Prevalence and predictors of adverse events following exposure to long-lasting insecticidal nets used for malaria prevention: a community based cross-sectional study in the Democratic Republic of the Congo.

BACKGROUND: Malaria morbidity and mortality increase in the Democratic Republic of the Congo (DRC) may be the consequence of the low utilization rate of long-lasting insecticidal nets (LLINs) resulting from poor compliance due to adverse events (AEs). This study aimed at determining the prevalence and predictors of AEs following the mass distribution of LLINs in the Kisantu Health Zone (KHZ), a high malaria-endemic region in the DRC. METHODS: A community-based cross-sectional study embedded was conducted within a randomized controlled trial (RCT) after the mass distribution of LLINs in 30 villages located in DRC KHZ. A three-stage sampling method was used without replacement to select 1790 children. Data was collected on adverse events (AEs) using a reporting form and information on demographics, nutritional status, and house characteristics. This was done using a structured questionnaire administered to household heads. Logistic regression models were used to identify predictors of AEs following the mass distribution of LLINs. RESULT: In a total of 1790 children enrolled, 17.8% (95% CI 16.1-19.7) experienced AEs. The most common AEs were respiratory-related (61%). Around 60% of AEs occurred within 24 h of use, and 51% were resolved without treatment. Sleeping under deltamethrin LLINs (Adjusted OR, 95% CI 5.5 [3.8-8.0]) and zinc roofing (Adjusted OR, 95% CI 1.98 [1.1-3.57]) were associated with the risk of reporting an AE following the mass distribution of LLINs. CONCLUSION: Approximately 1 out of 5 children had an AE within 24 h following LLIN use. These adverse events were often respiratory-related. LLINs and roofing types were associated with a higher risk of reporting AEs. However, further research using a robust study design is needed to confirm these findings. Future studies should design and implement interventions aiming to reduce AEs and improve compliance with LLINs.

Malaria among children under 10 years in 4 endemic health areas in Kisantu Health Zone: epidemiology and transmission.

BACKGROUND: The Democratic Republic of the Congo (DRC) is the second most malaria-affected country in the world with 21,608,681 cases reported in 2019. The Kongo Central (KC) Province has a malaria annual incidence of 163 cases/per 1000 inhabitants which are close to the national average of 153.4/1000. However, the malaria prevalence varies both between and within health zones in this province. The main objective of this study was to describe the epidemiology and transmission of malaria among children aged 0 to 10 years in the 4 highest endemic health areas in Kisantu Health Zone (HZ) of KC in DRC. METHODS: A community-based cross-sectional study was conducted from October to November 2017 using multi-stage sampling. A total of 30 villages in 4 health areas in Kisantu HZ were randomly selected. The prevalence of malaria was measured using a thick blood smear (TBS) and known predictors and associated outcomes were assessed. Data are described and association determinants of malaria infection were analysed. RESULTS: A total of 1790 children between 0 and 10 years were included in 30 villages in 4 health areas of Kisantu HZ. The overall prevalence in the study area according to the TBS was 14.8% (95% CI: 13.8-16.6; range: 0-53). The mean sporozoite rate in the study area was 4.3% (95% CI: 2.6-6.6). The determination of kdr-west resistance alleles showed the presence of both L1014S and L1014F with 14.6% heterozygous L1014S/L1014F, 84.4% homozygous 1014F, and 1% homozygous 1014S. The risk factors associated with malaria infection were ground or wooden floors aOR: 15.8 (95% CI: 8.6-29.2), a moderate or severe underweight: 1.5 (1.1-2.3) and to be overweight: 1.9 (95% CI: 1.3-2.7). CONCLUSION: Malaria prevalence differed between villages and health areas within the same health zone. The control strategy activities must be oriented by the variety in the prevalence and transmission of malaria in different areas. The policy against malaria regarding long-lasting insecticidal nets should be based on the evidence of metabolic resistance.

Performance of ultra-sensitive malaria rapid diagnostic test to detect Plasmodium falciparum infection in pregnant women in Kinshasa, the Democratic Republic of the Congo.

