Area Of Unstable Malaria Transmission Research Articles

Analysis of the spatial and temporal distribution of malaria in an area of Northern Guatemala with seasonal malaria transmission.

The risk of malaria infection displays spatial and temporal variability that is likely due to interaction between the physical environment and the human population. In this study, we performed a spatial analysis at three different time points, corresponding to three cross-sectional surveys conducted as part of an insecticide-treated bed nets efficacy study, to reveal patterns of malaria incidence distribution in an area of Northern Guatemala characterized by low malaria endemicity. A thorough understanding of the spatial and temporal patterns of malaria distribution is essential for targeted malaria control programs. Two methods, the local Moran's I and the Getis-Ord G*(d), were used for the analysis, providing two different statistical approaches and allowing for a comparison of results. A distance band of 3.5km was considered to be the most appropriate distance for the analysis of data based on epidemiological and entomological factors. Incidence rates were higher at the first cross-sectional survey conducted prior to the intervention compared to the following two surveys. Clusters or hot spots of malaria incidence exhibited high spatial and temporal variations. Findings from the two statistics were similar, though the G*(d) detected cold spots using a higher distance band (5.5km). The high spatial and temporal variability in the distribution of clusters of high malaria incidence seems to be consistent with an area of unstable malaria transmission. In such a context, a strong surveillance system and the use of spatial analysis may be crucial for targeted malaria control activities.

Naturally acquired immune responses to thrombospondin-related adhesion protein (TRAP) of Plasmodium vivax in patients from areas of unstable malaria transmission

A key tool for the control, elimination, and eradication of Plasmodium vivax is the development of an effective vaccine. The thrombospondin-related adhesion protein (TRAP) is one of the major sporozoite antigens that plays an important role in the invasion of mosquito salivary glands and hepatocytes by sporozoites. The main goal of this study was to evaluate the naturally acquired antibodies to the P. vivax TRAP (PvTRAP) in patients from malaria-endemic areas of Iran (n=116), Afghanistan (n=50), and Pakistan (n=50). The PvTRAP gene was expressed in Escherichia coli Rosetta (DE3)-pET23a and used as antigen in enzyme-linked immunosorbent assay (ELISA). The profile of immunoglobulin G (IgG) isotype and the avidity of IgG, IgG1, and IgG3 to PvTRAP, as well as the association between anti-PvTRAP isotype responses and host age were evaluated. Only 42.24% of Iranian, 38% of Afghani, and 44% of Pakistani patients infected with P. vivax had positive anti-PvTRAP IgG, and the prevalence of responders in the three countries did not differ significantly (P>0.05). Moreover, the prevalence of IgG1 and IgG3 antibody responses to PvTRAP showed no significant correlation with age (P>0.05). Individuals exposed to vivax malaria in the unstable malaria transmission areas are able to produce antibodies to the TRAP antigen at all ages in response to P. vivax infections. Finally, the presence of mature IgG1 and IgG3 antibodies with high to intermediate avidity against PvTRAP antigen (>60%) provide more information to understand the interactions between the host and P. vivax parasite. In summary, the present study provides data that support the rational development of an effective pre-erythrocytic stage vaccine based on PvTRAP antigen.

Population genetics structure of Plasmodium vivax circumsporozoite protein during the elimination process in low and unstable malaria transmission areas, southeast of Iran

In Iran, the prevalence of Plasmodium falciparum and Plasmodium vivax has dropped after a national malaria elimination program was launched. To estimate the likelihood of success and to measure the outcome of malaria intervention tools during elimination programs (2008–2012), the population genetic surveys of Iranian P. vivax isolates (n=60) were carried out using the CSP genetic marker. The results were compared with a similar work that was carried out during a control phase (2000–2003) in the same study areas. Based on PCR-RFLP analysis, 49 (81.67%) of 60 studied samples were VK210 and 11 (18.33%) were VK247 with no mixed genotypes. However, 10.97% of P. vivax isolates of control phase harbored the mixed genotypes. Sequencing analysis of 50 pvcsp gene showed 14 distinct haplotypes, of which 11 and 3 were VK210 and VK247 types, respectively. However, during the control phase, 19 distinct subtypes (11 VK210 and 8 VK247) were reported. Also, 7 of 11 VK210 and the VK247F subtypes were new, and 3 out of 7 new VK210 and VK247F were isolated from the patients with Pakistani nationality. The lower nucleotide diversity per site (π=0.02017±0.00436 and π=0.04525±0.00255) and haplotype diversity (Hd=0.513±0.093 and Hd=0.691±0.128) as well as lower In/Del haplotype [Hd(i)=0.243 and 0] and nucleotide diversity [π(i)=0.00078 and 0] were recorded for VK210 and VK247of the elimination samples, respectively. In conclusion, the comparison of PRMs and RATs in CRR along with the polymorphism analysis of the sequence lengths, SNPs, and In/Del polymorphisms in all analyzed samples showed lower genetic diversity for PvCSP in the elimination samples. Also, although there is a turnover of P. vivax parasite genotypes in the study areas, reduction in genetic diversity and transmission was detected due to scaling-up of the intervention tools during an elimination program in Iran. This notable challenge of the elimination program must be taken into account and controlled by active surveillance for limiting both reintroductions of new allelic forms as well as the spread of drug-resistant parasite to prevent any disease outbreaks.

