Clinico-epidemiological profiles & outcome of severe malaria in children under-five in the tribal area of Kalahandi, Odisha

Malaria is one of the most common and the oldest known, life-threatening tropical diseases. Despite a substantial decrease in the global malaria burden, it still is one of the significant public health problems in Africa and South Asia1. In India, Odisha is the epicentre of malaria contributing to about 25 per cent of the total (1.5-2 million) reported malaria cases and 30 per cent of deaths due to malaria annually in India2. Despite being preventable and curable, malaria causes significant morbidity and mortality, particularly in regions with limited resources, harbouring indigenous population. In India, districts with 30 per cent or more tribal populations contribute to 46 per cent of the total malaria burden, 70 per cent of Plasmodium falciparum cases and 47 per cent of the total malarial deaths in the country3.

In recent years 2017-2019, the State Government of Odisha, following the WHO (World Health Organization) Global Technical Strategy for malaria scaled-up efforts to prevent, promptly diagnose and treat malaria with impressive results in a short span of time45. The reported cases of malaria showed a 94 per cent reduction compared to the cases reported in 2016. The launching of Durgama Anchalare Malaria Nirakaran (DAMaN) programme by the State Government effected a drastic reduction in falciparum malaria cases, but still malaria continues to persist in remote tribal pockets6.

Thuamul Rampur Block in Kalahandi district is a malaria endemic area with high malaria burden where the transmission of malaria occurs throughout the year with peaks in July to August and also in December. The highest incidence of clinical malaria is in the month of July7. Malaria is a major public health concern in this Block of the Kalahandi district.

Five species of Plasmodium are prominent including (P. falciparum, P. vivax, P. ovale (curtisi and wallikeri), P. malariae, P. knowlesi). Of these P. falciparum is known to be biggest threat to public health globally. Accounting for over 90 per cent of the world’s malaria mortality8.

Being seldom life-threatening, only a small proportion of clinical malaria cases progress towards being a medical emergency. In children aged <5 years malaria is a leading cause of death and this group has 77 per cent of all global malaria deaths910.

Despite malaria and child mortality being major public health challenges in the tribal pockets of Kalahandi district, little is reported on severe malaria from this area, where children under-five are most vulnerable. The Swasthya Swaraj Society (a not-for-profit non-governmental organization) has worked in Thuamul Rampur of Kalahandi district of Odisha since 2014 focusing on comprehensive primary health facilitated through two 24×7 primary care health facilities and is a model for primary healthcare in the tribal areas.

This study present data from these two centres on the problem of severe malaria among malaria-positive children in malaria-endemic tribal areas, its clinical manifestations, its association with undernutrition, and the outcome of prompt and complete treatment.

Material & Methods

This study was undertaken at the two Primary Health Centres (PHC) facilities of Swasthya Swaraj Society in Thuamul Rampur Block, Kalahandi district, Odisha. Ethical clearance and waiver of informed consent were obtained from the Institutional Ethics Committee of St John’s Medical College and Hospital, Bengaluru.

A retrospective review of case records of children who were admitted with severe malaria between January 2017 to June 2022 was carried out to assess the clinical and epidemiological profiles of children with severe malaria and the outcome in the two health facilities of Swasthya Swaraj Society in Thuamul Rampur Block, Kalahandi district, Odisha. These two centres located deep in the tribal area are adequately equipped and staffed to provide emergency management of common medical and paediatric emergencies in resource-poor settings. Further, Swasthya Swaraj maintains all case records in its Health Management Information System. Data are entered manually into Excel and analyzed in SPSS, Version 25.0 (IBM Corp. Release 2017, Armonk, NY, USA). All malaria cases are reported to district and State National Vector Borne Disease Control Programme (NVBDCP).

The case records of all the cases with severe malaria admitted to the two primary care facilities were reviewed by two authors (AE and VG) independently. The period of the review covered five and half years (January 2017 to June 2022). All data from participants were adequately anonymized and delinked from personal identifiers to maintain confidentiality.

