**3. Current status of reference values in Africa**

Reference intervals for clinical laboratory parameters have traditionally been obtained from European and North American populations [2]. However, differences have been reported between these values when compared to healthy African population values [16]. These include lower hemoglobin, red blood cell counts, hematocrit, mean corpuscular volume, platelets and neutrophils, and higher monocyte and eosinophil levels for African population compared to their Western counterparts [16,24-26] and Africans of European decent [27, 28]. Moreover, variations in several indices have been reported between different African ethnic groups [26, 29-31]. These differences are postulated to occur due to factors such as genetics, dietary patterns, gender, age, ethnic origin and environmental pathogens which are known to influence hematological and immunologic indices [32-35].

Laboratory Reference Intervals in Africa 309

**p-value (gender)**  **p-value (age)** 

(MCH) by gender have been observed in several African studies, with adult males having higher values than adult females in East Africa [9, 16, 20, 31, 39, 40], Southern Africa [20, 36], West Africa [41] and Central Africa [42]. These gender differences in RBC parameters as illustrated in our findings (Table 2), are consistent with previously established evidence that males have higher values than females for these parameters and is partly attributed to the influence of the androgen hormone on erythropoiesis [43, 44] and to menstrual blood loss in women [16, 25, 39, 42, 45]. It has been reported that estrogens lower the Hb through hemodilution while testosterone increases the plasma volume but increases circulating RBC

**p-value** 

**Female** 57 12.2 (8.1 - 14.2) *<.0001* 83 12.1(8.0 – 14.2) *<.0001 0.3243*  **Male** 76 13.1 (10.6 - 15.6) 77 14.2 (11.4 - 16.9) *<.0001* 

**Female** 57 35.6 (24.8 - 43.1) *<.0001* 83 35.8 (23.2 - 44.3) *<.0001 0.8015*  **Male** 76 38.8 (29.3 – 48.1)77 41.7 (32.6- 51.5) *<.0001* 

**Female** 57 4.7 (3.3 - 5.4) *0.0001* 83 4.5 (3.4 - 5.7) *<.0001 0.2638*  **Male** 76 4.9 (4.1 - 5.8) 77 5.3 (4.3 - 6.5) *<.0001*

**Female** 57 233 (134 – 439) *0.2958* 83 220 (88 – 439) *0.0222 0.4034*  **Male** 76 224 (103 – 386) 77 201 (102 -307) *0.0094*

**Female** 57 5.2 (3.9-10.2) *0.6359* 83 5.6 (3.3-9.7) *0.0189 0.2038*  **Male** 76 5.6 (3.3-8.3) 77 5.3 (2.5-7.4) *0.6382* 

**Female** 57 2.2 (1.1 - 3.1) *0.9820* 83 2.2 (1.3 - 3.8) *0.6901 0.9388*  **Male** 76 2.2 (1.0 - 4.2) 77 2.2 (1.0 – 3.5) *0.585* 

**Female** 57 2.0 (1.0-6.2) *0.4991* 83 2.3 (1.3-5.4) *0.0004 0.0576*  **Male** 76 1.9 (0.8-5.0) 77 2.0 (0.8-3.9) *0.6575*

**Female** 58 934 (465- 1553) *0.4074* 83 866 (440-1602) *0.0141 0.509*  **Male** 76 874 (367-1571) 77 811 (462-1306) *0.0209* 

**Female** 58 506 (195-1068) *0.4506* 83 472 (262 - 1167) *0.8706 0.9213*  **Male** 76 468 (195-988) 77 468 (201-1104) *0.4194* 

**Female** 58 1.8 (0.9-3.2) *0.9215* 83 1.8 (0.8-3.0) *0.0728 0.4879*  **Male** 76 1.8 (0.8-2.8) 77 1.6 (0.8-2.8) *0.0543* 

**Table 2.** Test of difference in hematologic and immunologic parameters between gender and age-

groups from healthy 13-34 year olds in a rural western Kenya cohort (2003-2005).

