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.

A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics.

BACKGROUND: Although several experimental therapeutics for Ebola virus disease (EVD) have been developed, the safety and efficacy of the most promising therapies need to be assessed in the context of a randomized, controlled trial. METHODS: We conducted a trial of four investigational therapies for EVD in the Democratic Republic of Congo, where an outbreak began in August 2018. Patients of any age who had a positive result for Ebola virus RNA on reverse-transcriptase-polymerase-chain-reaction assay were enrolled. All patients received standard care and were randomly assigned in a 1:1:1:1 ratio to intravenous administration of the triple monoclonal antibody ZMapp (the control group), the antiviral agent remdesivir, the single monoclonal antibody MAb114, or the triple monoclonal antibody REGN-EB3. The REGN-EB3 group was added in a later version of the protocol, so data from these patients were compared with those of patients in the ZMapp group who were enrolled at or after the time the REGN-EB3 group was added (the ZMapp subgroup). The primary end point was death at 28 days. RESULTS: A total of 681 patients were enrolled from November 20, 2018, to August 9, 2019, at which time the data and safety monitoring board recommended that patients be assigned only to the MAb114 and REGN-EB3 groups for the remainder of the trial; the recommendation was based on the results of an interim analysis that showed superiority of these groups to ZMapp and remdesivir with respect to mortality. At 28 days, death had occurred in 61 of 174 patients (35.1%) in the MAb114 group, as compared with 84 of 169 (49.7%) in the ZMapp group (P = 0.007), and in 52 of 155 (33.5%) in the REGN-EB3 group, as compared with 79 of 154 (51.3%) in the ZMapp subgroup (P = 0.002). A shorter duration of symptoms before admission and lower baseline values for viral load and for serum creatinine and aminotransferase levels each correlated with improved survival. Four serious adverse events were judged to be potentially related to the trial drugs. CONCLUSIONS: Both MAb114 and REGN-EB3 were superior to ZMapp in reducing mortality from EVD. Scientifically and ethically sound clinical research can be conducted during disease outbreaks and can help inform the outbreak response. (Funded by the National Institute of Allergy and Infectious Diseases and others; PALM ClinicalTrials.gov number, NCT03719586.).

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.

Safety profile of fractional dosing of the 17DD Yellow Fever Vaccine among males and females: Experience of a community-based pharmacovigilance in Kinshasa, DR Congo.

BACKGROUND: In early 2016, there was a Yellow Fever (YF) outbreak in Central Africa with several deaths reported from Angola and the Democratic Republic of Congo. Due to a shortage in vaccine supply, fractional dosing (0.1 ml) of 17DD Yellow Fever Vaccine (YFV) was proposed in preventive vaccination campaign in Kinshasa in August 2016. A Pharmacovigilance surveillance at community level was implemented to track Adverse Events Following Immunization (AEFIs). The objective of this study was to describe AEFIs as captured from community-based pharmacovigilance and to compare the safety profile of the fractional dosing of YFV between gender. METHODS: PV information sessions were organized in churches, academic institutions, and pediatrician, obstetrician and friend networks. Prior to data collection, education about AEFI was provided through face-to-face discussions, phone calls, SMS and WhatsApp messages. Individuals reported AEFIs though the above communication channels to assigned individuals. Reported AEFIs were entered into VigiFlow and extracted for statistical analysis using Stata 12. Only vaccinees who received fractional dose (subjects from the age of 2-year-old and non-pregnant women) were included in analysis. Proportional t-test was used to compare AEFI preferred terms among males and females. RESULTS: A total of 4020 subjects reported 5409 AEFIs. Reporters were mostly males (54.9%) with an average age of 26 ±â€¯10.7 years. Fever and injection site pain were the most reported systemic and local AEFI respectively. The safety profile was similar between gender although females reported more diarrhea and dizziness whilst males reported more asthenia (P < 0.001). Five individuals reported serious AEFIs. Among them, 4 were less-immunocompetent. CONCLUSION: Fractional dosing of 17DD YFV has a good safety profile, which is similar between gender. These findings complement the documented immunogenicity profile to support recommendation of fractional dose of YFV for outbreak control.

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.

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.

Assessment of attitudes towards adverse events following immunization with oral poliovirus vaccine: a pilot study among high school students of Kinshasa, the Democratic Republic of Congo.

OBJECTIVE: The aim of this study is to evaluate the reaction of students to adverse events following immunization in order to offer a baseline for developing a communication and risk management plan. METHOD: This is a cross-sectional study conducted in Kinshasa. A survey was conducted between the third and the fourth rounds of Supplementary Immunization Activity. Nine hundred and fifty questionnaires were used and addressed students who attended this university from 1 to 10 June 2011. RESULTS: Completed questionnaires were received from 848 students, with 485 females (57·2%), 343 males (40·4%), and 20 unknown (2·4%); 46·9% of students were from the faculty of medicine and 24·7% was from the third graduate degree. From those who completed the questionnaire, 136 (16·4%) reported experiencing an adverse events following immunization. Concerning the attitude of students towards adverse events following immunization, 79 students (58·5%) did nothing; 54 (40·0%) opted for self-medication; 2 (1·5%) went to the hospital. CONCLUSION: The main finding of our study is the low rate of people referring to health-care providers for vaccine-related problems, more specially for adverse events following immunization. A risk management plan should be focused in strategies to increase communication between population and health-care providers.

Adverse events following immunization with oral poliovirus in Kinshasa, Democratic Republic of Congo: preliminary results.

AIM: We investigated the nature and frequency of adverse events following immunization (AEFI) associated with oral polio vaccines (OPV) in the general population in Kinshasa, Democratic Republic of Congo (DR Congo). METHODS: The DR Congo National Pharmacovigilance Centre organized active AEFI surveillance during mass immunization campaigns for the general population from March to June 2011. A patient individual case safety report was used as a questionnaire and addressed to pupils and students from high schools and universities who had any adverse events after OPV administration. We used the preferred term from the WHO Adverse Reaction Terminology for AEFI designation. Here is presented the results of the second step of the mass immunization campaign. RESULTS: A total of 767 patients reported AEFI during the second step. Sex distribution shows that 512 (66·8%) students were females, while 255 (33·2%) were males, giving a female/male ratio 2∶1. The average age was 16·8±5·19 years (ranged: 6-35·5 years). Each person reported a mean of 1·33±0·6 AEFI. The average AEFI onset duration was 1·74±1·16 days post-vaccination, ranging from 1 to 9 days. Headache (22·4%), abdominal pain (17·2%), fever (11·7%), diarrhea (9·9%), and asthenia (7·5%) were the common symptoms. Paralysis and asthma-like reactions were rare and serious adverse events in this study. The most affected systems were gastro-intestinal (33·5%) and nervous system (29·3%). Rechallenge was positive for 173 persons (22·6%). CONCLUSION: OPV-related AEFIs are not uncommon, although it is under-reported. Active AEFI surveillance during mass immunization campaigns is very important and may help to detect rare and serious adverse events. Further investigation will be important to identify risk of AEFI with OPV in adults and is warranted to elucidate the cause of this association in the Congolese environment.