The landscape of drug resistance in Plasmodium falciparum malaria in the Democratic Republic of Congo: a mapping systematic review.

CONTEXT: The Democratic Republic of Congo (DRC), one of the most malaria-affected countries worldwide, is a potential hub for global drug-resistant malaria. This study aimed at summarizing and mapping surveys of malaria parasites carrying molecular markers of drug-resistance across the country. METHODS: A systematic mapping review was carried out before July 2023 by searching for relevant articles through seven databases (PubMed, Embase, Scopus, African Journal Online, African Index Medicus, Bioline and Web of Science). RESULTS: We identified 1541 primary studies of which 29 fulfilled inclusion criteria and provided information related to 6385 Plasmodium falciparum clinical isolates (collected from 2000 to 2020). We noted the PfCRT K76T mutation encoding for chloroquine-resistance in median 32.1% [interquartile interval, IQR: 45.2] of analyzed malaria parasites. The proportion of parasites carrying this mutation decreased overtime, but wide geographic variations persisted. A single isolate had encoded the PfK13 R561H substitution that is invoked in artemisinin-resistance emergence in the Great Lakes region of Africa. Parasites carrying various mutations linked to resistance to the sulfadoxine-pyrimethamine combination were widespread and reflected a moderate resistance profile (PfDHPS A437G: 99.5% [IQR: 3.9]; PfDHPS K540E: 38.9% [IQR: 47.7]) with median 13.1% [IQR: 10.3] of them being quintuple IRN-GE mutants (i.e., parasites carrying the PfDHFR N51I-C59R-S108N and PfDHPS A437G-K540E mutations). These quintuple mutants tended to prevail in eastern regions of the country. Among circulating parasites, we did not record any parasites harboring mutations related to mefloquine-resistance, but we could suspect those with decreased susceptibility to quinine, amodiaquine, and lumefantrine based on corresponding molecular surrogates. CONCLUSIONS: Drug resistance poses a serious threat to existing malaria therapies and chemoprevention options in the DRC. This review provides a baseline for monitoring public health efforts as well as evidence for decision-making in support of national malaria policies and for implementing regionally tailored control measures across the country.

A roadmap for the digital management of long-lasting insecticide-treated mosquito nets (LLINs) distribution campaigns in the Democratic Republic of Congo.

The use of the long-lasting insecticide-treated mosquito net (LLIN) is one of the basic interventions recommended by the Global technical strategy for Malaria 2016-2030. Since the start of the LLIN distribution campaigns in 2006 in Democratic Republic of Congo (DRC), it was based on paper tools leading to poor quality data. The first digital campaigns date back to 2014 through "Interchurch medical assistance" (IMA), which used the ODK collect application for recording household count data and LLIN distribution data. In 2020 "Soins de santé primaire en milieu Rurale" (SANRU) developed both household registration and LLIN distribution data recording forms as well as additional modules for supervision, monitoring and training. This article briefly describes the status of the implementation process of this digital-based management of LIIN mass distribution. During the first half of 2020, a roadmap was developed between Sanru and the Global fund to fight Tuberculosis, AIDS and Malaria (GFTAM) on the objectives of digitization, the data to be digitized, and the timelines for implementing the changes. In the last quarter of 2021, an internal Sanru team composed of some members of its technical management, and staff in charge of the digitization of LLIN mass distribution campaign data participated in a document review of the deliverables in comparison with the roadmap and in group discussions. For recording household enumeration data and distribution data, forms configured on smartphones allow data recording and uploading without going through manual calculations and previously necessary transcriptions with management based on paper tools, thus removing sources of errors. Online data delivery and automated production of dashboards allow real-time sharing of information to all stakeholders and shorten data validation times. Feedback to actors in the field is possible thanks to access to information and maps generated on the basis of geolocation data from households. ODK forms for supervision and monitoring have been put in place to ensure that these activities are effectively deployed in the field in accordance with the standards set by geolocating the actors and using the data transmitted online for interactive feedback. The next step is to develop a material flow management module to improve the traceability of inputs.

