Malaria In Sudan Research Articles

Investigating the association between household exposure to Anopheles stephensi and malaria in Sudan and Ethiopia: A case-control study protocol.

Endemic African malaria vectors are poorly adapted to typical urban ecologies. However, Anopheles stephensi, an urban malaria vector formerly confined to South Asia and the Persian Gulf, was recently detected in Africa and may change the epidemiology of malaria across the continent. Little is known about the public health implications of An. stephensi in Africa. This study is designed to assess the relative importance of household exposure to An. stephensi and endemic malaria vectors for malaria risk in urban Sudan and Ethiopia. Case-control studies will be conducted in 3 urban settings (2 in Sudan, 1 in Ethiopia) to assess the association between presence of An. stephensi in and around households and malaria. Cases, defined as individuals positive for Plasmodium falciparum and/or P. vivax by microscopy/rapid diagnostic test (RDT), and controls, defined as age-matched individuals negative for P. falciparum and/or P. vivax by microscopy/RDT, will be recruited from public health facilities. Both household surveys and entomological surveillance for adult and immature mosquitoes will be conducted at participant homes within 48 hours of enrolment. Adult and immature mosquitoes will be identified by polymerase chain reaction (PCR). Conditional logistic regression will be used to estimate the association between presence of An. stephensi and malaria status, adjusted for co-occurrence of other malaria vectors and participant gender. Findings from this study will provide evidence of the relative importance of An. stephensi for malaria burden in urban African settings, shedding light on the need for future intervention planning and policy development.

Spatiotemporal mapping of malaria incidence in Sudan using routine surveillance data

Malaria is a serious threat to global health, with over 95% of the cases reported in 2020 by the World Health Organization in African countries, including Sudan. Sudan is a low-income country with a limited healthcare system and a substantial burden of malaria. The epidemiology of malaria in Sudan is rapidly changing due to factors including the rapidly developing resistance to drugs and insecticides among the parasites and vectors, respectively; the growing population living in humanitarian settings due to political instability; and the recent emergence of Anopheles stephensi in the country. These factors contribute to changes in the distribution of the parasites species as well as malaria vectors in Sudan, and the shifting patterns of malaria epidemiology underscore the need for investment in improved situational awareness, early preparedness, and a national prevention and control strategy that is updated, evidence based, and proactive. A key component of this strategy is accurate, high-resolution endemicity maps of species-specific malaria. Here, we present a spatiotemporal Bayesian model, developed in collaboration with the Sudanese Ministry of Health, that predicts a fine-scale (1 km times 1 km) clinical incidence and seasonality profiles for Plasmodium falciparum and Plasmodium vivax across the country. We use monthly malaria case counts for both species collected via routine surveillance between January 2017 and December 2019, as well as a suite of high-resolution environmental covariates to inform our predictions. These epidemiological maps provide a useful resource for strategic planning and cost-effective implementation of malaria interventions, thus informing policymakers in Sudan to achieve success in malaria control and elimination.

Modeling the Influence of Climate Factors on Malaria Transmission Dynamics in North Kordofan State, Sudan

Background: Despite great efforts by the government to control malaria in Sudan, the disease is the most significant human disease and was widespread in North Kordofan State. Morbidity and mortality of the disease are increasing in the State. Usually, the disease reached its peak after rainy season. This study aims to estimate the role of climate factors on malaria transmission dynamic by modeling the relationship between malaria cases and climatic variables, such as rainfall, relative humidity, and temperature, in Kordofan State. Methods: We used Pearson correlation coefficient and an ordinary least square method to assess this relationship. Results: The results show that there are statistically significant associations between malaria cases and rainfall, relative humidity, and minimum temperature (P-value < 0.001). The regression analysis results suggest that the appropriate model for predicting malaria incidence includes malaria cases lagged by one month, maximum temperature, and minimum temperature. This model explained 72% of the variance in monthly malaria incidence. Conclusion: The results of this study suggest that climatic factors have potential use for malaria prediction in the State.

