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Additional vector control tools (VCTs) are needed to supplement insecticide-treated nets (ITNs) and indoor residual spraying (IRS) to achieve malaria elimination in many settings. To identify options for expanding the malaria vector control toolbox, we conducted a systematic review of the availability and quality of the evidence for 21 malaria VCTs, excluding ITNs and IRS.Six electronic databases and grey literature sources were searched from January 1, 1980 to September 28, 2015 to identify systematic reviews, Phase I-IV studies, and observational studies that measured the effect of malaria VCTs on epidemiological or entomological outcomes across any age groups in all malaria-endemic settings. Eligible studies were summarized qualitatively, with quality and risk of bias assessments undertaken where possible. Of 17,912 studies screened, 155 were eligible for inclusion and were included in a qualitative synthesis.Across the 21 VCTs, we found considerable heterogeneity in the volume and quality of evidence, with 7 VCTs currently supported by at least one Phase III community-level evaluation measuring parasitologically confirmed malaria incidence or infection prevalence (insecticide-treated clothing and blankets, insecticide-treated hammocks, insecticide-treated livestock, larval source management (LSM), mosquito-proofed housing, spatial repellents, and topical repellents). The remaining VCTs were supported by one or more Phase II (n=13) or Phase I evaluation (n=1). Overall the quality of the evidence base remains greatest for LSM and topical repellents, relative to the other VCTs evaluated, although existing evidence indicates that topical repellents are unlikely to provide effective population-level protection against malaria.Despite substantial gaps in the supporting evidence, several VCTs may be promising supplements to ITNs and IRS in appropriate settings. Strengthening operational capacity and research to implement underutilized VCTs, such as LSM and mosquito-proofed housing, using an adaptive, learning-by-doing approach, while expanding the evidence base for promising supplementary VCTs that are locally tailored, should be considered central to global malaria elimination efforts.

Background: Additional vector control tools (VCTs) are needed to supplement insecticide-treated nets (ITNs) and indoor residual spraying (IRS) to achieve malaria elimination in many settings. To identify options for expanding the malaria vector control toolbox, we conducted a systematic review of the availability and quality of the evidence for 21 malaria VCTs, excluding ITNs and IRS. Methods: Six electronic databases and grey literature sources were searched from January 1, 1980 to September 28, 2015 to identify systematic reviews, Phase I–IV studies, and observational studies that measured the effect of malaria VCTs on epidemiological or entomological outcomes across any age groups in all malaria-endemic settings. Eligible studies were summarized qualitatively, with quality and risk of bias assessments undertaken where possible. Of 17,912 studies screened, 155 were eligible for inclusion and were included in a qualitative synthesis. Results: Across the 21 VCTs, we found considerable heterogeneity in the volume and quality of evidence, with 7 VCTs currently supported by at least one Phase III community-level evaluation measuring parasitologically confirmed malaria incidence or infection prevalence (insecticide-treated clothing and blankets, insecticide-treated hammocks, insecticide-treated livestock, larval source management (LSM), mosquito-proofed housing, spatial repellents, and topical repellents). The remaining VCTs were supported by one or more Phase II (n = 13) or Phase I evaluation (n = 1). Overall the quality of the evidence base remains greatest for LSM and topical repellents, relative to the other VCTs evaluated, although existing evidence indicates that topical repellents are unlikely to provide effective population-level protection against malaria. Conclusions: Despite substantial gaps in the supporting evidence, several VCTs may be promising supplements to ITNs and IRS in appropriate settings. Strengthening operational capacity and research to implement underutilized VCTs, such as LSM and mosquito-proofed housing, using an adaptive, learning-by-doing approach, while expanding the evidence base for promising supplementary VCTs that are locally tailored, should be considered central to global malaria elimination efforts.

Background Haemolysis risk with single dose or short course primaquine was evaluated in glucose-6-phosphate dehydrogenase (G6PD) deficient people. Methods Major electronic databases (to August 2016) were searched for single or short course 8-aminoquinolines (8-AQ) in (1) randomized comparisons against placebo in G6PD deficient people; and (2) observational comparisons in G6PD deficient compared to replete people. Two authors independently assessed eligibility, risk-of-bias, and extracted data. Results Five randomized controlled trials and four controlled observational cohorts were included. In G6PD deficient individuals, high-dose (0.75 mg/kg) PQ resulted in lower average haemoglobin levels at 7 days (mean difference [MD] −1.45 g/dl, 95% CI −2.17 to −0.74, 2 trials) and larger percentage fall from baseline to day 7 (MD −10.31%, 95% CI −17.69 to −2.92, 3 trials) compared to placebo. In G6PD deficient compared to replete people, average haemoglobin was lower at 7 days (MD −1.19 g/dl, 95% CI −1.94 to −0.44, 2 trials) and haemoglobin change from baseline to day 7 was greater (MD −9.10%, 95% CI −12.55 to −5.65, 5 trials). One small trial evaluated mid-range PQ dose (0.4–0.5 mg/kg) in G6PD deficient people, with no difference detected in average haemoglobin at day 7 compared to placebo. In one cohort comparing G6PD deficient and replete people there was a greater fall with G6PD deficiency (MD −4.99%, 95% CI −9.96 to −0.02). For low-dose PQ (0.1–0.25 mg/kg) in G6PD deficient people, haemoglobin change from baseline was similar to the placebo group (MD 1.72%, 95% CI −1.89 to 5.34, 2 trials). Comparing low dose PQ in G6PD deficient with replete people, the average haemoglobin was lower in the G6PD deficient group at 7 days (−0.57 g (95% CI −0.97 to −0.17, 1 trial)); although change from baseline was similar (MD −1.45%, 95% CI −5.69 to 2.78, 3 trials). Conclusions Falls in average haemoglobin are less marked with the 0.1 to 0.25 mg/kg PQ than with the 0.75 mg/kg dose, and severe haemolytic events are not common. However, data were limited and the evidence GRADE was low or very low certainty. Electronic supplementary material The online version of this article (doi:10.1186/s12936-017-1989-3) contains supplementary material, which is available to authorized users.

Background: Malaria is a leading cause of morbidity in Ethiopia. However, its transmission varies in both space and time, and large areas of the country are hypoendemic and epidemic-prone. The Ethiopia National Malaria Indicator Survey 2007 is a cross-sectional, nationally-representative household survey. The objective of the analyses presented here were to use the survey's data to identify factors associated with anemia presence in children under 6 years of age (U6); specifically, investigate the association between malaria and anemia; and discuss using anemia as a malaria proxy biomarker in the Ethiopian hypo-endemic transmission setting. Methods: The survey sampled 4185 households in 347 enumeration areas ≤2500 m above sea level. Primary outcome was increasing anemia severity in sampled children: no anemia (Hb: ≥11g/dl); mild anemia (Hb: ≥8g/dl and

In their Article Dicko and colleagues1 state that both primaquine and methylene blue were “highly efficacious for preventing Plasmodium falciparum transmission” when given alongside primary malaria treatment, implying an effect on malaria transmission in the community. However, the trial measured the infectiousness of individuals to mosquitoes, which is several steps removed from the dynamics of disease transmission. Other trials have also measured whether individuals are less infectious to mosquitoes after treatment with a gametocytocidal agent, but none have measured an effect on transmission in the community, the outcome of real interest.

We assessed malaria infection in relation to age, altitude, rainfall, socio-economic factors and coverage of control measures in a representative sample of 11437 people in Amhara, Oromia and SNNP regions of Ethiopia in December 2006-January 2007. Surveys were conducted in 224 randomly selected clusters of 25 households (overall sample of 27884 people in 5708 households). In 11538 blood slides examined from alternate households (83% of those eligible), malaria prevalence in people of all ages was 4.1% (95% CI 3.4-4.9), with 56.5% of infections being Plasmodium falciparum. At least one mosquito net or one long-lasting insecticidal net (LLIN) was present in 37.0% (95% CI 31.1-43.3) and 19.6% (95% CI 15.5-24.5) of households, respectively. In multivariate analysis (n=11437; 82% of those eligible), significant protective factors were: number of LLINs per household (odds ratio [OR] (per additional net)=0.60; 95% CI 0.40-0.89), living at higher altitude (OR (per 100 m)=0.95; 95% CI 0.90-1.00) and household wealth (OR (per unit increase in asset index)=0.79; 95% CI 0.66-0.94). Malaria prevalence was positively associated with peak monthly rainfall in the year before the survey (OR (per additional 10 mm rain)=1.10; 95% CI 1.03-1.18). People living above 2000 m and people of all ages are still at significant risk of malaria infection.

This article highlights systematic reviews of malaria research and what has been learned about applying methods of research synthesis in this particular infectious disease over the last 15 years. It illustrates how systematic reviews have been used to guide policy, shows what has been learned about synthesizing research in this area, and reflects on how best to maximize their uptake in policy and practice.

Objective: To assess the effectiveness of impregnated mosquito nets, indoor residual spraying and larval control relative to the impacts of climate variability in the decline of malaria cases in Eritrea. Methods: Monthly data on clinical malaria cases by subzoba (district) in three zobas (zones) of Eritrea for 1998–2003 were used in Poisson regression models to determine whether there is statistical evidence for reduction in cases by DDT, malathion, impregnated nets and larval control used over the period, while analysing the effects of satellite-derived climate variables in the same geographic areas. Results: Both indoor residual spraying (with DDT or malathion) and impregnated nets were independently and significantly negatively associated with reduction in cases, as was larval control in one zoba. Malaria cases were significantly positively related to differences in current and previous months’ vegetation (NDVI) anomalies. The relationship to rainfall differences 2 and 3 months previously was also significant, but the direction of the effect varied by zoba. Standardized regression coefficients indicated a greater effect of climate in the zoba with less intense malaria transmission. Conclusion: The results support the view that both indoor residual spraying and impregnated nets have been independently effective against malaria, and that larval control was also effective in one area. Thus climate, while significant, is not the only explanation for the recent decline in malaria cases in Eritrea. If appropriate statistical approaches are used, routine surveillance data from cases attending health facilities can be useful for assessing control programme success and providing estimates of the effectiveness of individual control measures. Effectiveness estimates suitable for use in cost-effectiveness analysis have been obtained.

