Showing papers in "Transactions of The Royal Society of Tropical Medicine and Hygiene in 1997"
TL;DR: The predisposing factors, clinical presentation, and outcome of severe malaria in a Karen community living on the western border of Thailand were studied over a period of 2 years, suggesting that P. vivax may attenuate the severity of P. falciparum malaria.
Abstract: The predisposing factors, clinical presentation, and outcome of severe malaria in a Karen community living on the western border of Thailand were studied over a period of 2 years. This was an area of low malaria transmission (approximately one infection per person per year), where asymptomatic malaria is unusual. In a population of 4728 persons, who had good access to facilities for malaria diagnosis and treatment, there were 2573 cases of vivax malaria, none of whom died, and there were 5776 cases of falciparum malaria, 303 (5%) of whom had severe malaria and 11 (0.2%) of whom died-a case fatality rate of 1.9 per 1000 (95% confidence interval [CI] 1.0-3.3). The risks of developing severe malaria and dying declined steadily with age. The clinical features of severe malaria differed between children and adults. Anaemia was more common in children under 5 years old than in older children and adults, whereas the incidence of cerebral involvement increased with age. Severe malaria was 3 times (95% CI 1.4-6.2) more common in pregnant than in non-pregnant women, but was 4.2 times (95% CI 2.3-7.9) less common in patients with mixed Plasmodium falciparum and P. vivax infections than in those with P. falciparum alone, suggesting that P. vivax may attenuate the severity of P. falciparum malaria.
304 citations
208 citations
TL;DR: Above 6 mg/kg, the macrofilaricidal effect of DEC did not increase with dose; a significant proportion of adult W. bancrofti were not susceptible to DEC during the study period.
Abstract: To assess directly the effect of various doses of diethylcarbamazine (DEC) on adult Wuchereria bancrofti, 31 infected men were randomly assigned to receive an initial single DEC dose of 1 mg/kg (n = 7), 6 mg/kg (n = 10), or 12 mg/kg (n = 14). Beginning 7 d later, the dosage of DEC and duration of treatment were progressively increased for 7–10 weeks. Physical examinations were performed to detect scrotal nodules and the scrotal area was examined by ultrasound (7·5 MHz transducer) to monitor the ‘filaria dance sign’ (FDS), the characteristic pattern of adult worm movement. Of 53 adult worm ‘nests’ that were detected by ultrasound, 22 (41·5%) were DEC-sensitive (FDS became non-detectable and a nodule became palpable at the site); 20 (37·7%) were not sensitive (FDS remained unchanged and detectable and no nodule developed), and 11 (20·8%) showed mixed responses (FDS remained detectable but a palpable nodule developed). All but one sensitive or mixed response occurred within 1 week after the initial single dose. Of 39 ‘nests’ in men who initially received a single 6 or 12 mg/kg dose of DEC, 20 (51·3%) had sensitive responses compared to 2 (14·3%) of 14 ‘nests’ in men who received a single 1 mg/kg dose (P = 0·04). Above 6 mg/kg, the macrofilaricidal effect of DEC did not increase with dose; a significant proportion of adult W. bancrofti were not susceptible to DEC during the study period.
179 citations
TL;DR: There has been no decline in the efficacy of the 3 d artesunate plus mefloquine regimen since it was introduced in 1992 and this regimen is safe, well tolerated, and highly effective in the treatment of multi-drug resistant falciparum malaria.
Abstract: On the western border of Thailand, in an area endemic for multi-drug resistant Plasmodium falciparum malaria, therapeutic responses were assessed in 1967 patients with uncomplicated falciparum malaria treated with 3 d of artesunate (total dose 12 mg/kg) plus mefloquine (total dose 25 mg/kg). The regimen was well tolerated and resulted in a rapid clinical response; within 48 h, 96% of patients were aparasitaemic and 94% were afebrile. After correcting for reinfections, the cure rate by day 42 was 89% (95% confidence interval [95% CI] 87-91%). Three independent factors were found to predict recrudescence: age 40,000/microL (AHR = 1.6, 95%, CI 1.2-2.2), and pure P. falciparum infections (AHR = 1.8, 95% CI 1.3-2.7). These 3 factors combined accounted for 62% of all treatment failures. Patients who received mefloquine on admission with a high admission parasitaemia (> 40,000/microL) had a three-fold (95% CI 1.3-7) risk of subsequent recrudescence compared with those who received their mefloquine on the second or third day (P = 0.01). There has been no decline in the efficacy of the 3 d artesunate plus mefloquine regimen since it was introduced in 1992. This regimen is safe, well tolerated, and highly effective in the treatment of multi-drug resistant falciparum malaria.
169 citations
TL;DR: The experience shows that a low-cost, community-based intervention aimed at providing children with prompt and adequate treatment of presumptive episodes of clinical malaria is feasible, and suggests that it may lead to a reduction in the morbidity from severe malaria.
