Background
Although significant advances have been made towards malaria elimination in several endemic countries, malaria remains a significant public health problem [
1]; the World Malaria Report 2018 estimated that the global malaria burden was around 219 million reported cases and 435,000 deaths worldwide [
2]. Besides, the situation in the Americas presents further challenges for control and malaria elimination, given the high proportion of cases of
Plasmodium vivax infection [
3]. Particularly in Colombia, the number of malaria cases officially reported in 2018 was 63,143; with Chocó, Nariño, Cordoba, and Antioquia, the departments with the highest number of malaria cases (27.0%, 20.6%, 15.6%, and 8.8%, respectively) [
4].
In the Americas, the indigenous population is considered one of the most vulnerable groups to suffer from malaria. The elevated vulnerability is not solely explained by the fact that individuals live in areas with a high
Anopheles bite exposure, but also because they have high poverty rates and little to no access to diagnostic and treatment services [
5]. Information about health conditions of these populations is not always collected, so their risk is not well understood, but in general, it is known that indigenous communities have poor health indicators as compared to non-indigenous populations, including the morbidity and mortality due to transmissible diseases, child undernutrition, infant mortality rates, and years of potential life lost [
6].
In Colombia, 3.4% of the population is indigenous, and there are around 710 indigenous communities located in 27 departments [
7], many of them living in malaria-endemic regions. Between 2009 and 2014, 75.8% of the Colombian indigenous population was at risk of being infected by any microorganism, where
Plasmodium spp. caused 46.7% of the total infections [
8]. Unfortunately, there are few studies in the indigenous population, so that the risk is not well understood. Only eight of the 21 malaria-endemic countries of the Americas Region reported cases of ethnic groups and indigenous peoples in 2014 [
5]. Without adequate data, it is difficult to follow up on malaria trends, recognize the risk factors in these communities, and establish malaria control strategies. In Colombia, the majority of malaria cases occur at the Pacific coast and Amazon region and affects mainly Afro-Colombian and indigenous populations [
1,
9]. In 2018, 62,141 malaria cases were reported, of these, 14,714 (23.7%) were in the indigenous population [
10]. Autochthonous malaria transmission has also been reported mainly among indigenous communities in Chocó (Pacific coast) [
11].
Antioquia was one of the departments with the highest malaria prevalence in Colombia for many years. However, the cases have decreased markedly from 20,511 in 2008 to 4971 in 2017 [
12]. This could be explained by the several malaria control strategies implemented between 2007 and 2010, such as vector control activities, strengthening of diagnosis network, distribution of insecticide-treated bed nets (ITNs), and chemoprophylaxis. Despite this reduction, a significant proportion of malaria cases is related to gold-mining activities, which play an important role in the maintenance of malaria transmission and are considered to be an important barrier to malaria elimination [
13]. Like miners, indigenous populations are also considered a significant reservoir of malaria transmission. Unfortunately, these populations have been scarcely studied, and there is not enough information about the
Plasmodium prevalence in them.
One of the main challenges of malaria control programs is the early diagnosis and treatment, not only for symptomatic but also for asymptomatic infections, which represent a silent reservoir of parasites [
14]. Compared to patients with acute malaria disease, who generally seek treatment in health facilities, people with low-density infections that often are asymptomatic, do not seek medical attention or anti-malarial treatment [
15,
16]. These infections can contribute to local transmission in an endemic region [
17]. It has been reported that in Peru, 50% of
Plasmodium falciparum and 22% of
P. vivax asymptomatic infections can harbor gametocytes [
18]; similarly, in Colombia, 57% of the samples from asymptomatic volunteers were infective to mosquitoes [
19].
In Colombia, the prevalence of low-density infections by
Plasmodium has been previously explored, finding frequencies from 2 to 15% in general population, with most of the infections being submicroscopic [
20‐
22]. In pregnant women frequencies reached from 1.1% in peripheral to a 2.1% in placental blood [
23]. In the Urabá region located in Antioquia-Colombia, the prevalence of asymptomatic infections detected by PCR was 2.6% [
24]. Together these studies suggest that in low endemic settings such as Colombia, molecular tests are more useful than microscopy to detect this kind of infection [
25‐
27].
