Reducing Malaria Incidence Research Articles

Prevalence of polymorphisms in glucose-6-phosphate dehydrogenase, sickle haemoglobin and nitric oxide synthase genes and their relationship with incidence of uncomplicated malaria in Iganga, Uganda

BackgroundHost genetics play an important role in Plasmodium falciparum malaria susceptibility. However, information on host genetic factors and their relationships with malaria in the vaccine trial site of Iganga, Uganda is limited. The main objective of this study was to determine the prevalence of selected host genetic markers and their relationship to malaria incidence in the vaccine trial site of Iganga, Uganda. In a 1-year longitudinal cohort study, 423 children aged below 9 years were recruited and their malaria episodes were investigated. Host genetic polymorphisms were assessed by PCR–RFLP, haemoglobin electrophoresis and DNA sequencing. Using a multivariate negative binomial regression model, estimates of the impact of human genetic polymorphisms on malaria incidence were performed. In all statistical tests, a P value of <0.05 was considered as significant.ResultsThe prevalences of sickle cell haemoglobin trait, G6PD c.202 G>A (rs 1050828) and NOS2 −954 G>C (rs 1800482) variants were 26.6, 22.7 and 17.3%, respectively. Inducible nitric oxide synthase 2 (NOS2 −954 G>C; rs 1800482) heterozygosity was associated with lower incidence of malaria in all age groups {Adjusted incident rates ratio (aIRR) 0.59; 95% CI [0.386–0.887]; P = 0.012)}. About 4% of study subjects had co-existence of sickle cell Hb trait and G6PD deficiency. Sickle cell Hb heterozygotes (Hb AS) aged less than 1 year experienced significantly more malaria episodes annually than children with normal haemoglobin (Hb AA) {aIRR = 1.98; 95% CI [1.240–3.175]; P = 0.004}. There was no significant influence of the sickle cell trait on malaria incidence among older children of 1–9 years.ConclusionsMutation (NOS2 −954 G>C; rs 1800482) of nitric oxide synthase 2 gene promoter was associated with a lower incidence of acute malaria. The normal haemoglobin (wild genotype; HbAA) was associated with reduced malaria incidence rates during the first year of life. More understanding of the interplay between host genetics and malaria susceptibility is required.

Rapid reduction of malaria following introduction of vector control interventions in Tororo District, Uganda: a descriptive study

BackgroundIn 2012, Tororo District had the highest malaria burden in Uganda with community Plasmodium prevalence of 48%. To control malaria in the district, the Ministry of Health introduced universal distribution of long lasting insecticide-treated nets (LLINs) in 2013 and added indoor residual spraying (IRS) in 2014. This study assessed malaria incidence, test positivity rates and outpatient (OPD) attendance due to malaria before and after vector control interventions.MethodsThis study was based on analysis of Health Management Information System (HMIS) secondary malaria surveillance data of 2,727,850 patient records in OPD registers of 61 health facilities from 2012 to 2015. The analysis estimated monthly malaria incidence for the entire population and also separately for <5- and ≥5-year-olds before and after introduction of vector control interventions; determined laboratory test positivity rates and annual percentage of malaria cases in OPD. Chi square for trends was used to analyse annual change in malaria incidence and logistic regression for monthly reduction.ResultsFollowing universal LLINs coverage, the annual mean monthly malaria incidence fell from 95 cases in 2013 to 76 cases per 1000 in 2014 with no significant monthly reduction (OR = 0.99, 95% CI 0.96–1.01, P = 0.37). Among children <5 years, the malaria incidence reduced from 130 to 100 cases per 1000 (OR = 0.98, 95% CI 0.97–1.00, P = 0.08) when LLINs were used alone in 2014, but declined to 45 per 1000 in 2015 when IRS was combined with LLINs (OR = 0.94, 95% CI 0.91–0.996, P < 0.0001). Among individuals aged ≥5 years, mean monthly malaria incidence reduced from 59 to 52 cases per 1000 (OR = 0.99, 95% CI 0.97–1.02, P = 0.8) when LLINs were used alone in 2014, but reduced significantly to 25 per 1000 in 2015 (OR = 0.91, 95% CI 0.88–0.94, P < 0.0001). Malaria test positivity rate reduced from 57% in 2013 to 30% (Chi = 15, P < 0.0001) in 2015. Slide positivity rate reduced from 45% in 2013 to 21% in 2015 (P = 0.004) while RDT positivity declined from 69 to 40%.ConclusionsA rapid reduction in malaria incidence was observed in Tororo District following the introduction of IRS in addition to LLINs. There was no significant reduction in malaria incidence following universal distribution of LLINs to communities before introduction of IRS.

