Showing papers in "American Journal of Tropical Medicine and Hygiene in 1996"
TL;DR: Of the 104 patients with falciparum malaria treated with atovaquone plus proguanil for 3-7 days, 101 were cured and had virtually no adverse side effects, but parasitemia recurred in most patients.
Abstract: The therapy of Plasmodium falciparum malaria continues to be a problem in many parts of Southeast Asia because of multidrug resistance to nearly all existing antimalarial drugs. Atovaquone is a novel hydroxynaphthoquinone with broad spectrum anti-protozoal activity. We recently evaluated the antimalarial activity of atovaquone in a series of dose-ranging studies in 317 patients with malaria at the Bangkok Hospital for Tropical Diseases. Originally, the drug was administered alone. Using atovaquone alone resulted in satisfactory, initial clinical responses in all patients; the mean parasite and fever clearance times were 62 and 53 hr, respectively. However, irrespective of the duration of therapy, overall cure rates were approximately 67%. In vitro sensitivity studies on parasites taken from patients prior to treatment and at the time of recrudescence showed a marked decrease in susceptibility to atovaquone in the recrudescent parasites. To improve cure rates, atovaquone was administered in combination with other drugs with antimalarial activity. Proguanil and tetracycline were chosen due to laboratory evidence of potentiation; doxycycline was selected because it has a longer half-life than tetracycline. Although pyrimethamine did not show laboratory evidence of potentiation with atovaquone, it was chosen as an alternative inhibitor of dihydrofolic acid reductase with a longer half-life than proguanil. The clinical studies with these drug combinations confirmed the laboratory results with marked improvement in cure rates for proguanil, tetracycline, and doxycycline; pyrimethamine showed only minimal improvement. Proguanil was subsequently selected as the preferred drug partner because of its long record of safety and the ability to use the drug in pregnant women and children. Of the 104 patients with falciparum malaria treated with atovaquone plus proguanil for 3–7 days, 101 were cured and had virtually no adverse side effects. The combination of atovaquone and proguanil also was effective in eliminating erythrocytic forms of P. vivax, but parasitemia recurred in most patients.
393 citations
TL;DR: Use of an effective antimalarial (MQ) was protective against LBW through its effect on reducing placental and umbilical cord blood malaria infection, and effective prevention of malaria in pregnant women in malaria-endemic settings may reduce the likelihood of LBW by 5-14%, and may reduced the amount of preventableLBW by more than 30%.
Abstract: While there is broad evidence for the adverse effects of Plasmodium falciparum infection in pregnancy, and the World Health Organization recommends preventive strategies, there is markedly reduced efficacy in sub-Saharan Africa of the most widely available, affordable and used antimalarial drug for chemoprophylaxis-chloroquine (CQ). During 1987-1990, we studied pregnant women in an area of high malaria endemicity in rural Malawi to compare the efficacy of CQ (the drug recommended by national policy) with mefloquine (MQ, a relatively new and highly effective antimalarial) in preventing low birth weight (LBW) due to prematurity and intrauterine growth retardation (IUGR). Among 1,766 women monitored during at least their last six weeks of pregnancy with observed ingestion of their regimen and facility delivery of a live born singleton, their babies had a mean +/- SD birth weight of 2,905 +/- 461 gm and 16.8% had LBW. In a multivariate analysis, factors significantly associated with LBW included: first birth (odds ratio [OR] = 4.27), female infant (OR = 2.92), maternal human immunodeficiency virus infection (OR = 2.66), low maternal weight (OR = 1.95), and placental blood P. falciparum infection (OR = 1.71). Factors significantly associated with IUGR-LBW included first birth, female infant, low maternal weight, and placental malaria. Factors significantly associated with preterm-LBW included maternal syphilis infection, umbilical cord blood malaria, first birth, low maternal weight, and female infant. Use of an effective antimalarial (MQ) was protective against LBW through its effect on reducing placental and umbilical cord blood malaria infection. The proportion of LBW babies born to women on MQ (12.5% [parity-adjusted for the population of delivering women]) was significantly lower than the proportion born to women on CQ (15.5%; P = 0.05). Effective prevention of malaria in pregnant women in malaria-endemic settings may reduce the likelihood of LBW by 5-14%, and may reduce the amount of preventable LBW by more than 30%. When evaluating antenatal care programs, health policy makers must consider providing an effective preventive drug (either MQ or other drugs identified in additional studies, e.g., sulfa-pyrimethamine compounds) as a means to prevent low birth weight and its consequences.
324 citations
TL;DR: The results indicate that the extensive use of PZQ in the Nile delta region of Egypt has not resulted in a dramatic change in the efficacy of this drug, and the isolation of schistosomes that are less susceptible to PZZ may be a warning signal that will require establishment of a monitoring system to determine if the percentage of patients that cannot be cured by PzQ is increasing.
