2018, Issue 12
One new review and one new protocol are available in Issue 12 of the Cochrane Database of Systematic Reviews
New Review
Das JK, Hadi YB, Salam RA, Hoda M, Lassi ZS, Bhutta ZA. Fly control to prevent diarrhoea in children. Cochrane Database of Systematic Reviews 2018, Issue 12. Art. No.: CD011654. DOI: 10.1002/14651858.CD011654.pub2
This new review, prepared by a team led by Zulfiqar Bhutta, investigates the impact of various housefly control measures on the incidence of diarrhoea and its related morbidity and mortality in children under five years of age. The role of houseflies in acting as mechanical vectors for many diarrhoea‐causing agents has been fairly well established, and the review considered interventions that work at one of many levels: reduction/elimination of fly breeding sites (manure); reduction of sources that attract houseflies (domestic waste); prevention of contact between flies and disease‐causing organisms, through improvements in sanitation and excreta disposal; and finally, protection of people, food, and food utensils from contact with flies, through the use of insecticides or fly traps. The review considered randomized controlled trials, cluster RCTs, quasi‐RCTs, and controlled before‐and‐after studies. Only one study met the inclusion criteria, a cluster RCT done in 8 villages in Pakistan, that evaluated the use of ultra‐low‐volume space spraying with insecticide to control flies in the first two years and baited fly traps in the third year. A total of 491 children under the age of five years were enrolled in the study. Insecticide spraying reduced the fly population in the intervention group during the four months of the year when both flies and cases of diarrhoea were more common, but not at other times. On average, this was associated with a reduction in the incidence of diarrhoea in the first and second year of the intervention. In the third year of the intervention, the baited fly traps did not demonstrate an effect on the fly population or on diarrhoea incidence. More research is needed.
New Protocol
Anton‐Vazquez V, Hine P, Krishna S, Richardson M, Planche T. Rapid versus standard antibiotic susceptibility testing for treating bloodstream infections. Cochrane Database of Systematic Reviews 2018, Issue 12. Art. No.: CD013235. DOI: 10.1002/14651858.CD013235
2018, Issue 11
Three new reviews, one review update and two new protocols are available in Issue 11 of the Cochrane Database of Systematic Reviews
New Reviews
Gleave K, Lissenden N, Richardson M, Choi L, Ranson H. Piperonyl butoxide (PBO) combined with pyrethroids in insecticide‐treated nets to prevent malaria in Africa. Cochrane Database of Systematic Reviews 2018, Issue 11. Art. No.: CD012776. DOI: 10.1002/14651858.CD012776.pub2
This new review, prepared by a team led by Katherine Gleave, evaluates whether adding PBO (a synergist that inhibits specific metabolic enzymes within mosquitoes) to pyrethroids to treat mosquito nets increases entomological effectiveness and malaria outcomes. Currently only one insecticide class, the pyrethroids, is commonly used to treat long‐lasting insecticidal nets (LLINs), but resistance to pyrethroids is now widespread in African malaria vectors, and innovations in the use of LLIN are essential to maintain their efficacy. Currently there are five pyrethroid‐PBO nets in production: Olyset® Plus; PermaNet® 3.0; Veeralin® LN; and DawaPlus 3.0 and 4.0. This review includes different study types, and 15 trials conducted between 2010 to 2018 met the inclusion criteria: two laboratory trials, eight experimental hut trials, and five cluster‐randomized controlled village trials. In areas of high levels of mosquito resistance to pyrethroids, pyrethroid‐PBO nets performed better than standard pyrethroid‐only nets at killing mosquitoes and preventing them from blood feeding, but this effect was not seen in areas of low or no resistance to the pyrethroid‐only insecticides. One trial with 3966 participants, in an area of high resistance to pyrethroids, found that fewer people were infected with malaria when the population used pyrethroid‐PBO nets compared to standard pyrethroid‐only nets. The findings of this review support the recent WHO policy recommendation that pyrethroid‐PBO nets should be considered for deployment in areas where pyrethroid resistance has been confirmed; questions remain about the durability of pyrethroid‐PBO nets, and their cost-effectiveness.
