Plasmodium falciparum parasitaemia and malaria among pregnant women at first clinic visit in the mount Cameroon Area

Pregnant women in malaria endemic areas are at high risk of P. falciparum infection and its complications which are severe and multiple [1]. These may include placental malaria, fever, maternal anaemia, foetal parasite exposure, congenital infection, low birth weight (LBW) (due to preterm delivery (PTD) and intrauterine growth retardation (IUGR)), infant mortality and anaemia [1]. It is generally assumed that due to acquisition of partial immunity to malaria, parasitaemic women living in areas of stable transmission are rarely symptomatic [2]. However, various studies show that in stable malaria endemic regions, pregnant women have frequent episodes of malaria from early to mid pregnancy [3–5]. It is recommended that pregnant women should be given antimalarial drugs at their first antenatal visit and perhaps earlier in pregnancy whether or not they show symptoms to prevent adverse effect of malaria on the mother and foetus [6]. In areas of stable malaria transmission of sub-Saharan Africa, intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) (IPTp-SP) is recommended for all pregnant women at each scheduled antenatal care visit (at least one month apart) up to the time of delivery [7]. Treatment of falciparum malaria involves administration of quinine plus clindamycin (if available) and if treatment fails, Artesunate combined therapy (ACT) is recommended [6, 8].

Longitudinal cohort studies investigating the clinical presentation of malaria parasite infection in pregnant women showed that during routine ANC (scheduled) visits, malaria is less common [4, 9, 10]. However, studies in Mozambique [4] and Benin [5] revealed that during unscheduled visits, about 90 % of pregnant women infected with malaria parasite had symptoms. Symptoms commonly associated with malaria parasitaemia include fever, headache and shivering [5]. It is possible that in malaria stable transmission areas, the burden of malaria is been underestimated, as most studies have been carried out in women reporting for scheduled visits or at delivery to investigate placental malaria [6, 9, 10].

Clinical manifestations of P.falciparum infection may largely depend on the intensity and stability of malaria transmission in the local environment [11]. Other factors commonly reported to increase risk of malaria among pregnant women include; younger age, primigravidity, second and third trimester of gestation [3, 10], level of education [10, 12] and rainy season [3]. Malaria alters haematological parameters with low platelet, WBCs and lymphocyte counts being the most important predictors of malaria infection. Furthermore, when used in combination with other clinical and microscopy methods, these parameters could improve malaria diagnosis and treatment in people living in malaria endemic areas [13, 14]. Most recent studies have reported haematological changes in malaria in children and adults [13–15]. Malaria-related haematotological alterations in pregnant women warrant investigation.

Previous findings in the mount Cameroon area show that fever history is common among pregnant women and this usually correlates with the time of first clinic visit [16, 17]. Pregnant women in this area may experience malarial fever episodes before their first ANC clinic visit. Thus, this study investigated the prevalence of P. falciparum infection and malaria among pregnant women reporting for first ANC clinic visit during scheduled and unscheduled clinic days at some health facilities in the study area. Secondly, the study assessed demographic, socio-economic, environmental, haematological factors to identify risk factors associated with P. falciparum infection and malaria in pregnancy in this setting.

It is generally assumed that due to acquisition of partial immunity to malaria, parasitaemic women living in areas of stable transmission do not often present with symptoms [2]. However, the present study demonstrates that, among pregnant women reporting for first clinic visit, malaria (16.0 %) was prevalent when compared with asymptomatic parasitaemic cases (10.5 %) and women with malaria frequently report for medical attention during unscheduled clinic days. Hnynh et al. [5] in Benin have reported similar findings. Malaria-associated acute symptoms such as fever will likely cause pregnant women to seek medical care during unscheduled days [5]. Comparable to previous reports in Cameroon by Leke et al. [9] (7.9 %) and Mbu et al. [10] (6.6 %) malaria cases were less common (7.5 %) among women reporting for ANC during routine clinic visits. Certainly, women who are apparently well (afebrile) will generally report for first ANC during scheduled visit days as observed in the present study. Women reporting at the clinic during unscheduled visits represent a high risk group and so prompt malaria diagnosis and proper treatment to avoid adverse consequences of early P. falciparum infection in pregnancy is justified [6, 8].