Inclusion/exclusion criteria: Clinical, laboratory, anthropometric data and outcomes of all children aged 0-5 yr diagnosed with severe malaria (n=182), documented in their case sheets were included in the analysis. Eleven records were not included in the study. The reasons for exclusion were ambiguity in age, diagnosis and incomplete data. Records with incomplete documentation were also excluded. Overall, 171 records were included in the study. The age of the child was documented in the case sheets as per the parents’ estimation, correlating the age with cultural events, while some had Aadhar cards. The exact date or month of birth was not available for all the children.

Diagnostic confirmation of severe malaria documented in the case records was done based on criteria for the diagnosis of severe malaria independently by two authors (AE and VG). Severe malaria was defined as, ‘one or more’ of the criteria laid down by WHO occurring in presence of malaria infection and in the absence of an identified alternative cause11. The clinical features and laboratory findings of all the children under study had one or more of the features (including prostration, severe aenemia, jaundice, etc.) as reported earlier12. All the children diagnosed with severe malaria were admitted to the emergency care of the two primary care facilities. Of the 171 records, 165 (96%) had documented asexual parasitaemia in the peripheral smear. Parasite load was calculated following WHO guidelines13. Six children had only rapid diagnostic test (RDT), so only the parasite type was available without the density of parasitaemia.

Uncomplicated malaria was defined as malarial infection without any of the criteria of severe malaria. The uncomplicated malaria cases were treated as outpatients based on standard guidelines (NVBDCP)14.

All the children had anthropometric records of their weight, length/height and mid-upper arm circumference in their case records. WHZ (weight- for- length/ height z-score) was assessed from the WHO growth monitoring tables and was documented in their case records. This was again analyzed using WHO Anthro Software (https://www.who.int/tools/child-growth-standards/software).

Statistical analysis: Demographic features of the study group were compared with the uncomplicated malaria group using Chi-square test. The comparison of mean anthropometric records, haemoglobin values and parasitaemia of study group children was compared with that of uncomplicated malaria group (n=2541) using t-test, ANOVA and Chi-square test and binary logistic regression.

Results

In the period between January 2017 and June 2022, a total number of 4858 (1893 in 2017, 1142 in 2018, 510 in 2019, 608 in 2020, 522 in 2021 and 183 in 2022, respectively) individuals were diagnosed with malaria in the two primary health facilities based on blood smear microscopy or RDT (Figure)15. During the COVID (Coronavirus disease) pandemic of 2020-2021, no change in the trend was noticed.

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Figure

Trend of malaria and severe malaria in the two primary care health facilities in Kalahandi, Odisha from 2017-2022. source: Ref15 (Swasthya Swaraj HMIS).

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More than half of the 4858 individuals with malaria in the two Swasthya Swaraj primary health facilities, 2712 (55.8%) were children under five years. Of the total cases of malaria, the number of cases diagnosed and admitted with severe malaria during this period was 242 (4.9%), of which 171 (70.7%) were children below 5 yr (Figure). The incidence of severe malaria across all age groups over the study period was: 3.4 per cent in 2017, 3.6 per cent in 2018, 7.6 per cent in 2019, 8.5 per cent in 2020, 6.5 per cent in 2021 and 13.6 per cent in 2022 (Figure). Among these, the proportion of under-five children with severe malaria during the same period was: 70.7 per cent in 2017, 73.8 per cent in 2018, 87.1 per cent in 2019, 76.9 per cent in 2020, 50 per cent in 2021 and 40 per cent in 2022.

The severe malaria group of children who were treated in the two health facilities were predominantly from Kutia Kondh tribes (87.1%) who are listed as particularly vulnerable tribal group. Analysis of demographic data of severe and uncomplicated malaria children during the same period (Table I) showed that the median age of the study children with severe malaria was 24 months [interquartile range (IQR):16-36]. The 1-2 yr age group had a significantly high risk of severe malaria (P=0.001). Children of <2 yr of age were 1.69 times (1.24-2.31) more likely to develop severe malaria (Table II). Of the children, 57.3 per cent were male and 42.7 per cent were female in the severe malaria group, and 47.4 per cent male and 52.6 per cent female in the uncomplicated malaria group (P=0.01), unadjusted odds ratio (OR): 0.67 (0.49-0.92). The median age of the children who were treated for uncomplicated malaria during the same period (n=2541) was 36 months (IQR: 24-48).

