RELEVANCE OF RAPID DIAGNOSTIC TESTS IN THE MANAGEMENT OF UNCOMPLICATED MALARIA AMONG CHILDREN AGED 1-5 YEARS IN WESLEY GUILD HOSPITAL

SUMMARY

 BACKGROUND: Accurate diagnosis of malaria is an essential prerequisite for proper treatment as well as prevention and monitoring of drug resistance. Microscopy is considered the gold standard for malaria diagnosis. It however has limitations, part of which includes the need for special training and retraining for microscopists and an increased patient waiting time. Rapid diagnostic tests (RDT) have however been brought into field operation and it has relevance especially in a high volume outpatient clinic like there is in Wesley Guild Hospital. This present study focuses on the relevance of RDT in the management of uncomplicated malaria among children in the Wesley Guild Hospital,

Ilesa.

OBJECTIVES: This study set out to determine the sensitivity and specificity of RDT in malaria diagnosis and determine the correlation between RDT and microscopy in detecting malaria among children aged one to five years in the Wesley Guild Hospital, Ilesa.

METHODOLOGY: Four hundred and seventy-five children aged one to five years

attending the paediatric outpatient clinic at the Wesley Guild Hospital, Ilesa who met the inclusion criteria were serially recruited over three months and studied with a structured questionnaire, malaria smear microscopy and malaria rapid diagnostic test which was performed using SD Bioline Ag Pf/ Pan. Socio-demographic information, family characteristics and malaria-related history were obtained from the caregivers while the patients’ vital signs were also measured. The data was analyzed using the Stata^® statistical software package, version 10.

RESULTS: Of the 475 children studied, 50.9% were males and 49.1% were females. The mean age was 32 (S.D 16.68) months. Majority of the children were between the ages 1223 months (37.9%), from the upper socio-economic class (76.0%), belonged to average sized families (60.8%) with both parents present (94.1%). Majority were of Yoruba ethnicity (92.4%) and urban dwellers (76.0%). Most (73.9%) had a history of malaria at least once in the preceeding six months with nearly half (44.1%) of the households possessing a Long lasting Insecticidal Net (LLIN). Fever was the commonest presenting symptom (98.5%), with 41.5% having temperature levels between 37.5-38.4°C. RDT was positive for Plasmodium falciparum malaria infection in 67.6% of the study subjects while microscopy detected Plasmodium falciparum infection in 70.5% of the study subjects. Two hundred and twenty one (46.5%) of all the study subjects had parasite density of less than 1000 per microlitre.

RDT sensitivity was 93.7%, specificity was 95.0% with a positive predictive value of 97.8% and a negative predictive value of 86.4%. The correlation coefficient between RDT and microscopy was 0.864, which showed a strong positive correlation between the two for malaria detection.

CONCLUSION: SD Bioline Ag Pf/Pan RDT was highly sensitive and specific for detecting Plasmodium species among children aged one to five years in Wesley Guild Hospital, Ilesa. There was also a positive correlation between RDT and microscopy in malaria detection. RDT is very useful in the prompt and accurate diagnosis of uncomplicated malaria in the study population. RDT is thus an important tool in prompt and appropriate management of childhood fevers. It has a great potential to reduce malaria overdiagnosis, misdiagnosis of childhood fevers, under-five morbidity and mortality.

TABLE OF CONTENTS

Title

page………………………………………………………… ……………………i

Declaration…………………………………………………

………………………….ii

Certification………………………………………………

…………………..……….iii

Dedication…………………………………………………

…………………………. .iv

Acknowledgement…………………………………………

………………………….v

Table of

contents……………………………………………………

…………………vi-vii

List of

Tables……………………………………………………………………….1——————————————————————————————— 2

Chapter One: Introduction ———————————————————- 3

Chapter Two: Literature ————————————————————- 9

review…………………………………………………………..——————

10Chapter Three: ——————————————————————– 36

……………………viii

List of

Figures………………………………………………………

………………….ix

List of

Abbreviations………………………………………………

…………………..x-xii

Summary

………………………………………………………………

Methodology………………………………………………

………….37-44

Chapter Four:

Results………………………………………………………

………….45-55

Chapter Five:

Discussion…………………………………………………

……………56-63

Chapter Six: Conclusions and

recommendations………….…………………………..64-

65

Limitations of the

study……………………………………………………….6

6

Area of further

study………………………………………………………

…..67

References…………………………………………..………

…………………………68-80

                                    Appendices:  

CHAPTER ONE INTRODUCTION

Malaria is an infectious disease caused by a protozoon of the genus Plasmodium. It is the world’s most important parasitic infection.¹ There are four identified species causing human malaria: Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale and Plasmodiummalariae.¹ Of these four species, Plasmodium falciparum is the commonest specie in virtually all parts of Africa, accounting for up to 98% of cases of malaria in the continent.² The disease is spread through the bite of the female anopheles mosquito while it is taking a blood meal from a human. Malaria is a worldwide disease, occurring in more than 100 countries across regions of Africa, Asia, Islands of the south, west and central

Pacific Ocean, Latin America, certain Caribbean Islands and Turkey.