Abstract: A community-based programme to ensure prompt and adequate treatment of presumptive episodes of clinical malaria in children has been established in a rural province of Burkina Faso. The implementation strategy was based on training a core group of mothers in every village and supplying community health workers with essential antimalarial drugs specially packed in age-specific bags containing a full course of treatment. Drugs were sold under a cost-recovery scheme. The programme was run in 1994 by the national malaria control centre (CNLP), and in 1995 it was developed to the provincial health team (PHT). Knowledge and awareness of malaria increased with the intervention. Drug consumption by age group was compatible with the distribution of disease, and no major problem of misuse emerged. The actual implementation costs of the intervention were US$ 0.06 per child living in the province. An evaluation of the impact of the intervention on the severity of malaria, using routine data from the health information system and taking as an indicator the proportion of malaria cases which were recorded as severe in health centres, was performed. In 1994, when the intervention was implemented on a provincial scale by CNLP, this proportion was lower than the average of the 4 preceding years (3.7% vs. 4.9%). In 1995, when the programme was implemented by the PHT, the proportion of severe cases was lower in health centres achieving a programme coverage of > or = 50% in their catchment area compared with the others (4.2% vs. 6.1%). Our experience shows that a low-cost, community-based intervention aimed at providing children with prompt and adequate treatment of presumptive episodes of clinical malaria is feasible, and suggests that it may lead to a reduction in the morbidity from severe malaria.
166 citations
TL;DR: Treatment with nitazoxanide was 71-100% effective in eliminating evidence of infection with Entamoeba histolytica/E.
Abstract: A study to evaluate the efficacy and safety of nitazoxanide as a single agent for the treatment of a broad spectrum of mixed parasitic infections, both protozoa and helminths, was conducted at a primary school in San Pedro Toliman, Queretaro, Mexico. Three faecal samples from 1824 adults and children were screened for the presence of oocysts, cysts, trophozoites, eggs or larvae of intestinal protozoa or helminths. Two hundred and forty-six adults and children infected with at least one protozoan and 2 helminths were given 7.5 mg/kg of nitazoxanide (500 mg to adults and 200 mg to children less than 12 years old) every 12 h for 3 consecutive days. Faecal samples were examined on days 6, 7, 8, 13, 14 and 15 (+/- 1) following initiation of treatment, using formalin-ether concentration and Kato-Katz egg counting. Treatment with nitazoxanide was 71-100% effective in eliminating evidence of infection with Entamoeba histolytica/E. dispar, Giardia duodenalis, Blastocystis hominis, Isospora belli, Enterobius vermicularis, Ascaris lumbricoides, Trichuris trichiura and Hymenolepis nana. Haematology and clinical chemistry values obtained before and after treatment remained unaffected by nitazoxanide. The drug was well tolerated, with only 15 patients (6.1%) reporting mild abdominal pain that lasted less than 24 h.
141 citations
TL;DR: The finding of an association between reduced risk of clinical malaria and infection with parasites of merozoite surface protein 1 (MSP-1) type RO33 or MSP-2 type 3D7 further suggests that the concomitant immunity is, at least in part, a consequence of a response to these major merozosite surface proteins.
Abstract: A prospective community study in a highly malaria endemic area of Papua New Guinea found that infection with multiple Plasmodium falciparum genotypes was an indicator of lowered risk of subsequent clinical attack. The results suggest that concurrent or very recent infections provide protection from superinfecting parasites. The finding of an association between reduced risk of clinical malaria and infection with parasites of merozoite surface protein 1 (MSP-1) type RO33 or MSP-2 type 3D7 further suggests that the concomitant immunity is, at least in part, a consequence of a response to these major merozoite surface proteins.
139 citations
TL;DR: A flavivirus related to the tick-borne encephalitis complex was isolated from the blood of 6 male butchers, aged 24-39 years, in Jeddah, Saudi Arabia in November and December 1995, and two of the patients died and the other 4 recovered completely.
Abstract: A flavivirus related to the tick-borne encephalitis complex was isolated from the blood of 6 male butchers, aged 24-39 years, in Jeddah, Saudi Arabia in November and December 1995. Two of the patients died and the other 4 recovered completely. Four more patients, 3 males and 1 female, were diagnosed serologically by immunoglobulin M capture enzyme-linked immunosorbent assay and seroconversion in acute and convalescent blood samples examined by indirect immunofluorescent test using Vero cells infected with the isolated virus. The virus identity was confirmed at the Centers for Disease Control and Prevention, Fort Collins, Colorado, USA, by the polymerase chain reaction; it was closely related to Kayasanur Forest disease virus. All infected patients had similar clinical and laboratory symptoms and signs, including fever, headache, generalized body aches, arthralgia, anorexia, vomiting, leucopenia, thrombocytopenia, elevated liver enzymes (serum glutamic oxalacetic and serum glutamic pyruvic transaminases), elevated creatinine phosphokinase, and elevated blood urea. One patient developed symptoms of encephalitis, but survived without any sequel. Skin rash developed in 2 patients, morbilliform on the hands, feet, and lower abdomen of one patient and purpuric associated with melaena in the second patient. Eight of the 10 confirmed patients were working with sheep, and the disease may be a zoonotic viral infection.