Millions of long-lasting insecticide treated nets (LLINs) have been distributed as part of the global malaria control strategy. LLIN ownership, however, does not necessarily guarantee use. Thus, even in the ideal setting in which universal coverage with LLINs has been achieved, maximal malaria protection will only be achieved if LLINs are used both correctly and consistently. This study investigated the factors associated with net use, independent of net ownership. Data were collected during a household survey conducted in Ebonyi State in southeastern Nigeria in November 2011 following a statewide mass LLIN distribution campaign and, in select locations, a community-based social behavior change (SBC) intervention. Logistic regression analyses, controlling for household bed net ownership, were conducted to examine the association between individual net use and various demographic, environmental, behavioral and social factors. The odds of net use increased among individuals who were exposed to tailored SBC in the context of a home visit (OR = 17.11; 95% CI 4.45–65.79) or who received greater degrees of social support from friends and family (ptrend < 0.001). Factors associated with decreased odds of net use included: increasing education level (ptrend = 0.020), increasing malaria knowledge level (ptrend = 0.022), and reporting any disadvantage of bed nets (OR = 0.39; 95% CI 0.23–0.78). The findings suggest that LLIN use is significantly influenced by social support and exposure to a malaria-related SBC home visit. The malaria community should thus further consider the importance of community outreach, interpersonal communication and social support on adoption of net use behaviors when designing future research and interventions.

The Malaria Policy Advisory Committee to the World Health Organization held its sixth meeting in Geneva, Switzerland from 10 to 12 September 2014. This article provides a summary of the discussions, conclusions and recommendations from that meeting. Meeting sessions covered the following: an update on drug resistance and containment including an assessment on the feasibility of elimination of Plasmodium falciparum malaria in the Greater Mekong Subregion; guidance on the control of residual malaria transmission by behaviourally resistant vectors; progress on the implementation of the Global Plan for Insecticide Resistance Management; updates on the Global Technical Strategy, Global Malaria Action Plan and the Plasmodium vivax technical brief; gaps in current World Health Organization Global Malaria Programme guidance for acceleration to elimination; surveillance, monitoring and evaluation; the updated World Health Organization Guidelines for the Prevention and Treatment of Malaria; Round 5 product testing for rapid diagnostic tests; and Intermittent Preventive Treatment for infants. Policy statements, position statements, and guidelines that arise from the Malaria Policy Advisory Committee meeting conclusions and recommendations will be formally issued and disseminated to World Health Organization Member States by the World Health Organization Global Malaria Programme.

Background The 8-aminoquinoline (8AQ) drugs act on Plasmodium falciparum gametocytes, which transmit malaria from infected people to mosquitoes. In 2012, the World Health Organization (WHO) recommended a single dose of 0.25 mg/kg primaquine (PQ) be added to malaria treatment schedules in low-transmission areas or those with artemisinin resistance. This replaced the previous recommendation of 0.75 mg/kg, aiming to reduce haemolysis risk in people with glucose-6-phosphate dehydrogenase deficiency, common in people living in malarious areas. Whether this approach, and at this dose, is effective in reducing transmission is not clear. Objectives To assess the effects of single dose or short-course PQ (or an alternative 8AQ) alongside treatment for people with P. falciparum malaria. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; and the WHO International Clinical Trials Registry Platform (ICRTP) portal using ‘malaria*', ‘falciparum', ‘primaquine', ‘8-aminoquinoline', and eight 8AQ drug names as search terms. We checked reference lists of included trials, and contacted researchers and organizations. Date of last search: 21 July 2017. Selection criteria Randomized controlled trials (RCTs) or quasi-RCTs in children or adults, adding PQ (or alternative 8AQ) as a single dose or short course alongside treatment for P. falciparum malaria. Data collection and analysis Two authors screened abstracts, applied inclusion criteria, and extracted data. We sought evidence on transmission (community incidence), infectiousness (people infectious and mosquitoes infected), and potential infectiousness (gametocyte measures assessed by microscopy or polymerase chain reaction [PCR]). We grouped trials into artemisinin and non-artemisinin treatments, and stratified by PQ dose (low, 0.2 to 0.25 mg/kg; moderate, 0.4 to 0.5 mg/kg; high, 0.75 mg/kg). We used GRADE, and absolute effects of infectiousness using trial control groups. Main results We included 24 RCTs and one quasi-RCT, comprising 43 arms. Fourteen trials evaluated artemisinin treatments (23 arms), nine trials evaluated non-artemisinin treatments (13 arms), and two trials included both artemisinin and non-artemisinin arms (three and two arms, respectively). Two trial arms used bulaquine. Seven PQ arms used low dose (six with artemisinin), 11 arms used moderate dose (seven with artemisinin), and the remaining arms used high dose. Fifteen trials tested for G6PD status: 11 excluded participants with G6PD deficiency, one included only those with G6PD deficiency, and three included all, irrespective of status. The remaining 10 trials either did not test or did not report on testing. No cluster trials evaluating community effects on malaria transmission met the inclusion criteria. With artemisinin treatment Low dose PQ Infectiousness (participants infectious to mosquitoes) was reduced (day 3 or 4: RR 0.12, 95% CI 0.02 to 0.88, 3 trials, 105 participants; day 8: RR 0.34, 95% CI 0.07 to 1.58, 4 trials, 243 participants; low certainty evidence). This translates to a reduction in percentage of people infectious on day 3 or 4 from 14% to 2%, and, for day 8, from 4% to 1%; the waning infectiousness in the control group by day 8 making the absolute effect smaller by day 8. For gametocytes detected by PCR, there was little or no effect of PQ at day 3 or 4 (RR 1.02, 95% CI 0.87 to 1.21; 3 trials, 414 participants; moderate certainty evidence); with reduction at day 8 (RR 0.52, 95% CI 0.41 to 0.65; 4 trials, 532 participants; high certainty evidence). Severe haemolysis was infrequent, with or without PQ, in these groups with few G6PD-deficient individuals (RR 0.98, 95% CI 0.69 to 1.39; 4 trials, 752 participants, moderate certainty evidence). Moderate dose PQ Infectiousness was reduced (day 3 or 4: RR 0.13, 95% CI 0.02 to 0.94; 3 trials, 109 participants; day 8 RR 0.33, 95% CI 0.07 to 1.57; 4 trials, 246 participants; low certainty evidence). Illustrative risk estimates for moderate dose were the same as low dose. The pattern and level of certainty of evidence with gametocytes detected by PCR was the same as low dose, and severe haemolysis was infrequent in both groups. High dose PQ Infectiousness was reduced (day 4: RR 0.2, 95% CI 0.02 to 1.68, 1 trial, 101 participants; day 8: RR 0.18, 95% CI 0.02 to 1.41, 2 trials, 181 participants, low certainty evidence). The effects on gametocyte prevalence showed a similar pattern to moderate and low dose PQ. Trials did not systematically report evidence of haemolysis. With non-artemisinin treatment Trials with non-artemisinin treatment have been conducted only for moderate and high dose PQ. With high dose, infectiousness appeared markedly reduced on day 5 (RR 0.09, 95% CI 0.01 to 0.62; 30 participants, very low certainty evidence), with similar reductions at day 8. For both moderate dose (two trials with 221 people) and high dose (two trials with 30 people), reduction in gametocytes (detected by microscopy) showed similar patterns as for artemisinin treatments, with little or no effect at day 4 or 5, and larger effects by day 8. No trials with non-artemisinin partner drugs systematically sought evidence of severe haemolysis. Two trials comparing bulaquine with PQ suggest bulaquine may have larger effects on gametocytes by microscopy on day 8 (RR 0.41, 95% CI 0.26 to 0.66; 2 trials, 112 participants). Authors' conclusions A single low dose of PQ (0.25 mg/kg) added to artemisinin-based combination therapy for malaria reduces infectiousness of people to mosquitoes at day 3-4 and day 8, and appears as effective as higher doses. The absolute effect is greater at day 3 or 4, and smaller at day 8, in part because of the lower infectiousness in the control group. There was no evidence of increased haemolysis at 0.25 mg/kg, but few G6PD-deficient individuals were included in the trials. The effect on infectiousness precedes the effect of PQ on gametocyte prevalence. We do not know whether single dose PQ could reduce malaria transmission at community level. What is the aim of this review? To assess the effects of adding a single dose of primaquine (PQ) to treatment for falciparum malaria to reduce disease transmission. This Cochrane Review update includes 25 controlled trials. The date of latest search was 21 July 2017. Key messages A single low dose of PQ, at 0.25 mg/kg, which the World Health Organization (WHO) recommends adding to artemisinin-based combination therapy for malaria, reduces infectiousness (transmission from people to mosquitoes). In the trials, the percentage of people who infected mosquitoes three to four days after treatment was reduced from 14% to 2%, with a smaller effect at day 8, from 4% to 1%, with no evidence of harm. What was studied in the review PQ kills gametocytes (malaria transmission stages) of the falciparum malaria parasite. Gametocytes infect mosquitoes during a bite, thus perpetuating transmission. There is concern that PQ may cause red blood cells to burst (haemolysis) in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency, a genetically-determined condition common in many malaria-endemic settings, which can lead to anaemia. Recognizing concerns about the risk of haemolysis, the WHO reduced the recommended PQ dose from 0.75 mg/kg to 0.25 mg/kg in 2012. Ideally, this approach would be tested by randomly assigning villages to standard malaria treatment, or standard treatment plus a low dose of PQ, then measuring the effect on malaria over time but this would be difficult and expensive. So, indirect indicators are used to shed light on effectiveness, including feeding studies, in which mosquitoes are allowed to feed on people (or their blood), comparing those who were assigned PQ with those who were not. Alternatively, researchers may simply monitor the presence (prevalence), number (density), and duration (time of persistence) of gametocytes in the blood of people after different treatments, assuming that gametocytes are viable irrespective of exposure to PQ. What the research says The 25 included trials span several decades and include a variety of treatments and PQ doses. Related to safety assessment, some trials tested participants for G6PD activity. Other trials reported results based on their G6PD status, others did not test (or did not say whether they did), and others tested and excluded people with G6PD deficiency. There were no ideal community-level studies that would answer the question directly. Five feeding trials with multiple arms included three low-dose, three medium-dose, and two high-dose comparisons, showing a markedly reduced proportion of people infectious who received PQ in trials with any events. Two trials using older malaria treatments and high dose PQ had similar results. The other trials focused on indirect measures of potential infectiousness of humans to mosquitoes. In these trials, PQ shortened the period of potential infectiousness, with a lower prevalence and density of gametocytes up to day 8 after treatment. The effect was similar at all PQ dose levels. Few serious haemolytic events occurred in these trials, but PQ did affect non-serious haemoglobin measures, even at low doses. What are the main results of the review? A single low dose of PQ added to an artemisinin regimen for malaria reduces infectiousness to mosquitoes and is relatively safe for most people. PQ at WHO-recommended dose reduces infectiousness to mosquitoes on day 3-4 and day 8 with no evidence of harm. It is unclear whether this reduction would materially reduce malaria transmission in communities.

