Manmohan Shukla

A Multicenter Study of Azithromycin, Alone and in Combination with Chloroquine, for the Treatment of Acute Uncomplicated Plasmodium falciparum Malaria in India

BACKGROUND Azithromycin has demonstrated in vitro and in vivo activity against Plasmodium falciparum, but small treatment studies have given mixed results. METHODS Participants with fever and with both a blood smear and a rapid diagnostic test positive for falciparum malaria were randomly assigned to groups that were treated with either azithromycin or chloroquine or to matched groups receiving a placebo. After an interim analysis, open-label combination therapy with both drugs was initiated. RESULTS At day 28, 5 (33%) of 15 participants in the azithromycin-treated group had remained free of fever, compared with 4 (27%) of 15 in the chloroquine-treated group. All subsequently enrolled participants then received combination therapy with azithromycin and chloroquine. In 61 (97%) of 67 participants, resolution of fever and parasitemia had occurred by day 7, and, through day 28, no clinical or parasitologic relapse had occurred in them. CONCLUSIONS Resolution of parasitemia was inadequate with monotherapy with either azithromycin or chloroquine, but combination therapy provided substantially improved clinical and parasitologic outcomes. The combination of azithromycin and chloroquine may be an effective alternative treatment for falciparum malaria and deserves further study.

The usefulness of a new rapid diagnostic test, the First Response® Malaria Combo (pLDH/HRP2) card test, for malaria diagnosis in the forested belt of central India

BackgroundMalaria presents a diagnostic challenge in tribal belt of central India where two Plasmodium species, Plasmodium falciparum and Plasmodium vivax, are prevalent. In these areas, rapid detection of the malaria parasites and early treatment of infection remain the most important goals of disease management. Therefore, the usefulness of a new rapid diagnostic (RDT), the First Response® Combo Malaria Ag (pLDH/HRP2) card test was assessed for differential diagnosis between P. falciparum with other Plasmodium species in remote villages of Jabalpur district.MethodsA finger prick blood sample was collected to prepare blood smear and for testing with the RDT after taking informed consent. The figures for sensitivity, specificity, accuracy and predictive values were calculated using microscopy as gold standard.ResultsAnalysis revealed that overall, the RDT was 93% sensitive, 85% specific with a positive predictive value (PPV) of 79%, and a negative predictive value (NPV) of 95%. The accuracy 88% and J-index was 0.74. For P. falciparum, the sensitivity and specificity of the test were 96% and 95% respectively, with a PPV of 85% and a NPV of 99%. The RDT accuracy 95% and J-index was 0.84. For non-falciparum malaria, the sensitivity, specificity and accuracy were 83%, 94% and 92% respectively with a PPV of 69% and a NPV of 97%.ConclusionThe RDTs are easy to use, reliable and simple to interpret. RDTs are more suited to health workers in situations where health services are deficient or absent. Therefore, the test can be used as an epidemiological tool for the rapid screening of malaria.

Burden of malaria in pregnancy in Jharkhand State, India

BackgroundPast studies in India included only symptomatic pregnant women and thus may have overestimated the proportion of women with malaria. Given the large population at risk, a cross sectional study was conducted in order to better define the burden of malaria in pregnancy in Jharkhand, a malaria-endemic state in central-east India.MethodsCross-sectional surveys at antenatal clinics and delivery units were performed over a 12-month period at two district hospitals in urban and semi-urban areas, and a rural mission hospital. Malaria was diagnosed by Giemsa-stained blood smear and/or rapid diagnostic test using peripheral or placental blood.Results2,386 pregnant women were enrolled at the antenatal clinics and 718 at the delivery units. 1.8% (43/2382) of the antenatal clinic cohort had a positive diagnostic test for malaria (53.5% Plasmodium falciparum, 37.2% Plasmodium vivax, and 9.3% mixed infections). Peripheral parasitaemia was more common in pregnant women attending antenatal clinics in rural sites (adjusted relative risk [aRR] 4.31, 95%CI 1.84-10.11) and in those who were younger than 20 years (aRR 2.68, 95%CI 1.03-6.98). Among delivery unit participants, 1.7% (12/717) had peripheral parasitaemia and 2.4% (17/712) had placental parasitaemia. Women attending delivery units were more likely to be parasitaemic if they were in their first or second pregnancy (aRR 3.17, 95%CI 1.32-7.61), had fever in the last week (aRR 5.34, 95%CI 2.89-9.90), or had rural residence (aRR 3.10, 95%CI 1.66-5.79). Malaria control measures including indoor residual spraying (IRS) and untreated bed nets were common, whereas insecticide-treated bed nets (ITN) and malaria chemoprophylaxis were rarely used.ConclusionThe prevalence of malaria among pregnant women was relatively low. However, given the large at-risk population in this malaria-endemic region of India, there is a need to enhance ITN availability and use for prevention of malaria in pregnancy, and to improve case management of symptomatic pregnant women.

