Accuracy of a rapid diagnosis test, microscopy and loop-mediated isothermal amplification in the detection of asymptomatic Plasmodium infections in Korhogo, Northern Côte d'Ivoire.

BACKGROUND: Highly sensitive and accurate malaria diagnostic tools are essential to identify asymptomatic low parasitaemia infections. This study evaluated the performance of histidine-rich protein 2 (HRP-2) based rapid diagnostic tests (RDTs), microscopy and loop-mediated isothermal amplification (LAMP) for the detection of asymptomatic Plasmodium spp. infections in Northern Côte d'Ivoire, using nested polymerase chain reaction (nPCR) as reference. METHODS: A household-based survey was carried out in July 2016, in the health district of Korhogo, involving 1011 adults without malaria symptom nor history of fever during the week before recruitment. The fresh capillary blood samples were collected to detect Plasmodium infections using on HRP-2-based RDTs, microscopy and LAMP and stored as dried blood spots (DBS). A subset of the DBS (247/1011, 24.4%) was randomly selected for nPCR analyses. Additionally, venous blood samples, according to LAMP result (45 LAMP positive and 65 LAMP negative) were collected among the included participants to perform the nested PCR used as the reference. RESULTS: The prevalence of asymptomatic Plasmodium spp. infections determined by RDT, microscopy, and LAMP were 4% (95% confidence interval (CI) 2.8-5.3), 5.2% (95% CI 3.9-6.6) and 18.8% (95% CI 16.4-21.2), respectively. Considering PCR on venous blood as reference, performed on 110 samples, the sensibility and specificity were, respectively, 17.8% (95% CI 6.1-29.4) and 100% for RDT, 20.0% (95% CI 7.8-32) and 100% for microscopy, and 93.3% (95% CI 85.7-100) and 95.4% (95% CI 92.2-100) for LAMP. CONCLUSION: In Northern Côte d'Ivoire, asymptomatic Plasmodium infection was found to be widely distributed as approximately one out of five study participants was found to be Plasmodium infected. LAMP appears currently to be the only available diagnostic method that can identify in the field this reservoir of infections and should be the method to consider for potential future active case detection interventions targeting elimination of these infections.

Prevalence and distribution of livestock schistosomiasis and fascioliasis in Côte d'Ivoire: results from a cross-sectional survey.

BACKGROUND: Schistosoma and Fasciola are zoonotic parasites of public health and veterinary importance. However, while the epidemiology of schistosomiasis in humans is well studied, little is known about fascioliasis and schistosomiasis in livestock in Côte d'Ivoire. This study aimed to determine the prevalence and the distribution of livestock schistosomiasis and fascioliasis across Côte d'Ivoire. In 2018, we conducted a cross-sectional survey in abattoirs and farms in 13 departments of Côte d'Ivoire. In abattoirs, the mesenteric veins and livers of slaughtered cattle, sheep and goats were examined for adult Schistosoma and Fasciola flukes. Faeces from live cattle, goats and sheep were collected and examined for Schistosoma and Fasciola eggs using a sedimentation technique. RESULTS: A total of 386 cattle, 174 goats and 151 sheep from abattoirs and 435 cattle, 22 goats and 176 sheep from farms were sampled. The observed prevalence of schistosomiasis was higher in slaughtered animals. Fascioliasis was more prevalent in farm animals. The prevalence of schistosomiasis in slaughtered cattle varied between 5.9% (95% confidence interval (CI): 0.7-19.7%) and 53.3% (95% CI: 37.9-68.3%) with the highest prevalence observed in Ouangolodougou in the North. Cattle from farms had a relatively low prevalence of schistosomiasis, with the highest prevalence found in Ouangolodougou (2.4%, 95% CI: 0.7-6.1%). The prevalence of fascioliasis varied considerably from one department to another, ranging from nil (95% CI: 0.0-18.5%) to 50.8% (95% CI: 43.4-58.2%), with the highest prevalence found in farm cattle in Dikodougou in the North. Sheep and goats had a lower prevalence of schistosomiasis and fascioliasis than cattle. In slaughtered animals, cattle aged 4 years and older were at highest risk for schistosomiasis (odds ratio (OR): 2.4; 95% CI: 1.0-5.6) and fascioliasis (OR: 2.1; 95% CI: 1.1-3.9). In farm animals, male cattle had higher odds of being infected with Schistosoma (OR: 4.3; 95% CI: 0.7-26.9) than females. CONCLUSIONS: Our study confirms that schistosomiasis and fascioliasis are endemic in livestock across Côte d'Ivoire. A strategic control programme should be considered, especially for cattle, including providing drinking water in troughs to reduce faecal contamination of water sources by cattle.