A parasitological cross-sectional survey was undertaken from September 2000 through February 2001 to estimate the prevalence of malaria parasitemia in Eritrea. A total of 12,937 individuals from 176 villages were screened for both Plasmodium falciparum and Plasmodium vivax parasite species using the OptiMal Rapid Diagnostic Test. Malaria prevalence was generally low but highly focal and variable with the proportion of parasitemia at 2.2% (range: 0.4% to 6.5%). Despite no significant differences in age or sex-specific prevalence rates, 7% of households accounted for the positive cases and 90% of these were P. falciparum. Multivariate regression analyses revealed that mud walls were positively associated with malaria infection (OR [odds ratio] = 1.6 [95% CI: 1.2, 2.2], P < 0.008). For countries with low and seasonal malaria transmission, such information can help programs design improved strategic interventions.

Papua New Guinea (PNG) has a significant malaria burden, is resource constrained, and has isolated populations with limited access to health services. Home-based management is a key element of the national program that supports strategies of early detection, diagnosis and treatment. We describe the epidemiology of malaria near Lake Kutubu in the Southern Highlands Province through reported data on suspected and confirmed malaria in patients accessing public health facilities or using a novel, incentivised, social marketing approach for malaria treatment at the village level. Monthly case data reported by nine health facilities and 14 village-based providers, known as Marasin Stoa Kipas (MSK), were extracted from outpatient registers and MSK malaria case forms. Descriptive statistics of diagnostic use, monthly incidence, test positivity rate and species distribution were estimated. Summary statistics of service delivery demonstrate patient access and diagnostic coverage in program areas. From May 2005 to September 2013, 15,726 individuals were tested with either rapid diagnostic test and/or microscopy at health facilities, and 42% had a positive result for malaria (n = 6604); of these 67.1% (n = 4431) were positive for P. falciparum (alone or mixed) and 32.9% were positive for non-P. falciparum species (alone or mixed). From October 2007 to September 2013, 9687 individuals were tested with either RDT and/or microscopy at MSK sites and 44.2% (n = 4283) tested positive for malaria; of these, 65.3% (n = 2796) were positive for P. falciparum, while 34.7% (n = 1487) were positive for non-P. falciparum species. Up to April 2010 there was an intermittent and upward trend in the reported incidence of all species of confirmed malaria, reaching 50 per 1000 population per month for both sites combined, followed by a steady decline to four per 1000 population per month in 2013, with P. vivax the most common infection. This study is the most recent longitudinal overview of malaria in the Southern Highlands since 2003. It outlines patient access to a community-based model of care. The analysis shows changes in health facility versus MSK use, a strongly decreasing trend in incidence of confirmed malaria from 2010 to 2013, and a shift from predominantly P. falciparum to P. vivax infection.

Background: Mosquitoes become infected with Plasmodium when they ingest gametocyte-stage parasites from an infected person's blood. Plasmodium falciparum gametocytes are sensitive to the drug primaquine (PQ) and other 8-aminoquinolines (8AQ); these drugs could prevent parasite transmission from infected people to mosquitoes, and consequently reduce the incidence of malaria. However, PQ will not directly benefit the individual, and could be harmful to those with glucose-6-phosphate dehydrogenase (G6PD) deficiency. In 2010, The World Health Organization (WHO) recommended a single dose of PQ at 0.75 mg/kg, alongside treatment for P. falciparum malaria to reduce transmission in areas approaching malaria elimination. In 2013 the WHO revised this to 0.25 mg/kg due to concerns about safety. Objectives To assess whether giving PQ or an alternative 8AQ alongside treatment for P. falciparum malaria reduces malaria transmission, and to estimate the frequency of severe or haematological adverse events when PQ is given for this purpose. Search methods: We searched the following databases up to 10 Feb 2014 for trials: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; LILACS; metaRegister of Controlled Trials (mRCT); and the WHO trials search portal using 'malaria*', 'falciparum', and 'primaquine' as search terms. In addition, we searched conference proceedings and reference lists of included studies, and contacted researchers and organizations. Selection criteria Randomized controlled trials (RCTs) or quasi-RCTs comparing PQ (or alternative 8AQ) given as a single dose or short course alongside treatment for P. falciparum malaria with malaria treatment given without PQ/8AQ in adults or children. Data collection and analysis Two authors independently screened all abstracts, applied inclusion criteria, and extracted data. We sought evidence of an impact on transmission (community incidence), infectiousness (mosquitoes infected from humans) and potential infectiousness (gametocyte measures). We calculated the area under the curve (AUC) for gametocyte density over time for comparisons for which data were available. We sought data on haematological and other adverse effects, as well as secondary outcomes of asexual clearance time and recrudescence. We stratified by whether the malaria treatment regimen included an artemisinin derivative or not; by PQ dose category (low < 0.4 mg/kg; medium ≥ 0.4 to < 0.6 mg/kg; high ≥ 0.6 mg/kg); and by PQ schedules. We used the GRADE approach to assess evidence quality. Main results: We included 17 RCTs and one quasi-RCT. Eight studies tested for G6PD status: six then excluded participants with G6PD deficiency, one included only those with G6PD deficiency, and one included all irrespective of status. The remaining ten trials either did not report on whether they tested (8), or reported that they did not test (2). Nine trials included study arms with artemisinin-based malaria treatment regimens, and eleven included study arms with non-artemisinin-based treatments. Only two trials evaluated PQ given at low doses (0.25 mg/kg in one and 0.1 mg/kg in the other). PQ with artemisinin-based treatments: No trials evaluated effects on malaria transmission directly (incidence, prevalence, or entomological inoculation rate), and none evaluated infectiousness to mosquitoes. For potential infectiousness, the proportion of people with detectable gametocytaemia on day eight was reduced by around two thirds with high dose PQ category (RR 0.29, 95% CI 0.22 to 0.37, seven trials, 1380 participants, high quality evidence), and with medium dose PQ category (RR 0.34, 95% CI 0.19 to 0.59, two trials, 269 participants, high quality evidence), but the trial evaluating low dose PQ category (0.1 mg/kg) did not demonstrate an effect (RR 0.67, 95% CI 0.44 to 1.02, one trial, 223 participants, low quality evidence). Reductions in log(10)AUC estimates for gametocytaemia on days 1 to 43 with medium and high doses ranged from 24.3% to 87.5%. For haemolysis, one trial reported percent change in mean haemoglobin against baseline, and did not detect a difference between the two arms (very low quality evidence). PQ with non-artemisinin treatments: No trials assessed effects on malaria transmission directly. Two small trials from the same laboratory evaluated infectiousness to mosquitoes, and report that infectivity was eliminated on day 8 in 15/15 patients receiving high dose PQ compared to 1/15 in the control group (low quality evidence). For potential infectiousness, the proportion of people with detectable gametocytaemia on day 8 was reduced by around half with high dose PQ category (RR 0.44, 95% CI 0.27 to 0.70, three trials, 206 participants, high quality evidence), and by around a third with medium dose category (RR 0.62, 0.50 to 0.76, two trials, 283 participants, high quality evidence), but the single trial using low dose PQ category did not demonstrate a difference between groups (one trial, 59 participants, very low quality evidence). Reduction in log(10)AUC for gametocytaemia days 1 to 43 were 24.3% and 27.1% for two arms in one trial giving medium dose PQ. No trials systematically sought evidence of haemolysis. Two trials evaluated the 8AQ bulaquine, and suggest the effects may be greater than PQ, but the small number of participants (n = 112) preclude a definite conclusion. Authors' conclusions: In individual patients, PQ added to malaria treatments reduces gametocyte prevalence when given in doses greater than 0.4 mg/kg. Whether this translates into preventing people transmitting malaria to mosquitoes has rarely been tested in controlled trials, but there appeared to be a strong reduction in infectiousness in the two small studies that evaluated this. No included trials evaluated whether this policy has an impact on community malaria transmission either in low-endemic settings approaching elimination, or in highly-endemic settings where many people are infected but have no symptoms and are unlikely to be treated. For the currently recommended low dose regimen, there is little direct evidence to be confident that the effect of reduction in gametocyte prevalence is preserved. Most trials excluded people with G6PD deficiency, and thus there is little reliable evidence from controlled trials of the safety of PQ in single dose or short course.

