Drug use in the management of uncomplicated malaria in public health facilities in the Democratic Republic of the Congo.

BACKGROUND: Malaria the first causes of death from parasitic infection worldwide. Interventions to reduce the burden of malaria have produced a tremendous drop in malaria morbidity and mortality. However, progress is slower in DRC, which shares with Nigeria 39% of deaths related to malaria globally. Inappropriate use of drugs may be one of the factors of this below-average performance. The aim of this study was to describe the use of drugs in the management of uncomplicated malaria in public health facilities in DRC. METHODS: A drug use study was carried out in DRC from January to March 2014. In each of the former 11 provinces of DRC, one Rural Health Centre, one Urban Health Centre and one General Hospital were selected. In each of them, 100 patient's files containing prescription of anti-malarials from January to December 2013 were randomly selected. Among them, all of the files with diagnosis of uncomplicated malaria were included in this study. Prescribed anti-malarials, co-prescribed drugs and their indications were collected. Descriptive analyses were performed. RESULTS: A total of 2300 files out of 3300 (69.7%) concerned uncomplicated malaria and were included in analysis. Malaria treatment was initiated after a positive RDT or microscopy in 51.5% of cases, upon suspicion without requesting biological confirmation in 37% and despite negative results in 11%. Twenty-nine (29) different treatment regimens were used. The drugs recommended by the National Malaria Control Programme were used in 54.3% of cases (artesunate-amodiaquine 37.4% or artemether-lumefantrine 16.9%). The second most used anti-malarial was quinine (32.4%). Apart from anti-malarials, an average of 3.1 drugs per patient were prescribed, among which antibiotics (67.9%), analgesics and non-steroidal anti-inflammatory (NSAIDs) (all abbreviations to be explicated on first use) (70.6%), vitamins (29.1%), anaemia drugs, including blood transfusion (9.1%) and corticosteroids (5.7%), In 51.4% of cases there was no indication for the concomitant medication. CONCLUSION: Management of uncomplicated malaria in DRC is characterized by a low adherence to treatment policy, numerous treatment regimens, and abundant concomitant medication potentially harmful to the patient. This may contribute to the low performance of DRC in malaria control. Determinant of this irrational use of drugs need to be assessed in order to formulate and implement efficient corrective measures.

Use of Medicinal Plants in Africa: A Case Study From the Democratic Republic of Congo (DRC).

Although medicinal plants are beneficial, they also can be important risk factors for the development of acute and chronic kidney injury, as well toxicity of other solid organs. There are a lack of reports of adverse kidney events and drug interactions resulting from medicinal plants owing to a lack of professional surveillance and specific data on kidney toxicity, especially in low-resource settings. Within the context of increased medicinal plant use and lack of effective regulatory control, safety is a key priority issue. We review the benefits and adverse effects of medicinal plants with particular reference to nephrotoxicity encountered in the Democratic Republic of Congo in sub-Saharan Africa.

Determinants of Patients' Adherence to Malaria Treatment in the Democratic Republic of the Congo.

(1) Background: Malaria heavily affects the Democratic Republic of the Congo (DRC) despite the use of effective drugs. Poor adherence to malaria treatment may contribute to this problem. (2) Methods: In one rural and one urban health area in each of the 11 former provinces of the DRC, all households with a case of malaria in the 15 days preceding the survey were selected and the patients or caregivers were interviewed. Adherence to malaria treatment was assessed by self-declaration about its completion. Logistic regression was used to assess predictors. (3) Results: 1732 households participated. Quinine was the most used drug; adherence to artesunate-amodiaquine was the lowest and the main reason for treatment discontinuation was adverse reactions. Predictors of adherence were residence in an urban area, university education, catholic religion, and adoption of recommended behaviour towards a malaria case. Adherence was significantly lower for responders who obtained information on antimalarials from Community Health Workers (CHW). (4) Conclusions: Usage of recommended drugs and adherence to malaria treatment need to be promoted, especially in rural areas, and CHW involvement needs to be improved. Awareness messages need to be made accessible and comprehensible to poorly educated populations and churches need to be involved.

Knowledge of Antimalarials and Health Seeking Behaviour of Households in Case of Suspected Malaria in Democratic Republic of the Congo.

(1) Background: The Democratic Republic of the Congo (DRC) is heavily affected by malaria despite availability of effective treatments. Ignorance and unrecommended behaviour toward a suspected malaria case in households may contribute to this problem. (2) Method: In communities of one rural and one urban Health Centres in each of the 11 previous provinces of DRC, all households with a case of malaria in the 15 days prior to the survey were selected. The patient or caregiver (responder) were interviewed. Logistic regression was used to assess predictors of knowledge of recommended antimalarials and adequate behaviour in case of suspected malaria. (3) Results: 1732 households participated; about 62% (1060/1721) of the responders were informed about antimalarials, 70.1% (742/1059) knew the recommended antimalarials and 58.6% (995/1699) resorted to self-medication. Predictors of knowledge of antimalarials were education to secondary school or university, information from media and smaller households. Predictors of good behaviour were Catholic religion and smaller households. Receiving information from Community Health Workers (CHWs) failed to be determinants of knowledge or adequate behaviour. (4) Conclusion: malaria control in DRC is hampered by ignorance and non-adherence to national recommendations. These aspects are influenced by unsuccessful communication, size of households and level of education.

