Malaria Disease Burden Research Articles

Fine-Scale Mapping by Spatial Risk Distribution Modeling for Regional Malaria Endemicity and Its Implications under the Low-to-Moderate Transmission Setting in Western Cambodia.

The disease burden of malaria has decreased as malaria elimination efforts progress. The mapping approach that uses spatial risk distribution modeling needs some adjustment and reinvestigation in accordance with situational changes. Here we applied a mathematical modeling approach for standardized morbidity ratio (SMR) calculated by annual parasite incidence using routinely aggregated surveillance reports, environmental data such as remote sensing data, and non-environmental anthropogenic data to create fine-scale spatial risk distribution maps of western Cambodia. Furthermore, we incorporated a combination of containment status indicators into the model to demonstrate spatial heterogeneities of the relationship between containment status and risks. The explanatory model was fitted to estimate the SMR of each area (adjusted Pearson correlation coefficient R2 = 0.774; Akaike information criterion AIC = 149.423). A Bayesian modeling framework was applied to estimate the uncertainty of the model and cross-scale predictions. Fine-scale maps were created by the spatial interpolation of estimated SMRs at each village. Compared with geocoded case data, corresponding predicted values showed conformity [Spearman’s rank correlation r = 0.662 in the inverse distance weighed interpolation and 0.645 in ordinal kriging (95% confidence intervals of 0.414–0.827 and 0.368–0.813, respectively), Welch’s t-test; Not significant]. The proposed approach successfully explained regional malaria risks and fine-scale risk maps were created under low-to-moderate malaria transmission settings where reinvestigations of existing risk modeling approaches were needed. Moreover, different representations of simulated outcomes of containment status indicators for respective areas provided useful insights for tailored interventional planning, considering regional malaria endemicity.

Effect of stable and fluctuating temperatures on the life history traits of Anopheles arabiensis and An. quadriannulatus under conditions of inter- and intra-specific competition

BackgroundConstant and fluctuating temperatures influence important life-history parameters of malaria vectors which has implications for community organization and the malaria disease burden. The effects of environmental temperature on the hatch rate, survivorship and development rate of Anopheles arabiensis and An. quadriannulatus under conditions of inter- and intra-specific competition are studied.MethodsThe eggs and larvae of laboratory established colonies were reared under controlled conditions at one constant (25 °C) and two fluctuating (20–30 °C and 18–35 °C) temperature treatments at a ratio of 1:0 or 1:1 (An. arabiensis: An. quadriannulatus). Monitoring of hatch rate, development rate and survival was done at three intervals, 6 to 8 h apart depending on developmental stage. Parametric ANOVAs were used where assumptions of equal variances and normality were met, and a Welch ANOVA where equal variance was violated (α = 0.05).ResultsTemperature significantly influenced the measured life-history traits and importantly, this was evident when these species co-occurred. A constant temperature resulted in a higher hatch rate in single species, larval treatments (P < 0.05). The treatment 18–35 °C generally reduced survivorship except for An. arabiensis in mixed, larval species treatments where it was similar to values reported for 25 °C. Survivorship of both species at 20–30 °C was not significantly impacted and the adult production was high across species treatments. The development rates at 25 °C and 20–30 °C were significantly different between species when reared alone and in mixed species from larvae and from eggs. The effect of temperature was more pronounced at 18–35 °C with An. arabiensis developing faster under both competitive scenarios and An. quadriannulatus slower, notably when in the presence of its competitor (P < 0.05).ConclusionsThe influence of temperature treatment on the development rate and survival from egg/larvae to adult differed across species treatments. Fluctuating temperatures incorporating the extremes influence the key life-history parameters measured here with An. arabiensis outcompeting An. quadriannulatus under these conditions. The quantification of the response variables measured here improve our knowledge of the link between temperature and species interactions and provide valuable information for modelling of vector population dynamics.

Critiquing the response to the Ebola epidemic through a Primary Health Care Approach.