Abstract: To determine if resistance/tolerance to the antischistosomal drug praziquantel (PZQ) is appearing in Egyptian villages within the Nile delta region, where it has been used extensively, we treated 1,607 infected villagers and observed that 321 required one additional treatment while 89 villagers required two additional treatments; 24 of the 89 were still not cured after a third dose of this drug. Eggs were isolated from fecal samples and serum was isolated from blood taken from seven villagers successfully treated after a single dose and from 14 villagers not successfully treated after two or three doses of PZQ. The eggs were used to establish infections in mice (isolates), which were then treated six weeks after infection with three different doses of PZQ. Serum was used to determine the concentration of PZQ in the infected humans. Three of the egg isolates from the 14 villagers that could not be treated with three doses of PZQ produced infections in mice that were statistically less responsive to PZQ when compared with isolates obtained from patients that were cured after a single dose of this drug. Pharmacokinetic parameters were the same in patients treated successfully after a single dose versus those not treated successfully following two or three doses, thus eliminating the possibility that poor cure rates among infected villagers was due to a decrease in PZQ bioavailability. From our data, approximately 1-2.4% of the villagers treated with PZQ could not be completely cured of their infection and three of every 1,000 treated villagers may harbor parasites that can tolerate high doses of PZQ. These results indicate that the extensive use of PZQ in the Nile delta region of Egypt has not resulted in a dramatic change in the efficacy of this drug. The isolation of schistosomes that are less susceptible to PZQ may be a warning signal that will require establishment of a monitoring system, similar to the one we have developed, to determine if the percentage of patients that cannot be cured by PZQ is increasing. Furthermore, if that percentage begins to increase over time, it will be critical to determine, by pharmacologic methods reported in this study, whether isolates obtained from uncured patients are becoming increasingly resistant to PZQ.
299 citations
TL;DR: Both killing vectors and reducing susceptibility (by whatever means) are more effective than killing dogs or treating them with drugs, and a dog vaccine is highly desirable in Europe, where vector control is less likely to be successful.
Abstract: Mathematical models are used to compare the effectiveness of various untested, unused, and undeveloped methods for controlling canine and human zoonotic visceral leishmaniasis (ZVL), including insecticides, vaccines, killing serologically positive and sick dogs, and drugs. For given percentage changes in control parameters, insecticides are the most effective control method. Where transmission occurs peridomestically and vectors are accessible to treatment, as in parts of tropical America, insecticides are expected to reduce the incidence of human ZVL even more effectively than they reduce the prevalence of canine leishmaniasis, a result that should encourage properly designed vector control trials. The second best strategy is to reduce susceptibility to leishmaniasis by vaccinating people or dogs, or by eliminating childhood malnutrition where it is common. Both killing vectors and reducing susceptibility (by whatever means) are more effective than killing dogs or treating them with drugs. In Europe, where vector control is less likely to be successful and canine leishmaniasis is a major veterinary problem, a dog vaccine is highly desirable. Better drugs for dogs will help case management but, with regard to bringing down the incidence in the dog population, immunization is the ultimate goal.
278 citations
TL;DR: An increase in midgut bacterial counts after mosquitoes were exposed to a bacteria/sugar suspension significantly reduced oocyst infection rates and densities in Plasmodium falciparum-infected mosquito cohorts.
Abstract: The functional role of bacteria in the midgut of adult mosquitoes is unknown. In this study, we examined the population dynamics of midgut bacteria of laboratory reared Anopheles stephensi, An. gambiae, and An. albimanus. Mosquito midguts were dissected under sterile conditions and examined for the presence of bacteria using standard microbiologic techniques. Ninety percent and 73% (n = 30) of newly emerged An. gambiae and An. stephensi, respectively, harbored bacteria. In contrast, only 17% (n = 23) of An. albimanus harbored any bacteria. The bacterial population increased 11-40-fold in the presence of a blood meal, but then decreased to pre-blood meal levels in 3-5 days. Pseudomonas cepacia, Enterobacter agglomerans, and Flavobacterium spp. were found in all three anopheline species. Midgut bacteria were acquired both transtadially and through the sugar meal. Transtadial transmission was demonstrated by successfully passaging Escherichia coli HS5 from the larval to the adult stage. However, midgut bacteria were acquired more efficiently through the sugar meal than through transtadial passage. An increase in midgut bacterial counts after mosquitoes were exposed to a bacteria/sugar suspension significantly reduced oocyst infection rates and densities in Plasmodium falciparum-infected mosquito cohorts. Since bacteria occur naturally in wild mosquitoes, it may be possible to modify anopheline vector competence using introduced or indigenous bacteria.
274 citations
TL;DR: The HIV infection diminishes a pregnant woman's capacity to control P. falciparum parasitemia and placental and newborn infection, the major determinants of the impact of P. Falconerum on fetal growth and infant survival.
Abstract: In Africa, the human immunodeficiency virus (HIV) is the most serious emerging infection and Plasmodium falciparum malaria is one of the most prevalent infectious diseases. Both infections have serious consequences in pregnant women, their fetuses, and infants. We examined the association between HIV and P. falciparum in pregnant women enrolled in a malaria chemoprophylaxis study in rural Malawi. Pregnant women (n = 2,946) were enrolled at their first antenatal clinic visit (mean 5.6 months of pregnancy), placed on one of three chloroquine regimens, and followed through delivery. Plasmodium falciparum parasitemia was measured at enrollment, monthly thereafter, at delivery, and 2-6 months postpartum; placental and newborn (umbilical cord blood) infection was measured for hospital-delivered infants. Serum collected during pregnancy was tested for antibodies to HIV by enzyme-linked immunoassay with Western blot confirmation. Parasitemia was detected in 46% of 2,946 women at enrollment and 19.1% at delivery; HIV seroprevalence was 5.5%. The prevalence and geometric mean density (GMPD) of parasitemia at enrollment and at delivery were higher in HIV-seropositive(+) than in HIV-seronegative(-) women (at enrollment: 57% prevalence and a GMPD of 1,558 parasites/mm3 versus 44% and 670/mm3, respectively; P < 0.0001; and at delivery: 35% and 1,589/mm3 versus 18% and 373/mm3; P < 0.0005). Placental infection rates were higher in HIV(+) compared with HIV(-) women, (38% versus 23%; P < 0.0005). This association was strongest in multigravidas. Compared with infants born to HIV(-) women, newborns born to HIV(+) women had higher rates of umbilical cord blood parasitemia. Both HIV(+) and HIV(-) women had similar rates of parasitemia 2-6 months postpartum. The HIV infection diminishes a pregnant woman's capacity to control P. falciparum parasitemia and placental and newborn infection, the major determinants of the impact of P. falciparum on fetal growth and infant survival.