UCT943, a Next-Generation Plasmodium falciparum PI4K Inhibitor Preclinical Candidate for the Treatment of Malaria.

The 2-aminopyridine MMV048 was the first drug candidate inhibiting Plasmodium phosphatidylinositol 4-kinase (PI4K), a novel drug target for malaria, to enter clinical development. In an effort to identify the next generation of PI4K inhibitors, the series was optimized to improve properties such as solubility and antiplasmodial potency across the parasite life cycle, leading to the 2-aminopyrazine UCT943. The compound displayed higher asexual blood stage, transmission-blocking, and liver stage activities than MMV048 and was more potent against resistant Plasmodium falciparum and Plasmodium vivax clinical isolates. Excellent in vitro antiplasmodial activity translated into high efficacy in Plasmodium berghei and humanized P. falciparum NOD-scid IL-2Rγ null mouse models. The high passive permeability and high aqueous solubility of UCT943, combined with low to moderate in vivo intrinsic clearance, resulted in sustained exposure and high bioavailability in preclinical species. In addition, the predicted human dose for a curative single administration using monkey and dog pharmacokinetics was low, ranging from 50 to 80 mg. As a next-generation Plasmodium PI4K inhibitor, UCT943, based on the combined preclinical data, has the potential to form part of a single-exposure radical cure and prophylaxis (SERCaP) to treat, prevent, and block the transmission of malaria.

Epidemiology of malaria in the Taabo health and demographic surveillance system, south-central Côte d'Ivoire.

BACKGROUND: A deep understanding of the local epidemiology of malaria is essential for the design and implementation of setting-specific control and elimination efforts. In Côte d'Ivoire, new initiatives are underway to reduce the burden of malaria, which requires high-quality longitudinal data. The epidemiology of malaria was studied in the Taabo health and demographic surveillance system (HDSS) in south-central Côte d'Ivoire and implications for control are discussed. METHODS: Two cross-sectional surveys were carried out in the rainy season of June/July in 2010 and 2011. Inhabitants of approximately 7% of randomly selected households in the Taabo HDSS were invited to participate. People were clinically examined, ear temperature was measured and spleen size determined. Finger-prick blood samples were collected and subjected to a rapid diagnostic test (RDT). Additionally, thick and thin blood films were prepared on microscope slides and diagnosed under a microscope for Plasmodium infection and parasitaemia. Haemoglobin (Hb) level was determined using a HemoCue device. RESULTS: A total of 1187 and 1264 people in 2010 and 2011, respectively, had complete data records. The prevalence of Plasmodium infection was 46.0% in 2010 and 56.6% in 2011, owing to a statistically significant difference (p < 0.05). Males showed a higher Plasmodium infection prevalence than females (49.6 and 62.8% versus 42.6 and 51.2%; respectively, in 2010 and 2011; both p < 0.05). The highest malaria prevalence was observed among infants and young children (aged ≤9 years). The risk of Plasmodium infection was significantly higher in villages compared to small hamlets and urban settings (p < 0.05). Fever, Hb level and splenomegaly were associated with parasitaemia. CONCLUSION: Malaria is highly endemic in the Taabo HDSS in south-central Côte d'Ivoire with considerable spatial heterogeneity of Plasmodium infection. There is a pressing need to scale-up control interventions against malaria.