**(gender) <sup>n</sup>Median (95th**

**percentile)** 

**Age 13-17 years Age 18-34 years** 

**percentile)** 

to an even greater extent [46].

**Hemoglobin (g/dL)** 

**Hematocrit (%)** 

**RBC (x1012/L)** 

**PLT(x109/L)** 

**WBC (x109/L)** 

**Lymphocytes (x109/L)** 

**Neutrophils (x109/L)** 

**Ab** 

**CD4: Absolute** 

**CD8: Absolute** 

**CD4/CD8 ratio** 

**Parameter Gender n Median (95th**

While the differences observed in some laboratory parameters between African and Caucasian/Western populations may be attributed to nutritional differences, genetic polymorphisms, or more intense environmental exposure to endemic pathogens, it must be stressed that these reference values are being derived from population-based statistical analyses of norms among healthy persons. For example, healthy Africans tend to have lower white blood cell counts than Caucasians, but there is no evidence that they suffer any additional risk of developing severe infection or other sequelae. Also, African American populations, with environmental exposures more like their white American counterparts, tend to have lower 'normal values' in hematologic parameters than Caucasian Americans, suggesting a genetic basis for these population differences.

#### **3.1 Variation in specific laboratory parameters**

a. Hematologic parameters

The normal values of red cell counts and indices (i.e., hemoglobin concentration, hematocrit, mean corpuscular volume, red blood cell count), white cell counts and platelet counts are known to vary with age, sex and pregnancy [9, 16, 20, 31, 36]. In addition, genetic and environmental factors can also affect the reference intervals in certain populations [32-34, 37]. It is of particular importance that these differences in reference intervals be considered by clinicians in different settings.

i. Red blood cell (RBC) components

African RBC component values were significantly lower when compared to reference intervals obtained from the Massachusetts General Hospital [6] from a North American population, and thus a significant proportion are misclassified when the NIH DAIDS toxicity tables are applied [9, 34, 38]. Differences observed in the RBC components between African and Caucasian populations may be attributed to lower dietary iron intake, genetic polymorphisms such as thalassemia and sickle cell trait or chronic exposure to endemic parasites including helminths, malaria and schistosomiasis.

Statistically significant differences in median RBC, hemoglobin concentration (Hb) and hematocrit (Hct), mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) by gender have been observed in several African studies, with adult males having higher values than adult females in East Africa [9, 16, 20, 31, 39, 40], Southern Africa [20, 36], West Africa [41] and Central Africa [42]. These gender differences in RBC parameters as illustrated in our findings (Table 2), are consistent with previously established evidence that males have higher values than females for these parameters and is partly attributed to the influence of the androgen hormone on erythropoiesis [43, 44] and to menstrual blood loss in women [16, 25, 39, 42, 45]. It has been reported that estrogens lower the Hb through hemodilution while testosterone increases the plasma volume but increases circulating RBC to an even greater extent [46].

308 Blood Cell – An Overview of Studies in Hematology

**3. Current status of reference values in Africa** 

to influence hematological and immunologic indices [32-35].

suggesting a genetic basis for these population differences.

parasites including helminths, malaria and schistosomiasis.

**3.1 Variation in specific laboratory parameters** 

a. Hematologic parameters

by clinicians in different settings.

i. Red blood cell (RBC) components

Reference intervals for clinical laboratory parameters have traditionally been obtained from European and North American populations [2]. However, differences have been reported between these values when compared to healthy African population values [16]. These include lower hemoglobin, red blood cell counts, hematocrit, mean corpuscular volume, platelets and neutrophils, and higher monocyte and eosinophil levels for African population compared to their Western counterparts [16,24-26] and Africans of European decent [27, 28]. Moreover, variations in several indices have been reported between different African ethnic groups [26, 29-31]. These differences are postulated to occur due to factors such as genetics, dietary patterns, gender, age, ethnic origin and environmental pathogens which are known

