BackgroundRecently, a number of Global Health Initiatives (GHI) have been created to address single disease issues in low-income countries, such as poliomyelitis, trachoma, neonatal tetanus, etc.. Empirical evidence on the effects of such GHIs on local health systems remains scarce. This paper explores positive and negative effects of the Integrated Neglected Tropical Disease (NTD) Control Initiative, consisting in mass preventive chemotherapy for five targeted NTDs, on Mali's health system where it was first implemented in 2007.Methods and FindingsCampaign processes and interactions with the health system were assessed through participant observation in two rural districts (8 health centres each). Information was complemented by interviews with key informants, website search and literature review. Preliminary results were validated during feedback sessions with Malian authorities from national, regional and district levels. We present positive and negative effects of the NTD campaign on the health system using the WHO framework of analysis based on six interrelated elements: health service delivery, health workforce, health information system, drug procurement system, financing and governance. At point of delivery, campaign-related workload severely interfered with routine care delivery which was cut down or totally interrupted during the campaign, as nurses were absent from their health centre for campaign-related activities. Only 2 of the 16 health centres, characterized by a qualified, stable and motivated workforce, were able to keep routine services running and to use the campaign as an opportunity for quality improvement. Increased workload was compensated by allowances, which significantly improved staff income, but also contributed to divert attention away from core routine activities. While the campaign increased the availability of NTD drugs at country level, parallel systems for drug supply and evaluation requested extra efforts burdening local health systems. The campaign budget barely financed institutional strengthening. Finally, though the initiative rested at least partially on national structures, pressures to absorb donated drugs and reach short-term coverage results contributed to distract energies away from other priorities, including overall health systems strengthening.ConclusionsOur study indicates that positive synergies between disease specific interventions and nontargeted health services are more likely to occur in robust health services and systems. Disease-specific interventions implemented as parallel activities in fragile health services may further weaken their responsiveness to community needs, especially when several GHIs operate simultaneously. Health system strengthening will not result from the sum of selective global interventions but requires a comprehensive approach.

Abstract. To assess pyrimethamine-sulfadoxine (PS) efficacy in Mali, and the role of mutations in Plasmodium falciparum dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) in in vivo PS resistance, 190 patients with uncomplicated P. falciparum malaria were treated with PS and monitored for 56 days. Mutation-specific polymerase chain reactions and digestion with restriction endonucleases were used to detect DHFR and DHPS mutations on filter paper blood samples from pretreatment and post-treatment infections. Only one case each of RI and RII level resistance and no cases of RIII resistance or therapeutic failure were observed. Post-PS treatment infections had significantly higher rates of DHFR mutations at codons 108 and 59. No significant selection for DHPS mutations was seen. Pyrimethamine-sulfadoxine is highly efficacious in Mali, and while the low level of resistance precludes assessing the utility of molecular assays for in vivo PS resistance, rapid selection of DHFR mutations supports their role in PS failure.Resistant Plasmodium falciparum has rendered the antifolate combination pyrimethamine-sulfadoxine (PS) useless in parts of South America and Southeast Asia, and threatens its utility in Africa, where PS has become the first-line drug in areas with widespread chloroquine resistance. 1 In Mali, where malaria is the leading cause of death, PS is recommended for cases of chloroquine failure. Although chloroquine remains effective here, PS is available in pharmacies in urban and periurban areas. 2 This is the first study of PS efficacy in Mali.Simple and reliable methods for drug resistance testing are needed in this setting, but both standard in vivo and in vitro methods have several disadvantages, many of which are overcome by molecular assays for resistance. 2 These polymerase chain reaction (PCR) and restriction digestion assays detect point mutations in parasite dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS), the enzymes targeted by pyrimethamine and sulfadoxine, respectively. [3][4][5][6] Briefly, DHFR Ser→Asn 108 causes moderate pyrimethamine resistance in vitro, with higher level resistance resulting from Asn→Ile 51 and/or Cys→Arg 59, and the addition of Ile→Leu 164 causes high level resistance to both pyrimethamine and cycloguanil, the active metabolite of proguanil. A five amino-acid insert at codon 30 and point mutations at codons 50 and 140 7,8 have recently been discovered in areas with widespread in vivo PS resistance, but not yet confirmed to play a role in resistance to the DHFR inhibitors. The DHPS mutations associated with in vitro resistance to sulfadoxine include Ser→Phe 436 paired with Ala→Thr/Ser 613, Ser→Ala 436, Ala→Gly 437, Lys→Glu 540, and Ala→Gly 581. 6,9,10 Digital puncture blood samples blotted onto filter paper can be analyzed by mutation-specific PCR and restriction digestion to detect all of these mutations.Because the DHFR Ser→Asn-108 mutation is associated with PS use and resistance and is selected for by PS treatment, it has been used as a...

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