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.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Diagnosis of neglected tropical diseases among patients with persistent digestive disorders (diarrhoea and/or abdominal pain ≥14 days): Pierrea multi-country, prospective, non-experimental case-control study.

BACKGROUND: Diarrhoea still accounts for considerable mortality and morbidity worldwide. The highest burden is concentrated in tropical areas where populations lack access to clean water, adequate sanitation and hygiene. In contrast to acute diarrhoea (<14 days), the spectrum of pathogens that may give rise to persistent diarrhoea (≥14 days) and persistent abdominal pain is poorly understood. It is conceivable that pathogens causing neglected tropical diseases play a major role, but few studies investigated this issue. Clinical management and diagnostic work-up of persistent digestive disorders in the tropics therefore remain inadequate. Hence, important aspects regarding the pathogenesis, epidemiology, clinical symptomatology and treatment options for patients presenting with persistent diarrhoea and persistent abdominal pain should be investigated in multi-centric clinical studies. METHODS/DESIGN: This multi-country, prospective, non-experimental case-control study will assess persistent diarrhoea (≥14 days; in individuals aged ≥1 year) and persistent abdominal pain (≥14 days; in children/adolescents aged 1-18 years) in up to 2000 symptomatic patients and 2000 matched controls. Subjects from Côte d'Ivoire, Indonesia, Mali and Nepal will be clinically examined and interviewed using a detailed case report form. Additionally, each participant will provide a stool sample that will be examined using a suite of diagnostic methods (i.e., microscopic techniques, rapid diagnostic tests, stool culture and polymerase chain reaction) for the presence of bacterial and parasitic pathogens. Treatment will be offered to all infected participants and the clinical treatment response will be recorded. Data obtained will be utilised to develop patient-centred clinical algorithms that will be validated in primary health care centres in the four study countries in subsequent studies. DISCUSSION: Our research will deepen the understanding of the importance of persistent diarrhoea and related digestive disorders in the tropics. A diversity of intestinal pathogens will be assessed for potential associations with persistent diarrhoea and persistent abdominal pain. Different diagnostic methods will be compared, clinical symptoms investigated and diagnosis-treatment algorithms developed for validation in selected primary health care centres. The findings from this study will improve differential diagnosis and evidence-based clinical management of digestive syndromes in the tropics. TRIAL REGISTRATION: ClinicalTrials.gov; identifier: NCT02105714 .

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.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Rapid and Comprehensive Screening for Urogenital and Gastrointestinal Schistosomiasis with Handheld Digital Microscopy Combined with Circulating Cathodic Antigen Testing.

Novel methods are required to aid the monitoring of schistosomiasis control and elimination initiatives through mass drug administration. Portable digital and mobile phone microscopy is a promising tool for this purpose. This cross-sectional study evaluated the diagnostic operating characteristics of a converted mobile phone microscope (the SchistoScope) for the detection of Schistosoma haematobium eggs, as determined by community-based field workers and expert microscopists, compared with a field gold standard of light microscopy. Three hundred sixty-five urine samples were evaluated by conventional light microscopy, with 49 (13.4%) positive for S. haematobium. Compared with light microscopy, the sensitivity and specificity of S. haematobium detection by field microscopists trained to use the SchistoScope were 26.5% (95% CI: 14.9-41.1%) and 98.4% (95% CI: 96.3-99.5%), respectively. The sensitivity and specificity of S. haematobium detection by expert microscopists using the SchistoScope was 74% (95% CI: 59.7-85.4%) and 98.1% (95% CI: 95.9-99.3%), respectively, compared with light microscopy. The sensitivity rose to 96.1% and 100% when evaluating for egg counts greater than five and 10 eggs per 10 mL, respectively. A point-of-care circulating cathodic anion (POC CCA) test was used to evaluate Schistosoma mansoni; however, there were too few positive samples to reliably comment on diagnostic characteristics. This study demonstrated that a "urine-only" approach to rapidly screen for schistosomiasis at the point of sample collection can be conducted with mobile phone microscopy (S. haematobium) coupled with POC CCA (S. mansoni). Such an approach may aid in streamlined schistosomiasis control and elimination initiatives.

