Clinical manifestations and outcomes of severe malaria among children admitted to Rungwe and Kyela district hospitals in south-western Tanzania

Malaria remains as an important public health and a major cause of childhood death and paediatric hospital admission in sub-Saharan Africa. This prospective hospital based cross sectional study was conducted from April 2007 to April 2008. The main objective was to assess clinical manifestations and outcomes of severe malaria in children admitted to district hospital in Rungwe and Kyela in south-western Tanzania. A total of 1371 children were selected as screening group of which 409 (29.8%) were tested positive for malaria. Mean age of the children was 2.7 (95%CI= 2.5, 2.8) years and the majority (86%) were under five years of age. The proportion of children severe malaria in Rungwe was significantly higher than that of Kyela by 21.3% (P=0.002). The common symptoms of severe malaria during admission were convulsions (50.9%) compensated shock (30.6%), prostration (29.1%) and symptomatic severe anaemia (14.9%). The case fatality rate (CFR) was 4.6% and the cure rate (CR) was 95.4%. Children with suspected severe acidosis and symptomatic severe anemia were 4.8 (95%CI=1.6, 14.6) and 5.5 (95%CI 1.1, 28.2), respectively, more likely to die compared to those without these symptoms. The proportion of deaths among children presenting ≥5 symptoms was 32.1% higher than among those presenting one symptom (OR =0.50, 95%CI 0.125-2.000; P=0.000). Convulsions and compensated shock were the leading symptoms at admission. Suspected severe acidosis and symptomatic severe anemia were the predictors of mortality for children. In order to reduce mortality among admitted children with severe malaria there is a need for health providers to deploy strategic management of fatal prognostic factors. In conclusion, convulsion and compensated shock were the leading symptoms among children at admission and that suspected severe acidosis and symptomatic severe anemia were the predictors of mortality. It is therefore important to emphasis early diagnosis and prompt treatment of severe cases of malaria to minimize mortality among children

Surveillance of artemether-lumefantrine associated Plasmodium falciparum multidrug resistance protein-1 gene polymorphisms in Tanzania.

BACKGROUND: Resistance to anti-malarials is a major public health problem worldwide. After deployment of artemisinin-based combination therapy (ACT) there have been reports of reduced sensitivity to ACT by malaria parasites in South-East Asia. In Tanzania, artemether-lumefantrine (ALu) is the recommended first-line drug in treatment of uncomplicated malaria. This study surveyed the distribution of the Plasmodium falciparum multidrug resistance protein-1 single nucleotide polymorphisms (SNPs) associated with increased parasite tolerance to ALu, in Tanzania. METHODS: A total of 687 Plasmodium falciparum positive dried blood spots on filter paper and rapid diagnostic test strips collected by finger pricks from patients attending health facilities in six regions of Tanzania mainland between June 2010 and August 2011 were used. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to detect Pfmdr1 SNPs N86Y, Y184F and D1246Y. RESULTS: There were variations in the distribution of Pfmdr1 polymorphisms among regions. Tanga region had exceptionally high prevalence of mutant alleles, while Mbeya had the highest prevalence of wild type alleles. The haplotype YFY was exclusively most prevalent in Tanga (29.6%) whereas the NYD haplotype was the most prevalent in all other regions. Excluding Tanga and Mbeya, four, most common Pfmdr1 haplotypes did not vary between the remaining four regions (χ² = 2.3, p = 0.512). The NFD haplotype was the second most prevalent haplotype in all regions, ranging from 17% - 26%. CONCLUSION: This is the first country-wide survey on Pfmdr1 mutations associated with ACT resistance. Distribution of individual Pfmdr1 mutations at codons 86, 184 and 1246 varies throughout Tanzanian regions. There is a general homogeneity in distribution of common Pfmdr1 haplotypes reflecting strict implementation of ALu policy in Tanzania with overall prevalence of NFD haplotype ranging from 17 to 26% among other haplotypes. With continuation of ALu as first-line drug this haplotype is expected to keep rising, thus there is need for continued pharmacovigilance studies to monitor any delayed parasite clearance by the drug

High Levels of Sulphadoxine-pyrimethamine Resistance Pfdhfr-Pfdhps Quintuple Mutations: A Cross Sectional Survey of Six Regions in Tanzania.