A systematic review on malaria sero-epidemiology studies in the Brazilian Amazon: insights into immunological markers for exposure and protection

BackgroundConsiderable success in reducing malaria incidence and mortality has been achieved in Brazil, leading to discussions over the possibility of moving towards elimination. However, more than reporting and counting clinical cases, elimination will require the use of efficient tools and strategies for measuring transmission dynamics and detecting the infectious reservoir as the primary indicators of interest for surveillance and evaluation. Because acquisition and maintenance of anti-malarial antibodies depend on parasite exposure, seroprevalence rates could be used as a reliable tool for assessing malaria endemicity and an adjunct measure for monitoring transmission in a rapid and cost-effective manner.MethodsThis systematic review synthesizes the existing literature on seroprevalence of malaria in the Brazilian Amazon Basin. Different study designs (cross-sectional surveys and longitudinal studies) with reported serological results in well-defined Brazilian populations were considered. Medline (via PubMed), EMBASE and LILACS databases were screened and the articles were included per established selection criteria. Data extraction was performed by two authors and a modified critical appraisal tool was applied to assess the quality and completeness of cross-sectional studies regarding defined variables of interest.ResultsFrom 220 single records identified, 23 studies were included in this systematic review for the qualitative synthesis. Five studies reported serology results on Plasmodium falciparum, 14 papers assessed Plasmodium vivax and four articles reported results on both Plasmodium species. Considerable heterogeneity among the evaluated malarial antigens, including sporozoite and blood stage antigens, was observed. The majority of recent studies analysed IgG responses against P. vivax antigens reflecting the species distribution pattern in Brazil over the last decades. Most of the published papers were cross-sectional surveys (73.9%) and only six cohort studies were included in this review. Three studies pointed to an association between antibodies against circumsporozoite protein of both P. falciparum and P. vivax and malaria exposure. Furthermore, five out 13 cross-sectional studies evidenced a positive association between IgG antibodies to the conserved 19-kDa C-terminal region of the merozoite surface protein 1 of P. vivax (PvMSP119) and malaria exposure.ConclusionsThis systematic review identifies potential biomarkers of P. falciparum and P. vivax exposure in areas with variable and unstable malaria transmission in Brazil. However, this study highlights the need for standardization of further studies to provide an ideal monitoring tool to evaluate trends in malaria transmission and the effectiveness of malaria intervention programmes in Brazil. Moreover, the score-based weighted tool developed and used in this study still requires further validation.

Passive case detection of malaria in Ratanakiri Province (Cambodia) to detect villages at higher risk for malaria

BackgroundCambodia reduced malaria incidence by more than 75% between 2000 and 2015, a target of the Millennium Development Goal 6. The Cambodian Government aims to eliminate all forms of malaria by 2025. The country’s malaria incidence is highly variable at provincial level, but less is known at village level. This study used passive case detection (PCD) data at village level in Ratanakiri Province from 2010 to 2014 to describe incidence trends and identify high-risk areas of malaria to be primarily targeted towards malaria elimination.MethodsIn 2010, the Cambodian malaria programme created a Malaria Information System (MIS) to capture malaria information at village level through PCD by village malaria workers and health facilities. The MIS data of Ratanakiri Province 2010–2014 were used to calculate annual incidence rates by Plasmodium species at province and commune levels. For estimating the trend at provincial level only villages reporting each year were selected. The communal incidences and the number of cases per village were visualized on a map per Plasmodium species and per year. Analysis of spatial clustering of village malaria cases by Plasmodium species was performed by year.ResultsOverall, malaria annual incidence rates per 1000 inhabitants decreased from 86 (2010) to 30 (2014). Falciparum incidence decreased (by 79% in 2014 compared to 2010; CI 95% 76–82%) more rapidly than vivax incidence (by 19% in 2014 compared to 2010; CI 95% 5–32%). There were ten to 16 significant spatial clusters each year. Big clusters tended to extend along the Cambodian–Vietnamese border and along the Sesan River. Three clusters appeared throughout all years (2010–2014): one with 21 villages appeared each year, the second shrunk progressively from 2012 to 2014 and the third was split into two smaller clusters in 2013 and 2014.ConclusionThe decline of malaria burden can be attributed to intensive malaria control activities implemented in the areas: distribution of a long-lasting insecticidal net per person and early diagnosis and prompt treatment. Dihydro-artemisinin piperaquine was the only first-line treatment for all malaria cases. No radical treatment with primaquine was provided for Plasmodium vivax cases, which could explain the slow decrease of P. vivax due to relapses. To achieve malaria elimination by 2025, priority should be given to the control of stable malaria clusters appearing over time.