Aves T, Tambe J, Siemieniuk RAC, Mbuagbaw L. Antiretroviral resistance testing in HIV‐positive people. Cochrane Database of Systematic Reviews 2018, Issue 11. Art. No.: CD006495. DOI: 10.1002/14651858.CD006495.pub5
This review prepared by a team led by Lawrence Mbuagbaw summarizes the relative merits of resistance testing in treatment‐naive and treatment‐exposed people living with HIV. Testing people for resistance to antiretroviral therapy (ART) may be used at the time of initiation of therapy, or when treatment failure occurs, to inform the choice of ART regimen and improve HIV outcomes; these tests are widely used in high‐income countries, but not in resource‐limited settings, because of their high costs. The review includes 11 randomized controlled trials (published between 1999 and 2006) with a total of 2531 people. Trials included only people who had detectable HIV despite being on antiretroviral drugs; no trials included patients starting therapy for the first time. Studies were conducted in Europe, USA, or South America. Length of follow‐up time, study settings, and types of resistance testing varied greatly. Resistance testing probably improved virological outcomes in people who have had virological failure; it did not demonstrate important patient benefits in terms of risk of death or progression to AIDS. The trials included very few participants from low‐ and middle‐income countries. Based on the findings of this review, the authors recommend further investigation of the role of resistance testing in treatment‐naive people with HIV and in subpopulations with a greater incidence of transmitted drug resistance, such as men who have sex with men (MSM), commercial sex workers (CSWs), and people who inject drugs (PWIDs), as well as studies to be conducted in low‐resource settings.
Pryce J, Choi L, Richardson M, Malone D. Insecticide space spraying for preventing malaria transmission. Cochrane Database of Systematic Reviews 2018, Issue 11. Art. No.: CD012689. DOI: 10.1002/14651858.CD012689.pub2
Joseph Pryce and colleagues from the Liverpool School of Tropical Medicine have completed this review, which summarizes the evidence of the impact of space spraying on malaria transmission. Space spraying refers to the process of dispersing liquid droplets of insecticide into an area as a fog, which can be delivered using equipment that is either hand‐held, vehicle‐mounted, or applied from an aircraft. For the purposes of this Cochrane Review, the term implies distribution of insecticide at a population level, rather than household use, and the primary objective is to evaluate the impact of space spraying on malaria transmission, in comparison to equivalent conditions with no space spraying. A secondary objective was to identify and summarize the range of space spraying strategies that have been tested so far. Four studies conducted between 1972 and 2000 were identified for inclusion in the review, which used a range of insecticide delivery methods such as handheld, vehicle‐mounted, and aircraft‐mounted spraying equipment, and a variety of different insecticides, doses, and spraying times to suit the local environment and the behaviour of the targeted mosquito species. In three studies, the evidence was unsuitable for reliably assessing the impact of space spraying on the number of cases of malaria. The remaining study, which took place in a single state in India and covered a combined population of 18,460 people, reported the number of malaria cases in the years preceding and following the introduction of space spraying, and showed that space spraying led to a decrease in the number of cases of malaria. However, as the trial was conducted over 30 years ago and within one location only, we cannot be certain that these findings are applicable in other malarial areas. There is a lack of high‐quality studies assessing the effectiveness of space spraying for disease control.
Updated Review
Pryce J, Richardson M, Lengeler C. Insecticide‐treated nets for preventing malaria. Cochrane Database of Systematic Reviews 2018, Issue 11. Art. No.: CD000363. DOI: 10.1002/14651858.CD000363.pub3
Joseph Pryce, Marty Richardson and Christian Lengeler have updated this review, first published in 1998. Previous version of this review showed that insecticide‐treated nets (ITNs) are effective at reducing child mortality, parasite prevalence, and uncomplicated and severe malaria episodes. ITN-treated nets have since become a core intervention for malaria control and have contributed greatly to the dramatic decline in disease incidence and malaria‐related deaths, but the rise in resistance to pyrethroids has raised questions over whether the evidence from earlier trials can be applied to estimate the impact of ITNs on malaria transmission today. This new version of the review aims to assess the impact of ITNs on mortality and malaria morbidity, incorporating any evidence published since the previous update into new and existing analyses, and assessing the certainty of the resulting evidence using GRADE. A total of 23 trials, all conducted between 1987 and 2001, and enrolling more than 275,793 adults and children are included. Results show that despite the increase in insecticide resistance frequency and intensity in populations of malaria vectors across the world, ITN, in comparison to either no nets or not treated nets, continue to be effective at reducing child mortality from all causes and malaria‐related illness in affected areas.
