Frequency of Malaria in Patients Presenting with Anemia in Pregnancy at a Tertiary-Care Hospital in Pakistan
*Dr. Sana Khan1, Dr. Ana Mehreen Rajput1, Dr. Najm Us Sehar1, Dr. Saba Naz2, Dr. Gulfishan huq1, Dr. Shagufta Ismail1
1. Civil Hospital, Karachi.
2. Jinnah Hospital, Karachi
*Correspondence Author.
Dr Sana Khan
Abstract
Malaria in pregnant women presenting with anemia is frequently observed as compared to the non-pregnant women due to lower immunity, chances of recurrence, or other complications of gestation. The aim of the current research was to determine the accurate frequency of malaria in patients presenting with anemia during pregnancy.It was a cross- sectional cohort study conducted in thedepartment of Obstetrics and Gynecology, Civil Hospital Karachi, Pakistan, from October 12, 2018, to April 11, 2019. For this purpose,a total of 161 pregnant women (18 to 35 years) with singleton pregnancies diagnosed with anemia were included. Other known causes of anemia like thalassemia trait, vitamin B12 and folate deficiency, worm infestation, thalassemia, aplastic anemia, sickle cell anemia, chronic renal and heart disease were excluded. In all patients, the blood sample was collected from the antecubital vein under aseptic precaution for determining malarial parasite (MP) by ICT (intracytoplasmic trophozoite). The outcome variable i.e. MP-ICT was noted. The majority of patients (95; 59.01%) were between 26 to 35 years of age, while the mean gestational age was 32.70±3.23 weeks with the mean parity of 4.67 ± 1.43. The frequency of malaria in patients presenting with anemia in pregnancy was observedina totalof 58 (36.02%) women. So,the study concluded that the patientspresenting with anemia in pregnancy are at higher risk to develop malaria than non-anemic pregnant women.
Keywords: Anemia; pregnancy; malaria; effect modifiers; age distribution
Introduction
Anemia is a condition characterized by deficient red blood cells to carry enough oxygen to the body tissues. It occurs frequently in pregnancy and about 40-60% of the outcome of maternal death is caused by this condition in developing countries. Overall, 35-75% of pregnant women in underdeveloped countries and 18% of pregnant women in developed countries are affected each year1. Due to a number of adverse health outcomes, timely diagnosis, and management of anemia have become a great concern. Generally saying, the hemoglobin concentration and anemic outcomes have a ‘U-shaped’ link; either very low or very high than normal maternal hemoglobin concentrations directly cause anemia.
Mostly, the lower hemoglobin concentration is associated with perinatal and maternal mortality, premature delivery, and lower birth weght2, 3.
Malaria is the most important medical condition caused by protozoan of genus Plasmodiumin erythrocytes, which is transmitted to humans by the bite of an infected female mosquitoAnopheles. During pregnancy, malarial infection is a major healthcare problem with a considerable risk of mortality for both mother and neonate. It’s a disease that is worldwide distributed mostly in tropical areas, where 3.3 billion people are at high risk for malaria4 of which pregnant women are being the second most at risk of illness, approximately 125 million worldwide5. It is estimated that over 50 million women reside in malarial endemic areas, 20% of which become pregnant annually and almost half of them progress malarial infections6. Thesoutheast Asian and Pacific countriesare at higher risk of malarial transmission demonstratingone-third of the world population1. In Pakistan probable figure of the yearly malarial episode is 1.5 million1 and WHO reported confirmed cases 202,0137. Malarial infection in pregnancy differs in complication from the non-pregnant state disease in a way of lower immunity, have a recurrence,severe complicationssuch assevere maternalanemia, acute pulmonary edema, DIC,intrauterine growth restriction,premature delivery, maternal death, miscarriage, stillbirth, lower birth weight, fetal and neonatal death5. Due to atypical and mostly asymptomatic presentation of malaria in pregnancy, it requires a high index of notion to identify malaria in pregnancy8. Anemia is the most prominent manifestation of malaria in pregnancy5. Anemia is more likely tooccur between 16-30 weeks due to hemolysis of parasitized cells
and increased demand of pregnancy iron/folate deficiency. In Africa and sub-Saharan vicinity, about 23 million pregnant women are diagnosed with malarial infection annually and approximately 0.4 millionwomen develop moderate to severe anemia in pregnancy9, which results in 10,000 cases of malaria-related mortality in pregnancy, primarily due to maternal anemia10,11. Various studies in India have proved malaria-associated anemia and its ultimate complications in pregnant women12, 13.According to a study in Ghana, pregnant girls with malarial infections were 3.5 times more likely to be anemic than non- pregnant women14. Likewise, many western studies reveala positive association between Malaria and anemia in pregnant women15.