Hidden reservoir of resistant parasites: the missing link in the elimination of falciparum malaria

BackgroundTo successfully eliminate malaria, an integrated system that includes a number of approaches and interventions—aimed at overcoming the threat of antimalarial drug resistance—is required. Significant progress has been made in reducing malaria incidence through large-scale use of artemisinin-based combination therapies and insecticide-treated nets. To consolidate these gains, attention should be paid to the missing links in the elimination of malaria. One of these gaps is the residual reservoir of submicroscopic resistant parasites, which remains after case management or other control measures have been carried out. Therefore, the present opinion piece highlights the importance of exploring the role that submicroscopic resistant parasites could play in hindering malaria elimination by allowing the persistence of transmission, particularly in areas of low transmission or in the pre-elimination and/or elimination phase.DiscussionIf malaria elimination interventions are to be effective, the relative role of the hidden reservoir of resistant parasites needs to be assessed, particularly in regions that are low-transmission settings and/or in pre-elimination and/or elimination phases. Various ongoing studies are focusing on the role of submicroscopic malaria infections in malaria transmission but overlook the possible build-up of resistance to antimalarial drugs among submicroscopic parasite populations. This is an important factor as it may eventually limit the effectiveness of malaria elimination strategies.ConclusionsAn evidence-based estimation of the “true” reservoir of resistant parasites can help target the existing and emerging foci of resistant parasites before they spread. Emergence and spread of artemisinin-resistant Plasmodium falciparum malaria in Southeast Asia underline the need to contain drug resistance.

37 NANP ve 4 NVDP Epitoplu Plasmodium falciparum Rekombinant Circumsporozoite Proteinin Ekspresyonu ve Moleküler Karakterizasyonu

Malaria is caused by the protozoan parasite Plasmodium, the leading cause of death amongst the parasitic diseases. The disease is transmitted to human by the bites of female Anopheles mosquitoes. According to the World Health Organization (WHO) data, there were an estimated 214 million malaria cases and estimated 438.000 deaths occurred worldwide, in 2015. It is observed that 90% of all the deaths due to malaria occur in Africa. 78% of these cases were children who are under five years old. Intensive malaria interventions helped to reduce malaria incidence by 37% between 2000 and 2015. Malaria is a curable disease if diagnosed and treated promptly and correctly. Drug resistance has developed against almost all anti-malarial drugs and an effective vaccine against malaria has not been developed yet. Vaccine studies initiated 40 years ago by sterile immunity against falciparum malaria through immunization by exposure to 1000 irradiated mosquitoes. Complex structures, complicated life cycles and various antigenic structures of Plasmodium species make vaccination studies difficult. Circumsporozoite protein (CSP), the most extensively studied protein is also present in the content of the vaccine candidate RTS,S which is currently closest to get license. CSP was the first described Plasmodium antigen because of its important role during initiation of the parasitic infection. CSP is the major surface coat protein of Plasmodium parasite. CSP is a soluble protein and recombinant form of the CSP can be produced in Escherichia coli. NANP repeat region is a target site for host antibodies. Recently many DNA, RNA and protein vaccine candidates are being developed against malaria. According to WHO, in the next 20 years period, malaria vaccine can be developed. In this study we aimed to produce recombinant CSP (rCSP). Initially, P.falciparum CSP gene was amplified by PCR. CSP gene was cloned in to the pJET cloning vector. The gene subcloned to the pET100 protein expression vector. E.coli cells were used for protein expression. After this process, purification and endotoxin removal protocols were performed. As a result, 1182 bp CSP gene was obtained from P.falciparum genomic DNA. Accuracy of cloning and DNA sequence of the CSP gene was determined with DNA sequence analysis. The gene sequence was recorded to the GenBank with a registration no KT315396. rCSP was expressed in E.coli cells. The existence of rCSP was verifiedwith Western Blot method and was purified and removed from endotoxins. rCSP aminoacid sequence and 3D shape was obtained.We believe that the production of recombinant CSP will enable us to contribute to the further malaria vaccine studies in our laboratory and country.

