The Therapeutic Efficacy of Sulfadoxine/Pyrimethamine against &lt;i&gt;Plasmodium falciparum&lt;/i&gt; in Yemen

Al-Kabsi, Abdulgodos M; Al-Shamahy, Hassan Abdulwahab; Al-Harazy, Abdulilah Hussein; Harmal, Nabil S.

doi:10.1159/000163049

Cited by 6 publications

(3 citation statements)

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“…The findings of high efficacy of AS + SP against falciparum malaria are supported by the fact that at present there is no evidence that SP has lost its efficacy against falciparum malaria in Yemen. In 2005, in vivo and in vitro tests were conducted by Al-Kabsi et al to determine the SP efficacy against P. falciparum isolates from 100 malaria patients in Tihamah, Yemen [ 27 ]. In the in vivo test, no clinical or parasitological failure occurred.…”

Section: Discussionmentioning

confidence: 99%

High efficacy of two artemisinin-based combinations: artesunate + sulfadoxine-pyrimethamine and artemether-lumefantrine for falciparum malaria in Yemen

Adeel

Saeed²,

Al-Jasari³

et al. 2015

Malar J

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BackgroundArtesunate + sulfadoxine-pyrimethamine (AS + SP) has been the first-line treatment and artemether-lumefantrine (AL) the second-line treatment for uncomplicated falciparum malaria in Yemen since 2005. This paper reports the results of studies conducted to monitor therapeutic efficacy of these two drugs in sentinel sites in Yemen.MethodsEight therapeutic efficacy studies were conducted in six sentinel sites during the period 2009–2013 in Yemen. Five studies were for the evaluation of AS + SP (total of 465 patients) and three studies (total of 268 patients) for the evaluation of AL. The studies were done according to standard WHO protocol 2009 with 28-day follow-up.ResultsIn the evaluation of AS + SP, the PCR-corrected cure rate was 98 % (95 % CI 92.2–99.5 %) in one site and 100 % in all of the other four sites. In the sites where AL was evaluated, the PCR-corrected cure rate was 100 % in all the sites. All patients were negative for asexual parasitaemia on day 3 in both the AS + SP and the AL groups. There was a higher rate of clearance of gametocytaemia in the AL-treated group when compared with the AS + SP groups from day 7 onwards.ConclusionAS + SP remains the effective drug for uncomplicated falciparum malaria in Yemen. AL is also highly effective and can be an appropriate alternative to AS + SP for the treatment of falciparum malaria. AL demonstrated a higher efficacy in clearing microscopic gametocytaemia than AS + SP.Trial registration: Trial registration number ACTRN12610000696099

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Section: Discussionmentioning

confidence: 99%

High efficacy of two artemisinin-based combinations: artesunate + sulfadoxine-pyrimethamine and artemether-lumefantrine for falciparum malaria in Yemen

Adeel

Saeed²,

Al-Jasari³

et al. 2015

Malar J

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“…The countries of the Arabian Peninsula are now considered to be malaria-free [ 18 ], with two exceptions: Yemen where malaria is still prevalent with high rates of mortality and morbidity, and Saudi Arabia where the cases, principally recorded in the southwestern districts bordering Yemen are considered to be mainly imported from the bordering Tehama region of Yemen and from Sudan [ 19 , 20 ]. The decline in chloroquine efficacy in Yemen [ 21 – 24 ] prompted the adoption in 2009 of artesunate in combination with sulfadoxine-pyrimethamine (AS + SP) as the first-line treatment of uncomplicated P. falciparum infections, with a combination of artemether with lumefantrine (AL) as a second-line treatment [ 25 ]. Although clinical efficacy of AS + SP treatment in Yemen has not diminished since its introduction [ 21 , 26 ], there are indications from the few molecular surveys of P. falciparum populations in Yemen that whereas no mutations associated with drug resistance occur for pfdhps , the prevalence of such mutations in pfdhfr is increasing [ 27 – 30 ].…”

