INTRODUCTION
Malaria is a major public health problem worldwide. It is caused by a protozoan parasite Plasmodiumspecies of which 5 major species are known to cause human infection such as Plasmodiumfalciparum (P. falciparum), Plasmodiumvivax (P. vivax), Plasmodiummalariae (P. malariae), Plasmodiumovale (P. ovale), and Plasmodiumknowlesi (P. knowlesi).[1] Malaria is known to be a human disease since time immemorial. The first description of the disease was found in the Chinese medical records of 2700 BC. In the ancient times, the illness was attributed to supernatural forces and angry deities, followed by the belief that it is caused by inhalation of vapors from the swamp.[1] It was a French army doctor Charles Louis Alphonse Laveran, who discovered malaria parasites in the blood of infected patients (1880), for which he was awarded the Nobel prize. Later in 1897, Surgeon-Major Ronald Ross of the British Indian Medical service discovered the life cycle of malarial parasites inside the mosquito.[2] Since then the fight against malaria has started, which led to various practical proposals for the interruption of transmission, appropriate diagnosis, and treatment of malaria, which witnessed several ups and downs. At present, according to the latest malaria report of 2021, there are 85 malaria-endemic countries, with 241 million cases in the year 2021 globally. In this, 95% of the burden is accounted from the WHO African region. The WHO South East Asian countries accounted for 2% of the global burden, among which 83% of cases are contributed from India (WHO, 2021). The trend of malaria in India has shown a lot of variations. India witnessed a peak of malaria in 1950s with a burden of 75 million cases and 0.8 million/year mortality. The National Malaria Control Programme came into force in 1953, following which there was a massive reduction of cases to <50,000 with no mortality (1961). Malaria was thought to be on the verge of eradication, but it made a comeback with 6.45 million cases in 1976.[3] Various factors are thought to have caused this resurgence such as urbanization and subsequent favorable environment for the breeding of the vector, disruption of the control program due to war or conflicts in the country, emergence of resistance to insecticides among the vectors, drug-resistant parasites.[4] A modified plan of action was introduced in 1977 which was not of much benefit, reintroduced in mid-1980 followed by in 1995. Since then the trend of malaria has shown a gradual decrease in India. Currently, the National Framework for Malaria Elimination introduced in 2016, intends to interrupt the transmission of indigenous cases and achieve malaria-free certificate by 2030.[4] The two major species causing malaria in India are P. falciparum and P. vivax and their distribution varies from place to place.[5] There are no many studies exploring the local epidemiology and burden of malaria in South India, especially in Puducherry. This study intends to look at the trend of malaria in Puducherry, a coastal Union territory in the Southern part of India, over a period of 7 years, the distribution of P. species over the years, and the influence of demographic characters and climate to the disease.
METHODOLOGY
A retrospective record-based observational study was conducted in the Department of Microbiology, of a Tertiary Care Health Centre, Puducherry. All the blood samples which were positive for malaria by any of the diagnostic methods, from 2015 to 2021 were included in the study. The demographic details as well as the reports of the laboratory tests performed for malaria were collected from the records retrospectively and analyzed. All the received samples from the malaria suspected patients were routinely subjected to immunochromatographic test detecting the Plasmodiumspp. Antigen (lactate dehydrogenase/aldolase) and P. falciparum specific antigen (histidine-rich protein 2 [HRP-2]) and peripheral blood examination by thin smear, thick smear, quantitative buffy coat examination. All these were screened by 2 independent persons before confirming. In the last 3 years of the study period, an automated instrument Parasight™ platform was used in addition to the above-mentioned methods.
