Epidemiology and treatment of malaria in Kinshasa, Democratic Republic of Congo

Sub-Saharan Africa is the region of the world with the highest burden of malaria (WHO, 2014), as well as some of the fastest growing cities. The 2011 United Nations report (UN, 2014a) estimated that by 2013 40% of the population of sub-Saharan Africa would live in urban areas, projected to become a total urbanised population of 760 million by 2030. Urbanisation has a significant impact on the economy, lifestyles, ecosystems and disease patterns (Omumbo et al., 2005).
Although historically considered a rural disease, malaria transmission does occur in urban Africa, causing specific challenges for inhabitants, notably the heterogeneous spatial distribution of risk and the low level of acquired immunity of citizens, who are therefore exposed to higher risk of severe disease (Robert et al., 2003). Kinshasa, the capital of the Democratic Republic of the Congo (DRC) and the third largest city in Africa, has undergone rapid urbanisation during the past decades, presenting today a heterogeneous pattern of land use. However, there is a paucity of information on the geographic distribution of malaria prevalence in urban Kinshasa and on the risk factors linked to its distribution.
The overall aim of the first part of this thesis was to update the distribution map of malaria in Kinshasa, since the latest epidemiological study was conducted in 2000 (Kazadi et al., 2004), and to update information on malaria control activities. Field research was initially conducted in 2009 by the School of Public Health of Kinshasa (KSPH), which sampled nine out of the 32 non-rural health zones (HZs); the remaining 23 were sampled during fieldwork conducted in 2011 by the Swiss Tropical and Public Health Institute (Swiss TPH) in collaboration with the KSPH. Two HZs already sampled in 2009 were resampled in the 2011 survey, bringing the total of HZs sampled in 2011 to 25.
In the first step (detailed in Chapter 3), which took place at the end of the 2011 rainy season, we undertook a cross-sectional survey to complete those urban and peri-urban HZs of Kinshasa that had not been sampled during the 2009 survey to assess the prevalence of malaria by Rapid Diagnostic Test (RDT) among children aged six to 59 months, anaemia and history of fever, and to obtain a comprehensive report on the state of key preventive malaria indicators. Point-referenced prevalence data from the two surveys and seasons were combined by indirect standardisation and mapped at the level of the health areas (HAs) by means of a geographic information system (GIS). The overall standardised malaria prevalence was found to be 11.7%, showing a decline over the previous two decades, with higher risk in the peri-urban areas compared to the more central urban areas. We observed considerable progress in key malaria indicators compared to the Demographic and Health Survey 2007 (DHS-DRC, 2007). Age groups with the highest prevalence were five to nine years and 15 to 19 years, an indication that malaria occurs more frequently in late childhood. This study presents the first comprehensive map of malaria risk in Kinshasa.
In the second step (discussed in Chapter 4), logistic regression with random effects was used to investigate predictors for malaria and anaemia among children aged six to 59 months and for malaria in individuals older than five years across zones in Kinshasa with a prevalence of malaria of less than 10% and 10% or greater. Accordingly, evidence was found of a different age pattern in the two transmission settings. The peak prevalence of malaria in children under five years was observed in the 48 to 59 months group in both transmission settings, but it increased more gradually for the lower transmission setting. In a separate analysis, in children over the age of five in two selected HZs, the peak prevalence was found to be in five to nine year-olds in the higher transmission setting and in 15 to 19 year-olds in the lower transmission setting. Reported fever in the last two weeks was associated with the risk of having malaria in all age groups in both transmission settings, with no evidence of a difference in these associations; in children older than five years however, there was a significant interaction with a stronger association in the low transmission HZ. Insecticide-treated net (ITN) use was associated with a lower risk of malaria infection among children aged six to 59 months in the high transmission settings. Similar estimates were found in children over five years and the lower transmission HZ but the associations there were not significant. No evidence was found of a difference in these associations by strata. The risk of anaemia was found to decrease with increasing age, and to increase with malaria infection and reported fever among children aged six to 59 months. However, ITN usage did not show evidence of protection against anaemia. Low socioeconomic status was associated with malaria in high transmission settings in children aged six to 59 months and anaemia in low transmission settings.
The aim of the second part of this thesis was to demonstrate the operational feasibility of introducing injectable artesunate in the DRC as the preferred treatment for severe malaria, to provide a national cost estimate and to assess the acceptability of the new drug among health-care providers and patients. Furthermore, to assess the potential risk of delayed anaemia in patients, haemoglobin (hb) measurement was included at follow-up visits scheduled at days 14, 21 and 28 after treatment with injectable artesunate had been received.
In Chapter 5 we compare the implementation of injectable quinine and injectable artesunate in patients aged two months and older, through the evaluation of key components before (IV quinine) and after (IV/IM artesunate) the introduction of the new regimen. The time to discharge was lower in the artesunate compared to the quinine group. Similarly, the interval between admission and the start of intravenous treatment and the parasite clearance time were lower in the artesunate group. The overall staff pre-administration time and the personnel time spent on patient management were also lower in the artesunate group. In hospitals and health centres, the mean total cost per patient treated for severe malaria was also found to be lower with injectable artesunate.
Chapter 6 discusses a sub-study, conducted within the MATIAS study, to assess the potential risk of delayed anaemia secondary to injectable artesunate in patients two months and older, through the measurement of hb levels at follow-up visits at days 7, 14, 21 and 28. Although the study was limited in its design (lack of follow-up information, no additional markers of haemolysis), we observed a decrease in hb levels in 23 (11.4%) out of 201 patients (out of 350, 57.4%) with complete hb measurements, from days 7 to 21. Of these 23 patients, five (2.5%) experienced a decrease in hb levels below 5 g/dl at at least one of the follow-up visits. At the day 28 clinical assessment, hb had recovered in all patients. These results point to the need for additional research to better understand the magnitude of delayed anaemia in African children.
In the last step (Chapter 7), qualitative methods were used to investigate the feasibility of implementing injectable artesunate from the perspective of health-care providers, as well as the acceptability of the new versus the old treatment from the perspective of both health-care providers and patients/caretakers. It was subsequently found that the use of artesunate was perceived to be easier by the health-care providers, with 75% of them reporting greater ease of use and preparation compared to quinine. Satisfaction with the injectable artesunate was high among both health-care providers (61.3%) and patients/caretakers (96.7%). Altogether, our work documented the feasibility, acceptability, greater operational simplicity and lower cost of injectable artesunate in the DRC, hence supporting its national deployment.
In conclusion, this thesis provides the first comprehensive map of malaria risk in Kinshasa and an overview of the state of malaria control activities. At the same time it allows for the identification of the health areas where malaria control interventions should be prioritised.
Furthermore, this thesis shows that introducing injectable artesunate in the routine care in the DRC is feasible and highly accepted by both health-care providers and patients/caretakers, thus providing the basis for practical recommendations for its rapid deployment within the country.