Locally, few studies conducted as in Sobhodero and in Faisalabad concluded that pregnant women with malarial infections are mostly anemic16, 17. However,sufficient data is not available up till now and also the international data is not applicable in our population due to demographic and genetic changes.Additionally, the prevalence of malaria is very high in Pakistan, so, the present study has been undertaken to bridge the gap and provide the basis to actively prevent, diagnose and treat malaria in pregnancy (MIP) with antimalarial drugs to improve maternal, fetal , and child health.
Materials and methods
Operational conditions
MIP was confirmedasinfection detected as HRP-2 from pregnant women diagnosed as malarial parasite (MP) by intracytoplasmic trophozoite (ICT). Anemia in pregnancy was confirmed referring toWHO specifications as hemoglobin (Hb) less than 11g/l in venous blood18, mild anemia as Hb 10.0-10.9 g/l, moderate anemia as Hb 7.0-9.9g/l, severe anemia as Hb < 7.0g/l, and very severe (decompensated) as Hb <4.0g/l. The presence of any one of these levels was labeled as positive.
Study design and sample size
It was a cross-sectional cohort study, conducted in thedepartment of Obstetrics and Gynecology, Civil Hospital Karachi fromOctober 12, 2018, to April 11, 2019.Non- probability, consecutive sampling was done with total 1615samples and calculated by using Openepi software, formula for estimating a proportion wit h specified absolute precision. The assumptions were set asconfidence interval to be 95% and anticipated population proportion of malaria in anemic pregnant women to be 5.4%2 with the
absolute precision as3.5%
Inclusion and exclusion criteria
Inclusion criteria were diagnosed case of anemia, pregnant women with singleton pregnancy, age 18-35, gestational age >12 weeks of pregnancy as calculated by LMP/early dating scan, whereas, exclusion criteria wereother known causes of anemia like thalassemia trait, B12 and folate deficiency, worm infestation, thalassemia, aplastic anemia, and sickle cell anemia diagnosed by lab test, multiple pregnancies confirmed by ultrasound, women with chronic renal failure (serum creatinine >1.1 mg/dl), andwomen with heart disease diagnosed on history and echocardiography.
Data collection protocol
After permission from the ethical review committee, patients admitted via OPD/ER fulfilling the inclusion criteria were selected. After taking informed written conse nt detailed history was taken, antenatal record was reviewed. Gestational age was determined by the last menstrual period (LMP) and confirmed by 1st-trimester scan. From all patients, blood sample was collected from antecubital vein under aseptic precaution that was sent to the Central Laboratory, Civil Hospital Karachi for the detection of malarial parasite (MP) by ICT, andthe outcome variable i.e. MP-ICT was noted. The data was logged on specialized predesigned proforma.
Statistical analysis
Statistical analysis was accomplished by using SPSS software version 21, and resultsfor quantitative variables were presented as mean and standard deviation i.e. age, parity, gestational age (GA). Frequency and percentage were calculated for the place of living (Rural/ Urban),the severity of anemia, MP (seen/ not seen). These effect modifiers were measuredthrough stratification and post-stratification Chi-square test to determine their effects on the outcome. P-value < 0.05 was considered as significant.
Results
The age range of patientsunder study was from 18 to 35 years with a mean age of 26.48 ± 4.36 years, whereas, the majority of the patients (95; 59.01%) was between 26 to 35 years of age, mean gestational age was 32.70 ± 3.23 weeks and mean parity was 4.67 ± 1.43 (Table 1). The distribution of patients according to the place of living and severity of anemia is shown in Figures 1 and 2 respectively, whereas, the frequency of malaria in
patients presenting with anemia in pregnancy was observed in 58 (36.02%) women as shown in Figure 3. When stratification of malaria was done on age groups, it was found that there was no significant difference between different age group, while, the stratification of malaria with respect to gestational age also showed no significant difference between different gestational ages, stratification of malaria with respect to parity, place of living and the severity of anemia is presented in Table 2.
Table 1: Distribution of pregnant women(n=161) according to effect modifier.
Effect modifier Subdivision No. of
Patients %age Age (in years)
18-25 66 40.99
26-35 95 59.01
Total 161 100.0
Mean ± SD: 26.48 ± 4.36 years GA (weeks)
≤30 29 18.01
>30 132 81.99
Total 161 100.0
Mean ± SD: 32.70 ± 3.23 weeks Parity
≤3 61 37.89
>3 100 62.11
Total 161 100.0
Mean ± SD: 4.67 ± 1.43
Figure 1: Distribution of patients according to the place of living (n=161), including rural and urban areas. The majority of the patients were from urban areas.
Figure 2: Distribution of patients according to the severity of anemia (n=161). The severity of anemia was categorized as mild, moderate, severe, and very severe. The majority of the cases were presenting a moderate form of anemia.
Figure 3: Frequency of malaria in patients presenting with anemia in pregnancy (n=161).In most cases, malaria was not diagnosed, still many cases were presenting malaria in addition to anemia in pregnancy.
