Helminth infection rates in grade three children are used as proxy indicators of community infection status and to guide treatment strategies in endemic areas. However knowledge, attitudes and practices (KAP) of this target age group (8-10 years) in relation to schistosomiasis, soil transmitted helminthiasis (STHs) and malaria is not known at a time when integrated plasmodium - helminth control strategies are being advocated. This study sought to assess KAP of grade 3 children in relation to schistosomiasis, STHs and malaria in order to establish an effective school based health education for disease transmission control.S. haematobium infection status. Infection with S. mansoni and STHs was determined using a combination of results from the Kato Katz and formol ether concentration techniques. P. falciparum was diagnosed by examination of Giemsa stained thick blood smears.Grade 3 children (n = 172) attending four randomly selected primary schools  in Zimbabwe were interviewed using a pre-tested interviewer administered questionnaire. The urine filtration technique was used to determine S. haematobium (77.8%), S. mansoni (33.3%) hookworms (29.6%) and P. falciparum (48.1%). Reports that participant had suffered from schistosomiasis and malaria before were significant predictors of these diseases . Report that participant had blood in urine on the day of examination was a significant predictor of schistosomiasis (p = 0.045).It was observed that 32.0%, 19.2% and 4.1% of the respondents had correct knowledge about the causes of schistosomiasis, malaria and STHs, respectively, whilst 22.1%, 19.2% and 5.8% knew correct measures to control schistosomiasis, malaria and STHs. Sixty-two percent and 44.8% did not use soap to wash hands after toilet and before eating food respectively, whilst 33.1% never wore shoes. There were no functional water points and soap for hand washing after toilet at all schools. There was a high prevalence distribution of all parasites investigated in this study at Msapa primary school - There is a critical need for targeting health messages through schools in order to reach the most susceptible schoolchildren. This will empower the schoolchildren with the basic knowledge and skills ultimately protecting them from acquiring schistosomiasis, STHs and malaria. More than 2 billion people are affected with schistosomiasis and soil transmitted helminthiasis (STHs) of whom more than 300 million suffer from associated morbidity and 155 000 deaths are reported annually . In areaS. haematobium is predominantly distributed in all provinces with some areas in the Northern -Eastern region registering up to 80% of the disease [P. falciparum which is responsible for the most severe and fatal form of the diseases accounts for 97% of malaria infection in the country [P. falciparum in primary school children has been described by Midzi et al, (2008) [Schistosomiasis is among the top 14 out patient treated diseases in Zimbabwe . S. haem disease . The age disease . Chandiw disease . The pre disease -15. Mala disease . P. falc country . Mixed i, (2008) .The World Health Organisation recommends that before any mass control programme is undertaken, the extent of helminthiasis distribution  must be determined in order to inform programme managers on the best intervention strategies ,18-20. IWhilst immense efforts are being made to control morbidity due to helminthiasis and the big three diseases with special emphasis on regular combined school based treatment of primary school children , it shouZimbabwe has drafted a national plan of action for the control of schistosomiasis and STHs. Ahead of this national programme, a pilot study to determine the effectiveness of combined regular school based de-worming for schistosomiasis, STHs, prompt malaria treatment and health education was conducted in areas endemic for schistosomiasis only and those co-endemic for schistosomiasis, STHs and malaria . During The survey was conducted in grade 3 children (n = 223) living in Nyamaropa rural area (47.1%) that is located in Shamva district, Mashonaland Central Province and Burma Valley commercial farming area (52.9%), which is located in Mutare district, Manicaland Province. The age of the study population ranged from 5 to 15 years and 47.1% were males. The study areas are described in detail elsewhere . EthicalP. falciparum among primary schoolchildren in rural and farming areas in Zimbabwe: Impact on anaemia and the effectiveness of regular school based deworming and prompt malaria treatment.The study was a descriptive cross-sectional survey part of a longitudinal intervention study investigating the distribution of polyparasitism with schistosomiasis, STHs and Manicaland Province was conveniently chosen for the study due to its geographical location (Eastern Highlands) characterised by high annual rainfalls, wet soils and malaria endemicity . MultistThis is part of a bigger study investigating the impact of school based integrated control of helminthiasis and malaria on anaemia in primary school children. However only grade 3 children (n = 223) were included in the KAP component of the main intervention study.Only grade 3 children were included in the KAP study. Their KAP were perceived as proxy of their parents/guardians since at this level the children's primary school syllabus does not include such diseases. Children who did not respond to the questionnaire were excluded.A questionnaire that contained questions on demographic data, sources of water, sanitary facilities, knowledge of participants about causes and preventive measures for schistosomiasis, STHs and malaria, and practice of children was designed and administered at the beginning of the main study (June 2004). Thus the main outcomes of the study were, knowledge of participants regarding causes and preventive measures of the diseases under investigation, experience (if the participants had suffered from the diseases before) and their practices in relation to schistosomiasis, STHs and malaria transmission.The following were considered correct causes and risk factors of schistosomiasis: swimming or bathing in ponds, streams, rivers or dams, playing in the river, contact with snail infested/contaminated water, crossing the river bare foot, washing clothes or dishes in the river, stream or pond, urinating or defecating near or in the river, fishing whilst standing in the river, worms in the river, fresh water snails. The following were considered correct preventive measures for schistosomiasis: avoid swimming, playing or bathing in the pond, stream, river or dam, avoid washing dishes or clothes in the pond, steam, river or dam, kill fresh water snails using chemicals, visit the health care centre for treatment, avoid playing in the river, avoid contact with contaminated water, avoid crossing the river bare foot, cross the river on a bridge, avoid fishing whilst standing in the river and use toilet when defecating or urinating.Mosquito and mosquito bite were considered as correct causes of malaria. The following responses in relationship to malaria prevention were considered correct: sleep under ITN, apply mosquito repellents, wear long robes, take prophylactic medicines when visiting malarious area, seek prompt treatment when infected, spray the walls of the house with chemicals to kill resting mosquitoes, fill all holes, ground openings and destroy empty tins that may act as breeding places for vector mosquitoes, burning local herbal plant leaves and clear grass around homes.The following responses were considered correct causes and risk factors of STHs: Eating with dirty hands, handling fruits with dirty hands, not wearing shoes, leaking dirty fingers, keeping fingernails dirty and long, not washing hands after toilet, not washing hands before eating food, drinking dirty water eating unwashed fruits and vegetables, defecating, using the bush as toilet for defecating. Preventive measures for STHs considered correct included the following: washing hands with soap before eating food, washing fruits in clean water before eating, washing hands with soap after toilet, using toilets when defecating or urinating instead of bush toilet, keeping fingers short and clean, drinking clean water, keeping drinking water protected from flies.S. haematobium, S. mansoni, soil transmitted helminths and P. falciparum using quantitative and qualitative parasitological techniques [S. haematobium infection status. Infection with S. mansoni and STHs was determined using a combination of results from the Kato Katz and formol ether concentration techniques. A person was considered positive for S. mansoni or STHs  if S. mansoni ova or ova of any of the STHs species were observed using either the Kato Katz or the formol ether concentration technique or if ova were observed in both the Kato Katz slide preparation or the formol ether concentration slide preparation. An individual was considered negative for S. mansoni, all or any of the STHs species if no ova were observed in slide preparations made using both techniques. P. falciparum was diagnosed by examination of Giemsa stained thick blood smears.As part of the main study, participants were screened for chniques . The uriData collected were entered and analysed using SPSS 8.0 software package. Chi-square, Fisher's Exact test and Multiple regression analysis were used where appropriate.2 = 7.513, p = 0.006. Demographic data revealed that the ages for the participants ranged from 7-15 years with the mean (SD) and median of 9.8 (1.28) and 10.0, respectively. Of the 172 participants 77.3% were aged 8-10 years. The distribution of grade 3 children by school was 106, 59, 30 and 28 for Nyamaropa , Valhalla, Msapa and Kaswa primary schools respectively. The main tribe was the Shona (81.3%) followed by the Zezuru (9.3%), Ndau (1.7%), Ndebele (1.2%). Of the 172 participants 88.4% were Christians.Out of 223 class three participants included in the study 172 (77.1%) responded to the KAP questionnaire. Of the 172 respondents, there were more females, 91 (52.9%) than males 81 (47.1%), χThe provisions of the school regarding water supply, sanitation and amenities for hygienic practices are described in Table S. haematobium, S. mansoni, STHs and P. falciparum in the study population stratified by school are shown in Table S. haematobium was the most prevalent parasite. An interesting observation was the distribution nature of schistosomiasis, STHs and P. falciparum in the same area represented by Msapa primary school, where the prevalence of each parasite investigated in this study was highest compared to other schools. When the study population was stratified by site, S. haematobium was higher in