Effect of Artemether-Lumefantrine Policy and Improved Vector Control on Malaria Burden in KwaZulu–Natal, South Africa

BACKGROUND: Between 1995 and 2000, KwaZulu–Natal province, South Africa, experienced a marked increase in Plasmodium falciparum malaria, fuelled by pyrethroid and sulfadoxine-pyrimethamine resistance. In response, vector control was strengthened and artemether-lumefantrine (AL) was deployed in the first Ministry of Health artemisinin-based combination treatment policy in Africa. In South Africa, effective vector and parasite control had historically ensured low-intensity malaria transmission. Malaria is diagnosed definitively and treatment is provided free of charge in reasonably accessible public-sector health-care facilities. METHODS AND FINDINGS: We reviewed four years of malaria morbidity and mortality data at four sentinel health-care facilities within KwaZulu–Natal's malaria-endemic area. In the year following improved vector control and implementation of AL treatment, malaria-related admissions and deaths both declined by 89%, and outpatient visits decreased by 85% at the sentinel facilities. By 2003, malaria-related outpatient cases and admissions had fallen by 99%, and malaria-related deaths had decreased by 97%. There was a concomitant marked and sustained decline in notified malaria throughout the province. No serious adverse events were associated causally with AL treatment in an active sentinel pharmacovigilance survey. In a prospective study with 42 d follow up, AL cured 97/98 (99%) and prevented gametocyte developing in all patients. Consistent with the findings of focus group discussions, a household survey found self-reported adherence to the six-dose AL regimen was 96%. CONCLUSION: Together with concurrent strengthening of vector control measures, the antimalarial treatment policy change to AL in KwaZulu–Natal contributed to a marked and sustained decrease in malaria cases, admissions, and deaths, by greatly improving clinical and parasitological cure rates and reducing gametocyte carriage

Antifolate antimalarial resistance in southeast Africa: a population-based analysis.

BACKGROUND: Sulfadoxine-pyrimethamine was first introduced for treatment of malaria in Africa during the early 1980s for cases when chloroquine treatment failed, and has since become the first-line treatment in many countries. Resistance to sulfadoxine-pyrimethamine is now increasing, especially in southeast Africa. METHODS: We characterised genetic change in dhfr and dhps genes in the Plasmodium falciparum population of KwaZulu-Natal, South Africa, during 1995-99, a period of rapid deterioration of the effectiveness of sulfadoxine-pyrimethamine. We assessed the evolutionary origin of the resistance by analysing polymorphic microsatellite repeats in the flanking region of the dhfr and dhps genes, which show whether resistance alleles originated through shared or independent ancestral mutation events. We then assessed the current extent of dispersal of dhfr and dhps resistance alleles by doing the same analysis in P falciparum sampled from communities in the Kilimanjaro region of northern Tanzania in 2001. FINDINGS: The large genetic change during 1995-99 in KwaZulu-Natal, South Africa, in both the health facility and the wider community surveys, was at the dhps locus, apparently because resistance at dhfr was established before 1995. The allelic determinants of resistance in this province share a common evolutionary origin with those found in Kilimanjaro, Tanzania, even though the two sites are 4000 km apart. INTERPRETATION: Three resistant dhfr alleles, and one resistant dhps allele, each derived from independent ancestral lineages, have been driven through through southeast Africa. The movement by the dhfr alleles (pyrimethamine resistance) preceded that of the dhps allele (sulfadoxine resistance). Our findings emphasise that gene flow rather than new mutations has been the most common originator of resistance in African countries

Therapeutic efficacy of sulfadoxine-pyrimethamine in uncomplicated Plasmodium falciparum malaria 3 years after introduction in Mpumalanga

Objectives. To assess therapeutic efficacy of sulfadoxineyrimethamine (SP) in treatment of uncomplicated Plasmodium falciparum malaria 3 years after introduction in Mpumalanga, South Africa.Se'tting. Tonga district with a population of 116 418 and subject to seasonal malaria, with an average annual incidence ; 3 200 cases.Subjects. One hundred and nineteen malaria patients presenting to a sentinel surveillance clinic and recruited according to World Health Organisation (WHO) criteria.Methodology. Patients satisfying WHO inclusion criteria were defeated with a single oral dose of SP and the response of infection to treatment in each patient was routinely monitored clinically and parasitologically on days 1, 2, 3, 7, 11, 21, 28 and 42 post-treatment. One hundred and ten patients completed follow-up to day 42 or evidence of clinical or parasitological failure.Results. The cure rate at day 42 was 93.6% (103/110). Two patients (1.8%, RII) were early treatment failures on day 3, while recrudescence (4.5%, RI) occurred in 5 patients on day 28 (N = 3) and on day 42 (N = 2).Conclusion. In Mpumalanga P. falciparum remains sensitive to SF, with no significant difference between the baseline cure rate (94.5%) and the cure rate in the present study (93.6%)

Therapeutic efficacy of sulfadoxine-pyrimethamine in uncomplicated Plasmodium falciparum malaria 3 years after introduction in Mpumalanga

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Exit Strategies

In a world of increasing capital mobility and broadening and more diversified trade, many (but not all) developing and transition economies are likely to find it desirable to move from relatively fixed exchange rate regimes to regimes of greater exchange rate flexibility. This paper suggests why, and considers strategies that countries may consider for such a move. It reinforces this discussion with a review of experience from teh past two decades with alternative exchange rate regimes. The paper also identifies policies that can facilitate the transition to greater exchange rate flexibility for countries that wish to pursue this option.

Scatter Plot of Individual Patient Gametocyte Densities

<p>The gametocyte densities (per microlitre) are given over time following treatment with SP (2000) and AL (2002).</p

Map of Umkhanyakude District, Northern KwaZulu–Natal, South Africa

<p>The map indicates the following: the malaria risk by section and the four sentinel facilities for malaria morbidity and mortality review (Ndumo clinic, and Mosvold, Manguzi, and Bethesda rural district hospitals); the communities selected for the household (HH) survey and FGDs; and the Manguzi district hospital where sentinel safety surveillance and Ndumo Clinic where the SP (2000) and AL (2002) in vivo therapeutic efficacy studies were conducted.</p