The effect of a mass distribution of insecticide-treated nets on insecticide resistance and entomological inoculation rates of Anopheles gambiae s.l. in Bandundu City, Democratic Repub`lic of Congo.

INTRODUCTION: insecticide-treated nets (ITNs) remain the mainstay of malaria vector control in the Democratic Republic of Congo. However, insecticide resistance of malaria vectors threatens their effectiveness. Entomological inoculation rates and insecticide susceptibility in Anopheles gambiae s.l. were evaluated before and after mass distribution of ITNs in Bandundu City for possible occurrence of resistance. METHODS: a cross-sectional study was conducted from 15th July 2015 to 15th June 2016. Adult mosquitoes were collected using pyrethrum spray catches and human landing catches and identified to species level and tested for the presence of sporozoites. Bioassays were carried out before and after distribution of ITNs to assess the susceptibility of adult mosquitoes to insecticides. Synergist bioassays were also conducted and target site mutations assessed using Polymerase chain reaction (PCR). RESULTS: a total of 1754 female An. gambiae s.l. were collected before and after deployment of ITNs. Fewer mosquitoes were collected after the distribution of ITNs. However, there was no significant difference in sporozoite rates or the overall entomological inoculation rate before and after the distribution of ITNs. Test-mosquitoes were resistant to deltamethrin, permethrin, and Dichlorodiphenyltrichloroethane but susceptible to bendiocarb. Pre-exposure of mosquitoes to Piperonyl butoxide increased their mortality after exposure to permethrin and deltamethrin. The frequency of the Kinase insert domain receptor (kdr)-West gene increased from 92 to 99% before and after the distribution of nets, respectively. CONCLUSION: seasonal impacts could be a limiting factor in the analysis of these data; however, the lack of decrease in transmission after the distribution of new nets could be explained by the high-level of resistance to pyrethroid.

Prevalence of Plasmodium falciparum isolates lacking the histidine rich protein 2 gene among symptomatic malaria patients in Kwilu Province of the Democratic Republic of Congo.

BACKGROUND: Malaria rapid diagnostic tests have become a primary and critical tool for malaria diagnosis in malaria-endemic countries where Plasmodium falciparum Histidine Rich Protein 2-based rapid diagnostic tests (PfHRP2-based RDTs) are widely used. However, in the last decade, the accuracy of PfHRP2-based RDTs has been challenged by the emergence of P. falciparum strains harbouring deletions of the P. falciparum histidine rich protein 2 (pfhrp2) gene, resulting in false-negative results. In the Democratic Republic of Congo (D.R. Congo), little is known about the prevalence of the pfhrp2 gene deletion among P. falciparum isolates infecting symptomatic patients, especially in low to moderate transmission areas where pfhrp2 deletion parasites are assumed to emerge and spread. Here we determine the local prevalence and factors associated with pfhrp2 gene deletions among symptomatic malaria patients in the Kwilu Province of the D.R. Congo. METHODS: We used secondary data from a prospective health facility-based cross-sectional study conducted in 2018. Blood was collected for microscopy, PfHRP2-RDT, and spotted onto Whatman filter paper for downstream genetic analysis. Genomic DNA was extracted and used to perform PCR assays for the detection and confirmation of pfhrp2 gene deletions. Fischer's exact and the Kruskal-Wallis tests were applied to look for associations between potential explanatory variables and the pfhrp2 gene deletion with a level of statistical significance set at P < 0.05. RESULTS: Of the 684 enrolled symptomatic patients, 391 (57.7%) were female. The majority (87.7%) reported the presence of mosquito breeding sites within the household's compound, and fever was the most reported symptom (81.6%). The overall prevalence of the pfhrp2 gene deletion was 9.2% (95% CI: 6.7%-12.1%). The deletion of the pfhrp2 gene was associated with health zone of origin (P = 0.012) and age (P = 0.019). Among false-negative PfHRP2-RDT results, only 9.9% were due to pfhrp2 gene deletion. CONCLUSIONS: P. falciparum isolates with pfhrp2 gene deletions are relatively common among symptomatic patients in Kwilu province. Further investigations are needed to provide enough evidence for policy change. Meanwhile, the use of RDTs targeting PfHRP2 and parasite lactate dehydrogenase (pLDH) antigens could limit the spread of deleted isolates.

Analysis of false-negative rapid diagnostic tests for symptomatic malaria in the Democratic Republic of the Congo.