Malaria endemicity is variable: Stable malaria denotes transmission all year round with some seasonal variation while unstable malaria is characterized by intermittent transmission (i.e. annual, bi-annual or variable). Malaria endemicity thus confers varying degrees of immunity against the causative organism, with people in the stable transmission zone having the highest immunity.^{3, 4}

Vulnerable groups of people with the greatest susceptibility to the severe forms of malaria are children, pregnant women and non-immune travelers from outside the malaria endemic zones.⁴ For the former, the family’s lifestyle and attitudes especially as regards environmental sanitation and health seeking behavior determines the extent of this susceptibility. In malaria- endemic countries of West Africa, 25-40% of all outpatient clinic visits involving under-five children is for malaria, and 20-50% of all hospital admissions in children are a consequence of malaria.⁴ Most often, the diagnosis of malaria is clinical.⁴ The Family is the social context in which illness occurs and where recovery takes place.⁵ Family characteristics such as income, socioeconomic status, maternal education and family lifestyle (especially environmental sanitation) affect not only the occurrence of disease but also the health seeking behaviour of caregivers and the utilization of health services. The lower socioeconomic groups are affected more by malaria.⁴ This can be adduced to the poor environmental hygiene characteristic of the living area of people in this social stratum. Such an environment allows the anopheles mosquito to thrive, thus favoring malaria transmission. Family lifestyle practices regarding environmental sanitation, netting of doors and windows and the use of long lasting insecticidal nets (LLIN) all contribute to the susceptibility of members of a family to malaria. A child reared in a mosquito breeding environment by a mother whose health seeking beliefs and practices are not ideal will have more episodes of malaria than one raised in a sanitary or healthy environment.⁴

The burden of malaria is enormous. Malaria kills at least one million people every year worldwide; 95% of malaria deaths occur in Africa.⁶ Nearly 500 million people suffer from acute malaria each year with majority of victims being children. Thirty to forty percent (30-40%) of all febrile illnesses in Africa are due to malaria.⁷ The failure of health systems, drug resistance and presumptive treatment without accurate diagnosis contribute to the burden of malaria.^{6, 7}

Malaria endemic countries are some of the world’s most impoverished nations. Many malaria stricken families sometimes spend an average of over one quarter of their income on malaria treatment.⁸ High infant mortality has demographic consequences, with households and families responding by having more children. The more the number of children, the lower the investment of the parent and society in the health and education of each child, resulting in lower wellbeing of the child. Short –term economic effects of malaria can result in a family being unable to afford the basic necessities of life.  Accurate and timely diagnosis of malaria is essential if severe complications and mortality are to be reduced. Malaria diagnosis can be empirical (clinical) or based on objective evidence of parasitaemia. Clinical diagnosis is based on the presence of fever and the other symptoms of malaria.^{1, 2}

Fever is the most constant symptom of malaria, but neither the degree nor the pattern of fever is of importance in establishing a diagnosis of malaria.² Vomiting, with or without nausea, is frequent in acute childhood malaria. Other symptoms include fatigue, chills, headache, myalgia, abdominal pain, back pain and diarrhea. Malaria is a great masquerade that can mimic most febrile ailments.⁹As mentioned earlier, patients with malaria usually present with fever. In complicated malaria, the clinical features may include convulsions, pallor, jaundice, dehydration and anaemia-induced cardiac failure.^1,2,3 In endemic areas where fever is very often due to malaria, clinical diagnoses reduces cost and delay in treatment as access to laboratory services is not needed. On the long run however, some believe that it is invariably an expensive way of diagnosing as the eventual overall cost of treating and re-treating febrile illness is high as clinical diagnosis has a poor specificity and predictive value.¹⁰ Laboratory support is needed to accurately diagnose malaria in every part of the world but more especially in areas of unstable transmission.¹¹

Laboratory-based diagnosis can be classified as microscopy tests and non-microscopy tests. The conventional thick and thin film for malaria parasite and the quantitative buffy coat method falls under the laboratory-based microscopy method.

Microscopy of stained thick and thin blood films prepared from a finger-prick capillary blood sample reveals the presence of Plasmodium species and also shows the different species present.¹¹ There are many methods for staining blood films for malaria diagnosis. These include the Giemsa, leishman and field staining methods.¹² Thick and thin films are regarded as the gold standard in malaria diagnosis and serve as the method of reference for other malaria diagnosis methods. One major drawback to malaria microscopy is that a good yield depends on proper and suitable slide preparation and scoring by an experienced microscopist with good expertise. In addition, laboratory equipment and electricity are needed. Lastly, immune individuals living in high transmission areas can have parasitaemia without clinical symptoms thus indicating that microscopy cannot be interpreted in

isolation.¹²

Polymerase chain reaction (PCR) is a non-microscopy based test that allows specific amplification of a selected region of the malaria genome. It can be used to detect and differentiate the Plasmodium specie. The equipments are however very sophisticated and expensive.¹¹