New Protocols
Ochodo EA, Kakourou A, Mallett S, Deeks JJ. Point‐of‐care viral load tests to detect high HIV viral load levels in HIV‐positive people on antiretroviral therapy. Cochrane Database of Systematic Reviews 2018, Issue 11. Art. No.: CD013208. DOI: 10.1002/14651858.CD013208
Ochodo EA, Kakourou A, Mallett S, Deeks JJ. Point‐of‐care tests detecting HIV nucleic acids for diagnosis of HIV infection in infants and children aged 18 months or less. Cochrane Database of Systematic Reviews 2018, Issue 11. Art. No.: CD013207. DOI: 10.1002/14651858.CD013207
2018, Issue 10
No pubications in this Issue
2018, Issue 9
One new protocol and one review update are available in Issue 9 of the Cochrane Database of Systematic Reviews
Updated Review
El Sayed I, Liu Q, Wee I, Hine P. Antibiotics for treating scrub typhus. Cochrane Database of Systematic Reviews 2018, Issue 9. Art. No.: CD002150. DOI: 10.1002/14651858.CD002150.pub2.
This is an update of a review first published in 2000; this review has new author team (Iman El Sayed, Qin Liu, Ian Wee and Paul Hine), and a revised protocol, reflecting new methodology. Scrub typhus, caused by Orientia tsutsugamushi, is an important cause of acute fever in Asia. This bacterium is transmitted by chiggers, and most cases occur in a region which extends from Japan to India, and to Northern Australia (the ‘tsutsugamushi triangle’). Incidence varies from 1.2 to 17.7 per 100,000 per year. This review evaluates the effects of different antibiotic currently used to treat scrub typhus (tetracyclines, chloramphenicol, macrolides, and rifampicin). The authors included 6 RCTs and one quasi‐RCT with 548 participants, taking place in Korea, Malaysia and Thailand. Tetracycline, doxycycline, azithromycin, and rifampicin were shown to be effective treatment options for scrub typhus and to result in few treatment failures. Because of the risk of inducing resistance in undiagnosed tuberculosis, rifampicin should only be considered as a second‐line treatment option after exclusion of active tuberculosis. Most available evidence was of low or very low certainty. Future research should focus on larger trials of good quality, including patients with severe scrub typhus, as well as standardized diagnostic techniques and reporting of clinical outcomes, to allow robust comparisons.
New Protocol
de Souza DK, Larbi I, Boakye DA, Okebe J. Ivermectin treatment in humans for reducing malaria transmission. Cochrane Database of Systematic Reviews 2018, Issue 9. Art. No.: CD013117. DOI: 10.1002/14651858.CD013117
2018, Issue 8
Two new reviews and one review update are available in Issue 8 of the Cochrane Database of Systematic Reviews
New Reviews
Xpert® MTB/RIF assay for extrapulmonary tuberculosis and rifampicin resistance (Kohli M, Schiller I, Dendukuri N, Dheda K, Denkinger CM, Schumacher SG, Steingart KR)
This new extensive review authored by Mikashmi Kohli and colleagues analysed the diagnostic accuracy of the Xpert assay for extrapulmonary TB by site of disease, or for rifampicin resistance. Extrapulmonary TB accounts for 15% of TB cases, but the proportion is increasing; this review includes diagnostic accuracy studies on TB meningitis, pleural, lymph node, bone or joint, genitourinary, peritoneal, pericardial, and disseminated TB, as well as rifampicin resistance. 66 unique studies that evaluated 16,213 specimen were identified for inclusion; 50 studies took place in low‐ or middle‐income countries. Xpert results were measured against culture results (benchmark). In cerebrospinal fluid, pleural fluid, urine, and peritoneal fluid, Xpert was highly specific (98% or more), that is, did not register positive in people who were actually negative. Pooled Xpert sensitivity (defined by culture) varied across different types of specimens (31% in pleural tissue to 97% in bone or joint fluid), that is, the test registered positive in people who actually had TB. Regarding rifampicin resistance, Xpert pooled sensitivity and specificity were 95.0% and 98.7% respectively (high‐certainty evidence). The authors conclude that the Xpert assay may be helpful in confirming the diagnosis in people presumed to have extrapulmonary TB, and is accurate for detection of rifampicin resistance, but for people with presumed TB meningitis, treatment should be based on clinical judgement.