BACKGROUND: Low peripheral parasitaemia caused by sequestration of Plasmodium falciparum in the placenta hampers the diagnosis of malaria in pregnant women, leading to microscopy or conventional rapid diagnostic tests (RDTs) false-negative results. Although mainly asymptomatic, maternal malaria remains harmful to pregnant women and their offspring in endemic settings and must be adequately diagnosed. Ultra-sensitive RDTs (uRDTs) are thought to be more sensitive than RDTs, and their diagnostic performance was assessed in the current study in pregnant women living in Kinshasa, a stable malaria transmission area in the Democratic Republic of the Congo. METHODS: To assess and compare the diagnostic performances of both RDTs and uRDTs, 497 peripheral blood samples were tested using microscopy and quantitative polymerase chain reaction (qPCR) as the index and the reference tests, respectively. The agreement between the different diagnostic tests assessed was estimated by Cohen's Kappa test. RESULTS: The median parasite density by qPCR was 292 p/µL of blood [IQR (49.7-1137)]. Using qPCR as the reference diagnostic test, the sensitivities of microscopy, RDT and uRDT were respectively [55.7% (95% CI 47.6-63.6)], [81.7% (95%CI 74.7-87.3)] and [88% (95% CI 81.9-92.6)]. The specificities of the tests were calculated at 98.5% (95% CI 96.6-99.5), 95.2% (95% CI 92.5-97.2) and 94.4% (95% CI 91.4-96.6) for microscopy, RDT and uRDT, respectively. The agreement between qPCR and uRDT was almost perfect (Kappa = 0.82). For parasite density (qPCR) below 100 p/µL, the sensitivity of RDT was 62% (95% CI 47.1-75.3) compared to 68% (95% CI 53.3-80.4) for uRDT. Between 100 and 200 p/µL, the sensitivity of RDT was higher, but still lower compared to uRDT: 89.4% (95% CI 66.8-98.7) for RDT versus 100% (95% CI 82.3-100) for uRDT. In both cases, microscopy was lower, with 20% (95% CI 10-33.7) and 47.3% (95% CI 24.4-71.1) respectively. CONCLUSIONS: uRDT has the potential to improve malaria management in pregnant women as it has been found to be slightly more sensitive than RDT in the detection of malaria in pregnant women but the difference was not significant. Microscopy has a more limited value for the diagnosis of malaria during the pregnancy, because of its lower sensitivity.

Etiological spectrum of persistent fever in the tropics and predictors of ubiquitous infections: a prospective four-country study with pooled analysis.

BACKGROUND: Persistent fever, defined as fever lasting for 7 days or more at first medical evaluation, has been hardly investigated as a separate clinical entity in the tropics. This study aimed at exploring the frequencies and diagnostic predictors of the ubiquitous priority (i.e., severe and treatable) infections causing persistent fever in the tropics. METHODS: In six different health settings across four countries in Africa and Asia (Sudan, Democratic Republic of Congo [DRC], Nepal, and Cambodia), consecutive patients aged 5 years or older with persistent fever were prospectively recruited from January 2013 to October 2014. Participants underwent a reference diagnostic workup targeting a pre-established list of 12 epidemiologically relevant priority infections (i.e., malaria, tuberculosis, HIV, enteric fever, leptospirosis, rickettsiosis, brucellosis, melioidosis, relapsing fever, visceral leishmaniasis, human African trypanosomiasis, amebic liver abscess). The likelihood ratios (LRs) of clinical and basic laboratory features were determined by pooling all cases of each identified ubiquitous infection (i.e., found in all countries). In addition, we assessed the diagnostic accuracy of five antibody-based rapid diagnostic tests (RDTs): Typhidot Rapid IgM, Test-itTM Typhoid IgM Lateral Flow Assay, and SD Bioline Salmonella typhi IgG/IgM for Salmonella Typhi infection, and Test-itTM Leptospira IgM Lateral Flow Assay and SD Bioline Leptospira IgG/IgM for leptospirosis. RESULTS: A total of 1922 patients (median age: 35 years; female: 51%) were enrolled (Sudan, n = 667; DRC, n = 300; Nepal, n = 577; Cambodia, n = 378). Ubiquitous priority infections were diagnosed in 452 (23.5%) participants and included malaria 8.0% (n = 154), tuberculosis 6.7% (n = 129), leptospirosis 4.0% (n = 77), rickettsiosis 2.3% (n = 44), enteric fever 1.8% (n = 34), and new HIV diagnosis 0.7% (n = 14). The other priority infections were limited to one or two countries. The only features with a positive LR ≥ 3 were diarrhea for enteric fever and elevated alanine aminotransferase level for enteric fever and rickettsiosis. Sensitivities ranged from 29 to 67% for the three RDTs targeting S. Typhi and were 9% and 16% for the two RDTs targeting leptospirosis. Specificities ranged from 86 to 99% for S. Typhi detecting RDTs and were 96% and 97% for leptospirosis RDTs. CONCLUSIONS: Leptospirosis, rickettsiosis, and enteric fever accounted each for a substantial proportion of the persistent fever caseload across all tropical areas, in addition to malaria, tuberculosis, and HIV. Very few discriminative features were however identified, and RDTs for leptospirosis and Salmonella Typhi infection performed poorly. Improved field diagnostics are urgently needed for these challenging infections. TRIAL REGISTRATION: NCT01766830 at ClinicalTrials.gov.

High frequency of Taenia solium antigen positivity in patients admitted for neurological disorders in the Rural Hospital of Mosango, Democratic Republic of Congo.

