Malaria Journal - Most accessed articles

Malaria resurgence: a systematic review and assessment of its causes

Justin Cohen — 2012-04-24T00:00:00Z

Background: Considerable declines in malaria have accompanied increased funding for control since the year 2000, but historical failures to maintain gains against the disease underscore the fragility of these successes. Although malaria transmission can be suppressed by effective control measures, in the absence of active intervention malaria will return to an intrinsic equilibrium determined by factors related to ecology, efficiency of mosquito vectors, and socioeconomic characteristics. Understanding where and why resurgence has occurred historically can help current and future malaria control programmes avoid the mistakes of the past. Methods: A systematic review of the literature was conducted to identify historical malaria resurgence events. All suggested causes of these events were categorized according to whether they were related to weakened malaria control programmes, increased potential for malaria transmission, or technical obstacles like resistance. Results: The review identified 75 resurgence events in 61 countries, occurring from the 1930s through the 2000s. Almost all resurgence events (68/75 = 91%) were attributed at least in part to the weakening of malaria control programmes for a variety of reasons, of which resource constraints were the most common (39/68 = 57%). Over half of the events (44/75 = 59%) were attributed in part to increases in the intrinsic potential for malaria transmission, while only 24/75 (32%) were attributed to vector or drug resistance. Conclusions: Given that most malaria resurgences have been linked to weakening of control programmes, there is an urgent need to develop practical solutions to the financial and operational threats to effectively sustaining today's successful malaria control programmes.

Artemether resistance in vitro is linked to mutations in PfATP6 that also interact with mutations in PfMDR1 in travellers returning with Plasmodium falciparum infections

Dylan Pillai — 2012-04-27T00:00:00Z

Background: Monitoring resistance phenotypes for Plasmodium falciparum, using in vitro growth assays, and relating findings to parasite genotype has proved particularly challenging for the study of resistance to artemisinins. Methods: Plasmodium falciparum isolates cultured from 28 returning travellers diagnosed with malaria were assessed for sensitivity to artemisinin, artemether, dihydroartemisinin and artesunate and findings related to mutations in pfatp6 and pfmdr1. Results: Resistance to artemether in vitro was significantly associated with a pfatp6 haplotype encoding two amino acid substitutions (pfatp6 A623E and S769N; (mean IC50 (95% CI) values of 8.2 (5.7 - 10.7) for A623/S769 versus 623E/769 N 13.5 (9.8 - 17.3) nM with a mean increase of 65%; p = 0.012). Increased copy number of pfmdr1 was not itself associated with increased IC50 values for artemether, but when interactions between the pfatp6 haplotype and increased copy number of pfmdr1 were examined together, a highly significant association was noted with IC50 values for artemether (mean IC50 (95% CI) values of 8.7 (5.9 - 11.6) versus 16.3 (10.7 - 21.8) nM with a mean increase of 87%; p = 0.0068). Previously described SNPs in pfmdr1 are also associated with differences in sensitivity to some artemisinins. Conclusions: These findings were further explored in molecular modelling experiments that suggest mutations in pfatp6 are unlikely to affect differential binding of artemisinins at their proposed site, whereas there may be differences in such binding associated with mutations in pfmdr1. Implications for a hypothesis that artemisinin resistance may be exacerbated by interactions between PfATP6 and PfMDR1 and for epidemiological studies to monitor emerging resistance are discussed.

Is the current decline in malaria burden in sub-Saharan Africa due to a decrease in vector population?

