Category Archives: Publications

This paper reviews the sensitivity and specificity of RDTs for detecting P. falciparum and P. vivax in two different settings ¿ at health centres and in a household survey. The study includes a large number of patients (2,394 participants) and provides useful additional information about the performance of these RDTs.

Woyessa A, Deressa W, Ali A, Lindtjørn B. Evaluation of CareStartTM malaria Pf/Pv combo test for Plasmodium falciparum and Plasmodium vivax malaria diagnosis in Butajira area, south-central Ethiopia. Malaria Journal 2013, 12:218 doi:10.1186/1475-2875-12-218

Abstact:

Malaria is a major public health problem in Ethiopia. Plasmodium falciparum and Plasmodium vivax co-exist and malaria rapid diagnostic test (RDTs) is vital in rendering parasite-confirmed treatment especially in areas where microscopy is not available. CareStartTM Malaria Pf/Pv combo test was evaluated compared to microscopy in Butajira area, south-central Ethiopia. This RDT detects histidine-rich protein-2 (HRP2) found in P. falciparum, and Plasmodium enzyme lactate dehydrogenase (pLDH) for diagnosis of P. vivax 2008-2010. The standard for the reporting of diagnostic accuracy studies was complied. Among 2,394 participants enrolled, 10.9% (n=87) were Plasmodium infected (household survey) and 24.5% (n=392) using microscopy. In the household surveys, the highest positivity was caused by P. vivax (83.9%, n=73), P. falciparum (15.0%, n=13), and the rest due to mixed infections of both (1.1%, n=1). In health facility, P. vivax caused 78.6% (n=308), P. falciparum caused 20.4% (n=80), and the rest caused by mixed infections 1.0% (n=4). RDT missed 9.1% (n=8) in household and 4.3% (n=17) in health facility-based surveys among Plasmodium positive confirmed by microscopy while 3.3% (n=24) in household and 17.2% (n=208) in health facility-based surveys were detected false positive. RDT showed agreement with microscopy in detecting 79 positives in household surveys (n=796) and 375 positives in health centre survey (n=1,598).RDT performance varied in both survey settings, lowest PPV (64.3%) for Plasmodium and P. falciparum (77.2%) in health centres; and Plasmodium (76.7%) and P. falciparum (87.5%) in household surveys. NPV was low in P. vivax in health centres (77.2%) and household (87.5%) surveys. Seasonally varying RDT precision of as low as 14.3% PPV (Dec. 2009), and 38.5% NPV (Nov. 2008) in health centre surveys; and 40-63.6% PPV was observed in household surveys. But the influence of age and parasite density on RDT performance was not ascertained. Establishing quality control of malaria RDT in the health system in areas with low endemic and P. falciparum and P. vivax co-exist is recommendable. CareStartTM RDT might be employed for epidemiological studies that require interpreting the results cautiously. Future RDT field evaluation against microscopy should be PCR corrected.

On May 30th, 2013, Adugna Woyessa defended his PhD thesis «The epidemiology of highland malaria in Ethiopia: a study from Butajira area».

New research uses almost 50 years of data to investigate how climate has affected cattle holdings in Africa since 1961. Such research is important also to understand the distribution of mosquitoes that transmit malaria.

Lunde TM and Lindtjørn B. Cattle and climate in Africa: How climate variability has influenced national cattle holdings from 1961–2008. PeerJ 2013; 1:e55 

The role of cattle in developing countries is as a source of high-quality food, as draft animals, and as a source of manure and fuel. Cattle represent important contribution to household incomes, and in drought prone areas they can act as an insurance against weather risk. So far, no studies have addressed how historical variations in temperature and rainfall have influenced cattle populations in Africa.

The focus of this study is to assess the historical impact of climate variability on national cattle holdings. We reconstruct the cattle density and distribution for two time periods; 1955–1960 and 2000–2005. Based on estimates from FAO and official numbers, we generated a time series of cattle densities from 1961–2008, and compared these data with precipitation and temperature anomalies for the same period.

We show that from 1961–2008 rainfall and temperature have been modulating, and occasionally controlling, the number of cattle in Africa.

This article is a validation of a mathematical model described earlier. Overall, the model gives a realistic representation of seasonal and year-to-year variability in mosquito densities and it can accurately predict the distribution of An. gambiae s.s. and An. arabiensis in sub-Saharan Africa. It may be used for seasonal and long-term predictions of changes in the burden of malaria.