BackgroundThe 2014/2015 West Africa Ebola epidemic has caused the global public health community to engage in difficult self-reflection. First, it must consider the part it played in relation to an important public health question: why did this epidemic take hold and spread in this unprecedented manner? Second, it must use the lessons learnt to answer the subsequent question: what can be done now to prevent further such outbreaks in the future? These questions remain relevant, even as scientists announce that the Guinea Phase III efficacy vaccine trial shows that rVSV-EBOV (Merck, Sharp & Dohme) is highly efficacious in individuals. This is a major breakthrough in the fight against Ebola virus disease (EVD). It does not replace but may be a powerful adjunct to current strategies of EVD management and control.DiscussionWe contribute to the current self-reflection by presenting an analysis using a Primary Health Care (PHC) approach. This approach is appropriate as African countries in the region affected by EVD have recommitted themselves to PHC as a framework for organising health systems and the delivery of health services. The approach suggests that, in an epidemic made complex by weak pre-existing health systems, lack of trust in authorities and mobile populations, a broader approach is required to engage affected communities. In the medium-term health system development with attention to primary level services and community-based programmes to address the major disease burden of malaria, diarrhoeal disease, meningitis, tuberculosis and malnutrition is needed. This requires the development of local management and an investment in human resources for health. Crucially this has to be developed ahead of, and not in parallel with, future outbreaks. In the longer-term a commitment is required to address the underlying social determinants which make these countries so vulnerable, and limit their capacity to respond effectively to, epidemics such as EVD.ConclusionThe PHC approach offers an insightful critique of the global and regional factors which have compromised the response of health systems in Guinea, Liberia and Sierra Leone as well as suggesting what a strengthened EVD response might involve in the short, medium and long-term.

Challenges to Achieving Malaria Elimination in Nigeria

Malaria remains the most important public health parasitic disease and a major global health problem with the greatest burden in sub-Saharan Africa. Over 90% of all malaria deaths still occur in Africa where it kills over half a million children less than 5 years of age each year. Nigeria accounts for 25 percent of the world’s malaria burden. Apart from the health burden, the socio-economic consequences of malaria are enormous such that it was part of the Millennium Development Goals (MDGs). Following the end of MDG target to halt and reverse the incidence of malaria by 2015 which was considered a success, a new global target has been set. The new global strategy aims to reduce the global disease burden of malaria by 40% by 2020, and by at least 90% by 2030. It also aims to eliminate malaria in at least 35 new countries by 2030. Nigeria remains endemic for malaria and has the ambition to eliminate malaria. There are however challenges to confront in order to make the desired progress. Drug resistance, treatment failure, insecticide resistance, global warming and change in climate, conflicts, insurgency, and internally displaced persons, migration, lack of political will, inadequate malaria leadership, funding, and adequate local research constitute the challenges. Addressing these challenges is central to achieving malaria elimination.

The Choice of Healthcare Providers for Febrile Children after Introducing Non-professional Health Workers in a Malaria Endemic Area in Papua New Guinea.

Disease burden of malaria in Papua New Guinea (PNG) is the highest in Asia and the Pacific, and prompt access to effective drugs is the key strategy for controlling malaria. Despite the rapid economic growth, primary healthcare services have deteriorated in rural areas; the introduction of non-professional health workers [village health volunteers (VHVs)] is expected to improve antimalarial drug deliveries. Previous studies on PNG suggested that distance from households negatively affected the utilization of health services; however, price effect on healthcare demand decisions has not been explored. Empirical studies on household's affordability as well as accessibility of healthcare services contribute to policy implications, such as efficient introduction of out-of-pocket costs and effective allocation of health facilities. Therefore, we investigate price responsiveness and other determinants of healthcare provider choice for febrile children in a malaria endemic rural area wherein VHVs were introduced. Cross-sectional surveys were conducted using a structured questionnaire distributed in a health center's catchment area of East Sepik Province in the 2011/2012 rainy seasons. Caretakers were interviewed and data on fever episodes of their children in the preceding 2 weeks were collected. Mixed logit model was employed to estimate the determinants of healthcare provider choice. Among 257 fever episodes reported, the main choices of healthcare providers were limited to self-care, VHV, and a health center. Direct cost and walking distance negatively affected the choice of a VHV and the health center. An increase of VHV's direct cost or walking distance did not much affect predicted probability of the health center, but rather that of self-care, while drug availability and illness severity increased the choice probability of a VHV and the health center. The results suggest that the net healthcare demand increases with the introduction of a VHV. Allocations from the government's budget are required to sustain VHV activities because the introduction of a small user fee could impede the utilization of a VHV. A large travel cost related to the choice of the health center suggests that resource allocation is required for the expansion of formal healthcare providers to adequately operate a referral system.

