Taming malaria in Nigeria

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Malaria has been a major threat in Africa, ravaging most of its population. According to recent figures from the World Health Organisation (WHO), about 3.4 billion people – half of the world’s population – are at risk of malaria. In 2012, there were about 207 million malaria cases (with an uncertainty range of 135 million to 287 million) and an estimated 627,000 malaria deaths (with an uncertainty range of 473,000 to 789,000). While increased prevention and control measures have led to a reduction in malaria mortality rates by 42 per cent globally, since 2000, and by 49 per cent in the WHO African Region.

Worried by the surge in malaria cases in Nigeria, the Federal Ministry of Health had launched various programmes, including the Roll Back Malaria campaign and other programmes aimed at controlling the disease in the country.

While deaths from malaria in Nigeria, as at 2010, were the highest recorded worldwide, the National Malaria Control Strategic Plan shifted the set date for the achievement of its redefined goals to 2013. One of the goals was that by the end of 2013, at least 80 per cent of patients attending any health facility would get appropriate testing and treatment for malaria, according to national guidelines.

Though the population of Nigerians who eventually received the planned treatment for malaria was not up to the projected percentage, many infected individuals actually got some treatment. However the war against is far from being won.

Malaria Consortium Ad 2010 Child Health

Facts about the disease

Malaria is a potentially fatal mosquito-borne parasitic disease that kills an estimated 655,000 people, mostly children, worldwide each year. It is transmitted through the bites of infectious female Anopheles mosquitoes. Only female mosquitoes bite, and when feeding, they can pick up malaria parasites from an infected person. After a development cycle in the mosquito lasting from seven to ten days, the mosquito becomes infectious and transfers malaria into the next human host, when feeding.

Malaria is probably the only infection that can be treated in just three days but still kills millions every year. Without prompt and appropriate treatment, malaria may become a medical emergency by rapidly progressing to complications and death. Malaria can also aggravate certain pre-existing illnesses and may even prove fatal for patients with end stage organ disease.

Malaria causes periodic fever, anaemia, and low birth weight. It can be particularly fatal in children under five years of age and pregnant women. Nigeria has the world’s largest malaria burden, containing nearly one-third of the cases in Africa. Nearly all Nigerians (97 per cent) are at risk of contracting the disease and half of the population will have at least one malaria attack per year. Malaria is also the leading cause of clinic attendance and absenteeism in Nigeria.

Malaria is caused by protozoan parasites called Plasmodia, belonging to the parasitic phylum Apicomplexa. More than 200 species of the genus Plasmodium (=plasma + eidos, form) have been identified that are parasitic to reptiles, birds and mammals. Four Plasmodium species have been well known to cause human malaria, namely, P. falciparum, P. vivax, P. ovale, and P. malariae. A fifth one, P. knowlesi, has been recently documented to cause human infections in many countries of Southeast Asia. Very rare cases of malaria have been reported due to other species such as Plasmodium brasilianum, Plasmodium cynomolgi, Plasmodium cynomolgi bastianellii, Plasmodium inui, Plasmodium rhodiani, Plasmodium schwetzi, Plasmodium semiovale, Plasmodium simium and Plasmodium eylesi. All malaria parasites infecting humans probably jumped from the great apes (in case of P. knowlesi, macaques) to man.

It is very important to remember that malaria is not a simple disease of fever, chills and rigors. In fact, in a malarious area, it can present with such varied and dramatic manifestations that malaria may have to be considered as a differential diagnosis for almost all the clinical problems! Malaria is a great imitator and trickster, particularly in areas where it is endemic.

All the clinical features of malaria are caused by the erythrocytic schizogony in the blood. The growing parasite progressively consumes and degrades intracellular proteins, principally haemoglobin, resulting in formation of the ‘malarial pigment’ and haemolysis of the infected red cell. This also alters the transport properties of the red cell membrane, and the red cell becomes more spherical and less deformable. The rupture of red blood cells by merozoites releases certain factors and toxins (such as red cell membrane lipid, glycosyl phosphatidyl inositol anchor of a parasite membrane protein), which could directly induce the release of cytokines such as TNF and interleukin-1 from macrophages, resulting in chills and high grade fever. This occurs once in 48 hours, corresponding to the erythrocytic cycle.

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In the initial stages of the illness, this classical pattern may not be seen because there could be multiple groups (broods) of the parasite developing at different times, and as the disease progresses, these broods synchronise and the classical pattern of alternate day fever is established.

