Malaria in the Nuba Mountains of Sudan: baseline genotypic resistance and efficacy of the artesunate plus sulfadoxine–pyrimethamine and artesunate plus amodiaquine combinations

Hamour, Sally; Melaku, Yoseph; Keus, Kees; Wambugu, Jesse; Atkin, Sara; Montgomery, Jacqui; Ford, Nathan; Hook, Christa; Checchi, Francesco

doi:10.1016/j.trstmh.2004.10.003

Cited by 34 publications

(19 citation statements)

References 20 publications

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“…The TF was also exclusively LTF (between day 14 and day 28), and the polymerase chain reactioncorrected TF rate (excluding new infections) was 7.5%. A comparable TF rate (8.8%) was reported in southern Sudan (Hamour et al 2005) and Eastern Sudan (Mukhtar et al 2007). …”

Section: Treatment Failure Rate Of Artesunate-sp In Suburban Khartoumsupporting

confidence: 70%

Artemisinin derivatives for treatment of uncomplicated Plasmodium falciparum malaria in Sudan: too early for too much hope

Giha

2009

Parasitol Res

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The artemisinin-based combination therapy (ACT) is adopted by several countries as first line for malaria treatment in the last decade. Concomitantly, the World Health Organization and other research reports showed a dramatic decline in malaria burden in terms of morbidity, mortality and treatment failure (TF). The optimistic features of ACT are regularly reported with great hopes, while the pessimistic facets either not existing or underreported. However, the dependence on ACT as a single chemotherapeutic agent for malaria control bears considerable risks. Occurrence and spread of artemisinin derivatives (AD) TF will be a major threat, whether it is due to parasite drug resistance or use of poor drug quality. In addition, the safety of AD is not yet fully known. In this short review, two clinical trials performed to evaluate the efficacy and safety of AD, dihydroartemisinin (DHA) plus chloroquine and artesunate (AS) plus fansidar, in Sudan are critically discussed. The conclusions from both studies were that, the TF rate of DHA indicates arrival of counterfeit AD to Africa, and both rate of TF and undesirable effects of AS/SP were recognized. Both findings indicate that it is too early for too much hope on AD.

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Section: Treatment Failure Rate Of Artesunate-sp In Suburban Khartoumsupporting

confidence: 70%

Artemisinin derivatives for treatment of uncomplicated Plasmodium falciparum malaria in Sudan: too early for too much hope

Giha

2009

Parasitol Res

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“…The 59R is associated with increased resistance to pyrimethamine, therefore absence of this mutation may be a good indicator for the in vivo efficacy of SP in this region. The pfdhfr 59R has been previously reported at low frequency in Khartoum, central Sudan in 1996/1997 [66] and Nuba mountains in western Sudan in 2003 [67]. However the 51I/108N haplotype has been observed at low frequencies in Kenya and Cameroon in the early 2000s where the pfdhfr -51I/59R/108N haplotype currently predominates [68,69].…”

Section: Discussionmentioning

confidence: 99%

Selection of pfdhfr/pfdhps alleles and declining artesunate/sulphadoxine-pyrimethamine efficacy against Plasmodium falciparum eight years after deployment in eastern Sudan

