Malaria parasite positivity among febrile neonates

Niger J Paed 2014; 41 (4):321 – 325

ORIGINAL

Enyuma COA

Malaria parasite positivity among

Meremikwu MM

Udo JJ

febrile neonates

Anah MU

Asindi A A

DOI:http://dx.doi.org/10.4314/njp.v41i4,6

Accepted: 3rd May 2014

Abstract Background: Malaria,

booked for antenatal care (ANC).

earlier considered rare in neo-

Most of the babies were from

Enyuma COA

(

)

nates, has been reported with in-

primiparous women (54.7%).

Meremikwu MM, Udo JJ

Six babies (4%) had malaria para-

Anah MU, Asindi AA

creasing frequency in the last dec-

Department of Paediatrics,

ade. Neonatal malaria diagnosis is

sitaemia with four (2.7%) being

University of Calabar Teaching

challenging because the clinical

congenital malaria and two (1.3%)

Hospital / College of Medical Sciences

features are non-specific, variable

acquired

malaria.

Plasmodium

University of Calabar, Calabar

and also overlap with bacterial

falciparum was the only species

Cross River State, Nigeria.

infection.

identified. All six with malaria

Email: drcarlenyuma@yahoo.com.

Aim: To determine the prevalence

were from the 136 booked moth-

callistusenyuma@unical.edu.ng

of neonatal malaria and the asso-

ers. Four of the affected six neo-

ciated clinical features in newborn

nates also had septicaemia.

babies with fever.

The clinical features in babies with

Patients and methods: One hun-

malaria only were, fever, fast

dred and fifty neonates with fever

breathing and jaundice while those

admitted into the Newborn unit of

with malaria and bacterial

the University of Calabar Teach-

co-infection had, in addition, poor

ing Hospital, over a six month

suck.

period, were recruited consecu-

Conclusion: Malaria infection and

tively. Symptoms and signs for

septicemia can coexist in some

each neonate were documented.

Nigerian newborns and since the

Blood film for malaria parasites

clinical presentation of each of

and investigation for sepsis work-

these condition are closely similar,

up were done before commence-

it is recommend that malaria para-

ment of drugs.

site investigation be included as

Results: One hundred and fifty

part of the investigation in the

babies

were

recruited.

Most

newborns with fever. This ap-

(85.3%) of the babies were aged

proach can help to avoid a delay in

≤ 7 days. One hundred and thirty

applying the appropriate therapeu-

six (90.7%) of the mothers were

tic intervention

Introduction

insecticides have however developed, contributing to the

increasing incidence .

Malaria remains a major global problem, exacting an

Diagnosis of newborns with malaria can be quite chal-

unacceptably high toll on the health and economic wel-

lenging because the clinical features are non-specific,

fare of the world’s poorest communities . P. falciparum

variable and also overlap with those of bacterial infec-

causes about 95% of malaria infection, and 18% of all

tion. These neonates are subjected to sepsis screening

causes of mortality in children less than five years

1-3

and empirically commenced on antibiotics pending

There are reports of an increasing but variable incidence

blood culture result. In some of these cases, even when

of newborn malaria from many parts of the world, ini-

fever persists despite the use of different antibiotic regi-

mens, malaria infection is rarely considered . It becomes

tially considered very rare in this age-group . Reasons

2-4

for the reported rarity include that the malaria prophy-

imperative to undertake further evaluation of the preva-

laxis taken by mothers during antenatal care lowers anti-

lence and clinical features that may be attributed to ma-

malarial immunoglobulin production in some mothers

laria among newborns with fever. This would increase

and consequently lowers the acquisition of passive im-

the index of suspicion and avert delays in early labora-

munity to malaria in their newborns . Drug resistance of

tory diagnosis and treatment. This study was therefore

P. falciparum to common antimalarial drugs and resis-

conducted to determine the prevalence of neonatal ma-

tance of the malaria vector, Anopheline mosquitoes, to

laria and the associated clinical features in newborns

322

with fever.

counted or if 500 parasites had been reached before

counting up to 200 leucocytes. A slide was declared

negative if after examining a minimum of 200 fields for

Materials and Methods

at least 15 minutes no malaria parasite was found, ac-

cording to standardized protocols.