Naturally Acquired Antibody Responses to Plasmodium vivax and Plasmodium falciparum Merozoite Surface Protein 1 (MSP1) C-Terminal 19 kDa Domains in an Area of Unstable Malaria Transmission in Southeast Asia.

Understanding naturally acquired immunity to infections caused by Plasmodia in different malaria endemicity settings is needed for better vaccine designs and for exploring antibody responses as a proxy marker of malaria transmission intensity. This study investigated the sero-epidemiology of malaria along the international border between China and Myanmar, where malaria elimination action plans are in place. This study recruited 233 P. vivax and 156 P. falciparum infected subjects with acute malaria at the malaria clinics and hospitals. In addition, 93 and 67 healthy individuals from the same endemic region or from non-endemic region, respectively, were used as controls. Acute malaria infections were identified by microscopy. Anti-recombinant PfMSP119 and PvMSP119 antibody levels were measured by ELISA. Antibody responses to respective MSP119 were detected in 50.9% and 78.2% patients with acute P. vivax and P. falciparum infections, respectively. There were cross-reacting antibodies in Plasmodium patients against these two recombinant proteins, though we could not exclude the possibility of submicroscopic mixed-species infections. IgG1, IgG3 and IgG4 were the major subclasses. Interestingly, 43.2% of the healthy endemic population also had antibodies against PfMSP119, whereas only 3.9% of this population had antibodies against PvMSP119. Higher antibody levels were correlated with age and parasite density, but not with season, gender or malaria history. Both total IgG and individual IgG subclasses underwent substantial declines during the convalescent period in three months. This study demonstrated that individuals in a hypoendemic area with coexistence of P. vivax and P. falciparum can mount rapid antibody responses against both PfMSP119 and PvMSP119. The significantly higher proportion of responders to PfMSP119 in the healthy endemic population indicates higher prevalence of P. falciparum in the recent past. Specific antibodies against PvMSP119 could serve as a marker of recent exposure to P. vivax in epidemiological studies.

Decline in childhood iron deficiency after interruption of malaria transmission in highland Kenya , ,

Achieving optimal iron status in children in malaria-endemic areas may increase the risk of malaria. Malaria itself may contribute to iron deficiency, but the impact of an interruption in malaria transmission on the prevalence of iron deficiency is unknown. We aimed to determine whether 1) iron status improved in children living in 2 Kenyan villages with a documented cessation in malaria transmission and 2) changes in iron status correlated with changes in hemoglobin. We measured iron [hemoglobin, ferritin, soluble transferrin receptor (sTfR)] and inflammatory [C-reactive protein (CRP)] markers in paired plasma samples from 190 children aged 4-59 mo at the beginning (May 2007) and end (July 2008) of a documented 12-mo period of interruption in malaria transmission in 2 highland areas in Kenya with unstable malaria transmission and ongoing malaria surveillance. Between May 2007 and July 2008, mean (±SD) hemoglobin increased from 10.8 ± 1.6 to 11.6 ± 1.6 g/dL. Median (25th, 75th percentile) ferritin increased from 17.0 (9.7, 25.6) to 22.6 (13.4, 34.7) μg/L (P < 0.001), whereas median sTfR decreased from 32.4 (26.3, 43.2) to 27.7 (22.1, 36.0) nmol/L (P < 0.001). Median CRP was low (<1 mg/L in both years) and did not change significantly. Iron deficiency prevalence (ferritin <12 μg/L, or <30 μg/L if CRP ≥10 mg/L) decreased from 35.9% (95% CI: 28.9%, 43.0%) to 24.9% (18.5%, 31.2%) (P = 0.005). The prevalence of iron deficiency with anemia (hemoglobin <11.0 g/dL) declined from 27.2% (20.7%, 33.8%) to 12.2% (7.4%, 17.1%) (P < 0.001). Improvement in iron status correlated with an increase in hemoglobin and was greater than explained by physiologic changes expected with age. In this area of unstable malaria transmission, the prevalence of iron deficiency in children decreased significantly after the interruption of malaria transmission and was correlated with an increase in hemoglobin. These findings suggest that malaria elimination strategies themselves may be an effective way to address iron deficiency in malaria-endemic areas.