Gadalla

Abdallah

Atwal

et al. 2013

Malar J

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BackgroundArtesunate/sulphadoxine-pyrimethamine (AS/SP) has been the first-line treatment for falciparum malaria in Sudan since 2004. The impact of this combination on anti-malarial resistance-associated molecular markers has not been investigated. In this study, an evaluation of the efficacy and prevalence of drug resistance alleles (pfcrt, pfmdr1, pfdhfr and pfdhps) eight years after the adoption of AS/SP in eastern Sudan is reported.MethodsA 28-day follow-up efficacy trial of AS/SP was conducted in eastern Sudan during the 2012 transmission season. Blood smears were collected from patients on days 0, 1, 2, 3, 7, 14, 21 and 28. Blood spots on filter paper were obtained pre-treatment and on the day the patient was parasite positive by microscopy. Genotyping of alleles was performed by qPCR (pfcrt 72–76 and pfmdr1 copy number) and direct sequencing of pfmdr1, pfdhfr and pfdhps.ResultsSixty-three patients out of 68 (93%) completed the 28-day follow-up, adequate clinical, and parasitological response occurred in 90.5% and 85.3% of the patients in the per-protocol and intent-to-treat analyses, respectively. PCR corrected per-protocol efficacy was 93.7%. The enrolment prevalence of pfcrt-CVMNK was 30.2% and pfmdr1-N86 was 40.3%. The pfmdr1 haplotype NFD occurred in 32.8% of pre-treatment samples and was significantly higher than previous reports (Fisher’s exact p = 0.0001). The pfdhfr-51I/108N combination occurred in all sequenced isolates and 59R was observed in a single individual. pfdhps substitutions 436A, 437G, 540E, 581G and 613S were observed at 7.8, 77.3, 76.9%, 33.8% and 0.0%, respectively. Treatment failures were associated with the pfdhps haplotype SGEGA at these five codons (OR 7.3; 95% CI 0.65 - 368; p = 0.048).ConclusionThe decrease of CQR associated genotypes reflects the formal policy of complete removal of CQ in Sudan. However, the frequency of markers associated with SP failure is increasing in this study area and may be contributing to the treatment efficacy falling below 90%. Further monitoring of AS/SP efficacy and of post-treatment selection of pfdhfr and pfdhps alleles in vivo is required to inform future treatment guidelines.

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“…32 A total of 40% of P. falciparum infections and 38% of P. vivax infections had a parasite density below 2000 par/l, and nearly 20% and 25% were below 500 par/l. This proportion is higher than in high-endemic areas such as in Africa: in studies in DRC and Sudan (data from [33][34][35] ) we saw that only 8-11% of P. falciparum infections of clinically ill children under 5 years were below 2000 par/l. Hence, in areas of low and moderate malaria transmission, such as South America and Asia, rapid tests require a high sensitivity at lower densities of infection, to serve the non-immune populations that can suffer from clinical disease at much lower infection grades, as opposed to people in high-endemic areas in sub-Saharan Africa.…”

mentioning

confidence: 97%

Evaluation of Three Rapid Tests for Diagnosis of P. Falciparum and P. Vivax Malaria in Colombia

Broek

Hill²,

Gordillo³

et al. 2006

The American Journal of Tropical Medicine and Hygiene

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Abstract. The diagnostic capacity of three malaria rapid diagnostic tests (RDTs), NOW-Malaria-ICT, OptiMAL-IT, and Paracheck-Pf, was evaluated against expert microscopy in Colombia. We tested 896 patients, of whom microscopy confirmed 139 P. falciparum, 279 P. vivax, and 13 mixed P.f/P.v infections and 465 negatives. Paracheck-Pf and NOWmalaria-ICT were more accurate in detecting P. falciparum (sensitivities 90.8% and 90.1%, respectively) in comparison with Optimal-IT (83.6%). NOW showed an acceptable Pf detection rate at low densities (< 500/L), but resulted in a higher proportion of false positives. For P. vivax diagnosis, Optimal-IT had a higher sensitivity than NOW (91.0% and 81.4%, respectively). The choice between the two Pf/Pv detecting RDTs balances P. falciparum and P. vivax detection rates. Considering some degree of P. falciparum overtreatment and failure to detect all P. vivax cases as more acceptable than missing some cases of P. falciparum, we recommend careful implementation of NOW-malaria-ICT in areas where microscopy is lacking. The price is however still a constraint.

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Malaria in the Nuba Mountains of Sudan: baseline genotypic resistance and efficacy of the artesunate plus sulfadoxine–pyrimethamine and artesunate plus amodiaquine combinations

Abstract: CitationMalaria

Cited by 34 publications

References 20 publications

Artemisinin derivatives for treatment of uncomplicated Plasmodium falciparum malaria in Sudan: too early for too much hope

Artemisinin derivatives for treatment of uncomplicated Plasmodium falciparum malaria in Sudan: too early for too much hope

Selection of pfdhfr/pfdhps alleles and declining artesunate/sulphadoxine-pyrimethamine efficacy against Plasmodium falciparum eight years after deployment in eastern Sudan

Evaluation of Three Rapid Tests for Diagnosis of P. Falciparum and P. Vivax Malaria in Colombia

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