Development of a pharmacovigilance system in a resource-limited country: the experience of the Democratic Republic of Congo.

Implementation of pharmacovigilance (PV) systems in resource-limited countries is a real endeavor. Despite country- and continent-specific challenges, the Democratic Republic of the Congo (DRC) has been able to develop one of the most active PV systems in the sub-Saharan Africa. The World Health Organization (WHO) regional Office identified the DRC experience to set up a PV system for antimalarial drugs safety monitoring as a 'best practice' that needed to be documented in order to help DRC improve its PV system and to be scaled up in other African countries. In response to the WHO request, a best practices and bottlenecks analysis was conducted in 2015. This analysis was updated in 2018 in the light of the minimum requirements of the WHO to set up a PV system taking into account other guidance for PV systems. The following themes were retained for analysis: (1) creation of the national PV center; (2) implementation of PV in the health system; (3) data collection and analysis; (4) collaboration with public health programs; (5) collaboration with the National Regulatory Authority. Lessons learnt from the DRC experience show that it is possible to implement PV systems in order to promote patients' safety in resource limited sub-Saharan African countries with no guaranteed funding. The ability of national PV centers to collaborate with Public health stakeholders, including public health authorities at all levels as well as public health programs, and to use existing health information systems are considered the main key to success and may substantially reduce the cost of PV activities.

Central and Peripheral Nervous System Disorders Following Ivermectin Mass Administration: A Descriptive Study Based on the Democratic Republic of Congo Pharmacovigilance System.

INTRODUCTION: The mainstay of onchocerciasis control currently is mass administration of ivermectin; however, this may be associated with serious adverse events, including deaths, when administered in areas where onchocerciasis and loiasis are co-endemic. OBJECTIVES: The objective of the current study was to describe the central and peripheral nervous system disorders that occurred after mass administration of ivermectin in Democratic Republic of Congo (DRC). METHODS: This is a retrospective descriptive study involving a review of data on adverse events related to mass administration of ivermectin. Data on reported serious adverse events following mass administration of ivermectin in the DRC were extracted from the World Health Organization (WHO) Global individual case safety report (ICSR) database (VigiBase). The review covered the period 2009-2013 and focused on central and peripheral nervous system disorders. Relevant demographic, clinical, and parasitological data, including age, sex, area of residence, adverse events, and parasite density were extracted. Descriptive statistics were analyzed using Stata 12. RESULTS: A total of 52 ICSRs related to ivermectin intake were available in VigiBase, with 51 (98.1%) from the Province of Equateur. All patients had central and peripheral nervous system disorders; 25 (48.1%) had altered mental status. Of these, 23 (92.0%) satisfied the criteria for "probable/possible Loa loa encephalopathy temporally related to mectizan®" (PLERM). The most frequent nervous system disorders among patients with PLERM were coma (74%), stupor (30%), headache (22%), and abnormal gait (22%). There were, on average, 2149.1 microfilariae per ml (mf/ml) in peripheral blood [95% confidence interval (CI) 463.6-3834.6; n = 23]. Post-treatment, 61% of PLERM cases had <1000 L. loa mf/ml of blood. One patient had microfilariae in the cerebrospinal fluid rather than the peripheral blood. We found 21.4% co-infection with Plasmodium falciparum and 4% mortality. CONCLUSION: PLERM may occur at even low peripheral blood concentrations of microfilaria.

Antimalarial activity of medicinal plants from the Democratic Republic of Congo: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Malaria is the most prevalent parasitic disease and the foremost cause of morbidity and mortality in the Democratic Republic of Congo. For the management of this disease, a large Congolese population recourses to traditional medicinal plants. To date the efficacy and safety of many of these plants have been validated scientifically in rodent malaria models. In order to generate scientific evidence of traditional remedies used in the Democratic Republic of Congo for the management of malaria, and show the potential of Congolese plants as a major source of antimalarial drugs, this review highlights the antiplasmodial and toxicological properties of the Congolese antimalarial plants investigated during the period of 1999-2014. In doing so, a useful resource for further complementary investigations is presented. Furthermore, this review may pave the way for the research and development of several available and affordable antimalarial phytomedicines. MATERIALS AND METHODS: In order to get information on the different studies, a Google Scholar and PubMed literature search was performed using keywords (malaria, Congolese, medicinal plants, antiplasmodial/antimalarial activity, and toxicity). Data from non-indexed journals, Master and Doctoral dissertations were also collected. RESULTS: Approximately 120 extracts and fractions obtained from Congolese medicinal plants showed pronounced or good antiplasmodial activity. A number of compounds with interesting antiplasmodial properties were also isolated and identified. Some of these compounds constituted new scaffolds for the synthesis of promising antimalarial drugs. Interestingly, most of these extracts and compounds possessed high selective activity against Plasmodium parasites compared to mammalian cells. The efficacy and safety of several plant-derived products was confirmed in mice, and a good correlation was observed between in vitro and in vivo antimalarial activity. The formulation of several plant-derived products also led to some clinical trials and license of three plant-derived drugs (Manalaria(®), Nsansiphos(®), and Quinine Pharmakina(®)). CONCLUSION: The obtained results partly justify and support the use of various medicinal plants to treat malaria in folk medicine in the Democratic Republic of Congo. Antimalarial plants used in Congolese traditional medicine represent an important source for the discovery and development of new antimalarial agents. However, in order to ensure the integration of a larger number of plant-derived products in the Congolese healthcare system, some parameters and trends should be considered in further researches, in agreement with the objectives of the "Traditional Medicine Strategy" proposed by the World Health Organization in 2013. These include evaluation of geographical and seasonal variation, investigation of reproductive biology, assessment of prophylactic antimalarial activity, evaluation of natural products as adjuvant antioxidant therapy for malaria, development of plant-based combination therapies and monitoring of herbal medicines in pharmacovigilance systems.

