Handbook on Falciparum Malaria Anupam Sachdeva, Nita Radhakrishnan, Manas Kalra
INDEX
Page numbers followed by f refer to figure and t refer to table
A
Abnormal
bleeding 111
spontaneous bleeding 34
Accelerated destruction of nonparasitized red blood cells 30
Acidosis 63, 111
Acidotic breathing 34, 111
Acute
hepatitis
A and E 89
B or C 89
kidney injury 62, 63
lung injury 94
malaria attacks 22
pulmonary edema 98f, 116
renal failure 28, 62, 178
respiratory distress syndrome 31, 63, 95, 111, 116, 139, 178
tubular necrosis 29
Adenosine triphosphate 66
Advantages of thick and thin film 143t
Albumin infusion 72
Algid malaria 111
Amodiaquine 187, 188
Anemia 68, 79
Annual parasite incidence 5, 200
Anopheles
funestus 215
gambiae 215, 216
mosquito 26
Antigen
detection 135
ELISA 136
enzyme linked immunoassay 135
Antimalarial drugs 70, 73, 214
APACHE II score 106
Artelinic acid 185
Artemether 42, 181, 187
Artemisinin
based combination therapy 43, 180, 185
combination therapy 173t
derivative 115, 180
Artemotil 185
Artesunate 42, 114, 115, 180, 187, 187t, 188t
Atovaquone 188, 219
Automated blood cell analysers 153
B
Bacillus thuringiensis israelensis 216
Behavior change communication 203, 211
Benzothiocarboxypurine 149
Berlin definition of acute respiratory distress syndrome 97t
Blackwater fever 29, 82
Blantyre coma scale 28t, 40t
Blood
borne transmission 11
glucose 32
schizonticides 219
urea 32
and serum creatinine 88
Bone marrow dysfunctions 30
C
Capillary blood collection 160
Cardiovascular system 103
Causes of multiorgan dysfunction syndrome 106
Central venous pressure 71
Cerebral
malaria 27, 37, 40, 41t, 63, 68, 98f, 116, 139
spinal fluid 39
Chemoprophylaxis 115, 219
Chikungunya 200
Chloroquine 115, 188, 219, 221, 223
sensitive malaria 172t
Chondroitin sulfate A 19
Chronic kidney disease 69
Circulatory collapse 32, 34, 111, 124
Circumsporozoite protein 194
Clindamycin 115
Coma 116
Complicated malaria 27
Complications of malaria 124
Concomitant viral hepatitis 30
Congenital
infection 113, 114
malaria 11, 156
Continuous positive airway pressure 97
Control of malaria epidemics 208
Controlled
low endemicity malaria 190
non-endemic malaria 190
Corneal reflexes 32
Correction of hypoglycemia 55
Cytomegalovirus 89
D
Deep breathing 34
Definition of hypoglycemia 47
Delivery system 192
Dengue 200
hemorrhagic fever 89
Diagnosis of
imported malaria 157
malaria in pregnancy 156
Diagnostic methods of falciparum malaria 141
Dialysis 72
Dichlorodiphenyltrichloroethane 200
Dihydroartemisinin 185
Diphtheria-tetanus-pertussis 214
Disseminated intravascular
coagulation 31, 178
coagulopathy 111
District vector borne disease consultants 210
Dominate Plasmodium vivax 183
Dopamine challenge 72
Doxycycline 219, 221
Drawbacks of thick and thin film 144t
Drug
induced hemolysis 86
reaction 89
E
Electroencephalogram 89
Electrolyte abnormality 69
Enlarged spleen 27
Enlargement of liver 27
Enzyme
immunoassay 134
linked immunosorbent assay 137, 160
Epidemiology of
jaundice in malaria 85
transfusion-transmitted P. falciparum malaria 132
Erythrocytic cycle 17
F
Falciparum malaria 33, 34, 62, 97f, 141, 155, 159
in adults 33
in children 120
in pregnancy 108
Fascioliasis 89
Fetal growth restriction 113
Field's stain 143, 144
Filariasis 200
Flow cytometers 153
Fluorescent microscopy 149
Formulation of artesunate 188
Fraction of inspired oxygen 97
Fulminant liver failure 30
Functioning of national vector borne disease control programme 201
G
Gastrointestinal bleeding 42