Design of a study to determine the impact of insecticide resistance on malaria vector control: a multi-country investigation.

BackgroundProgress in reducing the malaria disease burden through the substantial scale up of insecticide-based vector control in recent years could be reversed by the widespread emergence of insecticide resistance. The impact of insecticide resistance on the protective effectiveness of insecticide-treated nets (ITN) and indoor residual spraying (IRS) is not known. A multi-country study was undertaken in Sudan, Kenya, India, Cameroon and Benin to quantify the potential loss of epidemiological effectiveness of ITNs and IRS due to decreased susceptibility of malaria vectors to insecticides. The design of the study is described in this paper.MethodsMalaria disease incidence rates by active case detection in cohorts of children, and indicators of insecticide resistance in local vectors were monitored in each of approximately 300 separate locations (clusters) with high coverage of malaria vector control over multiple malaria seasons. Phenotypic and genotypic resistance was assessed annually. In two countries, Sudan and India, clusters were randomly assigned to receive universal coverage of ITNs only, or universal coverage of ITNs combined with high coverage of IRS. Association between malaria incidence and insecticide resistance, and protective effectiveness of vector control methods and insecticide resistance were estimated, respectively.ResultsCohorts have been set up in all five countries, and phenotypic resistance data have been collected in all clusters. In Sudan, Kenya, Cameroon and Benin data collection is due to be completed in 2015. In India data collection will be completed in 2016.DiscussionThe paper discusses challenges faced in the design and execution of the study, the analysis plan, the strengths and weaknesses, and the possible alternatives to the chosen study design.

A molecular survey of acute febrile illnesses reveals Plasmodium vivax infections in Kedougou, southeastern Senegal.

BackgroundControl efforts towards malaria due to Plasmodium falciparum significantly decreased the incidence of the disease in many endemic countries including Senegal. Surprisingly, in Kedougou (southeastern Senegal) P. falciparum malaria remains highly prevalent and the relative contribution of other Plasmodium species to the global malaria burden is very poorly documented, partly due to the low sensitivity of routine diagnostic tools. Molecular methods offer better estimate of circulating Plasmodium species in a given area. A molecular survey was carried out to document circulating malaria parasites in Kedougou region.MethodsA total of 263 long-term stored sera obtained from patients presenting with acute febrile illness in Kedougou between July 2009 and July 2013 were used for malaria parasite determination. Sera were withdrawn from a collection established as part of a surveillance programme of arboviruses infections in the region. Plasmodium species were characterized by a nested PCR-based approach targeting the 18S small sub-unit ribosomal RNA genes of Plasmodium spp.ResultsOf the 263 sera screened in this study, Plasmodium genomic DNA was amplifiable by nested PCR from 62.35% (164/263) of samples. P. falciparum accounted for the majority of infections either as single in 85.97% (141/164) of Plasmodium-positive samples or mixed with Plasmodium ovale (11.58%, 19/164) or Plasmodium vivax (1.21%, 2/164). All 19 (11.58%) P. ovale-infected patients were mixed with P. falciparum, while no Plasmodium malariae was detected in this survey. Four patients (2.43%) were found to be infected by P. vivax, two of whom were mixed with P. falciparum. P. vivax infections originated from Bandafassi and Ninefesha villages and concerned patients aged 4, 9, 10, and 15 years old, respectively. DNA sequences alignment and phylogenetic analysis demonstrated that sequences from Kedougou corresponded to P. vivax, therefore confirming the presence of P. vivax infections in Senegal.ConclusionThe results confirm the high prevalence of P. falciparum in Kedougou and provide the first molecular evidence of P. vivax infections in Senegal. These findings pave the ways for further investigations of P. vivax infections in Senegal and its contribution to the global burden of malaria disease before targeted strategies can be deployed.

