Malaria Control in Complex Humanitarian Emergencies

War, famine, civil conflict, and political persecution displacing large populations often leads to severe disruptions in health services, disease control programs, food distribution systems, and loss of shelter. When the dimensions of the crisis overwhelm the local and international communities' ability to respond quickly and effectively, significant morbidity and mortality result in what is termed a complex humanitarian emergency. The public health consequences have been most severe in underdeveloped nations where most deaths are caused by communicable diseases, which include malaria. This paper describes and analyses the factors that contribute to malaria morbidity and mortality and proposes effective measures to combat them.Les conflits armés, les famines, les guerres civiles, les persécutions politiques déplaçant de grandes portions de la population provoquent souvent de graves perturbations dans les services de santé, les programmes de contrôles sanitaires, les structures de distributions alimentaires, et entraînent fréquemment la perte du gîte ou de l'abris. Quand l'ampleur de la crise submerge les capacités locales et internationales à y répondre promptementet efficacement, le résultat de ce que l'on appelle une urgence humanitaire complexe est un accroissement significatif de la condition maladive et de la mortalité des populations en cause. Les conséquences en termes de santé publique sont particulièrement graves dans les nations sous-développées, où un plus grand nombre de pertes de vie sont dues à des maladies transmissibles, incluant notamment la malaria. Cet article décrit et analyse la série de facteurs contribuant à la condition maladive et à la mortalité liés à la malaria, et propose des mesures effectives pour combattre ces facteurs

Efficacy and effectiveness of the combination of sulfadoxine/pyrimethamine and a 3-day course of artesunate for the treatment of uncomplicated falciparum malaria in a refugee settlement in Zambia.

In the Maheba Refugee Settlement, in the clinics supported by Medecins Sans Frontieres, all children aged up to 5 years with a confirmed diagnosis of uncomplicated falciparum malaria are treated with the combination of sulfadoxine/pyrimethamine (SP) and artesunate (AS). We compared the treatment's efficacy and effectiveness. Patients were randomized in order to receive the treatment supervised (efficacy) or unsupervised (effectiveness). Therapeutic response was determined after 28 days of follow up. The difference between recrudescence and re-infection was ascertained by polymerase chain reaction (PCR). We also assessed genetic markers associated to SP resistance (dhfr and dhps). Eighty-five patients received treatment under supervision and 84 received it unsupervised. On day 28, and after PCR adjustment, efficacy was found to be 83.5% (95% CI: 74.1-90.5), and effectiveness 63.4% (95% CI: 52.6-73.3) (P < 0.01). Point mutations on dhfr (108) and dhps (437) were found for 92.0% and 44.2% respectively of the PCR samples analysed. The significant difference in therapeutic response after supervised and unsupervised treatment intake can only be explained by insufficient patient adherence. When implementing new malaria treatment policies, serious investment in ensuring patient adherence is essential to ascertain the effectiveness of the new treatment schedules

The genetic change in P. falciparum populations of rural Tanzania resulting from national policy on firstline malaria treatment and pilot Sulfadoxine/pyrimethamine and Artesunate combination

Malaria Journal 2010, 9(Suppl 2):P20Theory predicts that we can protect the efficacy of future antimalarials by changing treatment practice or drug formulation, but the potential success of such interventions rests upon their impact on drug pressure in the field. So far, gathering field data on the relationship between policy, drug pressure, recombination and the evolution of resistance has been entirely challenging. To test these predictions, dhfr and dhps frequency changes were measured in two rural districts of Rufiji and Kilombero/Ulanga during 2000-2006, and the frequencies of the two genes compared prior, during and after antimalarial policy change from first line CQ to first line SP in 2001. Furthermore, while SP first line was maintained in Kilombero/Ulanga, pilot combination therapy of SP+Artesunate (ART) was introduced in Rufiji in 2002 to replace SP and dhfr and dhps frequency changes compared between the two districts. Size polymorphisms at three sets of microsatellite loci linked to dhfr and three other sets of unlinked microsatellite loci were analysed. Genetic analysis of SP resistance genes was carried out on 9,662 Plasmodium falciparum infections identified in a series of annual cross sectional surveys conducted in the two districts between 2000-2006. The frequency of dhfr and dhps resistance alleles did not change significantly while SP was the recommended second-line treatment, but highly significant changes occurred during the subsequent year after the switch to first line SP. The frequency of the triple mutant dhfr allele increased by 37% -63% and that of double mutant dhps allele increased 200%-300%. A strong association between these unlinked alleles also emerged; confirming that they are co-selected by SP. Distribution of major lineages indicates that there is extensive genetic exchange among the geographic regions. Combination therapy had visible effect on the frequencies of dhfr and dhps resistance alleles. The findings of this study provide insight on the interplay between policy, drug pressure, recombination and the evolution of resistance

Cotrimoxazole for childhood febrile illness in Malaria-endemic regions

The efficacy of co-trimoxozole for the treatment of Plasmodium falciparum parasitaemia in children younger than 5 years of age was evaluated in Malawi. 46 children with P. falciparum parasitaemia, 37% of whom also met clinical criteria for a diagnosis of acute lower respiratory tract infection, were treated with 20 mglkg co-trimoxazole twice daily for five days. Parasitaemia (mean clearance time 2.7 days) and symptoms were rapidly abolished and improvement was maintained during follow-up for 14 days. Co-trimoxazole may be an effective single treatment for febrile illness in young children in areas where malaria is endemic, resources are few, and diagnosis must rely on clinical findings alone

