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Table 3 Characteristics of malaria publications from Malawi between 1994 and 2007

From: Malaria research and its influence on anti-malarial drug policy in Malawi: a case study

No.

Publication

Drug(s) under study

Study objective and type

Study population

Protocol used for assessment

Approach/methods

Outcome measured

Results found

Conclusion

1

Nwanyanwu et al. [14]; year of study, 1994

SP

To determine the level of SP efficacy amid numerous anecdotal reports of widespread parasite resistance to SP

145 children under five attending the outpatient clinics

28-day follow-up modified WHO in vivo test (1973)

Half a tablet of SP and half tablet of paracetamol for 3 days

Parasite density

97.9% exhibited parasitological resistance/sensitive pattern, 98.6% had parasite clearance by day 7

These data showed that after 1 year of widespread use of SP in Malawi, P. falciparum parasite resistance remained very low contradicting reports of widespread parasite resistance to SP

2

Verhoeff et al. [27]; year of study, 1995

SP

To determine the parasitological and haematological response to SP after being adopted as the first-line drug for treating uncomplicated malaria

84 children under five attending the outpatient clinic with uncomplicated malaria infection

28-day follow-up modified WHO in vivo test (1994)

SP was given according to guidelines of half a tablet to children under 4 years and one tablet to those over 4 years

Parasitological success rate clearance rate and the haematological recovery

90.5% parasitological success rate, while the haematological recovery was not significantly different for parasitological successes or failures

These results showed that, 2 years after the introduction of SP in Malawi for the treatment of uncomplicated P. falciparum malaria, the drug combination remained effective in 90.5% of cases

3

Nwanyanwu et al. [28]; study period, 1997–1998

SP

To assess the efficacy of SP 5 years after its widespread use as the first-line drug for uncomplicated malaria

641 children under five attending outpatient clinics in selected hospitals were studied

WHO (1996) 28-day modified in vivo test

Children were treated with the standard malaria treatment guidelines and follow-up examination on days 3, 7 and 14

Parasitological and clinical response

Parasitological resistance (RII and RIII) ranged from 7% to 19%, with one clinic reaching 36%); 0.9% of the patients met the WHO clinical failure by day 7

It was found that, after more than 5 years of widespread use of SP in Malawi, its efficacy remained acceptable for treatment of uncomplicated malaria, and it was therefore, recommended to be retained as first-line treatment

4

Takechi et al. [29]; year of study, 1998

SP, CQ, MF, QN, and HF

To assess the status of antimalarial drug resistance in Malawi

60 children under five attending the outpatient clinic, while in in vitro study, 29 isolates of P. falciparum were tested for SP, 29 for CQ, 31 for QN, 29 for HF, and 26 for MF

For in vivo study, WHO (1973) protocol for parasitological follow-up was done at days 3, 7, and 14 after treatment, while an in vitro micro test kit was used to assess susceptibility of P. falciparum to the drugs

In vivo efficacy study for SP and in vitro sensitivity study for SP, CQ, MF, QN and HF

Parasite clearance for the in vivo study, inhibition of schizont maturation for in vitro study

In vivo test showed 83.1% RI/S resistance, while in vitro, 62.1% isolates showed resistance to SP, 3.4% in CQ, 3.2% in MF, 5.7% in QN and 5.9% in HF

The results suggested possible recovery of CQ sensitivity after long-term absence of drug pressure, although resistance remained a major problem in malaria control, while in vitro monitoring provides early warning signs of drug efficacy loss, and may detect changing patterns in alternative drug resistance

5

MacArthur et al. [16]; year of study, 1998

SP and MF

A randomised trial to compare the efficacy of SP and MF, a potential successor amid reports of P. falciparum resistance to SP

102 children under five attending the outpatient clinic qualified for the study

A modified 14-day WHO (1996) in vivo protocol

40 children were randomized to receive SP 25 mg/kg, and 54 received MF 15 mg/kg

Parasitological response, clinical failure and haematological response

20% combined RII/RIII parasitological failure in SP and 22% in MF; 81.4% had Adequate Clinical Response in SP group and 89.8% in MF group; haemoglobin increase of 1.82 ± 2.29 g/dL in SP and 1.64 ± 1.67 g/dL in MF (P = 0.70)

With the decreasing efficacy of SP as the first-line antimalarial drug and the high failure rates of MQ at the tested lower dosage, Malawi should consider assessing the efficacy and feasibility of alternative drugs for treatment of uncomplicated malaria

6

Sulo et al. [30]; study period, 1997–1999

Lapdap and SP

A randomized clinical trial to assess whether Lapdap results in higher retreatment rate for malaria than SP

500 children under five with uncomplicated malaria at the outpatient clinic

WHO (1996) protocol follow-up on days 7 and 28 and thereafter active follow-up was every 28 days with the aim to complete 12 months of follow-up

A group of 222 given Lapdap, another group of 224 given SP

Annual malaria incidence and treatment failure

Mean annual malaria incidence was 2.2 in the Lapdap group and 2.8 in the SP group; 5.4% treatment failure in Lapdap group and 20.5% in the SP group

Despite the rapid elimination of Lapdap, children treated with Lapdap did not have a higher incidence of malaria episodes than those treated with SP; treatment failure was more common with SP

7

Plowe et al. [32]; period of efficacy monitoring, 1998–2002

SP

A prospective open label drug-efficacy study to measure the efficacy of SP in treating falciparum malaria from 1998 to 2002

1377 patients aged 3 months or over presenting at a health centre with uncomplicated malaria

The standard 14 days and 28 days of follow-up

Standard treatment SP doses

Therapeutic efficacy and parasitological resistance

80% of adequate clinical response rate throughout the 5 years and significant decrease in RI parasitological response

Contrary to expectations, SP retained good efficacy after 10 years of use in Malawi and other countries can benefit from interim use of SP while awaiting implementation of combination antimalarial treatments

8

Msyamboza et al. [33]; study period, 2004–2005

SP

To determine the rate of parasitological failure after SP treatment in pregnant women

74 pregnant women presenting with uncomplicated malaria at the clinic

WHO (2002) in vivo protocol

The standard treatment dose was used and a follow-up at days 3, 7 and 14

Parasitological failure

11% parasitological failure

The prevalence of anaemia was high at first antenatal visit and the rate of parasitological failure had increased from 5% in 1996 to 11% in 2004; but the low prevalence of malaria in the population could indirectly indicate acceptable SP drug sensitivity

  1. CQ, chloroquine; HF, halofantrine; QN, quinine; Lapdap, Chlorproguanil-dapsone; MF, mefloquine; SP, sulfadoxine-pyrimethamine