Increased Severity and Mortality in Adults Co-Infected with Malaria and HIV in Maputo, Mozambique: A Prospective Cross-Sectional Study

BackgroundCo-infection with falciparum malaria and HIV-1 increases the severity and mortality of both infections in unstable malaria-transmission areas. In contrast, in stable transmission areas, HIV co-infection increases the severity of both infections but has not been found to influence malaria mortality.MethodsIn a prospective cross-sectional study, clinical and laboratory data were consecutively collected for all adults admitted with fever and/or suspected malaria to the medical department of the Central Hospital of Maputo, Mozambique, during two malaria seasons from January 2011. Malaria and HIV PCRs were performed, and risk factors for fatal outcomes were analysed. The impact of HIV on the clinical presentation and mortality of malaria was assessed.FindingsA total of 212 non-pregnant adults with fever and/or suspected malaria and 56 healthy controls were included in the study. Of the 131 patients with confirmed falciparum malaria, 70 were co-infected with HIV-1. The in-hospital mortality of the co-infected patients was 13.0% (9/69) compared with 1.7% (1/59) in the patients without HIV (p = 0.018). Malaria severity (p = 0.016) and co-infection with HIV (p = 0.064) were independent risk factors for death although the association with HIV did not reach statistical significance. The co-infected patients had significantly more frequent respiratory distress, bleeding disturbances, hypoglycaemia, liver and renal failure and high malaria parasitemia compared with the patients with malaria alone.InterpretationsHIV co-infection is associated with increased disease severity in and mortality from malaria in an area of stable malaria transmission. This finding was not observed earlier and should motivate doctors working in malaria-endemic areas to consider early HIV testing and a closer follow-up of patients with malaria and HIV co-infection.

CD20, CD3, placental malaria infections and low birth weight in an area of unstable malaria transmission in Central Sudan

BackgroundMalaria during pregnancy is the main cause of low birth weight (LBW) in the tropics. There are few studies concerning B and T lymphocyte infiltrates in placental malaria infections or their potential association with LBW babies.MethodsA case–control study was conducted at the Medani Hospital, Central Sudan. Cases were women who had LBW deliveries (infants weighed < 2,500 g) and controls were parturient women with normal birth weight babies. Sociodemographic and medical characteristics were gathered from both groups of women using questionnaires. Cases and controls were investigated for malaria using microscopic blood film analysis, placental histology, and immunohistochemistry for detection of B (CD20) and T lymphocytes (CD3).ResultsThe two groups (97 in each arm) were well matched in their basic characteristics. There were no malaria-positive blood films in either the cases or the controls. Twenty-nine (30.0%) vs. 24 (24.7%), P = 0.519 of the cases vs. the controls had placental malaria infections on histological examination. Three (3.1%), two (2.1%) and 24 (24.7%) vs. two (2.1%), two (2.1%) and 20 (20.6%) of the placentae showed evidence of acute, chronic and past malarial infections on histopathological examination of the two groups (case–control), respectively, while 68 (70.1%) vs. 73 (75.3%) of them showed no signs of infection; P = 0.420. Women with placental malaria infections had significantly fewer CD20 cell infiltrates [6 (11.3% vs. 95 (67.4%), P < 0.001)] and higher numbers of CD3 cell infiltrates [50 (94.3%) vs. 42 (29.8%), P < 0.001] than those without placental malaria infection. Logistic regression analysis showed that neither placental malaria infections nor CD3 or CD20 were associated with LBW.ConclusionsSignificantly higher rates of CD3 T cells and lower rates of CD20 B cells were found in women with placental malaria infections compared with those without such infections. Neither placental malaria infection nor CD3 or CD20 are associated with LBW.Virtual slideshttp://www.diagnosticpathology.diagnomx.eu/vs/6879723961063755

