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.

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.

Evaluation of HRP2 and pLDH-based rapid diagnostic tests for malaria and prevalence of pfhrp2/3 deletions in Aweil, South Sudan.

BACKGROUND: Rapid diagnostic tests (RDT) for malaria are the primary tool for malaria diagnosis in sub-Saharan Africa but the utility of the most commonly used histidine-rich protein 2 (HRP2) antigen-based tests is limited in high transmission settings due to the long duration of positivity after successful malaria treatment. HRP2 tests are also threatened by the emergence of Plasmodium that do not carry pfhrp2 or pfhrp 3 genes. Plasmodium lactate dehydrogenase (pLDH)-based tests are promising alternatives, but less available. This study assessed the performances of HRP2 and pLDH(pan) tests under field conditions. METHODS: The study performed a prospective facility-based diagnostic evaluation of two malaria RDTs in Aweil, South Sudan, during the high transmission season. Capillary blood by fingerprick was collected from 800 children under 15 years of age with fever and no signs of severity. SD Bioline HRP2 and CareStart pLDH(pan) RDTs were performed in parallel, thick and thin smears for microscopy were examined, and dried blood was used for PCR testing. RESULTS: Using microscopy as the gold standard, the sensitivity of both tests was estimated at > 99%, but the specificity of each was lower: 55.0% for the pLDH test and 61.7% for the HRP2 test. When using PCR as the gold standard, the sensitivity of both tests was lower than the values assessed using microscopy (97.0% for pLDH and 96.5% for HRP2), but the specificity increased (65.1% for pLDH and 72.9% for HRP2). Performance was similar across different production lots, sex, and age. Specificity of both the pLDH and HRP2 tests was significantly lower in children who reported taking a therapeutic course of anti-malarials in the 2 months prior to enrollment. The prevalence of pfhrp2/3 deletions in the study population was 0.6%. CONCLUSIONS: The low specificity of the pLDH RDT in this setting confirms previous results and suggests a problem with this specific test. The prevalence of pfhrp2/3 deletions in the study area warrants continued monitoring and underscores the relevance of assessing deletion prevalence nationally. Improved malaria RDTs for high-transmission environments are needed.

Scale-up of a programme for malaria vector control using long-lasting insecticide-treated nets: lessons from South Sudan.

PROBLEM: Long-lasting insecticidal nets (LLINs) are important tools in malaria control. South Sudan, like many other endemic countries, has struggled to improve LLIN coverage and utilization. APPROACH: In 2006, Southern Sudan - known as South Sudan after independence in 2011 - initiated a strategic plan to increase LLIN coverage so that at least 60% of households had at least one LLIN each. By 2008, the target coverage was 80% of households and the Global Fund had financed a phased scale-up of LLIN distribution in the region. LOCAL SETTING: South Sudan's entire population is considered to be at risk of malaria. Poor control of the vectors and the large-scale movements of returnees, internally displaced people and refugees have exacerbated the problem. RELEVANT CHANGES: By 2012, approximately 8.0 million LLINs had been distributed in South Sudan. Between 2006 and 2009, the percentage of households possessing at least one LLIN increased from about 12% to 53% and LLIN utilization rates increased from 5 to 25% among children younger than 5 years and from 5 to 36% among pregnant women. The number of recorded malaria cases increased from 71 948 in 2008 to 1 198 357 in 2012. LESSONS LEARNT: In post-conflict settings, a phased programme for the national scale-up of LLIN coverage may not have a substantial impact. A nationwide campaign that is centrally coordinated and based on sound guidelines may offer greater benefits. A strong partnership base and effective channels for the timely and supplementary deployment of LLINs may be essential for universal coverage.

Addressing malaria vector control challenges in South Sudan: proposed recommendations.

Upon the signing of the Comprehensive Peace Agreement in 2005, the Republic of South Sudan (RSS) has faced a lot of challenges, such as a lack of infrastructure, human resources and an enormous burden of vector borne diseases including malaria. While a national malaria strategic plan 2006-2011 was developed, the vector control component has remained relatively weak. The strategy endorses the distribution of long-lasting insecticidal nets (LLINs) as the frontline intervention with other interventions recommended only when technical and institutional capacity is available. In 2006, a draft integrated vector management (IVM) strategic plan 2007-2012 was developed but never implemented, resulting in minimal coordination, implementation and coverage of malaria vector control tools including their inherent impact. To address this challenge, the vector control team of the National Malaria Control Programme (NMCP) is being strengthened. With the objective of building national capacity and technical collaboration for effective implementation of the IVM strategy, a national malaria vector control conference was held from 15-17th October 2012 in Juba. A range of NMCP partners, state ministries, acadaemia, private sector, national and international non-governmental organizations, including regional and global policymakers attended the meeting. The conference represented a major milestone and made recommendations revolving around the five key elements of the IVM approach. The meeting endorsed that vector control efforts in RSS be augmented with other interventions within the confines of the IVM strategy as a national approach, with strong adherence to its key elements.

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.

The Pan African Vivax and Ovale Network (PAVON): Refocusing on Plasmodium vivax, ovale and asymptomatic malaria in sub-Saharan Africa.

The recent World Malaria report shows that progress in malaria elimination has stalled. Current data acquisition by NMCPs depend on passive case detection and clinical reports focused mainly on Plasmodium falciparum (Pf). In recent times, several countries in sub-Saharan Africa have reported cases of Plasmodium vivax (Pv) with a considerable number being Duffy negative. The burden of Pv and Plasmodium ovale (Po) appear to be more than acknowledged. Similarly, the contribution of asymptomatic malaria in transmission is hardly considered by NMCPs in Africa. Inclusion of these as targets in malaria elimination agenda is necessary to achieve elimination goal, as these harbor hypnozoites. The Pan African Vivax and Ovale Network (PAVON) is a new consortium of African Scientists working in Africa on the transmission profile of Pv and Po. The group collaborates with African NMCPs to train in Plasmodium molecular diagnostics, microscopy, and interpretation of molecular data from active surveys to translate into policy. Details of the mission, rational and modus operandi of the group are outlined.