Accuracy of clinical diagnosis and malaria rapid diagnostic test and its influence on the management of children with fever under reduced malaria burden in Misungwi district, Mwanza Tanzania
Daniel Ndaki Nkonya1,&, Donath Samuel Tarimo2, Rogath Saika Kishimba1,3
1Tanzania Field Epidemiology and Laboratory Training Program, 2Department of Parasitology, School of Public Health & Social Sciences, Muhimbili University of Health & Allied Sciences, Dar es Salaam, Tanzania, 3Tanzania Ministry of Health, Community Development, Gender, Elderly and Children
Daniel Ndaki Nkonya, Tanzania Field Epidemiology and Laboratory Training Program
malaria diagnosis is known to be non-specific because of the overlap of symptoms of malaria with other infectious diseases that is made worse with declining malaria burden. Though the use of malaria rapid diagnostic test (mRDT) for malaria confirmation has universally been adopted, malaria decline may alter performance of mRDT. This study examined accuracy of clinical diagnosis and mRDT and its influence on prescription for febrile underfives.
a cross-sectional study of 600 underfives was carried out in 6 randomly selected health facilities in Misungwi district, Mwanza; from November - December 2014. Consecutive underfives with a fever consultation were recruited: for each fever and the clinical diagnosis entertained were recorded. Parasitological confirmation of malaria was done by mRDT and microscopic examination of finger prick blood samples. Treatment was based on mRDT results, drugs prescribed recorded. Accuracy of clinical diagnosis and mRDT in predicting malaria was assessed by performance indices against microscopy. Antimalarial and antibiotics prescriptions were assessed against parasitological findings.
clinically, 37.2% had malaria; 32.8% were mRDTpositive and 17.0% microscopically
positive. Sensitivity of clinical diagnosis was very high (97.0% [95%CI:
91.0-99.2]); specificity 66.7% [95%CI: 62.3-70.8], and positive predictive
value 37.4% (95%CI:
31.6-43.5). Sensitivity of mRDTwas very high (99.0% [95%CI: 93.9-99.9]),
specificity (80.7% [95%CI: 76.9-84.0]), positive predictive value 51.3%
[95% CI: 44.1-58.4])
and negative predictive 99.75% [95%CI: 99.4-100.0]. Those receiving antimalarial
prescription, 75.0% were mRDT positive; 39.4% microscopically positive.
Those receiving antibiotic, 78.8% were mRDT negative; 90.1% microscopically
decline in malaria lowered specificity of mRDT to < 95% against WHO recommendation. Though adherence to mRDT results was high, there was over prescription of antibiotics.
Fever (raised body temperature) has been the entry point for the clinical diagnosis of malaria for decades; thus the first suspicion of malarial illness in an individual is based on the history of fever and / or measured fever . Despite the decline in malaria burden in sub-Saharan Africa , fever has remained a major cause of outpatient attendance in health facilities , thus overemphasizing the need for a parasitological confirmation of malaria among patients of all age groups with fever in line with the World Health Organization (WHO) recommendation . In most health facilities in peripheral settings, the operationally feasible parasitological confirmation of malaria is by use of malaria rapid diagnostic test (mRDT) .
In Tanzania, available data show that malaria incidence and prevalence have declined in most parts of the country as shown in the national survey of 2007/8 whereby the overall prevalence of malaria among underfives was 18.1%, while in the 2011/12 survey the overall prevalence was 9.7% by mRDT and 4.2% by microscopy [6, 7]. Based on the surveys, the decline was recorded in all geographical zones; and in both surveys the Lake, Southern and Western zones had the highest prevalence while the Northern and Southern high land zones had the lowest prevalence. The decline in malaria parasites prevalence and the number of cases of malaria related fevers may conceivably lower the specificity and predictive value of the clinical diagnosis of malaria as well as the specificity and predictive value of mRDT for the prediction of malaria parasitaemia . The decrease in malaria prevalence, and declining proportion of fevers due to malaria [2, 6], which is known to affect the accuracy (sensitivity, specificity and predictive values) of clinical diagnosis and rapid malaria diagnostic tests , primarily prompted us to conduct this study. The secondary objective was to examine the influence of laboratory findings in the guidance of case management of underfives with fever in terms of prescribing antimalarial drug for the mRDT positives and an antibiotic for the mRDT negatives suspected to have a bacterial infection [9,10]. Findings from this study are envisaged to appraise on the influence of laboratory confirmation of malaria on the management of underfives with fever and provide an informed policy decision for improving management of fever in primary health facilities . Here we report the accuracy of a clinical malaria diagnosis and mRDT for malaria diagnosis under reduced malaria burden and its influence in the management of children attending to health facilities on account of fever.
the study was conducted in Misungwi district, Mwanza region, north-west Tanzania
located at an altitude of 1,178m above sea level; with a region malaria prevalence
of 18.6% by mRDT and 5.4% by microscopy . The district
has two annual rainy seasons, the long rains between February and May and the
short rains between November and December; the dry and relatively hot season
is from June to September. Malaria transmission is seasonal, with peaks in one
to two months after the rains .