This prospective, cross sectional, analytical hospital-

based study was conducted among neonates admitted

All the babies were commenced on intravenous Ceftri-

into the Newborn Unit of the University of Calabar

axone and Gentamycin (if urinary output was estab-

Teaching Hospital (UCTH) from the 3

of November

lished to be adequate). The babies whose blood film

2010 to the 8 of May 2011.The Unit which had earlier

results were positive for malaria parasite were in addi-

been described by Udo et al, has undergone much im-

tion, started on oral quinine at a dose of 10mg/kg/dose,

provement over time in terms of structural and man-

eight hourly for seven days in line with the National

Malaria Treatment Policy for newborns. Gentamycin

power development.

Inclusion criteria were neonates with temperature

was replaced with Ampiclox injection if a particular

≥ 37.5 C or recent history of fever, who had not received

baby was to receive Quinine. This was to reduce the risk

anti-malarials or antibiotics at least two weeks prior to

of ototoxicity.

enrolment into the study and whose parents or guardians

On retrieval of laboratory results, (full blood count

had given consent.

(FBC), cerebrospinal fluid (CSF), blood and urine cul-

Ethical clearance was obtained from the Ethics Review

tures), antibiotics were discontinued if results were

Committee of the University of Calabar Teaching hospi-

found to be normal. At the completion of the anti-

tal before commencement of the study.

malarial drug in babies with positive MP result, periph-

The study was explained to the parents to understand

eral blood films for malaria parasite were repeated to

what the study entailed and a signed informed consent

ascertain response to treatment.

was obtained from the parents or guardians who gave

consent.

Findings were collated with the aid of the case record

form designed for the study. Data was analysed using

All consecutive babies (0-28 days) who met the inclu-

SPSS version 14 statistical software. Frequency, sample

sion criteria were recruited until the desired sample size

means, and percentages were calculated as necessary.

was obtained. Detailed clinical history (presenting com-

Statistical significance of difference was determined

using Chi square(X ) for dichotomous variables, t-test

plaints, drug history, immunization history, nutritional

history, pregnancy history that includes investigations

for continuous variables and Wilcoxin rank-sum test

done, compliance with chemoprophylaxis/ folic acid,

was used to test the non parametric variables. The level

tetanus immunization, fever, blood film for MP in preg-

of significance was set at p ≤ 0.05.

nancy, drug treatment for malaria if taken. Others were

delivery history, family and social history which in-

cludes the parents age, marital status and mothers parity,

level of education attained and occupation) was obtained

Results

and anthropometric measurements performed on the

babies. The social classes of the babies were arrived at

A total of 150 subjects were recruited. The study popu-

based on the objective criteria of the father‘s occupation

lation was made of 87 (58.0%) males and 63 (42.0%)

and level of maternal education, as suggested by Olu-

females with M:F ratio of 1.4:1. The age category 0-

sanya O et al.

7days represented 128(85.3%) of the subjects. The study

population was not normally distributed. It had a mean

Two blood films (thick and thin film) for malaria para-

age of 4.2±5.9days, with a median of 2.0 days. The dif-

site (MP) and samples for sepsis work-up (full blood

ference in ages between the male and female population

count,

blood

culture,

urine

microscopy/culture/

was not statistically significant (p=0.71). (Table 1)

sensitivity via suprapubic tap, cerebrospinal fluid pro-

tein, sugar, microscopy, culture and sensitivity) were

Table 1: Anthropometric and clinical characteristics of the

taken before commencement of treatment. Both thick

study population

and thin blood films were prepared and stained with 2%

Patients character-

Mean ±SD

Total

istics

N=150

value*

freshly prepared Giemsa stain, Thereafter, they were

Male(n=87)

Female(n=63)

read using ×100 objective lens with oil immersion

Age (days)

4.4±6.2

4.0±5.5

4.2±5.9

0.71

within 24 hours of collection of blood by the investiga-

Examining Tem-

38.1±0.6

38.1±0.8

0.88

perature ( C)

tor, assisted by the laboratory scientist. The slides were

Weight (Kg)

3.1±0.8

3.0±0.7

3.1±0.8

0.39

validated independently by the microscopist with Insti-

Length (cm)

49.3±3.6

49.2±3.3

49.3±3.5

0.80

tute of Tropical Disease Research and Prevention and a

Occipito Frontal

34.4±2.0

34.0±2.0

34.2±2.0

0.17

Circumference

World Health Organisation certified laboratory scientist

(cm)

attached to Department of Paediatrics research labora-

Heart rate (bpm)

144.7±13.3

142.6±19.3

143.8±118

0.29

Respiratory Rate

54.8±14.1

54.4±13.3

54.6±13.7

0.85

tory. Asexual forms of the parasite (trophozoites or ring

(cpm)

forms) and the sexual forms (gametocytes) were counted

*Statistical test= Wilcoxin rank-sum test; characteristics similar in males and

in each field along with the leucocytes. Parasite count

females

was discontinued when 200 leucocytes had been

323

The average age of the mothers was 28.1±4.9 years.

