Evaluation of the usefulness of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine in a context with increased resistance of Plasmodium falciparum in Kingasani Hospital, Kinshasa in the Democratic Republic of Congo.

BACKGROUND: Increasing resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine (SP) threatens its usefulness for intermittent preventive treatment in pregnancy (IPTp-SP). The prophylactic effects of IPTp-SP on maternal malaria and adverse pregnancy outcomes were evaluated in Kingasani Hospital, Kinshasa in the Democratic Republic of Congo (DRC). METHODS: Laboring women (n = 844) and respective newborns were investigated. Blood samples collected from women were tested for malaria using rapid diagnostic test (RDT), blood smears examination, and real-time PCR. The hemoglobin level was measured by HemoCue© analyzer. A PCR-RFLP method was applied for detecting N51I, C59R, and S108N mutations on dhfr along with A437G and K540E mutations on dhps in P. falciparum positive samples. Logistic regression models assessed relationships between IPTp-SP uptake and pregnancy outcomes. RESULTS: P. falciparum malaria was detected at delivery in 10.8% of women and was statistically associated with fever during the pregnancy (OR = 2.9 [1.5; 6.3]; p = 0.004) and maternal anemia (OR = 3.9 [2.4; 6.3]; p < 0.001). One out of five parasites was a quintuple mutant encoding dhfr mutations 51I, 59R, and 108 N along with dhps mutations 437G and 540E. The molecular profile of parasites (i.e., 32.6% of parasites carrying dhps K540E) was suitable with continued use of SP for IPTp. IPTp-SP uptake was not associated with reduced maternal malaria, fever reported in pregnancy, or fetal deaths (p > 0.05). Conversely, three or more doses of SP were associated with reduced maternal anemia at delivery (OR = 0.4 [0.2; 0.9]; p = 0.024), shortened gestation (OR = 0.4 [0.2; 0.8]; p = 0.009), and low-birth weights (OR = 0.2 [0.1; 0.5]; p < 0.001). CONCLUSION: IPTp-SP was not associated with reduced maternal malaria in our study, but evidence was found of a prophylactic effect against adverse pregnancy outcomes. To counteract further loss of clinical effects of IPTp-SP in the study population, alternative strategies able to improve its anti-malarial efficacy such as combination of SP with partner molecules should be implemented.

Care-seeking behaviour and socio-economic burden associated with uncomplicated malaria in the Democratic Republic of Congo.

BACKGROUND: This study aimed to estimate the socio-economic costs of uncomplicated malaria and to explore health care-seeking behaviours that are likely to influence these costs in the Democratic Republic of Congo (DRC), a country ranked worldwide as the second most affected by malaria. METHODS: In 2017, a cross-sectional survey included patients with uncomplicated malaria in 64 healthcare facilities from 10 sentinel sites of the National Malaria Control Programme (NMCP) in the DRC. A standard questionnaire was used to assess health care-seeking behaviours of patients. Health-related quality of life (HRQL) and disutility weights (DW) of illness were evaluated by using the EuroQol Group's descriptive system (EQ-5D-3L) and its visual analogue scale (EQ VAS). Malaria costs were estimated from a patient's perspective. Probabilistic sensitivity analyses (PSA) evaluated the uncertainty around the cost estimates. Generalized regression models were fitted to assess the effect of potential predictive factors on the time lost and the DW during illness. RESULTS: In total, 1080 patients (age: 13.1 ± 14 years; M/F ratio: 1.1) were included. The average total costs amounted to US$ 36.3 [95% CI 35.5-37.2] per malaria episode, including US$ 16.7 [95% CI 16.3-17.1] as direct costs and US$ 19.6 [95% CI 18.9-20.3] indirect costs. During care seeking, economically active patients and their relatives lost respectively 3.3 ± 1.8 and 3.4 ± 2.1 working days. This time loss occurred mostly at the pre-hospital stage and was the parameter associated the most with the uncertainty around malaria cost estimates. Patients self-rated an average 0.36 ± 0.2 DW and an average 0.62 ± 0.3 EQ-5D index score per episode. A lack of health insurance coverage (896 out of 1080; 82.9%) incurred substantially higher costs, lower quality of life, and heavier DW while leading to longer time lost during illness. Residing in rural areas incurred a disproportionally higher socioeconomic burden of uncomplicated malaria with longer time lost due to illness and limited access to health insurance mechanisms. CONCLUSION: Uncomplicated malaria is associated with high economic costs of care in the DRC. Efforts to reduce the cost-of-illness should target time lost at the pre-hospital stage and social disparities in the population, while reinforcing measures for malaria control in the country.

The lack of K13-propeller mutations associated with artemisinin resistance in Plasmodium falciparum in Democratic Republic of Congo (DRC).

Artemisinin-based combination therapies (ACTs) have been recommended by the World Health Organization (WHO) as first-line treatment of uncomplicated Plasmodium falciparum (P. falciparum) malaria since 2005 in Democratic Republic of Congo (DRC) and a regular surveillance of the ACT efficacy is required to ensure the treatment effectiveness. Mutations in the propeller domain of the pfk13 gene were identified as molecular markers of artemisinin resistance (ART-R). This study investigated the pfk13-propeller gene polymorphism in clinical isolates of P. falciparum collected in the DRC. In 2017, ten geographical sites across DRC were selected for a cross-sectional study that was conducted first in Kinshasa from January to March, then in the nine other sites from September to December. Dried blood samples were collected from patients attending health centers for fever where diagnosis of Malaria was first made by rapid diagnostic test (RDT) available on site (SD Bioline malaria Ag Pf or CareStart Malaria Pf) or by thick blood smear and then confirmed by a P. falciparum real-time PCR assay. A pfk13-propeller segment containing a fragment that codes for amino acids at positions 427-595 was amplified by conventional PCR before sequencing. In total, 1070 patients were enrolled in the study. Real-time PCR performed confirmed the initial diagnosis of P. falciparum infection in 806 samples (75.3%; 95% CI: 72.6%- 77.9%). Of the 717 successfully sequenced P. falciparum isolates, 710 (99.0%; 95% CI: 97.9% - 99.6) were wild-type genotypes and 7 (1.0%; 95% CI: 0.4% - 2.1%) carried non-synonymous (NS) mutations in pfk13-propeller including 2 mutations (A578S and V534A) previously detected and 2 other (M472I and A569T) not yet detected in the DRC. Mutations associated with ART-R in Southeast Asia were not observed in DRC. However, the presence of other mutations in pfk13-propeller gene calls for further investigations to assess their implication in drug resistance.