INTRODUCTION

Malaria is a widespread disease throughout the world and especially in tropical and subtropical regions. In Peru, the cases represent 6% of the total for all of America. In 2021, the majority of cases occurred in Loreto (84.6%), Amazonas (9.8%), Junín (3.4%), and San Martín (0.8%)¹.

In particular, native communities are the most affected. These populations lack basic services (such as electricity or drinking water) and the main means of transportation is by the river. The province of Condorcanqui, on the northeastern side of the Amazon region in Peru, has more than 300 native communities and 42,700 inhabitants, with a majority population of the Awajun and Wampis ethnic groups. Here, malaria is endemic and P. vivax is more prevalent than P.falciparum infections. Between 2015 and 2018, only four imported cases of P.falciparum were reported. In 2020, an outbreak of P. falciparum, increased the risk of malaria severity and mortality². On the other hand, COVID-19 has had the considerable transmission in these populations, with a high cumulative incidence of 63.84/1000 inhabitants and a much lower mortality rate (0.95%) than the national average³.

Despite the possible concurrent infection of COVID-19 and malaria, little is known about the clinical course of coinfected patients. Malaria-induced immunomodulation has been shown to have a protective effect against severe manifestations of respiratory viral infections⁴. A study in Kenya showed that children hospitalized with a diagnosis of Influenza and Malaria were less likely to progress to respiratory distress than those with only influenza⁵.

Furthermore, co-infection was found to suppress the production of pulmonary cytokines and decrease the recruitment of immune cells to the lung⁶. The impact of malaria on clinical outcomes of COVID-19 has remained unaddressed by longitudinal studies.

In this article, we present a preliminary analysis of the epidemiology of malaria in the native communities of Condorcanqui, Amazonas, Peru, and assess the impact of the COVID-19 pandemic during the year 2020. This is the first study to describe the behavior of COVID -19 in an endemic area for malaria. Finally, we suggest a syndemic approach and additional studies to learn more about the effect of malaria and other tropical infections and their relationship with respiratory infections such as COVID-19.

METHODS

RESULTS

The descriptive analysis based on the information collected from the DIRESA-Amazonas open databases shows that during 2020 in the native communities located along the Santiago River, the transmission of the SARS-CoV-2 virus occurred in a population affected by malaria. Thus, 1,547 cases of malaria (97% due to P. vivax) and 5,968 cases of COVID-19 were reported in Condorcanqui (Figure 1, 2A).

Although they are official data, the restrictions caused by the state of emergency and the limited access to the communities could have caused the data to be underestimated. Santa María de Nieva is the capital of the province of Condorcanqui. In this city alone, 1,792 cases of COVID-19 were reported, with the rest of the cases being distributed among the other districts of the province. However, the communities of the Río Santiago district were affected by both Malaria and COVID-19 diseases (Figure 1).

Figure 1 COVID-19 and malaria in 54 localities in the province of Condorcanqui and its capital Nieva during 2020 

Nieva reported the highest number of COVID-19 cases with a total of 1,782 in 2020. COVID-19 cases on a red scale and malaria cases on a blue scale.

In 2020, the largest report of malaria cases occurred in the first 10 weeks and coincides with the active search for outbreak investigation where the re-emergence of P.falcip arum after 13 years. While the peak of COVID-19 cases was reported between weeks 25 and 30.

The decrease in the reporting of malaria cases during a state of emergency shows how malaria surveillance was affected (Figure 2A). As for the age group most affected by malaria, it was children under 11 years of age (48.4%) and for cases of COVID-19, it mostly affected adults between 30 and 59 years of age (62.3%) (Figure 2B).

Figure 2 COVID-19 and malaria in Condorcanqui. 

In order to measure the association between previous malaria infection and COVID-19 symptoms, an odds ratio analysis was applied. It was found that having previously suffered from malaria is significantly associated with the presence of COVID-19 symptoms such as fever, cough, sore throat, and shortness of breath.

However, regarding hospitalization or death from COVID-19, no significant association was found for these patients. Likewise, no significance is observed with symptoms such as chest pain or abnormal sounds in the lungs (Figure 3).

Figure 3 Odds ratio analysis. Risk of symptoms in cases of COVID-19 with a previous infection with malaria. Significant factors are in pink. 