Haematological changes in malaria, such as thrombocytopenia and leucocytosis or leucopenia are well-recognized [13–15]. Haemoglobin levels, WBC and platelet counts did not discriminate malaria from asymptomatic parasitaemia. This might be partly because most of the women with symptomatic infection were mild malaria cases. Significant morphological and numerical changes in all the blood cell lines observed in malaria are usually dependent on the disease severity (complicated versus uncomplicated malaria) [25] among other factors such as Plasmodium species [26, 27] and the immune status of an individual [28]. In a Ugandan study, P. falciparum uncomplicated malaria did not produce significant changes in the total WBC count, differential WBC count and RBC indices. The authors suggested that haematological changes are unreliable laboratory indicators of malaria in acute uncomplicated Plasmodium falciparum malaria [29]. Nevertheless, the level of malaria parasitaemia was associated with lymphocyte percentage. Lymphopenia which is sometimes profound but transient or temporary, is a common finding in acute malaria in non-immune adults [25, 30] as well as in children living in malaria endemic areas [13, 25]. The lymphocyte percentage being inversely proportional to the level of parasitemia reflects redistribution of lymphocytes (due to extravasation and homing either at inflammatory sites or at secondary lymphoid organs (e.g. peripheral lymph nodes and spleen)) or lymphocyte destruction due to Fas-induced apoptosis [31]. Lymphopenia is a classical feature in arthropod-borne viral infections [32]. Arboviruses can both cause lymphopenia and be associated with increase level of malarial parasitaemia. Co-infection of malaria and other febrile illness caused by arthropod-borne infections such as dengue has been reported [32].

This study investigated the risk factors for P. falciparum parasitaemia and malaria in pregnant women. The findings show that household proximity to bush and/or standing water increased risk of P. falciparum parasitaemia and malaria in the pregnant women residing in such areas. Similarly, previous findings from a study carried out in this area by Akenji et al. [33] revealed a positive significant association between state of house surrounding and risk of malaria parasite infection. Bushes and/or standing water serve as breeding sites for the malaria parasite vectors. Wanji et al. characterised anopheles breeding sites in the mount Cameroon area during peak to late rainy season period (August-November) [34]. The study showed that about 94 % of the breeding sites in this area are temporary water bodies, of which about 81 % are productive breeding sites (contained Anopheles larvae). The majority (86 %) of these breeding sites are found within 20 m from the nearest inhabited house while 21 % are located between 20 and 50 m from the nearest inhabited houses. Breeding sites are less likely to occur beyond a distance of 50 m. Furthermore, Tanga et al. [19] reported a high parous (an indication of haematophagy) rate (≤70 %) for all anopheline species further suggesting availability of potential breeding sites close to human residence.

In malaria endemic settings, studies have consistently shown that primigravid women are at increased risk of malaria [3, 4, 6, 10]. In conformity with previous findings, primgravidity was a significant factor associated with malaria. Greater risk of infection and adverse outcome in primigravidae has been attributed to the absence of pregnancy- specific malaria immunity to pregnancy-associated variant surface antigens (VSAPAM) that predisposes them to malaria severity [35]. The fact that human residence in areas with nearby bushes and/or standing water was an independent predictor of P. falciparum infection and malaria suggests that the environment may modify the risk of infection and disease in pregnant women in this setting rather than gravidity. Areas of intense malaria transmission risk have been associated with greater risk of infection [11]. The association observed between knowledge of MiP and malaria is not possibly a cause-effect relationship. Rather, it can be explained by the fact that the majority of the women who had some knowledge of MiP were multigravidae. Multigravid women are less likely to be susceptible to malaria in pregnancy due to acquired gravidity-dependent pregnancy associated immunity [35]. Women of older gravidity become enlightened about MiP either through past ANC clinic attendance or experiences. Reported IPTp-SP uptake was low. This is because the study population involved women reporting for their first clinic visit and about 90 % coverage of at least one SP dose is achieved after first ANC consultation in the study area [17]. SP uptake correlated with malaria at ANC enrolment. In peri-urban and rural communities, pregnant women with malaria often prefer to self medicate through drug store and herbs. Generally, these women seek treatment in health facilities as a last resort, usually when the disease poses a major threat to life [36]. SP is an inappropriate treatment for malaria [8] and misuse of SP may have implications on resistance against SP for malaria prevention in pregnancy. There is urgent need to evaluate SP efficacy as IPTp in this setting and to encourage pregnant women to seek appropriate diagnosis and treatment of febrile illness at the medical centre.