Study design and population:
a facility based quantitative cross sectional study was conducted in 6 randomly selected health facilities of Misungwi district between November and December 2014 among children under-five years of age attending to the respective health facilities on account of fever.
Sample size estimation:
the sample size was estimated based on the reported prevalence of malaria of
12.0% among underfives in one of the districts in Mwanza [13
The margin of error (ε) was taken to be 2% at 95% confidence interval.
The Sample size was computed using the formula:
n = z2
or n = z2
Where: Z = level of confidence (1.96 for 95% confidence level)
p = expected prevalence (=12%)
ε = margin of error = 2%
→N = 1.962 x 12(100 - 12) = 518
Adjustment for non-response: for a facility study it was expected that the response
rate (R) would be than 90%. To adjust for non-response, a factor F = 1/R was
multiplied by N to get an adjusted sample size. In this case, 1/R x N = 1/0.9
x 518 = 575 was the minimum sample size; in this study 600 participants were
to identify health facilities to be included in the study, a cluster sampling
technique was used. This was carried out by classifying health facilities in
three different clusters according to levels: hospital, health center or dispensary
from which 6 facilities; a hospital, two health centers and three dispensaries
were randomly selected. Thereafter the sample size allocated for each facility
was based on the catchment population.
Consecutive underfives attending to the selected facilities on account of fever
were recruited. A questionnaire was used to record the socio-demographic and
clinical characteristics of the underfives; for each a history of fever and axillary
temperature (digital thermometry) were recorded. Parasitological malaria confirmation
was done by mRDT and a prescription was given based on the mRDT findings. Blood
smears for microscopic malaria confirmation were sent to the Parasitology laboratory
at Muhimbili University of Health & Allied Sciences for expert microscopy. Two
experienced microscopist unaware of the mRDT results performed microscopy each
time comparing their results (Figure
data were cleaned, entered and processed using SPSS computer software version 13. Analysis was carried out using SPSS version 13 whereby descriptive analyses were done by using frequencies and proportions to estimate magnitude of the outcomes of interest. Accuracy of clinical malaria diagnosis and mRDT for the identification of underfives with malaria parasitaemia was assessed from the performance indices with their 95% CI. Influence of parasitological malaria confirmation on prescription of antimalarial and antibiotics was assessed against mRDT and microscopic findings.
the study ethically cleared the Institutional Review Board of the Muhimbili University
of Health and Allied Sciences. Informed consent for participation in the study
was sought from parents/caregivers on behalf of the underfives. Administrative
permission to carry out the study was sought from the appropriate Regional and
District authorities as well as the Medical Officers in charge of all selected
A total of 600 underfives with a history of fever in the last 48 hours were referred to laboratory for parasitological confirmation of malaria by mRDT and microscopy. The characteristics of the study participants are shown in Table 1. Less than a quarter (22.3%) had received an antimalarial two weeks prior to the survey. On visit, less than a half (42.8%) had fever with a body temperature of 37.5οC-40.3οC; about a third (37.2%) had a clinical diagnosis of malaria.
