Implications for policy and practice
This study confirms the high burden of malaria among tribal pregnant women in a chronic conflict corridor in India. It also shows that the burden of malaria among pregnant women varies according to seasonal patterns, being even more relevant during the high malaria season from October to March. In addition, it indicates that malaria infections among pregnant women in this area present a high risk, as the risk of malaria infection in pregnancy is especially high during first and second pregnancies [
15]. More than 50% of pregnant women presenting for ANC care in this setting are in the first and second pregnancies.
Most malaria cases identified (99%) were caused by
P. falciparum (isolated or mixed with other forms of malaria) which may add substantial risk to the patients. This finding is aligned with the results of other studies on malaria transmission dynamics made in this region in the past decades. Those studies show that in forested tribal areas in this region, malaria transmission seems to be perennial [
16], and increasingly dominated by
P. falciparum species [
17‐
20], while
P. vivax seems to be the predominant species in villages and urban settings [
21].Moreover, the burden of malaria in India seems to be unequally concentrated in tribal areas, as a recent study performed with nationally representative data recently demonstrated [
22]. This study demonstrates that the 8% Indian population living in districts with large tribal areas bear 46% of all malaria cases, 70% of all
P. falciparum cases and 47% of all malaria deaths in the country. The fact that
P. falciparum is the predominant species in tribal areas may add substantial risk to pregnant women.
P. vivax is theoretically less dangerous for this group of patientsbecause it does not cytoadhere in the placenta, yet it may also cause low birth weight and maternal anemia [
15]. The fact that the RDT used did not detect the pan pLDH antigen as often as the
P. falciparum (HRP-II) one, does not necessarily means that
P. vivax is not a common cause of malaria in the area but in this study, we could not isolate
P.vivax from other forms of malaria.. In some areas of the Indian subcontinent,
P. vivax malaria exhibit two seasonal peaks, the first of which is dominated by relapses (January to June) and the second one is shared with
P. falciparum in periods of high transmission after the monsoon rain (July–Nov) [
23]. The seasonal pattern of
P. vivax and its consequences for pregnant women should be further evaluated in this area by future studies. The only symptom strongly associated with malaria and with statistical significance was fever (either history of fever, measured fever, or both). It could be then used in diagnostic algorithms for increasing the pre-test probability, as it is already recommended in the national guidelines [
24]. Studies suggest that traditional healers may play an important role on the treatment of fever in tribal communities [
25], and efforts to reduce malaria burden in tribal areas should consider partnering and promoting health education activities with traditional healers for the management of fever cases. There is also a high prevalence of malaria in asymptomatic pregnant women (20.8%), which is aligned with other studies performed in the area [
26,
27]. It may possibily be attributed to the fact that malaria infections in healthy adults, including pregnant women, in moderate to high transmission areas rarely result in fever [
15]. Therefore, elimination of malaria is highly unlikely if diagnostic strategies do not include asymptomatic patients, because they will remain a reservoir of parasites contributing to the spread of the disease from one malaria season to the next. This seems to represents an opportunity for using ANC services in tribal areas for targeted approaches, and intermittent screening and treatment (IST), as recommended by WHO [
28], using RDT screening and artesimin-based combinations therapies during ANC care seems to a reasonable option. Despite of increased programmatic costs, it has been demonstrated that IST is a safe and effective intervention to pregnant women seeking malaria care in moderately high transmission areas [
29].Nevertheless, the national guideline for diagnosis and treatment of malaria do not consider targeted approaches for screening of vulnerable groups such as pregnant women or tribal areas [
24].
Another intervention opportunity is the use of IPT for pregnant women. The use of Sulfadoxine-Pyrimethamine (SP) as early as possible from the second trimester of pregnancy onwards with subsequent doses at least 1 month apart up to the time of delivery is recommended by WHO in areas of moderate to high malaria transmission in Africa, although the exact level of malaria transmission to indicate it is not yet clear [
30]. IPT is not yet recommended outside Africa because there is insufficient evidence for general recommendations in other areas. Nevertheless, a recent meta-analysis clearly demonstrated the benefits of IPT in maternal and child health in malaria endemic areas, mainly in first and second pregnancies [
2]. In addition, IPT remains an effective intervention in preventing the adverse consequences of malaria on maternal and fetal outcomes, even in locations where there is a high prevalence of SP resistance genetic mutations on
P. falciparum parasites, leading to in vivo resistance [
30], as it seems to be the case in India [
31]. We suggest the use of IPT in highly endemic areas in India, specifically for isolated tribal communities where access to health care has been compromised by conflicts, on the provision that it is submitted to subsequent evaluation on maternal and infant health outcomes, like maternal anemia and low birth weight. Mathematical modelling could help to understand the malaria transmission threshold below which IPT is no longer cost-effective.
The nutritional level of pregnant women in the study area seems to be very poor. Low MUAC levels have been demonstrated to generate low birth weight and preterm labor, along with anemia and post-partum endometritis in a recent meta-analysis [
13]. Levels of MUAC below 230 mm were consistently statistically significant for poor birth outcomes in previous studies [
12], and most of our patients are included in this group. A poor nutritional status seems to pose an even higher risk to pregnant women with malaria and their newborns [
32]. However, a previous study showed that nutritional supplements do not seem to impact the immunological response to malaria of undernourished pregnant women with less than 20 weeks of pregnancy [
33]. Perhaps an earlier supplementation could be more effective and should be further investigated. The high level of under-nutrition could help to explain the high level of anemia in the area, but the poor correlation between MUAC and hemoglobin levels suggests that nutritional status is unlikely to play a major role in hemoglobin levels.