Impact of Schistosoma mansoni on malaria transmission in Sub-Saharan Africa.

BackgroundSub-Saharan Africa harbors the majority of the global burden of malaria and schistosomiasis infections. The co-endemicity of these two tropical diseases has prompted investigation into the mechanisms of coinfection, particularly the competing immunological responses associated with each disease. Epidemiological studies have shown that infection with Schistosoma mansoni is associated with a greater malaria incidence among school-age children.MethodologyWe developed a co-epidemic model of malaria and S. mansoni transmission dynamics which takes into account key epidemiological interaction between the two diseases in terms of elevated malaria incidence among individuals with S. mansoni high egg output. The model was parameterized for S. mansoni high-risk endemic communities, using epidemiological and clinical data of the interaction between S. mansoni and malaria among children in sub-Saharan Africa. We evaluated the potential impact of the S. mansoni–malaria interaction and mass treatment of schistosomiasis on malaria prevalence in co-endemic communities.Principal FindingsOur results suggest that in the absence of mass drug administration of praziquantel, the interaction between S. mansoni and malaria may reduce the effectiveness of malaria treatment for curtailing malaria transmission, in S. mansoni high-risk endemic communities. However, when malaria treatment is used in combination with praziquantel, mass praziquantel administration may increase the effectiveness of malaria control intervention strategy for reducing malaria prevalence in malaria- S. mansoni co-endemic communities.Conclusions/SignificanceSchistosomiasis treatment and control programmes in regions where S. mansoni and malaria are highly prevalent may have indirect benefits on reducing malaria transmission as a result of disease interactions. In particular, mass praziquantel administration may not only have the direct benefit of reducing schistosomiasis infection, it may also reduce malaria transmission and disease burden.

Correlates of protective immunity following whole sporozoite vaccination against malaria.

Human infection with Plasmodium parasites remains a serious global health crisis, leading to more than 600,000 deaths annually. Currently, no licensed vaccine is available to alleviate this malaria disease burden and vaccination with the most advanced antimalarial vaccine candidate, RTS,S, provides limited protection that wanes over time. To date, the only vaccination strategy capable of inducing complete, long-lasting protection in human subjects is administration of attenuated whole sporozoites. Several approaches for vaccination with attenuated whole sporozoites have been clinically tested in humans and include vaccination with radiation or genetically attenuated sporozoites or with virulent sporozoites concurrent with administration of antimalarial drug cover. Rodent studies with these three attenuated whole sporozoite vaccination (WSV) approaches provide insights into the immune correlates of vaccine-induced protection. The majority of these studies have identified a critical role for liver-stage parasite-directed CD8 T cells in providing protection with possible contributions from Plasmodium-specific CD4 T cells or antibodies. Together, rodent and human vaccination studies with attenuated WSV may lead to an understanding of the correlates of protective immunity against malarial disease, and the development of new, highly efficacious vaccines.

Estimates of the changing age-burden of Plasmodium falciparum malaria disease in sub-Saharan Africa

Estimating the changing burden of malaria disease remains difficult owing to limitations in health reporting systems. Here, we use a transmission model incorporating acquisition and loss of immunity to capture age-specific patterns of disease at different transmission intensities. The model is fitted to age-stratified data from 23 sites in Africa, and we then produce maps and estimates of disease burden. We estimate that in 2010 there were 252 (95% credible interval: 171–353) million cases of malaria in sub-Saharan Africa that active case finding would detect. However, only 34% (12–86%) of these cases would be observed through passive case detection. We estimate that the proportion of all cases of clinical malaria that are in under-fives varies from above 60% at high transmission to below 20% at low transmission. The focus of some interventions towards young children may need to be reconsidered, and should be informed by the current local transmission intensity.

Mass primaquine preventive treatment for control of Plasmodium vivax malaria in the Democratic People's Republic of Korea: a country success story.