Progress Achieved in Gandhinagar District of Gujarat State for Elimination of Malaria, 2007 to 2015—A Case Study

Background: Government of India has lunched the frame work for eliminating malaria from the country by 2030 [1] [2]. But progressive States like Gujarat has to achieve the target by 2024. The first step in this direction is to bring down the Annual Parasitic Incidence less than 1.0. Under National Vector Borne Disease Control Programme (NVBDCP) various activities for Vector control coupled with complete treatment to confirm malaria cases within 24 hours were given more focus and implemented diligently and effectively. Aim: To evaluate the progress of the efforts being undertaken for malaria elimination in Gandhinagar district. Design: Impact of malaria control efforts in Gandhinagar district covering all areas were studied in detail. Setting: Malaria prone villages of Gandhinagar district where preventive actions were undertaken in an integrated manner during the period of 2005 to 2015. Exploratory: Data pertaining to rural and urban areas of the district covering all PHCs, UHCs and Towns were analyzed and interpreted. Outcome: Reduction in malaria incidence and scaling up of non chemical methods for control of malaria. Analysis: Percentage and proportions. Results: Area specific approach adopted in rural areas of Gandhinagar district by putting more emphasis on good surveillance, ensuring complete treatment to malaria cases within 24 hours and effective strategy for vector control mainly non chemical methods resulted in reducing Annual Parasitic Incidence (API) from 1.96 in 2005 to 0.17 in 2015 in Gandhinagar district. 226 villages (74.83%) out of 302 in the district are malaria free and only 9 villages are having API > 1.0. The district aims to achieve malaria elimination in the next five years. Conclusion: Gandhinagar district has made rapid stride towards malaria elimination in a cost effective manner by utilizing the available resources. The strategies adopted by the district can be replicated by other districts and States to achieve the goal of malaria elimination.

Generalized Linear Models of Malaria Incidence in Jubek State, South Sudan

Malaria is a leading cause of morbidity and mortality in South Sudan. This study is meant to focus on the trend of malaria incidence in Jubek state, South Sudan. Data on weekly malaria incidence for the period January 2011 to October 2015 were used in the study. Generalized linear models, Poisson and negative binomial regression models were employed to analyze the data. Results obtained suggest that malaria incidence has been still on increase by 0.0030 and 0.0032 per week respectively. Additionally, incidence rate ratio suggests an increase of 0.3% per week of malaria incidence in Jubek state. The study recommends malaria control programmes focused on reducing malaria incidence be introduced in South Sudan in general and in Jubek state in particular.

Predicting Malaria Risk and Utilization of Health Care Services among the Population in Uganda

Background: Incidence rate is the most commonly used direct measure of disease occurrences in the population at risk. Predicting malaria risk and utilization of health care services among the population is important in explaining the dynamics of the disease. Objective: The objective of this study was to predict malaria risk and utilization of health care services among the population in Uganda. Methods: We used a retrospective longitudinal study design that involved a secondary analysis of data from Ministry of Health (MoH) and Uganda Bureau of statistics (UBOS).The predicting model was derived taking limiting distribution of the partial derivative with respect to time of the malaria predicting model at the health facilities. Results: Our findings revealed that some of the infected individuals are infectious within the first 2 months but the infectiousness decreases with increasing time implying the individuals become susceptible again. The monthly model predicted new cases of malaria were more than the observed new cases of malaria. This implies that not all cases are routinely diagnosed and not all infected individuals in the population are seeking treatment for malaria at the health facilities. The observed new cases of malaria at the government facilities account for about 39% of the malaria risk in the population. Furthermore 61% of the new cases of malaria either sought treatment from non-government facilities or never sought treatment at all. Conclusions: The proposed model can be used to predict both the intensity and expected number of new cases of malaria at health facility and population level in the next month. The model can further be used to assess the monthly intensity of malaria; evaluate the effectiveness of the interventions in reducing the risk in the general population, and to provide timely statistics for better monitoring and design of targeted interventions that will reduce malaria incidence in Uganda. Therefore the observed stagnation in malaria incidence in the country could be attributable to the failure to monitor the 61% of the incidence that do not seek treatment from government health facilities.

Malaria morbidity and mortality trends in Manicaland province, Zimbabwe, 2005-2014.