While the differences observed in some laboratory parameters between African and Caucasian/Western populations may be attributed to nutritional differences, genetic polymorphisms, or more intense environmental exposure to endemic pathogens, it must be stressed that these reference values are being derived from population-based statistical analyses of norms among healthy persons. For example, healthy Africans tend to have lower white blood cell counts than Caucasians, but there is no evidence that they suffer any additional risk of developing severe infection or other sequelae. Also, African American populations, with environmental exposures more like their white American counterparts, tend to have lower 'normal values' in hematologic parameters than Caucasian Americans,

The normal values of red cell counts and indices (i.e., hemoglobin concentration, hematocrit, mean corpuscular volume, red blood cell count), white cell counts and platelet counts are known to vary with age, sex and pregnancy [9, 16, 20, 31, 36]. In addition, genetic and environmental factors can also affect the reference intervals in certain populations [32-34, 37]. It is of particular importance that these differences in reference intervals be considered

African RBC component values were significantly lower when compared to reference intervals obtained from the Massachusetts General Hospital [6] from a North American population, and thus a significant proportion are misclassified when the NIH DAIDS toxicity tables are applied [9, 34, 38]. Differences observed in the RBC components between African and Caucasian populations may be attributed to lower dietary iron intake, genetic polymorphisms such as thalassemia and sickle cell trait or chronic exposure to endemic

Statistically significant differences in median RBC, hemoglobin concentration (Hb) and hematocrit (Hct), mean corpuscular volume (MCV) and mean corpuscular hemoglobin


**Table 2.** Test of difference in hematologic and immunologic parameters between gender and agegroups from healthy 13-34 year olds in a rural western Kenya cohort (2003-2005).

Age-related differences in the RBC component have also been observed among male participants, with adults (≥18 years) having higher levels of Hb, Hct and RBC compared to male adolescents (13-17 years) as shown here (Table 2) [9]. This age variation is similar to that reported in a study of Caucasian adolescents [34]. This difference could be attributed to higher levels of androgen hormones among older males. This explanation is further strengthened by the absence of age-related hematological difference among female participants. It has also been postulated that an increase in the size and mass of muscle fibers as occurs in males is associated with an increase in the number of circulating red blood cells [47].

Laboratory Reference Intervals in Africa 311

African populations and those of African ancestry, including African Americans, than in Caucasian populations [24, 30, 51-53]. Because the reference interval for WBC counts is significantly different from that of Caucasian populations, it is advisable to use appropriate

Gender differences in the WBC counts exist in both African and Caucasian populations with females having higher values than males [9, 20, 54]. Age-related difference in WBC counts has been reported in several African studies [9, 25, 33]. Adolescents have higher WBC

Within the U.S., lower neutrophil counts are more common among blacks compared to Caucasians [28]. Thus, it is not unsurprising to observe a higher proportion of African study participants (22.5-35%) having neutrophil counts below the lower range of Massachusetts General Hospital's population-derived reference interval [9]. It is estimated that about 25% to 50% of Africans have "benign ethnic neutropenia," maintaining consistently low absolute neutrophil counts with no evidence of increased susceptibility to infection or other adverse events [28]. Possibile explanations for the lower neutrophil count include diet, genetic or

In general, there are significant differences in neutrophil counts between male and female adults, with the females having higher neutrophil counts than males. This increase in neutrophil counts observed in women may be related to estrogen since a decrease in counts has been reported after menopause [39]. Oral contraceptives have also been implicated in

Additionally, several studies in southern Africa have documented high rates of neutropenia in infants of women receiving Prevention of Mother to Child Transmission interventions [57-591]. Evaluation of neutropenia in infants receiving antiretroviral prophylaxis or treatment (directly or indirectly through maternal exposure in utero or through breastfeeding) remains a challenge. Neutropenia is a known side effect of zidovudine [60] and trimethoprim/sulfamethoxazole, which is often prescribed for prevention of opportunistic infections in HIV-infected and/or HIV-exposed infants/children. This problem is further compounded by the paucity of normative data for hematologic values

Basophil and eosinophil counts in African populations are significantly elevated in both genders when compared to the US-based reference intervals [9, 20]. This may be due to a high prevalence of parasitic infections in the environment including schistosomiasis, helminthic infections, perennial malaria and exposure to a broader range of environmental antigens [25, 39]. However, the eosinophil counts do not vary significantly by gender or by

age, as assessed between adolescent and adult African participants [9, 34].

ethnic group intervals when interpreting blood counts [31].

counts compared to adults as shown in our study (Table 2) [9].