Table 2: Stratification of malaria in pregnant women(n=161) with respect to effect modifiers.
Effect
modifier Subdivision Malaria p-value
0%
140 (86.96%)
21 (13.04%)
0%
0.00%
10.00%
20.00%
30.00%
40.00%
50.00%
60.00%
70.00%
80.00%
90.00%
100.00%
Mild Moderate Severe Very severe
58 (36.02%) 103 (63.98%)
seen not seen
Observed Not observed
Age (years) 18-25 23 43
0.796
26-35 35 60
GA (weeks) ≤30 08 21
0.296
>30 50 82
Parity ≤3 17 44
0.092
>3 41 59
Place of living Rural 31 47
0.341
Urban 27 56
Severity of anemia
Mild 00 00
Moderate 51 89 -
Severe 07 14
Very severe 00 00
Discussion
Malaria during pregnancy is the common complication of pregnancy19, 20, characterized by hypoglycemia, spontaneous abortion, pulmonary edema, anemia andstillbirths21. Anemia in pregnancy is of great concern22, particularly in developing countries where nutritional deficiency, worm infestation, and malaria are common23. Thus, accurate and early diagnosis of malarial illness is necessaryfor the effective management of the disease24. The current research wasaccompanied to evaluate the frequency of malaria in patients presenting with anemia in pregnancy.
The age range in the present study was from 18 to 35 years with a mean age of 26.48 ± 4.36 years,the majority of them were between 26 to 35 years of age. The frequency of malaria in patients presenting with anemia in pregnancy was observed in 58 (36.02%) women. According to a study in Ghana, pregnant girls with malarial infections were 3.5 times more probable to be anemic as compared to non-pregnant women14. According to a study in Burkino Faso, the occurrence ofFalciparum asymptomatic infection among pregnant women was 30% and 61% of them were anemic15. Likewise, many western studies reveala positive association between anemia and malaria in pregnant women16. A review of studies showed the prevalence of malaria in pregnancy was 29.5% in East and South Africa while 36.1% in West of central Africa21.
Malaria infection in pregnancy is connected with a broad range of clinical indicesthat range from acute asymptomatic to severe cases and death of both mothers and neonates25-
27. In P. vivax infected pregnant patients, severe anemia has been reported.Moreover, P.
vivaxis associated withsevere malaria,moderate-to-severe anemia, and low birth weights
in Latin America28. Inmany studies,Glover-Amengor et al29 and Uddenfeldt et al30 reported 35% and 41% in their study participants. Ofori et al31 reported 18.8% malaria infection casesof pregnant women in his study, while, Tay et al32 reported 12.6% total cases. The disparity in the occurrencemight be explained with aproclamation by Ofori et al31that there was a significantdifference in the frequency of malarial infection throughout the year. Morecasestypicallyarise after the rains thus the incidence might be affected at the time data was collected. Malaria might not be the only cause of anemia in pregnancy, as it may also be a result of other threateningconditionslikewisenutritional deficiency (folate and iron), placenta previa near the internalos of the cervical canal of the fetus, and worm infestation, especially in the developing nations. This form of anemia is probablycombinedwith malaria-induced anemia during pregnancy because in most cases,both malaria and iron deficiency causes anemia in pregnancy, which ultimatelyincreases the risk of premature delivery and adverse birth outcomes. A pregnant woman with sustained anemia further carries the risk of stillbirth,maternal death,fetal impairment, andlow birth weight33.
Generally, the mother’s immune system not only accepts the fetusbut also provides protection from infections, especially in malaria. In this way,T lymphocytesmaintain this fetal tolerance by migrating from the circulation towards the placenta and secreting immune-suppressive mediators like interleukin-1034. But in the case of some life- threatening infections like HIV, exposure to malarial antigens stimulates the innate immunity with impaired toll-like receptor-induced cytokines and dendritic cells which ultimately increases the susceptibility of neonatestowards other infections35. Other studies have reported a sudden decline in cell-mediated immune responses to malaria parasite antigens in pregnancy with anemia. It greatly depends on the living conditions, parity, patients’ age, and dietary habits36-42. As, in the present study,the majority of the patients were belonged to urban areas and alreadypresented a moderate form of anemia.Even in some cases, malaria was not diagnosed, still,other cases were presenting malaria in addition to anemia in pregnancy. Overall, pregnant women already presenting with anemia urgently need special care and timely diagnosis and treatmentin case of some comorbidities like malarial infections to improve maternal and neonatal health.
Conclusion and recommendation
It was concluded that thefrequency of malaria in patients presenting with anemia in pregnancy is quite higher than non-anemic pregnant women depending upon age group, parity, and, living standards. Pregnant women with older age, urbanized poor living conditions have a higher risk of developing malaria.So, we recommend theprevention, early diagnosis, and treatment of malaria in pregnancy with rational antimalarial drugs to progress maternal and fetal healthand to avoid morbidity and mortality due to malaria .
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