Table 2b: Common clinical signs elicited in the study popula-

Ninety three percent of the mothers had at least, secon-

tion

dary school education. The social class distribution

Clinical signs

Malaria

Sepsis only

No Ma-

P-value

only

+ Sepsis

(N=88)

laria/No

showed that 19(12.7%) babies were of the lower social

(N=2)

(N=4)

sepsis

class, 75 (50.0%) were of the middle social class and 56

(N=56)

(37.3%) were of the upper social class.

One hundred and thirty six (90.7%) mothers booked for

Low Birth

0.0

21.0

23.3

0.841*

Weight

antenatal care (ANC) either in UCTH or at other health

Abdominald-

0.0

3.4

3.6

1.000*

facilities. One baby was adopted and so the ANC status

istension

was not known. Primiparous mothers constituted 54.7%

Jaundice

50.0

25.0

46.6

42.9

0.847*

Pallor

0.0

4.5

0.0

0.289*

of the maternal population.

Tachypnoea

2 100.0

25.0

13.6

25.0

0.015*

Interview of the mothers revealed that 21(14.0%) of

Dyspnoea

0.0

4.5

1.8

0.714*

them had malaria or symptoms suggestive of malaria

Crepitation

0.0

2.3

0.0

0.559*

during pregnancy. Only three of these mothers had labo-

Murmur

0.0

1.1

1.8

1.000*

Lethargy

0.0

4.6

0.0

0.285*

ratory confirmation; the rest were treated presumptively.

Twelve of the 21 cases of suspected malaria (57%) oc-

*Fisher’s exact

curred during the second trimester while nine (43%)

were in the third trimester. Out of these 21 mothers, 19

One hundred and twenty eight (85.3%) mothers were

were booked for ANC and two were not. Eighteen

aged 20-35 years and four of their newborns had malaria

(85.7%) of the mothers used Lumefanthrine/Arthemeter

parasitaemia. Sixteen (10.7%) of the mothers were 35

combination, an Artemisinin based Combination Ther-

years and above, two of their babies had malaria parasi-

apy (ACT).

taemia. Six (4%) of the mothers were teenagers and

none of their babies had malaria parasitaemia.

Six (4.0%) of the newborn population had malaria para-

There were 31 (20.7%) low birth weight newborns, none

sitaemia, and all were from the 136 mothers that booked

of whom had malaria parasite identified in their blood

for ANC. Plasmodium falciparum was the only species

film. Five of the 99 (66.0%) term adequate for gesta-

identified. Four (66.6%) of the six babies with malaria

tional age babies compared to one of 20 (13.3%) macro-

parasitaemia were aged under seven days, indicating that

somic neonates had malaria parasitaemia.

that they were congenital infections. The other two ba-

All the 150 newborns recruited were followed-up at the

bies were aged 14 and 23 days respectively.

Newborn outpatient clinic as scheduled. None of six

A total of 92(61.3%) babies had septicemia: 54(58.7%)

with parasitaemia had malaria in the repeat peripheral

blood samples yielded Staphylococcus aureus and 38

thick blood smear. None of the babies died during the

(41.3%) grew unclassified Coliform species. Four neo-

period of study and follow-up.

nates had malaria and bacterial co-infection. Two of

these had Staphylococcus aureus while the other two had

unclassified Coliforms septicemia infections. The two

babies that had malaria alone were a day old female, and

Discussion

a 14 day old male. Fifty eight (38.7%) febrile newborns

had no growth in their blood cultures

The present study has revealed a prevalence of 4% for

neonatal malaria among newborns with fever, consisting

Fever (100.0%), fast breathing (100.0%) and yellowness

of 2.7% and 1.3% of congenital and probably acquired

of the skin (25.0%) were the commonest clinical fea-

malaria, respectively. None of the newborns had transfu-

tures presented by the newborns with malaria parasitae-

sional malaria since none had received blood transfu-

mia only. None in the study had hepatosplenomegaly.

