The study was carried out in Jos University Teaching Hospital (JUTH) and Bingham University Teaching Hospital (BhUTH) which are the two tertiary hospitals in Jos and account for the highest number of neonatal admissions in Jos. JUTH is a 500 bed-space hospital with three wards designated for neonatal care―the Special Care Baby Unit (SCBU) and two lying-in wards (Postnatal wards 1 and 2). The SCBU has 30 bed spaces while the postnatal wards have 32 bed spaces each. There were a total of 670 neonatal admissions in 2012. BhUTH is a 150 bed hospital. It has a 10 bed space SCBU with 177 neonatal admissions in 2012.

Jos Plateau metropolis is a tropical highland located near the geographical centre of Nigeria. Jos has an area of 7800 km² [13] . It lies at a general altitude of 1300 m above sea level, reaching its highest peak at the Shere Hills where it stands at 1766 m above sea level. It is characterised by a mean annual rainfall of about 1260 mm (1050 - 1400 mm), reaching its peak between July and August while the mean annual temperature is about 22˚C [13] . Malaria transmission in Jos is unique as it has two described patterns―an endemic perennial pattern and a seasonal epidemic pattern [14] . Malaria transmission is perennial in most parts of Jos due to presence of factors such as residence near mining ponds and poor housing and drainage that encourage the bionomics of the mosquito vector all year round. The seasonal pattern of transmission is noticed in some areas of southern part of Jos Plateau due to the predominant high altitude and cold climate―factors which have been observed to discourage malaria transmission [11] .

The study had a prospective hospital based longitudinal descriptive study design and was carried out between 2^nd January and 4^th July, 2013. All consecutive neonates (aged between 0 and 28 days) admitted into the selected hospitals were recruited within 24 hours of admission if they met the inclusion and exclusion criteria.

Inclusion Criteria

1) All babies aged between 0 - 28 days on admission with duly signed written informed consent form from parents/guardians.

Exclusion Criteria

2) Any newborn with major congenital anomalies;

3) Babies who received antimalarial medications within two weeks prior to recruitment.

The flowchart below (Figure 1) illustrates the recruitment process for the study.

Using a case record form, maternal demographic and obstetric history as well as the neonate’s presenting symptoms and examination findings were documented. Gestational age was calculated from mother’s last menstrual period for all babies and/or Ballard score for babies presenting within 7 days. Newborns with gestational age less than 37 weeks, 37 - 42 weeks, and over 42 weeks were classified as preterm, term and post term respectively.

Each baby was weighed using a precalibrated beam balance (SECA infant weighing scale, model 725, precision 0.005 kg, range 0.5 - 16 kg). For infants admitted aged less than 24 hours, weight on admission was considered as birth weight and for older infants, birth weight was obtained from birth records where available. Axillary temperature values were measured using a digital thermome-

ter (UMEC-DT-01A, Range 32˚C - 42˚C, Accuracy ± 0.1˚C) inserted into the axilla until it beeped (usually after about 2 - 3 minutes).

All blood samples were collected following standard aseptic procedures. Thick and thin blood films were prepared using clean grease-free unsilicated glass slides from each baby using heel pricks within 24 hours of admission. The films were air dried without convection, and stained with 10% freshly prepared Giemsa stain maintained at a PH of 7.2. Thin blood films were fixed with 100% methanol prior to staining. The stained blood films were viewed under a light microscope at x1000 magnification (X100 oil immersion lens). The diagnosis of malaria was based on the identification of asexual stages of Plasmodium on the thick blood smears, while thin blood smears were used to identify species of Plasmodium. Plasmodium parasite density was determined by counting the number of asexual parasites against 200 leucocytes on the thick blood film and converted to parasites per microlitre using an assumed total white blood cell (WBC) count of 8000/microlitre (µl). Blood films were declared negative if no parasite was seen after viewing 500 WBC. Each slide was read independently by two trained microscopists in Jos University Teaching Hospital. In the event of discordant results (either positive/negative discordance or greater than twofold density difference above 400 parasites/μl) the slide was examined by a third microscopist. The mean of the values obtained was used for parasite density. Also, Haematocrit was obtained for each of them at admission.

Subjects admitted with a diagnosis of probable sepsis (based on WHO guideline) [15] or considered at risk for sepsis had sepsis work up carried out. A neonate was considered to be at risk for sepsis if one of the following was present: a history of prolonged rupture of membranes for >24 hours, history of maternal malodorous vaginal discharge, maternal painful micturition, fever in mother within 2 weeks prior to delivery, prematurity, vigorous resuscitation at birth, and delivery outside a hospital. All subjects who had malaria parasitaemia demonstrated in their blood films also had sepsis work up done to exclude neonatal sepsis. Sepsis work up included a Complete Blood Count and Blood Culture. Cerebrospinal fluid (CSF) was also collected for microscopy culture and sensitivity when meningitis was suspected.

