Association between blood test parameters and intensity of Plasmodium falciparum infections in imported falciparum malaria cases in Tianjin City from 2015 to 2019 / 中国血吸虫病防治杂志

Objective To evaluate the association between blood test parameters and intensity of Plasmodium falciparum infections among imported falciparum malaria cases in Tianjin City from 2015 to 2019, so as to provide insights into the early diagnosis of imported P. falciparum malaria. Methods The epidemiological data of 37 imported cases with confirmed diagnosis of P. falciparum malaria in Tianjin City from 2015 to 2019 were collected, and the epidemiological features and clinical manifestations were retrospectively analyzed. In addition, the association between blood test parameters and intensity of P. falciparum infections was evaluated among the imported P. falciparum malaria cases. Results Among the 31 imported P. falciparum malaria cases, there were 31 cases (83.8%) with a reduction in platelet (PLT) counts, 16 cases (43.2%) with a reduction in red blood cell (RBC) counts, 16 cases (43.2%) with a reduction in hemoglobin (Hb) concentrations, 23 cases (62.2%) with a rise in neutrophil percentage (NEUT%), 32 cases (86.5%) with a rise in total bilirubin (TBIL) concentrations, 29 cases (78.4%) with a rise in alanine aminotransferase (ALT) concentrations, 28 cases (75.7%) with a rise in aspartate transaminase (AST) concentrations, and 23 cases (62.2%) with a rise in gamma-glutamyl transpetidase (GGT) concentrations. The PLT count and Hb concentration correlated negatively with the intensity of P. falciparum infections (Goodman-Kruskal γ = –0.568 and –0.521, both P values < 0.05) and the TBIL concentration and NEUT% correlated positively with the intensity of P. falciparum infections (Goodman-Kruskal γ = 0.496 and 0.610, both P values < 0.05) among imported falciparum malaria cases; however, there were no associations of ALT, AST, GGT levels or RBC count with the intensity of P. falciparum infections among the imported falciparum malaria cases (Goodman-Kruskal γ = 0.370, 0.497, 0.314 and –0.434, all P values > 0.05). Conclusions PLT, Hb, TBIL and NEUT% may serve as markers for early auxiliary diagnosis of imported P. falciparum malaria, and PLT and TBIL may provide valuable information for the diagnosis of severe imported P. falciparum malaria.

Efficacy, safety and tolerability of three regimens of artemisinin combination therapy in the management of Plasmodium falciparum malaria: a comparative study

Background: The WHO now recommends the use of artemisinin-based combination therapies for the first-line treatment of Plasmodium falciparum malaria to reduce the drug resistance. Hence, this study was designed to compare the efficacy, safety and tolerability of three regimens of artemisinin combination therapies in malaria diagnosed patients of Kamineni Institute of Medical Sciences Hospital, Narketpally.Methods: Total of 104 subjects had been allocated to 3 different artemisinin-based combinations regimens in a period of 2 years during December 2013 - November 2015. Out of 104 subjects, 34 received artemisinin-sulphadoxine pyrimethamine regimen, 33 subjects received artemisinin-lumefantrine regimen, and 37 subjects received artemisinin-doxycycline regimen. All the three regimens were studied for their efficacy, safety and tolerability.Results: The mean number of febrile days in artesunate-sulfadoxine pyrimethamine group (3.43±0.92) and artesunate-doxycycline group (3.51± 0.74) were comparatively less than artemether-lumefantrine group (4.33±0.77) which is statistically significant. The mean Hb%, RBC count, WBC count was not significantly different on day 7 in comparison to day 1 in all the three regimens of treatment groups. 14 subjects among the 104 had mild thrombocytopenia which was significantly improved on day 7 in all the three regimens of treatment groups.Conclusions: Artesunate-sulfadoxine-pyrimethamine and artesunate-doxycycline regimens showed better efficacy, safety and tolerability than artemether-lumefantrine regimen.

