Seroepidemiology of Asymptomatic Plasmodium falciparum Co- Infections with Hepatitis B And C Virus among Blood Donors in Modakeke Area Office, Ile Ife, Osun State, Nigeria

Introduction

Despite remarkable achievements in reducing malaria mortality, malaria remains the most common cause of morbidity and mortality in Africa. Coendemic falciparum malaria and acute hepatitis B occur through much of Southeast Asia, Africa, and the tropical Americas. Both diseases represent key threats to public health [1]. The majority of people with malaria are not admitted to the hospital. Instead, they receive oral therapy on an outpatient basis. People who develop severe malaria and enter the hospital represent a minority of patients [2].

In Nigeria, malaria has a high morbidity and mortality rate in children and pregnant women. (In non-immune subjects, infection with a Plasmodium falciparum at any age leads to clinical diseases associated with a high case fatality rate if untreated [3]. Infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) are major global health problems [4]. It is estimated that about 350 million people are chronically infected with HBV and about 200 million people are infected with HCV worldwide [5]. Moreover, infection with these viruses might associate with increased mortality rate as the infection may predispose to the development of serious liver diseases such as liver cirrhosis, liver failure and hepatocellular carcinoma (HCC) [6].

Most regions highly endemic for malaria are also endemic for other infectious diseases, which may affect the malaria infection [7]. Hepatitis B virus (HBV) infections are common in many of the malaria endemic areas. HBV induces a robust pro-inflammatory Type 1 immune response (Th1), which is important for Plasmodium clearance, but is also implicated in disease severity [8]. Therefore, the study was conducted to determine the asymptomatic plasmodium falciparum co_-_ infections with hepatitis b and c virus among blood donors in Ife Central Local Government Area, Ile Ife, Nigeria.

Results

A total of 400 blood donors; aged 18-62 years had participated in the study. Majority of the donors that participated 91.0% (364/ 400) were male, 56.30% (225/400) were married, 49.50% (198/400) were in the age range 27-35 years, 31.50% (126/400) were artisans, and 67.0% (268/400) were in secondary.

The overall mean parasitaemia of malaria infection among the donors was 786.2025 ± 46.209 (µl/blood) while that of Hepatitis virus infection was 53/400(13.3%), HBV and HCV are 25/400 (6.3%) and 21/400 (5.3%) and co- infection 7(1.8%) respectively Table 1.

Table1: Socio-Demographic Characteristics of the Study Population of Donors (N=400) Modakeke Area Office Osun State.

In Table 2, the prevalence of Hepatitis virus infection was highest (57.9%) in donors aged 18-26 years followed by (18.8%) in donors aged 54-62 years and the least (13.4%) in aged 36-44 years. HBV has the highest (15.8%) in donors aged 18-26 years followed by (11.8%) in aged 36-44 years and the least (4.0%) in 27-35 years. The highest HCV (31.6%) was recorded in aged 18-26 years and the least (7.6%) in 27-35 years. The co-infection was highest (18.8%) in donors aged 54-62years and the least (1.7%) was recorded in 36-44years. there is significant difference between Hepatitis (p<0.000), HBV (p<0.005), HCV (p<0.000), Co-infect (p<0.000). The malaria infection was highest with mean parasitaemia 1,882.7895± 4169.33331(µl of blood) in donors aged 18-26 years followed by 1,224.9583± 2714.49894 (µl of blood) in donors aged 45-53 years and the least 145.3125± 102.75454 in 54-62 years (µl of blood) Figure 1.