the rural area compared to the farming area although there was no statistical significant difference (63.5% vs 57.6% respectively), χ2 = 0.616, p = 0.433., It was also observed that hookworms and malaria were common in the farming area only and the prevalence of S. mansoni was higher in the rural area (21.0%) compared to the farming area (14.5%) although there was no significant difference (p = 0.273).The prevalence of A. lumbricoides and T. trichiura were not observed in grade three children even in the farming area.Further analysis was done to determine the difference in prevalence of parasites with sex and age. However there was no significant difference in parasitic infection between males and females. Neither was there any significant difference in parasitic infection between different age groups. Although diagnosed as well, Responses on where children defecated when at home revealed that of 172 respondents, 12% used bush toilets whilst 88% used toilets: pit latrine, improved ventilated pit latrine (VIP) or water closet. Of the 12% that used the bush toilets, 5.7% were living in the commercial farming area and 20.0% lived in the rural area. Communal pit and VIP toilets were commonly used in the commercial farming areas whilst more of VIP toilets were used in the rural area. Only 4 (4.6%) respondents in the commercial farming area reported that they used water closet type of toilet. The same was not used in the rural area. One school had a dysfunctional water tank for hand washing after using the toilet. Other schools did not have hand washing water points. All schools did not have running water points, soap basins and soap for convenient hand washing after toilet.After stratifying sources of water by school, it became evident that piped water was predominantly used in the commercial farming areas for drinking/cooking with the highest percentage of use of piped water being recorded for children living in farming areas surrounding Valhalla Primary school (73.0%). The percentage of piped water use by children attending Msapa, and Kaswa primary schools were 53.9% and 40.9% respectively. Children attending Nyamaropa Primary school frequently used boreholes and wells (51.2% and 32.6% respectively). Overall 98.9% of water sources used for drinking and cooking were safe for children living in the farming areas and 84.7% safe drinking water sources were used in the rural area. The percentages of respondents who indicated that they bathed or washed in the river/stream/dam were 74.1%, 72.7%, 45.9, and 31.8% for Msapa, Kaswa, Valhalla and Nyamaropa respectively. Overall, 63.2% of respondents in the farming areas and 36.5% of respondents in the rural area used unsafe water  for washing/bathing.2 = 11.832, p = 0.001). Ninety-seven (65.4%) participants said they new about malaria and this comprised of a higher proportion of children living in the farming area compared to those in the rural area . Overall, 45 (26.2%) children said they knew about STHs and more of these lived in the farming area compared to the rural area.Of the 172 grade 3 primary schoolchildren who responded to questions regarding their knowledge about schistosomiasis, STHs and malaria, 87(50.6%) were from the farming area whilst 85 (49.4%) were from the rural area. Of these 109 (63.4%) indicated that they new schistosomiasis. However a larger proportion of children in the farming area said they knew schistosomiasis than those in the rural area . Ninety-four children (54.7%) said they had suffered from malaria. A higher proportion of children from the farming area had suffered from the disease than those from the rural area, . Only 23 (13.4%) of the respondents said they had suffered from STHs and more of these participants were from a farming area .Figure 2 = 1.869, p = 0.0.172). Thirty-three children  correctly new the causes of malaria and this comprised of 26.4% (95%CI: 17.6-37.0) and 11.8 (95%CI: 5.8-20.6) of participants living in the farming and rural areas respectively . Only 7 participants  of 172 respondents new the causes of STHs. Of the 172 grade three children who responded to questions regarding the best ways to prevent schistosomiasis, malaria and STHs, 38 , 33  and 10  new the best ways to prevent schistosomiasis, malaria and soil transmitted helminthiasis, respectively  said they washed their hands some times before eating food. Only 20 (11.6%) of 172 respondents said they always washed their hands with soap before eating food. Regarding washing of hands after using toilet, 29 (16.9%) said they never washed their hands after using toilet whilst 69 (40.1%) said they sometimes washed their hands after using toilet. Of 143 participants who said they washed hands always or sometimes after using toilet, 89 (62.2%) said they never used soap when washing hands after toilet. Responses of participants regarding their swimming habits showed that 92 (53.5%) swam in the river and of these, 82.6% swam at least once per week. Response regarding use of ITNs revealed that only 15.1% used ITNs. One hundred and fifteen (66.9%) children said they never discussed health issues at home. Of the 57 respondents who said they discussed health issues at home 59.6% said they discussed with their mothers.S. haematobium infection as diagnosed parasitology . Although many respondents who said their urine was red were S. haematobium positive, there was no significant association between this response and S. haematobium infection based on microscopic examination of urine for schistosome ova. Neither was there any association between swimming in the river with schistosomiasis infection. Malaria infection as diagnosed by microscopy of the thick blood smear was associated with participants' knowledge and experience with the disease . There was no association between, observer's results on spot observation of whether children wore shoes or not, experience of participants with STHs, responses of participants on whether they possessed shoes or not with hookworm infection status.There was a significant association between people who reported that they had suffered from schistosomiasis with Multiple logistic regression analysis showed that the reports that participants had suffered from schistosomiasis before and that the participant's urine was red on the day of examination were significant predictors of the disease (p = 0.001 and p = 0.045 respectively).Although it was of borderline significance, report that participant had urinated near the river was a predictor of schistosomiasis (p = 0.058). Multiple regression analysis also revealed thathaving suffered from malaria was a significant predictor of malaria infection (p = 0.042).There have been a considerable number of studies about the KAP relating to schistosomiasis and malaria in different parts of the world, many of which indicate that misconceptions concerning these diseases still exist and practices for their control have been unsatisfactory -26. ResuThe fact that a greater proportion of children did not know the causes and prevention measures of schistosomiasis, malaria and STHs Tables  and 4 inOur study revealed that 32.0%, 19.2% and only 4.1% of the respondents knew about the causes of schistosomiasis, malaria and STHs respectively whilst 22.1%, 19.2% and 5.8% knew measures to control the same diseases respectively. Results obtained in Sierra Leone  showed tAlthough in this study swimming in the river/dam was not associated with schistosomiasis and similarly failure to own and use ITN was not associated with malaria, many children (84.9% of 143 respondents) did not sleep under ITNs whilst 53.5% of the 172 respondents said they swam in the river/dam. These practises pre-dispose the target population to malaria and schistosomiasis respectively. Thus, whilst considerable sums of money may be spend on sustained regular treatment of helminths  and malaResults from this study also show that many children discuss health issues with their mothers compared to other community members. This is import since some studies have revealed that most children's main contact with medical care is through their mothers . On the S. haematobium in the rural area than the farming area . The reason for these findings could be a desirability bias regarding water source used for washing and bathing by respondents in the rural area [The findings on the sources of water used by participants for washing showed that a greater proportion of children in the farming area 62.7% and 36.5% of respondents in the rural area used unsafe water for washing and bathing. However the prevalence results for schistosomiasis showed a significantly higher proportion of children infected with ral area ,22. Howeral area . Thus heral area ,33.S. haematobium were highest in the 8-10 year age group (67.6%) and 13.1 eggs/10 ml respectively [The demographic data obtained in this study shows that 77.3% of grade 3 children are aged 8-10 years. Chandiwana and Whoolhouse (1991) observed that the prevalence and mean intensity of ectively . Thus, gectively .P. falciparum in the same school (Msapa). These results could be contributed by the high risk behaviour of the community as a higher proportion of children from Msapa Primary school reported that they bathed or swam in the river. The clustering effect of helminths and Plasmodium in the same, school, house holds or individuals has significant implications on co-morbidity and severity of diseases [Table diseases -37. On tdiseases ,28,38,39In conclusion, this study has demonstrated a critical need for targeting health messages through schools in order to reach the most susceptible schoolchildren. This will empower high risk age group with the basic knowledge and skills ultimately protecting them from acquiring schistosomiasis, STHs and malaria.The authors declare that they have no competing interests.TM, NM, NK, KCB, FM contributed to the concept and design of the study protocol; NM, SZ, DS, NHP, GH, FT, MJM, VC and TM carried out the clinical assessment and parasitology; TM, NM, MG, and MPM carried out the analysis and interpretation of the data; NM and TM drafted the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/11/169/prepub