Introduction A single dose or short course of primaquine given to people infected with malaria may reduce transmission of Plasmodium falciparum through its effects on gametocytes. Primaquine is also known to cause haemolysis in people with variants of glucose-6-phosphate dehydrogenase (G6PD) deficiency. The objective of this systematic review was to assess the risk of adverse effects in people with G6PD deficiency given primaquine or other 8-aminoquinoline (8AQ) as a single dose or short course (less than 7 days). Methods and analysis We will search the following databases: Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and LILACS. Prospective cohort studies, randomised and quasi-randomised trials that evaluated 8AQs for whatever reason in adults or children with a known G6PD deficiency will be included. Two authors will independently assess each study for eligibility, risk of bias and extract data. Ethics and dissemination This systematic review will be published in a peer-reviewed journal. Brief reports of the review findings will be disseminated directly to the appropriate audiences and the WHO Technical Expert Group in Malaria Chemotherapy. As no primary data collection will be undertaken, no additional formal ethical assessment and informed consent are required. Protocol registration in PROSPERO The protocol is registered with PROSPERO, registration number CRD42013006518.

Background: Nigeria suffers the world’s largest malaria burden, with approximately 51 million cases and 207,000 deaths annually. As part of the country’s aim to reduce by 50% malaria-related morbidity and mortality by 2013, it embarked on mass distribution of free long-lasting insecticidal nets (LLINs). Methods: Prior to net distribution campaigns in Abia and Plateau States, Nigeria, a modified malaria indicator survey was conducted in September 2010 to determine baseline state-level estimates of Plasmodium prevalence, childhood anemia, indoor residual spraying (IRS) coverage and bednet ownership and utilization. Results: Overall age-adjusted prevalence of Plasmodium infection by microscopy was similar between Abia (36.1%, 95% CI: 32.3%–40.1%; n = 2,936) and Plateau (36.6%, 95% CI: 31.3%–42.3%; n = 4,209), with prevalence highest among children 5-9 years. P. malariae accounted for 32.0% of infections in Abia, but only 1.4% of infections in Plateau. More than half of children ≤10 years were anemic, with anemia significantly higher in Abia (76.9%, 95% CI: 72.1%–81.0%) versus Plateau (57.1%, 95% CI: 50.6%–63.4%). Less than 1% of households in Abia (n = 1,305) or Plateau (n = 1,335) received IRS in the 12 months prior to survey. Household ownership of at least one bednet of any type was 10.1% (95% CI: 7.5%–13.4%) in Abia and 35.1% (95% CI: 29.2%-41.5%) in Plateau. Ownership of two or more bednets was 2.1% (95% CI: 1.2%–3.7%) in Abia and 14.5% (95% CI: 10.2%–20.3%) in Plateau. Overall reported net use the night before the survey among all individuals, children

Lymphatic filariasis (LF) in rural southeastern Nigeria is transmitted mainly by Anopheles spp. mosquitoes. Potential coinfection with Loa loa in this area has prevented use of ivermectin in the mass drug administration (MDA) strategy for LF elimination because of potential severe adverse L. loa-related reactions. This study determined if long-lasting insecticidal net (LLIN) distribution programs for malaria would interrupt LF transmission in such areas, without need for MDA. Monthly entomologic monitoring was conducted in sentinel villages before and after LLIN distribution to all households and all age groups (full coverage) in two districts, and to pregnant women and children less than five years of age in the other two districts. No change in human LF microfilaremia prevalence was observed, but mosquito studies showed a statistically significant decrease in LF infection and infectivity with full-coverage LLIN distribution. We conclude that LF transmission can be halted in southeastern Nigeria by full-coverage LLIN distribution, without MDA.

Background Routine malaria surveillance data is useful for assessing incidence and trends over time, and in stratification for targeting of malaria control. The reporting completeness and potential bias of such data needs assessment. Methods Data on 17 malaria indicators were extracted from the Integrated Disease Surveillance and Response System database for July 2004 to June 2009 (Ethiopian calendar reporting years 1997 to 2001). Reporting units were standardized over time with 2007 census populations. The data were analysed to show reporting completeness, variation in risk by reporting unit, and incidence trends for malaria indicators. Results Reporting completeness, estimated as product of unit-month and health facility reporting, was over 80% until 2009, when it fell to 56% during a period of reorganization in the Ministry of Health. Nationally the average estimated annual incidence of reported total malaria for the calendar years 2005 to 2008 was 23.4 per 1000 persons, and of confirmed malaria was 7.6 per 1,000, with no clear decline in out-patient cases over the time period. Reported malaria in-patient admissions and deaths (averaging 6.4 per 10,000 and 2.3 per 100,000 per year respectively) declined threefold between 2005 and 2009, as did admissions and deaths reported as malaria with severe anaemia. Only 8 of 86 reporting units had average annual estimated incidence of confirmed malaria above 20 per 1,000 persons, while 26 units were consistently below five reported cases per 1,000 persons per year. Conclusion The Integrated Disease Surveillance and Response System functioned well over the time period mid 2004 to the end of 2008. The data suggest that the scale up of interventions has had considerable impact on malaria in-patient cases and mortality, as reported from health centres and hospitals. These trends must be regarded as relative (over space and time) rather than absolute. The data can be used to stratify areas for improved targeting of control efforts to steadily reduce incidence. They also provide a baseline of incidence estimates against which to gauge future progress towards elimination. Inclusion of climate information over this time period and extension of the dataset to more years is needed to clarify the impact of control measures compared to natural cycles on malaria.

Background: Mosquitoes become infected with malaria when they ingest gametocyte stages of the parasite from the blood of a human host. Plasmodium falciparum gametocytes are sensitive to the drug primaquine (PQ). The World Health Organization (WHO) recommends giving a single dose or short course of PQ alongside primary treatment for people ill with P. falciparum infection to reduce malaria transmission. Gametocytes themselves cause no symptoms, so this intervention does not directly benefit individuals. PQ causes haemolysis in some people with glucose-6-phosphate dehydrogenase (G6PD) deficiency so may not be safe. Objectives: To assess whether a single dose or short course of PQ added to treatments for malaria caused by P. falciparum infection reduces malaria transmission and is safe. Search methods: We searched the following databases up to 10 April 2012 for studies: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; LILACS; metaRegister of Controlled Trials (mRCT) and the WHO trials search portal using 'malaria*', 'falciparum', and 'primaquine' as search terms. In addition, we searched conference proceedings and reference lists of included studies, and we contacted likely researchers and organizations for relevant trials. Selection criteria: Trials of mass treatment of whole populations (or actively detected fever or malaria cases within such populations) with antimalarial drugs, compared to treatment with the same drug plus PQ; or patients with clinical malaria being treated for malaria at health facilities randomized to short course/single dose PQ versus no PQ. Data collection and analysis: Two authors (PMG and HG) independently screened all abstracts, applied inclusion criteria, and abstracted data. We sought data on the effect of PQ on malaria transmission intensity, participant infectiousness, the number of participants with gametocytes, and gametocyte density over time. We stratified results by primary treatment drug as this may modify any PQ effect. We calculated the area under the curve (AUC) for gametocyte density over time for comparisons for which data were available, and also sought data on haematologic and other adverse effects. We used GRADE guidelines to assess evidence quality, and this is reflected in the wording of the results: high quality ("PQ reduces .... "); moderate quality ("PQ probably reduces ... "); low quality ("PQ may reduce .... "); and very low quality ("we don't know if PQ reduces .... "). Main results: We included 11 individually randomized trials, with a total of 1776 individuals. The 11 trials included 20 comparisons with partner drugs, which included chloroquine (CQ), sulfadoxine-pyrimethamine (SP), mefloquine (MQ), quinine (QN), artesunate (AS), and a variety of artemisinin combination therapies (ACTs). For G6PD deficiency, studies either did not test (one study), tested and included all (one study), included only G6PD deficient (one study), excluded G6PD deficient (two studies), or made no comment (six studies). None of the trials we included assessed effects on malaria transmission (incidence, prevalence, or entomological inoculation rate (EIR)) in the trial area. With non-artemisinin drug regimens, PQ may reduce the infectiousness to mosquitoes of individuals treated, based on one small study with large effects (Risk Ratio (RR) 0.06 on day 8 after treatment, 95% confidence interval (CI) 0 to 0.89; low quality evidence). Participants who received PQ had fewer circulating gametocytes up to day 43 (log(10) AUC relative decrease from 24.3 to 27.1%, one study (two comparisons), moderate quality evidence); and there were 38% fewer people with gametocytes on day 8 (RR 0.62, 95% CI 0.51 to 0.76, four studies (five comparisons), moderate quality evidence). We did not identify any study that looked for effects of the drug on haemolytic anaemia. With artemisinin-based drug regimens, we do not know if PQ influences infectiousness to mosquitoes, as no study has examined this directly. PQ probably reduces infectiousness, based on reduction in log(10) AUC (relative decrease range from 26.1% to 87.5%, two studies (six comparisons), moderate quality evidence); and reduces by 88% the number of participants with gametocytes on day 8 (RR 0.12, 95% CI 0.08 to 0.20, four studies (eight comparisons), moderate quality evidence). When used with artemisinin-based regimens, we do not know if PQ results in haemolytic anaemia; one trial reported percent change in mean haemoglobin against baseline, and for the PQ group this indicated a significantly greater drop at day 8 in those given PQ (very low quality evidence). Overall, the safety of PQ used in single dose or short course was poorly evaluated. Authors' conclusions: We do not know whether PQ added to treatment regimens for patients with P. falciparum infection reduces transmission of malaria. In individual patients, it reduces gametocyte prevalence and density. In practical terms, even if PQ results in large reductions in gametocytes in people being treated for malaria, there is no reliable evidence that this will reduce transmission in a malaria-endemic community, where many people are infected but have no symptoms and are unlikely to be treated. Since PQ is acting as a monotherapy against gametocytes, there is a risk of the parasite developing resistance to the drug. In terms of harms, there is insufficient evidence from trials to know whether the drug can be used safely in this way in populations where G6PD deficiency occurs. In light of these doubts about safety, and lack of evidence of any benefit in reducing transmission, countries should question whether to continue to use PQ routinely in primary treatment of malaria. Further synthesis of observational data on safety and new trials may help elucidate a role for PQ in malaria elimination, or in situations where most infected individuals are symptomatic and receive treatment.

