High prevalence of asymptomatic malaria in south-eastern Bangladesh

The World Health Organization (WHO) estimated 660,000 deaths in 2011 directly attributed to malaria, approximately half of the world’s population being at risk of infection [1]. The disease has re-emerged in several Central Asian countries and in Southeast Asia partly because of relenting malaria control efforts and the emergence of parasite resistance to the most commonly used anti-malarial drugs [2]. In many regions the vectors have become resistant to the main insecticides and cases of artemisinin resistance have been reported from the Greater Mekong subregion [3‐6].

Resistance to chloroquine and sulphadoxine/pyrimethamine (S/P) has been reported from Bangladesh [1] but until now there is no evidence that artemisinin resistance has spread westwards to Bangladesh, which traditionally forms a gateway to the Indian Subcontinent [7].

In 2004 the Ministry of Public Health and Family Welfare of Bangladesh revised the malaria treatment guidelines, introducing artemisinin-based combination therapy (ACT) in areas with resistance against chloroquine and S/P [1]. However, ACT was not deployed on a major scale until 2007. Despite the introduction and distribution of ACT in the last years the WHO reports a 70% increase in case numbers between 2000 and 2010 in Bangladesh. However, it is difficult to discern the underlying trend in malaria incidence from improved reporting due to continuous improvements in diagnostic facilities [8]. A seemingly contradictory statement was given in the 2012 report where a decrease of 69% in malaria case incidence between 2000 and 2011 has been reported [1]. Due to a shortage of staff in health care facilities and shortcomings in surveillance and information systems there is still a significant lack of data on malaria from this area [9, 10]. Further increasing drug resistance is significantly aggravating the malaria situation and treatment alternatives to currently used anti-malarials are missing [11‐14].

In 2007 a rapid diagnostic test (RDT)-based, cross-sectional survey in 13 eastern districts of the country showed malaria to be endemic within the entire study area. Overall prevalence was reported to be approximately 4%, the majority of cases (90.2%) due to Plasmodium falciparum. Plasmodium vivax and mixed infections accounted for only 5.3%and 4.5%, respectively. Highest prevalence rates were reported from the Chittagong Hill Tract (CHT) with up to 15% [15]. Surveys among febrile patients in the region showed a malaria positivity rate of 26% by microscopy (Swoboda et al. personal communication), which increases to 50% when using polymerase chain reaction (PCR), a considerably more sensitive diagnostic tool [16].

The high sensitivity of PCR allows detecting subpatent infections that are frequently asymptomatic and it has been shown that those undetected infections represent a considerable fraction of overall infections and may therefore act as a reservoir for transmission [17‐21]. The aim of this study was therefore to assess prevalence and proportion of asymptomatic P. falciparum infections in the southernmost district of the CHTs.

Malaria is a major public health problem in southeastern Bangladesh and remains one of the most common reasons for hospital admissions during the malaria season [15]. Mapping of high-risk areas is essential for planning health interventions [37]. The primary objective of this investigation was to establish detailed baseline data on the prevalence and distribution of malaria in both symptomatic and asymptomatic carriers of Plasmodium parasites in southeastern Bangladesh.

Three major observations can be deducted from these cross-sectional surveys. First, this study demonstrates that malaria is meso-endemic in the region and is concentrated in rural communities [38] where the intensity of transmission is largely dependent on environmental variables. Haque et al. have previously reported for this region that environmental factors, such as proximity to forest, household density, and elevation tend to be significantly and positively correlated with malaria risk [39]. The development of immunity is insufficient to prevent the effect of malaria on all age groups [35]. A spleen rate of 18.6% (proportions of splenomegaly >10% are considered to be related to malaria [35]) and malaria prevalence by microscopy of 14.2% in the rainy and 7.8% in dry season, show that malaria is meso-endemic throughout the year in this part of Bangladesh. The spleen rate and the higher malaria prevalence in children are further indicators of meso-endemicity and suggest that transmission occurs within the villages [35, 38].

Second, malaria prevalence was significantly higher in the northern and eastern subdistricts that are located in the hilly areas bordering Myanmar and Rangamati, another endemic district, whereas endemicity was lower in western and southern subdistricts in or close to the coastal plains, which are more accessible and where access to health care facilities is better. The collected data indicate a level of malaria transmission similar to some African countries, such as Gabon [21], Somalia [40] or Mozambique [41]. Previous studies from India and Indonesia also detected similar parasite prevalence rates [42, 43].

Third, a large reservoir of asymptomatic, parasitaemic individuals that are likely to act as a source of infection, was observed in both surveys. The absence of malaria-like symptoms may be an indication of a certain level of immunity in rural communities. Although generally considered to be a typical feature of malaria in highly endemic regions in Africa, a number of studies from Brazil, Peru, Thailand, Cambodia, Myanmar, Vietnam, eastern Indonesia, and Papua New Guinea have reported the existence of asymptomatic malaria infections outside of Africa and in areas with lower endemicity [34, 43‐49]. This survey indicates a similar proportion of asymptomatic malaria carriers as previously reported from Vietnam [50], Indonesia [43] and Cambodia [45].

Naturally acquired immunity against P. falciparum, which is believed to build up with long-term exposure to malaria and presents with lower parasite densities and fewer clinical malaria episodes in older children and adults, has been reported from endemic areas in Myanmar, eastern Indonesia and India [42]. In areas with lower transmission intensity, the age at which clinical immunity develops tends to shift to an older age [42]. Malaria prevalence, parasite density and the number of clinical malaria cases were higher in children under 15 years.

As previously reported by Alves et al. [46], asymptomatic carriers may act as a reservoir for parasites and are a likely source of infection. However, treatment is typically only provided to symptomatic patients as asymptomatic carriers are rarely seen and/or diagnosed at health care facilities. Particularly in times of malaria elimination, asymptomatic malaria carrier with a low parasitaemia will present new challenges for malaria control in the region where malaria diagnosis is mainly based on microscopy and RDT.

Limitations of this study include all potential shortcomings of a point-prevalence study as well as the potential bias arising from the fact that only one district has been surveyed which may not be representative for all 13 malaria endemic districts in Bangladesh. Secondly, there was some overlap with the previously reported cross-sectional survey based on RDTs [15], which, however, provides far less detailed epidemiological data.

The surveys showed that there are areas in Bangladesh with prevalence rates comparable to those found in malaria-endemic regions of tropical Africa. This study indicates, in accordance with other studies from Southeast Asia, that there is still a substantial proportion of asymptomatic, parasitaemic individuals in Bangladesh that may act as a silent reservoir for malaria transmission. This has major implications for ongoing malaria control programs in Bangladesh that are based on prevention of infection through bed nets and treatment of symptomatic patients. Particularly considering ongoing elimination efforts these findings highlight the need for new intervention strategies targeting all infections, symptomatic as well as asymptomatic, for reducing potential sources of infection and for interrupting the transmission cycle. Based on this study, it is evident that malaria remains an important public health problem in the southeastern part of Bangladesh. Further research is needed to determine the role of asymptomatic individuals for malaria transmission in the area.