Malaria Infection Has Spatial, Temporal, and Spatiotemporal Heterogeneity in Unstable Malaria Transmission Areas in Northwest Ethiopia

BackgroundMalaria elimination requires successful nationwide control efforts. Detecting the spatiotemporal distribution and mapping high-risk areas are useful to effectively target pockets of malaria endemic regions for interventions.ObjectiveThe aim of the study was to identify patterns of malaria distribution by space and time in unstable malaria transmission areas in northwest Ethiopia.MethodsData were retrieved from the monthly reports stored in the district malaria offices for the period between 2003 and 2012. Eighteen districts in the highland and fringe malaria areas were included and geo-coded for the purpose of this study. The spatial data were created in ArcGIS10 for each district. The Poisson model was used by applying Kulldorff methods using the SaTScan™ software to analyze the purely temporal, spatial and space-time clusters of malaria at a district levels.ResultsThe study revealed that malaria case distribution has spatial, temporal, and spatiotemporal heterogeneity in unstable transmission areas. Most likely spatial malaria clusters were detected at Dera, Fogera, Farta, Libokemkem and Misrak Este districts (LLR =197764.1, p<0.001). Significant spatiotemporal malaria clusters were detected at Dera, Fogera, Farta, Libokemkem and Misrak Este districts (LLR=197764.1, p<0.001) between 2003/1/1 and 2012/12/31. A temporal scan statistics identified two high risk periods from 2009/1/1 to 2010/12/31 (LLR=72490.5, p<0.001) and from 2003/1/1 to 2005/12/31 (LLR=26988.7, p<0.001).ConclusionIn unstable malaria transmission areas, detecting and considering the spatiotemporal heterogeneity would be useful to strengthen malaria control efforts and ultimately achieve elimination.

Investing in malaria research in challenging financial times

The theme of the upcoming 6th MIM Pan-African Malaria Conference, ‘Moving towards malaria elimination: Investing in research and control,’ is full of challenges and, if the sixth gathering is like the fifth, participants will be excited by the answers. 1 Although the theme of the conference has two components, research and control, the fact remains that research is the overwhelming member of the pair as we move into somewhat uncharted waters. The reality is that control in an era of pre-elimination and elimination also requires the variously termed operational, intervention, applied or implementation research to determine practical methods that work. Research, of course, does not just happen. This year’s World Malaria Day (WMD) theme, in concert with the theme of the MIM conference, reminds us of the precarious financial position of the progress in all aspects of malaria programing and called on the malaria community to ‘Invest in the Future: Defeat Malaria’. 2 The WMD partners reminded us that, ‘These great strides are now under threat; the focus on malaria control is beginning to fade and has led to insufficient financial support. With an annual shortage of US$3.6 billion, particularly across Africa where highburden countries are facing critical funding gaps, all the impressive gains in malaria control over the past decade are threatening to grind to a halt and in some cases reverse.’ Moving into the pre-elimination phase of malaria control requires strong surveillance systems. This includes both the tools needed to detect the disease under circumstances of hopefully diminishing prevalence, and also appropriate health systems that can operate and sustain implementation of appropriate surveillance. The WHO’s Global Malaria Program is gearing up with its Test, Treat and Track (or 3T) effort. 3 WHO describes a malaria surveillance system with the following parts: ‘the tools, procedures, people and structures that generate information on malaria cases and deaths, which can be used for planning, monitoring and evaluating malaria control programmes’. 4 Continued research is needed to ensure that each of these four components is able to adapt to changing disease conditions as we approach elimination. Examples of such conditions are areas of unstable malaria transmission, such as recently documented in central Sudan. 5 Although none of the women who had recently delivered had positive blood slides for malaria, a large number tested positive using PCR. A positive PCR test for malaria was associated with low birth weight. The challenge of continued malaria infections that cannot be detected using a typical health center or hospital laboratory and the negative effects that these ‘sub-microscopic’ infections engender requires major research efforts as traditional control strategies (case management, indoor residual spraying, long-lasting insecticide-treated nets and intermittent preventive treatment) bring down malaria prevalence to low and seemingly undetectable levels. Malaria surveillance planning in the Solomon Islands also emphasizes the challenges of tracking the disease when many cases are asymptomatic. 6 Active detection based on perceived symptoms does not work well under such circumstances when fevers no longer signify malaria. While the researchers found that PCR prevalence was five times higher than that determined by microscopy, they also recognized that mass screening is costly and inconvenient. Whatever surveillance system evolves in low and/or unstable transmission areas, it needs to account for public perceptions. The study in the Solomon Islands also pointed out the challenges of such perceptions where people could recall what malaria was like in former times, but discounted its seriousness in the present. Some individuals who had never experienced malaria were identified: a part of the population that will grow over time. Swaziland is another setting where the malaria burden has been reduced to negligible levels and a surveillance system has been put in place where many ‘confirmed malaria cases were investigated at household level to identify the source of infection, using the strengthened surveillance system’. 7 Swaziland recognizes that, ‘new approaches are required to provide case-based risk maps to countries seeking to identify remaining hotspots of transmission while managing the risk of transmission from imported cases,’ and has completed research on high risk mapping that accounts for settings with low resources. 8