BACKGROUND: The epidemiology of human cysticercosis and neurocysticercosis, caused by the larval stage of the pork tapeworm Taenia solium, is not well known in the Democratic Republic of Congo (DRC). Within a multicenter etiological and diagnostic study conducted by the NIDIAG consortium ("Better Diagnosis for Neglected Infections") and investigating several challenging syndromes, we consecutively evaluated from 2012 to 2015 all patients older than 5 years presenting with neurological disorders (neurology cohort) and with fever > 7 days (persistent fever cohort) at the rural hospital of Mosango, province of Kwilu, DRC. In both cohorts, etiological diagnosis relied on a systematic set of reference laboratory assays and on pre-established clinical case definitions. No neuroimaging was available in the study hospital. In this study, we determined the frequency of T. solium infection in both cohorts and explored in the neurology cohort its association with specific neurological presentations and final etiological diagnoses. METHODS: We conducted a post-hoc descriptive and analytic study on cysticercosis in the neurology and persistent fever cohorts, based on the presence in serum samples of circulating T. solium antigen using the B158/B60 enzyme-linked immunosorbent assay (ELISA) and of cysticercosis IgG using the LDBIO Cysticercosis Western Blot IgG assay. RESULTS: For the neurology cohort, 340 samples (of 351 enrolled patients) were available for analysis (males: 46.8%; mean age: 38.9 years). T. solium antigen positivity was found in 43 participants (12.6%; 95% confidence interval [CI] 9.3-16.7%), including 9 of 60 (15%) patients with epilepsy. Among the 148 samples available from the persistent fever cohort (males: 39.9%; mean age: 19.9 years), 7 were positive in the T. solium antigen ELISA (4.7%; 95% CI 1.9-9.5%; P = 0.009 when compared to the neurology cohort). No significant association was found within the neurology cohort between positivity and clinical presentation or final diagnoses. Of note, the IgG antibody-detecting assay was found positive in only four (1.3%) of the participants of the neurology cohort and in none of the persistent fever cohort. CONCLUSIONS: T. solium antigen positivity was found in at least 10% of patients admitted with neurological disorders in the Kwilu province, DRC, with no specific pattern of presentation. Further neuroimaging studies should be used to confirm whether neurocysticercosis is prevalent in this region.

Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-Saharan Africa.

BACKGROUND: In 2012, the World Health Organization recommended blocking the transmission of Plasmodium falciparum with single low-dose primaquine (SLDPQ, target dose 0.25 mg base/kg body weight), without testing for glucose-6-phosphate dehydrogenase deficiency (G6PDd), when treating patients with uncomplicated falciparum malaria. We sought to develop an age-based SLDPQ regimen that would be suitable for sub-Saharan Africa. METHODS: Using data on the anti-infectivity efficacy and tolerability of primaquine (PQ), the epidemiology of anaemia, and the risks of PQ-induced acute haemolytic anaemia (AHA) and clinically significant anaemia (CSA), we prospectively defined therapeutic-dose ranges of 0.15-0.4 mg PQ base/kg for children aged 1-5 years and 0.15-0.5 mg PQ base/kg for individuals aged ≥6 years (therapeutic indices 2.7 and 3.3, respectively). We chose 1.25 mg PQ base for infants aged 6-11 months because they have the highest rate of baseline anaemia and the highest risks of AHA and CSA. We modelled an anthropometric database of 661,979 African individuals aged ≥6 months (549,127 healthy individuals, 28,466 malaria patients and 84,386 individuals with other infections/illnesses) by the Box-Cox transformation power exponential and tested PQ doses of 1-15 mg base, selecting dosing groups based on calculated mg/kg PQ doses. RESULTS: From the Box-Cox transformation power exponential model, five age categories were selected: (i) 6-11 months (n = 39,886, 6.03%), (ii) 1-5 years (n = 261,036, 45.46%), (iii) 6-9 years (n = 20,770, 3.14%), (iv) 10-14 years (n = 12,155, 1.84%) and (v) ≥15 years (n = 328,132, 49.57%) to receive 1.25, 2.5, 5, 7.5 and 15 mg PQ base for corresponding median (1st and 99th centiles) mg/kg PQ base of: (i) 0.16 (0.12-0.25), (ii) 0.21 (0.13-0.37), (iii) 0.25 (0.16-0.38), (iv) 0.26 (0.15-0.38) and (v) 0.27 (0.17-0.40). The proportions of individuals predicted to receive optimal therapeutic PQ doses were: 73.2 (29,180/39,886), 93.7 (244,537/261,036), 99.6 (20,690/20,770), 99.4 (12,086/12,155) and 99.8% (327,620/328,132), respectively. CONCLUSIONS: We plan to test the safety of this age-based dosing regimen in a large randomised placebo-controlled trial (ISRCTN11594437) of uncomplicated falciparum malaria in G6PDd African children aged 0.5 - 11 years. If the regimen is safe and demonstrates adequate pharmacokinetics, it should be used to support malaria elimination.

Forecasting Human African Trypanosomiasis Prevalences from Population Screening Data Using Continuous Time Models.