Drugs for treating Buruli ulcer (Mycobacterium ulcerans disease) (Yotsu RR, Richardson M, Ishii N)
Buruli ulcer is a disease caused by a mycobacterium, which results in lumps in the skin and deep ulcers, often on the arms or the face. When diagnosed late, those affected may be left with lifelong disfigurements and disabilities. The disease is most prevalent in West Africa, but it is also found in non‐tropical areas including Australia and Japan. This new review by Rie Yotsu, Marty Richardson and Norihisa Ishii summarizes the evidence of drug treatments for treating Buruli ulcer. The authors identified 18 studies for inclusion: five RCTs involving a total of 319 participants, and 13 prospective observational studies, with 1665 participants. Studies evaluated various drugs usually in addition to surgery, and were carried out across eight countries in areas with high Buruli ulcer endemicity in West Africa and Australia. The certainty of the evidence was very low. One RCT and one observational study evaluated monotherapy with clofazimine, and one RCT evaluated sulfamethoxazole/trimethoprim. All three studies had small sample sizes, and no treatment effect was demonstrated. Different combination therapies were evaluated: rifampicin with streptomycin, rifampicin with clarithromycin, rifampicin with streptomycin initially, changing to rifampicin with clarithromycin in consolidation phase, and novel therapies (rifampicin combined with either ciprofloxacin, clarithromycin, or moxifloxacin without surgery, or a combinations of two to three drugs from rifampicin, ciprofloxacin, clarithromycin, ethambutol, moxifloxacin, or amikacin). Antibiotic combination treatments appeared to be effective, but the evidence was insufficient to show that any particular drug is more effective than another. Surgery also plays an important role in treating Buruli ulcer, and consequently the independent effect of drugs is difficult to assess.
Updated Review
Primary antifungal prophylaxis for cryptococcal disease in HIV‐positive people (Awotiwon AA, Johnson S, Rutherford GW, Meintjes G, Eshun‐Wilson I)
Cryptococcal disease is one of the leading causes of death for HIV‐positive people who have low CD4 counts. The aim of this updated review is to find out if taking an antifungal drug regularly, such as fluconazole, prevented HIV‐positive people who have low CD4 cell counts from getting cryptococcal disease, and what the potential complications were. The original Cochrane review on this topic was published in 2005 (Chang 2005); the new review author team led by Ajibola Awotiwon has extensively revised the protocol. Nine trials, enrolling 5426 participants, met the inclusion criteria of this review. Six trials administered fluconazole, while three trials administered itraconazole. These trials were conducted in Australia, Canada, South Africa, the UK, the USA, Thailand, and sub‐Saharan Africa. Seven trials were conducted before the availability of modern antiretroviral therapy. The participants in two large trials received modern HIV treatment regimens. The results show that antifungal prophylaxis may have no effect on death overall, but it reduced the risk of those with low CD4 counts developing cryptococcal disease by 71%. Prophylaxis with an antifungal probably also reduced deaths specifically from cryptococcal disease. Generally, there were few side effects of taking antifungal prophylaxis, although there may be an increased risk of the vaginal tract becoming colonized with fluconazole‐resistant Candida organisms. The authors conclude that further research is not required to show the efficacy of primary antifungal prophylaxis in reducing the occurrence of cryptococcal disease, but analyses of the cost effectiveness and feasibility of implementing this intervention in different settings are needed.