IntroductionZimbabwe targets reducing malaria incidence from 22/1000 in 2012 to 10/1000 by 2017, and malaria deaths to near zero by 2017. As the country moves forward with the malaria elimination efforts, it is crucial to monitor trends in malaria morbidity and mortality in the affected areas. In 2013, Manicaland Province contributed 51% of all malaria cases and 35% of all malaria deaths in Zimbabwe. This analysis describes the trends in malaria incidence, case fatality and malaria outpatient workload compared to the general outpatient workload.MethodsWe analyzed routinely captured malaria data in Manicaland Province for the period 2005 to 2014. Epi Info version 7 was used to calculate chi-square trends for significance and Microsoft Excel was used to generate graphs. Permission to analyze the data was sought and granted by the Provincial Medical Directorate Institutional Review Board of Manicaland and the Health Studies office.ResultsMalaria morbidity data for the period 2005-2014 was reviewed and a total of 947,462 cases were confirmed during this period. However, malaria mortality data was only available for the period 2011-2014 and cumulatively 696 deaths were reported. Malaria incidence increased from 4.4/1,000 persons in 2005 to 116.3/1,000 persons in 2014 (p<0.001). The incidence was higher among females compared to males (p-trend<0.001) and among the above five years age group compared to the under-fives (p-trend<0.001). The proportion of all Outpatient Department attendances that were malaria cases increased 30 fold from 0.3% in 2005 to 9.1% in 2014 (p-trend<0.001). The Case Fatality Rate also increased 2-fold from 0.05 in 2011 to 0.1 in 2014 (p-trend<0.001).ConclusionDespite current malaria control strategies, the morbidity and mortality of malaria increased over the period under review. There is need for further strengthening of malaria control interventions to reduce the burden of the disease.

Results from the Workshop "Problem Formulation for the Use of Gene Drive in Mosquitoes".

Reducing the incidence of malaria has been a public health priority for nearly a century. New technologies and associated vector control strategies play an important role in the prospect of sustained reductions. The development of the CRISPR/Cas9 gene editing system has generated new possibilities for the use of gene-drive constructs to reduce or alter vector populations to reduce malaria incidence. However, before these technologies can be developed and exploited, it will be necessary to understand and assess the likelihood of any potential harms to humans or the environment. To begin this process, the Foundation for the National Institutes of Health and the International Life Sciences Institute Research Foundation organized an expert workshop to consider the potential risks related to the use of gene drives in Anopheles gambiae for malaria control in Africa. The resulting discussion yielded a series of consensus points that are reported here.

Time trends and changes in the distribution of malaria cases in the Brazilian Amazon Region, 2004-2013.

Recent efforts to reduce malaria incidence have had some successes. Nevertheless, malaria persists as a significant public health problem in the Brazilian Amazon. The objective of this study was to describe changes in malaria case characteristics and to identify trends in malaria incidence in the Brazilian Amazon. This study used data from the Malaria Epidemiological Surveillance and Case Notification Information System from 2004 to 2013. The annual parasite incidence (API) was calculated and joinpoint regression was used to assess the trends in API over time. There was a sharp increase in API in the state of Acre, followed by two periods of decrease. Pará also presented inconsistent decreases over the study period. Amapá, Amazonas, Rondônia, and Roraima showed statistically significant decreases over the period. The sharpest decrease occurred in Rondônia, with a reduction of 21.7% in the average annual percent change (AAPC) (AAPC: -21.7%; 95% confidence interval: -25.4%, -17.8%; p < 0.05). This panorama of malaria incidence highlights the importance of integrating evidence-based malaria surveillance and control. Malaria is highly preventable, and eliminating its transmission should be a goal in coming decades.

Analysis of Pvama1 genes from China-Myanmar border reveals little regional genetic differentiation of Plasmodium vivax populations.