To eliminate and eradicate gambiense human African trypanosomiasis (HAT), maximizing the effectiveness of active case finding is of key importance. The progression of the epidemic is largely influenced by the planning of these operations. This paper introduces and analyzes five models for predicting HAT prevalence in a given village based on past observed prevalence levels and past screening activities in that village. Based on the quality of prevalence level predictions in 143 villages in Kwamouth (DRC), and based on the theoretical foundation underlying the models, we consider variants of the Logistic Model-a model inspired by the SIS epidemic model-to be most suitable for predicting HAT prevalence levels. Furthermore, we demonstrate the applicability of this model to predict the effects of planning policies for screening operations. Our analysis yields an analytical expression for the screening frequency required to reach eradication (zero prevalence) and a simple approach for determining the frequency required to reach elimination within a given time frame (one case per 10000). Furthermore, the model predictions suggest that annual screening is only expected to lead to eradication if at least half of the cases are detected during the screening rounds. This paper extends knowledge on control strategies for HAT and serves as a basis for further modeling and optimization studies.

The perception of parents and teachers about intermittent preventive treatment for malaria in school children in a semi-rural area of Kinshasa, in the Democratic Republic of Congo.

BACKGROUND: Intermittent preventive treatment (IPT) is likely to be the most promising therapeutic strategy to prevent malaria and its related adverse outcomes in schoolchildren. However, its successful implementation will depend on acceptability to key stakeholders such as parents and teachers. METHODS: A qualitative research was conducted, following a clinical trial assessing the effectiveness of IPT in schoolchildren (IPTsc), to understand the perceptions and experiences of parents and teachers with IPTsc, in two schools of Mokali, in Kinshasa, Democratic Republic of the Congo. Eighty parents participated in 8 focus group discussions and 6 school staff were involved in 6 semi-structured interviews. RESULTS: Parents experiences with IPTsc divided them into two groups (owning positive experiences and owning negative experiences with IPTsc). Three major themes emerged as key factors associated with reluctance of parents to IPT use in schoolchildren. These included wrong malaria-related knowledge, bad experience with IPTsc administered during the trial and misunderstanding of IPTsc. The school staff were generally willing to be trained to give medicine to schoolchildren within the scope of IPT. However, most parents were more comfortable with the use of health workers than teachers for drug administration. More importantly, all parents accepting IPT suggested to diagnose malaria infection before any administration of IPT, which is not in line with IPT principal. CONCLUSION: These results suggest that more efforts are needed to improve overall malaria-related knowledge in the community, specifically chemo-prevention strategies and the safety of the drugs used, to ensure the success of health interventions.

The Challenges of Research Informed Consent in Socio-Economically Vulnerable Populations: A Viewpoint From the Democratic Republic of Congo.

In medical research, the ethical principle of respect for persons is operationalized into the process of informed consent. The consent tools should be contextualized and adapted to the different socio-cultural environment, especially when research crosses the traditional boundaries and reaches poor communities. We look at the challenges experienced in the malaria Quinact trial, conducted in the Democratic Republic of Congo, and describe some lessons learned, related to the definition of acceptable representative, the role of independent witness and the impact of socio-economic vulnerability. To ensure children's protection, consent is required by the parents or, in their absence, by a legally mandated representative. In our setting, children's responsibility is often entrusted permanently or temporarily to relatives or friends without a tribunal mandate. Hence, a notion of 'culturally acceptable representative' under supervision of the local Ethics Committee may be more suitable. To ensure protection of illiterate subjects, an independent witness is required to confirm that the consent was freely given. However, in low-literacy contexts, potential witnesses often don't have any previous relationship with patient and there may be power-unbalance in their relationship, rather than genuine dialogue. In poor communities, trial participation may be seen as an opportunity to secure access to healthcare. Poverty may also lead to 'competition' to access the research-related benefits, with a risk of disturbance at societal or household level. Adjusting consent procedures to sociocultural and socioeconomic realities is essential for fulfilling the underlying ethical principles. This requires a collaborative dialogue between researchers, regulators and ethics committees.

Participation in medical research as a resource-seeking strategy in socio-economically vulnerable communities: call for research and action.

The freedom to consent to participate in medical research is a complex subject, particularly in socio-economically vulnerable communities, where numerous factors may limit the efficacy of the informed consent process. Informal consultation among members of the Switching the Poles Clinical Research Network coming from various sub-Saharan African countries, that is Burkina Faso, The Gambia, Rwanda, Ethiopia, the Democratic Republic of Congo (DRC) and Benin, seems to support the hypothesis that in socio-economical vulnerable communities with inadequate access to health care, the decision to participate in research is often taken irrespectively of the contents of the informed consent interview, and it is largely driven by the opportunity to access free or better quality care and other indirect benefits. Populations' vulnerability due to poverty and/or social exclusion should obviously not lead to exclusion from medical research, which is most often crucially needed to address their health problems. Nonetheless, to reduce the possibility of exploitation, there is the need to further investigate the complex links between socio-economical vulnerability, access to health care and individual freedom to decide on participation in medical research. This needs bringing together clinical researchers, social scientists and bioethicists in transdisciplinary collaborative research efforts that require the collective input from researchers, research sponsors and funders.

