Seasonal malaria chemoprevention in a context of high presumed sulfadoxine-pyrimethamine resistance: malaria morbidity and molecular drug resistance profiles in South Sudan.

BACKGROUND: Seasonal malaria chemoprevention (SMC) using sulfadoxine-pyrimethamine plus amodiaquine (SP-AQ), is a community-based malaria preventive strategy commonly used in the Sahel region of sub-Saharan Africa. However, to date it has not been implemented in East Africa due to high SP resistance levels. This paper is a report on the implementation of SMC outside of the Sahel in an environment with a high level of presumed SP-resistance: five cycles of SMC using SPAQ were administered to children 3-59 months during a period of high malaria transmission (July-December 2019) in 21 villages in South Sudan. METHODS: A population-based SMC coverage survey was combined with a longitudinal time series analysis of health facility and community health data measured after each SMC cycle. SMC campaign effectiveness was assessed by Poisson model. SPAQ molecular resistance markers were additionally analysed from dried blood spots from malaria confirmed patients. RESULTS: Incidence of uncomplicated malaria was reduced from 6.6 per 100 to an average of 3.2 per 100 after SMC administration (mean reduction: 53%) and incidence of severe malaria showed a reduction from 21 per 10,000 before SMC campaign to a mean of 3.3 per 10,000 after each cycle (mean reduction: 84%) in the target group when compared to before the SMC campaign. The most prevalent molecular haplotype associated with SP resistance was the IRNGE haplotype (quintuple mutant, with 51I/59R/108N mutation in pfdhfr + 437G/540E in pfdhps). In contrast, there was a low frequency of AQ resistance markers and haplotypes resistant to both drugs combined (< 2%). CONCLUSIONS: The SMC campaign was effective and could be used as an additional preventive tool in seasonal malaria settings outside of the Sahel, especially in areas where access to health care is unstable. Malaria case load reduction was observed despite the high level of resistance to SP.

Screening for K13-Propeller Mutations Associated with Artemisinin Resistance in Plasmodium falciparum in Yambio County (Western Equatoria State, South Sudan).

Artemisinin-combined treatments are the recommended first-line treatment of Plasmodium falciparum malaria, but they are being threatened by emerging artemisinin resistance. Mutations in pfk13 are the principal molecular marker for artemisinin resistance. This study characterizes the presence of mutations in pfk13 in P. falciparum in Western Equatoria State, South Sudan. We analyzed 468 samples from patients with symptomatic malaria and found 15 mutations (8 nonsynonymous and 7 synonymous). Each mutation appeared only once, and none were validated or candidate markers of artemisinin resistance. However, some mutations were in the same or following position of validated and candidate resistance markers, suggesting instability of the gene that could lead to resistance. The R561L nonsynonymous mutation was found in the same position as the R561H validated mutation. Moreover, the A578S mutation, which is widespread in Africa, was also reported in this study. We found a high diversity of other pfk13 mutations in low frequency. Therefore, routine molecular surveillance of resistance markers is highly recommended to promptly detect the emergence of resistance-related mutations and to limit their spread.

Plasmodium falciparum pfhrp2 and pfhrp3 Gene Deletions in Malaria-Hyperendemic Region, South Sudan.

Pfhrp2 and pfhrp3 gene deletions threaten the use of Plasmodium falciparum malaria rapid diagnostic tests globally. In South Sudan, deletion frequencies were 15.6% for pfhrp2, 20.0% for pfhrp3, and 7.5% for double deletions. Deletions were approximately twice as prevalent in monoclonal infections than in polyclonal infections.

Malaria indicator survey 2009, South Sudan: baseline results at household level.

BACKGROUND: South Sudan has borne the brunt of years of chronic warfare and probably has the highest malaria burden in sub-Saharan Africa. Malaria is the leading cause of morbidity and mortality in the country. This nationally representative survey aimed to provide data on malaria indicators at household level across the country. METHODS: In 2009, data were collected using a two-stage random cluster sample of 2,797 households in 150 census enumeration areas during a Malaria Indicator Survey (MIS) in South Sudan. The survey determined parasite and anaemia prevalence in vulnerable population groups and evaluated coverage, use and access to malaria control services. Standardized Roll Back Malaria Monitoring and Evaluation Reference Group (RBM-MERG) MIS household and women's questionnaires were adapted to the local situation and used for collection of data that were analysed and summarized using descriptive statistics. RESULTS: The results of this survey showed that 59.3% (95% CI: 57.5-61.1) of households owned at least one mosquito net. The proportion of the population with access to an ITN in their household was 49.7% (95% CI: 48.2-51.2). The utilization of insecticide-treated nets was low; 25.3% (95% CI: 23.9-26.7) for children under five (U5) and 35.9% (95% CI: 31.9-40.2) of pregnant women (OR: 1.66 (1.36-2.01); P =0.175). Prevalence of infection was 24.5% (95% CI: 23.0-26.1) in children U5 and 9.9% (95% CI: 7.4-13.1) in pregnant women. About two thirds (64%) of children U5 and 46% of pregnant women were anaemic. Only 2% of households were covered by indoor residual spraying (IRS) the previous year. Data shows that 58% reported that malaria is transmitted by mosquitoes, 34% mentioned that the use of mosquito nets could prevent malaria, 41% knew the correct treatment for malaria, and 52% of the children received treatment at a health facility. CONCLUSION: The observed high malaria prevalence could be due to low levels of coverage and utilization of interventions coupled with low knowledge levels. Therefore, access and utilization of malaria control tools should be increased through scaling up coverage and improving behaviour change communication.

Malaria control in South Sudan, 2006-2013: strategies, progress and challenges.

BACKGROUND: South Sudan has borne the brunt of years of chronic warfare and probably has the highest malaria burden in sub-Saharan Africa. However, effective malaria control in post-conflict settings is hampered by a multiplicity of challenges. This manuscript reports on the strategies, progress and challenges of malaria control in South Sudan and serves as an example epitome for programmes operating in similar environments and provides a window for leveraging resources. CASE DESCRIPTION: To evaluate progress and challenges of the national malaria control programme an in-depth appraisal was undertaken according to the World Health Organization standard procedures for malaria programme performance review. Methodical analysis of published and unpublished documents on malaria control in South Sudan was conducted. To ensure completeness, findings of internal thematic desk assessments were triangulated in the field and updated by external review teams. DISCUSSION AND EVALUATION: South Sudan has strived to make progress in implementing the WHO recommended malaria control interventions as set out in the 2006-2013 National Malaria Strategic Plan. The country has faced enormous programmatic constraints including infrastructure, human and financial resource and a weak health system compounded by an increasing number of refugees, returnees and internally displaced people. The findings present a platform on which to tailor an evidence-based 2014-2018 national malaria strategic plan for the country and a unique opportunity for providing a model for countries in a post-conflict situation. CONCLUSIONS: The prospects for effective malaria control and elimination are huge in South Sudan. Nevertheless, strengthened coordination, infrastructure and human resource capacity, monitoring and evaluation are required. To achieve all this, allocation of adequate local funding would be critical.