Contains fulltext : 108727.pdf (Publisher’s version ) (Open Access) INTRODUCTION: In the era of malaria elimination and eradication, drug-based and vaccine-based approaches to reduce malaria transmission are receiving greater attention. Such interventions require assays that reliably measure the transmission of Plasmodium from humans to Anopheles mosquitoes. METHODS: WE COMPARED TWO COMMONLY USED MOSQUITO FEEDING ASSAY PROCEDURES: direct skin feeding assays and membrane feeding assays. Three conditions under which membrane feeding assays are performed were examined: assays with i) whole blood, ii) blood pellets resuspended with autologous plasma of the gametocyte carrier, and iii) blood pellets resuspended with heterologous control serum. RESULTS: 930 transmission experiments from Cameroon, The Gambia, Mali and Senegal were included in the analyses. Direct skin feeding assays resulted in higher mosquito infection rates compared to membrane feeding assays (odds ratio 2.39, 95% confidence interval 1.94-2.95) with evident heterogeneity between studies. Mosquito infection rates in membrane feeding assays and direct skin feeding assays were strongly correlated (p

To the Editor: In Ethiopia, malaria is unstable and commonly occurs as intraannual and interannual epidemics. Transmission is associated with altitude, temperature, and rainfall, generally peaking twice a year, after the 2 rainy seasons (March–May and July–September) (1). Cases are caused by Plasmodium falciparum and P. vivax. Anopheles arabiensis mosquitoes are the main vector for both species. Although malaria is the most common communicable disease in Ethiopia (2), few longitudinal case data has been published (3). We report a retrospective analysis of outpatient data for July 2001–June 2006 obtained from all secondary and tertiary government-run health facilities (152 health centers and 25 hospitals) in Oromia Regional State. Oromia has 17 administrative zones and 297 districts. Data were reported monthly on paper forms by health facility staff at district level to the Oromia Regional Health Bureau Zonal Health Offices, which aggregated zonal data before forwarding them to the Oromia Regional Health Bureau Malaria Control Department. Data obtained included number of outpatient cases (i.e., patients attending the health facility grouped by age 5 years); number of clinical malaria cases (i.e., patients with fever grouped by age and sex); number of clinical cases confirmed by microscopy; and number of cases caused by P. falciparum and P. vivax. If no outpatient data were reported, the case number was changed from zero to missing. The data were entered into Microsoft Excel (Microsoft, Redmond, WA, USA) and analyzed by using Stata version 9.0 (StataCorp LP, College Station, TX, USA). During 2001–2006, a total of 8,786,088 outpatient consultations were reported. A total of 905,467 and 562,996 clinical and confirmed malaria cases, respectively, were reported. Patients were predominantly seen at health centers rather than at hospitals, with 80.2% clinical and 72.2% confirmed malaria cases seen at health centers. Clinical malaria accounted for 10.3% of outpatient consultations in all facilities. However, this percentage varied between years (6.1%–16.0%) and zones (1.3%–21.9%) (Technical Appendix Figure 1). Of clinical malaria cases, 16.5% were in children 75% of the clinical cases seen at health facilities during 2001–2006. Malaria incidence varied between years: clinical and confirmed cases increased in 2003, the last epidemic year recorded in Oromia (5), before decreasing to 2001 levels in 2004 (Technical Appendix Figure 1). The P. falciparum to P. vixax ratio changed geographically and temporally (Technical Appendix Figure 1), and increases in the proportion of P. falciparum cases coincided with the peak malaria transmission season. In the epidemic year of 2003, the proportion of P. falciparum cases was larger than in other years, and children

Background In 2005, the Ministry of Health in Ethiopia launched a major effort to distribute over 20 million long-lasting insecticidal nets, provide universal access to artemisinin-based combination therapy (ACTs), and train 30,000 village-based health extension workers. Methods and Findings A cross-sectional, nationally representative Malaria Indicator Survey was conducted during the malaria transmission season in 2007. Multivariate logistic regression analyses were performed to assess the effect of women's malaria knowledge on household ITN ownership and women's ITN use. In addition, we investigated the effect of mothers' malaria knowledge on their children under 5 years of age's (U5) ITN use and their access to fever treatment on behalf of their child U5. Malaria knowledge was based on a composite index about the causes, symptoms, danger signs and prevention of malaria. Approximately 67% of women (n = 5,949) and mothers of children U5 (n = 3,447) reported some knowledge of malaria. Women's knowledge of malaria was significantly associated with household ITN ownership (adjusted Odds Ratio [aOR] = 2.1; 95% confidence interval [CI] 1.6–2.7) and with increased ITN use for themselves (aOR = 1.8; 95% CI 1.3–2.5). Knowledge of malaria amongst mothers of children U5 was associated with ITN use for their children U5 (aOR = 1.6; 95% CI 1.1–2.4), but not significantly associated with their children U5 seeking care for a fever. School attendance was a significant factor in women's ITN use (aOR = 2.0; 95% CI 1.1–3.9), their children U5′s ITN use (aOR = 4.4; 95% CI 1.6–12.1), and their children U5 having sought treatment for a fever (aOR = 6.5; 95% CI 1.9–22.9). Conclusions Along with mass free distribution of ITNs and universal access to ACTs, delivery of targeted malaria educational information to women could improve ITN ownership and use. Efforts to control malaria could be influenced by progress towards broader goals of improving access to education, especially for women.

Following recent large scale-up of malaria control interventions in Ethiopia, this study aimed to compare ownership and use of long-lasting insecticidal nets (LLIN), and the change in malaria prevalence using two population-based household surveys in three regions of the country. Each survey used multistage cluster random sampling with 25 households per cluster. Household net ownership tripled from 19.6% in 2006 to 68.4% in 2007, with mean LLIN per household increasing from 0.3 to 1.2. Net use overall more than doubled from 15.3% to 34.5%, but in households owning LLIN, use declined from 71.7% to 48.3%. Parasitemia declined from 4.1% to 0.4%. Large scale-up of net ownership over a short period of time was possible. However, a large increase in net ownership was not necessarily mirrored directly by increased net use. Better targeting of nets to malaria-risk areas and sustained behavioural change communication are needed to increase and maintain net use.

Two malaria rapid diagnostic tests (RDT), Parascreen Pan/Pf and Paracheck Pf, were tested in rural health centres in Ethiopia against independent expert microscopy (the gold standard). Participants (n =1997) presented with presumptive malaria to ten health centers in Amhara Regional State during the 2007 peak malaria season (October to December). By microscopy, 475 (23.8%) suspected malaria cases were positive, of which 57.7% were P. falciparum; 24.6% P. vivax and 17.7% mixed infections. Parascreen and Paracheck were positive for 442 (22.1%) and 277 (13.9%) febrile patients, respectively. For Parascreen, P. falciparum sensitivity was 79.6%, specificity 97.4%, positive predictive value (PPV) 86.9%, and negative predictive value (NPV) 95.6%. For Parascreen, P. vivax sensitivity was 74.4%, specificity 98.6%, PPV 76.3% and NPV 98.4%. For Paracheck, P. falciparum sensitivity was 73.7%, specificity 99.2%, PPV 95.3%, NPV 94.5%. Sensitivity was significantly higher for both tests (P0.05) when parasite density was100/microl of blood; in these cases Parascreen was 90.7% and 91.5% sensitive for P. falciparum and P. vivax, respectively, while Paracheck was 87.9% sensitive for P. falciparum. Parascreen thus performed adequately for both P. falciparum and P. vivax compared to expert microscopy and is more useful than Paracheck where microscopy is unavailable.

Background Malaria transmission in Ethiopia is unstable and seasonal, with the majority of the country's population living in malaria-prone areas. Results from DHS 2005 indicate that the coverage of key malaria interventions was low. The government of Ethiopia has set the national goal of full population coverage with a mean of 2 long-lasting insecticidal nets (LLINs) per household through distribution of about 20 million LLIN by the end of 2007. The aim of this study was to generate baseline information on malaria parasite prevalence and coverage of key malaria control interventions in Oromia and SNNPR and to relate the prevalence survey findings to routine surveillance data just before further mass distribution of LLINs. Methods A 64 cluster malaria survey was conducted in January 2007 using a multi-stage cluster random sampling design. Using Malaria Indicator Survey Household Questionnaire modified for the local conditions as well as peripheral blood microscopy and rapid diagnostic tests, the survey assessed net ownership and use and malaria parasite prevalence in Oromia and SNNPR regions of Ethiopia. Routine surveillance data on malaria for the survey time period was obtained for comparison with prevalence survey results. Results Overall, 47.5% (95% confidence interval (CI) 33.5–61.9%) of households had at least one net, and 35.1% (95% CI 23.1–49.4%) had at least one LLIN. There was no difference in net ownership or net utilization between the regions. Malaria parasite prevalence was 2.4% (95% CI 1.6–3.5%) overall, but differed markedly between the two regions: Oromia, 0.9% (95% CI 0.5–1.6); SNNPR, 5.4% (95% CI 3.4–8.5), p < 0.001. This difference between the two regions was also reflected in the routine surveillance data. Conclusion Household net ownership exhibited nearly ten-fold increase compared to the results of Demographic and Health Survey 2005 when fewer than 5% of households in these two regions owned any nets. The results of the survey as well as the routine surveillance data demonstrated that malaria continues to be a significant public health challenge in these regions–and more prevalent in SNNPR than in Oromia.