2018, Issue 7
Two updated reviews and three new protocols are available in Issue 7 of the Cochrane Database of Systematic Reviews
Updated Reviews
Treatment for HIV-associated cryptococcal meningitis (Tenforde MW, Shapiro AE, Rouse B, Jarvis JN, Li T, Eshun-Wilson I, Ford N).
HIV-associated cryptococcal meningitis is a severe fungal infection of the brain and surrounding membranes that causes about 15% of HIV-related deaths worldwide, mostly in resource-limited countries. Treatment includes initial antifungal therapy followed by continuation treatment with oral fluconazole. The objective of the review is to evaluate the best induction therapy to reduce mortality from HIV-associated cryptococcal meningitis, and to compare side effect profiles of different therapies. This is an update of a review on the same topic last published in 2011; the new author team, led by Mark Tenforde, updated the protocol extensively, with changes in the inclusion criteria and methodology. The authors identified 13 studies with 2426 people for inclusion, which directly compared 21 different therapies. All studies were carried out in adults, and 11 out of 13 were conducted in resource-limited settings. Results show that a shorter initial treatment with one week of combined amphotericin B deoxycholate and flucytosine probably results in lower risk of death, similar clearance of the infection, and less toxicity than longer treatment with two weeks of the same combination, that has traditionally been recommended in treatment guidelines. Where amphotericin B deoxycholate cannot be given, two weeks of combined flucytosine with fluconazole is likely a good treatment option. Given the absence of data from studies in children, and limited data from high-income countries, this review’s findings provide limited guidance for treatment in these patients and settings.
Early versus delayed antiretroviral treatment in HIV-positive people with cryptococcal meningtis (Eshun-Wilson I, Okwen MP, Richardson M, Bicanic T).
This is an update of a review last published in 2013; Ingrid Eshun-Wilson and colleagues have extensively revised the protocol. The aim of the review is to determine whether initiating antiretroviral therapy (ART) within four weeks of cryptococcal meningitis treatment results in a higher risk of dying or developing other complications than waiting more than four weeks to initiate ART. This higher risk of death in the early ART group has been attributed to the occurrence of a condition called immune reconstitution inflammatory syndrome (IRIS). The review includes 4 trials with 294 adult participants, all from low- and middle-income countries. Despite the low certainty of the evidence, results suggest that early ART initiation increases the risk of mortality compared to delaying ART beyond four weeks among HIV-positive adults with cryptococcal meningitis. Findings from this Cochrane Review contributed to the formulation of the current World Health Organization (WHO) guidelines for the diagnosis, prevention, and management of cryptococcal disease in HIV-positive adults, adolescents, and children (WHO 2018).
New Protocols
Drug therapy for Mycetoma (Scolding P, Fahal A, Yotsu RR).
Measures of antiretroviral adherence for detecting viral non-suppression in people living with HIV (Hine P, Smith R, Eshun-Wilson I, Orrell C, Cohen K, Leeflang MMG, Ford N.)
Contact tracing strategies in household and congregate environments to identify cases of tuberculosis in low- and moderate-incidence populations (Braganza Menezes D, Menezes B, Dedicoat M).
2018, Issue 6
New Review
One new review is available in Issue 6, of the Cochrane Database of Systematic Reviews
Ribavirin for treating Crimean Congo haemorrhagic fever (Johnson S, Henschke N, Maayan N, Mills I, Buckley BS, Kakourou A, Marshall R).
In this new review, Samuel Johnson and colleagues investigate the effects of ribavirin for treating people with Crimean Congo haemorrhagic fever (CCHF). Infection with CCHF in people is usually due to a tick bite or by contact with infected bodily fluids from humans or animals; those at highest risk of contracting the virus are people who work outdoors in CCHF-endemic areas, those who work with large domestic animals, and healthcare workers. The disease occurs in parts of Asia, Europe and Africa but it has become more common in the last 15 years, particularly in Turkey and parts of Eastern Europe. CCHF is managed with supportive medical care (use of fluids, good nursing care, and blood products in response to changes in the blood's ability to clot), but the antiviral drug ribavirin is widely used in healthcare settings as a form of post-exposure prophylaxis for those exposed to CCHF. Prompt treatment with ribavirin following diagnosis of CCHF is included in several national guidelines, but these recommendations are not based on a robust evidence base, and this reviews aimed to summarize the data available to address whether ribavirin reduces the number of deaths from CCHF, and also assess its potentially serious, life-threatening adverse effects. The review includes 23 studies, of various designs, but because of poor quality there was insufficient reliable evidence to show whether ribavirin is effective in treating Crimean Congo haemorrhagic fever.
