Spleen rates and infant parasite rates as surveillance tool for malaria control in remote hard to reach areas of central India

<p>Abstract</p> <p>Background</p> <p>Malaria due to both <it>Plasmodium falciparum </it>and <it>Plasmodium vivax </it>is a major public health problem in India. The quantification of malaria transmission for the classification of malaria risk has long been a concern for epidemiologists. Results are presented from 30 cross-sectional surveys which measured spleen rates (SR) and infant parasite rates (IPR) in the forested districts of Madhya Pradesh during malaria outbreaks to assess whether both IPR and SR can still be used as indicators of malaria endemicity as spleen examination has lost much of its value as an epidemiological indicator in areas where anti-malarials drugs are widely used.</p> <p>Methods</p> <p>Rapid fever surveys were carried out from door to door and all suspected malaria cases in the entire population of a village were screened for malaria parasites on the basis of clinical symptoms such as fever, chill, rigor, headache and body ache etc. Children between 2 and 9 years were examined for enlarged spleen according to Hacketts method. Finger prick blood smears were collected from all children with enlarged spleen with or without fever after obtaining written informed consent following institutional ethical guidelines. Infants less than 1 year were also screened for malaria with or without fever.</p> <p>Results</p> <p>Since malaria is local and focal, in some areas the outbreak waned quickly in few months and in some areas continued for 3 to 4 years. The analysis of trend revealed that when IPR decline over the years as a result of malaria intervention measures, SR also decline. In case splenomegaly continues without diminution in size, it is probably due to recrudescence or relapse, although it is not possible to separate malaria parasite species on the basis of SR.</p> <p>Conclusion</p> <p>Both the tools are of immense value in evaluating and assessing the malaria situation especially in remote areas where sophisticated molecular and serological techniques are difficult to establish. Therefore, in forested areas malaria surveillance system will require adoption of multiple approaches that have proven effective now or in the past.</p

The usefulness of a new rapid diagnostic test, the First Response® Malaria Combo (pLDH/HRP2) card test, for malaria diagnosis in the forested belt of central India

<p>Abstract</p> <p>Background</p> <p>Malaria presents a diagnostic challenge in tribal belt of central India where two Plasmodium species, <it>Plasmodium falciparum </it>and <it>Plasmodium vivax</it>, are prevalent. In these areas, rapid detection of the malaria parasites and early treatment of infection remain the most important goals of disease management. Therefore, the usefulness of a new rapid diagnostic (RDT), the First Response^®Combo Malaria Ag (pLDH/HRP2) card test was assessed for differential diagnosis between <it>P. falciparum </it>with other Plasmodium species in remote villages of Jabalpur district.</p> <p>Methods</p> <p>A finger prick blood sample was collected to prepare blood smear and for testing with the RDT after taking informed consent. The figures for sensitivity, specificity, accuracy and predictive values were calculated using microscopy as gold standard.</p> <p>Results</p> <p>Analysis revealed that overall, the RDT was 93% sensitive, 85% specific with a positive predictive value (PPV) of 79%, and a negative predictive value (NPV) of 95%. The accuracy 88% and J-index was 0.74. For <it>P. falciparum</it>, the sensitivity and specificity of the test were 96% and 95% respectively, with a PPV of 85% and a NPV of 99%. The RDT accuracy 95% and J-index was 0.84. For non-falciparum malaria, the sensitivity, specificity and accuracy were 83%, 94% and 92% respectively with a PPV of 69% and a NPV of 97%.</p> <p>Conclusion</p> <p>The RDTs are easy to use, reliable and simple to interpret. RDTs are more suited to health workers in situations where health services are deficient or absent. Therefore, the test can be used as an epidemiological tool for the rapid screening of malaria.</p

Field and laboratory comparative evaluation of rapid malaria diagnostic tests versus traditional and molecular techniques in India