Efficacy and safety of intermittent preventive treatment for malaria in schoolchildren: a systematic review.

BACKGROUND: Intermittent preventive treatment (IPT) is a proven malaria control strategy in infants and pregnancy. School-aged children represent 26 % of the African population, and an increasing percentage of them are scholarized. Malaria is causing 50 % of deaths in this age group and malaria control efforts may shift the malaria burden to older age groups. Schools have been suggested as a platform for health interventions delivery (deworming, iron-folic acid, nutrients supplementation, (boost-)immunization) and as a possible delivery system for IPT in schoolchildren (IPTsc). However, the current evidence on the efficacy and safety of IPTsc is limited and the optimal therapeutic regimen remains controversial. METHODS: A systematic search for studies reporting efficacy and safety of IPT in schoolchildren was conducted using PubMed, Web of Science, Clinicaltrials and WHO/ICTRP database, and abstracts from congresses with the following key words: intermittent, preventive treatment AND malaria OR Plasmodium falciparum AND schoolchildren NOT infant NOT pregnancy. RESULTS: Five studies were identified. Most IPTsc regimes demonstrated substantial protection against malaria parasitaemia, with dihydroartemisinin-piperaquine (DP) given monthly having the highest protective effect (PE) (94 %; 95 % CI 93-96). Contrarily, SP did not provide any PE against parasitaemia. However, no IPT regimen provided a PE above 50 % in regard to anaemia, and highest protection was provided by SP+ amodiaquine (AQ) given four-monthly (50 %; 95 % CI 41-53). The best protection against clinical malaria was observed in children monthly treated with DP (97 %; 95 % CI 87-98). However, there was no protection when the drug was given three-monthly. No severe adverse events were associated with the drugs used for IPTsc. CONCLUSION: IPTsc may reduce the malaria-related burden in schoolchildren. However, more studies assessing efficacy of IPT in particular against malaria-related anaemia and clinical malaria in schoolchildren must be conducted.

The relationship between Plasmodium infection, anaemia and nutritional status in asymptomatic children aged under five years living in stable transmission zones in Kinshasa, Democratic Republic of Congo.

BACKGROUND: Malaria is preventable and treatable when recommended interventions are properly implemented. Thus, diagnosis and treatment focus on symptomatic individuals while asymptomatic Plasmodium infection (PI) plays a role in the sustainability of the transmission and may also have an impact on the morbidity of the disease in terms of anaemia, nutritional status and even cognitive development of children. The objective of this study was to assess PI prevalence and its relationship with known morbidity factors in a vulnerable but asymptomatic stratum of the population. METHODS: A simple random sample, household survey in asymptomatic children under the age of five was conducted from April to September 2012 in two health areas of the health zone of Mont Ngafula 1, Kinshasa, Democratic Republic of Congo. RESULTS: The PI prevalence were 30.9% (95% CI: 26.5-35.9) and 14.3% (95% CI: 10.5-18.1) in Cité Pumbu and Kindele health areas, respectively, (OR: 2.7; p <0.001). All were Plasmodium falciparum infected and 4% were co-infected with Plasmodium malariae. In Cité Pumbu and Kindele, the prevalence of anaemia (haemoglobin <11 g/dL) was 61.6% (95% CI: 56.6-66.5) and 39.3% (95% CI: 34.0-44.6), respectively, (OR: 2.5; p <0.001). The health area of Cité Pumbu had 32% (95% CI: 27.5-37.0) of chronic malnutrition (HAZ score ≤ -2SD) compared to 5.1% (95% CI: 2.8-7.6) in Kindele. PI was predictor factor for anaemia (aOR: 3.5, p =0.01) and within infected children, there was an inverse relationship between parasite density and haemoglobin level (ß = -5*10(-5), p <0.001). Age older than 12 months (aOR: 3.8, p = 0.01), presence of anaemia (aOR: 3.4, p =0.001), chronic malnutrition (aOR: 1.8, p = 0.01), having a single parent/guardian (aOR: 1.6, p =0.04), and the non-use of insecticide-treated nets (aOR: 1.7, p = 0.04) were all predictors for PI in the overall population. CONCLUSION: PI in asymptomatic children was correlated with anaemia and chronic malnutrition and was thus a harmful condition in the study population. Malaria control initiatives should not only focus on treatment of symptomatic infections but also take into consideration asymptomatic but infected children.

SMS photograph-based external quality assessment of reading and interpretation of malaria rapid diagnostic tests in the Democratic Republic of the Congo.