1. Neutrophils

neutrophilia [56].

in African infants.

2. Basophils and eosinophils

environmental influences [53, 55].

There are limited data comparing reference intervals for hematologic values among African children compared to Caucasian children and also few studies on relevant local reference values for African infants. However, these studies, similar to the adult studies, have highlighted differences in RBC components compared to values obtained from Caucasian children [48]. The lower RBC parameters, as in the adolescent and adult groups, may be attributed to impaired hematopoiesis as a result of lower dietary iron intake, chronic blood loss due to hookworm infestation or chronic malaria infection [25]. Endemic sickle cell trait (HbS) and α-thalassemia may also play an important role [49].

#### ii. Platelets

In general, lower platelet counts are more common in African than in Western populations. While the lower platelet counts in African populations are consistent in several African studies [24, 25, 30, 31, 40], its etiology is unknown. Possibilities such as dietary, environmental and genetic factors have been proposed [24, 30, 31]. Nevertheless, the significant difference in the lower limit of the reference interval between African and Caucasian populations warrants consideration when interpreting platelet counts in patients or during clinical trial recruitment in African populations.

Among Africans males, significant age-related differences have been observed in platelet counts with adults having higher platelet counts compared to adolescents [9]. This variation is observed as a progressive increase with age from adolescence to young adulthood. In comparison, there is little age variation in platelet counts among females. However, females have higher platelet counts than males both in adolescence [9] and adulthood [9, 16]. These gender differences in platelet counts have been attributed to hormonal influences [50]. Platelet count have been observed to falls at the onset of menstruation while peak values are obtained in mid-cycle indicating that hormonal influences and/or menstrual blood loss may be involved [27]. While platelet levels remain stable during pregnancy, a decrease has been reported immediately after delivery, likely due to consumption during separation and delivery of the placenta.

#### iii. White Blood Cell (WBC) components

A high proportion of participants in the African studies have WBC counts below the lower range of the Massachusetts General Hospital US population-derived values [9, 20]. This phenomenon is consistent with a number of studies that have reported lower WBC counts in African populations and those of African ancestry, including African Americans, than in Caucasian populations [24, 30, 51-53]. Because the reference interval for WBC counts is significantly different from that of Caucasian populations, it is advisable to use appropriate ethnic group intervals when interpreting blood counts [31].

Gender differences in the WBC counts exist in both African and Caucasian populations with females having higher values than males [9, 20, 54]. Age-related difference in WBC counts has been reported in several African studies [9, 25, 33]. Adolescents have higher WBC counts compared to adults as shown in our study (Table 2) [9].

#### 1. Neutrophils

310 Blood Cell – An Overview of Studies in Hematology

ii. Platelets

delivery of the placenta.

iii. White Blood Cell (WBC) components

Age-related differences in the RBC component have also been observed among male participants, with adults (≥18 years) having higher levels of Hb, Hct and RBC compared to male adolescents (13-17 years) as shown here (Table 2) [9]. This age variation is similar to that reported in a study of Caucasian adolescents [34]. This difference could be attributed to higher levels of androgen hormones among older males. This explanation is further strengthened by the absence of age-related hematological difference among female participants. It has also been postulated that an increase in the size and mass of muscle fibers as occurs in males is

There are limited data comparing reference intervals for hematologic values among African children compared to Caucasian children and also few studies on relevant local reference values for African infants. However, these studies, similar to the adult studies, have highlighted differences in RBC components compared to values obtained from Caucasian children [48]. The lower RBC parameters, as in the adolescent and adult groups, may be attributed to impaired hematopoiesis as a result of lower dietary iron intake, chronic blood loss due to hookworm infestation or chronic malaria infection [25]. Endemic sickle cell trait