It has been observed that in primary attack of malaria, the symptoms may appear with lesser degree of parasitemia or even with submicroscopic parasitemia. However, in subsequent attacks and relapses, a much higher degree of parasitemia is needed for onset of symptoms. Further, there may be great individual variations with regard to the degree of parasitemia required to induce the symptoms.

Stages and symptoms of malaria development

The first symptoms of malaria after the pre-patent period (period between inoculation and symptoms, the time when the sporozoites undergo schizogony in the liver) are called the primary attack. It is usually atypical and may resemble any febrile illness. As the disease gets established, the patient starts getting relapse of symptoms at regular intervals of 48-72 hours.

The primary attack may spontaneously abort in some patients and the patient may suffer from relapses of the clinical illness periodically after eight to ten days, owing to the persisting blood forms of the parasite. These are called short term relapses (recrudescences). Some patients will get long term relapses after a gap of 20-60 days or more and these are due to the reactivation of the hypnozoites in the liver in case of vivax and ovale malaria. In falciparum and malariae infections, recrudescences can occur, due to persistent infection in the blood.

While most of the clinical manifestations of malaria are caused by the malarial infection per se, high grade fever, as well as the side effects of anti malarial therapy, can also contribute to the clinical manifestations. All these may act in unison, further confusing the picture. In some cases, secondary infections like pneumonia or urinary tract infection can add to the woes. All these facts should always be kept in mind.

Typical features of malaria

The characteristic, textbook picture of malarial illness is not commonly seen. It includes three stages, namely: the cold stage, the hot stage and the sweating stage. The febrile episode starts with shaking chills, usually at mid-day between 11am to 12 noon, and this lasts from 15 minutes to one hour (the cold stage), followed by high grade fever, even reaching above 1060 F, which lasts two to six hours (the hot stage). This is followed by profuse sweating and the fever gradually subsides over two to four hours.

These typical features are seen after the infection gets established for about a week. The febrile paroxysms are usually accompanied by headaches, vomiting, delirium, anxiety and restlessness. These are, as a rule, transient and disappear with normalisation of the temperature.

In vivax malaria, this typical pattern of fever recurs once every 48 hours and this is called benign tertian malaria. Similar pattern may be seen in ovale malaria too (ovale tertian malaria). In falciparum infection (malignant tertian malaria), this pattern may not be seen often and the paroxysms tend to be more frequent (sub-tertian). In P. malariae infection, the relapses occur once every 72 hours and it is called quartan malaria.

Diagnosis of malaria

Diagnosis of malaria involves identification of malaria parasite or its antigens/products in the blood of the patient. Although this seems simple, the efficacy of the diagnosis is subject to many factors. The different forms of the four malaria species; the different stages of erythrocytic schizogony; the endemicity of different species; the population movements; the inter-relation between the levels of transmission, immunity, parasitemia, and the symptoms; the problems of recurrent malaria, drug resistance, persisting viable or non-viable parasitemia, and sequestration of the parasites in the deeper tissues; and the use of chemoprophylaxis or even presumptive treatment on the basis of clinical diagnosis can all have a bearing on the identification and interpretation of malaria parasitemia on a diagnostic test.

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The diagnosis of malaria is confirmed by blood tests and can be divided into microscopic and non-microscopic tests.

  •  Microscopic tests

These include:

  1. Peripheral smear study
  2. Quantitative Buffy Coat (QBC) test
  •  Peripheral smear study

Light microscopy of thick and thin stained blood smears remains the standard method for diagnosing malaria. It involves collection of a blood smear, its staining with Romanowsky stains and examination of the Red Blood Cells for intracellular malarial parasites. Thick smears are 20–40 times more sensitive than thin smears for screening of Plasmodium parasites, with a detection limit of 10–50 trophozoites/ìl. Thin smears allow one to identify malaria species (including the diagnosis of mixed infections), quantify parasitemia, and assess for the presence of schizonts, gametocytes, and malarial pigment in neutrophils and monocytes. The diagnostic accuracy relies on the quality of the blood smear and experience of laboratory personnel.

Before reporting a negative result, at least 200 oil immersion visual fields at a magnification of 1000× should be examined on both thick and thin smears, which have a sensitivity of 90 per cent. The level of parasitemia may be expressed either as a percentage of parasitised erythrocytes or as the number of parasites per microlitre of blood.