Parasitological malaria diagnosis by mRDT and microscopy :
of the 600 underfives referred for parasitological malaria confirmation, 32.8%
were positive by mRDT while only 17.0% were microscopically positive. Among those
positive for malaria by microscopy, close to two thirds (62.7%) had parasite
counts 10,000-350,000 / µL of blood (Table 2
Performance of a clinical malaria diagnosis and mRDT for the prediction of
malaria parasitaemia among under-fives:
as expected, a clinical diagnosis of malaria had a very high sensitivity (97.0%
(95%CI: 91.0-99.2)) for correctly identifying underfives with malaria parasitaemia
(Table 3). However, a clinical malaria diagnosis could correctly identify underfives
without malaria parasitaemia in only about two thirds (66.7% [95%CI:
62.3-70.8]) of underfives. A clinical malaria diagnosis could predict presence
of malaria parasites in only about a third (37.4% (95%CI: 31.6-43.5)) of underfives,
but could predict absence of malaria parasites in a very high percentage (99.1%
[95%CI: 97.2-99.8]). The prevalence of malaria
parasitaemia was 17.0% by microscopy and 32.8 by mRDT. The mRDT had a very high
sensitivity (99.0% [95%CI: 93.9-99.9]) and specificity
(80.7% [95%CI: 76.9-84.0]) for correctly identifying
underfives with and without malaria parasitaemia (Table 3
). The mRDT could predict
presence of malaria parasite in just about a half (51.3% [95%CI:
44.1-58.4]) of underfives and could predict absence of malaria parasites
in a very high percentage (99.75% (95%CI: 99.4-100.0)).
Influence of parasitological findings on antimalarial and antibiotics prescription:
both antimalarial drugs and antibiotics were prescribed to the underfives attended
on account of fever (Table 4
). Of those receiving an antimalarial prescription,
75.0% were positive for mRDT while 39.4 were positive microscopically. Since
prescription was based on mRDT findings, a quarter of the underfives received
an antimalarial despite having a negative result. If microscopic findings were
to be used as the basis for antimalarial prescription, there would be a relative
reduction of mRDT based antimalarial use by 47.5%. Among underfives receiving
an antibiotic prescription, about one-fifth (21.2%) were mRDT positive; however
more than three quarters (78.8%) were negative for mRDT. If microscopic findings
were to be used as the basis for antibiotics prescription, there would be a relative
reduction of mRDT based antibiotic use by 53.3%
The present study show that malaria is still a problem as 22.3% of the underfives were reported to have been treated for malaria in the last two weeks; and during the study a clinical diagnosis of malaria was entertained in 32.7% of the consultations. The observed prevalence of parasitaemia by both microscopy (17.5%) and mRDT (32.8%) at facility level is higher than the microscopic prevalence of 5.4% and 18.6% mRDT observed at the community level for Mwanza region through a recent national survey .
Accuracy of Clinical Diagnosis for the prediction of malaria parasitaemia
among febrile under-fives
The Tanzania national guidelines for malaria diagnosis and treatment provides
that fever (history of fever or measured fever) is the entry point for suspecting
malaria in an underfive but other features such as gastroenteritis (diarrhea
/ vomiting), pallor (palms / conjunctiva), inactivity and inability to feed
together constitute a clinical malaria diagnosis .
The present study show that a clinical diagnosis of malaria, although not specific,
advantage of being highly sensitive (sensitivity 97.0% [95%CI: 91.0-99.2])
for correctly identifying underfives with malaria parasitaemia. In this situation,
sensitivity is more important than specificity particularly because, although
treatable, malaria is potentially fatal . This emphasizes
on the need for ensuring availability of guidelines and adherence to the
clinical algorithm for malaria diagnosis coupled with parasitological confirmation
diagnosis based on clinical features alone has a low specificity and increases
the risk of over-diagnosis especially under reduced malaria prevalence as
is the current situation [16, 17].
Accuracy of mRDT for the prediction of malaria parasitaemia among febrile
The Mwanza region had recorded a decline in malaria prevalence (by mRDT) among
underfives; from 31.4% in the year 2007/2008 to 18.6 % in the year 2011/2012
representing a relative reduction of 40.8% [6,7].
The primary goal of this study was to examine whether the decline of malaria
prevalence would have reduced the diagnostic performance of mRDT routinely
used in health facilities for parasitological malaria confirmation. The present
show that despite the decline in malaria prevalence in the study area, the
mRDT still retained high sensitivity (99.0% [95%CI: 93.9-99.9]) for correctly
underfives with malaria parasitaemia, and was at the level of sensitivity ≥95%
recommended by WHO . The mRDT also retained a high
specificity (80.7% [95%CI: 76.9-84.0]) for correctly identifying underfives
parasitaemia, but this was lower than the WHO recommendation of a specificity ≥95%
for an ideal mRDT.
Influence of parasitological malaria confirmation on antimalarial and antibiotics
Malaria rapid diagnostic tests (mRDT) have been rolled out in Tanzania following
the recommendations by the WHO to adopt universal testing to confirm presence
of malaria parasites before antimalarial treatment .