123 citations
TL;DR: From 1993 to 1996, an entomological survey was conducted in the village of Ndiop, Senegal, as part of a research programme on malaria epidemiology and the mechanisms of protective immunity.
Abstract: From 1993 to 1996, an entomological survey was conducted in the village of Ndiop, Senegal, as part of a research programme on malaria epidemiology and the mechanisms of protective immunity. Mosquitoes were captured on human bait and by indoor spraying. Species from the Anopheles gambiae complex were identified using the polymerase chain reaction, and Plasmodium falciparum infections were detected by enzyme-linked immunosorbent assay for circumsporozoite protein. The vector species identified were A. gambiae (33·9%), A. arabiensis (63·2%), A. melas (0·3%) and A. funestus (2·5%). Similar proportions of A. gambiae (74·2%) and A. arabiensis (73·8%) contained human blood; 27·0% of A. gambiae and 28·3% of A. arabiensis had fed on cattle. The sporozoite rates were similar for A. gambiae (3·2%) and A. arabiensis (3·7%).The annual entomological inoculation rates varied greatly depending on the year. There were 63, 17, 37 and 7 infected bites per person per year in 1993, 1994, 1995 and 1996 respectively. Transmission was highly seasonal, from July to October. A. arabiensis was responsible for 66% of malaria transmission, A. gambiae for 31%, and A. funestus for 3%.
122 citations
TL;DR: Blood donors from areas in and adjoining the Sinai peninsula, in the eastern and western desert, and in southernmost Egypt, had the lowest prevalence of HCV antibody, and the large urban governorates of Cairo and Alexandria had antibody prevalences of 19% and 11%, respectively.
Abstract: Markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections were sought in serum samples from 2644 blood donors in 24 of Egypt's 26 governorates. Of the 2644 samples, 656 (24·8%) were shown to contain anti-HCV immunoglobulin G antibody by Abbott second generation enzyme immunoassays (EIA). Of 85 EIA-positive samples tested by recombinant immunoblot assay, 72 (85%) were positive. HCV seroprevalence in the governorates ranged from zero to 38%; 15 governorates (62%) had an HCV antibody prevalence greater than 20%, and 6 (25%) greater than 30%. Governorates with higher seroprevalences were located in the central and north-eastern Nile river delta, and south of Cairo in the Nile river valley. Subjects from areas in and adjoining the Sinai peninsula, in the eastern and western desert, and in southernmost Egypt, had the lowest prevalence of HCV antibody. The large urban governorates of Cairo and Alexandria had antibody prevalences of 19% and 11%, respectively. A total of 39·4% subjects had evidence of HBV infection (and-HBV core antigen total antibody). HCV infections were detected more frequently in donors with markers for HBV infections than in uninfected subjects (36% versus 18%, P
120 citations
TL;DR: It is suspected that the CCHF virus may have been introduced to Saudi Arabia by infected ticks on imported sheep arriving at Jeddah seaport, and that it is now endemic in the Western Province.
Abstract: In 1990, an outbreak of suspected viral haemorrhagic fever involving 7 individuals occurred in Mecca in the Western Province of Saudi Arabia. Congo-Crimean haemorrhagic fever (CCHF), not previously known to be present in Saudi Arabia, was incriminated. A study of the epidemiology of this virus was therefore carried out in Mecca, and in nearby Jeddah and Taif in 1991-1993; 13 species of ixodid ticks (5 Hyalomma spp., 5 Rhipicephalus spp., 2 Amblyomma spp., 1 Boophilus sp.) were collected from livestock (camels, cattle, sheep, goats), and of these 10 were capable of transmitting CCHF. Camels had the highest rate of tick infestation (97%), and H. dromedarii was the commonest tick (70%). Attempts to isolate virus from pools of H. dromedarii and H. anatolicum anatolicum were unsuccessful. The source of infection in 3 confirmed cases of CCHF was contact with fresh mutton and, in a suspected case, slaughtering sheep. An investigation in Mecca, which included a serological survey of abattoir workers, identified 40 human cases of confirmed or suspected CCHF between 1989 and 1990, with 12 fatalities. Significant risk factors included exposure to animal blood or tissue in abattoirs, but not tick bites. It is suspected that the CCHF virus may have been introduced to Saudi Arabia by infected ticks on imported sheep arriving at Jeddah seaport, and that it is now endemic in the Western Province.
TL;DR: Examination of epidemiological aspects of Ascaris-induced intestinal obstruction through analysis of published reports on the subject found that both the proportion of AI-IO and the number of cases were significantly related to the local prevalence of ascariasis.