Giemsa stain 143
Gluconeogenesis 49
in infectious disease 53
Glucose
metabolism in malaria 50
production and
uptake in infectious disease 51
utilization 48
Glucose-6-phosphatase dehydrogenase deficiency 124, 175, 222
Glutamate-rich protein 196
Glycogenolysis in infectious disease 53
H
Hematologic system 103
Hematological manifestations of malaria 79
Hemoglobin polymorphisms 23
Hemoglobinuria 34, 35, 111, 178
Hemolysis
in malaria 86
of nonparasitized RBCs 86
Hemophagocytic lymphohistiocytosis 83
Henry's melanin flocculation test 160
Hepatic
dysfunction 30, 86
failure 124
system 103
Histidine rich protein 2, 135
HIV coinfection 112
Hybrid test formats 165
Hyperinsulinemia 29
Hyperlactatemia 35, 111
Hyperparasitemia 30, 32, 35, 111, 178
Hyperpyrexia 30, 116, 178
Hyper-reactive malarial splenomegaly syndrome 83
Hypnozoiticide 219
Hypoglycemia 29, 35, 46, 111, 116, 178
Hypotension 30
Hypovolemic shock 178
I
Immunofluorescence assay 159
Impaired
consciousness 111
marrow response 81
Incubation period 26, 34, 133
Indirect fluorescent antibody testing 137
Indoor residual spray 200, 203
Induction of fever 20
Infected red blood cell 19
Insecticide treated
bed nets 203
nets 215
Integrated
Disease Surveillance Project 202
management of neonatal and childhood illnesses 203
vector management 203, 209
Intersectoral collaboration 203, 211
Intravascular hemolysis 86
of parasitized erythrocytes 30
of parasitized RBCs 86
Intravenous dextrose administration 56
J
Janani Suraksha Yojana 203
Japanese encephalitis 200
Jaundice 30, 63, 68, 111
K
Kala-azar 200
Kupffer cells 89
L
Laser desorption mass spectrometry 155
Leishman stain 143, 144, 146
Leptospirosis 89
Life cycle of malaria 8, 8f, 128f
Light
emitting diode 150
microscopy 135
Long-lasting insecticidal nets 190, 214, 215
Loop-mediated isothermal amplification 154
Low-birth-weight 113
Lumefantrine 187
M
Magnetic resonance spectroscopy 50
Malaria 2, 26
associated acute kidney injury 64, 66
control strategies 203
cultivation 152
endemic countries in
eastern hemisphere 2f
western hemisphere 3f
epidemics 207
induced hypoglycemia 30
parasite 20, 21f, 63
on peripheral blood smear 122f
rapid diagnostic tests 135
technical supervisors 210
vaccines 190, 192
Malarial
hemoglobinuria 82
hepatitis 85, 86, 91
hepatopathy 90t
Management of
infection including pneumonia 70
severe malaria cases 207
Manifestation of malaria 31
in pediatric population 121
Maternal
anemia 113
death 113
mortality 114
Mature pigmented parasites 32
Mefloquine 115, 187, 219, 220, 223
Merozoite surface protein 196
Metabolic acidosis 29, 35, 116, 178
Metabolism of drug 188
Mild jaundice 27
Miscarriage 113
Mixed infection 183
Molecular
methods 153
tests 135
Mosquito
bite prevention 219
repellents 217
vector control 214, 215
Multiorgan dysfunction
score 106
syndrome 102
in malaria 102
Multiple convulsions 34, 111
N
National
Anti-malaria Programme 5, 200
Institute of
Communicable Diseases 201
Malaria Research 201
Malaria
Control Program 4, 200
Eradication Program 4, 200
Rural Health Mission 200
Vector Borne Disease Control Programme 5, 79, 200, 201, 210
Nitric oxide 67
synthase 65
Nonartemisinin-based combination 185, 188
O
Obstructive jaundice with infection 89
Oliguria 103
Optimal test 163
Organ dysfunction in MODS 102f
P
Packed
cell volume 32
red blood cells 67, 96
Parasite 38
index 106
viability in stored blood 133
Paratyphoid fevers 89
Parenteral treatment of severe malaria in pregnancy 115t
Partial pressure of arterial oxygen 97