Malaria congénita en un hospital de Iquitos, Perú / Congenital malaria in a hospital in Iquitos, Peru

Objetivos. Determinar la frecuencia y características clínicas de los recién nacidos con malaria congénita en el Hospital de Apoyo de Iquitos en la Amazonía peruana. Materiales y métodos. Estudio descriptivo, prospectivo y transversal. De enero de 2011 a diciembre de 2013 se estudiaron 14 017 recién nacidos y a sus madres, de quienes se seleccionaron 52 portadoras de malaria gestacional mientras que a sus recién nacidos se les hospitalizó en el Servicio de Neonatología del hospital, y fueron sometidos a evaluación clínica y estudios de laboratorio. Resultados. La frecuencia de malaria gestacional fue de 0,4% y una proporción de malaria congénita de 9,6%. Plasmodium vivax fue hallado en 80% de casos de malaria gestacional y en 60% de malaria congénita. Se observó un caso de óbito fetal con gota gruesa positiva para Plasmodium falciparum. El cuadro clínico en recién nacidos fue fiebre, hipoactividad, irritabilidad y pobre succión. Conclusiones. Se documenta la presencia de malaria congénita en recién nacidos de madres con malaria gestacional. El cuadro clínico se asemeja a una sepsis neonatal. El diagnóstico precoz de malaria congénita y el tratamiento oportuno cursan con buena evolución.

Objectives. To determine the frequency and clinical features of newborns with congenital malaria in the Hospital de Apoyo of Iquitos in the Peruvian Amazon. Materials and methods. Descriptive, prospective and cross-sectional study. From January 2011 to December 2013, 14.017 newborns and their mothers were studied, of whom 52 carriers of gestational malaria were selected while their infants were hospitalized in the Neonatology Unit, and underwent clinical assessment and laboratory studies. Results. Gestational malaria frequency was 0.4% and a proportion of 9.6% of congenital malaria. Plasmodium vivax was found in 80% of cases of gestational malaria and in 60% of congenital malaria. A case of fetal death with positive thick blood smear for Plasmodium falciparum was observed. The clinical presentation in newborns was fever, hypoactivity, irritability and poor suction. Conclusions. The presence of congenital malaria in infants born to mothers with gestational malaria is documented. The clinical picture resembled neonatal sepsis. Early diagnosis of congenital malaria and timely treatment present with good evolution.

Efficacy of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Northeast Ethiopia.

Background: The impact of resistance to antimalarials is insidious and unless efficacy studies are conducted, resistance may go unrecognized. The aim of this study was to assess the efficacy of artemether/lumefantrine, for the treatment of uncomplicated Plasmodium falciparum infections in Kemisie Health Center, Northeast Ethiopia. Methods: Artemether/lumefantrine efficacy study was conducted in Kemisie Health Center, Northeast Ethiopia from September, 2012 to May, 2013. The study participants were febrile people above the age of 6 months with confirmed uncomplicated P. falciparum infection. Patients were treated with artemether/lumefantrine. Clinical and parasitological parameters were monitored over a 28 days follow-up period to evaluate drug efficacy. The Kaplan–Meier method was used for statistical analysis of data on drug efficacy. Results: Among the 66 enrolled participants 72.7% were 15 and above years of age while 15.3% were less than 5 years old. Of these study participants, 53% were male. There was 89.4% fever clearance and 84.8% parasite clearance on day 1, whereas, there was 100% fever clearance and 96.8% parasite clearance on day 3 from the 62 participants who carried on the study. Among 66 participants who had started 28 days of follow-up one patient had an early parasitological failure (parasitemia on day 3) and another patient had a late parasitological failure (parasitemia on day 21). Conclusions: In general, this study discovered good clinical and parasitological response of P. falciparum to artemether/lumefantrine. Further polymeric chain reaction and plasma drug concentration based effectiveness study of artemether/ lumefantrine should be conducted throughout the country.

Assessment of efficacy and safety of artesunate plus sulfadoxine pyrimethamine combination for treatment of uncomplicated falciparum malaria.

Background: Resistance of Plasmodium falciparum to antimalarial drugs is common in India. World Health Organization (WHO) recommends artemisinin based combination therapy (ACT) to counter the development of resistance in P. falciparum. WHO recommends that ideally antimalarial drug treatment policy or guidelines should be reviewed regularly and updated at least once every 24 months. In consideration to the above recommendation, we planned to conduct the following study. The objective was to determine the efficacy and safety of artesunate + sulphadoxine pyrimethamine (AS + SP) in patients with uncomplicated P. falciparum malaria. Methods: The study included 60 patients of uncomplicated P. falciparum. Each patient received AS + SP as per WHO guidelines. Diagnosis was confirmed by peripheral blood film. All patients were followed up on days 1, 3, 14, and 28 for detailed clinical and parasitological examination. Results: Of a total 60 patients, 55 patients were followed up for 28 days. Remaining 5 patients were lost in follow up. As per protocol analysis, 91% (50) of patients had demonstrated adequate clinical and parasitological response. Remaining 9% (5) had treatment failure in which 5.5% (3) had late parasitological failure and 3.6% (2) had late clinical failure. In our study, mean parasite clearance time was 45.2 ± 4.2 hrs. Conclusion: AS + SP is safe and effective drug for the treatment of uncomplicated falciparum malaria. However, the efficacy of this ACT needs to be carefully monitored periodically since treatment failure can occur due to resistance.

