B. Adesina-Adewole1 , F.I. Olusola2 , A.D.A. Adedapo3 , and C.O. Falade2.3
- Department of Obstetrics and Gynaecology, College of Medicine, University of Ibadan, Ibadan.
- Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan.
- Department of Pharmacology and Therapeutics, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Background: Malaria in pregnancy has significant adverse consequences for the mother, foetus and baby. Presumptive diagnosis continues despite recommendation for parasite-based diagnosis. We performed Paracheck-Pf™, an HRP-II based malaria Rapid diagnostic test (Paracheck-Pf RDT) and microscopy among pregnant women in a prospective, cross sectional study, at the University College Hospital in Ibadan, Nigeria.
Methods: The study was conducted between 2009-2011. Consecutive pregnant women presumptively diagnosed as having malaria >18 years were enrolled after obtaining written informed consent. Demographic information, symptoms and clinical measurements were obtained. Capillary blood was obtained by finger prick for thick blood smear and RDT evaluation. Summary statistics included mean (standard deviation) for quantitative variables and percentages for categorical variables. Chi-square, analysis of variance (ANOVA), the odds ratio (OR) and 95% confidence intervals (CI) were computed with p-value less than 0.05 considered statistically significant.
Results: Of the 746 pregnant women aged 30.9 ± 4.6 years enrolled, 243 (32.7%) were primigravida. The mean gestational age was 23.3 ± 9.2 weeks with about 81% in the second and third trimester. The prevalence of malaria parasitaemia by microscopy and Paracheck-Pf ™ were 22.8% and 24.5% respectively. The geometric mean parasite density was 2,091/µL (range 40-156,975/µL). HIV positivity rate was 8.1 % and 16.1% of patients were anaemic (PCV <30%). Women with axillary temperature >37.40C were significantly more likely to have malaria parasitaemia [p<0.0001] by microscopy. Sensitivity and specificity of Paracheck overall were 69.9% and 88.2% respectively while those at of parasite densities >200/µL were 84.8% and 88.7% respectively. Positive and negative predictive values were 66.9% and over 90% respectively.
Conclusion: RDTs are a reasonable alternative in view of the need for parasite-based diagnosis of malaria.
Keywords: Malaria, Pregnancy, Microscopy, Paracheck-rapid diagnostic test
Malaria in pregnancy is a major public health challenge with significant adverse consequences for the pregnant woman, her foetus, and the new-born child.1 The adverse consequences of malaria during pregnancy include maternal anaemia, placental malaria, congenital malaria, low birth weight (LBW), preterm delivery, intrauterine growth restriction and increased infant and maternal mortality.2-4 Pregnant women are the adult population in malaria endemic areas who bear the brunt of malaria infection and its adverse consequences. Malaria parasite infected red blood cells are characteristically sequestered in the placenta of infected pregnant women. These parasitized erythrocytes are believed to express unique variant surface antigens (VSA) that can bind chondroitin sulphate A which enable their sequestration in the placenta. Pregnant women develop antibodies to VSA with each succeeding pregnancy with the result that susceptibility to malaria reduces with subsequent pregnancies. Primigravida or secundigravidae are thus more prone to having malaria and its deleterious consequences during pregnancy
About 30 million pregnant women are at risk of malaria in sub-Saharan Africa every year especially among primigravid, secundigravid and young women below 20 years of age.5 Other risk factors which increase susceptibility include gestational age, HIV status, host and parasite genetics as well as intensity and stability of malaria transmission in the environment.6-9 Malaria preventive measures if well implemented do modulate the prevalence and severity of episodes of infection.6-9
Malaria has been diagnosed presumptively in malaria endemic areas for a long time. This practice has continued despite the WHO recommendation that malaria diagnosis be confirmed by laboratory tests to identify the parasite or its antigen.10,11 In presumptive diagnosis of malaria during pregnancy, the patient is diagnosed based on the presence of symptoms like fever (elevated body temperature), vomiting, severe headache, aches and pains, chills and rigors, diarrhoea and abdominal pain. These symptoms however are not specific to malaria and may have resulted from other diseases.10
The WHO recommends microscopy of Giemsastained blood smear or malaria rapid diagnostic test (RDT) for parasite-based diagnosis of malaria. Microscopy of Giemsa-stained blood smears which remains the gold standard when carried out by competent persons identifies, quantifies and speciates malaria parasites. In addition, microscopy detects parasite recurrence during follow up. However, there are many challenges for the implementation of good quality microscopy especially in malaria endemic areas. Some of the challenges are shortage of resources such as well-trained microscopists, high quality reagents, and regular electricity to power microscopes that are often in short supply. In addition, malaria microscopy is tedious and time consuming as the standard recommendation is that 200 microscopic fields must be examined before a blood smear is pronounced free of malaria parasites. Malaria RDTs on the other hand do not require extensive training or equipment, are easy to read and the results are available within 15 to 20 minutes.12,13 These characteristics make malaria RDTs more practicable for deployment in malaria endemic regions where the burden of malaria is high and the requirements for quality assured microscopy are often not available. Malaria RDTs are immunochromatographic antigen-based single-use tests which detect circulating parasite antigen. Targeted antigens include P. falciparum histidine rich protein II (HRP-2), plasmodium lactate dehydrogenase (pLDH) and aldolase. HRP-2 is specific for P. falciparum while aldolase can detect all plasmodium species. pLDH on the other hand could be P. falciparum specific or pan malarial specific.
In sub-Saharan Africa, where there is stable and intense malaria transmission, most infections in adults, including pregnant women are asymptomatic as they have developed partial immunity against malaria. However, pregnant women are more prone to malaria infection and have increased parasite densities due to immune tolerance in pregnancy11,12 but may not be overtly symptomatic. Thus, a high index of suspicion is essential if most cases of malaria during pregnancy is not to be missed. In an effort to control malaria in pregnancy, the WHO has recommended that pregnant women should receive intermittent preventive therapy (IPT) using sulfadoxine-pyrimethamine at specified intervals after quickening.13,14 However, the WHO also recommends that every suspected malaria case should have parasitological diagnosis before treatment15 as presumptive diagnosis of malaria generally leads to over-diagnosis and misdiagnosis of malaria. Presumptive diagnosis also leads to insufficient investigation of alternative causes of the presenting complaints which can have adverse consequences for the pregnant woman and her unborn child/children.16- 18 It also causes inappropriate and irrational use of antimalarial drugs which may lead to avoidable adverse drug reactions and emergence of antimalarial resistant strains of the parasite.19
We report here the performance of Paracheck-Pf™, an HRP-II based malaria RDT (Paracheck-Pf RDT) and expert microscopy for parasite-based diagnosis of malaria among pregnant women presumptively diagnosed as having malaria in the antenatal and emergency obstetrics care setting of the University College Hospital in Ibadan, southwest Nigeria where malaria transmission is intense.