneficial effects of deworming are likely to be undermined in areas where malaria is co-endemic and nutritional deficiencies are widespread

Disparities of Plasmodium falciparum infection, malaria-related morbidity and access to malaria prevention and treatment among school-aged children : a national cross-sectional survey in Côte d'Ivoire

There is limited knowledge on the malaria burden of school-aged children in Côte d'Ivoire. The aim of this study was to assess Plasmodium falciparum infection, malaria-related morbidity, use of preventive measures and treatment against malaria, and physical access to health structures among school-aged children across Côte d'Ivoire.; A national, cross-sectional study was designed, consisting of clinical and parasitological examinations and interviews with schoolchildren. More than 5,000 children from 93 schools in Côte d'Ivoire were interviewed to determine household socioeconomic status, self-reported morbidity and means of malaria prevention and treatment. Finger-prick blood samples were collected and Plasmodium infection and parasitaemia determined using Giemsa-stained blood films and a rapid diagnostic test (RDT). Haemoglobin levels and body temperature were measured. Children were classified into wealth quintiles using household assets and principal components analysis (PCA). The concentration index was employed to determine significant trends of health variables according to wealth quintiles. Logistic and binomial negative regression analyses were done to investigate for associations between P. falciparum prevalence and parasitaemia and any health-related variable.; The prevalence of P. falciparum was 73.9% according to combined microscopy and RDT results with a geometric mean of parasitaemia among infected children of 499 parasites/μl of blood. Infection with P. falciparum was significantly associated with sex, socioeconomic status and study setting, while parasitaemia was associated with age. The rate of bed net use was low compared to the rate of bed net ownership. Preventive measures (bed net ownership, insecticide spray and the reported use of malaria treatment) were more frequently mentioned by children from wealthier households who were at lower risk of P. falciparum infection. Self-reported morbidity (headache) and clinical morbidity (anaemia) were more often reported by children from less wealthy households.; Seven out of ten school-aged children in Côte d'Ivoire are infected with P. falciparum and malaria-related morbidity is considerable. Furthermore, this study points out that bed net usage is quite low and there are important inequalities in preventive measures and treatment. These results can guide equity-oriented malaria control strategies in Côte d'Ivoire