BACKGROUND: The present External Quality Assessment (EQA) assessed reading and interpretation of malaria rapid diagnostic tests (RDTs) in the Democratic Republic of the Congo (DRC). METHODS: The EQA consisted of (i) 10 high-resolution printed photographs displaying cassettes with real-life results and multiple choice questions (MCQ) addressing individual health workers (HW), and (ii) a questionnaire on RDT use addressing the laboratory of health facilities (HF). Answers were transmitted through short message services (SMS). RESULTS: The EQA comprised 2344 HW and 1028 HF covering 10/11 provinces in DRC. Overall, median HW score (sum of correct answers on 10 MCQ photographs for each HW) was 9.0 (interquartile range 7.5 - 10); MCQ scores (the % of correct answers for a particular photograph) ranged from 54.8% to 91.6%. Most common errors were (i) reading or interpreting faint or weak line intensities as negative (3.3%, 7.2%, 24.3% and 29.1% for 4 MCQ photographs), (ii) failure to distinguish the correct Plasmodium species (3.4% to 7.0%), (iii) missing invalid test results (8.4% and 23.6%) and (iv) missing negative test results (10.0% and 12.4%). HW who were trained less than 12 months ago had best MCQ scores for 7/10 photographs as well as a significantly higher proportion of 10/10 scores, but absolute differences in MCQ scores were small. HW who had participated in a previous EQA performed significantly better for 4/10 photographs compared to those who had not. Except for two photographs, MCQ scores were comparable for all levels of the HF hierarchy and non-laboratory staff (HW from health posts) had similar performance as to laboratory staff. Main findings of the questionnaire were (i) use of other RDT products than recommended by the national malaria control programme (nearly 20% of participating HF), (ii) lack of training for a third (33.6%) of HF, (iii) high proportions (two-thirds, 66.5%) of HF reporting stock-outs. CONCLUSIONS: The present EQA revealed common errors in RDT reading and interpretation by HW in DRC. Performances of non-laboratory and laboratory staff were similar and dedicated training was shown to improve HW competence although to a moderate extent. Problems in supply, distribution and training of RDTs were detected.

Malaria policies versus practices, a reality check from Kinshasa, the capital of the Democratic Republic of Congo.

BACKGROUND: Artemisinin-based combination therapy (ACT) following a confirmed parasitological diagnosis is recommended by the World Health Organization (WHO) and the Congolese National Malaria Control Program (NMCP). However, commitment and competence of all stakeholders (patients, medical professionals, governments and funders) is required to achieve effective case management and secure the "useful therapeutic life" of the recommended drugs. The health seeking behaviour of patients and health care professionals' practices for malaria management were assessed. METHODS: This was an observational study embedded in a two-stage cluster randomized survey conducted in one health centre (HC) in each of the 12 selected health zones in Kinshasa city. All patients with clinical malaria diagnosis were eligible. Their health seeking behaviour was recorded on a specific questionnaire, as well as the health care practitioners' practices. The last were not aware that their practices would be assessed. RESULTS: Six hundred and twenty four patients were assessed, of whom 136 (21.8%) were under five years. Three hundred and thirty five (55%) had taken medication prior to the current consultation (self -medication with any product or visiting another HC) of whom 47(14%) took an antimalarial drug, and 56 (9%) were treated presumptively. Among those, 53.6% received monotherapy either with quinine, artesunate, phytomedicines, sulfadoxine-pyrimethamine or amodiaquine. On the other side, when clinicians were informed about laboratory results, monotherapy was prescribed in 39.9% of the confirmed malaria cases. Only 285 patients (45.7%) were managed in line with WHO and NMCP guidelines, of whom 120 (19.2%) were prescribed an ACT after positive blood smear and 165 (26.4%) received no antimalarial after a negative result. CONCLUSION: This study shows the discrepancy between malaria policies and the reality on the field in Kinshasa, regarding patients' health seeking behaviour and health professionals' practices. Consequently, the poor compliance to the policies may contribute to the genesis and spread of antimalarial drug resistance and also have a negative impact on the burden of the disease.

Performance of HRP2-based rapid test in children attending the health centre compared to asymptomatic children in the community.

BACKGROUND: The Democratic Republic of the Congo (DRC) is one of the five countries carrying half of global malaria burden with children 0-5 years old being most at risk. Rapid diagnostic tests (RDTs) are currently routinely used for the detection of Plasmodium infection in health centres and may be a useful tool for population-based survey. METHODS: This study assessed, in a stable transmission zone of Kinshasa, whether a HRP2-based RDT matches the selection criteria of the National Malaria Control Programme (NMCP), DRC and assessed the most relevant fever threshold in this context. RESULTS: RDTs and microscopy were concordant in 84.3% and 83.4% children in the health centre and at the community level, respectively. The sensitivity was high (>95%), but the specificity was too low and lower in the community (66.9%; 95%CI: 58.5-75.2) compared to the HC (79.4%; 95%CI: 75.7-83.2). The estimated parasitic threshold of 5,414 parasites/µl was with a sensitivity of 63.3% and a specificity of 71.8% not very discriminative, and thus not a threshold. CONCLUSION: HRP-based RDT gives a satisfactory proxy to estimate and monitor malaria endemicity, but the low specificity, far below the selection criteria of the NMCP, DRC is problematic for use in a clinical setting.