BackgroundWith the premise of diminishing parasite genetic diversity following the reduction of malaria incidence, the analysis of polymorphic antigenic markers may provide important information about the impact of malaria control on local parasite populations. Here we evaluated the genetic diversity of Plasmodium vivax apical membrane antigen 1 (Pvama1) gene in a parasite population from the China-Myanmar border and compared it with global P. vivax populations.MethodsWe performed evolutionary analysis to examine the genetic diversity, natural selection, and population differentiation of 73 Pvama1 sequences acquired from the China-Myanmar border as well as 615 publically available Pvama1 sequences from seven global P. vivax populations.ResultsA total of 308 Pvama1 haplotypes were identified among the global P. vivax isolates. The overall nucleotide diversity of Pvama1 gene among the 73 China-Myanmar border parasite isolates was 0.008 with 41 haplotypes being identified (Hd = 0.958). Domain I (DI) harbored the majority (26/33) of the polymorphic sites. The McDonald Kreitman test showed a significant positive selection across the ectodomain and the DI of Pvama1. The fixation index (F ST) estimation between the China-Myanmar border, Thailand (0.01) and Myanmar (0.10) showed only slight geographical genetic differentiation. Notably, the Sal-I haplotype was not detected in any of the analyzed global isolates, whereas the Belem strain was restricted to the Thai population. The detected mutations are mapped outside the overlapped region of the predicted B-cell epitopes and intrinsically unstructured/disordered regions.ConclusionsThis study revealed high levels of genetic diversity of Pvama1 in the P. vivax parasite population from the China-Myanmar border with DI displaying stronger diversifying selection than other domains. There were low levels of population subdivision among parasite populations from the Greater Mekong Subregion.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1899-1) contains supplementary material, which is available to authorized users.

Effectiveness of Seasonal Malaria Chemoprevention in Children under Ten Years of Age in Senegal: A Stepped-Wedge Cluster-Randomised Trial.

BackgroundSeasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ), given each month during the transmission season, is recommended for children living in areas of the Sahel where malaria transmission is highly seasonal. The recommendation for SMC is currently limited to children under five years of age, but, in many areas of seasonal transmission, the burden in older children may justify extending this age limit. This study was done to determine the effectiveness of SMC in Senegalese children up to ten years of age.Methods and FindingsSMC was introduced into three districts over three years in central Senegal using a stepped-wedge cluster-randomised design. A census of the population was undertaken and a surveillance system was established to record all deaths and to record all cases of malaria seen at health facilities. A pharmacovigilance system was put in place to detect adverse drug reactions. Fifty-four health posts were randomised. Nine started implementation of SMC in 2008, 18 in 2009, and a further 18 in 2010, with 9 remaining as controls. In the first year of implementation, SMC was delivered to children aged 3–59 months; the age range was then extended for the latter two years of the study to include children up to 10 years of age. Cluster sample surveys at the end of each transmission season were done to measure coverage of SMC and the prevalence of parasitaemia and anaemia, to monitor molecular markers of drug resistance, and to measure insecticide-treated net (ITN) use. Entomological monitoring and assessment of costs of delivery in each health post and of community attitudes to SMC were also undertaken. About 780,000 treatments were administered over three years. Coverage exceeded 80% each month. Mortality, the primary endpoint, was similar in SMC and control areas (4.6 and 4.5 per 1000 respectively in children under 5 years and 1.3 and 1.2 per 1000 in children 5-9 years of age; the overall mortality rate ratio [SMC: no SMC] was 0.90, 95% CI 0.68–1.2, p = 0.496). A reduction of 60% (95% CI 54%–64%, p < 0.001) in the incidence of malaria cases confirmed by a rapid diagnostic test (RDT) and a reduction of 69% (95% CI 65%–72%, p < 0.001) in the number of treatments for malaria (confirmed and unconfirmed) was observed in children. In areas where SMC was implemented, incidence of confirmed malaria in adults and in children too old to receive SMC was reduced by 26% (95% CI 18%–33%, p < 0.001) and the total number of treatments for malaria (confirmed and unconfirmed) in these older age groups was reduced by 29% (95% CI 21%–35%, p < 0.001). One hundred and twenty-three children were admitted to hospital with a diagnosis of severe malaria, with 64 in control areas and 59 in SMC areas, showing a reduction in the incidence rate of severe disease of 45% (95% CI 5%–68%, p = 0.031). Estimates of the reduction in the prevalence of parasitaemia at the end of the transmission season in SMC areas were 68% (95% CI 35%–85%) p = 0.002 in 2008, 84% (95% CI 58%–94%, p < 0.001) in 2009, and 30% (95% CI -130%–79%, p = 0.56) in 2010. SMC was well tolerated with no serious adverse reactions attributable to SMC drugs. Vomiting was the most commonly reported mild adverse event but was reported in less than 1% of treatments. The average cost of delivery was US$0.50 per child per month, but varied widely depending on the size of the health post. Limitations included the low rate of mortality, which limited our ability to detect an effect on this endpoint.ConclusionsSMC substantially reduced the incidence of outpatient cases of malaria and of severe malaria in children, but no difference in all-cause mortality was observed. Introduction of SMC was associated with an overall reduction in malaria incidence in untreated age groups. In many areas of Africa with seasonal malaria, there is a substantial burden in older children that could be prevented by SMC. SMC in older children is well tolerated and effective and can contribute to reducing malaria transmission.Trial RegistrationClinicalTrials.gov NCT00712374

Insecticide resistance in Anopheles mosquitoes: additional obstacles in the battle against malaria.