In nonfalciparum malaria, parasitemia rarely exceeds two per cent, whereas it can be considerably higher (>50 per cent) in falciparum malaria. In nonimmune individuals, hyperparasitemia (>5 per cent parasitemia or >250,000 parasites/ìl) is generally associated with severe disease.

In falciparum malaria, parasitised erythrocytes may be sequestered in tissue capillaries resulting in a falsely low parasite count in the peripheral blood (‘visible’ parasitemia). In such instances, the developmental stages of the parasite seen on blood smear may help to assess disease severity better than parasite count alone. The presence of more mature parasite forms (>20 per cent of parasites as late trophozoites and schizonts) and of more than 5 per cent of neutrophils containing malarial pigment indicates more advanced disease and a worse prognosis. One negative blood smear makes the diagnosis of malaria very unlikely (especially the severe form); however, smears should be repeated every six to 12 hours for 48 hours if malaria is still suspected.

The smear can be prepared from blood collected by venipuncture, finger prick and ear lobe stab. In obstetric practice, cord blood and placental impression smears can be used. In fatal cases, post-mortem smears of cerebral grey matter obtained by needle necropsy through the foramen magnum, superior orbital fissure, ethmoid sinus via the nose or through fontanelle in young children can be used.

Sometimes no parasites can be found in peripheral blood smears from patients with malaria, even in severe infections. This may be explained by partial antimalarial treatment or by sequestration of parasitised cells in deep vascular beds. In these cases, parasites, or malarial pigment may be found in the bone marrow aspirates. Presence of malarial pigment in circulating neutrophils and monocytes may also suggest the possibility of malaria.

 

  • Non-microscopic tests

Several attempts have been made to take the malaria diagnosis out of the realm of the microscope and the microscopist. Important advances have been made in diagnostic testing, including fluorescence microscopy of parasite nuclei stained with acridine orange, rapid dipstick immunoassay, and Polymerase Chain Reaction assays.

These tests involve identification of the parasitic antigen or the antiplasmodial antibodies or the parasitic metabolic products. Nucleic acid probes and immunofluorescence for the detection of Plasmodia within the erythrocytes; gel diffusion, counter-immunoelectrophoresis, radio immunoassay, and enzyme immunoassay for malaria antigens in the body fluids; and hemagglutination test, indirect immunofluorescence, enzyme immunoassay, immunochromatography, and Western blotting for anti-plasmodial antibodies in the serum have all been developed. These tests have found some limited applications in research, retrograde confirmation of malaria, investigation of cryptic malaria, transfusion blood screening, and investigation of transfusion acquired infections.

Rapid Diagnostic Tests (RDTs) detect species-specific circulating parasite antigens targeting either the histidine-rich protein-2 of P. falciparum or a parasite-specific lactate dehydrogenase. Although the dipstick tests may enhance diagnostic speed, microscopic examination remains mandatory in patients with suspected malaria, because occasionally these dipstick tests are negative in patients with high parasitemia, and their sensitivity below 100 parasites/ìl is low. Tests based on polymerase chain reaction for species-specific Plasmodium genome are more sensitive and specific than are other tests, detecting as few as 10 parasites/ìl blood. Antibody detection has no value in the diagnosis of acute malaria. It is mainly used for epidemiologic studies.

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Therefore, the simplest and surest test is the time-honoured peripheral smear study for malarial parasites. None of the other newer tests have surpassed the ‘gold standard’ peripheral smear study.

 Malaria prevention

Mosquito control is an important component of malaria control strategy, although elimination of malaria in an area does not require the elimination of all Anopheles mosquitoes. In North America and Europe for example, although the vector Anopheles mosquitoes are still present, the parasite has been eliminated. Socio-economic improvements (e.g., houses with screened windows, air conditioning) combined with vector reduction efforts and effective treatments have led to the elimination of malaria without the complete elimination of the vectors.

On the other hand, controlling these highly adapted, flying and hiding vectors is indeed a formidable task. Development of resistance to insecticides has compounded the problem. Ban on non-biodegradable and non-eco-friendly insecticides like DDT also may have contributed to the resurgence of malaria.

 Mosquito control measures

The following are the steps in mosquito control:

  • Discourage egg laying
  • Prevent development of eggs into larvae and adults
  • Kill the adult mosquitoes
  • Do not allow adult mosquitoes into places of human dwelling
  • Prevent mosquitoes from biting human beings and deny blood meal

 Treatment of Malaria

     The effectiveness of early diagnosis and prompt treatment, as the principal technical components of the global strategy to control malaria, is highly dependent on the efficacy, safety, availability, affordability and acceptability of antimalarial drugs. The effective antimalarial therapy not only reduces the mortality and morbidity of malaria, but also reduces the risk of resistance to antimalarial drugs. Therefore, antimalaria chemotherapy is the KEYSTONE of malaria control efforts.