In 1998, the resurgence of Plasmodium vivax malaria in the Democratic People's Republic of Korea quickly increased to an epidemic, with 601 013 cases reported I during 1999-2001. The introduction of mass primaquine preventive treatment (MPPT) in 2002 was followed by a rapid reduction of malaria disease burden. The intervention has been well accepted by the community. Doctors were part of a strong functional health system with the ability to deliver interventions at the household J level. MPPT was considered for control of malaria after a study conducted in two J neighbouring endemic villages (ris) involving 320 healthy adults demonstrated that presence of parasitaemia was significantly lower among those receiving MPPT than those who did not. Similarly, in a mass blood survey conducted in the study sites during May, 2002 involving 5138 persons in study and 4215 in comparison areas, the total positive results were 7-10 times rarer in the treatment group both before and after the malaria transmission season. In addition, the number of malaria cases in the MPPT treatment ris was strikingly lower than control ris in every month during the malaria transmission season of 2002. The prevalence of G6PDD deficiency in DPR Korea is low, haemolytic events are rare and deaths due to MPPT have not been reported. MPPT in itself is a powerful intervention and the decision to deploy it depends on the epidemiology of malaria, urgency of malaria control and resources available in the country.

Mutation of the Catalytic Cysteine in Anopheles gambiae Transglutaminase 3 (AgTG3) Abolishes Plugin Crosslinking Activity without Disrupting Protein Folding Properties

Malaria is a devastating parasitic infectious disease with an enormous impact on public health and economic growth, particularly in Sub-Saharan Africa. Besides advances in anti-malarial drugs and vaccine development, a successful malaria eradication program relies on controlling the mosquito vector. In this study, we pursue a novel approach for malaria vector control by inhibiting an enzyme important for ensuring reproductive success of the mosquito Anopheles gambiae. The enzyme, A. gambiae transglutaminase 3 (AgTG3), catalyzes the cross-linking of its native substrate Plugin, which is then transferred to a female mosquito in a coagulated mass known as the mating plug. Interfering with AgTG3-catalyzed mating plug formation prevents efficient sperm storage, with a direct consequence on fertility. This study demonstrates that the mutation of a highly conserved cysteine residue in AgTG3 (Cys323) abolishes its cross-linking activity without disrupting other properties of the enzyme such as protein folding and oligomeric assembly. These results suggest that Cys323 is an active site residue and support the design of specific inhibitors targeting this site as a promising strategy to reduce the malaria disease burden worldwide.

Repeated mass distributions and continuous distribution of long-lasting insecticidal nets: modelling sustainability of health benefits from mosquito nets, depending on case management

BackgroundStagnating funds for malaria control have spurred interest in the question of how to sustain the gains of recent successes with long-lasting insecticidal nets (LLINs) and improved case management (CM). This simulation study examined the malaria transmission and disease dynamics in scenarios with sustained LLINs and CM interventions and tried to determine optimal LLIN distribution rates. The effects of abruptly halting LLIN distribution were also examined.MethodsDynamic simulations of malaria in humans and mosquitoes were run on the OpenMalaria platform, using stochastic individual-based simulation models. LLINs were distributed in a range of transmission settings, with varying CM coverage levels.ResultsIn the short-term, LLINs were beneficial over the entire transmission spectrum, reducing both transmission and disease burden. In the long-term, repeated distributions sustainably reduced transmission in all settings. However, because of the resulting reduction in acquired immunity in the population, the malaria disease burden, after initially being reduced, gradually increased and eventually stabilized at a new level. This new level was higher than the pre-intervention level in previously high transmission settings, if there is a maximum disease burden in the relationship between transmission and disease burden at intermediate transmission levels. This result could lead one to conclude that sustained LLIN distribution might not be cost-effective in high transmission settings in the long term. However, improved CM rendered LLINs more cost-effective in higher transmission settings than in those without improved CM and the majority of the African population lives in areas where CM and LLINs are sustainably combined. The effects of changes in LLIN distribution rate on cost-effectiveness were relatively small compared to the effects of changes in transmission setting and CM. Abruptly halting LLIN distribution led to temporary morbidity peaks, which were particularly large in low to intermediate transmission settings.ConclusionsThis study reaffirms the importance of context specific intervention planning. Intervention planning must include combinations of malaria vector control and CM, and must consider both the pre-intervention transmission level and the intervention history to account for the loss of immunity and the potential for rebounds in disease burden.