In Burkina Faso, a recent Demography and Health Survey (DHS) gave the opportunity to assess the performance of the ParacheckA national representative sample of 14,947 households was selected using a stratified two-stage cluster sampling. In one out of two households, all under five children were eligible to be tested for malaria using both RDT and microscopy diagnosis. Paracheck® performance was assessed using miscroscopy as the gold standard. Sensitivity and specificity were calculated as well as the diagnosis accuracy (DA) and the Youden index.The malaria infection prevalence was estimated at 66% (95% CI: 64.8-67.2) according to microscopy and at 76.2% (95% CI: 75.1-77.3) according to Paracheck®. The sensitivity and specificity were estimated at 89.9% (95% CI: 89.0-90.8) and 50.4% (95% CI: 48.3-52.6) respectively with a Diagnosis Accuracy of 77% and a Youden index of 40%. The positive predictive value for malaria infection was 77.9% (95% CI: 76.7-79.1) and the negative predictive value was 72.1% (95% CI: 69.7-74.3). Variations were found by age group, period of the year and urban and rural areas, as well as across the 13 regions of the country.® test was high, its specificity was poor in the general under five population of Burkina Faso. These results suggest that Paracheck® is not suitable to assess malaria infection prevalence at community level in areas with high malaria transmission. In such settings, malaria prevalence in the general population could be estimated using microscopy.While the sensitivity of the Paracheck In Burkina Faso, malaria is the main cause of consultations. In 2011, according to statistics from the ministry of health, this disease was responsible for 61.4% of consultations, 77.7% of hospitalizations, and more than three quarters (79.8%) of deaths occurring in health facilities among under five children[Early diagnosis and correct treatment are, therefore, a major public health need in this country in order to reduce morbidity and mortality due to malaria. However, the lack of laboratory equipment in primary health care facilities prevents the biological diagnosis of malaria using microscopy. Clinical diagnosis and presumptive treatment of fever are the rule, leading to a large proportion of over diagnosis due to the non-specific symptoms of malaria-5. In ruIn the last decade, there has been an increase in the number of companies manufacturing malaria Rapid Diagnosic Tests (RDT). A wide range of field and laboratory trials have been conducted to assess the accuracy and effectiveness of RDTs in order to establish their use in endemic areas. Over thIn Burkina Faso, the performance of RDT has been largely documented in clinical settings-19, but Burkina Faso’s fourth DHS was carried out from May 2010 to January 2011[At the day of the visit, fieldworkers tested children in their household using a RDT and thick and thin blood films were used by a laboratory technician to assess malaria infection prevalence by microscopy later.Plasmodium falciparum accounts for 95% of malaria infections in children less than five years old[P. falciparum-specific HRP-2 protein (PfHRP-2), was used to detect infected children. This test requires approximately 5 μl of blood and is readable after 15 minutes.In Burkina Faso, ears old. ParacheBlood slides were labelled and air-dried horizontally in a slide tray. Thin films were fixed with methanol immediately after drying. Slides were stained with 2% Giemsa for 20 minutes in the field. Later, at the reference laboratory  in Ouagadougou, two independent technicians read twice each blood slide and classified them as either negative or positive. Another reading was performed by a third microscopist in case of any discrepancy.(J) is a function of sensitivity (p) and specificity (q) (J = p + q-1), is not related to prevalence and is commonly used to measure diagnostic performance[Analyses were performed using STATA 12. Prevalence was reported based on RDT results and microscopy. Paracheck® performance was assessed using microscopy as the gold standard. Sensitivity and specificity were calculated as well as the diagnosis accuracy (DA) and the Youden index. DA is the proportion of true results, either positive or negative, among RDT results. It measures the proportion of correct diagnoses and depends on the prevalence of the disease. The Youden index formance-24. ThisResults were calculated by age group, urban and rural areas, region, and month of data collection and period of the year. Three periods were defined according to the month of data collection: before the rainy season, in May and June, during the rainy season, from July to October, and after the rainy season, from November to January.Survey procedures in STATA were used to account for the two-stage cluster sampling as well as the unequal probability of selection between children in rural and urban areas due to weighting. Proportions were compared using a Pearson chi-squared test or a Fischer Exact test. Means were compared using a Student test or Anova and the correlation between prevalence and sensibility or specificity was investigated by a Pearson correlation coefficient.6,102 children aged from 6 to 59 months were screened with both Paracheck® test and microscopy during the study period. There were no differences in the mean age (p = 0.93) and the sex distribution (p = 0.98) of recruited children across the 13 regions of the country  were performed during the rainy season and slightly less than a third 31.8%) after the rainy season  according to microscopy and at 76.2% (95% CI: 75.1-77.3) according to Paracheck®. According to microscopy, the prevalence increased with age group, from 58.6% in 6 to 12 months old children to 69.7% in 48 to 59 months old children  before the rainy season to 92.8% (95% CI: 91.3-94.3) after the rainy season. Sensitivity was slightly higher in rural areas compared to urban areas. By contrast, specificity did vary markedly by period of the year and area. The highest specificity was estimated to 71.3% (95% CI: 65.6-77.0) before the rainy season and decreased to 44.3% (95% CI: 41.4-47.2) and 51.9% (95% CI: 48.1-55.7) during and after the rainy season respectively. Specificity in urban areas was good but decreased drastically to 41.5% in rural areas.A large variation across regions was found. The sensitivity ranged from 74.1% in the Cascades region to 97.5% in the Centre-South region Table . While tOverall the diagnosis accuracy was estimated at 77% and the Youden index at 40%. The DA did not vary by age group, period of the year or area Table . By contA large variation across regions was found, the DA varying from 70% in the East region to 86% in the South-West region and the Youden index from 21% in the East to 55% in both Plateau Central and Hauts-Bassins regions Figure .® test in under five children nationwide at community level. Overall, the test showed a high sensitivity (89.9%) with a low specificity (50.4%) for the detection of malaria infection. Malaria infection prevalence was high: 66.0% and 76.2% according to microscopy and Paracheck® respectively, reflecting an intense transmission of malaria in Burkina Faso, in particular during and after the rainy season.The 2010 DHS undertaken in Burkina Faso gave the opportunity to assess the performance of the Parachecket al. found similar results with a sensitivity and a specificity of the Paracheck® test estimated at 96.1% and 63.1% respectively[® sensitivity and specificity were estimated at 86% and 90% respectively during the dry season, and 94% and 78% respectively during the rainy season[In other countries, a few studies were undertaken at community level. In Tanzania, in an area of intense malaria transmission, Laurent ectively. Howeverectively and Angoectively, while tectively. In Souty season. In the y season.et al. showed that the sensitivity of HRP-2 tests increased with increasing parasite density, from 74.6% when the parasite density was low (0 to 99/μl) to 99.1% when the parasite density was higher [® sensitivity was found higher in rural areas, where transmission is higher than in urban areas, and slightly higher in younger children with no or a low level of acquired semi-immunity.Sensitivity results must be interpreted in relation to parasite density. Indeed, Tiono ,999/μl). This re,999/μl) as well ,999/μl). Althoug® test, about half of the children with a positive RDT result had a negative blood slide. This high proportion may be related to the well-known limitation of Pf HRP-2 tests which detect persistent HRP-2 antigenicity in the bloodstream for a few weeks after previous infections[et al. also showed an increase in specificity with decreasing prevalence[With 50% specificity for the Paracheckfections,25,31. Ifections which mafections. Low parfections. In Burkfections. The malSpecificity, as well as positive predictive value, results should however be interpreted bearing in mind one limitation of this study. Indeed, due to the capacity of the test to detect both low parasitaemia and persistent HRP2 antigenicity existing at community level, the discordant cases (positive RDT result/negative microscopy) could not be classified accurately in the absence of a second gold standard such as Polymerase Chain Reaction (PCR).Variations in the sensitivity, specificity and Youden index were found across the 13 regions of Burkina Faso, whereas diagnosis accuracy was 70% or above. This is certainly due to the difference in the distribution of month of data collection and therefore differences in the transmission level, prevalence and parasite density. While tests were mainly performed before the rainy season in the Centre region, the prevalence was the lowest and the specificity the highest. In addition, under field condition, the performance of RDTs may vary from one user to the other and the quality of the tests may be affected by temperature, humidity, substandard transport or storage condition.® test was high, its specificity was poor in the general under five population of Burkina Faso. These results suggest that Paracheck® is not suitable to assess malaria infection prevalence at community level in areas with high malaria transmission. In such settings, malaria prevalence in the general population should be estimated using microscopy. However, in other countries where elimination of malaria is targeted, detecting malaria infection at community level, even at very low parasite density levels, is certainly useful.While the sensitivity of the ParacheckP. falciparum specific HRP-2 protein; PCR: Polymerase chain reaction; RDT: Rapid diagnostic test; WHO/FIND: World Health Organization/ Foundation for Innovative New Diagnostics.DA: Diagnostic accuracy; DHS: Demography and Health Survey; Pf.HRP-2: The authors declare that they have no competing interests.SS (first author) and FKS conceived the study, performed the statistical analysis and drafted the manuscript. SS (third author), HT, and FB contributed to the manuscript by giving substantial intellectual content. IN supervised the fieldwork and carried out microscopy diagnosis. AR contributed to intellectual content, supervised the statistical analysis and the writing up of the manuscript. All authors read and approved the final manuscript.