273 citations
TL;DR: This study provides strong evidence that dengue 2 and 3 viruses have neurovirulent properties and behave similarly to other members of the Flaviviridae.
Abstract: Involvement of the central nervous system in dengue fever and dengue hemorrhagic fever has always been thought to be secondary to vasculitis with resultant fluid extravasation, cerebral edema, hypoperfusion, hyponatremia, liver failure, and/or renal failure. Thus, the condition has been referred to as dengue encephalopathy. Encephalitis or direct involvement of the brain by the virus was thought to be unlikely. This paper reports on six children who were seen over a period of two years presenting on the second or third day of illness with dengue encephalitis. The diagnosis was based upon a clinical picture of encephalitis and confirmed by cerebrospinal fluid (CSF) microscopy and electroencephalography changes. All six cases were confirmed dengue infections. Dengue 3 virus was isolated from the CSF of four cases and in one case, dengue 2 was detected by the polymerase chain reaction in both the CSF and blood. In the sixth case, virologic evidence was negative but dengue immunoglobulin M was detected in the CSF and blood. Since the onset of encephalitis appears early in the course of illness coinciding with the viremic phase, we postulate that the virus crosses the blood-brain barrier and directly invades the brain causing encephalitis. This study provides strong evidence that dengue 2 and 3 viruses have neurovirulent properties and behave similarly to other members of the Flaviviridae.
271 citations
TL;DR: ivermectin provides a safe and a highly effective single dose treatment for S. stercoralis and A. lumbricoides, while it is not an alternative for the treatment of T. trichiura and hookworm infections.
Abstract: A randomized trial carried out in rural Zanzibar comparing a single dose of 200 micrograms/kg of ivermectin and 400 mg/day for three days of albendazole for treatment of strongyloidiasis and other intestinal nematodes is described. In 301 children with Strongyloides stercoralis infection, treatment with ivermectin or albendazole resulted in cure rates of 83% and 45%, respectively. While both drugs were very effective against Ascaris lumbricoides, Trichuris trichiura was cured only in 11% (ivermectin) and 43% (albendazole) of the subjects, although the mean eggload was reduced by 59% and 92%, respectively. Ivermectin was ineffective against hookworms, while albendazole resulted in a cure rate of 98%. No severe side effects were recorded and mild side effects were of transient nature for both treatments. Therefore, ivermectin provides a safe and a highly effective single dose treatment for S. stercoralis and A. lumbricoides, while it is not an alternative for the treatment of T. trichiura and hookworm infections.
267 citations
TL;DR: Evidence is provided for an age-dependent threshold effect of parasitemia that allows parasite density to be used to distinguish malaria attacks from other causes of fever within an individual and should facilitate the accurate evaluation of the incidence of clinical malaria in highly endemic areas.
Abstract: The high prevalence of asymptomatic malaria infections and the nonspecific signs and symptoms of the disease make the individual diagnosis of clinical malaria uncertain in highly endemic areas. Longitudinal data obtained during a four-month period from a daily survey of 200 permanent inhabitants (one month-83 years old) living in a holoendemic area were analyzed in a random-effects logistic regression model to investigate the relationship between the level of Plasmodium falciparum parasitemia and risk of fever. It was not possible to build a model that described/summarized correctly this relationship by a continuous function. Findings provide evidence for an age-dependent threshold effect of parasitemia on the occurrence of fever. The level of this threshold varied by 2.45 trophozoites per leukocyte, maximum at one year of age, to 0.5 trophozoites per leukocyte, minimum at 60 years of age. When the parasite density of a person crossed the threshold level corresponding to his or her age, the individual's risk of fever was multiplied by 44 (95% confidence interval = 13.6–144.8). The existence of this threshold effect allows parasite density to be used to distinguish malaria attacks from other causes of fever within an individual and should facilitate the accurate evaluation of the incidence of clinical malaria in highly endemic areas.
201 citations
TL;DR: In a study group of 183 people in a Schistosoma mansoni-endemic area in Burundi, stool examinations were performed with duplicate 25-mg Kato-Katz slides on seven occasions and validate recently developed statistical models and charts predicting true prevalences.
Abstract: In a study group of 183 people in a Schistosoma mansoni-endemic area in Burundi, stool examinations were performed with duplicate 25-mg Kato-Katz slides on seven occasions (days 1, 3, 5, 8, 10, 32, and 37). Point prevalences detected by single examinations of 25 mg and 50 mg of stool varied from 41.0% to 57.9% and from 55.7% to 63.9%, respectively. The cumulative prevalence for all seven measurements was 82.0%. The individual day-to-day variation in egg output was important. The majority of infections missed by the examination of single slides and specimens were light ones. The Kato-Katz method applied on a single stool specimen is more suitable for morbidity control, but less suitable for control of infection. When a precise quantitative diagnosis on the individual level is required, several measurements on different days are necessary. The data presented validate recently developed statistical models and charts predicting true prevalences.
