Rickettsial diseases, caused by a variety of obligate intracellular, g0 ram-negative bacteria from the genera Rickettsia, Orientia, Ehrlichia, Neorickettsia, Neoehrlichia, and Anaplasma, belonging to the Alphaproteobacteria, are considered some of the most covert emerging and re-emerging diseases and are being increasingly recognized. Among the major groups of rickettsioses, commonly reported diseases in India are scrub typhus, murine flea-borne typhus, Indian tick typhus and Q fever. Rickettsial infections are generally incapacitating and difficult to diagnose; untreated cases have case fatality rates as high as 30-45 per cent with multiple organ dysfunction, if not promptly diagnosed and appropriately treated. The vast variability and non-specific presentation of this infection have often made it difficult to diagnose clinically. Prompt antibiotic therapy shortens the course of the disease, lowers the risk of complications and in turn reduces morbidity and mortality due to rickettsial diseases. There is a distinct need for physicians and health care workers at all levels of care in India to be aware of the clinical features, available diagnostic tests and their interpretation, and the therapy of these infections. Therefore, a Task Force was constituted by the Indian Council of Medical Research (ICMR) to formulate guidelines for diagnosis and management of rickettsial diseases. These guidelines include presenting manifestations, case definition, laboratory criteria (specific and supportive investigations) and treatment.

In this study, by characterizing several human monoclonal antibodies (mAbs) isolated from single B cells of the COVID-19–recovered individuals in India who experienced ancestral Wuhan strain (WA.1) of SARS-CoV-2 during early stages of the pandemic, we found a receptor binding domain (RBD)–specific mAb 002-S21F2 that has rare gene usage and potently neutralized live viral isolates of SARS-CoV-2 variants including Alpha, Beta, Gamma, Delta, and Omicron sublineages (BA.1, BA.2, BA.2.12.1, BA.4, and BA.5) with IC ₅₀ ranging from 0.02 to 0.13 μg/ml. Structural studies of 002-S21F2 in complex with spike trimers of Omicron and WA.1 showed that it targets a conformationally conserved epitope on the outer face of RBD (class 3 surface) outside the ACE2-binding motif, thereby providing a mechanistic insights for its broad neutralization activity. The discovery of 002-S21F2 and the broadly neutralizing epitope it targets have timely implications for developing a broad range of therapeutic and vaccine interventions against SARS-CoV-2 variants including Omicron sublineages.

Vector-borne diseases (VBDs) exert a substantial burden across the world, especially in tropical countries. Malaria, chikungunya, dengue, visceral leishmaniasis, lymphatic filariasis and Japanese encephalitis are among the public health concerns for India. One of the major pillars for the containment of VBDs is vector control and different tools have been employed for several decades. These range from chemical insecticides used in indoor residual sprays, space sprays, fogging, treated bednets and larvicides to biological control methods such as larvivorus fishes and environmental control and modification measures such as source reduction. However, these methods are increasingly becoming less effective due to several reasons such as insecticide resistance, outdoor biting, behavioural changes in vectors for biting and resting, climate change, movement of population, vector incursion to newer areas and others. It is essential to develop and test new tools for vector control to surmount these challenges. Though focusing on India’s public health concerns, the new tools enumerated here can be tested by any country with similar epidemiological and environmental conditions. The promising new vector control tools are insecticide-treated nets with synergist and/or pyrrole chlorfenapyr, alternatives/additions to synthetic pyrethroids like neonicotinoids, clothianidin for indoor residual spray, newer formulations such as Bacillus sphaericus for use in larvicides, attractive toxic sugar baits, especially to curtail outdoor transmission, endectocides like ivermectin for use in animals/humans, insecticidal paints, spatial repellents, insecticide-treated wearables and others. Genetic modification technologies (Sterile Insect Technique/Incompatible Insect Technique/Wolbachia transfection) are also upcoming strategies. Among the six VBDs, India is committed to the elimination of three (malaria, visceral leishmaniasis and lymphatic filariasis) and it will require additional and/or novel tools to overcome the roadblocks in our current journey to the goal of control/elimination of these VBDs.