Serologic tests for malaria are non-microscopy tests which rely on the detection of antibodies against asexual blood stages of the malaria parasite. Immunofluorescence assay is an example of this and it uses specific antigen prepared on a slide coated with patient’s serum.¹³ However, this test is cumbersome and time consuming. Rapid diagnostic tests have been used in the diagnosis of tuberculosis (TB – Quantiferon test), Human Immunodeficiency virus infection (HIV rapid test), syphilis, influenza, multiple myeloma and malaria.¹⁴ Rapid diagnostic tests (RDTs) offer the potential to provide accurate and timely diagnosis to everyone at risk, reaching those previously unable to access good quality microscopy services. In malaria-endemic regions, the use of RDTs is very helpful for the cost-effective use of anti-malarial drugs as treatment is based on parasite diagnosis and not just fever alone. In these regions, a considerable proportion of antimalarials are wasted in patients with non-malarial disease due to lack of prompt and accurate laboratory diagnosis.¹⁵

STATEMENT OF THE PROBLEM AND PROBLEM ANALYSIS

The most vulnerable groups of people with the greatest susceptibility for the severe forms of malaria are children, pregnant women and non-immune travelers from non-endemic zones for malaria. Malaria is responsible for up to one-million childhood deaths each year globally.⁸ Malaria kills an African child every 30 seconds, often in combination with other diseases. Children can suffer as many as six bouts of malaria attacks annually and this interferes with their growth and learning.⁹ In view of these, rapid diagnosis and prompt treatment of malaria become imperative.

In the past, many patients with malaria, especially among children younger than five years old were treated presumptively for malaria based on a list of symptoms, most notably fever. The World Health Organisation now recommends a diagnostic test for suspected malarial illness prior to treatment.⁴ Reserving treatment for confirmed malaria illness is important in delaying the development of resistance to the current antimalarials, by prescribing them only when necessary. The resistance of Plasmodium falciparum to the older and cheap antimalarial drugs had led to the development of newer more expensive medications. The poor socio-economic status in the malaria-endemic regions of the world calls for an urgent need to protect existing potent drugs through their proper and appropriate use. This underlies the WHO policy of accurate diagnosis before treatment. RDTs become vitally important in the achievement of this goal.

Wesley Guild Hospital unit paediatric outpatient clinic has a high patient load with nearly 500 patients attended to weekly. As a result of this, the microbiology laboratory (which serves the whole hospital) is usually overwhelmed by the number of people requiring microscopic malaria parasite detection, the only laboratory-based malarial diagnostic method available in the hospital. This warrants patients having to wait a longer time, creating a high degree of dissatisfaction regarding the quality of service offered to patients. This study therefore proposes to use RDT strips in the paediatric outpatient clinic in order to assess its relevance in the management of uncomplicated malaria. Local studies on RDT for malaria diagnosis in the outpatient setting were not found in literature and as such no data on how useful or otherwise RDTs are in the hospital are available.

AIM

This study aimed at assessing the relevance of RDT in the management of uncomplicated malaria among children aged one to five years in the Wesley Guild Hospital Unit of Obafemi Awolowo University Teaching Hospitals’ Complex, Ile-Ife in order to promote appropriate and timely treatment of malaria.

OBJECTIVES

1. To determine the sensitivity and specificity of RDT in malaria diagnosis in Wesley     Guild Hospital Unit, Ilesa.
2. To determine the correlation between RDT and microscopy in detecting malaria.

JUSTIFICATION FOR THE STUDY

Bearing in mind that one of the six elements of roll back malaria is prompt diagnosis and appropriate treatment of malaria episodes with safe and effective antimalaria drugs, malaria morbidity, mortality and transmission can be reduced if prompt diagnosis and adequate treatment are readily available. ⁴ Clinical diagnosis in determining who to treat for malaria based on signs and symptoms results in wastage of ACTs. Laboratory diagnosis is therefore preferred over clinical diagnosis. Microscopy entails the use of equipments and reagents by skilled laboratory workers who usually have a heavy workload and are not widely available to facilitate prompt treatment of malaria.

Consequently, there is a prolongation of patient waiting times at these health facilities thus leading to decreased patient satisfaction with healthcare services. This in turn hinders evidence-based care. Most treatment of malaria occurs in primary health care settings lacking an ideal laboratory. These will benefit more from RDT. It may also be useful in secondary and tertiary settings outside working hours or in outpatient clinics for objective diagnosis and prompt treatment of malaria. As frontline doctors who have to cope with the greater proportion of patients suffering from malaria, promoting the utilization of a faster, less cumbersome diagnostic method will make Family Physicians more efficient and ensure appropriate drug use.

RELEVANCE OF RAPID DIAGNOSTIC TESTS IN THE MANAGEMENT OF UNCOMPLICATED MALARIA AMONG CHILDREN AGED 1-5 YEARS IN WESLEY GUILD HOSPITAL