2018, Issue 5
Updated Review
One updated review is available in Issue 5, of the Cochrane Database of Systematic Reviews
Vaccines for preventing typhoid fever (Milligan R, Paul M, Richardson M, Neuberger A)
This is an update of the 2014 review, with some changes in the methods and inclusion criteria, and a new author team led by Rachel Milligan of the LSTM. The review now includes randomized and quasi-randomized controlled trials (RCTs) of the following typhoid vaccines: Live oral vaccine Ty2la or genetic modifications, Vi polysaccharide vaccine, and conjugate vaccines. It excludes trials that evaluated killed whole-cell vaccines, because these vaccines are no longer in use. 18 RCTs are included: 13 evaluated efficacy, and 9 reported on adverse events. All trials but one took place in typhoid-endemic countries. There was no information on vaccination in adults aged over 55 years of age, pregnant women, or travellers; only one trial included data on children under two years of age. Results show that the two main vaccines currently licensed for use, Ty21a and Vi polysaccharide, were effective in reducing typhoid fever in adults and children over two years in endemic countries; adverse events such as nausea, vomiting, and fever were rare. The Vi-rEPA vaccine is just as efficacious, although data is only available for children. The new Vi-TT vaccine (PedaTyph) requires further evaluation to determine if it provides protection against typhoid fever. At the time of writing, there were only efficacy data from a human challenge setting in adults on the Vi-TT vaccine (Tybar), which is being tested in an ongoing field trial.
2018, Issue 4
New Reviews
Two new reviews , are available in Issue 4, of the Cochrane Database of Systematic Reviews
Ivermectin and permethrin for treating scabies (Rosumeck S, Nast A, Dressler C)
In this new review, Stefanie Rosumeck and co-authors assess the efficacy and safety of topical permethrin and topical or systemic ivermectin to treat scabies in people of all ages. Scabies is an intensely itchy parasitic infection of the skin. It occurs throughout the world, but is particularly problematic in areas of poor sanitation, overcrowding, and social disruption. The review includes 15 relevant studies, nearly all set in South Asia or North Africa, with 1896 participants, comparing topical permethrin, systemic ivermectin, or topical ivermectin. Risk of bias in the included trials was moderate, and reporting was poor in many studies. Overall, there was no difference detected in the efficacy of permethrin compared to systemic or topical ivermectin, and all lead to high clearance rates in the treatment of scabies. Only few and mild adverse events were reported. The choice of one of these three treatments can be guided by considerations of practicability, availability, drug licensing, and costs depending on the individual setting: systemic ivermectin may be given preference if proper application cannot be ensured or if very large groups of patients need to be treated, but it is not indicated during pregnancy or for children weighing less than 15 kg. The included studies were mostly small and poorly reported, which affects the certainty of the level of evidence: further studies with clear and strict treatment regimens will help address the question of repeated treatment, and provide better documentation and classification of adverse events.