Abstract: We examined epidemiological aspects of Ascaris-induced intestinal obstruction (AI-IO) through analysis of published reports on the subject. In 9 studies of > or = 100 patients admitted to hospital due to ascariasis, intestinal obstruction was the single most common complication and accounted for 38-87.5% of all complications (weighted mean 72%). The proportion of intestinal obstruction caused by ascariasis was identified in 14 studies from 7 countries with varying degrees of endemic ascariasis. Using relevant data on the duration of the study, the number of beds in the reporting hospital, and the number of hospital beds/1000 population in the area, the number of cases of AI-IO/year/1000 population was estimated from 11 studies. Both the proportion of AI-IO (range 0-0.71) and the number of cases of AI-IO/year/1000 population (range 0-0.25) were significantly related, in a non-linear manner, to the local prevalence of ascariasis (range 0.01-0.92). In 12 studies of > or = 30 patients with AI-IO, the case fatality rates ranged from 0 to 8.6% (weighted mean 5.7%). The mean age of patients with AI-IO was < or = 5 years in 6 of 7 studies in which age was specified.
TL;DR: The ParaSight-F test had a consistently higher sensitivity and speed, was easiest to learn, and required no laboratory facility to evaluate, and is recommended as the diagnostic tool for the future.
Abstract: Four diagnostic techniques for Plasmodium falciparum infection were evaluated against serial parasite dilutions and on identical field samples. These were (i) Giemsa-stained thick blood films (GTF), (ii) acridine orange-stained thick (AOTF) and thin (AOTnF) blood films, (iii) the quantitative buffy coat technique (QBC); and (iv) the ParaSight-F dipstick test (PS). PS had a consistently higher sensitivity and speed, was easiest to learn, and required no laboratory facility. The 100% sensitivity cut-off points against known parasite densities (per mm3) were: PS, 30; GTF, 84; QBC, 84; AOTnF, 84; AOTF, 149. In the field study, test sensitivities compared with examination of 800 microscope fields of a Giemsa-stained thin blood film were PS, 96.6%; AOTF, 93.1%; GTF, 91.4%; QBC, 89.7%; AOTnF, 82.8%. In the dilution study, one false positive result was recorded with QBC; in the field study there was one false positive each with PS, AOTnF and AOTF. When a newly trained microscopist examined samples of the parasite dilutions, the 100% sensitivity cut-off points were AOTF, 84; GTF, 140; QBC, 390. Total handling time was shortest with PS regardless of whether samples were processed individually or in batches of 10 or 100. The ParaSight-F test is recommended as the diagnostic tool for the future.
TL;DR: Using chloroquine, oligonucleosomal DNA fragmentation was observed with a sensitive strain of P. falciparum, but not with a resistant one, suggesting that apoptosis may be involved in the action ofchloroquine on the parasite.
Abstract: As chemoresistance of Plasmodium falciparum to chloroquine has arisen, new ways of combating the infection are needed. Similarities exist between the multidrug resistance of mammalian cells and chloroquine resistance of P. falciparum, based on the occurrence of internucleosomal deoxyribonucleic acid (DNA) breakdown and the ability of some anticancer drugs and chloroquine to induce apoptosis. Using chloroquine, oligonucleosomal DNA fragmentation was observed with a sensitive strain of P. falciparum, but not with a resistant one. This suggests that apoptosis may be involved in the action of chloroquine on the parasite.
TL;DR: This study demonstrated the use of polymorphic markers to confirm whether parasites in patients with clinical recrudescences after drug treatment are genuinely resistant.
Abstract: Recrudescent Plasmodium falciparum parasites were sampled from 108 children taking part in a drug efficacy trial in Gabon. A finger-prick blood sample was taken from each child before treatment, and a posttreatment sample taken of the recrudescent parasites. Sample deoxyribonucleic acid was amplified by the polymerase chain reaction using primers specific to the P. falciparum antigen genes MSP-1, MSP-2 and GLURP. Seventy-seven children had identical parasites in their pre- and post-treatment samples, indicating genuine recrudescences of resistant parasites. Fourteen children had completely different parasites in their pre- and post-treatment samples, indicating either a fresh infection from a mosquito or growth of a population of parasites not detected in the pre-treatment sample, perhaps due to sequestration. The remaining 17 children had a mixture of pre-treatment and new parasites in their post-treatment samples. This study demonstrated the use of polymorphic markers to confirm whether parasites in patients with clinical recrudescences after drug treatment are genuinely resistant.
TL;DR: PCR is a powerful epidemiological tool for screening villages for the prevalence of W. bancrofti and could be used initially to locate endemic areas with transmission of bANCroftian filariasis.
Abstract: Human blood samples and indoor-resting Culex pipiens were collected in 33 randomly selected houses from different sectors of a village in the Nile Delta of Egypt which was endemic for Wuchereria bancrofti. Blood was also collected from subjects with no history of living in filarial endemic areas. Human blood samples were divided and assessed by both membrane filtration and polymerase chain reaction (PCR). Similarly, mosquito samples were assessed by both dissection and PCR. Blood pools representing each household were tested by PCR. If a pool gave a positive result, then individual blood specimens were also tested by PCR. Of the 33 houses tested, both membrane filtration and blood pools assayed by PCR identified 14 (42.4%) 'infected houses'. PCR detected parasite deoxyribonucleic acid (DNA) in blood pools from an additional 3 households that gave negative results by membrane filtration. Of 178 endemic blood samples tested by membrane filtration, 22 (12.3%) had microfilariae and all were individually positive by PCR. Although microfilaria counts were lower in blood collected during the day than in night-collected blood, the PCR results were consistent, regardless of time of collection. All non-endemic blood samples were negative by PCR. Among the 33 houses rested, mosquito pools assayed by PCR identified 17 (51.5%) as 'infected households'. Of these, 8 houses (47%) contained at least one microfilaraemic resident. One 'infected household' was identified by mosquito dissection. We concluded that PCR is a powerful epidemiological tool for screening villages for the prevalence of W. bancrofti. PCR detection of W. bancrofti DNA in blood-fed mosquitoes could be used initially to locate endemic areas with transmission of bancroftian filariasis. PCR detection of W. bancrofti DNA in blood collected during the day could then be used to assess W. bancrofti infection rates.