Most of the studies about low-density infections in Colombia have been conducted in the general population and pregnant women, but there are not reports in special populations such as indigenous people. This study aimed to determine the prevalence of microscopic and submicroscopic Plasmodium infections in indigenous and non-indigenous communities in two malaria-endemic areas in Antioquia-Colombia and to explore the associated factors to the Plasmodium infections.
Discussion
This study evaluated the prevalence of microscopic and submicroscopic
Plasmodium infections in indigenous and non-indigenous communities from Antioquia, Colombia, and its associated factors, to describe the distribution of disease prevalence among heterogeneous populations; this knowledge is necessary to implement proper control strategies for each context [
35]. We found that the prevalence of
Plasmodium infections it was increased 12-fold in indigenous communities as compared to non-indigenous communities in both municipalities. Even more, all infections in El Bagre were detected in indigenous communities (11/11), and most of them were asymptomatic and submicroscopic (9/11). On the contrary, most of the infections in indigenous communities in Turbo were symptomatic and microscopic (84.2%).
It is known that malaria transmission in Colombia varies among the endemic regions [
35]; in this way, these findings could be explained by differences in malaria profiles in each municipality. Although the general prevalence of malaria in Antioquia has decreased in recent years, the number of cases in El Bagre has been higher than in Turbo (from 190.45 cases/1000 people in 2007 to 21.29 cases/1000 people in 2017 in El Bagre and from 61.53 cases/1000 in 2007 to 0.77 cases/1000 people in 2017 in Turbo).
Most of the malaria cases were caused by
P. vivax and it is well known that the PQ used for the
P. vivax treatment can induce haemolytic crises in individuals with glucose 6-phosphate dehydrogenase (G6PD) deficiency. The G6PD deficiency is distributed worldwide, however, its frequency varies among regions and ethnic groups. A previous report in malaria-endemic areas of Colombia located on the Pacific coast, found a frequency of G6PD deficiency of 6.56% [
36], studies in indigenous populations (Amerindian) are lacking. Considering the high number of
P. vivax infections found in these populations, there is a need for further evaluation of the frequency of G6PD deficiency in malaria-endemic areas in view that the primaquine treatment (14 days) is required for the radical cure.
As previously reported, malaria immunity is determined by previous
Plasmodium exposure, where an anti-disease immunity is first achieved, resulting in a reduction of severe malaria and mortality. Then, an anti-parasitic immunity is slowly acquired and confers protection against high parasitic densities, which in turn protect against the severe disease [
37]; this could explain the highest prevalence of submicroscopic infections in El Bagre, where 50.3% of individuals had had more than one malaria episode over life compared to 35.8% in Turbo (Additional file
1: Table S1). Nevertheless, it was not found an association of this variable with the
Plasmodium infections using a GEE analysis. However, a previous study in Nariño- Colombia showed that having suffered from more than one malaria episode was associated with an increased risk of having asymptomatic infections (aOR 2.4, 95% CI 1.1–5.4) [
22]. These differences could be explained because this model included not only asymptomatic but also symptomatic infections.
Household factors are also associated with malaria risk [
38]. It was observed that having no access to electricity was associated with an increase in the malaria rate. These findings are in agreement with previous studies that reported that the poorest households had a 29% greater risk of microscopic parasitaemia compared to the poorest houses (aRR 1.29; 95% CI 1.07–1.55) [
39]. Additionally, lack of household electricity increased the childhood mortality in Rwanda, including malaria mortality (aOR: 1.4, 95% CI 1.0–1.8) [
40]. The above is important because housing quality can affect malaria risk through its effect on house entry of the malaria vector [
39].
Taken together, the individual and housing characteristics could help to understand why the indigenous population has a higher prevalence than its counterpart, the non-indigenous population does. Ethnicity is an important determinant of health conditions, influencing the morbidity and mortality rates in different ethnic groups and interfering with access to health services for some populations [
41]. In Colombia, the exclusion of indigenous people is reflected in poverty rates, lack of land and employment, school desertion, unsatisfied basic needs, a higher prevalence of transmissible diseases and limited access to health services compared to the general Colombian population [
42]. Regarding this last point, it was found that the indigenous villages were farther from the health services (1 to 2 h by motorcycle) compared to the non-indigenous villages, and the road conditions were far worse. Furthermore, the indigenous population frequently lives close to rainforests or wetlands where they have more vector exposure, resulting in an increased risk of getting sick with vector-borne diseases such as malaria [
8].