RESULTS
A total of 14,888 samples were received over the 7-year study from malaria suspected cases, of which 257 samples (1.73%) were tested positive for malaria by either/both the laboratory diagnostic method used. Among this majority were P. vivax (161/257, 62.65%), followed by P. falciparum (80/257, 31.13%). Species identification could not be done in 16 samples (6.23%). Out of the 257 malaria-positive samples, 215 were positive by both rapid card test as well as peripheral blood examination by conventional microscopy or automated Parasight™ platform, 38 samples were positive only by rapid card test, out of which 22 were positive for the HRP-2 antigen, thereby reported as P. falciparum. Four samples were negative by rapid card test but positive for P. vivax by peripheral blood examination. The year-wise distribution of the total number of samples tested, total number of positives, and the P. species distribution of each year are depicted in Table 1. Males (75.88%) were predominantly affected, with a male-to-female ratio of 3.15. The age of the patients ranged from 3 months to 75 years, with the major age group affected being 21–40 years (144/257, 56.03%). Extremes of age were comparatively less affected, 14/257 (5.45%) were children ≤10 years, among which 10 children were <5 years old. Four among them were infants. The elderly population (>60 years) affected were also meager, 11/257 (4%). The trend of occurrence of malaria cases based on the age over the years is depicted in Table 2. The distribution of different P. species based on various age groups and gender are depicted in Table 3. Although P. vivax was the predominant species affecting all the age groups, in consistence with the general trend, an equivalent number of P. falciparum was observed among the children (≤10 years). Among the 4 malaria-positive infants, 3 were caused by P. falciparum and one by unidentified nonfalciparum species.
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Table 1: The year-wise distribution of the total number of samples tested, total number of malaria-positive samples, and the Plasmodium species distribution
Table 2: Age group-wise distribution of the malaria cases over the years
Table 3: Distribution of Plasmodium species based on the different age groups and gender
The prevalence of occurrence of malaria cases over different seasons of the year was analyzed. A maximum number of cases were observed in the monsoon season (June–September) followed by the postmonsoon season (October–November). The seasonal trend of the occurrence of malaria cases each year is depicted in Figure 1. The distribution of the various P. species over the different seasons was analyzed and depicted in Figure 2.
Figure 1: The seasonal trend of malaria over the years
Figure 2: P.species distribution over the seasons. P.falciparum: Plasmodium falciparum, P.vivax: Plasmodium vivax, PS: Plasmodium species
DISCUSSION
Malaria is a major vector-borne disease in India for the past several years. India has witnessed a tremendous decline in the number of malaria cases over the past two decades. There was a decline of 71.8% in cases and 73.9% drop in mortality over the years 2000–2019.[6] In spite, India remains the greatest contributor of cases in the WHO South East Asian region (WHO, 2021). The diverse geography, human genetic diversity, and climatic conditions in India have been advantageous for the survival of parasites and its vectors.[7] India possesses a diverse malaria vector habitat of approximately 58 species of anopheline mosquitoes.[5] The trend of malaria prevalence has shown a fluctuating course over the years in our study. There was an increase in burden from 2015 to 2018 followed by a decline in 2019. A tremendous decline is observed in the year 2020, but this could be attributed to the effect of COVID-19 pandemic and the subsequent lockdown in the country. As per the latest malaria report of 2021 by the WHO, the incidence of malaria has increased globally from 56 in 2019 to 59 in 2020 (WHO, 2021), contrary to the results of this study. This increase in incidence could be attributed to the interruption of health-care services which were skewed toward the diagnosis, treatment, and control of the COVID-19 pandemic. However, the Indian statistics shows that there is a decline of 45.08% of cases in 2020 compared to 2019, contrary to the global scenario. Overlapping symptoms of COVID-19 infection and malaria could have led to underreporting of cases which resulted in this low number of cases.[6] In a systematic review and meta-analysis done to estimate the prevalence of malaria in COVID-19-infected patients, has shown a pooled prevalence of 11% co-infection between COVID-19 and Plasmodiumspp. Majority of the cases were reported from Nigeria followed by India.[8] Moreover, malaria and COVID-19 co-infections are found to be associated with a severe degree of coagulopathy and severe disease, given the procoagulant state contributed by both the infections.[9] Another interesting feature observed is low prevalence of COVID-19 in malaria high-endemic areas such as African countries, where COVID transmission is considered to be relatively less. Variable factors like polymorphisms associated with angiotensin-converting enzyme 1 and 2 in malaria patients, which also act as a receptor for COVID-19 virus, anti-Glycosylphosphatidylinositol (GPI) antibodies produced in malaria patients conferring protection against COVID-19 virus, prophylactic and therapeutic effect of hydroxychloroquine and chloroquine on COVID-19 infections are proposed to be the reason.[9] In our study, there was no co-infection with COVID-19 infection detected in any of the malaria-positive patients.