Pathogenesis of
acute knee injury 67
coagulopathy in MODS 105f
jaundice in malaria 86
Plasmodium falciparum 16
pulmonary edema in malaria 96
severe malaria 20f
Pathophysiology of
complicated malaria 28
malarial anemia 80
MODS in malaria 104
Perinatal
death 113
mortality 113
Peripheral schizontaenemia 32
Personal
mosquito protection 214
protection from infection 217
Perspiration 27
Piroplasmosis 146
Placental malaria 110
Plasmodium 16
falciparum 2, 5, 10, 12, 26, 33, 37, 38, 51, 52, 79, 89, 104106, 127, 141, 152, 159, 161, 183, 191, 204
life cycle 14f
malaria 4f
malaria 89, 132, 204
knowlesi 191
lactate dehydrogenase 136
malariae 26, 191
ovale 191
parasites 133, 191, 198
sporozoites 194
vivax 26, 79, 161, 191
malaria 87
Platelet endothelial cell adhesion molecule 19
Polymerase chain reaction 110, 136
Polymorphonuclear leukocytosis 32
Positive end expiratory pressure 97
Postpartum infection 112
Pre-erythrocytic stage vaccines 193
Presumptive
anti-relapse therapy 222
medication of blood recipients 138
Prevention
of malaria infection in travelers 217
strategies of
malaria 214
TTM 133
Primaquine 219, 221
Procalcitonin levels 106
Proguanil 188, 219
Prostration 111
Prothrombin time 90
index 90
Pulmonary
edema 31, 34, 94, 111, 124, 178
in malaria 94
nitric oxide 96
Q
Quantifying parasites 145
Quantitative bufffy coat analysis 150
Quinidine 115
gluconate 115
Quinine 42, 55, 114, 115, 181, 188
dihydrochloride 115
plus clindamycin 114
stimulated insulin secretion 29
R
Rapid diagnostic
kit 165f
tests 135, 160, 206
for malaria 162f
Reactive oxygen intermediates 67
Recurrent GTCs 178
Red blood cells 12, 80
Relapsing fever 89
Renal
blood flow index 72
failure 94, 116, 139
in falciparum malaria 62
impairment 35, 111
replacement therapy 70
system 103
Renin-angiotensin-aldosterone system 67
Respiratory
complications of malaria 95
distress 34, 63, 111
system 103
Role of
adjuvants 197
hemolysis 80
spleen 81
Romanowsky stains 143
S
Screening potential blood donors 159
Sequential organ failure assessment score 106
Serum creatinine 32
Severe
acute respiratory distress syndrome 105
anemia 30, 63, 111, 116
falciparum malaria 130
jaundice 94
malaria 43, 116t
normocytic anemia 35
pallor 178
Plasmodium falciparum malaria 106
Sexual stage vaccines 197
Shock 30, 34, 111, 116
Sinusoidal and portal infiltration 89
Small for gestational age infant 113
Spleen filtering function 23
Spontaneous bleeding and coagulopathy 116
Sporogonic cycle of malaria parasite 16
Sporozoites 63
Stages of Plasmodium falciparum 13f
Sterile insect technique 216
Sulfadoxine-pyrimethamine 117, 137, 188, 214
Sweating stage 27
Systemic inflammatory response syndrome 102
Systolic blood pressure 30, 34
T
Tachycardia 103
Targets for malaria vaccines 193t
Thrombocytopenia 111
Tissue schizonticides 219
Toxoplasmosis 89
Transfusion
reactions causing hemolysis 89
transmitted P. falciparum malaria 126
in nonendemic countries 132
Transmission
blocking vaccines 197
of infections 11
Treatment of
malaria and management of pregnancy 114
mixed infections 184
in malaria 183
Plasmodium falciparum 204
severe falciparum malaria 178
uncomplicated malaria in pregnant women 115t
Tropical splenomegaly syndrome 83
Trypanosoma brucei 23
Trypanosomiasis 89
Tumor necrosis factor 12, 30, 65
Types of
RDTS 161
traveler 218
vaccine 192
Typhoid 89
Typhus fever 89
U
Uncomplicated malaria 27, 115, 122f, 170
Use of antimalarial drugs 214
V
Vaccines against malaria 193
Vasopressin therapy 72
