Answer parts (a) and (b).

(a)	Write short notes on:

	(i)  Poliomyelitis vaccination.
	(ii) Western blot in HIV diagnosis.

(b)	Give two main reasons why malaria continues to be a serious problem in many areas. Briefly discuss the chemotherapy and chemoprophylaxis of this disease.

Suggested Answer:

(a)(i)	Poliomyelitis is an infection of the central nervous system caused by an enterovirus of the picornavirus group. There is no effective antiviral treatment. Prevention is by vaccination either with a live attenuated virus (Sabin vaccine) or with a killed virus (Salk vaccine). The Salk vaccine contains 3 polioviruses inactivated by formaldehyde. It is given intravenously usually in the vaccination of unimmunized adults and immunodeficient individiuals. The killed virus vaccine promotes humoral immunity without the intestinal mucosal reaction. The Sabin vaccine contains attenuated strains of 3 polioviruses. It is administered in 3 oral doses at 2, 3 and 4 months old, with single-dose boosters prior to school entry and overseas travel. The oral vaccine colonizes the gastrointestinal tract and stimulates mucosal IgA antibody production. It also protects unvaccinated individuals from spreading in communities. Very occasionally, live vaccine strains revert to original pathogenic status and may cause polio.

(a)(ii)	Western blot is an immunological method that uses a nitrocellulose strip containing microbial antigens separated by electrophoresis to detect the presence of antibodies in serum specimens. The method is used to confirm the presence of antibodies to a range of viral antigens in patients with HIV. A positive test requires presence of bands at gp24, gp31, gp41 and gp120.

(b)	Malaria is transmitted primarily by the bite of infected anopheles mosquitoes. It can also be transmitted by inoculation of infected blood and congenitally. Anopheles feed at night and their breeding sites are primarily in rural areas. The greatest risk of malaria is therefore from dusk to dawn in rural areas. The disease is still widely transmitted in the tropics and subtropics. In these areas malaria transmission may be endemic, occurring predictably every year, or it may be epidemic, occurring sporadically when conditions are correct. Endemic transmission of malaria may be year round or seasonal. Malaria is still a serious problem in many areas as a result of the development of drug resistance by both the mosquito and the parasite, and because of deteriorating social and economic conditions in many malaria-endemic countries. These changes have resulted in a dramatic increase in the incidence of malaria in many parts of the world, and an increase in malaria-related mortality in some of these areas.

	All patients with uncomplicated P malariae, P ovale, and P vivax and P falciparum from chloroquine sensitive areas should be treated with oral chloroquine. The drug is highly effective, well tolerated and inexpensive. Therapy of chloroquine-resistant P falciparum is complicated and depends primarily on area of disease acquisition. Patients with uncomplicated disease acquired in areas of chloroquine resistance can be treated with one of several regimens effective against chloroquine-resistant parasites: mefloquine alone, or quinine, plus doxycycline or pyrimethamine/sulfadoxine (FansidarR). Other effective drugs include halofantrine, artemisinin (qinghaosu) derivatives, and clindamycin. Chloroquine-resistant P vivax is highly prevalent on the island of New Guinea (Papua New Guinea and Irian Jaya, Indonesia) and may be present elsewhere. Recent studies in Indonesia have shown halofantrine, and chloroquine plus primaquine to be highly effective against these resistant strains. Although not specifically tested, the above regimens for chloroquine-resistant P falciparum should also be effective. Severe or complicated malaria is a medical emergency. It is caused almost exclusively by P. falciparum. Patients with complicated malaria should be treated with intravenous antimalarials and in an intensive care unit whenever possible. The drugs of choice are intravenous quinidine or quinine. Patients on these regimens must be observed closely for signs of hypotension or myocardial conduction abnormalities. Oral quinine, plus doxycycline or FansidarR, is substituted as soon as there is clinical improvement. If acquired in an area of chloroquine-sensitive parasites, parenteral chloroquine may also be given. Artemisinin compounds show promise for therapy of severe malaria because they decrease parasitemia faster than all other antimalarials. For infections due to P vivax or P ovale, primaquine should be given after therapy of the blood-stage infection to eradicate hypnozoites of these species and prevent relapses. Primaquine should be used with caution in persons who are G6PD deficient due to its potential to cause severe hemolysis. 
Chemoprophylaxis is not one hundred percent effective; regardless of prophylaxis, malaria must be considered in the differential diagnosis of any febrile illness in an individual who has been in an area endemic for malaria within the last 2-3 years. Chemoprophylaxis is designed to kill the parasite after it has gained access to the body but before it leads to the rupture of host RBCs, which causes the symptoms of malaria. Drugs may accomplish this by attacking the parasite in either the liver or the blood. Causal chemoprophylaxis refers to killing the parasite in the liver before it gains access to the blood. Suppressive chemoprophylaxis is accomplished by drugs which attack asexual parasites in the blood. Most antimalarial drugs attack parasites in the blood and are therefore suppressive chemoprophylactics. Primaquine is the only antimalarial drug currently available which reliably kills liver stage organisms. The choice of a chemoprophylactic regimen depends on several factors: the health of the individual (including factors such as pregnancy, age, and chronic illness); the risk and types of malaria in the areas to be visited; and the presence of drug-resistant P falciparum. Chloroquine is the recommended chemoprophylactic for those travelling to areas where plasmodia are still chloroquine sensitive (Mexico, Central America, Haiti, the Dominican Republic, and the Middle East). There are very few contraindications to chloroquine. Most travellers, however, visit areas where there is chloroquine resistance and other drugs, generally with greater toxicity, must be used. For most of these travelers, mefloquine is the drug of choice and doxycycline is as acceptable alternative. Extensive mefloquine resistance makes doxycycline the drug of choice for those visiting the borders of Thailand. Chloroquine plus proguanil (proguanil is not available in the U.S.) is another possible regimen for chloroquine-resistant areas, but this regimen is much less effective than mefloquine or doxycycline. Recent work also suggests that primaquine, apparently acting against liver-stage organisms, is as effective as mefloquine and doxycycline for chemoprophylaxis in areas of chloroquine resistance. Prophylaxis with chloroquine or mefloquine should begin 2 weeks before entering the malarious area (to ensure tolerance to the drug and to provide adequate blood levels) and should continue throughout the stay in the area and for 4 weeks after leaving. Doxycycline should be started 1 to 2 days before travel to a malarious area and should be taken daily during the stay in the area and for 4 weeks after leaving. Taking the drugs after leaving the malarious area is referred to as terminal prophylaxis and is necessary to kill organisms which emerge from the liver after the person returns home. When there has been a significant risk of exposure to P vivax or P ovale, primaquine should be taken for 14 days after returning home to eliminate remaining liver stage parasites. Primaquine may be taken any time during the 4 weeks in which the blood schizonticide is being taken.