P. falciparum malaria incidence in Ethiopia.Reservoirs created by damming rivers are often believed to increase malaria incidence risk and/or stretch the period of malaria transmission. In this paper, we report the effects of a mega hydropower dam on Plasmodium falciparum malaria incidence among children less than 10 years of age living near a mega hydropower dam in Ethiopia. A total of 2080 children from 16 villages located at different distances from a hydropower dam were followed up from 2008 to 2010 using active detection of cases based on weekly house to house visits. Of this cohort of children, 951 (48.09%) were females and 1059 (51.91%) were males, with a median age of 5 years. Malaria vectors were simultaneously surveyed in all the 16 study villages. Frailty models were used to explore associations between time-to-malaria and potential risk factors, whereas, mixed-effects Poisson regression models were used to assess the effect of different covariates on anopheline abundance.A longitudinal cohort study was conducted over a period of 2 years to determine P. falciparum malaria incidence showed no statistically significant association with distance from the dam reservoir (p = 0.32). However, P. falciparum incidence varied significantly between seasons (p < 0.01). The malaria vector, Anopheles arabiensis, was however more abundant in villages nearer to the dam reservoir.Overall, 548 (26.86%) children experienced at least one clinical malaria episode during the follow up period with mean incidence rate of 14.26 cases/1000 child-months at risk (95% CI: 12.16 - 16.36). P. falciparum malaria incidence dynamics were more influenced by seasonal drivers than by the dam reservoir itself. The findings could have implications in timing optimal malaria control interventions and in developing an early warning system in Ethiopia. Globally, 60% of the world’s large river systems are impacted by dams . Such daEthiopia has recently constructed a large number of dams to produce electricity, irrigate agricultural lands, control flood, reduce poverty and sustain economic growth. Examples of mega hydropower projects are Gilgel-Gibe I and II (completed), Gibe III and the Grand Ethiopian Renaissance Dam (under construction) with a capacity of generating 184MW, 420MW, 1870MW and 6000MW, respectively. More damming projects are underway, as Ethiopia currently uses only 3% of its hydroelectric potential .P. falciparum malaria incidence. This study is the first longitudinal study conducted in Ethiopia to investigate the effect of large hydropower dams and on malaria incidence risk. The findings of this study could assist the development of a dam-associated malaria control programme.In Ethiopia, little or no information is available on the effect of such large hydropower dams on Thus, the objective of this longitudinal study was: P. falciparum malaria incidence and/or on malaria vector abundance, and1. To investigate whether the distance from the dam reservoir has an influence on 2. To investigate the dynamics of malaria and its vectors with season.A longitudinal cohort study was conducted over a period of two years (July 2008 - June 2010) among children less than 10 years living in 16 study villages around the Gilgel-Gibe hydropower reservoir in south-western Ethiopia  was based on a foreseen P. falciparum malaria incidence rate of 15% and 10% in ’distant’ and ’nearby’ villages, respectively. A dropout rate of 10% and a design factor equal to three (to adjust for the clustering effect) were used to get a representative sample size of 2080 study participants. Hence, 130 children were randomly selected from a list of all children less than 10 years of age in each of the 16 villages for the follow-up study.The study was designed to detect a 5% difference in malaria incidence rate and the sample size calculation  were stained with Giemsa stain following a standard technique [The cohort of 2080 children was monitored longitudinally for echnique  and wereThe study was reviewed by the World Health Organization/TDR research ethics committee and ethical approval was obtained from the research and ethics committee of Jimma University. Verbal and written signed informed consent was obtained from the mother or caregiver of each child before enrollment of the child in the study.An. gambiae s.l complex were further assigned to sibling species using polymerase chain reaction (PCR) techniques as described by Hunt et al [Adult mosquitoes were collected monthly in all study villages to assess the effect of distance from the dam reservoir and season on mosquito density. Two houses, one located at the center and one at the periphery of the village were selected for mosquito collection in each of the 16 study villages. Mosquitoes were collected one day a month, from 1800 to 0600 hours from each of the two selected houses using light trap catches. Traps were hung from the roof supports or pillars at the foot end of the bed or traditional mud-made sleeping place. The trap was suspended about 1.5 meters above the bed. In all the selected houses occupants were provided with new untreated nets prior to the start of the entomological survey. Collection bags were retrieved from traps in the morning from 0800 to 0900 hours. The collected mosquitoes were then transferred into paper cups, killed using chloroform, sorted by genus and sex and then counted. The number of human occupants and potential hosts in each surveyed house during the previous night was recorded. Space spray catches (SSCs) were not included as the mosquito population in the study area showed high levels of insecticide resistance ,12. Morpnt et al  and modiMonthly rainfall (mm), relative humidity (%), maximum and minimum temperature (°C) of the study area were obtained from the south-western branch regional office of the Ethiopian Meteorological Agency for the two years of the follow-up study. Similar climatic conditions were assumed for all the sixteen villages.P. falciparum malaria incidence rates were expressed as the number of cases per 1000 child-months at risk. Two or more consecutive episodes occurring within 30 days of the first episode were considered recrudescent infections and treated as a single episode. The 95% confidence intervals of malaria incidence rates were calculated assuming that the number of new malaria cases is Poisson distributed.P. falciparum malaria risk was analysed through a time-to-event model, which is the most efficient way to model time-to-event data [The ent data . A pieceThe covariates used were: distance from the dam reservoir shore, season, sex, age, year, and mosquito density. Since children are clustered within villages, village was introduced in the piecewise constant hazard model as a gamma distributed random effect (frailty) to accommodate for the correlations in the data. The data were analyzed using STATA 10 .A mixed-effects Poisson regression model was used to explore the association between mosquito abundance and the following covariates: distance from the dam reservoir shore, year, climatic variables, and season. Village was treated as a random effect in the model. To get better insights in the specific role of the climatic variables, the relation between mosquito density and climatic variables at different lag periods was tested as well. The analysis was performed using PROC GENMOD .P. falciparum malaria clinical episodes recorded was 685 resulting in an overall incidence rate of 14 cases/1000 child-months at risk (95% CI: 12.16 - 16.36) and the annual parasite index (API) for year 1 and year 2 was 177/1000 children and 158/1000 children, respectively.Of 2080 children enrolled at the start of the study , 29 (1.4%) died due to various reasons and 15 (0.72%) migrated elsewhere. Of the migrant children, two children were tracked back and 13 were lost to follow up (until June 2010). Therefore, the effective number of children followed up was 2040 (97.98%) resulting in 48,960 person-months at risk. Of this cohort, 951 children (48.09%) were females and 1059 (51.91%) males. The median age of children in the cohort was five years. In total, 548 (26.86%) children experienced at least one clinical malaria episode during the follow up. The number of children with 1, 2 and 3 clinical malaria episodes were 421 (20.64%), 119 (5.83%) and 7 (0.34%), respectively. One child had five (0.26%) clinical malaria episodes over the two years follow up period. Overall, the number of new P. falciparum malaria incidence in the study area over the 2 years study period. Three malaria incidence climate seasons (MICS) could be identified consistently over the two years follow up: a high malaria incidence climate season (HMICS) from August to November, a moderate malaria incidence climate season (MMICS) from April to July, and a low malaria incidence climate season (LMCIS) from December to March. Malaria peaked in October/November following the main rains (25.8 vs. 29.4 cases per 1000 child-months at risk). In general, malaria in the study area also showed marked seasonality as more than 75% of clinical cases occurred in less than 6 months over the two years study period. Figure Figure P. falciparum risk  were found. No association between P. falciparum malaria incidence and the distance from the dam reservoir shore was found. The difference in malaria risk between the two sexes was not significant. However, the difference in malaria risk among the three age strata was significant with children above three years of age having significantly higher P. falciparum risk than children less than 3 years of age. A significant association was also observed between P. falciparum malaria risk and season (p < 0.001)  followed by An. demelloni (6.25%) and An. coustani (2.68%). All other anopheline species constituted 3.2% of all the collected anopheline species including An. funestus and An. pharoensis, which have a secondary role in malaria transmission in Ethiopia. Molecular identification of An. gambiae complex revealed that over 98.5% of the assayed specimens were An. arabiensis.Overall, 2353 adult female anopheline mosquitoes belonging to 10 species were collected in 2 years study period. Morphological identification showed that An. arabiensis) and different covariates. The first column shows the results of the univariable analyses while the second column shows results of the multivariable model with all covariates included. In column 3, the climatic variables were dropped from the multivariable model as they were highly correlated with season. There was a significant association between mosquito density and distance from the dam reservoir (p < 0.01). Mosquito density decreased by 53% at 6-7 km from the dam, compared with localities close to the dam reservoir. The strong effect of season was modified through the climatic variables indicating that a strong part of the seasonal effect was based on climate. Table Table P. falciparum malaria incidence is shown in Figure The spatio-temporal dynamics of Malaria transmission in the study setting occurs throughout the year but it has a seasonal pattern with an incidence peaking during October/November and with more than 75% of the cases occurring in six months. The seasonality of malaria incidence was consistent over the two years study period and is comparable to observations in other parts of the country .P. falciparum malaria incidence and the distance from the Gilgel-Gibe dam reservoir was found. This finding was in consistent with the often stated hypothesis that dams influence malaria incidence and/or prolong the seasonality of malaria transmission by increasing mosquito abundance. Other studies from the Rift Valley of Ethiopia [No association between the Ethiopia ,22 indicEthiopia ,24.Anopheles arabiensis, were recorded during the wet season in villages nearer to the dam reservoir. This could be explained by the larger number of temporary mosquito breeding sites due to the presence of the reservoir.Higher densities of the major local malaria vector, Although higher malaria vector abundance is associated with higher malaria incidence, and mosquito abundance is higher close to the dam, no effect of the distance to the dam is found on malaria incidence. This apparent paradox can be explained by the large seasonal effects. The effect of mosquito density on malaria incidence in the univariable model disappears when controlling for season in the multivariable model. There is indeed a large difference between mosquito density and malaria incidence between the rainy and dry season. In the rainy season, mosquito density is high everywhere, and the higher mosquito number near to the dam is therefore superfluous.Several studies also reported that only small populations of mosquitoes are required to maintain a high level of transmission ,26. DuriP. falciparum malaria incidence in different localities in Ethiopia. In our study, minimum temperature was correlated with higher mosquito density, while maximum temperature showed no effect on mosquito density. Minimum temperature predicts malaria risk mainly due to its direct effect on the survival and feeding frequency of malaria vectors [An. gambiae s.l. [Climate seems to be the most important determinant of malaria risk through its influence on mosquito density ,28, as i vectors  and by s vectors . In Uganiae s.l. . At highiae s.l. . Other siae s.l. ,36. On tiae s.l. .P. falciparum malaria incidence with 1-3 months lag period as was also observed in several other localities in Ethiopia [The contrasting effect of minimum and maximum temperature indicates that an optimal temperature might exist. Moreover, the climatic variables also showed a lag effect on malaria incidence. Rainfall was found to be a predictor of Ethiopia .In addition to climate, our findings indicate that the risk of malaria varied with age with older children being more at risk which is in agreement with other studies . No diffNo effect of the distance of the dam on malaria incidence was found. Anthropogenic environmental changes do not necessarily result in increased mosquito-borne disease incidence in the surrounding human population as the link between anthropogenic environmental changes and disease incidence is complex and can be influenced by several other variables . Hence, The authors declare that they have no competing interests.DY conceived and designed the study, was involved in the coordination and supervision and drafted the manuscript; YG performed the data cleaning, statistical analysis and critically reviewed the manuscript; KT was involved in the coordination, supervision and reviewed the manuscript; KW was involved in the study design, supervision, coordination and data entry; WK was involved in the study design, supervision, coordination and data entry; LD was involved in statistical analysis and critically reviewed the manuscript; NS was involved the statistical analysis, in drafting and critically reviewing the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/13/161/prepub