sion. The prevalence of congenital malaria of 2.7% in

The differences in the symptoms and signs between

this study is similar to earlier report of 2% prevalence of

newborns with malaria alone and those with septicaemia

congenital malaria by Oduwole et al using PCR and

were not statistically significant, except for fast breath-

3% reported by Bassey et al

both in Calabar. The

ing (p<0.05). (Table 2a and 2b)

lower prevalence rates observed in the current study

compared to 8% reported by Ibhanesebhor in Benin,

Table 2a: Presenting symptoms among the study populations

8.25% reported by Orogade

in Zaria, 24.8% reported

by Runsewe-Abiodun et al

Symptoms

Mal.only

Mal+Sep

Sep. only

Nil mal/

P-value

in Sagamu, 33.3% by

(N=2)

(N=4)

(N=84)

Nil Sep

Ojukwu et al in Ebonyi may be explained by the recent

(N=56)

improvements in malaria control practices in preg-

nancy, differences in the methodology and expertise of

Fever

100.0

98.9

96.4

0.212

the laboratory scientist . Microscopy in the present

Fast

100.0

25.0

14.8

19.6

0.043*

breathing

study was validated by two independent research labora-

Yellow

50.0

25.0

46.6

42.9

0.847

tories.

skin

Seizures

0.0

5.7

7.1

0.819

Poor suck

0.0

25.0

15.9

8.9

0.458

The prevalence from this study is higher than a preva-

Excessive

0.0

5.7

3.6

0.780

lence of 0.35% found in the newborns in a Kenyan

cry

study and 0.98% in Cote d’ Ivoire. These differences

*Proportion with fast breathing differ significantly across groups

may still be a reflection of differences in malaria trans-

324

mission pattern and local control efforts . This study

tal is 4% with P. falciparum being the only species im-

documented co-existence of malaria infection with septi-

plicated. It appears the clinical features in neonates with

cemia in some Nigerian newborns. This suggests that in

malaria parasitaemia cannot be differentiated from the

high malaria transmission areas such as ours, a number

presentation of neonates with septicaemia. It is therefore

of newborns with confirmed bacterial sepsis may also

recommend that in malaria endemic areas, malaria

have malaria co-infection. Furthermore, there is clearly

screening be made part of sepsis work-up in every ill

an overlap in clinical features between the infants with

newborns. This approach will help to avoid a delay in

isolated malaria infection, septicemia alone, or co-

applying the appropriate therapeutic intervention.

infection. This underscores the need to screen for ma-

laria in every febrile newborn infant in malaria endemic

areas. The combined clinical and therapeutic implication

Authors' contributions

of this is that if bacterial sepsis is the tentative diagnosis

Enyuma COA: Lead investigator, manuscript prepara-

and malaria is confirmed to coexist, antibiotics and anti-

tion

malarial are commenced simultaneously to achieve opti-

Meremikwu MM: Study design, investigation, editing

mum clinical response. Also if after commencing em-

and correction of manuscript.

pirical antimicrobials, laboratory reports later confirm

Udo JJ: Reviewed all the neonates and corrborated the

that all body fluids are sterile except for malaria, the

findings.

antibiotics maybe discontinued early enough to avoid

Anah MU: Cross checked the results, editing and correc-

wastage.

tion of manuscript.

Asindi AA: Editing and correction of manuscript.

In the current study, fever, jaundice and fast breathing

Conflict of interest: None

were more prevalent in newborns with malaria parasitae-

Funding: None

mia compared to those with septiceamia alone or co-

infection. The limitation of our study is that the number

of newborns with malaria parasitaemia only was too

small to make generalization on the clinical features that

are specific to neonatal malaria. Further large scale stud-

Acknowledgement

ies will be necessary to specifically look for the specific

features.

We gratefully acknowledge Prof Emmanuel E Ekanem

for assisting in preparing and correcting the manuscript,

Dr Udeme Ekrikpo for his contribution to data analysis

and all the Residents in department of Paediatrics for

Conclusions

their assistance in data collection.

The prevalence of neonatal malaria in febrile newborns

presenting in the University of Calabar Teaching Hospi-

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