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Biomedical subjects

M P Grobusch

Publications and source records attributed to M P Grobusch.

At least 19 recordsLinked to original sources

Association of a new mannose-binding lectin variant with severe malaria in Gabonese children.

Mannose-binding lectin (MBL2) variants that decrease the plasma level of the protein or encode dysfunctional proteins are frequently associated with the severity of a number of infections and autoimmune disorders. The high frequencies of these variants in most populations of the world are probably maintained by some selective advantage against widespread diseases. We found 14 new MBL2 allelic haplotypes, two of them with non-synonymous variants, by screening 136 children with uncomplicated malaria, 131 children with severe malaria and 39 older healthy schoolchildren. We also found a significant association of a novel variant with susceptibility to severe malaria (P=0.010). Increased MBL plasma levels and corresponding MBL2 genotypes were associated with lower concentration of several cytokines and chemokines in plasma of malaria patients. We suggest that malaria could have been one of the evolutionary driving forces shaping the MBL2 polymorphism in the African population.

Alleles↗

Evaluation of the use of RT-PCR for the early diagnosis of dengue fever.

RT-PCR was used to diagnose dengue virus infections confirmed serologically in 26 returning travellers. RT-PCR was positive for three (75%) of four samples taken on or before day 3 of the illness, for 15 (78.9%) of 19 samples taken between days 4 and 7, and for none of three samples tested on or after day 8 (p 0.0337). When applied early, RT-PCR seems to be a useful tool for the diagnosis of dengue fever.

Adolescent↗

Uncomplicated malaria.

All symptoms and signs of uncomplicated malaria are non-specific, as shared with other febrile conditions, and can occur early or later in the course of the disease. In endemic areas, the presence of hepatosplenomegaly, thrombocytopenia and anaemia is clearly associated with malaria, particularly in children. Fever, cephalgias, fatigue, malaise, and musculoskeletal pain constitute the most frequent clinical features in malaria. Following single exposure to Plasmodium falciparum infection, the patient will either die in the acute attack or survive with the development of some immunity. Elderly individuals are prone to a more severe course of disease. The non-fatal P. vivax and P. ovale cause similar initial illnesses, with bouts of fever relapsing periodically, but irregularly over a period of up to 5 years. Renal involvement of a moderate degree is more common in mild falciparum malaria than initially suspected. The liver is also afflicted in mild disease, but organ damage is limited and fully reversible after parasitological cure. Whereas the cardiotoxic adverse effects of antimalarial chemotherapeutics are well known, clinically relevant cardiac involvement in humans is rare in severe disease and even rarer in uncomplicated falciparum malaria. Co-infection can aggravate malaria. There is a growing body of evidence that there is significant interaction in terms of mutual aggravation of the course of disease between HIV and malaria, particularly in pregnant women. Children with a high level of exposure to P. falciparum have a lower risk of developing atopic disorders.

Anemia↗

Virus isolation for diagnosing dengue virus infections in returning travelers.

Dengue fever is recognized as one of the most frequent imported acute febrile illnesses affecting European tourists returning from the tropics. In order to assess the value of virus isolation for the diagnosis of dengue fever, 70 cases of dengue fever confirmed in German travelers during the period 1993-2001 were analyzed retrospectively. In 26 patients who had developed acute febrile illness within 2 weeks following their return from a trip to a dengue-endemic area, 9 of 13 attempts to isolate the virus were successful in sera drawn 1-5 days and 2 of 13 sera drawn 6-10 days after the onset of illness. DEN-1 was the most frequent serotype isolated. If performed early, virus isolation is a reliable tool for detecting dengue virus in returning travelers.

Adult↗

No evidence of Wolbachia endosymbiosis with Loa loa and Mansonella perstans.

Endosymbiotic Wolbachia bacteria from different filarial species, including major pathogens of humans such as Wuchereria bancrofti, Brugia malayi and Onchocerca volvulus, seem to play an important role in the development, viability and fertility of these worms. Wolbachia trigger inflammatory host responses as well as adverse reactions against standard treatment regimens and are therefore under investigation as novel treatment targets. We investigated whether Wolbachia are also endosymbiotic in Loa loa and Mansonella perstans. In both male and female adult L. loa, we found no evidence of bacteria by light or transmission electron microscopy. Furthermore, Wolbachia-specific PCR was negative in both L. loa and M. perstans microfilariae. The absence of Wolbachia in both filarial species therefore discourages the use of antibiotics as an adjunct or alternative approach to current treatment concepts for both loiasis and mansonelliasis perstans.

Animals↗

Age as a risk factor for severe manifestations and fatal outcome of falciparum malaria in European patients: observations from TropNetEurop and SIMPID Surveillance Data.