Evaluation of Loop Mediated Isothermal Amplification (LAMP) for Diagnosis of Plasmodium falciparum in Wad Medani City, Gezira State, Sudan

Plasmodium falciparum considered as the most serious form of species causes malaria compared with other species. Diagnosis of falciparum malaria in Sudan remain a major problem, the laboratory diagnosis depends solely on microscopy and RDTs. Loop mediated isothermal amplification (LAMP) assay is a molecular technique done in isothermal temperature using simple, inexpensive instruments for detection of falciparum malaria. The aim of the study is to evaluate the diagnostic performance of loop mediated isothermal amplification (LAMP) assay for detection of P. falciparum and compare with microscopic detection. A cross sectional hospital based study conducted on 220 blood samples collected from participants suspected to have falciparum malaria attending Wad Medani Teaching Hospitals and 26 healthy participants during the period November 2018 to January 2019. Thick blood films were done and used for P. falciparum detection. The extracted DNA by TE buffer was amplified by LAMP assay targeting 18S rRNA gene. Data were analyzed using Medical calculator (MedCalc) programs (V. 16). The results showed that the sensitivity, specificity, positive predictive value, negative predictive values were 99.1%, 84.6%, 53.2%, 99.8% respectively. Validation of LAMP diagnostic performance revealed that area under the curve is 0.919, while Weighted Kappa is 0.866. The study concluded that the LAMP assay had the identical diagnostic performance compared with microscopy in diagnosis of Plasmodium falciparum malaria. This gives a relative effortlessness application of LAMP assay in Sudan after availing the required logistics.

Epidemiology and distribution of Plasmodium vivax malaria in Sudan.

Plasmodium vivax malaria has been recognised as an important cause of morbidity in several African countries. The prevalence was previously estimated as 2-5% in eastern Sudan. These estimates are observed to be rising and spreading continuously. The present study was undertaken to investigate the situation of distribution and epidemiology of P. vivax malaria in Sudan. Cross-sectional malaria surveys carried out in hospitals and health centres covered 21 sites in 10 states. Data and blood samples were collected from 1226 clinically investigated suspected malaria cases of both genders and all ages. Microscopically detected malaria parasites were confirmed by PCR. The overall prevalence of P. vivax among the malaria cases was 26.6%. The prevalence showed significant variations between the states (p<0.001), which could be explained by differences in population movement, the presence of refugees and proximity to endemic neighbouring countries. It also varied significantly with residence status (p<0.001), reflecting the stability of transmission. Although malaria in Sudan is still largely attributed to Plasmodium falciparum, P. vivax has been rising with worrying proportions and spreading to new areas. The emergence and marked increase of P. vivax poses new challenges to malaria treatment and control in Sudan.

Anopheles arabiensis in Sudan: a noticeable tolerance to urban polluted larval habitats associated with resistance to Temephos

BackgroundIt has been documented that unplanned urbanization leads to the exposure of members of the Anopheles vectors to a range of water pollution in urban settings. Many surveys from African and Asian countries reported the presence of Anopheles larvae in polluted urban habitats. The present study documents an obvious tolerance of the melanic and normal forms of Anopheles arabiensis to urban polluted larval habitats accompanied by resistance to Temephos larvicide.MethodsA cross-sectional survey was carried out to inspect apparently polluted An. arabiensis larval habitats during the hot dry season of 2015. Larval specimens were collected from only apparently polluted habitats after visual inspection from 5 localities in Khartoum State. After morphological and molecular identification of random samples of larvae the magnitude of water pollution was determined using nine abiotic factors. The susceptibility status of An. arabiensis larval forms from normal and polluted habitats to Temephos was tested using the WHO standard diagnostic concentration doses.ResultsMorphological and PCR analysis of anopheline larvae revealed the presence of An. arabiensis, a member of the Anopheles gambiae complex. Seven out of 9 physiochemical parameters showed higher concentrations in polluted larval habitats in comparison to control site. Anopheles arabiensis larvae were found in water bodies characterized by high mean of conductivity (1857.8 ± 443.3 uS/cm), turbidity (189.4 ± 69.1 NTU) and nitrate (19.7 ± 16.7 mg/l). The range of mortality rates of An. arabiensis larvae collected from polluted habitats in comparison to An. arabiensis larvae collected from non-polluted habitats was 6.7–64% (LD50 = 1.682) and 67.6–96% (LD50 = 0.806), respectively.ConclusionsThe present study reveals that minor populations of An. arabiensis larval forms are adapted to breed in polluted urban habitats, which further influenced susceptibility to Temephos, especially for the melanic larval forms. This could have further implications on the biology of the malaria vector and on the transmission and epidemiology of urban malaria in Sudan.

