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Review
. 2014 Feb 7:13:51.
doi: 10.1186/1475-2875-13-51.

Mass primaquine treatment to eliminate vivax malaria: lessons from the past

Anatoly Kondrashin, Alla M Baranova, Elizabeth A Ashley, Judith Recht, Nicholas J White  1 , Vladimir P Sergiev
Affiliations
Review

Mass primaquine treatment to eliminate vivax malaria: lessons from the past

Anatoly Kondrashin et al. Malar J. .

Abstract

Recent successes in malaria control have put malaria eradication back on the public health agenda. A significant obstacle to malaria elimination in Asia is the large burden of Plasmodium vivax, which is more difficult to eliminate than Plasmodium falciparum. Persistent P. vivax liver stages can be eliminated only by radical treatment with a ≥ seven-day course of an 8-aminoquinoline, with the attendant risk of acute haemolytic anaemia in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Primaquine is the only generally available 8-aminoquinoline. Testing for G6PD deficiency is not widely available, and so whilst it is widely recommended, primaquine is often not prescribed. In the past, some countries aiming for vivax malaria eradication deployed mass treatments with primaquine on a massive scale, without G6PD testing. In Azerbaijan, Tajikistan (formerly USSR), North Afghanistan and DPR Korea 8,270,185 people received either a 14-day "standard" or a 17-day "interrupted" primaquine treatment to control post-eradication malaria epidemics. These mass primaquine preventive treatment campaigns were conducted by dedicated teams who administered the drugs under supervision and then monitored the population for adverse events. Despite estimated G6PD prevalences up to 38.7%, the reported frequency of severe adverse events related to primaquine was very low. This experience shows that with careful planning and implementation of mass treatment strategies using primaquine and adequate medical support to manage haemolytic toxicity, it is possible to achieve high population coverage, substantially reduce malaria transmission, and manage the risk of severe acute haemolytic anaemia in communities with a relatively high prevalence of G6PD deficiency safely.

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Figures

Figure 1
Figure 1
MPPT sites. The four countries (two were formerly Soviet republics) where MPPTs were conducted: Azerbaijan, Afghanistan, Tajikistan and DPR (North) Korea.
Figure 2
Figure 2
Prevalence of G6PD deficiency in Azerbaijan in 1971-72. Prevalence (%) of G6PD deficiency is shown for populations in the seven indicated districts: the first four were located in plains, one was in the foothills, and the remaining two in the highlands. In each district, proportions for urban areas are shown by red bars (u) and for rural areas by green bars (r). The number of people examined for G6PD deficiency ranged from 137-732 for urban areas, and 55-313 for rural areas.
Figure 3
Figure 3
Prevalence of G6PD deficiency by age in Azerbaijan in 1971-72. Prevalence (%) of G6PD deficiency is shown for the different age groups. For each group, a total of between 909 and 3,083 people were tested by the Berstein method.
Figure 4
Figure 4
Epidemiological assessment of efficacy of MPPT in Azerbaijan in 1970-1975. Malaria cases as assessed by slide positivity rates (P. vivax detection from total slides examined, %) is shown for each year from 1970-75. The total number of slides examined was over one million annually, varying between 1,026,834 and 1,212,864.
Figure 5
Figure 5
Results of the MPPT in Azerbaijan in 1980-86. MPPT was given to between 23,541 and 75,664 people annually between 1980 and 1986 resulting in a substantial reduction in the total number of malaria cases.
Figure 6
Figure 6
Prevalence of G6PD deficiency in indigenous ethnic groups in North Afghanistan. Between 50 and 175 people in each village (province indicated in parentheses) were tested for G6PD deficiency, the resulting prevalences (%) are shown. Results for Gavarchin, Bulla-Kuchi, Karok and Saidabad are from [24], and for Kunduz, Gumbat, Kulduman and Zardkomar from [25]. Villages are shown grouped by ethnicity: Pashtuns, Uzbeks, Tajiks, Chazars and Turkmen.
Figure 7
Figure 7
MPPT in Tajikistan in 2000. Reduction of malaria cases in two districts where MPPT was implemented is shown; 39,590 people were treated in Bachtar and 5,569 in Kofarnichon.
Figure 8
Figure 8
Comparing vivax malaria (cases) among the treated and untreated populations, 2002-2003; DPR Korea. From a total of 328,679 MPPT-treated people and 421,875 who were untreated, total cases of malaria and percentages are shown.
Figure 9
Figure 9
Slide positivity rates (%) in the treated and untreated population, 2002. DPR Korea. Slide positive rates (%) are shown for treated (N = 5,138) and untreated (N = 4,215) populations in May and September 2002.
Figure 10
Figure 10
MPPT impact in 2000-2006. DPR Korea. Total number of malaria cases are shown for the years 2000-2006 (black line, left Y axis) and malaria morbidity in the capital Pyonyang per 1,000 (redline, right Y axis).
Figure 11
Figure 11
Prevalence of side effects during MPPT in 2002. DPR Korea. Prevalence (%) reported for MPPT in 2002 is indicated for each side effect. There was a total of 4,291 headache cases, 2,451 epigastric pain, 1,801 nausea and vomiting, 1,753 dizziness, 1,702 anorexia, 254 change in urine colour (1.9%), and 15 black urine (0.1%).
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