Reduction of malaria prevalence after introduction of Romanomermis culicivorax (Mermithidae: Nematoda) in larval Anopheles habitats in Colombia

The worldwide resurgence of malaria has become a major public health problem. New methods of controlling the vectors of the disease are required, and we therefore studied the biological control of Anopheles albimanus by Romanomermis culicivorax in Colombia. The investigation was carried out in El Valle and Nuquí, two towns on the northern Pacific coast of the country. All of the mosquito larval habitats surrounding El Valle were seeded with the eggs and adults of R. culicivorax. The nematode established itself in the new habitat and recycled over 27 months. The larval population of A. albimanus, the only malarial vector detected in the two towns, decreased in El Valle. In contrast, no change in the larval populations of the vector was detected in ponds located near Nuquí, the untreated control town. A rapid and progressive decrease of the prevalence of malaria among schoolchildren in El Valle was observed during the 2-year evaluation period.     

Integrated malaria vector control with microbial larvicides and insecticide-treated nets in western Kenya: a controlled trial

Objective

To assess the contributions of both microbial larvicides and insecticide-treated nets (ITNs) in terms of reducing malaria incidence in an integrated vector management programme in an area moderately endemic for malaria in the western Kenyan highlands.

Methods

A pre-post, control group design was used. Larval and adult vector populations were surveyed weekly in six separate valley communities. The incidence of Plasmodium infections in children 6 months to 13 years of age was measured during the long and short rainy seasons each year. Baseline data were collected for 17 months, after which Bacillus-based larvicides were applied weekly to aquatic habitats in three of the valleys for another 19 months. At around the same time the larviciding was initiated, ITNs were introduced gradually into all study communities by the National Malaria Control Programme. The effect of larviciding, ITNs and other determinants of malaria risk was assessed by means of generalized estimating equations.

Findings

The risk of acquiring new parasite infections in children was substantially and independently reduced by ITN use (odds ratio, OR: 0.69; 95% confidence interval, CI: 0.48–0.99) and larvicide application (OR: 0.44; 95% CI: 0.23–0.82), after adjusting for confounders.

Conclusion

Vector control with microbial larvicides enhanced the malaria control achieved with ITNs alone. Anti-larval measures are a promising complement to ITN distribution in the economically important highland areas and similar transmission settings in Africa.     

Travel as a risk factor for uncomplicated Plasmodium falciparum malaria in the highlands of western Kenya

In the 1980s, highland malaria returned to the tea estates of western Kenya after an absence of nearly a generation. In order to determine the importance of travel for the spread of malaria in this region, we prospectively collected blood films and travel, demographic and geographic information on well persons and outpatients on tea estates near the western rim of the Rift Valley. Risk factors for malaria asexual parasitaemia included: tribal/ethnic group, home province and home district malaria endemicity. Travel away from the Kericho tea estates within the previous two months showed an odds ratio (OR) for parasitaemia of 1.59 for well persons and 2.38 for outpatients. Sexual stages of malaria parasites (gametocytes) had an OR of 3.14 (well persons) and 2.22 (outpatients) for those who had travelled. Increased risk of malaria parasitaemia with travel was concentrated in children aged <5 years. An increase in population gametocytaemia is possibly due to increased chloroquine resistance and suppressed infections contracted outside of the tea estates.     

媒介按蚊防控：中国疟疾消除的关键措施

疟疾是严重危害人类健康的全球性虫媒传染病,是联合国千年发展目标中重点防控的传染病之一,与艾滋病、结核病一起被世界卫生组织列为全球急需控制的三大公共卫生问题。该文就全球特别是我国疟疾的流行形势、主要疟疾媒介按蚊种类及分布特点、疟疾消除任务提出的背景、疟疾防治的主要内容及方法进行概括,强调了媒介生物监测与控制是疟疾消除不可取代的必要工具,并对当前消除疟疾媒介按蚊控制工作存在的主要问题、挑战及今后的重点研究方向做一评述。     

Using remote sensing to map larval and adult populations of Anopheles hyrcanus (Diptera: Culicidae) a potential malaria vector in Southern France