Digitalized long-lasting insecticidal nets mass distribution campaign in the context of Covid-19 pandemic in Kongo Central, Democratic Republic of Congo: challenges and lessons learned.

BACKGROUND: The Democratic Republic of the Congo (DRC) organized a first mass distribution campaign of long-lasting insecticidal nets (LLINs) with digitalized data management with coordinated support from the Ministry of Health (MOH) and Santé Pour Tous En Milieu Rural-an 'Association sans but lucratif' (SANRU Asbl), in the context of the Covid-19 pandemic in Kongo Central province. This article describes the planning and implementation process of this campaign as well as the challenges and lessons learned. METHODS: The planning and implementation process was performed in line with the standard guidance issued by the National Malaria Control Programme (NMCP) following the start of Covid-19. The changes and adaptations put in place as well as the challenges encountered are described. RESULTS: A total of 5,629,211 people were registered (7.7% above projection) in 1,065,537 households (6.2% below projection) giving an average of 5.3 people per household. Of a total of 3,062,850 LLINs ordered, 2,886,096 were distributed to households (94%). Out of 11,070 villages and 3,947 teams planned, 91.7% of villages were reached and 93% of teams were established. CONCLUSION: The revision of standards of campaign implementation during Covid-19, as well as effective coordination supported by real-time decision-making through digital data management, have been factors in the success of this campaign. Maintaining this momentum is essential to ensure the continuity of malaria prevention services for the population.

Therapeutic Efficacy of Artemisinin-Based Combination Therapies in Democratic Republic of the Congo and Investigation of Molecular Markers of Antimalarial Resistance.

Routine assessment of the efficacy of artemisinin-based combination therapies (ACTs) is critical for the early detection of antimalarial resistance. We evaluated the efficacy of ACTs recommended for treatment of uncomplicated malaria in five sites in Democratic Republic of the Congo (DRC): artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), and dihydroartemisinin-piperaquine (DP). Children aged 6-59 months with confirmed Plasmodium falciparum malaria were treated with one of the three ACTs and monitored. The primary endpoints were uncorrected and polymerase chain reaction (PCR)-corrected 28-day (AL and ASAQ) or 42-day (DP) cumulative efficacy. Molecular markers of resistance were investigated. Across the sites, uncorrected efficacy estimates ranged from 63% to 88% for AL, 73% to 100% for ASAQ, and 56% to 91% for DP. PCR-corrected efficacy estimates ranged from 86% to 98% for AL, 91% to 100% for ASAQ, and 84% to 100% for DP. No pfk13 mutations previously found to be associated with ACT resistance were observed. Statistically significant associations were found between certain pfmdr1 and pfcrt genotypes and treatment outcome. There is evidence of efficacy below the 90% cutoff recommended by WHO to consider a change in first-line treatment recommendations of two ACTs in one site not far from a monitoring site in Angola that has shown similar reduced efficacy for AL. Confirmation of these findings in future therapeutic efficacy monitoring in DRC is warranted.

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.

Prevalence of Congenital Malaria in Kisangani, A Stable Malaria Transmission Area in Democratic Republic of the Congo.

Background: Gestational malaria is a major public health problem. It produces fetal complications such as low birth weight, perinatal mortality, and congenital malaria. The present study is aimed at determining the prevalence of congenital malaria and its neonatal complications in the city of Kisangani. Methods: We conducted a cross-sectional study in Kisangani from 1 January to 30 September 2018. Our study population was composed of 1248 newborns born in our study sites, during the period of our study. Just after their birth, we performed the thick drop smear in the placental print and in umbilical blood smear. Results: The prevalence of congenital malaria was 13.98%; 69.23% of newborns who contracted congenital malaria were from 18- to 34-year-old mothers, 53.85% from primiparous mothers, 92.31% from mothers who took intermittent preventive treatment in pregnancy with Sulfadoxine-Pyrimethamine, all (100%) from mothers using the insecticide-treated mosquito nets and 7.69% from HIV-positive mothers. Low birth weight and perinatal mortality were recorded in 76.92% and 7.69% of congenital malaria cases, respectively. Intermittent preventive treatment in pregnancy with Sulfadoxine-Pyrimethamine had no effect on congenital malaria (FE = 0.5218; OR: 0.8, 95% CI: 0.1651-3.8769) and on low birth weight (FE = 0.3675; OR: 1.2308, 95% CI: 0.0037-0.1464); however, it seemed to have protective effect against perinatal mortality (FE = 0.0001; OR: 0.0233, 95% CI: 0.0037-0.1464). Conclusion: Congenital malaria remains a major problem in stable malaria transmission area like Kisangani, and it is grafted by major perinatal complications, particularly low birth weight and perinatal mortality. We recommend an extended study to clarify the relationship between the outcome of pregnancy and the intermittent preventive treatment in pregnancy with Sulfadoxine-Pyrimethamine.