Rapid appraisal of liver diseases using transient elastography, abdominal ultrasound, and microbiology in Côte d'Ivoire: A single-center study.

BACKGROUND: Liver diseases of infectious and non-infectious etiology cause considerable morbidity and mortality, particularly in low- and middle-income countries (LMICs). However, data on the prevalence of liver diseases and underlying risk factors in LMICs are scarce. The objective of this study was to elucidate the occurrence of infectious diseases among individuals with chronic liver damage in a rural setting of Côte d'Ivoire. METHODOLOGY: In 2021, we screened 696 individuals from four villages in the southern part of Côte d'Ivoire for hepatic fibrosis and steatosis, employing transient elastography (TE) and controlled attenuation parameter (CAP). We classified CAP ≥248 dB/m as steatosis, TE ≥7.2 kPa as fibrosis, and did subgroup analysis for participants with TE ranging from 7.2 kPa to 9.1 kPa. Clinical and microbiologic characteristics were compared to an age- and sex-matched control group (TE <6.0 kPa; n = 109). Stool samples were subjected to duplicate Kato-Katz thick smears for diagnosis of Schistosoma mansoni. Venous blood samples were examined for hepatitis B and hepatitis C virus. Additionally, an abdominal ultrasound examination was performed. PRINCIPAL FINDINGS: Among 684 individuals with valid TE measurements, TE screening identified hepatic pathologies in 149 participants (17% with fibrosis and 6% with steatosis). 419 participants were included for further analyses, of which 261 had complete microbiologic analyses available. The prevalence of S. mansoni, hepatitis B, and hepatitis C were 30%, 14%, and 7%, respectively. Logistic regression analysis revealed higher odds for having TE results between 7.2 kPa and 9.1 kPa in individuals with S. mansoni infection (odds ratio [OR] = 3.02, 95% confidence interval [CI] = 1.58-5.76, P = 0.001), while HCV infection (OR = 5.02, 95% CI = 1.72-14.69, P = 0.003) and steatosis (OR = 4.62, 95% CI = 1.60-13.35, P = 0.005) were found to be risk factors for TE ≥9.2 kPa. CONCLUSIONS/SIGNIFICANCE: Besides viral hepatitis, S. mansoni also warrants consideration as a pathogen causing liver fibrosis in Côte d'Ivoire. In-depth diagnostic work-up among individuals with abnormal TE findings might be a cost-effective public health strategy.

Genetic diversity of Plasmodium falciparum among school-aged children from the Man region, western Côte d'Ivoire.

BACKGROUND: The genetic diversity of Plasmodium falciparum allows the molecular discrimination of otherwise microscopically identical parasites and the identification of individual clones in multiple infections. The study reported here investigated the P. falciparum multiplicity of infection (MOI) and genetic diversity among school-aged children in the Man region, western Côte d'Ivoire. METHODS: Blood samples from 292 children aged seven to 15 years were collected in four nearby villages located at altitudes ranging from 340 to 883 m above sea level. Giemsa-stained thick and thin blood films were prepared and examined under a microscope for P. falciparum prevalence and parasitaemia. MOI and genetic diversity of the parasite populations were investigated using msp2 typing by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Plasmodium falciparum prevalence and parasitaemia were both found to be significantly lower in the highest altitude village. Genotyping of the isolates revealed 25 potentially new msp2 alleles. MOI varied significantly across villages but did not correlate with altitude nor children's age, and only to a limited extent with parasitaemia. An analysis of molecular variance (AMOVA) indicated that a small, but close to statistical significance (p = 0.07), fraction of variance occurs specifically between villages of low and high altitudes. CONCLUSIONS: Higher altitude was associated with lower prevalence of P. falciparum but not with reduced MOI, suggesting that, in this setting, MOI is not a good proxy for transmission. The evidence for partially parted parasite populations suggests the existence of local geographical barriers that should be taken into account when deploying anti-malarial interventions.