<p>Abstract</p> <p>Background</p> <p>Malaria presents a diagnostic challenge in most tropical countries. Microscopy remains the gold standard for diagnosing malaria infections in clinical practice and research. However, microscopy is labour intensive, requires significant skills and time, which causes therapeutic delays. The objective of obtaining result quickly from the examination of blood samples from patients with suspected malaria is now made possible with the introduction of rapid malaria diagnostic tests (RDTs). Several RDTs are available, which are fast, reliable and simple to use and can detect <it>Plasmodium falciparum </it>and non-falciparum infections or both. A study was conducted in tribal areas of central India to measure the overall performance of several RDTs for diagnosis of <it>P. falciparum </it>and non-falciparum infections in comparison with traditional and molecular techniques. Such data will be used to guide procurement decisions of policy makers and programme managers.</p> <p>Methods</p> <p>Five commercially available RDTs were tested simultaneously in field in parallel with peripheral blood smears in outbreak-affected areas. The evaluation is designed to provide comparative data on the performance of each RDT. In addition, molecular method i.e. polymerase chain reaction (PCR) was also carried out to compare all three methods.</p> <p>Results</p> <p>A total of 372 patients with a clinical suspicion of malaria from Bajag Primary Health Centre (PHC) of district Dindori and Satanwada PHC of district Shivpuri attending the field clinics of Regional Medical Research Centre were included in the study. The analysis revealed that the First Response Malaria Antigen pLDH/HRP2 combo test was 94.7% sensitive (95% CI 89.5-97.7) and 69.9% specific (95% CI 63.6-75.6) for <it>P. falciparum</it>. However, for non-falciparum infections (<it>Plasmodium vivax</it>) the test was 84.2% sensitive (95% CI 72.1-92.5) and 96.5% specific (95% CI 93.8-98.2). The Parascreen represented a good alternative. All other RDTs were relatively less sensitive for both <it>P. falciparum </it>and non-falciparum infections.</p> <p>Conclusions</p> <p>The results in this study show comparative performance between microscopy, various RDTs and PCR. Despite some inherent limitation in the five RDTs tested, First Response clearly has an advantage over other RDTs. The results suggest that RDTs could play and will play an important role in malaria diagnosis.</p

Availability and Utilization of Malaria Prevention Strategies in Pregnancy in Eastern India

BACKGROUND. Malaria in pregnancy in India, as elsewhere, is responsible for maternal anemia and adverse pregnancy outcomes such as low birth weight and preterm birth. It is not known whether prevention and treatment strategies for malaria in pregnancy (case management, insecticide-treated bednets, intermittent preventive therapy) are widely utilized in India. METHODS. This cross-sectional study was conducted during 2006-2008 in two states of India, Jharkhand and Chhattisgarh, at 7 facilities representing a range of rural and urban populations and areas of more versus less stable malaria transmission. 280 antenatal visits (40/site) were observed by study personnel coupled with exit interviews of pregnant women to assess emphasis upon, availability and utilization of malaria prevention practices by health workers and pregnant women. The facilities were assessed for the availability of antimalarials, lab supplies and bednets. RESULTS. All participating facilities were equipped to perform malaria blood smears; none used rapid diagnostic tests. Chloroquine, endorsed for chemoprophylaxis during pregnancy by the government at the time of the study, was stocked regularly at all facilities although the quantity stocked varied. Availability of alternative antimalarials for use in pregnancy was less consistent. In Jharkhand, no health worker recommended bednet use during the antenatal visit yet over 90% of pregnant women had bednets in their household. In Chhattisgarh, bednets were available at all facilities but only 14.4% of health workers recommended their use. 40% of the pregnant women interviewed had bednets in their household. Only 1.4% of all households owned an insecticide-treated bednet; yet 40% of all women reported their households had been sprayed with insecticide. Antimalarial chemoprophylaxis with chloroquine was prescribed in only 2 (0.7%) and intermittent preventive therapy prescribed in only one (0.4%) of the 280 observed visits. CONCLUSIONS. A disconnect remains between routine antenatal practices in India and known strategies to prevent and treat malaria in pregnancy. Prevention strategies, in particular the use of insecticide-treated bednets, are underutilized. Gaps highlighted by this study combined with recent estimates of the prevalence of malaria during pregnancy in these areas should be used to revise governmental policy and target increased educational efforts among health care workers and pregnant women.United States Agency for International Development/India mission (cooperative agreement GHS-A-00-03-00020-00); National Institute of Allergy and Infectious Disease (R03 HD52167-01); Indian National Institute of Malaria Research; Indo-US Program for Contraception and Reproductive Health Researc