Clinical manifestations varied in the children, and many had unusual manifestations mimicking many clinical conditions (Table III). Fever was present in all, with hyperpyrexia in five children (2.9%). Neurological manifestations were the most common, seen in 110 (64.4%), with lethargic children unable to breastfeed and/or sit up being the commonest finding. Seventy children (40.9%) presented with pneumonia with rapid breathing with or without chest indrawing and 15 (8.7%) had acute respiratory distress syndrome. Severe anaemia (Hb <5 g/dl) was present in 35 children (20.5%), adjusted OR:1.22 (0.79-1.9) (Table II). Splenomegaly was present in 101 children (59.1%). Grading of splenomegaly was not available. No child had severe hypoglycemia (blood sugar <40 mg/dl).

More than half of the severe malaria cases (60.2%) had a history of uncomplicated malaria in the past before being admitted with severe malaria. Out of these, 47 per cent had <2 episodes, 11 per cent had 2-5 episodes and 1.8 per cent (n=3) had 6-8 episodes of uncomplicated malaria. The parasite causing the uncomplicated malaria was predominantly P. falciparum (93.9%) while 1.9 per cent were mixed P. falciparum and P. vivax. Twenty-seven (18.8%) of the severe malaria cases had previous episodes of severe malaria, 24 had it once and three had it twice and recovered.

Anthropometric records and laboratory profiles of the study group children were compared with that of children treated for uncomplicated malaria (Table IV). The mean WAZ (weight for age SD score) was -2.1 (±1.2) in children admitted with severe malaria and -1.8 (±1.6) in the uncomplicated malaria group [P=0.001, unadjusted OR: 1.2 (1.08-1.36)]. The mean WHZ in the severe malaria group was -1.5 (±1.3) and in the uncomplicated malaria was -1.3 (±1.2), respectively (P=0.16). The mean haemoglobin was 6.9 (±2) in severe malaria children and 8.9 (±1.7) in the uncomplicated malaria group.

The association between nutritional status/wasting levels (WHZ) of severe malaria children and the parasite load on their peripheral smear (Table V) was not significant (P=0.87).

All 171 children were treated with intravenous (IV) artesunate (2.4 mg/kg) at 0, 12 and 24 h and other supportive management such as anticonvulsants, oxygen, antiemetics, IV fluids and nutrition care. Two were referred for blood transfusion. After 24 h the parasitaemia was assessed again and if the parasites cleared, the child was switched to oral age-specific artemisinin-based combination therapy (ACT) as per guidelines. The treatment outcome of the 171 cases of severe malaria showed that 167 (97.7%) children had parasite clearance in 24 h and 4 (2.3%) had delayed clearance (delayed up to 72 h). All the children recovered.

There were no deaths recorded in the children included in this study. All children were asymptomatic and without any sequelae at the time of discharge from the health centre. Severe acute malnutrition and moderate acute malnutrition children were followed up.

Discussion

Unprecedented intensive malaria control measures were launched by the Government of Odisha in the tribal areas (the DAMaN project) from 2017 to 2020 till COVID struck. This consisted of prompt diagnosis of malaria within 24 h of fever onset in the field by trained field workers using RDT and treatment with ACT kits, along with preventive measures. The extensive control activities spearheaded by Government and the Swasthya Swaraj Society collaboratively in this tribal area undoubtedly contributed to the reduction in malaria (Figure).

The number of total malaria cases diagnosed and treated in the two Swasthya Swaraj health facilities showed a steady decrease in the five-year period from 2017 to 2022. This downward trend also reflects the overall trend in Kalahandi district and Odisha State (NVBDCP)14.