Predictors of AIDS-related death among adult HIV-infected inpatients in Kisangani, the Democratic Republic of Congo.

INTRODUCTION: Human Immunodeficiency Virus (HIV) infection continues to be a major public health concern in sub-Saharan Africa. We aimed to evaluate potential factors associated with AIDS-related death among adult HIV-infected inpatients in Kisangani, the Democratic Republic of the Congo (DRC). METHODS: this is a hospital-based retrospective, observational analysis carried out between 1st January 2019 and 31st March 2020 among inpatients HIV, at 12 facilities integrating the HIV prevention and care packages in Kisangani. Factors associated with AIDS-related death were analyzed using the logistic regression models. RESULTS: a total of 347 HIV-infected inpatients were included. Among those, the rate of AIDS-related death was 25.1% (95% CI: 20.8-29.9). The rates of AIDS-related death were lower among patients with a university education (aOR: 0.03 [95% CI: 0.00-1.0]) and higher among patients in WHO clinical stage 4 (aOR: 15.4 [6.8-27.8]), patients with poor highly active antiretroviral therapy (HAART) observance (aOR: 14.5 [2.3-40.4), and patients suffering from opportunistic infections (aOR: 9.3 [95% CI: 3.4-25.1]), including cryptococcal meningitis (aOR: 27 [95% CI: 6.0-125.7]) and viral infections associated with zona and Kaposi sarcoma (aOR: 4.8 [95% CI: 2.2-10.4]). CONCLUSION: in our retrospective study on a large sample of inpatients hospitalized in Kisangani, classic causes of death were found. The association with the low level of education suggests that the economic level of the patients who die is a determining factor, difficult to correct. The identification of a limited number of other factors will allow a better medical management.

Trends in reported malaria cases and the effects of malaria control in the Democratic Republic of the Congo.

BACKGROUND: Considerable upscaling of malaria control efforts have taken place over the last 15 years in the Democratic Republic of Congo, the country with the second highest malaria case load after Nigeria. Malaria control interventions have been strengthened in line with the Millenium Development Goals. We analysed the effects of these interventions on malaria cases at health facility level, using a retrospective trend analysis of malaria cases between 2005 and 2014. Data were collected from outpatient and laboratory registers based on a sample of 175 health facilities that represents all eco-epidemiological malaria settings across the country. METHODS: We applied a time series analysis to assess trends of suspected and confirmed malaria cases, by health province and for different age groups. A linear panel regression model controlled for non-malaria outpatient cases, rain fall, nightlight intensity, health province and time fixed effects, was used to examine the relationship between the interventions and malaria case occurrences, as well as test positivity rates. RESULTS: Overall, recorded suspected and confirmed malaria cases in the DRC have increased. The sharp increase in confirmed cases from 2010 coincides with the introduction of the new treatment policy and the resulting scale-up of diagnostic testing. Controlling for confounding factors, the introduction of rapid diagnostic tests (RDTs) was significantly associated with the number of tested and confirmed cases. The test positivity rate fluctuated around 40% without showing any trend. CONCLUSION: The sharp increase in confirmed malaria cases from 2010 is unlikely to be due to a resurgence of malaria, but is clearly associated with improved diagnostic availability, mainly the introduction of RDTs. Before that, a great part of malaria cases were treated based on clinical suspicion. This finding points to a better detection of cases that potentially contributed to improved case management. Furthermore, the expansion of diagnostic testing along with the increase in confirmed cases implies that before 2010, cases were underreported, and that the accuracy of routine data to describe malaria incidence has improved.