Plasmodium falciparum and P.vivax are co-endemic. Bivalent Rapid Diagnostic tests (RDTs) showed promise as diagnostic tools for P.falciparum and P.vivax. To assist national malaria control programme in the selection of RDTs, commercially available seven malaria RDTs were evaluated in terms of their performance with special reference to heat stability.Malaria presents a diagnostic challenge in areas where both P.falciparum, and 17% for P.vivax. The highest sensitivity of any RDT for P.falciparum was 98%  and lowest sensitivity was 76% . For P.vivax highest and lowest sensitivity for any RDT was 80%  and 20%  respectively. Heat stability experiments showed that most RDTs for P.falciparum showed high sensitivity at 45°C upto 90 days. While for P.vivax only two RDTs maintained good sensitivity upto day 90 when compared with RDTs kept at room temperature. Agreement between observers was excellent for positive and negative readings for both P.falciparum and P.vivax (Kappa >0.6–0.9).This study was undertaken in four forested districts of central India . All RDTs were tested simultaneously in field along with microscopy as gold standard. These RDTs were stored in their original packing at 25°C before transport to the field or they were stored at 35°C and 45°C upto 100 days for testing the performance of RDTs at high temperature. In all 2841 patients with fever were screened for malaria of which 26% were positive for P.falciparum and P.vivax even at high temperature, the quality of RDTs should be regulated and monitored more closely.This is first field evaluation of RDTs regarding their temperature stability. Although RDTs are useful as diagnostic tool for  Plasmodium falciparum and P. vivax is a life threatening disease for individual with low immunity P. vivax and P. falciparum are co-endemic. Presumptive treatment of all fevers as malaria with chloroquine (CQ) becomes increasingly popular in resource poor setting because of lack of laboratory infrastructure and technical expertise Malaria due to both Malaria RDTs have the potential to provide a huge step forward in the management of febrile illness in malaria-endemic areas This study was carried out in tribal and forested areas of four malarious districts of Madhya Pradesh i.e. Jabalpur, Mandla, Balaghat and Rewa during July 2011 to March 2012 . A crossA one week training workshop was organized in the month of July 2011 to train the project staff for standard procedure of data collection and result interpretation. This was followed by two days training in field for screening and enrollment of study subjects, taking consent, collection of blood samples and RDT test procedures. The field clinic traveled 10 villages of each district for screening patients. All households of selected villages were visited by survey team and all clinically suspected malaria cases  were enrolled for the study. There were two teams, each consisting of two field workers, one technician and one research assistant.All 7 RDTs were tested simultaneously in field on all enrolled patients using whole blood collected by a finger prick in a single bleed after taking informed consent. RDTs were performed at each site by members of the study team i.e. field worker and technician as per manufacturers instruction, and results interpreted and recorded after 15 to 30 minutes. They were advised that if the background of the RDT test window remained pink after 15 min, they should wait till the background is clear before declaring the test results. The study team recorded each RDT result as either positive or negative or invalid. Thick and thin smears were prepared from the same finger prick blood and air-dried. At the central laboratory of Regional Medical Research Centre for Tribals, thick and thin smears were stained with JSB This study was approved by institutional review board of Regional Medical Research Centre for Tribals, Jabalpur India (IRB00006471). Written informed consent were obtained from all participants or the parents of children younger than 18 years, and assent were taken from children of age between 7 to <18 years as per Ethical Guidelines of Indian Council of Medical Research, New Delhi India.For temperature stability testing of the RDTs which were stored at 25°C on receipt, were then allocated to separate groups for storage at 35°C & 45°C upto100 days and at 60°C for 48 hrs. The incubators were stabilized at the required temperature for three days before the RDTs were placed inside. The log book was maintained for these incubators and temperature was monitored 3 times in a day. RDTs were removed from storage at 15 to 30 days time intervals allowed to reach at room temperature before testing. For all temperature/time combinations studied seven RDTs were tested for each temperature/time point and comparison was made with control RDTs (one for each temperature/time point). A micropipette was used to measure blood volume. The reading of the tests was undertaken by the same person to minimize inter-operator variability. The temperature during transport and in field were not monitored as it was not controlled.P. falciparum is more prevalent than P. vivax in most parts of Madhya Pradesh. Thus, assuming slide falciparum rate (SFR) as 25% and slide vivax rate (SVR) as 15% for the study area, we need to screen about 552 cases for P. falciparum and 920 cases for P. vivax. Thus, overall we need to screen about 1500 malaria suspected cases to test the sensitivity of different RDTs for both P. falciparum and P. vivax.We assumed that the sensitivity of RDT is approximately 90% (P = 0.90) and absolute precision of 5% (d = 0.05), i.e. the estimated sensitivity of RDT will vary between 85–95%. The minimum required number of cases (positive cases by gold standard) is 138. Our past experiences in the study area revealed that For heat stability testing, we assumed that the sensitivity of RDT kit is approximately 90% (P = 0.90) and absolute precision of 10% (d = 0.1), i.e. the estimated sensitivity of RDT kit will vary between 80–100%. The minimum required number of cases (positive cases by gold standard) is 35 at each level of temperature.P. falciparum and P. vivax were given treatment as per treatment guideline of National Vector Borne Disease Control Programme (NVBDCP) P. falciparum were administrated the oral dose of ACT  with single dose of Primaquine (45 mg). P. vivax cases were given 1,500 mg Chloroquine for three days, followed by 15 mg Primaquine daily for 14 days. Infants and children were given proportionally lower doses. Infants and pregnant women were not given Primaquine.All patients infected with The forms were double-entered using CS-Pro 4.1 , with range, consistency, and edit checks built into the data entry programme for quality control. The two databases were validated and all inconsistencies and differences were resolved. Statistical analyses were performed using STATA 11.2 (StataCorp Texas USA). Diagnostic performance characteristics i.e. sensitivity, specificity and positive & negative predictive values (PPV & NPV) were calculated against light microscopy as gold standard by using ‘diagt’ command in STATA. However for heat stability testing sensitivity and specificity were calculated against diagnostic performance of RDTs kept at room temperature.P. falciparum and P. vivax were taken as true positive for both P. falciparum and P. vivax species and P. falciparum only gametocyte cases were considered as true negative. P. malariae infections were excluded during the analysis of RDTs performance. Inter-observer agreement for both results of positive and negative reading as well as for stability was expressed by Kappa statistics for each pair of observers. A Kappa between 0.6 and 0.8 was considered a good agreement, higher than 0.8 was considered as excellent During calculation of sensitivity/specificity, matching mixed infections with In all 2841 patients aged 2 month to 80 years (median age 10 years) with fever/history of fever were screened for malaria. Only 2207 eligible subjects were enrolled for RDT testing in parallel with microscopy. The enrollment of study subjects are divided into two parts i.e. one for testing RDT diagnostic performance under normal field condition and another for heat stability testing by keeping RDTs at various temperature up to 100 days.P. falciparum, 16.6% P. vivax, 1.0% P. malariae, 1.9% mixed infection of P. falciparum and P. vivax and 0.9% mixed infection of P. malariae with P. falciparum and/or P. vivax. FIRST RESPONSE® detected 468 out of 480 microscopically confirmed asexual±sexual falciparum malaria infection  both at 35° and 45°C up to day 90 when compared with RDTs kept at room temperature. However, a sharp decline in sensitivity was recorded on day 100 at 35°C and 45°C by most of the RDTs. On the contrary all RDTs kept at 60°C for 48 hours showed no decline in the diagnostic performance.Results of heat stability testing was shown in P. vivax, the sensitivity of FIRST RESPONSE® was very good up to 90 days (100%) and a decline was noticed on day 100 (92%). Parascreen also performed well upto day 90 at 35°C (88%). However, a sharp decline in sensitivity was observed on day 90 at 45°C (75%). While other RDTs showed a steady decline in sensitivity from day 60 onwards  and plasmodium specific lactate dehydrogenase (pLDH) and species specific pLDH or aldolase based test P. falciparum was >95% and for P. vivax ≥80%. The high frequency of positive smears in this study is consistent with previous studies in Central India P. falciparum and frozen blood samples (200–2000 parasites/µl of blood) by experienced technicians in a research laboratory and not in field as done in the present study, the results of the WHO, FIND and CDC are comparable to this study with regard to diagnostic performance of five RDTs evaluated in both the studies. Additionally, first field based evaluation of commercially available RDTs regarding their temperature stability was also carried out in the present study. Among the 7 bivalent RDTs, most RDTs for P. falciparum showed a very high sensitivity over period at 35 and 45°C upto day 90 in terms of percentage of successful tests. While for P. vivax, the FIRST RESPONSE maintained good sensitivity over period at 35, 45°C upto day 90 and showed a decline in sensitivity on day 100. Parascreen was also good upto day 90 at 35°C only and showed a sharp decline in sensitivity on day 100. These results are consistent with those of WHO, FIND and CDC product testing of RDTs.The present study assessed the performance of various bivalent RDTs in field population. Overall, highest sensitivity for P. falciparum generally agreement and Kappa values were good for all RDTs however, for P. vivax the Kappa was not good for most RDTs on day 90 and 100. Thus the use of RDTs widely in the programme will require considerable regulation and quality control Heat stability is vital to maintaining sensitivity of the test in the field In view of this, while malaria RDTs can be applied in a number of settings, the greatest potential for impact on public health is in extension of access to accurate, parasite based diagnosis of malaria to regions and populations where good quality microscopy based testing is impractical to maintain, making possible the implementation of recent WHO/NVBDCP recommendation on parasite based diagnosis prior to anti-malarial therapy Nevertheless, the challenges associated with establishing the routine use of RDTs in rural remote setting where microscopy could not be established should be tackled carefully as the distribution of RDTs and antimalarials must occur hand in hand to ensure effective case management of febrile disease. These results also suggest that the quality of RDTs should be regulated and monitored more closely. We also noticed a wide range in pricing for RDTs ranging from 0.70$ to 2$. However, high price of RDTs is not an assurance of good performance. Therefore, continued search and eventually introducing other alternative and highly sensitive low cost malaria diagnostic methods should also be explored which are capable of detecting low parasitaemia at high ambient temperature.Table S1Details of bivalent Rapid Diagnostic Tests.(DOC)Click here for additional data file.