Dan Meyrowitsch — 2011-07-13T00:00:00Z

Background: In sub-Saharan Africa (SSA), malaria caused by Plasmodium falciparum has historically been a major contributor to morbidity and mortality. Recent reports indicate a pronounced decline in infection and disease rates which are commonly ascribed to large-scale bed net programmes and improved case management. However, the decline has also occurred in areas with limited or no intervention. The present study assessed temporal changes in Anopheline populations in two highly malaria-endemic communities of NE Tanzania during the period 1998-2009. Methods: Between 1998 and 2001 (1st period) and between 2003 and 2009 (2nd period), mosquitoes were collected weekly in 50 households using CDC light traps. Data on rainfall were obtained from the nearby climate station and were used to analyze the association between monthly rainfall and malaria mosquito populations. Results: The average number of Anopheles gambiae and Anopheles funestus per trap decreased by 76.8% and 55.3%, respectively over the 1st period, and by 99.7% and 99.8% over the 2nd period. During the last year of sampling (2009), the use of 2368 traps produced a total of only 14 Anopheline mosquitoes. With the exception of the decline in An. gambiae during the 1st period, the results did not reveal any statistical association between mean trend in monthly rainfall and declining malaria vector populations. Conclusion: A longitudinal decline in the density of malaria mosquito vectors was seen during both study periods despite the absence of organized vector control. Part of the decline could be associated with changes in the pattern of monthly rainfall, but other factors may also contribute to the dramatic downward trend. A similar decline in malaria vector densities could contribute to the decrease in levels of malaria infection reported from many parts of SSA.

Inaugural meeting of the malaria policy advisory committee to the WHO: conclusions and recommendations

Robert Newman — 2012-04-30T00:00:00Z

The Malaria Policy Advisory Committee to the World Health Organization met for the firsttime from 31 January to 2 February 2012 in Geneva, Switzerland. This article provides asummary of the discussions, conclusions and recommendations from that meeting, as part ofthe newly launched Malaria Journal thematic series "WHO Malaria Policy AdvisoryCommittee: Reports and Recommendations".Summaries are provided, referencing the relevant background documents, for the meetingsessions on global malaria control, drug resistance and containment, rapid diagnostic testprocurement criteria, larviciding, classification of countries for elimination, estimatingmalaria cases and deaths, and seasonal malaria chemoprevention. Policy statements, positionstatements, and guidelines that will arise from the MPAC meeting conclusions andrecommendations will be formally issued and disseminated to World Health Organizationmember states by the World Health Organization Global Malaria Programme.

Estimates of child deaths prevented from malaria prevention scale-up in Africa 2001-2010

Thomas Eisele — 2012-03-28T00:00:00Z

Background: Funding from external agencies for malaria control in Africa has increased dramatically over the past decade resulting in substantial increases in population coverage by effective malaria prevention interventions. This unprecedented effort to scale-up malaria interventions is likely improving child survival and will likely contribute to meeting Millennium Development Goal (MDG) 4 to reduce the < 5 mortality rate by two thirds between 1990 and 2015. Methods: The Lives Saved Tool (LiST) model was used to quantify the likely impact that malaria prevention intervention scale-up has had on malaria mortality over the past decade (2001-2010) across 43 malaria endemic countries in sub-Saharan African. The likely impact of ITNs and malaria prevention interventions in pregnancy (intermittent preventive treatment [IPTp] and ITNs used during pregnancy) over this period was assessed. Results: The LiST model conservatively estimates that malaria prevention intervention scale-up over the past decade has prevented 842,800 (uncertainty: 562,800-1,364,645) child deaths due to malaria across 43 malaria-endemic countries in Africa, compared to a baseline of the year 2000. Over the entire decade, this represents an 8.2% decrease in the number of malaria-caused child deaths that would have occurred over this period had malaria prevention coverage remained unchanged since 2000. The biggest impact occurred in 2010 with a 24.4% decrease in malaria-caused child deaths compared to what would have happened had malaria prevention interventions not been scaled-up beyond 2000 coverage levels. ITNs accounted for 99% of the lives saved. Conclusions: The results suggest that funding for malaria prevention in Africa over the past decade has had a substantial impact on decreasing child deaths due to malaria. Rapidly achieving and then maintaining universal coverage of these interventions should be an urgent priority for malaria control programmes in the future. Successful scale-up in many African countries will likely contribute substantially to meeting MDG 4, as well as succeed in meeting MDG 6 (Target 1) to halt and reverse malaria incidence by 2015.