Sickle Cell Trait (HbAS) is Associated with Increased Expression of Erythrocyte Complement Regulatory Proteins CR1 and CD55 Levels in Children.

Aims: Erythrocyte complement regulatory proteins, complement receptor 1 (CR1) and decay accelerating factor (CD55) protect red blood cells (RBCs) from complement mediated damage by controlling complement activation cascade and potentially protect RBCs from complement mediated damage that may occur when immune complexes are formed following malaria infection. Given the important role of RBCs in regulation of complement activation, we considered the competence of sickle cell trait RBCs in these functions. Methods: Children (age 0-192 months; n=116) were enrolled in a nested case controlled study conducted in Kombewa Division, Kisumu west District between October and December 2004. Based on hemoglobin (Hb) type, children were stratified into those with HbAS (n=47) and HbAA (n=69). The 47 HbAS individuals were matched to the 69 HbAA individuals of similar age (± 2 months or ± 24 months for those below or more than 192 months, respectively) at a ratio of 1:1 or 1:2. Circulating CR1 levels and CD levels were quantified using a FACScan cytometer under normal and reduced oxygen saturation. Results: The mean CR1 copy numbers per RBC was comparable in the two groups. However, between the ages of 49-192 months, the mean CR1 copy numbers per erythrocyte was significantly higher in children who had HbAS compared to those with HbAA (P=0.0332). The mean CD55 levels were comparable between the two groups but after deoxygenation, the mean CD levels in RBCs of individuals with HbAS was significantly higher than in the HbAA (P=0.011). Conclusion: The mean CR1 and CD55 copy numbers per RBC were comparable between the two groups under normal and reduced oxygen saturation. Beyond the age of 49 months, the CR1 copy numbers was higher in the HbAS compared to HbAA and this was also true for CD55 levels under deoxygenated conditions. Taken together, these results demonstrate that in the younger age groups, the protection afforded by HbAS against severe manifestations of malaria may be due to other factors other than complement regulatory proteins but beyond the age of 49 months, this protection may be partly due to the high CR1 copy numbers in the HbAS individuals.

Red Blood Cell Immune Complex Binding Capacity in Children with Sickle Cell Trait (HbAS) Living in P. falciparum Malaria Holoendemic Region of Western Kenya.

Aims: Malaria infection leads to the formation of circulating immune complexes (CICs) which have been implicated in the pathogenesis of complicated malaria which includes severe malarial anemia. Children with sickle cell trait (HbAS) are less predisposed to getting severe manifestations of malaria. We carried out a study to determine the competence of the red blood cells (RBCs) of children with HbAS to bind immune complexes (ICs) and compared this with normal hemoglobin (HbAA). Methods: Children (aged 0-192 months) were enrolled in a nested case controlled study conducted in Kombewa Division, Kisumu West District, Kenya. Based on hemoglobin (Hb) type, children were stratified into those with HbAS (n=47) and HbAA (n=69). The 47 HbAS individuals were matched to 69 HbAA of similar age. The children were further categorized into three cohorts (0-12, 13-48 and 49-192 months). Immune complex binding capacity (ICBC) was quantified using a FACScan flow cytometer under normal and reduced oxygen saturation. Results: The mean immune complex binding capacity for the HbAS cells was significantly higher than that of HbAA cells (P=0.0191) under normal oxygen saturation or under reduced oxygen saturation (P=0.0050). When a matching variable (UNIANOVA) was done to control for age, gender, the presence or absence of malaria parasitaemia, the binding capacity was again significantly higher for the HbAS than for HbAA under normal oxygen saturation (P=0.025) and under reduced oxygen saturation (P=0.003). The binding capacity was lowest in the 7-12 months age group for both HbAS and HbAA; however, the overall picture showed that HbAS individuals had higher immune complex binding capacity than HbAA in all the age cohorts. Conclusion: These results demonstrate that the protection afforded by HbAS against severe manifestations of malaria may be partly due to higher immune complex binding capacity of the HbAS compared to the HbAA cells. This high binding capacity may lead to the mopping up of ICs formed during malaria attacks and therefore protect these cells from deposition and subsequent destruction.