The majority of Plasmodium falciparum malaria diagnoses in Africa are made using rapid diagnostic tests (RDTs) that detect histidine-rich protein 2. Increasing reports of false-negative RDT results due to parasites with deletions of the pfhrp2 and/or pfhrp3 genes (pfhrp2/3) raise concern about existing malaria diagnostic strategies. We previously identified pfhrp2-negative parasites among asymptomatic children in the Democratic Republic of the Congo (DRC), but their impact on diagnosis of symptomatic malaria is unknown. We performed a cross-sectional study of false-negative RDTs in symptomatic subjects in 2017. Parasites were characterized by microscopy; RDT; pfhrp2/3 genotyping and species-specific PCR assays; a bead-based immunoassay for Plasmodium antigens; and/or whole-genome sequencing. Among 3627 symptomatic subjects, 427 (11.8%) had RDT-/microscopy + results. Parasites from eight (0.2%) samples were initially classified as putative pfhrp2/3 deletions by PCR, but antigen testing and whole-genome sequencing confirmed the presence of intact genes. 56.8% of subjects had PCR-confirmed malaria. Non-falciparum co-infection with P. falciparum was common (13.2%). Agreement between PCR and HRP2-based RDTs was satisfactory (Cohen's kappa = 0.66) and superior to microscopy (0.33). Symptomatic malaria due to pfhrp2/3-deleted P. falciparum was not observed. Ongoing HRP2-based RDT use is appropriate for the detection of falciparum malaria in the DRC.

Correlation of textile 'resistance to damage' scores with actual physical survival of long-lasting insecticidal nets in the field.

BACKGROUND: Attempts have been made to link procurement of long-lasting insecticidal nets (LLIN) not only to the price but also the expected performance of the product. However, to date it has not been possible to identify a specific textile characteristic that predicts physical durability in the field. The recently developed resistance to damage (RD) score could provide such a metric. This study uses pooled data from durability monitoring to explore the usefulness of the RD methodology. METHODS: Data from standardized, 3-year, prospective LLIN durability monitoring for six LLIN brands in 10 locations and four countries involving 4672 campaign LLIN were linked to the RD scores of the respective LLIN brands. The RD score is a single quantitative metric based on a suite of standardized textile tests which in turn build on the mechanisms of damage to a mosquito net. Potential RD values range from 0 to 100 where 100 represents optimal resistance to expected day-to-day stress during reasonable net use. Survival analysis was set so that risk of failure only started when nets were first hung. Cox regression was applied to explore RD effects on physical survival adjusting for known net use environment variables. RESULTS: In a bivariate analysis RD scores showed a linear relationship with physical integrity suggesting that the proportion of LLIN with moderate damage decreased by 3%-points for each 10-point increase of the RD score (p = 0.02, R2 = 0.65). Full adjustment for net care and handling behaviours as well as other relevant determinants and the country of study showed that increasing RD score by 10 points resulted in a 36% reduction of risk of failure to survive in serviceable condition (p < 0.0001). LLINs with RD scores above 50 had an additional useful life of 7 months. CONCLUSIONS: This study provides proof of principle that the RD metric can predict physical durability of LLIN products in the field and could be used to assess new products and guide manufacturers in creating improved products. However, additional validation from other field data, particularly for next generation LLIN, will be required before the RD score can be included in procurement decisions for LLINs.

Variation of physical durability between LLIN products and net use environments: summary of findings from four African countries.

BACKGROUND: Physical durability of long-lasting-insecticidal nets (LLIN) is an important aspect of the effectiveness of LLIN as a malaria prevention tool, but there is limited data on performance across locations and products. This secondary analysis of data from the VectorWorks project from 10 sites in four African countries involving six LLIN brands provides such data. METHODS: A total of 4672 campaign nets from 1976 households were recruited into prospective cohort studies 2-6 months after distribution through campaigns and followed for 3 years in Mozambique, Nigeria, DRC and Zanzibar, Tanzania. LLIN products included two 100 denier polyester LLIN (DawaPlus® 2.0, PermaNet® 2.0) distributed in five sites and four 150 denier polyethylene LLIN (Royal Sentry®, MAGNet®, DuraNet©, Olyset™ Net) distributed in five sites. Primary outcome was LLIN survival in serviceable condition and median survival in years. Net use environment and net care variables were collected during four household surveys. Determinants of physical durability were explored by survival analysis and Cox regression models with risk of failure starting with the first hanging of the net. RESULTS: Definite outcomes for physical durability were obtained for 75% of study nets. After 31 to 37 months survival in serviceable condition varied between sites by 63 percentage-points, from 17 to 80%. Median survival varied by 3.7 years, from 1.6 to 5.3 years. Similar magnitude of variation was seen for polyethylene and polyester LLIN and for the same brand. Cox regression showed increasing net care attitude in combination with exposure to net related messages to be the strongest explanatory variable of survival. However, differences between countries also remained significant. In contrast, no difference was seen for LLIN material types. CONCLUSIONS: Variation in net use environment and net care is the main reason for differences in the physical durability of LLIN products in different locations. While some of these factors have been identified to work across countries, other factors remain poorly defined and further investigation is needed in this area. Grouping LLIN brands by similar textile characteristics, such as material or yarn strength, is insufficient to distinguish LLIN product performance suggesting a more differentiated, composite metric is needed.