Section: Introductionmentioning

confidence: 99%

“…The decline in chloroquine efficacy in Yemen [ 21 – 24 ] prompted the adoption in 2009 of artesunate in combination with sulfadoxine-pyrimethamine (AS + SP) as the first-line treatment of uncomplicated P. falciparum infections, with a combination of artemether with lumefantrine (AL) as a second-line treatment [ 25 ]. Although clinical efficacy of AS + SP treatment in Yemen has not diminished since its introduction [ 21 , 26 ], there are indications from the few molecular surveys of P. falciparum populations in Yemen that whereas no mutations associated with drug resistance occur for pfdhps , the prevalence of such mutations in pfdhfr is increasing [ 27 – 30 ]. Finally, it is known that SP does not provide optimal clearance of gametocytes, even when combined with AS, prompting calls to include monitoring of the sexual stages in dug efficacy studies [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

Sustained efficacy of artesunate-sulfadoxine-pyrimethamine against Plasmodium falciparum in Yemen and a renewed call for an adjunct single dose primaquine to clear gametocytes

Atroosh

Al-Mekhlafi

Snounou

et al. 2016

Malar J

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BackgroundIn Yemen, artesunate plus sulfadoxine-pyrimethamine (AS + SP) has been used as first-line treatment for uncomplicated falciparum malaria, which accounts for about 99 % of malaria cases. There is evidence that resistance to SP is increasing, with potential negative impact on efficacy, and in particular on curbing transmission. This study aims: (a) to evaluate the therapeutic efficacy of AS + SP treatment for uncomplicated falciparum malaria in Yemen; (b) to investigate the frequency of mutations in Plasmodium falciparum genes associated with resistance to AS (Kelch 13 propeller domain, pfK13) and SP (dihydrofolate reductase, pfdhfr, and dihydropteroate synthase, pfdhps); and (c) to assess the adequacy of this ACT to clear gametocytes.MethodsA 28-day in vivo evaluation of the clinical and parasitological response to three-day course of AS + SP was carried out in two areas of high endemicity (Hodeidah and Al-Mahwit provinces, Tehama region) in Yemen according to standard WHO protocol 2009. Clinical and parasitological indices were monitored over a 28-day follow-up, and the outcome was PCR-corrected. The frequencies of mutations in the pfdhfr, pfdhps, and pfK13 genes were obtained by sequencing following amplification.ResultsEighty-six patients completed the study, with a cure rate of 96.5 % (94.2 % PCR-uncorrected). Whereas four (4.7 %) patients still showed parasitaemia on day 2 post-treatment, all were found negative for asexual malaria stages on days 3 and 7. The efficacy of gametocyte clearance was poor (14.5, 42.5 and 86.0 % on days 7, 14 and 28, respectively), with gametocytes persisting throughout the study in some patients. All the isolates sequenced had the pfk13 propeller domain wild-type allele, and mutations associated with SP failure were observed only for pfdhfr with the double mutation (S108N + N51I) found in 65.4 % of the isolates sequenced.ConclusionIn Yemen, AS + SP therapy remains effective for the treatment of uncomplicated falciparum malaria. Mutations were not detected in pfk13 or pfdhps, though double mutations were observed for pfdhfr. The observed persistent gametocytaemia re-enforces calls to add a single dose primaquine to this ACT in order to minimizes the potential for transmission and enhance regional efforts to eliminate malaria.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1344-0) contains supplementary material, which is available to authorized users.

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Mutant Plasmodium falciparum chloroquine resistance transporter in Hodeidah, Yemen: Association with parasitologic indices and treatment-seeking behaviors

et al. 2013

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The Therapeutic Efficacy of Sulfadoxine/Pyrimethamine against <i>Plasmodium falciparum</i> in Yemen

Abstract: studies be carried out to address the importance of dihydropteroate synthetase/dihydrofolate reductase mutations as predictive markers of sulfadoxine/pyrimethamine resistance in Yemen.

Cited by 6 publications

References 21 publications

High efficacy of two artemisinin-based combinations: artesunate + sulfadoxine-pyrimethamine and artemether-lumefantrine for falciparum malaria in Yemen

High efficacy of two artemisinin-based combinations: artesunate + sulfadoxine-pyrimethamine and artemether-lumefantrine for falciparum malaria in Yemen

Sustained efficacy of artesunate-sulfadoxine-pyrimethamine against Plasmodium falciparum in Yemen and a renewed call for an adjunct single dose primaquine to clear gametocytes

Mutant Plasmodium falciparum chloroquine resistance transporter in Hodeidah, Yemen: Association with parasitologic indices and treatment-seeking behaviors

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