While the emergence of drug resistant strains, as well as the costs and adverse reactions to medications, complicate falciparum prophylaxis use, there are virtually no drugs available for vivax prophylaxis, beside of primaquine.Malaria prevention in travelers to endemic areas remains dependent principally on chemoprophylaxis. Although malaria chemoprophylaxis refers to all malaria species, a distinction should be drawn between Based on traveler’s malaria data, a revised recommendation for using chemoprophylaxis in low risk areas should be considered. P. falciparum accounts for almost 70% of all the imports.2Every year, an estimated 50 million travellers visit malaria endemic areas. Some 30,000 malaria cases are reported annually in non-endemic, industrialised countries and imported malaria remains a public health problem associated with high case fatality rates.vaccine, on personal protection and on chemoprophylaxis. However, malaria vaccine is not on the near horizon, especially not for travelers, despite some encouraging new data.Theoretically malaria prevention could be based on N, N-diethyl-3-methylbenzamide (DEET) formulations. The use of insecticide-impregnated clothing can also be helpful.Personal protection refers to all measures that can be taken to reduce the risk of the anophline bites. Since the anophleles mosquito is a night feeder, protection is relatively easy when compared for example to protection from dengue mosquitoes, which are day feeders. Protective strategies include wearing clothing after sunset that covers as much bare skin as possible, and using mosquito repellents on exposed skin containing about 35% Malaria in many areas of the world is seasonal and usually reaches its peak at the end of the rainy season, thus avoiding travel during peak malaria seasons may reduce the risk.Malaria chemoprophylaxis in travelers to endemic areas is one of the most complicated and challenging aspects of travel medicine and poses several significant problems.Risk-benefit: the risk of malaria infection and severe consequences of the disease should be weighed against the risk to the traveler of the drug itself. Several drugs have had fatal outcomes to consumers; others have caused significant adverse events and an interruption of travel due to the adverse events. This side of the equation is not always weighed appropriately by those who prescribe these drugs.Cost-benefit: with the development of malaria-resistant species, new drugs have been made available, usually at a higher cost. Thus for budget travelers, especially with long-term trips, use of these drugs becomes a burden. When the malaria risk is minimal, the benefit of such an expense is often felt unjustified.falciparum prophylaxis” and not a pan –malaria prophylaxis. Travelers who take the recommended prophylactic drugs may still present with late-onset vivax infection.vivax malaria in most cases does not have a severe outcome, it remains a significant disease, and one that the traveler would like to prevent. Additionally, if a traveler contracts malaria despite taking prophylaxis, he or she may deem it useless and skip taking it for subsequent trips.Inadequacy of the current chemoprophylaxis: Although we use the term, “malaria prophylaxis,” in reality we have “vivax malaria are all probable reasons for low adherence to prophylaxis, and well-known to those practicing travel medicine. A survey done in our institute of travelers presenting post-travel, seeking medical advice for any reason [n= 1207], demonstrated that only 15% adhered to malaria prophylaxis [E. Schwartz unpublished data].Adverse events, cost-benefit calculations and the inadequacy of preventing late-onset These results highlight the discrepancy between the medical recommendations for malaria prophylaxis and the travelers’ perceptions.vivax and P. ovale, have persistent liver stages resulting in relapse months to years later.The parasite’s life cycle in humans occurs in two stages . In the falciparum infection and after 14± 3 days in P. vivax infection.The second, or erythrocytic stage occurs when the parasites are released into the bloodstream, invade erythrocytes, and cause clinical illness. This stage occur usually after 12 ± 3 days in P. It should be noted that:▪ The malaria parasite is different in its sensitivity to drugs in each form of its cycle. Thus a drug which acts on the parasite during the intra-erythrocytic stage will not necessarily act against it in its liver stage and vice versa.▪ Chemoprophylaxis does not prevent the infection (as in the case of vaccine preventable diseases), but rather works as having a killing effect against the parasite, either within the erythrocytes or within the hepatocytes, thus preventing the clinical disease.Based on the parasite’s life cycle, there are two types of malaria chemoprophylaxis, based on the site of action.Blood stage prophylaxis refers to drugs that act only on parasites within the red blood cells. These are the commonly known antimalarial drugs that have been used over the past 60 years or so. Among their disadvantages is that they must be continued for 4 weeks after travel to eliminate the parasites within the RBCs which may emerge from the liver as late as 2–4 weeks after exposure. Another major disadvantage is that since these drugs have no activity against the liver stage and development of hypnozoites, they actually prevent only primary vivax  infection, and they do not have the ability to prevent relapse. They are therefore a complete prevention only in the case of P. falciparum infection.Liver stage prophylaxis, refers to drugs that act on the parasite while invading the hepatocytes. Since these drugs kill the parasite early on during the infectious process, there is no need to continue taking the drug after leaving the endemic areas. For falciparum infection, it has the advantage of shortening the duration of the prophylaxis usage and instead of continuing medication for 1 month post-travel there is only a need to continue for several days, which may increase compliance with the full prophylaxis schedule. In the case of vivax  infection, liver stage prophylaxis is imperative. Only drugs that act early on the liver stage and prevent the hyponozoite formation offer complete prevention of this infection. There are currently only 2 drugs which act on the liver stage: atovaquone-proguanil and primaquine, but only primaquine has cidal activity against the hyponozoites ( as discussed further in the vivax prophylaxis section).falciparum to chloroquine is almost universal. It remains effective only in Central America, the Caribbean (mainly Haiti), and in some of the Middle Eastern countries where the prevalence of P. falciparum is in any case very low.6The introduction of chloroquine in the 1950’s brought great hope that falciparum prevention could be easily achieved with a long acting drug, that was well-tolerated and taken on a weekly basis. However, within one decade drug resistance appeared, first in South East Asia and within a few years this resistance spread throughout the endemic areas. Currently, the resistance of P. The history of the development of chemoprophylaxis since then includes trying to find new drugs that are both efficacious and well-tolerated. It should be remembered that a drug with even an infrequent severe adverse event, if used as prophylaxis for a very large volume of travelers, might quickly present as a harmful drug. Two drugs which were introduced after chloroquine, namely Amodiaquine and Sulfadoxin-Pyrimethamin (Fansidar), were excluded from use as prophylaxis due to severe adverse events, including fatal cases. With amodiaquine, fatalities were due to agranulocytosis, and with Fansidar they were due to fatal toxic epidermal necrolysis. Risk-benefit calculations that were done at that time showed that in some geographical areas, the risk of fatal outcomes from these drugs was higher than from the disease.7The principal drugs currently in use are mefloquine, doxycycline, atovaquone-proguanil , and to some extent Primaquine falciparum strains and due to its long half-life, it can be taken on a weekly basis. These characteristics of the drug created optimism, in the mid-1980’s when first introduced in Europe (and in the US in 1990), that an ideal replacement for chloroquine had been found. In addition, long-term prophylaxis usage among Peace Corps volunteers in Sub-Saharan Africa demonstrated its safety and good tolerability.8Mefloquine  was developed from a quinolone–methanol compound at the Walter Reed Institute. It was found to have potent anti-malaria activity, including against chloroquine-resistant P. However during the subsequent decades of its use, there arose several concerns.Mefloquine resistance: Resistance was occasionally reported first from the Thai-Cambodian border, followed by reports from other parts of Asia and to lesser extent from Africa and the Amazon region. The level of mefloquine resistance in the area of Thai-Cambodian and Thai-Burmese borders has reached 50%, thus precluding it from use as prophylaxis in this specific region. While in all other regions, the resistance level currently is more anecdotal and the drug can be used in these areas.However, the main concern for travelers regarding the use of mefloquine is its safety and tolerability.Mefloquine safety and tolerability: Mefloquine’s adverse side effects may include neuropsychiatric, gastrointestinal, and less commonly dermatological events.The neuropsychiatric adverse events (AE) associated with mefloquine are the worrisome complaints, and have received a vast amount of public attention, .The neurological disorders include headache, dizziness, confusion, vertigo and seizures. Peripheral neuropathies such as paresthesia, tremors and ataxia have also been reported.The psychiatric disorders may include insomnia, strange dreams, restlessness, anxiety, depression, and psychosis.The incidence of any AE due to the drug is hard to assess since results varied and ranged from about 10%–90% depending on the study design and whether a comparator was used.11The most concerning issue of chemoprophylaxis is the rate of serious AEs, resulting in a possible life threatening condition, or causing severe disability or prolonged hospitalization. Well-designed prospective studies of mefloquine’s adverse events may not identify a significantly higher number of events in comparison to other anti-malaria drugs, because of the small number of participants, and also it is easy to miss the relatively rare severe adverse events.Results of a study done by questionnaire among mefloquine users in British soldiers showed a rate of severe AEs as 1:6000,9Mefloquine AEs as reported in all studies are more common in women. In most cases, susceptible individuals have problems after the first 1–3 