The findings of our study (Table I) suggest that children in 1-2 yr age group have significantly high risk of getting severe malaria (P=0.001). After the age of 2 yr, with each year increase in age, there is 41 per cent less chance of the child developing severe malaria (Table II). This finding necessitates intensified malaria control activities targeting under-five children in tribal hamlets as they carry the brunt of the disease and death.

The significant decrease in the number of female children (P=0.01) with severe malaria (Table I) needs to be explored further. Any possible discrimination towards girl children in getting them admitted has to be looked for.

The decrease in the incidence of severe malaria in under-five children was proportionate to the fall in the incidence of malaria in general over the five-year period (Figure). The burden of severe malaria and deaths in young children seen in a high endemic region decreases with their increasing age1617. Of central interest to malaria control is how the overall burden of disease in childhood varies with transmission18. When the transmission intensity is higher, a larger population is exposed to infection and in such population the exposure to infection occurs earlier. Due to this, early exposure partial immunity also develops early, and the risk of severe malaria decreases with age.

Most malaria complications occur rapidly in non-immune individuals with severe falciparum malaria. These include cerebral malaria (central nervous system), respiratory failure, acute renal failure and/or severe anaemia. As the progression is rapid and the disease is potentially fatal, any case of malaria must be assessed and treated rapidly19. However since the progression is rapid, early treatment may not be feasible to prevent the development of complications.

The rapid development of severe malaria appears to be independent of past episodes of uncomplicated malaria. In high-transmission, malaria-endemic areas, repeated symptomatic malaria infections are common until the child acquires a degree of immunity against the disease. However, repeated episodes of uncomplicated malaria did not protect the children against developing severe malaria. Immunity to severe malaria appears to develop in children in high endemic areas before the development of immunity to the more common uncomplicated malaria. Variant surface antigens play a critical role in the pathogenesis of severe malaria. The acquisition of antibodies against the parasitic antigens expressed on the erythrocytic surface appears to be, at least in part, the basis of the natural immunity to severe malaria20.

Clinical presentations of severe malaria in children vary in different studies. In our study, neurological symptoms dominated (64.4%) followed by pneumonia-like presentation and severe malarial anaemia of Hb <5 g/dl in 20.5 per cent of children (Table III). In a recent study reported from Africa, respiratory distress was the most common symptom (83%)21. In high endemic areas, episodes of cerebral malaria and anemia associated with severe malaria are rare after the age of four. The age of the affected individual is an important factor that decides the presenting symptom in severe malaria, although the incidence and prognostic significance of coma and metabolic acidosis are similar at all ages22.

In our study, the clinical presentation of severe malaria included many unusual presentations, which are less reported (Table III). Clinical presentation resembling meningitis with nuchal rigidity is a rare phenomenon that was seen in this study. One child presented with hemiparesis and one infant with continuous focal seizures. In addition, acute abdomen, acute nephritis, nephrotic syndrome, and acute gastroenteritis-like presentation were also seen. Differentiating severe malaria from other acute infections is often a clinical and epidemiological challenge since, most of the malaria symptoms are almost indistinguishable from other major causes of morbidity in children23.

Malaria and malnutrition are co-existent and synergistic24. We found that children with severe malaria were significantly underweight (P=0.001, unadjusted OR:1.2 (1.08-1.36) (Table II), but the wasting levels (WHZ) showed no significant difference between the study group and the uncomplicated malaria group (Tables II and IV). Wasting levels of severe malaria afflicted children did not have a significant effect on the parasite load of these children (Table V). However, repeated episodes of malaria in tribal children worsen their nutritional status and severe malaria leads to further worsening of this situation. Undernutrition among tribal children is a major concern in India. Despite many national and State-level interventions, undernutrition remains a serious problem which in long term has adverse effects on productivity, incomes and national development2526. However, evidence on the effect of undernutrition on the risk of getting malaria is inconclusive2728.