High Sensitivity of Mobile Phone Microscopy Screening for Schistosoma haematobium in Azaguié, Côte d'Ivoire.

Schistosomiasis infections continue to impact African settings disproportionately, and there is an urgent need for novel tools to evaluate infection control and elimination strategies at the community level. Mobile phone microscopes are portable and semiautomated devices with multiple applications for screening neglected tropical diseases. In a community-based schistosomiasis screening program in Azaguié, Côte d'Ivoire, mobile phone microscopy demonstrated a sensitivity of 85.7% (95% CI: 69.7-95.2%) and specificity of 93.3% (95% CI: 87.7-96.9%) for Schistosoma haematobium identification compared with conventional light microscopy, and 95% sensitivity (95% CI: 74.1-99.8%) with egg concentrations of five or more per 10 mL of urine. Mobile phone microscopy is a promising tool for schistosomiasis control and elimination efforts.

Mapping malaria risk among children in Côte d'Ivoire using Bayesian geo-statistical models.

BACKGROUND: In Côte d'Ivoire, an estimated 767,000 disability-adjusted life years are due to malaria, placing the country at position number 14 with regard to the global burden of malaria. Risk maps are important to guide control interventions, and hence, the aim of this study was to predict the geographical distribution of malaria infection risk in children aged <16 years in Côte d'Ivoire at high spatial resolution. METHODS: Using different data sources, a systematic review was carried out to compile and geo-reference survey data on Plasmodium spp. infection prevalence in Côte d'Ivoire, focusing on children aged <16 years. The period from 1988 to 2007 was covered. A suite of Bayesian geo-statistical logistic regression models was fitted to analyse malaria risk. Non-spatial models with and without exchangeable random effect parameters were compared to stationary and non-stationary spatial models. Non-stationarity was modelled assuming that the underlying spatial process is a mixture of separate stationary processes in each ecological zone. The best fitting model based on the deviance information criterion was used to predict Plasmodium spp. infection risk for entire Côte d'Ivoire, including uncertainty. RESULTS: Overall, 235 data points at 170 unique survey locations with malaria prevalence data for individuals aged <16 years were extracted. Most data points (n = 182, 77.4%) were collected between 2000 and 2007. A Bayesian non-stationary regression model showed the best fit with annualized rainfall and maximum land surface temperature identified as significant environmental covariates. This model was used to predict malaria infection risk at non-sampled locations. High-risk areas were mainly found in the north-central and western area, while relatively low-risk areas were located in the north at the country border, in the north-east, in the south-east around Abidjan, and in the central-west between two high prevalence areas. CONCLUSION: The malaria risk map at high spatial resolution gives an important overview of the geographical distribution of the disease in Côte d'Ivoire. It is a useful tool for the national malaria control programme and can be utilized for spatial targeting of control interventions and rational resource allocation.

Limited efficacy of repeated praziquantel treatment in Schistosoma mansoni infections as revealed by highly accurate diagnostics, PCR and UCP-LF CAA (RePST trial).

