Poor quality vital anti-malarials in Africa - an urgent neglected public health priority

Abstract

Background: Plasmodium falciparum malaria remains a major public health problem. A vital component of malaria control rests on the availability of good quality artemisinin-derivative based combination therapy (ACT) at the correct dose. However, there are increasing reports of poor quality anti-malarials in Africa.

Methods: Seven collections of artemisinin derivative monotherapies, ACT and halofantrine anti-malarials of suspicious quality were collected in 2002/10 in eleven African countries and in Asia en route to Africa. Packaging, chemical composition (high performance liquid chromatography, direct ionization mass spectrometry, X-ray diffractometry, stable isotope analysis) and botanical investigations were performed.

Results: Counterfeit artesunate containing chloroquine, counterfeit dihydroartemisinin (DHA) containing paracetamol (acetaminophen), counterfeit DHA-piperaquine containing sildenafil, counterfeit artemether-lumefantrine containing pyrimethamine, counterfeit halofantrine containing artemisinin, and substandard/counterfeit or degraded artesunate and artesunate+amodiaquine in eight countries are described. Pollen analysis was consistent with manufacture of counterfeits in eastern Asia. These data do not allow estimation of the frequency of poor quality anti-malarials in Africa.

Conclusions: Criminals are producing diverse harmful anti-malarial counterfeits with important public health consequences. The presence of artesunate monotherapy, substandard and/or degraded and counterfeit medicines containing sub-therapeutic amounts of unexpected anti-malarials will engender drug resistance. With the threatening spread of artemisinin resistance to Africa, much greater investment is required to ensure the quality of ACTs and removal of artemisinin monotherapies. The International Health Regulations may need to be invoked to counter these serious public health problems.

Figure 1

Map of Africa with reports of poor quality artemisinin derivatives and ACT to October 2011. Red = counterfeit, blue = substandard, black = poor quality (ie uncertain whether substandard or counterfeit).

Figure 2

Frequency of reports of poor quality anti-malarials in Africa per year 1988-2010, for all anti-malarials (black), non-artemisinin derivatives (blue) and artemisinin derivative montherapies and ACTs (red). Each poor quality medicine type (by API or brand name per country per report) included. Reports of more than one poor quality medicine of the same brand name/API/formulation per paper classed as one report. The fall in frequency in 2010 is probably an artifact of investigations-up to October 2011 there have already been 64 reports of poor quality anti-malarial types in Africa. See Additional file 1.

Figure 3

Genuine artesunate 'Mekophar Chemical Pharmaceutical Joint-Stock Company' packet (Mek 10/03).

Figure 4

Counterfeit artesunate packet labelled as made by 'Mekophar Chemical Pharmaceutical Joint-Stock Company' (Cam S5/07). Counterfeit hologram in red circle.

Figure 5

Genuine artesunate with 'Mekophar Chemical Pharmaceutical Joint-Stock Company' and 'Neros' packet hologram (Mek 10/03).

Figure 6

Counterfeit hologram on packet labelled as made by 'Mekophar Chemical Pharmaceutical Joint-Stock Company' (Cam S5/07).

Figure 7

Counterfeit artesunate packet labelled as made by 'AT17'. (DRC 07/01).

Figure 8

Genuine dihydroartemisinin (DHA) made by 'Jiaxing Nanhu Pharmaceutical Co. Ltd.' packet (Ken 07/01).

Figure 9

Counterfeit DHA packet labelled as made by 'Jiaxing Nanhu Pharmaceutical Co. Ltd.' (Ken 07/02). Different shades of green, e.g. in red circle, from Ken 07/01.

Figure 10

Genuine halofantrine Halfan GlaxoSmithKline hologram.

Figure 11

Counterfeit 'Halfan 'hologram labelled as made by 'GSK' (4040 & 4023). GSK = GlaxoSmithKline.

Figure 12

Counterfeit 'Halfan' hologram labelled as made by 'SB' (4024). SB = SmithKline Beecham.

Figure 13

Counterfeit 'Halfan' hologram labeled as made by 'GSK' (5070, 5312). GSK = GlaxoSmithKline.

Figure 14

Genuine 'Duo-Cotecxin' dihydroartemisinin-piperaquine packet made by 'Zheijiang Holley Nanhu Pharmaceutical Group Ltd Under license of Holleypharm' (China 07/14). Genuine hologram in red circle.

Figure 15

Counterfeit dihydroartemisinin-piperaquine labeled as 'Duo-Cotecxin' made by 'Jiaxing Nanhu Pharmaceutical Group Ltd Under license of Holleypharm' (China 07/18). 'Franglais' in red circle.

Figure 16

Genuine artemether-lumefantrine 'Coartem' made by 'Beijing Novartis Pharma Ltd, Beijing, China for Novartis Pharma AG, Basle, Switzerland' (Ken 06/01).

Figure 17

Counterfeit 'Coartem' labelled as made by 'Beijing Novartis Pharma Ltd, Beijing, China for Novartis Pharma AG, Basle, Switzerland' (Gh 09/01). Differences from genuine sample (Figure 16) in red circles.

Figure 18

Counterfeit 'Coartem' labelled as made by 'Beijing Novartis Pharma Ltd, Beijing, China for Novartis Pharma AG, Basle, Switzerland' (Gh 09/02). Differences from genuine sample (Figure 16) in red circles.