Vector-borne diseases 203
Vulnerable community plan 209
W
White cells 82
Y
Yellow fever 89
Z
Zygote 63
×
Chapter Notes

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Overview of MalariaCHAPTER 1

Dhwanee Thakkar
Anupam Sachdeva
Nita Radhakrishnan
 
INTRODUCTION
Malaria is a complex and deadly disease that puts billions of people at risk in several countries and territories around the world, contributing to the cycle of poverty and limiting economic development. Several countries lose billions per year in direct losses (e.g. illness, treatment, premature death) and many times more than that in lost economic growth. Malaria is endemic throughout most of the tropics. Malaria imposes great socioeconomic burden on humanity. 1,2
Malaria continues to be one of the important public health problems in India. As per World Health Organization report 2011 to 2012, South-East Asian region bears the second largest burden of malaria (13%), being next to African region (81%). Among South-East Asian regions, India shares two-thirds of the burden (66%).3,4
As the second most populous country in the world, with a population exceeding one billion people, India's public health system faces several challenges including implementation of surveillance programs to accurately estimate and control the national malaria burden.5
 
ETIOLOGY
Malaria is a vector borne disease caused by one of the protozoan species of the genus Plasmodium, transmitted to humans by female Anopheles mosquitoes. Malaria in humans is caused by one of the following species of Plasmodium: P. falciparum, P. malariae, P. ovale, P. vivax and P. knowlesi.3,6 Malaria is transmitted via the bite of an infective female Anopheles mosquito, which occurs mainly between dusk and dawn. Other comparatively rare mechanisms for transmission include: congenitally-acquired disease, blood transfusion, sharing of contaminated needles, and organ transplantation.4,6,72
The clinical features of malaria vary according to the species of parasite present, patient's state of immunity, the intensity of infection, presence of concomitant conditions like malnutrition and other diseases.8 Plasmodium falciparum is by far the deadliest of all the human malarial species.
 
EPIDEMIOLOGY
 
World Scenario
Malaria is a major international public health problem. About 3.4 billion people—half of the world's population—are at risk of malaria. In 2013, 97 countries had on-going malaria transmission. Despite the apparent progress in reducing the global prevalence of malaria, many areas still remain malaria endemic. Globally 207 million malaria cases have been reported in 2012 (uncertainty range: 135–287 million) and 627000 deaths have been reported globally attributed to malaria (uncertainty range: 473,000–789,000). Ninety percent of all malaria deaths occur in sub-Saharan Africa and 77 percent occur in children under five. 9,10 An estimated 2.5 billion people worldwide were at risk of P. falciparum malaria, in 201011 (Figs 1.1 to 1.3).
Malaria transmission occurs in large areas of Africa, Central and South America, parts of the Caribbean, Asia (including South-Asia, South-East Asia, and the Middle East), Eastern Europe, and the South Pacific (Figs 1.1 and 1.2).7
The malaria mortality rate was reduced in 2000 to 2012 globally by 45 percent. Fifty-two countries are on track to reduce their malaria case incidence rates by 75 percent, in line with World Health Assembly and Roll Back Malaria targets for 2015.