In 2006, the first-line anti-malarial drug treatment in Tanzania was changed from sulphadoxine-pyrimethamine (SP) to artemether-lumefantrine (ALu), an artemisinin-based combination (ACT), since when the use of SP has been restricted for intermittent preventive treatment in pregnancy (IPTp). A number of Plasmodium falciparum mutations are known to be associated with resistance to SP, but it is not known if the prevalence of these mutations is increasing or decreasing under the conditions of reduced levels of SP use. This study reports on the current SP resistant quintuple Pfdhfr-Pfdhps mutations in six regions of Tanzania. Finger-prick blood on filter paper and rapid diagnostic test strips from P. falciparum-positive individuals of all age groups attending health facilities in six regions of Tanzania between June 2010 and August 2011 were obtained. Using chelex-100 extracted DNA, genotyping was done for mutations on codons 51, 59 and 108 of Pfdhfr and 437 and 540 of Pfdhps genes using PCR-RFLP technique. A total of 802 malaria-positive samples were screened and genotyped. The prevalence of Pfdhfr 51I, Pfdhps 437G and 540E varied between the regions (p < 0.001) whereas Pfdhfr 59R (FE 10.79, p = 0.225) and 108 N (FE 10.61, p = 0.239) did not vary between the regions. The Pfdhfr triple mutant was above 84% and close to fixation levels in all regions, whereas the Pfdhps double mutation ranged from 43.8 to 97% between the regions. The quintuple mutant (IRNGE) was the most prevalent in all regions and it varied significantly from 37.5 to 90.2% (χ2 = 1.11, p <0.001). There is evidence of persistent high levels of SP resistance markers in Tanzania with evidence of quintuple mutations that are likely to become fixed in the population. This threatens the future of SP not only in IPTp programmes, but as a combination drug for ACT. Continuous monitoring of SP-IPTp efficacy should be encouraged subsequent to searching for alternative drugs for IPTp in East Africa

Esperanza Window Traps for the collection of anthropophilic blackflies (Diptera: Simuliidae) in Uganda and Tanzania.

There is an increasing need to evaluate the impact of chemotherapeutic and vector-based interventions as onchocerciasis affected countries work towards eliminating the disease. The Esperanza Window Trap (EWT) provides a possible alternative to human landing collections (HLCs) for the collection of anthropophilic blackflies, yet it is not known whether current designs will prove effective for onchocerciasis vectors throughout sub-Saharan Africa. EWTs were deployed for 41 days in northern Uganda and south eastern Tanzania where different Simulium damnosum sibling species are responsible for disease transmission. The relative efficacy of EWTs and HLCs was compared, and responses of host-seeking blackflies to odour baits, colours, and yeast-produced CO2 were investigated. Blue EWTs baited with CO2 and worn socks collected 42.3% (2,393) of the total S. damnosum s.l. catch in northern Uganda. Numbers were comparable with those collected by HLCs (32.1%, 1,817), and higher than those collected on traps baited with CO2 and BG-Lure (25.6%, 1,446), a synthetic human attractant. Traps performed less well for the collection of S. damnosum s.l. in Tanzania where HLCs (72.5%, 2,432) consistently outperformed both blue (16.8%, 563) and black (10.7%, 360) traps baited with CO2 and worn socks. HLCs (72.3%, 361) also outperformed sock-baited (6.4%, 32) and BG-Lure-baited (21.2%, 106) traps for the collection of anthropophilic Simulium bovis in northern Uganda. Contrasting blackfly distributions were observed on traps in Uganda and Tanzania, indicating differences in behaviour in each area. The success of EWT collections of S. damnosum s.l. in northern Uganda was not replicated in Tanzania, or for the collection of anthropophilic S. bovis. Further research to improve the understanding of behavioural responses of vector sibling species to traps and their attractants should be encouraged

The blackfly vectors and transmission of Onchocerca volvulus in Mahenge, south eastern Tanzania.