P. species distribution varies greatly from place to place in India. P. falciparum and P. vivax are the two most common species known to cause malaria in India, followed by P. malariae reported mainly from the Eastern part of India. Reports of P. ovale are rare and P. knowlesi even rarer.[5]P. vivax was the predominant species historically, but the incidence of vivax malaria had shown a decreasing trend in India.[3] In 1985 the ratio of P. falciparum to P. vivax was 0.41 which increased to 1.01 in 2010. Still, 47% of vivax malaria cases reported globally are from India.[4] In our study, the overall ratio of P. falciparum to P. vivax is 0.49.[5] Identification of P. species is important from the treatment point of view as well as the implementation of control measures. In addition, P. vivax which was earlier thought to cause benign malaria are now known to cause serious manifestations as well.[10] The frequent relapses encountered due to the persistence of hypnozoites also pose a challenge in therapy as well as control programs.[11] Other than P. falciparum and P. vivax, no other species or mixed infections were detected in our study. The use of only conventional methods for the diagnosis of malaria during most of the study period could be a reason for this. In a study conducted in a high malaria burden state in India has shown that the sensitivity of detection of P. falciparum is >80% using peripheral blood smear examination and rapid diagnostic test compared to the molecular method, but for the identification of vivax malaria as well as mixed infections, the sensitivity was very poor using nonmolecular methods - 57% and 18% respectively.[12]
On analyzing the age and gender distribution of malaria, majority of the population affected were young adult males overall as well as in each year. This is in concordance with other reports.[13–15] The male preponderance of infection could be due to various factors such as difference in vector exposure risk, different travel habits, distinction in mosquito attraction, hormonal or host genetic factors.[16] Children are considered to be the most vulnerable population owing to their immature immune system and are prone to develop severe malaria and subsequent developmental and cognitive impairment.[17] Young infants <6 months of age are at lesser risk, due to the protective maternal antibodies passed on. Six months to five-year children are considered to be at maximum risk of developing severe malaria as well as its complications.[18] But in our study, only 3.5% of the affected population consisted of children of age from 6 months to 5 years. On analyzing the species distribution gender wise, there was no variation from the general trend. However, the distribution of P. vivax and P. falciparum was found to be equal among children <10 years. The causative agents in majority of the infants were P. falciparum.
Vector-borne diseases are dependent on climate variations. Therefore, weather factors such as optimum rainfall, temperature, and humidity are important determinants of malaria transmission.[19] The minimum temperature beyond which P. vivax fails to develop inside the anopheline mosquito is 14.5°C–16.5°C, whereas for P. falciparum it is 16.5°C–19°C. However, as the temperature rises to 20°C–30°C, the duration of the lifecycle of the Plasmodiumspp inside the mosquito decreases. Similarly, at this temperature, the rate of blood digestion as well as reproductive development of the vector also occurs in a faster pace resulting in frequent blood meals and wide transmission of infection. However, if the temperature is increased beyond 32°C–39°C, it is detrimental to the survival of the mosquito.[19] Like wise, a moderate amount of rainfall is beneficial to the breeding of mosquitoes whereas heavy rainfall/flooding can lead to washing away of the mosquito larva.[20] These factors vary from place to place. Therefore, it is essential to understand the malaria transmission dynamics according to seasons or climatic conditions of a particular area, which will help in anticipating the burden of cases and to adopt appropriate control measures. In our study, peak malaria cases were noted in the monsoon season in all the years except in 2020, where the data may be a misrepresentation of the actual burden due to the COVID pandemic. This was in concordance with many other studies from India.[21,22] In a study conducted in New Delhi, it was noted that P. falciparum malaria peaked during the post-monsoon season, whereas P. vivax peaked during monsoon season.[15] However, in our study, there was no such distinction observed with respect to the difference in species.
CONCLUSION
Knowledge on the precise burden of the disease in each region, as well as the understanding of the determinants of disease risk is important to reach the goal of malaria elimination. Even though India has attained progress in reducing the case burden and mortality in the past two decades, unfortunately, a huge gap exists between the true case scenario and the one which has been represented. For example, a surveillance-based estimation of the malaria burden by a nodal research body in 2015/2016 India, has revealed that the estimated malaria burden in India is four times higher than that reported by the national program.[23] Overall, the trend of malaria in our area shows a declining pattern, but the possibility of underreporting of cases cannot be ruled out.
Ethics clearance
The study was approved by the institute ethics committee of Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, JIP/IEC/2018/397.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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