The anaemia of Plasmodium vivax malaria

Nicholas Douglas — 2012-04-27T00:00:00Z

Plasmodium vivax threatens nearly half the world's population and is a significantimpediment to achievement of the millennium development goals. It is an important, butincompletely understood, cause of anaemia. This review synthesizes current evidence on theepidemiology, pathogenesis, treatment and consequences of vivax-associated anaemia.Young children are at high risk of clinically significant and potentially severe vivaxassociatedanaemia, particularly in countries where transmission is intense and relapses arefrequent. Despite reaching lower densities than Plasmodium falciparum, Plasmodium vivaxcauses similar absolute reduction in red blood cell mass because it results in proportionatelygreater removal of uninfected red blood cells. Severe vivax anaemia is associated withsubstantial indirect mortality and morbidity through impaired resilience to co-morbidities,obstetric complications and requirement for blood transfusion. Anaemia can be averted byearly and effective anti-malarial treatment.

Performance of a malaria microscopy image analysis slide reading device

William Prescott — 2012-05-06T00:00:00Z

Background: Viewing Plasmodium in Romanovsky-stained blood has long been considered the gold standard for diagnosis and a cornerstone in management of the disease. This method however, requires a subjective evaluation by trained, experienced diagnosticians and establishing proficiency of diagnosis is fraught with many challenges. Reported here is an evaluation of a diagnostic system (a "device" consisting of a microscope, a scanner, and a computer algorithm) that evaluates scanned images of standard Giemsa-stained slides and reports species and parasitaemia. Methods: The device was challenged with two independent tests: a 55 slide, expert slide reading test the composition of which has been published by the World Health Organization ("WHO55" test), and a second test in which slides were made from a sample of consenting subjects participating in a malaria incidence survey conducted in Equatorial Guinea (EGMIS test). These subjects' blood was tested by malaria RDT as well as having the blood smear diagnosis unequivocally determined by a worldwide panel of a minimum of six reference microscopists. Only slides with unequivocal microscopic diagnoses were used for the device challenge, n=119. Results: On the WHO55 test, the device scored a "Level 4" using the WHO published grading scheme. Broken down by more traditional analysis parameters this result was translated to 89% and 70% sensitivity and specificity, respectively. Species were correctly identified in 61% of the slides and the quantification of parasites fell within acceptable range of the validated parasitaemia in 10% of the cases. On the EGMIS test it scored 100% and 94% sensitivity/specificity, with 64% of the species correct and 45% of the parasitaemia within an acceptable range. A pooled analysis of the 174 slides used for both tests resulted in an overall 92% sensitivity and 90% specificity with 61% species and 19% quantifications correct. Conclusions: In its current manifestation, the device performs at a level comparable to that of many human slide readers. Because its use requires minimal additional equipment and it uses standard stained slides as starting material, its widespread adoption may eliminate the current uncertainty about the quality of microscopic diagnoses worldwide.

Artemisinin-based combination therapy does not measurably reduce human infectiousness to vectors in a setting of intense malaria transmission

Bernadette Huho — 2012-04-18T00:00:00Z

Background: Artemisinin-based combination therapy (ACT) for treating malaria has activity againstimmature gametocytes. In theory, this property may complement the effect of terminatingotherwise lengthy malaria infections and reducing the parasite reservoir in the humanpopulation that can infect vector mosquitoes. However, this has never been verified at apopulation level in a setting with intense transmission, where chronically infectiousasymptomatic carriers are common and cured patients are rapidly and repeatedly re-infected. Methods: From 2001 to 2004, malaria vector densities were monitored using light traps in threeTanzanian districts. Mosquitoes were dissected to determine parous and oocyst rates.Plasmodium falciparum sporozoite rates were determined by ELISA. Sulphadoxinepyrimethamine(SP) monotherapy was used for treatment of uncomplicated malaria in thecontiguous districts of Kilombero and Ulanga throughout this period. In Rufiji district, thestandard drug was changed to artesunate co-administered with SP (AS + SP) in March 2003.The effects of this change in case management on malaria parasite infection in the vectorswere analysed. Results: Plasmodium falciparum entomological inoculation rates exceeded 300 infective bites perperson per year at both sites over the whole period. The introduction of AS + SP in Rufiji wasassociated with increased oocyst prevalence (OR [95%CI] = 3.9 [2.9-5.3], p < 0.001), but hadno consistent effect on sporozoite prevalence (OR [95%CI] = 0.9 [0.7-1.2], p = 0.5). Theestimated infectiousness of the human population in Rufiji was very low prior to the changein drug policy. Emergence rates and parous rates of the vectors varied substantiallythroughout the study period, which affected estimates of infectiousness. The latterconsequently cannot be explained by the change in drug policy. Conclusions: In high perennial transmission settings, only a small proportion of infections in humans aresymptomatic or treated, so case management with ACT may have little impact on overallinfectiousness of the human population. Variations in infection levels in vectors largelydepend on the age distribution of the mosquito population. Benefits of ACT in suppressingtransmission are more likely to be evident where transmission is already low or effectivevector control is widely implemented.