Universal testing to confirm presence of malaria parasites is envisaged to
guide the prescription
of an antimalarial drug to those with positive mRDT results, while those
with negative mRDT results with a suspected bacterial infection would receive
The present findings show that of the 254 underfives who received an antimalarial
prescription, three quarters (75.0%) had positive mRDT results; only a quarter
(25.0%) had negative mRDT results, implying a major adherence to test results
by prescribers. Similar observations have been made in Rufiji, southeastern
Tanzania whereby adherence to mRDT findings resulted in reduction of overtreatment
antimalarial drugs by more than two thirds (71.5%) conceivably resulting
from the early health promotion campaigns as Rufiji was one of the districts
mRDT was first introduced as part of the national mRDT rollout .
Since the rollout of malaria rapid diagnostic tests for routine use in all
levels of health care was envisaged as a strategy for targeting antimalarial
this case ACT, to only those with positive mRDT results ,
the present findings show that adherence to test results has lead to a reduction
of antimalarial drug over use by three quarters as demonstrated by other
studies [19, 20].
Of those receiving antibiotic prescription on suspicion of invasive bacterial
disease, the large majority (90.1%) had negative mRDT results. This represents
an over-treatment with antibiotics as it has been shown that even in low
to moderate malaria transmission settings, invasive bacterial disease is
uncommon in underfives
with non-severe illness . Giving an antibiotic prescription
to all febrile underfive with a negative mRDT result is not justifiable because
recently it has been shown that most underfives with fever probably have
pathogens that do not require treatment with an antibiotic .
The fact that only about a third (32.8%) of the underfives were parasitologically
confirmed by mRDT to have malaria implies that two thirds of the of those
evaluated for malaria on account of fever were suffering from a condition
other than malaria.
Various non-malarial infections have been found to be major causes of febrile
syndromes in tropical settings but often clinically indistinguishable without
confirmatory tests . There is therefore a need to
develop RDTs for other tropical infections for the individual case-management
tropical infections presenting with fever .
Findings reaffirm that a clinical malaria diagnosis is a poor marker of malarial disease that is likely to be worse under reduced malaria burden. The decline in malaria prevalence has altered the performance of mRDT to a specificity < 95% below the WHO recommendation. There was a reduction in over prescription of antimalarial by three quarters due to a high adherence to mRDT results. There was an over prescription of antibiotics as not all mRDT negatives would necessarily have an invasive bacterial disease.
What is known about this topic
- Presumptive (clinical) diagnosis of malaria is non-specific because of the
overlap of the symptoms of malaria with other infectious diseases;
- There is a decline in malaria burden in sub-Saharan Africa, including Tanzania;
- The performance of clinical diagnosis and mRDT is known to change with the
prevalence of malaria.
What this study adds
- To what extent the decline in malaria burden alters the performance of clinical
diagnosis for the prediction of malaria parasitaemia under reduced malaria
- To what extent the decline in malaria burden alters the performance of mRDT
for the prediction of malaria parasitaemia under reduced malaria burden;
- To what extent parasitological confirmation of malaria by mRDT guides the management of febrile underfives in terms of antimalarial and antibiotic prescriptions in settings of reduced malaria burden.
Authors declared they have no conflict of interests.
Daniel Ndaki Nkonya: made substantial contributions to conception and design, acquisition of data, analysis and interpretation of data; and have given final approval of the version to be published.
Donath Samuel Tarimo: made substantial contributions to conception and design, acquisition of data, analysis and interpretation; drafted the manuscript and revising it critically for important intellectual content; and have given final approval of the version to be published.
Rogath Saika Kishimba: made substantial contributions to conception and design, acquisition of data, analysis and interpretation of data; and have given final approval of the version to be published.
We are grateful to the parents and guardians who permitted their children to participate in the study. We are thankful to the Mwanza Region and Misungwi District administrative authorities for granting us permission to carry out this study in the respective health facilities. Special thanks go to the staff of the respective health facilities for kindly offering the space and other logistical support during the study. This study received financial support from the Directorate of Postgraduate Studies, MUHAS through the Tanzania Field Epidemiology & Laboratory Training Program.
Tables and figures
1: characteristics of the study population (N = 600)
distribution of parasites counts among underfives microscopically positive for
malaria parasites (n =102)
performance of clinical malaria diagnosis and mRDT for the prediction of malaria
parasitaemia among underfives
influence of parasitological findings on antimalarial and antibiotics prescription
according to mRDT and microscopic findings
Figure 1: patient flow
in the study
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