The Mahenge Mountains onchocerciasis focus in south eastern Tanzania was historically one of the most heavily infected areas in the country. The vectors of Onchocerca volvulus are mainly Simulium damnosum complex blackflies, but a species of the Simulium neavei group may also contribute to transmission in some areas. The only detailed studies of parasite transmission in Mahenge were conducted in the late 1960s. The taxonomy of the S. damnosum complex has since been revised and onchocerciasis control through annual community directed treatment with ivermectin (CDTI) commenced in 1997. This study aimed to provide a cytogenetic and molecular update of the S. damnosum complex cytoforms present in Mahenge, and to evaluate the current status of O. volvulus transmission by blackflies following 19 years of annual CDTI. Rivers were surveyed to identify sites of S. damnosum s.l. breeding among the eastern slopes of the mountains, and human landing collections of adult female blackflies were made close to breeding sites. Identification of S. damnosum complex cytoforms was by cytotaxonomy of late-instar larvae and ITS1 amplicon size polymorphisms of larvae and adults. Adult blackflies were pool screened for O. volvulus infection using a triplex real-time PCR. The cytoforms 'Nkusi', Simulium kilibanum and 'Turiani' were found breeding in perennial rivers. 'Nkusi' and S. kilibanum were collected on human bait at 7/7 catch sites and possessed ITS1 profiles most closely resembling the molecular forms 'Nkusi J' and S. kilibanum 'T'. Whereas 'Turiani' was present in rivers, it was not collected on human bait and appears to be zoophilic. Simulium nyasalandicum was collected in low numbers on human bait at 3/7 catch sites. In total, 12,452 S. damnosum s.l. were pool screened and O. volvulus infection was detected in 97/104 pools of bodies and 51/104 pools of heads. The estimated percentage of S. damnosum s.l. carrying infective L3 stage parasites was 0.57% (95% CI 0.43%-0.74%). Onchocerca volvulus transmission by S. damnosum s.l. is continuing in the Mahenge Mountains after 19 years of annual CDTI. Infection rates appear similar to those reported in the 1960s, but a more detailed study is required to fully understand the epidemiological significance of the ongoing transmission. These results provide further evidence that annual CDTI may be insufficient to eliminate the parasite in formerly hyperendemic foci

Prevalence of asymptomatic malaria infections in selected military camps in Tanzania

Background: Despite a decrease in malaria burden reported between 2000 and 2015, an increasing trend of malaria transmission has been recently reported in some endemic countries including Tanzania. Periodic monitoring to identify pocket areas for asymptomatic Plasmodium falciparum infection&nbsp; &nbsp;is vital for malaria elimination efforts. The objective of this study was to determine prevalence of asymptomatic malaria infections among military recruits in selected camps in Tanzania. Methods: A cross-sectional study was conducted in 2015 at four military camps (Bulombora, Mgambo, Ruvu, and Rwamkoma) of National Service located in regions with varying malaria endemicity in Tanzania.&nbsp; Finger prick blood samples collected from asymptomatic military recruits who had been at the camps for over two months were simultaneously tested using microscopy and malaria rapid diagnostic tests (mRDTs) to detect malaria parasite infections. Results: Malaria parasite prevalence among asymptomatic recruits was 20.3% and 19.4% by microscopy and mRDT respectively. There was moderate agreement (Kappa=0.724) between microscopy and mRDT test results. A significant difference (p&lt;0.001) of malaria parasite prevalence among the four study camps was observed; ranging from 1.9% in Bulombora to 39.4% in Rwamkoma. The geometric mean parasite density was 11,053 asexual parasites/µl and most recruits (56.8%) had 200 to 1999 asexual parasites/µl. P. falciparum was the predominant (99.2%) malaria parasite species. Conclusion: Our study found high prevalence of asymptomatic malaria infections among military recruits in the selected camps, and this varied from one camp to another. The study has highlighted that public residence institutions such as military camps can be potential hotspots for malaria infection and therefore should not be skipped in routine national malaria surveillance system for monitoring trends of infection