Previous studies have indicated that age is a risk factor for severe falciparum malaria in nonimmune patients. The objectives of this study were to reevaluate previous findings with a larger sample and to find out how strongly clinical outcomes for elderly patients differ from those for younger patients. Results of adjusted analyses indicated that the risks of death due to falciparum malaria, of experiencing cerebral or severe disease in general, and of hospitalization increased significantly with each decade of life. The case-fatality rate was almost 6 times greater among elderly patients than among younger patients, and cerebral complications occurred 3 times more often among elderly patients. Antimalarial chemoprophylaxis was significantly associated with a lower case-fatality rate and a lower frequency of cerebral complications. Women were more susceptible to cerebral complications than were men. Our study provides evidence that falciparum malaria is more serious in older patients and demonstrates that clinical surveillance networks are capable of providing quality data for investigation of rare events or diseases.

Age Factors↗

Myocardial damage in falciparum malaria detectable by cardiac troponin T is rare.

OBJECTIVES: To estimate the prevalence of myocardial damage in falciparum malaria by serum concentration of cardiac troponin T. METHODS: Retrospective study of stored sera and patient files; assessment of acute myocardial damage by serum concentration or activity of cardiac troponin T, creatine kinase, creatine kinase MB and myoglobin and by routine electrocardiography. RESULTS: A total of 161 patients with falciparum malaria were included in the study; troponin T was elevated in one case (0.6%), no CK-MB elevations were found, myoglobin was elevated in 10 of 161 patients (6.2%), all of whom were elderly and had concomitant elevated serum concentration levels of cystatin C; ECG abnormalities were seen in 23 patients. CONCLUSION: Assessed by troponin T, myocardial damage in falciparum malaria is rare.

Adolescent↗

Rapid immunochromatographic malarial antigen detection unreliable for detecting Plasmodium malariae and Plasmodium ovale.

In order to determine the reliability of two commercial tests for the rapid detection of plasmodial antigen in cases of infection with Plasmodium ovale and Plasmodium malariae, the products were evaluated in four centers and a search of the relevant literature was performed. The results of the present and previous studies were compared. With overall sensitivities ranging between 18.8% and 47.6% for Plasmodium malariae and between 20% and 31.3% for Plasmodium ovale, it is evident that neither test is reliable for the detection of Plasmodium ovale and Plasmodium malariae infections.

Animals↗

Epidemiology and clinical features of imported dengue fever in Europe: sentinel surveillance data from TropNetEurop.

Travelers have the potential both to acquire and to spread dengue virus infection. The incidence of dengue fever (DF) among European travelers certainly is underestimated, because few centers use standardized diagnostic procedures for febrile patients. In addition, DF is currently not reported in most European public health systems. Surveillance has commenced within the framework of a European Network on Imported Infectious Disease Surveillance (TropNetEurop) to gain information on the quantity and severity of cases of dengue imported into Europe. Descriptions of 294 patients with DF were analyzed for epidemiological information and clinical features. By far the most infections were imported from Asia, which suggests a high risk of DF for travelers to that region. Dengue hemorrhagic fever occurred in 7 patients (2.4%) all of whom recovered. Data reported by member sites of the TropNetEurop can contribute to understanding the epidemiology and clinical characteristics of imported DF.

Adolescent↗

Two cases of imported gnathostomiasis in Spanish women.

Reported here are two new cases of imported cutaneous gnathostomiasis that occurred in two Spanish women. The first patient acquired the helminth infection while travelling in Southeast Asia and the second in Mexico. Although the highest prevalence of gnathostomiasis infection is in Southeast Asia, the disease is now an emerging public health problem in some countries of Latin America. The cases reported here demonstrate the increasing frequency with which human gnathostomiasis is being diagnosed in nonendemic countries as a result of more extensive international travel and migration.

Adult↗

Amebic liver abscess--rare need for percutaneous treatment modalities.

BACKGROUND: Given the often unspecific symptoms of amebic liver abscess, an analysis was done to recognize the most common patterns of presentation. Since treatment recommendations are still inconsistent comparing conservative and interventional treatment modalities, we evaluated treatment modalities in our patients. METHODS: A retrospective case series of all patients with confirmed amebic liver abscess was conducted. Age, sex, country of origin or travel, symptoms, and physical and laboratory findings were recorded. Particular attention was given to the need for interventional measures. RESULTS: 62 patients were reviewed, and nearly all of them (95%) had a travel history. The most common findings were fever (97%), abdominal pain (95%), and hepatomegaly (79%). 11% still had no amebic antibodies on presentation but an increase in the follow-up examinations. In 5% needle aspiration was performed to allow differentiation between amebic and pyogenic etiology. Metronidazole alone quickly cleared symptoms in 92% of the patients. In 8% only, there was a therapeutic need for interventional procedures (3% already ruptured, 5% large abscess formation with the danger of rupture). CONCLUSIONS: In travelers with fever, abdominal pain, and hepatomegaly amebic liver abscess must be considered. Medical treatment with metronidazole is effective in more than 90%. Only in very few cases there is a need for invasive therapeutic modalities.

