M. Ridwanur Rahman

N-Acetylcysteine as adjunctive treatment in severe malaria: A randomized double blinded placebo controlled clinical trial

Objective:Markers of oxidative stress are reported to be increased in severe malaria. It has been suggested that the antioxidant N-acetylcysteine (NAC) may be beneficial in treatment. We studied the efficacy and safety of parenteral NAC as an adjunct to artesunate treatment of severe falciparum malaria. Design:A randomized, double-blind, placebo-controlled trial on the use of high-dose intravenous NAC as adjunctive treatment to artesunate. Setting:A provincial hospital in Western Thailand and a tertiary referral hospital in Chittagong, Bangladesh. Patients:One hundred eight adult patients with severe falciparum malaria. Interventions:Patients were randomized to receive NAC or placebo as an adjunctive treatment to intravenous artesunate. Measurements and Main Results:A total of 56 patients were treated with NAC and 52 received placebo. NAC had no significant effect on mortality, lactate clearance times (p = 0.74), or coma recovery times (p = 0.46). Parasite clearance time was increased from 30 hours (range, 6–144 hours) to 36 hours (range, 6–120 hours) (p = 0.03), but this could be explained by differences in admission parasitemia. Urinary F2-isoprostane metabolites, measured as a marker of oxidative stress, were increased in severe malaria compared with patients with uncomplicated malaria and healthy volunteers. Admission red cell rigidity correlated with mortality, but did not improve with NAC. Conclusion:Systemic oxidative stress is increased in severe malaria. Treatment with NAC had no effect on outcome in patients with severe falciparum malaria in this setting.

Temporal trends in severe malaria in Chittagong, Bangladesh

BackgroundEpidemiological data on malaria in Bangladesh are sparse, particularly on severe and fatal malaria. This hampers the allocation of healthcare provision in this resource-poor setting. Over 85% of the estimated 150,000-250,000 annual malaria cases in Bangladesh occur in Chittagong Division with 80% in the Chittagong Hill Tracts (CHT). Chittagong Medical College Hospital (CMCH) is the major tertiary referral hospital for severe malaria in Chittagong Division.MethodsMalaria screening data from 22,785 inpatients in CMCH from 1999–2011 were analysed to investigate the patterns of referral, temporal trends and geographical distribution of severe malaria in Chittagong Division, Bangladesh.ResultsFrom 1999 till 2011, 2,394 malaria cases were admitted, of which 96% harboured Plasmodium falciparum and 4% Plasmodium vivax. Infection was commonest in males (67%) between 15 and 34 years of age. Seasonality of malaria incidence was marked with a single peak in P. falciparum transmission from June to August coinciding with peak rainfall, whereas P. vivax showed an additional peak in February-March possibly representing relapse infections. Since 2007 there has been a substantial decrease in the absolute number of admitted malaria cases. Case fatality in severe malaria was 18% from 2008–2011, remaining steady during this period.A travel history obtained in 226 malaria patients revealed only 33% had been to the CHT in the preceding three weeks. Of all admitted malaria patients, only 9% lived in the CHT, and none in the more remote malaria endemic regions near the Indian border.ConclusionsThe overall decline in admitted malaria cases to CMCH suggests recent control measures are successful. However, there are no reliable data on the incidence of severe malaria in the CHT, the most endemic area of Bangladesh, and most of these patients do not reach tertiary health facilities. Improvement of early treatment and simple supportive care for severe malaria in remote areas and implementation of a referral system for cases requiring additional supportive care could be important contributors to further reducing malaria-attributable disease and death in Bangladesh.

Snake bite in Chittagong Division, Bangladesh: a study of bitten patients who developed no signs of systemic envenoming.

The demographics, epidemiology, first aid, clinical management, treatment and outcome of snake bites causing no significant signs of systemic envenoming were documented in Chittagong Medical College Hospital, Bangladesh, between May 1999 and October 2002. Among 884 patients admitted, 350 were systemically envenomed and 534 were without signs of either systemic or significant local envenoming. The average age of patients with physical evidence of snake bite but no systemic envenoming was 26.4 years. Most had been bitten on their feet or hands. Ligatures had been applied proximal to the bite site in >95% of cases and the bite site had been incised in 13%. Patients were typically discharged at 24h. Those with clinical signs of systemic envenoming resembled the non-envenomed cases demographically and epidemiologically except that they arrived at hospital significantly later than non-envenomed patients, having spent longer with traditional healers. No non-envenomed patient was treated with antivenom and none went on to develop symptoms of systemic envenoming after discharge. The potential complications and confusing signs caused by ligatures and incision demand that all patients admitted with a history of snake bite be kept under observation for 24h after admission even if they have no signs of systemic envenoming.

The geography of malaria elimination in Bangladesh: combining data layers to estimate the spatial spread of parasites

Malaria control programs face difficult resource allocation decisions. Of particular concern for countries aiming for malaria elimination, the regular movement of individuals to and from endemic areas undermines local interventions by reintroducing infections and sustaining local transmission. Quantifying this movement of malaria parasites around a country has become a priority for national control programs, but remains methodologically challenging, particularly in areas with highly mobile populations. Here, we combined multiple data sources to measure the geographical spread of malaria parasites, including epidemiological surveillance data, travel surveys, parasite genetic data, and anonymized mobile phone data. We collected parasite genetic barcodes and travel surveys from 2,090 patients residing in 176 unions in southeast Bangladesh. We developed a genetic mixing index to quantify the likelihood of samples being local or imported. We then inferred the direction and intensity of parasite flow between locations using an epidemiological model, and estimated the proportion of imported cases assuming mobility patterns parameterized using the travel survey and mobile phone calling data. Our results show that each data source provided related but different information about the patterns of geographic spread of parasites. We identify a consistent north/south separation of the Chittagong Hill Tracts region in Bangladesh, and found that in addition to imported infections from forested regions, frequent mixing also occurs in low transmission but highly populated areas in the southwest. Thus, unlike risk maps generated from incidence alone, our maps provide evidence that elimination programs must address ongoing movement of parasites around the lower transmission areas in the southwest.