Sorry folks. I have been out of commission with knee replacement surgery. Now that the severe pain has subsided and I am walking again I have rejoined the human race. I hope to be writing regularly again.
Doctors working in rural clinics are often faced with the need to make a clinical diagnosis of malaria promptly.
- What is the “gold standard ” for making this diagnosis?
- What is the harm that can be done if the diagnosis is not made correctly?
- How useful are the rapid diagnostic tools in confirming a definite diagnosis of malaria?
It is the responsibility of each general physician to make an effort to control malaria. Patients trust us and also feel that the doctor is the authority figure who will think for them and make the effort to prevent the disease as well as treat it. Teams of medical personnel sent by central authorities are often resented as they are seen as outsiders and people in the community do not cooperate with them. Hence it behoves the doctor who cares for them daily to have the relevant information. Let us explore some of these problems.
Clinical diagnosis of malaria can be made easier if we know when to exclude malaria. If the patient has sneezing, coughing, a sore throat, watery red eyes along with the fever then a diagnosis of malaria is highly unlikely. Likewise nausea, vomiting and diarrhoea are very unlikely to be caused by uncomplicated malaria though in complicated malaria cholera like diarrhoea may occur. Prominent symptoms of a urinary tract infection like dysuria, frequency of urine, flank pain or suprapubic pain will also exclude malaria. It is well to remember that UTIs (urinary tract infections) can also cause fever with rigors. Rigors also occur in fevers caused by an abscess specially an internal one like in or around the liver or kidneys, pus in the paracolic gutters or pleura or peritoneum. Be careful to exclude these conditions by taking a relevant history from the patient and a careful examination. The liver may be palpable in malaria but is not tender and does not keep increasing rapidly as it does in a liver abscess. Tenderness in one flank should cause a suspicion of a renal abscess.
The clinical manifestations of malaria vary with parasite species, epidemiology, immunity, and age. In areas where malaria is highly endemic, groups at highest risk include young children (6 to 59 months), who can develop severe illness, and pregnant women, who are at risk for anemia and delivering low birth weight newborns. A liaison with the obstetrician or midwife in the hospital is a good idea as women can be diagnosed even if they do not have fever but have significant anemia which is not nutritional in origin. The newborn baby of a mother suffering from malaria is usually underweight, will need to be treated as the malaria parasites cross the placenta and can cause congenital infection. Anticipatory treatment is advisable so don’t wait for a diagnosis.
You will encounter malaria in people who are immune to it and those who have not encountered the parasite before hence have no immunity or have lost their immunity. Malaria in immune subjects presents with the classical onset with a severe rigor accompanied by the cold stage during which the patient, in the tropics wants the air conditioning and fan turned off, and usually wants a blanket or quilt. During this period the body temperature rises as the body thermostat is reset. There is fever which may be as high as 103/4 degrees F. This is followed by the hot stage; the patient is hot and flushed, throws off the bed-clothes, is thirsty and wants the cooling turned on again. The thermostat is again reset to normal body temperature, the patient sweats, there is defervescence and the temperature returns to normal. These are the classical rigor, cold stage, hot stage and sweating which all med students are taught about. Duration of this cycle varies from as short as an hour in a highly immune to 24 hours. It will recur every 3rd day in tertian malaria (vivax and ovale) or every 4th day quartan malaria (malaraie). In non immune subject such as infants and babies, travellers to a malarious country and people who live in countries where malaria transmission is interrupted because the ambient temperature falls below 10 degrees in the winter malaria does not present as the classical stages of malaria. Non immune subjects are at a high risk of severe malaria and Pl falciparum malaria of which the most dreaded manifestation is cerebral malaria with its neurological manifestations and likely fatality.
After the bite of an anopheles mosquito carrying the malaria parasites, sporozoites travel in the blood and enter the liver where they develop. While they are developing individuals are generally asymptomatic for 12 to 35 days but can commence symptoms as early as 7 days (depending on parasite species), until the erythrocytic stage of the parasite life cycle. Release of merozoites from infected red cells when they rupture causes fever and the other manifestations of malaria.
As in most cases, the incubation period for P. falciparum infection is about 12 to 14 days (range 7 to 30 days) a non immune patient has to have been in a malarious area for at least one week before the fever begins. Most infections due to P. falciparum become clinically apparent within one month after exposure. Longer incubation periods are more likely in semi-immune individuals and individuals taking ineffective malaria prophylaxis. Keep this in mind when dealing with travellers.
Two nonhuman primate malarias, Plasmodium knowlesi and Plasmodium simium, have been shown to infect humans in Southeast Asia and Brazil, respectively; P. knowlesi resembles P. malariae, and P. simium resembles P. vivax (microscopically and by polymerase chain reaction)
Malaria should be suspected in patients with any febrile illness if they have had exposure to a region where malaria is endemic. The initial symptoms of malaria are nonspecific and may also include tachycardia, tachypnea, chills, malaise, fatigue, diaphoresis (sweating), headache, mild cough, anorexia, nausea, vomiting, abdominal pain, arthralgia, and myalgia. Patients are considered to have uncomplicated malaria in the setting of symptoms of malaria and a positive parasitological test in the absence of signs of severe malaria. The spleen becomes palpable, anemia develops usually without a low platelet count (which should lead to a suspicion of dengue fever), a tinge of jaundice may be seen. In tropical and semitropical countries abdominal pain , diarrhoea with mucus and blood should make one think of dysentery. Early in the course of malaria infection, febrile paroxysms occur at irregular intervals each day. The temperature of non immune individuals and children may rise above 40ºC and may occur in conjunction with tachycardia and/or delirium. Febrile convulsions may occur among children in the setting of malaria due to any species. However, generalized seizures are associated with falciparum and may herald the development of cerebral malaria. Later in the course of infection, rupture of infected red cells can become synchronous following concurrent schizont rupture and release of merozoites from erythrocytes. Febrile paroxysms may occur every other day for P. vivax, P. ovale, and P. falciparum and every third day for P. malariae. Paroxysms occurring at regular intervals are more common in the setting of infection due to P. vivax or P. ovale than P. falciparum. With improvements in early diagnosis and treatment, this traditional description of cyclic fever is seen infrequently.