193 citations
TL;DR: Both PCR and immunoblot are sensitive enough to detect asyptomatic infection and could be valuable tools for studies monitoring the transmission of the disease and vaccination trials.
Abstract: A major limitation to the study of the epidemiology of canine visceral leishmaniasis is the inability to identify and count asymptomatic carriers because classic diagnositc tests are insufficiently sensitive. We investigated the capacity of the polymerase chain reaction (PCR) to detect the parasite and immunoblotting to detect specific antibodies in samples from dogs living in an endemic area without any symptoms of leishmaniasis. Results of classic serologic tests (immunofluorescence and enzyme-linked immunosorbent assay) were negative. Two independent PCR assays detected the parasite in skin and conjunctival samples from 80% of the dogs. We found specific antibodies by immunoblot in 66% and 56% of the dogs had both specific antibodies and parasite DNA. As controls, samples from dogs with clinical manifestations of the disease before and after treatment were assayed. The frequency of positive PCR samples decreased after treatment, and although antibody levels decreased with cure of the disease, they remained detectable by immunoblot. Results showed that most of the dogs living in an endemic area had been exposed to Leishmania. Both PCR and immunoblot are sensitive enough to detect asyptomatic infection and could be valuable tools for studies monitoring the transmission of the disease and vaccination trials.
TL;DR: The reservoir parasite population was thus larger and more stable than previously thought, a finding that is consistent with the high levels of genetic variation at polymorphic loci reported from analysis of P. falciparum parasites in this area.
Abstract: We have used the nested polymerase chain reaction (PCR) to assay for low level Plasmodium falciparum infections that were below the threshold of detection of blood film examination. This revealed a substantial group of asymptomatic, submicroscopically patent infections within the population of a Sudanese village present throughout the year although clinical malaria episodes were almost entirely confined to the transmission season. In our September, January, April, and June surveys, the PCR-detected prevalences were 13%, 19%, 24%, and 19%, respectively. These figures reveal a much higher prevalence of dry season infection than previous microscopic surveys have indicated. Furthermore, 20% of a cohort of 79 individuals were healthy throughout the September to November transmission season but were PCR-positive for P. falciparum in a least one of a series of samples taken in the ensuing months. Levels of exposure to P. falciparum infection were therefore higher than was previously believed in this region, highlighting the fact that many individuals were infected but healthy for most of the year. The reservoir parasite population was thus larger and more stable than previously thought, a finding that is consistent with the high levels of genetic variation at polymorphic loci reported from analysis of P. falciparum parasites in this area.
TL;DR: Seroepidemiologic data suggest that whereas the total IgG-specific activity is not indicative of any given level of protection against malaria, the level of IgG3 was significantly associated with the relative susceptibility to clinical P. falciparum malaria attacks.
Abstract: Three cross-sectional studies were conducted in a representative cohort of individuals living continuously in an area holoendemic for malaria in Senegal Plasma from 145 children and adults were tested The pattern of antimalarial immunoglobulin class (IgM and IgG) and subclass (IgG1 to IgG4) antibody distribution was determined by enzyme-linked immunosorbent assay using a crude blood-stage antigen of Plasmodium falciparum-infected red blood cells Adults had higher levels of specific antibodies than children, and IgM, IgG2, and IgG3 accounted for the highest difference (29, 65, and 45 times, respectively) Differences in antibody levels were significant for IgG1 to IgG4 between the lowest and the highest transmission season No particular isotype distribution pattern could be found associated with any given parasitemia level The relationship between the optical density (OD) values of each isotype and the risk of clinical malaria attack was tested using a Poisson regression model Only the IgG3 OD increases were found associated with a significantly reduced risk of malaria attack These seroepidemiologic data suggest that whereas the total IgG-specific activity is not indicative of any given level of protection against malaria, the level of IgG3 was significantly associated with the relative susceptibility to clinical P falciparum malaria attacks
TL;DR: The results strongly contrast with the stability of the parasite types harbored by asymptomatic individuals living in Pikine, Senegal during a period in which malaria transmission was interrupted, and therefore suggest that the rapid turnover observed in Dielmo may reflect the introduction of new parasite populations by mosquitoes.
Abstract: A polymerase chain reaction (PCR) typing technique, based on the amplification of polymorphic regions from the merozoite surface protein 1 (MSP-1) and MSP-2 Plasmodium falciparum genes, was used to characterize parasites collected in a longitudinal study of asymptomatic carriers of malaria parasites living in two distinct epidemiologic situations. Blood samples were collected from children and adults living in the village of Dielmo, Senegal, when malaria transmission was 3-6 infective bites/week/individual. For each individual, every sample collected at two-week intervals over a period of three months showed a specific PCR pattern. Changes involved both appearance and disappearance of specific alleles. Analysis of blood samples collected at a few-days interval showed that modifications of the PCR patterns occurred rapidly. Most alleles were detected over a period of 2-3 weeks, but some alleles could be detected only for a few days. The frequent modifications of the PCR patterns indicate significant changes in allelic balance over time, and importantly, this was observed both in children and adults. These results strongly contrast with the stability of the parasite types harbored by asymptomatic individuals living in Pikine, Senegal during a period in which malaria transmission was interrupted, and therefore suggest that the rapid turnover observed in Dielmo may reflect the introduction of new parasite populations by mosquitoes.
