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.

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.

Incidence and Predictors of Loss to Follow Up among Patients Living with HIV under Dolutegravir in Bunia, Democratic Republic of Congo: A Prospective Cohort Study.

This study aimed to examine the incidence and predictors of loss to follow up (LTFU) in the context of ongoing atrocities caused by armed conflict, where HIV treatment programs and HIV-infected patients may face unique challenges in terms of ART adherence and retention in care. We conducted an observational prospective cohort study of 468 patients living with HIV (PLWHIV) under dolutegravir (DTG) in all health facilities in Bunia between July 2019 and July 2021. Kaplan-Meier plots were used to determine the probability of LTFU as a function of time as inclusive of the cohort. The main outcome variable was LTFU, defined as not taking an ART refill for a period of 3 months or longer from the last attendance for refill, and not yet classified as 'dead' or 'transferred-out.' The log-rank test was used to compare survival curves based on predictors. Cox proportional hazard modeling was used to measure predictors of LTFU from the baseline until 31 July 2021 (the endpoint). A total of 3435.22 person-months (p-m) were involved in follow up, with an overall incidence rate of 33.48 LTFU per 1000 p-m. Patients who had less experience with ART at enrolment and the ethnically Sudanese, had a higher hazard of being LTFU compared to their reference groups. This study reports a high LTFU rate in this conflict setting. An ART program in such a setting should pay more attention to naive patients and other particularly vulnerable patients such as Sudanese during the pre-ART phase. The study implies the implementation of innovative strategies to address this high risk of being LTFU, reducing either the cost or the distance to the health facility.

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.

Predictors of Viral Non-Suppression among Patients Living with HIV under Dolutegravir in Bunia, Democratic Republic of Congo: A Prospective Cohort Study.

The Democratic Republic of the Congo adopted the integrase inhibitor dolutegravir (DTG) as part of its preferred first-line HIV treatment regimen in 2019. This study aimed to identify predictors of viral non-suppression among HIV-infected patients under a DTG-based regimen in the context of ongoing armed conflict since 2017 in the city of Bunia in the DRC. We conducted a cohort study of 468 patients living with HIV under DTG in all health facilities in Bunia. We calculated the proportion of participants with an HIV RNA of below 50 copies per milliliter. About three in four patients (72.8%) in this cohort had a viral load (VL) of <50 copies/mL after 6-12 months. After controlling for the effect of other covariates, the likelihood of having non-suppression remained significantly lower among the 25-34 age group and self-reported naïve patients with a baseline VL of ≥50 copies/mL. The likelihood of having non-suppression remained significantly higher among those who were at advanced stages of the disease, those with abnormal serum creatinine, those with high baseline HIV viremia over 1000 copies/mL, and the Sudanese ethnic group compared to the reference groups. This study suggests that we should better evaluate adherence, especially among adolescents and economically vulnerable populations, such as the Sudanese ethnic group in the city of Bunia. This suggests that an awareness of the potential effects of DTG and tenofovir is important for providers who take care of HIV-positive patients using antiretroviral therapy (ART), especially those with abnormal serum creatinine levels before starting treatment.

Determinants of Survival of HIV Patients Receiving Dolutegravir: A Prospective Cohort Study in Conflict-Affected Bunia, Democratic Republic of Congo.

This study aims to determine the factors influencing HIV-related mortality in settings experiencing continuous armed conflict atrocities. In such settings, people living with HIV (PLHIV), and the partners of those affected may encounter specific difficulties regarding adherence to antiretroviral therapy (ART), and retention in HIV prevention, treatment, and care programs. Between July 2019 and July 2021, we conducted an observational prospective cohort study of 468 PLHIV patients treated with Dolutegravir at all the ART facilities in Bunia. The probability of death being the primary outcome, as a function of time of inclusion in the cohort, was determined using Kaplan-Meier plots. We used the log-rank test to compare survival curves and Cox proportional hazard modeling to determine mortality predictors from the baseline to 31 July 2021 (endpoint). The total number of person-months (p-m) was 3435, with a death rate of 6.70 per 1000 p-m. Compared with the 35-year-old reference group, older patients had a higher mortality risk. ART-naïve participants at the time of enrollment had a higher mortality risk than those already using ART. Patients with a high baseline viral load (≥1000 copies/mL) had a higher mortality risk compared with the reference group (adjusted hazard ratio = 6.04; 95% CI: 1.78-20.43). One-fourth of deaths in the cohort were direct victims of armed conflict, with an estimated excess death of 35.6%. Improving baseline viral load monitoring, starting ART early in individuals with high baseline viral loads, the proper tailoring of ART regimens and optimizing long-term ART, and care to manage non-AIDS-related chronic complications are recommended actions to reduce mortality. Not least, fostering women's inclusion, justice, peace, and security in conflict zones is critical in preventing premature deaths in the general population as well as among PLHIV.

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.

Effectiveness of pyronaridine-artesunate against Plasmodium malariae, Plasmodium ovale spp, and mixed-Plasmodium infections: a post-hoc analysis of the CANTAM-Pyramax trial.

BACKGROUND: High-quality evidence for the therapeutic efficacy and effectiveness of antimalarials for infections caused by Plasmodium malariae, Plasmodium ovale spp, and mixed-Plasmodium infections is scarce. In this study, we aimed to analyse the efficacy of pyronaridine-artesunate for the treatment of non-falciparum and mixed-species Plasmodium infections from a large phase 3b/4 clinical trial in central Africa. METHODS: This post-hoc analysis was done in a random subset of samples from two sites (in the Democratic Republic of the Congo and in Gabon) of the CANTAM-Pyramax trial assessing pyronaridine-artesunate therapy. We randomly selected paired dried blood spot samples from day 0 and day 28 (or unforeseen visit) and analysed them by quantitative PCR for mixed Plasmodium infections or non-falciparum mono-infections. Day 28 (or unforeseen visit) samples positive for non-falciparum malaria were re-assessed by microscopy to identify microscopic versus submicroscopic infections. Analyses were done on two sample sets: a per-protocol set and an intention-to-treat set. FINDINGS: Among 1502 randomly selected samples, 192 (12·8%) showed mixed-Plasmodium infections or non-falciparum mono-infections. We did not detect P vivax in the samples. For both the per-protocol and intention-to-treat sets, the overall day 28 cure rates for P malariae, P ovale curtisi, and P ovale wallikeri were 96·3% or higher (95% CIs from 81·0-99·9 to 95·7-100). Cure rates were consistently high in P malariae (99·2%, 95·7-100) and P ovale spp (97·9%, 88·7-99·9, for P ovale curtisi and 96·3%, 81·0-99·9, for P ovale wallikeri) infections. INTERPRETATION: This post-hoc analysis provides important evidence supporting the high efficacy of pyronaridine-artesunate against mono-infections with P malariae, P ovale curtisi, or P ovale wallikeri and mixed-Plasmodium infections in a real-world setting. FUNDING: Medicines for Malaria Venture.

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.

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.

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.