doses.In a case control study among travelers with serious AEs due to mefloquine prophylaxis, no difference in the level of mefloquine in the blood was found between the patients and the control groups. Also, no significant difference was found between mefloquine levels in the blood of men and women. These results suggest that blood levels of mefloquine do not correlate with its severe adverse events.15One of the advantages of mefloquine is the fact that this is the only drug that can be taken during pregnancy when traveling to chloroquine-resistant areas. It is officially recommended for the 2nd and 3rd trimesters of pregnancy. Limited data also suggest that its use during the first trimester is safe. Therefore, mefloquine should be recommended to a pregnant woman who cannot avoid traveling to endemic areas during her first trimester.16Due to the possible drug-associated neuropsychiatric effects, it is contraindicated in travelers who have seizure disorders. In addition, it should not be given to travelers with active psychiatric disorders such as depression, anxiety, psychosis or any other major psychiatric disorders. It is advisable not to prescribe this drug to patients with a history of the above-mentioned psychiatric disorders, even if they are currently stable.16Since the drug is related to quinine, it should not be given to persons with a known hypersensitivity to mefloquine or to quinine compounds. It is also not recommended for travelers with cardiac conductions abnormalities.falciparum, indicating that it is as efficacious as the other drugs currently available, such as mefloquine and atovaquone–proguanil.Doxycycline, a synthetically derived tetracycline, is a highly effective drug for the prevention of malaria. In studies conducted in non-immune populations, the dosage used was 100mg daily, resulting in greater than 95% efficacy against P.Malaria resistance to doxycycline has not been reported yet in any of the malaria endemic areas.The most common adverse events are gastrointestinal-related complaints such as abdominal pain, nausea, vomiting and diarrhea. A severe complication is esophageal ulceration, and therefore the recommendation is to take it in an upright position, with food or full glass of water and not before bedtime.Dermatological complications include photosensitivity, which is a concern for the travelers exposed to the sun in tropical countries. The reported dermatological complications vary and may reach 21%,12An important adverse effect of the drug among female travelers is the risk for vaginal candidiasis, which estimated to occur in 2.8%.18The requirement to take doxycycline daily and the fact that it must be continued for one month after leaving a malaria endemic area, are also drawbacks in terms of its use.An extra-benefit of using doxycycline for malaria prophylaxis might be its preventive measure against leptospirosis, which is a common hazard in the tropics, and its potential protection against rickettsial diseases and traveler’s diarrhea.Contraindications are for pregnant women, breastfeeding mothers, children under 8 years old, and those with a history of allergy to any of the tetracycline classes.falciparum malaria, and the widespread reluctance to use the known anti-malaria drugs due to their side effects, led to the pursuit of new antimalaria drugs. Atovaquone-proguanil  is the latest anti-malarial drug to be developed.The spread of drug –resistant falciparum strains.This drug is well-tolerated, and has good efficacy for resistant liver stage of the malaria parasite thus shortening considerably the amount of time needed to continue it post-travel (An added advantage of this drug is the fact that it acts on the t-travel . It is tThe drug is a fixed combination of Atovaquone 250 mg and of Proguanil 100mg. Pediatric tablet contain the same combination with a quarter of the dose of each component (62.5/25 mg).Pneumocystitis carinii.Atovaquone alone was well-established drug against Its mode of action against the plasmodia spp. is via inhibition of the mitochondrial electron transport system, at the level of cytochrome-b complex.Proguanil is an old anti-malaria drug, which acts by inhibiting the parasite’s dehydrofolate reductase.falciparum malaria.falciparum. This study was the basis for recommending the drug atovaquone-proguanil to be continued for 7 days after leaving the endemic areas. However, a very recent study done as the same method described above showed that even taking it at the last day should be enough.23Each of these drugs has weak anti-malarial activity but in combination there is a synergistic effect, with an efficacy of 95–100%.Several studies of atovaquone-proguanil have been conducted among travelers to evaluate its safety and tolerability in comparison to other antimalrial drugs. In a four-armed multicenter randomized controlled trial comparing the 4 drugs commonly used in travelers, namely mefloquine, doxycycline, chloroquine-proguanil and atovaquone –proguanil, the latter had the lowest withdrawal rate due to adverse events (2%).24The drug has been in use for about a decade and seems to maintain a very good safety and tolerability record. However, the main drawback for using it is the higher cost in comparison to the other anti malarial drugs, which obviously increases with increase the length of travel.The most common adverse events are related to gastrointestinal complaints, such as abdominal pain, nausea or vomiting and therefore it is recommended that it be taken with a meal.Dermatological complaints such as rashes and pruritus may occur, probably due to the proguanil component.falciparum prohylaxis. In the US, it is indicated without a time limitation, meaning that long–term travelers, expatriates and military personnel on long-term missions can use it. In several countries in Europe, its use is limited only to short-term travelers (30–90 days), since data on its safety with prolonged use are lacking.Atovaquone-proguanil is indicated for P. It is indicated for children above 5 kg, but dose should be modified according to weight .The drug is contraindicated in patients with severe renal failure (creatinine clearance <30 mL/min), and in those with known allergies to one of the drug components.The drug is contraindicated in pregnancy, since there is not sufficient information about it safety in pregnancy.vivax infection. However, since its introduction in the early 1950’s, primaquine has been found to be active against the early liver stages of both P. falciparum and P. vivax malaria.Primaquine, as viewed by many clinicians, has its only role in regard to its activity against P. falciparum malaria but were given primaquine, at a daily dose of 30 mg before the sporozoite inoculation, the infection was prevented.25Primaquine is an 8-aminoquinoline and was developed in the 1940’s. In a study conducted in 1954, healthy volunteers who were inoculated with P. falciparum and P. vivax), it never gained widespread use as chemoprophylaxis. This was most likely for two principal reasons. The first was the reporting of severe adverse effects, including methemoglobinemia and hemolytic anemia occurring in glucose-6-phosphate dehydrogenase (G6PD)-deficient patients.Despite the fact that primaquine was highly effective against the early liver stages of the parasite , an area endemic for both P. falciparum, and 85% against P. vivax. Another study, again with transmigrants to Irian Jaya, showed similar results. Participants received 20 weeks of primaquine or placebo. Primaquine showed an overall protective efficacy of 93%, with> 92% protective efficacy against P. vivax and 88% against P. falciparum.31A similar study was conducted in 1997 with Colombian soldiers.The most common adverse effects of primaquine are gastrointestinal effects that are dose dependent. In studies done during the early 1950’s, it was found that doses of up to 30 mg/day were associated with minimal gastrointestinal upset and only doses of 45 mg/day or higher were associated with a significant rate of adverse effects.7Recent studies also have shown minimal adverse effects. In the Colombian study,In the author’s study among travelers,Primaquine has gained more recognition in recent years and was listed in Canada and the US as an option for malaria prophylaxis. Its role was reemphasized in a report from a CDC expert meeting on malaria chemoprophylaxis33Primaquine can produce marked hemolysis when the drug is administered daily to individuals with G6PD deficiency; therefore, testing for G6PD before treatment is necessary.Methemoglobinemia occurs in normal individuals, but without clinical significance.Since primaquine is a drug that acts on the liver stage of the malaria parasite, there is no need to continue taking it for 1 month after departure from the malarious area . Therefore, the traveler should start taking it 1 day prior to entering the malarious area and to continue taking it daily for 3–7 days after departure from the malrious area. The recommended dose is 30mg (2 tablets) per day for adults. Due to the short half-life of primaquine, it must be taken daily, preferably with food to avoid gastrointestinal upset.The CDC recommends taking it for 7 days after departure from the malarious area.34The pediatric dose is 0.5 mg/kg/day.Pregnant women should not take it due mainly to the fear of G6PD deficiency in the fetus. Lactating women can use it if the infant has been tested for G6PD.Special populations who may need particular attention are pregnant women, and children for whom not all drugs mentioned above can be recommended. . Breast 35Another special population are long-term travelers , or expatriates who remain for several years in endemic areas. Two questions arise; which drug is considered to be safe for long-term use, and secondly, what is the best approach either taking chemoprophylaxis continuously, or use only personal protection measures and seek medical care in the case of a febrile illness.36Mefloquine, and chloroquine  are the only drugs that have a good long-term follow-up record37The safety of doxycycline has been demonstrated in patients taking it for long periods for acne, for malaria prophylaxis there are reports of long-term use among soldiers taking it for up to 1 year.38The safety of long term primaquine use was tested in Indonesia where it was given for 52 weeks.29It is evident that expatriates who live for long periods of time even in Sub-Saharan Africa typically do not take malaria chemoprophylaxis continuously, but rather rely on identifying symptoms and seeking medical care  when needed. However, even in these cases it is advisable to use chemoprophylaxis, at least at their first few months of their stay.Long term travelers who are traveling in endemic areas and moving from one place to the other including remote