Reliability of rapid diagnostic test for diagnosing peripheral and placental malaria in an area of unstable malaria transmission in Eastern Sudan

BackgroundDiagnosing Plasmodium falciparum malaria during pregnancy is a great challenge for clinicians because of the low density of parasites in the peripheral blood and parasite sequestration in the placenta. Nevertheless, few data on the use of malaria rapid diagnostic test (RDT) during pregnancy have been published.MethodsP. falciparum infections were assessed in 156 febrile pregnant women by microscopic examination of their blood smears and by RDT and polymerase chain reactions (PCR). In addition, 150 women were assessed at the time of delivery by microscopy, RDT, PCR and placental histology investigations. The study was conducted at the Gadarif Hospital, Eastern Sudan. The SD Bioline P. f / P. v (Bio Standard Diagnostics, Gurgaon, Korea) RDT kit was evaluated in this study.ResultsAmong the febrile pregnant women, 17 (11.0%), 26 (16.7%) and 18 (11.5%) positive cases of P. falciparum were detected by microscopy, RDT, and PCR, respectively. The sensitivity and specificity of the microscopy was 94.4% and 100%, respectively. The corresponding values for RDT evaluation were 83.3% and 92.0%, as compared with PCR as the gold standard.While there were no detected cases of malaria by microscopic examination of blood smears, 27 (18.0%), 21(14.0%) and 46 (30.7%) out of the 150 placentae investigated had P. falciparum as determined by RDT, PCR, and histology, respectively. The sensitivity and specificity for RDT was 17.4% and 81.7%, respectively. The corresponding values for PCR were 6.5% and 82.7%, where histology was used as the gold standard.ConclusionsThe RDT kit used in this study has poor performance for peripheral and placental P. falciparum malaria detection in this setting.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1092363465928479

HUMAN RESOURCE CAPACITY TO EFFECTIVELY IMPLEMENT MALARIA ELIMINATION: A POLICY BRIEF FOR ETHIOPIA

The aim of this study was to investigate malaria elimination in Ethiopia. Ethiopia has planned to eliminate malaria by 2015 in areas of unstable malaria transmission and in the entire country by 2020. However, there is a shortage and maldistribution of the health workforce in general and malaria experts in particular. Training, motivating, and retaining the health workforce involved in malaria control is one strategy to address the shortage and maldistribution of the health workforce to achieve the goal of elimination. Policy options include the following: (i) in-service training (educational outreach visits, continuing education meetings and workshops, audit and feedback, tailored interventions, and guideline dissemination) may improve professional practice; (ii) recruiting and training malaria specialists together with academic support, career guidance, and social support may increase the number of malaria experts; and (iii) motivation and retention packages (such as financial, educational, personal, and professional support incentives) may help motivate and retain malaria professionals. Implementation strategies include the following: (i) massive training of health personnel involved in malaria elimination and malaria experts (requiring special training) at different levels (national, sub-national, District & community levels), and (ii) recruiting highly qualified health personnel and retention and motivation mechanisms are needed. The lack of adequately trained human resources and personnel attrition are major challenges to effectively implement the planned multi-faceted malaria elimination by 2020 strategy in Ethiopia. Although a reduction in malaria incidence has been observed in the last 3-4 years, maintaining this success and achieving the malaria elimination goal with the present human resource profile will be impossible. A clear strategy for developing the capacity of the health workers in general, and malaria experts in particular, and retaining and motivating staff are crucial for malaria control and elimination.