Translating health research evidence into policy and practice in Uganda

BackgroundUganda experiences a high disease burden of malaria, infectious and non-communicable diseases. Recent data shows that malaria is the leading cause of morbidity and mortality among all age groups, while HIV prevalence is on the increase and there is re-emergence of viral haemorrhagic fevers and cholera epidemics. In order to respond to the above situation, a team of researchers, policy makers, civil society and the media was formed in order to build a collaboration that would help in discussing appropriate strategies to mitigate the high disease burden in Uganda.MethodsA preparatory secretariat composed of individuals from Ministry of Health, Malaria Research Centre and School of Public Health was formed. The secretariat identified researchers, key resource persons to guide the workshops and the format for presentation. The criteria for selection of the research topics were: National public health importance and had been published in peer-reviewed journals. The presentations were structured as follows: research questions, hypotheses, methodology, major findings and policy implications. The secretariat compiled all the proceedings of the workshops including attendance, address of participants including telephone and email contacts. During the last workshop, an evaluation was conducted to assess the impact of the workshops.ResultsFour workshops were held between 2006 and 2009. A total of 322 participants attended of whom mid-level policy makers, researchers and the media were consistently high. The workshops generated a lot of interest that lead to presentation and discussion of nationally relevant health research results. The workshops had an impact on the participants’ skills in writing policy briefs, participating in the policy review process and entering into dialogue with policy makers.ConclusionThe following lessons have been learned: getting health research into policy is feasible but requires few self-motivated individuals to act as catalysts. Adequate funding and a stable internet are necessary to support the process. Mid-level policy makers and programme managers had interest in this initiative and are likely sustain it as they move to senior positions in policy making.

Malaria burden and case management in the Republic of Congo: limited use and application of rapid diagnostic tests results

BackgroundThere have been few investigations evaluating the burden of malaria disease at district level in the Republic of Congo since the introduction of artemisinin-based combination therapies (ACTs). The main objective of this study was to document laboratory-confirmed cases of malaria using microscopy and/or rapid diagnostic tests (RDTs) in children and pregnant women attending selected health facilities in Brazzaville and Pointe Noire, the two main cities of the country. Secondly, P. falciparum genetic diversity and multiplicity of infection during the malaria transmission season of October 2011 to February 2012 in these areas were described.MethodsThree and one health facilities were selected in Brazzaville and Pointe-Noire as sentinel sites for malaria surveillance. Children under 15 years of age and pregnant women were enrolled if study criteria were met and lab technicians used RDT and/or microscopy to diagnose malaria. In order to determine the multiplicity of infection, parasite DNA was extracted from RDT cassette and msp2 P.falciparum genotyped.ResultsMalaria prevalence among more than 3,000 children and 700 pregnant women ranged from 8 to 29%, and 8 to 24% respectively depending on health center locality. While health workers did not optimize use of RDTs, microscopy remained a reference diagnostic tool. Quality control of malaria diagnosis at the reference laboratory showed acceptable health centre performances. P. falciparum genetic diversity determination using msp2 gene marker ranged from 9 to 20 alleles and remains stable while multiplicity of infection (mean of 1.7clone/infected individual) and parasite densities in clinical isolates were lower than previously reported.ConclusionsThese findings are consistent with a reduction of malaria transmission in the two areas. This study raises the issue of targeted training for health workers and sustained availability of RDTs in order to improve quality of care through optimal use of RDTs.