Impact of biomass fuels on pregnancy outcomes in central East India

Background: Smoke from biomass burning has been linked to reduced birth weight; association with other birth outcomes is poorly understood. Our objective was to evaluate effects of exposure to biomass smoke on birth weight, preterm birth and stillbirth. Methods: Information on household cooking fuel was available for secondary analysis from two cohorts of pregnant women enrolled at delivery in India (n = 1744). Birth weight was measured and the modified Ballard performed to assess gestational age. Linear and logistic regression models were used to explore associations between fuel and birth outcomes. Effect sizes were adjusted in multivariate models for socio-demographic characteristics using propensity score techniques and for medical/obstetric covariates. Results: Compared to women who use gas (n = 265), women cooking with wood (n = 1306) delivered infants that were on average 112 grams lighter (95% CI -170.1, -54.6) and more likely to be preterm (OR 3.11, 95% CI 2.12, 4.59). Stillbirths were also more common in the wood group (4% versus 0%, p < 0.001). In adjusted models, the association between wood use and birth weight was no longer significant (14 g reduction; 95% CI -93, 66); however, the increased odds for preterm birth persisted (aOR 2.29; 95% CI 1.24, 4.21). Wood fuel use did not increase the risk of delivering either a low birth weight or small for gestational age infant. Conclusions: The association between wood fuel use and reduced birth weight was insignificant in multivariate models using propensity score techniques to account for socio-demographic differences. In contrast, we demonstrated a persistent adverse impact of wood fuel use on preterm delivery. If prematurity is confirmed as a consequence of antenatal exposure to household air pollution, perinatal morbidity and mortality from household air pollution may be higher than previously appreciated

Plasma levels of angiopoietin-1 and -2 predict cerebral malaria outcome in Central India

<p>Abstract</p> <p>Background</p> <p>The mechanisms underlying the pathogenesis of cerebral malaria (CM) syndrome are not well understood. Previous studies have shown a strong association of inflammatory chemokines, apoptotic markers and angiogenic molecules with CM associated mortality. Recognizing the importance of angiopoietins (ANG) in the pathogenesis of CM, a retrospective investigation was carried out in a hospital cohort of malaria patients with <it>Plasmodium </it>infection in central India to determine if these factors could be suitable markers of CM associated severity.</p> <p>Methods</p> <p>Patients enrolled in the study were clinically characterized as healthy controls (HC), mild malaria (MM), CM survivors (CMS) and CM non-survivors (CMNS) based on their malaria status and hospital treatment outcome. Plasma ANG-1 and ANG-2 levels were assessed using sandwich ELISA. Receiver operating characteristic (ROC) curve analysis was used to calculate area under the curve (AUC) for each biomarker in order to assess predictive accuracy of individual biomarkers.</p> <p>Results</p> <p>The plasma levels of ANG-1 were lower in CMS and CMNS compared to control groups (mild malaria and healthy controls) at the time of hospital admission. On the contrary, ANG-2 levels positively correlated with malaria severity and were significantly higher in CMNS. The ratio of ANG-2/ANG-1 was highest in CMNS compared to other groups. Receiver operating characteristic curves revealed that compared to ANG-1 (AUC = 0.35), ANG-2 (AUC = 0.95) and ratio of ANG-2/ANG-1 (AUC = 0.90) were better markers to discriminate CMNS from MM cases. However, they were less specific in predicting fatal outcome amongst CM cases at the time of hospital admission.</p> <p>Conclusion</p> <p>These results suggest that at the time of admission plasma levels of ANG-2 and ratio of ANG-2/ANG-1 are clinically informative biomarkers to predict fatal CM from MM cases while they have limited usefulness in discriminating fatal CM outcomes in a pool of CM cases in endemic settings of Central India.</p

Plasma IP-10, apoptotic and angiogenic factors associated with fatal cerebral malaria in India