areas, should be encouraged to take chemoprophylaxis continuously throughout their trip especially when it is done in Sub Saharan Africa.P. Vivax  has a more complicated life cycle than P. falciparum due to the formation of liver hypnozoites, which can result in a clinical relapse several months after the primary infection. Therefore, complete prevention of this infection is much more challenging and can be achieved only if both primary and late infections are prevented.P.vivax has a bimodal incubation time:The life cycle of P. falciparum this incubation time is of 12± 3 days).The primary attack, which follows exposure to infectious sporozoites, occurs about 14± 3 days after the mosquito bite ( for The late infection is a relapse following activation and maturation of the dormant liver stage hypnozoite .P. vivax strains tend to have a higher probability of relapse (>30%), a shorter period between primary attack and relapse (17–45d), and a higher incidence of multiple relapses (>2), while the temperate strains (such as the Korean strain) tend to have fewer relapses, and a longer period before relapse, about 9 months.vivax malaria attacks several months or even a year or more following travel to an endemic area.The chance of, and incubation time for relapse largely depends upon the geographic origin of the infection. The tropical apse 17–4d, and a falciparum and vivax malaria. While chloroquine-resistant P. falciparum appeared quite quickly, in the late 1950’s, chloroquine-resistant P. vivax presented only in the late 1980’s. It is a significant problem in eastern Indonesia where more than half of infections with P. vivax appears to be resistant. Resistance has been occasionally reported from other areas in Southeast Asia, South Asia, and in South America.40Blood stage prophylaxis is the most common type of prophylaxis in use. Chloroquine, was the first drug in this group to be extensively used. It was introduced in the early 1950’s for the prevention of both falciparum and found to be effective against vivax malaria as well. During the 1990’s, well-controlled trials of all of these drugs were conducted in northeastern Indonesian New Guinea, where vivax malaria is heavily endemic and notoriously resistant to chloroquine. They demonstrated 100% protective efficacy.primary infection and not late relapses. In fact in recent years, with the increase of travel to the tropics, it has become more evident that using recommended prophylaxis, which is almost exclusively blood stage prophylaxis, only postpones the first clinical attack of malaria to several months after return. This was clearly demonstrated in a study among US and Israeli travelers where the majority of all imported vivax cases [60–80%] were late infections (more than 2 months after return) in travelers who took recommended prophylaxis. This clearly illustrates the deficiency of the currently recommended prophylaxis in fully preventing vivax infection.5Mefloquine and doxycycline, are also common blood stage drugs for prophylaxis and are effective against p. vivax prevention is based on the sensitivity of vivax spp. to chloroquine, but it ignores the fact that chloroquine can not prevent the hypnozoite formation and therefore can not prevent late infection.The common recommendation of chloroquine use for vivax is very limited , and should not be regard as vivax prophylaxis.Thus, the role of chloroquine or other blood stage prophylaxis in complete prevention of Terminal prophylaxis, meaning presumptive standard treatment with primaquine upon leaving an endemic area. The term “presumptive anti-relapse therapy” (PART) has been proposed to better describe this treatment strategy.P. vivax and thus prevent relapse. The dose of primaquine for this purpose is under re-evaluation. The common knowledge of dosing with 15mg daily for 14 days, is probably insufficient, especially for the high body weight of typical travelers from industrialized countries. The current preferred recommendation is a single 30mg dose of primaquine (base) taken daily for 2 weeks after leaving the endemic area.To overcome this problem there are 2 options ; one is vivax take it, or should it be reserved for high risk populations, such as long term travelers or those who have been to highly endemic vivax area (such as in our experience the Omo region in Ethiopia).There remains with this approach a grey area regarding which travelers would benefit. Should everyone who was in a malaria endemic area where there is p. Liver stage Prophylaxis. This prophylaxis can eliminate both primary attacks and relapses of P. vivax and can be effective for P. falciparum prevention as well. Primaquine is the only available drug known to have this prophylactic activity against vivax malaria. Atovaquone-proguanil, despite being a known liver stage prophylaxis against falciparum malaria (as mentioned above), does not prevent late vivax infection. Although studies, which looked at the efficacy of the drug for vivax malaria, found it to be 82% efficacious in Indonesia and 100% in Colombia.The second approach and more convenient one is by using On the other hand, primaquine studies of the last 10 years show effective protection against primary attacks in transmigrants in Indonesia and in travelers.falciparum malaria as well,Since the early clinical trials of primaquine demonstrated its activity against The dose and contraindications are mentioned above .vivax-predominant areas; short-term travelers, a daily dose of primaquine  seems to be the most convenient option.In conclusion, for travelers to For long-term travelers, a weekly dose of chloroquine (depends on the area), or of mefloquine (if there are no contraindications) followed by terminal prophylaxis with primaquine, would be the most convenient and efficacious .Malaria chemoprophylaxis should not be used in areas where there is no malaria., therefore, the practitioner who sees the traveler prior to his departure should be familiar with the non-endemic areas. It should be remembered that even within endemic countries, there are often areas free of malaria. For example, travelers who trek in Nepal are not at risk due to the high altitude. The same holds true for travelers to high altitude areas even within Sub-Saharan Africa such as Addis Ababa and the Ethiopian plateau which are highland areas above 2000 m., etc.falciparum malaria is in West Africa, estimated to be 2.4% per month of stay, while in East Africa is 1.5% per month of stay, risk is also high in travelers to the Pacific islands (Solomons and Papua New Guinea), but is 10–20 times less in travelers to Asia, and 30–40 times less in travelers to Latin America.45In the endemic areas, the risk for travelers varies significantly. The higher risk for Thus, the more complicated issue is the decision about malaria chemoprophylaxis in those who travel to low risk areas, and what should be decided as the threshold(if any) for using chemoprophylaxis. There is no consensus yet about this issue. According to the policy of the US CDC, the world is divided to “All or None” in regard to recommending chemoprophylaxis; one should either take it or not.16The real challenge in travel medicine is making recommendations for low risk malaria areas such as Central and South America, and several parts of East Asia. In these regions the risk of malaria definitely exists and there are cases of imported malaria from those areas, however the overall risk for travelers is low. A study from Europe suggests that the risk of adverse events from hemoprophylaxis is likely to be significantly higher than the risk of acquiring malaria in the most popular tourist destinations in Central and South America.6P. falciparum cases accounted for only 13% of all cases from the region. Thus, the calculated risk of malaria in UK residents visiting the region was > 1 case per 1,000 years exposed.46A similar conclusion came from an analysis of malaria imported into eight European countries from the Indian sub-continent (ISC) .Therefore, the TropNet group recommends that the non-selective prescribing chemoprophylaxis for visitors to the India subcontinent, should be dropped.46“emergency standby treatment” to be used in case malaria symptoms occur during travel. This assures treatment of a life threatening attack of falciparum malaria, and avoids adverse events associated with excessive chemoprophylaxisAn alternate strategy adopted by a number of European countries, for example Switzerland,There is no consensus about the use of stand by therapy. However the strategy of bite prevention measures remains important, as these are effective, safe and have the added benefit of reducing other vector borne diseases. In addition, travelers have to be educated to seek medical advice in the case of a febrile illness.


Plasmodium falciparum infection and contributes to the highest number of deaths by falciparum malaria. This study aims to evaluate the relationship between ABO blood group and severe malaria in an adult population at the tertiary care centre in Odisha.Erythrocyte-associated antigenic polymorphisms or their absence have perhaps evolved in the human population to protect against malarial infection. Studies in various populations consistently demonstrate that blood group ‘O’ confers resistance against severe falciparum infection. In India, Odisha state has one of the highest incidences of P. falciparum infected subjects and 174 healthy controls were screened for ABO blood group. Falciparum-infected individuals were categorized as severe malaria and uncomplicated malaria. Severe malaria was further clinically phenotyped into cerebral malaria, non-cerebral severe malaria and multi-organ dysfunction. A meta-analysis was performed to assess the role of ABO blood group in severe malaria.A total of 353 Frequency of blood group ‘B’ was significantly higher in patients with severe malaria compared to the uncomplicated cases  and healthy controls . Irrespective of the level of clinical severity, blood group ‘B’ was significantly associated with cerebral malaria , multi-organ dysfunction  and non-cerebral severe malaria patients  compared to the uncomplicated category. Prevalence of ‘O’ group in uncomplicated malaria  and healthy controls  was significantly high compared to severe malaria. Meta-analysis of previous studies, including the current one, highlighted the protective nature of blood group ‘O’ to severe malaria (P = 0.01). On the other hand, carriers of blood group ‘A’ (P = 0.04) and ‘AB’ (P = 0.04) were susceptible to malaria severity.Results of the current study indicate that blood group ‘O’ is associated with reduced and ‘B’ blood group with increased risk of development of severe malaria in Odisha, India. Meta-analysis also supports the protective nature of blood group ‘O’ from severe falciparum infection.