Review of the malaria epidemiology and trends in Zambia

A comprehensive desk review of malaria trends was conducted between 2000–2010 in Zambia to study malaria epidemiology and trends to guide strategies and approaches for effective malaria control. This review considered data from the National Health Information Management System, Malaria Surveys and Programme Review reports and analyzed malaria in-patient cases and deaths in relation to intervention coverage for all ages. Data showed three distinct epidemiological strata after a notable malaria reduction (66%) in in-patient cases and deaths, particularly between 2000–2008. These changes occurred following the (re-)introduction and expansion of indoor residual spraying up to 90% coverage, scale-up of coverage of long-lasting insecticide-treated nets in household from 50% to 70%, and artemisin-based combination therapy nationwide. However, malaria cases and deaths re-surged, increasing in 2009–2010 in the northern-eastern parts of Zambia. Delays in the disbursement of funds affected the implementation of interventions, which resulted in resurgence of cases and deaths. In spite of a decline in malaria disease burden over the past decade in Zambia, a reversal in impact is notable in the year 2009–2010, signifying that control gains are fragile and must be sustained toeliminate malaria.

Plasmodium falciparum Malaria in Infants Under 5 Kg: Retrospective Surveillance of Hospital Records in Five Sub-Saharan African Countries

To investigate the disease burden, clinical features, treatment and outcomes of Plasmodium falciparum malaria in neonates and infants weighing <5 kg in five sub-Saharan African countries. Pediatric hospital records were retrospectively reviewed for relevant cases. Details of clinical features, treatment and clinical outcomes were collected, and a descriptive analysis of data was carried out. The annual number of malaria cases ranged from 12 to 120 cases across hospitals and calendar years. The most frequent reason for seeking care was fever. Parasite density was low. Quinine was the most common treatment, followed by artemisinin-based combination therapy. The majority of patients recovered from their illness following treatment. Plasmodium falciparum malaria exists in this subpopulation. Further epidemiological data are needed to estimate malaria morbidity and mortality in young infants. Moreover, clinical evidence on the efficacy and safety of artemisinin-based combination therapies in this subpopulation is warranted.

Field evaluation of permethrin long-lasting insecticide treated nets (Olyset®) for malaria control in an endemic area, southeast of Iran

Long lasting insecticide treated nets (LLINs) have been advocated as an effective tool for prevention and control of malaria. Olyset net was the first LLINs which became commercially available and obtained WHO approval. According to the national strategic plan on evaluation of Olyset net, a field trial was conducted to determine the efficacy of these nets against malaria vectors in an endemic area in the southeast of Iran.Fourteen villages with similar topographical and epidemiological situations were selected and randomly assigned to two clusters of the study: Olyset net and untreated net. Distribution of nets was carried out to cover 100% of the population in Olyset net and untreated net cluster.Anopheline mosquitoes were collected monthly using different WHO standard methods in both areas to determine their abundance, feeding pattern and resting behaviour. Human blood index was determined using ELISA test. Additionally, Olyset nets were evaluated for their biological activity using WHO cone bioassay test by susceptible colony of Anopheles stephensi (Beech strain) and then for insecticide residues by employing high performance thin layer chromatography. Malaria incidence was measured by passive and active case detection from all study population.In total 2115 adult anopheline mosquitoes were collected and identified using morphological characters. They comprised of seven species: Anopheles dthali (Liston), A. culicifacies (Giles), A. stephensi (Liston), A. superpictus (Grassi), A.fluviatilis (James), A. moghulensis (Christophers) and A. turkhudi (Liston). A. dthali, A. culicifacies and A. stephensi were most prevalent species in both areas.In the Olyset net study area, there was a significant reduction of 41.1%, 54.4%, 59.39% and 64.1% in the indoor-resting density of A. culicifacies, A. stephensi, A. dthali and A. superpictus, respectively, with an overall reduction of 39.3% in total mosquitoes in comparison with untreated net area. A significant reduction was also observed in human blood index of vector species in the Olyset net villages. Bioefficacy test results of Olyset nets showed that the median knockdown time was 1.48 and 3.25min, while the average mortality rate was 100% and 72.3%±7.07 in baseline and after 1 year of intervention, respectively. The average permethrin content reached to 68.31% (683.1mg/m2) of the initial insecticide dose of 937±21.69mg/m2 (nearly 1000mg/m2) at the end of intervention.Malaria incidence was reduced by 96.6% and 64.8% in the village with Olyset nets and in the villages with untreated nets, respectively. During intervention period, there was a reduction of 93.2% in malaria incidence in Olyset net area as compared to the untreated area.This study indicated that Olyset nets have a major impact on malaria vectors and disease burden; therefore it could be recommended as an effective personal protection tool for malaria control in malarious areas.

