Background
Conceptual framework
Methods
Systematic review
Selection criteria
Analysis approach
Document review
Key informant interviews
KI | Sex | Current position | Experience | Role during policy change |
---|---|---|---|---|
1 | Male | Child health and development specialist | 9 years current position | Researcher |
2 | Male | Pharmacologist, College of Medicine (COM) | Over 10 years in malaria research | Researcher |
3 | Male | Medical epidemiologist – Director of Malaria Alert Center (MAC), COM | 10 years current position | Researcher and advisor |
4 | Male | Senior Scientist, Malawi-Liverpool-Wellcome Trust Clinical Research Programme | More than 40 years in paediatric malaria research | Researcher and advisor |
5 | Female | Retired Paediatrician and Director of MAC, COM | More than 30 years in clinical and malaria research | Researcher and advisor |
6 | Male | Paediatrician, Ministry of Health | More than 30 years in clinical and malaria research | Researcher and advisor |
7 | Male | Paediatrician, Ministry of Health | More than 40 years in clinical and malaria research | Researcher and advisor |
8 | Male | Clinical Trialist | 6 years in current position | Researcher |
9 | Male | Entomologist, MAC, College of Medicine | Over 10 years current position | Researcher |
10 | Male | Medical epidemiologist, College of Medicine | More than 15 years in maternal and child health | Researcher |
11 | Male | Chief of Health Services – Ministry of Health | More than 10 years in clinical and malaria research | Researcher and policymaker |
12 | Female | Director of the National Malaria Control Programme, Ministry of Health | 5 years current position | Policymaker |
Ethics and consent approval
Themes covered in the in-depth interviews
Data management and analysis
Results
Systematic review
Publications between 1984 and 1993
No. | Publication | Drug(s) under study | Study objective and type | Study population | Protocol used for assessment | Approach | Outcome measured | Results found | Conclusion |
---|---|---|---|---|---|---|---|---|---|
1 | Khoromana et al. [23]; year of study, 1984 | CQ | To assess the appropriate CQ dosage to be used in the Combating Childhood Communicable Diseases program in Malawi | 224 children under five presenting at the six outpatient facilities | Modified WHO 7-day in vivo test (1984) | Two CQ dosages of 10 mg/kg and 25 mg/kg were administered | Parasite reduction and clinical response | 84% of children given the 10 mg/kg dosage had detectable parasites on day 7, while 57% of 25 mg/kg dosage had a detectable parasite density | Considering the study results and the higher cost and limited availability of alternative therapies, CQ 25 mg/kg therapy was adopted as the primary therapy for malaria |
2 | Heymann et al. [24]; year of study, 1985 | CQ, AQ, SP or Fansidar | To test alternative drugs in children under five | Children under five (39 receiving CQ, 39 at 10 mg/kg AQ, 36 at 25 mg/kg AQ, and 34 at 25 mg/kg SP) | WHO (1984) modified 7-day in vivo test and 21-day follow-up for recrudescence | A comparative trial of AQ in doses of 10 and 25 mg/kg, SP at 25 mg/kg, and CQ at 25 mg/kg | Parasite clearance by day 7; recrudescence at day 21 for AQ 25 mg/kg and SP 25 mg/kg | Parasite clearance of 59% in 25 mg/kg CQ dose, 90% in 10 mg/kg AQ dosage, 97% in 25 mg/kg AQ dosage, and 100% clearance in 25 mg/kg dosage; 34% of recrudescence in the 25 mg/kg AQ group and no recrudescence in the SP group (the results were significant; P = 0.01) | The results suggested that, in Malawi, AQ and SP are superior to CQ in producing prompt parasite clearance among young children, and that SP alone is superior to the 4-aminoquinolines in sustaining P. falciparum clearance |
3 | Heymann et al. [26]; year of study, 1988 | CQ | Experimental study to evaluate the protective efficacy of CQ on P. falciparum
| 334 pregnant women in four antenatal clinics |
P. falciparum infection rates were measured before and after a 4-week period of CQ prophylaxis |
P. falciparum parasites in thick smear | 48% had P. falciparum infection before prophylaxis and 37% had the infection after prophylaxis, making the protective efficacy of CQ at 23% | Research needs to be further conducted to define more cost-effective interventions, including more effective drugs, and health education programmes to improve compliance among pregnant women | |
4 | Bloland et al. [25]; year of study, 1990 | CQ and SP | Evaluation of drug efficacy for both short-term parasitological and clinical response to therapy and the long-term implications of the persistent parasitemia | 153 children under five attending the outpatient department | Modified WHO in vivo test (1973) | 28-days follow-up period on two groups; 124 given CQ and 37 SP | Parasitological resistance | 82.3% on parasitological resistance occurred in the CQ group, while 70% in SP group exhibited a parasitological response | Children treated with SP maintained clinical improvement and improved haemoglobin concentration during the follow-up period than those treated with CQ; therefore, CQ was no longer considered as an adequately effective therapy of clinical treatment of malaria in very young children |
Publications between 1994 and 2007
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 |
Document review
The change from CQ to SP
Sentinel surveillance report for the change of SP to LA
Policy and guideline documents
Findings from the key informant interviews
Availability of evidence for justification of policy changes
“In the mid-1980s, around 1985, clinicians across the country started observing that people treated with chloroquine were coming back complaining that they do not feel better”.
Timing of policy changes
“It was timely, the evidence was clear that chloroquine wasn’t working at the time, I’m a child specialist so I actually see the effects or the complications, if the drug is not working, the children do not get well, some even die against severe forms of malaria, so seeing that we decided to make a change, it was quite obvious we needed the change”.
“And then of course there a was also need for the research to be done to back up the actual change and again for Malawi that change came about because of drug efficacy studies that were carried out over the years which then meant that it was easy for the policy makers to certainly say hey its indeed high time to change because this drug is obviously not working”.
Challenges during policy changes
“The first challenge was the fact that there was no buy-in from WHO.... so WHO was saying who is going to pay if we are not supporting it…who is going to pay for this?”
“That then prompted government to consult Center for Disease Control to help out with investigations on what was happening, why are several patients treated coming back complaining of the same signs and symptoms?”
“Well at this stage from SP to LA they were following the WHO recommendations so I suppose people didn’t worry too much about it, you know, getting track with what actually was happening but with the earlier period when we had to change from chloroquine to SP this was new but the advantage we had was that we had locally generated data that could not be refuted”.