TL;DR: The prevalence of iron deficiency anemia increased steadily as hookworm infection intensity and intestinal blood loss increased, and determination of fecal heme is a useful tool for measuring the impact of hookworm control activities.
Abstract: Iron deficiency remains the most prevalent form of human malnutrition, and current interventions to control it have not decreased the global prevalence. Hookworm control activities are becoming more widely implemented, but the importance of these efforts to prevent anemia in populations is not well-defined. We studied the relationships among hookworm infection, intestinal blood loss, and iron status of 203 Zanzibari school children. Helminth infection intensity was quantified by fecal egg counts, and iron deficiency anemia was defined by low hemoglobin and serum ferritin concentrations. Intestinal blood loss was quantified by measuring fecal heme and heme breakdown products as porphyrin, a noninvasive method that has not been used previously to assess hookworm blood loss. Intestinal blood loss was strongly and linearly related to hookworm egg counts. The degree of degradation of fecal heme indicated that blood loss occurred in the upper gastrointestinal tract, compatible with the behavior of hookworms. Trichuris trichiura and Ascaris lumbricoides infections were also common, but did not contribute significantly to intestinal blood loss in this population. The prevalence of iron deficiency anemia increased steadily as hookworm infection intensity and intestinal blood loss increased. In the context of a poor diet, as exists in Zanzibar and many tropical countries, hookworm-related blood loss contributes dramatically to anemia. In such contexts, hookworm control is a feasible and essential component of anemia control. Determination of fecal heme is relatively simple and noninvasive and may be a useful tool for measuring the impact of hookworm control activities.
TL;DR: The results of this model indicated that the greatest sand fly activity and thus the highest risk of sandfly fever and leishmania infections occurred during the spring/summer months before U.S. troops were deployed to the Persian Gulf.
Abstract: Sandfly fever and leishmaniasis were major causes of infectious disease morbidity among military personnel deployed to the Middle East during World War II. Recently, leishmaniasis has been reported in the United Nations Multinational Forces and Observers in the Sinai. Despite these indications of endemicity, no cases of sandfly fever and only 31 cases of leishmaniasis have been identified among U.S. veterans of the Persian Gulf War. The distribution in the Persian Gulf of the vector, Phlebotomus papatasi, is thought to be highly dependent on environmental conditions, especially temperature and relative humidity. A computer model was developed using the occurrence of P. papatasi as the dependent variable and weather data as the independent variables. The results of this model indicated that the greatest sand fly activity and thus the highest risk of sandfly fever and leishmania infections occurred during the spring/summer months before U.S. troops were deployed to the Persian Gulf. Because the weather model produced probability of occurrence information for locations of the weather stations only, normalized difference vegetation index (NDVI) levels from remotely sensed Advanced Very High Resolution Radiometer satellites were determined for each weather station. From the results of the frequency of NDVI levels by probability of occurrence, the range of NDVI levels for presence of the vector was determined. The computer then identified all pixels within the NDVI range indicated and produced a computer-generated map of the probable distribution of P. papatasi. The resulting map expanded the analysis to areas where there were no weather stations and from which no information was reported in the literature, identifying these areas as having either a high or low probability of vector occurrence.
TL;DR: The genetic characteristics of the parasite populations detected during phases of asymptomatic carriage differed from those causing a clinical episode, suggesting that the various factors that control of parasite growth in these children are strain-specific.
Abstract: A narrow epidemiologic survey was conducted during a four-month period of intense malaria transmission in Dielmo, a holoendemic Senegalese village. Longitudinal clinical and parasitologic follow-up indicate that clinical malaria episodes always occurred after an abrupt increase in parasite densities. Polymerase chain reaction analysis of Plasmodium falciparum parasites was carried out in blood samples collected longitudinally from 10 children who had experienced several clinical episodes during this period. Our data show that the genetic diversity of the parasites circulating in this village is very large. The successive clinical episodes experienced by each child were caused by genetically distinct parasite populations that were recently inoculated and multiplied in an apparently unrestricted manner. Importantly, the genetic characteristics of the parasite populations detected during phases of asymptomatic carriage differed from those causing a clinical episode, suggesting that the various factors that control of parasite growth in these children are strain-specific.
TL;DR: Three major risk factors in Gueckedou favoring Lassa virus transmission were observed: rodent infestation was much higher, food was more often stored uncovered and peridomestic rodents were hunted as a protein source by 91.5% of the population as opposed to 0% in Pita.
Abstract: In this population-based study, we correlated possible risk factors for rodent-to-human transmission of Lassa virus with markers of Lassa fever in two different regions of the Republic of Guinea (Prefectures of Pita and Gueckedou). Antibody prevalence was 2.6% (6 of 232) in Pita compared with 14.0% (105 of 751) in Gueckedou, with up to 35.0% seropositivity in selected villages of the higher prevalence area. We observed three major risk factors in Gueckedou favoring Lassa virus transmission: rodent infestation was much higher, food was more often stored uncovered and most strikingly, peridomestic rodents were hunted as a protein source by 91.5% of the population as opposed to 0% in Pita. To control for the confounding effects of differences in rodent infestation and food storage, rodent consumption was analyzed as a risk factor for transmission of Lassa virus comparing rodent consumers (RC) and nonconsumers (NC) in Gueckedou only: 14.6% of RC had Lassa virus antibodies versus 7.4% of NC (P = 0.1) and 23.0% of RC reported a history of a febrile illness with hearing loss (the most common sequel of Lassa fever) versus 6.1% of NC (P = 0.003).