The Plasmodium falciparum Antigen MB2 Induces Interferon-γ and Interleukin-10 Responses in Adults in Malaria Endemic Areas of Western Kenya

Background:MB2 is a novel Plasmodium falciparum antigen of unknown function expressed in pre-erythrocytic and blood stages of infection in the human host. Interferon-gamma (IFN-γ) and interleukin (IL)-10 responses to other P. falciparum antigens have been associated with protection from clinical malaria, but these responses have not been studied for MB2. The present study was undertaken to characterize IFN-γ and IL-10 responses to P. falciparum MB2 antigen in adults living in areas of differing malaria transmission in Western Kenya.Materials and Methods:Cytokine responses to two 9-mer MB2 peptides predicted to be human leukocyte antigen (HLA) class I restricted T-cell epitopes were measured by enzyme-linked immunosorbent assay (ELISA) (IFN-γ and IL-10) and enzyme-linked immunosorbent spot (ELISPOT) (IFN-γ) in adults (n = 228) in areas of unstable and stable malaria transmission. HLA class I restriction of responses was assessed in a sub-group of the study population.Results:IFN-γ and IL-10 responses to MB2 peptides by ELISA were observed in both sites with no significant difference in prevalence (IFN-γ, unstable transmission area, 18.8%, stable transmission area, 27.5%, P = 0.33; IL-10, unstable transmission area, 22.5%, stable transmission area, 25.0%, P = 0.78). Prevalence of IFN-γ responses by ELISPOT was also similar in both areas (unstable, 10.8%, stable, 10.9%, P = 0.98). Neither IFN-γ nor IL-10 responses showed evidence of HLA class I restriction.Conclusions:MB2 induces IFN-γ and IL-10 responses in adults living in both stable and unstable malaria transmission areas. Future studies should assess if these responses are associated with protection from clinical malaria.

Zinc, Copper and C-reactive Protein in Children with Severe Plasmodium falciparum Malaria in an Area of Unstable Malaria Transmission in Eastern Sudan

Few data exist on the role of trace element in the pathogenesis of severe malaria. The study was conducted at Kassala Hospital, eastern Sudan, to investigate the role of zinc, copper and C-reactive protein levels in children with severe Plasmodium falciparum malaria. Zinc, copper and C-reactive protein levels were measured in sera of three groups of children (35 in each arm): those with severe malaria, those with uncomplicated P. falciparum malaria and healthy controls. Although the zinc levels were significantly lower, the levels of copper and C-reactive protein were significantly higher in patients with severe P. falciparum. There was a significant inverse correlation between zinc and C-reactive protein and significant positive correlation between copper and C-reactive protein. The change in zinc and copper may play a role in pathogenesis of P. falciparum malaria.

Thrombocytopenia in pregnant women with Plasmodium falciparum malaria in an area of unstable malaria transmission in eastern Sudan.

BackgroundBlood platelet levels are being evaluated as predictive and prognostic indicators of the severity of malaria infections in humans. However, there are few studies on platelets and Plasmodium falciparum malaria during pregnancy.MethodsA case–control study was conducted at Gadarif Hospital in Eastern Sudan, an area characterized by unstable malaria transmission. The aim of the study was to investigate thrombocytopenia in pregnant women with P. falciparum malaria (cases) and healthy pregnant women (controls).ResultsThe median (interquartile) platelet counts were significantly lower in patients with malaria (N = 60) than in the controls (N = 60), 61, 000 (43,000–85,000) vs. 249,000 (204,000–300,000)/μL, respectively, p < 0.001. However, there was no significant difference in the platelet counts in patients with severe P. falciparum malaria (N = 12) compared with those patients with uncomplicated P. falciparum malaria (N = 48), 68, 000 (33,000-88,000)/μL vs. 61, 000 (45,000–85,000)/μL, respectively, p = 0.8. While none of the control group had thrombocytopenia (platelet count <75, 000/μL), it was found that 6/12 (50%) and 27/48 (56.2%) (p <0.001) of the patients with severe malaria and uncomplicated malaria had thrombocytopenia, respectively. Pregnant women with P. falciparum malaria, compared with the pregnant healthy control group, were at higher risk (OR = 10.1, 95% CI = 4.1–25.18; p < 0.001) of thrombocytopenia. Two patients experienced bleeding, and there was one maternal death due to cerebral malaria where the patient’s platelet count was only 28,000/μL.ConclusionP. falciparum malaria is associated with thrombocytopenia in pregnant women in this setting. More research is needed.