To assess the effectiveness of impregnated mosquito nets, indoor residual spraying and larval control relative to the impacts of climate variability in the decline of malaria cases in Eritrea.Monthly data on clinical malaria cases by subzoba (district) in three zobas (zones) of Eritrea for 1998-2003 were used in Poisson regression models to determine whether there is statistical evidence for reduction in cases by DDT, malathion, impregnated nets and larval control used over the period, while analysing the effects of satellite-derived climate variables in the same geographic areas.Both indoor residual spraying (with DDT or malathion) and impregnated nets were independently and significantly negatively associated with reduction in malaria cases, as was larval control in one zoba. Malaria cases were significantly positively related to differences in current and previous months' vegetation (NDVI) anomalies. The relationship to rainfall differences 2 and 3 months previously was also significant, but the direction of the effect varied by zoba. Standardized regression coefficients indicated a greater effect of climate in the zoba with less intense malaria transmission.The results support the view that both indoor residual spraying and impregnated nets have been independently effective against malaria, and that larval control was also effective in one area. Thus climate, while significant, is not the only explanation for the recent decline in malaria cases in Eritrea. If appropriate statistical approaches are used, routine surveillance data from cases attending health facilities can be useful for assessing control programme success and providing estimates of the effectiveness of individual control measures. Effectiveness estimates suitable for use in cost-effectiveness analysis have been obtained.

Eritrea has a successful malaria control program, but it is still susceptible to devastating malaria epidemics. Monthly data on clinical malaria cases from 242 health facilities in 58 subzobas (districts) of Eritrea from 1996 to 2003 were used in a novel stratification process using principal component analysis and nonhierarchical clustering to define five areas with distinct malaria intensity and seasonality patterns, to guide future interventions and development of an epidemic early warning system. Relationships between monthly clinical malaria incidence by subzoba and monthly climate data from several sources, and with seasonal climate forecasts, were investigated. Remotely sensed climate data were averaged over the same subzoba geographic administrative units as the malaria cases. Although correlation was good between malaria anomalies and actual rainfall from ground stations (lagged by 2 months), the stations did not have sufficiently even coverage to be widely useful. Satellite derived rainfall from the Climate Prediction Center Merged Analysis of Precipitation was correlated with malaria incidence anomalies, with a lead time of 2-3 months. NDVI anomalies were highly correlated with malaria incidence anomalies, particularly in the semi-arid north of the country and along the northern Red Sea coast, which is a highly epidemic-prone area. Eritrea has 2 distinct rainy seasons in different parts of the country. The seasonal forecasting skill from Global Circulation Models for the June/July/August season was low except for the Eastern border. For the coastal October/November/December season, forecasting skill was good only during the 1997-1998 El Niño event. For epidemic control, shorter-range warning based on remotely sensed rainfall estimates and an enhanced epidemic early-detection system based on data derived for this study are needed.

Background Amhara Regional State of Ethiopia has a population of approximately 19.6 million, is prone to unstable and epidemic malaria, and is severely affected by trachoma. An integrated malaria and trachoma control program is being implemented by the Regional Health Bureau. To provide baseline data, a survey was conducted during December 2006 to estimate malaria parasite prevalence, malaria indicators, prevalence of trachoma, and trachoma risk factors in households and people of all ages in each of the ten zones of the state, excluding three urban centers (0.4% of the population). Methodology/Principal Findings The study was designed to provide prevalence estimates at zone and state levels. Using multi-stage cluster random sampling, 16 clusters of 25 households were randomly selected in each of the ten zones. Household heads were interviewed for malaria indicators and trachoma risk factors (N = 4,101). All people were examined for trachoma signs (N = 17,242), and those in even-numbered households provided blood films for malaria parasite detection (N = 7,745); both thick and thin blood films were read. Zonal malaria parasite prevalence ranged from 2.4% to 6.1%, with the overall state-wide prevalence being 4.6% (95% confidence interval (CI): 3.8%–5.6%). The Plasmodium falciparum: Plasmodium vivax ratio ranged from 0.9–2.1 with an overall regional ratio of 1.2. A total of 14.8% of households reported indoor residual spraying in the past year, 34.7% had at least one mosquito net, and 16.1% had one or more long-lasting insecticidal net. Zonal trachoma prevalence (trachomatous inflammation follicular [WHO grade TF] in children aged 1–9 years) ranged from 12.6% to 60.1%, with the overall state-wide prevalence being 32.7% (95% CI: 29.2%–36.5%). State-wide prevalence of trachomatous trichiasis (TT) in persons aged over fifteen was 6.2% (95% CI: 5.3–7.4), and 0.3% (95% CI: 0.2–0.5) in children aged 0–14 years. Overall, an estimated 643,904 persons (lower bound 419,274, upper bound 975,635) have TT and require immediate corrective surgery. Conclusions/Significance The results provide extensive baseline data to guide planning, implementation, and evaluation of the integrated malaria and trachoma control program in Amhara. The success of the integrated survey is the first step towards demonstration that control of priority neglected tropical diseases can be integrated with one of the “big three” killer diseases., Author Summary The “big three” killer diseases are malaria, HIV/AIDS, and tuberculosis; control programs for these diseases are usually well developed and financed. The neglected tropical diseases (NTDs) are a group of ancient afflictions that are frequently sidelined by planners and are under-resourced. Opportunities of integrating the big three with NTDs have been talked about but not widely acted upon. There is potential synergy for an integrated trachoma and malaria control program since control of both diseases is community-based. The first step in accessing these synergies has been an integrated malaria prevalence and indicator and trachoma prevalence and risk factor survey. This has been achieved at the incremental cost of one additional staff member per field team. The results give unprecedented precision for the calculation of intervention targets for the integrated program and demonstrate that it is possible to integrate NTDs with the “big three.”

We have studied the properties of epitopes on Plasmodium falciparum gamete surface protein Pfs 48/45, a target antigen of malaria transmission blocking antibodies. Using a two site immunoradiometric assay we have defined three spacially separate, non-repeated, epitope regions on the peptides representing this antigen. Epitope region I is a target of monoclonal antibodies (MoAbs) which strongly suppress infectivity of gametocytes of P. falciparum to mosquitoes; the effect is complement independent and is mediated as effectively by the monovalent Fab fragments as by intact MoAb. Epitope region II consists of two spacially close subregions, IIa and IIb; variant forms of epitopes IIa and IIb occurred in different isolates of P. falciparum. Epitope region III also showed slight structural modification between isolates. MoAbs against regions II or III were relatively ineffective in suppressing gametocyte infectivity compared to MoAbs against region I. However, certain combinations of MoAbs against regions II and III together acted synergistically to suppress infectivity to mosquitoes. All these epitopes failed to react with MoAb when the antigen was presented in reduced form. A fourth epitope, however, was identified which reacted strongly with MoAb when the antigen was presented in reduced form. The MoAb against this epitope had no effect on the infectivity of gametocytes of P. falciparum to mosquitoes.

Background Vaccines against all stages of the malaria parasite are in development, mainly for Plasmodium falciparum, which causes the most serious form of malaria. Pre-erythrocytic vaccines act to prevent or delay a malaria attack by attacking the sporozoite and liver stages before the parasite reaches the bloodstream. Objectives To assess the efficacy and safety of pre-erythrocytic malaria vaccines against any type of human malaria. Search methods In March 2006, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE, EMBASE, LILACS, and the Science Citation Index. We also searched conference proceedings and reference lists of articles, and contacted organizations and researchers in the field. Selection criteria Randomized controlled trials comparing pre-erythrocytic vaccines with placebo, control vaccine, or routine antimalarial control measures in people of any age receiving an artificial challenge or natural exposure to malaria infection. Data collection and analysis Both authors independently assessed trial quality and extracted data. Results of meta-analyses were expressed as risk ratios with 95% confidence intervals (CI) using an intention-to-treat analysis. Main results Nine safety and efficacy trials, and two safety trials, with over 3000 participants were included. In semi-immune children, RTS,S vaccine reduced clinical episodes of malaria by 26% (95% CI 13% to 37%) and severe malaria by 58% (95% CI 15% to 79%) for up to 18 months. Prevalence of parasitaemia was also reduced by 26% (95% CI 11% to 38%) at six months after immunization. RTS,S also reduced clinical malaria episodes by 63% (95% CI 18% to 83%) in semi-immune adult men in the second year of follow up after a booster dose. No severe adverse events were judged to be related to RTS,S vaccine, although the frequencies of injection site pain, swelling, arm motion limitation, headache, and malaise were increased in the vaccine groups. There was no evidence for effect of the CS-NANP vaccines (307 participants, 3 trials), CS102 peptide vaccine (14 participants, 1 trial), or the ME-TRAP vaccine (372 participants, 1 trial). Authors' conclusions RTS,S vaccine was effective in preventing a significant number of clinical malaria episodes, including good protection against severe malaria in children for 18 months. No severe adverse events were attributable to the vaccine. Progression of this vaccine towards licensing is justified while efforts to increase its efficacy continue. The other vaccines do not look promising and further research is a priority.