Asymptomatic Plasmodium falciparum infection is associated with anaemia in pregnancy and can be more cost-effectively detected by rapid diagnostic test than by microscopy in Kinshasa, Democratic Republic of the Congo.

BACKGROUND: In areas of high malaria transmission, Plasmodium falciparum infection during pregnancy is characterized by malaria-related anaemia, placental malaria and does not always result in clinical symptoms. This situation is associated with poor pregnancy outcomes. The aim of this study was to determine the extent of asymptomatic P. falciparum infection, its relation with anaemia as well as the most cost-effective technique for its diagnosis in healthy pregnant women living in Kinshasa, Democratic Republic of the Congo. METHODS: In a cross-sectional study design, information on socio-demographic characteristics and cost data were collected in healthy pregnant women attending antenatal care consultations. Plasmodium falciparum infection was diagnosed using rapid diagnostic test (RDT), microscopy and polymerase chain reaction (PCR). Haemoglobin concentration was also determined. RESULTS: In total, 332 pregnant women were enrolled. RDT and microscopy data were available for all the blood samples and 166 samples were analysed by PCR. The prevalence of asymptomatic P. falciparum infection using microscopy, RDTs and PCR, were respectively 21.6%, 27.4% and 29.5%. Taking PCR as a reference, RDTs had a sensitivity of 81.6% and a specificity of 94.9% to diagnose asymptomatic P. falciparum infection. The corresponding values for microscopy were 67.3% and 97.4%. The prevalence of anaemia was 61.1% and asymptomatic malaria increased five times the odds (p < 0.001) of having anaemia. RDTs were more cost-effective compared to microscopy. Incremental cost-effectiveness ratio was US$ 63.47 per microscopy adequately diagnosed case. CONCLUSION: These alarming results emphasize the need to actively diagnose and treat asymptomatic malaria infection during all antenatal care visits. Moreover, in DRC, malaria and anaemia control efforts should be strengthened by promoting the use of insecticide-treated nets, intermittent preventive treatment with sulphadoxine-pyrimethamine and iron and folic acid supplements.

Persistent digestive disorders in the tropics: causative infectious pathogens and reference diagnostic tests.

BACKGROUND: Persistent digestive disorders account for considerable disease burden in the tropics. Despite advances in understanding acute gastrointestinal infections, important issues concerning epidemiology, diagnosis, treatment and control of most persistent digestive symptomatologies remain to be elucidated. Helminths and intestinal protozoa are considered to play major roles, but the full extent of the aetiologic spectrum is still unclear. We provide an overview of pathogens causing digestive disorders in the tropics and evaluate available reference tests. METHODS: We searched the literature to identify pathogens that might give rise to persistent diarrhoea, chronic abdominal pain and/or blood in the stool. We reviewed existing laboratory diagnostic methods for each pathogen and stratified them by (i) microscopy; (ii) culture techniques; (iii) immunological tests; and (iv) molecular methods. Pathogen-specific reference tests providing highest diagnostic accuracy are described in greater detail. RESULTS: Over 30 pathogens may cause persistent digestive disorders. Bacteria, viruses and parasites are important aetiologic agents of acute and long-lasting symptomatologies. An integrated approach, consisting of stool culture, microscopy and/or specific immunological techniques for toxin, antigen and antibody detection, is required for accurate diagnosis of bacteria and parasites. Molecular techniques are essential for sensitive diagnosis of many viruses, bacteria and intestinal protozoa, and are increasingly utilised as adjuncts for helminth identification. CONCLUSIONS: Diagnosis of the broad spectrum of intestinal pathogens is often cumbersome. There is a need for rapid diagnostic tests that are simple and affordable for resource-constrained settings, so that the management of patients suffering from persistent digestive disorders can be improved.

Schistosoma Infection Burden and Risk Factors among School-Aged Children in a Rural Area of the Democratic Republic of the Congo.

