Cotrimoxazole versus sulfadoxine-pyrimethamine for intermittent preventive treatment of malaria in HIV-infected pregnant women in Bangui, Central African Republic: A pragmatic randomised controlled trial.

OBJECTIVE: The main objective of the MACOMBA (Maternity and Control of Malaria-HIV co-infection in Bangui) trial was to show that cotrimoxazole (CTX) is more effective than sulphadoxine-pyremethamine-IPTp (IPTp-SP) to prevent placental malaria infection (primary end point) among HIV-positive pregnant women with a CD4+ count ≥350 cells/mm3 in Bangui, CAR. METHODS: MACOMBA is a multicentre, open-label randomised trial conducted in four maternity hospitals in Bangui. Between 2013 and 2017, 193 women were randomised and 112 (59 and 53 in CTX and IPTp-SP arms, respectively) were assessed for placental infection defined by microscopic parasitaemia or PCR. RESULTS: Thirteen women had a placental infection: five in the CTX arm (one by microscopic placental parasitaemia and four by PCR) and eight by PCR in the SP-IPTp (8.5% vs. 15.1%, p = 0.28). The percentage of newborns with low birthweight (<2500 g) did not differ statistically between the two arms. Self-reported compliance to CTX prophylaxis was good. There was a low overall rate of adverse events in both arms. CONCLUSION: Although our results do not allow us to conclude that CTX is more effective, drug safety and good compliance among women with this treatment favour its widespread use among HIV-infected pregnant women, as currently recommended by WHO.

Malaria case management by community health workers in the Central African Republic from 2009-2014: overcoming challenges of access and instability due to conflict.

BACKGROUND: In the Central African Republic (CAR), decades of armed conflict have crippled the public health system. This has left the population without timely access to life-saving services and therefore vulnerable to the numerous consequences of infectious diseases, including malaria. As a response, in 2008 an international non-governmental organization started a network of community health workers (CHWs) in the highly malaria-endemic region of northwest CAR. The area has experienced years of violent clashes between rebel groups and seen hundreds of thousands of people displaced. METHODS: Data from routine patient registers from 80 CHWs working in Paoua and Markounda sub-prefectures were entered and retrospectively reviewed. The time period covered December 2009-April 2014 and hence different stages of conflict and unrest. Several indicators were measured over time, including malaria rapid diagnostic test (RDT) positivity rates, CHW reporting rates, and malnutrition indicators. RESULTS: Among nearly 200,000 people who consulted a CHW during this period, 81% were found to be positive for malaria parasites by RDT. In total, 98.9% of these positive cases were appropriately treated with artemisinin-based combination therapy (ACT). Only 1.2% of RDT negative cases were incorrectly treated with an ACT. Monthly data from each CHW were regularly reported, with more than 96% of CHWs reporting each month in the first 3 years of the project. However, since the coup d'état in March 2013, the number of CHWs reporting each month decreased as the programme battled the additional constraints of civil war. CONCLUSIONS: Although the political crisis affected the CHWs, the programme showed that it could reach those most vulnerable and continue some level of care at all times. In addition, this programme revealed that surveillance could be maintained in conflict zones. This paper fills a significant gap in the knowledge of malaria control in CAR and this is especially important for agencies which must often decide in a short space of time how to respond effectively to complex emergencies.

A brief review on features of falciparum malaria during pregnancy.

Malaria in pregnancy is a serious public health problem in tropical areas. Frequently, the placenta is infected by accumulation of Plasmodium falciparum-infected erythrocytes in the intervillous space. Falciparum malaria acts during pregnancy by a range of mechanisms, and chronic or repeated infection and co-infections have insidious effects. The susceptibility of pregnant women to malaria is due to both immunological and humoral changes. Until a malaria vaccine becomes available, the deleterious effects of malaria in pregnancy can be avoided by protection against infection and prompt treatment with safe, effective antimalarial agents; however, concurrent infections such as with HIV and helminths during pregnancy are jeopardizing malaria control in sub-Saharan Africa.

A brief review on features of falciparum malaria during pregnancy

Malaria in pregnancy is a serious public health problem in tropical areas. Frequently, the placenta is infected by accumulation of Plasmodium falciparum-infected erythrocytes in the intervillous space. Falciparum malaria acts during pregnancy by a range of mechanisms, and chronic or repeated infection and co-infections have insidious effects. The susceptibility of pregnant women to malaria is due to both immunological and humoral changes. Until a malaria vaccine becomes available, the deleterious effects of malaria in pregnancy can be avoided by protection against infection and prompt treatment with safe, effective antimalarial agents; however, concurrent infections such as with HIV and helminths during pregnancy are jeopardizing malaria control in sub-Saharan Africa

Knowledge and perceptions about malaria in communities in four districts of the Central African Republic.