Background

Recent advances in GIS technology and remote sensing have provided new opportunities to collect ecologic data on agricultural pesticide exposure. Many pesticide studies have used historical or records-based data on crops and their associated pesticide applications to estimate exposure by measuring residential proximity to agricultural fields. Very few of these studies collected environmental and biological samples from study participants. One of the reasons for this is the cost of identifying participants who reside near study fields and analyzing samples obtained from them. In this paper, we present a cost-effective, GIS-based method for crop field selection and household recruitment in a prospective pesticide exposure study in a remote location. For the most part, our multi-phased approach was carried out in a research facility, but involved two brief episodes of fieldwork for ground truthing purposes. This method was developed for a larger study designed to examine the validity of indirect pesticide exposure estimates by comparing measured exposures in household dust, water and urine with records-based estimates that use crop location, residential proximity and pesticide application data. The study focused on the pesticide atrazine, a broadleaf herbicide used in corn production and one of the most widely-used pesticides in the U.S.

Results

We successfully used a combination of remotely-sensed data, GIS-based methods and fieldwork to select study fields and recruit participants in Illinois, a state with high corn production and heavy atrazine use. Our several-step process consisted of the identification of potential study fields and residential areas using aerial photography; verification of crop patterns and land use via site visits; development of a GIS-based algorithm to define recruitment areas around crop fields; acquisition of geocoded household-level data within each recruitment area from a commercial vendor; and confirmation of final participant household locations via ground truthing. The use of these procedures resulted in a sufficient sample of participants from 14 recruitment areas in seven Illinois counties.

Conclusion

One of the challenges in pesticide research is the identification and recruitment of study participants, which is time consuming and costly, especially when the study site is in a remote location. We have demonstrated how GIS-based processes can be used to recruit participants, increase efficiency and enhance accuracy. The method that we used ultimately made it possible to collect biological samples from a specific demographic group within strictly defined exposure areas, with little advance knowledge of the location or population.     

Anopheles culicifacies Giles: a release-recapture experiment with cohorts of known age with implications for malaria epidemiology and genetical control in Pakistan

A mark-release-recapture experiment with the progeny of wild collected Anopheles culicifacies was performed during the monsoon season of 1978 at the village of Khano-Harni, a malarious area situated in Lahore District, Punjab Province, Pakistan. The recapture rates of males and females released at breeding and resting sites were statistically comparable and totalled 8·0% for females and 5·9% for males collected resting in houses and cattle sheds. Mating occurred mostly on the night following the evening of release when the females were about two days old. Insemination rates for females released at resting and breeding sites were statistically comparable. The initial gonotrophic cycle required four days; subsequent cycles occurred at two-day intervals with re-feeding on the same night as oviposition. Constant daily survivorship estimated from the decline in recaptures per day was 0·568 for females and 0·676 for males. Female survivorship estimated by vertical age grading methods ranged from 0·472 to 0·820. Horizontal life tables were calculated from the decline in recaptures and from vertical age-grading techniques and indicated that female or male life expectancy at emergence was less than 2·5 days. Population size was calculated using the Lincoln Index, Jackson's positive and negative methods and Ito's modification of Jackson's positive method and averaged from 1045·5 to 1049·6 females and from 449·1 to 1323·7 males. The relationship of these results to malaria transmission and genetical control is discussed.     

Chlorproguanil/dapsone for the treatment of non-severe Plasmodium falciparum malaria in Kenya: a pilot study

Chlorocycloguanil, the active metabolite of chlorproguanil, was synergistic in vitro with dapsone against 2 culture-adapted Plasmodium falciparum isolates from Kenya; maximal synergy occurred at lower concentrations that it did with pyrimethamine and sulfadoxine. 48 children with asymptomatic P. falciparum infections were treated with chlorproguanil (at a target dose of 1.2 mg/kg) and dapsone (target dose of 1.2 or 2.4 mg/kg); all were free of parasitaemia by day 7. The following numbers had recurrences on days 14, 21, and 28, respectively: 1 of 48, 7 of 47, and 7 of 40. All 39 children treated with pyrimethamine (target dose 1.2 mg/kg) and sulfadoxine (target dose 24 mg/kg) were cleared of infection, while the following had recurrences on days 14, 21, and 28: 1 of 39, 2 of 38, and 2 of 36. The rate of decrease in parasitaemia was the same in the 2 groups, and there was no change in haematocrit or haemoglobin during the follow-up. The rate of recurrence in the children receiving chlorporguanil/dapsone was higher, probably because these drugs have a much shorter clearance time than pyrimethamine/sulfadoxine. Chlorproguanil/dapsone is an effective combination for treating P. falciparum malaria and deserves further study.     