Abdominal Pain↗

Imported Falciparum malaria in Europe: sentinel surveillance data from the European network on surveillance of imported infectious diseases.

Malaria continues to have a high morbidity rate associated among European travelers. Thorough recording of epidemiological and clinical aspects of imported malaria has been helpful in the detection of new outbreaks and areas of developing drug resistance. Sentinel surveillance of data collected prospectively since 1999 has begun within TropNetEurop, a European network focusing on imported infectious diseases. TropNetEurop appears to cover approximately 10% of all patients with malaria seen in Europe. Reports of 1659 immigrants and European patients with Plasmodium falciparum malaria were analyzed for epidemiological information and data on clinical features. Regional data were quite diverse, reflecting local patterns of immigration and international travel. By far, the most infections were imported from West Africa. Europeans had more clinical complications; consequently, all deaths occurred in this group. Compared with European standards, the mortality rate was low (0.6% in Europeans). Data from TropNetEurop member sites can contribute to our understanding of the epidemiological and clinical findings regarding imported falciparum malaria.

Adolescent↗

Renal dysfunction in falciparum--malaria is detected more often when assessed by serum concentration of cystatin C instead of creatinine.

OBJECTIVES: To estimate the frequency of renal dysfunction in falciparum malaria by serum concentration of cystatin C, a new sensitive indicator of the glomerular filtration rate (GFR). METHODS: Retrospective study of stored sera and patient files. Assessment of renal function by serum concentration of creatinine and cystatin C and comparison of the results from both indicators of GFR. RESULTS: A total of 108 adult patients with falciparum malaria were included in the study. Concentration of creatinine and cystatin C correlated well (r = 0.706; P < 0.001). Elevated cystatin C was more frequent than elevated creatinine (54.6%vs. 20.4%; P < 0.001). Patients older than 50 years developed renal dysfunction more often (P < 0.05) than younger ones. Results from cystatin C and creatinine were concordant in 63 (58.3%) and contradictory in 45 (41.6%) cases. Four (3.7%) patients had elevated creatinine but normal cystatin C levels, hence 63 patients (58.3%) showed elevation of at least one indicator of GFR. The frequency of elevated cystatin C and elevated creatinine was unrelated to body weight, gender or bilirubin level. CONCLUSIONS: The prevalence of impaired renal function in patients with falciparum malaria seems to have been underestimated in the past. Using a sensitive marker, 55% of the patients have a reduced GFR.

Adolescent↗

Relative frequency of malaria pigment-carrying monocytes of nonimmune and semi-immune patients from flow cytometric depolarized side scatter.

BACKGROUND: Recently, it was observed that malaria can be detected by performing automated complete blood count analysis including depolarization measurement of scattered laser light. To explain large discrepancies in sensitivity and specificity observed in semi-immune and nonimmune malaria patients, we determined the relative frequencies of malaria pigment-carrying monocytes (PCM) by flow cytometric measurements combined with rare event analysis. METHODS: An experimental cell-sorting unit utilizing argon, krypton, and helium-neon lasers measured the relative frequencies of leukocytes of malaria patients. Single white blood cells showing high intensity in their depolarized side scatter were sorted for subsequent microscopic analysis. RESULTS: From microscopic inspection of sorted cells, we identified malaria PCM as a distinct cluster in scatter diagrams that is well separated from normal leukocytes. For nonimmune patients, the average relative frequency of PCM is 1.5 x 10(-4) (median), for semi-immune patients 8.8 x 10(-4), and for malaria-negative persons 4.4 x 10(-6). Results derived from depolarized side scatter at 488, 633, or 647 nm agree well. Furthermore, malaria pigment-carrying neutrophilic granulocytes were identified microscopically after sorting. We discuss briefly how pigment-carrying neutrophils might be differentiated from normal leukocytes and PCM by using flow cytometry and measuring depolarized side scatter at two wavelengths. CONCLUSION: Our results confirm the feasibility of malaria detection by flow cytometry for semi-immune patients and extend malaria detection to nonimmune patients with low frequencies of PCM. High sensitivity and specificity for malaria detection were obtained.

Cell Separation↗