Cross sectional study to determine chloroquine resistance among Plasmodium falciparum clinical isolates from Khartoum, Sudan

Background: Malaria continues to present a global health threat; the World Health Organization (WHO) reported 214 million cases of malaria by the year 2015 with a death rate of 438000. Sudan is endemic to malaria with over 95% of malaria cases due to Plasmodium falciparum. Chloroquine is a well-established drug in the treatment of P. falciparum malaria although its use has declined since its introduction as the drug of choice in treatment of malaria in Sudan. The mechanism of resistance has been attributed to mutations in P. falciparum Chloroquine resistance transporter gene coding for a key food vacuole proteins. In current study we aimed at verifying the genetic cause of resistance to Chloroquine in field isolates of P. falciparum. Methods: Twenty P. falciparum cases were diagnosed from East Nile hospital in Khartoum and recruited in the investigation. Nested PCR was conducted to isolate mutation region in the PfCRT gene and the amplicons were sequenced using Sanger sequencing technique (Macrogen, Soule Korea). Results: 16/20 (80%) of the field isolates contained base pair mutation of codon 76 in the pfcrt gene thus being resistant to chloroquine treatment and only 4/20 (20%) did not contain such mutation. Conclusions: High treatment failures associated with Chloroquine treatment is evident of the high prevalence of mutant strains of P. falciparum field isolates thus suggesting the reduced relevance of Chloroquine as a treatment choice in the management of P. falciparum malaria.

Efficacy and safety of artemisinin-based combination therapy for uncomplicated Plasmodium falciparum malaria in Sudan: a systematic review and meta-analysis

BackgroundMalaria is a major public health problem in endemic countries including Sudan, where about 75% of populations are at risk. Due to widespread of chloroquine-resistant strains of Plasmodium falciparum, artemisinin-based combination therapy (ACT) is currently treatment of choice for malaria in the vast majority of malaria-endemic countries. This systematic review and meta-analysis is performed to obtain an overall stronger evidence of the outcomes of ACT in the treatment of uncomplicated falciparum malaria from the existing literature in Sudan.MethodsThe preferred reporting items for systematic review and meta-analysis statement were used to select studies to be included in this review. A computerized systematic strategy was adopted to search articles from PubMed, Google Scholar and Science Direct databases. Unpublished materials were also included. Open Meta-Analyst software was used to perform the meta-analysis. Random effects model was used to combine the included studies and the heterogeneity of studies was assessed using Cochrane Q and I2 (χ2 = 73.05, df (19), P < 0.001 and I2 = 73.99).ResultsTwenty studies fulfilled the inclusion criteria (ACT in the treatment of uncomplicated falciparum malaria) and were included in the final analysis with a total number of 4070 participants. Malaria treatment outcome was assessed using World Health Organization guidelines. Adequate clinical and parasitological response was used to assess treatment success at the 28th day. Treatment success of all combined studies was 98% [(95% CI 97.2–98.8%), P < 0.001]. Treatment success was higher in malaria patients treated with artemether + lumefantrine (AL) than patients treated with artesunate + sulfadoxine–pyrimethamine (AS + SP) (98.9% (95% CI 98.4–99.4%) vs 97.1% (95% CI 95.5–98.6%), P < 0.001). Eleven studies reported adverse drug reactions (ADRs) to ACT (184 participants out of 3957 (4.65%). The ADRs were mild and resolved spontaneously. There was no severe ADRs or deaths.ConclusionBased on this review, the overall malaria treatment success was high (98%). AL regimen showed higher efficacy compared to AS + SP. The overall regimens were associated with mild low rates ADRs.

Cross sectional study to determine chloroquine resistance among Plasmodium falciparum clinical isolates from Khartoum, Sudan.