TL;DR: There seems to be little evidence to date of the existence of acquired primaquine resistance in P. vivax, but the possibility of its emergence in the future can certainly not be ruled out, and its timely detection and confirmation will be most important, albeit quite difficult because of the relatively covert sites of drug effect.
Abstract: Reports have appeared calling attention to what has been termed primaquine resistance in Plasmodium vivax in several geographic areas The possibility exists that primaquine tolerant strains (often referred to as the tropical zone type from the South Pacific and Southeast Asian regions characterized by early and frequent relapses) may have become widely disseminated to areas where they had not previously existed through the widespread population mobility that has characterized the last 50 years The appearance in the relatively recent past of strains of P vivax, particularly from the South Pacific area, that are resistant to the 4-aminoquinolines has added a new dimension to the resistance problem While there seems to be little evidence to date of the existence of acquired primaquine resistance in P vivax, the possibility of its emergence in the future can certainly not be ruled out, and its timely detection and confirmation will be most important, albeit quite difficult because of the relatively covert sites of drug effect The occurrence of relapses in P vivax after primaquine therapy would be assumed to be the most reliable indication of resistance Reports of the sporontocidal or gametocytocidal activity of primaquine when used alone (ie, without concomitant administration of an effective suppressive) against a P vivax infection have been few and inconclusive The establishment of baselines of this activity in P vivax might be useful in detecting and evaluating primaquine resistance in this species
TL;DR: The background of knowledge regarding malaria infection in pregnant African women and the important elements of an intervention and prevention strategy are described.
Abstract: Plasmodium falciparum infection in pregnant women frequently leads to placental infection and low birth weight (< 2,500 grams) of the infant, particularly in the areas of high malaria transmission found in sub-Saharan Africa. Low birth weight is widely known to be an important risk factor for early infant mortality. To reduce the risk that maternal infection poses to child survival, many antenatal clinic programs recommend and provide antimalarial chemoprophylaxis, often with chloroquine (CQ) as a recommended element for antenatal care. Prior to the 1980s, despite widespread advocacy for this intervention, little was known about the effect of this intervention strategy. As an introduction to the Mangochi Malaria Research Project, which examined the efficacy of several antimalarial regimens using CQ or mefloquine in pregnant women in Malawi, we describe the background of knowledge regarding malaria infection in pregnant African women and the important elements of an intervention and prevention strategy.
TL;DR: Cases of intestinal taeniasis were significantly more likely to be anti-cysticercus antibody-positive than the general population and individuals with a history of seizures had a higher rate of abnormalities suggestive of neuro Cysticercosis.
Abstract: Taenia solium taeniasis and cysticercosis are known to be endemic in Guatemala but no studies had been undertaken in rural communities where transmission was thought to occur. Two adjacent communities, Quesada and El Jocote, in the Department of Jutiapa were selected. The former had considerably better sanitary infrastructure than the latter. The seroprevalence of antibodies detected in humans by immunoblot to T. solium metacestode glycoprotein antigens was 10% and 17% and the prevalence of intestinal taeniasis was 1% and 2.8% in the two villages, respectively. Both of these represented statistically greater rates in El Jocote. Females were significantly more likely to be seropositive than males in the study as a whole. The majority of cases of intestinal taeniasis were due to T. solium. Cases of intestinal taeniasis were significantly more likely to be anti-cysticercus antibody-positive than the general population. Epilepsy was recorded in 2.8% and 2.9% of the populations of Quesada and El Jocote, respectively. Follow-up of this group and a group of asymptomatic individuals by computed tomography scan indicated that individuals with a history of seizures had a higher rate of abnormalities suggestive of neurocysticercosis. Cysts were present in the tongues of 4% of live pigs sampled in Quesada and 14% in El Jocote. In these two communities, which are probably representative of many others in Guatemala, T. solium appeared to be a significant public health problem.
TL;DR: Climatologic changes in the area appear to have made conditions for transmission of P. falciparum more favorable, and may account for the increase in incidence observed in the NWFP in recent years.
Abstract: Following a striking increase in the severity of autumnal outbreaks of Plasmodium falciparum during the last decade in the Northwest Frontier Province (NWFP) of Pakistan, the role of climatologic variables was investigated. A multivariate analysis showed that during the transmission season of P. falciparum, the amount of rainfall in September and October, the temperature in November and December, and the humidity in December were all correlated (r2 = 0.82) with two measures of P. falciparum, the falciparum rate (percent of slides examined positive for P. falciparum) since 1981 and the annual P. falciparum proportion (percent of all malaria infections diagnosed as P. falciparum) since 1978. Climatologic records since 1876 show an increase in mean November and December temperatures by 2°C and 1.5°C, respectively, and in October rainfall. Mean humidity in December has also been increasing since 1950. These climatologic changes in the area appear to have made conditions for transmission of P. falciparum more favorable, and may account for the increase in incidence observed in the NWFP in recent years.
TL;DR: The presence of genetically well-characterized bacteria in the midgut flora of mosquitoes may provide a means of expressing novel genetic products in vector species.
