New paper: Reversal of Choroquine resistance in Zambia

Sitali L, Mwenda MC, Miller JM, Bridges DJ, Hawela MB, Chizema-Kawesha E, Chipeta J &  Lindtjørn B. En-route to the ‘elimination’ of genotypic chloroquine resistance in Western and Southern Zambia, 14 years after chloroquine withdrawal. Malar J. 2019;18(1):391. Epub 2019/12/05.

Background  Anti-malarial resistance is, and continues to be a significant challenge in the fight against malaria and a threat to achieving malaria elimination. In Zambia, chloroquine (CQ), a safe, affordable and well-tolerated drug, was removed from use in 2003 due to high levels of resistance evidenced with treatment failure. This study sought to investigate the prevalence of chloroquine resistance markers in Southern and Western Provinces of Zambia 14 years after the withdrawal of CQ.

Methods  Data from a cross-sectional, all-age household survey, conducted during the peak malaria transmission season (April–May 2017) was analysed. During the all-age survey, socio-demographic information and coverage of malaria interventions were collected. Consenting individuals were tested for malaria with a rapid diagnostic test and a spot of blood collected on filter paper to create a dried blood spot (DBS). Photo-induced electronic transfer–polymerase chain reaction (PET–PCR) was used to analyse the DBS for the presence of all four malaria species. Plasmodium falciparum positive samples were analysed by high resolution melt (HRM) PCR to detect the presence of genotypic markers of drug resistance in the P. falciparum chloroquine resistance transporter (Pfcrt) and P. falciparum multi-drug resistance (Pfmdr) genes.

Results  A total of 181 P. falciparum positive samples were examined for pfcrt K76T and MDR N86. Of the 181 samples 155 successfully amplified for Pfcrt and 145 for Pfmdr N86. The overall prevalence of CQ drug-resistant parasites was 1.9% (3/155), with no significant difference between the two provinces. No N86Y/F mutations in the Pfmdr gene were observed in any of the sample.

Conclusion  This study reveals the return of CQ sensitive parasites in Southern and Western Provinces of Zambia 14 years after its withdrawal. Surveillance of molecular resistant markers for anti-malarials should be included in the Malaria Elimination Programme so that resistance is monitored country wide.

Bed nets, indoor spraying and malaria mosquitoes

Kenea O, Balkew M, Tekie H, Deressa W, Loha E, Lindtjørn B, et al. Impact of combining indoor residual spraying and long-lasting insecticidal nets on Anopheles arabiensis in Ethiopia: results from a cluster randomized controlled trial. Malaria Journal. 2019;18(1):182.

Background Indoor residual house spraying (IRS) and long-lasting insecticidal nets (LLINs) are the key front-line malaria vector interventions against Anopheles arabiensis, the sole primary malaria vector in Ethiopia. Universal coverage of both interventions has been promoted and there is a growing demand in combinations of interventions for malaria control and elimination. This study compared the impact on entomological outcomes of combining IRS and LLINs with either intervention alone in Adami Tullu district, south-central Ethiopia. The epidemiological outcomes were recently published on a separate paper.

Methods This factorial, cluster-randomized, controlled trial randomized villages to four study arms: IRS + LLIN, IRS, LLIN, and control. LLINs (PermaNet 2.0) were provided free of charge. IRS with propoxur was applied before the main malaria transmission season in 2014, 2015 and 2016. Adult mosquitoes were collected in randomly selected villages in each arm using CDC light trap catch (LTC) set close to a sleeping person, pyrethrum spray catch (PSC), and artificial pit shelter (PIT), for measuring mosquito host-seeking density (HSD), indoor resting density (IRD), and outdoor resting density (ORD), respectively. Human landing catch (HLC) was performed in a sub-set of villages to monitor An. arabiensis human biting rates (HBR). Mean vector densities and HBR were compared among study arms using incidence rate ratio (IRR) calculated by negative binomial regression.

Results  There were no significant differences in mean densities (HSD, IRD, ORD) and HBR of An. arabiensis between the IRS + LLIN arm and the IRS arm (p > 0.05). However, mean HSD, IRD, ORD, and HBR were significantly lower in the IRS + LLIN arm than in the LLIN alone arm (p < 0.05). All An. arabiensis tested for malaria infection were negative for Plasmodium species. For this reason, the entomological inoculation rate could not be determined.