zoom view
Fig. 1.1: Malaria endemic countries in eastern hemisphere (CDC) 7
3
zoom view
Fig. 1.2: Malaria endemic countries in the Western Hemisphere (CDC) 7
However, these 52 countries only account for 4 percent of the total estimated malaria cases. Fifty-nine countries are on track to meet the Millennium Development Goal target of reversing the incidence of malaria (between 2000 and 2015).4
zoom view
Figs 1.3A and B: The spatial distribution of Plasmodium falciparum malaria endemicity in 201011
Between 2000 and 2012, an estimated 3.3 million lives were saved as a result of a scale-up of malaria interventions. Ninety-percent of these lives saved are in the under-five age group, in Sub-Saharan Africa. 9,10
 
Indian Scenario
The malaria cases were brought down from 2,031,790 cases in 2000 to 1,816,569 cases in 2005 and further brought down to 1,067,824 cases in 2012. The annual incidence rate (cases of malaria/1000 population) of malaria has come down from 2.57 per thousand in 1990 to 1.10 per thousand in 2011, and to 0.88 cases per 1000 population in 2012. The malaria death rate in the country was0.09 deaths per lakh population in 2000 which has come down to 0.04 deaths per lakh population in 2012.12
Malaria was a major scourge in India contributing 75 million cases with about 0.8 million deaths annually, prior to the launching of the National Malaria Control Program (NMCP) in 1953. The implementation of NMCP resulted in a sharp decline in malaria cases in India and as a result the Government of India (GOI) converted the NMCP into the National Malaria Eradication Program (NMEP) in 1958. The NMEP was initially a great success with the malaria incidence dropping to a 0.1 million cases and no deaths due to malaria reported in 1965. 5The resurgence of malaria in the country resulted in escalation of incidence to 6.4 million cases in 1976. The resurgence was attributed to various operational, administrative and technical reasons, including emergence of drug resistance in the parasites and insecticide resistance in the vectors. In 1977, the Modified Plan of Operation (MPO) was implemented with the immediate objectives of preventing deaths due to malaria and reducing morbidity due to malaria. The national programme was also integrated with the primary health care delivery system. The malaria incidence declined to 1.66 million cases in 1987. By 1996, there was another malaria upsurge with 3.03 million cases and 2,803 deaths reported. Since the focus shifted from eradication to control, the programme was renamed as National Anti-Malaria Programme (NAMP) during year 1999.
With the convergence of responsibilities and strategies to prevent other vector borne diseases, NAMP was renamed as National Vector Borne Disease Control Programme (NVBDCP) in 2003. The NVBDCP is presently one of the most comprehensive and multi-faceted public health programmes in the country. The NVBDCP became an integral part of the NRHM launched in 2005. The special focus of the NVBDCP is on resource challenged settings and vulnerable groups. The incidence of malaria in the country started halting and sustaining reversal of cases for last one decade.
The total positive cases of malaria and deaths due to malaria have shown declining trend from 2011 and 2010 respectively. The indicators Annual Parasite Incidence (API) per 1000 population and deaths due to malaria are showing declining trend (Fig. 1.4) in the recent past and the challenge is to sustain that trend.12
As may be seen the annual incidence has been constantly declining, which reveals that the increasing trend of malaria incidence has already been halted and being reversed (Table 1.1).
At present, malaria control strategies are being implemented under the National Vector Borne Diseases Control Programme (NVBDCP). The strategies for control of malaria depend largely on the vector bionomics as well as the disease burden present in a particular area. NVBDCP has established different strategies based on different ecotypes of malaria. With the decline in the annual positive cases over a period of time, much progress has been made in the field of malaria. However, major challenges remain in the form of chloroquine-resistance, increasing proportion of Plasmodium falciparum cases in recent years and cases of fifth Plasmodium species (P. knowlesi) which need to be addressed at the earliest. As a result of these, major changes have been made in the strategic action plan for control of malaria. Future interventions in the form of malaria vaccine and development of genetically modified mosquito which is almost100 percent immune to malaria will be a boon for effective malaria control.36
zoom view
Fig. 1.4: Declining trend of malaria in the countrySource: Ministry of Health and Family Welfare, India
Table 1.1   Trends in malaria over the last decade
Malaria status in the country 2000–2012
Year