In females, Hepatitis viral infection was highest (22.2%) and HBV (6.3%) while HCV (16.7%) (Table 3), the mean parasitaemia 2,382.8056 ± 4957.86751(µl of blood) was highest among female (Figure 2). There is significant difference between marital status and HCV (p< 0.001). Among single donors, the prevalence of Hepatitis virus infection was highest (17.1%), HCV (8.6%) and HBV (6.3%) and co-infection (2.3%) (Table 4), while the malaria infection was highest with mean parasitaemia 786.8978± 2263.50513(µl of blood) among married donors (figure 3), there is significant difference between marital status and hepatitis infection (p< 0.043) and between HCV (p<0.009). In Table 2, the prevalence of Hepatitis virus infection was highest (21.4%) among artisan followed by (15.3%) among student and the least (2.3%) among trader. The highest HBV (14.6%) was recorded among civil servant followed by (8.7%) among artsan and the least (2.3%) among trader. The highest HCV (14.3%) was recorded among donors who are trader followed by (8.3%) among student and the least (7.1%) among artisan. The highest co-infection (5.6%) was recorded among artisan (Table 5). there is significant difference between Hepatitis (P<0.001), HBV (p<0.017), HCV (p<0.003), and Co- Infection ( P<0.008). The malaria infection was highest with mean parasitaemia 1,150.1591± 3148.98107 (µl/blood) in donors who are trader followed by 76.4306± 2278.26096 (µl/blood) in student and the least 22.6250 ± 151.01189 (µl/blood) among driver (Figure 4).

The prevalence of Hepatitis virus infection was highest (38.5%) in primary education followed by (15.7%) in secondary education and the least (5.0%) in tertiary education. The highest HCV (6.7%) was recorded in secondary education and the least (2.5%) in tertiary education. The highest HBV (15.4%) was recorded in primary education followed by (7.5%) in secondary education and the least (2.5%) in tertiary education. The highest co- infection (23.1%) was recorded in donors with primary education and the least (1.5%) was recorded in secondary education (Table 2). The malaria infection was highest with mean parasitaemia 2,096.8462± 3793.91187(µl of blood) in donors with primary education followed by 817.2015± 2418.19338(µl of blood) in donors with secondary education and the least 573.2101 ± 1155.90451(µl of blood) in donors with tertiary education (Figure 5). There was significant difference between marital status and hepatitis infection (p= 0.000) and between Co-infection (p=0.000).

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Age Group (years) Figure 1: Mean parasitaemia of Malarial infection among blood donors according to age in Modakeke Area Office.

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Gender Figure 2: Mean parasitaemia of Malarial infection among blood donors according to sex in Modakake Area Office.

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Occupation Figure 4: Mean parasitaemia of Malarial infection among blood donors according to occupation in Modakeke Area Office, Osun State.

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Education Figure 5: Mean parasitaemia of Malarial infection among blood donors according to Education in Modakeke, Area Office.

Keys: A+ (A Rhesus D positive), B+ (B Rhesus D Positive), O+ (O Rhesus D positive), AB + (AB Rhesus D positive), A- (A Rhesus D negative) B- (B Rhesus D negative), O - (O Rhesus D negative), AB- (AB Rhesus D negative. Table 3: Prevalence of Hepatitis B virus and Hepatitis C virus among Malarious blood donors according to Blood group in Modakeke Area Office. Osun State.

HCV (X2)= 20.159, p= 0.001

In Table 3, the prevalence of Hepatitis infection was highest (21.7%) in B+ve, followed by 16.5% in A+ve and the least 10.6% in O+ve. In HBV, (7.8%) in O+ve was the highest followed by (6.6%) in A+ve and the least (2.9%) in B+ve, The highest HCV (13.9%) was recorded in B+ve, followed by 9.9% in A+ve and the least (0.8%) in O+ve. co-infection (5.8%) was recorded in B+ve donors. The malaria infection was highest with mean parasitaemia 1,378.5000±1382.63527 (µl of blood) among B-ve donors followed by 940.7615±2566.70775 (µl of blood) in O+ve and the least 47.0000±34.76492 (µl of blood) in O-ve donors.

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In Table 4, the highest mean PCV in the study was 44.33±2.828 in aged 54-62 years followed by 42.61±4.211 in aged 45-53 years and the least 42.22±3.804 in aged 36- 44 years. The highest mean WBC was 6,222.22 ±  706.714 in aged 54-62 years followed by 5,372.09±  1047.710 in aged 27-35 years and the least 5,063.64± 871.270 in aged 45-53 years. The highest mean eosinophil was 2.37±2.565 in aged 18-26 years followed by 1.99±4.036 in aged 27-35 years and the least 0.58±  1.048 in aged 45-53 years. The highest mean lymphocyte count 46.19± 7.756 in aged 54-62 years followed by 43.84±8.037 in aged 27-35 years and the least 40.16± 5.294 in aged 18-26 years. The highest mean neutrophil count 57.71± 7.477 was recorded in aged 36-44 years followed by 56.95± 6.187 in aged 18-26 years and the least 53.63±7.089 in aged 54-62 years.