On the other hand, not many new drugs have been developed to tackle malaria. Of the 1223 new drugs registered between 1975 and 1996, only three were antimalarials! Hence the need for a national antimalaria treatment policy.

Antimalarial drugs can be classified according to antimalarial activity and structure.

 Classification according to antimalarial activity

  1. Tissue schizonticides for causal prophylaxis: These drugs act on the primary tissue forms of the plasmodia which, after growth within the liver, initiate the erythrocytic stage. By blocking this stage, further development of the infection can be theoretically prevented. Pyrimethamine and Primaquine have this activity. However since it is impossible to predict the infection before clinical symptoms begin, this mode of therapy is more theoretical than practical.
  2. Tissue schizonticides for preventing relapse: These drugs act on the hypnozoites of P. vivax and P. ovale in the liver that cause relapse of symptoms on reactivation. Primaquine is the prototype drug; pyrimethamine also has such activity.
  3. Blood schizonticides: These drugs act on the blood forms of the parasite and thereby terminate clinical attacks of malaria. These are the most important drugs in anti malarial chemotherapy. These include chloroquine, quinine, mefloquine, halofantrine, pyrimethamine, sulfadoxine, sulfones, tetracyclines etc.
  4. Gametocytocides: These drugs destroy the sexual forms of the parasite in the blood and thereby prevent transmission of the infection to the mosquito. Chloroquine and quinine have gametocytocidal activity against P. vivax and P. malariae, but not against P. falciparum. Primaquine has gametocytocidal activity against all plasmodia, including P. falciparum.
  5. Sporontocides: These drugs prevent the development of oocysts in the mosquito and thus ablate the transmission. Primaquine and chloroguanide have this action.

Essentially, therefore, treatment of malaria would include a blood schizonticide, a gametocytocide and a tissue schizonticide (in case of P. vivax and P. ovale). A combination of chloroquine and primaquine is thus needed in all cases of malaria.

 

Classification according to the structure

  • Aryl amino alcohols: Quinine, quinidine (cinchona alkaloids), mefloquine, halofantrine.
  • 4-aminoquinolines: Chloroquine, amodiaquine.
  • Folate synthesis inhibitors: Type 1 – competitive inhibitors of dihydropteroate synthase – sulphones, sulphonamides; Type 2 – inhibit dihydrofolate reductase – biguanides like proguanil and chloroproguanil; diaminopyrimidine like pyrimethamine
  • 8-aminoquinolines: Primaquine, WR238, 605
  • Antimicrobials: Tetracycline, doxycycline, clindamycin, azithromycin, fluoroquinolones
  • Peroxides: Artemisinin (Qinghaosu) derivatives and analogues – artemether, arteether, artesunate, artelinic acid
  • Naphthoquinones: Atovaquone
  • Iron chelating agents: Desferrioxamine

 

Report compiled by Temitope Obayendo with additional information from: World Health Organisation, Africa; Malaria site; Annals of African Medicine and The Nigeria Voice

 

 

 

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  1. The severity of malaria varies based on the species of plasmodium. Symptoms are chills, fever, and sweating, usually occurring a few weeks after being bitten. It is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause yellow skin, seizures, coma, or death.

  2. Harrow’s Sangster said the board was likely concerned the Indigenous men would pick up potentially deadly diseases, a justified fear given several players became ill during the initial tour in 1866 and 1867. Lawrence decided to take them anyway.

  3. tasked with managing the local Aboriginal population ruled the team couldn’t leave the colony to play a game in the neighboring state of New South Wales.

  4. Much of what is known of the Aboriginal cricket team’s almost two year-long tour of Victoria, New South Wales and then England is recorded by Lawrence, their White coach, in his memoirs, and press clippings in Australian and English papers.

  5. There is one glaring gap in the story of Australia’s First XI — almost no record exists of what the Aboriginal players thought of their journey.

  6. Hayman then took the team south to the regional hub of Hamilton, where they thrashed the local club 123 runs to 66, according to Cricket Walkabout. Mullagh alone took five wickets. “Within a couple of years they were beating teams, people who had played cricket all their lives,” said Kennedy.

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