Malaria control in complex emergencies: appropriate tools for the acute and post-emergency phases

This thesis examined appropriate tools for the control of malaria in complex emergencies, focusing on the refugee camp environment. Tools that may reduce the transmission of malaria, both through vector control as well as antimalarial drug treatment with regimens demonstrating gametocytocidal activity were evaluated. Field work took place in Pakistan. Insecticide pre-treated plastic sheeting, canvas tents and blankets were examined in insectary bioassay and overnight outdoor platform tests to determine their potential for personal protection and "mass-effect" malaria vector control. These materials may be useful for use at the early stages of an emergency when an insecticide spray campaign or delivery of insecticide-treated nets may be hampered by logistic and organisational constraints and/or be inappropriate due to the shelters in use at this time. Insecticide-treated plastic sheeting (ITPS) resulted in treatment induced anopheline mortalities between 17 and 43% in 5 of 7 overnight platform trials with wild hostseeking mosquitoes. Induced mortality in wild mosquito populations on insecticidetreated tents also fell within this range. A treatment induced 4-fold reduction in blood-feeding on tents was seen but an inconsistent impact on blood-feeding was seen for ITPS. A decline in insecticidal efficacy of pre-treated ITPS over a period of 13.5 months weathering was demonstrated, though persistence was considerably better than on sheeting sprayed with insecticide. Promising initial data of treatment induced mortality on insecticide-treated blankets were not replicable and more work is needed, perhaps with a revised testing protocol. Insecticide-treated nets may be a feasible option during more sustained emergencies when procurement has been possible, people live in shelters suitable for erecting nets and the environment allows delivery of nets with appropriate health education. Long-lasting insecticidal nets (LUNs) are particularly suitable for a transient population in which retreatment of conventionally treated nets is problematic, for example in internally displaced people (IDPs) or refugees who may return home. Two candidate deltamethrin LUNs were compared to conventionally treated nets in insectary bioassay, overnight platform assays and high pressure liquid chromatography assays. PermaNetTM 2.0 was shown to have superior performance by all test criteria than conventionally treated nets. Dawa TM net was not superior to conventionally treated nets. Two randomised controlled trials of antimalarial drug treatment regimens were carried out; in falciparum patients and in vivax patients. The study against falciparum malaria was a six arm study including the current first and second line treatments in the region, chloroquine (CO) and sulphadoxine-pyrimethamine (SP), as well as combinations of each of these drugs with primaquine or artesunate (AS). Chloroquine resistance was high; CO monotherapy achieved only 23% clinical cure. CO+AS gave an improved cure rate (72% clinical cure) over CO alone (P<0.001). Some resistance to SP was seen, with 10% clinical failure. SP+AS achieved 100% clinical cure. The odds of a patient carrying gametocytes on or after day 7 is associated with the presence of gametocytes on day 0, regardless of treatment given. Both primaquine and artesunate treatment regimens reduced gametocyte persistence compared to the monotherapies. This was most marked for artesunate and in patients without patent gametocytaemia on day o. The study against vivax malaria compared the standard CO regimen with a combination of SP+AS, promoted as the 1st line regimen for falciparum malaria in the region. With approximately 80% of the malaria in the region caused by the vivax parasite the likelihood of misdiagnosis or incorrect treatment of vivax cases as falciparum malaria is high. This would also be the case in many post-emergency settings, where both parasites occur, where the quality of the health systems are unlikely to ensure a good level of accurate differential diagnosis. Where the falciparum first line treatment remains chloroquine this issue is irrelevant, however, with SP+AS concerns over the efficacy of a combination including SP, thought to have relatively poor activity against vivax, needed to be addressed. Chloroquine treatment is known to clear vivax gametocytes rapidly, but it is not clear if SP+AS would have the same effect. Both CO and SP+AS had high efficacy for vivax malaria with SP+AS performing better over an extended period of follow-up (42 days) than CO. No difference was seen in gametocyte carriage after treatment in the 0-28 day period, though patients with reappearance of trophozoites in the 28-42 day period were also carrying gametyocytes. Fewer patients had reappearance of any parasites in the SP+AS group than in the CO group. The results of these studies are discussed alongside other work in this field and recommendations for suitable malaria control tools for emergencies are given. Future research needs are highlighted.