Smectite for acute infectious diarrhoea in children (Pérez-Gaxiola G, Cuello-García CA, Florez ID, Pérez-Pico VM)
Smectite is a medicinal clay commonly prescribed throughout the world as an adjuvant treatment to adults and children with infectious diarrhoea. Smectite has three possible mechanisms of action: an anti-inflammatory activity, alteration of the gut mucus barrier to reduce penetration of toxins, and adsorptive properties, which would reduce stool output in children, thereby providing symptomatic relief and possibly preventing dehydration. This new review by Giordano Pérez-Gaxiola and colleagues analysed randomized and quasi-randomized trials comparing smectite to a control group in children aged one month to 18 years old with acute infectious diarrhoea. Eighteen trials with 2616 children are included; they were conducted in both ambulatory and in-hospital settings, in both high-income and low- or middle-income countries, and most of them included children with rotavirus infections. Results show that smectite used as an adjuvant to rehydration therapy may reduce the duration of diarrhoea in children with acute infectious diarrhoea by a day; may increase cure rate by day 3; and may reduce stool output, but has no effect on hospitalization rates or need for intravenous therapy. There were no reports of serious adverse effects. The included studies were of low-certainty evidence, and the authors conclude that more high-quality studies are still needed, including studies that assess different causes of diarrhoea and the economic effects of this treatment.
2018, Issue 3
New Reviews
Two new reviews , are available in Issue 3, of the Cochrane Database of Systematic Reviews
Mefloquine for preventing malaria in pregnant women (González R, Pons-Duran C, Piqueras M, Aponte JJ, ter Kuile FO, Menéndez C)
In this new review, Raquel González and colleagues assess the effects of mefloquine for preventing malaria in pregnant women. Mefloquine is a possible alternative to sulfadoxine-pyrimethamine (SP), which is recommended by the World Health Organization for intermittent preventive treatment in pregnancy (IPTp) with for malaria for all women who live in moderate to high malaria transmission areas in Africa. Parasite resistance to SP has been increasing steadily in some areas, and there are potential drug interactions between SP and cotrimoxazole, which is used for prophylaxis in HIV-infected women. This review evaluates the efficacy, safety, and tolerability of mefloquine for preventing malaria in pregnant women, also considering the impact of HIV status, gravidity, and use of insecticide-treated nets. Six trials conducted between 1987 and 2013, with a total of 8192 pregnant women, are included in this review. Mefloquine prophylaxis compared with SP in HIV-uninfected women, and mefloquine prophylaxis plus cotrimoxazole compared with cotrimoxazole alone in HIV-infected women, reduced risks of maternal peripheral parasitaemia, made no difference in the prevalence of adverse maternal outcomes such as low birth weight, prematurity, stillbirths and abortions, and congenital malformations, and in the incidence of clinical malaria episodes during pregnancy, but increased risks of drug-related adverse events, especially vomiting and dizziness. The authors conclude that mefloquine was efficacious and safe in terms of pregnancy outcomes, but the high proportion of mefloquine-related adverse events constitutes an important barrier to its effectiveness for malaria preventive treatment in pregnant women. Future research should concentrate on optimizing the dose of mefloquine that would provide the same antimalarial beneficial effects while reducing its drug-related adverse events.
Nutritional supplements for patients being treated for active visceral leishmaniasis (Custodio E, López-Alcalde J, Herrero M, Bouza C, Jimenez C, Storcksdieck genannt Bonsmann S, Mouratidou T, López-Cuadrado T, Benito A, Alvar J)
Visceral leishmaniasis (VL), also known as kala-azar, is caused by protozoan parasites of the genus Leishmania, transmitted by sandflies. VL has a worldwide distribution but 90% of the cases occur in just six countries: India, Bangladesh, Sudan, South Sudan, Ethiopia, and Brazil, causing an estimated 20,000 to 40,000 deaths annually, and 357,000 disability-adjusted life years lost (DALYs). Malnutrition is one of the poor prognostic factors identified for leishmaniasis, and this new review prepared by a team led by Estefanía Custodio, aimed to assess the effects of nutritional supplementation in people treated for VL. Searches for randomized controlled trials, quasi-randomized controlled trials, and non-randomized controlled trials, of any oral nutritional supplement, compared to no nutritional intervention, placebo, or dietary advice alone, in people being treated for VL, found no studies, either completed or ongoing, eligible for inclusion in the review. The authors conclude that this absence of evidence should not be interpreted as evidence of no effect for nutritional supplements in people under VL treatment.