Conclusions The IRS + LLIN were as effective as IRS alone in reducing densities and HBR of An. arabiensis. However, the effectiveness of the two interventions combined was higher than LLINs alone in reducing densities and HBR of the vector. Added impact of the combination intervention against malaria infectivity rates of An. arabiensis compared to either intervention alone remains unknown and warrants further research.

Trial registration PACTR201411000882128. Registered 8 September 2014,

Difficult to eradicate malaria

Loha E, Deressa W, Gari T, Balkew M, Kenea O, Solomon T, Hailu A, Robberstad B, Assegid M, Overgaard HJ, Lindtjørn B: Long-lasting insecticidal nets and indoor residual spraying may not be sufficient to eliminate malaria in a low malaria incidence area: results from a cluster randomized controlled trial in Ethiopia. Malaria Journal 2019, 18.

Background  Conflicting results exist on the added benefit of combining long-lasting insecticidal nets (LLINs) with indoor residual spraying (IRS) to control malaria infection. The main study objective was to evaluate whether the combined use of LLINs and IRS with propoxur provides additional protection against Plasmodium falciparum and/or Plasmodium vivax among all age groups compared to LLINs or IRS alone.

Methods  This cluster-randomized, controlled trial was conducted in the Rift Valley area of Ethiopia from September 2014 to January 2017 (121 weeks); 44 villages were allocated to each of four study arms: LLIN + IRS, IRS, LLIN, and control. Each week, 6071 households with 34,548 persons were surveyed by active and passive case detection for clinical malaria. Primary endpoints were the incidence of clinical malaria and anaemia prevalence.

Results  During the study, 1183 malaria episodes were identified, of which 55.1% were P. falciparum and 25.3% were P. vivax, and 19.6% were mixed infections of P. falciparum and P. vivax. The overall malaria incidence was 16.5 per 1000 person-years of observation time (PYO), and similar in the four arms with 17.2 per 1000 PYO in the LLIN + IRS arm, 16.1 in LLIN, 17.0 in IRS, and 15.6 in the control arm. There was no significant difference in risk of anaemia among the trial arms.

Conclusions  The clinical malaria incidence and anaemia prevalence were similar in the four study groups. In areas with low malaria incidence, using LLINs and IRS in combination or alone may not eliminate malaria. Complementary interventions that reduce residual malaria transmission should be explored in addition to LLINs and IRS to further reduce malaria transmission in such settings.

Trial registration PACTR201411000882128 (08 September 2014)


Plasmodium species in Zambia

Sitali L, Miller JM, Mwenda MC, Bridges DJ, Hawela MB, Hamainza B, Chizema-Kawesha E, Eisele TP, Chipeta J, Lindtjørn B: Distribution of Plasmodium species and assessment of performance of diagnostic tools used during a malaria survey in Southern and Western Provinces of Zambia. Malaria Journal 2019, 18:130.

Background  Zambia continues to make strides in reducing malaria burden through the use of proven malaria interventions and has recently pledged to eliminate malaria by 2021. Case management services have been scaled up at community level with rapid diagnostic tests (RDTs) providing antigen-based detection of falciparum malaria only. Key to national malaria elimination goals is the ability to identify, treat and eliminate all Plasmodium species. This study sought to determine the distribution of non-falciparum malaria and assess the performance of diagnostic tests for Plasmodium falciparum in Western and Southern Provinces of Zambia, two provinces planned for early malaria elimination.

Methods  A sub-set of individuals’ data and samples from a cross-sectional household survey, conducted during peak malaria transmission season in April and May 2017, was used. The survey collected socio-demographic information on household members and coverage of malaria interventions. Malaria testing was done on respondents of all ages using blood smears and RDTs while dried blood spots were collected on filter papers for analysis using photo-induced electron transfer polymerase chain reaction (PET-PCR). Slides were stained using Giemsa stain and examined by microscopy for malaria parasites.