The highest mean PCV 42.90±3.213 was recorded among Trader, mean WBC 5,348.41  ±  1180.694  among Artisan, mean eosinophil 1.41 ± 2.396 among trader, mean lymphocyte count 43.94±  7.154 among trader and mean neutrophil count 56.27± 9.617was recorded among artisan (Table 4).

The highest mean PCV 44.44±  2.988 was recorded among donors with primary education, mean WBC 5,715.38 ± 1138.600, among donors with primary education. Mean eosinophil 1.68  ±  1.961 among tertiary, mean lymphocyte count 46.00±3.873 among donors with primary and mean neutrophil count 55.85±  5.886 was recorded among donors with primary education (Table 4).

Normal ranges: WBC = 4000-10,000/mm 3, Neutrophil = 40-70% Lymphocyte = 20-45%, Eosinophil= 1-6%, Packed cell volume (PCV) Women = (36-46%), Men = (40-54%).

(Table 5), present the logistic regression model for variables and Blood group as shown below. Aged range 27- 35 years was significantly associated with Hepatitis infection (p<0.022), then Sex, where female and male has association with hepatitis infection (p<0.006). Occupation, trading has association with Hepatitis infection (p<0 .001), Tertiary and secondary also has association with the infection (p<0.003), A rhesus D positive and B rhesus D positive blood groups has association with the infection (p<0.018) and (p <0.001) respectively.

Model Coefficients - INFECTED HEPATITIS (Hepatitis B and C)

Predictor Estimate SE Z p

AGE:

27-35 – 18-26 -1.88982 0.822 -2.2978 0.022

36-44 – 18-26 -1.15673 0.919 -1.2587 0.208

45-53 – 18-26 -18.7203 1339.16 -0.014 0.989

54-62 – 18-26 -0.69743 1.225 -0.5696 0.569

SEX:

MARITALSTAT:

single – married 0.41918 0.453 0.92567 0.355

OCCUPATION:

Trading – Artisan -2.63274 0.797 -3.3039 < .001

Civil servant – Artisan 0.4923 0.651 0.7568 0.449

Driver – Artisan -18.1751 1935.23 -0.0094 0.993

Intercept -0.60405 0.959 -0.6302 0.529

f – m 1.93443 0.702 2.75738 0.006

Discussion and Conclusion

In this study, the overall prevalence of Malaria infection was 786.2025 ± 46.209(µl/blood), Hepatitis infection was 13.3%, this value was higher than 4.5% reported by Abate, et al. in their study on Hepatitis b and c viral infections among blood donors at bahir dar, in Ethiopia and lesser than 40.67% observed among the donors in Benue state Nigeria by Paulyn, et al. [9]. Hepatitis B virus was 6.3%, Hepatitis C virus was 5.3%, and co-infection of both was 1.8% among blood donors, whereas, Biadgo, et al. [10] reported that 3.6% were positive for HBV, 0.8% for HCV and 0.062% of the study’s participants were co-infected with HBV and HCV in Ethiopia.

