Background
Malaria caused by
Plasmodium vivax spans the greatest geographic range [
1]. Worldwide infections of
P. vivax are estimated between 130 and 390 million, with 2.6 billion individuals living at risk of infection [
1,
2]. Severe and complicated malaria is generally caused by
Plasmodium falciparum; however, an increasing number of
P. vivax cases with severe manifestations have been reported recently [
1,
3]. It should also be noted that some researchers have cited cases of persons with malaria who do not present the typical symptoms caused by infection with
P. vivax becoming asymptomatic patients [
4‐
10].
The first cites of malarial disease in Argentina occurred between the end of the 19th Century and the beginning of the 20th Century and included reports on the geography of the disease within the country [
11], the presence of both gametocytic and zygotic forms of
Plasmodium parasites in
Anopheles mosquitoes [
12], and the parasitological, epidemiological and entomological conditions of malaria in north-western Argentina, recognizing the presence of “tropic malaria” (produced by
P. falciparum), a “tertian malaria” (produced by
P. vivax) and a “quartan malaria” (produced by
Plasmodium malariae), with all types co-existing at the same time [
13].
Plasmodium vivax was the only malaria parasite reported in the north-west region of the country since the 1970s [
14‐
19]. Positive testing of blood samples for
P. vivax was due to active searches for sick people conducted by technicians of the Ministry of Health of Argentina.
Anopheles pseudopunctipennis is the main malaria vector in north-western Argentina [
14‐
16]. Malaria caused by
P. vivax and transmitted by
A. pseudopunctipennis is much more benign compared to infections caused by other malarial parasites; commonly observed manifestations include intermediate episodes of fever and chills.
Nematodes that cause filariasis have been reported throughout the tropical regions of the world [
20‐
22]. Generally, they are found accidentally when patients with symptoms of malaria visit the physician and thick and thin blood smears reveal the presence of
Plasmodium parasites with the larval forms of the nematodes called microfilaria. The presence of microfilaria infection in Argentina was recognized by malaria surveys in the north-western region of the country [
23], with the species
Microfilaria tucumana first described [
24] followed by
Microfilaria dermaquayi[
13,
25], a homonym of
Mansonella ozzardi[
26], being described later. The high prevalence in the Tucumán, Salta, and Jujuy provinces in north-western Argentina were reported by Mühlens
et al.[
13].
Mansonella ozzardi is endemic to the subtropical mountainous rainforest in the north-west region of Argentina [
27]. In this region, transmission is related to ceratopogonid midges,
Culicoides lahillei (main vector) and
Culicoides paraensis (secondary vector) and black flies,
Simulium exiguum (secondary vector) [
28]. Although
M. ozzardi is considered a relatively non-pathogenic filarial parasite, its pathogenicity is still a controversial subject requiring further study [
29,
30]. There is currently a lack of information about this disease, with the latest reports being those of Krolewiecki
et al.[
31] and Veggiani
et al. (personal communication) on the influence of ivermectin in patients and the epidemiology of the disease in Argentina, respectively. A high prevalence of filariasis (20.7%) was observed in one locality in the north-west region of the country [
27]. A similar result has been observed (a prevalence of 26.0%) in a rural community in the Bolivian Chaco region [
32].
Plasmodium nematodes co-infection was widely reported in America [
33‐
37]. Aráoz and Biglieri [
23] and Rosenbusch [
25] have cited numerous cases of people with microfilaria co-infection in the north-west region of Argentina. Later, Mühlens
et al.[
13] reported the finding of this microfilaria in blood smears with malaria parasites in the same region. Since this last paper, there were no reports of co-infections of
Plasmodium microfilaria in the country; thus, the current study is the first report of the presence of
P. vivax and
M. ozzardi after several decades.
According to the World Health Organization (WHO) [
19], Argentina is involved in the National Pre-Elimination Programme of Malaria with the aim to focus on the active detection of autochthonous cases. It has implemented several studies where the existence of co-infection of
P. vivax with others parasites is considered important.
The present study aimed to detect co-infection with P. vivax and M. ozzardi in patients with a diagnosis of malaria who received anti-malaria treatment with primaquine-cloroquine in north-western Argentina from 1983 to 2001.
Discussion
In north-western Argentina, the diagnosis of malaria is directly related to intermediate fever episodes, but the diagnosis of filariasis is a consequence of blood smear analysis for malaria. The first reports of malaria in Argentina showed that the disease was the most important parasitic disease of the time, not only because of the number of cases reported but also because of their wide geographical distribution across the country. The majority of malaria reports cited
P. vivax as the most abundant parasite that appeared in blood smears, as well as the high prevalence of co-infection with
M. ozzardi[
26].
After the malaria eradication programme in 1959, malaria cases decreased considerably before a resurgence in disease in 1967 [
38]. Since 1967, the active search for malaria patients by technicians of the Ministry of Health of Argentina, with adequate primaquine/chloroquine treatment, and the spraying in dwellings of the mosquito vector with 2.5% deltamethrin has reduced the incidence of malaria cases. The latest research indicates that the few autochthonous malaria cases were positive for
P. vivax. This species seems to be the only parasite incriminated in malaria in human beings, and the most tolerant to the climatic and environmental changes, enabling its survival during this time in north-western Argentina [
17‐
19,
39]. The number of malaria cases with
M. ozzardi co-infection also decreased dramatically during the last few decades, with the latest studies reporting high prevalence of microfilaria only within isolated communities, but affecting both sexes and with increasing infection rates progressively with increasing patient age [
27,
40‐
42].
Acknowledgements
We want to thank F Vianconi, N Vianconi, E Laci and J C Hitzamatzu (Coordinación Nacional de Control de Vectores (CNCV), Ministerio de Salud de Argentina) for carried out the collections of the hematic samples. We also thank laboratory technician N García (CNCV, Ministerio de Salud de Argentina) for her invaluable help in confirmation of parasite identification.
This work was supported by Grants (PICT 01–04,347; PICT 02–12,605) from Agencia Nacional de Promoción Científica y Tecnológica (FONCyT), Consejo Nacional de Investigaciones Científicas Técnicas (CONICET), Consejo de Investigaciones de la Universidad Nacional de Tucumán (CIUNT), Coordinación Nacional de Control de Vectores (Ministerio de Salud de la Nación) and Fundación Roemmers of Argentina to MJDJ.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
MJDJ is a Research Assistant of CONICET and a Consultant of the Ministry of Health, this research is part of the studies that are ongoing in the country included in the Malaria Pre-elimination Phase according to the World Health Organization. She conceived the study and drafted the manuscript. CAVA checked all the human samples and also prepared the manuscript. ESO and GBG reviewed the literature and references. MOZ as a part of Ministry of Health of the Argentina contributed with the human samples to be analysed and participated in the edition of the manuscript. All authors read and approved the final manuscript.