It is possible to suggest that the diversity of epidemiologic characteristics of malarial infection among the Colombian subpopulations account for an ideal environment for parasite evolution. In this environment, the parasite can interact with susceptible populations from different ethnicities and under different public health interventions [
35]. The prevention efforts should be population-specific and vary according to the individual, housing, and environmental characteristics. Given the heterogeneity of the prevalence of malaria in Colombia, it has become necessary to adjust malaria control activities according to each population and context.
Further studies are needed to evaluate the potential integration of molecular tests into the surveillance programs to promptly detect malaria infection in the community in order to contribute to the control and future elimination strategies. However, due the low prevalence of infection in this region of Colombia, there is also a need to evaluate the costs per assay comparing to conventional test, including equipment, reagents, staff, training, and maintenance in order to evaluate the cost-effectiveness of molecular test for their potential integration into surveillance strategies and explore alternatives as serological surveillance. A previous study in a low transmission setting in Indonesia, suggested that reactive-active detection of cases in the community using molecular test had high costs per individual screened, however, compared to microscopy, molecular test was most cost-effective for the detection of infections [
43]. Also, another study in a low transmission setting in Africa concludes that standards test, such as rapid diagnosis test (RDTs), are not useful to detect infections in the community and suggest that the achievement of malaria elimination may require active case detection using more sensitive point-of-care diagnostics, especially in high-risk groups [
44], that in our cases are the indigenous communities among others.
This study has some limitations. First, due to cross-sectional design, the association with malaria status should be interpreted with caution, as they do not imply causality. Second, it was no possible to analyse the risk factors for asymptomatic infections exclusively due to the low number of this type of infection. This last could, in turn, affect the accuracy of confidence intervals for some of the factors analysed due to the sample size. Third, as mentioned before, the villages in this study were selected based on the historical records of malaria cases, the distance to the urban area, and the accessibility for field staff, and a random selection of the villages included in the study was not performed. The results of this study cannot be extrapolated to the general population; nevertheless, they are useful to exhibit the problems around the asymptomatic infections in the indigenous and non-indigenous people. Fourth, considering that nowadays there are ultra-sensitive molecular tests for the detection of low-density infections, the prevalence in this study could be underestimated due to the limit of detection of the nPCR used, nevertheless, the nPCR used in this study was able to detect 1.6 times more infections than microscopy showing the presence of a significant Plasmodium reservoir in the region. At last, it is possible that other variables which were not considered in the GEE model could explain the associated factors to Plasmodium infections. Future studies are required to improve the knowledge about the risk factors of the Plasmodium infections in indigenous communities. Despite these limitations, these results are useful to understand malaria transmission in studied places and to suggest prevention efforts according to the individual, housing, and environmental characteristics.
Conclusion
This study reveals that in both municipalities, most of the Plasmodium infections were in indigenous communities. Nevertheless, the infection profile was different for each town. A substantial proportion of asymptomatic and submicroscopic carriers were detected in El Bagre, while most of the symptomatic and microscopic infections were identified in Turbo. These findings provide an understanding of the key characteristics of asymptomatic, submicroscopic, and microscopic infections in the study population: to live in an indigenous community, having had previous malaria episodes and not having access to electricity, sewage system, and water services. The current malaria control efforts could benefit from the implementation of targeted interventions in indigenous villages using molecular tests to identify submicroscopic reservoirs that could be contributing to malaria transmission, although further studies are needed to evaluate the potential integration of molecular test into the surveillance programs to promptly detect malaria infection in the community, especially in high-risk groups. Additionally, the identification of these infections not only in indigenous but also in the non-indigenous populations, as well as demographic, social and household factors related to them, could help to implement specific malaria strategies for each context.
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