Malaria epidemic outbreaks in the Democratic Republic of Congo, part I: cross-sectional survey in Mweka District.

Background: A series of outbreaks of fever has previously been reported in the DR Congo. The occurrence of similar outbreaks in Mweka district presented the opportunity to investigate these occurrences. Materials and Methods: Health facilities and communities were visited. Permission was obtained to access to health records and a questionnaire was competed in the community. Blood samples for malaria, salmonellosis, Chikungunya, dengue and filovirus testing were obtained both in health facilities and the communities. Capture of mosquitoes and larvae in breeding sites was done and used bednets were collected. Excel, SPSS and Stats Direct were used for analyses of epidemiological data and malaria case management, with the Chi-square test and Fisher's Exact test used for assessing relationships resulting from contingency table analyses. Results: An increase in the number of malaria cases beyond the expected number for the study period was observed in the two health districts located in the savannah zone (p<0.05) and in one health centre among sixteen located in the forest zone (p<0.05). In the health facilities and households visited (653 people), 141 persons had fever of which 82.2% was attributed to Plasmodium falciparum malaria. An incidence of 5.87% was recorded in the first half of 2013. Hundred and sixty patients (6.9%) died among 2,304 admitted for severe malaria in the three referral hospitals, 118 of them were children of under five years old. PCR testing of the blood samples obtained during home visits revealed malaria parasites in 63 (73.3%) of the 86 analysed samples. The test was negative for other parasites and bacteria and one dengue virus case was detected. Anopheles gambiae from Mweka were found to be resistant to permethrin using the WHO susceptibility test, with a knock down rate of ≤ 50% and mortality of ≤ 30%. Conclusion: These investigations confirmed epidemic outbreaks in Mweka District caused by malaria with a high mortality rate in children below five years of age.

Antimalarial activity and toxicity evaluation of a quantified Nauclea pobeguinii extract.

AIM OF THE STUDY: To evaluate the in vitro and in vivo antiplasmodial activity and toxicity of the aqueous and 80% EtOH extract of the stem bark of Nauclea pobeguinii (Pob. Ex. Pell.) Petit (Rubiaceae), a plant used in traditional medicine in DR Congo against malaria. MATERIALS AND METHODS: The aqueous and 80% EtOH extract from N. pobeguinii stem bark, and its constituents (5S)-5-carboxystrictosidine, 19-O-methylangustoline, 3-O-beta-fucosylquinovic acid, 3-ketoquinovic acid and strictosamide, were evaluated for their in vitro activity against Plasmodium falciparum (chloroquine-sensitive Ghana-strain). The 80% EtOH extract, containing 5.6% strictosamide, was evaluated in vivo in the 4-day P. berghei mouse model, and in the P. yoelii N67 model. RESULTS: All compounds were inactive or only moderately active in vitro. The aqueous and 80% EtOH extract displayed moderate in vitro activity with IC(50) values of 44 and 32 microg/mL, respectively, without apparent cytotoxicity on MRC-5 cells (CC50>64 microg/mL). Daily oral dosing of the 80% EtOH extract, at 300 mg/kg, resulted in 86% reduction of parasitaemia in the 4-day P. berghei mouse model, and 75% reduction in the P. yoelii N67 model. Prolonging oral dosing to 2 x 5 days, with an interval of 2 days, and oral administration of the 80% EtOH extract at 300 mg/kg induced 92% reduction of parasitaemia, and a mean survival time of 17 days. Strictosamide, the putative active constituent, may be metabolically activated in the gastrointestinal tract after oral administration. Levels of creatinin, urea, ALAT and ASAT remained unchanged after treatment. No acute toxicity was observed in mice after a single 2g/kg oral dose, nor after 4 weekly doses. No significant macroscopic or microscopic lesions were observed in heart, lung, spleen, kidney, liver, large intestine and brain. CONCLUSIONS: These results can partly support and justify the use of N. pobeguinii in traditional medicine in the DR Congo for the treatment of uncomplicated malaria.