Total positivecases of malaria
Annual parasite incidence (per 1000 population)
Deaths due to malaria
Deaths due to malaria (per 100,000) populaton
2000
2031790
2.09
932
0.09
2001
2085484
2.12
1005
0.1
2002
1841229
1.82
973
0.09
2003
1869403
1.82
1006
0.1
2004
1915363
1.84
949
0.09
2005
1816569
1.68
963
0.09
2006
1785129
1.66
1707
0.16
2007
1508927
1.39
1311
0.12
2008
1526210
1.36
1055
0.09
2009
1563574
1.36
1144
0.09
2010
1599986
1.37
1018
0.08
2011
1310656
1.1
754
0.06
2012
1067824
0.88
519
0.04
Source: Ministry of Health and Family Welfare, India
7
zoom view
Figs 1.5A and B: Parasite prevalence of Malaria and proportion of cases due to Plasmodium falciparum WHO Malaria Guidelines 20134
In India, the most common and deadliest species is P. falciparum (Figs 1.5A and B) contributing to 52 percent of the total malaria cases in 2010 which is closely followed by P. vivax. Other two species; P. malariae and P. ovale which contribute to <10 percent of the burden with very few cases being due to ovale species. Recently a fifth Plasmodium species, P. knowlesi which usually infects macaques has been identified and over the past few years hundreds of human cases have been reported in South and South-East Asian countries.3
Malaria distribution in India depends much upon vector bionomics. In India, Anopheles species have been described, six of which have been implicated to be main malaria vectors, namely: An. culicifacies, An. dirus, An. fluviatilis, An. minimus, An. sundaicus and An. stephensi. Besides, some are of local importance, viz. An. philippinensis-nivipes, An. varuna, An. annularis and An. jeyporiensis. The study of vector bionomics plays an important role in implementation of control strategies. As can be seen around 80 percent of malaria burden is confined to 20 percent of population residing in high-risk areas like Odisha, Jharkhand, Chhattisgarh, Madhya Pradesh, North-Eastern States except Sikkim, Maharashtra, Rajasthan and certain parts of Gujarat.38
 
Life Cycle of Malaria (Fig. 1.6)
The malaria parasite exhibits a complex life cycle. It undergoes 2 cycles of development—the human cycle (asexual cycle) and the mosquito cycle (sexual cycle). Man is the intermediate host and mosquito the definitive host.
 
Asexual cycle:
The infection is initiated when sporozoites are injected with the saliva of a feeding mosquito. Sporozoites are carried by the circulatory system to the liver and invade hepatocytes. The intracellular parasite undergoes an asexual replication known as exoerythrocytic schizogony producing shizonts within the hepatocyte. Exoerythrocytic schizogony culminates in the production of merozoites which are released into the bloodstream. A proportion of the liver-stage parasites from P. vivax and P. ovale go through a dormant period instead of immediately undergoing asexual replication. These hypnozoites will reactivate several weeks to months (or years) after the primary infection and are responsible for relapses. Once the merozoites are released into the blood stream, many of them are destroyed, but a significant number invade erythrocytes and form trophozoites and shizonts. Merozoites bud from the mature schizont and the merozoites are released following rupture of the infected erythrocyte.
zoom view
Fig. 1.6: Life cycle of malariaCourtesy: The Carter Center/Graphic by Al Granberg
9
Invasion of erythrocytes reinitiates another round of the blood-stage replicative cycle. The blood stage is responsible for the pathology associated with malaria. The intermittent fever paroxysms are due to the synchronous lysis of the infected erythrocytes. P. malariae exhibits a 72-hour periodicity, whereas the other three species exhibit 48 hours cycles. However, P. falciparum often exhibits a continuous fever rather than the periodic paroxysms. P. falciparum also is responsible for more morbidity and mortality than the other species. Some erythrocytic forms do not divide but become male and female gametocytes. These are the sexual forms of the parasite which are infective to mosquito.
 
Sexual cycle:
Sporogony begins when the gametocytes are ingested by the vector mosquito when feeding on an infected person. Microgametes, formed by a process known as exflagellation of the male gametocyte are flagellated forms which will fertilize the mature female gamete—the macrogamete leading to a zygote. The zygote develops into a motile ookinete which penetrates the gut epithelial cells and develops into an oocyst. The oocyst undergoes multiple rounds of replication resulting in the production of sporozoites within it. Rupture of the mature oocyst releases the sporozoites into the hemocoel (i.e. body cavity) of the mosquito. The sporozoites migrate to and invade the salivary glands, thus completing the life cycle and the mosquito now becomes infective to man (Fig. 1.6).6,8
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