In the relationship between recurrent malaria infections and COVID-19 symptoms, no statistical significance was found either. Finally, four people were diagnosed with malaria and COVID-19 in a period of fewer than 30 days. They did not present severe symptoms of COVID-19 and recovered without requiring hospitalization.

DISCUSSION

By 2022, in America, Peru ranks fifth in a number of confirmed infections by Sars-COV-2 with 3,581,524 cases, while Peru ranks second in a number of deaths with 213,205¹¹.

The north-eastern region of the country is home to around 210,000 natives of different ethnic groups. These communities often live in isolation and in conditions that make them vulnerable to various tropical communicable diseases and currently to COVID-19¹². During the pandemic, worldwide, the focus of attention was on COVID-19, so efforts to cut community transmission caused the neglect of other diseases such as malaria, accentuating the problem in endemic countries, such as in many countries of Africa^13,14and in Peru¹⁵.

After Iquitos, Amazonas is the second region with the most cases of malaria, mainly concentrated in the district of Río Santiago, province of Condorcanqui. This behavior has been evidenced since 2010 due to the transmission of P. vivax infections P. falciparum in the region². Although it is possible that the restrictive measures due to the pandemic affect the real impact on malaria transmission, an underestimation of the situation cannot be ruled out, due to the reduction of control measures and a consequent resurgence of malaria or expansion to other bordering areas such as Amazon.

As reported for Iquitos, where there is a notable reduction in the number of cases after the intervention by the Ministry of Health's "Malaria Cero" program¹⁵. Malaria circulation could increase susceptibility to COVID-19 disease and affect morbidity and mortality rates.

However, there are reports of the importance of the balance of the immune response against infections, and the possibility that the preparation with Plasmodiummay has favorable effects.

It has recently been reported that the immune response that appears during malaria infection could protect against Sars CoV-2 infection, and decrease the risk of severe COVID-19^16,17,18. Likewise, co-infection with Plasmodium spp could suppress the production of pulmonary cytokines and decrease the recruitment of inflammatory cellular components to the lungs^4,5.

In the analysis carried out in the province of Condorcanqui in Amazonas, Peru, we found that in the communities of the Rio Santiago district, where the majority of malaria cases occur in the region, they have also reported cases of COVID-19.

Interestingly, reported Malaria cases primarily affect children under 11 years of age, while COVID-19 cases affect adults. This is due to the fact that children with COVID-19 produce a rapid and effective immune response to the virus, with the majority of cases being asymptomatic.

This could be due to the low immune status of children against malaria, while more is known about the immunological susceptibility of adults and older adults against COVID-19. Among the patients who reported a previous malaria infection, no cases of death were reported and no significant association was found with hospitalization or with severe symptoms of the disease.

However, there is an association between malaria infection and recurrent symptoms of COVID-19 (fever, chills, cough, sore throat, and shortness of breath), suggesting that patients from these native communities who have had at least a case of malaria, when sick with COVID-19 they may report symptoms compatible with mild or moderate COVID-19, without evidence of severe COVID-19 or death. In this sense, DIRESA reported for Rio Santiago during 2020, 839 cases of COVID-19 and 8 deaths (lethality of 0.95%)¹⁹.

Although one of the limitations of the study is the inability to associate co-infection with malaria in the 8 deaths, the low case fatality reported and our analysis suggest further research on the clinical context of patients with malaria or other infections and how they influence the pathology of COVID-19. Some researchers have proposed the term “syndemic” (syndemic) to describe the occurrence of two or more concurrent epidemics in a detrimental interaction⁽⁴⁾. For this reason and due to the importance that malaria represents for low- and middle-income countries, more studies are required to determine the implication of these co-infections, especially in endemic populations, either to determine the types and quality of antibodies, investigate the regulation of cytokines or behavior of T lymphocytes, or about the knowledge of traditional medicine that these communities safeguard.

Finally, our preliminary analysis reveals that recurrent Plasmodium spp are frequent in the Condorcanqui communities along the Santiago River and that a controlled study is necessary to determine if these can be considered recrudescences or relapses instead of reinfections. Furthermore, our analysis suggests that previous malaria infections could affect COVID-19 symptomatology, highlighting the importance of an ongoing monitoring and surveillance program for malaria to avoid potential syndemics with COVID-19.