Treatment outcome data of severe malaria in the two primary care health facilities from 2017 to 2022 show no deaths among the children treated for severe malaria, which is evidence of the effectiveness of good quality primary healthcare. Primary healthcare to be effective should be specific to the context in which it functions. Only limited data on health outcomes and quality of primary healthcare services are available. High-quality primary healthcare is the outcome of good service delivery. This is possible only when the services are well-organized and well-managed and backed by a committed and competent team of staff 24×7, infrastructure, diagnostic facilities and medicine supplies2930.

However, all children with severe malaria are unable to reach health facilities in tribal areas where the geographic terrain is difficult and the district hospital, which is the only referral centre is located far away. Even when a child manages to reach the PHC in a critical condition, the child is referred to the District hospital. Under-five mortality rates in tribal pockets are high. In the predominantly tribal population that Swasthya Swaraj Society caters to, the under-five chil d mortality was 141/1000 live births (2017-2018), 127/1000 live births (2018-2019), 116/1000 live births (2019-2020) and 116/1000 live births (2020-2021) (Swasthya Swaraj HMIS)15. Deaths do occur in homes without accessing the health system or on their way to health centres. A study by Greenwood et al31 in Gambia found that four per cent of infant deaths and 25 per cent of deaths in the 1-4 yr age group occurring in homes were attributable to malaria. Poor health-seeking behaviour, inaccessibility of healthcare facilities, lack of transportation facilities, and illiteracy of tribal parents contribute to not availing of health services. Prospective studies using verbal autopsies are needed to assess the malaria deaths in children that occurred before reaching the health facility.

Parasite clearance occurred in 97.7 per cent cases within 24 h and in 2.3 per cent of children, it was delayed up to 72 h, indicating the possibility of in vivo development of artemisinin resistance. A prevalence survey on antimalarial drug resistance markers carried out in Swasthya Swaraj primary health facilities during 2018-2019 in 400 malaria cases of all age groups did not reveal mutations in the pfk13 sequence, indicating that antimalarial drug resistance is not yet developed in this area (unpublished data). However, as artemisinin resistance has been reported in eastern India, ongoing surveillance is needed to watch for this serious problem in centres treating severe malaria3233.

Children with severe malaria typically present a short history of illness of 1-4 days, when they are critically ill with life-threatening complications. However, in tribal areas PHCs may not always be equipped well to manage this medical emergency. Managing this clinical problem in endemic areas can be challenge to health services and clinicians34. Our experience in such settings suggests that the critical factors in the management of severe malaria include prompt diagnosis, early treatment initiation and early supportive, which can reduce the risk of adverse outcomes.

As the long-awaited malaria vaccine is being considered, remote tribal pockets where the need is the highest must be prioritized. However, administering multiple doses of the current RTS, S/AS01 vaccine35 is a daunting task in these pockets, where achieving even the routine immunization targets is a challenge.

This study had a few limitaions. The retrospective record review could have resulted in the misclassification of cases as severe malaria. It is also likely that all cases of severe malaria were not captured in this study. Sickly children who were not brought to the hospital and/or the parents refused the admission of the children could not be included. Mortality that occurred at home or on the way to the hospital or in the district hospital was also not captured in this study. As the exact dates of birth were not available, there may have been an under or over-estimation of the age of a few children.

Despite rigorous efforts towards controlling malaria, it continues to remain a significant public health concern in under-served tribal areas of the country. Only a small proportion of malaria cases progress rapidly to severe malaria, and children under five years are most vulnerable to developing this medical emergency in highly endemic areas. Under-five mortality rates are high in tribal areas and most deaths occur in children in tribal areas before they can reach the health system.

The fact that there was no mortality in severe malaria managed in the resource-poor primary care health facilities shows that if primary health centres are equipped with round-the-clock well-trained staff and diagnostic facilities, severe malaria can be managed successfully, and child mortality can be reduced. In malaria control activities, children under five years should be prioritized. The programme activities should be uninterrupted in the tribal areas till the endemicity comes down. The present control agenda is unfinished and warrants an intensified effort.

Further, effective collaborations between malaria control and nutrition intervention programmes are essential for proper case management of malaria in children.