The epidemiology of postpartum malaria: a systematic review

Machteld Boel — 2012-04-13T00:00:00Z

Pregnant women are more susceptible to malaria than their non-pregnant counterparts. Less is known about the risk of malaria in the postpartum period. The epidemiology of postpartum malaria was systematically reviewed. Eleven articles fitted the inclusion criteria. Of the 10 studies that compared malaria data from the postpartum period with pregnancy data, nine studies suggested that the risk for malaria infection decreased after delivery. All three studies that compared postpartum data with non-pregnant non-postpartum women concluded that the risk did not return to pre-pregnancy levels immediately after delivery. The results of this review have to be carefully interpreted, as the majority of studies were not designed to study postpartum malaria, and there was large variability in study designs and reported outcomes. Current evidence suggests an effort should be made to detect and radically cure malaria during pregnancy so that women do not enter the postpartum period with residual parasites.

Successful field trial of attractive toxic sugar bait (ATSB) plant-spraying methods against malaria vectors in the Anopheles gambiae complex in Mali, West Africa

Gunter Muller — 2010-07-21T00:00:00Z

Background: Based on highly successful demonstrations in Israel that attractive toxic sugar bait (ATSB) methods can decimate local populations of mosquitoes, this study determined the effectiveness of ATSB methods for malaria vector control in the semi-arid Bandiagara District of Mali, West Africa. Methods: Control and treatment sites, selected along a road that connects villages, contained man-made ponds that were the primary larval habitats of Anopheles gambiae and Anopheles arabiensis. Guava and honey melons, two local fruits shown to be attractive to An. gambiae s.l., were used to prepare solutions of Attractive Sugar Bait (ASB) and ATSB that additionally contained boric acid as an oral insecticide. Both included a color dye marker to facilitate determination of mosquitoes feeding on the solutions. The trial was conducted over a 38-day period, using CDC light traps to monitor mosquito populations. On day 8, ASB solution in the control site and ATSB solution in the treatment site were sprayed using a hand-pump on patches of vegetation. Samples of female mosquitoes were age-graded to determine the impact of ATSB treatment on vector longevity. Results: Immediately after spraying ATSB in the treatment site, the relative abundance of female and male An. gambiae s.l. declined about 90% from pre-treatment levels and remained low. In the treatment site, most females remaining after ATSB treatment had not completed a single gonotrophic cycle, and only 6% had completed three or more gonotrophic cycles compared with 37% pre-treatment. In the control site sprayed with ASB (without toxin), the proportion of females completing three or more gonotrophic cycles increased from 28.5% pre-treatment to 47.5% post-treatment. In the control site, detection of dye marker in over half of the females and males provided direct evidence that the mosquitoes were feeding on the sprayed solutions. Conclusion: This study in Mali shows that even a single application of ATSB can substantially decrease malaria vector population densities and longevity. It is likely that ATSB methods can be used as a new powerful tool for the control of malaria vectors, particularly since this approach is highly effective for mosquito control, technologically simple, inexpensive, and environmentally safe.