In general, lower platelet counts are more common in African than in Western populations. While the lower platelet counts in African populations are consistent in several African studies [24, 25, 30, 31, 40], its etiology is unknown. Possibilities such as dietary, environmental and genetic factors have been proposed [24, 30, 31]. Nevertheless, the significant difference in the lower limit of the reference interval between African and Caucasian populations warrants consideration when interpreting platelet counts in patients

Among Africans males, significant age-related differences have been observed in platelet counts with adults having higher platelet counts compared to adolescents [9]. This variation is observed as a progressive increase with age from adolescence to young adulthood. In comparison, there is little age variation in platelet counts among females. However, females have higher platelet counts than males both in adolescence [9] and adulthood [9, 16]. These gender differences in platelet counts have been attributed to hormonal influences [50]. Platelet count have been observed to falls at the onset of menstruation while peak values are obtained in mid-cycle indicating that hormonal influences and/or menstrual blood loss may be involved [27]. While platelet levels remain stable during pregnancy, a decrease has been reported immediately after delivery, likely due to consumption during separation and

A high proportion of participants in the African studies have WBC counts below the lower range of the Massachusetts General Hospital US population-derived values [9, 20]. This phenomenon is consistent with a number of studies that have reported lower WBC counts in

associated with an increase in the number of circulating red blood cells [47].

(HbS) and α-thalassemia may also play an important role [49].

or during clinical trial recruitment in African populations.

Within the U.S., lower neutrophil counts are more common among blacks compared to Caucasians [28]. Thus, it is not unsurprising to observe a higher proportion of African study participants (22.5-35%) having neutrophil counts below the lower range of Massachusetts General Hospital's population-derived reference interval [9]. It is estimated that about 25% to 50% of Africans have "benign ethnic neutropenia," maintaining consistently low absolute neutrophil counts with no evidence of increased susceptibility to infection or other adverse events [28]. Possibile explanations for the lower neutrophil count include diet, genetic or environmental influences [53, 55].

In general, there are significant differences in neutrophil counts between male and female adults, with the females having higher neutrophil counts than males. This increase in neutrophil counts observed in women may be related to estrogen since a decrease in counts has been reported after menopause [39]. Oral contraceptives have also been implicated in neutrophilia [56].

Additionally, several studies in southern Africa have documented high rates of neutropenia in infants of women receiving Prevention of Mother to Child Transmission interventions [57-591]. Evaluation of neutropenia in infants receiving antiretroviral prophylaxis or treatment (directly or indirectly through maternal exposure in utero or through breastfeeding) remains a challenge. Neutropenia is a known side effect of zidovudine [60] and trimethoprim/sulfamethoxazole, which is often prescribed for prevention of opportunistic infections in HIV-infected and/or HIV-exposed infants/children. This problem is further compounded by the paucity of normative data for hematologic values in African infants.

2. Basophils and eosinophils

Basophil and eosinophil counts in African populations are significantly elevated in both genders when compared to the US-based reference intervals [9, 20]. This may be due to a high prevalence of parasitic infections in the environment including schistosomiasis, helminthic infections, perennial malaria and exposure to a broader range of environmental antigens [25, 39]. However, the eosinophil counts do not vary significantly by gender or by age, as assessed between adolescent and adult African participants [9, 34].

#### 3. Monocytes

Generally, no ethnic or age differences are observed between Caucasian and African populations [46]. Monocyte counts in Eastern and Southern Africa are comparable to the US derived valuesand thus there is no need for separate reference intervals [9, 20].