[Effectiveness of vaccine management and quality of immunization services in the Expanded Programme on Immunization (EPI) antenna in the Kisangani region, Democratic Republic of Congo]. / Efficacité de la gestion de vaccins et qualité de vaccination à l'antenne PEV Kisangani en République Démocratique du Congo.

INTRODUCTION: The quality of vaccines is critical for good immunization outcomes. It is dependent on the effectiveness of technical and logistics management system put in place. This study aimed to assess the effectiveness of vaccine management and to learn something from this. METHODS: We conducted a retrospective study of logistic management of vaccines in the Expanded Programme on Immunization (EPI) antenna in the Kisangani region over the period 2010-2014. A literature review completed by semi-structured interviews of immunization services managers and providers helped to evaluate vaccine management using the WHO GEV model in order to identify the gaps. RESULTS: Provider's demonstrated low level of knowledge of the vaccines that cannot be frozen, of freezing tests and of other vaccine damages. Computerized data management was properly ensured in the antenna. No evaluation criteria reached the goal of 80%. Compliance with the storage temperature was 70% in the antenna; the criterion for vaccine management was 65% and 67% in the health area central office and in the health centre respectively. The maintenance criterion was zero at all levels. CONCLUSION: Malfunctioning of the logistic system is remarkable at all levels of the health pyramid; this could interfere with the quality and the expected impact of vaccination. Particular attention should be paid to the maintenance of the equipment.

The malaria testing and treatment market in Kinshasa, Democratic Republic of the Congo, 2013.

BACKGROUND: The Democratic Republic of Congo (DRC) is one of the two most leading contributors to the global burden of disease due to malaria. This paper describes the malaria testing and treatment market in the nation's capital province of Kinshasa, including availability of malaria testing and treatment and relative anti-malarial market share for the public and private sector. METHODS: A malaria medicine outlet survey was conducted in Kinshasa province in 2013. Stratified multi-staged sampling was used to select areas for the survey. Within sampled areas, all outlets with the potential to sell or distribute anti-malarials in the public and private sector were screened for eligibility. Among outlets with anti-malarials or malaria rapid diagnostic tests (RDT) in stock, a full audit of all available products was conducted. Information collected included product information (e.g. active ingredients, brand name), amount reportedly distributed to patients in the past week, and retail price. RESULTS: In total, 3364 outlets were screened for inclusion across Kinshasa and 1118 outlets were eligible for the study. Among all screened outlets in the private sector only about one in ten (12.1%) were stocking quality-assured Artemisinin-based Combination Therapy (ACT) medicines. Among all screened public sector facilities, 24.5% had both confirmatory testing and quality-assured ACT available, and 20.2% had sulfadoxine-pyrimethamine (SP) available for intermittent preventive therapy during pregnancy (IPTp). The private sector distributed the majority of anti-malarials in Kinshasa (96.7%), typically through drug stores (89.1% of the total anti-malarial market). Non-artemisinin therapies were the most commonly distributed anti-malarial (50.1% of the total market), followed by non quality-assured ACT medicines (38.5%). The median price of an adult quality-assured ACT was $6.59, and more expensive than non quality-assured ACT ($3.71) and SP ($0.44). Confirmatory testing was largely not available in the private sector (1.1%). CONCLUSIONS: While the vast majority of anti-malarial medicines distributed to patients in Kinshasa province are sold within the private sector, availability of malaria testing and appropriate treatment for malaria is alarmingly low. There is a critical need to improve access to confirmatory testing and quality-assured ACT in the private sector. Widespread availability and distribution of non quality-assured ACT and non-artemisinin therapies must be addressed to ensure effective malaria case management.