BACKGROUND: Implementation of malaria control strategies may face major social and cultural challenges. Hence, understanding local knowledge about malaria helps in designing sustainable community-based malaria control programmes. We designed a pilot survey in communities in the Central African Republic to evaluate recognition of malaria symptoms, perceptions of the causes of malaria and knowledge of key preventive measures. METHODS: This cross-sectional study was conducted in four districts. Households were selected by multi-stage cluster random sampling, with villages (in Lobaye, Ouham and Ouaka) and boroughs (in Bangui City) as first-stage units and households as second-stage units. A total of 2920 householders were interviewed. RESULTS: Most of the respondents attributed malaria to mosquito bites (65.5%), but less than 50% were familiar with the classical symptoms of malaria. Hygiene and sanitation were the most frequently mentioned methods for preventing malaria (81.1%). Despite the relatively high rate of ownership of insecticide-treated nets (72.1%), community perception of these nets as a preventive measure against mosquito bites was very low (6.5%). CONCLUSIONS: The correct perceptions that mosquitoes cause malaria transmission and of environmental management for prevention are encouraging; however, awareness about the usefulness of insecticide treated-nets for malaria prevention must be raised. This study provided the national malaria control programme with baseline data for planning appropriate health education in communities.

Performance of Paracheck™-Pf, SD Bioline malaria Ag-Pf and SD Bioline malaria Ag-Pf/pan for diagnosis of falciparum malaria in the Central African Republic.

BACKGROUND: Rapid diagnostic tests (RDTs) are the current complement to microscopy for ensuring prompt malaria treatment. We determined the performance of three candidate RDTs (Paracheck™-Pf, SD Bioline malaria Ag-Pf and SD Bioline malaria Ag-Pf/pan) for rapid diagnosis of malaria in the Central African Republic. METHODS: Blood samples from consecutive febrile patients who attended for laboratory analysis of malaria at the three main health centres of Bangui were screened by microscopy and the RDTs. Two reference standards were used to assess the performance of the RDTs: microscopy and, a combination of microscopy plus nested PCR for slides reported as negative, on the assumption that negative results by microscopy were due to sub-patent parasitaemia. RESULTS: We analysed 436 samples. Using the combined reference standard of microscopy + PCR, the sensitivity of Paracheck™-Pf was 85.7% (95% CI, 80.8-89.8%), that of SD Bioline Ag-Pf was 85.4% (95% CI, 80.5-90.7%), and that of SD Bioline Ag-Pf/pan was 88.2% (95% CI, 83.2-92.0%). The tests performed less well in cases of low parasitaemia; however, the sensitivity was > 95% at > 500 parasites/µl. CONCLUSIONS: Overall, SD Bioline malaria Ag-Pf and SD Bioline malaria Ag-Pf/pan performed slightly better than Paracheck™-Pf. Use of RDTs with reinforced microscopy practice and laboratory quality assurance should improve malaria treatment in the Central African Republic.

Effectiveness of two antifolate prophylactic strategies against malaria in HIV-positive pregnant women in Bangui, Central African Republic: study protocol for a randomized controlled trial (MACOMBA).

BACKGROUND: Co-infection with malaria parasite and HIV is an emerging public health problem in tropical areas, particularly in pregnant women, and management of the concurrent effects of these two infections is challenging. Co-trimoxazole is a sulfamide preparation used to prevent opportunistic infections in HIV-infected patients, and many studies have reported that it has significant activity against malaria. As the efficacy of intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) against malaria is decreasing, co-trimoxazole might be an alternative for preventing malaria among HIV-infected populations. The aim of this study is to compare the effectiveness of SP-IPT, which is recommended for the prevention of malaria during pregnancy in the Central African Republic, with that of a daily dose of co-trimoxazole against P. falciparum infections among HIV-infected pregnant women in Bangui, the capital of the Central African Republic. METHODS/DESIGN: The MACOMBA study (MAternity and COntrol of Malaria-HIV co-infection in BAngui) is a multicentre open-label randomized clinical trial conducted at four maternity hospitals in Bangui. All HIV-infected pregnant women presenting for an antenatal clinic visit between the weeks 16 and 28 of amenorrhoea, with a CD4 count of more than 350 cells/mm3, will be eligible. All the women will provide written consent before being enrolled in the study and will then be randomly allocated to either SP-IPT (25 mg of sulfadoxine and 1.25 mg of pyrimethamine) or daily co-trimoxazole doses (960 mg per dose). The primary end-point is the placental malaria parasitaemia rate at delivery. Other main outcome measures include the number of malaria episodes during pregnancy, safety, and treatment compliance. Furthermore, the frequency of molecular resistance markers dhfr and dhps will be measured. DISCUSSION: In this trial, we seek to confirm whether co-trimoxazole is operationally suitable to replace SP-IPT in order to prevent malaria among pregnant women infected with HIV in the Central African Republic. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01746199.