According to Age of the donors, the prevalence of Hepatitis virus infection was highest 57.9%, HBV 15.8% and HCV 31.6% in donor aged 18-26years whereas co-infection (18.8%) was highest in donors aged 54-62years, whereas, Paulyn, et al. [9] recorded that more youthful age groups 18-22years, 23-27years and 28-32years had higher prevalence of infection at 11.90%, 13.05% and 6.53%, respectively, also, Sial, et al. [11] reported that HBV and HCV were positive in 1.24% and 2.51% subjects respectively whereas co-infection of HBV and anti HCV was found in 0.03% cases in Rashid Latif Medical College, Lahore. Moreover, it was also reported by Amazigo and Chime in the year 1990 that by the age of 40 years, 87 % of the Nigerian population has at least one HBV serologic markers. Malaria infection was highest with mean parasitaemia 1,882.7895± 4169.33331 (µl of blood) in donors aged 18-26 years but Barcus, et al. [12], in there study on the prevalence of infection with hepatitis B virus among adult Vietnamese patients hospitalized for severe Plasmodium falciparum malaria reported that the mean age of severe malaria subjects was 33 years with a range of 15–78 years, they also reported that the prevalence of HBsAg in subjects with severe malaria was 23.77%. Obimakinde, et al. [13] in there study on the prevalence of malaria Infection among Patients attending the health centre of the federal university of technology, Akure, Nigeria reported that the highest prevalence of 91.1% was recorded among the children aged 1-10years, while the lowest prevalence of 56.8% was recorded among the age group above 60 years.

In this study, according to sex, In females, Hepatitis viraemia was highest 22.2% and HBV 6.3% while HCV 16.7% and co-infection 1.9% was recorded among the male, this is in agreement with Nkrumah, et al. [14] who reported that the prevalence of Hepatitis B viral (HBV) infection was highest in females with 21.4% in 2006 than males in the same year with 13.2% while Hepatitis C viral (HCV) infection was highest among males with 11.6% in 2007. HBV and HCV co-infection was highest in males 2.6% than females 1.3% in 2007. The rate of co-infection of HBV and HCV however increased from 1.6% in 2006 to 2.2% in 2008 in males and from 0% in 2006 to 1.2% in 2008 in females. Moreover, a recent study done by Alemeshet, et al. [15], in Southwest Ethiopia showed a high prevalence of the HBV in male 2.5% than the female 0.8% donors. However, the high prevalence of HCV in males might be due to the likelihood of men to have multiple sex partners and might be involved in unprotected sex. The mean parasitaemia 2,382.8056 ± 4957.86 (µl of blood) was highest among female in this study, this is in conjuction with the report of Obimakinde, et al. [13] where the prevalence 51% of malaria among the female patients was higher than the prevalence 49% among the male patients.

Among single donors in this study, the prevalence of Hepatitis virus infection was highest (17.1%), HCV (8.6%) and HBV (6.3%) and co-infection (2.3%) compared to the married, this in conjuctions with the reports of Abate, et al. where the prevalence of HBV was higher in single 4.2% than married and Negash, et al. [16] where the sero-positivity for HBV was significantly associated with marital status by which many of the infected donors were among single group, on the contrary, Kesete, et al. [17] reported that Married were found to be more exposed to both HBsAg and anti-HCV with seropositivity of 8.4% and 2.4% respectively, while the malaria infection was highest with mean parasitaemia 786.8978± 2263.50 (µl of blood) among married donors. there is significant difference between marital status and hepatitis infection (p= 0.043) and between HCV (p=0.009). According to this study, the prevalence of highest Hepatitis viraemia (21.4%) and coinfection 5.6% recorded among artisan, HBV (14.6%) among civil servant and HCV 14.3% was recorded among donors who are trader. The malaria infection was highest with mean parasitaemia 1,150.1591± 3148.98 (µl/blood) in donors who are trader.

The highest prevalence of Hepatitis virus infection (38.5%), HBV (15.4%) and co-infection (0.4%) was recorded in primary education while HCV (6.7%) was recorded in donors with secondary education. Moreover, Kesete, et al. [18] reported that the highest prevalence of HBsAg was observed in subjects with higher level of education (9.8%). In contrast, anti-HCV seroprevalence decreased with increasing level of education. The malaria infection was highest with mean parasitaemia 931.69± 136.23 (µl of blood) in donors with secondary education. There was significant difference between marital status and hepatitis infection (p= 0.000) and between Co-infection (p=0.000). According to the Blood group of the donors, the highest prevalence of Hepatitis infection (21.7%), HCV (13.9%) and co-infection (5.8%) was recorded in B+ve, while HBV (7.8%) was recorded in O+ve. The highest malaria infection with mean parasitaemia 1,378.5000±1382.63 (µl of blood) was recorded among B-ve donors. Blood group screening is a mandatory process in blood donation and transfusion because certain blood groups influence the pathogenesis of HBV, HCV and other transfusion-transmitted infections [18, 19]. Blood group antigens influence the transmission of viruses and other infectious agents by modulating the inflammatory and immune responses or by acting as ligands and receptors for such agents [20, 21, 22, 23]. For instance, some ABO antigens are capable of blocking the binding of transfusion-transmitted disease-causing organisms to polysaccharides on the host’s cells while others are not [22]. For HBV, Blood group O carriers have been found with a higher risk of infection than other blood group carriers [24].