Polymerase chain reaction and histology in diagnosis of placental malaria in an area of unstable malaria transmission in Central Sudan

BackgroundPrevalence of placental malaria has been widely used as a standard indicator to characterize malaria infection in epidemiologic surveys. Placental malaria poses a greater diagnostic challenge, accurate and sensitive diagnostic tool for malaria infections in pregnancy is needed.MethodsA cross sectional study was conducted at Medani Hospital, which serves catchment area which is characterized by unstable malaria transmission. One hundred and seven placentae were investigated for malaria infection using polymerase chain reaction (PCR) and histology.Resultsout of 107 investigated placentae, 33 (30.8%) and 34 (31.8%) were positive for malaria by histology (two (2%) and 31(29.0%) were acute and past infections, respectively) and PCR, respectively. Out of 33 positive by histology, 15 were positive by the PCR while 18 were negative. The sensitivity of the PCR was 45.5% (95% CI: 29.2%- 62.5%). Out of 74 which were negative by histology, 19 were positive by the PCR. This is translated in specificity of 74.3% (95% CI: 63.5%- 83.3%). Of those tested positive by the PCR, 15 were positive by the histology, while 19 were negative. This is translated into a positive predictive value of 44.1% (95% CI: 28.3%- 61.0%). Of those 73 tested negative by the PCR, 55 were negative according to histology while 23 were positive. This is translated into a negative predictive value of 75.3% (95% CI: 64.5%-84.2%).ConclusionPCR had low sensitivity and specificity in comparison to placental histology, perhaps because the vast majority of the placental infections were past infections. Further research is needed.

Monocytes and macrophages and placental malaria infections in an area of unstable malaria transmission in eastern Sudan

BackgroundMaternal immunity is thought to play a major role in the increased susceptibility of pregnant women to Plasmodium falciparum malaria. Few studies exist on immunohistochemical characterization of the placental inflammatory infiltrate. The current study was conducted in Gadarif hospital in an area characterized by unstable malaria transmission in eastern Sudan.MethodNinety three placentae were investigated for malaria histological changes and immunohistochemical study for monocytes and macrophages (CD68).ResultsWhile 1(1.1%), 2(2.2%) and 20(21.5%) of the 93 placentae had acute, chronic and past malaria infections, 70(75.2%) had no malaria infections. Monocytes and macrophage (CD 68) were detected in 29 (31.2%) of these 93 placentae. Significantly higher rate of monocytes and macrophage were detected in placentae with malaria infections [11/23 (47.8%) vs. 18/70 (25.7%); P = 0.047] especially in placentae with past malaria infections. Placental malaria infections and monocytes and macrophages cells infiltration were not different between primiparae and multiparae. There was no significant difference in the birth weight between the women with placental malaria infections/monocytes and macrophages cells infiltration and those who had no placental malaria infections/cellular infiltrations.ConclusionSignificantly higher rate of monocytes and macrophage were detected in placentae with malaria infections. Neither placental malaria infections nor cellular infiltrates were associated with parity or lead to reduction of birth weight.

Malaria and pre-eclampsia in an area with unstable malaria transmission in Central Sudan

BackgroundPlacental malaria and pre-eclampsia occur frequently in women in tropics and are leading causes of maternal and perinatal morbidities and mortality. Few data exist concerning the interaction between placental malaria and pre-eclampsia.MethodsA case control study was conducted in Medani Hospital, which locates in an area of unstable malaria transmission in Central Sudan. Case (N = 143) were women with pre-eclampsia, which was defined as systolic blood presure≥140 mm Hg or diastolic blood pressure ≥ 90 mm Hg and proteinuria. Controls were parturient women (N = 143) without any blood pressure values > 139/89 mm Hg or proteinuria. Obstetrical and medical characteristics were gathered from both groups through structured questionnaires. Placental histopathology examinations for malaria were performed.ResultsTwenty-eight (19.6%) vs. 16 (11.2%); P = 0.04 of the cases vs. controls, had placental malaria infections. Five (2%), 1 (2%) and 22 (28.0%) vs. 1, 2 and 13 of the placentae showed acute, chronic and past infection on histopathology examination in the two groups respectively, while 115 (80.4%) vs.127 (88.8%) of them showed no infection, P = 0.04. In multivariate analysis, while there were no associations between age, parity, educational level, lack of antenatal care, blood groups and body mass index and pre-eclampsia; family history of hypertension and placental malaria (OR = 2.3, 95% CI = 1.0-5.2; P = 0.04) were significantly associated with pre-eclampsia.ConclusionPlacental malaria was associated with pre-eclampsia. Further research is needed.

Hypoglycaemia and severe Plasmodium falciparum malaria among pregnant Sudanese women in an area characterized by unstable malaria transmission.