Background: Malaria continues to present a global health threat; the World Health Organization (WHO) reported 214 million cases of malaria by the year 2015 with a death rate of 438000. Sudan is endemic to malaria with over 95% of malaria cases due to Plasmodium falciparum. Chloroquine is a well-established drug in the treatment of P. falciparum malaria although its use has declined since its introduction as the drug of choice in treatment of malaria in Sudan. The mechanism of resistance has been attributed to mutations in P. falciparum Chloroquine resistance transporter gene coding for a key food vacuole proteins. In current study we aimed at verifying the genetic cause of resistance to Chloroquine in field isolates of P. falciparum. Methods: Twenty P. falciparum cases were diagnosed from East Nile hospital in Khartoum and recruited in the investigation. Nested PCR was conducted to isolate mutation regionin the PfCRT gene and the amplicons were sequenced using Sanger sequencing technique (Macrogen, Soule Korea). Results: 16/20 (80%) of the field isolates contained base pair mutation of codon 76 in the pfcrt gene thus being resistant to chloroquine treatment and only 4/20 (20%) did not contain such mutation. Conclusions: High treatment failures associated with Chloroquine treatment is evident of the high prevalence of mutant strains of P. falciparum field isolates thus suggesting the reduced relevance of Chloroquine as a treatment choice in the management of P. falciparum malaria.

Efficacies of DHA\u2013PPQ and AS/SP in patients with uncomplicated Plasmodium falciparum malaria in an area of an unstable seasonal transmission in Sudan

BackgroundArtemisinin-based combination therapy (ACT), together with other control measures, have reduced the burden of falciparum malaria in sub-Saharan countries, including Sudan. Sudan adopted ACT in 2004 with a remarkable reduction in mortality due to falciparum malaria. However, emergence of resistance to the first-line treatment artesunate and sulfadoxine/pyrimethamine (AS/SP) has created new challenges to the control of malaria in Sudan. A search for an alternative drug of choice for treating uncomplicated malaria has become inevitable. The objective of this study was to evaluate the therapeutic efficacies of dihydroartemisinin/piperaquine (DHA–PPQ) and AS/SP in an area of unstable transmission in Blue Nile State, Sudan in 2015–16.MethodsA total of 148 patients with uncomplicated malaria were recruited in the study from November 2015 to end of January 2016. Seventy-five patients received DHA–PPQ while 73 received AS/SP. Patients were monitored for clinical and parasitological outcomes following the standard WHO protocol for a period of 42 days for DHA–PPQ and 28 days for AS/SP; nested PCR (nPCR) was performed to confirm parasite re-appearance from day 7 onwards.ResultsFifty-five patients completed the DHA–PPQ arm protocol with success cure rate of 98.2% (95% CI 90.3–100%) and one late clinical failure 1.8% (95% CI 0.0–9.7%). The AS/SP showed adequate clinical and parasitological response (ACPR) of 83.6% (95% CI 71.9–91.8%), early treatment failure was 1.6% (95% CI 0.0–8.8%) and late parasitological failure (LPF) was 14.8% (95% CI 7–26.2%). The respective PCR uncorrected LPF was 20%.ConclusionDHA–PPQ is an efficacious ACT and candidate for replacement of first-line treatment in Sudan while AS/SP showed high treatment failure rate and must be replaced.

High efficacy of artemether-lumefantrine and declining efficacy of artesunate+sulfadoxine-pyrimethamine against Plasmodium falciparum in Sudan (2010-2015): evidence from in vivo and molecular marker studies.

BackgroundThe present paper reports on studies that evaluated artesunate + sulfadoxine-pyrimethamine (AS + SP) which is the first-line drug and artemether-lumefantrine (AL) which is a second-line drug against uncomplicated falciparum malaria in Sudan. This evaluation was performed in twenty studies covering six sentinel sites during five successive annual malaria transmission seasons from 2010 to 2015.MethodsThe standard World Health Organization protocol was used for a follow-up period of 28 days. The frequency distribution of molecular markers for antifolate resistance in dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes was studied in pre-treatment samples in four sites in 2011.ResultsIn the nine studies of AL conducted at five sites (n = 595), high PCR-corrected cure rates were found, ranging from 96.8 to 100 %. Among the eleven studies of AS + SP (n = 1013), a decline in the PCR-corrected cure rates was observed in Gedaref in Eastern Sudan: 91.0 % in the 2011–12 season and 86.5 % in the 2014–15 season. In the remaining sites, the AS + SP cure rates ranged between 95.6 and 100 %. The rate of clearance of microscopic gametocytaemia after treatment was not significantly different with AL or AS + SP on days 7, 14, 21 and 28 of follow-up. A total of 371 pre-treatment samples were analysed for molecular markers of SP resistance. The temporal changes and geographical differences in the frequency distribution of SP-resistance genotypes showed evidence of regional differentiation and selection of resistant strains.ConclusionThe findings of this study call for a need to review the Sudan malaria treatment policy. Epidemiological factors could play a major role in the emergence of drug-resistant malaria in eastern Sudan.Australian New Zealand Clinical Trials RegistryTrial registration numbers 2011–2012: ACTRN12611001253998, 2013–2015: ACTRN12613000945729