Comparing the durability of the long-lasting insecticidal nets DawaPlus® 2.0 and DuraNet© in northwest Democratic Republic of Congo.

BACKGROUND: Anecdotal reports from DRC suggest that long-lasting insecticidal nets (LLIN) distributed through mass campaigns in DRC may not last the expected average three years. To provide the National Malaria Control Programme with evidence on physical and insecticidal durability of nets distributed during the 2016 mass campaign, two brands of LLIN, DawaPlus® 2.0 and DuraNet©, were monitored in neighbouring and similar health zones in Sud Ubangi and Mongala Provinces. METHODS: This was a prospective cohort study of representative samples of households from two health zones recruited at baseline, 2 months after the mass campaign. All campaign nets in these households were labelled, and followed up over a period of 31 months. Primary outcome was the "proportion of nets surviving in serviceable condition" based on attrition and integrity measures and the median survival in years. The outcome for insecticidal durability was determined by bio-assay from subsamples of campaign nets. RESULTS: A total of 754 campaign nets (109% of target) from 240 households were included in the study. Definite outcomes could be determined for 67% of the cohort nets in Sud Ubangi and 74% in Mongala. After 31 months all-cause attrition was 57% in Sud Ubangi and 76% in Mongala (p = 0.005) and attrition due to wear and tear was 26% in Sud Ubangi and 48% in Mongala (p = 0.0009). Survival in serviceable condition at the last survey was 37% in Sud Ubangi and 17% in Mongala (p = 0.003). Estimated median survival was 1.6 years for the DawaPlus® 2.0 in Mongala (95% CI 1.3-1.9) and 2.2 years for the DuraNet in Sud Ubangi (95% CI 2.0-2.4). Multivariable Cox proportionate hazard models suggest that the difference between sites was mainly attributable to the LLIN brand. Insecticidal effectiveness was optimal for DuraNet©, but significantly dropped after 24 months for DawaPlus® 2.0. CONCLUSIONS: In the environment of northwest DRC the polyethylene LLIN DuraNet© performed significantly better than the polyester LLIN DawaPlus® 2.0, but both were below a three-year median survival. Improvement of net care behaviours should be able to improve physical durability.

Factors Associated with Postpartum Health Problems among Married Women of Reproductive Age in the Democratic Republic of the Congo: A Cross-sectional Study in Kenge City.

Maternal mortality is attracting attention worldwide, but maternal health problems after delivery have received less attention. Most studies focus on prenatal maternal health problems. We aimed to identify factors associated with postpartum health problems among married women of reproductive age in Democratic Republic of the Congo. We employed a cross-sectional study design and randomly enrolled 700 married women of reproductive age in Kenge city. Data collection instrument was developed using the UNICEF Multiple Indicator Cluster Survey. T-test, chi-square test, and binary logistic regression analysis were performed using the SPSS version 24.0. Significant risk factors associated with postpartum health problems were initial postnatal care period; within 24 hours (Odds Ratio [OR]=2.197, 95% confidence interval [CI]: [1.156-4.174], p=.016); within 7 days (OR=1.972, 95% CI: [1.102-3.528, p=.022]; within 14 days (OR=2.124, 95% CI: [1.082-4.172], p=.029) among reproductive health and health service utilization characteristics. Health education by RECO (Relais Cmunataure) was associated with postpartum health problems including PCIME (Prise en Charge Integree des Maladies de l'Enfant; OR=1.845, 95% CI: [1.038- 3.282], p=.037); hand washing (OR=1.897, 95% CI: [1.060-3.396], p=.031); malaria (OR=2.003, 95% CI: [1.192-3.366], p=.009) among Maternal and Child Health intervention characteristics. In conclusion, it is necessary to develop and promote health policies and educational programs focusing on PNC service within 24 hours, PNC services within 7 days, PCIME, hand washing, prevention of malaria.

Analysis of severe adverse effects following community-based ivermectin treatment in the Democratic Republic of Congo.