Background A malaria vaccine is needed because of the heavy burden of mortality and morbidity due to this disease. This review describes the results of trials of blood (asexual)-stage vaccines. Several are under development, but only one (MSP/RESA, also known as Combination B) has been tested in randomized controlled trials. Objectives To assess the effect of blood-stage malaria vaccines in preventing infection, disease, and death. Search strategy In March 2006, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE, EMBASE, LILACS, and the Science Citation Index. We also searched conference proceedings and reference lists of articles, and contacted organizations and researchers in the field. Selection criteria Randomized controlled trials comparing blood-stage vaccines (other than SPf66) against P. falciparum, P. vivax, P. malariae, or P. ovale with placebo, control vaccine, or routine antimalarial control measures in people of any age receiving a challenge malaria infection. Data collection and analysis Both authors independently assessed trial quality and extracted data. Results for dichotomous data were expressed as relative risks (RR) with 95% confidence intervals (CI). Main results Five trials of MSP/RESA vaccine with 217 participants were included; all five reported on safety, and two on efficacy. No severe or systemic adverse effects were reported at doses of 13 to 15 microg of each antigen (39 to 45 microg total). One small efficacy trial with 17 non-immune participants with blood-stage parasites showed no reduction or delay in parasite growth rates after artificial challenge. In the second efficacy trial in 120 children aged five to nine years in Papua New Guinea, episodes of clinical malaria were not reduced, but MSP/RESA significantly reduced parasite density only in children who had not been pretreated with an antimalarial drug (sulfadoxine-pyrimethamine). Infections with the 3D7 parasite subtype of MSP2 (the variant included in the vaccine) were reduced (RR 0.38, 95% CI 0.26 to 0.57; 719 participants) while those with the other main subtype, FC27, were not (720 participants). Authors' conclusions The MSP/RESA (Combination B) vaccine shows promise as a way to reduce the severity of malaria episodes, but the effect of the vaccine is MSP2 variant-specific. Pretreatment for malaria during a vaccine trial makes the results difficult to interpret, particularly with the relatively small sample sizes of early trials. The results show that blood-stage vaccines may play a role and merit further development.

Background A malaria vaccine is badly needed. SPf66 was one of the earliest vaccines developed. It is a synthetic peptide vaccine containing antigens from the blood stages of malaria linked together with an antigen from the sporozoite stage, and is targeted mainly against the blood (asexual) stages. Objectives To assess the effect of SPf66 malaria vaccines against Plasmodium falciparum, P. vivax, P. malariae, and P. ovale in preventing infection, disease, and death. Search strategy We searched the Cochrane Infectious Diseases Group Specialized Register (September 2005), CENTRAL (The Cochrane Library 2005, Issue 3), MEDLINE (1966 to September 2005), EMBASE (1980 to September 2005), LILACS (1982 to September 2005), Science Citation Index (1981 to September 2005), and reference lists of articles. We also contacted organizations and researchers in the field. Selection criteria Randomized and quasi-randomized controlled trials comparing SPf66 vaccine with placebo or routine antimalarial control measures in people of any age receiving an artificial challenge or natural exposure to malaria infection (any species). Data collection and analysis Two people independently assessed trial quality and extracted data, including adverse events. Results were expressed as relative risks (RR) with 95% confidence intervals (CI). Main results Ten efficacy trials of SPf66 involving 9698 participants were included. Results with SPf66 in reducing new episodes of P. falciparum malaria were heterogeneous: it was not effective in four African trials (RR 0.98, 95% CI 0.90 to 1.07; 2371 participants) or in one Asian trial (RR 1.06, 95% CI 0.90 to 1.25; 1221 participants). In four trials in South America the number of first attacks with P. falciparum was reduced by 28% (RR 0.72, 95% CI 0.63 to 0.82; 3807 participants). It did not reduce episodes of P. vivax malaria or admission to hospital with severe malaria. Trials have not indicated any serious adverse events with SPf66 vaccine. Authors' conclusions There is no evidence for protection by SPf66 vaccines against P. falciparum in Africa. There is a modest reduction in attacks of P. falciparum malaria following vaccination with SPf66 in South America. There is no justification for further trials of SPf66 in its current formulation. Further research with SPf66 vaccines in South America or with new formulations of SPf66 may be justified.

Garner and Graves discuss the implications of a new study in PLoS Medicine that found that artemisinin combination treatment reduces infectiousness.

The incidence of malaria in Solomon Islands has been decreasing since 1992. The control program used a combination of methods including DDT residual house spraying and insecticide-treated mosquito nets. To determine how much each method contributed to malaria control, data were analyzed on monthly incidence and on control activities for 41 of 110 malaria zones over the same time period (January 1993 to August 1999). After correction for endogeneity, then spraying, insecticide treatment of nets, and education about malaria are all independently associated with reduction in incident cases of malaria or fever, while larviciding with temephos is not. The evidence suggests that although impregnated bed nets cannot entirely replace DDT spraying without substantial increase in incidence, their use permits reduced DDT spraying. The paper shows that non-experimental data can be used to infer causal links in epidemiology, provided that instrumental variables are available to correct for endogeneity.

The incidence of malaria in Solomon Islands has been declining since 1992, but there is a large geographical variation between areas in the incidence level and the rate of decline. The authors used a mix of control interventions, including DDT residual house spraying and insecticide-treated mosquito nets. Data on monthly incidence and control activities performed from January 1993 to August 1999 were gathered for 41 out of the 110 malaria zones in the country. Monthly reports on the number of fevers seen at outpatient health clinics in the same zones over the same period were also extracted from the clinical health information system. The authors used multivariate random effects regression, including calendar month as an instrumental variable, to investigate the relationship between the number of malaria or fever cases and the control measures applied by month and zone, while adjusting for rainfall and proximity to water. The results showed that DDT house spraying, insecticide treatment of nets, and education about malaria were all independently associated with reduction in incident cases of malaria or fever, while larviciding with temephos was not. This was true for confirmed malaria cases even when a variable representing the passage of time was included in the models. The results show how much each method used was contributing to malaria control in Solomon Islands and how it can be used to design the most cost-effective package of interventions. The evidence suggests that impregnated bednets cannot easily replace DDT spraying without substantial increase in incidence, but impregnated nets do permit a substantial reduction in the amount of DDT spraying. This paper is a product of Public Services, Development Research Group.

BACKGROUND: Four types of malaria vaccine, SPf66 and MSP/RESA vaccines (against the asexual stages of the Plasmodium parasite) and CS‐NANP and RTS,S vaccines (against the sporozoite stages), have been tested in randomized controlled trials in endemic areas. OBJECTIVES: To assess malaria vaccines against Plasmodium falciparum, P. vivax, P. malariae and P ovale in preventing infection, disease and death. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register (April 2004), CENTRAL (The Cochrane Library Issue 2, 2004), MEDLINE (1966 to April 2004), EMBASE (1980 to April 2004), Science Citation Index (1981 to April 2004), and reference lists of articles. We also contacted organizations and researchers in the field. SELECTION CRITERIA: Randomized controlled trials comparing vaccines against Plasmodium falciparum, P. vivax, P. malariae or P. ovale with placebo or routine antimalarial control measures in people of any age receiving a challenge malaria infection. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Eighteen efficacy trials involving 10,971 participants were included. There were ten trials of SPf66 vaccine, four trials of CS‐NANP vaccines, two trials of RTS,S vaccine, and two of MSP/RESA vaccine. Results with SPf66 in reducing new malaria infections (P. falciparum) were heterogeneous: it was not effective in four African trials (Peto odds ratio (OR) 0.96, 95% confidence interval (CI) 0.81 to 1.14), but in five trials outside Africa the number of first attacks was reduced (Peto OR 0.77, 95% CI 0.67 to 0.88). Trials to date have not indicated any serious adverse events with SPf66 vaccine. In three trials of CS‐NANP vaccines, there was no evidence for protection by these vaccines against P. falciparum malaria (Peto OR 1.12, 95% CI 0.64 to 1.93). In a small trial in non‐immune adults in the USA, RTS,S gave strong protection against experimental infection with P. falciparum. In a trial in an endemic area of the Gambia in semi‐immune people, there was a reduction in clinical malaria episodes in the second year of follow up, corresponding to a vaccine efficacy of 66% (CI 14% to 85%). In a trial in Papua New Guinea, MSP/RESA had no protective effect against episodes of clinical malaria. There was evidence of an effect on parasite density, but this differed according to whether the participants had been pretreated with sulfadoxine/pyrimethamine or not. The prevalence of infections with the parasite subtype of MSP2 in the vaccine was reduced compared with the other subtype (Peto OR 0.35, CI 0.23 to 0.53). AUTHORS' CONCLUSIONS: There is no evidence for protection by SPf66 vaccines against P. falciparum in Africa. There is a modest reduction in attacks of P. falciparum malaria following vaccination with SPf66 in other regions. Further research with SPf66 vaccines in South America or with new formulations of SPf66 may be justified. There was not enough evidence to evaluate the use of CS‐NANP vaccines. The RTS,S vaccine showed promising result, as did the MSP/RESA vaccine, but it should include the other main allelic form of MSP2. The MSP/RESA trial demonstrated that chemotherapy during a vaccine trial may reduce vaccine efficacy, and trials should consider very carefully whether this practice is justified. This review is in the process of being updated and divided into three reviews. The details are in the 'What's new' section.

The diseases malaria, babesiosis and theileriosis are caused by parasitic protozoa in the genera Plasmodium, Babesia and Theileria, respectively. All have complex life cycles in which both vertebrates and bloodsucking arthropods serve as hosts. The vectors of Plasmodium species are mosquitoes (of the genus Anopheles for human malarias), while ticks in a wide range of genera transmit babesial and theilerial parasites. These important human and veterinary pathogens share characteristics in their structure, antigenicity and the diseases they cause. However, malaria is a greater source of morbidity in humans than babesiosis, and theileriosis is strictly a disease of veterinary importance. Insects transmit a number of species in 3 related genera (Leucocytozoon, Hepatocystis and Hemoproteus) to birds and mammals. In some cases, these infections can cause serious diseases in domestic animals, especially fowl.