It was also not possible to establish a clear association between malaria and anemia, perhaps because the burden of anemia in the study area was very high (92.4%) and impossible to justify with only malaria active cases. Nevertheless, the association of malaria with mean hemoglobin level was small (0.6 mg/dl), but statistically significant. Malaria seems to be also associated with severe anemia with a prevalence ratio of 2.56. This finding is consistent with other studies which have already demonstrated the association of malaria with severe anemia in pregnancy [
15,
18]. This suggests that malaria active cases may not be the cause for most anemia cases, but it seems to contribute to the severity of some of them. Malaria infection diagnosed by both HRP-II and pLDH were not significantly associated with severe anemia, but this unusual finding may be due to a reduced sample size of the subgroup analysis. Improving access to malaria prevention, care and treatment could potentially reduce the need of hospitalisations and improve maternal health; however other causes of anemia may be playing an important role in the morbidity of pregnant women. Different studies have suggested a high prevalence of hemoglobinopathies in central India, including sickle cell disease and thalassemia [
34,
35]. Sickle cell anemia is especially high in patients from Chhattisgarh, with some studies suggesting a prevalence as high as 35% in some communities [
36]. Parasitic infections [
37], recurrent malaria and other chronic diseases [
38] have been suggested as causes of anemia in other studies and should be further investigated.
The low prevalence of HIV infections demonstrates the low burden of AIDS in this area; however, the test was not performed in many of our patients. For few patients, the test was not performed because the team was unable to provide counselling and testing before the closing time of the clinic which had to be respected due to security constraints. Some of the patients opted out of the test while others preferred to perform the test in government settings. These alleged reasons for refusal demonstrate that there is HIV stigma in those communities, which should be addressed by health promotion interventions.
The results of this study also show that, close to the community level, malaria burden is much worse than previous facility-based studies could demonstrate. One study performed in governmental ANC clinics in two different districts of the state of Chhattisgarh involving rural and urban population showed a malaria prevalence of 1.3% [
6]. Another study performed in the state of Jharkhand in different ANC clinics identified a malaria prevalence of 1.8% (53%
P. falciparum and 37.2%
P. vivax and 9.3% mixed infections), being four times higher in rural than urban areas [
39]. Still in Jharkhand, a study performed in a semi-urban ANC and Delivery Unit clinic showed a malaria prevalence of 4.3% (87% caused by
P. vivax). The majority of cases in this study (85%) were identified in asymptomatic patients. However, the authors stated that less than 60% of women in this state search the hospital for deliveries [
27]. Another study suggested that, among tribal pregnant women in this area, the prevalence was 20.6%. However, this study had a targeted approach of testing only febrile patients with RDT [
7]. In another study of tribal populations (not only pregnant women) in the district of Purulia in the state of West Bengal, among 1040 asymptomatic patients, 81 (8.4%) were positive for
P. falciparum and only 4 cases were positive for
P. vivax [
26]. Our study shows a higher prevalence of malaria among pregnant women (29.3%) compared to all previous studies in this conflict area, perhaps because we offer easily accessible services, free of charge and close to the community level. Previous studies results could be influenced by a lack of access of disadvantaged population to the ANC clinics and efforts should be made to bring ANC services as close to the community level as possible.
Limitations
This study has some limitations. According to some projections made in the project, it is estimated that around one quarter of the pregnant women in the area access the MC ANC services every year. Despite being placed close to the community level, and with some degree of community involvement, our study was still mainly facility-based, and most of the local population still only looks for MC services when they have health problems. This helps to explain the high level of symptomatic patients (54%) in our ANC service, and this could overestimate the prevalence of malaria and anemia. Nevertheless, the high level of malaria and anemia in asymptomatic patients reduces the impact of this limitation.In addition, the RDT used for malaria diagnosis (SD BIOLINE® 05FK60) has some limitations. Firstly, the sensitivity of the test may be reduced depending on some conditions. The overall sensitivity of the test is 99.7% for
P.falciparum and 95.5% for non
P.falciparum malaria according to its specifications. However, studies performed in programmatic conditions using a combination of microscopy and PCR as a gold standard showed that the sensitivity of the test may range from 83.3 to 100% [
43‐
45]. One study in the Central African Republic showed a sensitivity of 69.6% for
P. falciparum patients with a parasitemia below 100 parasites per micro litre of blood on microscopy [
46]. In the case of this study region, where transmission seems to be moderate to high, and consequently parasitemia levels of patients may be generally low, there is a possibility that some cases have been missed. Considering its specificity, the test specification suggests a value of 99.5%.Nevertheless different studies on programmatic conditions shows that it may range from 86.8 to 98.9%[
43‐
45], thus it is also likely that some false positives results also occurred. Secondly, as this RDT may take some time to become negative after the patient has been treated because of the persistence of HRP-II, in the case of a patient accessing recent treatment for malaria before knowing her pregnancy status, the test may also present a false positive result. However the low level of health access in the area suggests a very limited impact of this limitation. Thirdly, as the study has used RDT results based on common antigen for different
Plasmodium species, it was impossible to isolate the burden of isolated
P. falciparum infections from mixed malaria. This limitation has less importance in pregnant women, as the clinic protocol does not change depending on the type of malaria and primaquine cannot be offered to pregnant women. It was also impossible to separate the burden of
P. vivax from
P.malariae and
P. ovale. Although most studies in the area demonstrate the presence of only P.falciparum and P.vivax;
P.ovale was also recently isolated in the Chhattisgarh area and its burden is not yet known [
47].
Finally, this was a retrospective study based on routinely collected data and it is possible that some clinical history data were missing from the ANC cards, which could compromise the analysis on asymptomatic cases. It is very hard to estimate the size of this effect, but the general low level of missing results of exams suggests that the data are, in general, of reasonable quality.