TL;DR: Mass treatment of the human population with niclosamide was carried out in 2 villages in rural Guatemala where Taenia solium was endemic, to determine how this would affect the epidemiology of the parasite.
Abstract: Mass treatment of the human population with niclosamide was carried out in 2 villages in rural Guatemala where Taenia solium was endemic, to determine how this would affect the epidemiology of the parasite. Intestinal taeniasis was diagnosed by microscopy and coproantigen testing, and porcine cysticercosis by a specific Western blot. Before mass treatment, the prevalence of human taeniasis was 3·5%; 10 months after treatment it was 1%, a significant decrease (P < 10−4. All tapeworms that could be identified to the species level were T. solium. Similarly, the seroprevalence of antibodies to cysticercosis in pigs declined from 55% before treatment to 7% 10 months after treatment, once again a significant decrease (P < 10−6). These effects were seen in both villages. The possible use of mass chemotherapy as a tool in the control of T. solium is discussed.
TL;DR: A rapid immunodiagnostic test developed by ICT Diagnostics is simple, easy to learn and accurate, and may prove to be an important tool in the battle against falciparum malaria.
Abstract: A rapid immunodiagnostic test (ICT Malaria PfTest) has been developed by ICT Diagnostics (Sydney, Australia) for the diagnosis of Plasmodium falciparum infection. The test is an antigen capture assay based on the detection of P. falciparum histidine-rich protein 2 in peripheral blood. This study was undertaken to assess the performance and usefulness of the test as a diagnostic method in highly malarious, inaccessible forested villages of Mandla district, central India. In all, 353 patients with fever were scanned by the test in parallel with thick blood film examination. The sensitivity and specificity were 100% and 84.5%, respectively. The whole test took about 5 min. The test results became negative in most cases (70%) within 7 d after initiation of curative chemotherapy. The test is simple, easy to learn and accurate, and may prove to be an important tool in the battle against falciparum malaria.
TL;DR: The study confirmed the high prevalence ofHBV infection in Tunisia; it occurs mainly in children and teenagers, and vertical and perinatal transmission of HBV does not appear to be significant.
Abstract: Serum samples from 33,363 healthy people in Tunisia have been tested for serological markers of hepatitis B, C and delta viruses (HBV, HCV and HDV). Hepatitis B surface antigen (HBsAg) was detected in 6.5% of sera. The overall seroprevalence of HBV was 37.5%. Vertical and perinatal transmission of HBV in the first 3 months of life occurred in only 0.4% of 177 mother and child pairs. HBV seroprevalence was 10.7% in infants under 5 years old and increased with age rapidly till 25 years of age and then more slowly in adulthood, reaching 54% for people aged over 40 years. HBsAg seropositivity varied throughout the country, ranging from 3% to 13% with higher prevalences in the south and central-west regions. Overall seroprevalences for HDV and HCV were 17.7% and 0.4%, respectively. HDV superinfection occurred later than HBV and increased with age in parallel with HBV. Overall, HCV and HBV infections had different geographical distributions throughout the country. The study confirmed the high prevalence of HBV infection in Tunisia; it occurs mainly in children and teenagers, and vertical and perinatal transmission of HBV does not appear to be significant. HDV superinfection is quite common in Tunisia and occurs in almost 44% of individuals infected with HBV. In contrast, seroprevalence of HCV in the Tunisian general population was low (0.4%). These results indicate differences in the distribution of the viruses and/or different routes of transmission.
TL;DR: These data provide the first evidence of vertical transmission of YF virus in nature by A. aegypti, its main vector to humans, and strongly suggest that vertical transmission played a major role in the spread of the epidemic.
Abstract: Entomological investigations were conducted in 1995 in Senegal, following a yellow fever (YF) outbreak A total of 1125 mosquitoes collected in the field, including males, females and 12–48 h old newly emerged adults reared from wild-caught larvae, were tested for YF virus Among the 22 species captured, Aedes aegypti was the most common ‘Wild’ vectors of YF were also captured, including A furcifer, A metallicus and A luteocephalus In all, 28 YF virus isolations were made: 19 from A aegypti females, including 2 from newly emerged specimens; 5 were obtained from A aegypti males, including one from a pool of newly emerged specimens, 2 from A furcifer females, and one each from a female A metallicus and a female A luteocephalus The true infection rates (TIRs) were much higher in adult A aegypti than in specimens reared from larvae—8·2% and 31·4% for female and male A aegypti captured on human volunteers, respectively (P 0·05) This outbreak was an intermediate YF epidemic, involving 4 vector species Our data provide the first evidence of vertical transmission of YF virus in nature by A aegypti, its main vector to humans, and strongly suggest that vertical transmission played a major role in the spread of the epidemic
TL;DR: Artemisinin suppositories are easy to administer, cheap, and very effective for treating children with severe malaria and in rural areas where medical facilities are lacking these drugs will allow antimalarial therapy to be instituted earlier in the course of the disease and may therefore save lives.