Pharmacokinetics of Artesunate Alone and in Combination with Sulfadoxine/Pyrimethamine in Healthy Sudanese Volunteers

Artesunate (AS) in combination with sulfadoxine/pyrimethamine (SP) is the first-line therapy for management of uncomplicated Plasmodium falciparum malaria in Sudan. The objective of this study was to assess the potential impact of SP on the pharmacokinetics of AS and its active metabolite, dihydroartemisinin (DHA), in healthy adults. A single-dose, randomized, open-label, crossover study design with a washout period of three weeks was performed with 16 volunteers. After oral administration of AS alone or in combination with SP, Tmax values of AS and DHA were significantly prolonged in the combination group (P < 0.05). However, there was no significant effect on the other pharmacokinetic parameters (P > 0.05). The t1/2 values of AS and DHA were significantly higher in females than in males (P < 0.05). The present findings suggest that co-administration of SP with AS has no clinically relevant impact on the pharmacokinetics of AS or DHA in healthy persons.

Selection of pfdhfr/pfdhps alleles and declining artesunate/sulphadoxine-pyrimethamine efficacy against Plasmodium falciparum eight years after deployment in eastern Sudan

BackgroundArtesunate/sulphadoxine-pyrimethamine (AS/SP) has been the first-line treatment for falciparum malaria in Sudan since 2004. The impact of this combination on anti-malarial resistance-associated molecular markers has not been investigated. In this study, an evaluation of the efficacy and prevalence of drug resistance alleles (pfcrt, pfmdr1, pfdhfr and pfdhps) eight years after the adoption of AS/SP in eastern Sudan is reported.MethodsA 28-day follow-up efficacy trial of AS/SP was conducted in eastern Sudan during the 2012 transmission season. Blood smears were collected from patients on days 0, 1, 2, 3, 7, 14, 21 and 28. Blood spots on filter paper were obtained pre-treatment and on the day the patient was parasite positive by microscopy. Genotyping of alleles was performed by qPCR (pfcrt 72–76 and pfmdr1 copy number) and direct sequencing of pfmdr1, pfdhfr and pfdhps.ResultsSixty-three patients out of 68 (93%) completed the 28-day follow-up, adequate clinical, and parasitological response occurred in 90.5% and 85.3% of the patients in the per-protocol and intent-to-treat analyses, respectively. PCR corrected per-protocol efficacy was 93.7%. The enrolment prevalence of pfcrt-CVMNK was 30.2% and pfmdr1-N86 was 40.3%. The pfmdr1 haplotype NFD occurred in 32.8% of pre-treatment samples and was significantly higher than previous reports (Fisher’s exact p = 0.0001). The pfdhfr-51I/108N combination occurred in all sequenced isolates and 59R was observed in a single individual. pfdhps substitutions 436A, 437G, 540E, 581G and 613S were observed at 7.8, 77.3, 76.9%, 33.8% and 0.0%, respectively. Treatment failures were associated with the pfdhps haplotype SGEGA at these five codons (OR 7.3; 95% CI 0.65 - 368; p = 0.048).ConclusionThe decrease of CQR associated genotypes reflects the formal policy of complete removal of CQ in Sudan. However, the frequency of markers associated with SP failure is increasing in this study area and may be contributing to the treatment efficacy falling below 90%. Further monitoring of AS/SP efficacy and of post-treatment selection of pfdhfr and pfdhps alleles in vivo is required to inform future treatment guidelines.

A population pharmacokinetic model of piperaquine in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum malaria in Sudan

