Effect of artemether-lumefantrine policy and improved vector control on malaria burden in KwaZulu-Natal, South Africa

Abstract

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.

Figure 1. Number of Notified Malaria Cases in KwaZulu–Natal by Month (January 1993–December 2003)

The number of cases is given in relation to season (peak transmission from January to May, inclusive) and timing of significant malaria control interventions: A indicates reintroduction of DDT for IRS of traditional structures in KwaZulu–Natal in March 2000; B indicates introduction of IRS in southern Mozambique in October 2000; and C indicates implementation of AL as first-line treatment of uncomplicated falciparum malaria in KwaZulu–Natal in January 2001.

Figure 2. Map of Umkhanyakude District, Northern KwaZulu–Natal, South Africa

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.

Figure 3. Kaplan-Meier Survival Analysis of Time to Clinical or Parasitological Failure

Following treatment with SP in 2000 (n = 98) and artemether-lumefantrine in 2001 (n = 100), the proportion of patients with an adequate clinical and parasitological response to treatment at each day of follow up is shown.

Figure 4. Scatter Plot of Individual Patient Gametocyte Densities

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