Results  From the 1567 individuals included, the overall prevalence of malaria was 19.4% (CI 17.5–21.4) by PCR, 19.3% (CI 17.4–21.4) by RDT and 12.9% (CI 11.3–14.7) by microscopy. Using PET-PCR as the gold standard, RDTs showed a sensitivity of 75.7% (CI 70.4–80.4) and specificity of 94.2% (CI 92.8–95.4). The positive predictive value (PPV) was 75.9% (CI 70.7–80.6) and negative predictive value (NPV) was 94.1% (CI 92.1–95.4). In contrast, microscopy for sensitivity, specificity, PPV, and NPV values were 56.9% (CI 51.1–62.5), 97.7% (CI 96.7–98.5), 85.6% (CI 80.0–90.2), 90.4% (CI 88.7–91.9), respectively. Non-falciparum infections were found only in Western Province, where 11.6% of P. falciparum infections were co-infections with Plasmodium ovale or Plasmodium malariae.

Conclusion  From the sub-set of survey data analysed, non-falciparum species are present and occurred as mixed infections. As expected, PET-PCR was slightly more sensitive than both malaria RDTs and microscopy to detecting malaria infections.

New PhD by Alemayehu Hailu: Economic evaluation of malaria prevention in Ethiopia


Hailu A, D. Economic evaluation of malaria prevention in Ethiopia: Economic burden, equity, and cost-effectiveness analysis of malaria prevention in south-central Ethiopia [PhD]. Bergen: University of Bergen; 2018.

Background: Despite remarkable efforts in the global fight against malaria and achievements in the reduction of morbidity and mortality in the last decade, the disease remains to be a huge challenge to the health systems of malaria-endemic low-income countries in Africa and in all corners of the globe. Beyond the wide range of consensus on the disease burden and prioritization of malaria, the available evidence on the economic burden of malaria in Ethiopia is scanty. No clear evidence yet exists about the additional resources required for a combined implementation of long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) with respect to the added protection afforded. In addition, little is known about the prevailing status of LLINs and IRS across different levels of wealth strata.

Objectives: The aims of this thesis were to estimate the economic burden of malaria; to evaluate the cost-effectiveness of a combined implementation malaria prevention interventions (LLINs and IRS); and analyse the distributional (equity) implications of the interventions in the Adami Tullu district, south-central Ethiopia.

Methods: Studies included in this thesis were conducted from 2014 – 2016 in the Adami Tullu district of Oromia Region, in south-central Ethiopia as part of and partly in conjunction with the MalTrials project. We conducted a cost of illness using 190 malaria patients in the first study. In Paper II, we carried out a combination of trial-based and literature-based cost-effectiveness analysis using Markov modelling. In the third study, using a cross-sectional data from 6069 households we did an inequality analysis of ownership of LLINs and IRS status. The principal component analysis technique was used for ranking households based on socioeconomic position. We measured the inequality in LLINs and IRS using concentration indices and concentration curve (Paper I&III).

Results: The median cost of malaria per episode to the household was USD 5.06 (IQR: 2.98 – 8.10) and the direct cost was significantly higher among the poor. The trial-based analysis had shown that the routine practice dominates both the combined intervention and singleton intervention while the literature-based analysis had indicated that combined intervention had an Incremental Cost-Effectiveness Ratio of USD 1403 per DALY averted. Immediately before we started the trial, the LLIN ownership was 11.6% and IRS coverage was 72.5%. We found a concentration index of 0.0627 for LLINs and – 0.0383 for the IRS. Inequality in LLIN ownership was mainly associated with a variability in a housing situation, the size of the household, and access to mass media and telecommunication service.

Conclusions: The economic burden of malaria to the rural households in Ethiopia is huge—mainly to the poor. Based on the trial-based cost-effectiveness analysis, we conclude that the combination of LLINs and IRS is not likely to be a cost-effective option compared with singleton intervention. However, based on the literature-based analysis, the combined intervention had potential to be a cost-effective alternative at 3 times GDP per capita per DALY averted. Furthermore, the ownership of LLIN was very low and significantly pro-rich, while IRS status was equitable across socioeconomic strata.

New and important publication from the Arba Minch group

Mulchandani R, Massebo F, Bocho F, Jeffries CL, Walker T, Messenger LA. A community-level investigation following a yellow fever virus outbreak in South Omo Zone, South-West Ethiopia. PeerJ. 2019;7. doi: 10.7717/peerj.6466.


