The administration of drugs to whole populations irrespective of disease status is referred to as mass drug administration (MDA) or mass dispensing.
This article describes the administration of antimalarial drugs to whole populations, an intervention which has been used as a malaria-control measure for more than 70 years. Recent proposals to eliminate, or even to eradicate, malaria have led to a renewed interest in mass drug administrations in areas with very high malaria endemicity.
Drugs have been administered either directly as a full therapeutic course of treatment, or indirectly through the fortification of salt. Mass drug administrations were generally unsuccessful in interrupting transmission, but, in some cases, had a marked effect on parasite prevalence and on the incidence of clinical malaria. MDAs are likely to encourage the spread of drug-resistant parasites and so have only a limited role in malaria control. They may have a part to play in the management of epidemics and in the control of malaria in areas with a very short transmission season. In order to reduce the risk of spreading drug resistance, MDAs should use more than one drug and, preferably include a drug, such as an artemisinin, which has an effect on gametocytes. MDAs have low acceptance in areas with low malaria endemicity.
Other examples of MDAs are mass deworming of children to remove helminth infections (intestinal worms), and community-wide mass treatments to control scabies.
Background and history Reports of attempts to control malaria through mass treatment with antimalarial drugs date back to at least 1932.Barber, M. et al. (1932) Malaria studies on the Firestone rubber plantation in Liberia, West Africa. Am J Hyg 15 (3), 601n = 1 fallacy633 In the 1950s, the WHO included mass drug administration (MDA) of antimalarial drugs as a tool for malaria eradication in exceptional conditions when conventional control techniques have failed. In 1971, the WHO expert committee on malaria still recommended MDA in special circumstances. Subsequently, MDA was linked to the emergence of drug resistance and its overall benefit was questioned. Concomitantly, the goal of malaria eradication was replaced by one of prevention of malaria morbidity and mortality through the provision of effective treatment. Considering the short lasting benefit of mass drug administration, one modification has been to repeat mass drug administrations which has led to the development of intermittent preventive therapy.
Methods Two methods of mass drug treatment (MDA), direct and indirect, have been used. In direct MDA, a therapeutic dose of the antimalarial drug, usually in the form of tablets, is given to an entire population. In indirect MDA, the antimalarial drug is added to food, such as the fortification of salt.
Direct drug administration The first, well documented use of direct MDA took place in a rubber plantation in Liberia in 1931. Two doses of the 8-aminoquinoline plasmoquine were given weekly to workers and their families in two camps. The prevalences of malaria parasite infections in humans and anopheline mosquitoes before and after treatment were studied. The authors concluded that "the fall in the mosquito infection rate of the two plasmoquine treated camps was so large as to indicate a local disappearance, or at least a great reduction, in gametocyte carriers in the treated population". No long-term follow up data were provided for this study or most of the trials reported subsequently. The next documented use of MDA in sub-Saharan Africa took place in 1948 and 1949 in tea estates in Kericho, Kenya. Ten thousand inhabitants of the tea estates received twice weekly proguanil from April to July 1948. The intervention was supplemented with DDT spraying in March and June of the following year. Before the intervention the mean malaria incidence in July, the peak of the malaria transmission season, was 56 cases per 1000 population. Following the intervention 4 malaria cases were detected in July 1949. The author therefore recommended continuation of twice weekly proguanil prophylaxis on the estates.
The Nandi district of Kenya was the scene of a large MDA in 1953 and 1954. The target population of 83,000 received a single dose of pyrimethamine at the beginning of the malaria season in 1953 and 1954. The coverage was estimated to be around 95%. Before the intervention severe malaria epidemics had been reported in the area. Following the intervention the parasite prevalence dropped from 23% to 2.3%. The author states that in a control area parasite prevalence rose over the same period to over 50%. It was felt that the MDA was effective in curbing severe malaria epidemics. In the following three years, 1955 to 1957, pyrimethamine administration was replaced with Dieldrin spraying to consolidate malaria control, which makes an assessment of the long-term effect of this MDA impossible.
During a pilot programme in Uganda in 1959 mass administration of chloroquine / pyrimethamine was combined with spraying of residual insecticides (DDT). The success of the pilot programme led to a larger study targeted at a population of 16,000. Because of logistic problems, only half of the target population received the first round of MDA. According to the investigators, the intervention resulted in the eradication of the vector and rapid elimination of malaria from the area.
Two large trials of MDA combined with household spraying with DDT were conducted in Cameroun and Upper Volta (Burkina Faso) in 1960–1961.Escudie, A. et al. (1962) Resultat d'une chimoprophylaxie antipaludique de masse par l'association amino-4-quinoleine/amino-8-quinoleine en milieu rural africain de la region de Bobo-Dioulasso (Haute Volta). Méd. Trop. 22, 268–305 In both trials, substantial reductions in the prevalence of parasitaemia were achieved but transmission was not interrupted. In Bobo-Dioulasso, where primaquine was used in combination with either chloroquine or amodiaquine, the prevalence of gametocytes and Anopheles gambiae sporozoites were reduced substantially. A MDA was also combined with DDT spraying in Zanzibar (Dola 1974). After the MDA, the parasite prevalence in children decreased, but the overall parasite prevalence increased slightly, thus failing to deplete the reservoir of infection.