Abstract: The midgut bacterial flora of wild-caught Aedes triseriatus, Culex pipiens, and Psorophora columbiae mosquitoes was investigated. Dissected midgut contents were examined using quantitative aerobic bacterial cultures. Individual colonies (n = 134) were subcultured and identified to species. Midgut bacterial counts changed dramatically during mosquito development. A 280-1,100-fold decrease in the bacterial population occurred between the larval stage and pupal emergence, whereas a subsequent 70-16,000-fold increase occurred after blood-feeding. Bacterial identifications revealed a complex flora with up to nine genera identified during any stage of development. Species most frequently isolated were Serratia marcescens, Klebsiella ozonae, Pseudomonas aeruginosa, and Enterobacter agglomerans. The presence of genetically well-characterized bacteria in the midgut flora of mosquitoes may provide a means of expressing novel genetic products in vector species.
TL;DR: Deep breathing, which was sensitive and specific for the presence of severe metabolic acidosis (base excess < or = -12), is the best candidate sign to represent the prognostically important syndrome of malarial respiratory distress.
Abstract: Despite the frequent association of respiratory symptoms and signs with malarial morbidity and mortality in sub-Saharan Africa, the value of individual symptoms and signs has rarely been assessed. We have prospectively examined the association of individual clinical findings with the summary diagnosis of respiratory distress, outcome, and the presence of metabolic acidosis in children admitted with severe malaria to a Kenyan district hospital. Respiratory distress was present in 119 of the 350 children included in the study and in 23 of the 30 deaths (relative risk = 6.5, 95% confidence interval = 2.8-14.4). The features of a history of dyspnea, nasal flaring, and indrawing or deep breathing (Kussmaul's respiration) were individually most closely associated with the summary diagnosis of respiratory distress. Of these, deep breathing, which was sensitive (91%) and specific (83%) for the presence of severe metabolic acidosis (base excess < or = -12), is the best candidate sign to represent the prognostically important syndrome of malarial respiratory distress. Therefore, it warrants further prospective evaluation in different clinical settings and areas of different malaria endemicity.
TL;DR: Results indicate that genetic exchange could contribute to the generation of genetic diversity during the sylvatic cycle of T. cruzi, and this may have epidemiologic and taxonomic implications.
Abstract: Thirty six stocks of Trypanosoma cruzi isolated from sylvatic mammals (32 Didelphis marsupialis and one Philander opossum) and triatomine bugs (Rhodnius robustus and one unidentified bug) in the Amazonian forest of Carajas, Brazil were characterized by isoenzyme and random amplified polymorphic DNA (RAPD) analysis as belonging to principal zymodeme 1 (Z1) Two different homozygous phenotypes and the corresponding heterozygous phenotype were found for phosphoglucomutase with an observed frequency almost identical with that predicted by the theoretical Hardy-Weinberg distribution Parental and hybrid profiles were also suggested by RAPD analysis, which allowed exclusion of mixed parental strains from the hybrids: isoenzyme and RAPD profiles of biological clones were also indistinguishable from those of uncloned stocks Trypanosoma cruzi stocks from widely separated geographic origins in Central and South America gave similar RAPD profiles that allowed them to be recognized as being Z1 These results indicate that genetic exchange could contribute to the generation of genetic diversity during the sylvatic cycle of T cruzi, and this may have epidemiologic and taxonomic implications
TL;DR: Investigation of immature stage indices for Aedes (Stegomyia) aegypti surveillance in four north Queensland, Australia towns found that Spearman's correlations of indices that considered larval or immature (larvae and pupae) numbers had a better relationship with immature abundance but this was not necessarily the case against adult abundance.
Abstract: The following immature stage indices for Aedes (Stegomyia) aegypti surveillance were evaluated in four north Queensland, Australia towns with respect to their relationship to immature and adult female densities: Breteau, House, Container, Larval Density, Stegomyia (and modifications thereof), and a newly created Adult Productivity Index. Spearman's correlations of indices that considered larval or immature (larvae and pupae) numbers had a better relationship with immature abundance but this was not necessarily the case against adult abundance. To examine the robustness of the indices, data from 758 premises in Townsville, Charters Towers, Ravenswood, and Mingela were pooled and 30 random subsamples, each consisting of 50 premises were taken. After each subsample was taken, the premises selected were reintroduced into the original data bank of 758 premises, and therefore, were available for further selection, i.e., sampling with replacement. Indices were calculated for each of the 30 subsamples and the coefficients of variation of each index were estimated from these. The Breteau, Adult Productivity, House, and Adult density indices proved to have the smallest coefficients compared with index size. No alternate index was regarded as being superior to the Breteau, including the Adult Productivity Index measuring both container type frequency and immature density. For this reason and in view of the labor intensiveness of estimating immature indices that incorporate productivity, it is recommended that new and cost-effective methods of adult surveillance be pursued.
TL;DR: Effective drug therapy for P. falciparum with regimens that are parasitocidal in areas with a high prevalence of severe anemia and chloroquine resistance can significantly improve the survival of children in Africa.