The cost-effectiveness of two different methods of prevention of morbidity and mortality due to Plasmodium falciparum malaria, vaccination and impregnation of mosquito nets with permethrin, was compared. The analysis was performed with reference to the cohort of all children born in The Gambia in 1990 and protected for 5 years, using estimates of costs from studies in The Gambia. The vaccine was assumed to be given in three doses before the age of 6 months, through the Expanded Programme of Immunization, and to remain effective up to the age of 5 years. The bednets were assumed to be impregnated at 6-monthly intervals over the 5-year period. The expected number of deaths and attacks due to P. falciparum in the first 5 years of the 1990 cohort's lives were estimated from published literature. The numbers of deaths and attacks averted by the two strategies were then estimated by decision analysis, using the best estimates of effectiveness available in the literature. The vaccine strategy would have averted an estimated 743 deaths and 50,502 malaria attacks, whereas the net impregnation would have averted 1537 deaths and 69,415 attacks. The estimated cost per death averted was U.S. $252 for the vaccine and U.S. $711 for net impregnation. The estimated cost per P. falciparum attack averted was U.S. $3.71 for the vaccine and U.S. $15.75 for net impregnation. Sensitivity analysis, examining the effect of varying the vaccine cost or insecticide cost, the efficacy of the vaccine or net impregnation, and the percentage coverage of the population, confirmed the greater cost-effectiveness of the vaccine strategy for either of the outcomes examined under the conditions of the model. However, limitations on the absolute number of deaths and malaria attacks which can averted by currently available vaccines demonstrate that a vaccine of higher efficacy would be highly desirable.

Background Ethiopia scaled up net distribution markedly starting in 2006. Information on expected net life under field conditions (physical durability and persistence of insecticidal activity) is needed to improve planning for net replacement. Standardization of physical durability assessment methods is lacking. Methods Permanet®2.0 long-lasting insecticidal bed nets (LLINs), available for distribution in early 2007, were collected from households at three time intervals. The number, size and location of holes were recorded for 189 nets used for three to six months from nine sites (2007) and 220 nets used for 14 to 20 months from 11 sites (2008). In 2009, a “finger/fist” sizing method classified holes in 200 nets used for 26 to 32 months from ten sites into small ( = 2 to 10 cm) sizes. A proportionate hole index based on both hole number and area was derived from these size classifications. Results After three to six months, 54.5% (95% CI 47.1-61.7%) of 189 LLINs had at least one hole 0.5 cm (in the longest axis) or larger; mean holes per net was 4.4 (SD 8.4), median was 1.0 (Inter Quartile Range [IQR] 0–5) and median size was 1 cm (IQR 1–2). At 14 to 20 months, 85.5% (95% CI 80.1-89.8%) of 220 nets had at least one hole with mean 29.1 (SD 50.1) and median 12 (IQR 3–36.5) holes per net, and median size of 1 cm (IQR 1–2). At 26 to 32 months, 92.5% of 200 nets had at least one hole with a mean of 62.2 (SD 205.4) and median of 23 (IQR 6–55.5) holes per net. The mean hole index was 24.3, 169.1 and 352.8 at the three time periods respectively. Repairs were rarely observed. The majority of holes were in the lower half of the net walls. The proportion of nets in ‘poor’ condition (hole index >300) increased from 0% at three to six months to 30% at 26 to 32 months. Conclusions Net damage began quickly: more than half the nets had holes by three to six months of use, with 40% of holes being larger than 2 cm. Holes continued to accumulate until 92.5% of nets had holes by 26 to 32 months of use. An almost complete lack of repairs shows the need for promoting proper use of nets and repairs, to increase LLIN longevity. Using the hole index, almost one third of the nets were classed as unusable and ineffective after two and a half years of potential use.

Estimating malaria transmission in the human is fraught with problems of reconciling clinical illness with parasitological status. It follows that there is a role for entomological assessments as an independent outcome variable and as a process indicator. Advances in DNA technology have expanded our capacity to identify vectors rapidly, while immunoassays allow the inoculation rate to be measured simultaneously in a number of villages with a precision 3-fold greater than measurements of vectorial capacity. The rapid specific identification of parasites in vectors has been utilized to estimate survivorship in mosquitoes per extrinsic incubation period (EIP), circumventing the need for estimates of survivorship per feeding cycle, lengths of feeding cycles or the length of the EIP. While lack of accuracy does not universally preclude the utility of estimates of the components of vectorial capacity in serving as relative estimates of transmission, particularly as process indicators, more accurate estimates of these parameters, particularly for density-dependent variables, may diminish the associated bias in their measurement. When this is accomplished, we will come closer to obtaining true rather than relative estimates of transmission.

BackgroundDiagnostic tests are recommended for suspected malaria cases before treatment, but comparative performance of microscopy and rapid diagnostic tests (RDTs) at rural health centers has rarely been studied compared to independent expert microscopy.MethodsParticipants (N = 1997) with presumptive malaria were recruited from ten health centers with a range of transmission intensities in Amhara Regional State, Northwest Ethiopia during October to December 2007. Microscopy and ParaScreen Pan/Pf® RDT were done immediately by health center technicians. Blood slides were re-examined later at a central laboratory by independent expert microscopists.ResultsOf 1,997 febrile patients, 475 (23.8%) were positive by expert microscopists, with 57.7% P. falciparum, 24.6% P. vivax and 17.7% mixed infections. Sensitivity of health center microscopists for any malaria species was >90% in five health centers (four of which had the highest prevalence), >70% in nine centers and 44% in one site with lowest prevalence. Specificity for health center microscopy was very good (>95%) in all centers. For ParaScreen RDT, sensitivity was ≥90% in three centers, ≥70% in six and ConclusionsHealth center microscopists performed well in nine of the ten health centers; while for ParaScreen RDT they performed well in only six centers. Overall the accuracy of local microscopy exceeded that of RDT for all outcomes. This study supports the introduction of RDTs only if accompanied by appropriate training, frequent supervision and quality control at all levels. Deficiencies in RDT use at some health centers must be rectified before universal replacement of good routine microscopy with RDTs. Maintenance and strengthening of good quality microscopy remains a priority at health center level.

The human malaria parasite life cycle appears deceptively simple because it involves only one species of vertebrate host (humans) and anopheline mosquitoes to transmit the pathogen. However, a number of host, vector, and pathogen factors have evolved that interact with ecological and logistic considerations to determine whether transmission of the parasite from a mosquito to a human, or the converse, will successfully occur.

Publisher Summary Malaria is a disease of major global proportions. Estimates vary, but possibly as many as 500 million people throughout the world are infected with malaria parasites, and as a result 2 to 3 million children die annually. It is still less than 10 years since the first malaria genes were cloned and expressed in the laboratory, opening the way for possible vaccine development, and during this time, there has been tremendous development in knowledge of malaria immunity, in discovery of vaccine candidates, and in the development of adjuvants required for a successful vaccine program. Coupled with this, there has been resolve from scientists, industry, and governments for the development of such a vaccine. This chapter explores the prospects for a vaccine separately for each stage of the parasite's life cycle. The chapter also discusses some future directions for vaccine development, some of which are general, while others are specific for each stage in the life cycle.

Anopheline survivorship, vectorial capacity, and mosquito infection probability estimates from mosquito infection rates were determined 4 times in 1 year in a Papua New Guinea village. Estimates of survivorship over the length of the extrinsic incubation period differed significantly during the year. However, survivorship per feeding cycle, individual mosquito vectorial capacity, and mosquito infection probability did not vary significantly. Estimates of these parameters were then compared to estimates of survivorship, individual vectorial capacity, and mosquito infection probability in mosquito populations in other villages in the study area. Since survivorship per feeding cycle did not vary significantly among the mosquito populations in these villages, changes in malaria transmission potential can be better gauged from estimates of survivorship over the length of the extrinsic incubation period. However, as measurements of relative inoculation rates are easier to perform and have been related to parasite prevalences in children in this area, estimates of inoculation rates are a preferred option for estimating malaria transmission in the Madang area of Papua New Guinea.

Summary Thirty serum samples collected from adult patients attending the Hospital for Tropical Diseases, London, with P. falciparum malaria, were studied. Sera were screened by indirect immunofluorescence for anti-gametocyte antibodies. Twelve of the serum samples taken from 14 patients with primary infections were found to have both IgM and IgG antibodies to gametocyte antigens and total Ig titres comparable with those of patients who had had previous malaria attacks. Sera of individuals from hyperendemic areas have been found to immunoprecipitate the 230 and 48/45 kD gametocyte surface antigens which are known targets of transmission blocking antibodies. To investigate the epitope specificity of the serum samples from our adult patients, competitive ELISAs with 3 monoclonal antibodies (MAbs) that block transmission and recognize different epitopes on the 48/45 Kd antigen, were carried out. Specific antibodies for these epitopes were found in 60% of the sera while nearly a third were able to inhibit the binding of at least two MAbs.

Sera from 62 adult Papua New Guinea highlanders with suspected acute malaria were tested by competitive ELISA for the presence of antibodies capable of inhibiting binding of 8 monoclonal antibodies (Mabs) directed against epitopes on gametocytes of Plasmodium falciparum. Between 33% and 72% of the malaria cases were inhibitory, depending on the Mab. There was no difference between the proportion of persons with P. falciparum (asexuals or gametocytes) and P. vivax whose sera inhibited Mab binding, but all 3 categories had a significantly higher proportion of inhibitors than persons who were malaria negative. The amount of gametocyte antibody recognizing epitopes on Pfs 48/45 and Pfs 230 increased with increasing numbers of previous malaria episodes. The proportion of sera from these relatively nonimmune adults which had gamete antibodies was similar to the proportion seen in sera from a highly endemic area, suggesting that antibody responses to these epitopes are a part of the initial response observed after a limited number of malaria episodes.