2018, Issue 2
Two new protocols, one new review and one updated review are available in Issue 2, of the Cochrane Database of Systematic Reviews
New Protocols
Rapid initiation of antiretroviral therapy for people living with HIV (Mateo-Urdiales A, Johnson S, Nachega JB, Eshun-Wilson I)
Impact of diagnostic test Xpert MTB/RIF® on health outcomes for tuberculosis (Haraka F, Nathavitharana RR, Schumacher SG, Kakolwa M, Denkinger CM, Gagneux S, Reither K, Ross A)
New Review
Mosquito repellents for malaria prevention (Maia MF, Kliner M, Richardson M, Lengeler C, Moore SJ)
In this new review, Marta Maia and colleagues assess the impact of mosquito repellents (which include topical repellents, insecticide-treated clothing, and mosquito coils) on malaria transmission. Considerable success against malaria has been achieved within the past decade mainly through long-lasting insecticide-treated nets (LLINs), but elimination of the disease is proving difficult, as people are not protected against mosquitoes biting when outdoors or outside sleeping hours. Also, there are situations where LLINs cannot be used, such as after a natural disaster or amongst displaced populations. Ten trials are included: 6 trials investigated topical repellents, 2 trials investigated insecticide-treated clothing, and 2 trials investigated spatial repellents. There was no conclusive evidence that topical repellents such as lotions can prevent clinical malaria or malaria infection. Insecticide-treated clothing (ITC) were investigated in trials conducted in refugee camps in Pakistan and amongst military based in the Colombian Amazon, which showed that ITC may reduce risk of malaria infection in the absence of insecticide-treated nets. Two studies, one in China and one in Indonesia, investigated the practice of burning mosquito coils to reduce malaria infections; the study designs were substantially different and one study had high risk of bias, and it is not possible to draw any conclusions. The authors were unable to make well-informed recommendations with regard to including or not including topical repellents, ITC, or spatial repellents in malaria control programmes; the use of ITC in refugee camps or disaster situations may be useful, but further research is needed.
Updated Review
Primaquine or other 8-aminoquinolines for reducing Plasmodium falciparum transmission (Graves PM, Choi L, Gelband H, Garner P)
The last version of this review by Tricia Graves, Hellen Gelband and Paul Garner was published in 2015. This update adds a new author (Leslie Choi) to the team. In 2012, the World Health Organization (WHO) recommended a single dose of 0.25 mg/kg primaquine (PQ) be added to malaria treatment schedules in low-transmission areas or those with artemisinin resistance, in order to reduce malaria transmission, replacing the previous recommendation of 0.75 mg/kg, with the aim of reducing haemolysis risk in people with glucose-6-phosphate dehydrogenase deficiency, common in people living in malaria-endemic areas. This updated review includes 7 new trials, for a total of 25 trials: 2 trials comparing PQ and bulaquine (BQ), and 23 trials comparing PQ versus arms without PQ. The results show that a single low dose of PQ (0.25 mg/kg) added to artemisinin-based combinations reduces infectiousness of people to mosquitoes at day 3-4 and day 8, and appears as effective as the higher doses. The absolute effect is greater at day 3 or 4, and smaller at day 8, in part because of the lower infectiousness in the control group. There was no evidence of increased haemolysis at 0.25 mg/kg, but few G6PD-deficient individuals were included in the trials. However, there were no ideal studies reporting malaria transmission intensity in communities, and infectiousness to mosquito was measured by direct or membrane feeding, or using measures of potential infectiousness. It is unclear whether the observed reduction in infectiousness would actually have an impact on reducing community prevalence of malaria.
2018, Issue 1
Three new protocols are available in Issue 1, of the Cochrane Database of Systematic Reviews
New Protocols
Symptom screening for active tuberculosis in pregnant women living with HIV (LaCourse SM, Cranmer LM, Bekker A, Steingart KR, Black D, Horne DJ, Oren E, Pals S, Modi S, Mathad J)
Shortened treatment regimens versus the standard regimen for drug-sensitive pulmonary tuberculosis (Grace AG, Mittal A, Jain S, Tripathy JP, Satyanarayana S, Tharyan P, Kirubakaran R)
MVA85A vaccine to enhance BCG for preventing tuberculosis (Kashangura R, Jullien S, Garner P, Young T, Johnson S)