Country planning for health interventions under development: lessons from the malaria vaccine decision-making framework and implications for other new interventions

Traditionally it has taken years or decades for new public health interventions targeting diseases found in developing countries to be accessible to those most in need. One reason for the delay has been insufficient anticipation of the eventual processes and evidence required for decision making by countries. This paper describes research into the anticipated processes and data needed to inform decision making on malaria vaccines, the most advanced of which is still in phase 3 trials. From 2006 to 2008, a series of country consultations in Africa led to the development of a guide to assist countries in preparing their malaria vaccine decision-making frameworks. The guide builds upon the World Health Organization’s Vaccine Introduction Guidelines. It identifies the processes and data for decisions, when they would be needed relative to the development timelines of the intervention, and where they will come from. Policy development will be supported by data (e.g. malaria disease burden; roles of other malaria interventions; malaria vaccine impact; economic and financial issues; malaria vaccine efficacy, quality and safety) as will implementation decisions (e.g. programmatic issues and socio-cultural environment). This generic guide can now be applied to any future malaria vaccine. The paper discusses the opportunities and challenges to early planning for country decision-making—from the potential for timely, evidence-informed decisions to the risks of over-promising around an intervention still under development. Careful and well-structured planning by countries is an important way to ensure that new interventions do not remain unused for years or decades after they become available.

Community screening and treatment of asymptomatic carriers of Plasmodium falciparum with artemether-lumefantrine to reduce malaria disease burden: a modelling and simulation analysis

BackgroundAsymptomatic carriers of Plasmodium falciparum serve as a reservoir of parasites for malaria transmission. Identification and treatment of asymptomatic carriers within a region may reduce the parasite reservoir and influence malaria transmission in that area.MethodsUsing computer simulation, this analysis explored the impact of community screening campaigns (CSC) followed by systematic treatment of P. falciparum asymptomatic carriers (AC) with artemether-lumefantrine (AL) on disease transmission. The model created by Okell et al (originally designed to explore the impact of the introduction of treatment with artemisinin-based combination therapy on malaria endemicity) was modified to represent CSC and treatment of AC with AL, with the addition of malaria vector seasonality. The age grouping, relative distribution of age in a region, and degree of heterogeneity in disease transmission were maintained. The number and frequency of CSC and their relative timing were explored in terms of their effect on malaria incidence. A sensitivity analysis was conducted to determine the factors with the greatest impact on the model predictions.ResultsThe simulation showed that the intervention that had the largest effect was performed in an area with high endemicity (entomological inoculation rate, EIR > 200); however, the rate of infection returned to its normal level in the subsequent year, unless the intervention was repeated. In areas with low disease burden (EIR < 10), the reduction was sustained for over three years after a single intervention. Three CSC scheduled in close succession (monthly intervals) at the start of the dry season had the greatest impact on the success of the intervention.ConclusionsCommunity screening and treatment of asymptomatic carriers with AL may reduce malaria transmission significantly. The initial level of disease intensity has the greatest impact on the potential magnitude and duration of malaria reduction. When combined with other interventions (e.g. long-lasting insecticide-treated nets, rapid diagnostic tests, prompt diagnosis and treatment, and, where appropriate, indoor residual spraying) the effect of this intervention can be sustained for many years, and it could become a tool to accelerate the reduction in transmission intensity to pre-elimination levels. Repeated interventions at least every other year may help to prolong the effect. The use of an effective diagnostic tool and a highly effective ACT, such as AL, is also vital. The modelling supports the evaluation of this approach in a prospective clinical trial to reduce the pool of infective vectors for malaria transmission in an area with marked seasonality.