Lunde TM, Balkew M, Korecha D, Gebre-Michael T, Massebo F, Sorteberg A and Lindtjørn B. A dynamic model of some malaria-transmitting anopheline mosquitoes of the Afrotropical region. II. Validation of species distribution and seasonal variations. Malaria Journal 2013, 12:78

Background  The first part of this study aimed to develop a model for Anopheles gambiae s.l. with separate parametrization schemes for Anopheles gambiae s.s. and Anopheles arabiensis. The characterizations were constructed based on literature from the past decades. This part of the study is focusing on the model’s ability to separate the mean state of the two species of the An. gambiae complex in Africa. The model is also evaluated with respect to capturing the temporal variability of An. arabiensis in Ethiopia. Before conclusions and guidance based on models can be made, models need to be validated.

 Methods  The model used in this paper is described in part one (Malaria Journal 2013, 12:28). For the validation of the model, a data base of 5,935 points on the presence of An. gambiae s.s. and An. arabiensis was constructed. An additional 992 points were collected on the presence An. gambiae s.l.. These data were used to assess if the model could recreate the spatial distribution of the two species. The dataset is made available in the public domain. This is followed by a case study from Madagascar where the model’s ability to recreate the relative fraction of each species is investigated. In the last section the model’s ability to reproduce the temporal variability of An. arabiensis in Ethiopia is tested. The model was compared with data from four papers, and one field survey covering two years.

Results  Overall, the model has a realistic representation of seasonal and year to year variability in mosquito densities in Ethiopia. The model is also able to describe the distribution of An. gambiae s.s. and An. arabiensis in sub-Saharan Africa. This implies this model can be used for seasonal and long term predictions of changes in the burden of malaria. Before models can be used to improving human health, or guide which interventions are to be applied where, there is a need to understand the system of interest. Validation is an important part of this process. It is also found that one of the main mechanisms separating An. gambiae s.s. and An. arabiensis is the availability of hosts; humans and cattle. Climate play a secondary, but still important, role.

This is a report on the Anopheles fauna found in three different villages located at three different altitudes ranging from 1,800 meters to 2,200 metres, showing the human/cattle blood meal preference for each species and the sporozoite rate and entomological inoculation rate for the vectors.

Animut A, Balkew M, Gebre-Michael T and Lindtjørn B. Blood meal sources and entomological inoculation rates of anophelines along a highland altitudinal transect in south-central Ethiopia. Malaria Journal 2013, 12:76 doi:10.1186/1475-2875-12-76

Background  The role of anophelines in transmitting malaria depends on their distribution, preference to feed on humans and also their susceptibility to Plasmodium gametocytes, all of which are affected by local environmental conditions. Blood meal source and entomological inoculation rate of anophelines was assessed along a highland altitudinal transect in south- central Ethiopia.

Methods  Monthly adult anopheline sampling was undertaken from July 2008 to June 2010 in Hobe (low altitude), Dirama (mid altitude) and Wurib (high altitude) villages located at average elevations of 1800 m, 2000 m and 2200 m, respectively. Anophelines were collected using CDC light trap, pyrethrum space spray catches (PSC) and artificial pit shelter methods. Upon collection, females were categorized according to their abdominal status and identified to species. Their human blood index, sporozoite rate and entomological inoculation rate was determined.

Results  A total of 4,558 female anophelines of which Anopheles arabiensis was the most prevalent (53.3%) followed by Anopheles demeilloni (26.3%), Anopheles christyi (8.9%), Anopheles pharoensis (7.9%) and Anopheles cinereus (3.6%) were caught and tested for blood meal source or sporozoite infection depending on their abdominal status. The proportions of human fed and bovine fed An. arabiensis were generally similar. In the low altitude village, there were 0.3% (1/300) and 0.2% (1/416) Plasmodium falciparum infected An. arabiensis among the CDC trap catches and PSC respectively. The percentage of Plasmodium vivax infected An. arabiensis were 3% (9/300) and 0.7(3/416) among the CDC and PSCs respectively in the village. In addition, there were 1.4% (1/71) and 50% (1/2) P. vivax infected An. pharoensis from the CDC light trap and PSCs, respectively. In the mid altitude village, 2.5% (1/40) and 1.7% (1/58) from among the CDC and PSCs of An. arabiensis respectively carried P. vivax sporozoites. Among the CDC light trap catches; there were 3.7 and 0 P. falciparum infective bites per year per household for An. arabiensis in the years July 2008 to June 2009 and July 2009 to June 2010 respectively in the low altitude village. The corresponding numbers for P. vivax infective bites for An. arabiensis were 33 and 14.5 in the same village. Space spray catches revealed 0.32 P. vivax infective bites per household for An. pharoensis during the first year in the low altitude village.

Conclusion  Anopheles arabiensis was the most prevalent vector of P. vivax and P. falciparum malaria in the low and mid altitude villages followed by An. pharoensis. Annual entomological inoculation rates showed that vivax malaria transmission was higher than that of the falciparum and both decreased with increase in altitude.

The greater tendency of An. arabiensis to feed on cattle justifies the application of insecticides on cattle to provide a significant protection from malaria infection. But, An. arabiensis has already developed resistance to the available insecticides, and alternative insecticides are needed.