Mosquitoes of the genus Anopheles are malaria vectors in tropical areas and were of course designated as primary targets by programs for malaria control. Repellent sprays, indoor use of insecticides, and massive delivery of mosquito nets are standard examples of the means widely used to combat malaria. This synthetic review supplies an overview of all of the modes of resistance developed by Anopheles mosquitoes against these human actions. The misuse of each available tool has gradually led to a decrease in its global effectiveness. Newly-emerging forms of resistance, due to modification or overexpression of molecular targets, as well as behavioral adaptations by mosquitoes, are some examples of the consequences. To enable a categorical reduction in malaria incidence, a thorough adjustment of the use of the various means of control should be envisioned.

Assessment of the impact of the malaria elimination programme on the burden of disease morbidity in endemic areas of Iran.

BackgroundControlling and preventive measures considerably reduced malaria incidence in Iran over the past few years, which confined the endemic areas to some regions in the southeastern Iran. The National Malaria Elimination Programme commenced in 2010. With regard to the presumption that the elimination programme interventions have accelerated the declining trend of malaria incidence across the endemic areas of Iran, the present study attempted to assess the effectiveness of the elimination programme by reviewing malaria incidence status, over a 14-year period, and comparing the trend of malaria incidence across malaria-endemic areas between the control and pre-elimination phase, and the elimination phase.MethodsA retrospective analysis of malaria surveillance data was conducted in a 14-year period (2001–2014), using multilevel Poisson regression. The epidemiological malaria maps and indicators also were developed and compared between the control and pre-elimination phase, and the elimination phase.ResultsThe mean of malaria incidence was 2.2 (1.7–2.7) for the entire study period. This rate was 3.4 (2.6–4.1) in the control and pre-elimination phase, and 0.41 (0.25–0.57) for the elimination phase. During the malaria elimination phase, the decline of annual malaria incidence had significantly accelerated and autochthonous cases had the greatest difference in malaria incidence decline (compared to the control and pre-elimination phase), whereas, falciparum cases had the lowest difference in malaria incidence decline, followed by non-Iranian and imported cases. Furthermore, there was a decline in Iranians to non-Iranians ratio and an increase in the ratios of over 15 to under 15, as well as male to female, in the elimination phase in comparison to the control and pre-elimination phase.ConclusionsIt seems that the decline of malaria transmission, which has been initiated over the past few years, has accelerated as a result of the elimination programme, and Iran is approaching the goals set regarding the elimination of this disease.

Effective Antimalarial Chemoprevention in Childhood Enhances the Quality of CD4+ T Cells and Limits Their Production of Immunoregulatory Interleukin 10.

Experimental inoculation of viable Plasmodium falciparum sporozoites administered with chemoprevention targeting blood-stage parasites results in protective immunity. It is unclear whether chemoprevention similarly enhances immunity following natural exposure to malaria. We assessed P. falciparum-specific T-cell responses among Ugandan children who were randomly assigned to receive monthly dihydroartemisinin-piperaquine (DP; n = 87) or no chemoprevention (n = 90) from 6 to 24 months of age, with pharmacologic assessments for adherence, and then clinically followed for an additional year. During the intervention, monthly DP reduced malaria episodes by 55% overall (P < .001) and by 97% among children who were highly adherent to DP (P < .001). In the year after the cessation of chemoprevention, children who were highly adherent to DP had a 55% reduction in malaria incidence as compared to children given no chemoprevention (P = .004). Children randomly assigned to receive DP had higher frequencies of blood-stage specific CD4(+) T cells coproducing interleukin-2 and tumor necrosis factor α (P = .003), which were associated with protection from subsequent clinical malaria and parasitemia, and fewer blood-stage specific CD4(+) T cells coproducing interleukin-10 and interferon γ (P = .001), which were associated with increased risk of malaria. In this setting, effective antimalarial chemoprevention fostered the development of CD4(+) T cells that coproduced interleukin 2 and tumor necrosis factor α and were associated with prospective protection, while limiting CD4(+) T-cell production of the immunoregulatory cytokine IL-10.