Two trials in Northern Nigeria combined multiple rounds of MDA and insecticide spraying. The first trial, in Kankiya, included 11 rounds of MDA combined with 8 rounds of DDT indoor spraying.Najera, J.A. et al. (1973) Mass drug administration and DDT indoor-spraying as antimalarial measures in the Northern savanna of Nigeria, WHO/MAL/73.817 (WHO/MAL/73.817) WHO The study was based on computer-aided models that showed that MDA could eradicate malaria in the study area if combined with an appropriate 'insecticide attack'.Macdonald, G. et al. (1967) The potential value of mass treatment in malaria eradication (WHO/MAL/67.615) WHO Following MDAs, parasite prevalence dropped from 19% to 1%. The investigators did not consider this a success because parasite prevalence increased again after the interventions were stopped. Entomological indices also showed only a temporary reduction in transmission, which was completely reversed after the control measures ceased. Because the investigators felt that the failure of the trial to interrupt transmission was due to operational inadequacies, they recommended a much larger and more sophisticated evaluation of insecticide spraying combined with MDA. This recommendation helped to launch the Garki project, also in Northern Nigeria, in 1969.Molineaux, L. and Gramiccia, G. (1980) The Garki Project. Research on the Epidemiology and Control of Malaria in the Sudan Savanna of West Africa., WHO In the Garki project, all 164 study villages in the catchment area were sprayed with propoxur, a residual insecticide. In addition, in 60 villages, MDA with sulfalene / pyrimethamine was given at 10-week intervals for two years. In two small village clusters, house spraying was supplemented with larvicide and MDA every two weeks. With biweekly MDA, parasite prevalence fell to 1% in the dry season and to 5% in the rainy season. MDA given every 10 weeks resulted in a parasite prevalence of 2% in the dry season and 28% in the rainy season. Transmission was not interrupted with either MDA regime. The authors concluded that spraying of residual insecticides and MDA did not result in a sustainable interruption of malaria transmission.
In 1999 in The Gambia residents living in 33 of 42 villages in the catchment area received a single dose of sulfadoxine / pyrimethamine (SP) combined with artesunate while the residents of nine control villages received placebo. Following the MDA, 1388 children ≤10 years of age living in nine control villages and in nine matched villages which had been allocated active treatment were kept under surveillance for clinical malaria throughout the transmission season. Initially, during July and August, the mean malaria incidence rate in treated villages was significantly lower than in the control villages. In subsequent months, the incidence was slightly higher in the MDA villages. The difference between the two groups was not statistically significant. Overall no benefit of the mass drug administration was detected over the course of the malaria transmission season.
A mass drug administration campaign using S/P, artesunate and primaquine was completed in Moshi district, Tanzania in 2008. The findings have yet to be published.
Outside of sub-Saharan Africa one of the larger reported malaria-control projects using MDA took place in Nicaragua in 1981 following the overthrow of the Somoza regime. An estimated 70% of Nicaragua's total population (1.9 million people) received chloroquine and primaquine during the peak period of disease transmission (November). An estimated 9200 cases of malaria were prevented. The campaign had better results in preventing and curing malaria infections than in interrupting transmission. However, the mass administration of antimalarials was not sustainable and, as with other malaria-control efforts, collapsed following the return of politically conservative forces.
In three malaria-control projects conducted in the Indian states of Andhra Pradesh, Uttar Pradesh, and Orissa in the early 1960s, MDA had an ancillary role and was mentioned only briefly in reports on these interventions.Lakshmanacharyulu, T. et al. (1968) Control of malaria in a river valley project. Bull. Indian Soc. Malaria & Other Communicable Dis. 5 (1–2)Singh, M.V. et al. (1968) Epidemiologic study of focal outbreak of malaria in consolidation phase area and evaluation of remedial measures in Uttar Pradesh (India). Bull. Indian Soc. Malaria & Other Communicable Dis. 5 (1–2), 207–220Sehgal, J.K. (1968) Progress of Malaria Eradication in Orissa State during 1965–66. Bull. Indian Soc. Malaria & Other Communicable Dis. 5 (1–2), 88–93 More detailed information is available following a focal outbreak in two villages in Gujarat State during 1978–1979. Here a mass administration of chloroquine was part of a programme of intensified surveillance, case management, health education, and residual spraying. The incidence of malaria decreased so that, by the end of 1979, the authors considered the intervention to be a success. In 1980, in areas of Andhra Pradesh State in India, residual spraying was combined with a MDA. During the period of lowest malaria incidence a single dose of chloroquine plus primaquine was distributed to the whole population in eight villages. A second dose was given after an interval of 2–3 months. This project failed to reduce malaria incidence and was considered to be a failure.