A historical review of the F-1 strain of Anopheles freeborni as a host and vector for studies of malaria.

A review was made of the use of a specific strain of Anopheles freeborni from California (F-1) that has been used extensively in experimental investigations of malaria for more than 50 years. The F-1 strain of An. freeborni has been shown to be a suitable experimental host and vector for different species of Plasmodium that cause malaria in humans and nonhuman primates for biologic, immunologic, and chemotherapeutic studies. Eleven species of Plasmodium fully completed sporogonic development; development of sporozoites within mature oocysts occurred in an additional 7 species. Transmission through An. freeborni from human to human, monkey to human, or monkey to monkey has been demonstrated for 9 species of Plasmodium.     

Adherence and efficacy of supervised versus non-supervised treatment with artemether/lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Bangladesh: a randomised controlled trial

As artemether/lumefantrine is now deployed as the first-line treatment for uncomplicated falciparum malaria in Bangladesh, information on its efficacy and adherence to its use is important. A randomised controlled non-inferiority trial comparing directly observed treatment (DOT) and non-directly observed treatment (NDOT) was conducted in 320 patients with uncomplicated falciparum malaria in Bandarban Hill Tract District, Bangladesh. Both regimens showed similar high levels of PCR-corrected 42-day parasitological and clinical cure rates (99.3% in the NDOT group and 100% in the DOT group; P=0.49). Survival analysis for the time to recurrence of infection showed no difference between treatment groups (log rank, P=0.98). Adherence, as assessed by counting remaining tablets and oral interviews, was 93% in the NDOT group and was confirmed by Day 7 lumefantrine concentrations. Adherence was independent of educational level. Patients with plasma lumefantrine concentrations <280ng/ml at Day 7 were at greater risk for re-infection (relative risk 5.62; P=0.027). The efficacy of artemether/lumefantrine for the treatment of uncomplicated falciparum malaria in Bangladesh is high and is similar for DOT and NDOT. Adherence to therapy is high.     

A mathematical model for Plasmodium vivax malaria transmission: estimation of the impact of transmission-blocking immunity in an endemic area.

We have developed a multi-state mathematical model to describe the transmission of Plasmodium vivax malaria; the model accommodates variable transmission-blocking/enhancing immunity during the course of a blood infection, a short memory for boosting immunity, and relapses. Using the model, we simulated the incidence of human malaria, sporozoite rates in the vector population, and the level of transmission-blocking immunity for the infected population over a period of time. Field data from an epidemiological study conducted in Kataragama in the south of Sri Lanka were used to test the results obtained. The incidence of malaria during the study period was simulated satisfactorily. The impact of naturally-acquired transmission-blocking immunity on malaria transmission under different vectorial capacities was also simulated. The results show that at low vectorial capacities, e.g., just above the threshold for transmission, the effect of transmission-blocking immunity is very significant; however, the effect is lower at higher vectorial capacities.     

Phase 1 randomized double-blind safety and immunogenicity trial of Plasmodium falciparum malaria merozoite surface protein FMP1 vaccine, adjuvanted with AS02A, in adults in western Kenya