Media, Health Workers, and Policy Makers' Relationship and Their Impact on Antimalarial Policy Adoption: A Population Genetics Perspective

Drug resistance negatively impacts malaria treatments, making treatment policy revision unavoidable. So far, studies relating sociopolitical and technical issues on policy change with malaria parasite genetic change are lacking. We have quantified the effect of malaria treatment policy on drug pressure and the influence of the media, policy makers, and health worker relationship on parasite population genetic change in Kilombro/Ulanga district. Cross-sectional surveys of asymptomatic infections conducted before, during and after the switch from chloroquine to sulphadoxine/pyrimethamine were used for genetic analysis of SP resistance genes in 4,513 asymptomatic infections identified, and their frequency change was compared with retrospective study of the documented process of policy change. Highly significant changes of dhfr and dhps resistance alleles occurred within one year of switch to SP first line, followed by a decline of their rate of selection caused by reduction of SP usage, as a result of negative media reports on SP usage and lack of adequate preparations

Quantification of markers of antimalarial drug resistance from an area of high malaria transmission: Comparing frequency with prevalence

Molecular monitoring of markers of antimalarial drug resistance offers an affordable alternative to the in vivo method for the detection of resistance, and has the potential to guide public health policy in a timely manner. However, the optimal way of analyzing and reporting these data, particularly those emanating from areas of moderate to high malaria transmission, has never been fully explored or agreed upon, given the potential of being confounded by coinfections. By using large number of real field samples, we quantified the difference between prevalence and frequency when reporting field data on antimalarial drug resistance obtained by direct counting of haplotypes. Polymerase chain reaction (PCR) and sequence specific oligonucleotide probing was used to generate point mutations which were used to construct haplotypes. Results indicate that frequency underestimates haplotypes present at low levels while also amplifying haplotypes present at high levels; prevalence on the other hand behaved in a vice versa manner. Both prevalence and frequency are therefore essential, as each may have relevance in different contexts in high malaria transmission settings. Frequency is essential to gauge the impact of intervention on antimalarial drug resistance while prevalence may be more relevant when the aim is to determine parasite clearance. Key words: Molecular markers, polymerase chain reaction (PCR) - sequence specific oligonucleotide probing (SSOP), prevalence, frequency

The rationale and plan for creating a World Antimalarial Resistance Network (WARN)

Drug resistant malaria was a major factor contributing to the failure of a worldwide campaign to eradicate malaria in the last century, and now threatens the large investment being made by the global community in the rollout of effective new drug combinations to replace failed drugs. Four related papers in this issue of Malaria Journal make the case for creating the World Antimalarial Resistance Network (WARN), which will consist of four linked open-access global databases containing clinical, in vitro, molecular and pharmacological data, and networks of reference laboratories that will support these databases and related surveillance activities. WARN will serve as a public resource to guide antimalarial drug treatment and prevention policies and to help confirm and characterize the new emergence of new resistance to antimalarial drugs and to contain its spread

Dispensary level pilot implementation of rapid diagnostic tests: an evaluation of RDT acceptance and usage by providers and patients – Tanzania, 2005

BACKGROUND\ud \ud Malaria rapid diagnostic tests (RDTs) may assist in diagnosis, improve prescribing practices and reduce potential drug resistance development. Without understanding operational issues or acceptance and usage by providers and patients, the costs of these tests may not be justified.\ud \ud OBJECTIVES\ud \ud To evaluate the impact of RDTs on prescribing behaviours, assess prescribers' and patients' perceptions, and identify operational issues during implementation.\ud \ud METHODS\ud \ud Baseline data were collected at six Tanzanian public dispensaries. RDTs were implemented for eight weeks and data collected on frequency of RDT use, results, malaria diagnoses and the prescription of antimalarials. Patients referred for RDTs completed a standardised exit interview. Qualitative methods assessed attitudes toward and satisfaction with RDTs, perceptions about the test and operational issues related to implementation.\ud \ud RESULTS\ud \ud Of 595 patients at baseline, 200 (33%) were diagnosed clinically with malaria but had a negative RDT. Among the 2519 RDTs performed during implementation, 289 (11.5%) had a negative result and antimalarials prescribed. The proportion of "over-prescriptions" at baseline was 54.8% (198/365). At weeks four and eight this decreased to 16.1% (27/168) and 16.4% (42/256) respectively.A total of 355 patient or parent/caregiver and 21 prescriber individual interviews and 12 focus group discussions (FGDs) were conducted. Patients, caregivers and providers trusted RDT results, agreed that use of RDTs was feasible at dispensary level, and perceived that RDTs improved clinical diagnosis. Negative concerns included community suspicion and fear that RDTs were HIV tests, the need for additional supervision in interpreting the results, and increased work loads without added compensation.\ud \ud CONCLUSION\ud \ud Overprescriptions decreased over the study period. There was a high degree of patient/caregiver and provider acceptance of and satisfaction with RDTs. Implementation should include community education, sufficient levels of training and supervision and consideration of the need for additional staff