Reduction in Malaria Incidence following Indoor Residual Spraying with Actellic 300 CS in a Setting with Pyrethroid Resistance: Mutasa District, Zimbabwe.

BackgroundMore than half of malaria cases in Zimbabwe are concentrated in Manicaland Province, where seasonal malaria epidemics occur despite intensified control strategies. Recently, high levels of pyrethroid and carbamate resistance were detected in Anopheles funestus, the major malaria vector in eastern Zimbabwe. In response, a single round of indoor residual spraying (IRS) using pirimiphos-methyl (an organophosphate) was implemented in four high burden districts of Manicaland Province from November 1, 2014 to December 19, 2014. The objective of this study was to evaluate the effect of this programmatic switch in insecticides on malaria morbidity reported from health care facilities in Mutasa District, one of the worst affected districts in Manicaland Province.MethodsThe number of weekly malaria cases for each health facility 24 months prior to the 2014 IRS campaign and in the subsequent high transmission season were obtained from passive case surveillance. Environmental variables were extracted from remote-sensing data sources and linked to each health care facility. Negative binomial regression was used to model the weekly number of malaria cases, adjusted for seasonality and environmental variables.ResultsFrom December 2012 to May 2015, 124,206 malaria cases were reported from 42 health care facilities in Mutasa District. Based on a higher burden of malaria, 20 out of 31 municipal wards were sprayed in the district. Overall, 87.3% of target structures were sprayed and 92.1% of the target population protected. During the 6 months after the 2014 IRS campaign, a period when transmission would have otherwise peaked, the incidence of malaria was 38% lower than the preceding 24 months at health facilities in the sprayed wards.ConclusionsPirimiphos-methyl had a measurable impact on malaria incidence and is an effective insecticide for the control of An. funestus in eastern Zimbabwe.

Knowledge, attitudes and practices regarding malaria in the indigenous Guna population of the Madungandí region, Panamá, 2012

Knowledge, attitudes and practices surveys allow to determine the degree of knowledge on the management of malaria in a given population, as well as the attitudes and practices that contribute or not to its transmission. To identify the knowledge, attitudes and practices that favor or not the transmission of malaria in the indigenous Guna population of Madungandí. A cross-sectional study was conducted by applying a survey to the heads of the families in a sample of 40% of households in three communities with high malaria incidence. Local Guna residents and translators were part of the research team that applied the questionnaires. The statistical analysis was performed in Epi-Info 6.04. The age range of those surveyed was between 20 and 70 years. All responders indicated that they belonged to and spoke the language of the Guna ethnic group, 64% were male and 30% were illiterate. Half (51%) of the responders declared they had suffered malaria at least once in the last eight years, and 89% accepted that malaria was a health problem. Sixty-three per cent responded that their traditional doctors, “inadule”, cured malaria and 7.0 % practiced the “pipe smoking” and “cocoa burn” rituals to prevent the disease. Considering the limited knowledge about malaria and its vector, as well as the willingness to collaborate shown by the Guna population, it is essential to initiate educational and participative programs to improve control and prevention activities in the communities aimed at achieving a reduction in malaria incidence in the Madungandí indigenous region.

Measuring the association between artemisinin-based case management and malaria incidence in southern Vietnam, 1991-2010.

In addition to being effective, fast-acting, and well tolerated, artemisinin-based combination therapies (ACTs) are able to kill certain transmission stages of the malaria parasite. However, the population-level impacts of ACTs on reducing malaria transmission have been difficult to assess. In this study on the history of malaria control in Vietnam, we assemble annual reporting on malaria case counts, coverage with insecticide-treated nets (ITN) and indoor residual spraying (IRS), and drug purchases by provincial malaria control programs from 1991 to 2010 in Vietnam's 20 southern provinces. We observe a significant negative association between artemisinin use and malaria incidence, with a 10% absolute increase in the purchase proportion of artemisinin-containing regimens being associated with a 29.1% (95% confidence interval: 14.8–41.0%) reduction in slide-confirmed malaria incidence, after accounting for changes in urbanization, ITN/IRS coverage, and two indicators of health system capacity. One budget-related indicator of health system capacity was found to have a smaller association with malaria incidence, and no other significant factors were found. Our findings suggest that including an artemisinin component in malaria drug regimens was strongly associated with reduced malaria incidence in southern Vietnam, whereas changes in urbanization and coverage with ITN or IRS were not.