Burden of malaria during pregnancy in perennial transmission settings of two densely forested and remote blocks (Baihar and Birsa) of district Balaghat, Madhya Pradesh, central India

INTRODUCTION

Women during their first and second pregnancy (especially up to second trimester) are more susceptible to malaria infection compared to non-pregnant women of the same reproductive age group.¹ The main attributing factor for the burden of malaria in pregnancy (MIP) is poor/declining immunity due to changes in hormonal balance in women, resulting in susceptibility to various complications in both mother and the foetus.^2,3 Worldwide, 125 million women are at risk of acquiring malaria infection during pregnancy.⁴

Plasmodium falciparum (Pf) is a major cause of morbidity and mortality among pregnant women and infants in subSaharan Africa, whereas in Southeast Asia and South America, P. vivax (Pv) also contributes in a large manner to this burden.^1,5,6 Diagnosis and treatment of malaria in pregnancy (mainly Pf), especially placental malaria is challenging due to parasite sequestration, excess white blood cells and thick viscous placental blood in a smear.^7,8

During pregnancy, adverse outcomes due to malaria exist for both the foetus and newborn (abortion, intrauterine foetal death, preterm deliveries, low birth weight, congenital malaria and neonatal death).^5,9 Often, mothers experience severe outcomes (severe anaemia, severe malaria involving vital organs such as brain and lungs, and maternal death).^1,9–12 About 40% of low birth weight newborns (LBW) in malaria-endemic areas may be attributable to malaria and are responsible for 62 000 to 363 000 newborn deaths each year.^13,14

In 2015, India was the third highest contributor of malaria globally after Nigeria and Democratic Republic of Congo. However, a 24% decline in malaria cases was noted in 2017 coinciding with a decline in malaria in Southeast Asia.^15,16 In the past two-and-a-half decades, species shift has been observed in many parts of India with Pf overlapping with Pv.¹⁷ Previous hospital and field-based studies from India have shown wide variations in malaria prevalence ranging from 1.8% to 58% among pregnant women in different regions with high risk for adverse outcomes.^18–23 However, field-based burden estimation of MIP specifically from perennial malaria transmission settings in India is lacking. This will enable planning for better combat strategies against malaria among pregnant women in similar settings.

Previously, very high malaria prevalence (mainly asymptomatic) among different age groups with increasing trends of malaria (>30% infant positivity rate) in the same study area (district Balaghat) has been reported.^24,25 However, no information about MIP is available for this region. We did this field-based investigation on MIP in two blocks of district Balaghat, Madhya Pradesh, central India to characterize the epidemiology and burden of MIP (in terms of infection prevalence with gravidity status during the antenatal and puerperium period, and identification of risk factors for malaria) to tailor specific policies for strengthening malaria control in densely forested and stable malaria transmission areas of India.

METHODS

Follow-up

A subset of pregnant women could be followed up (n=350) for malaria prior to delivery (Fig. 1). Women (n=808) and neonates/infants (n=361) were also screened for malaria after delivery. Only 331 women could be screened for malaria in the puerperium period.

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FIG 1.

Flowchart showing malaria screening (2015–2017) of pregnant women (PW)

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RESULTS

DISCUSSION

Previous studies on the burden of MIP from India were mainly hospital-based and only a few described community-based disease burden. Further, most of the community-based reports were related to outbreak/epidemic investigations. Our study attempted to identify the key gaps in the existing knowledge based on a larger sample size, particularly from remote and densely forested perennial transmission areas, with no or minimal health access. Malaria transmission in such areas is determined by the ecosystem, predominant vector prevalence, insecticide resistance and the presence of drug-resistant parasites.²⁸ In our study 1651 pregnant women were screened for malaria (symptomatic and asymptomatic) and the risk factors for malaria were recorded.

The first recorded evidence of malaria in pregnancy in India was about a century ago, wherein 300 premature births, and 1100 stillbirths, miscarriages and abortions occurred.²⁹ In the two epidemic-based field studies in central India of 274 and 456 pregnant women, respectively, revealed 21%–55% prevalence of malaria (Pf 64%–88%), being especially high in the second trimester (80% pregnant women were also anaemic). Abortion, stillbirths and neonatal deaths were higher in primigravidas being 2.6%–3%, 4%–11% and 2%, respectively among women.^21,30 A community-based study of 209 pregnant women from Southeast India showed seasonal parasite-index of 10.8% to 26% with significantly higher infection among primigravida.²⁰ Thus, acute malarial infections are associated with high risk for an adverse pregnancy outcome and therefore it is important to determine and document community-based burden of MIP in areas of different malaria endemicity.