BackgroundPregnant women are more susceptible to severe Plasmodium falciparum malaria, which can lead to poor maternal and fetal outcomes. Few data exist on the epidemiology of severe P. falciparum malaria in pregnant women.A hospital-based study was carried out to assess the pattern of severe P. falciparum malaria among pregnant women at the Kassala and Medani maternity hospitals, which are located in areas of unstable malaria transmission, in eastern and central Sudan, respectively. Pre-tested questionnaires were used to gather socio-demographic, clinical and obstetrical data. Suitable tests were performed for clinical and biochemical investigations.ResultsAmong 222 pregnant women diagnosed with malaria at the two hospitals, 40 (18.0%) women at mean (SD) gestational age of 29.3 (6.7) weeks fulfilled one or more of the WHO criteria for severe P. falciparum malaria. These were hypoglycaemia (14; 35.5%), severe anaemia (12; 30%), hypotension (10; 25%), jaundice (9; 22.5%), cerebral malaria (6; 15%), repeated convulsions (4; 10%), hyperparasitaemia (4; 10.0%) and more than one manifestation (9; 22.5%). While the mean (SD) presenting temperature was significantly lower for women presenting with hypoglycaemia [38.2(0.6) versus 38.8(0.7) °C, P = 0.04], other clinical and biochemical characteristics were not significantly different among women with different manifestations of severe P. falciparum malaria.ConclusionPreventive measures for pregnant women such as insecticide-treated bednets and chemoprophylaxis may be beneficial in areas of unstable malaria transmission. Early detection and prompt treatment of severe malaria, especially in pregnant women with hypoglycaemia, are needed.

Cortisol and uncomplicated Plasmodium falciparum malaria in an area of unstable malaria transmission in eastern Sudan

Objective To investigate the levels of serum cortisol in patients with uncomplicated Plasmodium falciparum (P. falciparum) malaria in an area of unstable malaria transmission in eastern Sudan. Methods The concentrations of cortisol were measured in sera of 25 patients with uncomplicated P. falciparum malaria (at presentation, 24 h and 7 d later) and 25 healthy volunteers using radioimmunoassay gamma counter. Results There was no significant difference in mean (SD) of total cortisol levels in patients with malaria in comparison with the control group; 602.2 (369.6) vs. 449.2(311.7) ng/mL, P=0.12. In patients with uncomplicated P. falciparum malaria, the mean (SD) presenting cortisol levels were significantly higher in comparison to the levels on day 7; 602.2 (369.6) vs. 373.6(139.1) ng/mL, P=0.009. In the patients with uncomplicated P. falciparum malaria (on presentation) cortisol levels were not correlated with initial temperature or the presenting parasitaemia. Conclusions Thus, cortisol levels were not significantly different between the patients and the controls.

Plasma Plasmodium falciparum Histidine-Rich Protein-2 Concentrations Do Not Reflect Severity of Malaria in Papua New Guinean Children

In areas of unstable malaria transmission, plasma Plasmodium falciparum histidine-rich protein 2 (PfHRP-2) concentrations parallel total parasite biomass and thus infection severity. However, where transmission is more intense, plasma PfHRP-2 might not reliably predict complications and mortality. As part of a prospective case-control study of severe pediatric illness in Madang, Papua New Guinea, we recruited 220 children aged 6 months to 10 years with severe falciparum malaria, 48 with uncomplicated malaria, and 139 healthy controls. Groups were matched by age, sex, and province of parental birth. Plasma PfHRP-2 levels were quantified by validated immunoassay. Detectable plasma PfHRP-2 concentrations were present in 21 healthy controls (15.1%). Although plasma PfHRP-2 levels were higher in the children with clinical malaria (P < .001), there was no difference between those with uncomplicated and severe infections (median, 584 and 456 ng/mL, respectively [interquartile range, 77-1114 and 113-1113 ng/mL, respectively]; P = .43). Log parasitemia, hemoglobin, log plasma bilirubin, and plasma creatinine levels were independently associated with plasma PfHRP-2 levels in multiple regression analysis (P ≤ .014), but coma, blood lactate level, and plasma bicarbonate level were not. The 1 severely ill child who died had a plasma PfHRP-2 concentration of 483 ng/mL, close to the group median. The clinical and prognostic utility of plasma PfHRP-2 concentrations depends on the epidemiologic circumstances. In areas of intense malaria transmission, plasma PfHRP-2 reflects recent as well as present infections.