BACKGROUND: The progress of mass, community-directed, treatment with ivermectin (CDTI) for onchocerciasis control was disrupted by severe adverse effects (SAE) in the Democratic Republic of Congo (DRC). The study aimed at determining the frequency of post-CDTI SAE as well as factors associated with the occurrence of SAE. METHODS: Our retrospective study relied on SAE collection cards, as archived by the DRC Ministry of Health, and compiled for people who benefited from ivermectin treatment then further developed SAE. The study included 945 post-CDTI SAE recorded in DRC between 2003 and 2017. These cases occurred in 15 projects out of 22 projects implemented in the country. All cards were reviewed and analysed. RESULTS: Between the years 2003 and 2017, the total average population treated was around 15,552,588 among which 945 cases of SAE were registered in DR Congo, i.e. 6 cases of SAE for 100,000 persons treated per year. 55 deaths related to post-CDTI SAE were recorded, which represents 5.8% of all cases of SAE. Non-neurological SAE were dominated by severe headaches (74.8%), myalgia (64.0%) and arthralgia (62.7%). Neurological SAE were mainly coma (94.1%), motor deficit (75.4%) and palpebral subconjunctival haemorrhages (38.8%). Factors associated with the occurrence of SAE were: male, age over 18 years old, alcohol consumption, hemp intake and the presence of loiasis. The study also highlighted weaknesses of the National Program for Onchocerciasis Control (NPOC)  in terms of awareness campaigns among the population. CONCLUSION: Co-endemicity of loiasis and onchocerciasis is one of the key factors responsible for the occurrence of SAE following ivermectin treatment. Mobilization of resources necessary to the appropriate management of SAE and awareness of populations are essential to achieve onchocerciasis control in DRC.

Community Participation in and Perception of Community-Directed Treatment with Ivermectin in Kinshasa, DRC.

The success of community-directed treatment with Ivermectin (CDTI) depends on active community participation. We conducted a case study nested in a cross-sectional study in the Binza Ozone Health Zone (ZS) in Kinshasa, Democratic Republic of Congo, in order to investigate community's knowledges and perceptions of onchocerciasis and on all CDTI's aspects. We interviewed 106 people aged 20 and over, purposively selected, through eight individual interviews and 12 focus groups. Themes used for collecting data were drawn for the Health Belief Model and data were analyzed using a deductive thematic approach. The term onchocerciasis was unknown to participants who called it "Mbitiri", the little black fly, in their local language. This disease is seen as curse put on the sufferer by a witch and perceived as a threat because of the "Mbitiri" bites. The afflicted participants were reluctant to seek treatment and preferred traditional practitioners or healers. CDTI is considered devastating because of adverse effects of ivermectin as well as inefficient after occurrence of deaths. This explains the low level of community adhesion and participation to this strategy. Recruitment procedures for community distributors are poorly understood and awareness and health education campaigns are either non-existent or rarely carried out. Nevertheless, the latter should be regularly done.

Review of the National Program for Onchocerciasis Control in the Democratic Republic of the Congo.

Here, we review all data available at the Ministry of Public Health in order to describe the history of the National Program for Onchocerciasis Control (NPOC) in the Democratic Republic of the Congo (DRC). Discovered in 1903, the disease is endemic in all provinces. Ivermectin was introduced in 1987 as clinical treatment, then as mass treatment in 1989. Created in 1996, the NPOC is based on community-directed treatment with ivermectin (CDTI). In 1999, rapid epidemiological mapping for onchocerciasis surveys were launched to determine the mass treatment areas called "CDTI Projects". CDTI started in 2001 and certain projects were stopped in 2005 following the occurrence of serious adverse events. Surveys coupled with rapid assessment procedures for loiasis and onchocerciasis rapid epidemiological assessment were launched to identify the areas of treatment for onchocerciasis and loiasis. In 2006, CDTI began again until closure of the activities of African Program for Onchocerciasis Control (APOC) in 2015. In 2016, the National Program for Neglected Tropical Diseases Control using Preventive Chemotherapy (PNMTN-CP) was launched to replace NPOC. Onchocerciasis and CDTI are little known by the population. The objective of eliminating onchocerciasis by 2025 will not be achieved due to the poor results of the NPOC. The reform of strategies for eliminating this disease is strongly recommended.