Abstract: Plasmodium falciparum infection is an important cause of the high childhood mortality rates in sub-Saharan Africa. Increasingly, the contribution of P. falciparum-associated severe anemia to pediatric mortality is being recognized while the impact of chloroquine resistance on mortality has not been evaluated. To address the issues of pediatric mortality, causes of death among hospitalized children less than five years of age in western Kenya were identified using standardized clinical examinations and laboratory evaluations. Follow-up examinations were conducted to determine the child's clinical status posthospitalization. Of the 1,223 children admitted to Siaya District Hospital from March to September 1991, 293 (24%) were severely anemic (hemoglobin level < 5.0 g/dL). There were 265 (22%) deaths; 121 (10%) occurred in-hospital and 144 (13%) occurred out-of-hospital within eight weeks after admission; 32% of all deaths were associated with malaria. Treatment for malaria with chloroquine was associated with a 33% case fatality rate compared with 11% for children treated with more effective regimens (pyrimethamine/sulfa, quinine, or trimethoprim/sulfamethoxazole for five days). The risk of dying was associated with younger age (P < 0.0001) and severe anemia (relative risk [RR] = 1.52, 95% confidence interval [CI] = 1.22, 1.90), and was decreased by treatment with an effective antimalarial drug (RR = 0.33, 95% CI = 0.19, 0.65). Effective drug therapy for P. falciparum with regimens that are parasitocidal in areas with a high prevalence of severe anemia and chloroquine resistance can significantly improve the survival of children in Africa.
TL;DR: Aminoquinoline resistance is one of the most important factors in the worldwide resurgence of malaria due to Plasmodium falciparum, and results indicate that AQs with 2-12 carbon side chains are as active as chloroquine against chlorquine-susceptible P. falcIParum.
Abstract: Aminoquinoline (AQ) resistance is one of the most important factors in the worldwide resurgence of malaria due to Plasmodium falciparum. We synthesized a series of AQs to define the structure-activity relationships responsible for AQ action against chloroquine-susceptible and -resistant P. falciparum. The AQs with ethyl, propyl, isopropyl, butyl, pentyl, isopentyl (chloroquine), hexyl, octyl, decyl, or dodecyl side chains were equally active against chloroquine-susceptible P. falciparum (50% inhibitory concentrations [IC50s] = 5–15 nM). The AQs with ethyl, propyl, isopropyl, decyl, or dodecyl side chains were also active against chloroquine-, mefloquine- and multiply-resistant P. falciparum (IC50s = 5–20 nM). Verapamil, which enhances the activity of chloroquine against chloroquine-resistant parasites, had no effect on the activity of AQs that were active against resistant parasites. These results indicate that AQs with 2–12 carbon side chains are as active as chloroquine against chloroquine-susceptible P. falciparum, and that AQs with side chains shorter or longer than chloroquine are often active against chloroquine-, mefloquine-, and multiply-resistant P. falciparum.
TL;DR: Based on abundance, susceptibility to infection, ability to transmit virus, and feeding behavior, Ae.
Abstract: Reintroduction of Rift Valley fever (RVF) into Egypt in 1993 raised concerns about the potential for Egyptian mosquitoes to transmit the virus. We evaluated the ability of Aedes caspius, Culex pipiens, Cx. antennatus, Cx. perexiguus, Cx. poicilipes, and Anopheles pharoensis collected in the Aswan area and Cx. pipiens collected in the Nile Delta to transmit RVF virus. All mosquito species tested were susceptible to RVF virus infection, with An. pharoensis and Ae. caspius being the most sensitive to infection. However, none of 12 An. pharoensis, including 10 with a disseminated infection, transmitted RVF virus by bite. In contrast, nearly all Cx. pipiens (87%, n = 15) and Cx. perexiguus (90%, n = 10) with a disseminated infection transmitted virus. Overall transmission rates for mosquitoes exposed to hamsters with a viremia > or = 10(7) plaque-forming units/ml were Ae. caspius, 20% (n = 5); Cx. pipiens, 7% (n = 102); Cx. antennatus, 7% (n = 30); Cx. perexiguus, 11% (n = 9); and An. pharoensis, 0% (n = 7). Based on abundance, susceptibility to infection, ability to transmit virus, and feeding behavior, Ae. caspius appeared to be the most efficient vector of the Egyptian mosquitoes evaluated. While less susceptible than Ae. caspius, Cx. pipiens, Cx. antennatus, and Cx. perexiguus were also potential vectors during this RVF outbreak in Egypt.
TL;DR: Plasmodium falciparum isolates from 24 Papua New Guinean patients with symptomatic malaria were tested for susceptibility to pyrimethamine and cycloguanil and a positive correlation suggesting cross-resistance was found.
Abstract: Plasmodium falciparum isolates from 24 Papua New Guinean patients with symptomatic malaria were tested for susceptibility to pyrimethamine and cycloguanil. Thirteen isolates were sensitive to both agents and the remainder exhibited varying degrees of resistance. No isolates were found to be resistant to one agent yet sensitive to the other and a positive correlation suggesting cross-resistance was found. Parasite DNA extracted from the patients' stained blood slides was amplified and sequenced to examine point mutations in the dihydrofolate reductase (DHFR) and dihydropteroate synthetase genes (DHPS) associated with antifolate resistance. All resistant isolates possessed mutations in the DHFR gene at codon 108, the majority changing from Ser to Asn, but one isolate from Ser to Thr, a change not previously reported in field isolates. A second mutation of the DHFR gene at Cys-59 to Arg was present in isolates with higher level resistance, but not exclusively so. Sequencing the DHPS gene, as a predictor of sulfadoxine resistance, revealed only one example that was different from DHPS alleles of sensitive isolates.