Massebo F, Balkew M, Gebre-Michael T and Lindtjørn B. Blood meal origins and insecticide susceptibility of Anopheles arabiensis from Chano in South-West Ethiopia. Parasites & Vectors 2013, 6:44 doi:10.1186/1756-3305-6-44

Background  Anopheles arabiensis, the main malaria vector in Ethiopia, shows both anthropophilic and zoophilic behaviours. Insecticide resistance is increasing, and alternative methods of vector control are needed. The objectives of this study were to determine the blood meal origins and the susceptibility to insecticides of An. arabiensis from Chano village near Arba Minch in South-West Ethiopia.

Methods  Blood meal sources of anopheline mosquitoes collected using Centers for Disease Control and Prevention (CDC) light traps and pyrethrum spray catches (PSC) from human dwellings, and hand-held mouth aspirators from outdoor pit shelters were analysed using a direct enzyme-linked-immunosorbent assay (ELISA). The susceptibility of An. arabiensis to pyrethroid insecticides (alphacypermethrin, lambdacyhalothrin, deltamethrin, and cyfluthrin) and DDT was assessed using females reared from larval and pupal collections from natural breeding sites.

Results  The blood meal origins of 2967 freshly fed Anopheles mosquitoes were determined. An. arabiensis was the predominant species (75%), and it fed mainly on cattle. The densities of both freshly fed An. arabiensis and those fed on human blood followed similar seasonal patterns. The overall human blood index (HBI) of An. arabiensis, including mixed blood meals, was 44% and the bovine blood index (BBI) was 69%. The HBI of An. arabiensis from CDC light trap collections was 75% and this was higher than those for PSC (38%) and outdoor pit shelter collections (13%), while the BBI was 65% for PSC, 68% for outdoor pit shelters and 72% for CDC light traps. More freshly fed and human blood-fed An. arabiensis were sampled from houses close to the shore of Lake Abaya (the major breeding site). A high proportion of An. arabiensis was resistant to the pyrethroid insecticides, with a mortality rate of 56% for lambdacyhalothrin, 50% for cyfluthrin and alphacypermethrin, 47% for deltamethrin, and 10% for DDT.

Conclusion  Anopheles arabiensis is the predominant species of anopheline mosquito in this region, and cattle are the main source of its blood meals. The greater tendency of this species to feed on cattle justifies the application of insecticides on cattle to control it. However, An. arabiensis has already developed resistance to the available pyrethroid insecticides, and alternative insecticides are needed for malaria vector control.

This study highlights some of the assumptions commonly used when constructing mosquito-malaria models and presents a realistic model of Anopheles gambiae s.s. and Anopheles arabiensis, and their interaction.

We make a case that this new mosquito model, OMaWa, may improve the understanding of vector dynamics, which in turn can be used to better understand the dynamics of malaria.

Lunde TM, Korecha D, Loha E, Sorteberg A and Lindtjørn B. A dynamic model of some malaria-transmitting anopheline mosquitoes of the Afrotropical region. I. Model description and sensitivity analysis. Malaria Journal 2013, 12:28

Background: Most of the current biophysical models designed to address the large-scale distribution of malaria assume that transmission of the disease is independent of the vector involved. Another common assumption in these type of model is that the mortality rate of mosquitoes is constant over their life span and that their dispersion is negligible. Mosquito models are important in the prediction of malaria and hence there is a need for a realistic representation of the vectors involved.

Results: We construct a biophysical model including two competing species, Anopheles gambiae s.s. and Anopheles arabiensis. Sensitivity analysis highlight the importance of relative humidity and mosquito size, the initial conditions and dispersion, and a rarely used parameter, the probability of finding blood. We also show that the assumption of exponential mortality of adult mosquitoes does not match the observed data, and suggest that an age dimension can overcome this problem.

Conclusions: This study highlights some of the assumptions commonly used when constructing mosquito-malaria models and presents a realistic model of An. gambiae s.s. and An. arabiensis and their interaction. This new mosquito model, OMaWa, can improve our understanding of the dynamics of these vectors, which in turn can be used to understand the dynamics of malaria.

With global warming a reality, we show how the projected changes in malaria transmission will depend on which Anopheles mortality model is used to make such predictions

Lunde TM, Bayoh NM and Lindtjørn B. How malaria models relate temperature to malaria transmission. Parasites & Vectors 2013, 6:20 doi:10.1186/1756-3305-6-20

Background It is well known that temperature has a major influence on the transmission of malaria parasites to their hosts. However, mathematical models do not always agree about the way in which temperature affects malaria transmission.

Methods In this study, we compared six temperature dependent mortality models for the malaria vector Anopheles gambiae sensu stricto. The evaluation is based on a comparison between the models, and observations from semi-field and laboratory settings.