Better drug regimens for mass drug administration (MDA) could accelerate the Global Programme to Eliminate Lymphatic Filariasis (LF). This community study was designed to compare the safety and efficacy of MDA with IDA (ivermectin, diethylcarbamazine and albendazole) or DA (diethylcarbamazine and albendazole) in India. This two-armed, open-labelled, block randomised, community study was conducted in LF endemic villages in Yadgir district, Karnataka, India. Consenting participants ≥5 years of age were tested for circulating filarial antigenemia (CFA) and microfilaremia (Mf) before treatment with a single oral dose of IDA or DA. Adverse events (AEs) were monitored actively for two days and passively for five more days. Persons with positive CFA or Mf tests at baseline were retested 12-months post-treatment to assess treatment efficacy. Baseline CFA and Mf-rates were 26.4% and 6.9% in IDA and 24.5% and 6.4% in DA villages respectively. 4758 and 4160 participants received IDA and DA. Most AEs were mild after both treatments; fewer than 0.1% of participants experienced AEs with severity > grade 1. No serious AEs were observed. Fever, headache and dizziness were the most common AEs. AE rates were slightly higher after IDA than DA (8.3% vs. 6.4%, P<0.01). AEs were more frequent in females and Mf-positives after either treatment, but significantly more frequent after IDA (40.5% vs 20.2%, P < 0.001). IDA was more effective for clearing Mf than DA (84% vs. 61.8%, P < 0.001). Geometric mean Mf counts per 60μl in retested Mf-positives decreased by 96.4% from 11.8 after IDA and by 90.0% from 9.5 after DA. Neither treatment was effective for clearing CFA. IDA had an acceptable safety profile and was more effective for clearing Mf than DA. With adequate compliance and medical support to manage AEs, IDA has the potential to accelerate LF elimination in India. Clinical Trial Registry of India (CTRI No/2016/10/007399) Lymphatic filariasis (LF) is a major neglected tropical disease that is caused by filarial nematode worms. The strategies of the Global Programme to Eliminate Lymphatic Filariasis, launched in 2000, are mass drug administration (MDA) of antifilarial medications to kill the parasites and reduce transmission and morbidity management and disability prevention for those who are already affected by the disease. Recent clinical trials have shown that a single co-administered dose of ivermectin, diethylcarbamazine and albendazole (IDA) is more effective for clearing microfilariae (Mf) from the blood than the traditional two-drug regimen (DA). That is important, because blood Mf are essential for mosquitoes to transmit the parasite. As part of a large multicenter study, we assessed the safety of IDA and compared the efficacy of IDA and DA for clearing parasites from the blood. We treated almost 9,000 people in Wuchereria bancrofti endemic villages with either IDA or DA. Adverse events (AE) were monitored actively for two days and passively for another five days. AE rates were slightly higher after IDA than DA, but AEs were mild and self-limited. Infected persons, adults and females had higher AE rates in both treatment areas. We retested infected persons one year after treatment. IDA was significantly more effective for clearing Mf and reducing blood Mf counts than DA. Neither treatment was effective for clearing circulating filarial antigenemia. Our large study showed that IDA was well tolerated and more effective than DA. This new treatment has the potential to hasten LF elimination in India and many other countries.

The prevalence of malaria in India is decreasing, but it remains a major concern for public health administration. The role of submicroscopic malaria and asymptomatic malaria parasitemia and their persistence is being explored. A cross-sectional survey was conducted in the Kandhamal district of Odisha (India) during May–June 2017. Blood samples were collected from 1897 individuals for screening of asymptomatic parasitemia. Samples were screened using rapid diagnostic tests (RDTs) and examined microscopically for Plasmodium species. Approximately 30% of randomly selected samples (n = 586) were analyzed using real-time PCR (qPCR), and the genetic diversity of Plasmodium falciparum was analyzed. The prevalence of Plasmodium species among asymptomatic individuals detected using qPCR was 18%, which was significantly higher than that detected by microscopy examination (5.5%) or RDT (7.3%). Of these, 37% had submicroscopic malaria. The species-specific prevalence among asymptomatic malaria-positive cases for P. falciparum, Plasmodium vivax, and mixed infection (P. falciparum and P. vivax) by qPCR was 57%, 29%, and 14%, respectively. The multiplicity of infection was 1.6 and 1.2 for the merozoite surface protein-1 gene (msp1) and (msp2), respectively. Expected heterozygosity was 0.64 and 0.47 for msp1 and msp2, respectively. A significant proportion of the study population, 105/586 (18%), was found to be a reservoir for malaria infection, and identification of this group will help in the development of elimination strategies.

Wolbachia, an intracellular maternally transmitted endosymbiont, has been shown to interfere with the replication of dengue virus inAedes aegyptimosquitoes. TheWolbachia-transinfectedAe. aegyptihas been currently released in many countries to test its effectiveness in preventing the transmission of dengue virus. ICMR-Vector Control Research Centre in collaboration with World Mosquito Program Monash University, Australia, has generated two newWolbachia-introgressedAe. aegyptiPuducherry (Pud) linesviabackcrossingAe. aegyptifemales of Australian (Aus) strains, infected withwMel andwAlbBWolbachiawith wild-typeAe. aegyptiPuducherry (Pud) males.Wolbachiainfections are known to induce a fitness cost and confer benefit on the host mosquito populations that will influence spread of theWolbachiainto native wild mosquito populations during the field release. Hence, the induced fitness cost or benefit/advantage in the two newly generatedAe. aegypti(Pud) lines was assessed in the laboratory in comparison with the wild-typeAe. aegypti(Pud) strain. In addition, maternal transmission (MT) efficiency, induced cytoplasmic incompatibility (CI), and insecticide resistance status of the two (Pud) lines were determined to assess the likely frequency ofwMel andwAlbB infections in the native wild population after field invasion. The study shows thatwMel andwAlbB infections did not induce any fitness cost on the two newly generated (Pud) lines. Rather, in terms of wing length, fecundity, egg hatch rate, and adult survival, theWolbachiaintrogression conferred fitness benefits on the (Pud) lines compared to uninfectedWolbachiafree wildAe. aegyptipopulation.wMel andwAlbB exhibited a high maternal transmission (99–100%) and induced nearly complete (98–100%) cytoplasmic incompatibility. Both the (Pud) lines were resistant to deltamethrin, malathion, DDT, and temephos, and the level of resistance was almost the same between the two lines as in the wild type. Overall, the stable association ofwMel andwAlbB established withAe. aegyptiand the reproductive advantages of the (Pud) lines encourage a pilot release in the field for population replacement potential.