Despite continuous efforts to control schistosomiasis (SCH) in the Democratic Republic of the Congo (DRC), it still poses a significant challenge. In order to enhance control measures, additional research is necessary. This study documents the burden of SCH infection and its predictors in a rural area of the DRC. We conducted a household cross-sectional study from June to August 2021 among 480 school-aged children (SAC) aged 5-15 years living in a rural area of Kisangi, in the southwest DRC. We collected and examined stool, urine, and blood samples of each child. Additionally, we obtained data on anthropometry, socio-demographics, household information, and individual water contact behaviors. The overall prevalence of SCH infection was 55.8% (95% CI: 51.4-60.3), with prevalences of 41% (95% CI: 36.6-45.5), 36.3% (95% CI: 31.9-40.6), and 38.4% (95% CI: 32.6-44.3) for S. haematobium and S. mansoni infections and both infections, respectively. Among those with SCH infection, most had a light (67.5%) or heavy (51.7%) infection intensity. The geometric mean egg count was 16.6 EP 10 mL (95% CI: 12.9-21.3) for S. haematobium and 390.2 EPG (95% CI: 300.2-507.3) for S. mansoni. However, age (10 years and above (aOR: 2.1; 95% CI: 1.5-3.1; p < 0.001)) was an independent risk factor for SCH infection. The overall prevalence of malaria infection was 16.9% (95% CI: 13.5-20.2), that of stunting was 28.7% (95% CI: 24.7-32.8), that of underweight was 17.1% (95% CI: 12.8-21.4), and that of thinness was 7.1% (95% CI: 4.8-9.4). Anemia was prevalent at 49.4% (95% CI: 44.9-5), and the median Hb level of all participants was 11.6 g/dL (IQR: 10.5-12.6 g/dL). Anemia was strongly associated with SCH infection (aOR: 3.4; 95% CI: 2.3-5.1; p < 0.001) yet there was no association with the risk for malaria infection (aOR: 1.0; 95% CI: 0.6-1.8; p = 0.563). In addition, the risk of anemia increased with heavy infection intensities (p < 0.026 and p < 0.013 for S. haematobium and S. mansoni, respectively). However, stunting had a protective factor for anemia (aOR: 0.3; 95% CI: 0.2-0.4; p < 0.001). To conclude, SCH infection was widespread among the SAC and strongly linked to anemia. These results provide evidence of the hyperendemicity of infection in the study area, which requires preventative measures such as chemotherapy to reduce the schistosomiasis-associated morbidity, and micronutrient supplements to avoid anemia.

Phylogeographic analysis of dengue virus serotype 1 and cosmopolitan serotype 2 in Africa.

OBJECTIVES: The origin and spread of dengue virus (DENV) circulating in Africa remain poorly characterized, with African sequences representing <1% of global sequence data. METHODS: Whole genome sequencing was performed on serum samples (n = 29) from an undifferentiated fever study in 2016 in the Democratic Republic of Congo (DRC), and from febrile travelers returning from Africa. The evolutionary history of the newly acquired African DENV-1 (n = 1) and cosmopolitan genotype DENV-2 (n = 18) genomes was reconstructed using a phylogeographic, time-scaled Bayesian analysis on a curated DENV panel including all known African sequences. RESULTS: A minimum of 10 and eight introductions could be identified into Africa for DENV-1 and cosmopolitan DENV-2, respectively, almost all originating from Asia. Three introductions were previously unknown. The currently circulating virus comprises mainly the recently introduced clades and one long-established African clade. Robust geographical clustering suggests limited spread of DENV after each introduction. Our data identified the DRC as the source of the 2018 Angolan DENV-2 epidemic, and similarly, the 2013 Angolan DENV-1 outbreak as the origin of our DRC study. CONCLUSION: Active genomic surveillance of DENV in Africa at the portals of entry might help early outbreak response and limit sero- and genotype spread and human disease burden.

Accuracy of malaria rapid diagnosis test Optimal-IT(®) in Kinshasa, the Democratic Republic of Congo.

BACKGROUND: Despite some problems related to accuracy and applicability, malaria rapid diagnostic tests (RDTs), are currently considered the best option in areas with limited laboratory services for improving case management and reducing over-treatment. However, their performance must be established taking into the account the particularities of each endemic area. In the Democratic Republic of Congo, the validity of Optimal-IT(®) and Paracheck-Pf(®), respectively based on the detection of lactate dehydrogenase and histidine-rich protein-2, was assessed at primary health care level (PHC). METHODS: This was a two-stage cluster randomized survey, conducted in one health centre in 12 health zones in Kinshasa city. All patients with malaria presumptive diagnosis were eligible. Gold standard was microscopy performed by experts from the parasitology unit, Kinshasa University. RESULTS: 624 patients were enrolled. 53.4% (95% CI: 49.4-57.3) owed a bed net, obtained in 74.5% of cases (95% CI: 69.4-79.1) through community-based distribution by the National Malaria Control Programme. Microscopy expert reading confirmed 123 malaria cases (19.7%; 95% CI: 16.7-23.1). Overall sensitivity were 79.7% (95% CI: 72.4-86.8), 87.8% (95% CI: 81.9-93.6) and 86.2% (95% CI: 79.9-92.3), respectively, for Optimal-IT(®), Paracheck-Pf(®) and microscopy performed at PHC. Specificity was 97.0% (95% CI: 95.5-98.5), 91.6% (95% CI: 89.1-94.0) and 49.1% (95% CI: 44.7-53.4). The proportion of confirmed cases seemed similar in under-fives compared to others. Any treatment prior to the current visit was a predictor for malaria (AOR: 2.3; 95% CI: 1.5-3.5), but not malaria treatment (AOR: 0.87; 95% CI: 0.4-1.8). Bed net ownership tended to protect against malaria (AOR: 0.67; 95% CI: 0.45-0.99). CONCLUSION: Although microscopy is considered as the "gold standard" for malaria diagnosis at point of care level, this study showed that its accuracy may not always be satisfactory when performed in health centres.