BACKGROUND: Most studies assessing praziquantel (PZQ) efficacy have used relatively insensitive diagnostic methods, thereby overestimating cure rate (CR) and intensity reduction rate (IRR). To determine accurately PZQ efficacy, we employed more sensitive DNA and circulating antigen detection methods. METHODOLOGY: A sub-analysis was performed based on a previously published trial conducted in children from Côte d'Ivoire with a confirmed Schistosoma mansoni infection, who were randomly assigned to a standard (single dose of PZQ) or intense treatment group (4 repeated doses of PZQ at 2-week intervals). CR and IRR were estimated based on PCR detecting DNA in a single stool sample and the up-converting particle lateral flow (UCP-LF) test detecting circulating anodic antigen (CAA) in a single urine sample, and compared with traditional Kato-Katz (KK) and point-of-care circulating cathodic antigen (POC-CCA). PRINCIPAL FINDINGS: Individuals positive by all diagnostic methods (i.e., KK, POC-CCA, PCR, and UCP-LF CAA) at baseline were included in the statistical analysis (n = 125). PCR showed a CR of 45% (95% confidence interval (CI) 32-59%) in the standard and 78% (95% CI 66-87%) in the intense treatment group, which is lower compared to the KK results (64%, 95% CI 52-75%) and 88%, 95% CI 78-93%). UCP-LF CAA showed a significantly lower CR in both groups, 16% (95% CI 11-24%) and 18% (95% CI 12-26%), even lower than observed by POC-CCA (31%, 95% CI 17-35% and 36%, 95% CI 26-47%). A substantial reduction in DNA and CAA-levels was observed after the first treatment, with no further decrease after additional treatment and no significant difference in IRR between treatment groups. CONCLUSION/SIGNIFICANCE: The efficacy of (repeated) PZQ treatment was overestimated when using egg-based diagnostics (i.e. KK and PCR). Quantitative worm-based diagnostics (i.e. POC-CCA and UCP-LF CAA) revealed that active Schistosoma infections are still present despite multiple treatments. These results stress the need for using accurate diagnostic tools to monitor different PZQ treatment strategies, in particular when moving toward elimination of schistosomiasis. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov, NCT02868385.

Efficacy and safety of mefloquine, artesunate, mefloquine-artesunate, and praziquantel against Schistosoma haematobium: randomized, exploratory open-label trial.

BACKGROUND: Morbidity control of schistosomiasis relies on a single drug, praziquantel. The antimalarial drug mefloquine possesses interesting antischistosomal properties, yet no clinical studies have been performed. METHODS: We conducted a randomized, exploratory open-label trial to assess the efficacy and safety of mefloquine (25 mg/kg), artesunate (3 doses of 4 mg/kg), mefloquine-artesunate (3 doses of 100 mg artesunate plus 250 mg mefloquine), and praziquantel (40 mg/kg) against Schistosoma haematobium. The effects on Schistosoma mansoni, malaria parasitemia, soil-transmitted helminths, and intestinal protozoa were also determined. RESULTS: A total of 83 S. haematobium-infected schoolchildren were included in the study. Cure rates of mefloquine, artesunate, mefloquine-artesunate, and praziquantel against S. haematobium at day 26 after treatment were 21%, 25%, 61%, and 88%, respectively. Both mefloquine-artesunate and praziquantel resulted in egg reduction rates >95%. Significantly lower egg reduction rates were seen in the artesunate (85%) and mefloquine groups (74%). In children coinfected with S. mansoni, praziquantel and mefloquine-artesunate, but not mefloquine and artesunate alone, resulted in high cure rates and egg reduction rates. Mefloquine, artesunate, and mefloquine-artesunate completely cured infections due to Plasmodium falciparum. No effects were found against soil-transmitted helminths and intestinal protozoa. Abdominal pain was the most frequent adverse event, with a higher incidence among children treated with mefloquine (89%), mefloquine-artesunate (83%), and artesunate (60%) than among children treated with praziquantel (46%). CONCLUSIONS: The high efficacy of mefloquine-artesunate against S. haematobium warrants further investigation. Individuals coinfected with Plasmodium and Schistosoma who were treated with a mefloquine-artesunate combination against malaria might have a dual benefit: clearance of malaria parasitemia and reduction of schistosomiasis-related morbidity. CLINICAL TRIALS REGISTRATION: Current Controlled Trials identifier: ISRCTN06498763.