[Incidence of rubella in 2010-2012 in Kinshasa, Democratic Republic of Congo: data from the measles case-based surveillance system]. / Fréquence de la rubéole a Kinshasa de 2010 a 2012, République Démocratique du Congo (RDC): données issues du système de surveillance de la rougeole.

INTRODUCTION: No surveillance system or survey data on the congenital rubella syndrome are available in the Democratic Republic of Congo. This article describes the incidence of primary rubella infection between 2010 and 2012 based on the measles case-based surveillance system in Kinshasa. METHODS: Suspected cases of measles notified in Kinshasa between 2010 and 2012 were retrospectively analyzed. RESULTS: From January 2010 to December 2012, 1,892 suspected cases of measles were reported, and 1013 serum samples were collected according to the surveillance standard and analyzed in the laboratory. There were more cases of confirmed rubella than measles among the investigated cases. The proportion of confirmed cases of rubella has increased significantly over the last 3 years. The proportion of affected individuals of childbearing age was 15.4%, with a female predominance in this age-group. CONCLUSION: The Democratic Republic of Congo should consider revising the definition of cases used in the measles surveillance system in order to take into account the incidence of measle, establish sentinel sites for surveillance of CRS and use measles eradication activities and other mass activities to introduce rubella vaccination.

[HIV seroprevalence among tuberculous patients in Kisangani in the Democratic Republic of Congo]. / Séroprévalence du VIH chez les tuberculeux à Kisangani en République Démocratique du Congo.

INTRODUCTION: HIV testing among TB patients is still low in DRC This study aimed to determine HIV infection prevalence among TB patients with positive microscopy (TPM+) in Kisangani city. METHODS: In the period of 15 h August to 31th December 2010, a cross-sectional study was conducted including pulmonary tuberculosis patients with positive microscopy (TPM+) from 15 to 49-years-old received in seven tuberculosis screening and treatment centers (STC). The Chi-square and Fisher's exact test were used to compare proportions and the Wilcoxon test to examine the relationships between quantitative variables with skewed distributions. RESULTS: HIV test has been proposed to 136 TPM+ patients. Among them, 118 (86.76%) agreed to be tested. 24 (20.3%) of them were HIV positive. HIV-positive patients were significantly older (P = 0.02), predominantly female (P < 0.001) unemployed (p = 0.01). There were more cases of TB treatment relapse (p < 0.01) and less knowledge of TB signs (p = 0.01) among HIV-positive patients. DISCUSSION: The Ministry of Health and its partners should extend to all STC provider-initiated HIV counceling and testing, ensure access to antiretroviral treatment for all HIV-positive TB patients and intensify TB screening in all patients living with HIV

[Determinants of adherence to treatment for uncomplicated malaria in northeastern Democratic Republic of Congo]. / Facteurs d'adhésion au traitement recommandé pour le paludisme simple au Nord-Est de la République Démocratique du Congo.

The purpose of this study was to identify the determinants of adherence to malaria treatment (co-blistered AS-AQ) among health care providers, medicine sellers and patients in the northeastern region of the Democratic Republic of Congo. A cross-sectional study was carried out on health care providers, medicine sellers and patients in 13 health zones between March and June 2009. Only 69% of the cases of uncomplicated malaria were treated with AS-AQ, including 62.3% of cases treated using the correct dosages. The availability of AS-AQ, the intention to prescribe AS-AQ, longer consultations, providing explanations to patients, working in rural areas, training on the new policy, and the availability of treatment guidelines were found to be significantly associated with treatment adherence among health care providers. The limited availability of AS-AQ, the adverse effects of the treatment, the use of low-quality AS-AQ and the availability of cheap illegal antimalarial drugs were the main factors associated with non-adherence. Among patients, non-adherence was related to the perceived adverse effects of malaria treatment. The results suggest that improving the?accessibility and quality of AS-AQ and the quality of communication with patients, the provision of appropriate training to healthcare providers, the provision of treatment guidelines and appropriate supervision are needed to promote the use of AS-AQ.