Abstract: Severe malaria remains a major cause of mortality and morbidity for children living in many tropical regions. With the emergence of strains of Plasmodium falciparum resistant to both chloroquine and quinine, alternative antimalarial agents are required. The artemisinin group of compounds are rapidly effective in severe disease when given by intramuscular or intravenous injection. However, these routes of administration are not always available in rural areas. In an open, randomized comparison 109 Vietnamese children, aged between 3 months and 14 years, with severe P.falciparum malaria, were allocated at random to receive artemisinin suppositories followed by mefloquine (n = 37), intramuscular artesunate followed by mefloquine (n = 37), or intravenous quinine followed by pyrimethamine/sulfadoxine (n = 35). There were 9 deaths: 2 artemisinin, 4 artesunate and 5 quinine-treated children. There was no difference in fever clearance time, coma recovery, or length of hospital stay among the 3 groups. However, parasite clearance times were significantly faster in artemisinin and artesunate-treated patients than in those who received quinine (P < 0.0001). Both artemisinin and artesunate were very well tolerated, but children receiving these drugs had lower peripheral reticulocyte counts by day 5 of treatment than those in the quinine group (P = 0.011). No other adverse effect or toxicity was found. There was no treatment failure in these 2 groups, but 4 patients in the quinine group failed to clear their parasites within 7 d of starting treatment and required alternative antimalarial therapy. Artemisinin suppositories are easy to administer, cheap, and very effective for treating children with severe malaria. In rural areas where medical facilities are lacking these drugs will allow antimalarial therapy to be instituted earlier in the course of the disease and may therefore save lives.
TL;DR: The BCS provided a better overall assessment of a child's incapacity from falciparum malaria, but the ACS was more useful in assessing neurological disturbances and was a worse predictor of neurological sequelae.
Abstract: The Blantyre coma scale (BCS) is used to assess children with severe falciparum malaria, particularly as a criterion for cerebral malaria, but it has not been formally validated. We compared the BCS to the Adelaide coma scale (ACS), for Kenyan children with severe malaria. We examined the inter-observer agreement between 3 observers in the assessment of coma scales on 17 children by measuring the proportion of agreement (PA), disagreement rate (DR) and fixed sample size kappa (kappa n). We assessed the sensitivity and specificity of the scales in detecting events (seizures and hypoglycaemia) in 240 children during admission and the usefulness of the scales in predicting outcome. There was considerable disagreement between observers in the assessment of both scales (BCS: PA = 0.55, DR = 0.09 and kappa n = 0.27; ACS: PA = 0.36, DR = 0.31, and kappa n = 0.31), particularly with the verbal component of the BCS (kappa n = 0.02). Compared to the ACS, the BCS was more specific (0.85 for BCS and 0.80 for ACS), but less sensitive (0.25-0.69 vs. 0.38-0.88 respectively) in detecting events and was a worse predictor of neurological sequelae. The BCS provided a better overall assessment of a child's incapacity from falciparum malaria, but the ACS was more useful in assessing neurological disturbances.
TL;DR: It is suggested that measurement of PfHRP2 in plasma could provide an alternative approach to the assessment of the parasite biomass, and thus prognosis, in severe malaria, and that this could be done simply by using the currently available dipsticks.
Abstract: Plasmodium falciparum histidine rich protein 2 (PfHRP2) antigen was measured semi-quantitatively in whole blood, plasma, and supernatants and red blood cells of cultures in vitro using the dipstick Para-Sight™-F test and also by a quantitative antigen-capture enzyme-linked immunosorbent assay (ELISA). In vitro, PfHRP2 was secreted mainly during the second half of the asexual cycle with a marked rise during schizont development and rupture. The total PfHRP2 secreted before schizogony corresponded to approximately 4% of that contained in the red blood cells. In samples from 55 patients with acute falciparum malaria, the level of detection by ELISA corresponded to parasitaemias of 100/μL for whole blood and 1600/μL for separated plasma. Whole blood PfHRP2 levels were correlated significantly with admission parasitaemia (r = 0 · 76, P < 0 · 0001) and the stage of parasite development (r = 0 · 43, P < 0 · 01). Although whole blood PfHRP2 concentrations were higher in severe malaria, plasma concentrations of PfHRP2 were considerably higher in severe malaria (median titre 1:320, range zero to 1:1280) than in uncomplicated malaria (median titre 1:5, range zero to 1:80; P < 0 · 0001). The ratio of whole blood to plasma PfHRP2 was lower in severe than in uncomplicated malaria (median 4, range 0.25 to 256, versus 64, range 4 to 1280; P < 0 · 0001). With plasma samples the intensity of colour change on the dipstick correlated well with more precise measurement of optical density in the ELlSA (r = 0 · 88, P < 0 · 0001). These results suggest that measurement of PfHRP2 in plasma could provide an alternative approach to the assessment of the parasite biomass, and thus prognosis, in severe malaria, and that this could be done simply by using the currently available dipsticks.