BackgroundPregnancy is associated with an increased risk of developing a malaria infection and a higher risk of developing severe malaria. The pharmacokinetic properties of many anti-malarials are also altered during pregnancy, often resulting in a decreased drug exposure. Piperaquine is a promising anti-malarial partner drug used in a fixed-dose combination with dihydroartemisinin. The aim of this study was to investigate the population pharmacokinetics of piperaquine in pregnant and non-pregnant Sudanese women with uncomplicated Plasmodium falciparum malaria.MethodSymptomatic patients received a standard dose regimen of the fixed dose oral piperaquine-dihydroartemisinin combination treatment. Densely sampled plasma aliquots were collected and analysed using a previously described LC-MS/MS method. Data from 12 pregnant and 12 non-pregnant women were analysed using nonlinear mixed-effects modelling. A Monte Carlo Mapped Power (MCMP) analysis was conducted based on a previously published study to evaluate the power of detecting covariates in this relatively small study.ResultsA three-compartment disposition model with a transit-absorption model described the observed data well. Body weight was added as an allometric function on all clearance and volume parameters. A statistically significant decrease in estimated terminal piperaquine half-life in pregnant compared with non-pregnant women was found, but there were no differences in post-hoc estimates of total piperaquine exposure. The MCMP analysis indicated a minimum of 13 pregnant and 13 non-pregnant women were required to identify pregnancy as a covariate on relevant pharmacokinetic parameters (80% power and p=0.05). Pregnancy was, therefore, evaluated as a categorical and continuous covariate (i.e. estimate gestational age) in a full covariate approach. Using this approach pregnancy was not associated with any major change in piperaquine elimination clearance. However, a trend of increasing elimination clearance with increasing gestational age could be seen.ConclusionsThe population pharmacokinetic properties of piperaquine were well described by a three-compartment disposition model in pregnant and non-pregnant women with uncomplicated malaria. The modelling approach showed no major difference in piperaquine exposure between the two groups and data presented here do not warrant a dose adjustment in pregnancy in this vulnerable population.

The Effects of Climate Changes on The Distribution and Spread of Malaria in Sudan

Many diseases in Africa such as malaria are known to be sensitive to climate factors there is a positive correlation between malaria, cholera and meningitis, and climatic elements. Regular limits of malaria allocation indicate that malaria could develop for several months in most areas of Sudan due to climate variables. The study found that the malaria cases related to temperature increasing was clearly recognized in the Northern State with 1.59% out of the state population. The highest endemic state was Blue Nile with 2.45% in the Rich Wet Savannah, and the lowest state of malaria infections was Western Darfur with 0.06% cases. The total of malaria infections in northern Sudan is 15.19% of 29 million population, the prevalence of malaria in southern Sudan was 24.5% of 9.5 million population (including 2004 and 2005 returnees) of those examined were infected. Whilst in Khartoum State the mean number of cases increased to reach 60869 in the study period 5.5 million of population as the largest inhibited state.

Factors Influencing the Usage of Insecticide Treated Mosquito Nets among Pregnant Women

Purpose: Malaria in Sudan is a leading cause of morbidity and mortality. Incidence remains very high especially among pregnant women and children under five. study was conducted to determine the factors influencing the usage of insecticide treated mosquito nets (ITNs) for prevention of malaria among pregnant women. Methods: A cross-sectional study design with convenience nts, prevalence of malaria was 71.2%. The coverage of ITNs was 58.7% but only 11.5% used ITNs regularly. Ninety six (92.3%) showed good knowledge on malaria causes, 103 (99%) had good knowledge on malaria complications and 62 (59.6%) showed good knowledge on the aim of ITNs usage. Only 23 (22.1%) knew the proper usage of ITNs. Maternal age, income, gravidity, parity, abortion, number of family members, usage of ITNs during last pregnancy, previous history of malaria, usage of ITNs by other family members and accessibility to ITNs were significantly associated with current usage of ITNs. Conclusion: Although there was good knowledge of ITNs among women in Sudan, proper usage of ITNs is poor. Factors influencing usage of ITNs among the pregnant women include maternal age, income, gravidity, parity, abortion, number of family members, usage of ITNs during last pregnancy, previous history of malaria, usage of ITNs by other family members and accessibility to ITNs. Keywords: ITN, malaria, pregnancy, Sudan.