Malaria control using indoor residual spraying and larvivorous fish: a case study in Betul central India.

Objectives  To assess the impact of intensified malaria control interventions in an ethnic minority community in Betul using existing tools.

A preliminary study on pro- and anti-inflammatory cytokine profiles in Plasmodium vivax malaria patients from central zone of India.

The aim of this preliminary study was to investigate the plasma cytokine profiles in a group of patients suffering from Plasmodium vivax malaria during the peak of its transmission season. Plasma samples of 173 P. vivax patients and 34 healthy individuals were analyzed for IFN-gamma, TNF-alpha, IL-10 and IP-10 levels by ELISA. Levels of both pro- and anti-inflammatory cytokines were significantly higher in P. vivax patients compared to controls. Children with P. vivax infection had significantly higher levels of IFN-gamma than adults (P=0.017). Asexual parasitaemia versus TNF-alpha (r=-0.31, P=0.01), IL-10 (r=-0.30, P=0.015) and gametocytaemia versus IFN-gamma (r=-0.26; P=0.034) levels showed significant negative correlation in children compared to adults. The median concentrations of IFN-gamma (P=0.001), IL-10 (P=0.032) and IP-10 (P</=0.05) were higher in children reported with chills and rigors, whereas in adults only IFN-gamma levels was higher (P<0.0001). The median plasma concentrations of IFN- gamma (P=0.02), IL-10 (P<0.0001) and IP-10 (P=0.068) were higher in patients with mild anaemia compared to non-anaemic patients. The results indicated that both pro- and anti-inflammatory cytokine responses are associated with clinical signs of mild anaemia and paroxysm during symptomatic P. vivax malaria in Central India.

An assessment of the usefulness of a rapid immuno-chromatographic test, "Determine™ malaria pf" in evaluation of intervention measures in forest villages of central India

BackgroundPlasmodium falciparum malaria, is a major health problem in forested tribal belt of central India. Rapid and accurate methods are needed for the diagnosis of P. falciparum. We performed a blinded evaluation of the recently introduced Determine™ malaria pf test (Abbott, Laboratories, Japan) compared with microscopy and splenomegaly in children in epidemic prone areas of district Mandla to assess the impact of intervention measures.MethodsChildren aged 2–10 yrs with and without fever were examined for spleen enlargement by medical specialist by establishing a mobile field clinic. From these children thick blood smears were prepared from finger prick and read by a technician. Simultaneously, rapid tests were performed by a field lab attendant. The figures for specificity, sensitivity and predictive values were calculated using microscopy as gold standard.ResultsIn all 349 children were examined. The sensitivity and specificity for Determine rapid diagnostic test were 91 and 80% respectively. The positive predictive values (PPV), negative predictive values (NPV) and accuracy of the test were respectively 79, 91 and 85%. On the contrary, the sensitivity and specificity of spleen in detecting malaria infection were 57 and 74 % respectively with PPV of 73%, NPV 59 % and an accuracy of 65%.ConclusionsDetermine™ malaria rapid diagnostic test is easier and quicker to perform and has other advantages over microscopy in not requiring prior training of personnel or quality control. Thus, highlighting the usefulness of a rapid antigen test in assessing prevailing malaria situation in remote areas.

Spleen rates and infant parasite rates as surveillance tool for malaria control in remote hard to reach areas of central India

BackgroundMalaria due to both Plasmodium falciparum and Plasmodium vivax is a major public health problem in India. The quantification of malaria transmission for the classification of malaria risk has long been a concern for epidemiologists. Results are presented from 30 cross-sectional surveys which measured spleen rates (SR) and infant parasite rates (IPR) in the forested districts of Madhya Pradesh during malaria outbreaks to assess whether both IPR and SR can still be used as indicators of malaria endemicity as spleen examination has lost much of its value as an epidemiological indicator in areas where anti-malarials drugs are widely used.MethodsRapid fever surveys were carried out from door to door and all suspected malaria cases in the entire population of a village were screened for malaria parasites on the basis of clinical symptoms such as fever, chill, rigor, headache and body ache etc. Children between 2 and 9 years were examined for enlarged spleen according to Hacketts method. Finger prick blood smears were collected from all children with enlarged spleen with or without fever after obtaining written informed consent following institutional ethical guidelines. Infants less than 1 year were also screened for malaria with or without fever.ResultsSince malaria is local and focal, in some areas the outbreak waned quickly in few months and in some areas continued for 3 to 4 years. The analysis of trend revealed that when IPR decline over the years as a result of malaria intervention measures, SR also decline. In case splenomegaly continues without diminution in size, it is probably due to recrudescence or relapse, although it is not possible to separate malaria parasite species on the basis of SR.ConclusionBoth the tools are of immense value in evaluating and assessing the malaria situation especially in remote areas where sophisticated molecular and serological techniques are difficult to establish. Therefore, in forested areas malaria surveillance system will require adoption of multiple approaches that have proven effective now or in the past.