TL;DR: The results suggest that the high prevalence of severe anaemia in young children, even in an area of very low endemicity, depends more on age and parasitaemia than on the transmission level.
Abstract: The influence of age on the clinical presentation of severe malaria and especially on its 2 most commonly encountered manifestations, cerebral malaria and severe anaemia, has been retrospectively examined in 161 children (< 16 years old) admitted to the paediatric department of Hopital Principal de Dakar from 1 January 1990 to 29 February 1996. They lived in Dakar and its suburbs, a region of Senegal where the malaria transmission rate is very low. Cases were defined by at least one of the World Health Organization criteria of severe malaria and the presence of Plasmodium falciparum in blood smears. Severe anaemia was present in 73.1%, 52.1% and 26.2% cases of severe malaria among children aged 0-3 years, 4-7 years and 8-15 years, respectively (P < 0.0001). The frequency of cerebral malaria was 11.3%, 28.2% and 60.6%, respectively, in the same age groups (P < 0.0001). Severe anaemia and cerebral malaria were associated in 8.7% of the cases of severe malaria. The fatality rate was significantly lower in cases of severe anaemia without cerebral malaria (3%) than in cases of cerebral malaria without severe anaemia (17.5%; P < 0.02). Among young children, severe anaemia was associated with brief hyperparasitaemia or with prolonged lower parasitaemia. Other things being equal, older children had a lower risk of severe anaemia. The results suggest that the high prevalence of severe anaemia in young children, even in an area of very low endemicity, depends more on age and parasitaemia than on the transmission level.
TL;DR: This study highlighted the 'law of unintended consequences', since 2 contrasting effects were observed: reduction of malaria vectors but concomitant increase of dengue vectors.
Abstract: Surveys were conducted of adult and immature mosquitoes in an area undergoing oil palm development in north Sarawak. Point prevalence data from 2 sites were collected annually, coinciding with annual phases of forest clearing, burning/cultivation, and maintenance. Major habitat perturbation during the forest/clearing transition shifted the major mosquito faunal equilibrium in terms of species composition, relative density and occurrence. Analyses of variance showed that the mean numbers of 4 species of Anopheles decreased significantly after forest clearing. Relative densities of immature stages decreased after forest clearing, but A. letifer and Culex tritaeniorhynchus remained relatively unchanged after the second year. Comparisons with the pre-development forest stage showed that the reductions in person-biting rates, adult survival and combined entomological inoculation rates (EIR) of A. donaldi and A. letifer decreased the risk of malaria transmission by 90% over the 4 years period. Concomitant reductions in EIR and annual malaria incidence were also correlated. This study highlighted the 'law of unintended consequences', since 2 contrasting effects were observed: reduction of malaria vectors but concomitant increase of dengue vectors.
TL;DR: Cutaneous leishmaniasis in Morocco occurs mainly in the south and is caused by Leishmania major and L. tropica, and the isoenzymic monomorphism of the parasite is suggested to be an emerging disease in Taza.
Abstract: Cutaneous leishmaniasis in Morocco occurs mainly in the south and is caused by Leishmania major and L. tropica. In 1995, for the first time, 4 autochthonous cases were confirmed by smear and/or culture from the province of Taza in north Morocco. An active survey revealed 128 more cases. The number had increased gradually since 1994. Most of the cases (86%) came from the suburbs of the city of Taza. All cultured and typed parasites were characterized as L. tropica MON-102. A leishmanin skin test survey among a random sample of the exposed population showed an overall positivity rate of 19.9%, with no correlation with age or gender. The spatial distribution of the cases and skin test positivity, their occurrence in all age groups, the highly variable clinical picture, the severity and large size of lesions in older patients, the slow recovery of some treated patients, and the isoenzymic monomorphism of the parasite, all suggested that cutaneous leishmaniasis caused by L. tropica is an emerging disease in Taza.
TL;DR: The enhanced efficacy of chloroquine-chlorpheniramine combination in treating acute uncomplicated P. falciparum infection in children from an endemic area of Nigeria is suggested.