Laboratory Reference Intervals in Africa 313

**p-value (gender)** **p-value (age)**

not clinically significant. There were no gender differences in BUN and glucose levels for all age groups and no significant differences in T-bil, AST, ALT and glucose between the two age groups for both males and females. However adult men and women had higher values

**percentile) <sup>n</sup> Median (95th**

**Female** 62 22.6 (12.0 – 43.1) *0.0102* 82 22.2 (13.5 - 48.5) *0.0822 0.5905* **Male** 77 26.9 (17.0 – 59.2) 77 26.7 (12.5-69.3) *0.9147*

**Female** 62 17.4 (4.2-65.3) *0.6289* 82 18.9 (10.7-61.3) *0.2247 0.1305* **Male** 77 20.5 (4.9-42.4) 77 22.4 (12.0-80.6) *0.0901*

**Female** 62 9.7 (3.7-38.5) *0.0331* 82 11.5 (5.8-36.1) *0.0368 0.7132* **Male** 77 13.9 (5.7 – 62.6) 77 13.8 (5.3 - 50.7) *0.6662*

**Female** 62 64.5 (48.0-87.6) *0.0229* 82 70.7 (52.4-96.8) *<.0001 0.0013* **Male** 77 66.3 (49.6-103.7) 77 83.1(54.2-137.8) *<.0001*

**Table 3.** Test of difference in clinical chemistry parameters between gender and age-groups from

**4. Should establishing separate normal ranges for African adolescents** 

A number of studies similar to our published data [9], have reported age-related variation between male adolescents as compared to adults for Hb, Hct and RBC levels [25, 34, 45]. This observation is physiologically grounded on hormonal influence and as per the CLSI guidelines, partitioning reference intervals by age (or other subgroup considerations) may be appropriate. While these observations may not be of any medical significance, it should be taken into consideration whenever clinical trials target this population. To satisfy the statistical requirement for partitioning, there is need for further research on reference values

Other than the RBC components mentioned above, no significant age differences have been observed in other laboratory parameters measured among males or in any parameters measured among females except for creatinine and BUN. Thus, for such parameters for which no differences are reported, adult values can be used in clinical trials involving

With the advent of antiretroviral therapy for HIV and other interventions to improve maternal and child health, pregnant women and infants have become the focus of many health programs. However, few data exist regarding these important populations, despite increased clinical trials aimed at reducing mother-to-child HIV transmission. Although pregnancy-induced changes occur in hematological values including Hb, Hct and RBC count, very few laboratories provide specific reference ranges for pregnant women [63, 64].

healthy 13-34 year olds in a rural western Kenya cohort (2003-2005).

among adolescents, as their participation in clinical trials increases.

**and pregnant women be considered?** 

**percentile)**

for creatinine and BUN compared to adolescent males and females, respectively.

**Age 13-17 years Age 18-34 years**

**Parameter Gender n Median (95th**

**AST/SGOT (μ/L)**

**ALT/SGPT (μ/L)**

**Creatinine (μmol/L)**

adolescents.

**Total Bilirubin (μmol/L)**

In the African studies, no differences are observed in absolute monocyte counts between adolescents and adults or by gender [9, 20]. Previous studies from Eastern and Southern African populations indicate an increase in monocyte counts in males compared with females but the difference is not significant [3, 24, 26, 29, 30].

#### 4. Lymphocytes

Among healthy, HIV-uninfected persons, there are no significant differences in lymphocyte counts between Caucasian and African populations but females generally have higher lymphocyte counts than males [54]. This is corroborated by studies within Africa that indicated higher CD4 cell percentage and absolute CD4 counts in females compared to males [9, 26, 61].

However, geographical variation exists in lymphocyte counts with some populations in Southern African showing significantly lower reference values than other parts of Africa [62]. In assessing age-related variability, younger age is associated with higher CD4 cell counts and a higher CD4:CD8 ratio. However, the differences are not significantly except for CD4 cell counts between male adolescent and male adults [9]. These age and geographical variations need to be considered when interpreting lymphocyte counts.

b. Clinical chemistry parameters

Most African studies [9, 15, 16, 20] report reference intervals for most parameters (creatinine, direct bilirubin, amylase and albumin) that are in agreement with reference intervals published in the United States [6]. However, certain parameters such as Creatine Kinase (CK) and Lactose Dehydrogenase (LDH) have upper intervals that are substantially higher than those published in the Massachusetts General Hospital intervals [16, 20]. Other parameters with a similar trend include total bilirubin (T-bil) and blood urea nitrogen (BUN). The upper range for T-bil is about twice as high as that of the US-derived upper reference limit while the lower range for BUN is a about a third of the US-derived lower reference limit [9, 15, 20]. The etiology of high T-bil in the African population may arise from a number of factors including RBC hemolysis caused by malaria infection or sickle cell disease, malnutrition or physical exertion. Moreover, the presence of similar trends among other African populations is suggestive of a common environmental or genetic factor.