Efficacy of single versus four repeated doses of praziquantel against Schistosoma mansoni infection in school-aged children from Côte d'Ivoire based on Kato-Katz and POC-CCA: An open-label, randomised controlled trial (RePST).

BACKGROUND: Preventive chemotherapy with praziquantel (PZQ) is the cornerstone of schistosomiasis control. However, a single dose of PZQ (40 mg/kg) does not cure all infections. Repeated doses of PZQ at short intervals might increase efficacy in terms of cure rate (CR) and intensity reduction rate (IRR). Here, we determined the efficacy of a single versus four repeated treatments with PZQ on Schistosoma mansoni infection in school-aged children from Côte d'Ivoire, using two different diagnostic tests. METHODS: An open-label, randomized controlled trial was conducted from October 2018 to January 2019. School-aged children with a confirmed S. mansoni infection based on Kato-Katz (KK) and point-of-care circulating cathodic antigen (POC-CCA) urine cassette test were randomly assigned to receive either a single or four repeated doses of PZQ, administered at two-week intervals. The primary outcome was the difference in CR between the two treatment arms, measured by triplicate KK thick smears 10 weeks after the first treatment. Secondary outcomes included CR estimated by POC-CCA, IRR by KK and POC-CCA, and safety of repeated PZQ administration. PRINCIPAL FINDINGS: During baseline screening, 1,022 children were assessed for eligibility of whom 153 (15%) had a detectable S. mansoni infection, and hence, were randomized to the standard treatment group (N = 70) and the intense treatment group (N = 83). Based on KK, the CR was 42% (95% confidence interval (CI) 31-52%) in the standard treatment group and 86% (95% CI 75-92%) in the intense treatment group. Observed IRR was 72% (95% CI 55-83%) in the standard treatment group and 95% (95% CI 85-98%) in the intense treatment group. The CR estimated by POC-CCA was 18% (95% CI 11-27%) and 36% (95% CI 26-46%) in the standard and intense treatment group, respectively. Repeated PZQ treatment did not result in a higher number of adverse events. CONCLUSION/SIGNIFICANCE: The observed CR using KK was significantly higher after four repeated treatments compared to a single treatment, without an increase in adverse events. Using POC-CCA, the observed CR was significantly lower than measured by KK, indicating that PZQ may be considerably less efficacious as concluded by KK. Our findings highlight the need for reliable and more accurate diagnostic tools, which are essential for monitoring treatment efficacy, identifying changes in transmission, and accurately quantifying the intensity of infection in distinct populations. In addition, the higher CR in the intense treatment group suggests that more focused and intense PZQ treatment can help to advance schistosomiasis control. TRIAL REGISTRATION: www.clinicaltrials.gov NCT02868385.

Spatial risk profiling of Plasmodium falciparum parasitaemia in a high endemicity area in Côte d'Ivoire.

BACKGROUND: The objective of this study was to identify demographic, environmental and socioeconomic risk factors and spatial patterns of Plasmodium falciparum parasitaemia in a high endemicity area of Africa, and to specify how this information can facilitate improved malaria control at the district level. METHODS: A questionnaire was administered to about 4,000 schoolchildren in 55 schools in western Côte d'Ivoire to determine children's socioeconomic status and their habit of sleeping under bed nets. Environmental data were obtained from satellite images, digitized ground maps and a second questionnaire addressed to school directors. Finger prick blood samples were collected and P. falciparum parasitaemia determined under a microscope using standardized, quality-controlled methods. Bayesian variogram models were utilized for spatial risk modelling and mapping of P. falciparum parasitaemia at non-sampled locations, assuming stationary and non-stationary underlying spatial dependence. RESULTS: Two-thirds of the schoolchildren were infected with P. falciparum and the mean parasitaemia among infected children was 959 parasites/microl of blood. Age, socioeconomic status, not sleeping under a bed net, coverage rate with bed nets and environmental factors (e.g., normalized difference vegetation index, rainfall, land surface temperature and living in close proximity to standing water) were significantly associated with the risk of P. falciparum parasitaemia. After accounting for spatial correlation, age, bed net coverage, rainfall during the main malaria transmission season and distance to rivers remained significant covariates. CONCLUSION: It is argued that a massive increase in bed net coverage, particularly in villages in close proximity to rivers, in concert with other control measures, is necessary to bring malaria endemicity down to intermediate or low levels.