Control of malaria in Central India (Madhya Pradesh): hope or hype?

Recent records (http://news.webindia123.com) show that larvivorous fish and drugs have cut the malaria burden in Madhya Pradesh (MP), which was until recently the second highest malarious state in India after Orissa1, steadily from 2005 to 2007. Malaria cases fell from 104 317 in 2005 to 96 042 in 2006 and 90 829 in 2007; the number of Plasmodium falciparum cases reduced from 32 223 in 2005 to 29 053 in 2006, however it increased to 36 622 in 2007 (http://www.health.mp.gov.in/malaria.htm). This decline in malaria cases was the result of appointing 4000 malaria link workers in 20 malaria-affected districts, the establishment of drug distribution centres for free distribution of chloroquine, and the release of a large number of larvivorous fish by the government of MP (http://news.webindia123.com). Effective malaria control leading to reduced malaria incidence has also recently been reported using larvivorous fish in Bangalore2 and Assam.3 However, in MP the number of deaths due to malaria is on the increase, mainly due to the frequent occurrence of outbreaks that cause high morbidity and mortality (http://www.health.mp.gov.in/malaria.htm). For instance, an outbreak in Sidhi district in 2005 and 2006 caused 25 deaths annually due to P. falciparum. The actual death toll was estimated to be much higher as these deaths were recorded only in the district hospital, which many patients could not reach because of inaccessibility and lack of a transport system. A rapid fever survey conducted in Sidhi by the National Institute of Malaria Research Field Station (NIMRFS), Jabalpur, during 2006 revealed a high prevalence of malaria (298/875), particularly P. falciparum (248/875). All age groups were affected, including infants aged <1 year (4/11). The infant parasite rate (IPR) was 36% (P. vivax:P. falciparum 50:50), indicating intense malaria transmission. A similar high prevalence was also recorded in 2007 from Sidhi (1022/3091) with a 20% IPR, indicating that control measures were inadequate. In 2008, a malaria outbreak was recorded in Shivpuri. Rapid fever surveys carried out by the NIMR-FS Jabalpur revealed a high prevalence of malaria (597/1820), with 78% P. falciparum and an IPR of 28% (25/90), of which 60% were P. falciparum. The presence of two highly efficient vectors (Anopheles culicifacies and A. fluviatilis) in an area where both P. falci-

Vector-borne diseases in central India, with reference to malaria, filaria, dengue and chikungunya

Background: Vector-borne diseases (VBDs) caused by parasites and viruses are a major cause of morbidity and mortality in Madhya Pradesh (MP), central India. These diseases are malaria, lymphatic filariasis, dengue and chikungunya. Epidemiological information is lacking on different VBDs that are commonly prevalent in rural-tribal areas of MP, except on malaria. Methods: The studies were carried out at the request of Government of Madhya Pradesh, in three locations where many VBDs are endemic. Data on malaria/filaria prevalence were collected by repeatedly undertaking cross-sectional parasitological surveys in the same areas for 3 years. For dengue and chikungunya, suspected cases were referred to the research centre. Results: Monitoring of results revealed that all the diseases are commonly prevalent in the region, and show year-to-year variation. Malaria slide positivity (the number of malaria parasitaemic cases, divided by the total number of blood smears made) was 18.7% (190/1018), 16.4% (372/2266) and 20.4% (104/509) respectively in the years 2011, 2012 and 2013. There was a strong age pattern in both Plasmodium vivax and P. falciparum. The slide vivax rate was highest among infants, at 5% (odds ratio [OR] = 3.8; 95% confidence interval [CI] – 1.5 to 9.4; P<0.05) and the highest slide falciparum rate was 20% in children aged 1–4 years (OR = 2.0; 95%CI 1.5 to 2.7; p<0.0001). This age-related pattern was not seen in other VBDs. The microfilaria rate was 7.5%, 7.6% and 7.8% in the years 2010, 2012 and 2013, respectively. Overall, microfilaria rates were higher in males (8.7%) as compared to females 6.4% (OR = 1.5; 95% CI = 1.1 to 2.0; P < 0.01). The prevalence of dengue was 48% (dengue viruses 1 and 4 – DENV-1 and DENV-4), 59% (DENV-1) and 34% (DENV-3) respectively, in the years 2011, 2012 and 2013 among referred samples, while for chikungunya very few samples were found to be positive. Conclusion: Despite recent advances in potential vaccines and new therapeutic schemes, the control of VBDs remains difficult. Therefore, interruption of transmission still relies on vector-control measures. A coordinated, consistent, integrated vector-management approach is needed to control malaria, filaria, dengue and chikungunya.