Despite the availability of a highly effective vaccine, yellow fever virus (YFV) remains an important public health problem across Africa and South America due to its high case-fatality rate. This study investigated the historical epidemiology and contemporary entomological and social determinants of a YFV outbreak in South Omo Zone (SOZ), Ethiopia.


A YFV outbreak occurred in SOZ, Ethiopia in 2012–2014. Historical epidemiological data were retrieved from the SOZ Health Department and analyzed. Entomological sampling was undertaken in 2017, including mosquito species identification and molecular screening for arboviruses to understand mosquito habitat distribution, and finally current knowledge, attitudes and preventative practices within the affected communities were assessed.


From October 2012 to March 2014, 165 suspected cases and 62 deaths were reported, principally in rural areas of South Ari region (83.6%). The majority of patients were 15–44 years old (75.8%) and most case deaths were males (76%). Between June and August 2017, 688 containers were sampled across 180 households to identify key breeding sites for Aedesmosquitoes. Ensete ventricosum (“false banana”) and clay pots outside the home were the most productive natural and artificial breeding sites, respectively. Entomological risk indices classified most sites as “high risk” for future outbreaks under current World Health Organization criteria. Adult mosquitoes in houses were identified as members of the Aedes simpsonicomplex but no YFV or other arboviruses were detected by PCR. The majority of community members had heard of YFV, however few activities were undertaken to actively reduce mosquito breeding sites.


Study results highlight the potential role vector control could play in mitigating local disease transmission and emphasize the urgent need to strengthen disease surveillance systems and in-country laboratory capacity to facilitate more rapid responses to future YFV outbreaks.


Taye Gari’s PhD thesis: Malaria, anaemia and undernutrition in Ethiopia

Taye Gari. Malaria, anaemia and undernutrition in a drought-affected area of the Rift Valley of Ethiopia: Experiences from a trial to prevent malaria.  PhD. University of Bergen, 2018. Bergen

Summary of PhD thesis

Background: In Ethiopia, malaria, anaemia and undernutrition are common childhood health problems. The country is planning to reduce these conditions to a level where they are not a public health problem. Meanwhile, for the success of this aim, a description of the occurrence and interaction of malaria, anaemia and undernutrition could help contribute to design tailored, efficient and effective control strategies. This study was done in the context of malaria prevention trial, which aimed to measure the effect of combining long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) in reducing the malaria incidence compared to LLINs or IRS alone. The study area was affected by a serious drought and famine during the first year of the study.

Objectives: The overall aim of this thesis is to improve our understanding of the effect of malaria prevention on anaemia, and to assess the association between malaria, anaemia and undernutrition among children in a drought-affected area in south-central, Ethiopia.

Methods: A cohort of 5309 residents was followed-up for 16 weeks to measure the variations in malaria incidence among villages (Paper I), and the results were used as a baseline to calculate the sample size needed for the trial. We followed a cohort of children aged 6 to 59 months for one year to describe anaemia and changes in haemoglobin (Hb) concentration (Paper II). A cohort of 4468 children was followed-up for 89 weeks to measure the relationship between malaria and undernutrition (Paper III). Weekly home visits and patient self-referral were also used to identify malaria cases. We conducted Hb concentration (once a year) and anthropometry (twice a year) surveys.

Results: In Paper I, we observed a variation in malaria incidence among villages. On the other hand, the insecticide-treated nets ownership was low (27%), with the distance from the lake or river and younger age being the main risk factors for malaria. The findings of this study were used as a baseline to calculate the sample size for the trial. In Paper II, despite the malaria prevention effort in the community, we observed an unexpected increase in anaemia prevalence over the period of a year, which could be due to the drought and famine that affected the area. A higher incidence of anaemia was observed among children with stunting, malaria infection, young age and in poor families. However, no significant difference in anaemia prevalence was observed among the different trial arms (LLIN+IRS, LLINs alone, IRS alone and routine arm). In Paper III, malaria infection was a risk factor for stunting and wasting, although undernutrition was not a risk for malaria infection. Furthermore, an increase in the prevalence of stunting, but no significant change in a prevalence of wasting was observed over time.