Clinical manifestations and outcomes of severe malaria among children admitted to Rungwe and Kyela district hospitals in south-western Tanzania

Malaria remains as an important public health and a major cause of childhood death and paediatric hospital admission in sub-Saharan Africa. This prospective hospital based cross sectional study was conducted from April 2007 to April 2008. The main objective was to assess clinical manifestations and outcomes of severe malaria in children admitted to district hospital in Rungwe and Kyela in south-western Tanzania. A total of 1371 children were selected as screening group of which 409 (29.8%) were tested positive for malaria. Mean age of the children was 2.7 (95%CI= 2.5, 2.8) years and the majority (86%) were under five years of age. The proportion of children severe malaria in Rungwe was significantly higher than that of Kyela by 21.3% (P=0.002). The common symptoms of severe malaria during admission were convulsions (50.9%) compensated shock (30.6%), prostration (29.1%) and symptomatic severe anaemia (14.9%). The case fatality rate (CFR) was 4.6% and the cure rate (CR) was 95.4%. Children with suspected severe acidosis and symptomatic severe anemia were 4.8 (95%CI=1.6, 14.6) and 5.5 (95%CI 1.1, 28.2), respectively, more likely to die compared to those without these symptoms. The proportion of deaths among children presenting ≥5 symptoms was 32.1% higher than among those presenting one symptom (OR =0.50, 95%CI 0.125-2.000; P=0.000). Convulsions and compensated shock were the leading symptoms at admission. Suspected severe acidosis and symptomatic severe anemia were the predictors of mortality for children. In order to reduce mortality among admitted children with severe malaria there is a need for health providers to deploy strategic management of fatal prognostic factors. In conclusion, convulsion and compensated shock were the leading symptoms among children at admission and that suspected severe acidosis and symptomatic severe anemia were the predictors of mortality. It is therefore important to emphasis early diagnosis and prompt treatment of severe cases of malaria to minimize mortality among children

Clinical manifestations and outcomes of severe malaria among children admitted to Rungwe and Kyela district hospitals in south-western Tanzania

Malaria remains as an important public health and a major cause of childhood death and paediatric hospital admission in sub-Saharan Africa. This prospective hospital based cross sectional study was conducted from April 2007 to April 2008. The main objective was to assess clinical manifestations and outcomes of severe malaria in children admitted to district hospital in Rungwe and Kyela in south-western Tanzania. A total of 1371 children were selected as screening group of which 409 (29.8%) were tested positive for malaria. Mean age of the children was 2.7 (95%CI= 2.5, 2.8) years and the majority (86%) were under five years of age. The proportion of children severe malaria in Rungwe was significantly higher than that of Kyela by 21.3% (P=0.002). The common symptoms of severe malaria during admission were convulsions (50.9%) compensated shock (30.6%), prostration (29.1%) and symptomatic severe anaemia (14.9%). The case fatality rate (CFR) was 4.6% and the cure rate (CR) was 95.4%. Children with suspected severe acidosis and symptomatic severe anemia were 4.8 (95%CI=1.6, 14.6) and 5.5 (95%CI 1.1, 28.2), respectively, more likely to die compared to those without these symptoms. The proportion of deaths among children presenting ≥5 symptoms was 32.1% higher than among those presenting one symptom (OR =0.50, 95%CI 0.125-2.000; P=0.000). Convulsions and compensated shock were the leading symptoms at admission. Suspected severe acidosis and symptomatic severe anemia were the predictors of mortality for children. In order to reduce mortality among admitted children with severe malaria there is a need for health providers to deploy strategic management of fatal prognostic factors. In conclusion, convulsion and compensated shock were the leading symptoms among children at admission and that suspected severe acidosis and symptomatic severe anemia were the predictors of mortality. It is therefore important to emphasis early diagnosis and prompt treatment of severe cases of malaria to minimize mortality among children