Factors associated with postpartum health problems among married women of reproductive age in the Democratic Republic of the Congo: a cross-sectional study in Kenge City

Maternal mortality is attracting attention worldwide, but maternal health problems after delivery have received less attention. Most studies focus on prenatal maternal health problems. We aimed to identify factors associated with postpartum health problems among married women of reproductive age in Democratic Republic of the Congo. We employed a cross-sectional study design and randomly enrolled 700 married women of reproductive age in Kenge city. Data collection instrument was developed using the UNICEF Multiple Indicator Cluster Survey. T-test, chi-square test, and binary logistic regression analysis were performed using the SPSS version 24.0. Significant risk factors associated with postpartum health problems were initial postnatal care period; within 24 hours (Odds Ratio [OR]=2.197, 95% confidence interval [CI]: [1.156­4.174], p=.016); within 7 days (OR=1.972, 95% CI: [1.102­3.528, p=.022]; within 14 days (OR=2.124, 95% CI: [1.082­4.172], p=.029) among reproductive health and health service utilization characteristics. Health education by RECO (Relais Cmunataure) was associated with postpartum health problems including PCIME (Prise en Charge Integree des Maladies de l'Enfant; OR=1.845, 95% CI: [1.038­3.282], p=.037); hand washing (OR=1.897, 95% CI: [1.060­3.396], p=.031); malaria (OR=2.003, 95% CI: [1.192­3.366], p=.009) among Maternal and Child Health intervention characteristics. In conclusion, it is necessary to develop and promote health policies and educational programs focusing on PNC service within 24 hours, PNC services within 7 days, PCIME, hand washing, prevention of malaria

Effects of improved sanitation on diarrheal reduction for children under five in Idiofa, DR Congo: a cluster randomized trial.

BACKGROUND: The lack of safe water and sanitation contributes to the rampancy of diarrhea in many developing countries. METHODS: This study describes the design of a cluster-randomized trial in Idiofa, the Democratic Republic of the Congo, seeking evidence of the impact of improved sanitation on diarrhea for children under four. Of the 276 quartiers, 18 quartiers were randomly allocated to the intervention or control arm. Seven hundred and-twenty households were sampled and the youngest under-four child in each household was registered for this study. The primary endpoint of the study is diarrheal incidence, prevalence and duration in children under five. DISCUSSION: Material subsidies will be provided only to the households who complete pit digging plus superstructure and roof construction, regardless of their income level. This study employs a Sanitation Calendar so that the mother of each household can record the diarrheal episodes of her under-four child on a daily basis. The diary enables examination of the effect of the sanitation intervention on diarrhea duration and also resolves the limitation of the small number of clusters in the trial. In addition, the project will be monitored through the 'Sanitation Map', on which all households in the study area, including both the control and intervention arms, are registered. To avoid information bias or courtesy bias, photos will be taken of the latrine during the household visit, and a supervisor will determine well-equipped latrine uptake based on the photos. This reduces the possibility of recall bias and under- or over-estimation of diarrhea, which was the main limitation of previous studies. TRIAL REGISTRATION: The study was approved by the Institutional Review Board of the School of Public Health, Kinshasa University (ESP/CE/040/15; April 13, 2015) and registered as an International Standard Randomized Controlled Trial (ISRCTN: 10,419,317) on March 13, 2015.

Associations between Household Latrines and the Prevalence of Diarrhea in Idiofa, Democratic Republic of the Congo: A Cross-Sectional Study.

Despite the importance of sanitation, few studies have assessed the effects of latrines on the health outcomes of children under 5 years of age. We assessed the relations between latrine coverage and the prevalence of diarrhea in children under 4 years of age. In this cross-sectional study, we analyzed the baseline data obtained as part of a longitudinal survey targeting 720 households in Idiofa, Bandundu, Democratic Republic of the Congo. We categorized latrines according to the presence of each major component and investigated whether diarrhea prevalence of children under 4 years of age is associated with latrine availability and improvement. Latrines have health benefits regardless of whether they are improved. Also worth noting is that comparatively well-equipped and more appropriately managed latrines could prevent child diarrhea more effectively than less equipped or inappropriately managed latrines. Households who have a latrine with a superstructure, roof, and no flies (a partly improved latrine) were found to be 52% less likely to report cases of diarrhea than households with unimproved latrines (adjusted odds ratio [OR] = 0.48, confidence interval [CI] = 0.31-0.76), which are all the other latrines not included in the partly improved latrine category. We have observed the profound protective effect of latrines with a superstructure. This study demonstrates that latrines are associated with significant improvements in health even when they do not fully meet the conditions of improved latrines. This study adds value to the limited evidence on the effect of latrines on health parameters by demonstrating that latrines have correlations with health benefits regardless of whether they are improved, as well as by elucidating the most essential components of improved latrines.