Our findings indicated gender and age variations in blood chemistry analytes of liver and renal function among African adolescents and adults. Male adolescents and adults had higher values for alanine aminotransferase (ALT), aspartate aminotransferase (AST), T-bil and creatinine than females adolescents and adults (Table 3). These gender differences were significantly greater for T-bil and creatinine in both adolescents and adults while for AST, the difference was significant only among the adolescents. However, these differences were not clinically significant. There were no gender differences in BUN and glucose levels for all age groups and no significant differences in T-bil, AST, ALT and glucose between the two age groups for both males and females. However adult men and women had higher values for creatinine and BUN compared to adolescent males and females, respectively.

312 Blood Cell – An Overview of Studies in Hematology

Generally, no ethnic or age differences are observed between Caucasian and African populations [46]. Monocyte counts in Eastern and Southern Africa are comparable to the US

In the African studies, no differences are observed in absolute monocyte counts between adolescents and adults or by gender [9, 20]. Previous studies from Eastern and Southern African populations indicate an increase in monocyte counts in males compared with

Among healthy, HIV-uninfected persons, there are no significant differences in lymphocyte counts between Caucasian and African populations but females generally have higher lymphocyte counts than males [54]. This is corroborated by studies within Africa that indicated higher CD4 cell percentage and absolute CD4 counts in females compared to

However, geographical variation exists in lymphocyte counts with some populations in Southern African showing significantly lower reference values than other parts of Africa [62]. In assessing age-related variability, younger age is associated with higher CD4 cell counts and a higher CD4:CD8 ratio. However, the differences are not significantly except for CD4 cell counts between male adolescent and male adults [9]. These age and geographical

Most African studies [9, 15, 16, 20] report reference intervals for most parameters (creatinine, direct bilirubin, amylase and albumin) that are in agreement with reference intervals published in the United States [6]. However, certain parameters such as Creatine Kinase (CK) and Lactose Dehydrogenase (LDH) have upper intervals that are substantially higher than those published in the Massachusetts General Hospital intervals [16, 20]. Other parameters with a similar trend include total bilirubin (T-bil) and blood urea nitrogen (BUN). The upper range for T-bil is about twice as high as that of the US-derived upper reference limit while the lower range for BUN is a about a third of the US-derived lower reference limit [9, 15, 20]. The etiology of high T-bil in the African population may arise from a number of factors including RBC hemolysis caused by malaria infection or sickle cell disease, malnutrition or physical exertion. Moreover, the presence of similar trends among

other African populations is suggestive of a common environmental or genetic factor.

Our findings indicated gender and age variations in blood chemistry analytes of liver and renal function among African adolescents and adults. Male adolescents and adults had higher values for alanine aminotransferase (ALT), aspartate aminotransferase (AST), T-bil and creatinine than females adolescents and adults (Table 3). These gender differences were significantly greater for T-bil and creatinine in both adolescents and adults while for AST, the difference was significant only among the adolescents. However, these differences were

variations need to be considered when interpreting lymphocyte counts.

derived valuesand thus there is no need for separate reference intervals [9, 20].

females but the difference is not significant [3, 24, 26, 29, 30].

3. Monocytes

4. Lymphocytes

males [9, 26, 61].

b. Clinical chemistry parameters


**Table 3.** Test of difference in clinical chemistry parameters between gender and age-groups from healthy 13-34 year olds in a rural western Kenya cohort (2003-2005).