Results Our results show how different mortality calculations can influence the predicted dynamics of malaria transmission.

Conclusions With global warming a reality, the projected changes in malaria transmission will depend on which mortality model is used to make such predictions.

The objective of this study was to characterize the pattern related to ITN use in one village in south Ethiopia. A huge discrepancy was reported between ownership versus utilization of insecticide-treated bed nets (ITNs). To acquire the benefits of ITNs, households need to use and not merely own them.

Eskindir Loha, Kebede Tefera and Bernt Lindtjørn. Freely distributed bed-net use among Chano Mille residents, south Ethiopia: a longitudinal study. Malaria Journal 2013, 12:23 doi:10.1186/1475-2875-12-23

Background: A huge discrepancy was reported between ownership versus utilization of insecticide-treated bed nets (ITNs). To acquire the benefits of ITNs, households need to use and not merely own them. The objective of this study was to characterize the pattern of, and assess factors related to ITN use in one village in south Ethiopia.

Methods: A prospective cohort study involving 8,121 residents (in 1,388 households) was carried out from April 2009 to April 2011 (101 weeks). Every week, individuals were asked whether they slept under an ITN the night before the interview. Descriptive statistics was used to report the availability and use of ITN. A negative, binomial, probability, distribution model was fitted to find out significant predictors of ITN use. Reasons for not using ITN were summarized.

Results: The total number of ITNs available at the beginning of the study was 1,631 (1.68 ITNs per household). On week 48, 3,099 new ITNs (PermaNet2.0) were distributed freely (2.3 ITNs per household). The number of households who received at least one new ITN was 1,309 (98.4%). The percentage of children <5 years and pregnant women not using ITNs exceeded that of other adults. The mean (range; SD) ITN use fraction before and after mass distribution was 0.20 (0.15-0.27; 0.03) and 0.62 (0.47-0.69; 0.04), respectively. Before mass ITN distribution, the most frequent reason for not using ITN was having worn out bed nets (most complained the bed nets were torn by rats); and after mass ITN distribution, it was lack of convenient space to hang more than one ITN. Males, younger age groups (mainly 15–24 years) and those living away from the vector-breeding site were less likely to use ITN.

Conclusions: The ITN use fraction reached to a maximum of 69% despite near universal coverage (98.4%) was achieved. Gender, age differences and distance from vector breeding site were associated with ITN use. Strategies may need to be designed addressing disproportions in ITN use, lack of convenient space to hang more than one ITN (for those receiving more than one), and measures to prolong usable life of ITNs.

Loha E, Lunde TM, Lindtjørn B. Effect of Bednets and Indoor Residual Spraying on Spatio-Temporal Clustering of Malaria in a Village in South Ethiopia: A Longitudinal Study. PLoSONE 2012; 7(10): e4735.

Background

Understanding the spatio-temporal pattern of malaria transmission where prevention and control measures are in place will help to fine-tune strategies. The objective of this study was to assess the effect of mass distribution of bednets and indoor residual spraying (IRS) with insecticides on the spatio-temporal clustering of malaria in one malaria endemic village in south Ethiopia.

Methods

A longitudinal study was conducted from April 2009 to April 2011. The average population was 6631 in 1346 locations. We used active and passive searches for malaria cases for 101 weeks. SatScan v9.1.1 was used to identify statistically significant retrospective space–time clusters. A discrete Poisson based model was applied with the aim of identifying areas with high rates. PASW Statistics 18 was used to build generalized Poisson loglinear model.

Results

The total number of both types of malaria episodes was 622, giving 45.1 episodes per 1000 persons per year; among these, episodes of Plasmodium falciparum and vivax infection numbered 316 (22.9 per 1000 per year) and 306 (22.2 per 1000 per year), respectively. IRS with Dichlorodiphenyltrichloroethane (DDT) and later with Deltamethrin and free mass distribution of insecticide-treated nets (ITNs) were carried out during the study period. There was space–time clustering of malaria episodes at a household level. The spatio-temporal clustering of malaria was not influenced by free mass distribution of ITNs; however, the time-span of the spatio-temporal clustering of malaria cases ended after IRS with Deltamethrin. The presence of clusters on the south-east edge of the village was consistent with the finding of an increasing risk of acquiring malaria infection for individuals who lived closer to the identified vector breeding site.

Conclusion

The risk of getting malaria infection varied significantly within one village. Free mass distribution of ITNs did not influence the spatio-temporal clustering of malaria, but IRS might have eliminated malaria clustering.

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(This paper was also been presented at a conference that BioMed Central, in conjunction with its journals Malaria Journal and Parasites & Vectors, hosted. The second malaria conference “Challenges in Malaria Research: Progress Towards Elimination” was held in Basel, Switzerland from 10 – 12 October 2012).