We found malaria prevalence and Pf parasitaemia were significantly higher among primigravida compared to multigravida. Further, the prevalence of malaria was higher in the first and second trimesters than the third trimester of pregnancy. The majority of infections were due to Pf (>87%). The malaria prevalence in our study (23.4%) was similar to a study conducted in other tribal belts of India (29.3%)³¹ but lower than that reported in central or west Africa (28.2%–41.9%) and comparable to that with East-Southern Africa (22.4%–36.5%) and other Southeast Asian countries (5%–37%).³²

The high prevalence of malaria was seen during ANC follow-up in our study, but declined by 50% after delivery. Moreover, Pf parasitaemia was significantly higher at enrolment than after delivery. Pregnancy presents higher risk of malaria infection among women in this region as previous studies in the same area revealed 7.6%–17.1% prevalence of malaria among non-pregnant adults (aged >14 years).^9,25

Community-based active surveillance revealed significantly higher burden of malaria than health centre-based passive surveillance in this region.³³ Earlier hospital-based studies in Chhattisgarh and Jharkhand states revealed a malaria prevalence in the range of 1.3%–3.5% at antenatal clinics and 2.4%–3.6% using placental microscopy at the delivery unit.^23,34,35 Whereas, active malaria case screening revealed a high prevalence ranging from 23.4% (our study) to 29.3% in forested areas of Chhattisgarh, Andhra Pradesh and Telangana.³¹

Fever, anaemia and splenomegaly are characteristic signs of malaria. In areas of stable malaria transmission, asymptomatic infections or afebrile parasitaemia is common among different age groups, including pregnant women (mainly due to placental sequestration of Pf) and is a major challenge for any control/elimination programme.^25,32 In our study, 81.5% infections were asymptomatic at the time of primary screening. A high slide positivity rate of 29.2% among asymptomatic individuals from the same area has been reported earlier.²⁵

Prevalence of anaemia in our study was similar to that observed in other parts of India and other endemic settings (60%–92%).^23,31,34,35 Anaemia is widely prevalent in developing countries, particularly among pregnant women and severe anaemia has been found to be significantly associated with lower birth weight.³⁶ Placental malaria may also increase the risk of maternal anaemia.³⁷ Infections, metabolic deficiencies and genetic causes are the other main factors causing anaemia. Unlike earlier reports from different geographical areas, severe anaemia was significantly higher in our study (4%–10% v. 17.3%).^23,34,38,39 However, anaemia and severe anaemia prevalence associated with Pf and Pf+Pv/Pm infections was relatively higher compared to Pv infections in our study although not statistically significant. In a hospital-based study done in western India, Pf malaria was found to be an important cause of the high mortality rate and severe anaemia among pregnant compared to non-pregnant women (37.8% v. 14.8% and 20% v. 4.1%, respectively).^22,40

In our study, 33 of 350 pregnant women who were followed up had repeated malaria infection (85% due to Pf), which may lead to chronic infection. However, we could not ascertain whether the second infection was due to a new infection or persistence of previous infection due to inappropriate compliance of antimalarial drug. Clinically, this subset of pregnant women had a higher degree of severe anaemia (32%). During MIP, chronic infections have been closely associated with decreased birth weight due to foetal growth restriction and are associated with lower maternal haemoglobin and severe anaemia in endemic areas.³⁰

Previous studies have also found that the malaria parasite (particularly Pf) is more likely to be present in placental smear than a mother’s peripheral smear and sometimes even after treatment.^23,34,41,42 Placental histology is even superior to detect malaria infection than blood smears.³⁷ However, we did not assess the burden of placental malaria during pregnancy. Malaria screening in our study was based on microscopy and RDT, which are considered less sensitive than polymerase chain reaction (PCR) to detect sub-microscopic asymptomatic malaria infections, but we could not do PCR.⁴³ RDT test was helpful in detecting malaria infection and treatment of pregnant women in this remote and forested field area at the time of enrolment and follow-up.

The majority of pathological consequences of Pf during MIP are due to the sequestration of infected red blood cells to placental intervillous space via molecular interactions of VAR2 to placental chondroitin sulphate A (CSA) and associated inflammatory responses.⁴⁴ Sequestration may result in hypoxia, anaemia and high fever. However, the exact pathogenesis (hypoxia, microvascular damage and angiogenic repair deficiencies mediated by VEGF, etc.) of placental malaria and associated adverse outcomes is still unknown.⁴⁵ Recently, a placental malaria protein ‘VAR2CSA’ showed promise for novel cancer diagnostics and therapeutics.⁴⁶ Thus, there is a need for molecular characterization of malaria parasites (Var 2 gene, especially from the placenta) from different endemic areas.

In our study, factors such as primigravida status, first and second trimester, women belonging to indigenous ethnic tribal groups and cash crop insufficiency (whole year) were independent risk factors for higher prevalence of malaria. Previous studies from eastern India revealed first and second pregnancies, fever within the past week and women belonging to rural areas were significant risk factors for higher prevalence of malaria among pregnant women.³⁹ Similarly, a longitudinal cohort study in central India found that individuals belonging to ethnic tribal groups, lower economic strength of family (yearly income) and larger family size are also independent risk factors for higher malaria prevalence.⁴⁷

Our study highlights high malaria prevalence, gravidity-wise trend of malaria and parasitaemia and risk factors for malaria among pregnant women in a remote and forested region of Madhya Pradesh. We also feel screening of asymptomatic carriers to be necessary for malaria control programmes. We found a high and perennial burden of malaria in pregnancy in this area, Anganwadi-based regular malaria screening using RDTs and complete treatment of pregnant women by an ANM or trained ASHA worker may be helpful in controlling malaria among pregnant women in this remote and forested region. Strengthening of health sub-centres operation in these areas may improve the malaria control programme’s effectiveness.