In this study, more than twice (OR = 2.6) as many unmarried pregnant women were infected compared with women with a husband or partner. More so, single women had higher parasite densities than did married women. Similarly, in Yaoundé, Mbu et al. [10] showed that single women had a 4-fold increase risk of developing malaria during pregnancy. Increased risk of P. falciparum among single women might be due to the fact they were significantly younger (≤20 years) and the majority were primigravidae. In areas of high and stable transmission, age and pregnancy-associated anti-parasite immunity may play an important role in limiting P. falciparum infection to low parasite densities [35, 37] in older and multigravid women respectively. Anchang-Kimbi et al. [16] reported higher prevalence of low-grade parasitaemia in older women (>20 years) than younger women (≤20 years) in the study area. The fact that single women had higher parasite densities when compared with married women irrespective of age and gravidity status suggests that other factors may account for high parasite load in single women. It will be interesting to investigate the role of marital status in the risk of malaria parasite infection in this study area. Numerous studies have shown advantages of being married on the health of individuals [38]. Marriage could improve health outcomes in a variety of ways: It may improve economic well-being [39], health outcomes by enhancing access to health care or lowering stress. In addition, a spouse may play an important role in monitoring and encouraging healthy behaviours [40]. Chepkemoi and Mutulei [41] suggested that partner support is critical for effective prevention of malaria in pregnancy. The support of a husband or partner may play a key role on the woman’s timing of her first ANC. Some studies show that women not supported by a partner are likely to report for late antenatal care enrolment [42]. This in turn could delay early uptake of IPTp-SP.

This study had few limitations. First, the study did not investigate other arthropod- borne infections that cause fever. In Africa, fever episodes are most often considered as malaria (without any laboratory confirmation) and some of the supposed malaria attacks could be actual dengue fever which remains largely unknown [43]. Two serotypes; dengue virus (DENV) -1 and DENV-2 have been, or are currently, circulating in Cameroon [43, 44] although unrecognized by individuals and even by medical personnel [43]. In Cameroon, the vast majority of DENV infections are unapparent or oligosymptomatic and this form of presentation of the disease may under represent its distribution and impact [43]. In addition, Fokam et al. [44] reported anti-viral antibodies against some members of Alphavirus (Chikungunya and O’nyong-nyong) in sera of patients from Mt Cameroon area. Secondly, the study did not survey the environment where people stay to ensure that the reported presence of standing water and bushes around human residence faithfully relate to the risk of P. falciparum and malaria. While anopheline mosquitoes are predominant (82.73 %) and diverse in the Mt Cameroon area, Tanga et al. [19] identified Aedes, Culex and Mansonia species in some mosquito breeding sites and thus the possibility of DENV transmission in the area cannot be rule out. It is imperative that future studies investigate the prevalence of arboviral infections among pregnant women in this study area, as these infections are important and overlooked public health problems.

In the study area, P. falciparum parasitaemia is a leading cause of febrile illness among pregnant women before first ANC clinic visit and women with malaria frequently seek for medical attention during unscheduled clinic days. Being unmarried and the presence of bush and/or standing water in house surroundings modify the risk of P. falciparum infection and malaria in pregnancy. Prompt malaria diagnosis and proper treatment as well as early ANC care attendance to avoid adverse consequences of early infection in pregnancy is justified. Education on early ANC attendance and environmental sanitation are important public health targets for malaria control in pregnancy in this setting.