We report the first trial of candidate malaria vaccine antigen FMP1, a 42kDa fragment from the C-terminus of merozoite surface protein-1 (MSP-1) from the 3D7 strain of Plasmodium falciparum, in an endemic area. Forty adult male and female residents of western Kenya were enrolled to receive 3 doses of either FMP1/AS02A or Imovax rabies vaccine by intra-deltoid injection on a 0, 1, 2 month schedule. Thirty-seven volunteers received all three immunizations and 38 completed the 12-month evaluation period. Slightly more recipients of the FMP1/AS02A vaccine experienced any instance of pain at 24 h post-immunization than in the Imovax group (95% versus 65%), but otherwise the two vaccines were equally safe and well-tolerated. Baseline antibody levels were high in both groups and were boosted in the FMP1/AS02A group. Longitudinal models revealed a highly significant difference between groups for both the average post-baseline antibody responses to MSP-1(42) (F1,335=13.16; P<0.001) and the Day 90 responses to MSP-1(42) (F1,335=16.69; P<0.001). The FMP1/AS02A vaccine is safe and immunogenic in adults and should progress to safety testing in children at greatest risk of malaria.     

A controlled trial of iodinated oil for the prevention of endemic cretinism: a long-term follow-up

A double blind controlled trial designed to examine the effectiveness of intramuscular iodinated oil as a prophylactic for the nervous type of endemic cretinism was begun in 1966 in the highlands of Papua New Guinea. Infants born into the trial between 1966 and 1972 were followed up until 1982. The results showed that if the iodine supplement was given before conception the nervous form of endemic cretinism was prevented. Also a striking difference in the 15-year cumulative survival rate in favour of the test (iodinated oil) group was observed. Measures of motor and intellectual function revealed that children born to mothers given an iodine supplement performed significantly better. This observation shows that iodine deficiency leads to sub-clinical as well as clinical deficits. It also justifies the use of the term iodine deficiency disorder to cover the polymorphic nature of the abnormalities attributable to iodine deficiency.     

A three year follow-up of chemotherapy with praziquantel in a rural Zambian community endemic for schistosomiasis mansoni

A resurvey for schistosomiasis mansoni was carried out in a community 2 years after chemotherapy with praziquantel was stopped. Data on infection status, morbidity, subjective symptoms, and liver and spleen enlargement were collected from participants. Results show that prevalence of Schistosoma mansoni infection and subjective symptoms of morbidity have returned to pretreatment levels. However, the population mean egg output remained low. Liver and spleen sizes in individuals who received treatment have shown a further decline compared to 2 years before. We conclude that selective mass chemotherapy with praziquantel can give the community as a whole a respite from schistosomiasis morbidity for at least 2 years despite an increase in prevalence.     

A study of the blood-feeding patterns of Anopheles mosquitos through precipitin tests: Results of collaborative work for the period 1955-59 and their application to malaria eradication programmes

The success of malaria eradication campaigns depends on the use of all methods which make for a better understanding of the biology and behaviour of mosquito vectors. One such method is precipitin testing, by which it is possible to identify the human or animal origin of blood meals of mosquitos and thereby to determine their host preferences and vectorial importance, both generally and locally.     

Comparison of comorbidity classification methods for predicting outcomes in a population-based cohort of adults with human immunodeficiency virus infection

PurposeWe compared the John's Hopkins' Aggregated Diagnosis Groups (ADGs), which are derived using inpatient and outpatient records, with the hospital record-derived Charlson and Elixhauser comorbidity indices for predicting outcomes in human immunodeficiency virus (HIV)-infected patients.MethodsWe used a validated algorithm to identify HIV-infected adults (n = 14,313) in Ontario, Canada, and randomly divided the sample into derivation and validation samples 100 times. The primary outcome was all-cause mortality within 1 year, and secondary outcomes included hospital admission and all-cause mortality within 1–2 years.ResultsThe ADG, Elixhauser, and Charlson methods had comparable discriminative performance for predicting 1-year mortality, with median c-statistics of 0.785, 0.767, and 0.788, respectively, across the 100 validation samples. All methods had lower predictive accuracy for all-cause mortality within 1–2 years. For hospital admission, the ADG method had greater discriminative performance than either the Elixhauser or Charlson methods, with median c-statistics of 0.727, 0.678, and 0.668, respectively. All models displayed poor calibration for each outcome.ConclusionsIn patients with HIV, the ADG, Charlson, and Elixhauser methods are comparable for predicting 1-year mortality. However, poor calibration limits the use of these methods for provider profiling and clinical application.