Conclusions: We showed a large variation in malaria incidence among villages. Conducting trials in a drought-prone area may bring an unexpected challenge. We observed an unexpected increase in anaemia prevalence over a year. There was no significant difference in anaemia prevalence among the trial arms. Moreover, a close follow-up of the nutritional status of children with malaria infection may be needed. There could hence be a need to prioritize villages nearer to the main mosquito breeding sites for malaria control.

Trial registration: PACTR 201411000882128 (8 September, 2014)

The Thesis can be downloaded here

Malaria, anaemia and undernutrition

On Friday June 22, 2018 Taye Gari Anaya will defend his PhD thesis at the University of Bergen. 

The title of his thesis is: “Malaria, anaemia and undernutrition in a drought-affected area of the Rift Valley of Ethiopia: Experiences from a trial to prevent malaria”.

Malaria, anaemia and malnutrition are interconnected, and often coexist in prevalent areas such as in sub-Saharan Africa, including Ethiopia. Although individuals in all ages of life are affected by these conditions, children under the age of 5 represent the most vulnerable group. Ethiopia is planning to reduce these conditions to a level where they are not public health problems Meanwhile, for the success of this aim, a description of the occurrence and interaction of malaria, anaemia and undernutrition could help to design tailored, efficient and effective control strategies.  

This thesis measures the effect of malaria prevention on anaemia reduction, and assesses the association between malaria, anaemia and undernutrition among a cohort of children aged 6 to 59 months old followed in a drought-affected rural area in south-central, Ethiopia.

The study showed a large variation in malaria incidence among villages in the same district. Despite community wide malaria prevention effort, an unexpected increase in anaemia prevalence was observed over a year. Malaria infection was a risk factor for undernutrition, although undernutrition was not a risk for malaria infection. There could be a need to prioritise villages nearer to the main mosquito breeding sites for malaria control. Moreover, a close follow-up of the nutritional status of children with malaria infection may be needed. 


Taye Gari Ayana is from Hawassa in south Ethiopia. He completed Master degree in Public Health from Addis Ababa University in Ethiopia. From 2013 he has been affiliated with the Centre for International Health as a PhD candidate. Now he is a lecturer at the School of Public Health, at Hawassa University in Ethiopia. His supervisors were Professor Bernt Lindtjørn, Dr Eskindir Loha and Dr Wakgari Deressa. 

Maternal Mortality and Stillbirths More than Halved

The 2017 Annual report from the Centre for International Health at the University of Bergen writes about the implementation reserach in south Ethiopia:

Making standard delivery services available for all is the most important factor for improving maternal mortality. Furthermore, the study suggests that stillbirths can also be reduced if the health services focus on improved obstetric care.

Professor Bernt Lindtjørn led a project in south-western Ethiopia studying how a number of interventions could reduce maternal mortality and stillbirths. As a result of the research efforts, there was 64% reduction in maternal mortality and a 46% reduction in stillbirths.

Lindtjørn explains that there are several reasons why mothers die in childbirth, but he highlights that the main causes are insufficient numbers of institutions and trained personnel, as well as a lack of access to services (i.e. transportation) as being the most important factors.

The project’s positive results were associated with increasing the numbers of trained staff, increasing the num- bers of institutions undertaking Comprehensive Emergency Obstetric Care (CEmOC), increasing the numbers of mothers having Caesarean sections, increasing in the numbers of antenatal controls and referrals, improving access to health service, decreasing in number of home deliveries and decreasing the use of traditional birth attendants.

The goals for the project were straight forward and included making small hospitals available for rural popu- lations, improving referrals (i.e. from health posts to health centres to hospitals when necessary), undertaking additional training for non-clinical physicians, nurses, midwives, and health extension workers, making essential equipment available, and supervising the health care services on offer.

The project was based on the principle of “learning by doing” and involved short courses in Basic Emergen- cy Obstetric Care (BEmOC) and Comprehensive Emergency Obstetric Care (CEmOC), as well as anaesthesiolo- gy, scrub nursing and Continuing Medical Education (CME). It also included Master and PhD training in Public Health: one PhD and 6 master degrees resulted from the project.

The publications from this project can be viewed here.