Sentinel network for monitoring in vitro susceptibility of Plasmodium falciparum to antimalarial drugs in Colombia: a proof of concept

Drug resistance is one of the principal obstacles blocking worldwide malaria control. In Colombia, malaria remains a major public health concern and drug-resistant parasites have been reported. In vitro drug susceptibility assays are a useful tool for monitoring the emergence and spread of drug-resistant Plasmodium falciparum. The present study was conducted as a proof of concept for an antimalarial drug resistance surveillance network based on in vitro susceptibility testing in Colombia. Sentinel laboratories were set up in three malaria endemic areas. The enzyme linked immunosorbent assay-histidine rich protein 2 and schizont maturation methods were used to assess the susceptibility of fresh P. falciparum isolates to six antimalarial drugs. This study demonstrates that an antimalarial drug resistance surveillance network based on in vitro methods is feasible in the field with the participation of a research institute, local health institutions and universities. It could also serve as a model for a regional surveillance network. Preliminary susceptibility results showed widespread chloroquine resistance, which was consistent with previous reports for the Pacific region. However, high susceptibility to dihydroartemisinin and lumefantrine compounds, currently used for treatment in the country, was also reported. The implementation process identified critical points and opportunities for the improvement of network sustainability strategies.

Frequencies of some human genetic markers and their association with Plasmodium falciparum malaria in the Niger Delta, Nigeria.

Background & objectives: There is paucity of information on the association between Plasmodium falciparum malaria and some human genetic markers in the Niger Delta region of Nigeria. Hence, a study was undertaken in children to assess the current level of subclinical malaria due to P. falciparum. Methods: Blood groups ABO and Rhesus factor, haemoglobin electrophoretic pattern, G-6-PD deficiency status and malaria were determined among 240 apparently healthy children in a crosssectional descriptive study using standard procedures. Results: The prevalence of P. falciparum malaria in this region was high (27.5%). Blood group O (51.3%) dominated the study population, followed by B (23.8%), A (21.3%), and AB (3.8%). Rhesus D positive accounted for 91.3% while Rh D negative was 8.7%. Sickle-cell trait (HbAS) prevalence was 12.5% while HbAA accounted for 87.5%. In all, 5.42% of the children were G-6- PD deficient while 94.58% had normal G-6-PD status. Chi-square analysis revealed that only blood group O and Rh D negative had a significant association with P. falciparum malaria (2= 4.3636, p <0.05 and 2 = 5.760, p <0.02 respectively). No significant association was found to exist between P. falciparum malaria and other genetic markers. Conclusion: This study has provided the current prevalence rates of some genetic markers in a malaria endemic region of Niger Delta, Nigeria. Of all the genetic markers tested, only Blood group O and Rh D negative had significant and positive associations with P. falciparum infection.

Salmonella infection in patients with plasmodium falciparum malaria.

Patients with P.falciparum malaria infection are unusually susceptible to a variety of infectious diseases. There is an increased incidence of salmonella infection and bacteremia in patients with malaria. The objective of the present study was to report 3 patients with P.falciparum malaria infection in association with salmonellosis. These patients presented with fever and their blood smears revealed P.falciparum. They were treated with anti-malarial drugs. The malarial parasites disappeared from the peripheral blood, however, the fever persisted or recurred within a few days. Blood cultures grew S.choleraesusis, S.enteritidis and S.paratyphi A, respectively. These patients were treated successfully with antibiotics. Blood cultures should therefore be performed in all patients with P.falciparum malaria whose fever persists after treatment with antimalarial drugs.

Internal viscosity of the red cell in patients with plasmodium falciparum malaria.

The viscosities of plasma and whole blood were determined in 37 patients with P. falciparum as well as in 24 normal subjects by using the Cone-plate LVT viscometer. Although plasma fibrinogen concentration was significantly elevated in the patient’s group, their plasma viscosity showed no significant difference from that of normal subjects. As there was no difference in the whole blood viscosity, therefore the relative blood viscosity in these 2 groups was similar. The production of the hydrodynamic volume of red cell (k) and the Tatlor’s factor (T), Tk, were significantly higher in the patient’s group. There was a reverse relationship between Tk values and haematocrit in both groups. The calculated relative blood viscosity at haematocrit 1% was also found to be significantly higher in these patients which resulted in the significantly elevated KTc, were Tc represents a cell flexibility factor. The internal viscosity calculated from the know Tc values in patients was significantly higher than that of normal subjects. All these finding indicated that red cells infected with P. falciparum had increased internal viscosiy and their deformability and flexibility were decreased relatively to those of normal red cells.