Abstract: Chlorpheniramine, a histamine H1 receptor antagonist, reverse chloroquine resistance in Plasmodium falciparum in vitro. However, the clinical significance of this remains unclear. We have evaluated the efficacy of chloroquine and a chloroquine-chlorpheniramine combination in 112 consecutive children with acute symptomatic uncomplicated falciparum malaria. There was no significant difference in the parasite and fever clearance times in the 2 treatment groups. However, the proportion of patients in whom parasitaemia increased 24 h after commencement of treatment was significantly higher in the chloroquine group than in the chloroquine-chlorpheniramine group (28.5% vs. 8.3%, chi 2 = 6.61, P < 0.01). There was also a higher proportion of children with RII and RIII responses to treatment in the chloroquine than in the chloroquine-chlorpheniramine group but the difference was not statistically significant. The cure rate on day 14 was higher in the chloroquine-chlorpheniramine group than in the chloroquine group. Chloroquine and its combination with chlorpheniramine were well tolerated, the only prominent adverse effect being pruritus, with equal incidence in both groups. Chlorpheniramine reversed chloroquine resistance in vitro in a similar manner to verapamil in isolates of P. falciparum obtained from the patients. Failure of a response in vivo to chloroquine correlated with resistance in vitro in patients treated with this drug. In contrast, all but one patient with isolates which were chloroquine resistant in vitro were successfully treated with chloroquine-chlorpheniramine combination. These data suggest the enhanced efficacy of chloroquine-chlorpheniramine combination in treating acute uncomplicated P. falciparum infection in children from an endemic area of Nigeria.
TL;DR: A significant increase in risk of malaria attacks among multigravidae was noted until the fifth pregnancy, and the incidence rate of malaria attack was, on average, 4.2 times higher during pregnancy than during the control period.
Abstract: The interaction between pregnancy and malaria attacks was investigated from 1990 to 1994 among women in the village of Dielmo, a holoendemic area in Senegal where malaria transmission is intense and perennial. Clinical and parasitological data collected during the daily follow-up of 48 pregnancies among 31 women were compared with those collected from the same women using the same methods during the year which preceded or followed their pregnancy. The parasite prevalence, mean and maximum parasite density in Plasmodium falciparum infections were significantly higher during pregnancy. The incidence rate of malaria attacks was, on average, 4.2 times higher during pregnancy than during the control period. Although most pregnancies were not associated with a malaria attack and the incidence of malaria attacks decreased as the number of previous pregnancies increased, a significant increase in risk of malaria attacks among multigravidae was noted until the fifth pregnancy.
TL;DR: Ophthalmic findings in 82 immunocompetent patients with C. neoformans var.
Abstract: In Papua New Guinea cryptococcal meningitis occurs predominantly in immunocompetent patients in whom Cryptococcus neoformans var, gattii is implicated in 95% of cases. Ocular complications are common. We have reviewed ophthalmic findings in 82 immunocompetent patients and have attempted to identify those features of the disease that predict an unfavourable visual outcome. Visual loss occurred in 52.6% of survivors and was associated with optic atrophy following optic disc swelling in 60.9%. Progression of disc swelling to optic atrophy was predicted by the presence of an abducens palsy (P = 0.049) and cerebrospinal fluid (CSF) cryptococcal antigen titres > 1:1024 (P = 0.036). Raised intracranial pressure (defined as opening CSF pressure > or = 300 mm on admission) was not associated with visual loss. Vision deteriorated in 17.3% of patients despite anticryptococcal therapy and in 3.7% it followed curative therapy. The high rate of visual loss in immunocompetent patients with C. neoformans var. gattii infection contrasts with others' experience of immunosuppressed patients with C. neoformans var. neoformans infection, in whom visual loss was rare. This difference may reflect immune mediated optic nerve dysfunction in C. neoformans var. gattii meningitis caused by either compression due to arachnoid adhesions or oedema and inflammatory cell-mediated damage.
TL;DR: The disposition of chlorproguanil/dapsone has been studied in young children with Plasmodium falciparum malaria, to provide data complementary to a clinical trial of this drug combination.
Abstract: The disposition of chlorproguanil/dapsone (one daily dose for 3 d of 1.2 and 2.4 mg/kg respectively) has been studied in young children with Plasmodium falciparum malaria, to provide data complementary to a clinical trial of this drug combination. Unbound concentrations of chlorcycloguanil (the active metabolite of chlorproguanil) and dapsone in clinical samples have been related to the unbound drug concentrations which produced defined outcomes in tests in vitro of drug efficacy and toxicity. Twelve children with uncomplicated malaria were treated: all cleared parasitaemia within 72 h and made uneventful recoveries. After the first dose of chlorproguanil/dapsone the maximum unbound chlorcycloguanil concentration in clinical samples (19 ng/mL [about 60 nM]) was 2 orders of magnitude above the 50% inhibitory concentration (IC50) value for this drug against the K39 stain of P. falciparum, while falling 2 orders of magnitude below its IC50 against human bone marrow cells; the maximum unbound dapsone concentration in clinical samples (160 ng/mL [about 645 nM]) was 10-fold higher than its IC50 against the K39 strain. However, because of the rapid elimination of chlorproguanil from the body (half-life 12.6 +/- 6.3 h), the minimum fractional inhibitory concentrations of unbound chlorcycloguanil/dapsone against the K39 strain were probably exceeded for no more than 6 d. These data, together with the clinical trial, will be helpful in deciding whether current chlorproguanil/dapsone doses are optimal for the treatment of falciparum malaria.