Presentation of complicated malaria.
The fever of complicated malaria is accompanied by altered consciousness with or without seizures and focal neurological deficits if cerebral malaria is developing. This is the result of the parasitized (and nonparasitized) RBCs adhering to small blood vessels (“cytoadherence”) causing small infarcts, capillary leakage, and brain and other dysfunction. Complicated malaria may present with respiratory distress or acute respiratory distress syndrome (ARDS). The patient will become breathless, may cough up frothy blood stained sputum and develop cyanosis with low or falling oxygen saturation levels. Circulatory collapse with a low BP and poor peripheral circulation. Fever with progressive metabolic acidosis may be seen. The most well-known form of complicated malaria is renal failure, hemoglobinuria popularly known as “blackwater fever”. The patient complains that his urine has turned the colour of a black “cola” drink. This is a dreaded symptom. The urine output is low and the patient rapidly goes into renal failure requiring dialysis. This is a real problem when there are no facilities for dialysis and the patient needs to be shifted to another hospital which may not be close by. Other manifestations of complicated malaria are the development of hepatic failure, coagulopathy with or without disseminated intravascular coagulation anemia or massive intravascular hemolysis or evidence of hypoglycemia.
A patient of mine a 28-year-old electric lineman was working on an electric pole 20 feet above the ground. He fell from there, unconscious. The doctor in the ER rushed him to the neurosurgeon suspecting a head injury. He appeared to have no bone injury and no focal neurological deficit. His hemoglobin was 2gm/dl, Pl falciparum were seen parasitising 10% of his RBCs. Blood transfusions, an exchange transfusion and IV quinine and artemisinin helped him to regain consciousness. Fortunately his kidneys were functioning. He recovered and went home.
Parasite based diagnosis;
- Identification of the parasite in a blood smear by light microscopy.
- Rapid diagnostic tests which are antigen based.
- Molecular tests.
- Parasitaemia density.
Laboratory evaluation may demonstrate parasitemia (usually <5000 parasites/microL of blood, <0.1 percent parasitized red blood cells [RBCs]), anemia, mild thrombocytopenia, elevated transaminases, mild coagulopathy, and elevated blood urea nitrogen (BUN) and creatinine.
Drugs used in the treatment of malaria.
- Chloroquine. This is useful for Pl vivax and ovale and malaraie which are sensitive to it. In areas where this drug is not being used sensitivity in Pl falciparum is being seen again and chloroquine may be used but identification of the parasite is essential.
- ACT (artemesanine combination therapy)
- Artesunate-sulfadoxine-pyrimethamine (SP), in areas with known SP sensitivity
- Quinine. Injectable quinine where available is a very effective treatment of chloroquine resistant malaria in combination with artemisinin.
ACTs have a low side effect profile, are potent against all blood stages (asexual forms) of malaria, and have the most rapid clearance time relative to other antimalarial drugs. Artemisinin should be administered with a second agent that has a longer half-life than the artemisinin drug to forestall development of artemisinin resistance and to provide an extended duration of drug level to clear parasitemia. Why use artemisinin for three days? This period covers 2 asexual cycles and prevents recrudescence.
How frequent can we encounter malaria?
Approximately 3.2 billion people live in malarious countries, 1.2 billion are at high risk of developing symptomatic malaria. In 2017, the World Health Organization (WHO) reported that, “between 2014 and 2016, substantial increases in case incidence occurred in the WHO Region of the Americas and marginally in the South-East Asia, Western Pacific, and African regions”. As incidence is measured by the effectiveness of reporting from the countries in the region, the reporting rate in India and Nigeria was only 50% leading to an apparent reduction in the incidence of malaria by 18% between 2000 and 2015. The principal determinants of the incidence of malaria are the number (density) of anopheles mosquitoes in the area, whether the vector bites indoors or outdoors and how long the female mosquito lives. In order to transmit malaria a female mosquito must live for at least 10 days to allow the development of the parasites in its body as the development cycle of the malaria parasite varies from 8 to 30 days. The anopheles bite indoors, at night and prefers human beings to feed on. The mosquito needs a temperature above 10 degrees Centigrade to survive.
The vast majority of these cases and deaths are due to Plasmodium falciparum and occur in Africa, but Plasmodium vivax and Plasmodium knowlesi can also cause severe disease.
Will we ever see malaria eliminated? An elimination program is mapped out below.
Strategies involved are:
Stringent environmental management and “integrated vector control” are required. concurrent use of
- residual spraying
- larval control
- genetic manipulation of the male mosquito so that fertilised eggs do not hatch
Long-lasting insecticidal nets, indoor residual spraying, the use of personal insecticides and effective treatment of clinical malaria are strategic components for all three groups. To consider interventions for malaria control, it is important to define goals of control, elimination, and eradication.
- Control is reduction of disease incidence and prevalence to levels that do not pose a threat to public health or that are acceptable to a community.
- Elimination is reduction to zero transmission in humans in a defined geographic area.
- Eradication is global elimination of human disease.