Pregnancy-Associated Malaria in Sudan: Prevalence and Possible Risk Factors

This study aimed to investigate the malaria infection prevalence and predisposing risk factors among some pregnant women in Greater Khartoum area, Sudan. Following informed consent, eight hundred thirty six pregnant women were interviewed and thick blood films were prepared and examined for malaria parasites. Parasite densities were determined by counting parasites against 200 leukocytes assuming a white blood cells count of 6,000/µl. PCR was performed using outer and nested primers to enhance detection of parasitemia below the microscopy threshold, after DNA extraction by chelex method. Microscopy and species-specific PCR results showed that 26.2% and 56.5% of women were positive respectively. Low parity and young-aged pregnant women were significantly associated with parasitemia (p=0.001, 0.004). Second trimester pregnancy (adjusted odd ratio (aOR), 3.2 (95% CI, 2.9-5.8,)) and season of antenatal visit ((aOR), 1.7 (95% CI, (0.9-1.1)) constituted a significant risk factor for contracting malaria. In a multivariate analysis, mothers <20 years ((aOR), 2.4 (95% CI, 1.3-3.0)), first and second pregnancies ((aOR), 2.0 (95% CI, 1.1-1.9)), poverty- related factors (low-income, illiteracy) were independent predictors for P. falciparum infection. Pregnancy-associated P. falciparum malaria is prevalent among Sudanese pregnant women with evidence of close correlation to low parity, young age and socioeconomic status.

Pregnancy-associated malaria in Sudan: prevalence and possible risk factors

Pregnancy-associated malaria in Sudan: prevalence and possible risk factors

Artemisinin derivatives for treatment of uncomplicated Plasmodium falciparum malaria in Sudan: too early for too much hope

The artemisinin-based combination therapy (ACT) is adopted by several countries as first line for malaria treatment in the last decade. Concomitantly, the World Health Organization and other research reports showed a dramatic decline in malaria burden in terms of morbidity, mortality and treatment failure (TF). The optimistic features of ACT are regularly reported with great hopes, while the pessimistic facets either not existing or underreported. However, the dependence on ACT as a single chemotherapeutic agent for malaria control bears considerable risks. Occurrence and spread of artemisinin derivatives (AD) TF will be a major threat, whether it is due to parasite drug resistance or use of poor drug quality. In addition, the safety of AD is not yet fully known. In this short review, two clinical trials performed to evaluate the efficacy and safety of AD, dihydroartemisinin (DHA) plus chloroquine and artesunate (AS) plus fansidar, in Sudan are critically discussed. The conclusions from both studies were that, the TF rate of DHA indicates arrival of counterfeit AD to Africa, and both rate of TF and undesirable effects of AS/SP were recognized. Both findings indicate that it is too early for too much hope on AD.

The effect of Point Mutations in Dihydrofolate reductase genes and Multidrug resistance gene 1-86 on treatment of falciparum malaria in Sudan

One of the major problems to the treatment of malaria is the emergence and spread of parasite resistant to antimalarial drugs. Due to increased chloroquine (CQ) resistance, the antifolate combinations are becoming important in the chemotherapy of falciparum malaria. However, resistance to antifolate exists and they are still effective in the above combinations. This study aimed at determining the prevalence of antimalarial drug resistance markers in P. falciparum isolates, involving the detection of mutations at the mdr 1- 86 which associates with amodiaquine resistance, and dhfr mutations associated with SP resistances. The dot-blot/ probe hybridization, which is more sensitive and specific; it detects parasitaemia of less than 100 parasites/microl of blood, and can identify a minority parasite genotype down to 1% in a mixture, was adopted to determine multi-drug resistance (mdr1-86) to show the correlation of Amodiaquine (AQ) resistance and PCR/ RFLP adopted to determine dihydrofolate reductase (dhfr) baseline resistance to Sulphadoxine- Pyrimethamine (SP) resistance in Nubian region of southern Sudan. A randomized open label trial of Artesunate (AS) + SP and AS+ SP was carried out in children less than 5 years. Molecular analysis of filter paper preserved blood samples collected was carried out to provide a baseline estimate of allele prevalences. Baseline of the allele prevalence of the mdr1 86 locus in the AS+ AQ was successful for 80 isolates: 71(8.11%) carried parasites harbouring the mdr1-86 Tyr resistance allele, while 7 (89.19%) carried mdr1-86 Asn sensitivity allele and 2 (2.7%) were of mixed infection, having both resistance and wild type allele. Overall, the prevalence of the dhfr point mutation, codon 51, 59 and 108: 82.5% (132/160) carried mutations at dhfr (N51I, C59R or S108N), but triple mutants were rare (3.1%) in the AS + SP arm. The research provides the evidence that mutations present in dhfr and mdr1 86 has a significant effect on the type of treatment following SP and AQ chemotherapy. SP resistance may spread rapidly, and AS + AQ is likely to be a better option, provided AQ use is restricted to the combination. The significance of the study shows that definitely combination of drugs improves SP therapy at the study site.