Subjects were managed afterwards in line with the pre-existing standard of care for malaria and neonatal sepsis as obtained in the study sites as outlined below:

1) Subjects who had malaria parasitaemia in their blood film were given amodiaquine syrup at a dose of 10 mg/kg given as a daily dose for 3 days. Subjects with treatment failure (persistence of malaria parasitaemia on thick blood film within 14 days of treatment) were given syrup Quinine at a dose of 10 mg/kg/dose 8 hourly for seven days. Clinical features were reviewed daily and thick blood film repeated on days 3, 7 and 14 to determine outcome of treatment. Outcomes evaluated were clinical cure (absence of clinical features by day 3 of treatment), parasitological cure (persistent absence of parasitaemia by day 14 of treatment with stated antimalarial drug), and treatment failure (presence of parasitaemia within 14 days of treatment with antimalarial drug).

2) Subjects with a diagnosis of probable sepsis were commenced on broad spectrum intravenous antibiotics on admission (ampicillin and gentamycin or ceftazidime and gentamycin) while awaiting blood culture results.

Data was entered into the computer using Microsoft Excel 2007 software and analysed using Epi Info 3.5.3 soft-ware. Chi square was used to test for determine differences between groups. Student’s t test was used to test for differences between means. Fischer’s exact test was used to obtain p values for cross-tables with cells containing <5 subjects. A p value of <0.05 was considered as statistically significant.

Ethical clearance certificates were obtained from JUTH and BhUTH ethical committees. Also, a written informed consent was obtained from a parent/ guardian of each neonate after due explanation of the nature, benefits and possible risks of the study to the neonate.

A total of 301 subjects (240 and 61 from JUTH and BhUTH respectively) were

recruited into the study. One hundred and ninety three (64.1%) were males and 108 (35.9%) were females. The median age of the subjects was 2 days (inter-quartile range 0.6 days) (Figure 2). Two hundred and thirty six (78.4%) were neonates aged ≤7 days. The mean birth weight was 2848.8 ± 924.6 grams. Table 1 summarizes the socio-demographic characteristics of the neonates. The socio-demographic characteristics of the neonates in the two hospitals were similar except their mean birth weight. The neonates in BhUTH had a statistically significant higher birth weight than those in JUTH (t = 2.197, p = 0.029).

Malaria parasitaemia was present in 16 out of the 301 neonates with a prevalence rate of 5.3%. Malaria parasitaemia was demonstrated in 11 and 5 subjects in JUTH and BhUTH respectively (p = 0.261, Table I). Congenital malaria was seen in 14 out of the 236 neonates age ≤7 days with a prevalence rate of 5.9%. Congenital malaria represents 87.5% of those with neonatal malaria. Acquired neonatal malaria (malaria parasitaemia in neonates aged 8 - 28 days) was present in 2 out of the 65 neonates aged 8 - 28 days with a prevalence rate of 3.1% (Table 2). Table 3 summarizes the sociodemographic risk factors of malaria in the studied neonates. The consistent use of ITNs was associated with protection against neonatal malaria (p = 0.025). The odds of malaria in neonates of mothers who always slept under an ITN during pregnancy was 0.3.

All 301 subjects had at least one clinical feature at presentation (Table 4). Fever and jaundice were the commonest clinical features at presentation. One (6.25%)

*Statistically significant, ^$Student’s t test.

of the 16 confirmed subjects with neonatal malaria also had blood culture confirmed neonatal sepsis. Therefore, the subject was excluded from analysis for clinical features attributable to neonatal malaria. Fever (axillary temperature > 37.5˚C) was the commonest clinical feature of confirmed malaria parasitaemia present in 10 (66.7%) of the 15 cases. Other clinical features seen include: jaundice 5 (33.3%), excessive crying 4 (26.7%), refusal to feed 1 (6.7%). Fever was the only statistically significant symptom of malaria (p = 0.031) (Table 5). When testing for the usefulness of fever in the diagnosis of malaria, values for sensitivity, specificity, positive predictive value and negative predictive value are 68.8%, 61.4%, 9.1% and 97.2% respectively.

P. falciparum was the only specie of Plasmodium responsible for all the 16 confirmed cases of malaria parasitaemia. The median parasite density was 255 (interquartile range= 72, 380) parasites/µl with modal parasite density class between 101 - 1000 parasites/µl (Figure 3).

^#Fisher’s exact test, *Statistically significant IPT-SP = intermittent preventive treatment of malaria with Sulfadoxine-pyrimethamine. ITN = insecticide-treated bed net.

(Total number of neonates with malaria = 16, 1 neonate was excluded due to confirmed neonatal sepsis which was a confounder.) *Statistically significant, ^#Fisher’s exact test.

Fifteen out of the sixteen (93.8%) neonates with confirmed malaria infection had clinical and parasitological cure following treatment with amodiaquine. One of the sixteen had both clinical and parasitological treatment failure with amodiaquine and achieved both clinical and parasitological cure on retreatment with quinine. There was no malaria recrudescence recorded in all 16 neonates with malaria after 14 days following treatment. None of the subjects with malaria died (Figure 4).