Antagonistic effects of Plasmodium-helminth co-infections on malaria pathology in different population groups in Côte d'Ivoire.

INTRODUCTION: Plasmodium spp. and helminths are co-endemic in many parts of the tropics; hence, co-infection is a common phenomenon. Interactions between Plasmodium and helminth infections may alter the host's immune response and susceptibility and thus impact on morbidity. There is little information on the direction and magnitude of such interactions and results are conflicting. This study aimed at shedding new light on the potential interactions of Plasmodium and helminth co-infections on anemia and splenomegaly in different population groups in Côte d'Ivoire. METHODOLOGY: Parasitologic and clinical data were obtained from four cross-sectional community-based studies and a national school-based survey conducted between 2011 and 2013 in Côte d'Ivoire. Six scenarios of co-infection pairs defined as Plasmodium infection or high parasitemia, combined with one of three common helminth infections (i.e., Schistosoma mansoni, S. haematobium, and hookworm) served for analysis. Adjusted logistic regression models were built for each scenario and interaction measures on additive scale calculated according to Rothman et al., while an interaction term in the model served as multiplicative scale measure. PRINCIPAL FINDINGS: All identified significant interactions were of antagonistic nature but varied in magnitude and species combination. In study participants aged 5-18 years from community-based studies, Plasmodium-hookworm co-infection showed an antagonistic interaction on additive scale on splenomegaly, while Plasmodium-Schistosoma co-infection scenarios showed protective effects on multiplicative scale for anemia and splenomegaly in participants aged 5-16 years from a school-based study. CONCLUSIONS/SIGNIFICANCE: No exacerbation from co-infection with Plasmodium and helminths was observed, neither in participants aged 5-18 years nor in adults from the community-based studies. Future studies should unravel underlying mechanisms of the observed interactions, as this knowledge might help shaping control efforts against these diseases of poverty.

Spatially-explicit risk profiling of Plasmodium falciparum infections at a small scale: a geostatistical modelling approach.

BACKGROUND: There is a renewed political will and financial support to eradicate malaria. Spatially-explicit risk profiling will play an important role in this endeavour. Patterns of Plasmodium falciparum infection prevalence were examined among schoolchildren in a highly malaria-endemic area. METHODS: A questionnaire was administered and finger prick blood samples collected from 3,962 children, aged six to 16 years, attending 55 schools in a rural part of western Côte d'Ivoire. Information was gathered from the questionnaire on children's socioeconomic status and the use of bed nets for the prevention of malaria. Blood samples were processed with standardized, quality-controlled methods for diagnosis of Plasmodium spp. infections. Environmental data were obtained from satellite images and digitized maps. Bayesian variogram models for spatially-explicit risk modelling of P. falciparum infection prevalence were employed, assuming for stationary and non-stationary spatial processes. FINDINGS: The overall prevalence of P. falciparum infection was 64.9%, ranging between 34.0% and 91.9% at the unit of the school. Risk factors for a P. falciparum infection included age, socioeconomic status, not sleeping under a bed net, distance to health care facilities and a number of environmental features (i.e. normalized difference vegetation index, rainfall and distance to rivers). After taking into account spatial correlation only age remained significant. Non-stationary models performed better than stationary models. CONCLUSION: Spatial risk profiling of P. falciparum prevalence data provides a useful tool for targeting malaria control intervention, and hence will play a role in the quest of local elimination and ultimate eradication of the disease.