There was an association between blood group and HCV (p< 0.001) in the current study. Previous reports on the association of blood groups with HBV have not been coherent. For example, among Asians, in a meta-analysis, blood group B was associated with a lower risk of HBV infection while blood group O was not significantly associated with HBV infection [25]. In another study, among Iranian blood donors, blood group O was associated with a lower risk of HBV infection [26]. On the contrary, blood group O was associated with a higher risk of HBV among Chinese.

Haematological changes are indicative feature of malaria and hepatitis infections. Various hematological abnormalities have been duly linked to the prevalence of malaria and hepatitis. They include Leucopenia, Neutropenia, Eosinophilia, leucocytosis, and Neutrophilia. The results of this study showed that the presence of malaria and hepatitis infection in the donors did not affect the hematological parameters evaluated. Lower neutrophil and leukocyte counts are usually indicative of leucopenia but this was not found in this study among donors with malaria and Hepatitis infections. In this study, the haematological parameters fall within the normal range for each. The highest mean PCV in the study was 44.33±2.82 in aged 54-62 years, the highest mean WBC was 6,222.22 ± 706.714 in aged 54-62 years, the highest mean eosinophil was 2.37±2.565 in aged 18-26 years, the highest mean lymphocyte count 46.19± 7.756 in aged 54- 62 years, the highest mean neutrophil count 57.71± 7.477 was recorded in aged 36-44 years.

According to marital status of the donors, the highest mean PCV 42.95±3.065, mean WBC 5,281.78±  1097.878, mean lymphocyte count 42.93±7.173 and mean Neutrophil count 56.14± 7.113 were recorded in married. While mean eosinophil 1.83±2.167 was recorded in single.

According to sex of the donors, the highest mean PCV 43.10±2.923 and mean lymphocyte count 42.93±7.557was recorded in male, while, mean WBC 5,513.89±  1018.725, mean eosinophil 1.94±2.137 and mean Neutrophil count 56.42± 6.822 were recorded in female.

In occupation status of the donors, the highest mean PCV 42.90±3.213, mean eosinophil 1.41 ± 2.396 and mean lymphocyte count 43.94± 7.154 were recorded among trader while, mean WBC 5,348.41 ± 1180.694 and mean neutrophil count 56.27± 9.617 were recorded among artisan.

In education status, the highest mean PCV 44.44±  2.988, mean WBC 5,715.38  ±  1138.600, mean lymphocyte count 46.00±3.873 and mean neutrophil count 55.85± 5.886 were recorded among donors with primary education while, Mean eosinophil 1.68 ± 1.961 was recorded among tertiary education.

The logistic regression shows that there was an association between hepatitis viral infection and aged group 27-35years (p=0.022), female (p=0.006), trading (p=0.001), tertiary (p=0.003) A+ve (p=0.018) and B+ve (p=0.001).

In conclusion, although the prevalence of malaria, hepatitis B and C viral infection was low in the local government, General surveillance through mass screening to identify those with infection and instituting appropriate treatment, mass immunisation against the virus and public health education to enlighten the public of the possible risk factors for and routes of infection are necessary. More aggressive strategies should be adopted in the fight against malaria such as extensive environmental insecticide spraying, de-clogging of water ways and drainages as well as widespread and effective distribution of Insecticide Treated Nets (ITNs) and other anti-malarials.