<p>Abstract</p> <p>Background</p> <p><it>Plasmodium falciparum </it>in a subset of patients can lead to cerebral malaria (CM), a major contributor to malaria-associated mortality. Despite treatment, CM mortality can be as high as 30%, while 10% of survivors of the disease may experience short- and long-term neurological complications. The pathogenesis of CM is mediated by alterations in cytokine and chemokine homeostasis, inflammation as well as vascular injury and repair processes although their roles are not fully understood. The hypothesis for this study is that CM-induced changes in inflammatory, apoptotic and angiogenic factors mediate severity of CM and that their identification will enable development of new prognostic markers and adjunctive therapies for preventing CM mortalities.</p> <p>Methods</p> <p>Plasma samples (133) were obtained from healthy controls (HC, 25), mild malaria (MM, 48), cerebral malaria survivors (CMS, 48), and cerebral malaria non-survivors (CMNS, 12) at admission to the hospital in Jabalpur, India. Plasma levels of 30 biomarkers ((IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, Eotaxin, FGF basic protein, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1 (MCAF), MIP-1α, MIP-1β, RANTES, TNF-α, Fas-ligand (Fas-L), soluble Fas (sFas), soluble TNF receptor 1 (sTNF-R1) and soluble TNF receptor 2 (sTNFR-2), PDGF bb and VEGF)) were simultaneously measured in an initial subset of ten samples from each group. Only those biomarkers which showed significant differences in the pilot analysis were chosen for testing on all remaining samples. The results were then compared between the four groups to determine their role in CM severity.</p> <p>Results</p> <p>IP-10, sTNF-R2 and sFas were independently associated with increased risk of CM associated mortality. CMNS patients had a significantly lower level of the neuroprotective factor VEGF when compared to other groups (P < 0.0045). The ratios of VEGF to IP-10, sTNF-R2, and sFas distinguished CM survivors from non survivors (P < 0.0001).</p> <p>Conclusion</p> <p>The results suggest that plasma levels of IP-10, sTNF-R2 and sFas may be potential biomarkers of CM severity and mortality. VEGF was found to be protective against CM associated mortality and may be considered for adjunctive therapy to improve the treatment outcome in CM patients.</p

Therapeutic efficacy of artemether–lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria from three highly malarious states in India

Additional file 1. Flowchart showing site-wise enrolment and follow-up profile

Science of malaria elimination: using knowledge of bottlenecks and enablers from the Malaria Elimination Demonstration Project in Central India for eliminating malaria in the Asia Pacific region

Malaria poses a major public health challenge in the Asia Pacific. Malaria Elimination Demonstration Project was conducted as a public-private partnership initiative in Mandla between State government, ICMR, and FDEC India. The project employed controls for efficient operational and management decisions. IEC campaigns found crucial in schools and communities. Capacity building of local workers emphasized for better diagnosis and treatment. SOCH mobile app launched for complete digitalization. Better supervision for Indoor Residual Sprays and optimized Long Lasting Insecticidal Nets distribution. Significant malaria cases reduction in Mandla. Insights from MEDP crucial for malaria elimination strategies in other endemic regions of the Asia Pacific

Burden of malaria in pregnancy in Jharkhand State, India

<p>Abstract</p> <p>Background</p> <p>Past studies in India included only symptomatic pregnant women and thus may have overestimated the proportion of women with malaria. Given the large population at risk, a cross sectional study was conducted in order to better define the burden of malaria in pregnancy in Jharkhand, a malaria-endemic state in central-east India.</p> <p>Methods</p> <p>Cross-sectional surveys at antenatal clinics and delivery units were performed over a 12-month period at two district hospitals in urban and semi-urban areas, and a rural mission hospital. Malaria was diagnosed by Giemsa-stained blood smear and/or rapid diagnostic test using peripheral or placental blood.</p> <p>Results</p> <p>2,386 pregnant women were enrolled at the antenatal clinics and 718 at the delivery units. 1.8% (43/2382) of the antenatal clinic cohort had a positive diagnostic test for malaria (53.5% <it>Plasmodium falciparum</it>, 37.2% <it>Plasmodium vivax</it>, and 9.3% mixed infections). Peripheral parasitaemia was more common in pregnant women attending antenatal clinics in rural sites (adjusted relative risk [aRR] 4.31, 95%CI 1.84-10.11) and in those who were younger than 20 years (aRR 2.68, 95%CI 1.03-6.98). Among delivery unit participants, 1.7% (12/717) had peripheral parasitaemia and 2.4% (17/712) had placental parasitaemia. Women attending delivery units were more likely to be parasitaemic if they were in their first or second pregnancy (aRR 3.17, 95%CI 1.32-7.61), had fever in the last week (aRR 5.34, 95%CI 2.89-9.90), or had rural residence (aRR 3.10, 95%CI 1.66-5.79). Malaria control measures including indoor residual spraying (IRS) and untreated bed nets were common, whereas insecticide-treated bed nets (ITN) and malaria chemoprophylaxis were rarely used.</p> <p>Conclusion</p> <p>The prevalence of malaria among pregnant women was relatively low. However, given the large at-risk population in this malaria-endemic region of India, there is a need to enhance ITN availability and use for prevention of malaria in pregnancy, and to improve case management of symptomatic pregnant women.</p